Handbook of Nutrition and Food PDF

HANDBOOK
of
NUTRITION
and
FOOD
2705_frame_FM Page 2 Thursday, September 20, 2001 2:09 PM
HANDBOOK
of
NUTRITION
and
FOOD
Edited by
CAROLYN D. BERDANIER
Editorial Board
Carolyn D. Berdanier, Ph.D.
Editor-in-Chief and Editor, Food and Metabolism
Elaine B. Feldman, M.D.

Editor, Human Nutrient Needs in the Life Cycle, Modified Diets,
and Clinical Nutrition
William P. Flatt, Ph.D.

Editor, Comparative Nutrition
Sachiko T. St. Jeor, Ph.D., R.D.

Editor, Human Nutritional Status Assessment
CRC PR E S S
Boca Raton London New York Washington, D.C.
2705_frame_FM Page 4 Friday, August 16, 2002 11:17 AM
Library of Congress Cataloging-in-Publication Data
CRC handbook of nutrition and food / edited by Carolyn D. Berdanier … [et al.].
p. cm.
Includes bibliographical references and index.
ISBN 0-8493-2705-9
1. Nutrition—Handbooks, manuals, etc. I. Title: Handbook of nutrition and food. II.
Berdanier, Carolyn D.
QP141 .C774 2001

612.3'9—dc21 2001035595
CIP
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Printed on acid-free paper
2705_frame_FM Page 5 Friday, August 16, 2002 11:17 AM
Preface
A number of years ago, Harvey Kane, an editor for CRC Press, approached me to organize
a reference text for nutrition along the lines of the CRC Handbook of Chemistry and Physics.
Little did I realize what a mammoth undertaking this would be. An initial Advisory Board
was convened and consisted of Ronald Entmiller, William P. Flatt, Terrance Yen, Mario
DiGirolamo, Malcolm Watford, Mary Francis Picciano, and myself. Once the Advisory
Board had outlined the Table of Contents, its work was complete. Together with Elaine
Feldman, Sachiko St. Joer, and William Flatt, the details of the book were finalized, authors
identified and contacted, and the book was put together. It was a four-year effort.
The Advisory Board met several times to discuss the target audience and what infor-
mation that audience would want in a reference book. We decided to include as much
material as possible that could be accessed using the World Wide Web. Hence, a number
of Web addresses are used in which large databases can be found. In the first section, for
instance, the data on food composition that has been accumulated by the United States
Department of Agriculture is not provided. Rather, the web addresses are given so that
the reader can find the specific information desired from this electronic alternative. A
number of uses exist for food composition data, and each user will have specific objectives
that we felt could be met if the electronic version was identified. In addition to these large
data sets, smaller tables of food composition are provided that may not be in the larger
data sets. Thus, the reader can find information about a food additive, tagatose, trans-
fatty acids, vitamin terminology, or tocopherol and tocotrienol content of selected foods.
In this first division of the book, the reader will also find several tables on food additives,
food contaminants, and toxins. These tables are supplemented by Section 55, prepared by
Venkitanarayanan and Doyle, that addresses food-borne illness and contains tables
describing bacterial, viral, fungal, and parasitic pathogens sometimes present in food.
These pathogens can cause a variety of clinical conditions; notably symptoms in the
digestive tract. The mechanisms of infection as well as how to avoid such infestation is
complemented by Sections 56 and 57, which describe nutrition and the hollow organs (the
upper and lower gastrointestinal tract). These sections, prepared by Mutlu et al., review
not only the anatomy and physiology of the gastrointestinal tract but also some of the
diseases that involve these organs with respect to nutrition.
In Section 1, the reader will find tables on plants — not only those that are edible and
those that are toxic, but also plants that some people believe have medicinal uses. Herbal
medicine is gaining popularity, and the reader should note that these tables contain certain
plants that meet all three definitions. They may have edible parts, they may have toxic
parts, and they may also be herbal remedies. The lines between these properties are
blurred mainly because the information about plants other than the traditional food plants
is minimal.
There are five tables in this section on vitamins and minerals. Summary tables give the
essentials of their use, chemical and physical properties, and so forth. These tables are
supplemented by Section 64 on vitamin deficiencies, Section 65, which describes the
rationale for the use of vitamin and mineral supplements, and Section 71, on trace mineral
deficiencies. These sections, prepared by Rivlin, Perelson and Ellenbogen, and Nielsen,
respectively, are in turn supplemented by sections that address the needs of humans at
various periods in the normal life cycle (Sections 5 through 10) and people who have
nutrition-related illnesses. In addition, the assessment of human nutritional status is

described using a variety of techniques, from food intake questionnaires to actual assess-
ment of body chemistry and physiology (Sections 15 through 26 and Sections 29 through
39). These sections provide not only the techniques for assessment but also some com-
mentary on the use of such data. The division on assessment also contains sections on the
use of assessment data in nutrition action programs. These programs are designed to
improve the health and wellbeing of the population through the use of a variety of
nutrition education tools.
For general reference, Section 2 provides metabolic maps for intermediary metabolism.
These are not as complete and detailed as one might want in biochemistry, but they provide
a frame of reference for the individual needing information to interpret the results of
clinical assessments of biological function. Section 3 provides a number of tables of clinical
interest to the reader. In keeping with today’s high interest in the genetic basis of health
and disease, this section contains several tables that list some genetic mutations associated
with diseases of nutritional interest. The reader will find lists of genetic diseases in
carbohydrate, lipid, and protein metabolism as well as tables listing mutations that asso-
ciate with obesity, diabetes, and lipemia. These tables are complemented by later sections
that describe the nutritional aspects of some of these diseases. For example, diabetes-
associated mutations (Table 3.7, Section 3) is complemented by Section 53, prepared by
Lopes-Virella et al., which describes the disease and its complications as well as the
nutrition strategies needed to optimize the health of the person with this disease. Similarly,
Section 3, Table 3.5 (Mutations that Phenotype as Obesity) is complemented by several
additional sections dealing with various aspects of obesity. In Section 8, on nutrition for
healthy children and adolescence, Baxter discusses the problem of obesity in this age
group. Obesity is addressed in Section 9, by Read, which describes nutrition for the adult.
Obesity assessment is discussed and described extensively in Part V. Section 27 deals with
the genetics of energy and nutrient intake, and Sections 29 through 38 describe various
ways to assess body composition as well as energy intake and expenditure. Sections 69
and 70 address the treatment of obesity in children and adults. Altogether the clinician
can acquire considerable information about the obesity problem, and each aspect is pre-
sented as a discrete section. The same is true for lipemia. Table 3.1 lists the lipid transport
proteins, and Table 3.6 in Section 3 gives mutations that phenotype as lipemia. These tables
are supplemented by Sections 26, 51, and 52, all prepared by Feldman. These sections
address the assessment of blood lipids and the role blood lipids have in the pathophysi-
ology of heart disease.
Section 3 contains some other tables that may be of interest to both the clinician and the
researcher. Table 3.22 shows how to convert clinical data into Standard International (SI)
units. Many research journals now require the use of SI units in their publications, yet
many researchers are still using assays that give results in mg/dl or some other traditional
unit. Hence, there is a need to convert these traditional units to the SI unit. Tables 3.21 and
3.22 should be quite useful in this respect. Lastly, although this is not a drug handbook,
there are some drugs that are of interest to the nutritionist, dietitian, and clinician. Table
3.12 is a list of drugs that influence nutrient use, and Table 3.23 is a list of drugs that have
anti-obesity properties. Drugs useful in the management of lipemia and diabetes are
described in the relevant sections, but the reader should consult a drug handbook for
additional information.
A number of large data sets exist describing the nutrient needs of non-human species.
These data sets have been compiled by the National Academy of Sciences. A list of the
web addresses for these data sets is provided in Part III, Section 4, by Flatt. Scientists
wishing to use any of these species in their nutrition research will find these data sets
particularly useful.
2705_frame_FM Page 7 Tuesday, September 25, 2001 11:44 AM
The nutrient needs of humans throughout the life cycle, from gestation to the later years,
are represented in Part IV. Each of these periods of life has special considerations and
these are summarized in Sections 5 through 10. Kolasa and Weismiller have discussed the
food and nutrition needs of the pregnant woman and her fetus. Bhatia et al. continue with
a description of the nutrition of the premature and full term infant (Sections 6 and 7).
Baxter addresses the nutrition concerns of the child and adolescent. This is followed by
an extensive discussion of a health-promoting diet throughout life (Section 9) and the later
years (Section 10).
Part VI contains information about modified diets. Included is a section on vegetarian
diets, sections on enteral and parenteral nutrition support, and a section devoted to the
elite athlete.
Lastly, Part VII, the largest division, is devoted to the clinical conditions that have a
nutrition component in either their management or development. The anemias are
addressed by Hendricks and Kutlar, alcoholism is described by Lieber, hypertension by
Prisant, diabetes, obesity, lipemias, and heart disease as mentioned above; cancer is dis-
cussed in Sections 49 and 50, and nutrition as related to oral medicine; the pancreas, liver,
kidney, skeletal system, teeth, and eyes are all given special treatment.
Altogether this broad range of nutrition concerns should be of interest to the clinician,
the dietician, the nutrition scientist, and the pharmacist. There is a degree of unavoidable
redundancy in the book since there are several different uses for the materials provided.
Rather than deleting these duplications, we felt that their inclusion with interpretive text
made sense. We hope that you, the reader, enjoy this book and find it a useful reference.
Carolyn D. Berdanier
Editors
Carolyn D. Berdanier, Ph.D., is Professor Emerita of Nutrition at the University of Georgia

(UGA) in Athens. She earned a B.S. degree from the Pennsylvania State University, and
M.S. and Ph.D. degrees from Rutgers University. After a postdoctoral fellowship with Dr.
Paul Griminger at Rutgers, she served as a Research Nutritionist with the United States
Department of Agriculture Human Nutrition Institute in Beltsville, Maryland. She also
served the University of Maryland in the graduate nutrition program while she was with
USDA. In 1975 she relocated to the University of Nebraska College of Medicine, and then
in 1977 assumed the post of department head for nutrition at the University of Georgia.
After eleven years in this position, she stepped down to continue her research in nutrient-
gene interactions, with a special interest in diabetes. Her research has been supported by
the National Institutes of Health, the U.S. Department of Agriculture, the Bly Fund, the
National Livestock and Meat Board, the U.S. Department of Commerce, the Southeast
Poultry and Egg Association, and the UGA Diabetes Research Fund.
Dr. Berdanier has authored over 150 publications in peer-reviewed scientific journals,
contributed 35 chapters to multiauthored books, and has edited/authored nine books. She
has served on the Editorial Boards of The FASEB Journal, The Journal of Nutrition, Biochemical
Archives, Nutrition Research, Nutrition Reviews, and the International Journal for Diabetes
Research. She also serves as an ad hoc reviewer for numerous other journals in her field
of metabolism and nutrient-gene interactions.
Elaine Bossak Feldman holds M.D., A.B. (magna cum laude) and M.S. degrees from New
York University, where she was elected to Phi Beta Kappa and Alpha Omega Alpha. She
trained in internal medicine, metabolism, and nutrition at the Mount Sinai Hospital in
New York, held research fellowships from the New York Heart Association and the
National Institutes of Health (Career Development Award, Department of Physiological
Chemistry, Lund University, Sweden), and served on the faculty of the Department of
Medicine, State University of New York Medical School in New York City. She is board
certified in internal medicine and clinical nutrition.
Dr. Feldman is Professor Emeritus of Medicine, Physiology, and Endocrinology at the
Medical College of Georgia in Augusta; she is Chief Emeritus of the Section of Nutrition
and Director Emeritus of the Georgia Institute of Human Nutrition. She was the founding
director of the Southeastern Regional Medical Nutrition Education Network of 15 medical
schools in the Southeast. At the Medical College she was the principal investigator of a
curriculum development grant from the Department of Health and Human Services, and
of a Clinical Nutrition Research Unit, as well as a number of diet and drug studies in
hyperlipidemia.
A noted author and lecturer on nutrition and lipidology, Dr. Feldman has published 82
articles in peer-reviewed biomedical journals and 56 invited articles. She currently serves
on the editorial boards of Nutrition Reviews, Nutrition Today, and Nutrition Update. She has
edited or written 32 books, book chapters, and monographs, including a textbook, Essen-
tials of Clinical Nutrition. Dr. Feldman is a Fellow of the American Heart Association’s
Council on Arteriosclerosis, the American College of Physicians, and the American Society
for Nutrition Sciences. She serves as a consultant for the American Institute for Cancer
Research and the American Medical Women’s Association.
Dr. Feldman served on the Nutrition Study Section of the National Institutes of Health
and is listed in Who’s Who in America. She has received the Goldberger Award in clinical
nutrition from the American Medical Association, the Calcium Nutrition Education Award
from the American Medical Women’s Association, the Special Recognition Award of the
Council on Arteriosclerosis, and the National Dairy Council’s award for Excellence in
Medical Nutrition Education from the American Society for Clinical Nutrition.
Sachiko T. St. Jeor, Ph.D., R.D. is Director of the Nutrition Education and Research
Program and Professor of Clinical Medicine at the University of Nevada School of Med-
icine in Reno, Nevada. Her research interests are in the areas of obesity, weight manage-
ment, nutrition assessment, and nutrition in medical education. Dr. St. Jeor has been
honored as an outstanding alumna from both the College of Human Development at the
Pennsylvania State University and the College of Health at the University of Utah. She
has also received the Medallion Award and Excellence in the Practice of Dietetic Research
and chaired the Council of Research of the American Dietetic Association. She is a founding
member of the Council on Renal Nutrition of the National Kidney Association. Dr. St. Jeor
was a member of the 1995 U.S. Dietary Guidelines Committee, and the Institute of Med-
icine’s Committee on Opportunities in the Nutrition and Foods Sciences and Committee
to Develop Criteria for Evaluating the Outcomes of Approaches to Prevent and Treat
Obesity. She has also served on the Behavioral Medicine Study Section, Epidemiology and
Disease Prevention Study Section, and Clinical Applications and Prevention Advisory
Committee for the National Institutes of Health. She has served on the editorial boards
of the Topics in Applied Nutrition, Journal of the American Dietetic Association, Behavioral
Medicine Abstracts, Obesity Research, and Weight Control Digest. Dr. St. Jeor holds a B.A. in
Nutrition from the University of Utah, Salt Lake City, an M.S. in Nutrition from the
University of Iowa, Iowa City; and a Ph.D. in Nutrition from Pennsylvania State Univer-
sity, University Park.
William P. Flatt, Ph.D. is Professor Emeritus, Department of Foods and Nutrition, and
D.W. Brooks Distinguished Professor, University of Georgia.
Dr. Flatt earned his Ph.D. in Animal Nutrition at Cornell University in 1955. He has
served on the faculty of the University of Georgia since 1974, during which time he was
department head for Animal Sciences, Experiment Station Director, and Dean of the
College of Agriculture. Following his tenure as dean, he affiliated with the Department
of Foods and Nutrition, where he maintains an active research agenda in energy metab-
olism, calorimetry, and obesity.
Acknowledgments
The editors would like to express their appreciation to the many authors who contributed
their expertise and time to the preparation of this reference text. Also appreciated are the
many secretaries who prepared the typed material and the artists who prepared the
illustrations. We also wish to acknowledge the contributions of the many journal and
textbook publishers who allowed us to include their copywrited material in this book. Of
course it goes without saying that this reference text would not have become a reality
without the encouragement and support of the editors at CRC Press. We especially appre-
ciate the efforts of Ira Wolinsky, Harvey Kane, Lourdes Franco, and Carol Hollander. Lastly,
let me say thanks to my faithful helpers here at the University of Georgia: Kathie Wickwire
and Tonya Dalton.
Contributors
Kelly Adams Carolyn D. Berdanier

Department of Nutrition Department of Nutrition
University of North Carolina University of Georgia
Chapel Hill, North Carolina Athens, Georgia
Maria Alexander Michael Bergeron

Division of Nutrition and Physical Medical College of Georgia
Activity Georgia Prevention Institute
National Center for Chronic Disease Augusta, Georgia
Prevention and Health Promotion Bryan C. Bergman
Centers for Disease Control and University of Colorado Health Sciences
Prevention Center
Atlanta, Georgia Center for Human Nutrition
Denver, Colorado
M. Joao Almeida
The Cooper Institute Odilla I. Bermudez
Dallas, Texas New England Medical Center Hospital
Boston, Massachusetts
Ross E. Andersen
Jatinder Bhatia
Johns Hopkins School of Medicine
Department of Pediatrics
Division of Geriatric Medicine and
Medical College of Georgia
Gerontology
Augusta, Georgia
Baltimore, Maryland
Karil Bialostosky
Judith Ashley National Centers for Disease Control and
University of Nevada School of Prevention
Medicine U.S. Senate Committee on Agriculture,
Nutrition Education and Research Nutrition, and Forestry
Program Aide to Senator Harkin
Reno, Nevada Washington, D.C.
Paule Barbeau Amy Binkoski

Medical College of Georgia Department of Nutrition
Augusta, Georgia The Pennsylvania State University
University Park, Pennsylvania
Stephen Barrett Steven N. Blair
Allentown, Pennsylvania The Cooper Institute
Dallas, Texas
Suzanne Domel Baxter
Medical College of Georgia Claude Bouchard
Georgia Prevention Institute The Pennington Biomedical Research
Department of Pediatrics Center
Augusta, Georgia Baton Rouge, Louisiana
Susan Bowerman Gail A. Cresci

UCLA Center for Human Nutrition Department of Surgery
Los Angeles, California Medical College of Georgia
Augusta, Georgia
George A. Bray
The Pennington Biomedical Research Gary R. Cutter
Center Center for Research Methodology and
Baton Rouge, Louisiana Biometrics
AMC Cancer Research Center
Ronette R. Briefel Denver, Colorado
Mathematics Policy Research Inc.
Washington, D.C.
Mark T. De Meo
University Gastroenterologists
Colleen Bucher
Rush-Presbyterian-St. Luke’s Medical
Department of Pediatrics
Center
Rush University
Augusta, Georgia
Chicago, Illinois
Chantrapa Bunyapen
Department of Pediatrics Dominick P. DePaola
Medical College of Georgia The Forsyth Institute
Augusta, Georgia Boston, Massachusetts
Ritva Butrum Michael P. Doyle

American Institute for Cancer Research Center for Food Safety and Quality
Washington, D.C. Enhancement
University of Georgia
G. Franklin Carl Griffin, Georgia
V.A. Medical Center
Augusta, Georgia Johanna Dwyer
Frances Stern Nutrition Center
Ronni Chernoff New England Medical Center
Geriatric Research Education and Clinical Hospital
Center Boston, Massachusetts
Arkansas Geriatric Education Center
Little Rock, Arkansas Alan R. Dyer
Department of Preventive Medicine
Chin-Ling Chen Northwestern University Medical
New England Medical Center Hospital School
Boston, Massachusetts Chicago, Illinois
Leh Chii Chwang Leon Ellenbogen

New England Medical Center Hospital Whitehall-Robbins
Boston, Massachusetts Madison, New Jersey
Stacie Coval Elaine B. Feldman

Department of Nutrition Medical College of Georgia
The Pennsylvania State University Department of Internal Medicine
University Park, Pennsylvania Augusta, Georgia
Valerie Fishell Bernard Gutin

The Pennsylvania State University Augusta, Georgia
David Heber
William P. Flatt
Division of Clinical Nutrition
Department of Nutrition
Department of Medicine
UCLA School of Medicine
Athens, Georgia
Los Angeles, California
Kim M. Forde
Johns Hopkins School of Medicine Linda K. Hendricks
Division of Geriatric Medicine and Section of Hematology and Oncology
Gerontology Department of Medicine
Baltimore, Maryland Medical College of Georgia
Augusta, Georgia
John P. Foreyt
Behavioral Medicine Research Center Victor Herbert
Baylor College of Medicine Bronx V.A. Medical Center
Houston, Texas Bronx, New York
Gary D. Foster James O. Hill

University of Pennsylvania University of Colorado Health Sciences
Philadelphia, Pennsylvania Center
Center for Human Nutrition
Shawn C. Franckowiak Denver, Colorado
Gerontology Deanna M. Hoelscher
Baltimore, Maryland University of Texas — Houston Health
Science Center
School of Public Health
Naomi K. Fukagawa Human Nutrition Center
Department of Medicine Houston, Texas
University of Vermont College of Medicine
Burlington, Vermont
Mary Horlick
Constance J. Geiger Institute of Human Nutrition
Geiger and Associates Department of Pediatrics
Salt Lake City, Utah Columbia University, College of Physicians
and Surgeons
New York, New York
Jane M. Greene
Nutrition Consultant
Augusta, Georgia Carolyn H. Jenkins
Division of Endocrinology, Diabetes, and
Sue Grossbauer Medical Genetics
The Grossbauer Group Department of Medicine
Chesterton, Indiana Medical University of South Carolina
Charleston, South Carolina
Eileen Kennedy Charles S. Lieber

Great Falls, Virginia Mount Sinai School of Medicine
Alcohol Research and Treatment Center
Karin Koehn Section of Liver Disease and Nutrition
Frances Stern Nutrition Center Bronx V.A. Medical Center
New England Medical Center Bronx, New York
Hospital
Boston, Massachusetts Kiang Liu
Department of Preventive Medicine
Kathryn M. Kolasa Northwestern University Medical
Nutrition Education and Services School
Department of Family Medicine Chicago, Illinois
The Brody School of Medicine
East Carolina University
Maria F. Lopes-Virella
Greenville, North Carolina
Ralph H. Johnson V.A. Medical Center
Division of Endocrinology, Diabetes and
Jessica Krenkel
Medical Genetics
University of Nevada School of
Medical University of South Carolina
Medicine
Nutrition Education and Research
Program
Reno, Nevada Robert G. Martindale
Department of Surgery
Penny Kris-Etherton Medical College of Georgia
Department of Nutrition Augusta, Georgia
Pennsylvania State University
University Park, Pennsylvania Susie McPherson
University of Texas School of Public
Abdullah Kutlar Health
Section of Hematology and Human Nutrition Center
Oncology Houston, Texas
Medical College of Georgia Marina Mironova
Augusta, Georgia Division of Endocrinology, Diabetes, and
Medical Genetics
Jenny H. Ledikwe Medical University of South Carolina
Diet Assessment Center Charleston, South Carolina
The Pennsylvania State University Diane C. Mitchell
University Park, Pennsylvania Diet Assessment Center
Christian R. Lemmon The Pennsylvania State University
Eating Disorders Program University Park, Pennsylvania
Augusta, Georgia Sohrab Mobarhan
Division of Gastroenterology, Hepatology,
Sandra B. Leonard and Nutrition
Nutrition Consultant Loyola University Medical Center
Augusta, Georgia Maywood, Illinois
Connie Mobley Allen M. Perelson

University of Texas Health Science Buckingham, Pennsylvania
Center
San Antonio, Texas Louis Perusse
Division of Kinesiology
Marlene M. Most Department of Preventative Medicine
The Pennington Biomedical Research Laval University
Center Quebec, Canada
Baton Rouge, Louisiana
Suzanne Perumean-Chaney
University of Nevada School of Medicine
Ece A. Mutlu
Nutrition Education and Research
Division of Gastroenterology and
Program
Hepatology
Reno, Nevada
Rush-Presbyterian-St. Luke’s Medical
Center
Chicago, Illinois Suzanne Phelan
University of Pennsylvania School of
Medicine
Gokhan M. Mutlu
Philadelphia, Pennsylvania
Division of Respiratory and Critical Care
Medicine
University of Chicago Stephen D. Phinney
Chicago, Illinois Galileo Labs
Santa Clara, California
Forest H. Nielsen
USDA, ARS, GFHNRC Claudia S. Plaisted
Grand Forks, North Dakota Department of Nutrition
University of North Carolina
Chapel Hill, North Carolina
Scott Owens
Department of Health and Human
Performance L. Michael Prisant
Western Carolina University Hypertension Unit
Cullowhee, North Carolina Section of Cardiology
Augusta, Georgia
Ruth E. Patterson
Fred Hutchinson Cancer Research
Marsha Read
Center
Seattle, Washington
University of Nevada
Reno, Nevada
Victor Pendleton
Behavioral Medicine Research Center Rebecca S. Reeves
Baylor College of Medicine Behavioral Medicine Research Center
Houston, Texas Baylor College of Medicine
Houston, Texas
Jean Pennington
Division of Nutrition Research Treva Rice
Coordination Division of Biostatistics
National Institutes of Health Washington University School of Medicine
Bethesda, Maryland St. Louis, Missouri
Richard S. Rivlin Sachiko T. St. Jeor

American Health Foundation University of Nevada School of
New York, New York Medicine
Reno, Nevada
Kelly S. Scanlon
Division of Nutrition and Physical Activity Margaret Tate
National Center for Chronic Disease Office of Nutrition Services
Prevention and Health Promotion Arizona Department of Health Services
Centers for Disease Control and Prevention Phoenix, Arizona
Atlanta, Georgia
Nicky Teuffel-Shone
Barbara J. Scott University of Arizona
University of Nevada School of Medicine Arizona Prevention Center
Department of Pediatrics Tucson, Arizona
Reno, Nevada
Lynn Thomas
Mary Serdula Department of Family and Preventative
Division of Nutrition and Physical Activity Medicine
National Center for Chronic Disease University of South Carolina
Prevention and Health Promotion Columbia, South Carolina
Centers for Disease Control and Prevention
Atlanta, Georgia Riva Touger-Decker
Department of Clinical Nutrition
Christopher T. Sempos School of Health Related Professions
Department of Social and Preventive University of Medicine and Dentistry of
Medicine New Jersey
SUNY-Buffalo Newark, New Jersey
Buffalo, New York
Marta D. Van Loan
Denise Shaffer Taylor USDA-WHNRC
Department of Nutrition University of California
The Pennsylvania State University Davis, California
Kumar S. Venkitanarayanan
Scott H. Sicherer Department of Animal Science
Division of Allergy and Immunology University of Connecticut
Department of Pediatrics Storrs, Connecticut
Jaffe Food Allergy Institute
Mount Sinai School of Medicine Stanley Wallach
New York, New York American College of Nutrition
Clearwater, Florida
Diane K. Smith
CSRA Partners in Health Elizabeth K. Weisburger
Augusta, Georgia Rockville, Maryland
Helen Smiciklas-Wright David G. Weismiller

Diet Assessment Center Department of Family Medicine
Department of Nutrition The Brody School of Medicine
The Pennsylvania State University East Carolina University
University Park, Pennsylvania Greenville, North Carolina
Christine L. Williams Guixiang Zhao

Columbia University Department of Nutrition
Babies and Childrens Hospital The Pennsylvania State University
New York, New York University Park, Pennsylvania
Contents
Part I Food
1 Food Constituents ................................................................................................3

Table 1.1 Web Addresses for Information on the Composition of
Food .............................................................................................5
Table 1.2 Sugar Content of Selected Foods, 100 Grams, Edible
Portion .........................................................................................5
Table 1.3 Tocopherols and Tocotrienols in Selected Food Products,
(mg/100 g)...................................................................................9
Table 1.4 Occurrence of D-Tagatose in Foods.............................................13
Table 1.5 Sweetening Agents, Sugar Substitutes ........................................15
Table 1.6 Terms Used to Describe the Functions of Food Additives ........18
Table 1.7 Specific Food Additives and Their Functions.............................19
Table 1.8 Mycotoxins/Bacterial Toxins in Foods........................................24
Table 1.9 Antinutrients in Food ...................................................................24
Table 1.10 Toxic Substances in Food .............................................................29
Table 1.11 Edible Weeds .................................................................................37
Table 1.12 Toxic Plants....................................................................................41
Table 1.13 Plants Used as Herbal Remedies .................................................54
Table 1.14 Vitamin Terminology ....................................................................67
Table 1.15 Nomenclature of Compounds with Vitamin A Activity ............69
Table 1.16 Chemical and Physical Properties of Vitamins ..........................70
Table 1.17 Summary of Vitamin Deficiency Signs and Need ......................78
Table 1.18 Essential Minerals and Their Functions......................................87
Table 1.19 Essential Fatty Acids ....................................................................95
Table 1.20 Structure and Names of Fatty Acids Found in Food .................95
Part II Metabolism
2 Metabolic Maps ..................................................................................................99

Figure 2.1 The glycolytic pathway .............................................................. 100
Figure 2.2 Reaction sequence of the hexose monophosphate shunt......... 101
Figure 2.3 Metabolism of fructose ............................................................... 102
Figure 2.4 Conversion of galactose to glucose ........................................... 103
Figure 2.5 Glycogen synthesis (glycogenesis) ............................................ 103
Figure 2.6 Stepwise release of glucose molecules from the glycogen
molecule................................................................................... 104
Figure 2.7 Pathway for gluconeogenesis..................................................... 105
Figure 2.8 Catabolism of branched-chain amino acids .............................. 106
Figure 2.9 Catabolism of threonine showing its relationship to that of serine

and glycine .............................................................................. 107
Figure 2.10 Phenylalanine and tyrosine catabolism..................................... 107
Figure 2.11 Catabolism of tryptophan showing conversion to the vitamin
niacin ....................................................................................... 108
Figure 2.12 Catabolism of histidine .............................................................. 109
Figure 2.13 Conversion of SH groups via methionine-cysteine
interconversion........................................................................ 109
Figure 2.14 The urea cycle ............................................................................. 110
Figure 2.15 Krebs citric acid cycle in the mitochondria .............................. 111
Figure 2.16 Oxidative phosphorylation: the respiratory chain showing
the points where sufficient energy has been generated
to support the synthesis of one molecule of ATP from ADP
and Pi....................................................................................... 112
Figure 2.17 Fatty acid synthesis .................................................................... 112
Figure 2.18 Pathways for synthesis of long-chain polyunsaturated fatty
acids (PUFA) through elongation and desaturation ............ 113
Figure 2.19 Pathway for β oxidation of fatty acids in the
mitochondria ........................................................................... 114
Figure 2.20 Pathways for the synthesis of triacylglycerides and
phospholipids.......................................................................... 115
Figure 2.21 Eicosanoid synthesis from arachidonic acid............................. 116
Figure 2.22 Cholesterol biosynthesis ............................................................. 116
Figure 2.23 Overview of protein synthesis ................................................... 117
Figure 2.24 Detailed structure of the components of a gene that is to be
transcribed ............................................................................... 118
Figure 2.25 Synthesis of messenger RNA and its migration to the ribosomes
in the cytoplasm ..................................................................... 118
Figure 2.26 Overview of translation involving mRNA, tRNA-amino acids,
and small and large ribosomal units .................................... 119
Figure 2.27 Synthesis of creatine and creatinine .......................................... 119
Figure 2.28 Modification of β oxidation for unsaturated fatty acid ........... 120
3 Tables of Clinical Significance ....................................................................... 121

Table 3.1 Proteins Involved in Lipid Transport........................................ 121
Table 3.2 Inherited Disorders of Carbohydrate Metabolism ................... 122
Table 3.3 Genetic Diseases in Lipid Metabolism ...................................... 123
Table 3.4 Genetic Mutations in Enzymes of Amino Acid
Metabolism .............................................................................. 124
Table 3.5 Mutations that Phenotype as Obesity ....................................... 125
Table 3.6 Mutations that Phenotype as Heart Disease............................. 127
Table 3.7 Mutations that Phenotype as Diabetes...................................... 129
Table 3.8 Normal Values for Micronutrients in Blood ............................. 133
Table 3.9 Normal Clinical Values for Constituents of Blood................... 134
Table 3.10 Normal Values for Micronutrients in Urine ............................. 134
Table 3.11 Normal Clinical Values for Constituents of Human
Urine ........................................................................................ 135
Table 3.12 Retinal Binding Proteins............................................................. 136
Table 3.13 Drugs That Alter Nutritional State............................................ 137
Table 3.14 Drugs That May Have Anti-Obesity Properties ....................... 138
Table 3.15 Micronutrient Interactions ......................................................... 139
Table 3.16 Preferred Ligand Binding Groups for Metal Ions .................... 140
Table 3.17 Food Components That Affect Calcium Absorption ................ 140
Table 3.18 Calcium-Binding Proteins .......................................................... 141
Table 3.19 The Body Content of Iron .......................................................... 141
Table 3.20 Body Mass Index for Adults ...................................................... 142
Table 3.21 Standard International Units (SI Units) for Reporting Clinical
Data .......................................................................................... 144
Table 3.22 Conversion Factors for Values in Clinical Chemistry
(SI Units).................................................................................. 145
Table 3.23 Small Animal Analogs of Human Degenerative Diseases ....... 160
Table 3.24 Composition of the AIN-93 Maintenance (M) and Growth
(G) Diets .................................................................................. 160
Part III Comparative Nutrition
4 Animal Needs and Uses (Comparative Nutrition) ....................................... 163

William P. Flatt
Overview: Nutritional Requirements for Different Species........................... 163
Sources of Information for the Nutrient Requirements of Various
Species............................................................................................................ 165
References .......................................................................................................... 172
Table 4.1 Web Addresses for Tables of Nutrient Requirements for a Variety
of Animals ............................................................................... 170
Table 4.2 Publications Providing Information on the Nutrient Needs of
Specific Animals ...................................................................... 171
Part IV Human Nutrient Needs in the Life Cycle
5 Nutrition During Pregnancy and Lactation .................................................. 175

Kathryn M. Kolasa and David G. Weismiller
Recommendations for Women before Pregnancy ........................................... 175
Risk Factors for Prenatal Nutrition Risk and Indications for Referral......... 175
Weight Gain and Pregnancy ............................................................................. 177
Dietary Requirements for Pregnancy and Lactation ...................................... 180
Dietary Assessment of the Pregnant Woman .................................................. 181
Complications of Pregnancy That May Impact Nutritional Status ............... 185
Vitamin and Mineral Requirements, Food Sources, and
Supplementation ........................................................................................... 190
Physical Activity during Pregnancy ................................................................ 194
Postpartum Weight Loss ................................................................................... 194
Nutrition and Lactation .................................................................................... 197
Resource Materials ............................................................................................ 199
References .......................................................................................................... 200
Table 5.1 Special Recommendations for Women before Pregnancy........ 175
Table 5.2 Nutritional Care at Preconception, Prenatal, and Postnatal

Visits ........................................................................................ 176
Table 5.3 Risk Factors for Prenatal Nutritional Risk ............................... 178
Table 5.4 Indications for a Referral of Pregnant Patients for Nutrition
Assessment and Counseling .................................................. 178
Table 5.5 Characteristics of Women, Infants, and Children (WIC)
Program ................................................................................... 178
Table 5.6 Pregnancy Weight Goals............................................................. 179
Table 5.7 Rate of Weight Gain (Pounds) ................................................... 180
Table 5.8 Weight Gain Distribution during Pregnancy (Pounds) ........... 180
Table 5.9 Nutritious Snacks of 100 Kcalories or Less .............................. 181
Table 5.10 Food and Nutrition Board, National Academy of Sciences —
National Research Council, Recommended Dietary Allowances
and Dietary Reference Intakes (DRIs)................................... 182
Table 5.11 Food Guide Pyramid Servings ................................................... 184
Table 5.12 Behavior Change Dietary Assessment Tool .............................. 184
Table 5.13 Nutritional Risk Score (Massachusetts Department of
Health) ..................................................................................... 186
Table 5.14 Nonpharmacological Remedies for Nausea and Vomiting...... 186
Table 5.15 Hyperemesis Gravidurum .......................................................... 187
Table 5.16 Dietary Sources of Fiber ............................................................. 188
Table 5.17 Caffeine Audit ............................................................................. 189
Table 5.18 Effects of Alcohol, Tobacco, and Drug Use on Nutritional
Status and Pregnancy Outcomes and Lactation................... 190
Table 5.19 Indications for Vitamin and Mineral Supplementation ........... 191
Table 5.20 Prenatal Vitamin Mineral Supplements .................................... 191
Table 5.21 Dietary Sources of Calcium........................................................ 193
Table 5.22 Dietary Sources of Folate ........................................................... 194
Table 5.23 Dietary Sources of Iron............................................................... 195
Table 5.24 Dietary Sources of Zinc .............................................................. 195
Table 5.25 Benefits of Physical Activity during Pregnancy ....................... 196
Table 5.26 Contraindications to Physical Activity...................................... 196
Table 5.27 Warning Signs to Stop Physical Activity .................................. 196
Table 5.28 Guidelines for Physical Activity ................................................ 196
Table 5.29 Guidelines for Recreational Activity ......................................... 197
Table 5.30 Strategies for Postpartum Weight Loss ..................................... 197
Table 5.31 Maternal Nutrition during Breastfeeding ................................. 198
Table 5.32 Benefits of Frequent, Early, Unrestricted Nursing ................... 198
Table 5.33 Signs of Insufficient Milk Intake in the Newborn ................... 198
Table 5.34 Breastfeeding Tips: Common Concerns about the Infant ........ 198
Table 5.35 Breastfeeding Tips: Common Discomforts That Lead to
Breastfeeding Termination ..................................................... 199
Figure 5.1 Graph for tracking weight and fundal height .......................... 179
6 Feeding the Premature Infant ......................................................................... 203

Jatinder Bhatia, Colleen Bucher, and Chantrapa Bunyapen
Nutritional Goals for the Premature Infant .................................................... 203
Growth and Nutrient Requirements ................................................................ 204
Provision of Nutrients ...................................................................................... 204
Summary ............................................................................................................ 216
References .......................................................................................................... 216

Table 6.1 Daily Increments of Body Weight and Body Composition
of the Reference Fetus ............................................................ 206
Table 6.2 Parenteral Nutrition Regimen .................................................... 208
Table 6.3 Fatty Acid Composition of Commonly Used Lipid
Emulsions ................................................................................ 209
Table 6.4 Initiation and Advancement of Parenteral and Minimal Enteral
Feedings in an Infant with a Birthweight of <1000 g.......... 210
Table 6.5 Parenteral Nutrition is Indicated in the Following
Conditions ............................................................................... 210
Table 6.6 Complications of Parenteral Nutrition...................................... 210
Table 6.7 Suggested Monitoring during Parenteral Nutrition ................ 211
Table 6.8 Composition of Formulas Commonly Used in Premature
Infants ...................................................................................... 212
Table 6.9 Composition of Human Milk ..................................................... 213
Table 6.10 Routes of Feeding Preterm Infants ............................................ 214
Figure 6.1 Classification of newborns by intrauterine growth and
gestational age ........................................................................ 205
Figure 6.2 Average composition of weight gain of the reference
fetus.............................................................................................. 206
7 Feeding the Term Infant .................................................................................. 219

Jatinder Bhatia, Colleen Bucher, and Chantrapa Bunyapan
Growth ............................................................................................................... 219
Energy ................................................................................................................ 225
Protein ................................................................................................................ 225
Fat ....................................................................................................................... 226
Carbohydrate ..................................................................................................... 230
Iron ..................................................................................................................... 231
Breastfeeding ..................................................................................................... 233
Formula Feeding ............................................................................................... 235
Weaning.............................................................................................................. 236
Failure to Thrive................................................................................................ 236
Summary ............................................................................................................ 237
References .......................................................................................................... 238
Table 7.1 Mean Body Weight and Selected Centiles for Males and
Females, 0-12 Months of Age................................................. 220
Table 7.2 Recommended Dietary Intakes of Protein ................................ 226
Table 7.3 Nutritional Composition of Human Milk and Commonly
Used Formulas ........................................................................ 227
Table 7.4 Usual Carbohydrates and Related Enzymes............................. 230
Table 7.5 Commonly Used Formulas and Their Indications ................... 231
Table 7.6 Stages of Iron Deficiency ............................................................ 232
Table 7.7 Unique Constituents of Breast Milk .......................................... 233
Table 7.8 Recommendations for Feeding Healthy Full-Term Infants ..... 237
Figure 7.1 Girls: birth to 36 months: physical growth NCHS
percentiles................................................................................ 221
Figure 7.2 Boys: birth to 36 months: physical growth NCHS
percentiles................................................................................ 223
8 Nutrition for Healthy Children and Adolescents Ages 2 to

18 Years .............................................................................................................. 241
Physical Growth and Development ................................................................. 241
Energy and Nutrient Needs ............................................................................. 242
Food Guide Pyramid for Young Children....................................................... 253
What Are Children and Adolescents Eating? ................................................. 255
Vitamin-Mineral Supplements.......................................................................... 267
Development of Preschool Children’s Food Preferences and Consumption
Patterns .......................................................................................................... 267
Feeding Toddlers and Preschool Children ...................................................... 270
Feeding School-Age Children........................................................................... 276
Feeding Adolescents ......................................................................................... 282
Health Promotion and Disease Prevention ..................................................... 287
References .......................................................................................................... 294
Table 8.1 Recommended Levels for Individual Intake for Children and
Adolescents ............................................................................. 243
Table 8.2 Tolerable Upper Intake Levels (ULs) for Children and
Adolescents ............................................................................. 244
Table 8.3 1989 Recommended Dietary Allowances (RDAs) for Children
and Adolescents for Nutrients without Dietary Reference
Intakes...................................................................................... 245
Table 8.4 Energy Requirements for Children and Adolescents ............... 246
Table 8.5 Total Fat, Saturated Fat, and Cholesterol Content of Various
Foods........................................................................................ 248
Table 8.6 Fiber Content of Foods That Most U.S. Children and
Adolescents Will Eat............................................................... 249
Table 8.7 Approximate Calcium Content for One Serving of Various
Foods........................................................................................ 251
Table 8.8 Changes Made in the New Food Guide Pyramid for Young
Children ................................................................................... 255
Table 8.9 Young Children’s Serving Sizes by Food Group ...................... 256
Table 8.10 Sample Meal and Snack Plan According to Food Group for
One Day for Four- to Six-Year-Old Children ....................... 258
Table 8.11 Healthy Eating Index (HEI): Overall and Component Mean
Scores for Children, 1994-1996 .............................................. 260
Table 8.12 Percentage of Children Ages 2-18 by Age, Poverty Status,
and Diet Quality as Measured by the Healthy Eating Index,
Three-Year Average, 1994-1996 .............................................. 260
Table 8.13 Nutrient Intakes: Mean Intakes as Percentages of the 1989
RDAs, Children 19 Years of Age and Under, One Day ....... 262
Table 8.14 Nutrient Intakes: Percentage of Children with Diets Meeting
100% of the 1989 RDAs, Two-Day Average .......................... 264
Table 8.15 Nutrient Intakes: Mean Percentage of Calories from Protein, Total
Fat, Saturated Fat, and Carbohydrates, One Day ................ 266
Table 8.16 Nutrient Intakes: Percentage of Children with Diets Meeting
Recommendations for Total Fat, Saturated Fatty Acids, and
Cholsterol, Two-Day Average ................................................ 266
Table 8.17 Five Groups of Children at Nutritional Risk Who May Benefit
from Vitamin-Mineral Supplementation ............................... 267
Table 8.18 Research Concerning Exposure to Food and Preschool Children’s

Food Preferences and Consumption ..................................... 268
Table 8.19 Research Concerning Social Environment of Eating and Preschool
Children’s Food Preferences and Consumption................... 270
Table 8.20 Research Concerning Adult Influences on Preschool Children’s
Ability to Self-Regulate Calorie Intake ................................. 271
Table 8.21 Suggestions for Concerns Parents Commonly Encounter When
Feeding Children .................................................................... 272
Table 8.22 Healthful Eating Tips to Use with Young Children ................. 273
Table 8.23 Choking in Young Children ....................................................... 274
Table 8.24 Five Practical Applications for Adults to Use When Feeding
Children ................................................................................... 280
Table 8.25 Results Regarding Dietary Behaviors from the Youth Risk
Behavior Survey, U.S., 1997 ................................................... 283
Table 8.26 Healthy People 2010 Nutrition Objectives for Children and
Adolescents ............................................................................. 288
Table 8.27 Common Values Shared by Supporters of Team
Nutrition .................................................................................. 290
Table 8.28 Details Regarding the Four Critical Messages of the
Fight Bac!™ Campaign ........................................................... 292
Table 8.29 Two Methods of Hand Washing ................................................ 293
Figure 8.1 Food guide pyramid for young children .................................. 254
9 The Health-Promoting Diet throughout Life: Adults .................................. 299

Marsha Read
Introduction ....................................................................................................... 299
Dietary Recommendations and Guidelines..................................................... 299
Nutrition Counseling for Adults...................................................................... 305
Estimates of Actual Intakes of Adults for Macronutrients ............................ 307
Health Implications of Current Macronutrient Intakes ................................. 309
Summary ............................................................................................................ 314
References .......................................................................................................... 315
Table 9.1 1980 U.S. Dietary Guidelines ..................................................... 300
Table 9.2 2000 U.S. Dietary Guidelines ..................................................... 300
Table 9.3 Meal Plans Based on the Food Guide Pyramid........................ 302
Table 9.4 WHO Dietary Recommendations............................................... 304
Table 9.5 Nutrition Facts Panel Information............................................. 305
Table 9.6 Total Energy Intake and Sources of Energy for Adult Men
and Women.............................................................................. 308
Table 9.7 Contribution (% kcal) of Breakfast, Snacks, and Foods
Consumed Away from Home to Total Energy Intake
(1 Day), 1994-1996................................................................... 308
Table 9.8 Total Protein, Carbohydrate, and Fat Intakes (gm) ................. 309
Table 9.9 Fiber Intake (gm) ........................................................................ 309
Table 9.10 Intake of Saturated Fatty Acids, Monounsaturated Fatty
Acids, Polyunsaturated Fatty Acids, and Cholesterol ......... 310
Table 9.11 Incidence of Overweight (%) ..................................................... 310
Figure 9.1 USDA food guide pyramid ........................................................ 301
10 Nutrition in the Later Years ............................................................................ 319

Elaine B. Feldman
Introduction ....................................................................................................... 319
Background ........................................................................................................ 319
The Biology of Aging ........................................................................................ 319
Mortality and Aging Statistics ......................................................................... 320
Lifestyle and Socioeconomic Changes Affecting the Nutritional Status
of the Elderly................................................................................................. 324
Pathophysiology of Aging ................................................................................ 325
The Geriatric Assessment ................................................................................. 326
The Recommended Dietary Allowances (RDAs) for the Elderly .................. 327
Body Composition and Aging .......................................................................... 327
Nutrient Requirements and Aging .................................................................. 327
Anorexia in the Elderly .................................................................................... 333
Nutritional Deficiencies in the Elderly............................................................ 334
Homebound and Institionalized Elderly ......................................................... 334
The Hospitalized Patient .................................................................................. 334
Conclusion ......................................................................................................... 335
References .......................................................................................................... 335
Table 10.1 Effects of Age on Intermediary Metabolism and Its
Control ..................................................................................... 321
Table 10.2 Hormone Changes with Age ...................................................... 321
Table 10.3 Leading Causes of Death and Numbers of Deaths, According
to Sex and Race, U.S. 1996 ..................................................... 322
Table 10.4 Leading Causes of Death, Death Rates, and Age-Adjusted Death
Rates, 1996 ............................................................................... 323
Figure 10.1 The change in blood pressure with age .................................... 325
Figure 10.2 The food pyramid modified for adults 70 years of age and
older ......................................................................................... 328
Figure 10.3 The age-related change in body composition in men.............. 329
Figure 10.4 Energy expenditure and aging................................................... 330
Figure 10.5 Exercise and the resting metabolic rate in older persons ....... 330
Figure 10.6 The effect of age on glucose uptake.......................................... 331
Figure 10.7 The effect of aging and physical training on body fat ............ 332
Figure 10.8 The effect of aging and physical training on aerobic
capacity .................................................................................... 333
Part V Human Nutritional Status Assessment
11 Dietary Guidelines, Food Guidance, and Diet Quality .............................. 339

Eileen Kennedy
History of the Dietary Guidelines for Americans .......................................... 339
Dietary Guidelines for Americans ................................................................... 340
Comparison with Other Dietary Guidelines ................................................... 342
Comparison of U.S. Dietary Guidelines with Disease-Specific
Guidelines ...................................................................................................... 343
Future Directions............................................................................................... 343
Summary ............................................................................................................ 351

References .......................................................................................................... 351
Table 11.1 Dietary Guidelines for Americans, 1980 to 2000 ...................... 340
Table 11.2 U.S. Dietary Guidelines 2000 and Countries Having Similar
Guidelines................................................................................ 341
Table 11.3 Comparison of Three Sets of Dietary Recommendations ........ 344
Table 11.4 History of USDA Food Guidance .............................................. 345
Table 11.5 Components of the Healthy Eating Index and Scoring
System...................................................................................... 349
Figure 11.1 Food guide pyramid: a guide to daily food choices................ 346
Figure 11.2 Food guide pyramid for young children .................................. 348
12 Dietary Guidelines in Three Regions of the World .................................... 353

Johanna Dwyer, Odilia I. Bermudez, Leh Chii Chwang, Karin Koehn,
and Chin-Ling Chen
Introduction and Overview .............................................................................. 353
The United States, Canada, Australia, and New Zealand ............................. 353
Latin America .................................................................................................... 357
Asian Countries ................................................................................................. 362
Conclusions........................................................................................................ 368
References .......................................................................................................... 369
Table 12.1 Development of Dietary Guidelines in the United States,
Canada, Australia, and New Zealand ................................... 355
Table 12.2 Dietary Guidelines of the United States, Canada, Australia,
and New Zealand ................................................................... 356
Table 12.3 Development of Dietary Guidelines in Latin American
Countries ................................................................................. 359
Table 12.4 Dietary Guidelines of Selected Latin American
Countries ................................................................................. 360
Table 12.5 Development of Dietary Guidelines in Asian Countries ......... 364
Table 12.6 Dietary Guidelines of Selected Asian Countries ...................... 365
13 Healthy People — Goals and Interpretations............................................... 373

Margaret Tate and Matthew P. Van Tine
Overview ............................................................................................................ 373
References .......................................................................................................... 390
Table 13.1 Healthy People 2010 Focus Areas.............................................. 374
Table 13.2 Leading Health Indicators.......................................................... 375
Table 13.3 Summary of Healthy People 2000 and 2010 Objectives .......... 376
Table 13.4 Abbreviations for Data Sources ................................................. 390
14 Food Labeling: Foods and Dietary Supplements ......................................... 393

Constance J. Geiger
Overview ............................................................................................................ 393
History of Food Labeling ................................................................................. 393
Required Portions of the Food Label .............................................................. 395
Labeling of Restaurant Foods and Fresh Foods ............................................. 398
Nutrient Content Claims Allowed for Foods and Dietary

Supplements .................................................................................................. 399
Health Claims Allowed for Foods and Dietary Supplements ....................... 399
Structure Function Claims ................................................................................ 401
Resources ........................................................................................................... 405
References .......................................................................................................... 406
Table 14.1 Major Food and Nutrition Labeling Laws/Selected
Regulations .............................................................................. 394
Table 14.2 Agencies Having Jurisdiction over Food Labeling .................. 395
Table 14.3 Labeling of Nutrients: Required and Voluntary....................... 397
Table 14.4 Selected Reference Amounts Customarily Consumed
(RACCs) ................................................................................... 397
Table 14.5 Daily Reference Values (DRIs) for Adults: Calculations and
Values....................................................................................... 397
Table 14.6 Reference Daily Intakes (RDIs) for Adults and Children
over 4 ....................................................................................... 398
Table 14.7 Allowed Nutrient Content Claims with Definitions ................ 400
Table 14.8 Other Nutrient Content Claims Definitions ............................. 401
Table 14.9 Health Claims Authorized through the Regulations
Implementing Nutrition Labeling and Education Act
(NLEA)..................................................................................... 402
Table 14.10 Health Claims Allowed to Pass through Food and Drug
Administration (FDA) ............................................................ 404
Table 14.11 Qualified Health Claims Allowed by the Pearson
Decision ................................................................................... 404
Figure 14.1 The new label format.................................................................. 396
15 Nutrition Monitoring in the United States................................................... 407

Karil Bialostosky, Ronette R. Briefel, and Jean Pennington
Goal of the Nutrition Monitoring Program .................................................... 407
Uses of Nutrition Monitoring Data ................................................................. 408
History of the Nutrition Monitoring Program: Milestones and
Publications ................................................................................................... 411
Nutrition Monitoring Measurement Components .......................................... 413
Food Supply Determinations ........................................................................... 420
Evolution of the Nutrition Monitoring Program............................................ 421
The Link Between Nutrition Monitoring, Research, and Policy ................... 423
Conclusion ......................................................................................................... 429
References .......................................................................................................... 429
Table 15.1 Uses of Nutrition Monitoring Data ........................................... 409
Table 15.2 Milestones and Publications of the National Nutrition
Monitoring and Related Research Program ......................... 412
Table 15.3 Federal Nutrition Monitoring Surveys and Surveillance
Activities Since 1990 ............................................................... 414
Table 15.4 Percent of the U.S. Population Meeting the Adequate Intake
(AI) for Calcium, 1988-1994 ................................................... 425
Figure 15.1 Food and health relationships ................................................... 408
Figure 15.2 Overlapping of nutrition monitoring, policymaking, and
research .................................................................................... 424
16 Clinical Nutrition Studies: Unique Applications ........................................ 435

Marlene M. Most, Valerie Fishell, Amy Binkoski, Stacie Coval,
Denise Shaffer Taylor, Guixiang Zhao, and Penny Kris-Etherton
Forms and Documentation for Assuring Dietary Protocol
Compliance .................................................................................................... 435
Unique Study Challenges and Strategies for Addressing Them ................... 447
Conclusions........................................................................................................ 452
Table 16.1 Resources for Information on the Conduct of Clinical
Nutrition Studies .................................................................... 436
Figure 16.1 Sample subject recruitment advertisement ............................... 437
Figure 16.2 Telephone interview form .......................................................... 438
Figure 16.3 General dietary questionaire...................................................... 441
Figure 16.4 Daily checklist ............................................................................. 442
Figure 16.5 Weekly monitoring form ............................................................ 443
Figure 16.6 Food production form ................................................................ 444
Figure 16.7 Tray assembly check sheet ......................................................... 445
Figure 16.8 Packed meal form ....................................................................... 445
17 Nutrition Monitoring and Research Studies: Observational

Studies ............................................................................................................... 453
Suzanne E. Perumean-Chaney and Gary Cutter
Purpose .............................................................................................................. 453
Observational Studies ....................................................................................... 453
Cohort Studies ................................................................................................... 454
Advantages and Disadvantages of the Cohort Studies ................................. 454
Examples of Cohort Studies Utilizing Nutrition Assessment ....................... 456
Summary ............................................................................................................ 459
References .......................................................................................................... 462
Table 17.1 The Question and Appropriate Design ..................................... 454
Table 17.2 Characteristics of a Cohort or Incidence Study ....................... 454
Table 17.3 Advantages and Disadvantages of a Cohort Study ................. 455
Table 17.4 Factors Associated with Causality............................................. 455
Table 17.5 Examples of Cohort Studies Utilizing Nutrition
Assessments ............................................................................ 457
Table 17.6 Selected Nutrition-Related Publications from Six Cohort
Examples.................................................................................. 460
18 Nutrition Monitoring and Research Studies: Nutrition Screening

Initiative ............................................................................................................ 463
Ronni Chernoff
The Nutrition Screening Initiative ................................................................... 463
Subjective Global Assessment (SGA)............................................................... 468
Mini Nutritional Assessment (MNA) .............................................................. 469
Nutritional Assessment in Older Adults ......................................................... 471
Summary ............................................................................................................ 472
References .......................................................................................................... 474
Table 18.1 Activities of Daily Living ........................................................... 473
Table 18.2 Instrumental Activities of Daily Living .................................... 474
Figure 18.1 Determine your nutritional health ............................................ 465

Figure 18.2 Determine your nutritional health checklist............................. 467
Figure 18.3 Features of subjective global assessment (SGA) ...................... 468
Figure 18.4 The mini nutritional assessment form ...................................... 470
19 Dietary Intake Assessment: Methods for Adults ......................................... 477

Helen Smiciklas-Wright, Diane C. Mitchell, and Jenny H. Ledikwe
Introduction ....................................................................................................... 477
Methods of Dietary Assessment....................................................................... 478
Issues Affecting Validity ................................................................................... 482
Current Issues in Assessment and Analysis ................................................... 487
References .......................................................................................................... 490
Table 19.1 Tools for Portion Size Estimation .............................................. 479
Table 19.2 Sample Instructions for the Administration of a Food
Record ...................................................................................... 479
Table 19.3 Self-Completed and Interviewer-Completed Data
Collection................................................................................. 483
Table 19.4 Benefits Derived from Minimizing Assessment Error ............. 483
Table 19.5 Considerations to Reduce Error when Collecting
Assessment Data ..................................................................... 487
Table 19.6 Categories of Supplements......................................................... 488
Figure 19.1 A sample probing scheme .......................................................... 481
20 Validity and Reliability of Dietary Assessment in School-Age

Children............................................................................................................. 495
R. Sue McPherson, Deanna M. Hoelscher, Maria Alexander, Kelley S. Scanlon,
and Mary K. Serdula
Introduction ....................................................................................................... 495
Review Methodology ........................................................................................ 495
Dietary Assessment Methodologies ................................................................. 496
Discussion .......................................................................................................... 514
Recommendations ............................................................................................. 519
Acknowledgment............................................................................................... 521
References .......................................................................................................... 521
Table 20.1 Definitions and Explanation of Tables ...................................... 496
Table 20.2 Recall Validity Studies among School-Age Children ............... 497
Table 20.3 Food Record Validity Studies among School-Age
Children ................................................................................... 502
Table 20.4 Food Frequency Questionaire (FFQ) Validity Studies
among School-Age Children .................................................. 504
Table 20.5 Food Frequency Questionaire (FFQ) Reliability Studies
among School-Age Children .................................................. 512
Table 20.6 Diet History and Observation Reliability Studies among
School-Age Children............................................................... 515
Table 20.7 Summary of Reviewed Dietary Assessment Methods for
School-Age Children............................................................... 516
21 Methods and Tools for Dietary Intake Assessment in Individuals vs.

Groups ............................................................................................................... 523
Ruth E. Patterson
Introduction ....................................................................................................... 523
Description of the Three Major Dietary Assessment Methods...................... 524
Use of Dietary Assessment Methods in Individuals vs. Groups .................. 530
Summary ............................................................................................................ 533
References .......................................................................................................... 538
Table 21.1 Summary of the Major Advantages and Disadvantages
of Dietary Assessment Methods ............................................ 535
Table 21.2 Summary of the Issues Regarding Use of Data from Dietary
Intake Assessment Methods................................................... 536
Table 21.3 Summary of Considerations Regarding Use of Dietary Intake
Assessment in Individuals vs. Groups ................................. 537
22 The Use of Food Frequency Questionnaires in Minority

Populations ....................................................................................................... 539
Rebecca S. Reeves
Diet History Questionnaire .............................................................................. 554
Harvard University Food Frequency Questionnaire (Willett
Questionnaire) ............................................................................................... 554
Fred Hutchinson Cancer Research Center Food Frequency Questionnaire
(Kristal Questionnaire) ................................................................................. 555
Cancer Research Center of Hawaii’s Dietary Questionnaire (The Hawaii Cancer
Research Survey) ........................................................................................... 555
New Mexico Women’s Health Study, Epidemiology and Cancer Control
Program, University of New Mexico Health Sciences Center................... 555
Insulin Resistance Atherosclerosis Study Food Frequency Questionnaire,
School of Public Health, University of South Carolina ............................. 556
References .......................................................................................................... 556
Table 22.1 Median and Reported Range of Correlation Coefficients........ 541
Table 22.2 Food Frequency Questionnaire (FFQ) Validity Studies
among Diverse Adult Populations in the U.S. ..................... 542
Table 22.3 Food Frequency Questionnaire (FFQ) Reliability Studies
among Adult Minority Populations in the U.S. ................... 551
23 Computerized Nutrient Analysis Systems .................................................... 559

Judith M. Ashley and Sue Grossbauer
Introduction ....................................................................................................... 559
Primary Characteristics and Operating Features of Software
Programs ........................................................................................................ 559
Basic Questions To Ask When Considering Different Software
Systems .......................................................................................................... 562
Importance of Nutrient Databases................................................................... 563
Limitations of Nutrient Analysis Software Reports ....................................... 564
Conclusion ......................................................................................................... 565
References .......................................................................................................... 565
Table 23.1 Comparison of Features in Five Selected Programs

Available Nationwide ............................................................. 560
Table 23.2 Examples of Dietray Components Available from
Computerized Nutrient Analysis .......................................... 561
24 Nutrient Data Analysis Techniques and Strategies ..................................... 567

Alan R. Dyer, Kiang Liu, and Christopher T. Sempos
Overview ............................................................................................................ 567
Quality Control.................................................................................................. 567
Identifying Outliers or Extreme Values........................................................... 568
Adjustment for Total Energy Intake ................................................................ 569
Modeling Nutrient Intake................................................................................. 571
Multicollinearity ................................................................................................ 572
Dietary Supplements......................................................................................... 573
Within-Person Variability in Intake ................................................................. 574
Types of Epidemiologic Studies ....................................................................... 575
Methods for Comparing Groups in Cross-Sectional Studies......................... 576
Methods for Comparing Cases and Controls in Case-Control Studies ........ 577
Methods for Assessing Associations in Epidemiologic Studies .................... 578
Analyses of Intervention Studies with Change in Nutrient Intake as
Outcome ......................................................................................................... 579
References .......................................................................................................... 580
Table 24.1 Methods for Comparing Nutrient Intake among Groups
in Cross-Sectional Studies ...................................................... 576
Table 24.2 Methods for Comparing Nutrient Intake between Cases
and Controls in Case-Control Studies................................... 577
Table 24.3 Methods for Assessing Associations in Epidemiologic
Studies ..................................................................................... 578
25 Medical Nutritional Evaluation...................................................................... 581

Elaine B. Feldman
Introduction ....................................................................................................... 581
Patient Evaluation ............................................................................................. 582
Medical History ................................................................................................. 583
Socioeconomic History...................................................................................... 584
Family History................................................................................................... 584
Diet History and Evaluation ............................................................................ 585
General Physical Examination.......................................................................... 585
Laboratory Tests ................................................................................................ 585
Nutrition Diagnosis and Prescription ............................................................. 587
Educating Physicians in Nutrition................................................................... 587
References .......................................................................................................... 588
Table 25.1 Physical Signs of Malnutrition .................................................. 586
Table 25.2 Laboratory Tests Useful in Clinical Nutritional
Assessment .............................................................................. 587
Table 25.3 Recommended Nutrition Guidelines for Family
Practice .................................................................................... 588
26 Assessment of Lipids and Lipoproteins ........................................................ 591

Elaine B. Feldman
Introduction ....................................................................................................... 591
Cholesterol ......................................................................................................... 591
Triacylglycerols (TG) ......................................................................................... 594
Lipoproteins ....................................................................................................... 594
Standardization of Assays ................................................................................ 598
Apoproteins ....................................................................................................... 599
Other Lipid Assays ........................................................................................... 600
Regulators of Lipid Metabolism ...................................................................... 600
References .......................................................................................................... 601
Table 26.1 Plasma Lipoproteins in Humans ............................................... 592
Table 26.2 Average Levels of Circulating Lipids........................................ 593
Table 26.3 Levels of Circulating Lipids Warranting Attention ................. 594
Table 26.4 Lipid Levels, U.S. National Health and Nutrition Evaluation
Surveys (NHANES III) Population........................................ 595
Table 26.5 Tests for Plasma Lipids, Lipoproteins, and Lipolytic
Enzymes................................................................................... 596
Table 26.6 Lipoprotein Subclasses ............................................................... 599
Table 26.7 Average Levels of Apoproteins in Plasma (mg/L) .................. 601
Figure 26.1 Production of lipoproteins, delivery into blood, and removal
by tissues ................................................................................. 597
Figure 26.2 The generation of HDL and the interrelations of the
lipoproteins, their production, and removal ........................ 598
27 Genetics of Energy and Nutrient Intake ....................................................... 603

Treva Rice, Louis Perusse, and Claude Bouchard
Introduction ....................................................................................................... 603
Genetic and Molecular Epidemiology ............................................................. 604
Familial Factors Underlying Macronutrient Intake ........................................ 606
Gene-Diet Interactions ...................................................................................... 607
Gene-Gene (G×G) Interactions ......................................................................... 615
Conclusions........................................................................................................ 616
References .......................................................................................................... 617
Table 27.1 Range of Heritability Estimates (%) for Macronutrients ......... 607
Table 27.2 Summary of Measured Gene-Diet Interactions ........................ 608
Figure 27.1 Hypothetical example of three genotypes plotted by energy
intake (X-axis) and fat mass (Y-axis) values......................... 605
28 Documentation to Improve Medical Assessment Access and

Reimbursement ................................................................................................. 621
Jessica A. Krenkel
Introduction ....................................................................................................... 621
Nutrition Diagnosis........................................................................................... 622
Care Standards .................................................................................................. 624
Medical Assessment Access .............................................................................. 624
Outcomes ........................................................................................................... 626
Reimbursement .................................................................................................. 627
Conclusion ......................................................................................................... 630

Terminology ....................................................................................................... 630
References .......................................................................................................... 631
Table 28.1 Nutrition Diagnoses.................................................................... 622
Table 28.2 Nutrition-Related International Classification of Disease, 9th ed.
(ICD-9) Diagnosis Code Examples ........................................ 623
Table 28.3 Major Classifications and Models of Managed Care
Systems .................................................................................... 625
Table 28.4 Types of Outcomes...................................................................... 627
29 Body Composition Assessment ...................................................................... 633

References .......................................................................................................... 635
Table 29.1 Proximate Body Composition of Adult Humans ..................... 633
Table 29.2 Size and Body Composition of Adult Men and Women ......... 634
Table 29.3 Indirect Methods for Determining Body Composition ............ 634
Table 29.4 General Formulas for Calculating Body Fatness from
Skinfold Measurements .......................................................... 634
30 The How and Why of Body Composition Assessment ............................... 637

Marta D. Van Loan
Introduction ....................................................................................................... 637
Ultrasound ......................................................................................................... 638
Bioelectrical Impedance Analysis (BIA), Multiple Frequency Impedance
(MF-BIA), and Bioimpedance Spectroscopy (BIS) ...................................... 639
Dual Energy X-Ray Absorptiometry (DXA) .................................................... 646
Computed Tomography .................................................................................... 650
Magnetic Resonance Imaging (MRI)................................................................ 652
Summary ............................................................................................................ 654
References .......................................................................................................... 655
Figure 30.1 A circuit equivalent model for conduction of an electrical
current through the body....................................................... 641
Figure 30.2 Conduction of low and high frequency currents through
the extracellular fluid and the total body water
compartments .......................................................................... 642
Figure 30.3 Cole-Cole Model of an impedance locus plot .......................... 642
Figure 30.4 Single photon absorptiometer using radionuclide source
from 125I.................................................................................... 647
Figure 30.5 Image of the spine from a dual energy x-ray absorptiometer
(DXA) ....................................................................................... 649
Figure 30.6 Magnetic resonance image of the abdominal cavity of an
individual ................................................................................ 653
31 Frame Size, Circumferences, and Skinfolds ................................................. 657

Barbara J. Scott
Introduction ....................................................................................................... 657
Frame Size.......................................................................................................... 660
Circumferences .................................................................................................. 662
Skinfold Measurements..................................................................................... 666

Conclusion ......................................................................................................... 671
References .......................................................................................................... 671
Table 31.1 Data Quality and Anthropometric Measurement Error........... 659
Table 31.2 Recommendations for Evaluating Measurement Differences
between Trainer and Trainee ................................................. 659
Table 31.3 Approximation of Frame Size by 1983 Metropolitan Height
and Weight Tables................................................................... 661
Table 31.4 Frame Size by Elbow Breadth by Gender and Age ................. 661
Table 31.5 Selected Validation Studies of Determinants of Frame Size
(FS) ........................................................................................... 663
Table 31.6 Selected Validation Studies of Circumference Measures ......... 667
Table 31.7 Reliability of Selected Skinfold Measurement Sites ................. 668
Table 31.8 Selected Studies Examining the Relationships between
Anthropometric Measures and Bone Mass or Bone
Mineral Density ...................................................................... 670
32 Height, Weight, and Body Mass Index (BMI) in Childhood ...................... 673
Christine L. Williams and Mary Horlick
Introduction ....................................................................................................... 673
Height................................................................................................................. 673
Weight ................................................................................................................ 676
Body Mass Index (BMI) .................................................................................... 677
Sources of Further Information........................................................................ 694
Figure 32.1 Weight-for-age percentiles, boys, birth to 36 months, Centers for
Disease Control (CDC) growth charts: U.S. ......................... 680
Figure 32.2 Weight-for-age percentiles, girls, birth to 36 months, CDC
growth charts: U.S. ................................................................. 681
Figure 32.3 Length-for-age percentiles, boys, birth to 36 months, CDC
growth charts, U.S. ................................................................. 682
Figure 32.4 Length-for-age percentiles, girls, birth to 36 months, CDC
growth charts: U.S. ................................................................. 683
Figure 32.5 Weight-for-length, boys, birth to 36 months, CDC growth
charts: U.S. .............................................................................. 684
Figure 32.6 Weight-for-length percentiles, girls, birth to 36 months,
CDC growth charts: U.S. ........................................................ 685
Figure 32.7 Weight-for-age percentiles, boys, 2 to 20 years, CDC growth
charts: U.S. .............................................................................. 686
Figure 32.8 Weight-for-age percentiles, Girls, 2 to 20 years, CDC growth
charts: U.S. .............................................................................. 687
Figure 32.9 Stature-for-age percentiles, boys, 2 to 20 years, CDC growth
charts: U.S. .............................................................................. 688
Figure 32.10 Stature-for-age percentiles, girls, 2 to 20 years, CDC growth
charts, U.S. .............................................................................. 689
Figure 32.11 Weight-for-stature percentiles, boys, CDC growth charts:
U.S. ........................................................................................... 690
Figure 32.12 Weight-for-stature percentiles, girls, CDC growth charts:
U.S. ........................................................................................... 691
Figure 32.13 Body mass index-for-age percentiles, boys, 2 to 20 years,
Figure 32.14 Body mass index-for-age percentiles, girls, 2 to 20 years,

33 Anthropometric Assessment: Height, Weight, Body Mass Index (BMI)

(Adults) .............................................................................................................. 695
George A. Bray
Historical Perspective ....................................................................................... 695
Measurement of Weight .................................................................................... 698
Measurement of Stature (Standing Height) .................................................... 700
Comments .......................................................................................................... 701
References .......................................................................................................... 708
Table 33.1 Body Mass Index Index (BMI) Values ....................................... 703
Table 33.2 Percent Body Fat for Men and Women of Different Ethnic
Groups and Three Age Ranges According to Body Mass
Index ........................................................................................ 704
Figure 33.1 The natural history of overweight ............................................ 704
Figure 33.2 Risk of diseases increases with BMI increase........................... 705
Figure 33.3 Curvilinear relationship of BMI to diastolic blood
pressure ................................................................................... 706
Figure 33.4 National Heart, Lung, and Blood Institute algorithm for
evaluating BMI........................................................................ 707
34 Glossary of Terms used in Energy Assessment............................................ 709

Table 34.1 Terms of Reference in Energy Metabolism ............................... 710
Table 34.2 Methods and Equations Used for Calculating Basal Energy
Need......................................................................................... 712
35 Metabolic Assessment of the Overweight Patient ....................................... 713

Shawn C. Franckowiak, Kim M. Forde, and Ross E. Andersen
Introduction ....................................................................................................... 713
Definitions of Energy Units and Components of Metabolism ...................... 714
Techniques for Measuring Resting Metabolic Rate (RMR) ............................ 716
Instrumentation Available ................................................................................ 717
Types of Collection Systems ............................................................................. 718
Clinical Applications and Usefulness of RMR................................................ 719
Predicting RMR ................................................................................................. 721
Pretesting Procedures for Measurement of RMR ........................................... 723
Factors Affecting RMR ...................................................................................... 724
RMR and Weight Loss ...................................................................................... 727
Summary ............................................................................................................ 732
References .......................................................................................................... 734
Acknowledgment............................................................................................... 734
Table 35.1 Respiratory Quotient and Energy Content of Various
Substrates ................................................................................ 717
Table 35.2 Factors for Estimating Total Daily Energy Needs of Activities
for Men and Women (Age 19 to 50)...................................... 720
Table 35.3 Equations for Estimating Resting Metabolic Rate (RMR)

kcal/24 Hours ......................................................................... 722
Table 35.4 Checklist for RMR Testing ......................................................... 725
Table 35.5 Collection of Some of the Studies Investigating Changes
in Physiological Variables Associated with Treatment ........ 733
Figure 35.1 The three major components of the total daily energy
expenditure. RMR: Resting Metabolic Rate, TEF: Thermic
Effect of Feeding, TEA: Thermic Effect of Activity ............. 714
Figure 35.2 Open circuit technique of indirect calorimetry using a
canopy hood ............................................................................ 718
Figure 35.3 Changes in resting metabolic rate following interventions of
diet plus exercise training or dietary restriction alone ....... 730
36 Energy Assessment: Physical Activity ........................................................... 737

M. Joao Almeida and Steven N. Blair
Introduction ....................................................................................................... 737
Concepts and Definitions.................................................................................. 737
Why it is Important to Assess Physical Activity ............................................ 738
Purpose .............................................................................................................. 739
Important Aspects to Consider in Choosing the Most Appropriate
Measure.......................................................................................................... 739
Methods Available ............................................................................................. 743
Conclusions........................................................................................................ 751
Acknowledgments ............................................................................................. 751
References .......................................................................................................... 754
Table 36.1 Methods for Assessing Physical Activity .................................. 752
37 Thermogenesis .................................................................................................. 757

Bryan C. Bergman and James O. Hill
Introduction ....................................................................................................... 757
Thermic Effect of Food (TEF) ........................................................................... 757
Meal Size and Frequency.................................................................................. 758
Meal Composition ............................................................................................. 758
Age, Gender, and Obesity ................................................................................ 759
Effects of Exercise on TEF ................................................................................ 759
Thermogenesis with Chronic Overfeeding ..................................................... 760
Cold-Induced Thermogenesis........................................................................... 761
Over-the-Counter Weight Loss Stimulants...................................................... 761
Prescription Drugs for Weight Loss ................................................................ 766
Uncoupling Proteins and Thermogenesis ....................................................... 767
UCP Up-Regulation and Knockout Experiments ........................................... 767
Thermogenesis and Obesity ............................................................................. 768
Thermogenesis, NEAT, and Alterations in Daily Energy Expenditure......... 768
Conclusions........................................................................................................ 769
References .......................................................................................................... 770
Figure 37.1 An illustration of how the TEF (thermic effect of food) curve
shifts depending on subject and meal characteristics ......... 758
Figure 37.2 Energy expenditure compartmented into the first 12-h d
period (0-12 h) and the subsequent night period (12-24 h)
in lean and post-obese subjects during a control study and

during administration of caffeine ......................................... 763
Figure 37.3 Changes in body weight of diet plus placebo, caffeine (C),
ephedrine (E), or E + C .......................................................... 764
Figure 37.4 The relation of the change in basal metabolic rate,
postprandial thermogenesis, and activity thermogenesis
with fat gain after overfeeding.............................................. 764
38 Environmental Challenges and Assessment ................................................. 773

Gary D. Foster and Suzanne Phelan
Introduction ....................................................................................................... 773
Etiology of Obesity ........................................................................................... 773
Environmental Factors ...................................................................................... 775
Assessment of Environmental Challenges ...................................................... 780
Summary and Conclusion ................................................................................ 782
References .......................................................................................................... 784
Table 38.1 Typical vs. Recommended Serving Sizes .................................. 776
Table 38.2 Energy Savers .............................................................................. 779
Figure 38.1 Prevalence of overweight and obesity in the U.S. from 1960
to 1994...................................................................................... 774
Figure 38.2 Prevalence of overweight and obesity in children and
adolescents in the U.S. 1963-1994.......................................... 774
Figure 38.3 Food energy per capita per day in the U.S. ............................. 775
Figure 38.4 Sources of food energy in the U.S. food supply ...................... 777
Figure 38.5 Relative changes in amount of home foods purchased,
1980 to 1992 ............................................................................. 777
Figure 38.6 Trends in leisure-time physical activity of adults age
18+ years.................................................................................. 778
Figure 38.7 Mode of travel in the U.S. from 1977 to 1995 .......................... 779
Figure 38.8 Percentage of households reporting expenditures,
1980 to 1990 ............................................................................. 780
Figure 38.9 Prevalence of overweight in the U.S. by race-ethnic group
for men and women age 20-27 years, 1998-1994.................. 781
Figure 38.10 Environmental influences on obesity ........................................ 783
39 Psychological Tests........................................................................................... 787

Victor R. Pendleton and John P. Foreyt
Mood .................................................................................................................. 789
Body Image ........................................................................................................ 790
Self-Esteem......................................................................................................... 791
Self-Efficacy........................................................................................................ 792
Eating Disorders ................................................................................................ 793
Restrained Eating .............................................................................................. 794
Locus of Control ................................................................................................ 795
Stage of Change................................................................................................. 796
References .......................................................................................................... 797
Table 39.1 Psychological Factors Contributing to Nutritional
Abnormalities .......................................................................... 788
Table 39.2 Psychological Instruments and What They Measure ............... 788
Part VI Modified Diets
40 Vegetarian Diets in Health Promotion and Disease Prevention ................ 801

Claudia S. Plaisted and Kelly M. Adams
Overview/Introduction .................................................................................... 801
Characteristics of Vegetarian Eating Styles..................................................... 801
Health Benefits and Risks of Vegetarianism ................................................... 802
Energy and Macronutrients in the Vegetarian Diet ....................................... 806
Micronutrients in the Vegetarian Diet ............................................................. 811
Non-Nutritive and Other Important Factors in the Vegetarian Diet ............ 811
The Effects of Cooking, Storage, and Processing on the Critical
Nutrients ........................................................................................................ 813
General Vitamin and Mineral Deficiency and Toxicity Symptoms ............... 825
Sample Meal Plans ............................................................................................ 828
Summary ............................................................................................................ 830
References .......................................................................................................... 830
Table 40.1 Types of Vegetarian Diets........................................................... 802
Table 40.2 Types of Popular Diets Incorporating Various Principles of
Vegetarianism .......................................................................... 802
Table 40.3 Nutrients Potentially at Risk in Vegetarian Diets, Dietary
Reference Intakes (DRIs), Functions and Sources ................ 803
Table 40.4 Health Risks of Vegetarianism ................................................... 804
Table 40.5 Health Benefits of Vegetarianism............................................... 805
Table 40.6 Protective Factors in the Typical Lacto-Ovo Vegetarian
Diet........................................................................................... 805
Table 40.7 Practical Concerns about Vegetarianism ................................... 805
Table 40.8 Nutrient Differences Between Omnivore, Lacto-Ovo, and
Vegan Dietary Patterns........................................................... 805
Table 40.9 Health Risks of Individuals Following Various Types of
Vegetarian Diets ...................................................................... 806
Table 40.10 Critical Periods of Importance for Selected Nutrients ............ 807
Table 40.11 Definitions Related to Protein Complementation .................... 807
Table 40.12 Limiting Essential Amino Acids and Vegan Sources ............... 807
Table 40.13 Guidelines for Protein Complementation ................................. 808
Table 40.14 Protein Intakes in the United States.......................................... 808
Table 40.15 Protein: Vegetarian Sources and Amounts................................ 808
Table 40.16 Vegetarian Sources of Energy-Dense, Nutrient-Dense
Foods........................................................................................ 810
Table 40.17 Riboflavin: Vegetarian Sources and Amounts .......................... 812
Table 40.18 Vitamin B 12: Vegetarian Sources and Amounts......................... 814
Table 40.19 Vitamin D: Vegetarian Sources and Amounts .......................... 815
Table 40.20 Calcium: Vegetarian Sources and Amounts .............................. 816
Table 40.21 Copper: Vegetarian Sources and Amounts ............................... 817
Table 40.22 Iodine: Vegetarian Sources and Amounts ................................. 818
Table 40.23 Iron: Nonheme Sources in the Vegetarian Diet ........................ 819
Table 40.24 Iron: Absorption Enhancers and Inhibitors .............................. 820
Table 40.25 Manganese: Vegetarian Sources and Amounts ......................... 821
Table 40.26 Selenium: Vegetarian Sources and Amounts ............................ 821
Table 40.27 Zinc: Vegetarian Sources and Amounts .................................... 823
Table 40.28 Zinc: Absorption Enhancers and Inhibitors.............................. 824
Table 40.29 Fiber: Types, Functions, and Sources ........................................ 825

Table 40.30 Common Phytochemicals in Foods ........................................... 825
Table 40.31 Omega-3 Fatty Acids: Vegetarian Sources and Amounts ........ 826
Table 40.32 Effects of Cooking, Storage, and Processing on the Critical
Nutrients.................................................................................. 826
Table 40.33 General Vitamin and Mineral Deficiency and Toxicity
Symptoms ................................................................................ 827
Table 40.34 Sample Meal Plan for Lacto-Ovo Vegetarian Adult................. 828
Table 40.35 Sample Meal Plan for Vegan Adult ........................................... 829
Table 40.36 Sample Meal Plan for Vegan Child Age 4 to 6......................... 829
Table 40.37 Sample Meal Plan for Lacto-Ovo Vegetarian Child Age
4 to 6 ........................................................................................ 829
41 Allergic Disorders ............................................................................................ 833

Scott H. Sicherer
Definition of Food Allergy ............................................................................... 833
Pathophysiology of Food Allergic Reactions .................................................. 833
Food Allergens................................................................................................... 835
Epidemiology..................................................................................................... 835
Food Allergic Disorders .................................................................................... 836
Multisystem Disorders ...................................................................................... 841
Disorders Not Clearly Related to Food Allergy ............................................. 841
Diagnostic Approach to Food Allergic Disorders........................................... 842
General Approach to Diagnosis ....................................................................... 842
Tests for Specific Immunoglobulin E (IGE) Antibody.................................... 843
Treatment of Food Allergy ............................................................................... 845
Natural History ................................................................................................. 846
Prevention of Food Allergy .............................................................................. 846
Future Therapies ............................................................................................... 847
References .......................................................................................................... 847
Table 41.1 Examples of Food Intolerance/Toxic Reactions ....................... 834
Table 41.2 Foods Responsible for the Majority of Significant Allergic
Reactions.................................................................................. 835
Table 41.3 Epidemiologic Role of Food Allergy in Various Disorders ..... 836
Table 41.4 Cross-Reactions Due to Proteins Shared by Pollens and Foods
Leading to Symptoms of the Oral Allergy Syndrome ......... 838
Table 41.5 Gastrointestinal Diseases Associated with Food Allergy ........ 840
Table 41.6 Symptoms Occurring in Anaphylaxis ....................................... 841
Table 41.7 Indications for Performing Physician-Supervised Oral Food
Challenges ............................................................................... 844
Table 41.8 Pitfalls in Dietary Allergen Avoidance...................................... 846
Figure 41.1 APC-antigen presenting cells, IL-interleukin ........................... 834
42 Enteral Nutrition .............................................................................................. 851

Gail A. Cresci and Robert G. Martindale
Introduction ....................................................................................................... 851
Enteral Access .................................................................................................... 852
Enteral Formulas ............................................................................................... 857
Methods of Administration .............................................................................. 867
Enteral Feeding Complications ........................................................................ 868

Summary ............................................................................................................ 871
References .......................................................................................................... 872
Table 42.1 Immune Benefits of Enteral Feeding ......................................... 852
Table 42.2 Enteral Feeding Indications ....................................................... 853
Table 42.3 Enteral Feeding Contraindications ............................................ 853
Table 42.4 Risk Factors for Aspiration ........................................................ 754
Table 42.5 Methods of Gastrointestinal (GI) Access................................... 855
Table 42.6 Percutaneous Enterogastrostomy (PEG) Indications and
Contraindications.................................................................... 856
Table 42.7 Overview of Select Enteral Formulas........................................ 858
Table 42.8 Common Complications Associated with Enteral
Feeding .................................................................................... 869
Table 42.9 Example Monitoring Protocol for Enteral Feeding .................. 871
Figure 42.1 Enteral access decision tree........................................................ 854
43 Parenteral Nutrition ......................................................................................... 875

Introduction ....................................................................................................... 875
Vascular Access.................................................................................................. 877
Parenteral Nutrient Components ..................................................................... 880
Summary ............................................................................................................ 890
References .......................................................................................................... 892
Table 43.1 Development of Total Parenteral Nutrition (TPN)
Guidelines................................................................................ 876
Table 43.2 Indications for TPN .................................................................... 876
Table 43.3 Factors that Contribute to Increased Gut Permeability ........... 877
Table 43.4 Typical Peripheral Parenteral Nutrition (PPN) Order ............. 878
Table 43.5 Indications for PPN .................................................................... 878
Table 43.6 Central Venous Catheter Placement .......................................... 879
Table 43.7 Central Venous Catheter Characteristics................................... 879
Table 43.8 Patient Factors for Vascular Access Device Selection .............. 880
Table 43.9 Intravenous Dextrose Solutions ................................................. 881
Table 43.10 Parenteral Electrolyte Recommendations.................................. 883
Table 43.11 Commercially Available Electrolyte Formulations ................... 884
Table 43.12 American Medical Association (AMA) Recommendations for
Parenteral Vitamin Intake ...................................................... 884
Table 43.13 AMA Recommendations for Parenteral Mineral Intake .......... 885
Table 43.14 Medications Compatible with Parenteral Solutions................. 886
Table 43.15 Medications Incompatible with Parenteral Solutions .............. 887
Table 43.16 Mechanical Complications of Parenteral Nutrition ................. 889
Table 43.17 Metabolic Complications of Parenteral Nutrition .................... 891
Table 43.18 Suggested Monitoring of TPN ................................................... 892
44 Sports — Elite Athletes ................................................................................... 895

Michael F. Bergeron
A Balanced Diet ................................................................................................. 895
Carbohydrates ................................................................................................... 896
Fats ..................................................................................................................... 896
Protein ................................................................................................................ 897

Carbohydrate and Fat: Primary Energy Sources ............................................ 898
Effects of Endurance Training on Carbohydrate, Fat, and Protein
Utilization ...................................................................................................... 898
Precompetition Nutrition.................................................................................. 899
Nutrition during Competition.......................................................................... 900
Postexercise Nutrition....................................................................................... 902
Nutrition and Fatigue ....................................................................................... 902
Fluid Balance ..................................................................................................... 903
Nutritional Ergogenic Aids .............................................................................. 905
Creatine .............................................................................................................. 906
Medium-Chain Tryglycerides ........................................................................... 906
Sodium Bicarbonate .......................................................................................... 907
Branched-Chain Amino Acids .......................................................................... 907
Vitamins and Minerals ...................................................................................... 908
Summary ............................................................................................................ 909
References .......................................................................................................... 910
Table 44.1 Glycemic Index of a Variety of Foods ....................................... 897
Table 44.2 Nutrition-Related Problems and Recommendations for the
Elite Athlete............................................................................. 909
Part VII Clinical Nutrition
45 Alcohol: Its Metabolism and Interaction with Nutrients ........................... 915

Charles S. Lieber
Respective Role of Alcohol and Nutrition in Organ Damage of the
Alcoholic ........................................................................................................ 915
The Alcohol Dehydrogenase (ADH) Pathway and Associated Metabolic
Disorders of Carbohydrates, Uric Acid, and Lipids .................................. 917
Nutritional Status of Alcoholics....................................................................... 921
Effects of Ethanol on Digestion and Absorption ............................................ 925
Effect of Alcohol on Nutrient Activation ........................................................ 925
Toxic Interaction of Alcohol with Nutrients ................................................... 928
Effects of Ethanol on the Metabolism of Proteins .......................................... 934
Effects of Dietary Factors on Ethanol Metabolism ......................................... 934
Nutritional Therapy in Alcoholism ................................................................. 934
Acknowledgment............................................................................................... 935
References .......................................................................................................... 935
Figure 45.1 Organ damage in the alcoholic .................................................. 916
Figure 45.2 Hepatic, nutritional, and metabolic abnormalities after
ethanol abuse .......................................................................... 919
Figure 45.3 Physiologic and toxic roles of CYP2E1, the main cytochrome
P450 of the microsomal ethanol oxidizing system
(MEOS)..................................................................................... 919
Figure 45.4 Lipid peroxidation and other consequences of alcoholic
liver disease............................................................................. 927
Figure 45.5 Hepatic vitamin A levels in subjects with normal livers,
chronic persistent hepatitis, and various stages of alcoholic
injury........................................................................................ 929
Valerie Fishell Bernard Gutin

The Pennsylvania State University Augusta, Georgia
David Heber
William P. Flatt
Division of Clinical Nutrition
UCLA School of Medicine
Athens, Georgia
Los Angeles, California
Kim M. Forde
Johns Hopkins School of Medicine Linda K. Hendricks
Division of Geriatric Medicine and Section of Hematology and Oncology
Gerontology Department of Medicine
Baltimore, Maryland Medical College of Georgia
Augusta, Georgia
John P. Foreyt
Behavioral Medicine Research Center Victor Herbert
Baylor College of Medicine Bronx V.A. Medical Center
Houston, Texas Bronx, New York
Gary D. Foster James O. Hill

University of Pennsylvania University of Colorado Health Sciences
Philadelphia, Pennsylvania Center
Center for Human Nutrition
Shawn C. Franckowiak Denver, Colorado
Gerontology Deanna M. Hoelscher
Baltimore, Maryland University of Texas — Houston Health
Science Center
School of Public Health
Naomi K. Fukagawa Human Nutrition Center
Department of Medicine Houston, Texas
University of Vermont College of Medicine
Burlington, Vermont
Mary Horlick
Constance J. Geiger Institute of Human Nutrition
Geiger and Associates Department of Pediatrics
Salt Lake City, Utah Columbia University, College of Physicians
and Surgeons
New York, New York
Jane M. Greene
Nutrition Consultant
Augusta, Georgia Carolyn H. Jenkins
Division of Endocrinology, Diabetes, and
Sue Grossbauer Medical Genetics
The Grossbauer Group Department of Medicine
Chesterton, Indiana Medical University of South Carolina
46 Anemias ............................................................................................................. 941

Linda K. Hendricks and Abdullah Kutlar
Introduction ....................................................................................................... 941
Anemia: Definition and Classification ............................................................. 941
Vitamin B 12 Deficiency ...................................................................................... 948
Folate Deficiency ............................................................................................... 951
Iron Deficiency Anemia .................................................................................... 954
Additional Sources of Information .................................................................. 959
Table 46.1 Nutrients Important for Normal Red Blood Cell (RBC)
Production ............................................................................... 942
Table 46.2 9Criteria for Anemia and Normal Mean Corpuscular Volume
(MCV) Values .......................................................................... 942
Table 46.3 Initial Laboratory Data in the Evaluation of Anemia .............. 942
Table 46.4 Classification of Anemias by Morphology................................ 943
Table 46.5 Functional Causes of Anemia .................................................... 844
Table 46.6 Categorizing Anemias by Reticulocyte Count.......................... 947
Table 46.7 Symptoms of Anemia ................................................................. 947
Table 46.8 Physical Findings in Anemia ..................................................... 948
Table 46.9 Causes of Vitamin B 12 Deficiency .............................................. 949
Table 46.10 Clinical Features of B 12 Deficiency ............................................ 949
Table 46.11 Laboratory Features of B 12 Deficiency ....................................... 950
Table 46.12 The Laboratory Difference Between Negative Nutritional
Balance and True Folate and B 12 Deficiency ......................... 950
Table 46.13 Treatment of B 12 Deficiency ........................................................ 951
Table 46.14 Causes of Folate Deficiency ....................................................... 952
Table 46.15 Clinical Features of Folate Deficiency ....................................... 953
Table 46.16 Laboratory Diagnosis of Folate Deficiency ............................... 953
Table 46.17 Treatment of Folate Deficiency .................................................. 953
Table 46.18 Causes for Treatment Failure ..................................................... 954
Table 46.19 Who Should Receive Prophylaxis for B12 and Folate
Deficiency?............................................................................... 954
Table 46.20 Causes of Iron Deficiency Anemia ............................................ 955
Table 46.21 Clinical Features of Iron Deficiency .......................................... 956
Table 46.22 Laboratory Features of Iron Deficiency..................................... 957
Table 46.23 Treatment of Iron Deficiency...................................................... 958
Table 46.24 Possible Side Effects of Iron Therapy ....................................... 958
Table 46.25 Nutritional Information on B 12, Folate, and Iron ..................... 959
Figure 46.1 A normal peripheral blood smear ............................................. 943
Figure 46.2 Erythropoiesis as it is affected by states of iron deficiency
and vitamin B 12 or folate deficiency ...................................... 944
Figure 46.3 Macrocytic RBCs ......................................................................... 945
Figure 46.4 Microcytic RBCs .......................................................................... 945
Figure 46.5 Reticulocytes................................................................................ 946
Figure 46.6 Understanding the reticulocyte index ....................................... 947
47 Nutritional Treatment of Blood Pressure: Nonpharmacologic

Therapy .............................................................................................................. 961
L. Michael Prisant
Nutrients and Blood Pressure .......................................................................... 962
Summary ............................................................................................................ 995

References .......................................................................................................... 996
Table 47.1 Randomized Double-Blind Trials of Sodium
Supplementation ..................................................................... 963
Table 47.2 Descriptive Summary of Sodium-Reduction Trials in
Normotensive Subjects ........................................................... 964
Table 47.3 Descriptive Summary of Sodium-Reduction Trials in
Hypertensive Subjects ............................................................ 965
Table 47.4 Characteristics of Trials of Sodium Restriction and Blood
Pressure in Normotensive Populations................................. 966
Table 47.5 Characteristics of Trials of Sodium Restriction in Hypertensive
Populations.............................................................................. 968
Table 47.6 Participant and Study Design Characteristics in 33 Potassium
Supplementation Trials........................................................... 972
Table 47.7 Urinary Electrolyte Excretion, Body Weight, and Blood
Pressure during Followup in 33 Potassium Supplementation
Trials ........................................................................................ 974
Table 47.8 Randomized Controlled Trials Examining the Relationship of
Calcium and Blood Pressure.................................................. 976
Table 47.9 Randomized Controlled Trials Studying the Effect of Calcium
Supplementation and Blood Pressure ................................... 977
Table 47.10 Randomized Controlled Trials of Calcium Supplementation
in Pregnancy............................................................................ 979
Table 47.11 Change in Blood Pressure in Randomized Controlled Trials
of Calcium Supplementation in Pregnancy .......................... 980
Table 47.12 Randomized Trials of Magnesium Supplementation ............... 981
Table 47.13 Characteristics of the 31 Trials used for the Meta-Analysis of Fish
Oil and Blood Pressure .......................................................... 983
Table 47.14 Observational Studies on Protein and Blood Pressure ............ 986
Table 47.15 Human Intervention Studies on Protein and Blood
Pressure ................................................................................... 987
Table 47.16 Trials of Ascorbic Acid and Blood Pressure ............................. 989
Table 47.17 Randomized Controlled Trials of Garlic and Blood
Pressure ................................................................................... 991
Table 47.18 Randomized Controlled Trials of Alcohol Reduction on
Blood Pressure ........................................................................ 993
Table 47.19 Controlled Studies of Coffee Consumption .............................. 994
Table 47.20 Meta-Analysis of Results of Studies on Nonpharmacologic
Intervention and Blood Pressure ........................................... 996
Figure 47.1 Multivariate adjusted relative risk of stroke of 43,738 U.S. men,
40 to 75 years, by quintile of potassium intake ................... 970
Figure 47.2 Effect of potassium supplementation on net blood pressure
reduction according to urinary sodium excretion during
followup .................................................................................. 975
Figure 47.3 Health and nutrition examination survey I: % mean difference in
average nutritional consumption between hypertensive and
normotensive persons, adjusted for age ............................... 988
Figure 47.4 The effect of ethanol consumption on the change in blood
pressure independent of other factors .................................. 992
48 Nutritional Treatment of Blood Pressure: Major Nonpharmacologic

Trials of Prevention or Treatment of Hypertension..................................... 999
L. Michael Prisant
Major Nonpharmacologic Trials of Prevention or Treatment of
Hypertension ................................................................................................. 999
References ........................................................................................................ 1010
Table 48.1 Nonpharmacologic Interventions in High Normal Blood
Pressure ................................................................................. 1000
Table 48.2 Hypertension Prevention Trial (HPT): Six-Month Change in
Interventions ......................................................................... 1001
Table 48.3 Intervention Outcome, Treatment Effect, and Blood Pressure
Effect in Trial of Hypertension Prevention, Phase I .......... 1003
Table 48.4 Trial of Hypertension Prevention, Phase 1: Effect of Weight
Change on Blood Pressure Reduction at 18 Months by
Gender ................................................................................... 1004
Table 48.5 Baseline Characteristics and Outcomes of Trials of Hypertension
Prevention (Phase II) ............................................................ 1004
Table 48.6 Dietary Intervention Study in Hypertension: Demographics
and Outcome ......................................................................... 1005
Table 48.7 Hypertension Control Program: Demographics and
Outcome................................................................................. 1006
Table 48.8 Trial of Antihypertensive Intervention and Management:
Change in Blood Pressure from Baseline by Treatment
Group at Six Months ............................................................ 1007
Table 48.9 Trial of Antihypertensive Intervention and Management:
Change in Diastolic Blood Pressure with >4.5 kg Weight
Change, Comparable to Low-Dose Drug Therapy............. 1007
Figure 48.1 The hypertension prevention trial: three-year rate of elevated
blood pressure or treatment for hypertension according to
BMI and intervention ........................................................... 1002
Figure 48.2 Trial of hypertension prevention, Phase 1 .............................. 1003
49 Chemoprevention of Cancer in Humans by Dietary Means..................... 1011

Elizabeth K. Weisburger and Ritva Butrum
Macronutrients ................................................................................................ 1011
Vitamins and Minerals .................................................................................... 1016
Nonnutritive Components .............................................................................. 1021
References ........................................................................................................ 1025
Table 49.1 Typical Dietary Fatty Acids...................................................... 1013
Table 49.2 Amino Acids .............................................................................. 1015
Table 49.3 B Vitamins ................................................................................. 1018
Table 49.4 Cancer Preventive Action of Vitamins .................................... 1024
Table 49.5 Chemopreventive Action of Nonnutritive Principles of
Foods...................................................................................... 1025
50 Nutrition and Cancer Treatment................................................................... 1029

David Heber and Susan Bowerman
Etiology of Malnutrition in the Cancer Patient ............................................ 1029
Metabolic Abnormalities in the Cancer Patient ............................................ 1029
Assessment of the Cancer Patient’s Nutritional Status ............................... 1034

Nutritional and Adjunctive Pharmacotherapy of Anorexia and
Cachexia ....................................................................................................... 1037
Food Supplements ........................................................................................... 1039
Nutrition Options and Alternative Therapies .............................................. 1041
References ........................................................................................................ 1042
Table 50.1 Metabolic Abnormalities in Cancer Patients .......................... 1030
Table 50.2 Research Stategies to Counter Metabolic Abnormalities ....... 1030
Table 50.3 Total Body Protein Turnover, Glucose Production and
3-Methylhistidine Excretion in the Fasting State on Day 5
of Constant Nitrogen and Kcalorie Intake in Lung Cancer
Patients Compared to Healthy Controls ............................. 1033
Table 50.4 Whole Body Lysine Flux in Lung Cancer Patients ................ 1033
Table 50.5 Nutritional Assessment Factors in the Cancer Patient .......... 1034
Table 50.6 Patient Characteristics in 644 Consecutive Cancer
Patients .................................................................................. 1036
Table 50.7 Nutritional Variables in 644 Consecutive Cancer
Patients .................................................................................. 1037
Table 50.8 Benefits, Methodology, and Risks of Nutrition
Interventions ......................................................................... 1038
Table 50.9 Foods Recommended to Increase Kcalorie and Protein Intake
of the Patient with Cancer ................................................... 1040
Table 50.10 Alternative Nutritional Therapies Used by Cancer
Patients .................................................................................. 1041
Table 50.11 Potential Side Effects and Concerns........................................ 1042
Figure 50.1 Mean nitrogen balance in grams per 24 hours in six patients
with head and neck cancer .................................................. 1031
Figure 50.2 Measured resting energy expenditure as a percentage of predicted
energy expenditure ............................................................... 1031
Figure 50.3 Whole-body protein turnover determined by lysine infusion in
the fasting state..................................................................... 1032
51 Cardiovascular Disease Risk — Prevention by Diet ................................. 1045

Elaine B. Feldman
Introduction ..................................................................................................... 1045
The Extended Lipid Hypothesis .................................................................... 1045
Dietary Effects on Serum Lipids and Lipoproteins...................................... 1048
Atherosclerosis ................................................................................................ 1049
National Cholesterol Education Program (NCEP) and Dietary
Guidelines .................................................................................................... 1050
Diet Trials......................................................................................................... 1053
Other Nutritional Factors and CVD Risk...................................................... 1055
Cardiovascular Disease (CVD) Risk Prevention by Non-Lifestyle
Modifications ............................................................................................... 1056
Clinical Trials, Lifestyle .................................................................................. 1057
Lessons from Large-Scale Clinical Trials of Lipid-Lowering Therapy ....... 1058
References ........................................................................................................ 1058
Table 51.1 Foods and Nutrients that Affect Cholesterol Levels.............. 1046
Table 51.2 Factors Affecting High Density Lipoproteins (HDL) Cholesterol
Levels ..................................................................................... 1047
Table 51.3 Mutations that Predispose to Atherosclerosis ........................ 1049

Table 51.4 National Cholesterol Education Program Guidelines ............ 1050
Table 51.5 Selected Foods High in Monounsaturated Fatty Acids ......... 1051
Table 51.6 Dietary Sources of Cholesterol ................................................ 1052
Table 51.7 Selected Foods High in Saturated Fatty Acids ....................... 1052
Table 51.8 Step I and Step II Diets ............................................................ 1053
Table 51.9 Step I American Heart Association (AHA) — Meal Plan...... 1054
Figure 51.1 Death rates from coronary heart disease (CHD) and the intake of
saturated fat in the seven countries study ......................... 1046
Figure 51.2 The saturated fatty acid content of various fats and oils ..... 1048
Figure 51.3 Homocysteine metabolism is regulated by enzymes
dependent on folate and vitamins B 6 and B 12 .................... 1055
52 Hyperlipidemias and Nutrient-Gene Interactions ..................................... 1061

Elaine B. Feldman
Hyperlipidemias .............................................................................................. 1061
References ........................................................................................................ 1074
Table 52.1 Factors Involved in the Formation and Metabolism of
Lipoproteins .......................................................................... 1062
Table 52.2 Effects of Diet and Lifestyle on Gene Lipoprotein
Expression ............................................................................. 1063
Table 52.3 Classification (Type) of Hyperlipidemia and the Underlying
Lipoprotein Abnormality ..................................................... 1063
Table 52.4 Genetic Basis of Familial Hyperlipidemias ............................ 1064
Table 52.5 Metabolic Syndrome Risk Factors ........................................... 1069
Table 52.6 Evaluation of Patient for Hyperlipidemia .............................. 1070
Table 52.7 Guidelines of Food Choices and Menu Plans For Patients
with Severe Hypercholesterolemia (FH) ............................. 1071
Table 52.8 Guidelines of Food Choices and Menu Plans for Patients
with Severe Hypertriglyceridemia (Type V) ...................... 1072
Figure 52.1 Lipidemia retinalis visualized in the optical fundus of a
patient with chylomicronemia with triaglyceride (TG or TAG)
levels exceeding 3000 mg/dl ............................................... 1064
Figure 52.2 Eruptive xanthomas observed in a patient with
chylomicronemia ................................................................... 1065
Figure 52.3 Eyelid xanthelasma from a woman with familial
hypercholesterolemia ............................................................ 1066
Figure 52.4 Corneal arcus observed in a 31-year-old man with familial
Figure 52.5 Xanthomas of the Achilles tendons of a patient with familial
Figure 52.6 Tuberous xanthomas in the skin of the elbows of a teenage
girl with familial hypercholesterolemia.............................. 1067
Figure 52.7 Yellow linear deposits in the creases of the fingers and
palms of the hands of a 33-year-old man with Type III
hyperlipoproteinemia ........................................................... 1068
Figure 52.8 The appearance of plasma, refrigerated overnight, from
fasting patients...................................................................... 1070
Figure 52.9 The efficacy of various lipid-lowering drugs in treating
patients with hypercholesterolemia .................................... 1073
53 Nutrition in Diabetes Mellitus..................................................................... 1077

Maria F. Lopes-Virella, Carolyn H. Jenkins, and Marina Mironova
Introduction ..................................................................................................... 1077
Classification and Diagnostic Criteria of the Several Subtypes of Diabetes
and Intermediate Syndromes ..................................................................... 1078
Criteria for Screening for Diabetes ................................................................ 1081
Diabetic Complications: Microvascular ......................................................... 1083
Diabetic Complications: Macrovascular Disease .......................................... 1088
Diabetic Complications: Hypoglycemia ........................................................ 1089
Standards of Medical Care for Diabetic Patients ......................................... 1091
Nutritional Recommendations and Principles for the Dietary Treatment
of Diabetics .................................................................................................. 1096
Food Guides and Planning Food Intake for Persons with Diabetes........... 1104
Food Labeling .................................................................................................. 1104
Diabetes and Physical Activity ...................................................................... 1105
Hospital Admission Guidelines for Persons with Diabetes ........................ 1108
Translation of Medical Nutrition Therapy for Diabetes to Health Care
Institutions................................................................................................... 1108
Third Party Reimbursement for Diabetes Care, Supplies, and
Self-Management Education....................................................................... 1110
References ........................................................................................................ 1111
Table 53.1 Etiologic Classification of Diabetes Mellitus .......................... 1079
Table 53.2 Criteria for the Diagnosis of Diabetes Mellitus ..................... 1081
Table 53.3 Estimated Prevalence of Diabetes in the U.S. in Individuals
40 to 74 Years of Age ............................................................ 1081
Table 53.4 Major Risk Factors for Diabetes Mellitus ............................... 1082
Table 53.5 Criteria for the Diagnosis of Diabetes Mellitus using
Glucose Tolerance Results.................................................... 1083
Table 53.6 Screening and Diagnosis Scheme for Gestational Diabetes
Mellitus (GDM) ..................................................................... 1083
Table 53.7 Screening and Followup of Patients with Diabetes for
Retinopathy ........................................................................... 1084
Table 53.8 Classification of Diabetic Neuropathy .................................... 1084
Table 53.9 Symptoms and Signs of Diabetic Polyneuropathy ................. 1084
Table 53.10 Functional Changes Associated with Autonomic Failure...... 1084
Table 53.11 Electrodiagnostic Studies, Sensory Testing, and
Autonomic Function Testing for the Diagnosis of Diabetic
Neuropathy ........................................................................... 1085
Table 53.12 Definition of Abnormalities in Albumin Excretion ................ 1085
Table 53.13 Indications for Cardiac Testing in Diabetic Patients ............. 1090
Table 53.14 Recommended Diabetes Management Guidelines ................. 1093
Table 53.15 Treatment Decisions Based on LDL Cholesterol Levels
in Adults ................................................................................ 1096
Table 53.16 Goals of Medical Nutrition Therapy for Diabetes ................. 1097
Table 53.17 Survival Skills for Managing Diabetes.................................... 1097
Table 53.18 Goals for Medical Nutrition Therapy in GDM....................... 1099
Table 53.19 Blood Glucose Goals for Pregnancy ........................................ 1099
Table 53.20 Summary of Intensive Nutritional Therapy for GDM ........... 1100
Table 53.21 Intensive Medical Nutrition Therapy for GDM ..................... 1100
Table 53.22 Medical Nutrition Therapy Recommendations ...................... 1101

Table 53.23 Energy Nutrients and Their Absorption ................................. 1104
Table 53.24 Meal Planning Approaches ...................................................... 1104
Table 53.25 Ways to Count Carbohydrates ................................................. 1105
Table 53.26 Food Adjustments for Exercise for Persons with Type 1
Diabetes ................................................................................. 1107
Table 53.27 Developing a Consistent Carbohydrate Diabetes Meal Plan
Menu for Health Care Facilities .......................................... 1109
Table 53.28 States That Have Enacted Diabetes Reform Laws (as of
January 2000)......................................................................... 1110
Figure 53.1 Nutrition therapy for type 1 diabetes ..................................... 1098
Figure 53.2 Nutrition therapy for type 2 diabetes ..................................... 1098
54 Nutrition and Oral Medicine ........................................................................ 1113

Dominick P. DePaola, Connie Mobley, and Riva Touger-Decker
Introduction ..................................................................................................... 1113
The Burden of Oral Disease ........................................................................... 1114
Chronic Oral Infectious Disease..................................................................... 1114
Environmental Oral Health Promotion: Fluoridation .................................. 1119
Systemic Diseases ............................................................................................ 1120
Neoplastic Diseases: Oral Cancer .................................................................. 1127
Craniofacial-Oral-Dental Birth Defects.......................................................... 1128
Health Promotion, Health Education, and Behavior Change...................... 1129
References ........................................................................................................ 1133
Table 54.1 Supplemental Fluoride Dosage Schedule (mg/daya) ............. 1120
Table 54.2 Selected Systemic Diseases with Potential Oral Manifestations
Affecting Nutrition Status.................................................... 1121
Table 54.3 Medications with Associated Oral Manifestations................. 1121
Table 54.4 Abnormal Oral Findings: Associated Local and Systemic
Diseases ................................................................................. 1122
Table 54.5 Possible Causes of Anorexia in HIV/AIDS ............................ 1122
Table 54.6 Impact of HIV Infection on Nutrition and Diet in the Upper
GI Tract .................................................................................. 1123
Table 54.7 Common HIV-Associated Oral Disorders ............................... 1123
Table 54.8 Oral Manifestations of Diabetes .............................................. 1124
Table 54.9 Autoimmune Disorders with Associated Oral and Nutritional
Side Effects ............................................................................ 1126
Table 54.10 Risk Factors for Osteoporosis .................................................. 1127
Table 54.11 Global Nutrition Messages Addressing Primary and Secondary
Prevention of Dental Caries ................................................. 1130
Table 54.12 Nutrition Messages to Integrate into Parenting Practices for
Primary Prevention of ECC ................................................. 1131
Table 54.13 Nutrition Messages for Targeted Oral Health Promotion
Topics ..................................................................................... 1132
Figure 54.1 The burden of disease .............................................................. 1115
Figure 54.2 The caries balance ..................................................................... 1116
Figure 54.3 Diet and dental health .............................................................. 1117
Figure 54.4 A new paradigm for the pathobiology of periodontitis ........ 1118
55 Foodborne Infections and Infestations........................................................ 1135

Kumar S. Venkitanarayanan and Michael P. Doyle
Introduction ..................................................................................................... 1135
Bacterial Foodborne Pathogens ...................................................................... 1135
Viral Foodborne Pathogens ............................................................................ 1147
Fungal Foodborne Pathogens ......................................................................... 1149
Parasitic Foodborne Pathogens ...................................................................... 1151
References ........................................................................................................ 1156
Table 55.1 Bacterial Foodborne Pathogens................................................ 1136
Table 55.2 Viral Foodborne Pathogens ...................................................... 1148
Table 55.3 Fungal Foodborne Pathogens................................................... 1150
Table 55.4 Parasitic Foodborne Pathogens ................................................ 1152
56 Nutrition and the Hollow Organs of the Upper Gastrointestinal

Tract.................................................................................................................. 1163
Ece A. Mutlu, Gökhan M. Mutlu, and Sohrab Mobarhan
Introduction ..................................................................................................... 1163
Nutrition in Selected Diseases of the Upper Gastrointestinal Tract ........... 1165
References ........................................................................................................ 1182
Table 56.1 Parts of the Digestion System and Their Functions .............. 1164
Table 56.2 Overview of Nutrient Absorption ........................................... 1167
Table 56.3 Gastrointestinal Secretions ....................................................... 1168
Table 56.4 Symptoms of Gastroesophageal Reflux Disease (GERD)....... 1168
Table 56.5 Histopathological Changes Related to GERD ........................ 1169
Table 56.6 Major Mechanisms Thought to be Involved in the
Pathogenesis of GERD.......................................................... 1169
Table 56.7 Major Complications of GERD ................................................ 1170
Table 56.8 Lifestyle Factors That May Adversely Affect Severity or
Frequency of GERD .............................................................. 1170
Table 56.9 Foods That May Worsen GERD ............................................... 1172
Table 56.10 Summary of Tips for the GERD Patient.................................. 1173
Table 56.11 Causes of Peptic Ulcer Disease (PUD) .................................... 1174
Table 56.12 Major Mechanisms of Tissue Damage and Repair Involved
in the Pathogenesis of PUD ................................................. 1175
Table 56.13 Major Complications Related to PUD ..................................... 1175
Table 56.14 Summary of Evidence on Diet and PUD ................................ 1178
Table 56.15 Summary of Nutritional Tips for PUD Patients ..................... 1179
Table 56.16 Causes of Gastroparesis............................................................ 1180
Table 56.17 Factors That Affect the Rate of Gastric Emptying ................. 1180
Table 56.18 Summary of Tips for the Gastroparesis Patient ..................... 1181
Table 56.19 Types of Dumping Syndrome .................................................. 1181
Table 56.20 Summary of Nutritional Tips in Dumping Syndrome ........... 1181
Figure 56.1 Digestion of macronutrients..................................................... 1166
57 Nutrition and the Hollow Organs of the Lower Gastrointestinal

Tract.................................................................................................................. 1185
Celiac Sprue (CS)............................................................................................. 1185
Inflammatory Bowel Disease (IBD)................................................................ 1192
Short Bowel Syndrome (SBS) ......................................................................... 1201

Acute Infectious Diarrhea............................................................................... 1207
Functional Disorders of the Gastrointestinal Tract (FGIDs) ........................ 1208
Diverticular Disease of the Colon.................................................................. 1212
References ........................................................................................................ 1214
Table 57.1 Histological Features of Celiac Sprue (CS) ............................. 1186
Table 57.2 Clinical Manifestations/Presentations of Celiac Sprue ......... 1186
Table 57.3 Patient Populations at Risk for CS .......................................... 1186
Table 57.4 Pathogenic Factors in Celiac Sprue ......................................... 1188
Table 57.5 Principles of the Gluten-Free Diet (GFD) ............................... 1189
Table 57.6 Manifestations of CS Responsive to GFD ............................... 1190
Table 57.7 Nutritional Tips for CS Patients .............................................. 1192
Table 57.8 Differences Between Ulcerative Colitis (UC) and Crohn’s
Disease (CD).......................................................................... 1192
Table 57.9 Factors Important in the Pathogenesis of IBD ....................... 1193
Table 57.10 Causes of Malnutrition in IBD Patients .................................. 1193
Table 57.11 Micronutrient Deficiencies in IBD ........................................... 1194
Table 57.12 Nutritional Tips for IBD Patients ............................................ 1201
Table 57.13 Factors That Affect the Type of Nutrition Required by SBS
Patients .................................................................................. 1202
Table 57.14 Phases of SBS with Their Characteristics................................ 1202
Table 57.15 Dosages for Antidiarrheals in SBS........................................... 1204
Table 57.16 Selected Complications of TPN in SBS and Their
Prevention/Treatment .......................................................... 1205
Table 57.17 Factors Important in Pathogenesis of FGIDs.......................... 1209
Table 57.18 Summary of Nutritional Tips for the IBS Patient .................. 1213
Figure 57.1 Taxonomy of grains .................................................................. 1187
Figure 57.2 Anatomic types of short bowel syndrome .............................. 1203
58 Nutrient Metabolism and Support in the Normal and Diseased

Liver ................................................................................................................. 1219
Mark T. DeMeo
Introduction ..................................................................................................... 1219
Role of the Liver in Normal Nutrient Metabolism ...................................... 1219
Impact of Liver Disease on Nutrient Metabolism ........................................ 1223
Nutritional Evaluation in Liver Disease ....................................................... 1226
Nutritional Intervention in Liver Disease ..................................................... 1229
Conclusion ....................................................................................................... 1236
References ........................................................................................................ 1237
Figure 58.1 Hormonal regulation of glucose homeostasis in the
liver ........................................................................................ 1220
Figure 58.2 Fatty acid synthesis .................................................................. 1221
Figure 58.3 Fatty acid transport .................................................................. 1222
Figure 58.4 Ammonia (NH 3) metabolism.................................................... 1224
Figure 58.5 S-adenosyl methionine (SAMe) synthase ................................ 1235
59 Nutrition and the Pancreas: Physiology and Interventional

Strategies ......................................................................................................... 1239
Mark.T. DeMeo
Introduction ..................................................................................................... 1239
Normal Pancreatic Function ........................................................................... 1239

Nutritional Implications and Ramifications in Pancreatic Disease ............. 1242
Nutritional Intervention in Pancreatic Disease ............................................ 1244
The Role of Antioxidants in Pancreatic Disease ........................................... 1252
References ........................................................................................................ 1253
Table 59.1 Digestive Enzymes Secreted by the Pancreas......................... 1240
Table 59.2 Pancreatic Replacement Enzymes and Strengths of Major
Constituents .......................................................................... 1250
Figure 59.1 Mechanism of monosaccharide absorption............................. 1240
Figure 59.2 Phospholipase A 2 action ........................................................... 1242
Figure 59.3 Ranson criteria and APACHE II severity of pancreatitis ...... 1245
60 Renal Nutrition............................................................................................... 1255

Jane M. Greene and Lynn Thomas
Introduction ..................................................................................................... 1255
Nutritional Assessment in the Renal Patient ................................................ 1255
Stages of Renal Failure ................................................................................... 1256
Peritoneal Dialysis: Daily Nutrient and Fluid Needs .................................. 1261
Hemodialysis: Daily Nutrient and Fluid Needs........................................... 1261
Special Nutrition Focus .................................................................................. 1263
Medications...................................................................................................... 1264
Enteral Nutrition Supplements for the Renal Patient .................................. 1267
Practical Application of the Diet ................................................................... 1268
Summary .......................................................................................................... 1271
References ........................................................................................................ 1271
Table 60.1 Explanation of Terms Used in this Section ............................. 1256
Table 60.2 Components of the Nutrition Assessment .............................. 1257
Table 60.3 Interpretation of Laboratory Results for Hemodialysis and
Peritoneal Dialysis Patients ................................................. 1257
Table 60.4 Daily Nutrient and Fluid Needs for Pediatric Patients with
Acute Renal Failure .............................................................. 1258
Table 60.5 Daily Nutrient and Fluid Needs for Adults with Acute Renal
Failure .................................................................................... 1259
Table 60.6 Daily Nutrient and Fluid Needs for Pediatric Patients with
Chronic Renal Failure........................................................... 1259
Table 60.7 Daily Nutrient and Fluid Needs for Adults with Chronic
Renal Failure ......................................................................... 1260
Table 60.8 Daily Nutrient and Fluid Needs for Pediatric Patients Post
Kidney Transplant ................................................................ 1260
Table 60.9 Daily Nutrient and Fluid Needs for Adults Post Kidney
Transplant .............................................................................. 1260
Table 60.10 Daily Nutrient and Fluid Needs for Pediatric Patients
Undergoing Peritoneal Dialysis........................................... 1261
Table 60.11 Daily Nutrient and Fluid Needs for Adults Undergoing
Peritoneal Dialysis ................................................................ 1262
Table 60.12 Daily Nutrient and Fluid Needs for Pediatric Patients
Undergoing Hemodialysis ................................................... 1262
Table 60.13 Daily Nutrient and Fluid Needs for Adults Undergoing
Hemodialysis......................................................................... 1263
Table 60.14 Pregnant Hemodialysis Patients .............................................. 1264

Table 60.15 Special Nutrition Focus: Adult Patients with Diabetes
Mellitus .................................................................................. 1264
Table 60.16 Special Nutrition Focus: Dialysis Patients with AIDS
Nephropathy ......................................................................... 1265
Table 60.17 List of Products to Provide Suitable Souce of Calcium for
Patients with Renal Disease ................................................. 1265
Table 60.18 Phosphate Binders (Non-Calcium Based) ............................... 1266
Table 60.19 Vitamin and Mineral Supplementation ................................... 1266
Table 60.20 Iron Supplements ...................................................................... 1267
Table 60.21A Enteral Nutrition Supplements for Renal Patients ................ 1268
Table 60.21B Enteral Nutrition Supplements for Renal Patients ................ 1268
Table 60.22 Some Foods Very High in Potassium ...................................... 1269
Table 60.23 Some Foods Very High in Phosphorus ................................... 1269
Table 60.24 Sample Menus ........................................................................... 1270
Table 60.25 Emergency Shopping List for the Dialysis Patient ................ 1271
61 Disorders of the Skeleton and Kidney Stones ........................................... 1275

Stanley Wallach
Introduction ..................................................................................................... 1275
Metabolic Bone Diseases................................................................................. 1275
Calcium and Vitamin D .................................................................................. 1277
Other Macronutrients...................................................................................... 1280
Micronutrients ................................................................................................. 1282
Nutritional Recommendations in Metabolic Bone Diseases ........................ 1283
Renal Stone Disease ........................................................................................ 1286
Table 61.1 Skeletal Composition ................................................................ 1276
Table 61.2 Metabolic Bone Diseases .......................................................... 1276
Table 61.3 Examples of Genetic Mutations Causing Metabolic Bone
Diseases ................................................................................. 1276
Table 61.4 Hormone, Growth Factor, and Cytokine Effects on Bone ..... 1277
Table 61.5 Risk Factors for Bone Loss ....................................................... 1278
Table 61.6 Vitamin D Deficits in Older Patients....................................... 1279
Table 61.7 Revised Recommended Daily Calcium and Vitamin D
Intakes.................................................................................... 1279
Table 61.8 Calcium-Rich Foods .................................................................. 1280
Table 61.9 Essentials of Adjusting Calcium and Vitamin D Intakes ...... 1280
Table 61.10 Comparison of Carbonate and Citrate-Based Calcium
Supplements .......................................................................... 1281
Table 61.11 Magnesium Effects on the Skeleton ........................................ 1281
Table 61.12 Magnesium Rich Foods ............................................................ 1281
Table 61.13 Lipid Effects on the Skeleton ................................................... 1282
Table 61.14 Nutrient, Vitamin, and Trace Element Effects on the
Skeleton ................................................................................. 1283
Table 61.15 Nonpharmacologic Approaches to the Prevention and
Treatment of Osteoporosis ................................................... 1284
Table 61.16 Treatment of Osteomalacia ....................................................... 1285
Table 61.17 Treatment Options for Renal Osteodystrophy........................ 1285
Table 61.18 Additional Sources of Information .......................................... 1287
Figure 61.1 Conversion cascade for the synthesis of the active metabolite
of vitamin D, 1,25-dihydroxy-cholecalciferol (DHCC) from
cholesterol.............................................................................. 1278
62 Nutrients and Eye Disease ............................................................................ 1291

Allen M. Perelson and Leon Ellenbogen
Introduction ..................................................................................................... 1291
Antioxidant Nutrients and Cataract Prevention........................................... 1291
Carotenoids and Acute Macular Degeneration............................................. 1294
Ongoing Trials ................................................................................................. 1294
References ........................................................................................................ 1295
Table 62.1 Vitamin E Intake or Plasma Concentration with Reduced
Cataract Risk ......................................................................... 1292
Table 62.2 Vitamin C Intake or Plasma Concentration with Reduced
Cataract Risk ......................................................................... 1293
Table 62.3 Antioxidant Levels and Intakes and Risk of Age-Related
Macular Degeneration (AMD) ............................................. 1294
Table 62.4 Ongoing Trials Investigating Antioxidant Vitamins and
Their Effect on Age-Related Cataract and AMD................ 1295
Figure 62.1 Anatomy of the eye .................................................................. 1292
63 Protein-Energy Malnutrition ......................................................................... 1297

Naomi K. Fukagawa
Introduction ..................................................................................................... 1297
Etiology and Epidemiology ............................................................................ 1299
Diagnosis.......................................................................................................... 1300
Management .................................................................................................... 1303
Monitoring ....................................................................................................... 1308
Impact on Prognosis, Morbidity, and Mortality for Other Illnesses,
Especially in the Elderly ............................................................................ 1309
References ........................................................................................................ 1311
Table 63.1 Classification of Protein-Energy Malnutrition (PEM) ............ 1298
Table 63.2 Causes of PEM .......................................................................... 1299
Table 63.3 Characteristics of Patients at High Risk for Developing
PEM........................................................................................ 1300
Table 63.4 Physical Findings Associated with PEM................................. 1301
Table 63.5 Adaptive Responses to Protein-Enery Starvation .................. 1302
Table 63.6 Approach to Treatment of Mild and Moderate PEM ............. 1303
Table 63.7 Life-Threatening Conditions Associated with Severe PEM... 1304
Table 63.8 General Approaches to Therapy .............................................. 1304
Table 63.9 Mineral Mix for Oral Dehydration Salt Solution and to
Complement Liquid Foods .................................................. 1305
Table 63.10 Approach to Oral Rehydration for Severe PEM..................... 1305
Table 63.11 Suggested Intravenous Rehydration Regimen ....................... 1306
Table 63.12 Dietary Treatment of Adolescents and Adults with Severe
PEM........................................................................................ 1308
Table 63.13 Characteristics Associated with Poor Prognosis in Patients
with PEM ............................................................................... 1308
Table 63.14 Guidelines for Creatinine-Height Index and Nitrogen

Balance ................................................................................... 1309
Table 63.15 Factors Contributing to PEM in End-Stage Liver
Disease ................................................................................... 1310
Table 63.16 SCALES: Rapid Screen for Risk of PEM ................................. 1310
Table 63.17 “Meals on Wheels” Mnemonic for the Causes of Weight
Loss ........................................................................................ 1311
Table 63.18 Checklist of Procedures to Prevent and Treat PEM ............... 1311
Figure 63.1 1. Kwashiorkor in a child; 2. Marasmic infant ....................... 1298
Figure 63.2 Examples of some of the physical findings associated
with PEM ............................................................................... 1302
64 Vitamin Deficiencies ...................................................................................... 1313

Richard S. Rivlin
General Comments on Vitamin Deficiencies................................................. 1313
Vitamin A ......................................................................................................... 1315
Vitamin D ......................................................................................................... 1317
Vitamin E ......................................................................................................... 1317
Vitamin K ......................................................................................................... 1319
Thiamin (Vitamin B 1) ...................................................................................... 1321
Riboflavin (Vitamin B 2) ................................................................................... 1322
Niacin ............................................................................................................... 1324
Pyridoxine (Vitamin B 6) .................................................................................. 1327
Folic Acid and Vitamin B 12 ............................................................................. 1328
Vitamin C (Ascorbic Acid).............................................................................. 1329
Sources of Additional Information ................................................................ 1331
Table 64.1 Features of Vitamin Deficiencies ............................................. 1314
Table 64.2 Some Considerations in Correction of Vitamin
Deficiencies............................................................................ 1314
Figure 64.1 Patient with severe vitamin K deficiency ............................... 1320
Figure 64.2 Patient with classical riboflavin (vitamin B2) deficiency ....... 1323
Figure 64.3 Patient with advanced pellagra resulting from niacin
deficiency ............................................................................... 1325
Figure 64.4 Hands of a patient with advanced pellagra ........................... 1326
Figure 64.5 Leg of an adult patient with severe scurvy............................ 1330
Figure 64.6 Mouth and teeth of a patient with far-advanced scurvy ...... 1330
65 Rationale for Use of Vitamin and Mineral Supplements ......................... 1333

Allen M. Perelson and Leon Ellenbogen
Introduction ..................................................................................................... 1333
Vitamin A ......................................................................................................... 1333
Beta-Carotene................................................................................................... 1334
Riboflavin ......................................................................................................... 1337
Niacin ............................................................................................................... 1337
Vitamin B 6 ........................................................................................................ 1338
Vitamin B 12 ....................................................................................................... 1339
Folic Acid ......................................................................................................... 1340
Vitamin C ......................................................................................................... 1342
Vitamin D ......................................................................................................... 1344

Vitamin E ......................................................................................................... 1346
Vitamin K ......................................................................................................... 1349
Calcium ............................................................................................................ 1350
Magnesium....................................................................................................... 1351
Zinc................................................................................................................... 1352
Selenium........................................................................................................... 1353
Chromium ........................................................................................................ 1354
References ........................................................................................................ 1355
Table 65.1 Vitamin A — Established Benefits ........................................... 1334
Table 65.2 Vitamin A — Emerging Benefits .............................................. 1334
Table 65.3 Beta-Carotene — Established Benefits..................................... 1335
Table 65.4 Important Beta-Carotene Cancer Trials ................................... 1335
Table 65.5 Beta-Carotene — Emerging Benefits........................................ 1336
Table 65.6 Important Beta-Carotene Cardiovascular Trials ..................... 1336
Table 65.7 Riboflavin — Established Benefits ........................................... 1337
Table 65.8 Riboflavin — Emerging Benefits .............................................. 1337
Table 65.9 Niacin — Established Benefits ................................................. 1338
Table 65.10 Niacin — Emerging Benefits .................................................... 1338
Table 65.11 Vitamin B 6 — Established Benefits .......................................... 1339
Table 65.12 Vitamin B 6 — Emerging Benefits ............................................. 1339
Table 65.13 Vitamin B 12 — Established Benefits ......................................... 1340
Table 65.14 Vitamin B 12 — Emerging Benefits ............................................ 1340
Table 65.15 Folic Acid — Established Benefits ........................................... 1342
Table 65.16 Folic Acid — Emerging Benefits .............................................. 1342
Table 65.17 Vitamin C — Established Benefits ........................................... 1343
Table 65.18 Vitamin C Intake Associated with Reduced Cardiovascular
Disease Risk .......................................................................... 1343
Table 65.19 Vitamin C Intake Associated with Reduced Cancer Risk...... 1345
Table 65.20 Vitamin D — Established Benefits ........................................... 1346
Table 65.21 Vitamin D — Emerging Benefits .............................................. 1346
Table 65.22 Vitamin E — Established Benefits ........................................... 1346
Table 65.23 Vitamin E and Coronary Heart Disease — Epidemiological1
Trials ...................................................................................... 1347
Table 65.24 Vitamin E Levels and Cancer Incidence ................................. 1348
Table 65.25 Vitamin K — Established Benefits ........................................... 1350
Table 65.26 Vitamin K — Emerging Benefits .............................................. 1350
Table 65.27 Calcium — Established Benefits .............................................. 1351
Table 65.28 Calcium — Emerging Benefits ................................................. 1351
Table 65.29 Magnesium — Established Benefits......................................... 1352
Table 65.30 Magnesium — Emerging Benefits............................................ 1352
Table 65.31 Zinc — Established Benefits..................................................... 1353
Table 65.32 Zinc — Emerging Benefits........................................................ 1353
Table 65.33 Selenium — Established and Emerging Benefits.................... 1354
Table 65.34 Chromium — Established and Emerging Benefits ................. 1355
66 Nutrition in Critical Illness .......................................................................... 1363

Introduction ..................................................................................................... 1363
Metabolic Response to Stress ......................................................................... 1363
Nutritional Intervention in Critical Illness ................................................... 1365

Route of Nutrient Delivery ............................................................................ 1370
Nutrition Support in Trauma and Burns....................................................... 1373
Estimating Nutrient Requirements ................................................................ 1374
References ........................................................................................................ 1378
Table 66.1 Metabolic Comparisons between Starvation and Stress ........ 1364
Table 66.2 Stress Phase Alterations ........................................................... 1364
Table 66.3 Selected Methods for Estimating Energy Requirements........ 1367
Table 66.4 Energy and Substrate Recommendations................................ 1367
Table 66.5 Electrolyte Recommendations for Critically Ill Patients........ 1369
Table 66.6 Recommended Vitamin and Mineral Supplementation in the
Critically Ill ........................................................................... 1370
Table 66.7 Indications for Parenteral Nutrition........................................ 1371
Table 66.8 Enteral vs. Parenteral Nutrition .............................................. 1371
Table 66.9 Factors Known to Affect Metabolic Rate in Burn Patients.... 1373
Table 66.10 Select Nutrients and Their Immune Effect During Critical
Illness ..................................................................................... 1374
Table 66.11 Benefits of Human Glutamine Supplementation.................... 1375
Table 66.12 Nutrient Recommendations for Burn Patients ....................... 1378
Figure 66.1 Metabolism of dietary long-chain fatty acids......................... 1377
67 Nutritional Therapies for Neurological and Psychiatric Disorders......... 1381

G. Franklin Carl
Epilepsies ......................................................................................................... 1381
Neurodegenerative Diseases .......................................................................... 1387
Neurodevelomental Diseases ......................................................................... 1394
Metabolic Diseases .......................................................................................... 1396
Inborn Errors (Genetic Diseases) ................................................................... 1398
References ........................................................................................................ 1403
Table 67.1 Classification of the Major Neurological and Psychiatric
Disorders and the Potential Response of Each to
Nutritional Therapy.............................................................. 1382
Table 67.2 Known Interactions between Antiepileptic Drugs and
Nutrients................................................................................ 1385
Table 67.3 Sample Menus for the Ketogenic Diet on a 3-Day Rotating
Meal Plan............................................................................... 1386
Table 67.4 Ketogenic Food Exchanges for Vegetables.............................. 1387
Table 67.5 Ketogenic Food Exchanges for Meats/Meat Substitutes ....... 1388
Table 67.6 Ketogenic Food Exchanges for Fruits...................................... 1388
Table 67.7 Ketogenic Food Exchanges for Starches.................................. 1389
Table 67.8 Ketogenic Food Exchanges for Dairy Products ...................... 1390
Table 67.9 Protein Content in Common Foods ......................................... 1391
68 Eating Disorders (Anorexia Nervosa, Bulimia Nervosa, Binge Eating

Disorder).......................................................................................................... 1407
Diane K. Smith and Christian R. Lemmon
Introduction ..................................................................................................... 1407
Diagnostic Criteria .......................................................................................... 1407
Epidemiology................................................................................................... 1410
Etiology ............................................................................................................ 1411

Comorbid Psychiatric Conditions .................................................................. 1413
Other Identified Problems in Patients with Eating Disorders..................... 1414
Bio-Psychosocial Assessment ......................................................................... 1414
Treatment ......................................................................................................... 1418
Prognosis .......................................................................................................... 1425
Additional Sources of Information ................................................................ 1425
References ........................................................................................................ 1425
Table 68.1 Diagnostic and Statistical Manual Version IV (DSM-IV) Criteria
for Anorexia Nervosa, including Subtypes ........................ 1408
Table 68.2 DSM-IV Criteria for Bulimia Nervosa, including
Subtypes ................................................................................ 1409
Table 68.3 DSM-IV Proposed Criteria for Binge-Eating Disorder........... 1409
Table 68.4 Medical Conditions and Weight Loss Methods...................... 1411
Table 68.5 Etiological Theories of the Eating Disorders .......................... 1411
Table 68.6 Common Comorbid Psychiatric Conditions Found in
Patients with Eating Disorders ............................................ 1414
Table 68.7 Other Identified Problems Commonly Found among Patients
with Eating Disorders .......................................................... 1414
Table 68.8 Bio-Psychosocial Assessment of the Eating Disorders........... 1415
Table 68.9 Comprehensive Nutritional Assessment ................................. 1417
Table 68.10 Comprehensive Clinical Interview of Patient with an
Eating Disorder ..................................................................... 1417
Table 68.11 Assessment of the Family of Eating Disorder Patients ......... 1419
Table 68.12 Determining the Most Appropriate Eating Disorder
Treatment Setting .................................................................. 1419
69 Adult Obesity ................................................................................................. 1429

Diane K. Smith and Sandra B. Leonard
Introduction ..................................................................................................... 1429
Etiology ............................................................................................................ 1429
Energy Balance ................................................................................................ 1431
Prevalence of Obesity ..................................................................................... 1434
Assessment....................................................................................................... 1435
Medical Risks of Obesity (Comorbidities) .................................................... 1436
Treatment ......................................................................................................... 1436
Outcomes ......................................................................................................... 1446
References ........................................................................................................ 1447
Table 69.1 Etiology of Obesity ................................................................... 1430
Table 69.2 Monogenetic Human Obesity .................................................. 1430
Table 69.3 Obesity-Related Factors Thought to be Genetically
Modulated ............................................................................. 1431
Table 69.4 Drugs That May Promote Weight Gain................................... 1432
Table 69.5 Neuromodulators of Appetite Regulation .............................. 1433
Table 69.6 Classification for Body Mass Index (BMI) .............................. 1435
Table 69.7 Metabolic Consequences of Upper Body Obesity .................. 1436
Table 69.8 Effects of Hyperinsulinemia..................................................... 1437
Table 69.9 National Institutes of Health (NIH) Guidelines for Choosing a
Weight-Loss Program ........................................................... 1438
Table 69.10 Food Group Exchanges for Various Caloric Levels ............... 1439
Table 69.11 Sample Meal Plan for 1500 Calories........................................ 1440
Table 69.12 Educational Topics for Weight Loss Counseling .................... 1440
Table 69.13 Sample Meal Plan for Low-Fat, High-Fiber Diet ................... 1441
Table 69.14 Contraindications to Very Low Calorie Diets (VLCDs) ......... 1442
Table 69.15 VLCD Sample Meal Plan .......................................................... 1443
Table 69.16 Proposed Mechanisms Linking Exercise with Successful
Weight Maintenance ............................................................. 1444
Table 69.17 Behavior Modification Techniques .......................................... 1445
Table 69.18 Weight Loss Agents .................................................................. 1446
Table 69.19 Predictors of Weight Loss ........................................................ 1446
Table 69.20 Predictors of Maintenance of Weight Loss ............................. 1447
70 Childhood Obesity and Exercise .................................................................. 1449

Scott Owens, Bernard Gutin, and Paule Barbeau
Introduction ..................................................................................................... 1449
Age, Gender, Ethnicity, and Socioeconomic Status ...................................... 1449
Health Risks of Childhood Obesity ............................................................... 1455
Etiology of Childhood Obesity ...................................................................... 1456
Treatment of Childhood Obesity.................................................................... 1457
References ........................................................................................................ 1461
Table 70.1 Unadjusted Prevalence of Overweight for National Health and
Nutrition Examination Survey III (NHANES III) .............. 1450
Table 70.2 Age-Adjusted Prevalence of Overweight from National
Surveys .................................................................................. 1451
Table 70.3 Anthropometric Definitions of Childhood
Overweight/Obesity ............................................................. 1452
Table 70.4 Hormonal and Genetic Causes of Childhood Obesity........... 1452
Table 70.5 Differential Diagnosis of Childhood Obesity ......................... 1452
Table 70.6 Smoothed 85th and 95th Percentiles of Body Mass Index
from NHANES I Male Subjects 6 to 18 Years .................... 1453
Table 70.7 Smoothed 85th and 95th Percentiles of Body Mass Index
from NHANES I Female Subjects 6 to 18 Years ................. 1454
Table 70.8 Regression Coefficients (β) and P Values from Linear Models
for Body Mass Index (BMI) (NHANES III) ........................ 1455
Table 70.9 Visceral Adipose Tissue in White and African-American
Youth ...................................................................................... 1455
Table 70.10 Health-Related Risk Factors Associated with Childhood
Obesity ................................................................................... 1456
Table 70.11 Visceral Adiposity and Increased Health Risk in Childhood
Obesity ................................................................................... 1456
Table 70.12 Mean Energy Intake by Age, 1976-1980 and 1988-1991 ......... 1457
Table 70.13 Selected Family-Based Interventions for Childhood
Obesity ................................................................................... 1458
Table 70.14 Two Studies of After-School Exercise (without Dietary
Intervention) in the Treatment of Childhood Obesity ....... 1459
Table 70.15 Behavior Modification Components for Treatment of
Childhood Obesity................................................................ 1460
Table 70.16 Selected Resources on Childhood Obesity.............................. 1461
71 Trace Mineral Deficiencies ............................................................................ 1463

Forrest H. Nielsen
Introduction ..................................................................................................... 1463
Biological Roles of Mineral Elements ............................................................ 1463
Homeostatic Regulation of Mineral Elements .............................................. 1464
Factors Affecting the Manifestation of Deficiency Signs ............................. 1464
Treatment of Trace Mineral Deficiencies ....................................................... 1465
Mineral Elements Essential for Humans ....................................................... 1465
Possibly Essential Ultra Trace Elements........................................................ 1478
Other Elements with Beneficial or Biological Actions ................................. 1480
Summary .......................................................................................................... 1483
References ........................................................................................................ 1485
Table 71.1 Biochemical, Clinical, and Nutritional Aspects of
Boron...................................................................................... 1466
Copper ................................................................................... 1468
Iron......................................................................................... 1469
Magnesium ............................................................................ 1470
Manganese ............................................................................. 1471
Table 71.6 Biochemical, Clinical, and Nutritional Aspects of Zinc ........ 1472
Chromium.............................................................................. 1474
Cobalt..................................................................................... 1475
Table 71.9 Biochemical, Clinical and Nutritional Aspects of
Iodine ..................................................................................... 1476
Molybdenum ......................................................................... 1477
Selenium ................................................................................ 1478
Table 71.12 Arsenic ....................................................................................... 1479
Table 71.13 Nickel ......................................................................................... 1481
Table 71.14 Silicon......................................................................................... 1482
Table 71.15 Vanadium................................................................................... 1483
Table 71.16 Reported Deficiency Signs in Experimental Animals and
Usual Dietary Intakes of Elements with Beneficial or
Biological Actions ................................................................. 1484
72 Questionable Practices in Foods and Nutrition: Definitions and

Descriptions .................................................................................................... 1489
Stephen Barrett and Victor Herbert
Pertinent Definitions ....................................................................................... 1489
Treatment Systems........................................................................................... 1491
Fad Diagnoses.................................................................................................. 1497
Dubious Tests .................................................................................................. 1499
Herbal Treatment............................................................................................. 1501
Other Questionable Methods ......................................................................... 1502

Consumer Protection Laws............................................................................. 1506
References ........................................................................................................ 1507
Table 72.1 Signs of Quackery ..................................................................... 1505
Table 72.2 More Ploys That Can Fool You ................................................ 1506
Table 72.3 Recipe for a New Fad Disease ................................................. 1507
Index ................................................................................................................ 1509

2705_frame_C01 Page 1 Wednesday, September 19, 2001 1:06 PM
Part I
Food
1
Food Constituents
Animals, including man, consume food to obtain the nutrients they need. Throughout the
world there are differences in food consumption related to socioeconomic conditions, food
availability, and cultural dictates. If a variety of fresh and cooked foods is consumed in
sufficient quantities to meet the energy needs of the consumer, then the needs for protein
and the micronutrients should be met. Having this in mind, it is surprising to learn that
some people are poorly nourished, and indeed may develop one or more nutrition-related
diseases. The early years of nutrition research focused on diseases related to inadequate
vitamin and mineral intake. An important component of this research was the determi-
nation of the vitamin and mineral content of a vast variety of foods. The composition of
these foods has been compiled by the USDA, and Table 1.1 provides web addresses to
access these data sets. Several data sets that may not be available on the web can be found
in this section. Table 1.2 provides the sugar content of selected foods in 100 g portions.
This may be a very large serving size or a very small one, depending on the food in
question. However, using a standard portion allows one to compare the sugar content of
a variety of foods. Those that are very rich sources, i.e., honey or table sugar (sucrose), of
course will have a very high value, yet one would not consume this much in a single food
under most circumstances. Usually, one would select a portion size compatible with the
need for sweetness in the particular food product. For example, one might add a teaspoon
of table sugar to a cup of coffee. That teaspoon of sugar might weigh 8 grams.Table 1.3
provides information on the tagatose content of food. Tagatose is a new food additive
used to reduce the amount of sugar in a food. It has a sweet taste, yet does not have the
same energy value as sucrose. Other sugar substitutes are also used in the preparation of
reduced-energy foods; however, data on their quantitative occurrence is not as readily
available because of the proprietary interests of food producers. A list of sweeteners added
to foods is provided in Table 1.5. Following this table is a list of the types of food additives
that change the properties of food (Table 1.6). This table describes compounds that increase
the shelf life of a class of foods, or additives that change the texture of a food. The specific
attributes of individual food additives are described in Table 1.7. This table provides
information on how these additives function in particular food products. Table 1.8 is a list
of mycotoxins and bacterial toxins that can occur in food. The reader should also review
Section 52 for an extensive description of foodborne illness. Table 1.9 provides a list of
antinutrients sometimes found in food, and Table 1.10 is a list of toxic substances that can
be present in food. Some of these toxic substances are added inadvertently by the food
processing methods, but some occur naturally. If consumed in minute quantities, some of
these toxic materials are without significant effect, yet other compounds (e.g., arsenic),
even in minute amounts, could accumulate and become lethal.
0-8493-2705-9/01/$0.00+$1.50
© 2002 by CRC Press LLC 3
4 Handbook of Nutrition and Food
Tables 1.11, 1.12, and 1.14 overlap to some extent. All contain information about plants.
Some of these plants can have both a food and a non-food use. Non-food use is defined
as a use that may have a real or imagined pharmacologic (drug/herbal) effect. The reader
should use this information with considerable caution. Plants can differ from variety to
variety, and indeed from one growing condition to another in the content of certain of
their herbal or nutritive ingredients. Over-the-counter herbal preparations can also vary.
There is little regulation of these preparations and few safeguards exist to protect the
consumer with respect to biopotency. Furthermore, the consumer should be aware of the
fact that some of these herbal remedies may interact with prescribed drugs, either nulli-
fying the drug effect or, worse, interacting to cause an unwarranted or even lethal effect.
Consumers of plants used for herbal remedies should consult their pharmacists and
physicians about these potentially dangerous uses.
The next six tables provide information about the micronutrients. Table 1.14 gives
vitamin terminology. Table 1.15 is a list of compounds that have vitamin A activity. Table
1.16 gives the structures and characteristics of the vitamins. The use of vitamin supple-
ments as well as descriptions of vitamin deficiency is covered in Sections 43, 61, and 62.
Table 1.17 summarizes vitamin deficiencies and needs. Table 1.18 summarizes the essential
minerals and their functions. A more detailed description of the minerals is provided in
Section 57. Table 1.19 lists the essential fatty acids, and Table 1.20 gives the common and
technical names for fatty acids. It should be noted that felines require arachidonic acid as
well as linoleic and linolenic acid in their diets. Other mammals only require linoleic and
linolenic acids.
Food Constituents 5
TABLE 1.1
Web Addresses for Information on the Composition of Food
Data Set Web Address
Composition of foods, raw, processed, prepared; 6200 http://www.nal.usda.gov/fnic/foodcomp/Data/
foods, 82 nutrients
Daidzein, genisten, glycitein, isoflavone content of 128 Use above address, click on this file to open
foods
Carotenoid content of 215 foods Use above address, click on this file to open
Trans fatty acid content of 214 foods Use above address, click on this file to open
Sugar content of 500+ foods Use above address, click on this file to open
Nutritive value of food in common household units; Use above address, click on Nutritive Value of Foods
more than 900 items are in this list (HG-72) to open
Vitamin K Use above address, click on vitamin K to open
List of key foods (foods that contribute up to 75% of Use above address, click on Key Foods to open
any one nutrient)
Nutrient retention factors: calculations of retention of Use above address, click on Nutrient Retention
specific micronutrients Factors, Release 4 (1998)
Primary nutrient datasets (results of USDA surveys) Use above address, click on Primary Nutrient for
USDA Nationwide Food Surveys Dataset
Selenium and vitamin D (provisional values) Use above address, click on selenium and vitamin D
to open
Food composition (foods from India) www.unu.edu/unupress/unupbooks/80633e/
80633Eoi.htm
European foods Cost99/EUROFOODS:Inventory of European Food
Composition food.ethz.ch/cost99db-inventory.htm
Foods in developing countries www.fao.org/DOCREP/W0073e/woo73eO6.htm
Other food data www.arborcom.com/frame/foodc.htm
Soy foods (beneficial compounds) See above, isoflavone, etc.
Individual amino acids and fatty acids http://www.infinite faculty.org/sci/cr/crs/1994
Note: Most of these databases can be accessed as subdirectories of:
http://www.Nal.USDA.gov/foodcomp/data/. A printed format can be obtained from the Superinten-
dent of Documents, U.S. Printing Office, Washington D.C. 20402. Request USDA Handbooks 8 through
16. A CD-ROM can also be obtained. None of these are free.
TABLE 1.2
Sugar Content of Selected Foods, 100 Grams, Edible Portion1
Moisture Monosaccharides (in grams) Disaccharides (in grams) Other Total
Food Item (%) Galactose Glucose Fructose Lactose Sucrose Maltose Sugars Sugars
Dairy Products
Cheese
Brie 47.7 — 1.0 0.3 0.2 0.1 TR — 1.6
Edam 41.1 — 0.1 — — 0.1 — — 0.2
Mozzarella 47.0 — 1.1 — TR — — — 1.1
Ice cream
Chocolate 53.7 — — — 3.7 14.9 TR — 18.6
Strawberry 56.9 — 1.5 0.8 4.1 8.5 TR — 14.9
Vanilla 60.5 — — — 5.1 8.9 TR — 14.0
Ice milk, vanilla 59.3 — 1.6 0.8 5.8 6.5 TR — 14.7
Yogurt
Plain 86.0 — 0.3 — 3.0 — — — 3.3
Strawberry 72.5 — 2.3 2.1 3.2 7.3 — — 14.9
TABLE 1.2 (Continued)

Grains and Baked Products
Bread
Banana 32.9 — TR 0.1 — 25.8 — — 25.9
Hamburger 34.7 — 1.7 1.3 0.2 — 0.2 — 3.4
buns
Pita 20.5 — 0.1 0.2 — — 1.0 — 1.3
Pumpernickel 37.1 — 0.6 0.1 — — 1.0 — 1.7
Raisin 31.5 — 7.3 6.6 — TR TR — 13.9
Rye 36.5 — 0.6 0.4 — 0.6 — — 1.6
White 36.3 — 1.8 1.2 — 0.4 0.2 — 3.6
Whole wheat 39.3 — 0.7 0.6 — — 0.6 — 1.9
Cake
Angel food 34.8 — — — — 33.7 — — 33.7
Sponge 21.1 — TR — — 23.6 — — 23.6
Yellow 33.9 — TR — — 25.8 — — 25.8
Cheesecake, 38.2 — TR — 0.1 7.0 — — 7.1
plain
Chocolate chip 3.7 — TR TR — 18.7 — — 18.7
cookies
Corn flakes 1.7 — 2.2 2.1 — 2.9 — — 7.2
Crude wheat 9.6 — 0.9 TR — 6.9 — — 7.8
germ
Donuts
Cake type 20.8 — 0.9 0.1 TR 8.6 TR — 9.6
Yeast type 26.3 — 1.4 1.4 1.0 — 1.4 — 5.2
Flour
Rye 11.0 — 0.2 0.1 — 0.6 — — 0.9
White 10.5 — TR TR — 0.1 TR — 0.1
Whole wheat 9.3 — TR TR — 0.4 — — 0.4
Graham 5.6 — 1.9 1.2 — 12.6 — — 5.7
crackers
Pasta
Egg noodles, 8.8 — — — — 0.1 0.8 — 0.9
raw
Egg noodles, 67.0 — 0.1 — — TR 0.2 — 0.3
cooked
Spaghetti, 9.8 — TR — — 0.1 0.4 — 0.5
raw
Spaghetti, 62.7 — 0.1 — — — 0.2 — 0.3
cooked
Rice
Parboiled, 9.8 — TR — — 0.1 — — 0.1
raw
Parboiled, 72.8 — 0.1 TR — 0.1 — — 0.2
cooked
Tortillas
Flour 18.5 — — TR — 0.1 0.5 — 0.6
Corn 49.6 — — TR — 0.5 — — 0.5
Fruits and Fruit Juices
Apples
Delicious, 84.5 — 1.8 6.4 — 1.8 — — 10.0
golden
Food Constituents 7

Delicious, red 84.9 — 2.4 6.2 — 2.0 — — 10.6
Winesap 84.7 — 3.5 6.7 — 3.6 — — 13.8
Apricot nectar 84.6 — 6.3 4.6 — 2.0 — — 12.9
Cantaloupe 90.0 — 1.1 1.3 — 5.9 — — 8.3
Dried apricots 26.5 — 13.1 7.6 — 5.8 — — 26.5
Dried peaches 22.6 — 9.9 11.4 — 17.6 — — 38.9
Dried pears 33.1 — 8.9 23.0 — — — — 31.9
Dried prunes 3.8 — 19.5 10.6 — — — — 30.1
Grapes, 74.9 — 7.9 7.8 — 1.1 — — 16.8
Thompson,
seedless
Grapefruit, 87.7 — 2.0 1.9 — 2.5 — — 6.4
white,
seedless
Kiwi 83.1 — 3.5 3.9 — 0.9 — — 8.3
Orange juice, 87.7 — 2.4 2.6 — 2.8 — — 7.8
canned
Peaches 87.5 — 0.9 0.9 — — — — 1.8
Pears, Bartlett 83.6 — 4.4 6.7 — 0.9 — — 12.0
Persimmon 78.9 — 5.4 5.6 — 1.5 — — 12.5
Plums 89.1 — 3.1 2.6 — 2.7 — — 8.4
Strawberries
Fresh, raw 91.7 — 1.6 1.8 — 0.2 — — 3.6
Frozen with 71.2 — 5.8 5.1 — 16.3 — — 27.2
sugar added
Frozen 90.4 — 1.9 1.8 — — — — 3.7
without
sugar added
Tangelos 86.5 — 1.5 1.6 — 4.0 — — 7.1
Tangerines 82.3 — 2.2 2.6 — 6.7 — — 11.5
Watermelon 91.1 — 1.6 3.4 — 3.7 — — 8.7
Vegetable Products
Broccoli
Raw 90.9 — 0.4 0.4 — 0.1 — — 0.9
Cooked 90.7 — 0.4 0.3 — 0.1 — — 0.8
Cabbage
Raw 92.7 — 1.5 1.1 — TR TR — 2.6
Cooked 93.8 — 1.0 0.7 — 0.1 — — 1.8
Carrots
Raw 88.3 — 0.6 0.5 — 3.1 — — 4.2
Cooked 90.1 — 0.3 0.3 — 1.6 — — 2.2
Mushrooms, 93.2 — 2.6 TR — — — — 2.6
raw
Spinach
Raw 93.5 — 0.1 TR — TR — — 0.1
Cooked 93.2 — 0.1 TR — TR — — 0.1
Sprouts
Alfalfa, raw 92.3 — 0.1 0.1 — TR — — 0.2
Mung bean, 91.0 — 1.0 0.5 — 0.2 — — 1.7
raw
Sweet potatoes
Raw 73.4 — 0.9 0.7 — 3.5 — — 5.1
Cooked 82.1 — 0.7 0.8 — 2.4 2.6 — 6.5

Beverages
Beer
Light 97.9 — TR TR — — TR — TR
Regular 96.1 — TR — — — — — TR
Sherry
Dry 72.2 — 0.6 0.5 — TR TR — 1.1
Medium 71.7 — 1.6 1.3 — — — — 2.9
Sweet 70.8 — 0.9 5.2 — — — — 6.1
Wine
Port, dessert 69.0 — 4.3 5.1 — TR — — 9.4
Red, dry 85.1 — 0.4 0.3 — 0.1 — — 0.8
Rose, dry 84.2 — 1.4 1.4 — — — — 2.8
White, dry 86.5 — 0.6 0.6 — — 0.1 — 1.3
Vermouth, dry 72.8 — 0.6 0.5 — — — — 1.1
Sweets
Honey 7.8 — 38.7 45.2 — TR TR — 83.9

Maple syrup 32.7 — TR TR — 55.4 — — 55.4
Milk chocolate, 1.4 — — — 6.6 46.4 — — 53.0
plain
Molasses 17.4 — 15.7 14.8 — 24.5 — — 55.9
Molasses, 23.0 — — 9.8 — 42.5 — — 52.3
blackstrap
Nuts and Seeds
Coconut, dried, 10.6 — 0.4 0.2 — 3.9 — — 4.5

sweetened
Sesame seeds
Dehulled 4.1 — 0.1 — — 0.1 — — 0.2
Whole 5.4 — TR — — 0.3 — — 0.3
Sunflower nuts, 1.4 — 1.5 — — 1.5 — — 3.0
dried roasted
Legumes
Baked beans
In tomato 73.8 — 0.6 0.5 — 4.2 — 0.3 5.6
sauce
With pork 69.0 — 1.4 1.0 — 4.2 — 0.3 6.9
Black-eyed peas 75.9 — — 0.2 — 0.3 — — 0.5
Chickpeas 65.0 — — 0.2 — 0.2 — — 0.4
Note: Dash denotes lack of data for sugar that may be present; (0.0) denotes lack of data for sugar thought not
to be present; TR denotes trace.
1 See also http://www.nal.usda./goo/fnic/foodcomp/data/sugar.
TABLE 1.3
Tocopherols and Tocotrienols in Selected Food Products (mg/100 g)
α Tocopherol
Product α-T α-T3 β-T β-T3 γ-T γ-T3 δ-T δ-T3 Total Equivalents
Breakfast Cereals
Food Constituents
Fortified
Total 104.50 ND ND 104.50 104.50
King Vitamin 35.10 ND ND 35.10 35.10
Non-Fortified
Post Natural Raisin Bran 1.50 ND ND 1.50 1.50
Kellogg’s 1.30 ND ND 1.30 1.30
Cheese
American
Low fat Weight Watchers 1.50 ND ND 1.50 1.50

Borden Lite Line 0.10 ND ND 0.10 0.10
Processed
Kraft 0.40 ND ND 0.40 0.40
American processed
Kroger 0.40 ND ND 0.40 0.40
Cheddar
Kraft 0.30 ND ND 0.30 0.30
Kroger 0.20 ND ND 0.20 0.20
Munster
Sargento 0.50 ND ND 0.50 0.50
Kroger 0.30 ND ND 0.30 0.30
Swiss
Kraft 0.60 ND ND 0.60 0.60
Beatrice City Line Old World 0.40 ND ND 0.40 0.40
Chips
Potato
Lay’s 1.30 4.60 1.30 7.20 1.80
Wise 7.40 1.20 0.10 8.70 7.52
Tortilla
Tostitos 1.10 2.40 0.50 4.00 1.36
Tostados 1.50 1.00 0.30 2.80 1.61
9
0.00
10

α Tocopherol
Fish
Salmon, waterpack
Chicken of the Sea 0.70 ND ND 0.70 0.70
Black Top 0.60 ND ND 0.60 0.60
Sardines, in tomato sauce
Spirit of Norway 3.60 0.20 0.10 3.90 3.62
Orleans 3.90 ND 0.10 4.00 3.90
Tuna, canned in oil 0.00
Starkist 1.00 4.80 1.90 7.70 1.54
Chicken of the Sea 0.98 2.60 1.10 4.68 1.27
Fruits and Fruit Juices
Grape juice, bottled

Welch’s ND ND ND 0.00 0.00
Seneca ND ND ND 0.00 0.00
Orange juice
Fresh Tropicana 0.20 ND ND 0.20 0.20
Frozen Minute Maid 0.20 0.10 ND 0.30 0.21
Plums 0.00
Variety 1 0.70 0.10 ND 0.80 0.71
Variety 2 0.50 0.04 ND 0.54 0.50
Milk chocolate, plain 0.50 2.00 ND 2.50 0.70
Nuts
Brazil nuts
Health food store 6.60 2.10 1.60 10.30 6.86
Dekalb Farmers Market 11.00 5.10 2.60 18.70 11.59
English walnuts
Diamond 1.40 9.20 0.60 11.20 2.34
Kroger 6.70 0.50 7.20 0.69
Hazelnuts
Health food store 21.50 0.10 0.01 21.61 21.51
Handbook of Nutrition and Food
Dekalb Farmers Market 16.80 0.70 ND 17.50 16.87

Oils
Margarine, stick
Mazzola 8.40 24.40 0.40 33.20 10.85
Fleischman 7.90 23.10 0.60 31.60 10.23
Mayonnaise
Kraft 1.30 6.60 1.00 8.90 1.99
Food Constituents
Hellman 1.60 9.80 1.90 13.30 2.64

Shortenings, Crisco 5.60 25.20 5.40 36.20 8.28
Vegetable oil 0.00
Crisco 2.90 33.30 7.00 43.20 6.44
Wesson 2.80 18.30 3.00 24.10 4.72
Protein Diet Powder
Slimfast 26.50 ND ND 26.50 26.50

Herbalife 24.60 ND ND 24.60 24.60
Salad Dressings
Bleu Cheese
Marie’s 4.70 57.50 25.40 87.60 11.21
Kraft 2.80 49.00 14.40 66.20 8.13
French
Wishbone 3.00 66.90 27.70 97.60 10.52
Kraft 3.10 61.90 18.20 83.20 9.84
Italian
Wishbone 4.40 60.60 30.00 95.00 11.36
Kraft 4.00 62.70 17.80 84.50 10.80
Tea
Tea leaves from tea bags

Tetley 2.40 0.60 ND 3.00 2.46
Lipton 12.30 3.20 ND 15.50 12.62
Tea brewed from tea bags
Tetley ND ND ND 0.00 0.00
Lipton ND ND ND 0.00 0.00
Tomato Products
Barbecue sauce
11
Kraft 1.00 0.80 0.10 1.90 1.08

12

α Tocopherol
Heinz 1.10 0.40 0.10 1.60 1.14
Catsup
Heinz 1.10 0.10 ND 1.20 1.11
Hunt’s 1.80 0.20 ND 2.00 1.82
Tomato chili sauce
Del Monte 2.70 0.20 ND 2.90 2.72
Heinz 3.20 0.30 ND 3.50 3.23
Tomato paste
Hunt’s 4.10 0.30 ND 4.40 4.13
Contadina 4.50 0.70 ND 5.20 4.57
Tomato sauce
Hunt’s 1.40 0.10 ND 1.50 1.41

Progresso 1.50 0.20 ND 1.70 1.52
Tomato soup
Campbell’s 0.70 0.30 0.10 1.10 0.73
Kroger 0.60 0.10 ND 0.70 0.61
Tomatoes, stewed
Del Monte 0.90 0.20 ND 1.10 0.92
Stokely’s 0.70 0.20 ND 0.90 0.72
Vegetables
Asparagus
Sample 1 1.00 0.10 ND 1.10 1.01
Sample 2 1.30 0.10 ND 1.40 1.31
Cabbage
Sample 1 0.12 ND ND 0.12 0.12
Sample 2 0.09 ND ND 0.09 0.09
Cucumbers
Sample 1 0.04 0.02 ND 0.06 0.04
Sample 2 0.09 0.02 ND 0.11 0.09
Turnip greens
Sample 1 2.90 0.10 ND 3.00 2.91
Sample 2 2.80 0.20 ND 3.00 2.82
Note: ND, not detectable.
Food Constituents 13
TABLE 1.4
Occurrence of D-Tagatose in Foods1
Food Result (mg/kg) Sample Preparation Apparatus
Sterilized cow’s milk 2 to 3000 Extracted with methanol; Gas chromatography (GC),
prepared trimethylsilyl fused silica capillary column
(TMS) derivatives (18m × 0.22mm) coated with
AT-1000; carrier gas-N2 ; flame
ionization detector (FID)
Hot cocoa (processed 140 Extracted with deionized (DI) High performance liquid
with alkali) prepared water chromatography (HPLC); used
with milk Bio-Rad Aminex® HPX-87C
column (300 mm × 7.8 mm)
heated to 85º C; mobile phase-
DI water; flow rate-0.6 mL/
min; refractive index (RI)
detector
Hot cocoa prepared 190 Extracted with DI water HPLC; Bio-Rad Aminex® HPX-
with milk 87C column heated to 85ºC;
mobile phase-DI water; flow
rate-0.6 mL/min; RI detector
Powdered cow’s milk 800 Extracted three times with Paper partition
distilled water for 3h at 60ºC; chromatography, descending
column chromatography to method on Whatman no.1
remove organic acids and paper; used three solvent
bases; fractionation by systems
partition chromatography
Similac® infant 4 Extracted with 90% ethanol; GC; DB-5 fused-silica capillary
formula prepared TMS derivatives column (15 m × 0.53 mm, 1.5
µm film thickness); carrier gas-
He; FID detector
Enfamil® infant 23 Extracted with 90% aqueous GC; DB-17 fused-silica capillary
formula ethanol; prepared TMS column (15 m × 0.53 mm,1 µm
derivatives film thickness); carrier gas-He;
FID detector
Parmesan cheese 10 Extracted with 80% aqueous GC; DB-5 fused silica capillary
methanol; prepared TMS column (30 m, 0.25 µm film
derivatives thickness); carrier gas-He; FID
detector
Gjetost cheese 15 Extracted with 80% aqueous GC; DB-5 fused silica capillary
detector
Cheddar cheese 2 Extracted with 80% aqueous GC; DB-5 fused silica capillary
detector
Roquefort cheese 20 Extracted with 80% aqueous GC; DB-5 fused silica capillary
detector
Feta cheese 17 Extracted with 80% aqueous GC; DB-5 fused silica capillary
detector

Occurrence of D-Tagatose in Foods1
Food Result (mg/kg) Sample Preparation Apparatus
Ultra high temperature ~5 Dried under vacuum; water GC; Rescom type OV1 capillary
milk was added, then volatile column (25 m × 0.25 mm, 0.1
derivatives extracted with or 0.25 µm film thickness);
isooctane carrier gas-H 2; FID detector
BA Nature® Yogurt 29 Extracted with DI water; HPLC; Bio-Rad Aminex® HPX-
passed through a strong 87C column heated to 85ºC;
cation exchange column mobile phase-DI water; flow
followed by an amine rate-0.6 mL/min; RI detector
column
Cephulac®, an orally- 6500 Deionized with Amberlite IR- HPLC; Waters Carbohydrate
ingested medication 120 (H) and Duolite A-561 Analysis Column (300 mm ×
for treatment of (free base); diluted to 20 mg/ 3.9 mm); mobile phase-water:
portal-systemic mL with a 50:50 mixture of acetonitrile, 77:23 (w/w); flow
encephalopathy acetonitrile and water rate-2 mL/min; RI detector
Chronulac®, an orally 6500 Deionized with Amberlite IR- HPLC; Waters Carbohydrate
ingested laxative 120 (H) and Duolite A-561 Analysis Column (300 mm ×
(free base); diluted to 20 mg/ 3.9 mm); mobile phase-water:
mL with a 50:50 mixture of acetonitrile, 77:23 (w/w); flow
acetonitrile and water rate-2 mL/min; RI detector
1 This table was prepared by Lee Zehner, Beltsville, MD.
TABLE 1.5
Sweetening Agents, Sugar Substitutes
Name Sweetness Classification Uses Comments
Food Constituents
Acesulfame-K (sold 130 Nonnutritive; artificial Tabletop sweetener, chewing gum, dry beverage This is actually the potassium salt of the 6-methyl
under brand Sunette) mixes, puddings derivative of a group of chemicals called
oxathiazinone dioxides; approved by the FDA in
1988
Aspartame 180 Nutritive; artificial In most diet sodas; also used in cold cereals, drink Composed of the two naturally occurring amino
mixes, gelatin, puddings, toppings, dairy products, acids, aspartic acid and phenylalanine; sweeter than
and at the table by the consumer; not used in sugar, therefore less required, hence fewer calories
cooking due to lack of stability when heated
Cyclamate 30 Nonnutritive; artificial Tabletop sweetener and in drugs in Canada and 40 Discovered in 1937; FDA banned all cyclamate-
other countries containing beverages in 1969 and all cyclamate-
containing foods in 1970

Cyclamate safety is now being reevaluated by the
FDA
Dulcin (4-ethoxy- 250 Nonnutritive; artificial None Not approved for food use in the U.S.; used in some
phenyl-urea) European countries; also called Sucrol and Valzin
Fructose 1.7 Nutritive; natural Beverages, baking, canned goods; anywhere invert A carbohydrate; a monosaccharide; naturally occurs
(levulose) sugar or honey may be used in fruits; makes up about 50% of the sugar in honey;
commercially found in high-fructose syrups and
invert sugars; contributes sweetness and prevents
crystallization
Glucose (dextrose) 0.7 Nutritive; natural Primarily in the confection, wine, and canning Acts synergistically with other sweeteners
industries; and in intravenous solutions
Glycine 0.8 Nutritive; natural Permissible to use to modify taste of some foods A sweet-tasting amino acid; tryptophan is also a
sweet-tasting amino acid
Mannitol 0.7 Nutritive; natural Candies, chewing gums, confections, and baked A sugar alcohol or polyhydric alcohol (polyol); occurs
goods; dietetic foods naturally in pineapples, olives, asparagus, and
carrots; commercially prepared by the
hydrogenation of mannose or glucose; slowly and
incompletely absorbed from the intestines; only
slightly metabolized, most excreted unchanged in
the urine; may cause diarrhea
15
16
Sweetening Agents, Sugar Substitutes

Name Sweetness1 Classification Uses Comments
Miraculin — Nutritive; natural None Actually a taste-modifying protein rather than a
sweetener; after exposing tongue to miraculin, sour
lemon tastes like sweetened lemon; responsible for
the taste-changing properties of mircale fruit, red
berries of Synsepalum dulcificum, a native plant of
West Africa; first described in 1852; one attempt
made to commercialize by a U.S. firm but FDA
denied approval and marketing was stopped
Monellin 3000 Nutritive; natural None; only a potential low-calorie sweetener Extract of the pulp of the light red berries of the
tropical plant Dioscoreophyllum cumminsii; also called
Serendipity Berry; first protein found to elicit a sweet
taste in man; first extracted in 1969; potential use
limited by lack of stability; taste sensation is slow

and lingering; everything tastes sweet after monellin.
Neohesperidin 1250 Nonnutritive; artificial None approved; potential for chewing gum, Formed from naringen isolated from citrus fruit; slow
dihydrochalone (Neo mouthwash, and toothpaste to elicit the taste sensation; lingering licorice-like
DHC, NDHC) aftertaste; animal studies indicate not toxic
P-4000 4100 Nonnutritive; artificial None approved Derivative of nitroaniline; used as a sweetener in
(5-nitro-2-pro- some European countries but banned in the U.S. due
poxyaniline) to toxic effects on rats; no bitter aftertaste; major
drawback of P-4000 is powerful local anesthetic
effect on the tongue and mouth; used in the
Netherlands during German occupation and Berlin
blockade
Phyllodulcin 250 Natural None approved Isolated from Hydrangea macrophylla Seringe in 1916;
displays a lagging onset of sweetness with licorice
aftertaste; not well studied; possible market for hard
candies, chewing gums, and oral hygiene products
Saccharin (0 benzo- 500 Nonnutritive; artificial Used in beverages, as a tabletop sweetener, and in Both sodium and calcium salts of saccharin used;
sulfimide) cosmetics, toothpaste, and cough syrup; used as a passes through body unchanged; excreted in urine;
sweetener by diabetics originally a generally recognized as safe (GRAS)
additive
Subsequently, saccharin was classed as a carcinogen
based on experiments with rats; however, recent
experiments indicate that saccharin causes cancer in
rats, but not in mice and people
Sorbitol 0.6 Nutritive; natural Chewing gum, dairy products, meat products, icing, A sugar alcohol or polyhydric alcohol (polyol); occurs
toppings, and beverages naturally in many fruits commercially prepared by
the hydrogenation of glucose; many unique
properties besides sweetness; on the FDA list of
GRAS food additives; the most widely used sugar
alcohol; slow intestinal absorption; consumption of
large amounts may cause diarrhea
Food Constituents
SRI Oxime V (Perilla 450 Nonnutritive; artificial None approved Derived from extract of Perilla namkinensis; clean
sugar) taste; needs research; used as sweetening agent in
Japan
Stevioside 300 Nutritive; natural None approved Isolated from the leaves of the wild shrub Stevia
rebaudiana Bertoni; used by the people of Paraguay
to sweeten drinks; limited evidence suggests
nontoxic to humans
Rebaudioside A is isolated from the same plant and
is said to taste superior to stevioside; its chemical
structure is very similar to stevioside and it is 190
times sweeter than sugar

Sucrose (brown sugar, 1.0 Nutritive; natural Many beverages and processed foods; home use in a The chemical combination of the sugars fructose and
liquid sugar, sugar, wide variety of foods glucose; one of the oldest sweetening agents; most
table sugar, white popular and most available sweetening agent;
sugar occurs naturally in many fruits; commercially
extracted from sugar cane and sugar beets
Thaumatins 1600 Nutritive; natural None Source of sweetness of the tropical fruit from the plant
Thaumatococcus daniellii; enjoyed by inhabitants of
western Africa; doubtful commercial applications
Xylitol (Also see 0.8 Nutritive; natural Chewing gums and dietetic foods A sugar alcohol or polyhydric alcohol (polyol); occurs
XYLITOL) naturally in some fruits and vegetables; produced in
the body; commercial production from plant parts
(oat hulls, corncobs, and birch wood chips)
containing xylans — long chains of the sugar xylose;
possible diarrhea; one British study suggests xylitol
causes cancer in animals
Adapted from Ensminger et al. Foods and Nutrition Encyclopedia, 2nd ed., CRC Press, Boca Raton, 1994, pp. 2082–2087.
17
TABLE 1.6
Terms used to Describe the Functions of Food Additives
Term Function
Anticaking agents and free-flow agents Substances added to finely powdered or crystalline food products to
prevent caking
Antimicrobial agents Substances used to preserve food by preventing growth of
microorganisms and subsequent spoilage, including fungicides,
mold and yeast inhibitors, and bacteriocides
Antioxidants Substances used to preserve food by retarding deterioration,
rancidity, or discoloration due to oxidation
Colors and coloring adjuncts Substances used to impart, preserve, or enhance the color or shading
of a food, including color stabilizers, color fixatives, color-retention
agents
Curing and pickling agents Substances imparting a unique flavor and/or color to a food, usually
producing an increase in shelf life stability
Dough strengtheners Substances used to modify starch and gluten, thereby producing a
more stable dough
Drying agents Substances with moisture-absorbing ability, used to maintain an
environment of low moisture
Emulsifiers and emulsifier salts Substances which modify surface tension of two (or more) immiscible
solutions to establish a uniform dispersion of components; called
an emulsion
Enzymes Substances used to improve food processing and the quality of the
finished food
Firming agents Substances added to precipitate residual pectin, thus strengthening
the supporting tissue and preventing its collapse during processing
Flavor enhancers Substances added to supplement, enhance, or modify the original
taste and/or aroma of a food without imparting a characteristic taste
or aroma of its own
Flavoring agents and adjuvants Substances added to impart or help impart a taste or aroma in food
Flour treating agents Substances added to milled flour, at the mill, to improve its color
and/or baking qualities, including bleaching and maturing agents
Formulation aids Substances used to promote or produce a desired physical state or
texture in food, including carriers, binders, fillers, plasticizers, film-
formers, and tableting aids
Fumigants Volatile substances used for controlling insects or pests
Humectants Hygroscopic substances incorporated in food to promote retention
of moisture, including moisture-retention agents and antidusting
agents
Leavening agents Substances used to produce or stimulate production of carbon
dioxide in baked goods to impart a light texture, including yeast,
yeast foods, and calcium salts
Lubricants and release agents Substances added to food contact surfaces to prevent ingredients and
finished products from sticking to them
Nonnutritive sweeteners Substances having less than 2% of the caloric value of sucrose per
equivalent unit of sweetening capacity
Nutrient supplements Substances which are necessary for the body’s nutritional and
metabolic processes
Nutritive sweeteners Substances having greater than 2% equivalent unit of sweetening
capacity
Oxidizing and reducing agents Substances which chemically oxidize or reduce another food
ingredient, thereby producing a more stable product
pH control agents Substances added to change or maintain active acidity or alkalinity,
including buffers, acids, alkalis, and neutralizing agents
Processing aids Substances used as manufacturing aids to enhance the appeal or
utility of a food or food component, including clarifying agents,
clouding agents, catalysts, flocculents, filter aids, and crystallization
inhibitors

Terms used to Describe the Functions of Food Additives
Term Function
Propellants, aerating agents, and gases Gases used to supply force to expel a product, or used to reduce the
amount of oxygen in contact with the food in packaging
Sequestrants Substances which combine with polyvalent metal ions to form a
soluble metal complex, to improve the quality and stability of
products
Solvents and vehicles Substances used to extract or dissolve another substance
Stabilizers and thickeners Substances used to produce viscous solutions or dispersions, to
impart body, improve consistency, or stabilize emulsions, including
suspending and bodying agents, setting agents, gelling agents, and
bulking agents
Surface-active agents Substances used to modify surface properties of liquid food
components for a variety of effects, other than emulsifiers but
including solubilizing agents, dispersants, detergents, wetting
agents, rehydration enhancers, whipping agents, foaming agents,
and defoaming agents
Surface-finishing agents Substances used to increase palatability, preserve gloss, and inhibit
discoloration of foods, including glazes, polishes, waxes, and
protective coatings
Synergists Substances used to act or react with another food ingredient to
produce a total effect different or greater than the sum of the effects
produced by the individual ingredients
Texturizers Substances which affect the appearance or feel of the food
Taken from Ensminger, et al. Foods and Nutrition Encyclopedia, 2nd ed., CRC Press, Boca Raton, 1994, p. 11.
TABLE 1.7
Specific Food Additives and Their Functions
Name Function1 Food Use and Comments2
Acetic acid pH control, preservative Acid of vinegar is acetic acid; miscellaneous and/or
general purposes; many food uses; GRAS additive
Adipic acid pH control Buffer and neutralizing agent; use in confectionery;
GRAS additive
Ammonium alginate Stabilizer and thickener, Extracted from seaweed; widespread food use; GRAS
texturizer additive
Annatto Color Extracted from seeds of Bixa crellana; butter, cheese,
margarine, shortening, and sausage casings; coloring
foods in general
Arabinogalactan Stabilizer and thickener, Extracted from Western larch; widespread food use;
texturizer bodying agent in essential oils, nonnutritive
sweeteners, flavor bases, nonstandardized dressings,
and pudding mixes
Ascorbic acid Nutrient, antioxidant, Widespread use in foods to prevent rancidity,
(Vitamin C) preservative browning; used in meat curing; GRAS additive
Aspartame Sweetener; sugar substitute Soft drinks, chewing gum, powdered beverages,
whipped toppings, puddings, gelatin; tabletop
sweetener
Azodicarbonamide Flour treating agent Aging and bleaching ingredient in cereal flour
Benzoic acid Preservative Occurs in nature in free and combined forms;
widespread food use; GRAS additive
Benzoyl peroxide Flour treating agent Bleaching agent in flour; may be used in some cheeses
Beta-apo-8′ carotenal Color Natural food color; general use not to exceed 30 mg/
lb or pt of food

BHA (butylated Antioxidant, preservative Fats, oils, dry yeast, beverages, breakfast cereals, dry
hydroxyanisole) mixes, shortening, potato flakes, chewing gum,
sausage; often used in combination with BHT; GRAS
additive
BHT (butylated Antioxidant, preservative Rice, fats, oils, potato granules, breakfast cereals,
hydroxytoluene) potato flakes, shortening, chewing gum, sausage;
often used in combination with BHA; GRAS additive
Biotin Nutrient Rich natural sources are liver, kidney, pancreas, yeast,
milk; vitamin supplement; GRAS additive
Calcium alginate Stabilizer and thickener, Extracted from seaweed; widespread food use; GRAS
texturizer additive
Calcium carbonate Nutrient Mineral supplement; general purpose additive; GRAS
additive
Calcium lactate Preservative General purpose and/or miscellaneous use; GRAS
additive
Calcium phosphate Leavening agent, sequestrant, General purpose and/or miscellaneous use; mineral
nutrient supplement; GRAS additive
Calcium propionate Preservative Bakery products, alone or with sodium propionate;
inhibits mold and other microorganisms; GRAS
additive
Calcium silicate Anticaking agent Used in baking powder and salt; GRAS additive
Canthaxanthin Color Widely distributed in nature; color for foods; more red
than carotene
Caramel Color Miscellaneous and/or general purpose use in foods
for color; GRAS additive
Carob bean gum Stabilizer and thickener Extracted from bean of carob tree (Locust bean);
numerous foods, e.g., confections, syrups, cheese
spreads, frozen desserts, and salad dressings; GRAS
additive
Carrageenan Emulsifier, stabilizer, and Extracted from seaweed; a variety of foods, primarily
thickener those with a water or milk base
Cellulose Emulsifier, stabilizer, and Component of all plants; inert bulking agent in foods;
thickener may be used to reduce energy content of food; used
in foods which are liquid and foam systems
Citric acid Preservative, antioxidant, pH Widely distributed in nature in both plants and
control agent, sequestrant animals; miscellaneous and/or general purpose food
use; used in lard, shortening, sausage, margarine,
chili con carne, cured meats, and freeze-dried meats;
GRAS additive
Citrus Red No. 2 Color Coloring skins of oranges
Cochineal Color Derived from the dried female insect, Coccus cacti;
raised in West Indies, Canary Islands, southern Spain,
and Algiers; 70,000 insects to 1 lb.; provides red color
for meat products and beverages
Corn endosperm oil Color Source of xanthophyll for yellow color; used in chicken
feed to color yolks of eggs and chicken skin
Cornstarch Anticaking agent, drying Digestible polysaccharide used in many foods, often
agent, formulation aid, in a modified form; these include baking powder,
processing aid, surface- baby foods, soups, sauces, pie fillings, imitation
finishing agent jellies, custards, and candies
Corn syrup Flavoring agent, humectant, Derived from hydrolysis of cornstarch; employed in
nutritive sweetener, numerous foods, e.g., baby foods, bakery products,
preservative toppings, meat products, beverages, condiments, and
confections; GRAS additive

Dextrose (glucose) Flavoring agent, humectant, Derived from cornstarch; major users of dextrose are
nutritive sweetener, confection, wine, and canning industries; used to
synergist flavor meat products; used in production of caramel;
variety of other uses
Diglycerides Emulsifiers Uses include frozen desserts, lard, shortening, and
margarine; GRAS additive
Dioctyl sodium Emulsifier, processing aid, Employed in gelatin dessert, dry beverages, fruit juice
sulfosuccinate surface active agent drinks, and noncarbonated beverages with cocoa fat;
used in production of cane sugar and in canning
Disodium guanylate Flavor enhancer Derived from dried fish or seaweed
Disodium inosinate Flavor adjuvant Derived from seaweed or dried fish; sodium guanylate
is a byproduct
EDTA Antioxidant, sequestrant Calcium disodium and disodium salt of EDTA
(ethylenediamine- employed in a variety of foods including soft drinks,
tetraacetic acid) alcoholic beverages, dressings, canned vegetables,
margarine, pickles, sandwich spreads, and sausage
FD&C colors: Color Coloring foods in general, including dietary
Blue No. 1 supplements
Red No. 40
Yellow No. 5
Gelatin Stabilizer and thickener, Derived from collagen by boiling skin, tendons,
texturizer ligaments, bones, etc. with water; employed in many
foods including confectionery, jellies, and ice cream;
GRAS additive
Glycerine (glycerol) Humectant Miscellaneous and general purpose additive; GRAS
additive
Grape skin extract Color Colorings for carbonated drinks, beverage bases, and
alcoholic beverages
Guar gum Stabilizer and thickener, Extracted from seeds of the guar plant of India and
texturizer Pakistan; employed in such foods as cheese, salad
dressings, ice cream, and soups
Gum arabic Stabilizer and thickener, Gummy exudate of Acacia plants; used in variety of
texturizer foods; GRAS additive
Gum ghatti Stabilizer and thickener, Gummy exudate of plant growing in India and
texturizer Ceylon; a variety of food uses; GRAS additive
Hydrogen peroxide Bleaching agent Modification of starch and bleaching tripe; GRAS
bleaching agent
Hydrolyzed Flavor enhancer Used to flavor various meat products
vegetable (plant)
protein
Invert sugar Humectant, nutritive Main use in confectionery and brewing industry
sweetener
Iron Nutrient Dietary supplements and food; GRAS additive
Iron-Ammonium Anticaking agent Used in salt
citrate
Karraya gum Stabilizer and thickener Derived from dried extract of Sterculia urens found
primarily in India; variety of food uses; a substitute
for tragacanth gum; GRAS additive
Lactic acid Preservative, pH control Normal product of human metabolism; numerous
uses in foods and beverages; a miscellaneous general
purpose additive; GRAS additive
Lecithin Emulsifier, surface active Normal tissue component of the body; edible and
(phosphatidyl- agent digestible additive naturally occurring in eggs;
choline) commercially derived from soybeans; margarine,
chocolate, and wide variety of other food uses; GRAS
additive

Mannitol Anticaking, nutritive Special dietary foods; GRAS additive; supplies 1/2 the
sweetener, stabilizer and energy of glucose; classified as a sugar alcohol or
thickener, texturizer polyol
Methylparaben Preservative Food and beverages; GRAS additive
Modified food starch Drying agent, formulation Digestible polysaccharide used in many foods and
aid, processing aid, surface stages of food processing; examples include baking
finishing agent powder, puddings, pie fillings, baby foods, soups,
sauces, candies, etc.
Monoglycerides Emulsifiers Widely used in foods such as frozen desserts, lard,
shortening, and margarine; GRAS additive
MSG (monosodium Flavor enhancer Enhances the flavor of a variety of foods including
glutamate) various meat products; possible association with the
Chinese restaurant syndrome
Papain Texturizer Miscellaneous and/or general purpose additive;
GRAS additive; achieves results through enzymatic
action; used as meat tenderizer
Paprika Color, flavoring agent Provides coloring and/or flavor to foods; GRAS
additive
Pectin Stabilizer and thickener, Richest source of pectin is lemon and orange rind;
texturizer present in cell walls of all plant tissues; used to
prepare jellies and jams; GRAS additive
Phosphoric acid pH control Miscellaneous and/or general purpose additive; used
to increase effectiveness of antioxidants in lard and
shortening; GRAS additive
Polyphosphates Nutrient, flavor improver, Numerous food uses; most polyphosphates and their
sequestrant, pH control sodium, calcium, potassium, and ammonium salts;
GRAS additive
Polysorbates Emulsifiers, surface active Polysorbates designated by numbers such as 60, 65,
agent and 80; variety of food uses including baking mixes,
frozen custards, pickles, sherbets, ice creams, and
shortenings
Potassium alginate Stabilizer and thickener, Extracted from seaweed; wide usage; GRAS additive
texturizer
Potassium bromate Flour treating agent Employed in flour, whole wheat flour, fermented malt
beverages, and to treat malt
Potassium iodide Nutrient Added to table salt or used in mineral preparations as
a source of dietary iodine
Potassium nitrite Curing and pickling agent To fix color in cured products such as meats
Potassium sorbate Preservative Inhibits mold and yeast growth in foods such as wines,
sausage casings, and margarine; GRAS additive
Propionic acid Preservative Mold inhibitor in breads and general fungicide; GRAS
additive; used in manufacture of fruit flavors
Propyl gallate Antioxidant, preservative Used in products containing oil or fat; employed in
chewing gum; used to retard rancidity in frozen fresh
pork sausage
Propylene glycol Emulsifier, humectant, Miscellaneous and/or general purpose additive; uses
stabilizer and thickener, include salad dressings, ice cream, ice milk, custards,
texturizer and a variety of other foods; GRAS additive
Propylparaben Preservative Fungicide; controls mold in sausage casings; GRAS
additive
Saccharin Nonnutritive sweetener Special dietary foods and a variety of beverages; baked
products; tabletop sweeteners
Saffron Color, flavoring agent Derived from plant of western Asia and southern
Europe; all foods except those where standards
forbid; to color sausage casings, margarine, or
product branding inks

Silicon dioxide Anticaking agent Used in feed or feed components, beer production,
production of special dietary foods, and ink diluent
for marking fruits and vegetables
Sodium acetate pH control, preservative Miscellaneous and/or general purpose use; meat
preservation; GRAS additive
Sodium alginate Stabilizer and thickener, Extracted from seaweed; widespread food use; GRAS
texturizer additive
Sodium aluminum Leavening agent Baking powders, confectionery; sugar refining
sulfate
Sodium benzoate Preservative Variety of food products; margarine to retard flavor
reversion; GRAS additive
Sodium bicarbonate Leavening agent, pH control Miscellaneous and/or general purpose uses;
separation of fatty acids and glycerol in rendered fats;
neutralize excess and clean vegetables in rendered
fats, soups, and curing pickles; GRAS additive
Sodium chloride Flavor enhancer, formulation Used widely in many foods; GRAS additive
(salt) acid, preservation
Sodium citrate pH control, curing and Evaporated milk; miscellaneous and/or general
pickling agent, sequestrant purpose food use; accelerate color fixing in cured
meats; GRAS additive
Sodium diacetate Preservative, sequestrant An inhibitor of molds and rope-forming bacteria in
baked products; GRAS additive
Sodium nitrate Curing and pickling agent, Used with or without sodium nitrite in smoked, cured
(Chile saltpeter) preservative fish, cured meat products
Sodium nitrite Curing and pickling agent, May be used with sodium nitrate in smoked or cured
preservative fish, cured meat products, and pet foods
Sodium propionate Preservative A fungicide and mold preventative in bakery
products; GRAS additive
Sorbic acid Preservative Fungistatic agent for foods, especially cheeses; other
uses include baked goods, beverages, dried fruits,
fish, jams, jellies, meats, pickled products, and wines;
GRAS additive
Sorbitan Emulsifier, stabilizer and Widespread food usage such as whipped toppings,
monostearate thickener cakes, cake mixes, confectionery, icings, and
shortenings; also many nonfood uses
Sorbitol Humectant, nutritive A sugar alcohol or polyol; used in chewing gum, meat
sweetener, stabilizer and products, icings, dairy products, beverages, and pet
thickener, sequestrant foods
Sucrose Nutritive sweetener, The most widely used additive; used in beverages,
preservative baked goods, candies, jams and jellies, and other
processed foods
Tagetes Color Source is flower petals of Aztec marigold; used to
(Aztec marigold) enhance yellow color of chicken skin and eggs,
incorporated in chicken feed
Tartaric acid pH control Occurs free in many fruits, free or combined with
calcium, magnesium, or potassium; used in the soft
drink industry, confectionery products, bakery
products, and gelatin desserts
Titanium dioxide Color For coloring foods generally, except standardized
foods; used for coloring ingested and applied drugs
Tocopherols Antioxidant, nutrient To retard rancidity in foods containing fat; used in
(vitamin E) dietary supplements; GRAS additive
Tragacanth gum Stabilizer and thickener, Derived from the plant Astragalus gummifier or other
texturizer Asiatic species of Astragalus; general purpose
additive

Turmeric Color Derived from rhizome of Curcuma longa; used to color
sausage casings, margarine or shortening, and ink for
branding or marking products
Vanilla Flavoring agent Used in various bakery products, confectionery, and
beverages; natural flavoring extracted from cured,
full grown unripe fruit of Vanilla panifolia; GRAS
additive
Vanillin Flavoring agent and adjuvant Widespread confectionery, beverage and food use;
synthetic form of vanilla; GRAS additive
Yellow prussiate of Anticaking agent Employed in salt
soda
1 Function refers to those defined in Table 1.3.
2 Adapted from Ensinger et al., Food and Nutrition Encyclopedia, 2nd ed., CRC Press, Boca Raton, 1994, pp. 13-18.
TABLE 1.8
Mycotoxins/Bacterial Toxins in Foods
Toxins from Bacteria
Staphylococcus aureus: α exotoxin (lethal, dermonecrotic, hemolytic, leucolytic)
β exotoxin (hemolytic)
γ exotoxin (hemolytic)
δ exotoxin (dermonecrotic, hemolytic)
leucocidin (leucolytic)
exfoliative toxin
enterotoxin
Clostridium botulinum (four strains): Toxins are lettered as A,B, Cα (1,2,D), Cβ, D(C1 and D), E, F, G. All of the
toxics are proteolytic and produce NH3, H2S, CO2, and volatile amines. The toxins are hemolytic and neurotoxic
Escherichi coli (several serotypes): Induce diarrhea, vomiting; produce toxins that are heat labile
Bacillus cereus (several types): Produces heat labile enterotoxins that induce vomiting and diarrhea
Mycotoxins Produced by Fungi
Aspergillus flavis
Claviceps purpura
Fusarium graminearum
Aspergillus ochraceus
Aspergillus parasiticus
Penicillium viridicatum
TABLE 1.9
Antinutrients in Food
Type of Factor(s) Effect of Factor(s) Legumes Containing the Factor(s)
Antivitamin factors Interfere with the actions of certain
vitamins
Antivitamin A Lipoxidase oxidizes and destroys Soybeans
carotene (provitamin A)
Antivitamin B12 Increases requirement for Vitamin Soybeans
B12
Antivitamin D Causes rickets unless extra vitamin Soybeans
D is provided
Antivitamin E Damage to the liver and muscles Alfalfa, Common beans (Phaseolus
vulgaris), Peas (Pisum sativum)

Antinutrients in Food
Type of Factor(s) Effect of Factor(s) Legumes Containing the Factor(s)
Cyanide-releasing glucosides Releases hydrocyanic acid. The All legumes contain at least small
poison may also be released by an amounts of these factors;
enzyme in E. coli, a normal however, certain varieties of lima
inhabitant of the human intestine beans (Phaseolus lunatus) may
contain much larger amounts
Favism factor Causes the breakdown of red blood Fava beans (Vicia faba)
cells in susceptible individuals
Gas-generating carbohydrates Certain indigestible carbohydrates Many species of mature dry
are acted upon by gas-producing legume seeds, but not peanuts; the
bacteria in the lower intestine immature (green) seeds contain
much lower amounts
Goitrogens Interfere with the utilization of Peanuts and soybeans
iodine by the thyroid gland
Inhibitors of trypsin The inhibitor(s) binds with the All legumes contain trypsin
digestive enzyme trypsin inhibitors; these inhibitors are
destroyed by heat
Lathyrogenic neurotoxins Consumption of large quantities of Lathyrus pea (L. sativus) which is
lathyrogenic legumes for long grown mainly in India
periods (several months) results Common vetch (Vicia sativa) may
in severe neurological disorders also be lathyrogenic
Metal binders Bind copper, iron, manganese, and Soybeans, Peas (Pisum sativum)
zinc
Red blood cell clumping agents The agents cause the red blood cells Occurs in all legumes to some
(hemagglutinins) to clump together extent
Adapted from Ensminger et al., Food and Nutrition Encyclopedia, 2nd ed., CRC Press, Boca Raton, 1994, pp.
1284–1285.
Type A antinutritives. Substances primarily interfering with the digestion of proteins

or the absorption and utilization of amino acids. Also known as antiproteins. People
depending on vegetables for their protein supply, as in less developed countries, are in
danger of impairment by this type of antinutritives. The most important type A antinu-
tritives are protease inhibitors and lectins.
Protease inhibitors, occurring in many plant and animal tissues, are proteins which
inhibit proteolytic enzymes by binding to the active sites of the enzymes. Proteolytic
enzyme inhibitors were first found in avian eggs around the turn of the century. They
were later identified as ovomucoid and ovoinhibitor, both of which inactivate trypsin.
Chymotrypsin inhibitors also are found in avian egg whites. Other sources of trypsin and/
or chymotrypsin inhibitors are soybeans and other legumes and pulses, vegetables, milk
and colostrum, wheat and other cereal grains, guar gum, and white and sweet potatoes.
The protease inhibitors of kidney beans, soybeans, and potatoes can additionally inhibit
elastase, a pancreatic enzyme acting on elastin, an insoluble protein in meat. Animals
given food containing active inhibitors show growth depression. This appears to be due
to interference in trypsin and chymotrypsin activities and to excessive stimulation of the
secretory exocrine pancreatic cells, which become hypertrophic. Valuable proteins may be
lost to the feces in this case. In vitro experiments with human proteolytic enzymes have
been shown that trypsin inhibitors from bovine colostrum, lima beans, soybeans, kidney
beans, and quail ovomucoid were active against human trypsin, whereas trypsin inhibitors
originating from bovine and porcine pancrease, potatoes, chicken ovomucoid, and chicken
ovoinhibitor were not. The soybean and lima bean trypsin inhibitors are also active against
human chymotrypsin. Many protease inhibitors are heat labile, especially with moist heat.
Relatively heat resistant protease inhibitors include the antitryptic factor in milk, the
alcohol-precipitable and nondialyzable trypsin inhibitor in alfalfa, the chymotrypsin inhib-
itor in potato, the kidney bean inhibitor, and the trypsin inhibitor in lima beans.
Lectin is the general term for plant proteins that have highly specific binding sites for
carbohydrates. They are widely distributed among various sources such as soybeans,
peanuts, jack beans, mung beans, lima beans, kidney beans, fava beans, vetch, yellow wax
beans, hyacinth beans, lentils, peas, potatoes, bananas, mangoes and wheat germ. Most
plant lectins are glycoproteins, except concanavalin A from jack beans, which is carbohy-
drate-free. The most toxic lectins in food include ricin in castor bean (oral toxic dose in
man: 150-200 mg; intravenous toxic dose: 20 mg), and the lectins of kidney bean and
hyacinth bean. The mode of action of lectins may be related to their ability to bind to
specific cell receptors in a way comparable to that of antibodies. Because they are able to
agglutinate red blood cells, they are also known as hemaglutinins. The binding of bean
lectin on rat intestinal mucosal cells has been demonstrated in vitro, and it has been
suggested that this action is responsible for the oral toxicity of the lectins. Such bindings
may disturb the intestines’ absorptive capacity for nutrients and other essential com-
pounds. The lectins, being proteins, can easily be inactivated by moist heat. Germination
decreases the hemaglutinating activity in varieties of peas and species of beans.
Type B antinutritives. Substances interfering with the absorption or metabolic utiliza-
tion of minerals are also known as antiminerals. Although they are toxic per se, the
amounts present in foods seldom cause acute intoxication under normal food consump-
tion. However, they may harm the organism under suboptimum nutriture. The most
important type B antinutritives are phytic acid, oxalates, and glucosinolates.
Phytic acid, or myoinositol hexaphosphate, is a naturally occurring strong acid which
binds to many types of bivalent and trivalent heavy metal ions, forming insoluble salts.
Consequently, phytic acid reduces the availability of many minerals and essential trace
elements. The degree of insolubility of these salts appears to depend on the nature of the
metal, the pH of the solution, and for certain metals, on the presence of another metal.
Synergism between two metallic ions in the formation of phytate complexes has also been
observed. For instance, zinc-calcium phytate precipitates maximally at pH 6, which is also
the pH of the duodenum, where mainly calcium and trace metals are absorbed. Phytates
occur in a wide variety of foods, such as cereals (e.g. wheat, rye, maize, rice, barley),
legumes and vegetables (e.g. bean, soybean, lentil, pea, vetch); nuts and seeds (e.g. walnut,
hazelnut, almond, peanut, cocoa bean), and spices and flavoring agents (e.g. caraway,
coriander, cumin, mustard, nutmeg). From several experiments in animals and man it has
been observed that phytates exert negative effects on the availability of calcium, iron,
magnesium, zinc, and other trace essential elements. These effects may be minimized
considerably, if not eliminated, by increased intake of essential minerals. In the case of
calcium, intake of cholecalciferol must also be adequate, since the activity of phytates on
calcium absorption is enhanced when this vitamin is inadequate or limiting. In many
foodstuffs the phytic acid level can be reduced by phytase, an enzyme occurring in plants,
that catalyzes the dephosphorylation of phytic acid.
Oxalic acid is a strong acid which forms water soluble Na+ and K+ salts, but less soluble
salts with alkaline earth and other bivalent metals. Calcium oxalate is particularly insol-
uble at neutral or alkaline pH, whereas it readily dissolves in acid medium. Oxalates
mainly exert effects on the absorption of calcium. These effects must be considered in
terms of the oxalate/calcium ratio (in milliequivalent/milliequivalent): foods having a
ratio greater than 1 may have negative effects on calcium availability, whereas foods with
a ratio of 1 or below do not. Examples of foodstuffs having a ratio greater than 1 are:
rhubarb (8.5), spinach (4.3), beet (2.5 to 5.1), cocoa (2.6), coffee (3.9), tea (1.1), and potato
(1.6). Harmful oxalates in food may be removed by soaking in water. Consumption of
calcium-rich foods (e.g. dairy products and seafood), as well as augmented cholecalciferol
intake, are recommended when large amounts of high oxalate food are consumed.
A variety of plants contain a third group of type B antinutritives, the glucosinolates,
also known as thioglucosides. Many glucosinolates are goitrogenic. They have a general
structure, and yield on hydrolysis the active or actual goitrogens, such as thiocyanates,
isothiocyanates, cyclic sulfur compounds, and nitriles. Three types of goiter can be iden-
tified: 1) cabbage goiter, 2) brassica seed goiter, and 3) legume goiter. Cabbage goiter, also
known as struma, is induced by excessive consumption of cabbage. It seems that cabbage
goitrogens inhibit iodine uptake by directly affecting the thyroid gland. Cabbage goiter
can be treated by iodine supplementation. Brassica seed goiter can result from the con-
sumption of the seeds of Brassica plants (e.g. rutabaga, turnip, cabbage, rape) which
contain goitrogens that prevent thyroxine synthesis. This type of goiter can only be treated
by administration of the thyroid hormone. Legume goiter is induced by goitrogens in
legumes like soybeans and peanuts. It differs from cabbage goiter in that the thyroid gland
does not lose its activity for iodine. Inhibition of the intestinal absorption of iodine or the
reabsorption of thyroxine has been shown in this case. Legume goiter can be treated by
iodine therapy. Glucosinolates which have been shown to induce goiter, at least in exper-
imental animals, are found in several foods and feedstuffs: broccoli (buds), brussels sprouts
(head), cabbage (head), cauliflower (buds), garden cress (leaves), horseradish (roots), kale
(leaves), kohlrabi (head), black and white mustard (seed), radish (root), rape (seed), ruta-
baga (root), and turnips (root and seed). One of the most potent glucosinolates is progoitrin
from the seeds of Brassica plants and the roots of rutabaga. Hydrolysis of this compound
yields 1-cyano-2-hydroxy-3-butene, 1-cyano-2-hydroxy-3,4-butylepisulfide, 2-hydroxy-
3,4-butenylisothiocyanate, and (S)-5-vinyl-oxazolidone-2-thione, also known as goitrin.
The latter product interferes, together with its R-enantiomer, in the iodination of thyroxine
precursors, so that the resulting goiter cannot be treated by iodine therapy.
Type C antinutritives. Naturally occurring substances which can decompose vitamins,
form unabsorbable complexes with them, or interfere with their digestive or metabolic
utilization. Also known as antivitamins. The most important type C antinutritives are
ascorbic acid oxidase, antithiamine factors, and antipyridoxine factors.
Ascorbic acid oxidase is a copper-containing enzyme that catalyzes the oxidation of free
ascorbic acid to diketogluconic acid, oxalic acid, and other oxidation products. It has been
reported to occur in many fruits (e.g. peaches, bananas) and vegetables (e.g. cucumbers,
pumpkins, lettuce, cress, cauliflowers, spinach, green beans, green peas, carrots, potatoes,
tomatoes, beets, kohlrabi). The enzyme is active between pH 4 and 7 (optimum pH 5.6 to
6.0); its optimum temperature is 38°C. The enzyme is released when plant cells are broken.
Therefore, if fruits and vegetables are cut, the vitamin C content decreases gradually.
Ascorbic acid oxidase can be inhibited effectively at pH 2 or by blanching at around 100°C.
Ascorbic acid can also be protected against ascorbic acid oxidase by substances of plant
origin. Flavonoids, such as the flavonoles quercetin and kempferol, present in fruits and
vegetables, strongly inhibit the enzyme.
A second group of type C antinutritives are the antithiamine factors, which interact with
thiamine, also known as vitamin B1. Antithiamine factors can be grouped as thiaminases,
catechols, and tannins. Thiaminases, which are enzymes that split thiamine at the meth-
ylene linkage, are found in many freshwater and saltwater fish species, and in certain
species of crab and clam. They contain a nonprotein coenzyme structurally related to
hemin. This coenzyme is the actual antithiamine factor. Thiaminases in fish and other
sources can be destroyed by cooking. Antithiamine factors of plant origin include catechols
and tannins. The most well known ortho-catechol is found in bracken fern. In fact, there
are two types of heat-stable antithiamine factors in this fern, one of which has been
identified as caffeic acid, which can also by hydrolyzed from chlorogenic acid (found in
green coffee beans) by intestinal bacteria. Other ortho-catechols, such as methylsinapate

occurring in mustard seed and rapeseed, also have antithiamine activity. The mechanism
of thiamine inactivation by these compounds requires oxygen and is dependent on tem-
perature and pH. The reaction appears to proceed in two phases: a rapid initial phase,
which is reversible by addition of reducing agents (e.g. ascorbic acid), and a slower
subsequent phase, which is irreversible. Tannins, occurring in a variety of plants, including
tea, similarly possess antithiamine activity. Thiamine is one of the vitamins likely to be
deficient in the diet. Thus, persistent consumption of antithiamine factors and the possible
presence of thiaminase-producing bacteria in the gastrointestinal tract may compromise
the already marginal thiamine intake.
A variety of plants and mushrooms contain pyridoxine (a form of vitamin B6) antagonists.
These antipyridoxine factors have been identified as hydrazine derivatives. Linseed contains
the water-soluble and heat-labile antipyridoxine factor linatine (γ-glutamyl-1-amino-D-pro-
line). Hydrolysis of linatine yields the actual antipyridoxine factor 1-amino-proline. Anti-
pyridoxine factors have also been found in wild mushrooms, the common commercial
edible mushroom, and the Japanese mushroom shiitake. Commercial and shiitake mush-
rooms contain agaritine. Hydrolysis of agaritine by γ-glutamyl transferase, which is endog-
enous to the mushroom, yields the active agent 4-hydroxymethylphenylhydrazine.
Disruption of the cells of the mushroom can accelerate hydrolysis; careful handling of the
mushrooms and immediate blanching after cleaning and cutting can prevent hydrolysis.
The mechanism underlying the antipyridoxine activity is believed to be condensation of
the hydrazines with the carbonyl compounds pyridoxal and pyridoxal phosphate (the active
form of the vitamin), resulting in the formation of inactive hydrazones.
TABLE 1.10
Toxic Substances in Food (Toxic if Consumed in Excess)
Poison (Toxin) Source Symptoms and Signs Distribution; Magnitude Prevention; Treatment Remarks
Aflatoxins (See Table 1.8).
Food Constituents
Aluminum (Al) Food additives, mainly pre- Abnormally large intakes of Distribution: Aluminum is Prevention: Based on the ev- Aluminum toxicity has been
sented in such items as aluminum irritate the di- widely used throughout idence presented, no pre- reported in patients receiv-
baking powder, pickles, gestive tract. Also, unusual the world. ventative measures are ing renal dialysis.
and processed cheeses. conditions have sometimes Magnitude: The U.S. uses recommended.
Aluminum-containing ant- resulted in the absorption more aluminum than any
acids. of sufficient aluminum other mineral except iron.
from antacids to cause However, known cases of
brain damage. Aluminum aluminum toxicity are rare.
may form non-absorbable
complexes with essential
trace elements, thereby cre-

ating deficiencies of these
elements.
Arsenic (As) Consuming contaminated Burning pains in the throat Distribution: Arsenic is Treatment: Induce vomit- Arsenic is known to partial-
foods and beverages. or stomach, cardiac abnor- widely distributed, but the ing, followed by an anti- ly protect against selenium
Arsenical insecticides used malities, and the odor of amount of the element con- dote of egg whites in water poisoning.
in vineyards exposing the garlic on the breath. Other sumed by man in food and or milk. Afterward, give The highest residues of ar-
workers (1) when spraying symptoms may be diarrhea water, or breathed, is very strong coffee or tea, fol- senic are generally in the
or (2) by inhaling contami- and extreme thirst along small and not harmful. lowed by Epsom salts in hair and nails.
nated dusts and plant de- with a choking sensation. Magnitude: Cases of arsenic water or castor oil. Arsenic in soils may sharply
bris. Small doses of arsenic taken toxicity in man are infre- decrease crop growth and
Arsenic in the air from three into the body over a long quent. Two noteworthy ep- yields, but it is not a hazard
major sources; smelting of period of time may pro- isodes occurred in Japan in to people or livestock that
metals, burning of coal, duce hyperkeratosis (irreg- 1955. One involved tainted eat plants grown in these
and use of arsenical pesti- ularities in pigmentation, powdered milk; the other fields.
cides. especially on the trunk); ar- contaminated soy sauce.
terial insufficiency; and The toxic milk caused
cancer. 12,131 cases of infant poi-
There is strong evidence that soning, with 130 deaths.
inorganic arsenic is a skin The soy sauce poisoned 220
and lung carcinogen in people.
man.
29
30

Chromium (Cr) Food, water, and air contam- Inorganic chromium salt re- Distribution: Chromium Prevention: It is unlikely that
inated by chromium com- duces the absorption of toxicity is not common. people will get too much
pounds in industrialized zinc; hence, zinc deficiency Magnitude: Chromium tox- chromium because (1) only
areas. symptoms may become ev- icity is not very common. minute amounts of the ele-
ident in chronic chromium ment are present in most
toxicity. foods, (2) the body utilizes
chromium poorly, and (3)
the toxic dose is about
10,000 times the lowest ef-

fective medical dose.
Copper (Cu) Diets with excess copper, Acute copper toxicity: Char- Distribution: Copper toxici- Prevention: Avoid foods Copper is essential to hu-
but low in other minerals acterized by headache, diz- ty may occur wherever and beverages that have man life and health, but
that counteract its effects. ziness, metallic taste, there is excess copper in- been in prolonged contact like all heavy metals, it
Acid foods or beverages excessive salivation, nau- take, especially when ac- with copper metal. may be toxic in excess.
(vinegar, carbonated bever- sea, vomiting, stomach- companied by low iron, Administration of copper
ages, or citrus juices) that ache, diarrhea, and weak- molybdenum, sulfur, zinc, chelating agents to remove
have been in prolonged ness. If the disease is al- and vitamin C. excess copper.
contact with copper metal lowed to get worse, there Magnitude: The incidence
may cause acute gastro- may also be racing of the of copper toxicity is ex-
intestinal disturbances. heart, high blood pressure, tremely rare in man. Its oc-
jaundice, hemolytic ane- currence in significant form
mia, dark-pigmented is almost always limited to
urine, kidney disorders, (1) suicide attempted by in-
and even death. gesting large quantities of
Chronic copper toxicity: copper salt, or (2) a genetic
May be contributory to defect in copper metabo-
iron-deficiency anemia, lism inherited as an autoso-
mental illness following mal recessive, known as
childbirth (postpartum Wilson's disease.
psychosis), certain types of
schizophrenia, and per-
haps heart attacks.
Ergot Rye, wheat, barley, oats and When a large amount of er- Distribution: Ergot is found Prevention: Consists of an Six different alkaloids are in-
triticale carry this mycotox- got is consumed in a short throughout the world ergot-free diet. volved in ergot poisoning.
in. period, convulsive ergot- wherever rye, wheat, bar- Ergot in food and feed Ergot is used to aid the uter-
Ergot replaces the seed in ism is observed. The symp- ley, oats, or triticale are grains may be removed by us to contract after child-
the heads of cereal grains, toms include itching, grown. screening the grains before birth, to prevent loss of
in which it appears as a numbness, severe muscle Magnitude: There is consid- processing. In the U.S., blood. Also, another ergot
purplish-black, hard, ba- cramps, sustained spasms erable ergot, especially in wheat and rye containing drug (ergotamine) is wide-
Food Constituents
nana-shaped, dense mass and convulsions, and ex- rye. But, normally, screen- more than 0.3% ergot are ly used in the treatment of
from 1/4-3/4 in. (6-9 mm) treme pain. When smaller ing grains before process- classed as "ergoty." In Can- migraine headaches.
long. amounts of ergot are con- ing alleviates ergotism in ada, government regula-
sumed over an extended people. tions prohibit more than
period, ergotism is charac- 0.1% ergot in feeds.
terized by gangrene of the Treatment: An ergot-free di-
fingertips and toes, caused et; good nursing; treatment
by blood vessel and muscle by a doctor.
contraction stopping blood
circulation in the extremi-
ties. These symptoms in-

clude cramps, swelling,
inflammation, alternating
burning and freezing sen-
sations ("St. Anthony's
fire") and numbness; even-
tually the hands and feet
may turn black, shrink, and
fall off.
Ergotism is a cumulative
poison, depending on the
amount of ergot eaten and
the length of time over
which it is eaten.
31
32

Fluorine (F) (fluorosis) Ingesting excessive quanti- Acute fluoride poisoning: Distribution: The water in Prevention: Avoid the use of Fluorine is a cumulative poi-
ties of fluorine through ei- Abdominal pain, diarrhea, parts of Arkansas, Califor- food and water containing son.
ther the food or water, or a vomiting, excessive saliva- nia, South Carolina, and excessive fluorine. The total fluoride in the hu-
combination of these. tion, thirst, perspiration, Texas contains excess fluo- Treatment: Any damage man body averages 2.57 g.
Except in certain industrial and painful spasms of the rine. Occasionally, may be permanent, but Susceptibility to fluoride
exposures, the intake of flu- limbs. throughout the U.S., high- people who have not de- toxicity is increased by de-
oride inhaled from the air Chronic fluoride poisoning: fluorine phosphates are veloped severe symptoms ficiencies of calcium, vita-
is only a small fraction of Abnormal teeth (especially used in mineral mixtures. may be helped to some ex- min C, and protein.
the total fluoride intake in mottled enamel) during the Magnitude: Generally tent if the source of excess Virtually all foods contain
man. first 8 years of life; brittle speaking, fluorosis is limit- fluorine is eliminated. trace amounts of fluoride.
Pesticides containing fluo- bones. Other effects, pre- ed to high-fluorine areas. High dietary levels of calci-
rides, including those used dicted from animal studies, Only a few instances of um and magnesium may
to control insects, weeds, may include loss of body health effects in man have reduce the absorption and
and rodents. weight and altered struc- been attributed to airborne utilization of fluoride.
Although water is the prin- ture and function of the fluoride, and they occurred
cipal source of fluoride in thyroid gland and kidneys. in persons living in the vi-
an average human diet in Water containing 3-10 ppm cinity of fluoride-emitting
the U.S., fluoride is fre- of fluoride may cause mot- industries.
quently contained in tooth- tling of the teeth.
paste, tooth powder, An average daily intake of
chewing gums, mouth- 20-80 mg of fluoride over a
washes, vitamin supple- period of 10-20 years will
ments, and mineral result in crippling fluoro-
supplements. sis.
Lead (Pb) Consuming food or medici- Symptoms develop rapidly Distribution: Predominant- Prevention: Avoid inhaling Lead is a cumulative poison.
nal products (including in young children, but ly among children who or consuming lead. When incorporated in the
health food products) con- slowly in mature people. may eat chips of lead-con- Treatment: soil, nearly all the lead is
taminated with lead. Acute lead poisoning: Col- taining paints, peeled off Acute lead poisoning: An converted into forms that
Inhaling the poison as a dust ic, cramps, diarrhea or con- from painted wood. emetic (induce vomiting), are not available to plants.
by workers in such indus- stipation, leg cramps, and Magnitude: The Centers for followed by drinking plen- Any lead taken up by plant
tries as painting, lead min- drowsiness. Disease Control, Atlanta, ty of milk and 1/2 oz (14 g) roots tends to stay in the
Food Constituents
ing, and refining. The most severe form of lead GA, estimates that (1) lead of Epsom salts in 1/2 glass roots, rather than move up
Inhaling airborne lead dis- poisoning, encountered in poisoning claims the lives of water. to the top of the plant.
charged into the air from infants and in heavy drink- of 200 children each year, Chronic lead poisoning: Re- Lead poisoning can be diag-
auto exhaust fumes. ers of illicitly distilled and (2) 400,000-600,000 move the source of lead. nosed positively by analyz-
Consuming food crops con- whiskey, is characterized children have elevated lead Sometimes treated by ad- ing the blood tissue for lead
taminated by lead being by profound disturbances levels in the blood. ministration of magnesium content; clinical signs of
deposited on the leaves of the central nervous sys- Lead poisoning has been re- or lead sulphate solution as lead poisoning usually
and other edible portions tem and permanent dam- duced significantly with a laxative and antidote on are manifested at blood
of the plant by direct fall- age to the brain; damage to the use of lead-free paint. the lead in the digestive lead concentrations above
out. the kidneys; and shortened system, followed by potas- 80 µg/100 grams.
Consuming food or water life span of the erthrocytes. sium iodide which cleanses
contaminated by contact Chronic lead poisoning: the tracts.
with lead pipes or utensils. Colic, constipation, lead Currently, treatment of lead
Old houses in which the in- palsy especially in the fore- poisoning makes use of
teriors were painted with arm and fingers, the symp- chemicals that bind the
leaded paints prior to 1945, toms of chronic nephritis, metal in the body and help
with the chipped wall paint and sometimes mental de- in its removal.
eaten by children. pression, convulsions, and
Such miscellaneous sources a blue line at the edge of
as illicitly distilled whis- the gums.
key, improperly lead-
glazed earthenware, old
battery casings used as fu-
el, and toys containing
lead.
33
34

Mercury (Hg) Mercury is discharged into The toxic effects of organic Distribution: Wherever Control mercury pollution Mercury is a cumulative poi-
air and water from indus- and inorganic compounds mercury is produced in in- from industrial operations. son.
trial operations and is used of mercury are dissimilar. dustrial operations or used FDA prohibits use of mercu-
in herbicide and fungicide The organic compounds of in herbicide or fungicide ry-treated grain for food or
treatments. mercury, such as the vari- treatments. feed.
Mercury poisoning has oc- ous fungicides (1) affect the Magnitude: Limited. But Grain crops produced from
curred where mercury central nervous system, about 1200 cases of mercu- mercury-treated seed and
from industrial plants has and (2) are not corrosive. ry poisoning identified in crops produced on soils
been discharged into water, The inorganic compounds of Japan in the 1950s were treated with mercury her-
then accumulated as meth- mercury include mainly traced to the consumption bicides have not been
ylmercury in fish and shell- mercuric chloride, a disin- of fish and shellfish from found to contain harmful
fish. fectant; mercurous chloride Japan's Minamata Bay con- concentrations of this ele-
Accidental consumption of (calomel), a cathartic; and taminated with methyl- ment.
seed grains treated with elemental mercury. mercury. Some of the off-
fungicides that contain Commonly the toxic symp- spring of exposed mothers
mercury, used for the con- toms are corrosive gastro- were born with birth de-
trol of fungus diseases of intestinal effects, such as fects, and many victims
oats, wheat, barley, and vomiting, bloody diarrhea, suffered central nervous
flax. and necrosis of the alimen- system damage. Another
tary mucosa. outbreak of mercury toxic-
ity occurred in Iraq, where
more than 6000 people
were hospitalized after eat-
ing bread made from
wheat that had been treat-
ed with methylmercury.
Polychlorinated biphenyls Sources of contamination to Clinical effects on people Distribution: PCBs are Although the production of
(PCBs), industrial chemi- man include: are: an eruption of the skin widespread. Their use by PCBs was halted in 1977
cals; chlorinated hydrocar- 1. Contaminated foods resembling acne, visual industry is declining. and the importing of PCBs
bons which may cause 2. Mammals or birds that disturbances, jaundice, was banned January 1,
cancer when taken into the have fed on contaminated numbness, and spasms. 1979, the chemicals had
food supply. foods of fish. Newborn infants from been widely used for 40
3. Residues on foods that mothers who have been years, and they are excep-
Food Constituents
have been wrapped in pa- poisoned show discolora- tionally long-lived.

pers and plastics contain- tion of the skin which re- PCBs have been widely
ing PCBs. gresses after 2-5 months. used in dielectric fluids in
4. Milk from cows that have PCBs are fat soluble. capacitors and transform-
been fed silage from silos ers, hydraulic fluids, and
coated with PCB-contain- heat transfer fluids. Also,
ing paint; and eggs from they have more than 50 mi-
layers fed feeds contami- nor uses including plasti-
nated with PCBs. cizers and solvents in
adhesives, printing ink,
sealants, moisture retar-

dants, paints, and pesticide
carriers.
PCB will cause cancer in lab-
oratory animals (rats,
mice, and rhesus mon-
keys). It is not known if it
will cause cancer in hu-
mans. More study is need-
ed to gauge its effects on
the ecological food chain
and on human health.
When fed Coho salmon
from Lake Michigan with
10-15 ppm PCB, mink in
Wisconsin stopped repro-
ducing or their kits died.
35
36

Salt (NaCl-sodium chlo- Consumption of high-salt Salt may be toxic (1) when it Distribution: Salt is used all Treatment: Drink large Even normal salt concentra-
ride) poisoning food and beverages. is fed to infants or others over the world. Hence, the quantities of fresh water. tion may be toxic if water
whose kidneys cannot ex- potential for salt poisoning intake is low.
crete the excess in the exists everywhere.
urine, or (2) when the body Magnitude: Salt poisoning
is adapted to a chronic low- is relatively rare.
salt diet.
Selenium (Se) Consumption of high levels Abnormalities in the hair, Distribution: In certain re- Treatment: Selenium toxici- Confirmed cases of seleni-
in food or drinking water. nails, and skin. gions of western U.S., espe- ty may be counteracted by um poisoning in people are
Presence of malnutrition, Children in a high-selenium cially in South Dakota, arsenic or copper, but such rare because (1) only traces
parasitic infestation, or oth- area of Venezuela showed Montana, Wyoming, Ne- treatment should be care- are present in most foods,
er factors which make peo- loss of hair, discolored skin, braska, Kansas, and per- fully monitored. (2) foods generally come
ple highly susceptible to and chronic digestive dis- haps areas in other states in from a wide area, and (3)
selenium toxicity. turbances. the Great Plains and Rocky the metabolic processes
Normally, people who have Mountains. Also, in Canada. normally convert excess se-
consumed large excesses of Magnitude: Selenium toxic- lenium into harmless sub-
selenium excrete it as tri- ity in people is relatively stances which are excreted
methyl selenide in the rare. in the urine or breath.
urine, and/or as dimethyl
selenide on the breath. The
latter substance has an
odor resembling garlic.
Tin (Sn) From acid fruits and vegeta- Methylated tin is a neuro- Distribution: Worldwide. Prevention: Tin cans are Currently, not much is
bles canned in tin cans. The toxin — a toxin that attacks Magnitude: The use of tin in rare. Many tin cans are known about the amount
acids in such foods as citrus the central nervous system, advanced industrial societ- coated on the inside with of tin in the human diet.
fruits and tomato products the symptoms of which are ies has increased 14-fold enamel or other materials.
can leach tin from the in- numbness of the fingers over the last 10 years. Most cans are steel.
side of the can. Then the tin and lips followed by a loss
is ingested with the canned of speech and hearing.
food. In the digestive tract Eventually, the afflicted
tin goes through a methy- person becomes spastic,
lation process in which then coma and death fol-
nontoxic tin is converted to low.
methylated tin, which is
toxic.
Adapted from Ensminger et al. Foods & Nutrition Encyclopedia, 2nd ed., CRC Press, Boca Raton, 1994, pp. 1790-1803.
TABLE 1.11
Edible Weeds
Common Name Scientific Name Use
Maple tree Acer (many varieties) Sap can be collected and reduced by evaporation
into syrup.
Sweetflag Acorus calamus Rootstocks or stems are edible with a sweet taste.
Young shoots can be used as salad.
Quackgrass Agropyron repens L. (has many Rootstocks can be chewed or scorched to use as
other names) coffee substitute; seeds can be used for breadstuffs
and for beer.
Waterplantain Alisma spp. Root is starchy and edible; should be dried to
reduce acrid taste. Three varieties of this plant can
be toxic.
Garlic mustard Alliaria petiolata Leaf, stem, flower, and fruit are spicy and hot. If
cooked, some of this spiciness is lost. Several
plants that resemble this one are not edible.
Wild garlic Allium vineale L. Used as an herbal seasoning; there are similar
plants that are not garlic in aroma; they can be
toxic.
Pigweed Amaranthus spp. Leaves from a young plant can be eaten raw as
salad or boiled like spinach.
Serviceberry Amelanchier spp. Berries are rich and sweet; pits and leaves contain
cyanide; also called shadbush or juneberry.
Hog peanut Amphicarpaea bracteata Fleshy seedpods found underground are edible.
Ground nut Apios americana Root can be eaten raw or cooked. Seeds can also be
Medik used. Europeans use the term ground nut to refer
to peanuts. This is not the same plant.
Common burdock Arctium minus Young leaves can be eaten as salad; roots are carrot-
like in shape and can be cooked (boiled) and
eaten. A little baking soda added to the cooking
water improves tenderness and flavor. Scorched
roots can be used as a coffee substitute.
Giant reed Arundo donax L. Young shoots and rootstalks are sometimes sweet
enough to be used as a substitute for sugar cane.
Infusions of the root stocks can have some herbal
properties; local weak anesthetic and in some
instances either a hypotensive agent or
hypertensive agent (depends on dose).
Milkweed Asclepias syriaca L. Young shoots, flower buds boiled with at least two
changes of water. The plant contains cardiac
glycosides and can be toxic.
Pawpaw Asimina triloba L. The aromatic fruits are quite tasty. Seeds and bark
have pesticide properties and should be handled
with caution.
Wild oat Avena Fatua L. Seeds are similar to cultivated oats. Useful when
dried and ground as a cereal. Seeds can be
scorched and used as a coffee substitute.
Wintercress/Yellow Barbarea spp. (B. vcma; B. Young leaves and stems can be used as a salad.
rocket vulgaris)
Birches Betula spp. (Betulacea) Spring sap can be reduced to a syrup; bark can be
boiled for tea.
Mustard; black or Brassica nigra Seeds used to prepare mustard; leaves can be
yellow boiled for consumption, as can young stalks.
Bromegrass Bromus japonicus Seeds can be dried, ground, and used as cereal.
Shepherd’s purse Capsella bursa-pastoris Seeds are used as a spicy pot herb. Tender young
shoots can be eaten raw. Has a peppery taste.
Bittercress Cardamme bulbosa Roots can be ground for a horseradish substitute;
leaves and stems can be added to salad. The roots
of some species (C. bulbosa) can be toxic.

Edible Weeds
Hornbeam Carpus caroliniana Nuts are edible.
Hickory Carya spp. Nuts are edible.
Chestnut Castanea spp. Nuts are edible but are covered by a prickly coat.
Roasting improves flavor and texture.
Sandbur Cenchrus spp. Seeds and burrs can be used as cereal grains.
Lambsquarter Chenopodium album L. Leaves can be eaten raw or cooked as spinach. The
Mexican version (Mexicantea, C. ambrosioides) is
toxic.
Oxeye daisy Chrysanthemum leucanthemum Leaves and flowers can be eaten raw or cooked.
Chicory Cichorium intybus L. Leaves are good salad ingredients.
Thistles Cirsium spp. The taproot is chewy but tasty.
Wandering jew Commelina communis Leaves can be used as potherbs; flowering shoots
can be eaten raw.
Hawthorn Crataegus spp. Berries are edible, thorns can be a problem when
gathering the berries. Some species contain heart
stimulants.
Wild chervil Cryototaenia canadensis Roots can be boiled, with a taste like parsnips;
young leaves and stems can be eaten as salad; has
an herb use in stews and soups.
Nutgrass Cyperus spp. Tubers can be eaten or ground up to make a
beverage called "chufa" or "horchata."
Queen Anne’s lace, also Daucus carota L. Root can be eaten after boiling; however, because
called wild carrot it looks like poisonous hemlock, one should be
cautious.
Crabgrass Digitaria snaguinalis L. Seeds can be dried and ground for use as a cereal.
Persimmon Diospyros virginiana L. Fruits when ripe are very sweet.
Barnyard grass Echinochloa crusgalli L. Seeds can be dried and used as cereal.
Russian olive Elaegnus angustifolia L. Fruits are edible though astringent.
American burnweed Erechtites hieracifolia Leaves can be eaten raw as salad or cooked.
Redstem filaree Erodium cicutarium Tender leaves are eaten as salad; can also be used
as potherb.
Wild strawberry Fragaria virginiana Fruits are small but delicious.
Catchweed bedstraw Galium aparine Young shoots are good potherbs; leaves and stems
can be steamed and eaten as vegetable.
Wintergreen Gaultheria procumbens L. Berries, foliage, and bark can be used to make tea.
Berries can be eaten raw.
Huckleberry Gaylussacia baccata Berries can be eaten raw or cooked.
Honey locust Gleditsia triacanthos The pulp around the seeds can be used as a
sweetener. (Tender green pods can also be cooked
and eaten as a vegetable.) The tree is similar in
appearance to the Kentucky coffee tree, and the
pods of this tree cannot be eaten.
Jerusalem artichoke Helianthus tuberosus The tubers are crisp and can be used in place of
chinese chestnuts in salads; can also be cooked
and mashed.
Daylily Hemerocallis fulva L. Flower buds can be used in salads. Tubers can be
cooked and eaten. Can cause diarrhea in sensitive
people.
Foxtail barley Hordeum jubatum Seeds can be dried and used as cereal.
Touch-me-not Impatients spp. Leaves can be used for an herbal tea; leaves can be
eaten as salad; pods are also edible.
Burning bush Kochia scoparia Young shoots can be used as a potherb; seeds can
be dried and used as cereal.
Prickly lettuce Lactuca scariola L. Young leaves can be used as salad, however may
have a bitter taste.

Edible Weeds
Virginia peppergrass Lepidium virginicum Has a pungent mustard-like taste; used as a
potherb.
Bugleweed Lycorise spp. Roots can be eaten raw or cooked.
Common mallow Malva neglecta Boiled leaves have a slimy consistency much like
okra. Flower buds can be pickled; leaves can be
used as a thickener for soup.
Black medic Medicago lupulina Sprouts can be added to salads for texture; leaves
can be used as a potherb.
Mulberry Mortis spp. Berries can be eaten out of hand.
Watercress Nasturtium officinale R. Leaves can be eaten raw or used as a potherb.
American lotus Nelumbo lutea Entire plant is edible.
Yellow water lily Nuphar luteum L. Tubers when cooked are a starch substitute.
Fragrant water lily Nymphaea odorata Flower buds and young leaves can be boiled and
eaten; seeds can be dried and used as cereal.
Evening primrose Oenothera biennis L. Seeds are a source of γ linolenic acid; tap roots can
be eaten raw or cooked.
Wood sorrel Oxalis spp. Leaves can be eaten cooked or raw; seed pods can
also be eaten.
Perilla mint Perilla frutescens L. Leaves can be eaten cooked or raw.
Common reed Phragmites communis Young shoots are edible. Plant is similar to the
poisonous Arundo, so the forager should be very
careful to correctly identify the plant.
Ground cherry Physalis heterophylla Berries can be eaten cooked or raw.
(Chinese lanterns)
Pokeweed Phytolacca americana L. Young shoots can be used as a potherb; berries and
roots may be poisonous.
Plantain Plantago major L. Leaves can be used in salads.
Mayapple Podophyllum peltatum Fruits are edible raw or cooked, rest of the plant
may be poisonous.
Japanese knotweed Polygonum cuspidatum Young sprouts can be cooked and eaten like
asparagus.
Purslane Portulaca oleracea L. Young leaves can be used as a potherb or salad
ingredient.
Healall Prunella vulgaris L. Boiled and used as a potherb.
Wild cherry Prunus serotina Fruits are edible.
Kudzu Pueraria lobata Roots and leaves are edible.
Rock chestnut oak Quercus prinus L. Nuts (acorns) are edible.
Sumac Rhus glabra L. Berries are edible as are the roots; however, some
people are allergic to all parts of the plant and will
develop skin rash.
Multiflora rose Rosa multifora The hips are edible in small quantities.
Raspberry, blackberry Rubus spp. Fruits are eaten raw or used to make juice or jam.
Red sorrel Rumex acetosella L. Leaves can be eaten as salad or cooked in water.
The leaves contain a lot of oxalic acid, so small
quantities would be preferred.
Arrowhead Sagittaria latifolia Willd Roots can be eaten raw or cooked. Plants resemble
the poisonous Jack-in-the-pulpit plant so
gatherers should beware.
Elderberry Sambucus canadensis Fruits can be eaten raw or cooked.
Hardstem bulrush Scrpus acutus Muhl Roots can be boiled and eaten.
Foxtail grass Setaria spp. Seed grains can be dried and used as cereal.
Tumble mustard Sisymbrium altissimum L. All parts of the plant are edible but have a strong
mustard flavor; better used as a potherb.
Roundleaf cabriar Smilax rotundiflora L. Young tender shoots can be eaten raw. Young
leaves can be eaten as salad; roots can be used for
tea.

Edible Weeds
Sowthistle Sonchus oleraceus L. Leaves are prickly and bitter but can be used as a
potherb.
Johnson grass Sorghum halepense L. Young shoots can be eaten raw; seeds can be dried
and used as cereal; mature stalks can be ground
and the liquid extracted for use as syrup.
Chickweed Stellaria media L. Leaves can be eaten raw or cooked.
Dandelion Taraxacum officinale All parts of the plant are edible.
Stinkweed Thlaspi arvense L. All parts of the plant are edible after cooking.
Westem salsify Tragopogon dubius Scopoli Roots can be eaten after boiling; leaves, flowers,
and stems can be eaten raw.
Red clover Trifolium pratense L. Flowers can be boiled to make a broth; powdered
leaves and flowers can be used as seasoning.
Coltsfoot Tussilago farfara L. Can be used as a potherb in small amounts.
Cattail Typha spp. Roots, stalks, and spears are edible.
Stinging nettle Urtica dioica L. Can be eaten cooked or used as a potherb.
Bellwort Uvularia perfoliata L. Young shoots can be cooked and eaten; leaves are
bitter.
Blueberry, gooseberry Vaccinium, stamineun Berries can be eaten raw or used to make juice, jam,
or jelly.
Violet Viola papilionacea Purish Flowers are edible.
Wild grapes Vitis spp. Fruits can be eaten raw or cooked.
Spanish bayonnet Yucca filimentosa L. Flower buds can be eaten raw.
1 Persons using this list should be aware that individuals may differ in their responses to these plants. For some
consumers allergic reactions may be elicited. For others, there may be chemicals in the plants that elicit an
undesirable physiological effect. Still other plants, especially the water plants, may harbor parasites that may
be injurious. The serious forager should consult a plant taxonomist to be sure that the plant gathered is an
edible plant. There are may similar plants that may in fact be poisonous, while others are safe to consume.
2 Weeds are plants that grow in places where we humans do not want them to grow. As such, we may not
recognize them as food. The above plants contain edible portions. Not all parts of these plants may be useful
as human food. Some varieties, in fact, may contain toxic chemicals that if consumed in large quantities may
cause problems. A number of the plants have been identified based on their use by native Americans. These
plants can have many different names as common names. This list is an abstract provided by James A. Duke
in Handbook of Edible Weeds, CRC Press, Boca Raton, 1992, 246 pages.
TABLE 1.12
Toxic Plants
Common and Scientific Name Description; Toxic Parts Geographical Distribution Poisoning; Symptoms Remarks
Baneberry Description: Perennial growing Native woodlands of North Poisoning: Attributed to a As few as 6 berries can cause
Food Constituents
Actaea sp. to 3 ft (1 m) tall from a thick America from Canada south to glycoside or essential oil which symptoms persisting for
root; compound leaves; small, Georgia, Alabama, Louisiana, causes severe inflammation of hours.
white flowers; white or red Oklahoma, and the northern the digestive tract. Treatment may be a gastric
berries with several seeds Rockies; red-fruited western Symptoms: Acute stomach lavage or vomiting.
borne in short, terminal baneberry from Alaska to cramps, headache, increased Bright red berries attract
clusters. central California, Arizona, pulse, vomiting, delirium, children.
Toxic parts: All parts, but Montana, and South Dakota. dizziness, and circulatory
primarily roots and berries. failure.
Buckeye; Horsechestnut Description: Shrub or tree; Various species throughout the Poisoning: Toxic parts contain By making a “tea” from the
Aesculus sp. deciduous, opposite, United States and Canada; the glycoside, esculin. leaves and twigs or by eating
palmately, divided leaves with some cultivated as Symptoms: Nervous twitching the seeds, children have been
5-9 leaflets on a long stalk; red, ornamentals, others growing of muscles, weakness, lack of poisoned.
yellow, or white flowers; 2- to wild. coordination, dilated pupils, Honey collected from the
3-valved, capsule fruit; with nausea, vomiting, diarrhea, buckeye flower may also cause
thick, leathery husk enclosing depression, paralysis, and poisoning.
1-6 brown shiny seeds. stupor. Roots, branches, and fruits have
Toxic parts: Leaves, twigs, been used to stupefy fish in
flowers, and seeds. ponds.
Treatment usually is a gastric
lavage or vomiting.
Buttercup Description: Annual or Widely distributed in woods, Poisoning: The alkaloid Sap and leaves may cause
Ranunculus sp. perennial herb growing to meadows, pastures, and along protoanemonin, which can dermatitis.
16–32 in. (41–81 cm) high; streams throughout temperate injure the digestive system and Cows poisoned by buttercups
leaves alternate entire to and cold locations. ulcerate the skin. produce bitter milk or milk
compound, and largely basal; Symptoms: Burning sensation with a reddish color.
yellow flowers borne singly or of the mouth, nervousness,
in clusters on ends of seed nausea, vomiting, low blood
stalks; small fruits, 1-seeded pressure, weak pulse,
pods. depression, and convulsions.
Toxic parts: Entire plant.
41
42

Toxic Plants
Castor bean Description: Shrublike herb 4- Cultivated as an ornamental or Poisoning: Seeds, pressed cake, Fatal dose for a child is 1-3
Ricinus communis 12 ft. (1.2-3.7 m) tall; simple, oilseed crop primarily in the and leaves poisonous when seeds, and for an adult 2-8
alternate, long-stalked leaves southern part of the United chewed; contain the seeds.
with 5 to 11 long lobes which States and Hawaii. phytotoxin, ricin. The oil extracted from the seeds
are toothed on margins; fruits Symptoms: Burning of the is an important commercial
oval, green, or red, and mouth and throat, nausea, product. It is not poisonous
covered with spines; 3 vomiting, severe stomach and it is used as a medicine
elliptical, glossy, black, white, pains, bloody diarrhea, (castor oil), for soap, and as a
or mottled seeds per capsule. excessive thirst, prostration, lubricant.
Toxic parts: Entire plant, dullness of vision, and
especially the seeds. convulsions; kidney failure
and death 1–12 days later.
Chinaberry Description: Deciduous tree A native of Asia introduced as Poisoning: Most result from Six to eight berries can cause the
Melia azedarach 20–40 ft (6–12 m) tall; twice, an ornamental in the United eating pulp of berries; toxic death of a child.
pinnately divided leaves and States; common in the principle is a resinoid with The berries have been used to
toothed or lobed leaflets, southern United States and narcotic effects. make insecticide and flea
purple flowers borne in lower altitudes in Hawaii; has Symptoms: Nausea, vomiting, powder.
clusters; yellow, wrinkled, become naturalized in old diarrhea, irregular breathing,
rounded berries which persist fields, pastures, around and respiratory distress.
throughout the winter. buildings, and along fence
Toxic parts: Berries, bark, rows.
flowers, and leaves.
Death camas Description: Perennial herb Various species occur Poisoning: Due to the alkaloids The members of Lewis and
Zigadenus paniculatus resembling wild onions but the throughout the United States zygadenine, veratrine, and Clark Expedition made flour
onion odor lacking; long, and Canada; all are more or others. from the bulbs and suffered the
slender leaves with parallel less poisonous. Symptoms: Excessive symptoms of poisoning. Later
veins; pale yellow to pink salivation, muscular some pioneers were killed
flowers in clusters on slender weakness, slow heart rate, low when they mistook death
seedstalks; fruit a 3-celled blood pressure, subnormal camas for wild onions or
capsule. temperature, nausea, garlic.
Toxic parts: Entire plant, vomiting, diarrhea,
especially the bulb. prostration, coma, and
sometimes death.
Dogbane (Indian hemp) Description: Perennial herbs Various species growing Poisoning: Only suspect since it Compounds extracted from
Apocynum cannabinum with milky juice and throughout North America in contains the toxic glycoside, roots of dogbane have been
somewhat woody stems; fields and forests, and along cymarin and is poisonous to used to make a heart
simple, smooth, and streams and roadsides. animals. stimulant.
oppositely paired leaves; bell- Symptoms: In animals,
shaped, small, white to pink increased temperature and
flowers borne in clusters at pulse, cold extremities,
Food Constituents
ends of axillary stems; paired, dilation of the pupils,

long, slender seed pods. discoloration of the mouth and
Toxic parts: Entire plant. nose, sore mouth, sweating,
loss of appetite, and death.
Foxglove Description: Biennial herb with Native of Europe commonly Poisoning: Due to digitalis Foxglove has long been known
Digitalis purpurea alternate, simple, toothed planted in gardens of the component. as a source of digitalis and
leaves; terminal, showy United States; naturalized and Symptoms: Nausea, vomiting, steroid glycosides.
raceme of flowers, purple, abundant in some parts of the dizziness, irregular heartbeat, It is an important medicinal
pink, rose, yellow, or white; western United States. tremors, convulsions, and plant when used correctly.
dry capsule fruit. possibly death.

Toxic parts: Entire plant,
especially leaves, flowers, and
seeds.
Henbane Description: Erect annual or Along roads, in waste places Poisoning: Caused by the A gastric lavage of 4% tannic
Hyoscyamus niger biennial herb with coarse, across southern Canada and alkaloids, hyoscyamine acid solution may be used to
hairy stems 1–5 ft (30–152 cm) northern United States, hyoscine, and atropine. treat the poisoning.
high; simple, oblong, alternate particularly common in the Symptoms: Increased
leaves with a few, coarse teeth, Rocky Mountains. salivation, headache, nausea,
not stalked; greenish-yellow or rapid pulse, convulsions,
yellowish with purple vein coma, and death.
flowers; fruit a rounded
capsule.
Iris (Rock Mountain Iris) Description: Lilylike perennial Wet land of meadows, marshes, Poisoning: An irritating Rootstalks have such an acrid
Iris missouriensis plants often in dense patches; and along streams from North resinous substance, irisin. taste that they are unlikely to
long, narrow leaves; flowers Dakota to British Columbia, Symptoms: Burning, be eaten.
blue-purple; fruit a 3-celled Canada; south to New Mexico, congestion, and severe pain in
capsule. Arizona, and California; the digestive tract; nausea and
Toxic parts: Leaves, but scattered over entire Rocky diarrhea.
especially the root stalk. Mountain area; cultivated
species also common.
43
44

Toxic Plants
Jasmine Description: A woody, trailing, Native to the southeastern Poisoning: Alkaloids, Jasmine has been used as a
Geisemium sempervirens or climbing evergreen vine; United States; commonly geisemine, gelseminine, and medicinal herb, but overdoses
opposite, simple, lance- grown in the Southwest as an gelsemoidine found are dangerous.
shaped, glossy leaves; ornamental. throughout the plant. Children have been poisoned by
fragrant, yellow flowers; Symptoms: Profuse sweating, chewing on the leaves.
flattened 2-celled, beaked muscular weakness,
capsule fruits. convulsions, respiratory
Toxic parts: Entire plant, but depression, paralysis, and

especially the root and flowers. death possible.
Jimmyweed (Rayless Description: Small, bushy, half- Common in fields or ranges Poisoning: Contains the higher Other species of Haplopappus
goldenrod) shrub with erect stems arising around watering sites and alcohol, tremetol, which probably are equally
Haplopappus heterophyllus from the woody crown to a along streams from Kansas, accumulates in the milk of dangerous.
height of 2–4 ft (61–122 cm); Oklahoma, and Texas to cows and causes human White snakeroot also contains
narrow, alternate, sticky Colorado, New Mexico, and poisoning known as “milk tremetol, and causes “milk
leaves; clusters of small, Arizona. sickness.” sickness.”
yellow flower heads at tips of
stems.
Jimsonwood (Thornapple) Description: Coarse, weedy Naturalized throughout North Poisoning: Due to the alkaloids Sleeping near the fragrant
Datura stramonium plant with stout stems and America; common weed of hyoscyamine, atropine, and flowers can cause headache,
foul-smelling foliage; large, fields, gardens, roadsides, and hyoscine (scopolamine). nausea, dizziness, and
oval leaves with wavy pastures. Symptoms: Dry mouth, thirst, weakness.
margins; fragrant, large, red skin, disturbed vision, Children pretending the flowers
tubular, white to purple pupil dilation, nausea, were trumpets have been
flowers; round, nodding or vomiting, headache, poisoned.
erect prickly capsule. hallucination, rapid pulse,
Toxic parts: Entire plant, delirium, incoherent speech,
particularly the seeds and convulsion, high blood
leaves. pressure, coma, and possibly
death.
Lantana (Red Sage) Description: Perennial shrub Native of the dry woods in the Poisoning: Fruit contains high In Florida, these plants are
Lantana camara with square twigs and a few southeastern United States; levels of an alkaloid, lantanin considered a major cause of
spines; simple, opposite or cultivated as an ornamental or lantadene A. human poisoning.
whorled oval-shaped leaves shrub in pots in the northern Symptoms: Stomach and The foliage of lantana may also
with tooth margins; white, United States and Canada; or a intestinal irritation, vomiting, cause dermatitis.
yellow, orange, red, or blue lawn shrub in the southeastern bloody diarrhea, muscular
flowers occurring in flat- coastal plains, Texas, weakness, jaundice, and
Food Constituents
topped clusters; berry-like California, and Hawaii. circulatory collapse; death

fruit with a hard, blue-black possible but not common.
seed.
Toxic parts: All parts, especially
the green berries.
Larkspur Description: Annual or Native of rich or dry forest and Poisoning: Contains the Poisoning potential of larkspur
Delphinium sp. perennial herb 2–4 ft meadows throughout the alkaloids delphinine, decreases as it ages, but
(61–122 cm) high; finely, United States but common in delphineidine, ajacine, and alkaloids still concentrated in
palmately divided leaves on the West; frequently cultivated others. the seeds.
long stalks; white, pink, rose, in flower gardens. Symptoms: Burning sensation Seeds are used in some
blue, or purple flowers each in the mouth and skin, low commercial lice remedies.
with a spur; fruit a many- blood pressure, nervousness,
seeded, 3-celled capsule. weakness, prickling of the
Toxic parts: Entire plant. skin, nausea, vomiting,
depression, convulsions, and
death within 6 hours if eaten
in large quantities.
Laurel (Mountain laurel) Description: Large evergreen Found in moist woods and Poisoning: Contains the toxic The Mountain laurel is the state
Kalmia latifolia shrubs growing to 35 ft (11 m) along streams in eastern resinoid, andromedotoxin. flower of Connecticut and
tall; alternate leaves dark green Canada southward in the Symptoms: Increased Pennsylvania.
on top and bright green Appalachian Mountains and salivation, watering of eyes By making “tea” from the leaves
underneath; white to rose Piedmont, and sometimes in and nose, loss of energy, slow or by sucking on the flowers,
flowers in terminal clusters; the eastern coastal plain. pulse, vomiting, low blood children have been poisoned.
fruit in a dry capsule. pressure, lack of coordination,
Toxic parts: Leaves, twigs, convulsions, and progressive
flowers, and pollen grains. paralysis until eventual death.
45
46

Toxic Plants
Locoweed (Crazyweed) Description: Perennial herb Common throughout the Poisoning: Contains Locoweeds are seldom eaten by
Oxtropis sp. with erect or spreading stems; southwestern United States. alkaloidlike substances — a humans, hence they are not a
pealike flowers and stems — serious threat to livestock. serious problem.
only smaller. Symptoms: In animals, loss of There are more than 100 species
weight, irregular gait, loss of of locoweeds.
sense of direction,
nervousness, weakness, and

loss of muscular control.
Lupine (Bluebonnet) Description: Annual or Wide distribution but most Poisoning: Contains lupinine Rarely have cultivated varieties
Lupinus sp. perennial herbs; digitately common in western North and related toxic alkaloids. poisoned children.
divided, alternate leaves; pear- America; many cultivated as Symptoms: Weak pulse, slowed Not all lupines are poisonous.
shaped blue, white, red, or ornamentals. respiration, convulsions, and
yellow flowers borne in paralysis.
clusters at ends of stems; seeds
in flattened pods.
particularly the seeds.
Marijuana Description: A tall coarse, Widely naturalized weed in Poisoning: Various narcotic Poisoning results form drinking
(hashish, Mary Jane, pot, grass) annual herb; palmately temperate North America; resins but mainly the extract, chewing the plant
divided and long stalked cultivated in warmer areas. tetrahydrocannabinol (THC) parts, or smoking a so-called
leaves; small, green flowers and related compounds. “reefer” (joint).
clustered in the leaf axils. Symptoms: Exhilaration, The hallucinogenic and narcotic
Toxic parts: Entire plant, hallucinations, delusions, effects of marijuana have been
especially the leaves, flowers, mental confusion, dilated known for more than 2000
sap and resinous secretions. pupils, blurred vision, poor years.
coordination, weakness, and Laws in the United States and
stupor; coma and death in Canada restrict the possession
large doses. of living or dried parts of
marijuana.
Mescal bean Description: Evergreen shrub Native to southwestern Texas Poisoning: Contains cytisine One seed, if sufficiently chewed,
(Frijolito) or small tree growing to 40 ft and southern New Mexico; and other poisonous alkaloids. is enough to cause the death of
Sophora secundiflora (12 m) tall; stalked, alternate cultivated as ornamentals in Symptoms: Nausea, vomiting, a young child.
leaves 4–6 in. (10–15 cm) long, the southwestern United diarrhea, excitement, delirium, The Indians of Mexico and the
which are pinnately divided States. hallucinations, coma, and Southwest have used the seeds
and shiny, yellow-green above death; deep sleep lasting 2–3 in medicine as a narcotic and
and silky below when young; days in nonlethal doses. as a hallucinatory drug.
Food Constituents
violet-blue, pealike flowers; Necklaces have been made from

bright red seeds. the seeds.
particularly the seed.
Mistletoe Description: Parasitic Common on the branches of Poisoning: Contains the toxic Mistletoe is a favorite Christmas
Phoradendron serotinum evergreen plants that grow on various trees from New Jersey amines, beta- decoration.
trees and shrubs; oblong, and southern Indiana phenylethylamine and It is the state flower of
simple, opposite leaves, which southward to Florida and tyrosamine. Oklahoma.
are leathery; small, white Texas; other species Symptoms: Gastrointestinal Poisonings have occurred when
berries. throughout North America. pain, diarrhea, slow pulse, and people eat the berries or make
Toxic parts: All parts, especially collapse; possibly nausea, “tea” from the berries.
the berries. vomiting, nervousness, Indians chewed the leaves to
difficult breathing, delirium, relieve toothache.
pupil dilation, and abortion; in
sufficient amounts, death
within a few hours.
Monkshood Description: Perennial herb Rich, moist soil in meadows and Poisoning: Due to several Small amounts can be lethal.
(Wolfsbane) about 2–5 ft (61–152 cm) high; along streams from western alkaloids, including aconine Death in humans reported from
Aconitum columbianum alternate, petioled leaves Canada south to California and aconitine. eating the plant or extracts
which are palmately divided and New Mexico. Symptoms: Burning sensation made from it.
into segments with pointed of the mouth and skin; nausea, It has been mistaken for
tips; generally dark blue vomiting, diarrhea, muscular horseradish.
flowers with a prominent weakness, and spasms, weak,
hood; seed in a short-beaked irregular pulse, paralysis of
capsule. respiration, dimmed vision,
Toxic parts: Entire plant, convulsions, and death within
especially roots and seeds. a few hours.
47
48

Toxic Plants
Mushrooms Description: Common types Various types throughout North Poisoning: Depending on type Wild mushrooms are extremely
(toadstools) with central stalk, and cap; flat America. of mushroom; complex difficult to identify and are
Amanita muscaria, Amantia plates (gills) underneath cap; polypeptides such as amanitin best avoided.
verna, Chlorophyllum molybdites some with deeply ridged, and possibly phalloidin; a toxic There is no simple rule of thumb
cylindrical top rather than cap. protein in some; the poisons for distinguishing between
Toxic parts: Entire fungus. ibotenic acid, muscimol, and poisonous and nonpoisonous
related compounds in others. mushrooms — only myths and
Symptoms: Vary with type of nonsense.

mushroom but include Only one or two bites are
deathlike sleep, manic necessary for death from some
behavior, delirium, seeing species. During the month of
colored visions, feeling of December 1981, three people
elation, explosive diarrhea, were killed, and two
vomiting, severe headache, hospitalized in California after
loss of muscular coordination, eating poisonous mushrooms.
abdominal cramps, and coma
and death from some types;
permanent liver, kidney, and
heart damage from other
types.
Nightshade Description: Annual herbs or Throughout the United States Poisoning: Contains the Some individuals use the
Solanum nigrum, Solanum shrublike plants with simple and southern Canada in waste alkaloid solanine; possibly completely ripe berries in pies
eleagnifolium alternate leaves; small, white, places, old fields, ditches, saponin, atropine, and perhaps and jellies.
blue or violet flowers; black roadsides, fence rows, or edges high levels of nitrate. Young shoots and leaves of the
berries or yellow to yellow- of woods. Symptoms: Headache, stomach plant have been cooked and
orange berries depending on pain, vomiting, diarrhea, eaten like spinach.
species. dilated pupils, subnormal
Toxic parts: Prinarily the unripe temperature, shock,
berries. circulatory and respiratory
depression, possible death.
Oleander Description: An evergreen A native of southern Europe but Poisoning: Contains the One leaf of an oleander is said
Nerium oleander shrub or small tree growing to commonly cultivated in the poisonous glycosides to contain enough poison to
25 ft (8 m) tall; short-stalked, southern United States and oleandrin and nerioside, kill an adult.
narrow, leathery leaves, California. which act similar to digitalis. In Florida, severe poisoning
opposite or in whorls of 3; Symptoms: Nausea, severe resulted when oleander
white to pink to red flowers at vomiting, stomach pain, branches were used as
tips of twigs. bloody diarrhea, cold feet and skewers.
Food Constituents
Toxic parts: Entire plant, hands, irregular heartbeat, Honey made from oleander
especially the leaves. dilation of pupils, drowsiness, flower nectar is poisonous.
unconsciousness, paralysis of
respiration, convulsions,
coma, death within a day.
Peyote (Mescal buttons) Description: Hemispherical, Native to southern Texas and Poisoning: Contains mescaline, The effects of chewing fresh or
Lophophora williamsii spineless member of the cactus northern Mexico; cultivated in lophophorine and other dried “buttons” of peyote are
family growing from carrot- other areas. alkaloids. similar to those produced by
shaped roots; low, rounded Symptoms: Illusions and LSD, only milder.
sections with a tuft of yellow- hallucinations with vivid color, In some states, peyote is
white hairs on top; flower from anxiety, muscular tremors and recognized as a drug.
the center of the plant, white to twitching, vomiting, diarrhea, Peyote has long been used by
rose-pink; pink berry when blurred vision, wakefulness, the Indians and Mexicans in
ripe; black seeds. forgetfulness, muscular religious ceremonies.
Toxic parts: Entire plant, relaxation, dizziness.
especially the buttons.
Poison hemlock Description: Biennial herb with A native of Eurasia, now a weed Poisoning: The poisonous Poisoning occurs when the
(poison parsley) a hairless purple-spotted or in meadows, and along roads alkaloid coniine and other leaves are mistaken for parsley,
Conium maculatum lined, hollow stem growing up and ditches throughout the related alkaloids. the roots for turnips, or the
to 8 ft (2.4 m) tall; turniplike, United States and southern Symptoms: Burning sensation seeds for anise.
long, solid taproot; large, Canada where moisture is in the mouth and throat, Toxic quantities seldom
alternate, pinnately divided sufficient. nervousness, dyscoordination, consumed because the plant
leaves; small, white flowers in dilated pupils, muscular has such an unpleasant odor
umbrella-shaped clusters, dry; weakness, weakened and and taste.
ribbed, 2-part capsule fruit. slowed heartbeat, convulsions, Assumed by some to be the
Toxic parts: Entire plant, coma, death. poison drunk by Socrates.
primarily seeds and root.
49
50

Toxic Plants
Poison ivy (poison oak) Description: A trailing or An extremely variable native Poisoning: Skin irritation due to Almost half of all persons are
Toxicondendron radicans climbing vine, shrub, or small weed throughout southern an oil-resin containing allergic to poison ivy.
tree; alternate leaves with 3 Canada and the United States urushiol. Skin irritation may also result
leaflets; flowers and fruits with the exception of the west Symptoms: Contact with skin from indirect contact such as
hanging in clusters; white to coast; found on flood plains, causes itching, burning, animals (including dogs and
yellowish fruit (drupes). along lake shores, edges of redness, and small blisters; cats), clothing, tools, or sports
Toxic parts: Roots, stems, woods, stream banks, fences, severe gastric disturbance and equipment.
leaves, pollen, flowers, and and around buildings. even death by eating leaves or
fruits. fruit.
Pokeweed Description: Shrublike herb Native to the eastern United Poisoning: Highest Young tender leaves and stems
(Pokeberry) with a large fleshy taproot; States and southeastern concentration of poison mainly of pokeweed are often cooked
Phytolacca americana large, entire, oblong leaves Canada. in roots; contains the bitter as greens.
which are pointed; white to glycoside, saponin and Cooked berries are used for pies
purplish flowers in clusters at glycoprotein. without harm.
ends of branches; mature fruit Symptoms: Burning and bitter It is one of the most dangerous
a dark purple berry with red taste in mouth, stomach poisonous plants because
juice. cramps, nausea, vomiting, people prepare it improperly.
Toxic parts: Rootstalk, leaves, diarrhea, drowsiness, slowed
and stems. breathing, weakness, tremors,
convulsions, spasms, coma
and death if eaten in large
amounts.
Poppy (common poppy) Description: An erect annual Introduced from Eurasia and Poisoning: Crude resin from The use of poppy extracts is a
Papaver somniferum herb with milky juice, simple, widely grown in the United unripe seed capsule source of double edged sword —
coarsely toothed, or lobed States until cultivation without narcotic opium alkaloids. addictive narcotics and
leaves; showy red, white, pink, a license became unlawful. Symptoms: From unripe fruit, valuable medicines.
or purple flowers; fruit an oval, stupor, coma, shallow and Poppy seeds used as toppings
crowned capsule; tiny seeds in slow breathing, depression of on breads are harmless.
capsule. the central nervous system;
Toxic parts: Unripe fruits or possibly nausea and severe
their juice. retching (straining to vomit).
Rhododendron, azaleas Description: Usually evergreen Throughout the temperate parts Poisoning: Contains the toxic Cases of poisoning are rare in
Rhododendron sp. shrubs; mostly entire, simple, of the United States as a native resinoid, andromedotoxin. this country but
leathery leaves in whorls or and as an introduced Symptoms: Watering eyes and rhododentrons should be
alternate; snowy white to pink ornamental. mouth, nasal discharge, suspected of possible danger.
flowers in terminal clusters; nausea, severe abdominal
fruit a wood capsule. pain, vomiting, convulsions,
Toxic part: Entire plant. lowered blood pressure, lack
Food Constituents
of coordination and loss of

energy; progressive paralysis
of arms and legs until death, in
severe cases.
Rosary pea Description: A twining, more or Native to the tropics, but Poisoning: Contains the The beans are made into
(precatory pea) less woody perennial vine; naturalized in Florida and the phytotoxin abrin and tetanic rosaries, necklaces, bracelets,
Abrus precatorius alternate and divided leaves Keys. glycoside, abric acid. leis, and various toys which
with small leaflets; red to Symptoms: Severe stomach receive wide distribution.
purple or white flowers; fruit a pain, in 1-3 days, nausea, Seeds must be chewed and
short pod containing ovoid vomiting, severe diarrhea, swallowed to cause poisoning.
seeds which are glossy, bright weakness, cold sweat, Whole seeds pass through the
scarlet over 3/4 of their drowsiness, weak, fast pulse, digestive tract without causing
surface, and jet black over the coma, circulatory collapse, symptoms. One thoroughly
remaining 1/4. death. chewed seed is said to be
Toxic parts: Seeds. potent enough to kill an adult
or child.
Snow-on-the-mountain Description: A tall annual herb, Native to the western, dry Poisoning: Toxins causing Milky juice of this plant is very
Euphorbia marginata browing up to 4 ft (122 cm) plains and valleys from dermatitis and severe irritation caustic.
high; smooth, lance-shaped Montana to Mexico; of the digestive tract. Outwardly resembles a
leaves with conspicuously sometimes escapes in the Symptoms: Blistering of the poinsettia.
white margins; whorls of white eastern United States. skin, nausea, abdominal pain,
petal-like leaves border fainting, diarrhea, possibly
flowers; fruit a 3-celled, 3- death in severe cases.
lobed capsule.
Toxic parts: Leaves, stems,
milky sap.
51
52

Toxic Plants
Skunkcabbage Description: Tall, broadleaved Various species throughout Poisoning: Contains such These plants have been used for
Veratrum californicum herbs of the lily family, North America in wet alkaloids as veradridene and centuries as a source of drugs
growing to 6 ft (183 cm) high; meadows, forests, and along veratrine. and as a source of insecticide.
large, alternate pleated, streams. Symptoms: Nausea, vomiting, Since the leaves resemble
clasping, and parallel-veined diarrhea, stomach pains, cabbage, they are often
leaves; numerous whitish to lowered blood pressure, slow collected as an edible wild
greenish flowers in large pulse, reduced body plant, but with unpleasant
terminal clusters; 3-lobed, temperature, shallow results.
capsule fruit. breathing, salivation,
Toxic parts: Entire plant. weakness, nervousness,
convulsions, paralysis,
possibly death.
Tansy Description: Tall, aromatic herb Introduced from Eurasia; Poisoning: Contains an oil, Tanys and oil of tansy are
Tanacetum vulgare with simple stems to 3 ft (91 widely naturalized in North tanacetin, or oil of tansy. employed as an herbal remedy
cm) high; alternate, pinnately America; sometimes found Symptoms: Nausea, vomiting, for nervousness, intestinal
divided, narrow leaves, flower escarped along roadsides, in diarrhea, convulsions, violent worms, to promote
heads in flat-topped clusters pastures, or other wet places; spasms, dilated pupils, rapid menstruation, and to induce
with numerous small, yellow grown for medicinal purposes. and feeble pulse, possibly abortion. Some poisonings
flowers. death. have resulted from the use of
Toxic parts: Leaves, stems, and tansy as a home remedy.
flowers.
Waterhemlock Description: A perennial with Wet meadows, pastures, and Poisoning: Contains the toxic One mouthful of the
Cicuta sp. parsleylike leaves; hollow, flood plains of western and resinlike higher alcohol, waterhemlock root is reported
jointed stems and hollow, eastern United States, cicutoxin. to contain sufficient poison to
pithy roots; flowers in generally absent in the plains Symptoms: Frothing at the kill a man.
umbrella clusters; stems states. mouth, spasms, dilated pupils, Children making whistles and
streaked with purple ridges; 2- diarrhea, convulsions, peashooters from the hollow
6 ft (61-183 cm) high. vomiting, delirium, stems have been poisoned.
Food Constituents
Toxic parts: Entire plant, respiratory failure, paralysis, The waterhemlock is often
primarily the roots and young and death. mistaken for the edible wild
growth. artichoke or parsnip. However,
it is considered to be one of the
poisonous plants of the North
Temperate Zone.
White snakeroot Description: Erect perrenial From eastern Canada to Poisoning: Contains the higher Recovery from a nonlethal dose
Eupatorium rogosum with stems 1-5 ft (30-152 cm) Saskatchewan and south to alcohol, tremetol and some is a slow process, due to liver
tall; opposite oval leaves with Texas, Louisiana, Georgia, and glycosides. and kidney damage.
pointed tips and sharply Virginia. Symptoms: Weakness, nausea, Poison may be in the milk of
toothed edges, and dull on the loss of appetite, vomiting, cows that have eaten white
upper surface but shiny on the tremors, labored breathing, snakeroot — “milk sickness.”
lower surface; showy, snow constipation, dizziness,
white flowers in terminal delirium, convulsions, coma,
clusters. and death.
Taken from Ensminger et al., Foods and Nutrition Encyclopedia, 2nd ed., CRC Press, Boca Raton, 1994, pp. 1776-1785.
53
TABLE 1.13
Plants Used as Herbal Remedies1
Common and Part(s) of
Scientific Name Description Production Plant Used Reported Uses
Agrimony Small yellow Needs good soil Whole plant A tonic, alterative,
Agrimonia flowers on a long and sunshine; including diuretic, and
gryposepala spike; leaves hairy grows in New roots astringent; infusions
and at least 5 in. England and from the leaves for sore
(13 cm) long, Middle Atlantic throats; treatment of
narrow and states. kidney and bladder
pointed; leaf stones; root for
edges toothed; a jaundice.
perennial.
Aletris root Grasslike leaves in Moist locations in Leaves, roots Poultice of leaves for
(whitetube a flat rosette woods, meadows, sore breast; liquid from
stargrass) around a spike- or bogs; New boiled roots for
Aletris farinosa like stem; white to England to stomach pains, tonic,
yellow tubular Michigan and sedative, and diuretic.
flowers along Wisconsin; south
stem. to Florida and
west to Texas.
Alfalfa Very leafy plant A legume Leaves Powdered and mixed
Medicago sativa growing 1–2 ft cultivated widely with cider vinegar as a
(30–61 cm) high; in the United tonic; infusions for a
small green States. tasty drink; leaves may
leaves; bluish- also be used green.
purple flowers;
deep roots.
Aloe vera A succulent plant A semidesert plant Mucilaginous Effective on small cuts
Aloe barbadensis with leathery which grows in juice of the and sunburn; speeds
sword-shaped Mexico and leaves healing; manufactured
leaves, 6–24 in. Hawaii; product for variety of
(15–61 cm) long. temperature must cosmetic purposes.
remain above 50°F
(10°C); can be a
house plant.
Angelica Shrub growing to 8 Grows in rich low Roots, seeds Small amount of dried
Angelica ft (2.4 m) high; soil near streams root or seeds for relief
atropurpurea stem purplish and swamps and of flatulence; roots for
with 3 toothed in gardens; from the induction of
leaflets at tip of New England vomiting and
each leaf stem; west to Ohio, perspiration; roots for
white or greenish Indiana, Illinois, treatment of toothache,
flowers in clusters and Wisconsin; bronchitis,
at end of each south to rheumatism, gout,
stalk. Delaware, fever, and to increase
Maryland, West menstrual flow.
Virginia, and
Kentucky.
Anise (Anise seed) Annual plant, 1–2 ft Grown all over the Seed As a hot tea to relieve
Pimpinella anisum (30–61 cm) high; world; grows wild flatulence or for colic.
belongs to carrot in countries
family; small around the
white flowers on Mediterranean;
long hairy stalk; much is imported
lower leaves egg- to United States.
shaped; upper
leaves feathery.

Asafetida A coarse plant Indigenous to Gummy resin As an antispasmodic; to
Ferula sp. growing to 7 ft (2.1 Afghanistan, but from the root ward off colds and flu
m) high with some species grow by wearing in a bag
numerous stem in other Asiatic around the neck.
leaves; pale green- countries.
yellow flowers;
flowers and seeds
borne in clusters
on stalks; large
fleshly root;
tenacious odor.
Bayberry (Southern Perennial shrub Grows in coastal Root bark, Decoction of root bark
wax myrtle) growing to 30 ft regions from New leaves, stems to treat uterine
Myrica cerifera (9.2 m) high; waxy Jersey, Delaware hemorrhage, jaundice,
branchlets; and Maryland to dysentery, and
narrow evergreen Florida, Alabama, cankers; leaves and
leaves tapering at Mississippi, and stems boiled and used
both ends; Arkansas. to treat fevers;
yellowish flowers; decoction of boiled
fruits are grayish leaves for intestinal
berries. worms.
Bearberry Creeping evergreen Grows in well- Leaves As a diuretic; also
Arctostaphylos shrub with stems drained soils at boiled infusions used
uva-ursi up to 6 in. (15 cm) higher altitudes; as a drink to treat
high; reddish from Oregon, sprains, stomach
bark; bright green Washington, and pains, and urinary
leaves, 1 in. (3 cm) California, to problems; poison oak
long; white Colorado and inflammations treated
flowers with red New Mexico. with leaf decoction by
markings, in pioneers.
clusters; smooth
red fruits.
Blackberry Shrubby or viny Grows wild or in Roots, root Infusion made from
(brambleberry, thorny perennial; gardens bark, leaves, roots used to dry up
dewberry, numerous species; throughout the fruit runny noses; infusion
raspberry) large white United States; from root bark to treat
Rubus flowers; red or wild in old fields, dysentery; fruit used
black fruit. waste areas, forest to treat dysentery in
borders, and children; leaves also
pastures. used in similar
manner.
Black cohosh Perennial shrub Grows throughout Rhizomes, Infusion and decoctions
Cimicifuga growing to 9 ft (2.7 eastern United roots used to treat sore
racemosa m) or more in States; commercial throat, rheumatism,
height; leaf has 2 supply from Blue kidney trouble, and
to 5 leaflets; plant Ridge Mountains. general malaise; also
topped with spike used for “women’s
of slender ailments” and malaria.
candlelike, white
or yellowish
flowers; rhizome
gnarled and
twisted.

Black Walnut A tree growing up Native to a large Bark, nut husk, Inner bark used as mild
Juglans nigra to 120 ft (36.6 m) section of the rich leaves laxative; husk of nut
high; leaflets woods of eastern used for treating
alternate 12–23 per and midwestern intestinal worms,
stem, finely United States. ulcers, syphilis, and
toothed and about fungus infections; leaf
3–3.5 in. (8–9 cm) infusion for bedbugs.
long; nut occurs
singly or in clusters
with fleshy,
aromatic husk.
Blessed thistle Annual plant Grows along Leaves and Infusions from leaves
Cnicus benedictus growing to 2 ft (61 roadsides and in flowering and tops for cancer
cm) high; spiny waste places in tops in full treatment, to induce
tooth, lobed eastern and parts bloom, seeds sweating, as a diuretic,
leaves; many of southwestern to reduce fever, and for
flowered yellow United States. inflammations of the
heads. respiratory system;
infusion of tops as
Indian contraceptive;
seeds induce vomiting.
Boneset Perennial bush Commonly found Leaves, Infusions made from
Eupatorium growing to 5 ft (1.5 in wet areas such flowering leaves used for
perfoliatum m) in height; as swamps, rich tops laxative and treatment
heavy stems with woods, marshes, of coughs and chest
leaves opposite; and pastures; illnesses — a cold
purplish to white grows from remedy; Negro slaves
flowers borne in Canada to Florida and Indians used it to
flat heads. and west to Texas treat malaria.
and Nebraska.
Borage Entire plant not Introduced in Leaves Most often used as an
Borago officinalis over 1 ft (30 cm) United States from infusion to increase
high; nodding Europe; sweating, as a diuretic,
heads of starlike occasionally or to soothe intestinal
flowers grow from grows in waste tract; can be applied to
clusters of hairy areas in northern swellings and
obovate leaves. states; cultivated inflamed areas for
widely in gardens. relief.
Buchu Low shrubs with Grown in rich soil Dried leaves Prepared as tincture or
Rutaceae angular branches in warm climate of infusion; used for
and small leaves South Africa. genito-urinary
growing in diseases, indigestion,
opposition; edema, and early
flowers from stages of diabetes.
white to pink.
Buckthorn Deciduous tree Grows usually with Bark, fruit Bark used as a laxative
Rhamnus growing to 25 ft conifers along and tonic; fruit
purshiana (7.6 m) high; canyon walls, rich (berries) used as a
leaves 2–6 in. bottom lands, and laxative.
(5–15 cm) long; mountain ridges
flowers small in western United
greenish yellow; States.
fruit globular and
black, about 1/4
in. (6 mm) across.

Burdock Biennial or Grows in Root Infusion of roots for
Arctium minus perennial growing wastelands, fields, coughs, asthma, and to
5–8 ft (1.5–2.4 m) and pastures stimulate
high; large leaves throughout the menstruation; tincture
resembling United States. of root for rheumatism
rhubarb; tube- and stomachache.
shaped white and
pink to purple
flowers in heads;
brown bristled
burrs contain
seeds.
Calamus Perennial growing Grows in swamps, Rhizomes Root chewed to clear
(Sweet flag) 3–5 ft (1.0–1.5 m) edges of streams phlegm (mucous) and
Acorus calamus high; long narrow and ponds from ease stomach gas;
leaves with sharp New England infusions to treat
edges; aromatic west to Oregon stomach distress;
leaves; flower and Montana, and considered useful as
stalk 2–3 in. (3–8 from Texas east to tonic and stimulant.
cm) long and Florida and north.
clublike; greenish-
yellow flowers.
Catnip Perennial growing Grows wild along Entire plant Infusions for treating
Nepeta cataria to 3 ft (1 m) in fences, roadsides, colds, nervous
height; stem waste places, and disorders, stomach
downy and streams in ailments, infant colic,
whitish; leaves Virginia, and hives; smoke
heart-shaped Tennessee, West relieves respiratory
opposite coarsely Virginia, Georgia, ailments; poultice to
toothed and 2–3 New England, reduce swellings.
in. (3–8 cm) long; Illinois, Indiana,
tubular whitish Ohio, New
with purplish Mexico, Colorado,
marked flowers in Arizona, Utah,
compact spikes. and California;
readily cultivated
in gardens.
Celery A biennial Cultivated in Seeds As an infusion to relieve
Apium graveolens producing flower California, rheumatism and
stalk second year; Florida, Michigan, flatulence (gas); to act
terminal leaflet at New York, and as a diuretic; to act as a
end of stem; fruit Washington. tonic and stimulant; oil
brown and round. from seeds used
similarly.

Chamomile Low growing, Cultivated in Leaves, Powdered and mixed
Anthemis nobilis pleasantly strong- gardens; some flowers with boiling water to
scented, downy, wild growing stimulate stomach, to
and matlike which escaped remedy nervousness in
perennial; from gardens. women, and stimulate
daisylike flowers menstrual flow, also a
with white petals tonic; flowers for
and yellow center. poultice to relieve
pain; chamomile tea
known as soothing,
sedative, completely
harmless.
Chaparral Shrubby perennial Grows in dry rock Flowering tips Infusions act as laxative;
Croton corynbulosus plant of the areas from Texas some claims as cancer
Spurge family. west. treatment.
Chickweed Annual growing Grows in shaded Entire plant in Poultice made to treat
Stellaria media 12–15 in. (30–38 areas, meadows, full bloom sores, ulcers,
cm) high; stems wasteland, infections, and
matted to cultivated land, hemorrhoids.
somewhat thickets, gardens,
upright; upper and damp woods
leaves vary but in Virginia to
lower leaves South Carolina
ovate; white, small and southeast.
individual
flowers.
Chicory Easily confused Introduced from Roots, leaves No great medicinal
Cichorium intybus with its close Europe, now value; some mention
relative the common wild of diuretic, laxative,
dandelion; in plant in United and tonic use; mainly
bloom bears blue States; some added to give coffee
or soft pink grown in gardens. distinctive flavor.
blooms not
resembling
dandelion.
Cinnamon An evergreen bush A native plant of Sri Bark Treatment for
Cinnamomum or tree growing to Lanka, India, and flatulence, diarrhea,
zeylanicum 30 ft (9 m) high. Malaysia; tree vomiting, and nausea.
kept pruned to a
shrub; bark of
lower branches
peeled and dried.
Cleaver’s herb Annual plant; weak Grows in rich Entire plant To increase urine
(Catchweed reclining bristled woods, thickets, during formation; to stimulate
bedstraw) stem with hairy seashores, waste flowering appetite; to reduce
Galium aparine joints; leaves in areas, and shady fever; to remedy
whorls of 8; white areas from vitamin C deficiency.
flowers in broad, Canada to Florida
flat cluster; and west to Texas.
bristled fruit.

Cloves Dried flower bud of Tree native to Flower bud To promote salivation
Syzygium a tropical tree Molucca, but and gastric secretion;
aromaticum which is a 30-ft (9 widely cultivated to relieve pain in
m) high red in tropics; flower stomach and
flowered bud picked before intestines; applied
evergreen. flower opens and externally to relieve
dried. rheumatism, lumbago,
toothache, muscle
cramps, and neuralgia;
clove oil used, too;
infusions with clove
powder relieves
nausea and vomiting.
Colt’s foot (Canada Low growing Found in moist Roots, leaves Infusion of root to
wild ginger) stemless woods from relieve flatulence;
Asarum canadense perennial; heart- Maine to Georgia powdered root to
shaped leaves; and west to Ohio. relieve flatulence;
flowers near root induce sweating, and
are brown and to relieve aching head
bell-shaped. and eyes; leaves
substitute for ginger.
Comfrey A perennial which Prefers a moist Roots, leaves Numerous uses
Symphytum reaches about 2 ft environment; a including treatments
officinale (61 cm) in height; European plant for pneumonia,
leaves are large now naturalized coughs, diarrhea,
and broad at base in the United calcium deficiency,
but lancelike at States. colds, sores, ulcers,
terminal; fine hair arthritis, gallstones,
on leaves; tail- tonsils, cuts and
shaped head of wounds, headaches,
white to purple hemorrhoids, gout,
flowers at burns, kidney stones,
terminal. anemia, and
tuberculosis; used as a
poultice, infusion,
powder, or in capsule
form.
Dandelion Biennial growing Weed throughout Flowers, roots, Root uses include
Taraxacum 2–12 in. (5–30 cm) the United States; green leaves diuretic, laxative,
officinale high; leaves the bane of lawns. tonic, and to stimulate
deeply serrated appetite; infusion from
forming a basal flower for heart
rosette in spring; troubles; paste of green
yellow flower but leaves for bruises.
turns to gray upon
maturing.
Echinacea (Purple Perennial from 2–5 Grows wild on Roots Treatment of ulcers and
echinacea) ft (0.6–1.5 m) high; road banks, boils, syphilis,
Echinacea purpurea alternate lance- prairies, and dry, snakebites, skin
shaped leaves; leaf open woods in diseases, and blood
margins toothed; Ohio to Iowa, poisoning; used as
top leaves lack south to powder and in
stems; purple to Oklahoma, capsules.
white flower. Georgia, and
Alabama.

Eucalyptus Tall, fragrant tree Native to Australia Leaves and oil Antiseptic value;
Eucalyptus growing up to 300 but grown in other distilled from inhaled freely for sore
globulus ft (92 m) high; semitropical and leaves throat; asthma relief;
reddish-brown warm temperate local application to
stringy bark. regions. ulcers; used on open
wounds.
Eyebright (Indian Branching annual Roadside weed of Entire plant in Treatment of whooping
tobacco) growing to 3 ft (1 eastern United full bloom or cough, asthma,
Lobelia inflata m) high with States, west to when seeds epilepsy, pneumonia,
leaves 1–3 in. (3–8 Kansas. are formed hysteria, and
cm) long; small convulsion; alkaloid
violet to pinkish- extracted for use in
white flowers in antismoking
axils of leaves; preparations.
seed capsules at
base of flower
containing many
tiny brown seeds.
Fenugreek Annual plant Native to the Seed Poultice for wounds;
Trigonella similar to clover in Mediterranean gargle for sore throat.
foenum-graceum size. regions and
northern India;
widely cultivated;
easily grown in
home gardens.
Flax (Linseed) Herbaceous Originated in Seed Ground flaxseed mixed
Linum annual; slender Mediterranean with boiling water for
usitatissimum upright plant with region; cultivated poultice on burns,
narrow leaves and widely for fiber boils, carbuncles, and
blue flowers; and oil. sores; internally as a
grows to about 2 ft laxative.
(61 cm) high.
Garlic Annual plant Throughout the Entire plant Fresh poultice of the
Allium sativum growing to 12 in. United States when in mashed plant for
(30 cm) high; long, under cultivation; bloom; bulbs treating snake bite,
linear, narrow some wild. hornet stings, and
leaves; bulb scorpion stings; eaten
composed of to expel worms, treat
several bulblets. colds, coughs,
hoarseness, and
asthma; bulb
expressed against the
gum for toothache.
Gentian (Sampson Perennial with Grows wild in Rhizomes and Treatment of
snakeroot) stems growing swampy areas roots indigestion, gout, and
Gentiana villosa 8–10 in. (20–25 cm) Florida west to rheumatism; induction
high; opposite Louisiana, north of vomiting; aid to
ovate, lance- to New Jersey, digestion; a tonic.
shaped leaves; Pennsylvania,
pale blue flowers. Ohio, and Indiana.
Ginger Perennial plant; Native to Rhizome An expectorant;
Zingiber officinale forms irregular- southeastern Asia; treatment of flatulence,
shaped rhizomes now grown all colds, and sore throats.
at shallow depth. over tropics.

Ginseng Hollow stems solid Grows in eastern Root As a tonic and
Panax quinquefolia at nodes; leaves Asia, Korea, stimulant; treatment of
alternate; root China, and Japan; convulsions, dizziness,
often resembles some grown in vomiting, colds,
shape of a man; United States. fevers, headaches, and
small, rheumatism.
inconspicuous
flowers; vivid,
shiny, scarlet
berries.
Goldenrod Grows 18–36 in. Grows throughout Leaves Infusions from dried
Solidago odora (46–91 cm) high the United States. leaves as aromatic
with narrow stimulant and a
leaves scented like diuretic.
anise;
inconspicuous
head with 6–8
flowers.
Goldenseal Perennial growing Grows in rich, Roots, leaves, Root infusion as an
Hydrastis canadensis to about 1 ft (30 shady woods of stalks appetite stimulant and
cm) high; one southeastern and tonic; root powder for
stem with 5–7 midwestern open cuts and wounds;
lobed leaves near United States; chewing root for
top; several single grown under mouth sores; leaf
leafstalks topped cultivation in infusion for liver and
with petalless Washington. stomach ailments.
flowers;
raspberrylike fruit
but inedible.
Guarana Climbing shrub of Grows in South Seeds Stimulant; seeds high in
Paullinia cupana the soapberry America, caffeine.
family; yellow particularly Brazil
flowers; pear- and Uruguay.
shaped fruit; seed
in 3-sided, 3-celled
capsules.
Hawthorn Hardy shrub or tree Originally grown Berry Tonic for heart ailments
Crataegus oxycantha depending upon throughout such as angina
growth England as pectoris, valve defects,
conditions; small, hedges; also rapid and feeble heart
berry fruit; cup- grows wild; some beat, and
shaped flowers introduced in the hypertrophied heart;
with 5 parts; United States. reverses
thorny stems. arteriosclerosis.
Hop Twining, perennial Grows throughout Fruit (hops) Straight hops or powder
Humulus lupulus growing 20 ft (6 the United States; used; hot poultice of
m) or more; 3 often a cultivated hops for boils and
smooth-lobed crop. inflammations;
leaves 4–5 in. treatment of fever,
(10–13 cm) long; worms, and
membranous, rheumatism; as a
conelike fruit. diuretic; as a sedative.

Horehound (White Shrub growing to 3 Grows wild Leaves and Decoctions to treat
horehound) ft (1 m) in height; throughout most small stems; coughs, colds, asthma,
Marrubium vulgare fuzzy ovate-round of United States in bark and hoarseness; other
leaves which are pastures, old uses include treatment
whitish above and fields, and waste for diarrhea,menstrual
gray below; places, except in irregularity, and
foliage aromatic arid southwest. kidney ailments.
when crushed.
Huckleberry Shrub or tree Grows wild in Leaves, root Decoctions of leaves
(Sparkleberry) growing to 25 ft woods, clearings, bark, berries and root bark to treat
Vaccinium arboreum (7.6 m) high; sandy and dry sore throat and
leathery; shiny, woods in Virginia, diarrhea; drink from
thick leaves; white Georgia, Florida, berry for treating
flowers; black Mississippi, chronic dysentery.
berries; other Indiana, Illinois,
species. Missouri, Texas,
and Oklahoma.
Hyssop Hardy, fragrant, Grows in various Leaves Infusions for colds,
Hyssopus bushy plants parts of Europe coughs, tuberculosis,
officinalis belonging to the including the and asthma; an
mint family; stem Middle East; some aromatic stimulant;
woody; leaves grown in United healing agent for cuts
hairy, pointed, States. and bruises.
and about 1/2 in.
(20 mm) long; blue
flowers in tufts.
Juniper Small evergreen Widely distributed Fruit (berries) Used as a diuretic, to
(Common juniper) shrub growing from New Mexico induce menstruation,
Juniperus 12–30 ft (3.7–9.2 to Dakotas and to relieve gas, and to
communis m) high; bark of east; dry areas. treat snake bites and
trunk reddish- intestinal worms.
brown and tends
to shred; needles
straight and at
right angles to
branchlets; dark,
purple, fleshy
berrylike fruit.
Lemon balm Persistent perennial Wild in much of the Leaves Infusion used as a
Melissa officinalis growing to 1 ft (30 United States; carminative,
cm) high; light grown in gardens. diaphoretic, or
green, serrated febrifuge.
leaves; lemon
smell and taste to
crushed leaves.
Licorice (Wild Erect perennial Grows wild on Root Root extract to help
licorice) growing to 3 ft (1 prairies, lake Caution: bring out phlegm
Glycyrrhiza lepidota m) high; pale shores, and Licorice raises (mucus); treatment of
yellow to white railroad right-of- the blood stomach ulcers,
flowers at end of ways throughout pressure of rheumatism, and
flower stalks; much of the some people arthritis; root
brown seed pods United States. dangerously decoctions for inducing
resemble high, due to menstrual flow,
cockleburs. the retention treating fevers, and
of sodium. expulsion of afterbirth.

Marshmallow Stems erect and 3–4 Introduced into Root Primarily a demulcent
Althaea officinalis ft (0.9–1.2 m) high United States from and emollient; used in
with only a few Europe; now cough remedies; good
lateral branches; found on banks of poultice made from
roundish, ovate- tidal rivers and crushed roots.
cordate leaves 2–3 brackish streams;
in. (5–8 cm) long grew wild in salt
and irregularly marshes, damp
toothed at margin; meadows, by
cup-shaped, pale- ditches, by the sea,
colored flowers. and banks of tidal
rivers from
Denmark south.
Motherwort Perennial growing Grows wild in Entire plant Used as a stimulant,
Leonurus cardiaca 5–6 ft (1.5–1.8 m) pastures, waste above ground tonic, and diuretic;
high; lobed, places, and road- Europeans used for
dented leaves, 5 sides from asthma and heart
in. (13 cm) long; northeastern palpitation; usually
very fuzzy white states west to taken as an infusion.
to pink flowers. Montana and
Texas, south to
North Carolina
and Tennessee.
Mullien At base a rosette of Grows wild Leaves, roots, Infusions of leaves to treat
(Aaron’s rod) woody, lance- throughout the flowers colds and dysentery;
Verbascum thapsus shaped, oblong United States in dried leaves and flowers
leaves with a dry fields, serve as a demulcent
diameter of up to meadows, and emollient; leaves
2 ft (61 cm); yellow pastures, rocky or smoked for asthma
flowers along a gravelly banks, relief; boiled roots for
clublike spike burned areas, etc. croup; oil from flowers
arising from the for earache; local
rosette to a height applications of leaves
of up to 7 ft (2.1 for hemorrhoids,
m). inflammations, and
sunburn.
Nutmeg Evergreen tree Native to Spice Seed For the treatment of
Muristica fragrans growing to about Islands of nausea and vomiting;
25 ft (7.6 m) high; Indonesia; now grated and mixed with
grayish-brown, cultivated in other lard for hemorrhoid
smooth bark; fruit tropical areas. ointment.
resembles yellow
plum, the seed of
which is known as
nutmeg.
Papaya Small tree seldom Originated in South Leaves Dressing for wounds,
Carica papaya above 20 ft (6.1 m) American tropics; and aid for digestion;
high; soft, spongy now cultivated in contains proteolytic
wood; leaves as tropical climates. enzyme, papain, used
large as 2 ft (61 as a meat tenderizer.
cm) in diameter
and deeply cut
into 7 lobes; fruit
oblong and dingy
green-yellow.

Parsley Biennial which is Originated in the Leaves, seeds, As diuretic with
Petroselinum usually grown as Mediterranean roots aromatic and
crispum an annual; finely area; now grown stimulating properties.
divided, often worldwide.
curled, fragrant
leaves.
Passion flower Perennial vine Grows wild in West Flowering and Crushed parts for
(Maypop passion- growing to 30 ft Indies and fruiting tops poultice to treat
flower) (9.2 m) in length; southern United bruises and injuries;
Passiflora incarnata alternate leaves States; cultivated other uses include
composed of 3–5 in many areas. treatment of
finely toothed nervousness,
lobes; showy, insomnia, fevers, and
vivid, purple, asthma.
flesh-colored
flowers; smooth,
yellow ovate fruit
2–3 in. (5–8 cm)
long.
Peppermint Perennial growing Originated in Flowering Infusions for relief of
Mentha piperita to about 3.5 ft (1 temperate regions tops, leaves flatulence, nausea,
m) high; dark, of the Old World headache, and
green, toothed where most is still heartburn; fresh leaves
leaves; purplish grown; grows in rubbed into skin to
flowers in spike- shady damp areas relieve local pain;
like groups. in many areas of extracted oil contains
the United States; medicinal properties.
grown in gardens.
Plantain Low perennial with Grows wild Leaves, seeds, Infusion of leaves for a
Plantago sp. broad leaves; throughout the root tonic; seeds for
flowers on erect United States in laxative; soaking seeds
spikes. poor soils, fields, provides sticky gum
lawns, and edges for lotions; fresh,
of woods. crushed leaves to
reduce swelling of
bruised body parts;
fresh, boiled roots
applied to sore
nipples.
Pleurisy root Leafy perennial Grows in sandy, Root Small doses of dried
(Butterfly growing to 3 ft (1 dry soils; pastures, root as a diaphoretic,
milkweed) m) high; alternate roadsides, and diuretic, expectorant,
Asclepias tuberosa leaves which are gardens; south to and alternative;
2–6 in. (5–15 cm) Florida and west ground roots fresh or
long and narrow; to Texas and dried for poultice to
bright orange Arizona. treat sores.
flowers in a
cluster; root
spindle-shaped
with knotty
crown.

Queens delight Perennial growing Grows wild in dry Root Treatment of infectious
Stillingia sylvatica to 3 ft (1 m) high; woods, sandy diseases.
contains milky soils, and old
juice; leathery, fields; Virginia to
fleshy, stemless Florida, Kansas,
leaves; yellow and Texas, north
flowers. to Oklahoma.
Red clover Biennial or Throughout United Entire plant in Infusions to treat
Trifolium pratense perennial legume States; some wild, full bloom whooping cough;
less than 2 ft (61 some cultivated. component of salves
cm) high; 3 oval- for sores and ulcers;
shaped leaflets flowers as sedative; to
form leaf; flowers relieve gastric distress
globe-shaped and and improve the
rose to purple appetite.
colored.
Rosemary Low-growing Native to Leaves Used as a tonic,
Rosmarinus perennial Mediterranean astringent,
officinalis evergreen shrub; region; now diaphoretic, stimulant,
leaves about 1 in. cultivated in most carminative, and
(3 cm) in height; of Europe and the nervine.
orange-yellow Americas.
flowers; white,
shiny seeds.
Saffron Annual with Wild in Flowers, seeds, Paste of flowers and
(Safflower) alternate spring Afghanistan; entire plant in water applied to boils;
Carthamus leaves; grows to 3 cultivated in the bloom flowers soaked in
tinctorius ft (1 m) in height; United States, water to make a drink
orange-yellow primarily in to reduce fever, as a
flowers; white, California. laxative, to induce
shiny seeds. perspiration, to
stimulate menstrual
flow, and to dry up
skin symptoms of
measles.
Sage (Garden sage) Fuzzy perennial Originated in the Leaves Treatment for wounds
Salvia officinalis belonging to the Mediterranean and cuts, sores,
mint family; area where it coughs, colds, and sore
leaves with grows wild and is throat; infusions used
toothed edges; cultivated; grown as a laxative and to
terminal spikes throughout the relieve flatulence;
bearing blue or United States, major use for
white flowers in some wild. treatment of
whorls. dyspepsia.
Sarsaparilla Climbing Grown in tropical Root Primarily an alterative
Smilax sp. evergreen shrub areas of Central for colds and fevers; to
with prickly and South relieve flatulence; best
stems; leaves America and in used as an infusion.
round to oblong; Japan and China.
small, globular
berry for fruit.

Sassafras Tree growing to 40 Originated in New Root bark Sassafras was formerly
Sassafras album ft (12.2 m) high; World; grows in used for medical
leaves may be 3- New England, purposes, but the use
lobed, 2-lobed, New York, Ohio, of the roots was
mitten-shaped, or Illinois, and banned by the FDA
unlobed; Michigan, south to because of their
yellowish-green Florida and Texas; carcinogenic qualities.
flowers in clusters; grows along
pea-sized, 1- roadsides, in
seeded berries in woods, along
fall. fences, and in
fields.
Saw palmetto Low-growing fan Grows in warm, Fruit (berries) To improve digestion; to
Serenoa serrulata palm; whitish swampy, low treat respiratory
bloom covers areas near the infections; as a tonic
sawtoothed, green coast. and as a sedative.
leaves; flowers in
branching
clusters; fruit
varies in size and
shape.
Senna (Wild senna) Perennial growing Grows along Leaves Infusions primarily
Cassia marilandica to 6 ft (1.8 m) in roadsides and in employed as a
height; alternate thickets from laxative.
leaves with Pennsylvania to
leaflets in pairs of Kansas and Iowa,
5–10; bright south to Texas and
yellow flowers. Florida.
Skullcap Perennial growing Native to most Entire plant in Powdered plant
Scutellaria lateriflora 1–2 ft (30–61 cm) sections of the bloom primarily a nervine.
high; toothed, United States;
lance-shaped prefers moist
leaves; blue or woods, damp
whitish flowers. areas, meadows,
and swampy
areas.
Spearmint Perennial Throughout the Above ground Primarily a carminative;
Mentha spicata resembling other United States in parts administered as an
mints; grows to 3 damp places; infusion through
ft (1 m) in height; cultivated in extracted oils.
pink or white Michigan,
flowers borne in Indiana, and
long spikes. California.
Tansy Perennial growing Grown or escaped Leaves and Infusions used as
Tanacetum vulgare to 3 ft (1 m) in into the wild in flowering stomachic,
height; pungent much of the tops emmenagogue, or to
fernlike foliage United States. expel intestinal
with tops of worms; extracted oil
composite heads induced abortion often
of buttonlike with fat results;
flowers. poultice for sprains
and bruises.

Valerian Coarse perennial Native to Europe Root As a calmative and as a
Valeriana officinalis growing to 5 ft and Northern carminative.
(1.5 m) high; Asia; cultivated in
fragrant, pinkish- the United States.
white flowers
opposite pinnate
leaves.
Witch hazel Crooked tree or Found in damp Leaves, bark, Twigs, leaves, and bark
Hamamelis shrub 8–15 ft woods of North twigs basis for witch hazel
virginiana (2.4–4.6 m) in America from extract which is
height; roundish Nova Scotia to included in many
to oval leaves; Florida and west lotions for bruises,
yellow, threadlike to Minnesota and sprains, and shaving;
flowers; fruits in Texas. bark sometimes
clusters along the applied to tumors and
stem eject shiny, skin inflammations;
black seeds. some preparations for
treating hemorrhoids.
Yerba santa Evergreen shrub Part of flora of the Leaves As an expectorant;
Eriodictyon with lance-shaped west coast of the recommended for
californicum leaves. United States. asthma and hay fever.
Adapted from Ensminger et al., Foods and Nutrition Encyclopedia, 2nd ed., CRC Press, Boca Raton, 1994, pp.
1430–1441.
1 Herbal remedies can vary widely in potency. Some may be toxic. These remedies should not be used without
the advice of a physician.
TABLE 1.14
Vitamin Terminology
Vitamins were named according to a) their function; b) their location; c) the order in which they were discovered;
or d) combinations of a, b, or c. Some of these names became obsolete as their proposed functions or their isolated
structures were found to duplicate already named and described vitamins. Obsolescence also occurred as research
showed that certain of these compounds were not needed dietary factors but were synthesized by the body in
needed amounts.
Name Comment
Vitamin A A number of compounds have vitamin A activity but differ in biopotency. All trans retinol
is the standard, and the activity of other compounds can be stated as retinol equivalents.
This includes the aldehyde (retinal), acid (retinoic acid), and provitamin (carotene) forms.
Vitamin B Although orginally thought to be a single compound, researchers found that eight major
compounds comprised this "vitamin."
Vitamin B complex A group of vitamins; includes thiamin, riboflavin, niacin, pyridoxine (3 forms),
pantothenic acid, biotin, cyanocobalamin (B12), folacin.
Vitamin B1 Aneurin; antineuritic factor. Obsolete synonym for thiamin.
Vitamin B2 Lactoflavin, Ovoflavin. Obsolete synonyms for riboflavin.
Vitamin B3 Antipellagra factor. Obsolete synonym for niacin.
Vitamin B4 Not proven to have vitamin activity; thought to be a mixture of arginine, glycine,
riboflavin, and pyridoxine.
Vitamin B5 Probably identical to niacin.
Vitamin B6 Synonym for pyridoxine, pyridoxal, pyridoxamine.
Vitamin B7 Not proven to have vitamin activity;1 sometimes referred to as Vitamin I, a factor which
improves food digestibility in pigeons.

Vitamin Terminology
Name Comment
Vitamin B8 1
Not proven to have vitamin activity; found to be adenylic acid.
Vitamin B10, B11 An unrefined mixture of folacin and cyanocobalamin; obsolete term.
Vitamin B12 Cyanocobalamin; B12a is aquacobalamin; B12b is hydroxocobalamin; B12c is nitritocobalamin.
Vitamin B13 Orotic acid; a metabolite of pyrimidine metabolism; not considered a vitamin.1
Vitamin B15 Synonym for "pangamic acid" a compound of no known biologic value; not a vitamin.1
Vitamin B17 Synonym for laetrile; a cyanogenic glycoside of no known biologic value; not a vitamin.1
Vitamin Bc Obsolete term for pteroylglutamic acid; a component of folacin.
Vitamin Bp A compound which prevents perosis in chicks, can be replaced by choline and manganese.
Vitamin Bf Shown to be carnitine.
Vitamin Bx Probably a mixture of pantothenic acid and p-aminobenzoic acid.
Vitamin C Synonym for ascorbic acid.
Vitamin C2 Unrecognized, unconfirmed compound purported to have antipneumonia activity; also
called vitamin J.
Vitamin D Antirachitic factor; a group of sterols (the calciferols) that serve to enhance bone
calcification.
Vitamin D2 Ergocalciferol; one of the D vitamins from plant sources.
Vitamin D3 Cholecalciferol; one of the D vitamins from animal sources.
Vitamin E A group of tocopherols that have an important function in the antioxidant system;
suppresses free radical formation.
Vitamin F Obsolete term for the essential fatty acids (linoleic and linolenic acids).
Vitamin G Obsolete term for riboflavin before riboflavin and niacin were recognized as separate
vitamins.
Vitamin H Obsolete term for biotin.
Vitamin I Obsolete term for a mixture of B vitamins.
Vitamin K A group of fat soluble compounds that function in the post translational carboxylation of
the glutamic acid residues of prothrombin.
Vitamin K1 Phylloquinone; vitamin K of plant origin.
Vitamin K2 Menaquinone; vitamin K of animal origin.
Vitamin K3 Menadione; synthetic vitamin K.
Vitamin L1 Unrecognized factor which may be related to anthranitic acid and which has been
proposed to be important for lactation; not proven to have vitamin activity.1
Vitamin L2 See above.
Vitamin M Obsolete term for pteroylglutamic acid (folacin).
Vitamin N Obsolete term used to designate an anticancer compound mixture; undefined and
unrecognized.
Vitamin P Not a vitamin;1 but is a metabolite of citrin.
Vitamin Q Not a vitamin;1 but is probably a synonym for coenzyme Q.
Vitamin R Obsolete term for folacin.
Vitamin S Not a vitamin;1 but does act to enhance chick growth; related to the peptide "streptogenin"
and also to biotin.
Vitamin T Not a vitamin;1 reported to improve protein utilization in rats; an extract from termites.
Vitamin U Not a vitamin;1 an extract from cabbage that has been reported to suppress gastric acid
production; may be important to folacin activity.
Vitamin V Not a vitamin.1
Bioflavinoids Not a vitamin.1
Carnitine Not a vitamin;1 except in preterm infants and in severely traumatized persons.
Choline Can be synthesized by the body but some conditions interfere with adequate synthesis.
Citrovorum factor Synonym for folacin; a B vitamin.
Extrinsic factor Obsolete term for vitamin B12, cyanocobalamin.
Factors U, R, X Obsolete terms for folacin.
Filtrate factor Obsolete term for riboflavin.
Flavin A general term for the riboflavin containing coenzymes, FMN, and FAD.
Hepatoflavin Obsolete term for riboflavin.
Intrinsic factor Not a vitamin;1 an endogenous factor needed for vitamin B12, cyanocobalamin, absorption.

Vitamin Terminology
Name Comment
LLD factor Obsolete term for vitamin B12, cyanocobalamin.
Lipoic acid Not a vitamin,1 but does serve as a cofactor in oxidative decarboxylation.
Myoinositol Sometimes a vitamin when endogenous synthesis is inadequate.
Norite eluate Not a vitamin.1
P-P factor Obsolete term for niacin.
Pyrroloquinoline Not a vitamin;1 component of metallo-oxido-reductases.
quinone
Rhizopterin Obsolete term for folacin.
SLR factor Obsolete term for folacin.
Streptogenin Not a vitamin.1
Wills factor Obsolete term for folacin.
Zoopherin Obsolete term for vitamin B12, cyanocobalamin.
1 A vitamin is an organic compound required in small amounts for the maintenance of normal biochemical and
physiological function of the body. These compounds must be present in food and if absent, well defined
symptoms of deficiency will develop. An essential nutrient such as a vitamin cannot be synthesized in amounts
sufficient to meet needs.
TABLE 1.15
Nomenclature of Compounds with Vitamin A Activity
Recommended Name Synonyms
Retinol Vitamin A alcohol
Retinal Vitamin A aldehyde, retinene, retinaldehyde
Retinoic acid Vitamin A acid
3-dehydroretinol Vitamin A2 (alcohol)
3-Dehydroretinal Vitamin A2 aldehyde, retinene2
3-Dehydroretinoic acid Vitamin A2 acid
Anhydroretinol Anhydrovitamin A
Retro retinol Rehydrovitamin A
5,6-Epoxyretinol 5,6-Epoxyvitamin A alcohol
Retinyl palmitate Vitamin A palmitate
Retinyl acetate Vitamin A acetate
Retinyl β-glucuronide Vitamin A acid β-glucuronide
11-cis-retinaldehyde 11-cis or neo β vitamin A aldehyde
4-Ketoretinol 4-Keto vitamin A alcohol
Retinyl phosphate Vitamin A phosphate
β-Carotene Provitamin A
α-Carotene Provitamin A
γ-Carotene Provitamin A
TABLE 1.16
70
Chemical and Physical Properties of Vitamins

Generic Molecular Absorption Melting
Name Compound Name Structure wt. (nm) Solubility pt. Biopotency Stability
Vitamin A all trans 3 CH3 CH3 CH3 CH3 286.4 325 Ether, 62–64 30 unstable to UV
dehydroretinol ethanol, light, oxygen,
OH
chloroform acids, metal
CH3 benzene
acetone
all trans retinol CH3 CH3 CH3 CH3 286.4 325 63–64 100
C CH2
hexane
C C C C OH |
CH3
|
|
13-cis retinol CH3 CH3 CH3 CH3 286.4 | 23–75
|
|
CH3
OH |
all trans retinal CH3 CH3 O 284.4 | 100
CH3 CH3
C |
H
|
CH3
|
|
11-cis retinal CH3 CH3 CH3 284.4 373 | 61–64
|
|
CH3 CH3
|
H O |
13-cis-retinoic acid 300.4 351 | 180–182
CH3 CH3 CH3 CH3
|
|
|
CH3 O OH |
all trans retinoic acid |
CH3 CH3 CH3 CH3 O 300.4 351
C |
OH
|
CH3 |
|
all trans retinyl O 364 10–100
|
phosphate O P OH
|
OH ↓
Provitamin A α carotene H3C 536.9 Ether, 187.5 26
H3C CH3 CH3 CH3 benzene
|
CH3 CH3 H 3C CH3
CH3
|
|
β carotene H 3C 536.9 | 184 50
H3C CH3 CH3 CH3
|
Food Constituents
CH3 CH3 H 3C CH3 |

CH3 |
γ carotene H3 C 536.9 ↓ 178 21
H3C CH3 CH3 CH3
Ethanol
Acetone
CH3 CH3 H 3C CH3
CH3
cryptoxanthin H3C 552.9 169 28

(β-carotene-3-ol) H 3C CH3 CH3 CH3
CH3 CH3 H3O CH3

HO CH3
Vitamin D2 Ergocalciferol 396.67 264 Alcohol 115–118 100 Unstable to UV

Ether light, oxygen,
Acetone iodine, heat,
| mild acid
|
|
|
CH2
|
HO |
|
25-OH-Vitamin D3 411.67 265 | 84–85 200–500
OH
|
|
|
|
CH2 |
|
OH ↓
71
72

Vitamin D3 Cholecalciferol 396.67 265 | 84–85 100
|
|
|
|
|
CH2 |
|
HO |
1,25-(OH)2 vitamin 426.67 265 ↓ 84–85 500–1000
D3 OH
CH2
HO OH
Vitamin E Tocopherols R1 Unstable to
HO oxygen, light,
metal, salts
R2 O
R3
Tocotrienols R1
HO
R2 O
R3
R1 R2 R3
Food Constituents
tocol or tocotrierol α CH3 CH3 CH3 430.7 294 Alcohol, 2.5–3.5 1.49 Unstable to O2,
tocol or tocotrierol β CH3 H CH3 416.7 ether, 0.12 light, metals,
tocol or tocotrierol γ H CH3 CH3 416.7 298 acetone 0.05 salts
tocol or tocotrierol δ H H CH3 416.7 | 0.32
↓ 0.05
Vitamin K Phylloquinone 325 240–270 Alcohol, 0°C 5 Unstable to light
n=1
CH3 396 ether, 10 and alkali, stable
O
n=2 acetone, 30 to heat
n=3 450.7 benzene –20 100
3 CH3
CH3 | 80
H n=4 | 50
O
n(1-6) n=5 |
repeats
|
n=6
|
Menaquinone 3-(preny1)n |
CH3 preny1n-1 n=2 |
| 15
O n=3 40
2 |
CH3 n=4 448.7 243–328 ↓ 54 100
CH3
120
H n=5
O 100
n=6 70
n(2-7)
repeats n=7
73
74

Menadione O |
172.2 ↓ 40–150
CH3
O
Vitamin C Ascorbic acid HO CH2OH 176.14 245 Water 190–192 100 Unstable to heat
O and alkali
O
|
|
C C |
HO OH |
Dehydroascorbic 174.14 245 Water 190–192 80 ↓
HO CH2OH
acid O
O
O O
Vitamin B1 Thiamin 337.27 — Water 177 100
NH2 CH3
N C-CH2-N+ C-CH2CH2-OH
H3C C S
N
Vitamin B2 Riboflavin CH2-(CHOH)3-CH2OH 376.4 220, 225, Water 278 100 Unstable to UV
266, 371, light and heat
C N N O 444, 475
H3C C C C C
H3C C C C NH
C N C
O
Food Constituents
Vitamin B3 Niacin OH 123.1 263 Water 237 100

Nicotinic acid C
O
N
Nicotinamide NH2 122.1 263 Water 128–131 100
C
O
N
Vitamin B6 Pyridoxal O 167.2 293 Water 165 100

C H
HO CH2OH
H3C H
N
Pyridoxamine 205.6 255, 326 Water 160 100
CH2NH
2
HO CH2OH
H3C N
Pyridoxine 169.18 — Water 160 100
CH2OH
HO CH2OH
H3C N H
75
76

Biotin 244.3 — Water 167 100 Unstable to acid
O
and alkaline
HN NH conditions
O
HO
S
Pantothenic acid 219.2 — Water — 100 Unstable to heat
OH CH3OH O
O
C C C C NH CH2-CH2-C
CH3 OH
as calcium salt 476.5 — Water 195 100
Folate O 441 256, 283, Water 250 100 Unstable to
Folacin O C 368 light, acid,
OH
(pteroylmonogluta- CH alkaline,
mic acid) N reducing agents,
OH NH (CH2)2
O heat
N H
C
N
NH
O
HO
H2N N N
O OH
Vitamin B12 Cyanocobalamin CH2CONH2 1355.4 278, 361, Water >300 100 Unstable to light
CH2-CH2-CONH2
CH3 CH 550
3
C
NH2CO CH2 CH2 CH2 CONH2
A B
N N
H3C
H3 C CN
Food Constituents
+
CoO
CH
N N
NH2CO CH2 C CH3
D
CH3
CH3 C CH2 CH2 CONH2
CH2 CH3
CH2
CH3 C O
CH CH2 NH N
CH3
O -
O
O N CH3
R
O
O HO
H
H H
O
HO CH2 H
77
78
TABLE 1.17
Summary of Vitamin Deficiency Signs and Need1
Functions Deficiency and Toxicity Symptoms Sources Comments
Fat-Soluble Vitamins
Vitamin A Deficiency symptoms: Night blindness Liver, carrots, dark-green leafy The forms of vitamin A are alcohol
Helps maintain normal vision in dim (nyctalopia) xerosis, and vegetables. Yellow vegetables: (retinol), ester (retinyl palmitate),
light — prevents night blindness and xerophthalmia. pumpkins, sweet potatoes, squash aldehyde (retinal or retinene), and acid
xerophthalmia. Stunted bone growth, abnormal bone (winter). Yellow fruits: apricots, (retinoic acid).
Essential for body growth. shape, and paralysis. peaches. Some seafoods (crab, halibut, Retinol, retinyl palmitate, and retinal are
Necessary for normal bone growth and Unsound teeth, characterized by oysters, salmon, swordfish); milk and readily converted from one form to
normal tooth development. abnormal enamel, pits, and decay. milk products, eggs. other forms. Retinoic acid fulfills some
Acts as a coenzyme in glycoprotein Rough, dry, scaly skin — a condition Supplemental sources: Synthetic of the functions of vitamin A, but it does
synthesis; functions like steroid known as follicular hyperkeratosis (it vitamin A, cod and other fish liver oils. not function in the visual cycle.
hormones, with a role in the cell nuclei, looks like “gooseflesh”); increased β carotene found in vegetables serves as
leading to tissue differentiation. sinus, sore throat, and abscesses in ears, a vitamin A precursor.
Necessary for (1) thyroxine formation mouth, or salivary glands; increased
and prevention of goiter; (2) protein diarrhea and kidney and bladder
synthesis; and (3) synthesis of stones.
corticosterone from cholesterol, and the Reproductive disorders, including poor
normal synthesis of glycogen. conception, abnormal embryonic
growth, placental injury, and death of
the fetus.
Toxicity: Characterized by loss of
appetite, headache, blurred vision,
excessive irritability, loss of hair,
dryness and flaking of skin (with
itching), swelling over the long bones,
drowsiness, diarrhea, nausea, and
enlargement of the liver and spleen.
Vitamin D Deficiency symptoms: Rickets in infants D-fortified foods: Milk (400 IU/qt) and Vitamin D includes both D2
Increases calcium absorption from the and children, characterized by enlarged infant formulas. Other foods to which (ergocalciferol, calciferol, or viosterol)
small intestine. joints, bowed legs, knocked knees, vitamin D is often added include: and D3 (cholecalciferol).
Promotes growth and mineralization of outward projection of the sternum breakfast and infant cereals, breads, Vitamin D is unique among vitamins
bones. (pigeon breast), a row of beadlike margarines, milk flavorings, fruit and because it can be formed in the body
Promotes sound teeth. projections on each side of the chest at chocolate beverages, and cocoa. and in certain foods by exposure to
Food Constituents
Increases absorption of phosphorus the juncture of the rib bones and joining Supplemental sources: Fish liver oils ultraviolet rays, and the active
through the intestinal wall; increases (costal) cartilage (called rachitic rosary), (from cod, halibut, or swordfish); compound of vitamin D (1, 25-(OH)2-
resorption of phosphates from the bulging forehead, pot belly; delayed irradiated ergosterol or 7-dehydro- D3) functions as a hormone.
kidney tubules. eruption of temporary teeth and cholesterol such as viosterol.
Maintains normal level of citrate in the unsound permanent teeth. Exposure to sunlight or sunlamp
blood. Osteomalacia in adults, in which the converts the vitamin D precursor to
Protects against the loss of amino acids bones soften, become distorted, and active vitamin D.
through the kidneys. fracture easily.
Tetany, characterized by muscle
twitching, convulsions, and low serum

calcium.
Toxicity: Excessive vitamin D may cause
hypercalcemia (increased intestinal
absorption, leading to elevated blood
calcium levels), characterized by loss of
appetite, excessive thirst, nausea,
vomiting, irritability, weakness,
constipation alternating with bouts of
diarrhea, retarded growth in infants
and children, and weight loss in adults.
79
80

Vitamin E (Tocopherols) Deficiency symptoms: Vegetable oils (except coconut oil), alfalfa There are 8 tocopherols and tocotrienols,
An antioxidant which protects body cells Newborn infants (especially the seeds, margarine, nuts (almonds, Brazil of which α-tocopherol has the greatest
from free radicals formed from the premature). Anemia caused by nuts, filberts, peanuts, pecans), vitamin E activity.
unsaturated fatty acids. Maintains the shortened life span of red blood cells, sunflower seed kernels.
integrity of red blood cells by its action edema, skin lesions, and blood Good sources: Asparagus, avocados,
as a suppressor of free radicals. abnormalities. beef and organ meats, blackberries,
An agent essential to cellular respiration, Patients unable to absorb fat have low butter, eggs, green leafy vegetables,
primarily in heart and skeletal muscle blood and tissue tocopherol levels, oatmeal, potato chips, rye, seafoods
tissues. decreased red blood cell life span, and (lobster, salmon, shrimp, tuna),
increased urinary excretion of creatine. tomatoes.
Toxicity: Relatively nontoxic. Some Supplemental sources: Synthetic di-
persons consuming daily doses of more alpha-tocopherol acetate, wheat germ,
than 300 IU of vitamin E have wheat germ oil.

complained of nausea and intestinal
distress. Excess intake of vitamin E
appears to be excreted in the feces.
Vitamin K Deficiency symptoms: Vitamin K is fairly widely distributed in Two forms: K1 (phylloquinone, or
Essential for the synthesis in the liver of 1. Delayed blood clotting foods and is available synthetically. phytylmenaquinone), and K2
four bloodclotting proteins: 2. Hemorrhagic disease of newborn (menaquinones), multiprenyl-
1. Factor II, prothrombin Vitamin K deficiency symptoms are menaquinones.
2. Factor VII, proconvertin likely in: Vitamin K is synthesized by bacteria in
3. Factor IX, Christmas factor 1. Newborn infants the intestinal tracts of human beings
4. Factor X, Stuart-Power. 2. Infants born to mothers receiving and other species.
Its action is on the post translational anticoagulants There are several synthetic compounds,
carboxylation of glutamic acid residues. 3. Obstructive jaundice (lack of bile) the best known of which is menadione,
4. Fat absorption defects (celiac disease, formerly known as K3.
sprue)
5. Anticoagulant therapy or toxicity
Toxicity: The natural forms of vitamin K1
and K2 have not produced toxicity even
when given in large amounts. However,
synthetic menadione and its various
derivatives have produced toxic
symptoms in rats and jaundice in
human infants when given in amounts
of more than 5 mg daily.

Water-Soluble Vitamins
Biotin Deficiency symptoms: The deficiency Rich sources: Cheese (processed), Avidin, found in raw egg white, binds
Functions as a coenzyme mainly in symptoms in man include a dry, scaly kidney, liver, soybean flour. biotin, making it unavailable. Avidin is
decarboxylation-carboxylation and in dermatitis, loss of appetite, nausea, Good sources: Cauliflower, chocolate, destroyed by cooking.
deamination reactions. vomiting, muscle pains, glossitis eggs, mushrooms, nuts, peanut butter,
Food Constituents
(inflammation of the tongue), pallor of sardine and salmon, wheat bran.

skin, mental depression, decrease in Supplemental sources — Synthetic
hemoglobin and red blood cells, high biotin, yeast (brewers’ torula), alfalfa
cholesterol level, and a low excretion of leaf meal (dehydrated).
biotin, all of which respond to biotin Considerable biotin is synthesized by the
administration. microorganisms in the intestinal tract.
Toxicity: There are no known toxic
effects.
Choline Deficiency symptoms: Poor growth and Rich sources: Egg yolk, eggs, liver (beef, The classification of choline as a vitamin
1. As part of the neurotransmitter acetyl fatty livers are the deficiency symptoms pork, lamb). is debated because it does not meet all
choline, transmits nerve impulses. in most species except chickens and Good sources: Soybeans, potatoes the criteria for vitamins, especially
2. Is essential for one of the membrane turkeys. Chickens and turkeys develop (dehydrated), cabbage, wheat bran, those of the B vitamins. The body
phospholipids (phosphatidylcholine) slipped tendons (perosis). In young navy beans, alfalfa leaf meal, dried manufactures choline from methionine,
3. Serves as a methyl donor. rats, choline deficiency produces buttermilk and dried skimmed milk, with the aid of folacin and vitamin B12.
hemorrhagic lesions in the kidneys and rice polish, rice bran, whole grains
other organs. (barley, corn, oats, rice, sorghum,
Toxicity: No toxic effects have been wheat), hominy, turnips, wheat flour,
observed. blackstrap molasses.
Supplemental sources: Yeast (brewers’,
torula), wheat germ, soybean lecithin,
egg yolk lecithin, and synthetic choline
and choline derivatives.
81
82

Folacin/Folate Deficiency symptoms: Megaloblastic Rich sources: Liver and kidney. There is no single vitamin compound
(Folic Acid) anemia (of infancy), also called Good sources: Avocados, beans, beets, with the name folacin; rather, the term
Folacin coenzymes are responsible for macrocyticanemia (of pregnancy), in celery, chickpeas, eggs, fish, green leafy folacin is used to designate folic acid
the following important functions: which the red blood cells are larger and vegetables (such as asparagus, broccoli, and a group of closely related
1. The formation of purines and fewer than normal, and also immature. Brussels sprouts, cabbage, cauliflower, substances which are essential for all
pyrimidines which, in turn, are The anemia is due to inadequate endive, lettuce, parsley, spinach, turnip vertebrates, including man.
needed for the synthesis of the nucleic formation of nucl-proteins, causing greens), nuts, oranges, orange juice, Ascorbic acid, vitamin B12, and vitamin
acids DNA and RNA. failure of the megaloblasts (young red soybeans, and whole wheat products. B6 are essential for the activity of the
2. The formation of heme, the iron- blood cells) in the one marrow to Supplemental sources: Yeast, wheat folacin coenzymes.
containing protein in hemoglobin. mature. The hemoglobin level is low germ, and commercially synthesized Folacin deficiencies are thought to be a
3. The interconversion of the three- because of the reduced number of red folic acid (pteroyl-glutamic acid, or health problem in the U.S. and
carbon amino acid serine from the blood cells and the white blood cell, PGA). throughout the world. Infants,
two-carbon amino acid glycine. blood platelet, and serum folate levels adolescents, and pregnant women are
4. The formation of the amino acids are low. particularly vulnerable.
tyrosine from phenylalanine and Other symptoms include a sore, red, The folacin requirement is increased by
glutamic acid from histidine. smooth red tongue (glossitis), tropical sprue, certain genetic
5. The formation of the amino acid disturbances of the digestive tract disturbances, cancer, parasitic infection,
methionine from homocysteine. (diarrhea), and poor growth. alcoholism, and oral contraceptives.
6. The synthesis of choline from Toxicity: Normally, no toxicity. Raw vegetables stored at room
ethanolamine. temperature for 2–3 days lose as much
7. The conversion of nicotinamide to N- as 50–70% of their folate content.
methylnicotinamide, one of the Between 50 and 95% of food folate is
metabolites of niacin that is excreted destroyed in cooking.
in the urine. Intestinal synthesis provides some
folacin.
Niacin Deficiency symptoms: A deficiency of Generally speaking, niacin is found in An average mixed diet in the U.S.
(Nicotinic acid; nicotinamide) is a niacin results in pellagra, the symptoms animal tissues as nicotinamide and in provides about 1% protein as
constituent of two important of which are: dermatitis, particularly of plant tissues as nicotinic acid. Both tryptophan. Thus, a diet supplying 60 g
coenzymes in the body; nicotinamide areas of skin which are exposed to light forms are of equal niacin activity. of protein contains about 600 mg of
adenine and dinucleotide (NAD) and or injury; inflammation of mucous Rich sources: Liver, kidney, lean meats, tryptophan, which will yield about 10
nicotinamide adenine dinucleotide membranes, including the entire poultry, fish, rabbit, corn flakes mg of niacin (on the average, 1 mg of
phosphate (NADP). These coenzymes gastrointestinal tract, which results in a (enriched), nuts, peanut butter, milk, niacin is derived from each 60 mg of
function as reducing equivalent (H+) red, swollen, sore tongue and mouth, cheese, and eggs, although low in niacin dietary tryptophan).
Food Constituents
acceptors or donors. diarrhea, and rectal irritation; and content, are good antipellagra foods, Niacin is the most stable of the B-
psychic changes, such as irritability, because their niacin is in available form. complex vitamins. Cooking losses of a
anxiety, depression, and in advanced Enriched cereal flours and products are mixed diet usually do not amount to
cases, delirium, hallucinations, good sources of niacin. more than 15–25%.
confusion, disorientation, and stupor. Supplemental sources: Both synthetic
Toxicity: Only large doses of niacin, nicotinamide and nicotinic acid are
sometimes given to individuals with commercially available. For
mental illness, are known to be toxic. pharmaceutical use, nicotinamide is
However, ingestion of large amounts usually used; for food nutrification,
may result in vascular dilation, or nicotinic acid is usually used. Also,
“flushing” of the skin, itching, liver yeast is a rich natural source of niacin.
damage, elevated blood glucose, elevated
blood enzymes, and/or peptic ulcer.
Pantothenic acid Deficiency symptoms: Organ meat (liver, kidney, and heart), Coenzyme A, of which pantothenic acid
(Vitamin B3) Pantothenic acid functions The symptoms: irritableness and cottonseed flour, wheat bran, rice bran, is a part, is one of the most important
as part of two enzymes — coenzyme A restlessness; loss of appetite, indigestion, rice polish, nuts, mushrooms, soybean substances in body metabolism. It
(CoA) and acyl carrier protein (ACP). abdominal pains, nausea; headache; flour, salmon, bleu cheese, eggs, functions in acetyl group transfer and
CoA functions in the following sullenness, mental depression; fatigue, buckwheat flour, brown rice, lobster, thus is important to fatty acid synthesis
important reactions: weakness; numbness and tingling of sunflower seeds. and degradation.
1. The formation of acetyl-choline, a hands and feet, muscle cramps in the Supplemental sources: Synthetic
substance of importance in arms and legs; burning sensation in the calcium pantothenate is widely used as
transmitting nerve impulses. feet; insomnia; respiratory infections; a vitamin supplementation. Yeast is a
2. The synthesis of porphyrin, a rapid pulse; and a staggering gait. Also, rich natural supplement.
precursor of heme, of importance in in these subjects there was increased Intestinal bacteria synthesize
hemoglobin synthesis. reaction to stress; increased sensitivity to pantothenic acid, but the amount and
3. The synthesis of cholesterol and other insulin, resulting in low blood sugar availability is unknown.
sterols. levels; increased sedimentation rate for
4. The steroid hormones formed by the erythrocytes; decreased gastric
adrenal and sex glands. secretions; and marked decrease in
5. The maintenance of normal blood antibody production.
sugar, and the formation of antibodies. Toxicity: Pantothenic acid is relatively
6. The excretion of sulfonamide drugs. nontoxic. However, doses of 10 to 20 g
ACP, along with CoA, required by the per day may result in occasional
83
cells in the synthesis of fatty acids. diarrhea and water retention.

84

Riboflavin Deficiency symptoms: Unlike all the Rich sources: Organ meats (liver, kidney, Riboflavin is destroyed by light, and by
(Vitamin B2) other vitamins, riboflavin deficiency is heart). heat in an alkaline solution.
Riboflavin fu as an integral part of the not the cause of any severe or major Good sources: Corn flakes (enriched),
coenzymes FAD and FMN. These disease of man. Rather, riboflavin often almonds, cheese, eggs, lean meat (beef,
coenzymes accept or donate reducing contributes to other disorders and pork, lamb), mushrooms (raw), wheat
equivalents. disabilities such as beriberi, pellagra, flour (enriched), turnip greens, wheat
scurvy, keratomalacia, and nutritional bran, soybean flour, bacon, cornmeal
megaloblastic anemia. (enriched).
Riboflavin deficiency symptoms are: Supplemental sources: Yeast (brewers’,
sores at the angles of the mouth torula). Riboflavin is the only vitamin
(angular stomatitis); sore swollen, and present in significant amounts in beer.
chapped lips (cheilosis); swollen,
fissured, and painful tongue (glossitis);
redness and congestion at the edges of

the cornea of the eye; and oily, crusty,
scaly skin (seborrheic dermatitis).
Toxicity: There is no known toxicity of
riboflavin.
Thiamin Deficiency symptoms: Moderate Thiamin is found in a large variety of
(Vitamin B1) thiamin deficiency symptoms include animal and vegetable products but is
As a coenzyme in transketolation (Keto- fatigue; apathy (lack of interest); loss of abundant in few.
carrying). appetite; nausea; moodiness; Rich sources: Lean pork, sunflower seed,
In direct functions in the body, including irritability; depression; retarded corn flakes (enriched), peanuts,
(1) maintenance of normal appetite growth; a sensation of numbness in the safflower flour, soybean flour.
(2) the tone of the muscles legs; and abnormalities of the Good sources: Wheat bran, kidney,
(3) a healthy mental attitude electrocardiogram. wheat flour (enriched), rye flour, nuts
Severe thiamin deficiency of long (except peanuts, which are a rich
duration culminates in beriberi, the source), whole wheat flour, cornmeal
symptoms of which are polyneuritis (enriched), rice (enriched), white bread
(inflammation of the nerves), (enriched), soybean sprouts.
emaciation and/or edema, and Supplemental sources: Thiamin
disturbances of heart function. hydrochloride, thiamin mononitrate,
Toxicity: None. yeast (brewers', torula), rice bran, wheat
germ, and rice polish.
Enriched flour (bread) and cereal has
been of special significance in
improving the dietary level of thiamin

in the U.S.
Vitamin B6 Deficiency symptoms: In adults: greasy Rice bran, wheat bran, sunflower seeds, In rats, the three forms of vitamin B6 have
(Pyridoxine; pyridoxal; pyridoxamine) scaliness (seborrheic dermatitis) in the avocados, bananas, corn, fish, kidney, equal activity; and it is assumed that the
Vitamin B6 functions as a coenzyme skin around the eyes, nose, and mouth, lean meat, liver, nuts, poultry, rice same applies to man.
(pyridoxal phosphate) which subsequently spread to other (brown), soybeans, whole grain. Processing or cooking foods may destroy
a. Transamination parts of the body; a smooth, red tongue; Supplemental sources: Pyridoxine up to 50% of the B6.
b. Decarboxylation loss of weight; muscular weakness; hydrochloride is the most commonly Because vitamin B6 is limited in many
c. Transsulfuration irritability; mental depression. available synthetic form, and yeast foods, supplemental B6 with synthetic
d. Tryptophan conversion to nicotinic In infants, the deficiency symptoms are (torula, brewers'), rice polish, and pyridoxine hydrochloride may be
acid irritability, muscular twitchings, and wheat germ are used as natural source indicated, especially for infants and
Food Constituents
e. Absorption of amino acids convulsions. supplements. during pregnancy and lactation.

f. The conversion of glycogen to Toxicity: B6 is relatively nontoxic, but
glucose-1-phosphate large doses may result in sleepiness and
g. The conversion of linoleic acid to be habit-forming when taken over an
arachidonic acid extended period.
Vitamin B12 Deficiency symptoms: Vitamin B12 Liver and other organ meats — kidney, Plants cannot manufacture vitamin B12.
(Cobalamins) deficiency in man may occur as a result heart, muscle meats, fish, shellfish, Vitamin B12 is the largest and the most
1. Synthesis or transfer of single carbon of (1) dietary lack, which sometimes eggs, and cheese. complex of all vitamin molecules.
units. occurs among vegetarians who Supplemental sources: Cobalamin, of Vitamin B12 is the only vitamin that
2. Biosynthesis of methyl groups (-CH3), consume no animal food; or (2) which there are at least three active requires a specific gastrointestinal
and in reduction reactions such as the deficiency of intrinsic factor due to total forms, produced by microbial growth; factor for its absorption (intrinsic
conversion of disulfide (S-S) to the or partial removal of the stomach by available at the corner drugstore. factor); and (2) that the absorption of
sulfhydryl group (-SH). surgery, or infestation with parasites Some B12 is synthesized in the intestinal vitamin B12 in the small intestine
such as the fish tapeworm. tract of human beings. However, little requires about 3 hours.
The common symptoms of a dietary of it may be absorbed.
deficiency of vitamin B12 are: sore
tongue, weakness, loss of weight, back
pains, tingling of the extremities,
apathy, and mental and other nervous
abnormalities. Anemia is rarely seen in
dietary deficiency of B12.
In pernicious anemia, the characteristic
symptoms are: abnormally large red
blood cells, lemon-yellow pallor,
anorexia, prolonged bleeding time,
abdominal discomfort, loss of weight,
glossitis, an unsteady gait, and
neurological disturbances, including
stiffness of the limbs, irritability, and
mental depression. Without treatment
death follows.
Toxicity: No toxic effects of vitamin B12
85
are known.
86
Summary of Vitamin Deficiency Signs and Need

Vitamin C Deficiency symptoms: Early symptoms, Natural sources of vitamin C occur All animal species appear to require
(Ascorbic acid) called latent scurvy: loss in weight, primarily in fruits (especially citrus vitamin C, but dietary need is limited
Formation and maintenance of collagen, listlessness, fatigue, fleeting pains in the fruits) and leafy vegetables: acerola to humans, guinea pigs, monkeys, fruit
the substance that binds body cells joints and muscles, irritability, shortness cherry, camu-camu, and rose hips, raw, bats, birds, certain fish, and certain
together. of breath, sore and bleeding gums, frozen, or canned citrus fruit or juice: reptiles.
Metabolism of the amino acids tyrosine small hemorrhages under the skin, oranges, grapefruit, lemons, and limes. Of all the vitamins, ascorbic acid is the
and tryptophan. bones that fracture easily, and poor Guavas, peppers (green, hot), black most unstable. It is easily destroyed
Absorption and movement of iron. wound healing. currants, parsley, turnip greens, poke during storage, processing, and
Metabolism of fats and lipids, and Scurvy: Swollen, bleeding and ulcerated greens, and mustard greens. cooking; it is water soluble, easily
cholesterol control. gums; loose teeth; malformed and weak Good sources: Green leafy vegetables: oxidized, and attacked by enzymes.
Sound teeth and bones. bones, fragility of the capillaries with broccoli, Brussels sprouts, cabbage
Strong capillary walls and healthy blood resulting hemorrhages throughout the (red), cauliflower, collards, kale, lamb's-
vessels. body; large bruises; big joints, such as quarter, spinach, Swiss chard, and
Metabolism of folic acid. the knees and hips, due to bleeding into watercress. Also, cantaloupe, papaya,
the joint cavity; anemia; degeneration of strawberries, and tomatoes and tomato
muscle fibers; including those of the juice (fresh or canned).
heart; and tendency of old wounds to Supplemental sources: Vitamin C
become red and break open. Sudden (ascorbic acid) is available wherever
death from severe internal hemorrhage vitamins are sold.
and heart failure.
Toxicity: Adverse effects reported of
intakes in excess of 8 g per day (more
than 100 times the recommended
allowance) include: nausea, abdominal
cramps, and diarrhea; absorption of
excessive amounts of iron; destruction
of red blood cells; increased
mobilization of bone minerals;
interference with anticoagulant
therapy; formation of kidney and
bladder stones; inactivation of vitamin
B12; rise in plasma cholesterol; and
possible dependence upon large doses
of vitamin C.
1
See also Section 64.

TABLE 1.18
Essential Minerals and Their Functions
Function Deficiencies and Toxicity Symptoms Sources Comments
Food Constituents
Macrominerals
Calcium (Ca) Deficiency symptoms: Cheeses, wheat-soy flour, blackstrap Calcium is the most abundant mineral in
The primary function of calcium is to 1. Stunting of growth. molasses, milk, and milk products. the body. It comprises about 40% of the
build the bones and teeth and to 2. Poor quality bones and teeth. total minerals present; 99% of it is in the
maintain the bones. 3. Malformation of bones — rickets. bones and teeth.
The clinical manifestations of calcium
Other functions are: Generally, nutritionists recommend a
related diseases are:
1. Blood clotting. calcium–phosphorus ratio of 1.5:1 in
1. Rickets in children.
2. Muscle contraction and relaxation, infancy, decreasing to 1:1 at 1 year of

especially the heartbeat. 2. Osteomalacia, the adult counterpart
of rickets. age and remaining at 1:1 throughout the
3. Nerve transmission.
3. Osteoporosis, a condition of too little rest of life; although they consider ratios
4. Cell wall permeability.
5. Enzyme activation. bone, resulting when bone between 2:1 and 1:2 as satisfactory.
6. Secretion of a number of hormones resorption exceeds bone formation.
and hormone-releasing factors. 4. Hypercalcemia, characterized by
high serum calcium.
5. Tetany, characterized by muscle
spasms and muscle pain.
6. Kidney stones.
Toxicity: Normally, the small intestine
prevents excess calcium from being
absorbed. However, a breakdown of
this control may raise the level of
calcium in the blood and lead to
calcification of the kidneys and other
internal organs.
High calcium intake may cause excess
secretion of calcitonin and very dense
bones.
87
88

Phosphorus (P) Deficiency symptoms: General Cocoa powder, cottonseed flour, fish Phosphorus comprises about 1/4 the
Essential for bone formation and weakness, loss of appetite, muscle flour, peanut flour, pumpkin and total mineral matter in the body.
maintenance. weakness, bone pain, and loss of squash seeds, rice bran, rice polish, Eighty percent of the phosphorus is in
Important in the development of teeth. calcium. Severe and prolonged soybean flour, sunflower seeds, wheat, the bones and teeth in inorganic
Essential for normal milk secretion. deficiencies of phosphorus may be and bran. combination with calcium.
Important in building muscle tissue. manifested by rickets, osteomalacia, Normally, 70% of the ingested
As a component of nucleic acids (RNA and other phosphorus related diseases. phosphorus is absorbed.
and DNA), which are important in Toxicity: There is no known phosphorus Generally, nutritionists recommend a
genetic transmission and control of toxicity per se. However, excess calcium–phosphorus ratio of 1.5:1 in
cellular metabolism. phosphate consumption may cause infancy, decreasing to 1:1 at 1 year of
Maintenance in many metabolic hypocalcemia (a deficiency of calcium age, and remaining at 1:1 throughout
functions, especially: in the blood). the rest of life, although they consider
1. Energy utilization ratios between 2:1 and 1:2 as
2. Phospholipid formation satisfactory.
3. Amino acid metabolism; protein
formation
4. Enzyme systems
Sodium (Na) Deficiency symptoms: Reduced growth, Table salt, processed meat products, and Deficiencies of sodium may occur when
Helps to maintain the balance of water, loss of appetite, loss of body weight due pickled/cured products. there has been heavy, prolonged
acids, and bases in the fluid outside the to loss of water, reduced milk sweating, diarrhea, vomiting, or
cells. production of lactating mothers, muscle adrenal cortical insufficiency. In such
As a constituent of pancreatic juice, bile, cramps, nausea, diarrhea, and cases, extra salt should be taken.
sweat, and tears. headache.
Associated with muscle contraction and Excess perspiration and salt depletion
nerve functions. may be accompanied by heat
Plays a specific role in the absorption of exhaustion.
carbohydrates. Toxicity: Salt may be toxic when (1) a
high intake is accompanied by a
restriction of water, (2) when the body
is adapted to a chronic low salt diet, or
(3) when it is fed to infants or others
whose kidneys cannot excrete the
excess in the urine.

Chlorine (Cl) Deficiency symptoms: Severe Table salt (sodium chloride) and foods Persons whose sodium intake is severely
Plays a major role in the regulation of deficiencies may result in alkalosis (an that contain salt. restricted (owing to diseases of the
osmotic pressure, water balance, and excess of alkali in the blood), heart, kidney, or liver) may need an
acid-base balance. characterized by slow and shallow alternative source of chloride; a number
Required for the production of breathing, listlessness, muscle cramps, of chloride-containing salt substitutes
hydrochloric acid in the stomach; this loss of appetite, and, occasionally, by are available for this purpose.
Food Constituents
acid is necessary for the proper convulsions.

absorption of Vitamin B12 and iron, for Deficiencies of chloride may develop
the activation of the enzyme that breaks from prolonged and severe vomiting,
down starch, and for suppressing the diarrhea, pumping of the stomach,
growth of microorganisms that enter injudicious use of diuretic drugs.
the stomach with food and drink. Toxicity: An excess of chlorine ions is
unlikely when the kidneys are
functioning properly.
Magnesium (Mg) Deficiency symptoms: A deficiency of Rich sources: Coffee (instant), cocoa Overuse of such substances as “milk of
Constituent of bones and teeth. magnesium is characterized by (1) powder, cottonseed flour, peanut flour, magnesia” (magnesium hydroxide) or
Essential element of cellular metabolism, muscle spasms (tremor, twitching) and sesame seeds, soybean flour, spices, “Epsom salts” (magnesium sulfate)
often as an activator of enzymes rapid heartbeat; (2) confusion, wheat bran, and wheat germ. may lead to deficiencies of other
involved in phosphorylated hallucinations, and disorientation; and minerals or even to toxicity.
compounds and of high energy (3) lack of appetite, listlessness, nausea,
phosphate transfer of ADP and ATP. and vomiting.
Involved in activating certain peptidases Toxicity: Magnesium toxicity is
in protein digestion. characterized by slowed breathing,
Relaxes nerve impulse, functioning coma, and sometimes death.
antagon-istically to calcium which is
stimulatory.
89
90

Potassium (K) Deficiency symptoms: Potassium Dehydrated fruits, molasses, potato Potassium is the third most abundant
Involved in the maintenance of proper deficiency may cause rapid and flour, rice bran, seaweed, soybean flour, element in the body, after calcium and
acid-base balance and the transfer of irregular heartbeats and abnormal spices, sunflower seeds, and wheat phosphorus, and it is present in twice
nutrients in and out of individual cells. electrocardiograms; muscle weakness, bran. the concentration of sodium
Relaxes the heart muscle — action irritability, and occasionally paralysis;
opposite to that of calcium which is and nausea, vomiting, diarrhea, and
stimulatory. swollen abdomen. Extreme and
Required for the secretion of insulin by prolonged deficiency of potassium may
the pancreas in enzyme reactions cause hypokalemia, culminating in the
involving the phosphorylation. heart muscles stopping.
Toxicity: Acute toxicity from potassium
(known as hyperpotassemia or
hyperkalemia) can result when kidneys
are not functioning properly. The
condition may prove fatal due to
cardiac arrest.
Cobalt (Co) A cobalt deficiency as such has never Cobalt is present in many foods. Cobalt is an essential constituent of
The only known function of cobalt is that been produced in humans. The signs Vitamin B12 and must be ingested in the
of an integral part of Vitamin B12, an and symptoms that are sometimes form of vitamin molecule inasmuch as
essential factor in the formation of red attributed to cobalt deficiency are humans synthesize little of the vitamin.
blood cells. actually due to lack of Vitamin B12, (A small amount of Vitamin B12 is
characterized by pernicious anemia, synthesized in the human colon by E.
poor growth, and occasionally coli, but absorption is very limited.)
neurological disorders.
Copper (Cu) Deficiency symptoms: Deficiency is Black pepper, blackstrap molasses, Brazil Most cases of copper poisoning result
Facilitating the absorption of iron from most apt to occur in malnourished nuts, cocoa, liver, and oysters (raw). from drinking water or beverages that
the intestinal tract and releasing it from children and in premature infants fed have been stored in copper tanks and/
storage in the liver and the exclusively on modified cow’s milk and or pass through copper pipes.
reticuloendothelial system. in infants breast fed for an extended Dietary excesses of calcium, iron,
Essential for the formation of period of time. cadmium, zinc, lead, silver, and
Food Constituents
hemoglobin, although it is not a part of Deficiency leads to a variety of molybdenum plus sulfur reduce the
hemoglobin as such. abnormalities, including anemia, utilization of copper.
Constituent of several enzyme systems. skeletal defects, demyelination and
Development and maintenance of the degeneration of the nervous system,
vascular and skeletal structures (blood defects in pigmentation and structure of
vessels, tendons, and bones). the hair, reproductive failure, and
Structure and function of the central pronounced cardiovascular lesions.
nervous system. Required for normal Toxicity: Copper is relatively nontoxic to
pigmentation of hair. Component of monogastric species, including man.
important copper-containing proteins. The recommended copper intake for

Reproduction (fertility). adults is in the range of 2–3 mg/day.
Daily intakes of more than 20–30 mg
over extended periods would be
expected to be unsafe.
Fluorine (F) Deficiency symptoms: Excess dental Fluorine is found in many foods, but Large amounts of dietary calcium,
Constitutes 0.02–0.05% of the bones and caries. Also, there is indication that a seafoods and dry tea are the richest food aluminum, and fat will lower the
teeth. Necessary for sound bones and deficiency of fluorine results in sources. absorption of fluorine.
teeth. Assists in the prevention of dental osteoporosis in the aged. Fluoridation of water supplies to bring Fluoridation of water supplies (1 ppm)
caries. Toxicity: Deformed teeth and bones, and the concentration of fluoride to 1 ppm. is the simplest and most effective
softening, mottling, and irregular wear method of providing added protection
of the teeth. against dental caries.
91
92

Iodine (I) Deficiency symptoms: Iodine deficiency Among natural foods the best sources of Certain foods (especially plants of the
The sole function of iodine is making the is characterized by goiter (an iodine are kelp, seafoods, and cabbage family) contain goitrogens,
iodine-containing thyroid hormones. enlargement of the thyroid gland at the vegetables grown in iodine-rich soils which interfere with the use of
base of the neck), coarse hair, obesity, and iodized salt. Stabilized iodized salt thyroxine and may produce goiter.
and high blood cholesterol. contains 0.01% potassium iodide Fortunately, goitrogenic action is
Iodine-deficient mothers may give birth (0.0076% l), or 76 mcg of iodine per prevented by cooking.
to infants with a type of dwarfism gram.
known as cretinism, a disorder
characterized by malfunctioning of the

thyroid gland, goiter, mental
retardation, and stunted growth. A
similar disorder of the thyroid gland,
known as myxedema, may develop in
adults.
Toxicity: Long-term intake of large
excesses of iodine may disturb the
utilization of iodine by the thyroid
gland and result in goiter.
Iron (Fe) Deficiency symptoms: Iron-deficiency Red meat, egg yolk, and dark green, leafy About 70% of the iron is present in the
Iron (heme) combines with protein (nutritional) anemia, the symptoms of vegetables. hemoglobin, the pigment of the red
(globin) to make hemoglobin, the iron- which are paleness of skin and mucous blood cells. The other 30% is present as
containing compound in red blood cells membranes, fatigue, dizziness, a reserve store in the liver, spleen, and
which transports oxygen. Iron is also a sensitivity to cold, shortness of breath, bone marrow.
component of enzymes which are rapid heartbeats, and tingling of the
involved in energy metabolism. fingers and toes.
An excess of iron in the diet can tie up
phosphorus in an insoluble iron-
phosphate complex, thereby creating a
deficiency of phosphorus.
Manganese (Mn) Deficiency symptoms: No clear Rice (brown), rice bran and polish, In average diets, only about 45% of the
Formation of bone and the growth of deficiency disease in man has been walnuts, wheat bran, and wheat germ. ingested magnesium is absorbed.
other connective tissues. reported. The manganese content of plants is
Blood clotting. Toxicity: Toxicity in man as a dependent on soil content.
Insulin action. consequence of dietary intake has not
Cholesterol synthesis. been observed. However, it has
Food Constituents
Activator of various enzymes in the occurred in workers (miners and

metabolism of carbohydrates, fats, others) exposed to high concentrations
proteins, and nucleic acids. of manganese dust in the air. The
symptoms resemble those found in
Parkinson’s and Wilson’s disease.
Molybdenum (Mo) Deficiency symptoms: Naturally The concentration of molybdenum in The utilization of molybdenum is
As a component of three different occurring deficiency in man is not food varies considerably, depending on reduced by excess copper, sulfate, and
enzyme systems which are involved in known. the soil in which it is grown. tungsten.
the metabolism of carbohydrates, fats, Molybdenum-deficient animals are Most of the dietary molybdenum intake In cattle, a relationship exists between
proteins, sulfur-containing amino acids, especially susceptible to the toxic effects is derived from organ meats, whole molybdenum, copper, and sulfur.
nucleic acids (DNA and RNA), and of bisulfite, characterized by breathing grains, leafy vegetables, legumes, and Excess molybdenum will cause copper
iron. difficulties and neurological disorders. yeast. deficiency. However, when the sulfate
Severe molybdenum toxicity in animals content of the diet is increased, the
(molybdenosis), particularly cattle, symptoms of toxicity are avoided
occurs throughout the world wherever inasmuch as the excretion of
pastures are grown on high- molybdenum is increased.
molybdenum soils. The symptoms
include diarrhea, loss of weight,
decreased production, fading of hair
color, and other symptoms of copper
deficiency.
93
94

Selenium (Se) Deficiency symptoms: There are no The selenium content of plant and The high selenium areas are in Great
Component of the enzyme glutathione clear-cut deficiencies of selenium, animal products is affected by the Plains and the Rocky Mountain states
peroxidase, the metabolic role of which because this mineral is so closely related selenium content of the soil and animal — especially in parts of the Dakotas and
is to protect against oxidation of to vitamin E that it is difficult to feed, respectively. Wyoming.
polyunsaturated fatty acids and distinguish deficiency due to selenium Brazil nuts, butter, flour, fish, lobster, and
resultant tissue damage. alone. smelt.
Toxicity: Poisonous effects of selenium
are manifested by (1) abnormalities of
the hair, nails, and skin; (2) garlic odor
on the breath; (3) intensification of
selenium toxicity by arsenic or mercury;
and (4) higher than normal rates of

dental caries.
Zinc (Zn) Deficiency symptoms: Loss of appetite, Beef, liver, oysters, spices, and wheat The biological availability of zinc in
Needed for normal skin, bones, and hair. stunted growth in children, skin bran. different foods varies widely; meats and
A component of several different enzyme changes, small sex glands in boys, loss seafoods are much better sources of
systems which are involved in digestion of taste sensitivity, lightened pigment in available zinc than vegetables. Zinc
and respiration. hair, white spots on the fingernails, and availability is adversely affected by
Required for the transfer of carbon delayed healing of wounds. In the phytates (found in whole grains and
dioxide in red blood cells, for proper Middle East, pronounced zinc beans), high calcium, oxalates (in
calcification of bones, for the synthesis deficiency in man has resulted in rhubarb and spinach), high fiber, copper
and metabolism of proteins and nucleic hypogonadism and dwarfism. In (from drinking water conveyed in
acids, for the development and pregnant animals, experimental zinc copper piping), and EDTA (an additive
functioning of reproductive organs, for deficiency has resulted in malformation used in certain canned foods).
wound and burn healing, for the and behavioral disturbances in
functioning of insulin, and for normal offspring.
taste acuity. Toxicity: Ingestion of excess soluble salts
may cause nausea, vomiting, and
purging.
Adapted from Ensminger, et al. Foods & Nutrition Encyclopedia, 2nd ed., CRC Press, Boca Raton, 1994, pp. 1511–1521.
TABLE 1.19
Essential Fatty Acids
H H H H
CH3CH2CH2CH2C=C–CH2–C=CCH2CH2CH2CH2CH2CH2CH2COOH linoleic acid [18:2, (9, 12)]
18 12 9
H H H H H H
CH3CH2CH2CH2CH2C=C–CH2–C=C–CH2–C=CCH2CH2CH2CH2COOH γ linolenic acid [18:3, (6, 9, 12)]
18 12 9 6 1
H H H H H H
CH3CH2C=C–CH2–C=C–CH2–C=C–(CH2)7COOH
18 15 12 9 linolenic acid [18:3 (9, 12, 15)]
TABLE 1.20
Structure and Names of Fatty Acids Found in Food
# Carbons:
Double Systematic Trivial
Structure Bonds Name Name Source
Saturated Fatty Acids
CH3(CH2)2COOH 4:0 n-Butanoic Butyric Butter

CH3(CH2)4COOH 6:0 n-Hexanoic Caproic Butter
CH3(CH2)6COOH 8:0 n-Octanoic Caprylic Coconut oil
CH3(CH2)8COOH 10:0 n-Decanoic Capric Palm oil
CH3(CH2)10COOH 12:0 n-Dodecanoic Lauric Coconut oil,
nutmeg, butter
CH3(CH2)12COOH 14:0 n-Tetradecanoic Myristic Coconut oil
CH3(CH2)14COOH 16:0 n-Hexadecanoic Palmitic Most fats and oils
CH3(CH2)16COOH 18:0 n-Octadecanoic Stearic Most fats and oils
CH3(CH2)18COOH 20:0 n-Eicosanoic Arachidic Peanut oil, lard
Unsaturated Fatty Acids
CH3(CH2)5CH=CH(CH2)7COOH 16:1 9-Hexadecenoic PalmitoleicButter and seed

oils
CH3(CH2)7CH=CH(CH2)7COOH 18:1 9-Octadecenoic Oleic Most fats and oils
CH3(CH2)5CH=CH(CH2)9COOH 20:1 11-Octadecenoic trans- Hydrogenated
Vaccenic vegetable oils
CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH 18:2 9,12- Linoleic Linseed oil, corn
Octadecadienoic oil, cottonseed oil
CH3CH2(CH=CHCH2)3(CH2)7COOH 18:3 9,12,15- Linolenic Soybean oil,
Octadecatrienoic marine oils
CH3(CH2)4(CH=CHCH2)4(CH2)2COOH 20:4 5,8,11,14- Arachidonic Cottonseed oil
Eicosatetraenoic
Part II
Metabolism
2
Metabolic Maps
The individual reactions of metabolisms have been studied extensively. The details of
their regulation within a given pathway has likewise received considerable attention. The
entire map can be obtained from Boehringer Manheim (BM) at minimal cost. (Boehringer
Mannheim, PO Box 31 01 20, D-6800 Mannheim 31 Germany.) The maps come complete
with citations of the works that provided the critical information for these maps as well
as notations on species differences and differences between mammals, plants, and micro-
organisms.
The maps that follow are general and lack the detail found in the BM maps. They are
provided to give the user an idea of where in metabolism the use of the various macro-
nutrients occur. They also provide some details about intermediary metabolism.
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FIGURE 2.1
The glycolytic pathway.
Metabolic Maps 101
FIGURE 2.2
Reaction sequence of the hexose monophosphate shunt commonly referred to as the “shunt.”
FIGURE 2.3
Metabolism of fructose.
Metabolic Maps 103
FIGURE 2.4
Conversion of galactose to glucose.
FIGURE 2.5
Glycogen synthesis (glycogenesis).
FIGURE 2.6
Stepwise release of glucose molecules from the glycogen molecule.
Metabolic Maps 105
FIGURE 2.7
Pathway for gluconeogenesis.
FIGURE 2.8
Catabolism of branched chain amino acids showing their use in the production of metabolites that are either
lipid precursors or metabolites than can be oxidized via the Krebs cycle.
Metabolic Maps 107
FIGURE 2.9
Catabolism of threonine showing its relationship to that of serine and glycine.
FIGURE 2.10
Phenylalanine and tyrosine catabolism. This pathway has a number of mutations that result in a variety of
genetic disease.
FIGURE 2.11
Catabolism of tryptophan showing conversion to the vitamin niacin. This conversion is not very efficient.
Tryptophan catabolism also results in picolinate, which is believed by some to play a role in trace-mineral
conservation.
Metabolic Maps 109
FIGURE 2.12
Catabolism of histidine. Note that 3-methyl histidine is not part of the pathway. This metabolite is formed in
the muscle when the contractile proteins actin and myosin are methylated.
FIGURE 2.13
Conservation of SH groups via methionine–cysteine interconversion. Spermine, putrescine, and spermidine are
polyamines that are important in cell and tissue growth.
FIGURE 2.14
The urea cycle. Locations of mutations in the urea cycle enzymes are indicated with a star. Persons with these
mutations have very short lives, with evidence of mental retardation, seizures, coma, and early death due to
the toxic effects of ammonia accumulation. Rate controlling steps are indicated with a circled cross.
Metabolic Maps 111
FIGURE 2.15
Krebs citric acid cycle in the mitochondria. This cycle is also called the tricarboxylate cycle (TCA).
ATP ATP ATP
F1F0 ATPase F1F0 ATPase F1F0 ATPase

+ FAD
NADH+H CoQH2
FMN Fe+++ Fe++ Fe+++ Fe++ 1/2 O2
Cytochrome Cytochrome Cytochrome Cytochrome

SITE I SITE II b C1 C aa3
+ FMNH2 Fe+++
NAD CoQ Fe++ Fe++ Fe+++
ADP, Pi FADH+H+ ADP, Pi
++ HOH
Krebs Cycle FADH
Pyruvate +
Fatty Acid 2H
Oxidation
FIGURE 2.16
The respiratory chain showing the points where sufficient energy has been generated to support the synthesis
of 1 molecule of ATP from ADP and Pi. Each of the segments generates a proton gradient. This energy is captured
by the F0 portion of the ATPase and transmitted to the F1 portion of the ATPase. If uncouplers are present, the
proton gradient is dissipated and all of the energy is released as heat.
FIGURE 2.17
Fatty acid synthesis.
Metabolic Maps 113
FIGURE 2.18
Pathways for synthesis of long-chain polyunsaturated fatty acids (PUFA) through elongation and desaturation.
Not all of these reactions occur in all species. The ω symbol is the same as the n symbol. Thus, 18:2ω6, linoleic
acid, could also be written 18:2n6.
FIGURE 2.19
Pathway for β oxidation of fatty acids in the mitochondria.
Metabolic Maps 115
FIGURE 2.20
Pathways for the synthesis of triacylglycerides and phospholipids.
FIGURE 2.21
Eicosanoid synthesis from arachidonic acid.
FIGURE 2.22
Cholesterol biosynthesis.
Metabolic Maps 117
FIGURE 2.23
Overview of protein synthesis. Signals are transmitted to the nucleus that stimulate the exposure of a gene for
a specific protein. A specific messenger RNA is synthesized. The mRNA moves out into the cytosol and attaches
to the ribosome, whereupon tRNAs attached to amino acids dock at appropriate complementary bases and the
amino acids are joined together to make protein.
FIGURE 2.24
Detailed structure of the components of a gene that is to be transcribed.
FIGURE 2.25
Synthesis of messenger RNA and its migration to the ribosomes in the cytoplasm.
Metabolic Maps 119
FIGURE 2.26
Overview of translation involving mRNA, tRNA-amino acids, and small and large ribosomal units.
FIGURE 2.27
Synthesis of creatine and creatinine.
FIGURE 2.28
Modification of β oxidation for unsaturated fatty acid.
3
Tables of Clinical Significance
In this section can be found a variety of tables with importance to the clinician and nutrition
scientist. There are no discussions of these tables because sections later in the book address
key issues related to them. Rather, these tables represent a quick look at topics essential
to an understanding of the health-related, nutrition-related human conditions.
TABLE 3.1
Proteins Involved in Lipid Transport
Protein Function
apo A-II Transport protein in HDL
apo B-48 Transport protein for chylomicrons; synthesized in the enterocyte in the human.
High density Binds HDL and functions in the removal of excess cellular cholesterol
lipoprotein
binding protein
(HDLBP)
apo D Transport protein similar to retinol-binding protein
apo (a) Abnormal transport protein for LDL
apo A-I Transport protein for chylomicrons and HDL; synthesized in the liver and its synthesis is
induced by retinoic acid
apo C-III Transport protein for VLDL
apo A-IV Transport protein for chylomicrons
CETP Participates in the transport of cholesterol from peripheral tissue to liver; reduces HDL size
LCAT Synthesized in the liver and is secreted into the plasma where it resides on the HDL.
Participates in the reverse transport of cholesterol from peripheral tissues to the liver;
esterifies the HDL cholesterol.
apo E Mediates high affinity binding of LDL's to LDL receptor and the putative chylomicron
receptor. Required for clearance of chylomicron remnant. Synthesized primarily in the
liver.
apo C-I Transport protein for VLDL
apo C-II Chylomicron transport protein required cofactor for LPL activity
Apo B-100 Synthesized in the liver and is secreted into the circulation as part of the VLDL. Also
serves as the ligand for the LDL receptor mediated hepatic endocytosis.
Lipoprotein lipase Catalyzes the hydrolysis of plasma triglycerides into free fatty acids
Hepatic lipase Catalyzes the hydrolysis of triglycerides and phospholipids of the LDL and HDL. It is
bound to the surfaces of both hepatic and non hepatic tissues.
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TABLE 3.2
Inherited Disorders of Carbohydrate Metabolism
Disease Mutation Characteristics
Digestion Lactose intolerance Lactase Chronic or intermittent diarrhea,
flatulence, nausea, vomiting, growth
failure in young children
Sucrose intolerance Sucrase Diarrhea, flatulence, nausea, poor
growth in infants
Intestinal Glucose-galactose Glucose-galactose Diarrhea, growth failure in infants,
transport intolerance carrier stools contain large quantities of
glucose and lactic acid
Interconversion Galactosemia Galactose-1-P-uridyl Increased cellular content of galactose
of sugars transferase 1-phosphate, eye cataracts, mental
retardation, increased cellular levels of
galactitol; three mutations have been
reported
Galactokinase Cataracts, cellular accumulation of
galactose and galactitrol; two
mutations have been reported
Galactoepimerase No severe symptoms; two mutations
have been reported
Fructosemia Fructokinase Fructosuria, fructosemia
Fructose-1-P-aldolase Hypoglycemia, vomiting after fructose
load, fructosemia, fructosuria; in
children: poor growth, jaundice,
hyperbilirubinemia, albuminuria,
amino-aciduria
Fructose-1,6- Hypoglycemia, hepatomegaly, poor
diphosphatase muscle tone, increased blood lactate
levels
Pentosuria NADP-lined xylitol Elevated levels of xylose in urine
dehydrogenase
Glucose Hemolytic anemia Glucose-6-phosphate Low erythrocyte levels of NADPH,
catabolism dehydrogenase hemolysis of the erythrocyte
Pyruvate kinase Nonspherocytic anemia, accumulation
of phosphorylated glucose metabolites
in the cell, jaundice in newborn
Type VII glycogenosis Phosphofructokinase Intolerance to exercise, elevated muscle
glycogen levels, accumulation of
hexose monophosphates in muscle
Gluconeogenesis Von Gierke's disease Glucose-6- Hypoglycemia, hyperlipemia, brain
(Type I glycogenosis) phosphatase damage in some patients, excess liver
glycogen levels, shortened lifespan,
increased glycerol utilization
Glycogen Amylopectinosis Branching enzyme Tissue accumulation of long-chain
synthesis (Type IV Liver amylo (1,4→1,6)- glycogen that is poorly branched,
glycogenosis) transglucosidase intolerance to exercise
Glycogenolysis Pompe's disease Lysosomal a-1,4- Generalized glycogen excess in viscera,
(Type II glucosidase (acid muscles, and nervous system, extreme
glycogenosis) maltase) muscular weakness, hepatomegaly,
Forbe's disease Amylo-1,6- enlarged heart
(Type III glucosidase Tissue accumulation of highly
glycogenosis) (debrancing enzyme) branched, short-chain glycogen,
hypoglycemia, acidosis, muscular
weakness, enlarged heart
Tables of Clinical Significance 123

Inherited Disorders of Carbohydrate Metabolism
McArdle's disease Muscle phosphorylase Intolerance to exercise
(Type V
glycogenosis)
Her's disease Liver phosphorylase Hepatomegaly, increased liver glycogen
(Type VI content, elevated serum lipids, growth
glycogenosis) retardation
(Type IX Phosphorylase kinase Hepatomegaly, increased liver glycogen
glycogenosis) levels, decreasd phosphorylase
activity in hepatocytes and leukocytes,
elevated blood lipids, hypoglycemia
after prolonged fasting, increased
gluconeogenesis
TABLE 3.3
Genetic Diseases in Lipid Metabolism
Tay-Sachs disease Hexosaminidase A deficiency Early death, CNS degeneration,
ganglioside GM2 accumulates
Gaucher's disease Glucocerebrosidase deficiency Enlarged liver and spleen; erosion
of long bones and pelvis; mental
retardation; glucocerebroside
accumulates
Fabry's disease α Galactosidase A deficiency Skin rash, kidney failure, pain in
legs and feet, ceramide
trihexoside accumulates
Niemann-Pick disease Sphingomyelinase deficiency Enlarged liver and spleen, mental
retardation, sphingomyelin
accumulates
Krabbe's disease (globoid Galactocerebroside deficiency Mental retardation, absence of
leukodystrophy) myelin
Metachromatic leukodystrophy Arylsulfatase A deficiency Mental retardation, sulfatides
accumulate
Generalized gangliosidosis Gmi,Gandioside: β galactosidase Mental retardation, enlarged liver
deficiency
Sandhoff-Jatzkewitz disease Hexosaminidase A and B Same as Tay-Sachs but develops
deficiency quicker
Fucosidosis α-L-Fucosidase Cerebral degeneration, spastic
muscles, thick skin
Acetyl CoA carboxylase deficiency Acetyl CoA carboxylase deficiency No de novo fatty acid synthesis
Hypercholesterolemia LDL receptor deficiency Premature atherosclerosis and
death from CVD
Refsum's disease α hydroxylating enzyme Neurological problems: deafness,
blindness, cerebellar ataxia,
phytanic acid accumulates
TABLE 3.4
Genetic Mutations in Enzymes of Amino Acid Metabolism
Maple syrup urine disease Branched chain keto acid Elevated levels of α ketoacids and
dehydrogenase (Several variants) their metabolites in blood and
urine; mental retardation,
ketoacidosis, early death
Methylmalonuria Methylmalonyl CoA mutase High blood levels of
(Several variants) Inability to use methylmalonate; pernicious
vitamin B12 anemia, early death
Nonketotic hyperglycinemia Glycine cleavage enzyme Severe mental retardation, early
death, high blood glycine levels
Hypermethioninemia Methionine adenosyltransferase Accumulation of methionine in
(↑ Km not deficiency per se) blood (condition is benign)
Homocysteinemia Cystathionine synthase Elevated blood levels of
methionine, homocysteine;
abnormal collagen (no cross
linking); dislocated lenses and
other ocular malformations;
osteoporosis; mental retardation,
thromboembolism and vascular
occlusions; short lifespan
Cystathioninuria Cystathionase Elevated levels of cystathionine in
urine (condition is benign)
Phenylketonuria Phenylalanine hydroxylase Increased levels of phenylalanine
(several variants) and deaminated metabolites in
blood and urine; mental
retardation; decreased
neurotransmitter synthesis;
shortened lifespan
Tyrosinemia Tyrosine transaminase Eye and skin lesions, mental
retardation
Fumarylacetoacetate hydrolase Liver failure, renal failure
p-hydroxylphenylpyruvate Increased need for ascorbic acid
oxidase
Albinism Tyrosinase Lack of melanin (skin pigment)
formation; increased sensitivity to
sunlight; lack of eye pigment
Alcaptonuria Homogentisate oxidase Elevated urine levels of
homogentisate; slow deposits of
homogentisate in bones,
connective tissue and internal
organs resulting in gradual
darkening of these structures.
Increased susceptibility to
arthritis
Histidenemia Histidase Elevated levels of histidine in
blood and urine. Can give false
positive result in test for
phenylketonuria. Elevated
urocanase levels in sweat.
Decreased histamine formation.
TABLE 3.5
Mutations that Phenotype as Obesity
Genotype Species Phenotype
Estrogen receptor β
Codons 238-244 — 21 bp deletion human obesity1
846G to A human obesity1
1421T to C human obesity1
1730A to G human obesity1
POMC (Proopiomelanocortin gene)
codon 73-74 (btwn. 6997 and 6998) human extreme childhood and adolescent obesity2
within codon 176 (btwn. 7304 and 7305) human extreme childhood and adolescent obesity2
G7316T human extreme childhood and adolescent obesity2
G7341G human extreme childhood and adolescent obesity2
C6982T human extreme childhood and adolescent obesity2
C7111G human extreme childhood and adolescent obesity2
LEP (Leptin gene)
G144A substitution in codon 48 human extreme obesity and very low serum leptin levels3
G328A substitution in codon 110 human extreme obesity and very low serum leptin levels3
c'some 6-10.5 mouse obesity4
c'some 7-q32 human obesity4
LEPR (Leptin receptor)
c'some 1-p31 human obesity4
UCP1 (Uncoupling protein)
Arg/Trp 40 human juvenile onset obesity5
Ala/Thr 64 human juvenile onset obesity5
Val/Met 137 human juvenile onset obesity5
Met/Leu 229 human juvenile onset obesity5
Lys/Asn 257 human juvenile onset obesity5
UCP2 (11q13) human obesity4
UCP3 (11q13) human obesity4
MC3R (20q13) human obesity4
NPYR5 (4q31-q32) human obesity4
MSTN (2q32.1) human obesity4
Chromosome 2p12-13 human Alstrom Syndrome (retinal pigment degeneration,
neurogenic deafness, infantile obesity,
hyperlipidemia, NIDDM6
fa mutation
269Gln to Pro Zucker rat Obesity: Severe insulin resistance,
hyperinsulinemia, hyperglycemia,
hyperlipidemia, hypercortisolemia7
Ob-Rb (269Gln to Pro) Zucker rat Obesity: Decreased cell-surface expression and
decreased leptin binding affinity7
C57 BLKS/J-Leprdb/Leprdb mouse hyperphagia, obesity, hyperinsulinemia,
hyperglycemia8
Gsalpha
R258W human Albright hereditary osteodystrophy: skeletal
abnormalities and obesity9
R258A human Albright hereditary osteodystrophy: skeletal
abnormalities and obesity9
PPARg2
Pro115Gln human extreme obesity10
CPE (carboxypeptidase E) mouse hyperproinsulinemia, late onset obesity, diabetes11
IRS 1 (insulin receptor substrate) S13 and human NIDDM and obesity12
972
Beta3 AR 64 (Beta 3 adrenergic receptor) human NIDDM and obesity12
OB D75514 — D7S530 human NIDDM, obesity, hypertension, and insulin
resistance13

Mutations that Phenotype as Obesity
Insulin receptor gene
Ile1153Met human obesity, insulin resistance, hypoandrogenism,
acanthosis nigricans14
ASIP (agouti signaling protein)
2-88.8 mouse obesity4
20q11.2-q12 human obesity4
TUB (tubby)
c'some 11p15.4-p15.5 human obesity4
TNFA (tumor necrosis factor)
c'some 6p21.3 human obesity4
4p16.3 (autosomal dominant) human obesity — Achondroplasia15
20q11 (autosomal dominant) human obesity — Posterior Polymorphous Corneal
Dystrophy15
15q11.2-q12(autosomal dominant) human obesity — Prader-Willi Syndrome15
12q23-q24.1(autosomal dominant) human obesity — Schinzel Syndrome15
11q13 (autosomal recessive) human obesity — BBS 1 (Bardet-Biedl Syn)15
16q21 (autosomal recessive) human obesity — BBS215
3p13-p12 (autosomal recessive) human obesity — BBS315
15q22.3-q23(autosomal recessive) human obesity — BBS415
8q22-q23(autosomal recessive) human obesity — Cohen Syndrome (CHS1)15
Xq26-q27 (X linked) human obesity — Borjeson-Forssman-Lehman15
Xq21 (X linked) human obesity15
Xq21.1-q22 (X linked) human obesity — Wilson-Turner Syndrome15
Xq26 (X linked) human obesity — Simpson-Golabi Behmel 15
HSD3B1 (1p13.1) human obesity15
ATP1A2 (1q21-q23) human obesity15
ACP1 (2p25) human obesity15
APOB (2p24-p23) human obesity15
APOD (3q27-qter) human obesity15
UCP (4q28-q31) human obesity15
TNFir24 (6p21.3) human obesity15
LPL (8p22) human obesity15
ADRB3 (8p12-p11.1) human obesity15
SUR (11p15.1) human obesity15
DRD2 (11q22.2-q22.3) human obesity15
APOA4 (11q23-qter) human obesity15
LDLR (19p13.2) human obesity15
1.Rosenkranz, K, Hinney, A, Ziegler, A, et al. J Clin Endocrinol Metab 83: 4524; 1998.
2. Hinney, A, Becker, I, Heibut, O, et al. J Endocrinol Metab 83: 3737; 1998.
3. Karvonen, MK, Pesonen, U, Heinonen, P, et al. J Endocrinol Metab 83: 3239; 1998.
4. Comuzzie, AG, Allison, DB, Science 280: 1374; 1998.
5. Urhammer, SA, Fridberg, M, Sorensen, TI, et al., J Clin Endocrinol Metab 82: 4069; 1997.
6. Macari, F, Lautier, C, Girardet, A, Hum Genet 103: 658; 1998.
7. da Silva, BA, Bjorbaek, C, Uotani, S, Flier, JS, Endocrinology 139: 3681; 1998.
8. Igel, M, Becker, W, Herberg, L, Joost, HG, Endocrinology 138: 4234; 1997.
9. Warner, DR, Weng, G, Yu, S, et al. J Biol Chem 273: 23976; 1998.
10. Ristow, M, Muller-Wieland, D, Pfeiffer, A, et al. N Eng J Med 339: 953; 1998.
11. Utsunomiya, N, Ohagi, S, Sanke, T, et al. Diabetologia 41: 701; 1998.
12. Zhang, Y, Wat, N, Stratton, IM, et al. Diabetologia 39: 1505; 1996.
13. Hani, EH, Boutin, P, Durand, E, et al. Diabetologia 41: 1511; 1998.
14. Cama, A, Sierra, ML, Ottini, L, J Clin Endocrinol Metab 73: 894; 1991.
15. Perusse, L, Chagnon, YC, Dionne, FT, Bouchard, C, Obesity Res 5: 1225; 1996.
TABLE 3.6
Mutations that Phenotype as Heart Disease
LPL gene
G188E (exon 5) human High plasma TG — heart disease1
P207L (exon 5) human High plasma TG — heart disease1
D250N (exon 6) human High plasma TG — heart disease1
Homocysteine gene
373C/T = R125W(autosomal recessive) human Homocystinuria2
456C/G = I152M (autosomal recessive) human Homocystinuria2
494G/A = C165Y(autosomal recessive) human Homocystinuria2
539T/C = V180A(autosomal recessive) human Homocystinuria2
833T/C = I278T(autosomal recessive) human Homocystinuria2
1105C/T = R369C(autosomal recessive) human Homocystinuria2
1111G/A = V137M(autosomal recessive) human Homocystinuria2
1301 C/A = T434N(autosomal recessive) human Homocystinuria2
1330 G/A = D444N(autosomal recessive) human Homocystinuria2
1471 C/T = R491C(autosomal recessive) human Homocystinuria2
MTHR gene
792+1G to A/? human Hyperhomocysteinemia/Hypomethioninemia3
G458T/G458T human Hyperhomocysteinemia/Hypomethioninemia3
C692T/C692T human Hyperhomocysteinemia/Hypomethioninemia3
249-IG to T/G164C human Hyperhomocysteinemia/Hypomethioninemia3
G428A/? human Hyperhomocysteinemia/Hypomethioninemia3
G167A/C1015T human Hyperhomocysteinemia/Hypomethioninemia3
G167A/C1081T human Hyperhomocysteinemia/Hypomethioninemia3
T980C/C1141T human Hyperhomocysteinemia/Hypomethioninemia3
C559T/N human Hyperhomocysteinemia/Hypomethioninemia3
833T to C = I278T human Mild hyperhomocysteinuria2
677C to T (A to V) human Mild hyperhomocysteinuria2
4p16.1 (btwn. D4S2957 and D4S827) human Ellis van Creveld Syn (cardiac malformations)4
9q31
TD1 = G1764del to Stop (autosomal human Tangier disease — premature CAD5
recessive)
TD2 = 3' del (autosomal recessive) human Tangier disease — premature CAD5
TD3 = N875S (autosomal recessive) human Tangier disease — premature CAD5
TD4 = A877V (autosomal recessive) human Tangier disease — premature CAD5
TD5 = W530S (autosomal recessive) human Tangier disease — premature CAD5
LDLR gene
Missense C240 to F (Cys to Phe) Exon 5 human Hypercholesterolemia/Premature CVD6
Missense G5218 to D (Gly to Asp) Exon 11 human Hypercholesterolemia/Premature CVD6
Nonsense C122 to X (Cys to stop) Exon 4A human Hypercholesterolemia/Premature CVD6
Missense E187 to K (Glu to Lys) Exon 4B human Hypercholesterolemia/Premature CVD6
Missense C356 to Y (Cys to Tyr) Exon 8 human Hypercholesterolemia/Premature CVD6
Missense w66 to G (Trp to Gly) Exon 3 human Hypercholesterolemia/Premature CVD6
Missense W66 to G (Trp to Gly) Exon3 human Hypercholesterolemia/Premature CVD6
Missense 187E to K (Glu to Lys) Exon 4B human Hypercholesterolemia/Premature CVD6
Missense W66 to G (Trp to Gly) exon 3 human Hypercholesterolemia/Premature CVD6
Insertion 785insG (frameshift) Exon 17 human Hypercholesterolemia/Premature CVD6
Missense W66 to G (Trp to Gly) Exon 3 human Hypercholesterolemia/Premature CVD6
Deletion 165delG (frameshift) Exon 4A human Hypercholesterolemia/Premature CVD6
Missense D245 to E (Asp to Glu) Exon 5 human Hypercholesterolemia/Premature CVD6

C-45T in promoter human Hypercholesterolemia/Premature CAD7
Trp66Gly human Hypercholesterolemia/Premature CAD7
Cys68Tyr human Hypercholesterolemia/Premature CAD7
Cys88Tyr human Hypercholesterolemia/Premature CAD7
Glu387Lys human Hypercholesterolemia/Premature CAD7
Ala519Thr human Hypercholesterolemia/Premature CAD7
Ala585Ser human Hypercholesterolemia/Premature CAD7
Pro587Arg human Hypercholesterolemia/Premature CAD7
Phe598Leu human Hypercholesterolemia/Premature CAD7
Trp599Arg human Hypercholesterolemia/Premature CAD7
Arg723Gln human Hypercholesterolemia/Premature CAD7
Cys660stop human Hypercholesterolemia8
Asp206Glu human Hypercholesterolemia8
Val208Met human Hypercholesterolemia8
DelGly197 human Hypercholesterolemia8
Glu80toLys human Hypercholesterolemia8
Asp206toGlu human Hypercholesterolemia8
Tyr807Lys human Hypercholesterolemia8
Glu207Lys human Hypercholesterolemia8
Pro664Leu human Hypercholesterolemia8
CBS gene
G919 to A human Homocystinuria9
Elastin Gene
7q11.23 human Williams Syn (Supravalvular aortic stenosis)10
11p15.5 human Long QT Syn (congenital heart & vascular
disease)10
7q35-36 human Long QT Syn (congenital heart & vascular
disease)10
3p21-24 human Long QT Syn (congenital heart & vascular
disease)10
Paraoxonase gene
Leu 54 to Met human CVD11
Troponin T gene
Ile79Asn human Hypertrophic cardiomyopathy12
Arg92Gln human Hypertrophic cardiomyopathy12
Phe110Ile human Hypertrophic cardiomyopathy12
Glu163Lys human Hypertrophic cardiomyopathy12
Glu244Asp human Hypertrophic cardiomyopathy12
Arg278Cys human Hypertrophic cardiomyopathy12
Alpha Tropomyosin gene
Asp175Asn human Hypertrophic cardiomyopathy12
Myosin gene
Arg719Trp human Hypertrophic cardiomyopathy12
Val606Met human Hypertrophic cardiomyopathy12
Phe513Cys human Hypertrophic cardiomyopathy12
Leu908Val human Hypertrophic cardiomyopathy12
ApoB gene
Arg3500 to Gln human hypercholesterolemia/peripheral vascular
disease13
arg3531 to Cys human hypercholesterolemia/peripheral vascular
disease13
Glu to Lys 4154 human CAD14
Arg to Glu 3611 human CAD14

11 βHSD
R208C human hypertension15
R213C human hypertension15
L250P human hypertension15
L251S human hypertension15
R337H human hypertension15
Y338 human hypertension15
hBENaC
C to T at Arg 564 (autosomal dominant) human Liddle's Syn (hypertension)16
Bradykinin receptor (14q32)
845C/T human CVD17
704C/T human CVD17
649insG human CVD17
640T/C human CVD17
536T/C human CVD17
412C/G human CVD17
143C/T human CVD17
78C/T human CVD17
Transcription factor NKX2-5
Thr178Met human Congenital heart disease18
Gln170ter human Congenital heart disease18
Gln198ter human Congenital heart disease18
1. Julien, P, Vohl, MC, Gaudet, D, et al. Diabetes 46: 2063; 1997.
2. Kluijtmans, LA, van den Heuvel, LP, Boers, GH, et al. Am J Hum Genet 58: 35; 1996.
3. Goyette, P, Christensen, B, Rosenblatt, DS, Rozen, R. Am J Hum Genet 59: 1268; 1996.
4. Howard, TD, Guttmacher, AE, McKinnon, W, et al. Am J Hum Genet 61: 1405; 1997.
5. Bodzioch, 1999.
6. Eckstrom, U, Abrahamsoon, M, Wallmark, A, et al. Eur J Clin Invest 28: 740; 1998.
7. Sun, XM, Patel, DD, Knight, BL, Soutar, AK. Atherosclerosis 136: 175; 1998.
8. Soutar, AK, J Intern Med 231: 633; 1992.
9. Folsom, AR, Nieto, FJ, McGovern, PG, et al. J Clin Invest 98(3): 204; 1998.
10. Keating, MT, Circulation 92: 142; 1995.
11. Garin, MC, James, RW, Dussoix, P, et al. J Clin Invest 99: 62; 1997.
12. Watkins, H, McKenna, WJ, Thierfelder, HJ, et al. N Eng J Med 332: 1058; 1995.
13. Pullinger, CR, Hennessy, LK, Chatterton, JE, et al. J Clin Invest 95: 1225; 1995.
14. Genest, JJ, Ordovas, JM, McNamara, JR, et al. Atherosclerosis 82: 7; 1990.
15. Mune, T, Rogerson, RM, Nikkila, H, et al. Nat Genet 10: 394; 1995.
16. Shimkets, RA, Warnock, DG, Bositis, CM. Cell 79: 407; 1994.
17. Erdmann, J, Hegemann, N, Weidemann, A, et al. Am J Med Genet 80: 521; 1998.
18. Schott, JJ, Benson, DW, Basson, CT, et al. Science 281: 108; 1998.
TABLE 3.7
Mutations that Phenotype as Diabetes
PC1 (prohormone convertase 1)

Gly483Arg human Extreme childhood obesity, abnormal glucose
homeostasis1
PC2 (prohormone convertase 2) mouse NIDDM: elevation of proinsulin level and/or
proinsulin/insulin ratio2
PC3 (prohormone convertase 3) mouse NIDDM: elevation of proinsulin level and/or
proinsulin/insulin ratio2

GCK (glucokinase) NIDDM: low prevalence of micro-and

macrovascular complications of diabetes3
A53S human MODY4
G80A human MODY4
H137R human MODY4
T168P human MODY4
M210T human MODY4
C213R human MODY4
V226M human MODY4
S336L human MODY4
V367M human MODY4
E248X human MODY4
S360X human MODY4
V401del1 human MODY4
L1221G to T human MODY4
K161+2del10 human MODY4
R186X human MODY4
G261R human MODY4
G279T human MODY5
Ala188Thr (autosomal dominant) human NIDDM6
7p (alleles z+4, z+2, Z22) (autosomal human NIDDM7
dominant)
IRS 1 (insulin receptor substrate)
S13 and 972 human NIDDM and obesity8
Beta3 AR 64 (Beta 3 adrenergic receptor) human NIDDM and obesity8
OB D75514 — D7S530 human NIDDM, obesity, hypertension, and insulin
resistance9
Insulin receptor gene
Codon 897 — nonsense mutation human Leprechaun/Minn 1:Leprechaunism-intrauterine
growth retardation, extreme insulin resistance
Death usually occurs before age 1.10
Glu460Lys human Leprechaun/Ark-1 Leprechaunism — intrauterine
growth retardation, extreme insulin resistance
Death usually occurs before age 110
Leu233Pro human insulin resistance/NIDDM10
Phe382Val human insulin resistance/NIDDM10
Lys460Glu human insulin resistance/NIDDM10
Gln672stop human insulin resistance/NIDDM10
Arg735Ser human insulin resistance/NIDDM10
Arg897stop human insulin resistance/NIDDM10
Gly1008Val human insulin resistance/NIDDM10
Trp1200Ser human insulin resistance/NIDDM10
Val382Ser human Rabson-Mendenhall Syndrome — insulin
resistance (NIDDM), abnormalities of teeth,
nails, and pineal hyperplasia10
Amber133/Ser462 human NIDDM, acanthosis nigricans, hypoandrogenism11
Ser735 human NIDDM, acanthosis nigricans, hypoandrogenism11
Thr1134Ala human NIDDM, acanthosis nigricans, hypoandrogenism11
Arg209His human Leprechaun/Winnipeg — leprechaunism, extreme
insulin resistance (NIDDM)12

Asn15Lys human Rabson-Mendenhall Syndrome — insulin

resistance (NIDDM), abnormalities of teeth, nails,
and pineal hyperplasia12
Asn462Ser human NIDDM — extreme insulin resistance, acanthosis
nigricans, Hyperandrogenism12
Trp133stop human NIDDM12
His209Arg human NIDDM12
Arg1000stop human NIDDM12
Gly996Val human NIDDM and acanthosis nigricans13
Glu 1135/WT human type A extreme insulin resistance14
Ile 1153 human type A extreme insulin resistance14
Del exon 3/WT human type A extreme insulin resistance14
Del codon 1109/WT human type A extreme insulin resistance14
Glu993/Opal 1000 human type A extreme insulin resistance14
Leu 1178/WT human type A extreme insulin resistance14
Ser 1200 human type A extreme insulin resistance14
Lys15/Opal 1000 human type A extreme insulin resistance14
AG to GG (intron4) human type A extreme insulin resistance14
Glu460/Amber 672 human type A extreme insulin resistance14
Pro223 human type A extreme insulin resistance14
Arg31 human type A extreme insulin resistance14
Opal897 human type A extreme insulin resistance14
Del codon 1109/Met910 human type A extreme insulin resistance14
Ala28/Arg366 human type A extreme insulin resistance14
KIR6.2
E23R human NIDDM15
L270V human NIDDM15
I337V human NIDDM15
20q12-q13.1 human MODY 116
7p15-p13 human MODY 216
12q24.2 human MODY 316
13q12.1 human MODY 416
17cen-q21.3 human MODY 516
HNF1 alpha
G31D human NIDDM- defective insulin secretion17
R159W human NIDDM- defective insulin secretion17
A161T human NIDDM- defective insulin secretion17
IVS5nt+2T to A human NIDDM- defective insulin secretion17
P379fsdelT human NIDDM- defective insulin secretion17
G292fsdelG human MODY18
Y122C human MODY18
R159Q human MODY18
S142F human MODY18
R55G56fsdelGACGG human MODY18
Q7X human MODY18
R171X human MODY18
P291fsdelC human MODY18
A443fsddCA human MODY19
P129T human MODY19

R131W human MODY 19
R159W human MODY19

P519L human MODY19
T620I human MODY19
I128N human MODY20
H143Y human MODY20
P447L human MODY20
A559fsinsA human MODY20
CD38 gene
Arg140Trp human Type II diabetes mellitus21
Insulin gene
ValA3Leu (autosomal dominant) human mild diabetes or glucose intolerance22
PheB24Ser (autosomal dominant) human mild diabetes or glucose intolerance22
PheB25Leu (autosomal dominant) human mild diabetes or glucose intolerance22
His 65 (autosomal dominant) human mild diabetes or glucose intolerance22
Xaa 65 (autosomal dominant) human mild diabetes or glucose intolerance23
AspB10 (autosomal dominant) human mild diabetes or glucose intolerance23
mGPDH gene
ACA:Thr243-ACG:Thr243 human NIDDM24
CAT: His264-CGT: Arg264 human NIDDM24
GCA:Ala305-GCC:Ala305 human NIDDM24
GCA:Ala306-TCA:Ser306 human NIDDM24
4p16 between D4S432 and D4S431 human Wolfram Syn (DM, DI, optic atrophy, deafness)25
Mitochondrial DNA mutations(phenotype depends on % mutation in the heteroplasmic individual) 26,27
tRNA Leu (UUR)
A3423G,A3252G,C3256T, T3271C, T3290C, human NIDDM and deafness
T3291C
ND 1
G3316A, A3348G, T3394C, T3396C, human Diabetes with varying degrees of severity; CNS,
G3423T,A3434G, G3438A, A3447G, A3480G Muscle, heart, and kidney involvement
G3483A, T4216
ND2
A4917 human same as above
tRNAcys
C5780A human same as above
tRNAser
C7476T human same as above
COX II
A8245G,G8251A human same as above
tRNAlys
A8344G human same as above
ATPase 6,8 (genes overlap on the mt
genome)
T8993G or C, A8860G,G8894A human same as above
G8204A, C8289T rat same as above but milder
ND3
C10398T, T11778C human same as above
ND4
T11778C human same as above
tRNA glu
T14709C human same as above

TRNAthr
C15904T, A15924G, G15927A human same as above
G15928A
D-loop
C16069T,T16093C,C16126T human same as above
1. Jackson, RS, Creemers, JW, Ohagi, S, et al. Nat Genet 16: 303; 1997.
2. Utsunomiya, N, Ohagi, S, Sanke, T, et al. Diabetologia 41: 701; 1998.
3. Froguel, P, Vaxillaire, M, Velho, G. Diabetes Rev 5: 123; 1997.
4. Velho, G, Blanche, H, Vaxillaire, M, et al. Diabetologia 40 : 217; 1997.
5. Vionnet, N, Stoffel, M, Takeda, J, et al. Nature 356: 721; 1992.
6. Shimada, F, Makino, H, Hashimoto, H. Diabetologia 36: 433; 1993.
7. Hattersley, AT, Turner, RC, Permutt, MA. Lancet 339:1307; 1993.
8. Zhang, Y, Wat, N, Stratton, IM, et al. Diabetologia 39: 1505; 1996.
9. Shitani, M, Ikegami, H, Yamato, E, et al. Diabetologia 39: 1398; 1996.
10. Taylor, SI, Kadowaki, H, Accili, D, et al. Diab Care 13: 257; 1990.
11. Cama, A, Sierra, ML, Ottini, L. J Clin Endocrinol Metab 73: 894; 1991.
12. Kadowaki, T, Kadowaki, H, Rechler, MM. J Clin Invest 86: 254; 1990.
13. Odawara, M, Kadowaki, T, Yamamoto, R. Science 245: 66; 1989.
14. Taylor, SI, Cama, A, Accili, D, et al. Endocr Rev 13: 566; 1992.
15. Hani, EH, Boutin, P, Durand, E, et al. Diabetologia 41: 1511; 1998.
16. Chevre, JC, Hani, EH, Boutin, P, et al. Diabetologia 41: 1017; 1998.
17. Velho, G, Froguel, P, Endocrinology 138: 233; 1998.
18. Vaxillaire, M, Rouard, M, Yamagata, K, et al. Hum Mol Genet 6: 583; 1997.
19. Frayling, TM, Bulamn, MP, Ellard, S, et al. Diabetes 46: 720; 1997.
20. Hansen, T, Eiberg, H, Rouard, M, et al. Diabetes 46: 726; 1997.
21. Yagui, K, Shimada, F, Mimura, M, et al. Diabetologia 41: 1024; 1998.
22. Steiner, DF, Tager, HS, Chan, SJ, et al. Diabetes Care 13: 600; 1990.
23. DeFronzo, RA, Diabetes Rev 5; 177; 1997.
24. Strom, TM, Hortnagel, K, Hofmann, S, et al. Hum Mol Genet 7: 2021; 1998.
25. van den Ouweland, JMW, Lemkes, HHPJ, Ruitenbeek, W, et al. Nat Genet 1: 368; 1992.
26. Mathews, CE, Berdanier, CD. Proc Soc Exp Biol Med 219: 97; 1998.
TABLE 3.8
Normal Values for Micronutrients in Blood
Ascorbic acid, plasma 0.6–1.6 mg/dl Phosphorus 3.4–4.5 mg/dl
Calcium, serum 4.5–5.3 meq/l Potassium 3.5–5.0 meq/l
β-Carotene, serum 40–200 µg/dl Riboflavin, red cell >14.9 µg/dl cells
Chloride, serum 95–103 meq/l Folate, plasma >6 ng/ml
Lead, whole blood 0–50 µg/dl Pantothenic acid, plasma ≥6 µg/dl
Magnesium, serum 1.5–2.5 meq/l Pantothenic acid, whole blood ≥80 µg/dl
Sodium, plasma 136–142 meq/l Biotin, whole blood >25 ng/ml
Sulfate, serum 0.2–1.3 meq/l B12, plasma >150 pg/ml
Vitamin A, serum 15–60 µg/dl Vitamin D 25(OH)–D3, plasma >10 ng/ml
Retinol, plasma >20 µg/dl α-Tocopherol, plasma >0.80 mg/dl
Note: For more information on blood analysis see: NHANES Manual for Nutrition Assessment,
CDC, Atlanta, GA (contact Elaine Gunter); ICNND Manual for Nutrition Surveys, 2nd
ed., 1963, U.S. Government Printing Office, Washington, D.C.; Sauberlich et al., 1974,
Laboratory Tests for the Assessment of Nutritional Status, CRC Press, Boca Raton, FL.
TABLE 3.9
Normal Clinical Values for Constituents of Blood
Common Units or SI Units
Ammonia 22-39 umol/L
Calcium 8.5-10.5 mg/dl or 2.25-2.65 mmol/L
Carbon dioxide 24-30 meq/l or 24-29 mmol/L
Chloride 100-106 meq/L or mmol/L
Copper 100-200 µg/dl or 16-31 µmol/L
Iron 50-150 µg/dl or 11.6-31.3 µmol/L
Lead 50 µg/dl or less
Magnesium 1.5-2.0 meq/L or 0.75-1.25 mmol/L
P CO2 35-40 mm Hg
pH 7.35-7.45
Phosphorus 3.0-4.5 mg/dl or 1-1.5 mmol/L
PO2 75-100 mm Hg
Potassium 3.5-5.0 meq/L or 2.5-5.0 mmol/L
Sodium 135-145 meq/L or 135-145 mmol/L
Acetoaetate less than 2 mmol
Ascorbic adic 0.4-15 mg/dl or 23-85 µmol/L
Bilirubin 0.4-0.6 mg/dl or 1.71-6.84 µmol/L
Carotinoids 0.8-4.0 µg/ml
Creatinine 0.6-1.5 mg/dl or 60-130 µmol/L
Lactic acid 0.6-1.8 meq/L or 0.44-1.28 µmol/L
Cholesterol 120-220 mg/dl or 3.9-7.3 mmol/L
Triglycerides 40-150 mg/dl or 6-18 mmol/L
Pyruvic acid 0-0.11 meq/L or 79.8-228 µmol/L
Urea nitrogen 8-25 mg/dl or 2.86-7.14 mmol/L
Uric acid 3.0-7.0 mg/dl or 0.18-0.29 mmol/L
Albumin 3.5-5.0 g/dl
Insulin 6-20 µU/dl
Glucose 70-100 mg/dl or 4-6 mmol/L
TABLE 3.10
Normal Values for Micronutrients in Urine
Calcium, mg/24 hr 100–250
Chloride, meq/24 hr 110–250
Copper, µg/24 hr 0–100
Lead, µg/24 hr < 100
Phosphorus, g/24 hr 0.9–1.3
Potassium, meq/24 hr 25–100
Sodium, meq/24 hr 130–260
Zinc, mg/24 hr 0.15–1.2
Creatinine, mg/kg bodyweight 15–25
Riboflavin, µg/g creatinine > 80
Niacin metabolite,a µg/g creatinine > 1.6
Pyridoxine, µg/g creatinine ≥ 20
Biotin, µg/24 hr > 25
Pantothenic acid, mg/24 hr ≥1
Folate, FIGLUb after histidine load < 5 mg/8 hr
B12, methylmalonic acid after a valine load ≤ 2 mg/24 hr
Note: For more information on urine analyses see: ICNNO, 1963,
Manual for Nutrition Surveys, 2nd ed., U.S. Government
Printing Office, Washington, D.C.; Sauberlich et al., 1974,
Laboratory Tests for the Assessment of Nutritional Status, CRC
Press, Boca Raton, FL; NHANES Manual for Nutrition As-
sessment, CDC, Atlanta, GA; Gibson, R.S., 1990. Principles
of Nutrition Assessment, Oxford University Press, New York.
a N1-methylnicotinamide.
b Formiminoglutamic acid.
TABLE 3.11
Normal Clinical Values for Constituents of Human Urine
Constituent Content
Aldosterone 2–26 µg/24 hr; 5.5–72 nmol/d
Catecholamines (total) < 100 µg/24 hr
Epinephrine < 10 µg/24 hr; <100 nmol/d
Norepinephrine < 100 µg/24 hr; <590 nmol/d
Cortisol, free 20–100 µg/24 hr; 0.55–2.76 µmol/d
11,17-Hydroxycorticoids men: 4–12 µg/24 hr; women, 4–8 µg/24 hr
17-Ketosteroids <8 yrs: 0–2 mg/24 hr; 9–20 yrs: 2–20 mg/24
Metanephrine < 1.3 mg/24 hr; 6.6 umol/d
Vanillylmandilic acid < 7 mg/24 hr; < 35 µmol/d
Lead < 80 µg/24 hr; 0.4 µmol/d
Sodium 190 mmol/l
Potassium 70 mol/l
Chloride 200 mmol/l
Phosphate (PO4) 35 mmol/l
Phosphorus 22.5 mmol/g creatinine/l urine
Sulfate (SO4) 21–34 mmol/l
Calcium 204 ± 73 mg/24 hr; 1.25–12.5 mmol/24 hr
Iodine >50 µg/g creatinine
Chromium 3.27–3.85 nmol/l
Manganese 7–10.6 nmol/24 hr
Urea 330–580 mmol/l (depends on diet)
Uric acid 0.4–5.8 mmol/l
Amino nitrogen 19–31 mmol/l (depends on diet)
Ammonia 29–72 mmol/l (depends on diet)
Creatinine 9.5–28.5 mmol/l
Porphyrins
D aminolevulinic acid 1.5–7.5 mg/24 hr; 11–57 umol/d
Coproporphyrin < 230 µg/24 hr; < 350 nmol/d
Uroporphyrin < 50 µg/24 hr; < 60 nmol/d
Porphobilinogen < 2 mg/24 hr; 8.8 µmol/d
Urobilinogen < 2.5 mg/24 hr; 70–470 µmol/d
Vitamins (well nourished adult subjects)
Riboflavin > 120 µg/24 hr
Niacin > 66 µg/g creatinine
B6 > 20 µg/g creatinine
Methylmalonic acid (B12 deficient) >5.0 ug/mg creatinine
Gla:creatinine (K deficient) Men: 3.16 ± 0.06; women 3.83±0.08
Specific gravity of urine 1.003–1.030
pH 5.5–7.0
Note: Values were from: Sauberlich, HE Assessment of Nutritional Status, 2nd Edition CRC
Press, Boca Raton, 1999; Banks, P, Bartley, W, Birt, LM, The Biochemistry of Tissues
2nd Edition John Wiley 1976; and Murray, RK, Granner, DK, Mayes, PA, Rodwell,
VW Harper’s Biochemistry 24th Edition Appleton & Lange, 1996.
136
TABLE 3.12
Retinol Binding Proteins
Acronym Protein Molecular Weight Location Function
RBP Retinol binding protein 21,000 Plasma Transports all-trans retinol from
intestinal absorption site to target
tissues
CRBP Cellular retinol binding protein 14,600 Cells of target tissue Transports all-trans retinol from plasma
membrane to organelles within the
cell
CRBP II Cellular retinol binding protein 16,000 Absorptive cells of small intestine Transports all-trans retinol from
Type II absorptive sites on plasma membrane
of mucosal cells
CRABP Cellular retinoic acid binding 14,600 Cells of target tissue Transports all-trans retinoic acid to the
protein nucleus
CRALBP Cellular retinal binding protein 33,000 Specific cells in the eye Transports 11-cis retinal and 11-cis
retinol as part of the visual cycle
IRBP Interphotoreceptor or interstitial 144,000 Retina Transports all-trans retinol and 11-cis
retinol binding protein retinal in the retina extracellular space
RAR Nuclear retinoic acid receptor, 3 All cells Binds retinoic acid and regions of DNA
main forms (α, β, γ) α-liver having the GGTCA sequence
β-brain
γ-liver, kidney, lung
RXR Nuclear retinoic acid receptors,
multiple forms
TABLE 3.13
Drugs that Alter Nutritional State
Drug Effect
Spironolactone Increases need for vitamin A
Thiazides Increases potassium excretion
Cholestyramine Increases fecal excretion of cholesterol, vitamin A, B12, folacin
Colestipol Increases fecal excretion of bile acids, cholesterol, Vitamin A, K, & D
Phenolphthalein Increases fecal excretion of ingesta (laxative effect) also affects
availability of vitamins A, D, K and increases potassium loss
Phenytoin, dilantin Impairs use of folate
Coumarin, dicoumarol Interferes with vitamin K in its role in coagulation
Cyclosporin Interferes with vitamin K metabolism
Isoniazid Increases need for niacin and B6
Sulfasalazine Increases need for folacin
p-aminosalicylic acid Increases need for vitamin B12
Neomycin Increases need for vitamin B12
Tetracycline Interferes with uptake of calcium, magnesium, iron, and zinc
EDTA Binds divalent ions in the intestine thus decreasing availability
Phenylbutazone Increases niacin need
Penicillamine Binds copper and B6 thus increasing need
Thiosemicarbazide Binds vitamin B6
L-DOPA Increases need for vitamin B6
Hydralazine Increases need for vitamin B6
Pyrimethane Increases need for folacin
Methotrexate Increases need for folacin
Theophylline Increases protein turnover, increases calcium mobilization in cells
Ametine Interferes with vitamin B12
Aluminum hydroxide Reduces folate availability as well as phosphate use
Magnesium hydroxide Counteracts phosphate in intestine
Sodium bicarbonate Reduces folate availability
Ethanol Drives up need for niacin, riboflavin, B6 and folacin
Mineral oil Impairs absorption of vitamin A & β carotene
Azulfidine Impairs absorption of folacin, B12 and fat soluble vitamins
Oral contraceptives Increases folacin turnover
Amphetamine Anorexia
Phenethylamine & related compounds Anorexia
Colchicine Promotes peristalsis thus reducing the absorption of all nutrients
Biguanides Promotes glucose use; decreases absorption of B12
Note: The information in this table provided by the Physicians’ Desk Reference; The Merck Index; Sauberlich, HE,
Assessment of Nutritional Status, 2nd ed., CRC Press, 1999; and Murray, RK, Granner, DK, Mayes, PA,
Rodwell, VW, Harper’s Biochemistry 24 ed. Appleton & Lange, Stamford, CN, 1997.
138
TABLE 3.14
Drugs that May Have Anti-Obesity Properties
Drug Example Effect
a) Anti Nutrition Drugs
1. Gastric emptying inhibitors (--) threochlorocitric acid Delays gastric emptying, induces satiety
2. Glucosidase inhibitors Acarbose, miglitol Inhibits carbohydrate digestion
3. Inhibitors of lipid uptake Cholestyramine Binds bile acids, disrupts micelle formation
4. Pseudonutrients Olestra Fat substitute with less energy
Artificial sweeteners Sugar substitute, no energy
Bulking agents, fibers Induce satiety at lower energy intake

5. Lipase inhibitor Xenecal Inhibits hydrolysis of triacylglycides
b) Drugs that Affect Nutrient Partitioning

1. Growth hormone Stimulates protein synthesis
2. Testosterone Stimulates protein synthesis in males only
3. α2 adrenergic antagonists Enhances lipolysis
4. Thermogenic drugs
β2 and β3 adrenergic BRL-26830A, terbutaline Stimulates protein synthesis and lipolysis; can have serious side effects
Dinitrophenol Metabolic poison; not recommended
c) Appetite Suppressors
1. β phenethylamine derivatives Fastin, Dexatrim Interferes with hunger signaling via norepinephrine
2. Serotonergic agents Fenfluramine, fluoxetine Increases serotonin release and signals satiety
3. Amine reuptake inhibitor Sibutramine Blocks reuptake of norepinephrine and 5-HT and suppresses appetite
TABLE 3.15
Micronutrient Interactions
Calcium
Phosphorus
Potassium
Sodium
Magnesium
Zinc
Iron
Copper
Iodine
Fluorine
Vitamin A
Vitamin D
Vitamin E
B12
Vitamin K
Riboflavin
Niacin
Thiamin
Ascorbic acid
B6
Folacin
Calcium X
↑a ↓a ↓a↑m ↑m↓a ↑a ↑a, m ↑m

Phosphorus ↑a X ↑m ↑m ↓a ↑a ↑m ↑m ↑m
Potassium ↑↓m ↑a X ↑a ↓a, ↑m ↑a ↑↓m
Sodium ↑↓m ↑a X ↓a, ↑m ↑m ↑↓m
Magnesium ↓a ↑m ↓a, ↑m X ↑m ↑a ↑m ↑m ↑m
Zinc X ↓a, ↑m ↑m ↑a ↑m ↑m ↑m
Iron ↑m ↓a ↓a X ↓a, ↑m ↑m ↑m ↑m ↑a ↓a ↑m
Copper ↓a ↓a, ↑m X ↑m ↑m ↑m
Iodine X ↓a ↑a ↑m ↑m
Fluorine ↓a X
Cobalt ↓a
Chromium ↓a
Manganese ↓a ↓a
Molybdenum ↑m ↓a
Selenium ↑m
Note: ↑ increase; ↓ decrease; a, absorption; m, metabolism.
139
TABLE 3.16
Preferred Ligand Binding Groups for Metal Ions
Metal Ligand Groups
K + Singly charged oxygen donors or neutral oxygen ligands

Mg2+ Carboxylase, phosphate, nitrogen donors
Ca2+ =Mg2+, but less affinity for nitrogen donors, phosphate, and other multidentate anions
Mn2+ Similar to Mg2+
Fe2+ –SH, NH2 > carboxylates
Fe3+ Carboxylate, tyrosine, –NH2, porphyrin (four ‘hard’ nitrogen donors)
Co3+ Similar to Fe3+
Cu+ –SH (cysteine)
Cu2+ Amines >> carboxylates
Zn2+ Imidazole, cysteine
Mo2+ –SH
Cd2+ –SH
TABLE 3.17
Food Components That Affect Calcium Absorption
Component Effect
Alcohol ↓
Ascorbic acid ↓↑
Cellulose ↓
Fata ↑↓
Fiber ↓
Lactose ↑
Medium-chain triglycerides ↑
Oxalates ↓
Pectin ↑↓
Phytate ↓
Proteinb ↑↓
Sodium alginate ↓
Uronic acid ↓
a In cases of steatorrhea, calcium absorption is reduced.
b Certain proteins, e.g., those in milk, enhance calcium
availability while others, e.g., those in plants, reduce it.
TABLE 3.18
Calcium Binding Proteins
Protein Function
α-Lactalbumin Carries calcium in milk

Casein Carries calcium in milk
Calmodulin Serves as major intracellular calcium receptor; activates cyclic
nucleotidephosphodiesterase
Calbindin D9k and D28k Facilitates intracellular Ca2+ translocation
Osteocalcin Essential for calcium deposition in bone
Ca2+Mg2+ ATPase Essential to movement of calcium across membranes
Prothrombin Essential to blood clot formation
Calcitonin Inhibits osteoclast-mediated bone resorption
Regulates blood calcium levels by preventing hypercalcemia
Parathyroid hormone Stimulates calcitonin synthesis, bone Ca resorption, renal Ca conservation
Albumin Carries calcium in the blood
Globulin Carries calcium in the blood
Osteopontin Essential for calcium mobilization from bone
Troponin C Muscle contraction
Alkaline phosphatase Mineralization of bone
Sialoprotein Embryonic bone growth
GLA-rich clotting proteins Binds calcium in the coagulation cascade (see vitamin K)
Villin, gelsolin Cytoskeleton stabilization
TABLE 3.19
The Body Content of Iron
Male Female
Types of Iron (70 kg) (60 kg)
Essential Iron 3.100 g 2.100 g

Hemoglobin 2.700 1.800
Myoglobin, cytochromes, and other enzymes 0.400 0.300
Storage and transport iron 0.900 0.500
Ferritin, Hemosiderin 0.897 0.407
Transferrin 0.003 0.003
Total iron 4.000 2.600
TABLE 3.20
Body Mass Index Calculated as Body Mass Index = Body Weight/Height.2 BMI for a given height
wt/lb wt/kg
Height 56 57 58 59 60 61 62 63 64 65 66 67 68
142.2 144.8 147.3 149.9 152.4 154.9 157.5 160.0 162.6 165.1 167.6 170.2 172.7
100 45.5 22.5 21.7 20.9 20.2 19.6 18.9 18.3 17.8 17.2 16.7 16.2 15.7 15.2
110 50.0 24.7 23.8 23.0 22.3 21.5 20.8 20.2 19.5 18.9 18.3 17.8 17.3 16.8
120 54.5 27.0 26.0 25.1 24.3 23.5 22.7 22.0 21.3 20.6 20.0 19.4 18.8 18.3
130 59.1 29.2 28.2 27.2 26.3 25.4 24.6 23.8 23.1 22.4 21.7 21.0 20.4 19.8
140 63.6 31.5 30.4 29.3 28.3 27.4 26.5 25.7 24.9 24.1 23.3 22.7 22.0 21.3
150 68.2 33.7 32.5 31.4 30.3 29.4 28.4 27.5 26.6 25.8 25.0 24.3 23.5 22.9
160 72.7 36.0 34.7 33.5 32.4 31.3 30.3 29.3 28.4 27.5 26.7 25.9 25.1 24.4
170 77.3 38.2 36.9 35.6 34.4 33.3 32.2 31.2 30.2 29.2 28.3 27.5 26.7 25.9
180 81.8 40.5 39.0 37.7 36.4 35.2 34.1 33.0 32.0 30.9 30.0 29.1 28.2 27.4
190 86.4 42.7 41.2 39.8 38.4 37.2 36.0 34.8 33.7 32.7 31.7 30.7 29.8 29.0
200 90.9 45.0 43.4 41.9 40.5 39.1 37.9 36.6 35.5 34.4 33.4 32.4 31.4 30.5
210 95.5 47.2 45.5 44.0 42.5 41.1 29.8 38.5 37.3 36.1 35.0 34.0 33.0 32.0
220 100.0 49.5 47.7 46.1 44.5 43.1 41.7 40.3 39.1 37.8 36.7 35.6 34.5 33.5
230 104.5 51.7 49.9 48.2 46.5 45.0 43.6 42.1 40.8 39.5 38.4 37.2 36.1 35.1
240 109.1 53.9 42.0 50.3 48.5 47.0 45.5 44.0 42.6 41.3 40.0 38.8 37.7 36.6
250 113.6 56.2 54.2 52.4 50.6 48.9 47.4 45.8 44.4 43.0 41.7 40.5 39.2 38.1
260 118.2 58.4 56.4 54.5 52.6 50.9 49.3 47.6 46.2 44.7 43.4 42.1 40.8 39.6
270 122.7 60.7 58.5 56.6 54.6 52.8 51.1 49.5 47.9 46.4 45.0 43.7 42.4 41.1
280 127.3 62.9 60.7 58.7 56.6 54.8 53.0 51.3 49.7 48.1 46.7 45.3 43.9 43.7
290 131.8 65.2 62.9 60.8 58.7 56.8 54.9 53.1 51.5 49.9 48.4 46.9 45.5 44.2
300 136.4 67.4 65.0 62.8 60.7 58.7 56.8 55.0 53.3 51.6 50.0 48.5 47.1 45.7
310 140.9 69.7 67.2 64.9 62.7 60.7 58.7 56.8 55.0 53.3 51.7 50.2 48.6 47.2
320 145.5 71.9 69.4 67.0 64.7 62.6 60.6 58.6 56.8 55.0 53.4 51.8 50.2 48.8
330 150.0 74.2 71.5 69.1 66.8 64.6 62.5 60.5 58.6 56.7 55.0 53.4 51.8 50.3
340 154.5 76.4 73.7 71.2 68.8 66.5 64.4 62.3 60.4 58.5 56.7 55.0 53.4 51.8
350 159.1 78.7 75.9 73.3 70.8 68.5 66.3 64.1 62.1 60.2 58.4 56.6 54.9 53.3
360 163.6 80.9 78.0 75.4 72.8 70.5 68.2 66.0 63.9 61.9 60.0 58.3 56.5 54.9
370 168.2 83.2 80.2 77.5 74.8 72.4 70.1 67.8 65.7 63.6 61.7 59.9 58.1 56.4
380 172.7 85.4 82.4 79.6 76.9 74.4 72.0 69.6 67.5 65.3 63.4 61.5 59.6 57.9
390 177.3 87.7 84.5 81.7 78.9 76.3 73.9 71.5 69.2 67.1 65.0 63.1 61.2 59.4
400 181.8 89.9 86.7 83.8 80.9 78.3 75.8 73.3 71.0 68.8 66.7 64.7 62.8 61.0
and weight is where the horizontal line intersects the vertical line.
69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84
175.3 177.8 180.3 182.9 185.4 188.0 190.5 193.0 195.6 198.1 200.7 203.2 205.7 208.3 210.8 213.4
14.8 14.4 14.0 13.6 13.2 12.9 12.5 12.2 11.9 11.6 11.3 11.0 10.7 10.5 10.2 10.0
16.3 15.8 15.4 14.9 14.5 14.1 13.8 13.4 13.1 12.7 12.4 12.1 11.8 11.5 11.3 11.0
17.7 17.3 16.8 16.3 15.9 15.4 15.0 14.6 14.3 13.9 13.5 13.2 12.9 12.6 12.3 12.0
19.2 18.7 18.2 17.7 17.2 16.7 16.3 15.9 15.4 15.1 14.7 14.3 14.0 13.6 13.3 13.0
20.7 20.1 19.6 19.0 18.5 18.0 17.5 17.1 16.6 16.2 15.8 15.4 15.0 14.7 14.3 14.0
22.2 21.6 21.0 20.4 19.8 19.3 18.8 18.3 17.8 17.4 16.9 16.5 16.1 15.7 15.3 15.0
23.7 23.0 22.4 21.7 21.2 20.6 20.0 19.5 19.0 18.5 18.1 17.6 17.2 16.8 16.4 16.0
25.1 24.4 23.8 23.1 22.5 21.9 21.3 20.7 20.2 19.7 19.2 18.7 18.3 17.8 17.4 17.0
26.6 25.9 25.2 24.5 23.8 23.1 22.5 22.0 21.4 20.8 20.3 19.8 19.3 18.9 18.4 18.0
28.1 27.3 26.6 25.8 25.1 24.4 23.8 23.2 22.6 22.0 21.4 20.9 20.4 19.9 19.4 19.0
29.6 28.8 28.0 27.2 26.4 25.7 25.1 24.4 23.8 23.2 22.6 22.0 21.5 21.0 20.5 20.0
31.1 30.2 29.4 28.5 27.8 27.0 26.3 25.6 24.9 24.3 23.7 23.1 22.6 22.0 21.5 21.0
32.5 31.6 30.8 29.9 29.1 28.3 27.6 26.8 26.1 25.5 24.8 24.2 23.6 23.0 22.5 22.0
34.0 33.1 32.2 31.3 30.4 29.6 28.8 28.1 27.3 26.6 26.0 25.3 24.7 24.1 23.5 23.0
35.5 34.5 33.6 32.6 31.7 30.9 30.1 29.3 28.5 27.8 27.1 26.4 25.8 25.1 24.5 24.0
37.0 35.9 35.0 34.0 33.1 32.2 31.3 30.5 29.7 29.0 28.2 27.5 26.9 26.2 25.6 25.0
38.5 37.4 36.4 35.3 34.4 33.4 32.6 31.7 30.9 30.1 29.3 28.6 27.9 27.2 26.6 26.0
39.9 38.8 37.8 36.7 35.7 34.7 33.8 32.9 32.1 31.3 30.5 29.7 39.0 28.3 27.6 26.9
41.4 40.3 39.2 38.0 37.0 36.0 35.1 34.2 33.3 32.4 31.6 30.8 30.1 29.3 28.6 27.9
42.9 41.7 40.5 39.4 38.3 37.3 36.3 35.4 34.5 33.6 32.7 31.9 31.2 30.4 29.7 28.9
44.4 43.1 41.9 40.8 39.7 38.6 37.6 36.6 35.6 34.7 33.9 33.0 32.2 31.4 30.7 29.9
45.9 44.6 43.3 42.1 41.0 39.9 38.8 37.8 36.8 35.9 35.0 34.1 33.3 32.5 31.7 30.9
47.3 46.0 44.7 43.5 42.3 41.2 40.1 39.0 38.0 37.1 36.1 35.2 34.4 33.5 32.7 31.9
48.8 47.4 46.1 44.8 43.6 42.4 41.3 40.3 39.2 38.2 37.2 36.3 35.5 34.6 33.8 32.9
50.3 48.9 47.5 46.2 45.0 43.7 52.6 41.5 40.4 39.4 38.4 37.4 36.5 35.6 34.8 33.9
51.8 50.3 48.9 47.6 46.3 45.0 43.8 42.7 41.6 40.5 39.5 38.5 37.6 36.7 35.8 34.9
53.2 51.8 50.3 48.9 47.6 46.3 45.1 43.9 42.8 41.7 40.6 39.6 38.7 37.7 36.8 35.9
54.7 53.2 51.7 50.3 48.9 47.6 46.3 45.2 44.0 42.9 41.8 40.7 39.7 38.8 37.8 36.9
56.2 54.6 53.1 51.6 50.3 48.9 47.6 46.4 45.1 44.0 42.9 41.8 40.8 39.8 38.9 37.9
57.7 56.1 54.5 53.0 51.6 50.2 48.8 47.6 46.3 45.2 44.0 42.9 41.9 40.9 39.9 38.9
59.2 57.5 55.9 54.4 52.9 51.4 50.1 48.8 47.5 46.3 45.1 44.0 43.0 41.9 40.9 39.9
TABLE 3.21
Standard International Units (SI Units) for Reporting Clinical Data
Physical Quantity Base Units SI Symbol
I. Base Units
Length Meter m
Mass Kilogram kg
Time Second s
Amount Moles mol
Thermodynamic Temperature Kelvin K
Electric Current Ampere A
Luminous Intensity Candela cd
II. Derived Units
Area Square Meter m2

Volume Cubic Meter m3
Force Newton (N) kg · m · s–2
Pressure Pascal (Pa) kg · m–2 · s–2 (N/m2)
Work, Energy Joule (J) kg · m2 · s–2 (N · m)
Mass Density Kilogram per cubic meter kg/m3
Frequency Hertz (Hz) s–1
TABLE 3.22
Conversion Factors for Values in Clinical Chemistry (SI Units)
Present
Reference SI Suggested
Intervals Conversion Reference SI Unit Significant Minimum
Component (examples) Present Unit Factor Intervals Symbol Digits Increment
acetaminophen (P) - toxic >5.0 mg/dL 66.16 >330 µmol/L XXO 10 µmol/L
acetoacetate (S) 0.3-3.0 mg/dL 97.95 30-300 µmol/L XXO 10 µmol/L
acetone (B,S) 0 mg/dL 172.2 0 µmol/L XXO 10 µmol/L
acid phosphatase (S) 0-5.5 U/L 16.67 0-90 nkat/L XX 2 nkat/L
adrenocorticotropin [ACTH] (P) 20-100 pg/mL 0.2202 4-22 pmol/L XX 1 pmol/L

alanine aminotransferase [ALT] (S) 0-35 U/L 0.01667 0-0.58 µkat/L X.XX 0.02 µkat/L
albumin (S) 4.0-6.0 g/dL 10.0 40-60 g/L XX 1 g/L
aldolase (S) 0-6 U/L 16.67 0-100 nkat/L XXO 20 nkat/L
aldosterone (S)
normal salt diet 8.1-15.5 ng/dL 27.74 220-430 pmol/L XXO 10 pmol/L
restricted salt diet 20.8-44.4 ng/dL 27.74 580-1240 pmol/L XXO 10 pmol/L
aldosterone (U) - sodium excretion

=25 mmol/d 18-85 µg/24 h 2.774 50-235 nmol/d XXX 5 nmol/d
=75-125 mmol/d 5-26 µg/24 h 2.774 15-70 nmol/d XXX 5 nmol/d
=200 mmol/d 1.5-12.5 µg/24 h 2.774 5-35 nmol/d XXX 5 nmol/d
alkaline phosphatase (S) 0-120 U/L 0.01667 0.5-2.0 µkat/L X.X 0.1 µkat/L
alpha1-antitrypsin (S) 150-350 mg/dL 0.01 1.5-3.5 g/L X.X 0.1 g/L
alpha-fetoprotein (S) 0-20 ng/mL 1.00 0-20 µg/L XX 1 µg/L
alpha-fetoprotein (Amf) Depends on mg/dL 10 Depends on mg/L XX 1 mg/L
gestation gestation
alpha2-macroglobulin (S) 145-410 mg/dL 0.01 1.5-4.1 g/L X.X 1 mg/L
aluminum (S) 0-15 µg/L 37.06 0-560 nmol/L XXO 10 nmol/L

amino acid fractionation (P)
alanine 2.2-4.5 mg/dL 112.2 245-500 µmol/L XXX 5 µmol/L
alpha aminobutyric acid 0.1-0.2 mg/dL 96.97 10-20 µmol/L XXX 5 µmol/L
arginine 0.5-2.5 mg/dL 57.40 30-145 µmol/L XXX 5 µmol/L
asparagine 0.5-0.6 mg/dL 75.69 35-45 µmol/L XXX 5 µmol/L
citrulline 0.2-1.0 mg/dL 75.13 0-20 µmol/L XXX 5 µmol/L
145
146

Present
cystine 0.2-2.2 mg/dL 57.08 15-55 µmol/L XXX 5 µmol/L
glutamic acid 0.2-2.8 mg/dL 67.97 15-190 µmol/L XXX 5 µmol/L
glutamine 6.1-10.2 mg/dL 68.42 420-700 µmol/L XXX 5 µmol/L
glycine 0.9-4.2 mg/dL 133.2 120-560 µmol/L XXX 5 µmol/L
histidine 0.5-1.7 mg/dL 64.45 30-110 µmol/L XXX 5 µmol/L
hydroxyproline 0-trace mg/dL 76.26 0-trace µmol/L XXX 5 µmol/L
isoleucine 0.5-1.3 mg/dL 76.24 40-100 µmol/L XXX 5 µmol/L
leucine 1.2-3.5 mg/dL 76.24 75-175 µmol/L XXX 5 µmol/L
lysine 1.2-3.5 mg/dL 68.40 80-240 µmol/L XXX 5 µmol/L
methionine 0.1-0.6 mg/dL 67.02 5-40 µmol/L XXX 5 µmol/L

ornithine 0.4-1.4 mg/dL 75.67 30-400 µmol/L XXX 5 µmol/L
phenylalanine 0.6-1.5 mg/dL 60.54 35-90 µmol/L XXX 5 µmol/L
proline 1.2-3.9 mg/dL 86.86 105-340 µmol/L XXX 5 µmol/L
serine 0.8-1.8 mg/dL 95.16 75-170 µmol/L XXX 5 µmol/L
taurine 0.9-2.5 mg/dL 79.91 25-170 µmol/L XXX 5 µmol/L
threonine 0.9-2.5 mg/dL 83.95 75-210 µmol/L XXX 5 µmol/L
tryptophan 0.5-2.5 mg/dL 48.97 25-125 µmol/L XXX 5 µmol/L
tyrosine 0.4-1.6 mg/dL 55.19 20-90 µmol/L XXX 5 µmol/L
valine 1.7-3.7 mg/dL 85.36 145-315 µmol/L XXX 5 µmol/L
amino acid nitrogen (P) 4.0-6.0 mg/dL 0.7139 2.9-4.3 mmol/L X.X 0.1 mmol/L
amino acid nitrogen (U) 50-200 mg/24 h 0.07139 3.6-14.3 mmol/d X.X 0.1 mmol/d
delta-aminolevulinate [as levulinic acid] (U) 1.0-7.0 mg/24 h 7.626 8-53 µmol/d XX 1 µmol/d
amitriptyline (P,S) therapeutic 50-200 ng/mL 3.605 180-270 µmol/L XO 10 nmol/L
ammonia (vP)
as ammonia [NH3] 10-80 µg/dL 0.5872 5-50 µmol/L XXX 5 µmol/L
as ammonium ion [NH4+] 10-85 µg/dL 0.5543 5-50 µmol/L XXX 5 µmol/L
as nitrogen [N] 10-65 µg/dL 0.7139 5-50 µmol/L XXX 5 µmol/L
amylase (S) 0-130 U/L 0.01667 0-2.17 µkat/L XXX 0.01 µkat/L
androstenedione (S)
male > 18 years 0.2-3.0 mg/L 3.492 0.5-10.5 nmol/L XX.X 0.5 nmol/L
female > 18 years 0.8-3.0 mg/L 3.492 3.0-10.5 nmol/L XX.X 0.5 nmol/L
angiotensin converting enzyme (S) <40 nmol/mL/min 16.67 <670 nkat/L XXO 10 nkat/L
arsenic (H) [as As] <1 µg/g (ppm) 13.35 <13 nmol/g XX.X 0.5 nmol/g
arsenic (U) [as As] 0-5 µg/24 h 13.35 0-67 nmol/d XX 1nmol/d
[as As2O3] <25 µg/dL 0.05055 <1.3 µmol/L XX.X 0.1 µmol/L
ascorbate (P) [as ascorbic acid] 0.6-2.0 µg/dL 56.78 30-110 µmol/L XO 10 µmol/L
aspartate amino-transferase [AST] (S) 0-35 U/L 0.0167 0-0.58 µkat/L O.XX 0.01 µkat/L
barbiturate (S) overdose total expressed as: Depends on

phenobarbital composition of
sodium phenobarbital mixture.
barbitone Usually not mg/dL 43.06 ... µmol/L XX 5 µmol/L
known. mg/dL 39.34 µmol/L XX 5 µmol/L
mg/dL 54.29 µmol/L XX 5 µmol/L

barbiturate (S) therapeutic
see phenobarbital
see pentobarbital ... ... ... ... ... ... ...
see thiopental
bile acids, total (S)

[as chenodeoxycholic acid] Trace-3.3 µg/mL 2.547 Trace-8.4 µmol/L X.X 0.2 µmol/L
cholic acid Trace-1.0 µg/mL 2.448 Trace-2.4 µmol/L X.X 0.2 µmol/L
chenodeoxycholic acid Trace-1.3 µg/mL 2.547 Trace-3.4 µmol/L X.X 0.2 µmol/L
deoxycholic acid Trace-1.0 µg/mL 2.547 Trace-2.6 µmol/L X.X 0.2 µmol/L
lithocholic acid Trace µg/mL 2.656 Trace µmol/L X.X 0.2 µmol/L
bile acids (Df) [after cholcystokinin
stimulation]
total as chenodeoxycholic acid 14.0-58.0 mg/mL 2.547 35.0-148 mmol/L XX.X 0.2 mmol/L
cholic acid 2.4-33.0 mg/mL 2.448 6.8-81.0 mmol/L XX.X 0.2 mmol/L
chenodeoxycholic acid 4.0-24.0 mg/mL 2.547 10.0-61.4 mmol/L XX.X 0.2 mmol/L
deoxycholic acid 0.8-6.9 mg/mL 2.547 2.0-18.0 mmol/L XX.X 0.2 mmol/L
lithocholic acid 0.3-0.8 mg/mL 2.656 0.8-2.0 mmol/L XX.X 0.2 mmol/L
bilirubin, total (S) 0.1-1.0 mg/dL 17.10 2-18 µmol/L XX 2 µmol/L
bilirubin, conjugated (S) 0-0.2 mg/dL 17.10 0-4 µmol/L XX 2 µmol/L
bromide (S), toxic
as bromide ion >120 mg/dL 0.1252 >15 mmol/L XX 1 mmol/L
as sodium bromide >150 mg/dL 0.09719 >15 mmol/L XX 1 mmol/L
>15 mEq/L 1.00 >15 mmol/L XX 1 mmol/L
cadmium (S) <3 mg/dL 0.08897 <0.3 µmol/L X.X 0.1 µmol/L
calcitonin (S) <100 pg/mL 1.00 <100 ng/L XXX 10 ng/L
147
148

Present
calcium (S)
male 8.8-10.3 mg/dL 0.2495 2.20-2.58 mmol/L X.XX 0.02 mmol/L
female <50 y 8.8-10.0 mg/dL 0.2495 2.20-2.50 mmol/L X.XX 0.02 mmol/L
female >50 y 8.8-10.2 mg/dL 0.2495 2.20-2.56 mmol/L X.XX 0.02 mmol/L
4.4-5.1 mEq/L 0.500 2.20-2.56 mmol/L X.XX 0.02 mmol/L
calcium ion (S) 2.00-2.30 mEq/L 0.500 1.00-1.15 mmol/L X.XX 0.01 mmol/L
calcium (U), normal diet
<250 mg/24 h 0.02495 <6.2 mmol/d X.X 0.1 mmol/d
carbamazepine (P)
- therapeutic 4.0-10.0 mg/L 4.233 17-42 µmol/L XX 1 µmol/L

carbon dioxide content (B, P, S)
[bicarbonate + CO2] 22-28 mEq/L 1.00 22-28 mmol/L X 1 mmol/L
carbon monoxide (B)
[proportion of Hb which is COHb] <15 % 0.01 <0.15 1 0.XX 0.01
beta carotenes (S) 50-250 mg/dL 0.01863 0.9-4.6 µmol/L X.X 0.1 µmol/L
catecholamines, total (U)
[as norepinephrine] <120 mg/24 h 5.911 <675 nmol/d XXO 10 mg/d
ceruloplasmin (S) 20-35 mg/dL 10.0 200-350 mg/L XXO 10 mg/L
Chlordiazepoxide (P)
- therapeutic 0.5-5.0 mg/L 3.336 2-17 µmol/L XX 1 µmol/L
- toxic >10.0 mg/L 3.336 >33 µmol/L XX 1 µmol/L
chloride (S) 95-105 mEq/L 1.00 95105 mmol/L XXX 1 mmol/L
chlorimipramine (P)
[includes desmethyl metabolite} 50-400 ng/mL 3.176 150-1270 nmol/L XXO 10 nmol/L
chlorpromazine (P) 50-300 ng/mL 3.136 150-950 nmol/L XXO 10 nmol/L
chlorpropamide (P)
-therapeutic 75-250 mg/L 3.613 270-900 mmol/L XXO 10 mmol/L
cholestanol (P) [as a fraction of total
cholesterol] 1-3 % 0.01 0.01-0.03 1 0.XX 0.01
cholesterol (P)
- <29 years <200 mg/dL 0.02586 <5.20 mol/L X.XX 0.05 mmol/L
- 30-39 years <225 mg/dL 0.02586 <5.85 mmol/L X.XX 0.05 mmol/L
- 40-49 years <245 mg/dL 0.02586 <6.35 mmol/L X.XX 0.05 mmol/L
- >50 years <265 mg/dL 0.02586 <6.85 mmol/L X.XX 0.05 mmol/L
cholesterol esters (P) [as a fraction of total
cholesterol]
60-75 % 0.01 0.60-0.75 1 0.XX 0.01
cholinesterase (S) 620-1370 U/L 0.01667 10.3-22.8 mkat/L XX.X 0.1 mkat/L
chorionic gonadotropin (P) [beta HCG] 0 if not pregnant mIU/mL 1.00 0 if not IU/L XX 1 IU/L
pregnant
citrate (B) [as citric acid] 1.2-3.0 mg/dL 52.05 60-160 µmol/L XXX 5 µmol/L
complement, C3 (S) 70-160 mg/dL 0.01 0.7-1.6 g/L X.X 0.1 g/L
complement, C4 (S) 20-40 mg/dL 0.01 0.2-0.4 g/L X.X 0.1 g/L
copper (S) 70-140 µg/dL 0.1574 11.0-22.0 µmol/L XX.X 0.2.µmol/L

copper (U) <40 µg/24 h 0.01574 <0.6 µmol/d X.X 0.2 µmol/L
coproporphyrins (U) <200 µg/24 h 1.527 <300 nmol/d XXO 10 nmol/d
cortisol (S)
-800 h 4-19 µg/dL 27.59 110-520 nmol/L XXO 10 nmol/L
-1600 h 2-15 µg/dL 27.59 50-410 nmol/L XXO 10 nmol/L

-2400 h 5 µg/dL 7.59 140 nmol/L XXO 10 nmol/L
cortisol, free (U) 10-110 µg/24 h 2.759 30-300 nmol/d XXO 10 nmol/d
creatine (S)
-male 0.17-0.50 µg/dL 76.25 10-40 mmol/L XO 10 mmol/L
-female 0.35-0.93 µg/dL 76.25 30-70 mmol/L XO 10 mmol/L
creatine (U)
-male 0-40 mg/24 h 7.625 0-300 µmol/d XXO 10 µmol/d
-female 0-80 mg/24 h 7.625 0-600 µmol/d XXO 10 µmol/d
creatine kinase [CK] (S)
creatine kinase isoenzymes (S) 0-130 U/L 0.01667 0-2.16 µkat/L X.XX 0.01 µkat/L
-MB fraction >5 in myocardial % 0.01 >0.05 1 O.XX 0.01
infarction
creatinine (S) 0.6-1.2 mg/dL 88.40 50-110 µmol/L XXO 10 µmol/L
creatinine (U) Variable g/24 h 8.840 Variable mmol/d XX.X 0.1 mmol/d
creatinine clearance (S, U) 75-125 mL/min 0.01667 1.24-2.08 mL/s X.XX 0.02 mL/s
creatinine clearance mmol / L (urine creatinine) 1.73 [where A is the body surface area in square meters
= × mL / s × (m2)]
corrected for body mmol / L (serum creatinine) A
cyanide (B) - lethal >0.10 mg/dL 384.3 >40 µmol/L XXX 5 µmol/L
cyanocobalamin (S)
149
150

Present
[vitamin B12] 200-100 pg/mL 0.7378 150-750 pmol/L XXO 10 pmol/L
cyclic AMP (S) 2.6-6.6 µg/L 3.038 8-20 nmol/L XXX 1 nmol/L
cyclic AMP (U)
-total urinary 2.9-5.6 µmol/g 113.1 330-630 nmol/mmol XXO 10 nmol/mmol
creatinine creatinine creatinine
-renal tubular <2.5 µmol/g 113.1 <280 nmol/mmol XXO 10 nmol/mmol
cyclic GMP (S) 0.6-3.5 µg/L 2.897 1.7-10.1 nmol/L XX.X 0.1 nmol/L
cyclic GMP (U) 0.3-1.8 µmol/g 113.1 30-200 nmol/mmol XXO 10 nmol/mmol

cystine (U) 10-100 mg/24 h 4.161 40-420 mmol/d XXO 10 mmol/d
dehydroepiandrosterone (P,S)
[DHEA]- 1-4 years 0.2-0.4 µg/L 3.467 0.6-1.4 nmol/L XX.X 0.2 nmol/L
4-8 years 0.1-1.9 µg/L 3.467 0.4-6.6 nmol/L XX.X 0.2 nmol/L
premenopausal female 2.0-15.0 µg/L 3.467 7.0-52.0 nmol/L XX.X 0.2 nmol/L
male 0.8-10.0 µg/L 3.467 2.8-34.6 nmol/L XX.X 0.2 nmol/L
dehydroepiandrosterone (U) See Steroids Fractionation ... ... ... ... ...
dehydroepiandrosterone sulphate [DHEA-S]
(P, S)
newborn 1670-3640 ng/mL 0.002714 4.5-9.9 µmol/L XX.X µmol/L
pre-pubertal children 100-600 ng/mL 0.002714 0.3-1.6 µmol/L XX.X µmol/L
male 2000-3500 ng/mL 0.002714 5.4-9.1 µmol/L XX.X µmol/L
female (premenopausal) 820-3380 ng/mL 0.002714 2.2-9.2 µmol/L XX.X µmol/L
female (post-menopausal) 110-610 ng/mL 0.002714 0.3-1.7 µmol/L XX.X µmol/L
pregnancy [term] 0-1170 ng/mL 0.002714 0.6-3.2 µmol/L XX.X µmol/L
11-deoxycortisol (S) 0-2 µg/dL 28.86 0-60 nmol/L XXO 10 nmol/L
desipramine (P)
-therapeutic 50-200 ng/mL 3.754 170-700 nmol/L XXO 10 nmol/L
diazepam (P)
-therapeutic 0.10-0.25 mg/L 3512 350-900 nmol/L XXO 10 nmol/L
-toxic >1.0 mg/L 3512 >3510 nmol/L XXO 10 nmol/L
dicoumarol (P)
-therapeutic 8-30 mg/L 2.974 25-90 µmol/L XX 5 µmol/L
digoxin (P)
-therapeutic 0.5-2.2 ng/mL 1.281 0.6-2.8 nmol/L X.X 0.1 nmol/L
0.5-2.2 µg/L 1.281 0.6-2.8 nmol/L X.X 0.1 nmol/L
-toxic >2.5 ng/mL 1.281 >3.2 nmol/L X.X 0.1 nmol/L
dimethadione (P)
-therapeutic <1.00 g/L 7.745 <7.7 mmol/L X.X 0.1 mmol/L
disopyramide (P)
-therapeutic 2.0-6.0 mg/L 2.946 6-18 µmol/L XX 1 µmol/L

doxepin (P)
-therapeutic 50-200 n/mL 3.579 180-720 nmol/L XO 10 nmol/L
electrophoresis, protein (S)
albumin 60-65 % 0.01 0.60-0.65 1 O.XX 0.01
alpha1-globulin 1.7-5.0 % 0.01 0.02-0.05 1 O.XX 0.01

alpha2-globulin 6.7-12.5 % 0.01 0.07-0.13 1 O.XX 0.01
beta-globulin 8.3-16.3 % 0.01 0.08-0.16 1 O.XX 0.01
gamma-globulin 10.7-20.0 % 0.01 0.11-0.20 1 O.XX 0.01
albumin 3.6-5.2 g/dL 10.0 36-52 g/L XX 1 g/L
alpha1-globulin 0.1-0.4 g/dL 10.0 1-4 g/L XX 1 g/L
alpha2-globulin 0.4-1.0 g/dL 10.0 4-10 g/L XX 1 g/L
beta-globulin 0.5-1.2 g/dL 10.0 5-12 g/L XX 1 g/L
gamma-globulin 0.6-1.6 g/dL 10.0 6-16 g/L XX 1 g/L
epinephrine (P) 31-95 (at rest for pg/mL 5.458 170-520 pmol/L XXO 10 pmol/L
15 min)
epinephrine (U) <10 µg/24 h 5.458 <55 nmol/d XX 5 nmol/d
estradiol (S)
male >18 yrs 15-40 pg/mL 3.671 55-150 pmol/L XX 1 pmol/L
estriol (U)
[non pregnant]
onset of menstruation 4-25 µg/24 h 3.468 15-85 nmol/d XXX 5 nmol/d
ovulation peak 28-99 µg/24 h 3.468 95-345 nmol/d XXX 5 nmol/d
luteal peak 22-105 µg/24 h 3.468 75-365 nmol/d XXX 5 nmol/d
menopausal woman 1.4-19.6 µg/24 h 3.468 5-70 nmol/d XXX 5 nmol/d
male 5-18 µg/24 h 3.468 15-60 nmol/d XXX 5 nmol/d
151
152

Present
estrogens (S) [as estradiol]
female 20-300 pg/mL 3.671 70-1100 pmol/L XXXO 10 pmol/L
peak production 200-800 pg/mL 3.671 750-2900 pmol/L XXXO 10 pmol/L
male <50 pg/mL 3.671 <180 pmol/L XXO 10 pmol/L
estrogens, placental (U) [as estriol] Depends on mg/24 h 3.468 Depends on µmol/d XXX 1 µmol/d
period of period of
gestation gestation
estrogen receptors (T)

negative 0-3 fmol estradiol 1.00 0-3 fmol estradiol/ XXX 1 fmol/mg
bound/mg mg cytosol protein
cytosol protein protein
doubtful 4-10 fmol estradiol 1.00 4-10 fmol estradiol/ XXX 1 fmol/mg
positive >10 fmol estradiol 1.00 >10 fmol estradiol/ XXX 1 fmol/mg
estrone (P, S)
- female 1-10 days of cycle 43-180 pg/mL 3.699 160-665 pmol/L XXX 5 pmol/L
-female 11-20 days of cycle 75-196 pg/mL 3.699 275-725 pmol/L XXX 5 pmol/L
-female 20-39 days of cycle 131-201 pg/mL 3.699 485-745 pmol/L XXX 5 pmol/L
-male 29-75 pg/mL 3.699 105-275 pmol/L XXX 5 pmol/L
estrone (U) female 2-25 µg/24 h 3.699 5-90 nmol/d XXX 5 nmol/d
ethanol (P)
legal limit [driving] <80 mg/dL 0.2171 <17 mmol/L XX 1 nmol/L
-toxic >100 mg/dL 0.2171 >22 mmol/L XX 1 mmol/L
ethchlorvynol (P) toxic >40 mg/L 6.915 >280 µmol/L XXO 10 µmol/L
ethosuximide (P)
therapeutic 40-110 mg/L 7.084 280-780 µmol/L XXO 10 µmol/L
ethylene glycol (P)
toxic >30 mg/dL 0.1611 >5 mmol/L XX 1 mmol/L
fat (F)
[as stearic acid] 2.0-6.0 g/24 h 3.515 7-21 mmol/d XXX 1 mmol/d
fatty acids, non-
esterified (P) 8-20 mg/dL 10.00 80-200 mg/L XXO 10 mg/L
ferritin (S) 18-300 ng/mL 1.00 18-300 µg/L XXO 10 µg/L
fibrinogen (P) 200-400 mg/dL 0.01 2.0-4.0 g/L X.X 0.1 g/L
fluoride (U) <1.0 mg/24 h 52.63 <50 µmol/d XXO 10 µmol/d
folate (S) [as pteroylglutamic acid] 2-10 ng/mL 2.266 4-22 nmol/L XX 2 nmol/L
µg/dL 22.66 nmol/L 2 nmol/L
folate (Erc) 140-960 ng/mL 2.266 550-2200 nmol/L XXO 10 nmol/L
follicle stimulating hormone
[FSH] (P)
female 2.0-15.0 mIU/mL 1.00 2-15 IU/L XX 1 IU/L

peak production 20-50 mIU/mL 1.00 20-50 IU/L XX 1 IU/L
male 1.0-10.0 mIU/mL 1.00 1-10 IU/L XX 1 IU/L
follicle stimulating hormone [FSH] (U)
follicular phase 2-15 IU/24 h 1.00 2-15 IU/d XXX 1 IU/d
midcycle 8-40 IU/24 h 1.00 8-40 IU/d XXX 1 IU/d

luteal phase 2-10 IU/24 h 1.00 2-10 IU/d XXX 1 IU/d
menopausal women 35-100 IU/24 h 1.00 35-100 IU/d XXX 1 IU/d
male 2-15 IU/24 h 1.00 2-15 IU/d XXX 1 IU/d
fructose (P) <10 mg/dL 0.05551 <0.6 mmol/L X.XX 0.1 mmol/L
galactose (P) [children] <20 mg/dL 0.05551 <1.1 mmol/L X.XX 0.1 mmol/L
gases (aB)
pO2 75-105 mm Hg (= Torr) 0.1333 10.0-14.0 kPa XX.X 0.1 kPa
pCO2 33-44 mm Hg (= Torr) 0.1333 4.4-5.9 kPa X.X 0.1 kPa
gamma-glutamyltransferase [GGT] (S) 0-30 U/L 0.01667 0-0.50 µkat/L X.XX 0.01 µkat/L
gastrin (S) 0-180 pg/mL 1 0-180 ng/L XXO 10 ng/L
globulins (S) [see immunoglobulins] ... ... ... ... ... ... ...
glucagon (S) 50-100 pg/mL 1 50-100 ng/L XXO 10 ng/L
glucose (P) fasting 70110 mg/dL 0.05551 3.9-6.1 mmol/L XX.X 0.1 mmol/L
glucose (Sf) 50-80 mg/dL 0.05551 2.8-4.4 mmol/L XX.X 0.1 mmol/L
glutethimide (P)
-therapeutic <10 mg/L 4.603 <46 µmol/L XX 1 µmol/L
-toxic >20 mg/L 4.603 >92 µmol/L XX 1 µmol/L
glycerol, free (S) <1.5 mg/dL 0.1086 <0.16 mmol/L X.XX 0.01 mmol/L
gold (S) therapeutic 300-800 µg/dL 0.05077 15.0-40.0 µmol/L XX.X 0.1 µmol/L
gold (U) <500 µg/24 h 0.005077 <2.5 µmol/d X.X 0.1 µmol/d
153
154

Present
palmitic acid (Amf) Depends on mmol/L 1000 Depends on µmol/L XXX 5 µmol/L
gestation gestation
pentobarbital (P) 20-40 mg/L 4.419 90-170 µmol/L XX 5 µmol/L
phenobarbital (P)
-therapeutic 2-5 mg/L 43.06 85-215 µmol/L XXX 5 µmol/L
phensuximide (P) 4-8 mg/L 5.285 20-40 µmol/L XX 5 µmol/L
phenylbutazone (P)
-therapeutic <100 mg/L 3.243 <320 µmol/L XXO 10 µmol/L
phenytoin (P)
-therapeutic 10-20 mg/L 3.964 40-80 µmol/L XX 5 µmol/L

-toxic >30 mg/L 3.964 >12 µmol/L XX 5 µmol/L
phosphate (S) [as
phosphorus, inorganic] 2.5-5.0 mg/dL 0.3229 0.80-1.60 mmol/L X.XX 0.05 mmol/L
phosphate (U) [as
phosphorus, inorganic] Diet dependent g/24 h 32.29 Diet mmol/d XXX 1 mmol/d
dependent
phospholipid phosphorus, total (P) 5-12 mg/dL 0.3229 1.60-3.90 mmol/L X.XX 0.05 mmol/L
phospholipid phosphorus, total (Erc) 1.2-12 mg/dL 0.3229 0.40-3.90 mmol/L X.XX 0.05 mmol/L
phospholipids (P)
substance fraction of
total phospholipid
phosphatidyl choline 65-70 %/total 0.01 0.65-0.70 1 O.XX 0.01
phosphatidyl ethanolamine 4-5 %/total 0.01 0.04-0.05 1 O.XX 0.01
sphingomyelin 15-20 %/total 0.01 0.15-0.20 1 O.XX 0.01
lysophosphatidyl choline 3-5 %/total 0.01 0.03-0.05 1 O.XX 0.01
phospholipids (Erc)
substance fraction of
total phospholipid
phosphatidyl choline 28-33 %/total 0.01 0.28-0.33 1 O.XX 0.01
phosphatidyl ethanolamine 24-31 %/total 0.01 0.24-0.31 1 O.XX 0.01
sphingomyelin 22-29 %/total 0.01 0.22-0.29 1 O.XX 0.01
phosphatidyl serine + phosphatidyl inositol 12-20 %/total 0.01 0.12-0.20 1 O.XX 0.01
lysophosphatidyl choline 1-2 %/total 0.01 0.01-0.02 1 O.XX 0.01
phytanic acid (P) Trace-0.3 mg/dL 32.00 <10 µmol/L XX 5 µmol/L
[human] placental lactogen (SO [HPL] >4.0 after 30 wk µg/mL 46.30 >180 nmol/L XXO 10 nmol/L
gestation
porphobilinogen (U) 0.0-2.0 mg/24 h 4.420 0-9.0 µmol/d X.X 0.5 µmol/d
porphyrins
coproporphyrin (U) 45-180 µg/24 h 1.527 68-276 nmol/d XXX 2 nmol/d
protoporphyrin (Erc) 15-50 µg/dL 0.0177 0.28-0.90 µmol/L X.XX 0.02 µmol/L
uroporphyrin (U) 5-20 µg/24 h 1.204 6-24 nmol/d XX 2 nmol/d
uroporphyrinogen
synthetase (Erc) 22-42 mmol/mL/h 0.2778 6.0-11.8 mmol/ (L.s) X.X 0.2 mmol/(L.s)
potassium ion (S) 3.5-5.0 mEq/L 1.00 3.5-5.0 mmol/L X.X 0.1 mmol/L
mg/dL 0.2558 mmol/L X.X 0.1 mmol/L
potassium ion (U)
[diet dependent] 25-100 mEq/24 h 1.00 25-100 mmol/d XX 1 mmol/d
pregnaediol (U)
-normal 1.0-6.0 mg/24 h 3.120 3.0-18.5 µmol/d XX.X 0.5 µmol/d

-pregnancy Depends on
gestation
pregnanetriol (U) 0.5-2.0 mg/24 h 2.972 1.5-6.0 µmol/d XX.X 0.5 µmol/d
primidone (P)
-toxic >10.0 mg/L 4.582 >46 µmol/L XX 1 µmol/L
procainamide (P)
-toxic >12.0 mg/L 4.249 >50 µmol/L XX 1 µmol/L
N-acetyl procainamide (P)
progesterone (P)
follicular phase <2 ng/mL 3.180 <6 nmol/L XX 2 nmol/L
luteal phase 2-20 ng/mL 3.180 6-64 nmol/L XX 2 nmol/L
progesterone receptors (T)
negative 0-3 fmol 1.00 0-3 fmol XX 1 fmol/mg
progesterone progesterone protein
bound/mg bound/mg
cytosol protein cytosol protein
155
156

Present
doubtful 4-10 fmol 1.00 4-10 fmol XX 1 fmol/mg
bound/mg bound/mg
positive >10 fmol 1.00 >10 fmol XX 1 fmol/mg

bound/mg bound/mg
prolactin (P) <20 ng/mL 1.00 <20 µg/L XX 1 µg/L
propoxyphene (P) toxic >2.0 mg/L 2.946 >5.9 µmol/L X.X 0.1 µmol/L
propranolol (P)
[Inderal] therapeutic 50-200 ng/mL 3.856 190-770 nmol/L XXO 10 nmol/L
protein, total (S) 6.0-8.0 g/dL 10.0 60-80 g/L XX 1 g/L
protein, total (Sf) <40 mg/dL 0.01 <0.40 g/L X.XX 0.1 g/L
protein, total (U) <150 mg/24 h 0.001 <0.15 g/d X.XX 0.01 g/d
protryptyline (P) 100-300 ng/mL 3.797 380-1140 nmol/L XXO 10 nmol/L
pyruvate (B) [as
pyruvic acid] 0.30-0.90 mg/dL 113.6 35-100 µmol/L XXX 1 µmol/L
quinidine (P)
-therapeutic 1.5-3.0 mg/L 3.082 4.6-9.2 µmol/L X.X 0.1 µmol/L
-toxic >6.0 mg/L 3.082 >18.5 µmol/L X.X 0.1 µmol/L
renin (P)
normal sodium diet 1.1-4.1 ng/mL/h 0.2778 0.30-1.14 ng/(L.s) X.XX 0.2 ng/(L.s)
restricted sodium diet 6.2-12.4 ng/mL/h 0.2778 1.72-3.44 ng/(L.s) X.XX 0.02 ng/(L.s)
salicylate (S) [salicylic acid]
toxic >20 mg/dL 0.07240 >1.45 mmol/L X.XX 0.05 mmol/L
serotonin (B) [5 hydroxytryptamine] 8-21 µg/dL 0.05675 0.45-1.20 µmol/L X.XX 0.05 µmol/L
sodium ion (S) 135-147 mEq/L 1.00 135-147 mmol/L XXX 1 mmol/L
sodium ion (U) Diet dependent mEq/24 h 1.00 Diet mmol/d XXX 2 mmol/d
dependent
steroids
17-hydroxy-corticosteroids (U) [as cortisol]
-female 2.0-8.0 mg/24 h 2.759 5-25 µmol/d XX 1 µmol/d
-male 3.0-10.0 mg/24 h 2.759 10-30 µmol/d XX 1 µmol/d
17-ketogenic steroids (U) [as dehydroepian-
drosterone]
17-ketosteroids (U) [as dehydroepian-
drosterone]

ketosteroid fractions (U) androsterone
dehydroepiandrosterone
etiocholanolone
sulfonamides (B) [as sulfanilamide]
-therapeutic 10.0-15.0 mg/dL 58.07 580-870 µmol/L XXO 10 µmol/L
testosterone (P)
-female 0.6 ng/mL 3.467 2.0 nmol/L XX.X 0.5 nmol/L
-male 4.6-8.0 ng/mL 3.467 14.0-28.0 nmol/L XX.X 0.5 nmol/L
theophylline (P)
thiocyanate (P) (nitroprusside toxicity) 10.0 mg/dL 0.1722 1.7 mmol/L X.XX 0.1 mmol/L
thiopental (P) individual mg/L 4.126 individual µmol/L XX 5 µmol/L
thyroid tests:
thyroid stimulating
hormone [TSH] (S) 2-11 µU/mL 1.00 2-11 mU/L XX 1 mU/L
thyroxine [T4] (S) 4.0-11.0 µg/dL 12.87 51-142 nmol/L XXX 1 nmol/L
157
158

Present
thyroxine binding globulin [TGB] (S) [as 12.0-28.0 µg/dL 12.87 150-360 nmol/L XXO 1 nmol/L
thyroxine]
thyroxine, free (S) 0.8-2.8 ng/dL 12.87 10-36 pmol/L XX 1 pmol/L

triiodothyronine [T3] (S) 75-220 ng/dL 0.01536 1.2-3.4 nmol/L X.X 0.1 nmol/L
T3 uptake (S) 25-35 % 0.01 0.25-0.35 1 O.XX 0.01
tolbuamide (P)
-therapeutic 50-120 mg/L 3.699 180-450 mmol/L XXO 10 mmol/L
transferrin (S) 170-370 mg/dL 0.01 1.70-3.70 g/L X.XX 0.01 g/L
triglycerides (P) [as triolein] <160 mg/dL 0.01129 <1.80 mmol/L X.XX 0.02 mmol/L
trimethadione (P)
- therapeutic <50 mg/L 6.986 <350 µmol/L XXO 10 µmol/L
trimipramine (P)
-therapeutic 50-200 ng/mL 3.397 170-680 nmol/L XXO 10 nmol/L
urate (S) [as uric acid] 2.0-7.0 mg/dL 59.48 120-420 µmol/L XXO 10 µmol/L
urate (U) [as uric acid] Diet dependent g/24 h 5.948 Diet mmol/d XX 1 mmol/d
dependent
urea nitrogen (S) 8-18 mg/dL 0.3570 3.0-6.5 mmol/L UREA X.X 0.5 mmol/L
urea nitrogen (U) 2.0-20.0 diet g/24 h 35.700 450-700 mmol/d UREA XXO 10 mol/d
dependent
urobilinogen (U) 0.0-4.0 mg/24 h 1.693 0.0-6.8 µmol/d X.X 0.1 µmol/d
valproic acid (P)
-therapeutic 50-100 mg/L 6.934 350-700 µmol/L XO 10 µmol/L
vanillylmandelic acid [VMA] (U)* <6.8 mg/24 h 5.046 <35 µmol/d XX 1 µmol/d
vitamin A [retinol] (P,S) 10-50 µg/dL 0.03491 0.35-1.75 µmol/L X.XX 0.05 µmol/L
vitamin B1 [thiamine hydrochloride] (U) 60-500 mg/24 h 0.002965 0.18-1.48 µmol/d ZX.XX 0.01 µmol/d
vitamin B2 [riboflavin] (S) 2.6-3.7 µg/dL 26.57 70-100 nmol/L XXX 5 nmol/L
vitamin B6 [pyridoxal] (B) 20-90 ng/mL 5.982 120-540 nmol/L XXX 5 nmol/L
vitamin B12 (P,S) [cyanocobalamin] 200-1000 pg/mL 0.7378 150-750 pmol/L XO 10 pmol/L
vitamin C [see ascorbate] (B,P,S) ... ... ... ... ... ... ...
vitamin D3 [cholecalciferol] (P) 24-40 mg/mL 2.599 60-105 nmol/L XXX 5 nmol/L
25 OH-cholecacliferol 18-36 ng/mL .496 45-90 nmol/L XXX 5 mmol/L
vitamin E [alpha-tocopherol] (P,S) 0.78-1.25 mg/dL 23.22 18-29 µmol/L XX 1 µmol/L
warfarin (P)
-therapeutic 1.0-3.0 mg/L 3.243 3.3-9.8 µmol/L XX.X 0.1 µmol/L
xanthine (U)
-hypoxanthine 5-30 mg/24 6.574 30-200 µmol/d XXO 10 µmol/d

hmg/24 h 7.347 µmol/d XXO 10 µmol/d
D-xylose (B) [25 g dose] 30-40 (30-60 min) mg/dL 0.06661 .0-2.7 (30-60 mmol/L X.X 0.1 mmol/L
min)
D-xylose excretion (U) [25 g dose] 21-31 % 0.01 0.21-0.31 1 0.XX 0.01
(excreted in
5 h)
zinc (S) 75-120 µg/dL 0.1530 11.5-18.5 µmol/L XX.X 0.1 µmol/L
zinc (U) 150-1200 µg/24 h 0.01530 2.3-18.3 µmol/d XX.X 0.1 µmol/d
159
TABLE 3.23
Small Animal Analogs of Human Degenerative Diseases*
Type 1 Diabetes Mellitus (IDDM) Obesity
Streptozotocin or alloxan treated animals of most Zucker rat
species db/db mouse
Pancreatectomy will also produce IDDM SHR/N-cp rat
BB rat, NOD mouse (Both of these develop diabetes LA/N-cp rat
as an autoimmune disease and both mimic Type I ob/ob mouse
diabetes mellitus as found in humans.) Ventral hypothalamus lesioned animals
db/db mouse Osborne-Mendel rats fed high fat diets
FAT mouse
Hypertension
NZO mouse
TUBBY mouse SHR rats WKY rats
Adipose mouse JCR:LA rats Transgenic rats
Chinese hampster (Cricetulus griseus)
Gallstones
South African hamster (Mystromys alb)
Tuco-Tuco (Clenomys tabarum) (The rat does not have a gall bladder nor does it
have stones.)
Gerbil fed a cholesterol-rich, cholic acid-rich diet
Type 2 Diabetes Mellitus Hamster, prairie dog, squirrel monkey, or tree
shrew fed a cholesterol-rich diet
ob/ob mouse
KK, yellow KK mouse Lipemia
Avy, Ay yellow mouse
P, PB 13/Ld mouse Zucker fatty rat
db PAS mouse BHE/Cdb rat
BHE/Cdb rat NZW mouse
Zucker diabetic rat Transgenic mice given gene for atherosclerosis
SHR/N-cp rat
Atherosclerosis
Spiny mouse
HUS rat Transgenic mice given gene for atherosclerosis
LA/N-cp rat NZW mouse
Wistar Kyoto rat JCR:LA cp/cp rat
* There are several compilations of animal models for human disease. See the series of books edited
by Shafrir having the general title Lessons from Animal Diabetes published by Smith Gordon, London.
See also the NIH Guide for Animal Resources, updated annually, and the Jackson Laboratory catalog,
Bar Harbor, Maine.
TABLE 3.24
Composition of the AIN-93 Maintenance (M) and Growth (G) Diets
Ingredient AIN-93M (g/kg) AIN-93G (g/kg)
Casein 140 200

Cornstarch 465.692 397.486
Dextrose 155 132
Sucrose 100 100
Cellulose 50 50
Soybean oil 40 70
Mineral mix 35 35
Vitamin mix 10 10
L-cystine 1.8 3
Choline bitartrate 2.5 2.5
t-Butylhydroquinone 0.008 0.014
Energy ~3.8 kcal or ~16 kJ/g ~3.9 kcal or ~16.4 kJ/g
From: Journal of Nutrition 123:1941-44, 1993.

Part III
Comparative Nutrition
4
Animal Needs and Uses (Comparative Nutrition)
William P. Flatt
Overview — Nutritional Requirements for Different Species

The nutritional requirements for different species of animals, including mammals, birds
and fish, vary markedly. Many factors influence the requirements for specific nutrients.
Within species, some of the factors affecting nutritional requirements are age, gender, stage
of maturity, level of activity (work), body size, type and level of production (i.e. lean or
adipose body tissue, milk, eggs, wool, bone growth, etc.), environment, physiological
function (i.e. maintenance, pregnancy, lactation), health, and endocrinological factors.
Between and among species, the type of gastrointestinal tract greatly influences the nutri-
tional requirements of the animal, and the type of food it may eat to provide the nutrients.
For example, ruminants (cattle, sheep, goats, and deer), as a result of microbial fermen-
tation in the upper gastrointestinal tract, have quite different nutritional requirements
than nonruminants (humans, swine, dogs, cats, non-human primates). Ruminants, and
other herbivores that have extensive microbial fermentation in the large intestine and
cecum, may utilize cellulose, hemicellulose, and other high fiber diets that nonruminants
cannot digest. This adaptation also results in differences in the requirements for dietary
sources of some of the B vitamins and amino acids.
Some species store bile from the liver in the gallbladder (humans, swine, cattle, sheep,
chickens), whereas others (rats, horses, deer, elk, moose, camels) have no reservoir to store
bile, and this in turn may affect lipid digestion. Another species difference is in nitrogen
utilization. For example, mammals excrete excess nitrogen resulting from protein metab-
olism as urea, whereas birds excrete uric acid. Many different species of animals have
been used extensively as research models to obtain data on the nutrient requirements of
humans, and to learn the mode of action of various dietary additives. The researcher must
be aware of differences in the nutritional requirements of different species, or erroneous
conclusions could be drawn. For example, vitamin C is required for humans, guinea pigs,
and monkeys but not for swine and rats, which are frequently used as animal models.
It is essential for livestock, poultry, and aquatic food producers as well as veterinarians,
animal caretakers, biomedical research scientists, and others involved in caring for and
feeding animals to know what nutrients are required and the amounts of each, the effects
of different factors on the efficiency of nutrient utilization, and how best to provide feeds
0-8493-2705-9/01/$0.00+$1.50
with the proper proportions of these nutrients to the animals. Because of the economic
importance of this knowledge, scientists throughout the world have conducted research
with different species of animals, birds, and fish, and feeding standards based on this
research have been developed to formulate diets and rations for domestic livestock, poul-
try, companion animals, laboratory animals, and other species.
During the past century, scientists from many nations have conducted research on the
specific nutritional requirements of numerous species of animals, but there are so many
interactions among nutrients — and so many factors that influence nutrient utilization by
different species — that tables or formulae for calculating nutritional requirements must
be modified periodically. The data presented in this section are based on research sum-
marized by groups of scientists who are most knowledgeable about the nutritional research
that has been conducted anywhere in the world on that particular species. In the United
States, the National Academy of Sciences, National Research Council (NRC), Board on
Agriculture, Committee on Animal Nutrition has been responsible for appointing com-
mittees of expert animal scientists to publish periodical reports that summarize the most
up-to-date information on nutritional requirements of various species. The nutrient com-
position of feeds usually consumed by these animals is also included in each of the
publications, because the feed evaluation system used to express the nutritional value of
feeds determines the manner in which the nutritional requirements of the animal are
expressed. Specific information on each species may be obtained by obtaining the most
recent NRC publication on that species.
The health and wellbeing of animals are affected markedly by their nutritional status.
It is important to know how to properly provide feed that contains the nutrients animals
need to meet their nutritional requirements. This applies to companion animals such as
dogs, cats, birds, and fish as well as recreational animals such as horses, ponies, donkeys,
and camels. The efficient and economical production of food and fiber by domestic live-
stock and poultry requires good management practices, and especially balanced rations
that contain adequate supplies of protein, minerals, vitamins, and energy. In most, if not
all, animal production systems a limited energy supply more frequently retards growth
and limits production than a deficiency of any other nutrient. Crampton (1956)1 stated
that “the basic need of animals fed normal rations is for energy, and this demand is the
basis for most, and perhaps all, of the other nutrient requirements.”
The National Research Council, Board on Agriculture, Committee on Animal Nutrition
subcommittees prepare reports periodically published by the National Academy Press,
2101 Constitution Avenue NW, Washington, D.C. 20055. The most recent publications
(dairy cattle, horses, beef cattle, and swine) have included computer disks with tables of
nutrient requirements and feed composition. The full text, including tables, for Nutrient
Requirements of Swine, 10th Revised Edition, 1998, and may be accessed on the web site of
the National Academy Press (http://books.nap.edu).
The most recent National Academy Press series of publications on Nutrient Require-
ments of Domestic Animals is summarized in Table 4.l. The pages of the tables of nutrient
requirements of each species are included, but in order to use this information most
effectively, the tables of nutrient composition of most commonly used feed ingredients
are needed. The feed composition tables are included in each of these publications. The
1999 Feedstuffs Reference Issue (Volume 71, Number 31, July 30, 1999, pages 40-84) has
tables based on the NRC publications for swine, beef cattle, dairy cattle, chickens and
turkeys, horses, and pets (dogs and cats). There are numerous publications, including
animal nutrition textbooks, that have used the tables of nutrient requirements of various
species of livestock as well as the tables of nutrient composition. One recent example is
Livestock Feeds and Feeding, 4th Edition, 1998, by Richard O. Kellems and D.C. Church,
Prentice Hall, New Jersey. The species included in this text are: beef cattle, dairy cattle,
Animal Needs and Uses (Comparative Nutrition) 165
sheep, goats, swine, poultry, horses, dogs and cats, and rabbits (pages 485–552). Tables of
the composition of feedstuffs commonly fed to livestock are on pages 468–484.
Sources of Information for the Nutrient Requirements of Various Species

Nutrient Requirements of Domestic Animals: A Series. Subcommittees of the Committee on
Animal Nutrition, Board on Agriculture, National Research Council. National Academy
Press. Washington, D.C.
Publications with details, including complete text of most of the current publications
are on the computer web site (URL) at http://books.nap.edu. To locate each publication
type “Nutrient Requirements” in the box labeled SEARCH ALL TITLES. Tables with
specific information on the nutrient requirements of each species as well as the compo-
sition of diet ingredients (feedstuffs) may be accessed by clicking on OPEN BOOK Search-
able READ.
Companion Animals (Cats and Dogs)

Cats
Nutrient Requirements of Cats, Revised Edition, 1986, 88 pp. 8.5 X 11, 1986 ISBN
0-309-03682-8 (SF 447.6 .N88 1986).
Subcommittee on Cat Nutrition

Quinton R. Rogers, Chairman, University of California, Davis
David H. Baker, University of Illinois
Kenneth C. Hayes, Brandeis University
Peter T. Kendall, Pedigree Foods
James C. Morris, University of California, Davis
Dogs
Nutrient Requirements of Dogs, Revised 1985, 79 pp. ISBN 0-309-03496-5 (S 95 .N28
1985).
Subcommittee on Dog Nutrition

Ben E. Sheffy, Chairman, Cornell University
Kenneth C. Hayes, Brandeis University
Joseph J. Knapka, National Institutes of Health
John A. Milner, University of Illinois at Urbana-Champaign
James G. Morris, University of California, Davis
Dale R. Romsos, Michigan State University
Mink and Foxes

Nutrient Requirements of Mink and Foxes, Second Revised Edition, 1982 (BOA) 72 pp.
ISBN 0-309-03325-X.
Subcommittee on Furbearer Nutrition, 1982

Hugh Travis, Chairman, USDA, SEA, Cornell University
E.V. Evans, University of Guelph, Ontario
Gunnar Joergensen, National Institute of Animal Science, Denmark
Richard J. Aulerich, Michigan State University
William L. Leoschke, Valparaiso University, Indiana
James E. Oldfield, Oregon State University
Rabbits
Nutrient Requirements of Rabbits, Second Revised Edition, 1977.
Subcommittee on Rabbit Nutrition, 1977

Arrington Lewis, Chairman
Peter R. Cheeke
Francois Lebas
Sedgwick E. Smith, Cornell University
Laboratory Animals
Rat, mouse, guinea pigs, hamster, gerbils, voles
Nutrient Requirements of Laboratory Animals, Fourth Revised Edition, 1995 (BOA),

Nutrient Requirements of Domestic Animals, National Research Council, Na-
tional Academy Press, Washington, D.C. 1995. 173 pp. ISBN 0-309-05126-6 (SF
406.2 .N88 1995).
Subcommittee on Laboratory Animal Nutrition

Norlin J. Benevenga, Chair, University of Wisconsin, Madison
Christopher Calvert, University of California, Davis
Curtis D. Eckhert, University of California, Los Angeles
Janet L. Greger, University of Wisconsin, Madison
Carl L. Keen, University of California, Davis
Joseph J. Knapka, National Institutes of Health, Bethesda, Maryland
Hulda Magalhaes, Bucknell University
Olav T. Oftedal, National Zoological Park, Washington, D.C.
Philip G. Reeves, Agricultural Research Service, U.S. Department of Agriculture,
Grand Forks, North Dakota
Helen Anderson Shaw, University of North Carolina, Greensboro
John Edgar Smith, Pennsylvania State University, University Park
Robert D. Steele, University of Wisconsin
Fish
Nutrient Requirements of Fish (BOA) 128 pp., ISBN-04891-5, 1993 (SH 156 .N86
1993).
Subcommittee on Fish Nutrition

Richard T. Lovell, Chair, Auburn University
C. Young Cho, University of Guelph and Fisheries Branch, Ontario
Ministry of Natural Resources, Canada
Colin B. Cowey, University of Guelph, Canada
Konrad Dabrowski, The Ohio State University
Steven Hughes, U.S. Fish and Wildlife Service, Monell Chemical
Senses Center, Philadelphia, Pennsylvania
Santosh Lall, Nova Scotia Department of Fisheries and Ocean, Canada
Takeshi Murai, National Institute of Fisheries Science, Tokyo, Japan
Robert P. Wilson, Mississippi State University
Avian Species
Poultry (chickens, turkeys, geese, ducks, pheasants, Japanese quail, bobwhite quail)
Nutrient Requirements of Poultry, Ninth Revised Edition, 1994 (BOA) 176 pp., ISBN
0-309-04892-3.
Subcommittee on Poultry Nutrition

Jerry L. Sell, Chair, Iowa State University
F. Howard Kratzer, University of California, Davis
J. David Latshaw, The Ohio State University
Steven L. Leeson, University of Guelph
Edwin T. Moran, Auburn University
Carl M. Parsons, University of Illinois
Park W. Waldroup, University of Arkansas
Domestic Livestock
Nonruminant Species
Swine
Nutrient Requirements of Swine, Tenth Revised Edition, 1998 (BOA) 210 pp., ISBN
0-309-05993-3, Computer laser optical disc (4 3/4 in.).
Subcommittee on Swine Nutrition

Gary L. Cromwell, Chair, University of Kentucky
David H. Baker, University of Illinois
Richard C. Ewan, Iowa State University
E.T. Kornegay, Virginia Polytechnic Institute and State University
Austin J. Lewis, University of Nebraska
James E. Pettigrew, Pettigrew Consulting International, Louisiana, Missouri
Norman C. Steele, U.S.D.A., A.R.S., Beltsville, Maryland
Philip A. Thacker, University of Saskatchewan, Canada
Horses
Nutrient Requirements of Horses, Fifth Revised Edition, 1989 (BOA) 112 pp., ISBN
03989-4.
Subcommittee on Horse Nutrition

Edgar, A. Ott, Chairman, University of Florida, Gainesville
John P. Baker, Uniiversity of Kentucky
Harold F. Hintz, Cornell University
Gary D. Potter, Texas A & M University
Howard D. Stowe, Michigan State University
Duane E. Ullrey, Michigan State University
Ruminant Species
Beef cattle
Nutrient Requirements of Beef Cattle, Seventh Revised Edition, 1996 (BOA) Note: The
7th Revised Edition Update 2000 was released and is on the web site. 242 pp.,
ISBN 0-309-05426-5, 1 computer disk (3 1/2 in.).
Subcommittee on Beef Cattle Nutrition, 1996

Jock G. Buchanan-Smith, Chair, University of Guelph, Canada
Larry L. Berger, University of Illinois
Calvin L. Ferrell, U.S.D.A., A.R.S., Clay Center, Nebraska
Danny G. Fox, Cornell University
Michael L. Galyean, Clayton Livestock Research Center, Clayton, New Mexico
David P. Hutcheson, Animal Agricultural Consulting, Inc., Amarillo, Texas
Terry J. Klopfenstein, University of Nebraska
Jerry W. Spears, North Carolina State University
Dairy cattle
Nutrient Requirements of Dairy Cattle, Sixth Revised Edition, Update l989 (BOA) 168
pp., ISBN 0-309-03826-X.
Subcommittee on Dairy Cattle Nutrition

Roger W. Hemken, Chairman, University of Kentucky
Clarence B. Ammerman, University of Florida
Donald L. Bath, University of California, Davis
Jimmy H. Clark, University of Illinois
Neal A. Jorgersen, University of Wisconsin
Paul W. Moe, U.S. Department of Agriculture, Beltsville, Maryland
Lawrence D. Muller, Pennsylvania State University
Dale R. Waldo, U.S. Department of Agriculture, Beltsville, Maryland
Sheep
Nutrient Requirements of Sheep, Sixth Revised Edition, 1985 (BOA) 112 pp., ISBN 0-
309-03596-1.
Subcommittee on Sheep Nutrition

Robert M. Jordan, Chairman, University of Minnesota
Millard C. Calhoun, Texas Agricultural Experiment Station, San Angelo
Donald G. Ely, University of Kentucky
David P. Heaney, Research Branch, Agriculture Canada, Ottawa
Frank C. Hinds, University of Wyoming
Donald E. Johnson, Colorado State University
Goats
Nutrient Requirements of Goats: Angora, Dairy, and Meat Goats in Temperate and Tropical
Countries (BOA) 84 pp., ISBN 0-309-03185-0 (SF 95. N28 no. 15).
Subcommittee on Goat Nutrition

George F.W. Haenlein, Chairman, University of Delaware, Newark
Canagasaby Devendra, Maylasian Agricultural Research and Development Insti-
tute, Serdang, Maylasia
James E. Huston, Texas A&M University, San Angelo
O.P.S. Sengar, Raja Balwant Singh College, Bichpuri (Agra), India
Maurice Shelton, Texas A&M University, San Angelo
S.N. Singh, Raja Balwant Singh College, Bichpuri (Agra), India
Nonhuman Primates
Nutrient Requirements of Nonhuman Primates 1978 ix, 83 p.: ill. :28 cm. 1978 ISBN
0-309-02786-1 (SF 95 .N28 1978).
Panel on Nonhuman Primates

George R. Kerr, Chairman, University of Texas School of Public Health
Coy D. Fitch, St. Louis University
Ronald D. Hunt, New England Regional Primate Center
Nutrient Requirement Table 1 pages 18-19.
Nutrient Requirements of Nonhuman Primates: Second Revised Edition, 2000, 300 pages
(not yet available).
TABLE 4.1
Web Addresses for Tables of Nutrient Requirements for a Variety of Animals
National Academy Press. Washington, D.C. List of publications with tables of nutrient requirements of each
species. http://books.nap.edu. To obtain complete text, including tables, fill in the box labeled SEARCH ALL
TITLES with “Nutrient Requirements” and all the following publications with hyperlinks will appear at URL
http://books.nap.edu/catalog/910.html.
Nutrient Requirements of Cats, Revised Edition, 1986 (SF 447.6 .N88 1986) Nutrient Requirement Tables, pages 41-
44. (http://www.nap.edu/openbook/0309036828/html)
Nutrient Requirements of Dogs, Revised 1985 (S 95 .N28 1985) Nutrient Requirement Tables, pages 44-45. (http://
www.nap.edu/openbook/0309034965/html/44.html)
Nutrient Requirements of Mink and Foxes, Second Revised Edition, 1982 (SF 95 .N28 1982) Nutrient Requirement
Tables, pages 33-36. (http://www.nap.edu/openbook/030903325X/html/33.html)
Nutrient Requirements of Rabbits, Second Revised Edition, 1977 (SF 95 .N32 1977) Nutrient Requirement Tables,
pages 14-15. (http://www.nap.edu/openbook/0309026075/html/14.html)
Nutrient Requirements of Laboratory Animals, Fourth Revised Edition, 1995 (SF 406.2 .N88 1995) Nutrient Requirement
Tables for Rats, page 13; Mice, page 82; Guinea Pigs, page 104-105; (Hamsters, Gerbils, and Voles — text rather
than tables) (http://www.nap.edu/openbook/0309051266/html/11.html)
Nutrient Requirements of Fish, 1993 (SH 156 .N86 1993) Nutrient Requirements Table, pages 62-63. (http://
www.nap.edu/openbook/0309048915/html/62.html)
Nutrient Requirements of Poultry, Ninth Revised Edition, 1994 (SF 95 .N28 1994) Nutrient Requirement Tables for
Chickens, pages 19-34 for Tables 2-1 through 2-8; for Turkeys, pages 35-39, Tables 3-1 through 3-3; for Geese
pages 40-41; for Ducks, pages 42-43; for Ring-Necked Pheasants, page 44; for Japanese Quail, page 45; for
Bobwhite Quail, page 45. (http://www.nap.edu/openbook/0309048923/html/19.html)
Nutrient Requirements of Swine, 10th Revised Edition, 1998 (SF 396.5 .N87 1998). Nutrient Requirement Tables,
pages 110-123. Computer laser optical disc (4 3/4 in.). (http://www.nap.edu/openbook/0309059933/html/
110.html)
Nutrient Requirements of Horses, Fifth Revised Edition, 1989 (SF 285.5 .N37 1989). Nutrient Requirement Tables,
pages 39-48. Computer disk (5 1/4 in.). (http://www.nap.edu/openbook/0309039894/html/39.html)
Nutrient Requirements of Beef Cattle, Seventh Revised Edition, 1996 (SF 203 .N88 1996) Nutrient Requirement Tables,
pages 102-112. Prediction Equations and Computer Models, pages 113-131. Computer disk (3 1/2 in.). (http:
//www.nap.edu/openbook/0309069343/html/102.html)
Nutrient Requirements of Beef Cattle, Seventh Revised Edition: Update 2000, NRC Model Application software
available on line at http://stills.nap.edu/readingroom/books/beefmodel/
Nutrient Requirements of Dairy Cattle, Sixth Revised Edition, Update 1989 (SF 203 .N34 1988) Nutrient Requirement
Tables, pages 78-88. Computer disk (5 1/4 in.). (http://www.nap.edu/openbook/030903826X/html/78.html)
Nutrient Requirements of Sheep, Sixth Revised Edition, 1985 (SF 376 .N85 1985) Nutrient Requirement Tables, pages
45-53. (http://www.nap.edu/openbook/0309035961/html/45.html)
Nutrient Requirements of Goats: Angora, Dairy, and Meat Goats in Temperate and Tropical Countries, 1981 (S 95 .N28
1981) Nutrient Requirement Tables, pages 10-12. (http://www.nap.edu/openbook/0309031850/html/10.html)
Nutrient Requirements of Nonhuman Primates 1978 (SF 95 .N28 1978) Nutrient Requirement Table 1 pages 18-19.
Print-On-Demand. (http://books.nap.edu/catalog/34.html)
Nutrient Requirements of Nonhuman Primates: Second Revised Edition, 2000 300 pages In press, not yet available.
TABLE 4.2
Publications Providing Information on the Nutrient Needs of Specific Animals
A. Nutrient requirements of companion animals (cats and dogs), rabbits, mink and foxes, and
laboratory animals (rats, mice, guinea pigs, hamsters, gerbils, and voles) and rabbits, mink, and
foxes. Tables of nutrient requirements from Nutrient Requirements of Domestic Animals: A Series.
National Research Council, National Academy Press (http://books.nap.edu)
Year last Pages of Computer NAP Web
Species NRC Publication revised Tables disk site of Tables
Companion Animals
Cats Nutrient Requirements of Cats 1986 41–44 No Yes

Dogs Nutrient Requirements of Dogs 1985 44–45 No Yes
Laboratory Animals
Nutrient Requirements of Laboratory 1995 13–105 No Yes

Animals
Rats Nutrient Requirements of Laboratory 1995 13 No Yes
Animals
Mice Nutrient Requirements of Laboratory 82 No Yes
Animals
Guinea pigs Nutrient Requirements of Laboratory 104–105 No Yes
Animals
Hamsters Nutrient Requirements of Laboratory Text No Yes
Animals
Gerbils Nutrient Requirements of Laboratory Text No Yes
Animals
Voles Nutrient Requirements of Laboratory Text No Yes
Animals
Other Small Animals
Rabbits Nutrient Requirements of Rabbits 1977 14–15 No Yes

Mink Nutrient Requirements of Mink and 1982 33–34 No Yes
Foxes
Foxes Nutrient Requirements of Mink and 1982 35–36 No Yes
Foxes
B. Nutrient requirements of poultry (chickens, turkeys, geese, ducks, ring-necked pheasants,

Japanese quail and bobwhite quail), fish, nonhuman primates, horses and swine. Tables of nutrient
requirements from Nutrient Requirements of Domestic Animals: A Series. National Research Council,
National Academy Press (http://books.nap.edu)
Avian Species
Nutrient Requirements of Poultry 1994 19–45 No Yes

Chickens Nutrient Requirements of Poultry 1994 19–34 No Yes
Turkeys Nutrient Requirements of Poultry 1994 35–39 No Yes
Geese Nutrient Requirements of Poultry 1994 40–41 No Yes
Ducks Nutrient Requirements of Poultry 1994 42–43 No Yes
Ring-necked Nutrient Requirements of Poultry 1994 44 No Yes
pheasants
Japanese quail Nutrient Requirements of Poultry 1994 45 No Yes
Bobwhite quail Nutrient Requirements of Poultry 1994 45 No Yes
B. Nutrient requirements of poultry (chickens, turkeys, geese, ducks, ring-necked pheasants,

Japanese quail and bobwhite quail), fish, nonhuman primates, horses and swine. Tables of nutrient
Other Species
Fish Nutrient Requirements of Fish 1993 62–63 No Yes

Nonhuman Nutrient Requirements of Nonhuman 1978 18–19 No No
Primates Primates (2000 in (Yes, soon for
press) 2000)
Horses Nutrient Requirements of Horses 1989 39–48 Yes Yes
(5 1/4 in.)
Swine Nutrient Requirements of Swine 1998 110–123 Yes Yes
(Laser optical
disk, 4 3/4 in.
C. Nutrient requirements of ruminants (beef cattle, dairy cattle, sheep and goats). Tables of nutrient
Ruminant Species
Beef Cattle Nutrient Requirements of Beef Cattle 2000 102–112 Yes Yes
(3 1/2 in.)
Dairy Cattle Nutrient Requirements of Dairy 1989 78–88 Yes Yes
Cattle (5 1/4 in.)
Sheep Nutrient Requirements of Sheep 1985 45–53 No Yes
Goats Nutrient Requirements of Goats: 1981 10–12 No Yes
Angora, Dairy and Meat Goats in
Temperate and Tropical Countries
References
1. Crampton, EW. 1956. Applied Animal Nutrition. The Use of Feedstuffs in the Formulation of Livestock
Rations. W.H. Freeman and Co., San Francisco, CA.
Part IV
Human Nutrient Needs

in the Life Cycle
5
Nutrition during Pregnancy and Lactation
Kathryn M. Kolasa and David G. Weismiller
Recommendations for Women before Pregnancy

It seems logical that the nutritional status of a woman prior to pregnancy as well as
maternal nutrition should affect fetal development and subsequent pregnancy outcome.
However, many confounding variables are common to the investigation of maternal nutri-
tion and fetal development.1 This section briefly summarizes recommendations for mater-
nal nutrition.2-7 It also includes comments about lactation, since maternal diet plays a
central role in the transfer of nutriments to the infant. Table 5.1 includes special recom-
mendations for women during childbearing years. Suggestions for counseling and treat-
ment during a preconception care office visit are given in Table 5.2.
Risk Factors for Prenatal Nutrition Risk and Indications for Referral
Table 5.2 includes nutrition assessment, counseling, and treatment strategies for women
seeking care in both the prenatal and postnatal stages. Fetal growth is affected by the
TABLE 5.1
Special Recommendations for Women before Pregnancy
Maintain a healthy weight.
Engage in physical activity regularly.
If you need to gain or lose weight, do so gradually (no more than 1–2 pounds/week).
If trying to become pregnant and ordinarily drink alcoholic beverages, stop drinking or cut back on the amount
you drink.
If you smoke, quit or cut back to improve health.
To minimize risk of having an infant with a neural tube defect, eat a highly fortified breakfast cereal that provides
100% of the Daily Value (DV) for folate or take a vitamin supplement that provides 400 µg/day of folic acid.
Folic acid, the synthetic form of folate, is obtained only from fortified foods or vitamin supplements. It is not
yet known whether naturally occurring folate is as effective as folic acid in the prevention of neural tube defects.
0-8493-2705-9/01/$0.00+$1.50
TABLE 5.2
Nutritional Care at Preconception, Prenatal, and Postnatal Visits
Visit Assessment Counseling/Treatment
Preconception Determine BMI If <18 or >25, counsel on appropriate weight
care
Evaluate diet/supplement Develop a concrete plan for eating enough food to
intake achieve/maintain a healthy weight
Begin prenatal vitamin/mineral supplement
Prescribe calcium supplement if intake <1000 mg
Prescribe synthetic folic acid supplement of 400 µg per day
Botanical use Discontinue those with known or potential toxicities
Evaluate for anemia Hgb <12 g/dl, start therapeutic regimen of approximately
60–120 mg/day of ferrous iron; give multivitamin/
mineral supplement that contains ~15 mg of zinc and ~2
mg of copper
When anemia has resolved, discontinue high-dose iron
Use of harmful substances Reinforcement for any constructive steps already taken;
provide assistance with quitting, and refer for further
evaluation
Prenatal Evaluate diet Utilize dietary intake questionnaire, e.g. Diet Score, food
frequency questionnaires
Optimal weight gain during BMI <19.8 28–40 lbs
pregnancy 19.8–26.0 25–35 lbs
26.1–29.0 15–25 lbs
>29 ~15 lbs
Rate of weight gain First trimester 1 1/2–5 lbs
Second and third trimester 1/2–2 lbs/week
Poor weight gain Intensive assessment and counseling
< 2 lbs/month
< 10 lbs by mid-pregnancy
Nutritional needs/barriers If patient is economically unable to meet nutritional needs
— referral to federal food and nutrition programs (WIC)
Increase knowledge with dietary counseling
Vitamin/mineral No requirement for routine supplementation except folate
supplementation (400 µg/day) and iron (30–60 mg elemental iron/day)
Dietary supplements should be given if the adequacy of
a patient’s diet is questionable or if she is at high
nutritional risk
Excessive vitamin and mineral intake (more than twice
the RDA) should be avoided
Prophylaxis for iron deficiency Supplement of ferrous iron — 30 mg elemental iron daily
Iron deficiency anemia 60–120 mg elemental iron daily
Evaluate use of alcohol, Effects of substance use/abuse on perinatal outcomes
tobacco, drugs Abstinence from alcoholic beverages
Caffeine intake Consumption of 2–3 servings of caffeinated beverages is
unlikely to have adverse effects; in general, caffeinated
beverages provide few essential nutrients and often
crowd out better sources of nutrients
Lactose intolerance May result in insufficient calcium intake
Supplemental calcium necessary if insufficient calcium
consumed from food sources
Gestational diabetes mellitus Referral for nutrition assessment and counseling
Nausea/emesis Eat crackers before getting out of bed in the morning; eat
frequent small meals; eat low-fat, bland foods; eat ginger
(soda, tea, or ginger snaps); suck on hard candy; eat
salty/tart foods combined (e.g., potato chips with
lemonade); supplement with vitamin B6 (25 mg three
times daily); wear Sea Band® (an elastic band worn on
wrists to counter nausea caused by sea-sickness)
Nutrition during Pregnancy and Lactation 177

Nutritional Care at Preconception, Prenatal, and Postnatal Visits
Visit Assessment Counseling/Treatment
Hyperemesis gravidarum Doxylamine (Unisom), 12.5–25 mg three times daily;
ginger in any form (tea, soda, tablets [250-mg capsule, 4
times daily for 4–5 days]); emetrol, 5–10 mL in the
morning and every 3–4 hours as needed; anti-emetic/
anti-nausea medications (e.g., trimethobenzamine
[Tebamide, Tigan, Trimazide], 200 mg suppository three
times daily, or promethazine, 12.5–25 mg orally, rectally,
or intravenously every 4–6 hours)
Constipation Foods high in dietary fiber, including cereals, bread, fruits,
and vegetables; adequate fluids; moderate exercise;
soluble fiber (e.g., Metamucil, Citrucel); docusate; change
brand of iron supplement
Postpartum Diet Utilize dietary intake questionnaire
Dietary guidelines are similar to those established during
pregnancy
Balanced, nutritious diet will ensure both the quality and
quantity of milk produced without depletion of maternal
stores
Caloric requirement Minimal caloric requirement for adequate milk
production in a woman of average size is 1800 kcal/day
Vitamin/mineral supplement Not needed routinely; mothers at nutritional risk should
be given a multivitamin supplement with particular
emphasis on calcium and vitamins B12 and D
Weight retention There is no relationship between BMI or total weight gain
and weight retention
Aging, rather than parity, is the major determinant of
increases in a woman’s weight over time
Residual postpartum weight Special attention to lifestyle, including exercise and eating
retention habits
quality and quantity of the maternal diet, the ability of the mother to digest and absorb
nutrients, maternal cardiorespiratory function, uterine blood flow, placental transfer, pla-
cental blood flow, and appropriate distribution and handling of nutrients and oxygen by
the fetus. Factors that put women at nutritional risk for pregnancy are listed in Table
5.3.5,8-10 Patients at high nutritional risk should be provided professional nutritional coun-
seling and/or referral to a nutrition intervention program. (Table 5.4). The Women, Infants,
and Children (WIC) Program is a food prescription program designed and proven to
reduce poor pregnancy outcomes (Table 5.5).
Weight Gain and Pregnancy

Pregnancy Weight Goals
There is a lack of consistent findings concerning relationships of birth interval, parity,
prepregnancy weight or body mass index (BMI), height, and physical activity to maternal
weight or weight gain.11-24 The Cochrane Pregnancy and Childbirth Group25 summarized
the findings on the effects of advising pregnant women to increase their energy and protein
intakes, on gestational weight gain, and on the outcome of pregnancy. They found that
nutritional advice appears to be effective in increasing pregnant women’s energy and
TABLE 5.3
Risk Factors for Prenatal Nutritional Risk
Risk Factor Low Risk High Risk
Is patient pre- or adolescent or less than 3 yrs post menarche? No Yes
Is patient economically disadvantaged or have limited income for food? No Yes
Does patient have history of anemia or is anemic (hematocrit <32 mg/% during No Yes
pregnancy)?
Is patient’s BMI <19.8 or >26.1? No Yes
Does patient have history of fad dieting, or restrictive eating? No Yes
Does patient have illness or medication that will interfere with absorption; is she No Yes
HIV+ ?
Does patient use tobacco, alcohol, or drugs? No Yes
Does patient practice pica (consume ice, starch, clay, or other substances in large No Yes
amounts)?
Does patient experience nausea and/or vomiting? No Yes
Is patient lactose intolerant? No Yes
Is weight gain 0.8–1.0 lb/wk? No Yes
Does patient stay within the weight gain range recommended for her prepregnancy Yes No
BMI?
Weight gain less than 15 lbs or more than 45 lbs? No Yes
TABLE 5.4
Indications for a Referral of Pregnant Patients for Nutrition Assessment and Counseling
Patient has interest in and desire to see a nutritionist
Patient has inappropriate weight gain
Patient has gestational diabetes
Patient has chronic condition managed with diet (e.g., diabetes, hyperlipidemia)
Patient has history of anemia
Patient has inadequate or inappropriate food supply
Patient has history of prepregnancy anorexia or bulimia
Patient has significant discomforts of pregnancy (e.g., heartburn, nausea, vomiting)
Patient has preeclampsia
Patient has multiple gestation
Patient is adolescent
Patient is vegetarian
Patient is interested in or undecided about breastfeeding
TABLE 5.5
Characteristics of Women, Infants, and Children (WIC) Program
Target Audience Pregnant women
Breastfeeding women
Non-breastfeeding mothers of infants <6 months old
Infants <1 y/o
Children <5 y/o
Purpose Provide nutritious foods, health checks, referrals, nutrition education, and counseling
Eligibility Criteria Low income: <185% U.S. federal poverty level for women and children
Food Nutrient rich, high in protein, calcium, iron and vitamins A & C
Limited brand names
Patient-purchased food and infant formula from local supermarkets
Nutrition Education Individual and group
Specific to risk
Health Checks Height, weight, and anemia testing for women, infants and children
Height, weight, and anemia testing for women and children
1 yr old test for lead
TABLE 5.6
Pregnancy Weight Goals
Optimal Weight Gain
(pounds) Characteristic
25–35 Most women and normal pregnancy
Prepregnancy BMI 19.8–26.0 or 100% prepregnancy
ideal body weight
28–40 Women at higher risk for low birth weight babies
including adolescents and African American women
Prepregnancy BMI <19.8 (underweight) or 90% ideal
body weight
Twin pregnancy
15–25 Prepregnant BMI >26.1 (overweight or obese) or
>120% ideal body weight
15 Prepregnant BMI >29 or >135% ideal body weight
Date
Weeks'
gestation 6 8 10 12 14 16 18 20 22 24 26 28 30 32 33 34 35 36 37 38 39 40 41 42 43
Fundal height (cm)
40
+50 lb 35
ight 50 lb
al he
+40 lb 30 Fund 40 lb
+30 lb 25 30 lb
+20 lb 20 Weight 20 lb
+10 lb 10 lb
FIGURE 5.1
Graph for tracking weight and fundal height. (From Kolasa, K.M. and Weismiller, D.G., Nutrition during
pregnancy, Am Fam Phys, 56(1): 206, July 1995. With permission.)
protein intakes but the implications for fetal, infant, or maternal health cannot be judged
from the available trials.26
Some researchers question the recommendation that African American women gain
more weight than caucasian women, suggesting that the data only show questionable
benefit in reducing risks for low birth weight babies. Obese women have a greater risk of
pregnancy complications, especially gestational diabetes, hypertensive disorders, cesarean
deliveries, and postoperative morbidity. Infants of obese women may be at greater risk
for macrosomia and perinatal death.21,25
The recommendations in Table 5.6 were established by the National Academy of Sciences
of the National Institute of Medicine in 1990.16 They were reviewed and left unchanged
by the Maternal Weight Gain Expert Group in 1996.24 Weight gain goals are determined
to provide optimal risk reduction for delivering a low birth weight baby while avoiding
adverse effects on the mother’s health. The recommendations vary based on prepregnancy
weight, age, and ethnicity. The weight gain expected is essentially linear, as demonstrated
in Figure 5.1.4
Women with prepregnant body mass index (BMI) >35 are at increased risk for gestational
diabetes, preeclampsia, placenta abrupta, cesarean delivery, and endometriosis.
Rate of Weight Gain

In 1996, the Maternal and Weight Gain Expert Group24 suggested a weight gain of 1.5
pounds/week for normal weight women during the second half of a twin pregnancy.
TABLE 5.7
Rate of Weight Gain (Pounds)
Timing
(trimester) Appropriate Inadequate Excessive
1st 3–5 Total Less More
2nd, 3rd 1/wk Less than 2 lbs in a single month for normal More than 6.5 in a single month
wt women or less than 1 lb in obese
TABLE 5.8
Weight Gain Distribution during Pregnancy (Pounds)
Source Pounds
Amniotic fluid 2–2.6
Baby 7–8.5
Fat/breast tissue stores for breastfeeding 1–4
Increased blood volume 4–5
Increased weight of uterus 2
Maternal fat stores 4–7
Placenta 0.7–1.0
Tissue fluid 3–5
Total 25–35
Weight gain is the single most reliable indicator of pregnancy outcome.11,23 Weight status
should be routinely assessed for amount and rate. Figure 5.1 depicts an example of a graph
for tracking weight. Weight charts should be shown to women and their support partners.
Table 5.7 gives recommended weight gains. The optimal weight for a newborn infant of
39 to 41 weeks gestation is 6.6 to 8.8 pounds.9
Women with inadequate weight gain should eat more frequently, be referred to a die-
titian for nutrient assessment and counseling, choose more nutrient-dense foods, avoid
alcohol and tobacco use, limit activity, and avoid caffeine or other appetite depressants.
Women with excessive gain should reduce portion sizes, limit intake of sweets and foods
high in fat, increase activity, and be evaluated by a registered dietitian.
Weight Gain Distribution during Pregnancy

Weight gain by pregnant women consists of water, protein, and fat. Measurements of
maternal water gain may predict birth weight better than measurements of composite
weight gain. The total amount of weight gained, the composition of gain, and the rate of
energy metabolism all differ among healthy pregnant women. Table 5.8 is a typical teach-
ing tool about weight gain distribution.
Nutrition Snacks
Pregnant women may need suggestions for healthy snacks. Table 5.9 includes snacks of
about 100 calories.
Dietary Requirements for Pregnancy and Lactation

Dietary Reference Intake (DRI)
Dietary Reference Intakes are the levels of intake of essential nutrients considered adequate
to meet or exceed known nutritional needs of practically all healthy people. Table 5.10
TABLE 5.9
Nutritious Snacks of 100 kcalories or Less
Food Item Serving Size
Applesauce 2/3 cup
Bagel 1 /2
Carrot, raw 1 cup or 1 large

Cheese, low-fat 1 oz.
Cottage cheese, low-fat 1/3 cup
Entenmann’s® fat-free cakes/pastries 1 small slice
Figs, low-fat or other Newton® cookies 1-1/2 tsp
fruit, dried (like apricots, raisins, prunes) 4 tsp.
Fruit, fresh 1 medium
Graham crackers 2
Grits 1 package
Milk, skim 1 cup
Pretzels 15
Pudding made w/skim milk 1/3 cup
Rice cakes, flavored 2
Tortilla chips, baked, low-fat and w/salsa 12
Tuna 1/2 cup
Yogurt, frozen 1/2 cup
Yogurt, low-fat 1/2 cup
includes the Recommended Dietary Allowances (RDA) and Adequate Intakes (AI) as
available in 1999 for pregnancy and lactation.27,28 These levels are set by the Food and
Nutrition Board of the National Academy of Sciences.
Nutrient needs that are increased during pregnancy and/or lactation include protein,
folate, vitamins A, B6, C, and D, calcium, iron, and zinc.18,29-34 Energy needs are also
increased by 300 kcal/day at the second trimester of pregnancy and by 850 kcal/day
during lactation to produce adequate breast milk supply. During lactation 500 calories
should be consumed as nutrient-dense foods, with the remaining 350 calories coming from
maternal fat stores accumulated during pregnancy.35
The Food Guide Pyramid Servings

The Food Guide Pyramid (Table 5.11) provides guidelines for the number of servings from
each food group that should be eaten daily during pregnancy and lactation. Pregnant
women should drink 8 to 10 glasses of water each day.
Dietary Assessment of the Pregnant Woman

Individualized nutrition assessment and planning is important because of the strong
associations between extremes in prepregnancy BMI, extremes in weight gain, and adverse
pregnancy outcomes.3,4,7,36,37
Behavior Change Tool

Assessment relies on the woman’s medical record, history, and physical examination.
Nutritional factors of importance include previous nutritional challenges, eating disorders,
pica, fad dieting, strict vegetarian diet, medications, and quantity and quality of current
diet. The Institute of Medicine provides a sample dietary history tool (Table 5.12).3
182
TABLE 5.10
Food and Nutrition Board, National Academy of Sciences — National Research Council Recommended Dietary
Allowances,a revised 1989 (abridged) and Dietary Reference Intakes (DRI)
Designed for the maintenance of good nutrition of practically all healthy people in the United States
Protein Vitamin A Vitamin E Vitamin K Vitamin C Iron Zinc Iodine Selenium
Category Condition (g) (µg RE)b (mg α-TE)c (µg) (mg) (mg) (mg) (µg) (µg)
Pregnant 60 800 10 65 70 30 15 175 65
Lactating 1st 6 months 65 1300 12 65 95 15 19 200 75
2nd 6 months 62 1200 11 65 90 15 16 200 75
Note: Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride [1997] and Dietary Reference Intakes for Thiamin,
Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline [1998].
a The allowances, expressed as average daily intakes over time, are intended to provide for individual variations among most normal
persons as they live in the U.S. under usual environmental stresses. Diets should be based on a variety of common foods in order to
provide other nutrients for which human requirements have been less well defined.
b Retinol equivalents. 1 retinol equivalent = 1 µg retinol or 6 µg β-carotene.
c α-Tocopherol equivalents. 1 mg d-α tocopherol = α-TE.
Food and Nutrition Board, Institute of Medicine — National Academy of Sciences
Dietary Reference Intakes: Recommended Intakes For Individuals

Vitamin Vitamin Vitamin
Life-Stage Calcium Phosphorus Magnesium D Fluoride Thiamin Riboflavin Niacin B6 Folate B12 Pantothenic Biotin Cholinec
Group (mg/d) (mg/d) (mg/d) (µg/d)a,b (mg/d) (mg/d) (mg/d) (mg/d)c (mg/d) (µg/d)d (µg/d) Acid (mg/d) (µg/d) (mg/d)
Pregnancy
≤ 18 yr 1300* 1250 400 5* 3* 1.4 1.4 18 1.9 600h 2.6 6* 30* 450*
Nutrition during Pregnancy and Lactation
19-30 yr 1000* 700 350 5* 3* 1.4 1.4 18 1.9 600h 2.6 6* 30* 450*
31-50 yr 1000* 700 360 5* 3* 1.4 1.4 18 1.9 600h 2.6 6* 30* 450*
Lactation
≤ 18 yr 1300* 1250 360 5* 3* 1.5 1.6 17 2.0 500 2.8 7* 35* 550*
19-30 yr 1000* 700 310 5* 3* 1.5 1.6 17 2.0 500 2.8 7* 35* 550*
31-50 yr 1000* 700 320 5* 3* 1.5 1.6 17 2.0 500 2.8 7* 35* 550*
Note: This table presents Recommended Dietary Allowances (RDAs) in bold type and Adequate Intakes (AIs) in ordinary type followed by an asterisk (*).
a As cholecalciferol. 1µg cholecalciferol = 40 IU vitamin D.
b In the absence of adequate exposure to sunlight.
c As niacin equivalents (NE). 1 mg of niacin = 60 mg of tryptophan; 0-6 months = preformed niacin (not NE).
d As dietary folate equivalents (DFE). 1 DFE = 1µg food folate = 0.6 µg of folic acid (from fortified food or supplement) consumed with food = 0.5 µg of synthetic (supplemental)
folic acid taken on an empty stomach.
e In view of evidence linking folate intake with neural tube defects in the fetus, it is recommended that all women capable of becoming pregnant consume 400 µg of synthetic
folic acid from fortified foods and/or supplements in addition to intake of food folate from a varied diet.
f It is assumed that women will continue consuming 400 µg of folic acid until their pregnancy is confirmed and they enter prenatal care, which ordinarily occurs after the
end of the periconceptional period — the critical time for formation of the neural tube.
183
TABLE 5.11
Food Guide Pyramid Servings
Number of Servings
During Adolescent During During
Food Group Serving Size Pregnancy Pregnancy Pregnancy
Milk/dairy 1 milk, cottage cheese, or 5 4 4
yogurt; 1 oz. cheese
Protein-rich 3 oz. meat, fish, or poultry; 4 3–4 3–4
1 dried beans
Breads/cereals, 1/2 cooked rice, cereal, or pasta; 9–11 6–11 6–11
rice/pasta 1 slice bread; 4 crackers
Fruits 1 small piece fresh fruit; 2–4 2–4 2–4
1/2 canned fruit; 1/3 fruit juice
Vegetables 1/2 fresh, cooked, or canned 3–5 3–5 3–5

Fats/oils/sweets 1 tsp margarine, mayonnaise, use in moderation use sparingly use sparingly
salad dressing or gravy
TABLE 5.12
Behavior Change Dietary Assessment Tool
What you eat and some of the lifestyle choices you make can affect your nutrition and health now
and in the future. Your nutrition can also have an important effect on your baby’s health. Please
answer these questions by circling the answers that apply to you.
Eating Behavior
1. Are you frequently bothered by any of the following? (circle all that apply)
Nausea Vomiting Heartburn Constipation
2. Do you skip meals at least 3 times a week? No Yes
3. Do you try to limit the amount or kind of food you eat to control your weight? No Yes
4. Are you on a special diet now? No Yes
5. Do you avoid any foods for health or religious reasons? No Yes
Food Sources
6. Do you have a working stove? No Yes

Do you have a working refrigerator? No Yes
7. Do you sometimes run out of food before you are able to buy more? No Yes
8. Can you afford to eat the way you should? No Yes
9. Are you receiving any food assistance now? (circle all that apply)
Food stamps School breakfast School lunch
Donated food Commodity Supplemental Food Program
Food from a food pantry, soup kitchen, or food banks
10. Do you feel you need help in obtaining food? No Yes
Food and Drink
11. Which of these did you drink yesterday? (circle all that apply)
Soft drinks Coffee Tea Fruit drink
Orange juice Grapefruit juice Other juices Milk
Kool-Aid® Beer Wine Alcoholic drinks
Water Other beverages (list) ________________________
12. Which of these foods did you eat yesterday (circle all that apply):
Cheese Pizza Macaroni and cheese
Yogurt Cereal with milk
13. Other foods made with cheese (such as tacos, enchiladas, lasagna, cheeseburgers)
Corn Potatoes Sweet potatoes Green salad
Carrots Collard greens Spinach Turnip greens
Broccoli Green beans Green peas Other vegetables
Apples Bananas Berries Grapefruit
Melon Oranges Peaches Other fruit
Meat Fish Chicken Eggs
Peanut butter Nuts Seeds Dried beans
Cold cuts Hot dog Bacon Sausage
Cake Cookies Doughnut Pastry
Chips French fries Deep fried foods, such as fried chicken or egg rolls
Bread Rolls Rice Cereal
Noodles Spaghetti Tortillas
Were any of these whole grain? No Yes
13. Is the way you ate yesterday the way you usually eat? No Yes
Lifestyle
14. Do you exercise for at least 30 minutes on a regular basis — 3 times a week or more? No Yes
15. Do you ever smoke cigarettes or use smokeless tobacco? No Yes
16. Do you ever drink beer, wine, liquor, or any other alcoholic beverages? No Yes
17. Which of these do you take? (circle all that apply)
Prescribed drugs or medications
Any over the counter products (such as aspirin, acetaminophen, antacids, or vitamins)
Street drugs (such as marijuana, speed, downers, crack, or heroin)
From: Institute of Medicine, 1992.
Systematic assessment of the diet is preferable to questions like “How are you eating?”
The 24-hour dietary recall method is commonly used to recall the types and amounts of
foods and beverages consumed during the previous day. The food frequency questionnaire
has been demonstrated to detect pregnancy-related changes in diet.
Nutritional Risk Tool

Table 5.13 is an example of a more quantitative method for assessing the diet.37 The
mother’s usual intake is determined for each of the food groups (meats and alternatives,
dairy, bread and cereal, fruits and vegetables) and the score is tallied. A patient with fewer
than 80 points is at nutritional risk. The evaluator should determine whether the patient
has problems such as nausea/vomiting, lactose intolerance, constipation, or cravings for
non-food items. Women with a score of fewer than 50 points should be referred to a
registered dietitian for counseling.
Complications of Pregnancy that May Impact Nutritional Status

A number of complications of pregnancy may impact nutritional status. Some of these
include nausea and vomiting, constipation, caffeine intake, and alcohol intake.
Nausea and Vomiting

About 70% of pregnant women report nausea during the first 14–16 weeks of pregnancy,
and 37–58% experience vomiting. The etiology is unknown. The remedies include diet,
fluids, and reassurance.38,39 Table 5.14 is a collection of remedies.
TABLE 5.13
Nutritional Risk Score (Massachusetts Department of Health)
Foods Usually Eaten Amount
Meat or alternates
meats, fish, poultry (fresh or processed), liver, eggs, nuts, ________ servings
peanut butter, legumes
1 oz = 5 points ________ oz. meat, fish, cheesea
maximum score = 40 points ________ oz. alternate
Milk (type) 1 unit = 5 points ________ fluid

1 unit = 8 fl oz. ________ cups
Cheeseb (type) _______________ ________ oz.

maximum score = 15 points
Bread and cerealc whole grain, enriched, other maximum ________ servings
score = 15 points
Fruits and vegetables

citrus and/or vitamin C-rich vegetables ________ servings
green and yellow vegetables ________ servings
all other, including potato ________ servings
________ Total fruits
vitamin A vitamin C
1 unit = 5 points 1 unit = 5 points
2 units = 15 points 2 units = 15 points ________ servings
Supplementsd (type) ________ amount
Other foods and beverages
total score: more than 80 = no risk, less, less than 80 = risk, less than 50 = high risk
a Cheese in excess of the 3 units scored in milk; 1 oz. cheese equals 1 unit
b Maximum of 3 oz. scored
c Unit = 1 slice of bread or 1 oz cereal. Less than 3 units = 0, 3 units = 5 points, 4 units = 10
points, 5 units = 15 points
d Not given a score
From JADA: 86(10), 1986, with permission.
TABLE 5.14
Nonpharmacological Remedies for Nausea and Vomiting
Eat small, frequent meals
Eat dry foods/cold foods
Take dietary supplements after meals
Suck on candy
Switch brands of iron supplements
Eat combinations of foods that are salty and tart
Eat vitamin B6-rich foods
Try seabands or accupressure bands
Avoid beverages with meat
Avoid caffeine
Avoid spicy, acidic foods, strong odors
Sniff lemon
Drink ginger root tea, ginger ale; eat ginger snaps; take ginger tablets
(250 mg tablets 4x daily for 4–5 days)
Drink plenty of fluids to avoid dehydration
TABLE 5.15
Hyperemesis Gravidurum
Medication Dosage
Vitamin B6 25 mg tid
Doxylamine 12.5–25 mg tid
Emetrol 5–10 cc in the morning and
every 3–4 hrs as needed
Anti-emetic/anti-nausea medications, 200 mg suppository q 8 prn
e.g., trimethobenyamine (Tigan)
Promethazine 12.5–25 mg po. Pr or iv q 4-6
Hyperemesis Gravidarum
Vomiting that produces weight loss, dehydration, acidosis from starvation, alkalosis from
loss of hydrochloric acid in vomitus, and/or hypokalemia may be treated pharmacolog-
ically. Management is to correct dehydration, fluid and electrolyte deficits, acidosis, and
alkalosis. Table 5.15 includes some pharmacological approaches.
Constipation
Constipation is extremely common in pregnancy due to decreased motility of the gas-
trointestinal (GI) tract. Constipation can be exacerbated by iron supplementation. Consti-
pation is often related to low dietary fiber intake and low fluid intake. Table 5.16 includes
foods rich in dietary fiber. The recommended intake is 20 to 30 grams of dietary fiber daily.
Caffeine during Pregnancy and Lactation

The literature is mixed on the effects of caffeine during pregnancy. The official FDA
position advises pregnant women to avoid caffeine or consume it sparingly. Most experts
agree that caffeine should be limited to less than two servings per day. Caffeine is known
to decrease availability of calcium, iron, and zinc. It is not known to exert effects on the
fetus. The relationship of caffeine to spontaneous abortion remains controversial. A recent
report suggests that risk increases with the consumption in the range of 6 to 18 cups of
coffee per day.40
Caffeine does pass into breast milk, and therefore consumption during lactation should
be limited. Table 5.17 lists caffeine values for popular beverages.
Some suggestions for reducing caffeine consumption include: 1) switching to decaffein-
ated coffee or soft drinks; 2) cutting down on caffeinated beverages; 3) mixing caffeinated
and decaffeinated coffee grounds together before making coffee; or 4) limiting consump-
tion of caffeinated beverages to a preselected number and then switching to decaffeinated
beverages over time.
Alcohol
Consumption of alcohol during pregnancy and lactation is controversial.
Pregnancy
A safe lower limit of alcohol during pregnancy is not known. Therefore, the only sure
way to avoid the possible harmful effects of alcohol on the fetus is to abstain. Binge
TABLE 5.16
Dietary Sources of Fiber
Serving Size Food Grams of Fiber
Breads, Cereals, Pastas
3 cups Air-popped popcorn 4

1 medium Bran muffin 3
2/3 cup Brown rice 3
1 slice Whole wheat bread 3
1/2 cup Cooked legumes 5
1/2 cup Baked beans 10
1/2 cup Great northern beans 7
1/2 cup Lima beans 7
Fruits
1 cup Raisins 6
3 Dried prunes 5
1 medium Pear with skin 4
1 medium Apple with skin 3
1 cup Strawberries 3
1 medium Banana 3
1 medium Orange 3
Vegetables
1 2
/ cup Cooked frozen peas 4
1 medium Baked potato w/ skin 4
1/2 cup Brussels sprouts 3
1/2 cup Cooked broccoli tops 3
1/2 cup Cooked carrots 3
1/2 cup Cooked corn 3
drinking or excessive drinking during pregnancy results in fetal alcohol syndrome. How-
ever, even small amounts of alcohol can temporarily alter fetal function. Adverse outcomes
have not been found with daily consumption of fewer than two standard drinks. The
danger from light drinking should not be overstated. This may cause undue stress in some
patients who had a few drinks before realizing they were pregnant (see Table 5.18).
Lactation
Alcohol does not increase milk volume. Chronic consumption can inhibit milk ejection
reflex. The American Academy of Pediatrics does, however, consider minimal alcohol (no
more than 2 to 2.5 oz liquor, 8 oz wine, or 2 cans of beer on any day) compatible with
lactation.
Hypertension
In 1999 the National High Blood Pressure Education Committee issued an advisory on
diagnoses and treatment of high blood pressure.41 Using evidence-based medicine and
consensus, this report updates contemporary approaches to hypertension control during
pregnancy by expanding on recommendations made in the Sixth Report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI).
TABLE 5.17
Caffeine Audit
Approximate the caffeine you consume by filling in the table. Recall caffeine consumption during
the past 24 hours and record in column A, the number of servings or doses for each listed item.
Then multiply the column A value by its corresponding column B value and record the product
in column C. Add all values in column C to estimate your intake.
Column A Column B Column C
Number of Servings Amount of Caffeine Total Caffeine
Sources of Caffeine per Day per Serving (mg) (mg)
Coffee (6 oz.)
Automatic drip _______________ × 180 = ___________

Automatic perk _______________ × 135 = ___________
Instant _______________ × 125 = ___________
Decaffeinated _______________ × 5 = ___________
Soft Drinks (12 oz.)
Regular colas _______________ × 37 = ____________

Diet colas _______________ × 50 = ____________
Cocoa Products
Chocolate candy (2 oz.) _______________ × 45 = ___________

Baking chocolate (1 oz.) _______________ × 30 = ___________
Milk chocolate (2 oz.) _______________ × 10 = ___________
South American cocoa (6 oz.) _______________ × 40 = ___________
Drugs (one tablet or capsule)
Dexatrim (not caffeine free) _______________ × 200 = ___________

NoDoz _______________ × 100 = ___________
Anacin _______________ × 35 = ___________
Midol _______________ × 30 = ___________
Coricidin _______________ × 30 = ___________
Tea (6 oz.)
Iced tea _______________ × 36 = ___________

Hot tea (moderate steeping time) _______________ × 65 = ___________
Total = ___________
The recommendations to use K5 for determining diastolic pressure and to eliminate edema
as a criterion for diagnosing preeclampsia are discussed. In addition, the use of blood
pressure increases of 30 mm Hg systolic or 15 mm Hg diastolic as a diagnostic criterion
has not been recommended, as available evidence shows that women in this group are
not likely to suffer increased adverse outcomes. Management considerations are made
between chronic hypertension present before pregnancy and hypertension occurring as
part of the pregnancy-specific condition preeclampsia, as well as management consider-
ations in women with comorbid conditions. A discussion of the pharmacologic treatment
of hypertension in pregnancy includes recommendations for specific agents. The use of
low-dose aspirin, calcium, or other dietary supplements in the prevention of preeclampsia
is described, and expanded sections on counseling women for future pregnancies and
recommendations for future research are included.14
TABLE 5.18
Effects of Alcohol, Tobacco, and Drug Use on Nutritional Status and Pregnancy Outcomes and
Lactation
Effect Cause
Increased nutrient requirements/impaired nutrient Smokers have reduced vitamin C levels
absorption
Drinkers have reduced serum folate, vitamin C levels
Impaired growth of the fetus/stunted growth of child Drinkers (1–2 alcoholic beverages/day) associated
with LBW, and slow weight gain and failure to thrive
Smokers
Infant sleep disruption/increased arousal Consumption of one drink/day in first trimester
Delayed development/mental retardation Drinkers have children who are more at risk for
hyperactivity, poor attention span, language
dysfunction
Reduced fertility Chronic drinking and smoking associated with lower
fertility in men and women
Transfer to baby during lactation disrupted sleep Alcohol found in breast milk about 30 min after
pattern of infant consumption; if woman chooses to drink during
lactation, limit to 1.5 oz distilled spirits, 5 oz wine, or
12 oz beer, and consume after breastfeeding
Vitamin and Mineral Requirements, Food Sources, and Supplementation

In the United States, vitamin and mineral supplementation is common among pregnant
women. During pregnancy, maternal requirements for all nutrients increase. For some
nutrients, the evidence indicates a direct link between chronic maternal deficiency and
poor outcome for the mother and infant. Excessive intake (usually defined as more than
twice the RDA) of some nutrients may be harmful to the fetus, especially very early in
the pregnancy.16,26
Supplementation is recommended only after assessment of dietary practices of pregnant
women. The Institute of Medicine does not recommend routine use of prenatal vitamins;
however, many physicians prescribe them because of the marginal nutritional status of
their patients or because it is difficult to be completely sure of their patients’ nutritional
status.3 Prenatal vitamins and minerals are indicated for high risk populations and those
with an obstetric history of high parity, previous delivery of a low-birth-weight infant, a
short interval between births, and smokers, drug or alcohol abusers, and those with
multiple pregnancies.
Prenatal Vitamins
Indications for vitamin and mineral supplementation are in shown Table 5.19, which lists
nutrient dose and indication for use. The contents of typical prenatal vitamin-mineral
supplements are shown in Table 5.20, which includes usual formation of an over-the-
counter (OTC) and a prescription supplement recommended to pregnant women.
Vitamin A
Most pregnant women do not need supplemental vitamin A, the teratogenic threshold of
which may be lower than previously thought. Vitamin A is essential for embryogenesis,
TABLE 5.19
Indications for Vitamin and Mineral Supplementation
Indication Nutrient Dose
Inadequate diet; during first two Prenatal Supplements Read label
trimesters for women at risk for preterm
labor or low birth weight baby
Up to 1200 mg/day if dairy or fortified Calcium 250–300 mg
foods not consumed
For women receiving supplemental iron Copper 2 mg
For all women of child bearing age Folate 400 ug
Inadequate diet; anemia Irona 30–60 mg elemental
Inadequate diet Vitamin B6 2 mg
Inadequate diet Vitamin C 50 mg
Inadequate diet; no exposure to sunlight Vitamin D 10 µg
For women receiving supplemental iron Zinc 15 mg
a Supplements containing high levels of folate or iron negatively affect zinc metabolism.
Supplementary forms of folic acid are better absorbed than folate occurring in food.
TABLE 5.20
Prenatal Vitamin Mineral Supplements
Flintstones Complete Prenatal Vitamin
Chewables (PreCare®)
Vitamin A 5000 IU —
Vitamin C 60 mg 50 mg
Vitamin D 400 IU 6 µg
Thiamin 1.5 mg —
Riboflavin 1.7 mg —
Niacin 20 mg —
B6 2 mg 2 mg
Folic acid 400 µg 1 mg
B12 6 µg —
Biotin 40 µg —
Pantothenic acid 10 mg —
Calcium (as carbonate) 100 mg 250 mg
Iron 18 mg 40 mg
Phosphorus 100 mg —
Iodine 150 µg —
Magnesium 20 mg 50 mg
Zinc 15 mg 15 mg
Copper 2 mg 2 mg
Vitamin E — 3.5 mg
growth, and epithelial differentiation. Case reports have suggested an association between
high doses of vitamin A (> 25,000 IU) during pregnancy and birth defects. The American
College of Obstetricians and Gynecologists established 10,000 IU as the cutoff for supple-
mental vitamin A (retinol) prior to or during pregnancy.2
Calcium and Magnesium

About 99% of calcium in pregnant women and their fetus is located in their bones and
teeth. Pregnancy and lactation are associated with increased bone turnover to meet fat
needs. If dietary deficiencies occur, maternal bone will supply the calcium to the fetus.
Calcium supplementation during pregnancy has been shown to lead to an important
reduction in systolic and diastolic blood pressure.29,31 Controlled clinical trials to test the
hypothesis that calcium supplements during pregnancy reduce the incidence of preg-
nancy-induced hypertension have had mixed results. Therefore there is no support for
routine supplementation with 2000 mg/day for all pregnant women. In pregnant women
who have diets deficient in calcium, prepregnancy hypertension, history of preeclampsia,
or chronic use of heparin and steroids, supplemental calcium is recommended.42
The fetus absorbs 6 mg of magnesium each day. Maternal magnesium levels remain
constant during pregnancy despite reported inadequate intakes. Magnesium supplemen-
tation has been associated with fewer hospitalizations, fewer preterm births, and more
perinatal hemorrhages compared with placebo-supplemented women. Thus, further study
is needed before routine supplementation is recommended.
Folate
The available data from controlled trials provide clear evidence of an improvement in
hematological indices in women receiving routine iron and folate supplementation in
pregnancy.30 No conclusions can be drawn in terms of any beneficial or harmful effects
on clinical outcomes for mother and baby. However, the Cochrane Pregnancy and Child-
birth Group concludes that there is no evidence to advise against a policy of routine iron
and folate supplementation in pregnancy.25 Both folate intake from food and synthetic
folic acid should be included in assessing and planning diet. The literature contains a
variety of recommendations. The DRI is higher than can usually be obtained from food.
The current recommendation during pregnancy is 600 µg/day of folic acid per day. It is
well established that periconceptional use of folic acid supplementation reduces the risk
of first occurrence and recurrence of neural tube defect (NTD)-affected pregnancies. The
Center for Disease Control (CDC) recommends supplementation with 400 µg/day.
Research is needed to determine effective strategies for disseminating information about
the protective effects of folate.26
Iron
Additional iron is needed by most pregnant women in the U.S. A substantial amount
of iron is required, given the amount of erythropoiesis. For example, a term infant
contains an average of 225 mg of iron, the placenta and cord contain 50 mg of iron
through the pregnancy, and the maternal red blood count volume increases 500 mL.
Although maternal absorption of iron from the GI tract is increased by about 15%, it
remains difficult to meet the increased iron need through diet alone. Iron absorption is
increased in the presence of ascorbic acid. Adverse pregnancy outcomes are associated
with hemoglobin levels below 10.4 g/dL or above 13.2 g/dL. Clinical diagnosis of
anemia is made based on hemoglobin below 10.5 g/dL, a low MCV, and serum ferritin
level below 12 µg/dL. Supplementation of 30 to 60 mg per day of elemental iron is
usually prescribed, although the benefit of routine iron supplementation for healthy,
well nourished women during pregnancy is unproven.26,32 Common side effects include
stomach upset, nausea, and constipation. These effects may be relieved by reducing the
dosage or switching the brand of iron supplement. Some, but not all, sustained release
preparations have been clinically shown to be associated with fewer discomforts. The
safety of iron supplementation at dosages greater than 100 mg per day has been ques-
tioned. Researchers suggest that excess iron may lead to zinc depletion, which is asso-
ciated with intrauterine growth retardation.
Zinc
The prevalence and effects of mild zinc deficiency in pregnancy are poorly defined.
However, there have been a few case reports of severe human zinc deficiency in pregnancy
that led to major obstetric complications and congenital malformations in the fetus. Sup-
plementation studies have yielded mixed results. Iron appears to depress plasma zinc in
pregnant women; therefore, zinc supplementation is recommended when >30 mg supple-
mental iron is taken.43 Higher birth weights in infants of women with low prepregnancy
weight (BMI <26) and low plasma zinc levels have been reported in women who received
25 mg zinc daily.
Vitamin B6
The value of supplementation with Vitamin B6 in pregnancy is controversial. However, it
is included in most prenatal vitamins.
Vitamin C
Taking iron tablets along with a source of vitamin C facilitates iron absorption.
Vitamin D
Vitamin D is critical in the absorption, distribution, and storage of calcium. Relatively few
foods are good sources of vitamin D.
Food Sources of Selected Nutrients

There are a variety of published recommendations for calcium in pregnancy and lactation.
The optimal calcium intake recommended by the National Institutes of Health is 1200 mg
per day. This is difficult to meet with a diet containing little dairy or calcium-fortified
foods. The recommended daily intake (RDI) for pregnancy and lactation varies based on
age from 1000 to 1300 mg/day. The usual calcium intake in the U.S. averages less than
700 mg per day. The benefit of meeting calcium needs has been demonstrated in reducing
pregnancy induced hypertension. However, no benefit in reducing preeclampsia is seen
with supplementing greater than 1200 mg calcium daily. Table 5.21 lists common dietary
TABLE 5.21
Dietary Sources of Calcium (DRI = 1000–1300 mg/d)
Good: > 200 mg
Broccoli/greens 2 cups
Calcium fortified foods (juice, cereal) varies, read label
Canned salmon w/bones 3 oz.
Canned sardines w/bones 3 oz.
Cheese (cheddar, edam, Monterey jack, mozzarella, Parmesan, provolone, ricotta) 1 oz.
Ice cream 1 cup
Ice milk 1 cup
Milk (skim, 2%, whole, buttermilk) 1 cup
Yogurt 6-8 oz.
TABLE 5.22
Dietary Sources of Folate (DRI = 500–600 µg/d of
dietary folate equivalents (DFE)
Excellent >100 µg
Asparagus 1/2 cup
Baked beans 1 cup

Bean burritos 2
Black-eyed peas 1 cup
Fortified grain and cereal products varies, read label
Kidney beans 1 cup
Lentils 1 cup
Liver and other organ meats:
beef 3.5 oz.
chicken 3.5 oz.
Orange Juice 1 cup
Peanuts 4 oz.
Spinach 1/2 cup
Good: 15–99 µg
Almonds 4 oz.
Bread, fortified 1 slice
Beets 1/2 cup
Broccoli, cooked 1/2 cup
Cantaloupe/Honeydew melon 1 cup

Cauliflower 1/2 cup
Egg 1
French fries large order
Lettuce (romaine) 1/2 cup
Orange 1 med
Turnip greens 1/2 cup
sources of calcium. Table 5.22 lists common food sources of folate, Table 5.23 includes
common dietary sources of iron, and Table 5.24 includes common dietary sources.
Physical Activity during Pregnancy

Several factors influence physical activity during pregnancy, including prepregnancy exer-
cise levels, current exercise levels, personal preferences, risk, limitations, and contraindi-
cations.13 Tables 5.25 through 5.29 include guidelines for physical activity.
Postpartum Weight Loss

While a great deal of attention is given to counseling women about appropriate weight
gain for pregnancy, clinicians have typically given less assistance in achieving postpartum
weight loss. Researchers are beginning to link failure to return to prepregnancy weight
TABLE 5.23
Dietary Sources of Iron (DRI = 15–30 mg/d)
Excellent >4 mg
Beef liver 3 oz.

Clams 1/2 cup
Figs (dried) 10
Iron-fortified infant cereal 1/2 cup
Iron-fortified infant cereal 3 Tsp

Kidney beans 1 cup
Molasses (blackstrap) 3 Tbsp
Peaches (dried) 10 halves
Pinto beans 1 cup
Ready-to-eat, fortified cereals (like Product 19®, Total ®) 3 4

/ cup
Sunflower seeds (dried, hulled) 2 3
/ cup
Good: 2–4 mg
Beef 3 oz.
Egg yolks 3
Iron-fortified infant formula 4 oz.
Lamb 3 oz.
Lima beans 1/2 cup
Oysters 3 oz.
Peas 1 cup
Pork 3 oz.
Prune juice 1 cup
Raisins 2/3 cup
Soybeans 1/2 cup
TABLE 5.24
Dietary Sources of Zinc (DRI = 15–19 mg/d)
Food Item Serving Size mg/Serving
Excellent: >4 mg
Beef (lean, cooked) 3 oz. 5.1

Calves’ liver (cooked) 3 oz. 5.3
Lamb (lean, cooked) 3 oz. 4.0
Oysters, Atlantic 3 oz. 63.0
Oysters, Pacific 3 oz. 7.6
Good: 0.9–3.4 mg
Black-eyed peas (cooked) 1/2 cup 3.4

Chicken 3 oz. 2.4
Crabmeat 1/2 cup 3.4
Green peas (cooked) 1/2 cup 0.9
Lima beans (cooked) 3 oz. 0.9
Milk (whole) 1 cup 0.9
Pork loin (cooked) 3 oz. 2.6
Potato (baked with skin) 1 medium 1.0
Shrimp 1/2 cup 1.4
Tuna (oil-packed, drained) 3 oz. 0.9
Whitefish 3 oz. 0.9
Yogurt (plain) 1 cup 1.1
TABLE 5.25
Benefits of Physical Activity during Pregnancy
Improvement in circulation
Improved posture
Improved or maintained cardiovascular fitness
Reduced risk of cesarean section, decreased labor time, decreased use of epidural and forceps
Positive effects on mood, energy level
Release of tension and reduction of stress
Prevention of injury
TABLE 5.26
Contraindications to Physical Activity
Active myocardial disease, congestive heart failure, rheumatic heart disease
Thrombophlebitis
Risk of premature labor; incompetent cervix; uterine bleeding; ruptured membranes
Intrauterine growth retardation
Severe hypertensive disease
Suspected fetal distress
TABLE 5.27
Warning Signs to Stop Physical Activity
Vaginal bleeding
Uterine contractions
Nausea, vomiting
Dizziness or faintness
Difficulty walking
Decreased fetal activity
Palpitations or rapid heart rate
Numbness in any part of the body
Problems with vision
TABLE 5.28
Guidelines for Physical Activity
Activity Guideline
Intensity Reduce the intensity of exercise by 25%
Heart rate Not to exceed 140 beats per minute
Temperature Not to go above 101 degrees
Time Moderate activity should not exceed 30 minutes; intersperse
with low-intensity exercise and rest periods
Position Avoid lying on back for more than 5 minutes after entering the
2nd trimester
Frequency Exercise should be performed consistently at least three times
per week and include a warm-up and a cool-down period
TABLE 5.29
Guidelines for Recreational Activity
Activity Guideline
General conditioning exercises Kegel, breathing, calf pumping, abdominal, bridging, lower trunk rotation,
tail wagging
Jogging May be continued moderately, however should not be started as a new activity
after pregnancy; watch out for joint pain and decrease overall distance —
recommendation is 2 miles or less per day
Aerobics Avoid high impact or step aerobics; as for jogging, look out for joint pain or
signs of over exertion; avoid exercises that involve lying on the back for more
than 5 minutes
Bicycling In the third trimester it may be necessary to switch to a stationary bike due
to problems with balance
Weight lifting Can be continued during pregnancy — use light weights and moderate
repetitions; avoid heavy resistance
Avoid during pregnancy Downhill skiing, gymnastics, horseback riding, scuba diving, any contact
sports
TABLE 5.30
Strategies for Postpartum Weight Loss
Encourage a healthy diet based on current dietary guidelines
Make energy intake less than energy expenditure
Reduce portion size but do not restrict kcalories to less than 1800 per day
Determine foods high in fats and calories and substitute with fruits, vegetables, lean meats and fish, skinless
poultry
Avoid cooking in oil, butter, margarine
Drink 8–10 glasses fluid per day
Discuss feasible physical activity
Monitor women who
Restrict intake to less than 1800 kcalories per day
Are vegans (avoid all animal products including dairy, eggs, and meats)
Avoid foods enriched with Vitamin D and have limited exposure to sunlight
with increased risks for chronic disease later in life. Table 5.30 includes currently recom-
mended strategies for post partum weight loss.
Nutrition and Lactation

The RDA and AI for lactation are listed in Table 5.10. Suggestions for maternal nutrition
to meet the increased energy and nutrient needs are listed in Table 5.31. Until relatively
recently, breastfeeding has been considered too imprecise to study. A wealth of information
is being developed about lactation and breast milk.50 Table 5.32 lists some of the benefits
of unrestricted nursing for the infant. Many women and their clinicians still are concerned
about ways to identify whether an infant is obtaining enough nutriture. Table 5.33 lists
signs of insufficient milk intake. The social history of infant feeding from the late 1800s
to the 1950s in the U.S. shows a transition from breastfeeding to scientific feeding of infants.
As a result of that, much cultural knowledge and support for breastfeeding had been lost.
Guidebooks are important for women and clinicians.46-50 Tables 5.34 and 5.35 include
common concerns and recommended actions to support breastfeeding.
TABLE 5.31
Maternal Nutrition during Breastfeeding
Encourage a healthy diet based on current dietary guidelines
Reinforce that milk quality is generally not affected by the mother’s diet
Suggest eating meals and snacks that are easy to prepare
Provide patient with information on normal postpartum weight loss in a breastfeeding woman
Drink enough fluids to keep from getting thirsty
Eat at least 1800 kcalories per day
Use appetite as a guide to amount of food eaten in first six weeks
Keep intake of coffee, cola, or other sources of caffeine to 2 servings or less per day. Caffeine accumulates in the
infant and use should be discontinued if infant becomes wakeful, hyperactive, or has disturbed sleep patterns.
This reaction is intensified with a smoking mother.
TABLE 5.32
Benefits of Frequent, Early, Unrestricted Nursing
Provides colostrum that the baby needs
Helps decrease newborn jaundice because of the laxative effect of colostrum
Provides a period of practice time before milk volume increases
Stimulates uterine contractions, lessening chances of maternal postpartum hemorrhage
Prevents infant hypoglycemia
TABLE 5.33
Signs of Insufficient Milk Intake in the Newborn
Failure to regain birth weight by 2 weeks of age
Weight gain of less than 7 oz per week after regaining birth weight and less than 4 lbs in 4 months
Fewer than 3–4 stools per day after day 5
Fewer than 6 urinations per day after day 5. (During the first 5 days wet and soiled diapers should increase in
number each day.)
TABLE 5.34
Breastfeeding Tips: Common Concerns about the Infant
Concern Recommended Action
Jaundice Continue to breastfeed at least every 2 hours around the clock. If breastfeeding is
stopped, pump breasts to maintain milk supply. Avoid water or formula feedings.
Latch-on Latch-on is necessary for baby to begin sucking at the breast. Poor latch-on is a
major cause of sore nipples. Baby’s mouth should be at nipple level. Support the
breast by placing the thumb on the top and four fingers underneath. Tickle baby’s
bottom lip with nipple until baby opens mouth very wide. Center nipple quickly
and bring baby very close. Baby’s nose and chin should be touching breast.
Leaking Leaking is a sign of normal letdown in the early weeks of breastfeeding. Use breast
pads in bra between feedings. Avoid pads with plastic lining. During sexual
activity, leaking may occur; breastfeed your baby first.
Duration of breastfeeding: Frequent (every 2–3 hours) and unrestricted breastfeeding for the first weeks. Baby
how long and how should empty one breast, be burped, and offered the second breast. Watch baby
often? for signs that he is full, like falling asleep, losing interest in feeding, or stopping
breastfeeding.
Early first feeding Put baby to breast soon after delivery, if possible within the first 2 hours. Cuddling,
licking, and brief sucking are good signs that baby is learning to breastfeed. Offer
your breast often to let your baby practice. Ask a supportive nurse for help.
Extra feedings Healthy breastfed newborns do not need formula, water, or juice. Breastfeed at
least every 2–3 hours during the first month. Older breastfed babies will be ready
for solid foods and juices between 4-6 months of age.
TABLE 5.35
Breastfeeding Tips: Common Discomforts That Lead to Breastfeeding Termination
Concern Recommended Action
Hospital survival skills “Rooming-in” with your baby is your right as a consumer. Keep your baby with
you as much as possible so you can breastfeed often. Do not give bottles of
formula or water. Do not limit feeding time at breast. Ask a supportive nurse for
help. Do not accept formula gift packs.
Mastitis Mastitis is a swollen, inflamed, or infected area in the breast. Watch for flu-like
symptoms such as fever above 101°F, chills and muscle aches, and a reddened,
hot, tender, or swollen area in the breast. Rest, breastfeed often, and drink more
fluids. Avoid tight bra or clothing. Apply warm water soaks, heating pad.
Massage affected area. Antibiotics may be needed. No reason to stop
breastfeeding.
Myths and misconceptions Breast sagging is not a result of breastfeeding. Breast size does not affect ability
to breastfeed. Drinking beer, manzanilla tea, or large amounts of fluids does not
make more milk.
Nipples, flat or inverted Flat or inverted nipples retract or move in toward the breast. Breast shells (milk
(before birth) cups) may be worn during the last month of pregnancy to help minimize inverted
nipples. Gradually increase time of use from a few hours to 8–10 hours/day. Do
not wear while sleeping. Air-dry nipples if leaking occurs. Breast shells should
not be used by women at risk for preterm labor.
Nipples, flat or inverted Begin breastfeeding as soon as possible after birth. Breastfeed frequently to avoid
(after birth) engorgement. Use nipple rolling or stretching before each breastfeeding. Pump
breast for a short period before breastfeeding, or apply ice wrapped in a cloth
and placed on the nipple before feeding. Breast shells (milk cups) may be used
between feedings. Remove the breast shell just before placing baby at breast.
Engorgement Engorgement may occur when milk first comes in or when feedings are missed
or delayed. Use warm compresses or shower before feedings. Hand-express to
soften areola, making it easier for baby to latch on. Breastfeed every 1–2 hours
for 10–20 minutes per breast. Apply ice to breast and under arm after feeding
until swelling decreases. Gentle breast massage toward nipple. Take non-aspirin
pain reliever.
Breast care Nipple pulling, tugging, or rolling during pregnancy is not necessary to prepare
for breastfeeding. Avoid soaps or lotions to the nipples. Air dry nipples after
breastfeeding.
Breast creams Vitamin E, breast creams, or ointments are not recommended. No evidence exists
that they heal the nipple. May make soreness worse by keeping the nipple moist.
Use pure lanolin. Can massage drops of breast milk on nipples.
Breast surgery Any type of breast surgery may interfere with milk supply.
Cesarean section Breastfeed baby as soon as possible after delivery, preferably in the recovery room.
Hold baby in a comfortable position. Use pillows across abdomen to protect the
incision and support baby.
Resource Materials
American College of Obstetricians and Gynecologists, Office of Public Information, 409 12th Street
SW, Washington, DC 20024-2188; 202-638-5577.
Best Start Social Marketing. 3500 E. Fletcher Avenue, Suite 519, Tampa, FL 33613; 1-800-277-4975.
Best Start is a not-for-profit corporation. One of its largest social marketing projects was
developed in 1997 for USDA as part of the WIC National Breastfeeding Promotion Project. A
wide variety of campaign and professional materials is available.
Beststart@mindspring.com; Also see http://www.opc.on.ca/beststart/info_sheets/feed.html
Erick M. No More Morning Sickness. A Survival Guide for Pregnant Women, Plume Book, NJ. 1-800-
245-6476.
Food and Nutrition Information Center, National Agricultural Library, ARS, USDA, Beltsville, MD
20705-2351. 301-504-5719.
http://www.nal.usda.gov/fnic
La Leche League International, 1400 N Meacham Rd, PO Box 4079, Schaumburg IL 60168-4079.
http://www.lalecheleague.org
Lopes GL. Gestational Diabetes and You. NCES, Inc. 1995. 913-782-4385.
March of Dimes Birth Defects Foundation Resource Center, 1275 Mamoroneck Ave, White Plains,
NY 10605.
http://modimes.org
National Maternal and Child Health Clearinghouse, 2070 Chain Bridge Road, Suite 450, Vienna, VA
22182-2536. 703-356-1964; fax: 703-821-2098.
e-mail: nmchc@circsol.com; Web site: http://www.circsol.com/mch.
National Center for Nutrition and Dietetics, The American Dietetic Association, 216 W Jackson Blvd,
Suite 800, Chicago, IL 60606-6995.
http://www.eatright.org
USDA. Is Someone You Know At Risk for Foodborne Illness? Food Safety and Inspection Service,
April 1990.
http://www.fightbac.org
References
1. Am Coll OB-GYN. ACOG Technical Bulletin No. 205, May, 1995.
2. Am Acad Ped. Am Coll OB-GYN. Chapter 11, pages 279-284. In Guidelines for Perinatal Care,
1997.
3. Institute of Medicine, Subcommittee for a Clinical Application Guide. Nutrition During Preg-
nancy and Lactation: An Implementation Guide, National Academy Press, Washington, DC, 1992.
4. Kolasa KM, Weismiller D. AFP 56:205; 1997.
5. Newton E. Maternal nutrition. In Management of High Risk Pregnancy. (Queen, JT, Ed) Blackwell
Science, 4th ed. 1999.
6. Peshicka D, Riley J, Thomson C. Obstetrics/Gynecology Nutrition Handbook. Chapman and Hall,
New York, NY 10003, 1996.
7. Suitor CW. Update for Nutrition during Pregnancy and Lactation: An Implementation Guide.
National Center for Education in Maternal and Child Health. Maternal and Child Health
Bureau, Health Resources and Services Administration, Public Health Service, U.S. Depart-
ment of Health and Human Services.
8. Homan RK, Korenbrot CC. Medical Care 36: 190; 1998.
9. Luke B. Clin Obstet Gynecol 37: 538; 1994.
10. Matthews F, Yudkin P, Neil A. Brit Med J 319: 339; 1999.
11. Abrams B, Carmichael S, Selvin S. Obstet Gynecol 86: 170; 1995.
12. Ananth CV, Vintzileos AM, Shen-Schwarz S, et al. Obstet Gynecol 91: 917; 1998.
13. Boardley DJ, Sargent RG, Coker AL, et al. Obstet Gynecol 86: 834; 1995.
14. Cattingius S, Bergstrom R, Lipworth L, Kramer M. 338: 147; 1998.
15. Cogswell ME, Serdula MK, Hungerford DW, Yip R. Am J Ob-Gyn 172: 705; 1995.
16. Keppel KG, Taffel SM. AJPHA 83: 1100; 1993.
17. King JC, Butte NF, Bronstein MN, et al. Am J Clin Nutr 59(suppl): 439S; 1994.
18. Luke B, Hediger ML, Scholl TO. J Mat Fetal Med 5: 168; 1996.
19. Parker JD, Abrams B. Obstet Gynecol 79: 664; 1992.
20. Schieve LA, Cogswell ME, Scanlon KS. Obstet Gynecol 91: 878; 1998.
21. Scholl TO, Hedinger ML, Schall JI, et al. Obstet Gynecol 86: 423; 1995.
22. Siega-Riz AM, Adair LS, Hobel CJ. Nutrition 126: 146; 1996.
23. Taffel SM, Keppel KG, Jones GK. Ann NY Acad Sci 678: 293; 1993.
24. Suitor CW. Maternal Weight Gain: A Report of an Expert Work Group, National Center for
Education in Maternal and Child Health, Arlington, VA, 1997.
25. Cochrane Pregnancy and Childbirth Group. Cochrane Database of Systematic Reviews. Issue
3, 1999.
26. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin,
Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy
Press, Washington, DC, 1998.
27. Institute of Medicine, Food and Nutrition Board, Dietary References Intakes for Calcium, Phos-
phorus, Magnesium, Vitamin D, and Fluoride. National Academy Press, Washington, DC, 1997.
28. Allen L. Am J Clin Nutr 67: 591; 1998.
29. Kloeblen AS. J Am Diet A 99: 33; 1999.
30. Levine RJ, Hauth JC, Curet LB, et al. N Engl J Med 337: 69; 1997.
31. Long PJ. J Nurse Midwifery 40: 36; 1995.
32. Matthews F. Nutr Res Rev 9: 175; 1996.
33. Rose NC, Mennuti MT. Clin Obstet Gynecol 37: 605; 1998.
34. Brown JE, Buzzard M, Jacobs DR, et al. JADA 96: 262; 1996.
35. Kennedy E. JADA 86: 1372; 1986.
36. Erick M. Nutrition Rev 53: 289; 1995.
37. Stainton MC, Neff EJA. Health Care for Women International 15: 563; 1994.
38. Klebanoff MA, Levine RJ, DerSimonian R, et al. N Engl J Med 341: 1639; 1999.
39. Bucher HC, Guyatt GH, Cook RJ, et al. JAMA 275: 1113 1996.
40. Goldenberg RL, Tamura T, Neggers Y, et al. JAMA 274: 463; 1995.
41. Institute of Medicine, Subcommittee on Nutrition During Lactation. Nutrition During Lactation.
National Academy Press: Washington, DC, 1991.
42. National Academy of Sciences, Institute of Medicine, Food and Nutrition Board, Committee
on Nutritional Status During Pregnancy and Lactation. Nutrition Services in Perinatal Care (2nd
ed.). National Academy Press, Washington, DC, 1992.
43. Lawrence, RA . Maternal and Child Health Technical Information Bulletin. National Center
for Education in Material and Child Health, Arlington, VA, 1997.
44. Lawrence RA and Lawrence RM. Breastfeeding: A Guide for the Medical Profession. C.V. Mosby,
St. Louis, MO, 1998.
45. Mohrbacher N and Stock J. The Breastfeeding Answer Book. La Leche League International.
Schaumburg, IL, 1997.
46. Am Acad Ped. Work Group on Breastfeeding. Pediatrics 100: 1035; 1997.
47. Riordan J and Auerbach KG. Pocket Guide to Breastfeeding and Human Lactation, Jones and
Bartlett, Boston, MA, 1997.
48. Prentice A. N Engl J Med 337: 558; 1997.
6
Feeding the Premature Infant
Nutritional management of the premature infant has become an integral part of the
medical care provided to these infants. With the ever increasing survival of low-birth-
weight and very-low-birth-weight infants, understanding the principles of nutritional
therapy becomes all the more important. It is estimated that there are four million births
in the United States every year; with an estimated prematurity rate of 9%, the number of
infants requiring such management is enormous. This section focuses on nutritional goals,
nutrient requirements, and enteral and parenteral routes of nutritional therapy.
Nutritional Goals for the Premature Infant

Prematurity is defined as an infant with a gestational age of less than 38 weeks born before
completion of 37 weeks gestation. A post-term infant is one whose birth occurs from the
beginning of the first day of week 43 (>42 weeks). Classifying infants as preterm, term,
or post-term assists in establishing the level of risk for neonatal morbidity, nutritional
needs, and long-term sequelae. Assessment of gestational age is based on maternal dates,
obstetric dating by ultrasonography, and physical examination.1 Ultrasonography has
improved the ability to estimate gestational age. Estimation by physical exam relies on
the predictable changes in the pattern of physical and neurological changes that occur
with advancing gestation and form the basis of the examinations for the estimation of
gestational age. The Ballard exam may overestimate the age of premature infants and, on
the other hand, may underestimate that of post-term infants.2 Because of the error in
gestational age assessment, particularly in very-low-birth-weight infants, a New Ballard
Score is currently used.3 This modified examination is particularly suited for the very
small premature infant, and the estimated gestational age is accurate to within one week.
Items of neuromuscular maturity and physical maturity are scored from –1 to 5, a total
score obtained, and gestational age estimated based on maturity rating score.
Infants are considered low birth-weight if birth weight is less than 2500 g regardless of
gestational age. Very-low-birth-weight defines infants with weight less than 1500 g, with
an additional classification of extremely low-birth-weight describing infants less than
1000 g.
Crown–heel length performed by two examiners is measured by achieving full extension
of the infant on a measuring board with a fixed headpiece and movable footpiece. The
0-8493-2705-9/01/$0.00+$1.50
infant needs to be supine, head held in the Frankfurt plane vertical, legs extended, and
ankles flexed, and the movable footpiece is brought to rest firmly against the infant’s heels.
An average of two measurements documents the length. If crown–heel length cannot be
measured due to limb anomalies or if there is a discrepancy between weight and length,
a crown–rump length is sometimes measured.
Head circumference measured with a non-stretchable tape is the largest of three mea-
surements around the head, with the tape held snugly above the ears.
Weight, length, and head circumference are then plotted on standard curves to classify
an infant as appropriate, small, or large for gestational age for each measurement. Most
measurements define appropriate for age as measurements that fall within the 10th to
90th percentiles, ideally based on charts constructed for similar race and height above sea
level. Infants who are appropriate for age on the three measures are at the lowest risk,
within that gestational age grouping, for problems associated with neonatal morbidity
and mortality. An example of growth curves commonly used in neonatal nurseries is
depicted in Figure 6.1.
Growth and Nutrient Requirements

Estimation of nutrient requirements in premature infants is based on the goals for growth
of this cohort of infants. The common goal has been to achieve growth similar to that of
the "reference fetus."4,5 These growth standards serve as a reference to judge the adequacy
of growth; however, postnatal changes in energy requirements as well as environmental
stresses are likely to be different, and the ideal growth of these infants remains to be
defined. An alternative approach may be to achieve the best possible growth without
adverse metabolic consequences.
Nutrient requirements for preterm infants have been estimated by various methods,
including the factorial method based on the reference fetus, nitrogen balance studies, and
turnover studies, or based on nutrient values in the serum. For example, Figure 6.2 depicts
the composition of weight gain in normal human fetuses.4 This reference fetus (Table 6.1)
has not only served as a basis for calculation of nutrient needs, but also as a measure of
sufficiency of particular nutrients, as discussed above. The factorial approach is based on
the assumption that the requirement for a nutrient is the sum of losses (fecal, urine, dermal,
and other, if any) and the amount required for growth, i.e., incorporation into new tissues.
An example of such an approach to calculate protein requirements of preterm infants is
that of Ziegler.6 Advisable intakes of protein are obtained by adding 8–10% of the estimated
requirement.
Provision of Nutrients
Energy Needs
Energy needs are based on basal metabolic rate, cost of growth, and losses in stool and
urine. The factorial method cannot be used to estimate energy requirements. It is gen-
erally recognized that preterm infants have higher energy requirements compared to
their term counterparts.7 To gain the predicted growth in weight for premature infants
Feeding the Premature Infant 205
CLASSIFICATION OF NEWBORNS (BOTH SEXES)

BY INTRAUTERINE GROWTH AND GESTATIONAL AGE 1.2
NAME DATE OF EXAM LENGTH
HOSPITAL NO. SEX HEAD CIRC.
RACE BIRTH WEIGHT GESTATIONAL AGE
DATE OF BIRTH
WEIGHT PERCENTILES LENGTH PERCENTILES

4600 54
90
4400 53
4200 52
75
4000 90 51
3800 50 50
75
3600 49
25
3400 50 48
3200 47
25 10
3000 46
2800 45
Length (cm)
10
Weight (g)
2600 44
2400 43
2200 42
2000 41
1800 40
1600 39
1400 38
1200 37
1000 36
800 35
600 34
PRETERM TERM
400 33
0 32
24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 PRETERM TERM
Gestational Age (week) 31
0
24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43
Gestational Age (week)
HEAD CIRCUMFERENCE PERCENTILES
38
37
90 CLASSIFICATION OF INFANT* Weight Length Head Circ.
36
75
35 50 Large for
34
25 Gestational Age (LGA)
Head Circumference (cm)
33 (>90th percentile)
10
32
31
Appropriate for
30
Gestational Age (AGA)
29 (10th to 90th percentile)
28
27
Small for
26
Gestational Age (SGA)
25
(<10th percentile)
24
23
PRETERM TERM * Place an ''X'' in the appropriate box (LGA, AGA or SGA) for weight, for
22 length and for head circumference.
0
24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43
Gestational Age (week)
FIGURE 6.1
Classification of newborns by intrauterine growth and gestational age.
(10 to 15g/kg/d), it is estimated that premature infants would need 110 to 130 kcal/kg/
d. Energy requirements must take into account the route of administration, enteral vs.
parenteral, since 90 to 95 kcal/kg/d may satisfy energy requirements by the parenteral
route. Disease states such as sepsis, chronic lung disease,8,9 and concomitant use of
corticosteroids will increase energy needs. The mainstay of energy support should be
balanced between carbohydrates, fat, and amino acids.
30
13.3
13.9 13.9
DAILY INCREMENTS (gm/day)
12.2
20 19.8
11.4
10.8
7.8
10
79.0 74.0 69.9 62.5
24-28 28-32 32-36 36-40
AGE INTERVAL (weeks)
FIGURE 6.2
Average composition of weight gain of the reference fetus; numbers indicate percentages of gained accounted
for by components. From Ziegler E.E., O’Donnell A.M., Nelson S.E., Fomon S.J. Growth 40: 329; 1976. With
permission.
TABLE 6.1
Daily Increments of Body Weight and Body Composition of the Reference Fetus
Age
Interval Weight Protein Lipid Ca P Mg Na K Cl
(Weeks) (g) (g) (g) (mg) (mg) (mg) (mEq) (mEq) (mEq)
24–25 11.4 1.25 0.5 61 39 1.8 0.9 0.5 0.8
25–26 15.7 1.67 1.2 84 54 2.4 1.3 0.6 1.0
26–27 18.6 2.00 1.6 101 65 2.8 1.5 0.8 1.1
27–28 21.4 2.37 2.0 119 76 3.3 1.7 0.9 1.3
28–29 22.6 2.59 2.3 129 83 3.5 1.7 0.9 1.3
29–30 23.1 2.76 2.6 138 89 3.7 1.7 1.0 1.3
30–31 24.3 3.00 2.9 152 97 4.0 1.8 1.0 1.3
31–32 25.7 3.28 3.2 171 109 4.4 1.8 1.1 1.3
32–33 27.1 3.55 3.5 193 123 4.8 1.9 1.1 1.3
33–34 30.0 3.97 4.0 228 144 5.5 2.1 1.2 1.4
34–35 31.4 4.23 4.4 258 162 6.0 2.2 1.3 1.4
35–36 34.3 4.62 5.1 301 189 6.9 2.4 1.4 1.4
36–37 35.7 4.83 5.6 341 212 7.5 2.5 1.5 1.4
37–38 31.4 4.34 5.6 344 211 7.1 2.1 1.3 1.1
38–39 24.3 3.44 5.4 325 197 6.1 1.6 1.0 0.7
39–40 17.1 2.50 5.0 302 179 5.0 1.0 0.6 0.3
From Ziegler E.E., O’Donnell A.M., Nelson S.E., Fomon S.J. Growth 40: 329; 1976. With permis-
sion.
Amino Acid Needs

The factorial approach is commonly used to estimate protein requirements. The protein
need will be greater if catch-up growth is also to be produced. It is generally accepted that
the newborn infant will lose up to 10% of his/her body weight. In sick premature infants
where nutrition cannot be provided or is not tolerated, the amount of catch-up may be
greater. Several studies suggest that endogenous protein losses in the absence of exogenous
protein intake are at least 1 g/kg/d.10,11 When fed in the conventional manner, premature
infants run the risk of under-nutrition. Therefore, strategies to optimize amino acid intakes
to include provision for catch-up growth need to be developed, since early initiation of
parenteral nutrition results in positive nitrogen balance and has been shown to be safe.11,12-14
Cysteine and tyrosine are provided as cysteine hydrochloride (40 mg/g/amino acid,
not to exceed 100 mg/kg/d) and N-acetyl-L-tyrosine (0.24 g%);15 it has been demonstrated
that infants receiving cysteine retain significantly more nitrogen that do infants receiving
an isonitrogenous amino acid intake without cysteine.11
It is generally accepted that infants receiving 80 to 90 kcal/kg/d from parenteral nutri-
tion with an adequate amino acid intake should gain weight similar to the intrauterine
rate.16 Most of this energy intake is provided by glucose and lipids. However, premature
and sick infants may not tolerate increasing glucose concentrations/delivery without
concomitant hyperglycemia, making the goal of achieving adequate energy intake difficult
in the first week of life.
Lipid Needs
Lipid emulsions are used in conjunction with glucose and amino acid solutions. Generally,
lipids are started at 0.5 g/kg/d intravenously, increasing by 0.5 g/kg to a maximum of
3.0 g/kg/d. Infusion rates are maintained between 0.15 to 0.25 g/kg/h in order to avoid
hypertriglyceridemia (triglycerides > 175 mg/dL). Essential fatty acid deficiency may be
prevented by lipid intakes as low as 0.5 to 1.0 g/kg/d.
Fat particle size is between 0.4 and 0.5µ in diameter, similar to that of endogenous
chylomicrons. Clearance of lipids by premature infants may be limited, thereby requiring
frequent assessment of tolerance. Emulsions of 20% are preferred due to lower total
phospholid and liposome content per gram of triglyceride.17,18
Parenteral Nutrition
It is common practice to provide initial nutrient requirements, especially in a sick neonate,
by the parenteral route. A typical parenteral regimen is depicted in Table 6.2. Commonly
available lipid products are listed in Table 6.3. Currently, two amino acid formulations are
available in the U.S. specifically designed for preterm infants: Trophamine® and Amino-
syn-PF®. These amino acid formulations were designed to result in a plasma amino acid
profile similar to that of a 30-day-old breastfed infant.19 It is generally recommended that
parenteral nutrition be started within the first two days of life in preterm infants and
advanced in a systematic fashion to achieve 3.0–4.0 g/kg/d of amino acids, 90–100 kcal/
kg/d of energy. Most preterm infants do not achieve these intakes until well into the
second week of life because of issues such as glucose and lipid intolerance.
Mineral Requirements
Mineral requirements have also been estimated based on body composition and the
reference fetus.4,5 From a practical standpoint, daily needs for sodium, potassium, and
TABLE 6.2
Parenteral Nutrition Regimen
Component Amount/kg/d
Amino acids (g) 3–4
Glucose (g) 15–25
Lipid (g) 0.5–3.0
Sodium (mEq)1 2–5
Potassium (mEq)2 2–4
Calcium (mg) 80–100
Magnesium (mg) 3–6
Chloride (mEq) 2–3
Phosphorus (mg)2 40–60
Zinc (µg) 200–400
Copper (µg) 20
Iron (µg) 100–200
Other trace minerals3
Vitamins4
Total Volume 120–150 mL
Nutrient <14 d >14 d
Manganese (µg) 0.0–0.75 1.0
Chromium (µg) 0.0–0.05 0.2
Selenium (µg) 0.0–1.3 2.0
Iodide (µg) 0.0–1.0 1.0
Molybdenum (µg) 0 0.25
C (mg) 80
A (mg) 0.7
D (µg) 10 (= 400 µ)
B1 (mg) 1.2
B2 (mg) 1.4
B6 (mg) 1
Niacin (mg) 17
1 Sodium requirements may vary between infants and
within the same infant, and should be tailored to
serum values.
2 Phosphorus intakes are maintained in a ratio of 1:2
to 1:2.6 with calcium (mEq:mM) and may be limiting
in parenteral nutrition because of insolubility; in gen-
eral, the more acidic the TPN, the more calcium and
phosphorus can be dissolved in the solution without
precipitation. Care must be taken to avoid hyper-
phosphatemia with its resultant hypocalcemia.
3 amount/kg/d.
4 Provided as MVI-Pediatric®; each 5 mL provides
(MVI is to be provided in amounts not exceeding 2.0
ml/kg/d).
chloride are based on serum measurements, while calcium and phosphorus needs are
based on the factorial method.4,5 Requirements are listed in Table 6.2. In general, the
preterm infant has higher requirements of most minerals than term infants. During total
parenteral nutrition, requirements for calcium and phosphorus may not be met because
of the insolubility of calcium salts. Human milk may not provide adequate amounts of
sodium, and hyponatremia has been reported.20 Calcium and phosphorus needs of preterm
infants cannot be met by human milk from mothers delivering preterm or term infants,
and will need to be supplemented.21 Since calcium transfer across the placenta occurs in
the third trimester, the very premature infant is relatively osteopenic, and prolonged
TABLE 6.3
Fatty Acid Composition of Commonly Used Lipid Emulsions
Intralipid® 20% Liposyn III® 20%
Oils % — —
Safflower 0 0
Soybean 20 20
Fatty acid content (%) — —
Linoleic 50 54.5
Oleic 26 22.4
Palmitic 10 10.5
Linolenic 9 8.3
Stearic 3.5 4.2
Egg yolk phospholipid % 1.2 1.2
Glycerine % 2.25 2.5
kcal/mL 2 2
mOsm/L 260 292
parenteral nutrition and/or unfortified human milk feedings puts the infant at great risk
for metabolic bone disease.
Iron is accumulated in the fetus in the third trimester with an iron content of 75 mg/
kg at term. Small-for-gestational-age infants, preterm infants, and infants of diabetic moth-
ers have low iron stores at birth. Coupled with the need for frequent blood sampling, the
premature infant is at great risk for the development of iron deficiency anemia, and the
exact time for supplementation remains controversial. However, given that the criteria for
blood transfusion have become more stringent,21 iron should be supplemented as early
as two weeks. If recombinant erythropoietin is used to stimulate endogenous iron pro-
duction,22 iron requirements may be 6.0 mg/kg/d or higher.
Nutrient Delivery
Delivery of enteral nutrients is based on gestational age. In general, infants of 33 weeks
gestation and beyond can be fed orally soon after birth. However, if medical or surgical
illness precludes enteral feedings, parenteral nutrition is indicated. Parenteral nutrition
can be considered as total (where all nutrients are delivered, for example in an infant with
a surgical condition precluding enteral nutrition: gastroschisis) or supplemental (to com-
plement enteral nutrition). It can be further described as peripheral parenteral nutrition
(provided by a peripheral intravenous line) or central (where the tip of the catheter is in
a central location or deep vein). The latter should be the route if long-term parenteral
nutrition (for example, greater than 2 weeks) is anticipated, since it allows for higher
glucose delivery compared to the peripheral vein (>12.5% dextrose in water). A typical
nutrition plan for a very-low-birth weight infant is depicted in Table 6.4, and indications
for parenteral nutrition are listed in Table 6.5.
The metabolic complications (Table 6.6) can be avoided by careful assessment of toler-
ance to the macronutrients as nutrition delivery is advanced. Premature infants do not
tolerate high concentrations of glucose or rapid advances in glucose delivery; similarly,
rates of fat infusion of greater than 2.0 g/kg/d may result in hypertriglyceridemia, par-
ticularly in the small or ill preterm infant (triglycerides >175 mg/dL). A suggested regimen
of monitoring parenteral nutrition is depicted in Table 6.7. A multidisciplinary approach
with physicians, pharmacists, nutritionists, and nursing staff who are knowledgeable in
parenteral nutrition and monitoring should be implemented for the care of such infants.
Early recognition of metabolic effects (pharmacist/nutritionist) or catheter-related effects
TABLE 6.4
Initiation and Advancement of Parenteral and Minimal Enteral Feedings in an Infant with a
Birthweight of <1000 g
Parenteral Enteral
Age, d Amino Acid [g/kg] Glucose Lipids [g/kg] Electrolytes mL/h
1 0.0 D 5W 0.0 0.0 0.0
2 1.0 D 5W 0.5 Add if Na <130 mEq/l 0.25
3 1.5 Increments of 2.5% 1.0a Standard 0.25
4 2.0 Increase as tolerated 1.5a Standard 0.5
7 3.0 or higherb Same or higher 3.0a Standard 0.75
a Monitor triglycerides to assess lipid tolerance.
b Optional; infants requiring catch up growth, on corticosteroids or demonstrating low BUN despite ade-
quate protein intakes may need higher amino acid intakes at later stages.
TABLE 6.5
Parenteral Nutrition is Indicated in the Following Conditions
Condition Indication
Medical Inadequate enteral nutrition
Necrotizing enterocolitis
Feeding intolerance/difficulty
Ileus
Surgical Omphalocele
Gastroschisis
Tracheo-esophageal fistula
Atresias of the intestine (duodenal/jejunal/ileal)
Diaphragmatic hernia
Hirschsprung’s disease
TABLE 6.6
Complications of Parenteral Nutrition
Type Complication
Metabolic Hypo- or hyperglycemia
Electrolyte imbalance
Metabolic bone disease
Hepatic dysfunction
Infectious Bacterial sepsis
Fungal sepsis
Mechanical Extravasation
Thrombosis
Pericardial effusion
Diaphragmatic palsy
(nursing) could help to minimize the potential complications of parenteral nutrition. The
most common metabolic complications observed are hepatic dysfunction and metabolic
bone disease.
Hepatic dysfunction is defined as an increase in serum bile acids followed by an
increase in direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase. The
hepatocellular enzymes, ALT and AST, are late to increase, and are often seen in the more
severe cases. Gamma-glutamyl transferase is probably the most sensitive but least specific
TABLE 6.7
Suggested Monitoring during Parenteral Nutrition
Component Initial Later
Weight Daily Daily
Length Weekly Weekly
Head circumference Weekly Weekly
Na, K, Cl, CO2 Daily until stable Weekly
Glucose Daily PRN
Triglycerides With every lipid change Weekly or biweekly
Ca, PO4 Daily until stable Weekly or biweekly
Alkaline phosphatase Initial Weekly or biweekly
Bilirubin Initial Weekly or biweekly
Mg Initial Weekly or biweekly
Ammonia PRN PRN
Gamma GT Initial Weekly or biweekly
ALT/AST Initial Weekly or biweekly
Complete blood count Initial Weekly or PRN
indicator, whereas elevation in direct bilrubin is the most specific and least sensitive
indicator of hepatic dysfunction. The etiology is multi-factorial,23-25 but the incidence
appears to be declining as a result of both specialized amino acid solutions and early
provision of enteral nutrients.
Premature infants are at high risk for the development of metabolic bone disease most
commonly due to inadequate intakes of calcium and phosphorus during parenteral nutri-
tion. Infants born before 32 weeks of gestation have some degree of hypomineralization
which is worsened during the subsequent period of hospitalization, especially coupled
with inadequate intakes of calcium and phosphorus. In general, both calcium and phos-
phorus levels are maintained in serum, while the bones appear more osteopenic on
radiographs, and ultimately hypophosphatemia with increasing alkaline phosphatase is
observed. Rising alkaline phosphatase in the absence of elevated liver enzymes is a strong
indicator of metabolic bone disease. Incidence of rickets (metabolic bone disease) is
inversely proportional to birth-weight, and has been reported to be as high as 50–60% in
very-low-birth-weight infants.26 Diagnosis is made by routine radiographs which in the
initial stages would demonstrate bone undermineralization, especially in the ribs and
scapula, subsequently showing the classic forms of rickets in the wrists and long bones.
Strategies to increase calcium and phosphorus delivery should be considered. Unfortu-
nately, the very small preterm infant is more often at risk for these complications, given
the duration of parenteral nutrition and the coexistence of hepatic dysfunction.
Enteral Nutrition
Even if enteral nutrition is started in the first days after birth, it is suggested that supple-
mental parenteral nutrition be started because immaturity, feeding intolerance, and GI
motility may affect the rate of advancement of enteral nutrition. Further, intakes are also
dictated by the feedings used: human milk or formula. Composition of formulas available
in the U.S. is depicted in Table 6.8. Composition of human milk (Table 6.9), especially from
a mother delivering a preterm infant, is different from that of mothers delivering at term;
further, differences between and within the same woman makes the average content
difficult to estimate. The route of enteral nutrition is dictated not only by the gestational
age of the infant, but also the coexistence of medical or surgical morbidity. Routes and
types of delivery are depicted in Table 6.10.
TABLE 6.8
Composition of Formulas Commonly Used in Premature Infants
Enfamil®
Premature Similac®
Nutrients per Formula 24 Similac® Special Enfamil 22™ NeoCare™
100 Calories with Iron Care® 24 with Iron with Iron 22 with Iron
Protein, g 3 2.71 2.8 2.6
Whey:casein 60:40 60:40 60:40 50:50
Fat, g 5.1 5.43 5.3 5.5
Source MCT, soy, coconut MCT, soy, coconut High oleic Soy, MCT, coconut
oils oils sunflower, soy, oils**
MCT, coconut oils
Carbohydrate, g 11.1 10.6 10.7 10.3
Source Corn syrup, solids, Corn syrup, solids, Corn syrup solids,* Corn syrup solids,
lactose lactose lactose lactose
Water, g 108 109 120 120
Lineoleic acid, mg 1060 700 950 750
Vitamin A, IU 1250 1250 450 460
Vitamin D, IU 270 150 80 70
Vitamin E, IU 603 4 4 3.6
Vitamin K, mcg 8 12 8 11
Thiamin (B1), mcg 200 250 200 220
Riboflavin (B2), 300 620 200 150
mcg
Vitamin B6, mcg 150 250 100 100
Vitamin B12, mcg 0.25 0.55 0.3 0.4
Niacin, mcg 4000 5000 2000 1950
Folic acid, mcg 35 37 26 25
Pantothenic acid, 1200 1900 850 800
mcg
Biotin, mcg 4 37 6 9
Vitamin C, mg 20 37 16 15
Choline, mg 12 10 15 16
Inositol, mg 17 5.5 30 6
Calcium, mg 165 180 120 105
Phosphorus, mg 83 100 66 62
Calcium: 2:1 1.8:1 1.8:1 1.7:1
phosphorus
Magnesium, mg 6.8 12 8 9
Iron, mg 108 1.8 1.8 1.8
Zinc, mg 105 1.5 1.25 1.2
Manganese, mcg 603 12 15 10
Copper, mcg 125 250 120 120
Iodine, mcg 25 6 15 15
Selenium, mcg 1.8 1.8 2.3 2.3
Sodium, mg 39 43 35 33
Potassium, mg 103 129 105 142
Chloride, mg 85 81 78 75
Osmolality, 310 280 260 250
m0sm/kg water
* Powder form only. Ready-to-use form contains maltodextrin.
** Ready to feed.
TABLE 6.9
Composition of Human Milk
Human milk
(2 wks postpartum)
Term Preterm
Volume (ml) 147–161 139–150
Water (ml) 133–145 125–135
Protein
Content (gm) 1.8–2.5 2.4–3.1

% of energy 7–11 9.6–12
Whey/casein ratio 80:20 80 : 20
Lipid
Content (gm) 4.4–6 4.9–6.3

% of energy 44–56 42–55
Composition
Saturated (%) 43 41–47

Monosaturated (%) 42 39–40
Polyunsaturated (%) 15 12–14
Carbohydrate
Content (gm) 9–10.6 8–9.8

% of energy 38–44 31–38
Lactose (%) 100 100
Minerals and Trace Elements
Calcium (mg) 39–42 31–40

(mmol) 0.9–1 0.7–1
Chloride (mg) 69–76 76–127
(mmol) 1.9–2.1 2.1–3.6
Copper (mg) 37–85 107–111
Iodine (µg) 16 —
(mmol)
Iron (mg) 0.04–0.12 0.13–0.14
Magnesium (mg) 3.9–4.5 4.3–4.7
(mmol) 0.16–0.18 0.17–0.2
Manganese (µg) 0.9 —
Phosphorus (mg) 22–25 20–23
(mmol) 0.7–0.9 0.6–0.7
Potassium (mg) 90–91 81–93
(mmol) 2.2–2.4 2.1–2.4
Sodium (mg) 37–43 44–77
(mmol) 1.6–1.9 1.9–3.3
Zinc (mg) 0.18–0.50 0.61–0.69
Vitamins
Fat-soluble
Vitamin A (IU) 155–333 72–357
Vitamin D (IU) 0.7–3.3 0.7–12
Vitamin E (IU) 0.45–0.75 0.42–1.42
Vitamin K (µg) 0.29–3 0.29–3

Composition of Human Milk
Human milk
(2 wks postpartum)
Term Preterm
Water-soluble
Vitamin B6 (µg) 15–119 9–129
Vitamin B12 (µg) 0.01–1.2 0.01–0.07
Vitamin C (mg) 6.6–7.8 6.3–7.4
Biotin (µg) 0.01–1.2 0.01–1.2
Folic Acid (µg) 7.5–9 5–8.6
Niacin (mg) 0.2–0.25 0.24–0.3
Pantothenic acid (mg) 0.26 0.33
Riboflavin (µg) 15–104 14–79
Thiamin (µg) 3–31 1.4–31
Other
Carnitine (mg) 1.04 —

Choline (mg) 13.4 10–13
Inositol (mg) 22.2–83.5 21.3
TABLE 6.10
Routes of Feeding Preterm Infants
Route <34 weeks >34 weeks
Per os No Yes
Continuous gastric <1250 g Failure to tolerate bolus gastric,
significant GER
Bolus gastric (every 3 h) >1250 g; infants <1250 g not tolerating Failure to tolerate per os
continuous
Transpyloric, continuous Failure to tolerate gastric feeds, gastric Same as <34 weeks
distention due to positive pressure,
poor gastric emptying
Motor responses to feedings are similar whether feedings are provided by the gastric
or transpyloric route.27 However, when feeds are provided slowly over 120 min as com-
pared to 15 min, gastric emptying is better, suggesting that in the smaller premature infant,
slow infusions may be better tolerated.28,29
Oral Feeding
Term and preterm infants greater than 33 to 34 weeks gestation may be fed soon after
birth by the oral route. This should be attempted in the delivery room in healthy infants
or initiated soon after birth. Human milk feedings (i.e., breast feeding) should be encour-
aged, and all steps should be taken by the medical team and hospital staff to encourage
breast feeding once the decision is made.30 If breast feeding is precluded due to craniofacial
anomalies such as cleft lip or palate, feeding devices are available and speech and/or
feeding teams may need to be involved. Lactation consultation should be sought for
mothers who have difficulty in either initiation or maintenance of breast feeding. Hospitals
should avoid supplementing breastfed infants and the use of pacifiers.30
Most mothers delivering preterm infants have not made a decision about breast feeding,
and should be counseled appropriately. All delivery sites should have facilities to pump
breast milk if actual breastfeeding is not possible and the mother wishes to breastfeed.
Teaching should include appropriate techniques for pumping and storing milk.
Nutrient Delivery
For infants born after 33 to 34 weeks of gestation, enteral feedings may be started per os.
Although it is recognized that infants at this gestational age can coordinate their suck,
swallow, and respiratory activities, thus enabling feedings, not all infants respond in such
a fashion and careful assessment is warranted. In the event that nipple feedings are not
achieved, the infant may be fed by the gastric route.
In general, the alternatives to feedings by mouth are gastric and transpyloric. Gastric
feedings can be further described as bolus or continuous, where the feedings are either
provided intermittently every 2 to 3 hours, or by a pump continuously. Transpyloric feeds
are provided continuously, with the tip of the feeding tube in the second part of the
duodenum. General indications for the latter include failure to tolerate gastric feeding
due to delayed gastric emptying, gastric distention due to positive pressure ventilation,
or gastroesophageal reflux. Feedings can also be planned based on birth-weight. In general,
infants below 1250 g are fed by the continuous gastric method, whereas bigger infants are
fed by the intermittent method.
Special Considerations
Vegetable oils contain the precursor essential fatty acids linoleic acid (18:2w-6) and in most
cases alpha linolenic acid (18:3w-3). Linoleic and linolenic acids serve as precursors for
the synthesis of long-chain polyunsaturated fatty acids (LC-PUFA) including arachdonic
(20:4w-6), eicosopentaenoic (20:5w-3), and docosahexaenoic (22:6w-3) acids. Human milk
lipids contain preformed LC-PUFA; LC-PUFA are essential components of membrane
systems and are incorporated in membrane-rich tissues such as the brain during early
growth.31,32 Some of the LC-PUFA serve as precursors for prostaglandins, prostacyclin,
thromboxanes, and leukotrienes. The fetus and the fully breastfed infant do not depend
on active synthesis of LC-PUFA, since the placenta and human milk provide LC-PUFA in
amounts considered appropriate.33-36 Premature infants fed formulas without LC-PUFA
develop depletion of LC-PUFA in plasma and red cell membranes, indicating limited
endogenous LC-PUFA synthesis.37 Recent studies by Carlson et al. demonstrate that pre-
term infants have high cord blood phosphatidlyethalonamine (PE), phosphatidlycholine
(PC), docosahexanoic acid (DHA), and arachadonic acid (AA), but that these levels decline
rapidly.38 Further, PE, PC, DHA, and PC AA declined in formula-fed infants, but were
maintained in human milk-fed infants;38 at the end of the six-week study period, although
PE, PC DHA, and AA were significantly higher in human milk-fed than formula-fed
infants, these levels did not reach cord blood levels.38 These declines in erythrocyte PE
DHA could be prevented with supplementation of DHA.39 However, supplementation
with DHA (0.5% total fatty acids) resulted in decreased AA concentrations compared to
feeding with 0.2% DHA, suggesting adverse effects on AA synthesis at the higher con-
centration.40 Similar effects on AA were observed in premature infants fed formulas with
similar linoleic acid content (16%) but different alpha-linolenic acid contents (1 vs. 3.2%);
high alpha-linolenic acid-supplemented infants had lower AA and despite a higher DHA
content, rate of weight gain was significantly less than the lower-supplemented infants
throughout the study.41 There were no demonstrable effects on visual evoked potential or
latency at 56 weeks between the two groups of infants, although mean latency in both
groups was higher and mean amplitude lower than in age-matched breastfed term infants
or in term infants fed similar formulas. Higher visual acuity in DHA-supplemented infants
has been reported at 2 and 4 months42-44 but not at 6, 9, and 12 months. Further studies
are required before the optimal dose of DHA can be determined on growth and longer
term followup of premature infants.
Carnitine
Current parenteral nutrition regimens do not contain carnitine. Low plasma concentrations
of carnitine and its decline with postnatal age has been demonstrated in infants receiving
carnitine-free nutrition.45,46 Although fatty acid metabolism has not been shown to be
impaired in short-term parenteral nutrition, carnitine is an accepted additive for infants
requiring parenteral nutrition for longer periods.47-49 Carnitine is provided at doses of 8.0
to 20 mg/kg/d.
Glutamine
Glutamine is the most abundant amino acid in the human body and is the most important
"nitrogen shuttle," accounting for 30 to 35% of all amino acid nitrogen transported in the
blood.50 Glutamine concentrations in blood and tissue fall following starvation, surgery,
infection, and trauma.51,52 In addition, glutamine plays an important role in protein and
energy metabolism, nucleotide synthesis, and lymphocyte function.53 Glutamine is known
to be an important fuel for small intestinal enterocytes;54 however, an absolute need of
glutamine for gut growth has not been demonstrated with either detrimental or negligible
effects reported in the literature.55-57 Nonetheless, absence of glutamine in the diet has
been shown to cause villous atrophy, fall in lumina propria lymphocyte populations, and
increased bacterial translocation.58-62 While optimal intakes of glutamine for premature
infants is not known, enteral supplementation with glutamine has been shown to decrease
feeding intolerance,63 and there is a possible decrease in hospital costs64 with glutamine
supplemented up to 0.3 g/kg/d. Further studies on optimal supplementation of
glutamine, enterally and parenterally, in preterm infants are required.
Summary
Despite the many questions that remain regarding optimal nutritional management of the
neonate, it is nonetheless important to develop rational protocols for the management of
nutritional issues that arise. This chapter has provided some guidelines and the framework
from which these guidelines arose. There are numerous different approaches to feeding
a neonate. The ultimate goal should be to optimize nutrition, and hence growth and
ultimately development in this ever-increasing population of small premature infants.
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23. Grant J. P., Cox C. E., Kleinman L. M. et al., Surg Gynecol Obstet 145: 573; 1977.
24. Balistreri W. F., Bove K. E. Prog Liver Dis 9: 567; 1990.
25. Bhatia J., Moslen M. T., Haque A. K. Pediatr Res 33: 487; 1993.
26. Greer F. R. Ann Rev Nutr 14: 169; 1994.
27. Koenig W. J., Amarnath R. P., Hench V., Berseth C. L. Pediatrics 95: 203; 1995.
28. Berseth C. L. J Pediatr 117: 777; 1990.
29. Berseth C. L., Ittmann P. I. J Pediatr Gastroenterol Nutr 14: 182; 1992.
30. American Academy of Pediatrics. Work Group on Breastfeeding. Pediatrics 100: 1035; 1997.
31. Clandinin M. T., Chappell J. E., Leong S., et al. Human Dev 4: 121; 1980.
32. Martinez M., Ballabriga A. Lipids 22: 133; 1987.
33. Koletzko B., Thiel I., Springer S. Eur J Clin Nutr 46: S45; 1992.
34. Jensen R. G., The Lipids of Human Milk, CRC Press, Boca Raton, 1995.
35. Sanders T. A., Naismith D. J. Br J Nutr 41: 619; 1979.
36. Putnam J. C., Carlson S. E., DeVoe P. W., Barness L. A. Am J Clin Nutr 36: 106; 1982.
37. Koletzko B., Schmidt E., Bremer H. J., et al. Eur J Pediatr 148: 669; 1989.
38. Carlson S. E., Rhodes P. G., Ferguson M. G. Am J Clin Nutr 44: 798; 1986.
39. Carlson S. E., Rhodes P. G., Rao V. S., Goldgar D. E. Pediatr Res 21: 507; 1987.
40. Liu C. C., Carlson S. E., Rhodes P. G., et al. Pediatr Res 22: 292; 1987.
41. Jensen C. L., Chen H. M., Prager T. C., et al. Pediatr Res 37: 311A, 1995.
42. Uauy R. D., Birch D. G., Birch E. E. et al., Pediatr Res 28: 485; 1990.
43. Carlson S. E., Werkman S. H., Tolley E. A. Am J Clin Nutr 63: 687; 1996.
44. Carlson S. E., Werkman S. H., Rhodes P. G., Tolley E. Am J Clin Nutr 58: 35; 1993.
45. Penn D., Schmidt-Sommerfeld E., Pascu F. Early Hum Develop 4: 23; 1979.
46. Shenai J. P., Borum P. R. Pediatr Res 18: 679; 1984.
47. Orzali A., Donzelli F., Enzi G., Rubaltelli F. Biol Neonate 43: 186; 1983.
48. Orzali A., Maetzke G., Donzelli F., Rubaltelli F. F. J Pediatr 104: 436; 1984.
49. Schmidt-Sommerfeld E., Penn D., Wolf H. J Pediatr 102: 931; 1983.
50. Souba W. W. J Parent Enteral Nutr 11: 569; 1987.
51. Askanazi J., Carpentier Y. A., Michelsen C. B., et al. Ann Surg 192: 78; 1980.
52. Roth E., Funovics J., Muhlbacher F., et al. Clin Nutr 1:25; 1982.
53. Neu J., Shenoy V., Chakrabarti R. FASEB J 10: 829; 1996.
54. Souba W. W., Herskowitz, K., Salloum, R. M., et al. J Parent Enteral Nutr 14: 45S; 1990.
55. Bark T., Svenberg T., Theodorsson E., et al. Clin Nutr 13:79; 1994.
56. Burrin D. G., Shulam R. J., Storm M. C., Reeds P. J. J Parent Enteral Nutr 15: 262; 1991.
57. Vanderhoof J. A., Blackwood D. J., Mohammadpour H., Park, J. H. J Am Coll Nutr 11: 223;
1992.
58. Hwang T. L., O’Dwyer S. T., Smith R. J., et al. Surg Forum 38: 56; 1987.
59. Grant J. J Surg 44: 506; 1988.
60. Burke D. J., Alverdy J. C., Aoys E., Moss G. S. Arch Surg, 124: 1396; 1989.
61. Alverdy J. C., Aoys E., Weiss-Carrington P., Burke D. A. J Surg Res 52: 34; 1992.
62. Neu J., Roig J. C., Meetze W. H., et al. J Pediatr 131: 691; 1997.
63. Dallas M. J., Bowling D., Roig J. C., et al. J Parent Enteral Nutr 22: 352; 1998.
7
Feeding the Term Infant
Growth, particularly in weight, length, and additional anthropometric measurements,

remains a measure of adequacy of nutritional regimens for the growing infant and child.
Infant feeding decisions have an impact on lifelong medical illnesses, growth, and devel-
opmental abilities well beyond infancy. This section will review normal growth and
requirements in healthy term infants.
Growth
The average weight of a healthy term infant is 3.5 kg. With an anticipated loss of 10% in
body weight in the first week of life, birth weight is regained by two weeks of age in both
breast-fed and formula-fed infants, with the formula-fed infants demonstrating a tendency
to regain birth weight sooner than their breast-fed counterparts.
Body weight should be measured with an electronic scale or a beam balance without
detachable weights, with the balances capable of weighing to the nearest 10 g. Even with
the use of electronic scales, balances should be tared with calibrated weights at least two
times a year. Mean weight and selected centiles for weight are summarized in Table 7.1.
In clinical practice, however, weight and other anthropometric measurements including
length, head circumference, and weight for length are plotted on growth charts (Figures
7.1 and 7.2) adapted from Hamill et al.1 The plotting of growth on these charts will suffice
for monitoring of normal infants; however, a different and more sensitive approach will
be needed for infants with faltering growth. The “reference data” provided by Fomon2
combine data from the University of Iowa and the Fels Longitudinal Study, the latter data
used in the growth charts.
Length
Length should be measured by two examiners using a calibrated length board with a fixed
headpiece and a movable foot board. The head is held by one examiner with the Frankfort
plane (defined as a line that passes through the left porion, the right porion, and the orbits)
0-8493-2705-9/01/$0.00+$1.50
TABLE 7.1
Mean Body Weight and Selected Centiles for Males and Females, 0–12 Months of Age
Age Mean 5th centile (g) 50th centile (g) 95th centile (g)
Mean body weight and selected centiles for males, 0–12 months of age
Birth 3350 2685 3530 4225

1 mo 4445 3640 4448 5238
2 mo 5519 4574 5491 6475
3 mo 6326 5321 6323 7393
6 mo 7927 6670 7877 9146
9 mo 9087 7785 9008 10,448
12 mo 10,059 8606 9978 11,676
Mean body weight and selected centiles for females, 0–12 months of age
Birth 3367 2750 3345 4095

1 mo 4160 3548 4123 4885
2 mo 5049 4301 5009 5878
3 mo 5763 4837 5729 6712
6 mo 7288 6063 7239 8547
9 mo 8449 7072 8373 9723
12 mo 9425 7942 9362 10,863
Modified from Fomon S.J. and Nelson S.E. In Nutrition of Normal Infants, CV Mosby, 1993, 36, p. 155.
in the vertical position, and gentle traction is placed to bring the head into contact with
the headpiece. A second examiner holds the infant’s feet with the toes pointing upwards,
and while applying gentle traction, brings the footpiece to rest firmly against the infant’s
heels. Measurements agreeing to within 0.4 cm are considered adequate, and the impor-
tance of length measurements is underscored, particularly when serial measurements are
made in a longitudinal fashion. It is generally agreed that faltering in length as well as
weight suggests growth faltering of a longer duration than when weight alone is affected.
Head Circumference
Head circumference is measured by a narrow flexible steel or paper tape applied to the
head above the supraorbital ridges and encircling the most prominent parts of the forehead
and the occiput. The maximum of three measurements should be used as the maximal
circumference. Weight-for-length measurements (Figures 7.1 and 7.2) are also available
and are useful in defining obesity as well as leanness.
A variety of other measures to define growth include skin fold thickness, limb length
and circumference, and body mass index. The latter, body mass index, is calculated by
dividing weight in kilograms by length in meters squared, replacing weight for length in
older children. In any case, accurate measurements are essential to the interpretation of
growth charts.
Normal growth is a strong indicator of nutritional sufficiency and overall health of an
infant. Since infancy is a period of rapid growth, particularly early infancy, identifying
growth failure is important and requires prompt medical attention. As we understand
more about the complex interactions between genetic, immunologic, metabolic, physio-
logic, and psychologic factors and their effects on long-term outcomes of infant feeding
decisions, defining appropriate growth becomes a very important issue for health care
providers of children.
Feeding the Term Infant 221
Birth to 36 months: Girls NAME

Length-for-age and Weight-for-age percentiles RECORD #
Birth 3 6 9 12 15 18 21 24 27 30 33 36
in cm AGE (MONTHS)
cm in
41 41 L
40 40 E
100 95 100
39 90 39 N
38 G
75 38
95 95 T
37 50 37 H
36 25 36
90 90
35 10 35
5
34
85
33
32 38
80 95 17
31
L 30 36
75 90 16
E
N
29
34
G 28
70 75
15
T 27 32
H 26 65 14
25 50 30 W
24 E
60 13
23 25 28 I
G
22 55 12 H
10 26
21 5 T
20 50 11 24
19
18 45 10 22
17
16 40 9 20
15
8 18
16 16
7 AGE (MONTHS)
kg lb
12 15 18 21 24 27 30 33 36
14
6 Mother’s Stature Gestational
W Father’s Stature Age: Weeks Comment
E 12
Date Age Weight Length Head Circ.
I 5 Birth
G 10
H
T
4
8
3
6
2
lb kg
Birth 3 6 9
FIGURE 7.1
Girls: birth to 36 months: physical growth NCHS percentiles.
Birth to 36 months: Girls

Head circumference-for-age and NAME
Weight-for-length percentiles RECORD #
Birth 3 6 9 12 15 18 21 24 27 30 33 36
in cm AGE (MONTHS) cm in H
E
A
52 52
D
95
20 90 20
50 50 C
75 I
50 R
H 19 19
48 48 C
E 25 U
A 10 M
D 18 46 5 46 18 F
E
R
C 44 44 E
I 17 17 N
R C
C 42 42 E
U 16
M 40 50
F 22 48
E
15 38 21 46
R
E 20 44
N 36 19 42
14
C 95
E 18 40
34 90
17 38
13 75 36
32 16
50 34
12 25
15
30 32
10 14
5 30 W
13 28 E
12 I
26 G
24 11 11 24 H
22 10 10 22 T
20 9 9 20
18 8 8 18
16 7 7 16
W
E 14 14
6 6
I 12
14 12
G 5 5
10 kg lb
H 4 LENGTH
T 8 cm
64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98100
6 3
26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 in
4 2
Date Age Weight Length Head Circ. Comment
2 1
lb kg
cm 46 48 50 52 54 56 58 60 62
in 18 19 20 21 22 23 24
FIGURE 7.1
Continued.
Birth to 36 months: Boys NAME

Length-for-age andWeight-for-age percentiles RECORD #
Birth 3 6 9 12 15 18 21 24 27 30 33 36
in cm AGE (MONTHS)
cm in
41 41 L
40 95 40 E
100 90 100 N
39 39
75 G
38 38
95 50 95 T
37 37 H
25
36 36
90 10 90
35 5 35
34
85
33
32 95 38
80 17
31
L 90 36
30
E 75 16
N
29
75
34
G 28
70 15
T 27 32
H 26 50
65 14
25 30 W
24 25 E
60 13
23 28 I
10 G
22 55 12 H
5 26
21 T
20 50 11 24
19
18 45 10 22
17
16 40 9 20
15
8 18
16 16
7 AGE (MONTHS)
kg lb
12 15 18 21 24 27 30 33 36
14
6 Mother’s Stature Gestational
W Father’s Stature Age: Weeks Comment
E 12
Date Age Weight Length Head Circ.
I 5 Birth
G 10
H
T
4
8
3
6
2
lb kg
Birth 3 6 9
FIGURE 7.2
Boys: birth to 36 months: physical growth NHS percentiles.
Birth to 36 months: Boys

Head circumference-for-age and NAME
Weight-for-length percentiles RECORD #
Birth 3 6 9 12 15 18 21 24 27 30 33 36
in cm AGE (MONTHS) cm in H
E
95 A
52 90 52
D
20 75 20
50 50 C
50
I
25 R
H 19 19
48 48 C
E 10 U
A 5 M
D 18 46 46 18 F
E
R
C 44 44 E
I 17 17 N
R C
C 42 42 E
U 16
M 40 50
F 22 48
E
15 38 21 46
R
E 20 44
N 36 19 42
14
C
E
95
18 40
34 90
17 38
13 75
36
32 50
16
34
12 25 15
30 10 32
5 14
30 W
13 28 E
12 I
26 G
24 11 11 24 H
22 10 10 22 T
20 9 9 20
18 8 8 18
16 7 7 16
W
E 14 14
6 6
I 12
14 12
G 5 5
10 kg lb
H 4 LENGTH
T 8 cm
64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98100
6 3
26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 in
4 2
Date Age Weight Length Head Circ. Comment
2 1
lb kg
cm 46 48 50 52 54 56 58 60 62
in 18 19 20 21 22 23 24
CDC
FIGURE 7.2
Continued.
Energy
Energy requirements during infancy may be partitioned into basal metabolism, thermic
effect of feeding, thermoregulation, physical activity, and growth. The energy requirements
for growth relative to maintenance, except in early infancy, are small, and satisfactory
growth can be considered a sensitive indicator that energy requirements are being met.
Energy balance may be defined as gross energy intake = energy excreted + energy
expended + energy stored. Gross energy intake, measured by the heat of combustion, is
greater than energy available when fed because most foods are not completely digested,
and protein oxidation is incomplete. Fat absorption varies widely among infants fed
various formulas, particularly in infancy. Urea and other nitrogenous compounds are
excreted in the urine. Gross intake is calculated as 5.7 kcal/g, 9.4 kcal/g, and 4.1 kcal/g
obtained from protein, fat, and carbohydrate, respectively, and therefore it varies given
the type of diet fed. The term “digestible energy” refers to gross energy intake minus
energy excreted in the feces. Metabolizable energy is defined as digestible energy minus
energy lost in urine. The metabolizable energy values for protein, fat, and carbohydrate
are close to 4, 9, and 4 kcal/g, respectively. Losses of energy, other than feces and urine,
are negligible and are ignored for practical purposes.
The energy intake of normal infants per unit body weight is much greater than in adult
counterparts. Energy requirements for term infants have been estimated by various groups
and vary from 100–116 kcal/kg/d from 0–3 months and decline to about 100 kcal/kg/d
by the end of the first year.3-7 These recommendations are based on the median intake of
thriving infants; the intakes of breast-fed infants are lower than that of formula-fed infants,
with an average of 3–4% lower in the first three months, and 6–7% from three to six
months. As new, more precise estimates of energy expenditure become available, these
recommendations are apt to change, given that current recommendations are higher than
the “gold” standard — the breast-fed infant. Energy intakes of infants from 6 to 12 months
of age have been reported to be between 91 and 100 kcal/kg/d.8-10
Protein
Intakes of protein and essential amino acids are generally sufficient in developed countries,
in contrast to developing countries where protein and protein-energy malnutrition are still
a frequent occurrence. In appropriately fed infants, protein is not a limiting dietary com-
ponent in infancy and is clearly essential for normal growth and development. For the
human infant, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine,
tryptophan, and valine are considered essential amino acids. The data for cysteine are
conflicting11,12 for the term infant, although the data are clear for the preterm infant.
Conditionally essential amino acids are those that become essential under certain circum-
stances, since they may be produced in inadequate amounts endogenously. An example
of this is taurine, which is now added to formulas based on reports of greater concentrations
of taurine in the plasma and urine of preterm13,14 and term15 infants. The concern about
taurine depletion stems from the observations of growth retardation, abnormal retinal
findings, and impaired bile acid metabolism in taurine-deficient animals and humans.
Recommended dietary intakes of protein are summarized in Table 7.2. In contrast,
intakes recommended by WHO16 are 2.25, 1.86, 1.65, and 1.48 g/100 kcal from 1–2, 3–6,
TABLE 7.2
Recommended Dietary Intakes of Protein
Age Interval Recommended Dietary Intake
(mo) (g · kg–1 · d–1) (g/100 kcal)
0 to 1 2.6 2.2
1 to 2 2.2 2.0
2 to 3 1.8 1.8
3 to 4 1.5 1.6
4 to 5 1.4 1.6
5 to 6 1.4 1.6
6 to 9 1.4 1.5
9 to 12 1.3 1.5
Reproduced with permission from Fomon, S. J.
Pediatric Research 30, 391, 1991.
6–9, and 9–12 months, respectively. Both of these recommendations are generally higher
than the intakes observed in human milk-fed infants.
Fat
The importance of dietary fat is underscored by the fact that 35% of the weight gain of an
infant in early infancy is accounted for by fat.17 Most of the dietary fat is in the form of
triglyceride formed by three fatty acids esterified to a glycerol backbone. In the body, trig-
lycerides are the main form of storage and transport of fatty acids. Phospholipids and
cholesterol are indispensable components of the lipid bi-layer of all cell membranes, and the
amount of different phospholipids and cholesterol, as well as the fatty acid pattern of incor-
porated phospholipids, modulate membrane fluidity, permeability, enzyme and receptor
activity, and signal transduction. Cholesterol is required for the synthesis of steroids and bile
acids, although the majority of the cholesterol pool in tissue and plasma is derived from
endogenous synthesis; dietary cholesterol contributes to the pool, and diet modifies liver
synthesis.18 Fatty acids (4-26 carbon atoms) are either saturated (no double bonds in the
carbon chain), mono-unsaturated (one double bond) or polyunsaturated (two or more double
bonds). Double bonds occur in two isomeric forms: cis and trans; unsaturated fatty acids are
folded at the site of each double bond, cis, and trans-fatty acids have straight carbon chains.
Human milk contains approximately 4% lipids, but the reported variation is between
3.1 and 5.2%,19,20 with 99% of the fat present in the form of triglycerides and the rest in
the form of diglycerides, monoglycerides, free fatty acids, phospholipids, and cholesterol.
The fat content of human milk increases with duration of lactation.19,21 During this period,
the average size of the fat globules increases, and the ratio of phospholipids and cholesterol
to triglycerides decreases.22 The concentration of fat in human milk remains similar regard-
less of maternal diet or nutritional status, although poor nutrition has been shown to
decrease fat content.23 Fatty acid content of human milk has been reported by numerous
investigators and demonstrates a wide range, as summarized by Fomon.2 Fatty acid
content of human milk is also altered by dietary manipulation.24-27 Human milk fat pro-
vides the essential fatty acids linoleic and α-linolenic acids, along with the long-chain
polyunsaturated fatty acids such as arachidonic and docosahexaenoic acids. The decrease
of milk phospholipid content during the first few weeks after birth is accompanied by a
decrease in arachidonic and docosahexaenoic acids.28 Fat content of human milk and
commonly used formulas is summarized in Table 7.3.
TABLE 7.3
Nutritional Composition of Human Milk and Commonly Used Formulas
Kilocalories/ Protein Fat Carbohydrate Na K Phosphorus Calcium Osmolality
oz. Source gm/dl Source gm/dl Source gm/dl mEq/dl mEq/dl mg/dl mg/dl mOsm/kg water
Mature human 20 Human milk 1.0 Human milk 4.4 Lactose 6.9 0.7 1.3 14 32 300
milk
Enfamil (Mead 20 Whey, nonfat 1.5 Palm olein, soy 3.6 Lactose 7.3 0.8 1.9 36 53 300
Johnson) milk coconut,
high-oleic
sunflower oils
Enfamil AR 20 Nonfat milk 1.7 Palm olein, soy 3.5 Lactose, rice 7.4 1.2 1.9 36 53 240
(Mead coconut, starch
Johnson) sunflower oils maltodextrin
Good Start 20 Enzymatically 1.6 Palm olein, 3.4 Lactose, 7.4 0.7 1.7 24 43 265
(Nestle/ hydrolyzed soybean, maltodextrin
Carnation) reduced coconut,
mineral whey high-oleic
safflower oils
Lactofree 20 Milk protein 1.4 Palm olein, soy 3.6 Corn syrup 7.4 0.9 1.9 37 55 200
(Mead isolate coconut, high- solids
Johnson) oleic
sunflower oils
Similac 20 Nonfat milk, 1.4 High-oleic 3.7 Lactose 7.3 0.7 1.8 28 53 300
Improved whey safflower,
(Ross) coconut, soy
oils
Similac Lactose 20 Milk protein 1.4 Soy, coconut 3.6 Corn syrup 7.2 0.8 1.8 38 57 230
Free (Ross) isolate oils solids, sucrose
Similac PM/ 20 Whey, sodium 1.5 Soy, corn, 3.8 Lactose 6.9 0.7 1.5 19 38 280
60/40 (Ross) caseinate coconut oils
Alsoy (Nestle/ 20 Soy protein 1.9 Palm olein, soy, 3.3 Corn 7.5 0.9 2.0 41 71 200
Carnation) isolate with coconut, maltodextrin,
L-methionine high-oleic sucrose
safflower oils
227
228

Nutritional Composition of Human Milk and Commonly Used Formulas
Kilocalories/ Protein Fat Carbohydrate Na K Phosphorus Calcium Osmolality
oz. Source gm/dl Source gm/dl Source gm/dl mEq/dl mEq/dl mg/dl mg/dl mOsm/kg water
Babysoy (pwd) 20 Soy protein 2.1 Oleo, coconut, 3.6 Corn syrup 6.9 0.9 1.8 42 60 228
(Wyeth isolate with high-oleic solids, sucrose
Nutritionals, L-methionine (saff. or sun.),
Inc.) soybean oils
Isomil (Ross) 20 Soy protein 1.7 High-oleic 3.7 Corn syrup, 7.0 1.3 1.9 51 71 230
isolate with safflower, sucrose
L-methionine coconut, soy
oils
Isomil DF 20 Soy protein 1.8 Soy, coconut 3.7 Corn syrup, 6.8 1.3 1.9 51 71 240
(Ross) isolate with oils sucrose, soy
L-methionine fiber
ProSobee 20 Soy protein 1.7 Palm olein, soy, 3.7 Corn syrup 7.3 1.0 2.1 56 71 200
(Mead isolate with coconut, solids
Johnson) L-methionine high-oleic
sunflower oils
Alimentum 20 Casein 1.9 MCT 33%, 3.7 Sucrose, 6.9 1.3 2.0 51 71 370
(Ross) hydrolysate safflower, soy modified
with added oils tapioca starch
amino acids
Nutramigen 20 Casein 1.9 Palm olein, soy, 3.4 Corn syrup 7.5 1.4 1.9 43 64 320
(Mead hydrolysate coconut, solids,
Johnson) with added high-oleic modified corn
amino acids sunflower oils starch
Pregestimil 20 Casein 1.9 MCT (55%), 3.8 Corn syrup 6.9 1.4 1.9 51 78 340
Powder hydrolysate corn, soy, solids,
(Mead with added high-oleic oils dextrose,
Johnson) amino acids modified corn
starch
Pregestimil 20 Casein 1.9 MCT (55%), 3.8 Corn syrup 6.9 1.4 1.9 51 78 280
Liquid (Mead hydrolysate soy, high-oleic solids,
Johnson) with added safflower oils modified corn
amino acids starch
Neocate (SHS) 20 L-amino acids 2.1 Hybrid 3.0 Corn syrup 7.8 1.1 2.7 62 82 342
safflower, solids
refined
vegetable oils,
(coconut, soy)
Follow-Up 20 Nonfat milk 1.8 Palm olein, soy, 2.8 Corn syrup 8.9 1.2 2.3 61 91 326
(Nestle/ coconut, solids, lactose
Carnation) high-oleic
safflower oils
Follow-Up Soy 20 Soy protein 2.1 Palm olein, soy, 3.0 Corn 8.1 1.2 2.0 61 91 200
(Nestle/ isolate with coconut, maltodextrin,
Carnation) L-methionine high-oleic sucrose
safflower oils
Whole cow’s 20 Cow’s milk 3.3 Cow’s milk 3.7 Lactose 4.7 2.1 3.9 93 119 288
milk
Next Step 20 Nonfat milk 1.8 Palm olein, soy, 3.4 Lactose, corn 7.5 1.2 2.3 57 81 270
(Mead coconut, syrup solids
Johnson) high-oleic
sunflower oils
Next Step Soy 20 Soy protein 2.2 Palm olein, soy, 3.0 Corn syrup 8.0 1.3 2.6 61 78 260
(Mead isolate with coconut, solids, sucrose
Johnson) L-methionine high-oleic
sunflower oils
229
Essential Fatty Acid Metabolism

Human milk lipids contain preformed long-chain polyunsaturated fatty acids (LC-PUFA)
in considerable amounts, whereas vegetable oils (with the exception of coconut oil) are also
rich in PUFA. The latter has a higher percentage of medium- and short-chain fatty acids.
For the healthy full term infant, the concerns of the premature infant may not apply
given the larger body stores of LC-PUFA at birth and the lower requirements compared
to the preterm infant because of slower growth. However, nutritional requirements for
PUFAs are not clearly defined for infants, and the issue is complicated by the fact that
linoleic acid (18:2n-6) and α-linolenic acid (18:3n-3) can be converted to both 20 and 22
carbon length long-chain PUFAs with significant biological activities. The absence of
linoleic acid in the diet results in growth retardation and dermatologic manifestations.
Intakes of linoleic acid, as low as 0.6% of daily energy intake, can obviate essential fatty
acid deficiency as defined by the triene to tetraene ratio, and current recommendations29
specify the minimum level of 0.3g/100 kcal in infant formulas.
Fully breastfed infants have a dietary lipid intake of approximately 50% of their energy
intake (3.1 to 5.2g/dL, see earlier discussion), whereas formulas contain between 3.4 and
3.8 g/dL. Although the importance of limiting the dietary intake of saturated and total
fats to prevent cardiovascular disease, obesity, and diabetes is well recognized, adverse
effects of limiting fat on weight gain and growth30,31 should be balanced against providing
increased amounts of fat.
Carbohydrate
Carbohydrates generally account for 35 to 42% of the energy intake of breast- or formula-
fed infants, and the usual carbohydrates in infants’ diets are listed in Table 7.4. Carbohy-
drates may be classified as monosaccharides, oligosaccharides, and polysaccharides.
Monosaccharides can be further defined as aldoses (glucose, galactose, xylose, for example)
or ketoses (fructose). Oligosaccharides are consumed in the diet mainly in milk with lactose,
maltose and sucrose being the main sugars present. Polysaccharides are starches, starch
hydrolysates, glycogen, or components of fiber. The major carbohydrate in human milk
is lactose, although small amounts of glucose and other oligosaccharides are also present.
Carbohydrate content of human milk and various formulas is listed in Table 7.3. Carbo-
hydrate malabsorption, apart from genetic causes, is unusual. When the colonic capacity
to ferment carbohydrate is exceeded by the unabsorbed load, symptoms of carbohydrate
intolerance, usually in the form of diarrhea, occur. The diarrhea improves when dietary
carbohydrates are reduced or eliminated from the diet, making the diagnosis of carbohy-
drate intolerance. Normally, electrolytes in the distal gastrointestinal tract and unabsorbed
TABLE 7.4
Usual Carbohydrates and Related Enzymes
Carbohydrate Enzyme
Lactose Lactase
Sucrose Sucrase-isomaltase
Isomaltose Sucrase-isomaltase
Maltose Maltase-glucoamylase
Amylose α-Amylase
Amylopectin β-Amylase
TABLE 7.5
Commonly Used Formulas and Their Indications
Commonly Used Formulas and Their Indications
Formula Carbohydrate Protein Fat Indication
Bovine milk-based Lactose Bovine whey and Vegetable, animal Normal function
casein
Soy-protein-based Sucrose, glucose Soy Soy Lactose intolerance
Hydrolyzed Sucrose, glucose Hydrolyzed whey or Medium chain Cow milk and soy
protein casein triglycerides protein
hypersensitivity;
pancreatic
insufficiency
Casein-based Modified tapioca Casein hydrolysate MCT oil, corn oil Lactase, sucrase and
(modular) starch, added with added amino maltase deficiency,
carbohydrate acids impaired glucose
transport
Elemental Lactose- and sucrose- Hydrolyzed casein Vegetable Cow milk allergy
free, corn syrup
solids, modified
corn starch
“Metabolic” Depends on Corn syrup solids/ Corn oil/ coconut oil Specific metabolic
condition sucrose disorders
carbohydrates (fermented to volatile fatty acids) are rapidly absorbed. Inadequate colonic
salvage results in diarrhea. In young infants and children with disorders of carbohydrate
metabolism, the ultimate goal of carbohydrate digestion and absorption is to render all
available carbohydrates into smaller compounds that the body can use; chiefly, glucose
and fructose. Lactase deficiency is exceedingly rare in newborn infants. Infants usually
develop diet-induced diarrhea following introduction of lactose-containing milk. The
disease, thought to be autosomal recessive, is treated with the elimination or limitation
of lactose in the diet. More commonly, a transient lactose intolerance can occur after acute
or repeated bouts of diarrhea. Sucrase-Isomaltase deficiency is a rare disease that does not
appear until diets containing sucrose, dextrin, or starch are begun. Bouts of diarrhea may
be observed in infants with this deficiency, and management includes eliminating sucrose
and limiting starch in the diet. Older affected children and adults usually tolerate normal
quantities of carbohydrates. Glucose-Galactose deficiency manifests itself with diet-induced
diarrhea soon after birth and responds to withdrawal of these carbohydrates from the
diet. The defect appears to be a specific absence of glucose and galactose transport mech-
anisms, whereas amino acid transport is normal. Fructose transport is normal, and these
infants respond to a diet containing fructose with relief from diarrhea. With age, variable
amounts of starch and milk may be tolerated. Commonly used formulas for various forms
of intolerance are listed in Table 7.5.32
Iron
Iron deficiency is the most common nutritional deficiency in the U.S. and worldwide, with
young children the most susceptible. The increased susceptibility comes from an increased
iron requirement for the rapid growth during this period and inadequate amounts of iron
in the diet unless adequately supplemented.33 According to the third National Health and
Nutrition Examination Survey (NHANES, 1991), ~5% of children between one and two
TABLE 7.6
Stages of Iron Deficiency
Iron Nutritional Status Indices
Adequate stores Normal
Decreased stores Decreased ferritin (10–20 ng/mL), transferrin normal, erythtrocyte
protoporphyrin normal, MCV normal, hemoglobin normal, transferrin
receptor normal
Iron deficiency Decreased ferritin, transferrin saturation decreased, erythrocyte
protoporphyrin increased, MCV normal, hemoglobin normal,
transferrin receptor increased
Iron deficiency anemia Decreased ferritin, transferrin saturation decreased, erythrocyte
protoporphyrin increased, MCV decreased, hemoglobin decreased,
transferrin receptor increased
years of age had evidence of iron deficiency, and about half were also anemic. However,
between the two previously published studies, NHANES II and I, prevalence of iron
deficiency was observed to be decreasing.34 Stages of iron nutritional status are listed in
Table 7.6.
One should distinguish between anemia and iron deficiency anemia, since the latter
occurs when hemoglobin concentration falls below the 90 to 95% range for the same age
and sex.34 A diagnosis of iron deficiency is made when the anemia is accompanied by
evidence of iron deficiency or when there is a rise in hemoglobin following treatment with
iron. In this regard, serum transferrin receptor may offer an advantage for screening for
iron deficiency, since it rises with iron deficiency and is not affected by infection or acute
liver disease.35
Iron deficiency peaks between six and nine months of age and is a consequence of
multiple factors: rapid growth, depleted stores, low iron content of the diet, and early
feeding of cow’s milk.36,37 Since a milk-based diet is the predominant source of energy, at
least in the first six months of life, the iron content and its bioavailability are strong
predictors of iron nutritional status.38 The estimated requirement of absorbed iron from
birth to one year is 0.55 to 0.75 mg/d, thereby underscoring the need for adequate iron
in the diet to meet these needs. Iron concentration in human milk is low (0.3 to 0.5 mg/
L), and although well absorbed, iron content declines between 14 and 183 days of age.39
Therefore, even given the better absorption as milk intake increases and iron content
decreases, it is easy to see that the amount of absorbed iron will be inadequate to meet
the estimated requirements. Therefore, breastfed infants who do not receive iron supple-
ments or iron from other sources are at risk of becoming iron deficient between 6 and 12
months of age.40 Iron-fortified cow’s milk or soy-based formulas are effective in preventing
iron deficiency, and the decline in iron deficiency anemia over the past few decades has
been attributed to their use.34 Systemic manifestations of iron deficiency anemia include
behavioral and cognitive abnormalities expressed as lower scores on tests of psychomotor
development. These effects have to be interpreted keeping the confounding variables of
poor nutrition, environment, and poor socioeconomic background that often coexist. The
studies suggest that infants with iron deficiency anemia, but not iron deficiency without
anemia, have impaired performance of mental and psychomotor development.41-45 These
deficiencies do not improve with iron therapy, and follow-up studies at five to six years
of age still demonstrate poorer scores in the children who were previously anemic.43,44
Strategies to prevent iron deficiency could include the feeding of iron-fortified formulas,
avoidance of non-iron fortified milks and cow’s milk (the latter, at least, till beyond 12
months of age), the feeding of meats and iron-fortified foods, and, if needed, medicinal
iron supplementation in the form of ferrous sulfate.
TABLE 7.7
Unique Constituents of Breast Milk
Unique Constituents of Breast Milk
Docosahexanoic acid Necessary for growth and development of the brain and retina and for
myelinization of nervous tissue
Cholesterol Enhances myelinization of nervous tissue
Taurine Second most abundant amino acid in human milk, important for bile acid
conjugation
Choline May enhance memory
Enzymes Numerous enzymes such as lipases that are important in digestion and
absorption of fat
Lactoferrin Prevents iron from being available to bacteria
Inositol Enhances synthesis and secretion of surfactant in immature lung tissue
Poly- and Oligosaccharides Inhibit bacterial binding to mucosal surfaces
Protein (such as α- Supply amino acids to the infant, help synthesize lactose in the mammary gland,
lactalbumin) and bind calcium and zinc
Bifidobacterium species Predominant bacterial flora in the gastrointestinal tract of breastfed infants,
creates unfavorable pH conditions for the growth of enteric pathogens
Macrophages Macrophages in human colostrum have high concentrations of slgA which is
released during phagocytosis
Epidermal growth factor Promotes cell proliferation in the gastrointestinal mucosa
Breastfeeding
The benefits of breastfeeding to the infant, mother, family, and society are numerous and
impressive, but they must be put into context when making individual decisions about
breast feeding. These include ready availability, possible enhancement of intestinal devel-
opment, resistance to infection, and bonding between mother and infant. It is the preferred
feeding method for the normal infant. Breast milk, in addition to providing the required
nutrients for the healthy infant, has unique constituents, as listed in Table 7.7.
Protein
Approximately 20% of the total nitrogen in human milk is in the form of non-protein
nitrogen compounds such as free amino acids, and urea, which is considerably greater
than the 5% found in bovine milk,46 although there remains a debate about their contri-
bution to nitrogen utilization.47 The quality of the protein differs from that of bovine milk
as well, with the whey-to-casein protein ratios being 70:30 and 18:82 in human and bovine
milk, respectively. These differences in whey-to-casein ratio are reflected in the plasma
amino acid profile of infants and are readily observed within the first three days of age.48
Further, plasma amino acid patterns in human milk-fed infants has been used as a refer-
ence in infant nutrition.49,50 In addition, specific human whey proteins — lactoferrin,
lysozyme, and slgA — are involved in host defense.51,52
Lipids
Lipids in human milk provide 40 to 50% of the energy content and are vehicles for fat
soluble vitamins. The total fat content varies from 2% in colostrum to 2.5–3.0% in transi-
tional milk, and 3.5–4.5% in mature human milk.19 Cholesterol, phospholipids, and essen-
tial fatty acids are highest in colostrum, and more than 98% of human milk fat comes from
11 major fatty acids of 10-20 carbon length. Human milk lipids can inactivate enveloped
viruses including herpes simplex I, measles, and cytomegalovirus, to name a few.
Monoglycerides also exert antiviral activity.
Fat content of human milk is variable, with the fat content rising throughout lactation
but with changes apparent within the course of one day, within feeds and between
women.53 The effects of these differences in thriving infants is not clear, even given that
hind milk has a higher fat content than fore milk. Human milk lipids provide preformed
LC-PUFAs in amounts sufficient to meet nutrient needs. In term infants, plasma concen-
trations of essential fatty acids (arachidonic acid) at two and four weeks of age were
significantly lower in infants fed formula without LC-PUFA compared to breastfed infants.
Docosahexanoic acid concentrations were similarly lower at four and eight weeks of age.
Neuringer and colleagues showed that visual acuity and learning abilities correlate well
with the amount of DHA in the retina and brain phospholipids.54
Nucleotides
Nucleotides represent 2 to 5% of the non-protein nitrogen in human milk.55 Nucleotides
participate in many biological functions such as forming the basis of genetic information
(DNA, RNA) and storing energy (AMP, GMP), and they play roles in immunity as well
as cellular activities. Although they can be produced by the liver, the body’s requirements
vary considerably, especially during infancy.56 The effect of nucleotides on immune func-
tion is not well understood, but infants fed breast milk or nucleotide-supplemented for-
mula have been shown to exhibit increased natural killer cell activity compared to infants
fed unsupplemented formula.57 Infants fed nucleotide formulas had enhanced Haemophi-
lus influenza type B and diphtheria humoral responses compared to non-supplemented
infants.58 Feeding of human milk resulted in significantly higher neutralizing antibody
titers to polio virus at six months of age than were found in control or formula-fed cohorts.
These data suggest that dietary factors play a role in the antibody response to immuni-
zation, and more studies are needed to better understand the mechanisms involved.
Infection
There are several enzymes present in human milk that appear to be important in the
prevention of infection. These include glutathione peroxidase, alkaline phosphatase, and
xanthine oxidase. In addition, other anti-inflammatory agents such as catalase, lactoferrin,
immunoglobulins, and lysozyme are also present in human milk. The antimicrobial activ-
ities of these are generally found at mucosal surfaces, such as the gastrointestinal, urinary,
and respiratory tracts. Specific factors, such as lactoferrin, lysozyme, and slgA, resist
proteolytic degradation and can line the mucosal surfaces, preventing microbial attach-
ment and inhibiting microbial activity. Each of the mammary immune systems is active
against a variety of antigens. Prospective studies in developing countries indicate that
breast milk feeding reduces the incidence or severity of diarrhea,59 lower respiratory tract
infection,60 otitis media,61 bacteremia,62 bacterial meningitis,63 botulism,64 urinary tract
infection,65 and necrotizing enterocolitis.66
Hyperbilirubinemia is more common in breast-fed than formula-fed infants. This is
usually transient, and discontinuation of breast feeding is not recommended unless biliru-
bin values reach excessively high levels or the jaundice persists. Usually, switching to a
formula for one to two days is therapeutic and diagnostic, and breastfeeding can be safely
resumed. Other causes of jaundice should be sought before making a firm diagnosis of
breast-milk jaundice.
Certain chemicals, drugs, foreign proteins, and viruses may be present in human milk.67
However, the risk–benefit ratio of artificial milk needs to be weighed, especially if the
water sources for mixing the milk are contaminated. Breastfeeding is currently contra-
indicated in disease states such as active herpes, tuberculosis, and AIDS.
Formula Feeding
A variety of formulas are available for feeding infants (Table 7.3). The most commonly
used formulas are from bovine milk, and nutrient specifications for infant formulas are
available.68 Commercially available formulas are recommended when breast feeding is
not chosen. Cow’s milk is not recommended in the first year of life due to its nutritional
limitations and inappropriate nutrient concentrations. Cow’s milk has higher concentra-
tions of protein and phosphorus, a lower calcium-to-phosphorus ratio, limited iron, less
essential fatty acids, vitamin C, and zinc than human milk. Increased renal solute load
due to cow’s milk and increased occult blood loss via the gastrointestinal tract leading to
iron deficiency and anemia in infants fed cow’s milk unsupplemented by other nutrients
are additional reasons to discourage the feeding of cow’s milk in early infancy.
Soy Protein-Based Formulas

The Committee on Nutrition of the American Academy of Pediatrics reviewed the indi-
cations of soy protein-based formulas.69 Some of the conclusions include:
1. Isolated soy protein-based formulas are safe and effective alternatives to provide
appropriate nutrition if breast milk or cow milk-based formulas do not meet the
nutritional needs in term infants. However, no advantage is provided over cow’s
milk protein-based formulas as a supplement for breast feeding.
2. Soy protein-based formulas are appropriate for use in infants with galactosemia
and hereditary lactase deficiency.
3. There is no proven value of the routine use of soy-protein based formula in the
prevention or management of infantile colic.
4. There is no proven value of the routine use of soy protein-based formula in the
prevention of atopic disease in healthy or at-risk infants.
5. Infants with documented cow milk protein-induced enteropathy or enterocolitis
should not be given soy protein-based formula routinely.
The nutritional needs of infants zero to six months can be met by breast milk or infant
formulas. Although both groups of infants need to have health surveillance including
growth and development, breastfed infants need to be followed closely over the first few
weeks to assure appropriate feeding practices and resultant growth. Appropriate counsel-
ing for common breast feeding problems needs to be provided, and community support
groups can be involved if needed. Beyond six months, recommendations for infant feeding
are variable, and the recommendations are largely based on extrapolation from data on
younger infants. Nutritional composition of “follow-up” formulas is specified with mini-
mum lower limits for energy (60 kcal/dL), higher minimum limits for protein (2.25 to 3.0
g/100 kcal) and lower minimum limits for fat (3.0 to 4.0 g/100 kcal) compared to formulas
for younger infants. Nonetheless, iron-fortified formulas designed for younger infants may
be safely fed from 6 to 12 months. Infants by this age are physiologically and develop-
mentally ready to accept a variety of dietary items, and feeding practices vary based on
ethnic, cultural, and economic reasons. As stated earlier, feeding of bovine milk is discour-
aged during this period, although a substantial number of infants are indeed fed bovine
milk.70 In addition, there are concerns about the substitution of low-fat or skimmed milks
during this period because of higher intakes of protein and sodium and lower intakes of
iron and essential fatty acids. However, if infants are being fed non-milk foods, the actual
intake of energy may not be lower than of infants fed bovine milk or formula.71
Weaning
The transition from suckling to eating of non-milk foods occurs during the first year of
life based on cultural beliefs and practices, physicians beliefs, mothers’ perceptions of their
infants’ needs, and economic realities. Complementary foods are introduced from before
three months to by six months of age, and a variety of foods are offered.72-74 In the U.S.,
the total transition to beikost usually occurs by the end of the first year of life and continues
during the second year.
The weaning process can be considered in three ways. First, it could be the weaning
from breast feeding to other milks which may replace breast feeding partially or com-
pletely. In the second form, weaning could be considered the transition from liquid to
non-liquid diet. Health concerns may arise during this period if the added foods are too
nutrient dense (protein or energy) or nutrient-deficient (iron, protein), thus altering the
protein:energy ratio or causing deficiency of specific nutrients. The third aspect of weaning
may be the transition from human milk or formula to bovine milk in addition to the
provision of beikost. Since weaning typically occurs during a period of rapid growth,
attention to both nutritional and developmental issues during this period is warranted.
Complementary foods, in addition to providing the required nutrients, are also important
in establishing lifelong patterns of eating.
Failure to Thrive
Growth, as assessed by weight, length (and subsequently height) and head circumference,
is an important part of anticipatory guidance provided in well child care. These anthro-
pometric measurements, especially weight, can be used to detect inadequate attained
growth or reduced growth velocity. The average birth weight of a full term infant is 3300
to 3500 g; after a weight loss of ~10%, infants should regain their birth weight by two
weeks, with formula-fed infants tending to regain their birth weight a little sooner than
their breastfed counterparts. On an average, infants gain about 1 kg per month for the
first three months, 1/2 kilogram per month for the next three months, 1/3 kilogram per
month from 6 to 9 months and 1/4 kilogram per month from 9 to 12 months. Full term
infants double their weight by 4 months and triple their weight by 12 months, while
doubling their length during the same period. Both weight and length gain are slower in
the second year of life, underscoring the anticipatory nutritional guidance needed during
that period. Growth faltering, or failure to thrive, a descriptive term, is then identified by
the following criteria: (1) weight less than 80 to 85% of the 50th percentile on the National
Center for Health Statistics (NCHS) growth charts, (2) weight for age less than the 3 to 5
percentile on the NCHS growth charts, (3) drop in weight that crosses two or more
percentile categories on standard growth charts from previously established pattern of
adequate growth, and (4) a Z-score of –2 SD below the normal 50th percentile. If growth
velocity is used, a decrement of 2 SD over a 90-day period and loss of >1 SD Z score over
90 days is used as a measure of growth faltering.
Since decline in rate of weight gain or growth velocity is more sensitive than decline in
length or head circumference, serial measurements of weight are an important part of the
anticipatory guidance given during well child checks, and provide an early warning of
growth faltering.75,76 The Body Mass Index (BMI), calculated by dividing weight in kilo-
grams by length/height in meters squared, has largely replaced weight for stature. It should
be recognized that there are growth differences between breast and formula-fed infants. As
reported by Nelson et al.,77 mean gains in both weight (g/d) and length (cm/d) were greater
in formula-fed males and females than their breastfed counterparts from 8–122 days of age.
Since the NCHS growth charts were made from data that was cross-sectional and the infants
were fed formulas, attention to growth faltering in the breastfed infant requires both under-
standing of the growth of breastfed infants and the early recognition of decrease in weight
or growth velocity.78 There are numerous organic and non-organic causes of growth failure
or faltering which need to be addressed during such an evaluation. It is important to realize
that failure to thrive or malnutrition may occur in hospitalized infants and children, as well,
and efforts to recognize and nourish these infants and children should be made.
Summary
In summary, the period of infancy is one of rapid changes in growth and attainment of
developmental milestones. This period imposes unique nutritional needs and challenges
for the health care provider. Understanding nutritional needs, ways of meeting these needs
(Table 7.8), deviations in growth and their causes, and providing nutrition in age-appro-
TABLE 7.8
Recommendations for Feeding Healthy Full-Term Infants
Breastfeeding is strongly recommended.
Infant formulas that meet AAP guidelines are recommended when breastfeeding is not chosen or breast milk
is not available.
Breast milk or infant formula is the preferred feeding in the first year of life.
Adequate intakes of human milk or formula meet all nutrient requirements for the first 6 months of life (exception
may be vitamin D in dark-skinned, sun deprived breast fed infants). Infant formula or “follow-up” formula
may be fed in the second 6 months of life.
Introduction of complementary foods should be based on growth, developmental, cultural, social, psychological
and economic considerations. As a general rule, when an infant is consuming 32 ounces of milk per day and
appears to want more, supplemental feedings may be indicated. This usually occurs between 4 and 6 months
of age.
priate, culturally and ethnically sensitive ways while addressing economic issues is the
task of the health care team. Ideally, the infant’s nutritional need (expressed as hunger),
developmental progress (as observed in attainment of feeding skills), and mother’s and
care provider’s beliefs within the context of the family will guide the infant’s feeding
experience and transition to the next phase in life.
Acknowledgment
The authors thank Tina Corbin for her tireless secretarial support in the preparation of
this manuscript.
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8
Nutrition for Healthy Children and Adolescents
Ages 2 to 18 Years
Physical Growth and Development

A child’s first year of life is marked by rapid growth, with birth weight tripling and birth
length increasing by 50%. After the rapid growth of the first year, physical growth slows
down considerably during the preschool and school years, until the pubertal growth spurt
of adolescence. Birth weight does not quadruple until two years of age, and birth length
does not double until four years of age. A one-year-old child has several teeth, and his/
her digestive and metabolic systems are functioning at or near adult capacity. By one year
of age, most children are walking or beginning to walk; with improved coordination over
the next few years, activity increases dramatically. Although increased activity in turn
increases energy needs, a child’s rate of growth decreases. Growth patterns vary in indi-
vidual children, but each year children from two years to puberty gain an average of 4
1/2 to 6 1/2 pounds (2 to 3 kg) in weight and 2 1/2 to 3 1/2 inches (6 to 8 cm) in height.
As the growth rate declines during the preschool years, a child’s appetite decreases and
food intake may become unpredictable and erratic. Parents and other caregivers need to
know that these changes are normal so that they can avoid struggles with children over
food and eating.
After the first year of life, more significant development occurs in fine and gross motor,
cognitive, and social-emotional areas than during the first year of life. During the second
year of life, children learn to feed themselves independently. By 15 months of age, children
can manage a cup, but with some spilling. At 18 to 24 months of age, children learn to
tilt cups by manipulating their fingers. Children are able to transfer food from bowls to
their mouths with less spilling by 16 to 17 months of age, when well-defined wrist rotation
develops. However, two-year-old children often prefer foods that can be picked up with
their fingers without having to chase it across their plates.
The normal events of puberty and the simultaneous growth spurt are the primary
influences on nutritional requirements during the second decade of life. During puberty,
height and weight increase, many organ systems enlarge, and body composition is altered
due to increased lean body mass and changes in the quantity and distribution of fat. The
0-8493-2705-9/01/$0.00+$1.50
timing of the growth spurt is influenced by genetic as well as environmental factors.

Children who weigh more than average for their height tend to mature early, and vice
versa. Although stature tends to increase most rapidly during the spring and summer,
weight tends to increase either at a fairly steady rate over the entire year or undergoes a
more rapid increase during the autumn. The most rapid linear growth spurt for an average
American boy occurs between 12 and 15 years of age. For the average American girl, the
growth spurt occurs about two years earlier, between 10 and 13 years of age. The growth
spurt during adolescence contributes about 15% to final adult height, and approximately
50% to adult weight. During adolescence, boys tend to gain more weight than girls, and
gain it at a faster rate. Furthermore, the skeletal growth of boys continues for a longer
time than that of adolescent girls. Adolescent boys deposit more muscle mass, and ado-
lescent girls deposit relatively more total body fat. Menarche, which is closely linked to
the growth process, has a lasting impact on nutritional requirements of adolescent girls.
Adolescence is a period of various cognitive challenges. For example, when an adoles-
cent realizes that his or her body is in the process of maturing, he or she may begin to
assess changes in his or her own body size and shape, compare them with those of others,
and form opinions about any differences. Adolescent girls and boys may be very self-
conscious, especially during early and mid-adolescence. According to Piaget’s develop-
mental levels, it is usually during adolescence that abstract thinking supersedes concrete
thinking. Thus, an adolescent may consider his or her body not just as it is, but also as it
might be. In addition, an adolescent can contemplate new or different ways of combining
or eating food. Furthermore, an adolescent can more easily conceptualize nutrients such
as calories and fat, and skillfully manipulate their dietary intake.
Energy and Nutrient Needs

Dietary Reference Intakes and Recommended Dietary Allowances
The Dietary Reference Intakes (DRIs) expand and replace the series of Recommended
Dietary Allowances (RDAs) published beginning in 1941 through 1989 by the Food and
Nutrition Board.1 Although previous RDAs focused on preventing classical nutrient
deficiencies, the DRIs go beyond this to include current knowledge about the role of
nutrients and food components in long-term health. The DRIs are reference values that
are quantitative estimates of nutrient intakes to be used for planning and assessing diets
for healthy people in America and Canada.2 The DRIs include RDAs as goals for intake
by individuals, but also present the following new types of reference values: Estimated
Average Requirement (EAR), Adequate Intake (AI), and Tolerable Upper Intake Level
(UL); these are discussed in detail in another section. Briefly, within the DRI framework,
the RDA serves as a goal for individuals; it is the average daily dietary intake level that
is sufficient to meet the nutrient needs of almost all (97 to 98%) healthy individuals in a
lifestage and gender group. The EAR is a nutrient intake value that is estimated to meet
the nutrient needs of 50% of the healthy individuals in a lifestage and gender group; it
is used to assess adequacy of intakes of population groups, and to develop RDAs. The
AI is used instead of an RDA when sufficient scientific evidence is not available to
calculate an EAR; the AI is based on observed or experimentally determined approxima-
tions of nutrient intake by a lifestage and gender group (or groups) of healthy people.
The UL is the highest level of nutrient intake per day that is likely to pose no risks of
adverse health effects to almost all individuals in the general population. The risk of
Nutrition for Healthy Children and Adolescents Ages 2 to 18 Years 243
TABLE 8.1
Recommended Levels for Individual Intakea for Children and Adolescents
Children Boys Girls
1–3 years 4–8 years 9–13 years 14–18 years 9–13 years 14–18 years
Calcium (mg/d) 500* 800* 1300* 1300* 1300* 1300*
Phosphorus (mg/d) 460 500 1250 1250 1250 1250
Magnesium (mg/d) 80 130 240 410 240 360
Vitamin D (µg/d)bc 5* 5* 5* 5* 5* 5*
Fluoride (mg/d) 0.7* 1* 2* 3* 2* 3*
Thiamin (mg/d) 0.5 0.5 0.9 1.2 0.9 1.0
Riboflavin (mg/d) 0.5 0.6 0.9 1.3 0.9 1.0
Niacin (mg/d)d 6 8 12 16 12 14
Vitamin B6 (mg/d) 0.5 0.6 1.0 1.3 1.0 1.2
Folate (µg/d)e,f 150 200 300 400 300 400
Vitamin B12 (µg/d) 0.9 1.2 1.8 2.4 1.8 2.4
Pantothenic acid (mg/d) 2* 3* 4* 5* 4* 5*
Biotin (µg/d) 8* 12* 20* 25* 20* 25*
Choline (mg/d)g 200* 250* 375* 550* 375* 400*
Vitamin C (mg/d) 15 25 45 75 45 65
Vitamin E (mg/d of α- 6 7 11 15 11 15
tocopherol)h
Selenium (µg/d) 20 30 40 55 40 55
Vitamin A (µg/d) 300 400 600 900 600 700
Vitamin K (µg/d) 30* 55* 60* 75* 60* 75*
Chromium (µg/d) 11* 15* 25* 35* 21* 24*
Copper (µg/d) 340 440 700 890 700 890
Iodine (µg/d) 90 90 120 150 120 150
Iron (mg/d)i 7 10 8 11 8 15
Manganese (mg/d) 1.2* 1.5* 1.9* 2.2* 1.6* 1.6*
Molybdenum (µg/d) 17 22 34 43 34 43
Zinc (mg/d) 3 5 8 8 11 9
a Recommended Dietary Allowances (RDAs) are presented in bold type and Adequate Intakes (AIs) in ordinary
type followed by an asterisk (*). RDAs and AIs may both be used as goals for individual intake. RDAs are
set to meet the needs of almost all (97-98%) individuals in a group. The AI for other life-stage and gender
groups is believed to cover needs of all individuals in the group, but lack of data or uncertainty in the data
prevent being able to specify with confidence the percentage of persons covered by this intake. Adapted from:
Food and Nutrition Board, Institute of Medicine, Dietary Reference Intakes for Calcium, Phosphorus, Magnesium,
Vitamin D, and Fluoride, National Academy Press, Washington, DC, 1997; Food and Nutrition Board, Institute
of Medicine, Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic
Acid, Biotin, and Choline, National Academy Press, Washington, DC, 1998; Food and Nutrition Board, Institute
of Medicine, Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids, National Academy
Press, Washington, DC, 2000; Food and Nutrition Board, Institute of Medicine, Dietary Reference Intakes for
Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon,
Vanadium, and Zinc, National Academy Press, Washington, DC, 2001.
b As cholecalciferol. 1 µg cholecalciferol = 40 IU vitamin D.
c In the absence of adequate exposure to sunlight.
d As niacin equivalents (NE). 1 mg niacin = 60 mg tryptophan.
e As dietary folate equivalent (DFE). 1 DFE = 1 µg food folate = 0.6 µg folic acid (from fortified food or
supplement) consumed with food = 0.5 µg synthetic (supplemental) folic acid taken on an empty stomach.
f In view of evidence linking folate intake with neural tube defects in the fetus, it is recommended that all
women capable of becoming pregnant consume 400 µg synthetic folic acid from fortified foods and/or
supplements in addition to intake of food folate from a varied diet.
g Although AIs have been set for choline, there are few data to assess whether a dietary supply of choline is
needed at all states of the life cycle, and it may be that the choline requirement can by met by endogenous
synthesis at some of these stages.
h DRIs for vitamin E are based on α-tocopherol only and do not include amounts obtained from the other seven
naturally occurring forms historically called vitamin E. RDAs and AIs apply only to intake of 2 R-stereoisomeric
forms of α-tocopherol from food, fortified food, and multivitamins.
i For girls under 14 years who have started to menstruate, one might advise an increased intake to approxi-
mately 2.5 mg/d to what would be advised for a girl of the same characteristics before menarche.
TABLE 8.2
Tolerable Upper Intake Levelsa,b (ULs) for Children and Adolescents
1–3 years 4–8 years 9–13 years 14–18 years
Calcium (g/d) 2.5 2.5 2.5 2.5
Phosphorus (g/d) 3 3 4 4
Magnesium (mg/d)c 65 110 350 350
Vitamin D (µg/d) 50 50 50 50
Fluoride (mg/d) 1.3 2.2 10 10
Niacin (mg/d)d 10 15 20 30
Vitamin B6 (mg/d) 30 40 60 80
Synthetic folic acid (µg/d)d 300 400 600 800
Choline (g/d) 1.0 1.0 2.0 3.0
Vitamin C (mg/d) 400 650 1200 1800
Vitamin E (mg/d α-tocopherol)e 200 300 600 800
Selenium (µg/d) 90 150 280 400
Vitamin A (µg/d performed A) 600 900 1700 2800
Copper (µg/d) 1000 3000 5000 8000
Iodine (µg/d) 200 300 600 900
Iron (mg/d) 40 40 40 45
Manganese (mg/d) 2 3 6 9
Molybdenum (µg/d) 300 600 1100 1700
Zinc (mg/d) 7 12 23 34
Boron (mg/d) 3 6 11 17
Nickel (mg/d soluble nickel salts) 0.2 0.3 0.6 1.0
Vanadium (mg/d)f
a UL = the maximum level of daily nutrient intake that is likely to pose no risk of adverse
effects. Unless otherwise specified, the UL represents total intake from food, water, and
supplements. Currently, ULs are not available for other nutrients. In the absence of ULs, extra
caution may be warranted in consuming levels above recommended intakes.
b Adapted from: Food and Nutrition Board, Institute of Medicine, Dietary Reference Intakes for
Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride, National Academy Press, Washing-
ton, DC, 1997; Food and Nutrition Board, Institute of Medicine, Dietary Reference Intakes for
Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline,
National Academy Press, Washington, DC, 1998; Food and Nutrition Board, Institute of
Medicine, Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids, National
Academy Press, Washington, DC, 2000; Food and Nutrition Board, Institute of Medicine,
Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron,
Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc, National Academy Press, Wash-
ington, DC, 2001.
c The UL for magnesium represents intake from a pharmacological agent only and does not
include intake from food and water.
d The ULs for niacin and synthetic folic acid apply to forms obtained from supplements, fortified
foods, or a combination of the two.
e DRIs for vitamin E are based on α-tocopherol only and do not include amounts obtained from
the other seven naturally occurring forms historically called vitamin E. The ULs apply to any
form of supplementary α-tocopherol.
f The UL for adults is 1.8 mg/d of elemental vanadium. It was not possible to establish ULs
for children for vanadium, but the source of intake should be from food only.5
adverse effects increases as intake increases above the UL.2 Although the DRIs are based
on data, scientific judgment was required in setting all reference values because data
were often scanty or drawn from studies with limitations; this is especially true in
deriving DRIs for children and adolescents.2
In 1997, DRIs were published for calcium, phosphorus, magnesium, vitamin D, and
fluoride.2 In 1998, DRIs were published for thiamin, riboflavin, niacin, vitamin B6, folate,
vitamin B12, pantothenic acid, biotin, and choline.3 In 2000, DRIs were published for
vitamin C, vitamin E, and selenium.4 No DRIs were proposed for carotenoids, although
TABLE 8.3
1989 Recommended Dietary Allowances (RDAs) for Children and
Adolescents for Nutrients without Dietary Reference Intakesa
Weightb Heightb Calories Protein
Category Age (years) (kg) (lb) (cm) (in) (kcal/day) (g/day) (g/kg)
Children 1–3 13 29 90 35 1300 16 1.2
4–6 20 44 112 44 1800 24 1.1
7–10 28 62 132 52 2000 28 1.0
Boys 11–14 45 99 157 62 2500 45 1.0
15–18 66 145 176 69 3000 59 0.9
Girls 11–14 46 101 157 62 2200 46 1.0
15–18 55 120 163 64 2200 44 0.8
a Adapted from Food and Nutrition Board, National Research Council, Recom-
mended Dietary Allowances, 10th ed, National Academy Press, Washington, DC,
1989. The RDAs, expressed as average daily intakes over time, are intended
to provide for individual variations among most normal persons as they live
in the U.S. under usual environmental stresses. Diets should be based on a
variety of common foods in order to provide other nutrients for which human
requirements have been less well defined. The RDAs are designed for the
maintenance of good nutrition of practically all healthy people in the U.S.
b The median weights and heights of those under 19 years of age were taken
from Hamill, P. V. V., Drizd, T. A., Johnson, R. B., et al., Am J Clin Nutr, 32,
607, 1979. The use of these figures does not imply that the height-to-weight
ratios are ideal.
existing recommendations for increased consumption of carotenoid-rich fruits and vege-

tables are supported. However, β-carotene supplements are not advisable.4 In 2001, DRIs
were published for vitamin A, vitamin K, boron, chromium, copper, iodine, iron, manga-
nese, molybdenum, nickel, vadadium, and zinc.5 No DRIs were set for arsenic or silicon.5
For boron, nickel, and vanadium, ULs were proposed, but EARs, RDAs, or AIs were not
set.5 The RDAs and AIs for children and adolescents are provided in Table 8.1. The ULs
for children and adolescents are provided in Table 8.2. Additional groups of nutrients and
food components slated for review over the next several years include energy and macro-
nutrients, electrolytes, and other food components.2
Energy
Daily energy needs depend on three major factors: energy expended when at rest, during
physical activity, and as a result of thermogenesis. Resting energy expenditure is the largest
of the three factors unless the physical activity level is very high; thermogenesis is the
smallest. In turn, these factors are affected by individual variables which include age, sex,
body size and composition, genetics, energy intake, physiologic state (e.g., growth, preg-
nancy, lactation), coexisting pathological conditions, and ambient temperature.
Recommended energy allowances for children and adolescents from the 1989 RDAs are
stipulated as kilocalories (kcal)/day based on reference weights for children ages 1 to 10
years in three age groups for both genders combined, and for adolescents ages 11 to 18
years in two age groups for boys and girls separately (see Table 8.3). According to Heald
and Gong, the best way to calculate individual energy requirements for adolescents may
be to use kcal/centimeter (cm) of height; thus, boys 11 to 14 years of age need 15.9 kcal/
cm, boys 15 to 18 years of age need 17.0 kcal/cm, girls 11 to 14 years of age need 14.0
kcal/cm, and girls 15 to 18 years of age need 13.5 kcal/cm.6 In Table 8.4, energy require-
ments for children and adolescents from Pellett7 are stipulated in terms of kcal/day (mean
TABLE 8.4
Energy Requirements for Children and Adolescentsa
Estimated Energy Allowance
Age Weightb Height By Time By Weight By Height
(years) (kg) (cm) (kcal/d (range)) (kcal/kg) (kcal/cm)
Children
1–1.9 11 82 1200 (900–1600) 105 14.0

2–3.9 14 96 1400 (1100–1900) 100 14.6
4–5.9 18 109 1700 (1300–2300) 92 15.6
6–7.9 22 121 1800 (1400–2400) 83 14.9
8–9.9 28 132 1900 (1400–2500) 69 14.4
Boys
10–11.9 36 143 2200 (1700–2900) 61 15.4

12–17.9c 57 169 2700 (2000–3600) 47 16.0
Girls
10–14.9 44 155 2200 (1700–2900) 50 14.2

15–17.9c 56 162 2300 (1700–3000) 41 14.2
a Adapted from Pellett, P. L., Am J Clin Nutr, 51, 711, 1990. Data originate from
original median weights and heights (see original document).
b Weight is rounded to nearest kilogram for age.
c During these years, individual growth rates can vary enormously; thus, allow-
ances should be based on individual weights and the requirements per kg body
weight.
and range), kcal/kilogram (kg), and kcal/cm for children ages 1 to 9.9 years in five groups
for both genders combined, for adolescent boys ages 10 to 17.9 years in two groups, and
for adolescent girls ages 10 to 17.9 years in two groups.
Physical activity patterns are quite variable among children and adolescents, and there
is considerable variability in both the timing and magnitude of the growth spurt. Thus,
recommended energy allowances for children and adolescents assume a wide range within
which energy can be adjusted individually to account for body weight, activity, and rate
of growth. An accepted and practical method for assessing the adequacy of a child’s or
adolescent’s energy intake is to monitor growth by tracking height and weight on growth
charts developed by the National Center for Health Statistics; these charts are provided
in Section 32.
Protein
Protein is essential for growth, development, and maintenance of the body; it also provides
energy. Protein yields 4 kcal/gram (g). Food sources of protein include meat, fish, poultry,
milk, cheese, yogurt, dried beans, peanut butter, nuts, and grain products. Animal proteins
are called “high-quality” or “complete” because they contain all the essential amino acids
in the proportions needed by humans. Vegetable proteins, with the exception of soybeans,
are called “low-quality” or “incomplete” because they have low levels of one or more
essential amino acids. A vegetable protein may be paired with another vegetable protein
or with a small amount of animal protein to provide adequate amounts of all the essential
amino acids. For example, black-eyed peas can be paired with rice, peanut butter with
wheat bread, pasta with cheese, or cereal with milk.
Proteins in the body are continuously being degraded and resynthesized. Because the
process is not entirely efficient and some amino acids are lost, a continuous supply of
amino acids is needed to replace these losses, even after growth has stopped. The primary
factor that influences protein needs is energy intake because when energy intake is insuf-
ficient, protein is used for energy. Thus, all protein recommendations are based on the
assumption that energy needs are adequately met. In addition, protein recommendations
are based on high-quality protein intakes; appropriate corrections must be made for diets
which customarily provide low-quality proteins.
Table 8.3 provides the 1989 RDAs for high-quality protein in g/day and g/kg of body
weight for children and adolescents. As Table 8.3 indicates, requirements slowly decline
relative to weight during the preschool and elementary school-age years. During the
adolescent years, protein recommendations do not emphasize the growth spurt because
it is small relative to body size. A 14-year-old adolescent who weighs 54 kilograms (kg)
(118.8 pounds) needs 54 g of protein each day; assuming that energy needs are met, this
protein need is met by eating a hamburger (3-ounce meat patty on a bun) and two slices
of cheese pizza.
According to Heald and Gong,6 the most useful method for determining protein needs
for adolescents is to use the 1989 RDAs for protein as they relate to height. For adolescent
boys ages 11-14 and 15-18 years, the protein daily recommendation based on height is
0.29 and 0.34 g/cm height, respectively. For adolescent girls ages 11-14 and 15-18 years,
the protein daily recommendation based on height is 0.29-0.27 g/cm height, respectively.6
Carbohydrates
Children and adolescents should get 55-60% of their daily calories from carbohydrates.8
Complex carbohydrates (starchy foods such as pasta, breads, cereals, rice, and legumes)
should provide the majority of kcal from carbohydrates, and simple carbohydrates (nat-
urally occurring sugars in fruits and vegetables) should provide the rest. Carbohydrate
yields 4 kcal/g. A 4- to 6-year-old child who needs 1800 kcal/day would need about 990
to 1080 kcal (or 248 to 270 g) from carbohydrates daily. An 11- to 14-year-old adolescent
who needs 2500 kcal/day would need about 1375 to 1500 kcal (or 344 to 375 g) from
carbohydrates daily.
Fat and Cholesterol

To promote lower cholesterol levels in all healthy U.S. children ages 2-18 years, the
American Academy of Pediatrics recommends that children older than two years should
gradually adopt a diet that by the age of five years reflects the following five guidelines.9
1. Nutritional adequacy should be achieved by eating a wide variety of foods.

2. Caloric intake should be adequate to support growth and development and to
reach or maintain desirable body weight.
3. Total fat intake over several days should be no more than 30% of total calories
and no less than 20% of total calories.
4. Saturated fat intake should be less than 10% of total calories.
5. Dietary cholesterol intake should be less than 300 milligrams (mg) per day.9
These recommendations are consistent with those of the Dietary Guidelines for Americans,
which were designed to provide advice for healthy Americans age two years and over
about food choices that promote health and prevent disease.10 A precise percentage of
dietary fat intake that supports normal growth and development while maximally reduc-
ing atherosclerosis risk is unknown. Thus, a range of appropriate values averaged over
several days for children and adolescents is recommended based on the available scientific
information. More information regarding the safety of low-fat diets for children is found
in “Low Fat Diets” in this section.
Fat yields 9 kcal/g. Dietary sources of fat include oils, margarine, butter, fried foods,
egg yolks, mayonnaise, salad dressings, ice cream, hard cheese, cream cheese, nuts, fatty
meats, chips, and doughnuts. Table 8.5 provides the fat, saturated fat, and cholesterol
content of various foods.
TABLE 8.5
Total Fat, Saturated Fat, and Cholesterol Content of Various Foods
Total Saturated Cholesterol
Food Amount Fat (g) Fat (g) (mg) Kcal
Almonds, roasted, salted 1 oz 15.3 1.1 0 172
Bacon 2 slices 6.3 2.2 11 73
Bread, white 1 slice 0.9 0.0 0 64
Butter 1t 4.1 2.5 11 36
Cheese, American 1 oz 8.9 5.6 27 106
Cheese, cheddar 1 oz 9.4 6.0 30 114
Chicken breast with skin, roasted 1/2 breast 7.6 2.2 83 193
Chicken breast without skin, roasted 1/2 breast 3.1 0.9 73 142
Coconut, dried, sweetened, flaked 1/3 c 8.1 7.2 0 115
Corn oil 1t 13.6 1.7 0 120
Cottonseed oil 1t 13.6 3.5 0 120
Egg, whole, boiled 1 large 5.3 1.6 213 77
Egg, white only, boiled 1 large 0.0 0.0 0 17
Egg, yolk only, boiled 1 large 5.1 1.6 213 59
Fish, flounder or sole, cooked 3 oz 1.3 0.3 58 99
Ground beef, regular, broiled 3.5 oz 19.5 7.7 101 292
Ground beef, extra lean, broiled 3.5 oz 15.8 6.2 99 265
Ice cream, vanilla, 10% fat 1/2 c 7.3 4.5 29 132
Ice milk, vanilla 1/2 c 2.8 1.7 9 92
Lard (pork fat) 1t 12.8 5.0 12 115
Margarine, corn & hydrogenated corn 1t 3.8 0.7 0 34
Margarine, liquid oil 1t 3.8 0.7 0 34
Milk, whole 1 cup 8.2 5.1 33 150
Milk, 2% 1 cup 4.7 2.9 18 121
Milk, 1% 1 cup 2.6 1.6 10 102
Milk, skim 1 cup 0.4 0.3 4 86
Olive oil 1t 13.5 1.8 0 119
Peanut butter 2t 16.0 3.1 0 188
Peanuts, dry roasted 1 oz 13.9 1.9 0 164
Pecans, raw 1 oz 19.0 2.0 0 190
Pork, lean, roasted 3.5 oz 4.8 1.7 93 166
Safflower oil 1t 13.6 1.2 0 120
Shrimp, boiled 3 oz 0.9 0.2 166 84
Soybean oil 1t 13.6 2.0 0 120
Tuna fish, oil pack, drained 3 oz 7.0 1.3 15 169
Tuna fish, water pack, drained 3 oz 0.7 0.2 25 99
Turkey breast with skin, roasted 3.5 oz 3.5 1.0 42 126
Yogurt, frozen, vanilla, soft serve 1/2 c 4.0 2.5 2 114
Adapted from Bowes, A. D. P., Bowes and Church’s Food Values of Portions Commonly Used, 16 ed,
revised by Pennington, J. A. T., J. B. Lippincott Company, Philadelphia, 1994.
TABLE 8.6
Fiber Content of Foods that Most U.S. Children and
Adolescents Will Eat
Approximate grams of
Food source Serving size dietary fiber
Baked Beans 1c 13
Chili with beans 1c 7
Refried beans 4 oz 6
Brown rice 1c 4
Peanuts (dry roasted) 2 oz 4
Strawberries 1c 4
Whole-wheat bread 2 slices 4
Potato, baked, with skin 1 medium 3.5
Apple 1 medium 3
Banana 1 large 3
Carrot (raw) 1 medium 3
Corn 1/2 c 3
Kiwi 1 large 3
Raisins 1/3 c 3
Whole-grain crackers 1/2 oz 2–3
Cereal 1c 2–3a
Applesauce 1/2 c 2
Broccoli 1/2 c 2
Orange 1 medium 2
Peanut butter 2 Tbsp 2
a Dietary fiber content of cereal varies widely. Best fiber choice for
children has 3+ g per cup.
b Adapted from Williams, C. L., J Am Diet Assoc, 95, 1140, 1995.
Fiber
Fiber has important health benefits such as promoting normal laxation which can be a
problem for many children. In addition, fiber may help reduce the risk of certain chronic
diseases of adulthood such as some cancers, cardiovascular disease, and diabetes. The
American Health Foundation recommends that children ages two years and older consume
a minimal amount of fiber equal to their age plus 5 g/day, and a maximum amount of
age plus 10 g/day, to achieve intakes of a maximum of 35 g/day after the age of 20 years.11,12
This range is thought to be safe even if intake of some vitamins and minerals is marginal.
According to the American Academy of Pediatrics,13 a reasonable daily fiber intake for
children is 0.5 g/kg of body weight to a maximum of 35 g/day. The two recommendations
are similar for children up to age 10 years, but the age plus 5 recommendation is lower
for older adolescents than the recommendation for 0.5 g/kg of body weight.
Fiber intake should be increased gradually through consumption of a variety of fruits,
vegetables, legumes, cereals, and other whole-grain products such as breads and crackers.
Fiber supplements for children are not recommended as a means of meeting dietary fiber
goals.11 Increased intakes of dietary fiber should be accompanied by increased intakes of
water because dietary fiber increases water retention in the colon, which leads to bulkier
and softer stools.11 For most children and adolescents, dietary fiber goals can be met if the
daily diet includes two servings of vegetables, three servings of fruits, two slices of whole
wheat bread, and a serving of breakfast cereal containing three or more grams of fiber.12
Table 8.6 provides a list of foods containing fiber that most U.S. children and adolescents
will eat.
High-fiber diets do have the potential for reduced energy density, reduced kcal intake,
and poor growth, especially in very young children. Furthermore, high-fiber diets may
reduce the bioavailability of minerals such as iron, calcium, and zinc. However, the
potential health benefits of a moderate increase in dietary fiber intake in childhood are
thought to outweigh the potential risks significantly, especially in highly industrialized
countries such as the U.S.11
Selected Vitamins and Minerals

Vitamin D
Throughout the world, the major source of vitamin D for humans is the exposure of the
skin to sunlight; vitamin D that is synthesized in the skin during the summer and fall
months can be stored in the fat for use in the winter, which minimizes requirements for
vitamin D. In nature, very few foods contain vitamin D; thus, children and adolescents
who live in far northern latitudes (e.g., northern Canada and Alaska) may need vitamin
D supplements. Food sources of vitamin D include some fish liver oils, eggs from hens
that have been fed vitamin D, the liver and fat from aquatic mammals such as seals and
polar bears, and the flesh of fatty fish. Foods fortified with vitamin D include milk products
and other foods such as margarine and breakfast cereals; the majority of human intake of
vitamin D is from fortified foods. Fortified milk is supposed to contain 10 µg (400 IU) per
quart regardless of the fat content of milk; however, several recent surveys have indicated
that many milk samples contained less than 8 µg per quart. Although it is well recognized
that vitamin D deficiency causes abnormalities in calcium and bone metabolism, it is
premature to suggest that cancer risk is increased by vitamin D deficiency. The AIs for
vitamin D for children and adolescents (see Table 8.1) were set to cover the needs of almost
all children and adolescents regardless of exposure to sunlight. Currently, there is no
scientific evidence that demonstrates an increased requirement for vitamin D during
puberty even though metabolism of vitamin D increases during puberty to enhance intes-
tinal calcium absorption to provide adequate calcium for the rapidly growing skeleton.2
Folate
Folate is important during periods of increased cell replication and growth due to its role
in DNA synthesis and the formation of healthy red blood cells; thus, the 1998 RDAs for
folate are 1.5 times greater for children age 9 to 13 years than for children age 4 to 8 years
(see Table 8.1). There is strong evidence that the risk of having a fetus with a neural tube
defect decreases with increased intake of folate during the periconceptional period; thus,
it is recommended that all women capable of becoming pregnant take 400 µg of synthetic
folic acid daily, from fortified foods and/or supplements, in addition to consuming food
folate from a varied diet. Folate fortification became mandatory for enriched grain products
in the U.S. effective January 1, 1998. Besides fortified grains and cereals, other food sources
of folate include leafy green vegetables, orange juice, liver, cantalope, yeast, and seeds.3
Calcium
Over 99% of total body calcium is found in teeth and bones. Approximately 45% of adult
skeletal mass is accounted for by skeletal growth during adolescence; thus, achieving and
maintaining adequate calcium intake during adolescence is necessary for the development
of a maximal peak bone mass which may help reduce the risk of osteoporosis later in
adulthood.
TABLE 8.7
Approximate Calcium Content for One Serving of Various Foods
Approximate Calcium Content
Food Serving Size (mg)
Cheese (Swiss) 1.5 oz 405
Cheese (cheddar or jack) 1.5 oz 310
Milk (whole, 1%, 2%, or buttermilk) 1c 300
Yogurt 8 oz 300
Cheese (part skim mozzarella) 1.5 oz 280
Tofu, raw, firm 1/2 c 260
Cheese (American) 2 oz 250
Calcium-fortified orange juice 6 oz 200
Canned sardines (with bones) 2 oz 180
Canned salmon (with bones) 3 oz 180
Cooked greens (collards) 1/2 c 180
Pudding 1/2 c 150
Spinach (cooked) 1/2 c 120*
Frozen yogurt (vanilla, soft serve) 1/2 c 100
Ice cream (vanilla, 10% fat) 1/2 c 85
Cooked greens (mustard, kale) 1/2 c 80
Cottage cheese 1/2 c 75
Spinach (raw) 1c 60*
Orange 1 medium 55
Beans, canned (baked, pinto, or navy) 1/2 c 50
Sweet potatoes (mashed) 1/2 c 40
Broccoli (cooked) 1/2 c 35
Broccoli (raw) 1/2 c 20
* The calcium from spinach is essentially nonbioavailable.
Adapted from Bowes, A. D. P., Bowes and Church’s Food Values of Portions Commonly Used,
16th ed, revised by Pennington, J. A. T., J. B. Lippincott Company, Philadelphia, 1994.
The calcium AIs for adolescents are higher than for children because from age 9 through
18 years (see Table 8.1), calcium retention increases to a peak and then declines. However,
the calcium AIs remain the same for adolescents from age 9 to 18 years because calcium
absorption efficiency decreases. Thus, during this developmental period, measures of
sexual maturity are better predictors of calcium retention than chronological age.2
Major food sources of calcium include milk, yogurt, cheese, and green leafy vegetables.
Calcium-fortified orange juice is also an excellent source of calcium, as is tofu. Table 8.7
contains approximate calcium contents for one serving of various common foods. Vitamin
D (discussed previously in this section) is needed for the body to absorb calcium.
The calcium content of food is generally of greater importance than bioavailability when
evaluating food sources of calcium. The efficiency of calcium absorption is fairly similar
from most foods, including milk and milk products and grains, which are major food
sources of calcium in North American diets. Calcium may be poorly absorbed from foods
such as spinach, beans, sweet potatoes, and rhubarb which are rich in oxalic acid, and
from unleavened bread, raw beans, seeds, nuts and grains, and soy isolates which are rich
in phytic acid. Calcium absorption is relatively high from soybeans, although they contain
large amounts of phytic acid. Compared to calcium absorption from milk, calcium absorp-
tion from spinach is about one tenth, and from dried beans is about half.2
When developing the AIs for calcium, the Food and Nutrition Board of the Institute of
Medicine reviewed concerns regarding factors that affect the calcium requirement.2 For
example, they discussed racial differences in calcium metabolism, that sodium and calcium
excretion are linked in the proximal renal tubule and that many commonly consumed
processed foods are high in sodium, that protein increases urinary calcium excretion, that
caffeine has a modest negative impact on calcium retention, that calcium bioavailability
is reduced in vegetarian diets due to the high oxalate and phytate content, and that exercise
and calcium both influence bone mass. However, the Board concluded that available
evidence did not warrant different calcium intake requirements for individuals according
to their race, sodium consumption, protein intake, caffeine intake, level of physical activity,
or for individuals who consume a vegetarian diet.2
Children and adolescents (and adults) with lactose intolerance develop symptoms of
diarrhea and bloating after ingesting large doses of lactose such as the amount present in
a quart of milk (~46 g). People who generally are lactose digesters include Northern
Europeans, Finns, Hungarians, probably Mongols, the Fulani and Tussi tribes of Africa,
and the Punjabi of India; the remainder of the world’s population are lactose nondigest-
ers.14 However, as digesters intermix reproductively with nondigesters, the rate of lactose
malabsorption falls.14 In general, evidence for lactose malabsorption as a clinical problem
is not manifest until after five to seven years of age, although this age can vary.14 Individ-
uals with lactose intolerance can increase their tolerance to dairy products by drinking
smaller doses of milk (such as eight ounces), or by ingesting fermented products such as
yogurt, hard cheeses, cottage cheese, and acidophilus milk.14 In addition, lactose-free dairy
products are available. Although lactose intolerance may influence intake, lactose-intol-
erant individuals absorb calcium normally from milk; thus, there is no evidence to suggest
that it influences the calcium requirement.2
Iron
According to the American Academy of Pediatrics,15 iron deficiency is the most common
nutritional deficiency in the U.S. Children aged one to two years are the most susceptible
to iron deficiency due to increased iron needs related to rapid growth during the first
two years of life and a relatively low iron content in most infant diets when iron is not
added by supplementation or fortification. Children age 3 to 11 years are at less risk for
iron deficiency until the rapid growth of puberty. Preadolescent school-age children who
consume a strict vegetarian diet are at greater risk for iron deficiency anemia. Adolescent
boys are at risk for iron deficiency anemia during their peak growth period when iron
stores may not meet the demand of rapid growth; however, the iron deficiency anemia
generally corrects itself after the growth spurt. Adolescent girls are at greater risk for
iron deficiency anemia due to blood losses during menstruation. A major consequence
of iron deficiency is that significant iron deficiency adversely affects child development
and behavior. Furthermore, iron deficiency leads to enhanced lead absorption, and
childhood lead poisoning is a well-documented cause of neurologic and developmental
deficits. These consequences, along with evidence that dietary intake during infancy is
a strong determinant of iron status for older infants and younger children, emphasize
the importance of prevention. Significant improvements have been made in the iron
nutritional status of infants and young children in the U.S. during the past two decades,
perhaps because during this same time frame, several changes were made in infant
feeding patterns.15 These changes included increased dietary iron content or iron bio-
availability, increased incidence of breastfeeding, increased use of iron-fortified formula,
and reduced use of whole milk and low-iron formula during the first year of life.15
Dietary iron is classified as “heme” or “non-heme” iron. Heme iron is found in foods
from animals such as meat, fish, and poultry. Non-heme iron is provided by plants; good
sources include dark-green leafy vegetables, tofu, lentils, white beans, dried fruits, and
iron-fortified breads and cereals. On average, healthy people absorb about 5 to 10% of
the iron consumed, and people who are iron deficient absorb about 10 to 20%. Heme iron
is more easily absorbed than non-heme iron. About 20% of heme iron consumed is
absorbed regardless of how it is prepared and served; however, the absorption rate of
non-heme iron can be increased by eating foods with non-heme iron with either meat,
foods rich in vitamin C, or foods that contain some heme iron at the same meal. Non-
heme iron absorption can be hindered by as much as 50% when tannins, phytates, and
calcium (which are found in foods such as tea, bran, and milk, respectively) are eaten at
the same meal.
The RDAs for iron for children and adolescents are included in Table 8.1. Because the
amount of iron available in the American diet is estimated to be about 5 to 7 mg/1000
kcal, it may be difficult for adolescent girls to obtain 15 mg of iron from dietary sources
alone if their caloric intake is between 2000 and 2400 kcal/day. Groups of adolescents at
special risk of iron deficiency include 1) older adolescent girls due to their increased iron
need and their low dietary intake, 2) pregnant adolescents, and 3) girl athletes such as
runners who may lose iron through occult gastrointestinal bleeding.
The Committee on the Prevention, Detection, and Management of Iron Deficiency Ane-
mia Among U.S. Children and Women of Childbearing Age was established under the
Food and Nutrition Board of the Institute of Medicine; its recommended guidelines were
published in 1993.16 The committee concluded that iron enrichment and fortification of
the U.S. food supply should remain at current levels rather than increasing or decreasing
the levels. Furthermore, it was recommended that dietary sources of iron be consumed
instead of supplemental sources when possible. Iron supplements should be kept out of
reach of children because iron is a very common cause of poisoning in children.16
Zinc
Zinc is needed for protein synthesis, wound healing, and sexual maturation; thus, zinc is
especially important during adolescence due to the rapid rate of growth and sexual
maturation.6 (See Table 8.1 for the RDAs for zinc for children and adolescents.) Adolescents
undergoing rapid growth are at risk for inadequate zinc levels, and should be encouraged
to include zinc-rich foods in their daily diet. Foods high in zinc include red meats, certain
seafood, and whole grains; many breakfast cereals are fortified with zinc. The bioavail-
ability of zinc in foods varies widely. Zinc from whole grain products is less available
than zinc from meat, liver, eggs, and seafood (especially oysters). Furthermore, consump-
tion of phytate-rich foods limits absorption and maintenance of zinc balance.5
Food Guide Pyramid for Young Children

Figure 8.1 illustrates the Food Guide Pyramid for Young Children released by the United
States Department of Agriculture (USDA) in March, 1999.17 The pyramid targets children
two to six years of age; it is an adaptation of the original Food Guide Pyramid18 released
in 1992. The purpose of the new pyramid is to simplify educational messages and focus
on young children’s food preferences and nutritional needs. The new pyramid was devel-
oped by adapting existing food guidance recommendations to meet the specific needs of
young children after actual food patterns of young children were analyzed by USDA’s
Center for Nutrition Policy and Promotion. Table 8.8 provides an overview of changes
made in the new pyramid. The new pyramid continues to emphasize eating a variety of
foods. However, it de-emphasizes fat restriction, recognizing that some fats are necessary
for early growth and development.
Guide P Y R A M I D
F O O D
A Daily Guide for
2-to 6-Year-Olds
U.S. Department of Agriculture USDA is an equal opportunity provider and employer.

Center for Nutrition Policy and Promotion
January 2000
Program Aid 1651
W H AT C O U N T S A S O N E S E R V I N G ?
GRAIN GROUP FRUIT GROUP MEAT GROUP
1 slice of bread 1 piece of fruit or melon wedge 2 to 3 ounces of cooked lean
1/2 cup of cooked rice or pasta 3/4 cup of juice meat, poultry, or fish.
FOOD IS FUN and learning about food 1/2 cup of cooked cereal
1 ounce of ready-to-eat cereal

1/2 cup of canned fruit
1/4 cup of dried fruit 1/2 cup of cooked dry beans,
or 1 egg counts as 1 ounce of lean

is fun, too. Eating foods from the Food VEGETABLE GROUP MILD GROUP meat. 2 tablespoons of peanut
1/2 cup of chopped raw butter count as 1 ounce of meat.
Guide Pyramid and being physically or cooked vegetables
1 cup of milk or yogurt
2 ounces of cheese
1 cup of raw leafy vegetables
active will help you grow healthy and FATS AND SWEETS
Limit calories from these.
strong.
Four- to 6-year-olds can eat these serving sizes. Offer 2- to 3-year-olds less, except for milk.
Two- to 6-year-old children need a total of 2 servings from the milk group each day.
E AT a variety of F O O D S AND ENJOY!

FIGURE 8.1
Food guide pyramid for young children.
TABLE 8.8
Changes Made in the New Food Guide Pyramid for Young Children
• The food groups have shorter names.
• A single number of servings is given for each food group rather than a range of servings.
• Foods are drawn in a realistic style.
• Foods are illustrated in single serving portions when possible.
• Foods included are those commonly eaten by young children such as fruit juice, green beans, breads, cereals,
and pasta. (Although the baked potato is not the most commonly served form of potato, it is illustrated to
encourage children to consume a lower fat version of potato. Also, dark-green leafy vegetables and whole-
grain products are illustrated to encourage children to eat them more often.)
• Abstract symbols for fat and added sugars in the original pyramid have been eliminated.
• The tip of the pyramid has drawings of food items rather than symbols.
• The pyramid is surrounded with illustrations of children engaged in active pursuits, to show the importance
of physical activity.
From Tips for Using the Food Guide Pyramid for Young Children 2 to 6 Years Old, USDA, Center for Nutrition Policy
and Promotion, Washington, DC, 1999, Program Aid 1647.
A booklet entitled Tips for Using the Food Guide Pyramid for Young Children 2 to 6 Years Old
was developed to go along with the new pyramid.19 It includes tips to encourage healthful
eating, basic information about the new pyramid, “child-size” serving sizes, lists of foods
by group to encourage children to eat a variety of foods, suggested kitchen activities for
parents to do with children, snack and meal planning ideas, a chart to track foods eaten
over several days, and “hands-on” food activities for home or child care centers.
Both the original and the new pyramid show how adults, adolescents, and children can
make food choices for a healthful diet as described in the Dietary Guidelines for Americans.10
The five food groups in the pyramid include grains, vegetables, fruits, milk, and meat.
Each group provides some, but not all, of nutrients and energy that children need. No
one food group is more important than another. The grain group forms the base of the
pyramid because the largest number of servings needed each day comes from this group.
Grain products provide vitamins, minerals, complex carbohydrates, and dietary fiber.
Foods from the fruit and vegetable groups provide vitamins, minerals, and dietary fiber.
Foods from the milk group provide calcium. Foods from the meat group (meat, poultry,
fish, eggs, dry beans/peas, and peanut butter) provide protein, iron, and zinc. The small
tip of the pyramid shows fats and sweets (e.g., salad dressing, cream, butter, margarine,
soft drinks, and candy); these foods contain kcal but few vitamins and minerals.
Table 8.9 contains young children’s serving sizes by food group, along with the number
of servings needed from each food group each day. Two- to three-year-olds need the same
variety of foods as four- to six-year-olds but fewer kcal, so offer them smaller amounts
(about 2/3 serving). The one exception is that two- to six-year-olds need a total of two
servings from the milk group each day. Offer children a variety of foods from the five
food groups, and let children decide how much to eat. Table 8.10 contains a sample meal
and snack plan according to food group for one day for four- to six-year-old children.
What are Children and Adolescents Eating?

1989–1991 Continuing Survey of Food Intakes by Individuals (CSFII)
The 1989–1991 CSFII sample consisted of individuals residing in households in the 48
contiguous United States; it included two separate samples, basic and low income. All
TABLE 8.9
Young Children’s Serving Sizes by Food Group
Grain Group (6 servings each day)

Offer whole or mixed grain products for at least 3 of the 6 grain group servings each day.
Whole grain: Enriched:

1/2 cup cooked brown rice 1/2 cup cooked rice, pasta, or grits
2-3 graham cracker squares 1/2 English muffin or bagel
5-6 whole grain crackers 1 slice white, wheat, French or Italian bread
1/2 cup cooked oatmeal 1/2 hamburger or hot dog bun
1/2 cup cooked bulgur 1 small roll
3 cups popped popcorn* 6 crackers (saltine size)
3 rice or popcorn cakes* 1 4-inch pita bread or 1 4-inch pancake
1 ounce ready-to-eat whole grain cereal 1/2 cup cooked farina or other cereal
1 slice pumpernickel, rye, or whole wheat bread 9 3-ring pretzels*
2 taco shells* 1 7-inch flour tortilla
1 7-inch corn tortilla 1 ounce ready-to-eat, unfrosted cereal
Grain products with more fat and sugars:
1 small biscuit, muffin, or piece of cornbread
1/2 medium doughnut
9 animal crackers
Vegetable Group (3 servings each day)
1/2 cup of chopped raw or cooked vegetable

1 cup raw leafy greens
1/2 cup tomato or spaghetti sauce
3/4 cup vegetable juice
1 cup vegetable soup
1 medium (ear of corn, potato)
2 cooked broccoli spears
7-8 raw carrot or celery sticks (3” long)*
10 french fries
5 cherry tomatoes*
Fruit Group (2 servings each day)
1 medium orange, apple, banana, or peach

1/2 grapefruit
1/2 cup cut-up fresh, canned, or cooked fruit
3/4 cup fruit juice
1/4 cup dried fruit*
12 grapes or 11 cherries*
7 medium strawberries
1/2 cup blueberries or raspberries
1 large kiwi
1 small pear
Milk Group (2 servings each day)
For this amount of food … Count this many milk group servings
1 cup milk or 1 cup soy milk (calcium fortified) 1
1/2 cup milk 1/2
1 cup yogurt (8 ounces) 1
1.5 ounces natural cheese 1
2 ounces processed cheese 1
1 string cheese (1 ounce) 2/3
1/2 cup cottage cheese 1/4
1/2 cup ice cream 1/3
1/2 cup frozen yogurt or 1/2 cup pudding 1/2

Young Children’s Serving Sizes by Food Group
Meat Group (2 servings each day)

Two to three ounces of cooked lean meat, poultry, or fish equal one serving of meat. Amounts from the meat group
should total 5 ounces a day for 4- to 6-year-olds and about 3 1/2 ounces a day for 2- to 3-year-olds.
For this amount of food … Count this many ounces

2 ounces cooked lean meat, poultry, or fish 2 ounces
1 egg (yolk and white) 1 ounce
2 tablespoons peanut butter* 1 ounce
1 1/2 frankfurters (2 ounces)* 1 ounce
2 slices bologna or lunchmeat (2 ounces) 1 ounce
1/4 cup drained canned salmon or tuna 1 ounce
1/2 cup cooked kidney, pinto, or white beans 1 ounce
1/2 cup tofu 1 ounce
1 soy burger patty 1 ounce
* May cause choking in 2- and 3-year-old children.
Adapted from Tips for Using the Food Guide Pyramid for Young Children 2 to 6 Years Old, USDA, Center for Nutrition
Policy and Promotion, Washington, DC, 1999, Program Aid 1647.
household members were asked to provide intake information. Each individual provided
three consecutive days of dietary data which consisted of one 24-hour recall and a two-
day food record. A knowledgeable adult (usually the primary meal planner/preparer)
reported the food intakes of household members younger than 12 years.20
Data from the 1989–1991 CSFII have been analyzed numerous ways to provide insight
into what children and adolescents are eating. For example, data were analyzed to deter-
mine dietary sources of nutrients among 4008 U.S. children age 2 to 18 years.21 Results
indicated that fortified foods (e.g., ready-to-eat cereals) were influential contributors of
many vitamins and minerals. Furthermore, low nutrient-dense foods were major contrib-
utors of energy, fats, and carbohydrate, which compromises intakes of more nutrient-dense
foods, and may impede compliance with current dietary guidance.
Data from CSFII 1989–1991 were also analyzed to determine fruit and vegetable con-
sumption among 3148 U.S. children age 2 to 18 years.22 Results indicated that only one in
five children met the recommendation of consuming five or more servings of fruits and
vegetables per day. Intakes of all fruits and of dark green and/or deep yellow vegetables
were very low compared with recommendations. Furthermore, almost one-fourth of all
vegetables consumed by children and adolescents were french fries.
Finally, data from the CSFII 1989–1991 were analyzed to determine what percentage of
children ages 4-6 (n = 603) and 7-10 (n = 782) met the American Health Foundation’s age
plus 5 recommendation for fiber,11,12 and what the leading contributors to total dietary
fiber intake were.23 Results indicated that only 45% of 4- to 6-year-olds and 32% of 7- to
10-year-olds met the age plus 5 rule. Children who met the rule did so by consuming
significantly more high- and low-fiber breads and cereals, fruits, vegetables, legumes, nuts,
and seeds. Furthermore, children who met the rule had significantly higher energy-
adjusted intakes of vitamins A and E, folate, magnesium, and iron compared to children
with low fiber intakes who had significantly higher energy-adjusted intakes of fat and
cholesterol. Surprisingly, low-fiber breads and cereals provided 21 and 19% of total dietary
fiber for 4- to 6-year-olds and 7- to 10-year-olds, respectively, whereas high-fiber breads
and cereals provided only 6% of total dietary fiber for both age groups. Conclusions from
these results include that substituting high-fiber breads and cereals for low-fiber ones
would increase children’s fiber intakes and should be relatively easy to accomplish.23
TABLE 8.10
Sample Meal and Snack Plan according to Food Group for One Day
for Four- to Six-Year-Old Children (Offer two- to three-year-old
children the same variety but smaller portions.)
Grain Vegetable Fruit Milk Meat
Breakfast
Orange juice, 3/4 cup 1

Whole-grain toast, 1 slice 1
Cheerios, 1 oz 1
Milk, 1/2 cup 1/2
Mid-Morning Snack
Graham crackers, 2 squares 1

Cold water, 1/2 cup
Lunch
Tuna Casserole with:

Tuna fish, 2 oz (1/2 cup) 2 oz
Macaroni, 1/2 cup 1
Green peas, 1/2 cup 1
Processed cheese, 1 oz 1/2
Banana, 1 medium 1
Milk, 1/2 cup 1/2
Mid-Afternoon Snack
Animal crackers, 9 1
Peanut butter, 2 Tbsp 1 oz
Cold water, 1/2 cup
Dinner
Chicken, 2 oz 2 oz
Baked potato, 1 medium 1
Broccoli, 1/2 cup 1
Milk, 1/2 cup 1/2
Evening Snack
Whole grain crackers (5) 1

Cold water, 1/2 cup
Total Food Group Servings 6 3 2 2 5 oz

Adapted from Tips for Using the Food Guide Pyramid for Young Children 2 to 6
Years Old, USDA, Center for Nutrition Policy and Promotion, Washington,
DC, 1999, Program Aid 1647.
1994–1996 Continuing Survey of Food Intakes by Individuals (CSFII)

The 1994–1996 CSFII sample consisted of individuals residing in households in the 50
United States, and included an oversampling of the low-income population. Only
selected household members were asked to provide intake information. Each individual
provided two nonconsecutive days of dietary data obtained by the 24-hour recall method
through in-person interviews.20 Proxy interviews were conducted routinely for subjects
under 6 years of age, and children 6 to 11 years of age were asked to describe their own
food intake assisted by an adult household member (referred to as the assistant). The
preferred proxy or assistant was the person responsible for preparing the subject’s
meals.24
To determine how the dietary intake of children and adolescents compared with nutri-
tion recommendations, the Healthy Eating Index (HEI) was used to examine the diets of
5354 American children ages 2 to 18 from USDA’s 1994–1996 CSFII.25 The HEI is computed
on a regular basis by USDA as a summary measure of people’s diet quality. It consists of
10 components, each representing different aspects of a healthful diet. Components 1 to
5 measure the degree to which a person’s diet conforms to USDA’s Food Guide Pyramid
serving recommendations for the five major food groups: grains, vegetables, fruits, milk,
and meat/meat alternatives. Components 6 and 7 measure total fat and saturated fat
consumption, respectively, as percentages of total kcal intake. Components 8 and 9 mea-
sure total cholesterol and sodium intake, respectively. Component 10 measures the degree
of variety in a person’s diet. Each component has a maximum score of ten and a minimum
score of zero. High component scores indicate intakes close to recommended ranges or
amounts; low component scores indicate less compliance with recommended ranges or
amounts. The maximum combined score for the 10 components is 100. An HEI score above
80 implies a good diet, a score between 51 and 80 implies a diet that needs improvement,
and a score less than 51 implies a poor diet.25
Results indicate that most children have a diet that is poor or needs improvement. As
children get older, their overall HEI score declines; thus, the percentage of children with
a diet that needs improvement or is poor increases, and the percentage of children with
a good diet declines. For children ages 2 to 3, 35% have a good diet, and 5% have a poor
diet. For boys 15 to 18 years old, only 6% have a good diet, and 21% have a poor diet.
The decline in diet quality begins between the 2-3 and 4-6 age groups, with the percentage
of children having a good diet falling from 35 to 16%, and the percentage having a diet
that needs improvement rising from 60 to 75%. The decline continues between the 7-10
and 11-14 age groups, with the percentage of children having a good diet falling from 14
to 7%. As indicated by the HEI component scores in Table 8.11, the decline in the quality
of children’s diets as they get older is linked to declines in their fruit and milk consumption.
Fifty-three percent of children ages 2 to 3 meet the recommendation for fruit compared
to only 11 to 12% of children ages 15 to 18. Although 44% of children ages 2 to 3 meet the
recommendation for milk, only 12 and 28% of girls and boys, respectively, ages 15 to 18,
do so. Except for cholesterol and variety to a smaller extent, most children do not meet
most recommendations.25
Further analyses of data from the 1994–1996 CSFII indicated that the quality of a child’s
diet is related to the income of his or her family.26 As indicated in Table 8.12, poor children
are less likely than nonpoor children to have a diet rated as good. For children ages 2-5,
19% of those in a poor household had a good diet compared to 28% of those in a nonpoor
household.
Data from the 1994–1996 CSFII were also analyzed to determine whether carbonated
soft drink consumption was associated with consumption of milk, fruit juice, and the
nutrients concentrated in these beverages among children and adolescents age 2-18 years
(n = 1810).27 Results indicated that adolescents (13-18 years) were more likely to consume
soft drinks than preschool-age children (2-5 years) and school-age children (6-12 years).
Among preschool-age children, school-age children, and adolescents, 49.5, 35.9, and 17.5%,
respectively, did not consume any soft drinks during the two days of dietary recall;
furthermore, the majority of children in each age category were nonconsumers of diet soft
TABLE 8.11
Healthy Eating Index (HEI): Overall and Component Mean Scores for Children, 1994–1996a,b
Children Children Children Girls Boys Girls Boys
Age (years) 2–3 4–6 7–10 11–14 11–14 15–18 15–18
Overall HEI Score 73.8 67.8 66.6 63.5 62.2 60.9 60.7
1. Grains 8.3 7.2 7.6 6.7 7.2 6.3 7.5
(54) (27) (31) (16) (29) (17) (34)
2. Vegetables 5.9 4.9 5.1 5.5 5.4 5.8 6.3
(31) (16) (20) (24) (23) (26) (35)
3. Fruits 7.0 5.3 4.3 3.9 3.5 3.1 2.8
(53) (29) (18) (14) (9) (12) (11)
4. Milk 7.2 7.4 7.6 5.2 6.2 4.2 6.1
(44) (44) (49) (15) (27) (12) (28)
5. Meat 6.3 5.3 5.5 5.7 6.5 5.8 6.9
(28) (14) (17) (15) (28) (21) (36)
6. Total fat 7.4 7.3 7.2 7.2 6.8 7.1 6.8
(40) (38) (35) (37) (33) (38) (34)
7. Saturated fat 5.4 5.6 5.7 5.8 5.7 6.6 6.0
(27) (28) (28) (31) (32) (42) (35)
8. Cholesterol 9.0 8.9 8.7 8.5 7.6 8.4 6.7
(83) (83) (80) (78) (69) (77) (58)
9. Sodium 8.8 8.1 6.8 7.1 5.2 6.9 3.7
(64) (53) (34) (39) (21) (37) (15)
10. Variety 8.4 7.9 8.1 7.8 8.1 6.7 7.8
(64) (53) (54) (51) (58) (37) (51)
a Parentheses contain % of children meeting dietary recommendations for each component.
b From Report Card on the Diet Quality of Children. Nutrition Insights, Insight 9, October, 1998, issued by the
Center for Nutrition Policy and Promotion, USDA, http://www.usda.gov/cnpp (accessed July 21, 1999).
TABLE 8.12
Percentage of Children Ages 2 to 18 by Age, Poverty Status, and
Diet Quality as Measured by the Healthy Eating Index, Three-Year
Average 1994–1996
Characteristic Good Dieta Needs Improvementa Poor Dieta
Ages 2-5
At or below poverty 19 70 11
Above poverty 28 65 7
Ages 6-12
At or below poverty 10 78 12
Ages 13-18
At or below poverty 3b 72 25
a A Healthy Eating Index (HEI) score above 80 implies a good diet, a score
between 51 and 80 implies a diet that needs improvement, and a score
less than 51 implies a poor diet.
b Sample size relatively small to make reliable comparisons.
Adapted from Federal Interagency Forum on Child and Family Statistics,
America’s Children: Key National Indicators of Well-Being, 1999. Federal Inter-
agency Forum On Child and Family Statistics, Washington, DC, US Gov-
ernment Printing Office. The report is also available on the World Wide
Web: http://childstats.gov.
drinks (94.9, 89.0, and 85.9%, respectively). White preschool-age children and adolescents
were more likely to consume soft drinks than black preschool-age children and adoles-
cents. Among adolescents, boys were more likely than girls to consume soft drinks.
Among preschool-age children and adolescents, those who resided in central city metro-
politan statistical areas (within a metropolitan area containing the largest population)
were more likely to consume soft drinks than those residing in noncentral city metropol-
itan statistical areas (within a metropolitan area not containing the largest population).
No significant differences in soft drink consumption were found by poverty status or
region of the country. In general, soft drink consumption was inversely associated with
consumption of milk, fruit juice, and the nutrients concentrated in these beverages. For
all age groups, energy intake was higher among those in the highest soft drink consump-
tion category compared with nonconsumers. These results indicate that nutrition educa-
tion messages for children and/or their parents should encourage limited consumption
of soft drinks.27
1994–1996 and 1998 Continuing Survey of Food Intakes by Individuals (CSFII)

The Supplemental Children’s Survey to the 1994–1996 CSFII (CSFII 1998) was con-
ducted to add intake data from 5559 children age birth through 9 years to the intake
data collected from 4253 children of the same age who participated in the CSFII
1994–1996. The CSFII 1998 was designed to be combined with the CSFII 1994–1996;
thus, approaches to sample selection, data collection, data file preparation, and weight-
ing were consistent.28
Analyses of data from the 1994–1996 and 1998 CSFII provide some of the most recent
insight into the dietary intake of children and adolescents nationwide. Tables 8.13 through
8.17 include national probability estimates based on all four years of the CSFII (1994–1996
and 1998) for children ages 9 years and under, and on CSFII 1994–1996 only for individ-
uals age 10 years and over.28 As indicated in Table 8.13, mean intakes as percentages of
the 1989 RDAs meet or exceed the RDAs for most nutrients for both girls and boys of
all ages. The most notable exception is for calcium for girls ages 12 to 19 years, for which
mean intake as a percentage of the RDA for this group is only 64%, down from 102% for
girls ages 6 to 11 years. As indicated in Table 8.14, the percentages of children with diets
meeting 100% of the 1989 RDAs is around or below 50% for energy, vitamin E, and zinc
for both boys and girls, and for vitamin A and calcium for girls. For all nutrients for all
ages of children, the percentages of children with diets meeting 100% of the 1989 RDAs
is higher for males than females. Furthermore, in general, the percentages of children
with diets meeting 100% of the 1989 RDAs decreases as children get older, especially
between the 6-11 and 12-19 year age groups, and more so for girls than boys. As indicated
in Table 8.15, the mean percentages of kcal from protein, total fat, saturated fat, and
carbohydrate in the diets of children and adolescents closely follows nutrition recom-
mendations. However, as indicated in Table 8.16, although the diets of many children do
meet recommendations for cholesterol, most children do not meet recommendations for
total fat or saturated fat. Breakfast consumption declines as children get older; ~97% of
children ages 2 to 5 years eat breakfast, compared to ~93% of children ages 6 to 11 years
and ~76% of children ages 12 to 19 years (data not shown). Although ~80% of children
of all ages from 2 to 18 years consume vegetables, the percentages of children consuming
fruits and fruit juices declines as children get older, from ~73% for children ages 2 to 5
years to ~59% for children ages 6 to 11 years, to ~45% for children ages 12 to 19 years
(data not shown).28
TABLE 8.13
Nutrient Intakes: Mean Intakes as Percentages of the 1989 Recommended Dietary Allowances
Intakes by Individuals 1994–1996, 1998
Sex and
Age Sample Food Vitamin A Vitamin Vitamin
(Years) Size Energy Protein (µg RE) E C Thiamin Riboflavin Niacin
- - - - - - Number - - - - - - - - - - - - - - - - - - - - - Percentages of 1989 RDA - - - - - - - - - - - - - - - - - - - - -
Boys & Girls
1–2 2118 102 307 185 79 257 161 213 142

3–5 4574 103 281 179 88 240 170 193 155
Boys
6–9 787 103 258 147 98 227 175 190 164

6–11 1031 101 244 139 96 226 172 186 161
12–19 737 99 184 108 93 213 150 155 148
Girls
6–9 704 91 227 127 89 214 150 162 139

6–11 969 91 214 121 91 208 149 160 138
12–19 732 87 145 100 88 171 131 135 126
Adapted from USDA, Agricultural Research Service, Food and Nutrient Intakes by Children 1994–96, 1998, 1999,
bhnrc/foodsurvey/home.htm (accessed December 22, 1999).
(RDAs), by Sex and Age, Children 19 Years of Age and Under, One Day, Continuing Survey of Food
Sex and
Age Vitamin Vitamin
(Years) B6 Folate B12 Calcium Phosphorus Magnesium Iron Zinc Selenium
- - - - - - Number - - - - - - - - - - - - - - - - - - - - - Percentages of 1989 RDA - - - - - - - - - - - - - - - - - - - - -
Boys & Girls
1–2 130 396 457 107 121 234 108 74 299

3–5 144 424 421 108 136 204 132 92 375
Boys
6–9 136 319 337 122 159 156 158 109 334
6–11 133 298 326 116 152 146 161 107 318
12–19 117 180 292 95 136 92 169 96 263
Girls
6–9 115 237 307 106 138 140 136 94 297

6–11 114 248 283 102 134 129 130 93 276
12–19 104 138 190 64 92 77 91 82 178
Online, ARS Food Surveys Research Group, available on the “Products” page at http://www.barc.usda.gov/
TABLE 8.14
Nutrient Intakes: Percentage of Children with Diets Meeting 100% of the 1989 Recommended Dietary
Individuals 1994–1996, 1998
Sex and
Age Sample Food Vitamin A Vitamin Vitamin
(Years) Size Energy Protein (µg RE) E C Thiamin Riboflavin Niacin
- - - - - - Number - - - - - - - - - - - - - - - - - - - - - Percentage of Children - - - - - - - - - - - - - - - - - - - - -
Boys & Girls
1–2 2023 45.1 98.9 78.5 19.0 81.4 85.7 95.1 71.8
3–5 4386 44.6 99.1 75.5 25.2 79.6 89.6 93.1 82.7
Boys
6–9 758 46.3 98.7 66.3 35.5 77.4 93.4 93.5 87.2
10–11 991 42.9 97.8 63.2 33.4 78.3 90.2 92.2 86.0
12–19 696 39.4 90.4 35.9 35.4 67.5 76.0 76.8 75.8
Girls
6–9 665 26.3 98.9 53.5 28.0 77.8 83.4 85.7 77.0
10–11 922 27.9 95.3 50.4 27.7 75.1 80.5 83.8 74.7
12–19 702 25.2 76.2 30.6 24.0 57.7 68.0 64.4 61.9
Adapted from USDA, Agricultural Research Service, Food and Nutrient Intakes by Children 1994-96, 1998, 1999,
Allowances (RDAs), by Sex and Age, Two-Day Average, Continuing Survey of Food Intake by
Sex and
Age Vitamin Vitamin
(Years) B6 Folate B12 Calcium Phosphorus Magnesium Iron Zinc Selenium
- - - - - - Number - - - - - - - - - - - - - - - - - - - - Percentage of Children - - - - - - - - - - - - - - - - - - - -
Boys & Girls
1–2 65.5 99.0 99.0 49.9 65.6 97.4 44.5 15.2 97.9
3–5 75.7 99.1 98.0 48.4 75.3 95.2 65.7 30.4 99.7
Boys
6–9 68.9 96.6 97.9 63.0 89.9 85.6 82.9 49.6 99.4
10–11 67.9 95.5 97.8 57.2 83.3 77.2 81.6 47.0 99.1
12–19 53.8 73.2 92.5 36.2 72.9 33.4 83.2 34.6 97.4
Girls
6–9 56.1 95.6 96.9 47.3 78.9 80.2 69.5 32.7 99.3
10–11 55.1 90.6 93.9 43.2 73.1 68.3 61.5 31.9 98.3
12–19 42.4 58.3 73.9 13.4 33.6 17.8 27.5 23.9 86.4
TABLE 8.15
Nutrient Intakes: Mean Percentage of Calories from Protein, Total Fat, Saturated
Fat, and Carbohydrate, by Sex and Age, One-Day, Continuing Survey of Food
Intakes by Individuals 1994–1996, 1998
Sex and Age Sample Size Protein Total Fat Saturated Fat Carbohydrate
(Years) Number - - - - - - - - - - - - - Percentage of kcal - - - - - - - - - - - - -
Boys & Girls
1–2 2118 14.8 32.4 13.3 54.3

3–5 4574 14.2 32.2 12.1 55.2
Boys
6–9 787 14.0 32.5 12.0 54.9

6–11 1031 14.0 32.6 12.0 54.8
12–19 737 14.4 33.1 11.7 53.2
Girls
6–9 704 13.9 32.4 11.9 55.2

6–11 969 13.9 32.6 11.9 54.9
12–19 732 14.0 32.2 11.3 55.0
Adapted from USDA, Agricultural Research Service, Food and Nutrient Intakes by Children 1994-
96, 1998, 1999, Online, ARS Food Surveys Research Group, available on the “Products” page
at http://www.barc.usda.gov/bhnrc/foodsurvey/home.htm (accessed December 22, 1999).
TABLE 8.16
Nutrient Intakes: Percentage of Children with Diets Meeting Recommendations for Total Fat,
Saturated Fatty Acids, and Cholesterol, by Sex and Age, Two-Day Average, Continuing Survey of
Food Intakes by Individuals 1994–1996, 1998
Total Fat Intake at or Saturated Fatty Acid Intake Cholesterol Intake at or
Sex and Age below 30% of kcal below 10% of kcal below 300 Milligrams
(Years) Sample Size - - - - - - - - - - - - - - - - - - Percentage of Children - - - - - - - - - - - - - - - - - -
Boys & Girls
1–2 2023 34.2 18.2 85.5

3–5 4386 33.0 22.6 84.6
Boys
6–9 758 30.5 22.5 80.4

10–11 991 31.3 24.9 79.1
12–19 696 30.4 27.6 55.9
Girls
6–9 665 32.6 23.4 86.2

10–11 922 33.5 24.5 85.5
12–19 702 35.4 33.5 80.9
Adapted from USDA, Agricultural Research Service, Food and Nutrient Intakes by Children 1994-96, 1998, 1999,
Vitamin-Mineral Supplements
According to the Food and Nutrition Board, the “RDAs can typically be met or closely
approximated by diets that are based on the consumption of a variety of foods from diverse
food groups that contain adequate energy.”1,29 According to the American Dietetic Asso-
ciation,30 children can best achieve healthful eating habits by consuming a varied diet in
moderation10 that includes foods from each of the major food groups, as illustrated by the
Food Guide Pyramid.18 Routine supplementation is not necessary for healthy growing
children who consume a varied diet, according to the American Academy of Pediatrics.31
If parents wish to give supplements to their children, a standard pediatric vitamin-mineral
product with nutrients in amounts no larger than the RDA may be given. Megadose levels
should be discouraged due to potential toxic effects. Parents should be cautioned to keep
vitamin-mineral supplements out of the reach of children because the taste, shape, and
color of most pediatric preparations make them quite appealing to children.
Although the American Academy of Pediatrics advocates that routine vitamin-mineral
supplementation is not necessary for healthy growing children who eat a varied diet, it
does identify five groups of children at nutritional risk who may benefit from supplemen-
tation.31 These groups are identified in Table 8.17. Dietary intake over several days should
be assessed by a Registered Dietitian to determine if an individual child from one of these
groups needs to take a supplement.
TABLE 8.17
Five Groups of Children at Nutritional Risk Who May Benefit from Vitamin-Mineral
Supplementation
• Children from deprived families or who suffer parental neglect or abuse
• Children with anorexia or an inadequate appetite or who consume a fad diet
• Children with chronic disease (e.g., cystic fibrosis, inflammatory bowel disease, hepatic disease)
• Children who participate in a dietary program for managing obesity
• Children who consume a vegetarian diet without adequate dairy products
From Committee on Nutrition, American Academy of Pediatrics, Feeding from Age One Year to Adolescence,
Pediatric Nutrition Handbook, 4th ed., Kleinman, R. E., Ed., American Academy of Pediatrics, Elk Grove Village,
IL, 1998, pg 125, with permission.
Development of Preschool Children’s Food Preferences and Consumption

Patterns
Widespread evidence indicates that the nutrition guidelines are not being followed by
most children. For example, most children consume far too few fruits and vegetables,22,32-
34 and the majority of children still exceed daily recommendations for total fat, saturated
fat, and cholesterol.35 Furthermore, the incidence of childhood obesity has increased dra-
matically during the last three decades.36,37 To help understand why children eat less of
what is recommended by nutrition guidelines and more of what is not recommended,
and why the incidence of childhood obesity is increasing, Birch and Fisher38 recommend
that consideration be given to factors that impact children’s food preferences and con-
sumption patterns. Extensive evidence suggests that children’s food preferences are
shaped by early experience with food and eating, and that family environment and
practices used by parents and other adults (e.g., school staff) may permanently affect
dietary practices of children.39 Birch and colleagues40 have repeatedly found that exposure
to food, as well as the social environment in which it is eaten, are crucial in the develop-
ment of preschool children’s food preferences and consumption patterns. Research indi-
cates that children’s food preferences are major determinants of consumption;41-45
therefore, not eating certain items (such as vegetables) is related to low preferences.
Furthermore, research indicates that preschool children’s preferences for dietary fat are
related to their levels of body fat.45
Learning to Eat
During the first years of life, an enormous amount of learning about food and eating
occurs as infants transition from consuming only milk to consuming a variety of foods,38
and from eating when depleted or hungry to eating due to a variety of social, cultural,
environmental, and/or physiological cues.46 According to Birch and Fisher,38 this transition
from univore to omnivore is shaped by the infant’s innate preference for sweet and salty
tastes and the rejection of sour and bitter tastes,47 and by the predisposition of infants and
children to be neophobic or to reject new foods.48 A child’s experience with food and
flavors is shaped beginning with the parents’ decision to breastfeed or formula-feed.38
Limited research indicates that breastfed infants eat more of new foods than formula-fed
infants, which suggests that the varied flavors in breastmilk facilitate the breastfed infant’s
acceptance of new foods during the weaning period.49
Exposure to Food and Preschool Children’s Food Preferences and Consumption

Table 8.18 includes three studies by Birch and colleagues50-52 which indicate that preschool
children’s neophobia or rejection of new foods can be overcome by exposure. Results from
TABLE 8.18
Research Concerning Exposure to Food and Preschool Children’s Food Preferences and
Consumption
Reference Authors and Year Subjects Study Design Results
50 Birch and Marlin, 14 two-year-olds Each child received Later, children ate
1982 2-20 exposures to 5 more of items with
novel fruits or higher exposures
cheeses over 25-26 when given pairs of
days items and asked to
taste both and pick
one to eat more of
51 Birch et al., 1987 43 children in 3 age Each child received 5, For all age groups,
groups: 26, 38, or 64 10, or 15 exposures to preferences increased
months old 7 new fruits; asked to significantly only
taste some and look at when foods were
others tasted
52 Sullivan and Birch, 39 children, 4-5 years Each child tasted 1 of 3 Preferences increased
1990 old versions of tofu with exposure
(sweetened, salty, or regardless of added
plain) 15 times over sugar, salt, or plain;
several weeks 10 exposures needed
these studies indicate that preschool children’s food preferences are learned through
repeated exposure to foods.
Social Environment of Eating and Preschool Children’s Food Preferences and

Consumption
Although exposure and availability are necessary for children to learn to accept new foods,
the social environment of eating is also important. Children learn about what to eat and
why to eat, and receive reinforcements and incentives for eating from their families and
the larger environment.53 Most of this learning occurs during routine mealtime experi-
ences, in the absence of formal teaching.40 For example, adults who want children to eat
healthful foods (e.g., vegetables) may bribe children with rewards for eating healthful
foods. However, research indicates that such practices actually lead children to dislike the
healthful foods, which is not what adults intend. The five studies54-58 included in Table
8.19 indicate the importance of the social environment of eating and food contingencies
(i.e., “if you eat __, then you can __”) on preschool children’s food preferences and
consumption. Results from another study of influential factors of caregiver behavior at
lunch in early child-care programs indicated that although caregivers believed they pos-
itively influenced children’s eating behaviors, observed behaviors of caregivers at meal-
times were inconsistent with expert recommendations.59
Adult Influences on Preschool Children’s Ability to Self-Regulate Caloric

Intake
Infants are born with the ability to self-regulate their kcal intake by adjusting their formula
intake when the kcal level of the formula changes60 and when solid foods are added.61
Preschool children are able to adjust the kcal eaten in a snack or meal, based on the kcal
eaten in a preload snack.62,63 Furthermore, preschool children are able to adjust the kcal
eaten at various meals and snacks during the day so that the number of kcal consumed
in a 24-hour period is relatively constant.64 Although children have the ability to self-
regulate their kcal intake, the two studies65,66 included in Table 8.20 indicate that this ability
may be negatively impacted by child-feeding practices that encourage or restrict children’s
eating. Using observations of family meal times, Klesges and colleagues67 found that
parental prompts, especially encouragements to eat, were highly correlated to preschool
children’s relative weight, and increased the probability that a child would eat. Further-
more, a child’s refusal to eat usually led to a parental prompt to eat more food, whereas
a child’s food request was not likely to elicit either a parental prompt to eat or subsequent
eating by the child.
According to Birch,46 child feeding practices that encourage children to eat in response
to external cues instead of internal cues regarding hunger and satiety “may form the basis
for the development of individual differences in styles of intake control that exist among
adults. Some of the problems of energy balance seen in adulthood may result from styles
of intake control in which hunger and satiety cues are not particularly central.” According
to the American Dietetic Association,30 “perhaps some of the best advice regarding child
feeding practices continues to be the division of parental and child responsibility advo-
cated by Satter.” Satter advocates that parents (or adults) are responsible for presenting a
variety of nutritious and safe foods to children at regular meal- and snack-times, as well
as the physical and emotional setting of eating; children are responsible for deciding how
much, if any, they will eat.68,69
TABLE 8.19
Research Concerning Social Environment of Eating and Preschool Children’s Food Preferences and
Consumption
54 Birch et al., 1980 64 children, 3-4 years Children given sweet Preferences increased
old; 16 per context or nonsweet foods when foods
(with initially neutral presented as rewards,
preferences) over or paired with adult
several weeks in 1 of greeting; effects
4 contexts: lasted longer than 6
1) as reward for weeks after contexts
behavior, 2) paired ended; suggest
with adult greeting, positive social
3) as nonsocial contexts can be used
behavior (put in to increase
child’s locker), or 4) at preferences for foods
snack time not liked but more
nutritious
55 Birch et al., 1982 12 children, 3-5 years Children told if they Instrumental (“if”) use
old drank juice, then they of juice reduced
could play preferences for it
56 Birch et al., 1984 31 children, 3-5 years Children told if they Instrumental (“if”) use
old drank milk drink, of milk beverage
then they received reduced preferences
verbal praise or a for it
movie
57 Newman and 86 children, 4-7 years Children told that if “If” snacks became less
Taylor, 1992 old they ate one snack, preferred and “then”
then they could eat snacks became more
another snack (with preferred
both of neutral
preference initially)
58 Hendy, 1999 64 preschool children To encourage Choice-offering and
acceptance of 4 new reward were more
fruits and vegetables effective than other
during 3 preschool actions; Hendy
lunches, teachers concluded that
used 1 of 5 actions: dessert rewards are
1) choice-offering not needed because
(“Do you want any of the less expensive
this?”), 2) reward and more nutritious
(special dessert), action of choice-
3) insisting children offering works as
try one bite, 4) well
modeling by teacher,
or 5) simple exposure
Feeding Toddlers and Preschool Children

Young children cannot innately choose a well-balanced diet. They depend on adults to
offer them a variety of nutritious and developmentally appropriate foods. A child’s intake
at individual meals may vary considerably, but the total daily caloric intake remains fairly
constant.64 Many parents become anxious about the adequacy of their young child’s diet
or frustrated with their child’s unpredictable eating behavior which may include refusals
TABLE 8.20
Research Concerning Adult Influences on Preschool Children’s Ability to Self-Regulate Caloric
Intake
65 Birch et al., 1987 22 children, 4 years old Flavored pudding Only children
preload of different encouraged to focus
kcal followed by ad on internal cues
lib snacks; children showed sensitivity to
encouraged to focus kcal density of
on either internal preload by
cues (hunger, satiety) decreasing kcal eaten
or external cues (time in snack after preload
of day, amount left, that was high in kcal
rewards) (and vice versa)
66 Johnson and Birch, 77 children, 3-5 years Preload snacks of Children with greater
1994 old different kcal body fat stores were
followed by ad lib less able to regulate
foods; children’s kcal consumption in
body fat measured; response to
mothers completed alterations in preload
questionnaire snacks; more
regarding their controlling mothers
degree of control of had children who
what and how much showed less ability to
their children ate self-regulate
(r = 0.67).
to eat certain foods, and food jags. Parents may resort to feeding tactics such as bribery,
clean your plate rules, struggles, or short-order cooking to encourage their child to eat. A
more healthful approach is Satter’s division of feeding responsibility (see “Adult Influ-
ences on Preschool Children’s Ability to Self-Regulate Caloric Intake” in this section).
Table 8.21 contains suggestions for concerns parents commonly encounter when feeding
young children. Table 8.22 contains healthful eating tips to use with young children.
Snacks
Most young children fare best when fed four to six times a day, due to their smaller
stomach capacities and fluctuating appetites. Snacks should be considered minimeals by
contributing to the total day’s nutrient intake. Snacks generally accepted by many children
include fresh fruit, cheese, whole-grain crackers, breads (e.g., bagels, tortilla), milk, raw
vegetables, 100% fruit juices, sandwiches, peanut butter on crackers or bread, and yogurt.
Choking
Young children should always be watched while eating meals and snacks because they
are at risk for choking on food. Children remain at risk for choking on food until around
age four years when they can chew and swallow better. Foods most likely to cause
problems include ones that are hard, round, and do not readily dissolve in saliva. Table
8.23 contains a list of foods that may cause choking, along with some tips to decrease
young children’s risk of choking. Any food can cause choking if the child is not supervised
while eating, if the child runs while eating, or if too much food is stuffed in the mouth.
TABLE 8.21
Suggestions for Concerns Parents Commonly Encounter when Feeding Children
If a child refuses to try new foods
• Remember, this is normal! Continue to offer each new food twice per week for a total of 10-12 times.
• Serve a new food with familiar ones.
• Ask the child if s/he would like to try some of the new food, but avoid forcing or bribing the child to eat the
new food. Be an effective role model and eat some of the new food yourself.
• Involve the child in shopping for and preparing the new food.
If a child refuses to eat what is served
• Remember, children may have strong likes and dislikes, but this does not mean they need to be served different
foods than the rest of the family.
• Allow the child to choose from the foods available at a meal what s/he will eat, but avoid forcing or bribing
him/her to eat.
• Include at least one food at each meal that you know your child will eat, but do not cater to a child’s likes
or dislikes. Avoid becoming a short-order cook. The less attention paid to this behavior, the better.
If a child is stuck on a food jag or wants to eat the same food over and over
• Children may want to eat only one or two foods day after day, meal after meal; common food jags occur with
peanut butter and jelly sandwiches, pizza, macaroni and cheese, and dry cereal with milk.
• Relax, and realize this is normal and temporary. Refuse to call attention to the behavior.
• Continue to offer regular meal, but do not force or bribe the child to eat it.
• Serve the food jag item as you normally would (maybe once or twice a week).
If a child refuses to eat meat
• Tough meat is often difficult for children to chew. Offer bite-size pieces of tender, moist meat, poultry, or fish.
• Use meat in casseroles, meatloaf, soup, spaghetti sauce, pizza, or burritos.
• Try other high-protein foods such as eggs, beans, and peanut butter.
If a child refuses to drink milk
• Offer cheese, cottage cheese, yogurt, or pudding either alone or in combination dishes (such as macaroni and
cheese, pizza, cheese sauce, banana pudding).
• Use milk when cooking hot cereals, scrambled eggs, macaroni and cheese, soup, and other recipes.
• Use calcium-fortified juices.
If a child refuses to eat vegetables and fruits
• Offer more fruits if a child refuses vegetables, and vice versa.

• Avoid over-cooking vegetables; serve vegetables steamed or raw (if appropriate). Include dips or sauces (e.g.,
applesauce with broccoli or carrots).
• Include vegetables in soups and casseroles.
• Continue to offer a variety of fruits and vegetables.
If a child eats too many sweets
• Avoid using sweets as a bribe or reward.

• Limit the purchase and preparation of sweet foods in the home.
• Incorporate sweets into meals instead of snacks for better dental health.
• Try using fruit as dessert.
Adapted from Lucas, B., Normal Nutrition from Infancy through Adolescence, Handbook of Pediatric Nutrition,
Queen, P. M., Lang, C. E., Eds., Aspen, Gaithersburg, MD, 1993, pg 145.
TABLE 8.22
Healthful Eating Tips to Use with Young Children
Be Patient
Because young children are often afraid to try new foods...

• Offer a new food more than once; food may be accepted when it becomes familiar to the child.
• Offer new foods in small “try me” portions (one to two tablespoons) and let the child ask for more.
• Show the child how the rest of the family enjoys the new food.
Be a Planner
Most children need three regular meals plus one or two snacks each day.
• For breakfast and lunch, offer foods from three or more of the five pyramid food groups.
• For the main meal, offer foods from four or more of the five pyramid food groups.
• For snacks, offer foods from two or more of the five pyramid food groups. Make sure that snacks are not
served too close to mealtime.
Be a Healthful Role Model
Remember, what you do can mean more than what you say.
Children learn about how and what to eat from routine eating experiences.
• Eat meals with children whenever possible.
• Try new foods and new preparation methods.
• Walk, run, and play with children instead of just watching them.
Be Adventurous
• Take children grocery shopping and let them choose a new vegetable or fruit from two or three choices.
• Have a weekly “family try-a-new-food” night.
• At home, allow children to help you wash and prepare food.
Be Creative
• Encourage children to invent a new snack or sandwich from three or four healthful ingredients you provide.
• Try a new bread or whole grain cracker.
• Talk about food groups in the new snack or sandwich, how they taste — smooth, crunchy, sweet, juicy, chewy,
and how colorful the items are.
Adapted from Tips for Using Food Guide Pyramid for Young Children, USDA, Center for Nutrition Policy and
Promotion, Washington, DC, 1999, Program Aid 1647.
Excessive Fruit Juice Consumption

Fruit juice, especially apple, is a common beverage for young children. Although fruit
juice is a healthful, low-fat, nutritious beverage, there are some health concerns regarding
excessive fruit juice consumption by young children. For example, drinking fruit juice
helps fulfill nutrition recommendations to eat more fruits and vegetables. However, as
children increase their intake of fruit juices, they may decrease their intake of milk,70 which
can decrease their intake of calcium unless the juice is calcium-fortified. This is a concern
because results from the CSFII 1994–1996, 1998 indicated that only ~50% of children ages
one to five years met the 1989 RDAs for calcium.28 Carbohydrate malabsorption is common
following the ingestion of several fruit juices in young children with chronic nonspecific
diarrhea as well as in healthy young children.71 In 1991, a policy statement by the Com-
mittee on Nutrition of the American Academy of Pediatrics recommended that parents
be cautioned about young children’s potential gastrointestinal problems associated with
the ingestion of excessive amounts of juices containing sorbitol (e.g., apple, pear, and
prune), which is a naturally occurring but nonabsorbable sugar alcohol.72 Excess fruit juice
TABLE 8.23
Choking in Young Children
Foods that May Cause Choking in Young Children
• frankfurters (hot dogs) • raisins • popcorn

• chunks of meat • whole grapes • chips
• nuts and seeds • cherries with pits • pretzels
• peanut butter (spoonful) • large pieces of fruit • marshmallows
• raw carrots or celery • round or hard candy
Tips to Decrease Young Children’s Risk of Choking
• Cut frankfurters lengthwise into thin strips.

• Cook carrots or celery until slightly soft and then cut into sticks.
• Cut grapes or cherries into small pieces.
• Spread a thin layer of peanut butter on a cracker instead of allowing young
children to eat peanut butter from a spoon.
• Insist that young children sit down while eating so they can concentrate on
chewing and swallowing.
• Always watch young children while they eat meals and snacks.
• Discourage allowing a young child to eat in the car if the only adult present is
driving because it may be difficult for the adult to quickly aide a choking child.
Adapted from Tips for Using the Food Guide Pyramid for Young Children 2 to 6 Years
Old, USDA, Center for Nutrition Policy and Promotion, Washington, DC, 1999,
Program Aid 1647.
consumption may present a contributing factor in nonorganic failure to thrive.73 Drinking

12 or more fluid ounces of fruit juice per day is associated with short stature and with
obesity in young children;74 thus, it is recommended that parents and caretakers limit
young children’s consumption of fruit juice to less than 12 ounces per day.70,74
Low-Fat Diets
Emphasis regarding low-fat, low-cholesterol diets has increased during the past decade,
as has the debate over whether low-fat diets are appropriate for children.75-80 Parental
concern about later atherosclerosis or obesity has led to failure to thrive in some infants
age 7 to 22 months who were fed very low-fat, calorie-restricted diets.81 The American
Academy of Pediatrics Committee on Nutrition supports recommendations that children
older than two years follow a diet with a maximum of 30% of calories from fat and no
more than 300 mg of cholesterol per day.9 (Ages two to five years represent a transition
between the higher fat intake during infancy and the population-based recommended fat
intake). Nonfat and low-fat milks are not recommended for use during the first two years
of life.
The Special Turku coronary Risk factor Intervention Project for Babies (STRIP Baby Trial)
evaluated the effects of a low-saturated fat diet on growth during the first three years of
life in 1062 healthy infants who were randomized at age seven months into an intervention
group (n = 540) or control group (n = 522).82 The intervention consisted of individualized
dietary counseling provided to parents at one- to six-month intervals to reduce risk factors
to atherosclerosis. Results indicated that mean fat intake of children in both groups was
lower than expected, especially during the first two years of life. The true mean of the
height of intervention boys was at most 0.34 cm more or 0.57 cm less, and the weight was
at most 0.19 kg more or 0.22 kg less than that of control boys. The respective values for
girls were at most 0.77 cm more or 0.16 cm less and at most 0.42 kg more or 0.04 kg less.
Furthermore, there were similar numbers of slim children in both groups. The authors
concluded that a supervised, low-saturated fat, low-cholesterol diet had no influence on
growth of children in the study between 7 and 36 months of age.82 Follow-up analyses
were conducted on intervention and control children who were followed for more than
two years (n = 848) to study the fat and energy intakes of children with different growth
patterns. Results indicated that relative fat intakes (as percent of energy intake) were
similar in children showing highly different height gain patterns. Furthermore, children
with consistently low fat intake grew equally to the children with higher fat intake. The
authors concluded that moderate supervised restriction of fat intake to values between
25 and 30% of kcal is compatible with normal growth in children ages 7 to 36 months.83
The safety and efficacy of lower fat diets in pubertal children have been indicated by
results from the Dietary Intervention Study in Children (DISC). The three-year, six-center
randomized controlled trial involved 663 children; at baseline, boys (n = 362) and girls (n
= 301) had a mean age of 9.7 and 9.0 years, respectively.84 An intervention group (n = 334)
followed a diet with 28% of kcal from total fat, ~10% of kcal from saturated fat, and 95
mg/day of cholesterol. A comparable usual care group (n=329) consumed ~33% of kcal
from total fat, ~12% of kcal from saturated fat, and 113 mg/day of cholesterol. The
intervention group had significant but modestly lower levels of LDL-cholesterol and
maintained a psychologic well-being; however, there were no differences in height, weight,
or serum ferritin levels in the two groups. The authors concluded that a properly designed
dietary intervention is effective in achieving modest lowering of LDL cholesterol levels
over three years while maintaining adequate growth, iron stores, nutritional adequacy,
and psychological well-being during the critical growth period of adolescence. Further-
more, “an important public health inference from the DISC results is that current dietary
recommendations for healthy children, which are less restricted in total fat than the DISC
diet, can be advocated safely, particularly when children are under health care that follows
their growth and development.”84 Follow-up analyses were conducted to assess the rela-
tionship between energy intake from fat and anthropometric, biochemical, and dietary
measures of nutritional adequacy and safety.85 Results indicated that lower fat intakes
during puberty were nutritionally adequate for growth and maintenance of normal levels
of nutritional biochemical measures; furthermore, they were associated with beneficial
effects on blood folate and hemoglobin. Lower fat diets were related to lower self-reported
intakes of several nutrients (i.e., calcium, zinc, magnesium, phosphorus, vitamin B12,
thiamin, niacin, and riboflavin); however, no adverse effects were observed on blood
biochemical measures of nutritional status. The authors concluded that “current public
health recommendations for moderately lower fat intakes in children during puberty may
be followed safely.”85
Further evidence regarding the safety and efficacy of lower fat diets in upper elementary
school children (third through fifth grades) has been provided by the Child and Adolescent
Trial for Cardiovascular Health (CATCH), which is described more fully later in this
section. Results from CATCH failed to indicate any evidence of deleterious effects of the
three-year intervention on growth or development of children who were third-graders at
the beginning of the intervention.86
Group Feeding
Many young children spend some or most days away from home in child care centers,
preschools, Head Start programs, or home child care centers, where they may eat up to
two meals and two snacks daily. Federal and state regulations or guidelines exist for food
service in child care centers, Head Start programs, and preschool programs in public
schools. Some centers participate in USDA-sponsored child nutrition programs. When

choosing a child care center or preschool, parents should be encouraged to consider the
feeding program, including food variety, quality, safety, cultural aspects, and develop-
mental appropriateness. Peer pressure regarding food and eating among preschoolers is
evident in a study by Birch which indicated that the food selections and eating behaviors
of preschool children influenced the food preferences and eating behaviors of other
preschool children.87
Portion Sizes
Portion sizes for young children are small, especially when compared with adult portions.
A rule-of-thumb method is to initially offer one tablespoon of each food for every year of
age for preschool children; more food may be provided according to appetite.
Limited research indicates the effects of portion size on children’s food intake.88 Sixteen
younger (three years) and 16 older (five years) preschool children participated in three
lunches during their usual lunchtime at day-care. Each lunch consisted of macaroni and
cheese served in either small, medium, or large portion sizes, along with set portion sizes
of carrot sticks, applesauce, and milk. Results indicated that older preschoolers consumed
more macaroni and cheese when served the large portion compared to the small portion
(p<0.002). However, portion sizes did not significantly affect food intake among younger
preschoolers. These results indicate the important role of portion size in shaping children’s
dietary intake, and imply that portion size can either promote or prevent the development
of overweight among older preschool children. Furthermore, these results indicate the
importance of encouraging preschool children to focus on their own internal cues of
hunger and satiety instead of “eating everything to clean the plate.”88
Feeding School-Age Children

During the school-age years (ages 6-12), steady growth is paralleled by increased food
intake. Although children tend to eat fewer times a day, after-school snacks are common.
Studies indicate that eating breakfast is related positively to children’s cognitive function
and school performance, especially for undernourished children (for a review, see Refer-
ence 89). Specifically, schoolchildren who had fasted both overnight and in the morning,
particularly children who were nutritionally at risk, demonstrated slower stimulus dis-
crimination, increased errors, and slower memory recall.90 According to Grantham-McGre-
gor, “studies to date have provided insufficient evidence to determine whether children’s
long-term scholastic achievement is improved by eating breakfast daily.”91
Although eating breakfast is important, research indicates that between 6 and 16% of
elementary school children skip breakfast.92-94 Furthermore, between 1965 and 1991, break-
fast consumption declined significantly for each age group of children (1-4 years, 5-7 years,
8-10 years) and adolescents (11-14 years and 15-18 years), especially for older adolescents
age 15-18 years; breakfast was consumed by 89.7% of boys and 84.4% of girls in 1965, and
by 74.9 and 64.7%, respectively, in 1991.95 Children who skip breakfast tend to have a
lower kcal intake and consume fewer nutrients than children who eat breakfast.92,93 During
the upper elementary years, children may skip breakfast due to time constraints, because
school starts early, due to the responsibility of getting themselves ready in the morning,
or simply because they do not feel like eating. When breakfast nutrient consumption
patterns of third graders were examined using baseline data from CATCH, 94% of the
1872 children from 96 public schools in four states reported eating breakfast on the day
of the survey.92 Of the 94% who ate breakfast, 80% ate at home, 13% ate at school, 3% ate
at both home and school, and 4% ate breakfast elsewhere.
National School Lunch and Breakfast Programs

One in ten children gets two of their three major meals in school, and more than half get
one of their three major meals in school.96 The National School Lunch Program (NSLP) is
a federally assisted meal program available in almost 99% of all public schools and to
about 92% of all students in the country.97 On a typical day, about 58% of the students to
whom it is available participate. Regulations stipulate that a NSLP lunch provide one-
third of the RDAs for kcal, protein, iron, calcium, and vitamins A and C. Schools may
choose one of four systems for planning their menus; two options are based on a com-
puterized nutritional analysis of the week’s menu, and the other two options are based
on minimum component quantities of meat or meat alternate, vegetables and fruits, grains
and breads, and milk.97
The School Breakfast Program (SBP) is available to approximately half of the nation’s
students in more than 70,000 schools.98 On a typical day, about 7.2 million children par-
ticipate. Regulations stipulate that a SBP breakfast provide one-fourth of the RDAs for
kcal, protein, iron, calcium, and vitamins A and C.98
Any child at a participating school may purchase a NSLP lunch or SBP breakfast.
Children from families with incomes at or below 130% of the poverty level are eligible for
free breakfasts and lunches. Those between 130 and 185% of the poverty level are eligible
for reduced-price breakfasts and lunches. The federal government reimburses the schools
for each breakfast and lunch that meets SBP and NSLP requirements, respectively.97,98
Impact of School Meals on Children’s Dietary Intake

The School Nutrition Dietary Assessment Study (SNDAS) collected information on school
meals from a nationally representative sample of schools (n=545) and 24-hour recalls
from approximately 3350 students from these schools in spring, 1992.99 Results from the
SNDAS regarding dietary intakes of NSLP participants and nonparticipants100 indicated
that 1) NSLP participants had higher lunch intakes of vitamin A, calcium, and zinc, and
lower intakes of vitamin C than nonparticipants who ate lunch; 2) NSLP participants’
lunches provided a higher percentage of kcal from fat and saturated fat, and a lower
percentage of carbohydrate than nonparticipants’ lunches; 3) NSLP participants were
more than twice as likely as nonparticipants to consume milk and milk products at lunch;
and 4) NSLP participants also consumed more meat, poultry, fish, and meat mixtures
than nonparticipants.
Results from the SNDAS regarding dietary intakes of SBP participants and
nonparticipants100 indicated that 1) SBP participants had higher average breakfast intakes
of kcal, protein, and calcium, and derived a greater proportion of kcal from fat and saturated
fat than nonparticipants; 2) SBP participants were three times more likely than nonpartic-
ipants to consume meat, poultry, fish, or meat mixtures at breakfast; and 3) SBP participants
were also more likely than nonparticipants to consume milk or milk products at breakfast.
The most surprising finding from the SNDAS was that the presence of the SBP in schools
did not affect the likelihood that a student ate breakfast before starting school. Research is
needed to determine the best ways to encourage elementary school students to consume
healthful breakfasts. Universal school breakfast, which allows all students to eat school
breakfast for free, has been advocated by some as a means to increase the percentage of
children who eat breakfast. However, results from the SNDAS indicated that approximately
42% of children who were eligible for free or reduced price school breakfast did not eat
it.94 Perhaps scheduling the SBP for classes to eat as a part of regular school hours (similar
to the NSLP) is needed to increase the percentage of children who eat breakfast.
Results from a study by Baranowski et al.101 indicate the important contribution that
school lunch makes in increasing children’s consumption of fruits and vegetables. Differ-
ences in children’s consumption of fruits and vegetables by meal and day of the week
were assessed using seven-day food records completed by 2984 third-graders from 48
elementary schools in the Atlanta, Georgia area. Results indicated that fruits and vegeta-
bles were most frequently consumed at weekday lunch, and second most frequently at
dinner. Participation in school lunch accounted for a substantial proportion of fruits and
vegetables consumed at lunch. Few fruits and vegetables were consumed at breakfast or
snack.101
Impact of Elementary Schools on Older Children’s Food Preferences and Consumption

Patterns
The impact of exposure and social environment on preschool children’s food preferences
and consumption is discussed earlier in this section. Limited research indicates that expo-
sure to food also plays a role in older children’s food preferences and consumption. Results
from a study by Hearn et al.102 indicated that availability and accessibility to fruits and
vegetables (as assessed by telephone interviews with parents) was positively related to
upper elementary school children’s preferences and consumption. Furthermore, children
ate more fruits and vegetables for lunch at schools that offered more fruits and vegetables
for lunch.
Research with upper elementary school children indicates that they prefer vegetables
less than fruits.43,103,104 Results from focus groups with ~600 fourth- and fifth-grade students
from Georgia, Alabama, and Minnesota indicate that children predominantly believe that
vegetables taste “nasty”104 and “if it’s good for you, then it must taste bad”103,104 which is
related to statements made by adults such as “I don’t care if they don’t taste good; eat
your vegetables because they’re good for you.”104 Research concerning the influence of a
variety of psychological and social factors on children’s fruit and vegetable consumption
indicates that preferences are the strongest predictors.44,105 This implies that interventions
that alter children’s preferences for fruits and vegetables will be more effective in increas-
ing their consumption than other strategies pursued to date. However, intensive school-
based interventions designed to specifically increase children’s preferences for fruits and
vegetables have had limited success.32,106,107 Furthermore, although some elementary
school programs have helped children to improve their dietary intake,108 intensive inter-
ventions specifically designed to increase children’s fruit and vegetable consumption have
had only limited success.32,106,107,109-111 Finally, schools may represent a potentially useful
setting for preventing childhood obesity, but comprehensive elementary school programs
in the U.S. such as CATCH and Know Your Body have not had major effects on children’s
body weight.108,112,113 Perhaps the limited success of elementary school-based interventions
to date to increase children’s preferences for and consumption of fruits and vegetables,
and to help prevent childhood obesity is because the interventions have not attempted to
educate school staff and parents about how their behaviors impact children’s food pref-
erences and consumption patterns.
Children have acquired knowledge about eating and have developed food preferences
by the time they enter school; however, their food preferences and consumption patterns
are continually modified because they eat daily.114 More than 95% of children in the U.S.
are enrolled in school, where they may eat one or two meals per school day.115 Thus,
elementary schools play a critical role in shaping children’s food acceptance patterns and
can therefore help to improve their diet.116 No other public institution has as much con-
tinuous and intensive contact with children during their first two decades of life than
public schools.113 Elementary school staff have a greater potential influence on a child’s
health than any other group outside of the home.117 School-based programs offer a sys-
tematic and efficient means to improve the health of youth in America by promoting
positive lifestyles.118 Health promotion programs in elementary schools have the potential
to help prevent chronic diseases in U.S. adults.117 Although school-based health programs
may promote healthful lifestyles, classroom lessons are not sufficient to produce lasting
changes in students’ eating behaviors.53 In fact, curriculum-based nutrition education in
schools has had minimal effects on student’s eating behavior.119 Children’s food prefer-
ences and consumption are influenced by the elementary school environment through
familiarity and reinforcement.120 Students of public elementary schools generally attend
for 7 hours a day, 180 days a year. Although students have options for obtaining food in
schools, the most prominent federally supported programs are the SBP and the NSLP.
Elementary school breakfast and lunch menus typically follow a cycle that repeats
several times during the school year; thus, children are provided with repeated exposures
to healthful foods (e.g., fruits and vegetables).121 However, elementary schools also provide
children with repeated exposures to other foods (e.g., candy and pizza) which are used
by school staff as rewards.53,122-124 Unfortunately, the social context in which vegetables are
often offered at school (e.g., “If you eat your peas, then you can eat your cookie”) probably
negatively affects preferences for them, thereby potentially decreasing their consump-
tion.121 However, the social context in which candy and pizza are offered probably posi-
tively affects preferences for those foods, thereby potentially increasing their
consumption.121 These repeated exposures to vegetables and foods such as candy and
pizza in negative and positive social contexts, respectively, provide the associative learning
that help children develop food consumption patterns that are inconsistent with nutrition
guidelines40 which recommend increased intake of vegetables but moderation in sugar
and fat intake.10,29,125,126 In addition, school staff often encourage children to finish all of
their food, regardless of whether or not the children are still hungry,122 which encourages
children to disregard their own feelings of hunger and satiety.
Concern regarding the impact of school staff on children’s food preferences and con-
sumption patterns has been voiced by several government and professional groups.
According to the Centers for Disease Control and Prevention,116 students need exposure
to healthful foods as well as the support of people around them, and teachers need to be
discouraged from using food for disciplining or rewarding students. According to the
American Dietetic Association, “… the nutrition goals of the National School Lunch
Program and School Breakfast Program should be supported and extended through school
district policies that create an overall school environment with learning experiences that
enable students to develop lifelong, healthful eating habits.”127 Furthermore, the American
Dietetic Association recommends that school meals be served in an environment that
encourages their acceptance,128 or a setting and atmosphere that encourages their con-
sumption,127 which may be interpreted to mean an environment that avoids the use of
food contingencies. A joint statement by the American Dietetic Association, Society for
Nutrition Education, and the American School Food Service Association indicates that
schools are to be healthful environments where the cafeteria and food-related policy allow
students the opportunity to make healthful food choices and provide them with models
of healthful food practices.129
Considerable research has been conducted concerning the impact of exposure and the
social context of eating on preschool children’s food preferences, consumption, self-regu-
lation of intake, and adiposity. However, research of this type is needed with older
children. According to Hill and Trowbridge,39 insights gained from research concerning
children’s food preferences and consumption patterns “can assist in developing interven-
tions to improve child-feeding practices, which may lead to development of healthier
eating patterns.” Parents and school staff need to expose children to healthful foods,
provide opportunities for children to learn to like rather than dislike healthful foods,
encourage children to respect their own feelings of hunger and satiety, and reduce the
extent to which learning and experience potentiate children’s liking for high-sugar and/
or high-fat foods.130 Interventions to increase children’s consumption of foods consistent
with nutrition guidelines and to prevent childhood obesity must educate adults about
their role in the development of children’s food preferences and consumption patterns,
specifically exposure to food, the social context of eating (e.g., food rewards and contin-
gencies), and adult influences on children’s ability to self-regulate caloric intake. Table
8.24 provides five practical applications for adults to use when feeding children.
TABLE 8.24
Five Practical Applications for Adults to Use when Feeding Children
• Offer a variety of healthful foods in a positive environment at regular meal and snack times.
• Instead of requiring children to finish all of their food, encourage them to respect their own feelings of hunger
and satiety. Use choice-offering statements such as “If you’re still hungry, there’s more ___” or “If you’re full,
then you don’t have to eat any more.”
• To help children learn to eat a variety of foods, continue to offer new foods even if a new food is initially
rejected. Ten to 12 exposures at two per week may be needed before a child learns to accept a new food.
• To encourage children to eat or to try new foods, use choice-offering statements such as “Would you like to
try/taste your ___?” Avoid rewarding or bribing children for eating. Also, avoid using food contingencies
(e.g., “If you eat your ___, then you can ___.”)
• Instead of using food as a reward, use non-food items such as stickers or a token economy (e.g., wherein
tokens are exchanged for tangible non-food rewards such as shoe laces, wrist bands, play time).
Childhood Obesity
Overwhelming evidence indicates that the incidence of obesity among children and ado-
lescents has increased dramatically during the last three decades.36,37 According to Dietz,
“obesity is now the most prevalent nutritional disease of children and adolescents in the
United States.”131 Critical periods during the childhood years for the development of
obesity include the period of adiposity rebound that occurs between five and seven years
of age, and adolescence.131 The causes of childhood obesity are multifactorial, including
both genetics and environment. Inactivity appears to play a major role in the increasing
rate of childhood obesity, as does television viewing. Results from the Third National
Health and Nutrition Examination Survey indicated that children ages 8 to 16 years who
watched four or more hours of television each day had greater body fat and greater body
mass index than children who watched television less than two hours each day.132 With
the advances in technology, especially regarding computers, more children are spending
more hours in sedentary states. Preventing childhood obesity is more desirable than trying
to treat obesity during adolescence and adulthood. One critical component of obesity
prevention is increased physical activity; another is educating adults regarding the devel-
opment of children’s food preferences and food consumption patterns. The topic of child-
hood obesity is covered thoroughly in Section 70.
Influences from Peers and Media

Children’s food preferences and consumption patterns can be altered either positively or
negatively by peers and the media. For example, results from the Third National Health
and Nutrition Examination Survey indicated that approximately 26% of U.S. children ages
8 to 16 years watched four or more hours of television each day, and that as hours of
television viewing increased, so did body fat and body mass index.132 Unfortunately,
research indicates that food advertisements aired during children’s Saturday morning
television programming are generally contrary to nutrition recommendations.133
Sugar and Aspartame

Although there are widespread beliefs that both sugar (i.e., sucrose) and aspartame pro-
duce hyperactivity and other behavioral problems in children, both dietary challenge and
dietary replacement studies have demonstrated that sugar has little if any adverse effects
on behavior.134 For example, Wolraich et al.135 conducted a double-blind controlled trial
with 25 normal preschool children and 23 school-age children who were described by
their parents as sensitive to sugar. The different diets that children and their families
followed for each of three consecutive three-week periods were either high in sucrose,
aspartame, or saccharin (placebo). Children’s behavior and cognitive performance were
evaluated weekly. Results strongly indicated that even when intake exceeded typical
dietary levels, neither sucrose nor aspartame had discernible cognitive or behavioral
effects in normal preschool children or in school-age children who were believed to be
sensitive to sugar. Furthermore, the few differences associated with the ingestion of sucrose
were more consistent with a slight calming effect than with hyperactivity.135 Results from
a 1995 meta-analytic synthesis of 16 reports containing 23 controlled double-blind chal-
lenge studies found that sugar did not affect the behavior or cognitive performance of
children; however, a small effect of sugar or effects on subsets of children could not be
ruled out.136
According to Kanarek,134 the strong belief of parents, educators, and medical profession-
als that sugar has adverse effects on children’s behavior may be attributed to several
factors. First, adults may misconceive the relationship between sugar and behavior. Chil-
dren in general have difficulty altering their behavior in response to changing environ-
mental conditions, such as shifting from the unstructured nature of a party or snack time
at school to the more rigorous demands of classwork. If the party or snack included foods
with a high sugar content, adults may relate the child’s sugar intake with behavioral
problems as the child tries to adapt from an unstructured activity to one with structure.
Second, sugar-containing foods such as candy are often forbidden or given to children in
very limited amounts; the prohibited nature of these foods may contribute to the belief
which associates them with increased activity. Finally, expectations of both adults and
children could promote the idea that sugar leads to hyperactivity. Children hear adults
comment that “too much sugar makes children hyper” and children believe them and act
accordingly to fulfill the prophecy.134
Although experimental evidence fails to indicate that sugar affects children’s behavior
and cognition, children should not have unlimited access to sugar, because undernutrition
may occur if foods with essential nutrients are replaced by kcal from sugar; furthermore,
sugar (and starch) can promote tooth decay. On the Food Guide Pyramid,18 sweets are
located at the tip along with fats and oils, indicating that these foods should be used
sparingly. According to the Dietary Guidelines for Americans,10 the diet should be mod-
erate in sugars, especially if kcal needs are low. The position of the American Dietetic
Association regarding the use of nutritive and nonnutritive sweeteners137 is that “consum-
ers can safely enjoy a range of nutritive and nonnutritive sweeteners when consumed in
moderation and within the context of a diet consistent with the Dietary Guidelines for
Americans.”
Feeding Adolescents
Characteristics of Food Habits of Adolescents
Adolescents often experience newly found independence, busy schedules, searches for
self-identification, dissatisfaction with body image, difficulty accepting existing values,
and a desire for peer acceptance. Each of these events may help explain changes in food
habits of adolescents. Common characteristics of food habits of adolescents include an
increased tendency to skip meals (especially breakfast and lunch), eating more meals
outside the home, increased snacking (especially on candy), consumption of fast foods,
and dieting.138
Insight regarding adolescents’ perceptions about factors influencing their food choices
and eating behaviors was provided from focus groups with 141 seventh- or tenth-graders
(40% white, 25% Asian-American, 21% African-American, 7% multiracial, 6% Hispanic,
1% Native American) from two urban schools in St. Paul, Minnesota.139 Factors identified
by the adolescents as being most influential on their food choices included hunger and
food cravings, appeal of food (primarily taste), time considerations of themselves and their
parents, and convenience of food. Factors identified by the adolescents to be of secondary
importance included food availability, parental influences on eating behavior (including
the family’s culture or religion), perceived benefits of food (e.g., for health, energy, body
shape), and situational factors (e.g., place, time). Additional factors discussed included
mood, body image concerns, habit, cost, media influences, and vegetarian lifestyle choices.
A sense of urgency about personal health in relation to other concerns, and taste preferences
for other foods were major barriers to eating more fruits, vegetables, and dairy products
and eating fewer high-fat foods. Suggestions provided by the adolescents to help adoles-
cents eat a more healthful diet included making healthful food taste and look better, making
healthful food more available and convenient, limiting the availability of unhealthful
options, teaching them good eating habits at an early age, and changing social norms to
make it “cool” to eat healthfully. These results suggest that if interventions to improve
adolescent nutrition are to be effective, they need to have adolescent input and address a
broad range of factors, especially environmental factors (e.g., increased availability and
promotion of appealing, convenient foods in homes, schools, and restaurants).139
The Minnesota Adolescent Health Survey (MAHS) was completed by more than 30,000
adolescents from 1986 through 1987. The MAHS was a comprehensive assessment of
adolescent health status, health behaviors, and psychosocial factors; although it included
relatively few nutrition-related items, a wealth of knowledge about adolescent nutrition
was gained. Neumark-Sztainer et al. summarized the knowledge learned from a decade
of subsequent analyses of data collected in the MAHS, as well as implications for working
with youth.140 Major concerns identified included overweight status, unhealthful weight-
control practices, and high prevalence rates of inadequate intakes of fruits, vegetables,
and dairy products. Risk factors for inadequate food intake patterns or unhealthful weight-
control practices included low socioeconomic status, minority status, chronic illness, poor
school achievement, low family connectedness, weight dissatisfaction, overweight, homo-
sexual orientation among boys, and use of health-compromising behaviors. The results
suggest a need for innovative outreach strategies that include educational and environ-
mental approaches to improve adolescent eating behaviors. A critical issue that needs to
be addressed is the validity of adolescents’ self-reported behaviors.140
Youth Risk Behavior Surveillance — United States, 1997

The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority
health-risk behaviors among high school youth in grades 9 through 12.141 In 1997, as part
of the YRBSS, the Centers for Disease Control and Prevention conducted a national school-
based Youth Risk Behavior Survey (YRBS) that resulted in 16,262 questionnaires completed
by students in 151 schools. Table 8.25 provides an overview of results from the YRBS for
dietary behaviors including fruit and vegetable consumption, fat consumption, perceived
overweight, attempted weight loss, laxative use or vomiting, diet pill use, dieting, and
exercising to either lose weight or keep from gaining it.141
TABLE 8.25
Results Regarding Dietary Behaviors from the Youth Risk Behavior Survey, United States, 1997
Dietary Behavior Percentage of Students*
Ate five or more servings of fruits and vegetables (defined as fruit, fruit juice, green
salad, or cooked vegetables) during day prior to survey:
Overall 29
Boys 32a
Girls 26a
Ate two or fewer servings of foods typically high in fat content (defined as
hamburgers, hot dogs, or sausage; french fries or potato chips; and cookies,
doughnuts, pie, or cake) during day prior to survey:
Overall 62
Girls 71a
Boys 56a
Hispanics 64b
Whites 63b
Blacks 55b
White girls 73c
Black girls 63c
Hispanic boys 60d
Black boys 47d
Girls in grade 12 77e
Girls in grade 9 65e
Boys in grade 12 59f
Boys in grade 10 52f
Boys in grade 11 61g
Boys in grade 9 50g
Boys in grade 10 52g
Considered themselves overweight:
Overall 27
Girls 34a
Boys 22a
Hispanics 30b
Blacks 24b
Hispanic boys 27c
White boys 22c
Black boys 15c
Tried to lose weight during the 30 days preceding the survey:
Overall 40
Girls 60a
Boys 23a

Results Regarding Dietary Behaviors from the Youth Risk Behavior Survey, United States, 1997
Dietary Behavior Percentage of Students*
Hispanics 46b
Blacks 36b
White girls 62c
Hispanic girls 61c
Black girls 51c
Hispanic boys 33d
White boys 22d
Black boys 20d
Used laxatives or vomited during the 30 days preceding the survey to lose weight
or keep from gaining it:
Overall 5
Girls 8a
Boys 2a
Hispanics 7b
Whites 4b
Hispanic girls 10c
Black girls 6c
Black boys 4d
White boys 2d
Used diet pills during the 30 days preceding the survey to lose weight or keep from
gaining it:
Overall 5
Girls 8a
Boys 2a
Dieted to either lose weight or keep from gaining it during the 30 days preceding
the survey:
Overall 30
Girls 46a
Boys 18a
Hispanics 33b
Whites 30b
Blacks 25b
White girls 48c
Hispanic girls 46c
Black girls 34c
Hispanic boys 23d
White boys 17d
Black boys 16d
Exercised to either lose weight or keep from gaining it during the 30 days preceding
the survey:
Overall 52
Girls 65a
Boys 40a
Hispanics 56b
Whites 52b
Blacks 44b
White girls 70c
Hispanic girls 65c
Black girls 49c
Hispanic boys 48d
White boys 39d
Black boys 38d
* Percentages with the same letter within a dietary behavior are significantly different.
Adapted from Kann, L., Kinchen, S. A., Williams, B. I., et al, Youth Risk Behavior Surveillance - United States, 1997,
In CDC Surveillance Summaries, MMWR 47 (No. SS-3), 1998; available at http://www.cdc.gov/.
Health Behaviour in School-Aged Children: A WHO Cross-National Study International

Report, 1997–1998
The Health Behaviour in School-Aged Children Study is a unique cross-national research
study conducted in collaboration with the World Health Organization (WHO) Regional
Office for Europe.142 The first survey was carried out in 1983–1984; since 1985, surveys
have been conducted at four-year intervals in a growing number of countries. The study
looks at 11-, 13-, and 15-year old children’s attitudes and experiences concerning a wide
range of health related behaviors and lifestyle issues. The 1997–1998 survey included more
than 123,227 children from 26 European countries and regions, Canada, and the U.S. The
1997–1998 sample of children from the U.S. included 5168 children; of these, there were
2395 boys and 2774 girls, 1558 11-year-olds, 1803 13-year-olds, and 1808 15-year-olds.
Results indicated that for the most part, U.S. children were less likely to have a good diet
than were children in other countries. Specifically, U.S. children were less likely to eat fruit
and vegetables each day than were children in the majority of other countries. Children
in the U.S. were more likely to eat potato chips and french fries every day, as well as
sweets or chocolate, than were children in most other countries. Children in the U.S.
ranked among the top three or four countries for consuming soft drinks every day. For
all countries, boys were more likely to drink more milk and eat more junk foods and fried
foods, and girls were more likely to eat fruit and vegetables each day. However, fruit and
vegetable consumption decreased with age. Concerns about body size and dieting behav-
ior increased with age for girls in all countries, but decreased for boys. Children in the
U.S. were more likely than children in any other country to report that they were dieting
or should be on a diet (47, 53, and 62% of 11-, 13-, and 15-year-old U.S. girls, respectively,
and 34, 33, and 29% of 11-, 13-, and 15-year-old U.S. boys, respectively). For all countries,
children with mothers or fathers with high socioeconomic status had the highest levels
of daily consumption of healthy food items, and those with mothers or fathers whose
status was low had the highest daily consumption of less nutritious food items. These
results emphasize important relationships between age, gender, country, and socioeco-
nomic status on food intake and dieting habits.142
Feeding Adolescents at School

Some research regarding feeding adolescents at school has been conducted. For example,
one study surveyed 2566 adolescents in grades 6, 7, and 8 (which covers ages 10 to 15
years) to assess their perceptions of school food service and nutrition programs.143 Results
indicated that the top predictors of satisfaction were school menus which include food
that students like, quality of the food choices, and prices that are acceptable for what
students get. Girls were more satisfied with school-prepared foods than boys, perhaps
because girls mature faster than boys during these years, which may be reflected as
willingness to try new foods at an earlier age. Sixth-grade students were more satisfied
than either seventh- or eighth-grade students. This may be because as adolescents move
into the early teenage years, they become more independent from their parents and begin
making their own decisions instead of eating school meals because their parents want or
expect them to do so.143
Another study examined the effects of pricing strategies on sales of fruits and vegetables
with adolescents in two high schools (1431 students at one urban school and 1935 students
at the other suburban school).144 Fruit, carrot, and salad purchases were monitored in
each school cafeteria during an initial baseline period. Next, prices for these items were
reduced by 50%, and sales were monitored. Finally, prices were returned to baseline, and
sales were monitored for an additional three weeks. Results indicated that even though
promotion was minimal, lower pricing significantly increased sales for fruit and carrots
but not salads among high school students. However, the magnitude of the intervention
effects differed by school, which suggests that contextual factors (e.g., packaging, display)
may modify pricing effects. These results imply that adolescents can be encouraged to
select fruits and vegetables when the prices of these items are lowered, and that this may
occur without measurable changes in the overall a la carte sales revenue or the number
of meal pattern customers, which are both important considerations for school food
service revenues.144
Caffeine
Caffeine is a stimulant for the central nervous system; it tends to decrease drowsiness
and reduce the sense of fatigue, but too much can cause palpitations, stomach upset,
insomnia, and anxiety. Its effects vary among individuals, depending on the amount
ingested, body size of the individual, and personal tolerance. Some people are able to
build up a tolerance to caffeine through regular use; others are more sensitive to it. If
someone who has regularly consumed caffeine suddenly stops using it, mild withdrawal
symptoms (e.g., headaches, craving for caffeine) may occur. Substantial amounts of caf-
feine are found in several soft drinks, coffee, tea, and some pain relievers; smaller amounts
are found in chocolate and foods with cocoa. Consumption of caffeine increases during
adolescence with greater intakes of soft drinks, tea, and coffee. This can be a concern
because caffeine has a modest negative impact on calcium retention, yet consumption of
milk and other foods high in calcium decreases as children get older.25,28 Furthermore, the
stimulating effect of caffeine may set the stage for needing stimulation; although caffeine
is classified as a drug, society is very accepting of this stimulant and has not considered
it a nuisance.145
Vegetarian Diets
During the adolescent years, when there is increased independence and decision making
and greater influence by peers and role models, vegetarian diets may be relatively com-
mon. There is considerable variation in the eating patterns of vegetarians. For the lacto-
ovo-vegetarian, the eating pattern is based on grains, vegetables, fruits, legumes, seeds,
nuts, dairy products, and eggs; meat, fish, and poultry are excluded. For the vegan, or
total vegetarian, the eating pattern is similar to the lacto-ovo-vegetarian pattern except
for the additional exclusion of eggs, dairy, and other animal products. However, consid-
erable variation may exist in the extent to which animal products are avoided within both
of these patterns.146
According to the American Dietetic Association, “well-planned vegan and lacto-ovo-
vegetarian diets are appropriate for all stages of the life cycle, including pregnancy and
lactation.”146 Appropriately planned vegan and lacto-ovo-vegetarian diets satisfy nutrient
needs of infants, children, and adolescents and promote normal growth.147 Dietary defi-
ciencies are more common in populations with very restrictive diets. All vegan children
need a reliable source of vitamin B12; in addition, vitamin D supplements or fortified foods
should be used if sun exposure is limited. Emphasis should be placed on foods rich in
calcium, iron, and zinc. Vegetarian children can be helped to meet energy needs through
frequent meals and snacks, as well as the use of some refined foods and foods higher in
fat.146 Section 40 contains additional information regarding vegetarian diets.
Eating Disorders
Anorexia nervosa and bulimia may affect about one million adolescents. Eating disorders
are thought to occur for a variety of reasons which include poor self-concept, pressure to
be thin, body shape and size, depression, and biological errors in organ function or
structure. Up to 10% of these adolescents may die prematurely as a result of eating
disorders.145 Most eating disorder patients develop the problem during adolescence; how-
ever, it may be difficult to distinguish an adolescent with “normal” eating habits from one
with an eating disorder, due to some of the psychologic changes which occur during
adolescence.6 More information regarding eating disorders may be found in Section 68.
Teen Pregnancy
Nutrient needs rise considerably during pregnancy; for adolescents who are pregnant,
nutritional considerations are paramount, especially if they are still growing. For adoles-
cent girls, linear growth typically is not completed until approximately four years after
the onset of menarche. Some indication of physiologic maturity and growth potential may
be obtained from gynecologic age, which is the difference between chronologic age and
age at menarche. A young adolescent girl (i.e., gynecologic age of two years or less) who
becomes pregnant may still be growing; thus, her nutrient requirements must meet her
own needs for growth and development, as well as the extra demands of fetal growth.6
Eating habits of adolescents (e.g., skipped meals, increased snacking, consumption of fast
foods, and dieting) create a health risk for pregnant adolescents because during pregnancy,
nutritional needs for the fetus are met before needs of the mother.145 Adolescents who are
pregnant should be cautioned against skipping meals, especially breakfast, because skip-
ping meals may increase the risk of ketosis.138 More information regarding teen pregnancy
may be found in Section 5.
Health Promotion and Disease Prevention

Healthy People 2010 Nutrition Objectives for Children and Adolescents
Table 8.26 includes Healthy People 2010 nutrition objectives, as well as dental objectives
related to nutrition, for children and adolescents.126 The nutrition objectives address reduc-
ing weight, reducing growth retardation, improving eating behavior (e.g., increasing con-
sumption of fruit, vegetables, grain products, and calcium products; decreasing
consumption of fat, saturated fat, and sodium), reducing iron deficiency, and improving
meals and snacks at school. The dental objectives related to nutrition address dental caries,
untreated dental decay, and school-based health centers with oral health components.
“5 A Day for Better Health” Program

The national “5 A Day for Better Health” Program was instituted in 1991 to encourage
Americans to eat five or more servings of fruits and vegetables every day. The program
is a public-private partnership between the National Cancer Institute (NCI) and the Pro-
duce for Better Health Foundation (a nonprofit foundation representing the fruit and
vegetable industry); it includes retail, media, community, and research components.148 At
TABLE 8.26
19-3. Reduce the proportion of children and adolescents who are overweight or obese (defined as at or
above the gender- and age-specific 95th percentile of BMI).
Reduction in Overweight or
Objective Obese Children and Adolescents* 2010 Target 1988–1994 Baseline
19-3a. Children and adolescents aged 6 to 11 years 5% 11%
19-3b. Children and adolescents aged 12 to 19 years 5% 10%
19-3c. Children and adolescents aged 6 to 19 years 5% 11%
* Defined as at or above the gender- and age-specific 95th percentile of BMI based on the revised
CDC growth charts for the U.S.
19-4. Reduce growth retardation (defined as height-for-age below the fifth percentile in the age-gender
appropriate population using the 1977 NCHS/CDC growth charts) among low-income children under
age 5 years.
Target: 5% Baseline: 8%
19-5. Increase the proportion of persons age 2 years and older who consume at least two daily servings of
fruit.
19-6. Increase the proportion of persons age 2 years and older who consume at least three daily servings
of vegetables, with at least one-third being dark green or orange vegetables.
19-7. Increase the proportion of persons age 2 years and older who consume at least six daily servings of
grain products, with at least three being whole grains.
19-8. Increase the proportion of persons age 2 years and older who consume less than 10 percent of calories
from saturated fat.
19-9. Increase the proportion of persons age 2 years and older who consume no more than 30 percent of
calories from total fat.
19-10. Increase the proportion of persons age 2 years and older who consume 2400 mg or less of sodium
daily (from foods, dietary supplements, tap water, and salt use at the table).
19-11. Increase the proportion of persons aged two years and older who meet dietary recommendations for
calcium (based on consideration of calcium from foods, dietary supplements, and antacids).
19-12. Reduce iron deficiency among young children and females of childbearing age.
Objective Reduction in Iron Deficiency* 2010 Target 1988-1994 Baseline

19-12a. Children age 1 to 2 years 9% 5%
19-12b. Children age 3 to 4 years 1% 4%
19-12c. Nonpregnant females age 12 to 49 years 7% 11%
* Iron deficiency is defined as having abnormal results for two or more of the following tests: serum
ferritin concentration, erythrocyte protoporphyrin, or transferrin saturation.
19-15. (Developmental) Increase the proportion of children and adolescents aged 6 to 19 years whose intake
of meals and snacks at school contributes to good overall dietary quality.
21-1. Reduce the proportion of children and adolescents who have dental caries experience in their primary
or permanent teeth.
Reduction of Dental Caries in Primary and/or

Objective Permanent Teeth 2010 Target 1988–1994 Baseline
21-1a. Young children 11% 18%
21-1b. Children 42% 52%
21-1c. Adolescents 51% 61%

21-2. Reduce the proportion of children, adolescents, and adults with untreated dental decay.
Objective Reduction of Untreated Dental Decay 2010 Target 1988-1994 Baseline

21-2a. Young children 9% 16%
21-2b. Children 21% 29%
21-2c. Adolescents 15% 20%
21-13. (Developmental) Increase the proportion of school-based health centers with an oral health component.
Adapted from US Department of Health and Human Services, Healthy People 2010, 2nd ed., US Government
Printing Office, Superintendent of Documents, Washington, DC, November, 2000. Available online at
http://www.health.gov/healthypeople (accessed July 30, 2001).
the beginning of the program in 1991, a baseline survey with adults indicated that only
23% reported consuming five or more daily servings of fruits and vegetables.149 The NCI
funded nine studies in the spring of 1993 to develop, implement, and evaluate interventions
in specific community channels to increase the consumption of fruits and vegetables in
specific target populations; four of the nine projects used school-based programs to target
children or adolescents.150 Of these four projects, one targeted fourth-grade students and
their parents,110 two targeted fourth- and fifth-grade students,106,109 and one targeted high
school students.111 Although all four interventions increased daily consumption of fruits
and vegetables, the increases were small for three interventions and ranged from 0.2 servings
for “Gimme 5 Fruit, Juice, and Vegetables for Fun and Health” in Georgia,106 0.4 servings
for “Gimme 5: A Fresh Nutrition Concept for Students” in New Orleans,111 and 0.6 servings
for “5 A Day Power Plus” in Minnesota.109 Increases were larger, at 1.4 servings for “High
Five” in Alabama, possibly because classroom lessons were delivered by trained curriculum
coordinators instead of classroom teachers.110 Perhaps the limited success of school-based
interventions to date is because they have not attempted to educate school staff about how
their behaviors impact children’s food acceptance patterns as discussed earlier.
Child Nutrition and Health Campaign

Launched in October, 1995, the Child Nutrition and Health Campaign is sponsored by
the American Dietetic Association/Foundation, Kellogg Company, and National Dairy
Council.151 The campaign focuses on five major objectives:
1. Convene a nationally recognized panel of experts on child nutrition to address

the nutritional needs of children, provide leadership to the campaign, and guide
the development of messages for the campaign.
2. Educate parents, children, and health care professionals about the links among
healthful childhood nutrition, classroom performance, and health during the
adult years.
3. Publicize the important roles of high-carbohydrate, low-fat breakfast foods and
healthful snacks for children’s nutrition.
4. Fund research on the behavioral aspects of achieving healthful nutrition in chil-
dren and on the development of lifelong healthful eating habits.
5. Launch a multi-year, multifaceted campaign to improve children’s nutrition and
health and to build strategic coalitions to spread the messages of the campaign.151
Five papers which review the scientific literature regarding links between nutrition and
cognition have been published.12,35,89,152,153 An intensive media program was developed to
bring three key messages to various audiences through publications, public service
announcements, news releases, consumer education activities, professional kits, and a
video. The three key messages are: 1) give children a healthy start to their day, 2) get
children (and adults) moving for the fun of it, and 3) grownups: be a role model.151
USDA School Meals Initiative for Healthy Children and Team Nutrition
The USDA School Meals Initiative (SMI) for Healthy Children underscores the national
health responsibility to provide children with school meals consistent with the Dietary
Guidelines for Americans and current scientific nutrition recommendations; the vision of
the SMI is to “improve the health and education of children through better nutrition.”154
Team Nutrition was established by USDA as a nationwide integrated initiative to help
implement the SMI; the goal of Team Nutrition is to “improve the health and education
of children by creating innovative public and private partnerships that promote food
choices for a healthful diet through the media, schools, families, and the community.”
Team Nutrition exists to empower schools in all 50 states to serve meals that meet the
Dietary Guidelines for Americans, and to teach and motivate children in grades pre-
kindergarten through 12 to make healthy eating choices. The four Dietary Guidelines for
Americans that Team Nutrition focuses on are 1) eat a variety of foods, 2) eat more fruits,
vegetables and grains, 3) eat lower fat foods more often, and 4) be physically active.
Helping every child in the nation to have the opportunity to learn how to eat for good
health is made possible by extensive, strategic public-private partnerships and approxi-
mately 300 Team Nutrition Supporters who represent all of the industries that touch
children’s lives, including nutrition and health, education, food and agriculture, consumer,
media and technology, and government.154 Table 8.27 lists common values shared by
supporters of Team Nutrition.
TABLE 8.27
Common Values Shared by Supporters of Team Nutrition
• Children should be empowered to make food choices that reflect the Dietary Guidelines for Americans.
• Good nutrition and physical activity are essential to children’s health and educational success.
• School meals that meet the Dietary Guidelines for Americans should appeal to children and taste good.
• Programs must build upon the best science, education, communication and technical resources available.
• Public/private partnerships are essential to reaching children to promote food choices for a healthful diet.
• Messages to children should be age appropriate and delivered in a language they speak, through media they
use, in ways that are entertaining and actively involve them in learning.
• The focus should be on positive messages regarding food choices children can make.
• It is critical to stimulate and support action and education at the national, state, and local levels to successfully
change children’s eating behaviors.
From http://www.fns.usda.gov/tn/Missions/index.htm (accessed January 29, 2000).
The Child and Adolescent Trial for Cardiovascular Health (CATCH)

CATCH was a four-center, randomized field trial that evaluated the effectiveness of a
school-based cardiovascular health promotion program.155 A total of 5106 ethnically
diverse students (who were third-graders at baseline and fifth-graders at the end of the
intervention) participated in 56 intervention and 40 control public schools in California,
Louisiana, Minnesota, and Texas. Of the 56 intervention schools, 28 schools participated
in a third-grade through fifth-grade intervention which included school food service

modifications, enhanced physical education, and classroom health curricula; the other 28
schools received these components plus family education. Results at the end of the three-
year intervention indicated that the percentage of energy from fat in intervention school
lunches fell significantly more (from 38.7 to 31.9%) than in control school lunches (from
38.9 to 36.2%) (p<0.001). The intensity of physical activity in physical education classes
increased significantly in intervention schools compared with control schools (p<0.02).
The percentage of energy from fat from 24-hour recalls among intervention school students
was significantly reduced (from 32.7 to 30.3%) compared with that among control school
students (from 32.6 to 32.2%, p<0.001). Intervention students reported significantly more
daily vigorous activity than controls (58.6 vs. 46.5 minutes, p<0.003). However, no signif-
icant differences were detected in blood pressure, body size, and cholesterol measures for
students at the intervention schools compared to those at the control schools.86
A three-year followup was conducted with 3714 students (73%) of the initial CATCH
cohort of 5106 students.156 End-point comparisons were made between students from
intervention and control schools to determine whether changes at the end of intervention
in grade five were maintained through grade eight. Results for eighth-graders indicated
that self-reported daily energy intake from fat remained lower for intervention than control
students (30.6 vs. 31.6%, p = 0.01). Intervention students maintained significantly higher
daily vigorous physical activity than controls (p = .001), although differences narrowed
over time. Significant differences in favor of intervention students persisted at grade eight
for dietary knowledge and dietary intentions, but not for social support for physical
activity. No significant differences were noted for BMI, blood pressure, or serum lipid and
cholesterol levels. In summary, followup of the CATCH cohort suggests that behavior
changes from the intervention were sufficient to produce effects detectable three years
later. However, differences between the intervention and control groups were narrowing
in magnitude over time. Additional research is needed to determine how best to maintain
the intervention effects long-term.156
Food Safety
The Fight Bac!™ campaign is a partnership of industry, government, and consumer groups
dedicated to reducing the incidence of foodborne illness.157 The multifaceted campaign
includes television and radio public service announcements in several languages, media
mailings, newspaper articles, publications, World Wide Web (www.fightbac.org), commu-
nity action kits, supermarket action kits, exhibit and convention kits, and educator kits
for grades kindergarten through three and four through six. Launched in October, 1997,
the eye-catching Fight Bac!™ cartoon character teams up with the following four critical
messages to teach consumers about safe food handling: clean, separate, cook, and chill.157
Table 8.28 provides more details regarding these four messages.
Children, adolescents, and adults of all ages need to understand the important role they
play in decreasing the incidence of foodborne illnesses through proper hand washing as
well as safe food preparation and storage. According to the Hospitality Institute of Tech-
nology and Management,158 hands should be washed with soap, a fingernail brush with
soft bristles, and a large volume of flowing warm water to ensure adequate removal of
pathogenic microorganisms (e.g., those from fecal sources) from fingertips and under
fingernails. Fingernails should be neatly trimmed to less than 1/16 inch to make them
easier to clean. When working with food, hand washing without the fingernail brush is
sufficient because the pathogen count is much lower. Table 8.29 describes the double and
single methods of hand washing. Although young children may be encouraged to wash
TABLE 8.28
Details Regarding the Four Critical Messages of the Fight Bac!™ Campaign
Clean: Wash Hands and Surfaces Often
• Wash hands with hot soapy water before handling food.

• Wash hands with hot soapy water after using the bathroom, changing diapers, and touching animals.
• Wash dishes, utensils, cutting boards, and counter tops with hot soapy water after preparing each food item
and before preparing the next food item.
• Use paper towels to dry hands and clean kitchen surfaces.
Separate: Don’t Cross-Contaminate
• Keep raw meat, poultry, and seafood separate from other foods in grocery carts and refrigerators.
• Use a different cutting board for preparing raw meats.
• Wash hands, cutting boards, dishes, and utensils with hot soapy water after they come in contact with raw
meat, poultry, or seafood.
• Do not place cooked food on a plate or serving dish that previously held raw meat, poultry, or seafood.
Cook: Cook to Proper Temperatures
• To make sure that meat, poultry, casseroles, etc. are cooked all the way through, use a clean thermometer.
• Cook roasts and steaks to at least 145°F; cook whole poultry to 180°F.
• Cook ground beef to at least 160°F. Do not eat ground beef that is still pink inside.
• Cook eggs until the white and yolk are firm.
• Do not eat foods that contain raw eggs or only partially cooked eggs.
• Cook fish until it is opaque and flakes easily with a fork.
• When microwaving foods, make sure there are not cold spots by stirring and rotating food for even heating.
• Reheat sauces, soups, and gravies to a boil. Heat other leftovers thoroughly to at least 165°F.
Chill: Refrigerate Promptly
• Refrigerate or freeze prepared foods and leftovers within two hours or sooner.
• Defrost food in the refrigerator, under cold running water, or in the microwave, but never at room temperature.
• Marinate foods in the refrigerator.
• Divide large amounts of leftovers into small, shallow containers for quick cooling in the refrigerator.
• Avoid packing the refrigerator because cool air must circulate to keep food safe.
Adapted from Fight Bac!™ Four Simple Steps to Food Safety, Partnership for Food Safety Education,
www.fightbac.org (accessed January 11, 2000).
their hands long enough for them to sing their “A, B, Cs” slowly, the amount of lathering
and the volume of water used to wash off the lathering appear to be more important than
the length of time spent washing.158
Dental Health
Nutrition is an integral component of oral health.159 Nutrition and diet may affect the
development and progression of diseases of the oral cavity. Likewise, oral infectious
diseases and acute, chronic, and terminal systemic diseases with oral manifestations, affect
diet and nutritional status. The primary factors to be considered in determining the
cariogenic, cariostatic, and anticariogenic properties of the diet include the form of the
food (liquid, solid and sticky, long lasting), frequency of consumption of sugar and other
fermentable carbohydrates, nutrient composition, sequence of food intake, and combina-
tions of foods.159
Because children of all ages eat frequently, snacks should emphasize foods that are low
in sucrose, are not sticky, and that stimulate saliva flow which helps limit acid production
in the mouth.160 Protein foods such as nuts and cheese may provide nutritional and dental
TABLE 8.29
Two Methods of Hand Washing
Double Wash Procedure (to be used to remove fecal pathogens and other pathogenic microorganisms
from skin surfaces when entering the kitchen, after using the toilet, after cleaning up vomitus or fecal
material, or after touching sores or bandages):
First wash using the fingernail brush (~7 seconds required to complete):
• Turn on water so it runs at 2 gallons per minute with a temperature of 110 to 115°F. Place hands, lower arms,
and fingernail brush under flowing water and thoroughly wet them.
• Apply 1/2 to 1 teaspoon of hand soap or detergent to fingernail brush.
• Brush and lather hand surfaces with tips of bristles on fingernail brush under flowing water, especially
fingertips and around and under fingernails. Build a good lather.
• Continue to use fingernail brush under water until there is no more soapy lather on hands, lower arms, or
nail brush. Hazardous microorganisms in the lather are only removed to a safe level when all the soap is
rinsed off the hands, arms, and fingertips.
• Place nail brush on holder with bristles up so bristles can dry.
Second wash without the fingernail brush (~13 seconds required to complete):
• Apply 1/2 to 1 teaspoon of hand soap or detergent to hands.
• While adding warm water as necessary, rub hands together to produce a good lather; lathering must extend
from fingertips to shirt sleeves.
• After lathering, rinse all of lather from fingertips, hands, and arms in flowing water. The volume of water
used for rinsing hands, not the time of the wash, is the critical factor.
• Thoroughly dry hands and arms using disposable paper towels. Discard paper towels in waste container
without touching container.
Single Wash Procedure (to be used to remove normal low levels of pathogens before and after eating
and drinking; after handling garbage; after handling dirty dishes or utensils; between handling raw and
cooked foods; after blowing or wiping nose; after touching skin, hair, or soiled clothes; and as often as
necessary to keep hands clean after they become soiled):
• Wet hands and lower arms with warm water.
• Follow directions above for “Second wash without the fingernail brush.”
Adapted from Snyder, O. P., Hospitality Institute of Technology and Management, 1998, http://www.hi-tm.com/
Documents/Safehands.html (accessed January 11, 2000).
benefits because some protein foods are thought to have a protective effect against caries.
When desserts are consumed, it is best if they are eaten with meals. Chewing sugarless
gum after snacks containing fermentable carbohydrate may benefit school-age children
and adolescents. The efforts of dietary control are complemented by good oral hygiene.
A fluoride supplement is recommended into the teen years if the water supply is not
fluoridated.160
Maxillary anterior caries (baby bottle tooth decay or BBTD) is the major nutrition-related
dental disease found in infants and preschool children; it appears to be related to feeding
behaviors after longer bottle or breastfeeding.159 The primary cause of BBTD is prolonged
exposure of the teeth to a sweetened liquid such as formula, milk, juice, soda pop, or other
sweetened drinks.160 This often occurs when a child is routinely given a bottle at bedtime
or naptime, because the liquid pools around the teeth during sleep, saliva flow decreases,
and the child may continue to suck liquid over an extended period of time. Toddlers are
also at high risk if they hold their own bottle and have access to it anytime throughout
the day. The primary strategy to prevent BBTD is education. Parents and child care
providers should be encouraged to avoid putting an infant or young child to sleep with
a bottle, and to use a cup to offer juices and liquids other than breast milk or formula.160
Section 54 provides additional information regarding the prevention of dental caries in
children and adolescents.
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9
The Health-Promoting Diet throughout Life: Adults
Marsha Read
Introduction
The normal diet for adults is based on the need to provide sufficient nutrients to sustain
life and an appropriate balance of nutrient intake to support optimal health. The first
Surgeon General’s Report on Nutrition and Health in 19881 brought together a substantial
body of research that documented that diet, aside from providing the essential nutrients
for daily functioning, was a key factor with respect to chronic diseases such as coronary
heart disease, cancer, diabetes, and obesity. The underlying premise of the various dietary
guidelines/recommendations that have been developed has been to provide adequate
nutrient intake while avoiding dietary patterns that might place an individual at greater
risk for chronic disease. The following subsections describe the most commonly used
dietary guidelines/recommendations, guidelines for counseling healthy adults, informa-
tion on current food and nutrient consumption patterns of adults, and current research
with respect to health implications of inappropriate macronutrient intake.
Dietary Recommendations and Guidelines

Dietary Guidelines
Dietary guidelines have undergone several revisions from the late 1970s to the recently
released Dietary Guidelines for Americans 2000.2 The 1970s Dietary Goals provided recom-
mendations with respect to energy intake, carbohydrate, fat, and sodium intakes. Specific
percent of calories from carbohydrate and fat were put forth, 48 and 30% respectively.
Cholesterol intake was recommended at 300 mg/day and sodium intake was recom-
mended not to exceed 5 g/day.3 The first set of the U.S. Dietary Guidelines was published
in 19804 (Table 9.1).
The first guidelines were followed by several revisions. The most recent iteration of
dietary guidelines for Americans adopts a basic “ABC” concept — Aim for Fitness, Build
0-8493-2705-9/01/$0.00+$1.50
TABLE 9.1
1980 U.S. Dietary Guidelines
Eat a wide variety of foods
Maintain ideal weight
Avoid too much fat, saturated fat, and cholesterol
Eat foods with adequate starch and fiber
Avoid too much sugar
Avoid too much sodium
If you drink alcohol, do so in moderation
TABLE 9.2
2000 U.S. Dietary Guidelinesa
Aim for Fitness
Aim for a healthy weight
Be physically active each day
Build a Healthy Base
Let the Pyramid guide your food choices
Eat a variety of grains daily, especially whole grains
Eat a variety of fruits and vegetables daily
Keep food safe to eat
Choose Sensibly
Choose a diet low in saturated fat and cholesterol, and moderate in total fat
Choose beverages and foods that limit your intake of sugars
Choose and prepare foods with less salt
If you drink alcoholic beverages, do so in moderation
a www.ars.usda.gov/dgac/dgacguideexp.pdf
a Healthy Base, and Choose Sensibly as the key constructs2 (Table 9.2). These current
dietary guidelines continue to emphasize sensible dietary choices, variety, and moderation.
From the first edition of the guidelines to the current, the focus has been on a variety
of foods to supply adequate nutrient intake, increased complex carbohydrate consump-
tion, moderate fat intake, and moderate alcohol consumption if you drink. A new concept
added to the 2000 guidelines deals with the issue of food safety. This introduces a new
concept on diet and health and reflects the current issues with respect to maintaining a
safe food supply from production to consumption. The concept “Keep Food Safe” adds
discussion on prevention of foodborne illness consistent with the concerns arising from
several recent food poisoning outbreaks in the United States.
The Food Guide Pyramid

The Food Guide Pyramid sets forth recommendations for a pattern of daily food choices
based on servings from five major food groups — bread, cereal, rice and pasta; fruit;
vegetable; milk, yogurt and cheese; and meat, poultry, fish, dry beans, eggs and nuts5
(Figure 9.1). The visual presentation as a pyramid was meant to convey that from the five
food groups emphasis should be placed on those shown in the lower three levels/sections
of the pyramid. The Food Guide Pyramid was also meant to be used in concert with the
dietary guidelines, i.e., to eat a variety of foods and balance the foods eaten with physical
activity, and either maintain or improve weight. Each food group suggests a range of
servings. Selecting the lower number of recommended servings is estimated to provide
approximately 1600 kcals, with the mid-range providing approximately 2200 kcals, and
2800 kcals at the upper range. Refer to Table 9.3 for examples of menu plans at the lower
and upper caloric range based on the Food Guide Pyramid. These estimates are intended
The Health-Promoting Diet throughout Life: Adults 301
Fats, Oils & Sweets KEY

Fat (naturally occuring and added)
USE SPARINGLY
Sugars (added)
These symbols show fats and added sugar in foods
Milk, Yogurt & Meat, Poultry, Fish, Dry Beans,

Cheese Group Eggs & Nuts Group
2-3 SERVINGS 2-3 SERVINGS
Vegetable Group Fruit Group

Bread, Cereal
Rice & Pasta
Group
6-11
SERVINGS
FIGURE 9.1
USDA Food Guide Pyramid.
to help consumers choose an appropriate level of caloric intake while maintaining an

appropriate variety of foods to support health. In addition, the visual representation of
the food guide as a pyramid was meant to imply that appropriate nutritional choices build
upon a base of nutrient dense food choices before consuming foods from the less nutrient
dense foods of fats, oils, and sweets at the top of the pyramid. Cited advantages and
disadvantages of the Food Guide Pyramid according to Kant, Block, Schatzkin, et al.6
include:
Advantages:
• The pyramid depicts foods, which makes it easier for consumers to relate to
rather than nutrients and numbers such as recommended dietary allowances
(RDAs).
• The pyramid is relatively simple and easy to read and to remember.
• The pyramid food groups and recommended servings from each food group are
likely to represent a variety of foods that can subsequently provide adequate
nutrient intake.
• The pyramid food groups allow for personal choice within a food group and
thereby supports individual food choices.
Disadvantages:
• Applicability of the food groups within the pyramid to alternate dietary patterns
such as vegetarianism and ethnic food patterns may be unclear.
• The Food Guide Pyramid does not address the dietary guideline regarding
alcohol intake.
TABLE 9.3
Meal Plans Based on the Food Guide Pyramid
1600 kcalorie Menu (Minimum Servings from Each Food Group)
Breakfast
1 cup Raisin Bran cereal
4 oz skim milk
1/2 grapefruit
Lunch
Turkey sandwich with mustard
2 pieces of whole wheat bread
3 ounces lean turkey
1 tablespoon mustard
Carrot sticks (1 medium)
Apple (1 medium)
Snack
1 cup low fat yogurt
1/2 sesame bagel
Dinner
3 ounces grilled salmon
Green salad (romaine, iceberg lettuce, tomato, cucumber)
1 tablespoon low-fat dressing
1/2 cup green beans
1 cup wild rice
2800 kcalorie Menu (Upper Serving Recommendations from Each Food Group)
Breakfast
1 bowl oatmeal cereal with 1/4 cup raisins
4 ounces skim milk
2 pieces whole wheat toast
2 teaspoons margarine
1 tablespoon jam
4 ounces orange juice
Lunch
1 peanut butter and jelly sandwich
2 pieces whole wheat bread
1 tablespoon jelly
2 tablespoons peanut butter
Apple (1 medium)
Celery sticks (1 stalk)
Snacks (a.m. and p.m.)
1 ounce low fat cheese
4 crackers
banana
plain bagel
Dinner
3 ounces grilled chicken breast
1/2 cup peas
1 cup herb rice
Green salad (romaine, iceberg lettuce, sliced tomatoes, cucumber)
1 tablespoon of low-fat dressing
Melon slices
Dinner roll
• Interpretation of combination foods as pizza, stews, etc., is not clear within the
framework of the pyramid food groups.
• Dietary adequacy may not be obtained if individuals make poor choices within
the pyramid food groups.
While there is only one Food Guide Pyramid published by the U.S. Department of
Agriculture, variations of the pyramid have arisen. These variations have been constructed
to help Americans with alternative dietary preferences build a healthy dietary pattern.
These are described in other sections of this handbook (see Section 11 on Guidelines).
Recommended Dietary Allowances (RDA), Estimated Safe and Adequate Daily Dietary
Intakes (ESADDIs), Daily Reference Intake (DRI), and Daily Values (DV)
The most common reference standard for nutrient intake has been the recommended
dietary allowance (RDA). This standard was first established by the Food and Nutrition
Board in 1941, with the most recent edition in 1989.7 The original intent was to review and
revise the RDAs every four to five years, taking into account current research. The constructs
used in formulating a specific RDA were: (a) an estimation of how much of each essential
nutrient the average healthy person requires to maintain health and how those require-
ments vary among people; (b) an increase in the average requirement to cover the needs
of almost all members of the population, based on a bell curve distribution; (c) an increase
in the RDA again to cover cooking losses and inefficient body utilization, as well as provide
for cases of greater nutrient need such as in pregnancy and infancy; and (d) use of scientific
judgment in establishing the RDA. Three central premises underlie the RDAs:
1. The RDA is an amount intended to be consumed as part of a normal diet

2. The RDA is neither a minimal requirement nor an optimal level of intake, but
instead represents a safe and adequate level of intake based on current scientific
knowledge
3. The RDA is most appropriately used as a nutrient intake guide applied to
subgroups of the population, but can be used to estimate the probable risk of
nutrient deficiency for an individual.
For nutrients in which scientific evidence provides support for their essentiality but are
insufficient to establish an RDA, there are estimated safe and adequate daily dietary
intakes (ESADDIs). Most ESADDIs are shown as a range of intake values that represent
the upper and lower limits of safe intake. ESADDIs are established for biotin, copper,
manganese, and molybdenum.7
The current iteration of recommended intakes includes the dietary reference intake
(DRI). DRI encompasses four types of nutrient recommendations for healthy individuals:
adequate intake (AI); estimated average intake (EAR); recommended dietary allowance
(RDA); and tolerable upper intake levels (UL).8,9 AI is a nutrient recommendation based
on observed or experimentally determined approximation of nutrient intake by a group
(or groups) of healthy people when sufficient scientific evidence is not available to calculate
an RDA or an EAR. The EAR is the average requirement of a nutrient for healthy indi-
viduals in which a functional or clinical assessment has been conducted and measures of
adequacy have been made at a specified level of dietary intake. The EAR is an amount of
intake of a nutrient at which approximately 50% of subjects would have their needs met
and 50% would not. The EAR is intended to be used for assessing nutrient adequacy of
populations and not individuals. The new RDA is the amount of a nutrient needed to
meet the requirements of nearly all (97 to 98%) of the healthy population of individuals
TABLE 9.4
WHO Dietary Recommendations
Total Energy: sufficient to support normal growth, physical activity, and body weight
(body mass index = 20-22)
Total Fat: 15-30% of total energy
Saturated fatty acids: 0-10% total energy
Polyunsaturated fatty acids: 3-7% total energy
Dietary cholesterol: 0-300 milligrams per day
Total Carbohydrate: 55-75% total energy
Complex carbohydrates: 50-75% total energy
Dietary fiber: 27-40 grams/day
Refined sugars: 0-10% total energy
Protein: 10-15% total energy
Salt: upper limit of 6 grams/day (no lower limit set)
for whom it was developed. An RDA for a nutrient should serve as an intake goal for
individuals and not as a standard of adequacy for diets of populations. This is different
than the previous or old RDA. UL values are established in cases where there is adequate
scientific evidence to suggest an upper level of intake that is consistent with adverse or
toxic reactions. The UL represents the maximum level of intake for a nutrient that will
not cause adverse effects in almost all of the population ingesting that amount.
The daily values (DV) are used as standards in food labeling. DVs provide reference
intake standards for nutrients that have an RDA, in which case they are referred to as
reference daily intakes (RDIs), and for nutrients for which no RDA exists, in this case referred
to as daily reference values (DRVs). DRVs are established for fat, saturated fat, cholesterol,
carbohydrate, dietary fiber, sodium, and potassium. As a rule the RDIs are greater than the
RDA for specific nutrients and provide a large margin of safety. The term RDI replaces the
term U.S. Recommended Daily Allowances (USRDAs) used on earlier food labels.10
World Health Organization (WHO) Recommendations

The World Health Organization (WHO) has also published diet recommendations with
the goal of reducing risk for chronic disease.11 WHO recommendations are expressed as
a range of average daily intakes from lower to upper limits (Table 9.4).
Food Labels
Food labeling became mandatory in 1993 with the enactment of the Nutrition Labeling
and Education Act (NLEA).10 The legislation required food labeling on most foods with
the exceptions of low nutrient-dense foods such as coffee, spices, and ready-to-eat foods
prepared on site. Nutrition information remains voluntary on many raw foods. The nutri-
tion facts panel on food labels provides information to help the consumer make more
informed choices, including information on calories per serving, calories from fat, satu-
rated fat and cholesterol, and protein among other nutrients (Table 9.5).
American Cancer Society and National Cancer Institute Guidelines

In the 1980s the American Cancer Society issued the following dietary guidelines aimed
at reducing cancer risk within the populace:12
1. Choose most of the foods you eat from plant sources.

• Eat five or more servings of fruits and vegetables every day.
TABLE 9.5
Nutrition Facts Panel Informationa
Serving size (based on amounts commonly used)
Number of servings per container
Kcalories per serving
Kcalories from fat
% Daily value of total fat, saturated fat, cholesterol, sodium, total carbohydrate, dietary fiber, sugars, protein,
vitamin A, vitamin C, calcium and iron
Reference values for total fat, saturated fat, cholesterol, sodium, total carbohydrate, and fiber
Kcaloric conversion guide for protein, fat, and carbohydrates
a www.healthfinder.gov/searchoptions/topicsaz.htm — search for food labels.
• Eat foods from plant sources, such as breads, cereals, grain products, rice,
pasta, or beans several times each day.
2. Limit your intake of high-fat foods, particularly from animal sources.
• Choose foods low in fat.
• Limit consumption of meats, especially high-fat meats.
3. Be physically active: achieve and maintain a healthy weight.
• Be at least moderately active for 30 minutes or more on most days of the week.
• Stay within your healthy weight range.
4. Limit consumption of alcoholic beverages, if you drink at all.
The National Cancer Institute endorses the following guidelines, which reflect in large
part the recommendations of the American Cancer Society:13
1. Avoid obesity.
2. Reduce fat intake to 30% of total energy intake as a start. Then consider a
reduction closer to 20% of total energy intake if at high risk, such as a family
history of cancer.
3. Eat more higher-fiber foods, such as fruits, vegetables, and whole-grain cereals.
4. Include foods rich in vitamins A, E, and C, as well as carotenoids, in the daily diet.
5. If alcohol is consumed, do not drink excessively.
6. Use moderation when consuming salt-cured, smoked, and nitrite-cured foods.
There are also guidelines set forth by the National Cholesterol Education Program and
the American Heart Association (refer to the section on cardiovascular disease).
Nutrition Counseling for Adults

Determining Energy Requirements
To plan a diet consistent with dietary guidelines, the nutrition professional should first
determine the caloric requirements of a client. The total energy requirements will be the
sum of the resting energy requirement, energy needs for physical activity and the energy
needed for the thermic effect of foods. To determine the total energy requirement:
Step 1: Estimating Appropriate Body Weight

The Hamwi method is a common tool to estimate appropriate body weight. For females,
the estimation is 100 lb for the first 5 feet of height and 5 lb per inch over 5 feet; e.g., a
5’6” woman would be calculated as: (100 lbs for first five feet) + (5 lbs/inch over 5 ft = 5
× 6 = 30) = 130 lbs. For men the estimation is 106 lbs for the first 5 feet of height and 6
lbs per inch over 5 feet; e.g., a 6’0” man’s desirable weight would be calculated as: (106
lbs for first five feet) + (6 lbs/ inch over 5 feet = 6 × 12 = 72) = 178 lbs. Adjustments are
made for a large frame (+10%) or a small frame (–10%).
Step 2: Estimating Energy Needs Based on Body Weight

To estimate energy needs, the first step is to determine resting energy requirements (REE).
While several methods exist to calculate energy requirements based on weight, the abbre-
viated or quick method is probably useful for normal adults. The abbreviated method is
as follows:
For adults:
Women wt in kg × 23
Men wt in kg × 24
Step 3: Estimating Energy Required for Physical Activity

Once the REE requirements are determined, an estimate of the energy needs for physical
activity must be made. Again there are several alternatives to use to estimate caloric needs
for physical activity. The Physical Activity Levels (PALs)14 method is shown below:
• Seated work with no option of moving around and little or no strenuous leisure
activity (PAL factor = 1.4 to 1.5 × REE)
• Seated work with ability or requirement to move around but little or no strenuous
leisure activity (PAL factor = 1.6 to 1.7 × REE)
• Standing work (housework, shop clerks) (PAL factor 1.8 to 1.9 × REE)
• Significant amounts of sport or strenuous leisure activity (30 to 60 minutes four
to five/week) (PAL factor + 0.3 increment over 1.8 to 1.9 × REE)
• Strenuous work or highly active leisure (PAL factor 2.0 to 2.4)
Step 4: Add REE (Step 2) and Physical Activity (Step 3)
Step 5: Calculate Thermic Effect of Food

To estimate the thermic effect of food multiply the sum of the REE and physical activity
by 10% and add that amount to the total.
Determining Protein, Fat, and Carbohydrate Requirements

After the total energy requirements are determined, the contributions from protein, fat,
and carbohydrate need to be determined.
1. Protein: by converting grams of protein into its caloric equivalent, the percent
of protein from total calories can be derived.
2. Fat: the recommendation for fat is 30% or less of total energy requirements.
3. Carbohydrate: the percent of calories that will come from carbohydrate will be
the difference between total energy requirements minus the percent of kcalories
from protein and fat.
Estimates of Actual Intakes of Adults for Macronutrients

Nutrition monitoring has been going on since the early 1900s in the United States, when
the USDA’s Food Supply Series was initiated.15 Currently the National Nutrition Moni-
toring and Related Research Program (NNMRRP) is the umbrella for activities that provide
regular information about the contribution that diet and nutritional status make to health.16
Energy Intake
With respect to total energy intake, for adult men, caloric consumption consistently exceeds
that of adult women by approximately 400 kcalories. With one age group exception (ages
>70 years), men consumed in excess of 2000 kcalories on average, while women consistently
averaged less than 2000 kcalories per day. Fat was contributing slightly above the recom-
mended 30% of kcalories for both men and women. Adult men derive somewhat more
kcalories from alcohol compared to women, but women are considerably higher in their
carbohydrate intake than men. Men consumed not quite a third of their total energy intake
from foods consumed away from home. For women, the contribution of energy from foods
eaten away from home is one fourth of their total energy intake. Men were more likely
than women to consume a diet that met 100% of the RDA. Table 9.6 provides energy intake
data on age cohorts for adult men and women based on the 1994-96 Continuing Survey of
Food Intake for Individuals (CSFII). Foods eaten away from home are contributing approx-
imately 30 to 40% of total kcalories consumed by young adults. The percent of kcalories
derived from foods eaten away from home decreases with age (Table 9.7).
Total Protein, Carbohydrate, and Fat Intakes

Protein intake is higher for adult men compared to adult women, yet the mean protein
intake for both men and women exceeds the 1989 RDA (Table 9.8). With their higher mean
protein intake, more men (80.2%) than women (69.2%) met 100% of the 1989 RDA for
protein. As with total energy intake, foods consumed away from home contribute at least
25% of the overall protein intake. For men, 29% of the total protein intake was derived
from foods eaten away from home. For women, this was 24.6%.
Total carbohydrate intake is higher for men than women, consistent with their higher
total energy intake. The mean intake of carbohydrate for adult men was roughly 50 to 60
grams/day higher than the adult female intake (Table 9.8). The mean fiber intake per day
for both men and women is below even the lower level of the recommended 24 to 70
grams per day (Table 9.9).
Fat intake for adult men and women, as with protein and carbohydrate intakes, reflects
the gender differences in total energy intake pattern, i.e., men consume more than women.
The majority of adult men and women exceed the 30% of energy from fat recommendation.
Only 29.4% of adult men and 36.8% of adult women maintained a diet within the 30%
TABLE 9.6
Total Energy Intake and Sources of Energy for Adult Men and Womena
Age Males Females
20–29 yrs 2821 1841
30–39 yrs 2665 1710
40–49 yrs 2435 1682
50–59 yrs 2270 1600
60–69 yrs 2072 1489
70 > yrs 1834 1384
20 < yrs 2455 1646
Sources of Energy Intake (% of Total kcalories)
Protein Total Fat Carbohydrate Alcohol

Age M F M F M F M F
20–29 yrs 15.2 14.7 32.4 31.8 49.8 63.0 3.4 1.9
30–39 yrs 15.9 15.7 34.0 32.4 48.8 61.8 2.4 1.5
40–49 yrs 16.0 15.6 33.1 33.4 49.2 51.1 2.8 1.4
50–59 yrs 16.3 16.5 33.8 32.4 48.7 51.2 2.5 1.6
60–69 yrs 16.6 16.7 33.5 32.6 49.3 61.2 2.1 1.3
70 > yrs 16.3 16.7 33.0 31.4 50.9 63.3 1.6 1.5
20 < yrs 16.0 15.9 33.3 32.4 49.3 51.9 2.6 1.4
Percent of Individuals Meeting 100% of the 1989 RDA for Energy (2-Day Average)
Age Males Females

20–29 yrs 35.4 20.5
30–39 yrs 32.5 17.4
40–49 yrs 26.4 14.0
50–59 yrs 39.0 21.4
60–69 yrs 32.5 15.2
70 > yrs 19.5 12.4
20 > yrs 31.5 17.0
M = males, F = females
a http://www.barc.usda.gov/bhnrc/foodsurvey/home.htm
TABLE 9.7
Contribution (% kcal) of Breakfast, Snacks, and Foods
Consumed Away from Home to Total Energy Intake (1
day) 1994–1996; M = males; F = femalesa
Foods Away
Breakfast Snacks From Home
Age M F M F M F
20–29 yrs 14.2 16.0 18.2 17.0 40.0 34.3
30–39 yrs 15.5 16.9 15.5 16.9 31.4 26.6
40–49 yrs 16.3 16.9 15.5 17.1 29.4 25.4
50–59 yrs 18.2 19.1 15.4 15.2 26.7 23.0
60–69 yrs 20.9 19.9 15.0 15.1 20.0 17.6
70 > yrs 23.8 23.0 12.2 12.3 14.2 12.5
20 < yrs 17.1 18.2 15.7 15.9 29.4 24.5
recommendation. Foods eaten away from home contributed 30.9% of the total fat intake
for men and 26.2% for women (Table 9.8). Cholesterol intake is considerably less for
women than men. Women of all age groups consumed under 300 mg/day, whereas, adult
men generally consumed slightly more than 300 mg/day on average (Table 9.10). More
TABLE 9.8
Total Protein, Carbohydrate, and Fat Intakes (gm)a
Protein Intake Carbohydrate Fat
(gm) (gm) (gm)
Age M F M F M F
20–29 yrs 104.1 65.9 344.9 241.6 103.3 65.9
30–39 yrs 102.7 65.3 322.3 218.8 102.7 63.2
40–49 yrs 95.3 63.5 294.7 213.8 95.3 63.5
50–59 yrs 90.3 64.1 273.1 201.5 90.3 59.4
60–69 yrs 83.5 60.4 252.5 188.7 83.5 56.2
70 > yrs 72.9 56.6 239.2 183.5 72.9 49.2
20 < yrs 94.9 63.8 298.8 211.7 94.9 50.5
TABLE 9.9
Fiber Intake (gm)a
Age M F
20–29 yrs 18.3 13.2
30–39 yrs 19.4 13.6
40–49 yrs 18.3 14.0
50–59 yrs 18.5 14.5
60–69 yrs 18.5 14.2
70 > yrs 17.7 14.2
20 < yrs 18.6 13.9
adults consumed a diet consistent with the recommended cholesterol intake (55.1% of
men; 79.4% of women) than for total fat, where only 29.4% of adult men and 36.8% of
adult women maintained a diet within 30% of the total energy intake. The intake of the
types of fat — saturated, polyunsaturated, monounsaturated, and cholesterol is presented
in Table 9.10.
Health Implications of Current Macronutrient Intakes

Energy and Obesity Issues
Overweight is associated with several chronic diseases — coronary heart disease, hyper-
tension, noninsulin-dependent diabetes mellitus, and some forms of cancer.17,18 An esti-
mated 300,000 Americans per year die from obesity-related conditions.18 Obesity is also
an associated risk factor for joint disease, gallstones, and obstructive sleep apnea.19 In
1995, the economic cost associated with obesity was estimated at $62.3 billion.20
From 1976-1980 and 1988-1994, the Centers for Disease Control and Prevention (CDC)
reported an increase of 10% in the incidence of overweight in the American population.21
Data from the CSFII, 1994 (http://www.barc.usda.gov/bhnrc/foodsurvey/home.htm)
indicate among adults, both men and women, the incidence of overweight is approxi-
mately 30% (Table 9.11). If the incidence of obesity continues to rise at current rates, it is
predicted that by 2230, every adult in the U.S. will be overweight.22
TABLE 9.10
Intake of Saturated Fatty Acids, Monounsaturated Fatty Acids,
Polyunsaturated Fatty Acids, and Cholesterola,b
Saturated Monounsaturated Polyunsaturated
Fatty Acids Fatty Acids Fatty Acids Cholesterol
Age M F M F M F M F
20–29 yrs 35.4 22.3 40.1 25.2 19.6 13.5 348 219
30–39 yrs 35.3 21.3 39.4 24.1 20.1 12.8 362 217
40–49 yrs 30.6 21.0 35.6 24.0 18.3 13.6 331 222
50–59 yrs 28.6 19.1 33.9 22.6 18.1 13.1 332 200
60–69 yrs 25.9 17.9 30.1 20.8 16.5 12.1 307 218
70 > yrs 22.8 15.9 26.4 18.7 13.9 10.6 270 188
20 < yrs 31.3 20.0 36.8 23.0 18.4 12.8 331 213
Percent of Individuals Meeting the Recommendations for Total Fat, Saturated Fat, and
Cholesterol
Total Saturated
Fat Fatty Acids Cholesterol
Age M F M F M F
20–29 yrs 29.3 40.1 34.1 42.3 63.1 77.0
30–39 yrs 28.1 35.9 30.7 39.7 62.6 80.9
40–49 yrs 27.4 30.5 31.7 38.5 53.5 76.0
50–59 yrs 28.0 36.5 36.2 46.0 54.2 80.7
60–69 yrs 33.9 38.0 42.1 46.1 58.1 78.7
70 > yrs 34.4 42.2 41.6 47.9 67.1 84.5
20 > yrs 29.4 36.8 34.5 42.7 55.1 79.4
a Saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids
in grams; cholesterol in milligrams.
b http://www.barc.usda.gov/bhnrc/foodsurvey/home.htm
TABLE 9.11
Incidence of Overweight (%)a
Age Men Women
20–29 yrs 21.5 22.1
30–39 yrs 32.3 27.4
40–49 yrs 37.0 36.1
50–59 yrs 39.9 37.8
> 60 yrs 40.7 33.4
< 20 yrs 31.8 31.7
The prevalence of overweight/obesity among Americans is at odds with the perceptions

of the importance of maintaining an appropriate body weight. When Americans were sur-
veyed as part of the 1994-96 USDA Diet and Health Knowledge survey, 68.1% of adult males
over 20 years of age reported that “maintaining a healthy weight” was very important. For
that same survey, 77% of the adult women over 20 years of age reported maintenance of a
healthy body weight as very important. Given the importance Americans place on main-
taining healthy body weight and given the high incidence of overweight/obesity, it is little
wonder that Americans spend in excess of $33 billion a year on weight loss schemes.23 Among
these are the myriad of weight loss diets that appear on the market every year. In 1992,
33-40% of American women and 20-24% of American men reported being on a diet.24
Fad Diets Used for Weight Loss Promotion

While numerous fad diets come and go, several categories tend to remain fairly common.
These include high protein/low carbohydrate diet regimens, low fat diets, and very low
calorie diets.
High Protein/ Low Carbohydrate

These diets generally restrict the carbohydrate intake to 100 grams or less per day. Restric-
tion of carbohydrate leads to an initial mobilization of glycogen and then to gluconeo-
genesis and ketosis, all of which promote water loss and some lean tissue loss, which
constitute a significant portion of the weight loss. Some of the low carbohydrate diets
promote high protein and consequently a higher animal fat intake which is inconsistent
with the dietary guidelines for fat intake.25 Examples of high protein/low carbohydrate
diets are Atkins’ Diet Revolution, Calories Don’t Count, and The Doctor’s Quick Weight
Loss Diet (Stillman’s).
Low Fat Diets

Generally these diets restrict fat intake to 20% or less of total energy intake. Examples of
these types of diets include the T-factor Diet, the Pasta Diet, the Pritikin Diet, and Fit or
Fat. The average weight loss on these types of diets is 0.1 to 0.2 kg per week. With the
limited fat intake, one drawback is the low satiety factor which may prompt noncompliant
diet behavior.26
Very Low Calorie Diets

These diets arose during the 1970s and were known as protein-sparing-modified fasts or
liquid protein diets. These diet plans generally rely on liquid supplements to substitute
for food intake and restrict the overall caloric level to less than 800 kcalories per day. These
diets may be indicated for moderately to several obese patients (BMI >30). The severe
caloric restriction does lead to weight loss, but generally this level of caloric intake cannot
be sustained, and weight regain is a potential problem. These diets may also lead to weight
loss from lean tissue mass.23, 27
The Zone Diet

The Zone Diet is a modified approach to the low carbohydrate-high protein type of diet.
The diet promotes a macronutrient intake of 30% protein, 30% fat, and 40% carbohydrate.
At this ratio of protein: fat: carbohydrate, the author contends that insulin levels will
remain stable, and this, in turn, dampens insulin’s potential to promote the conversion of
carbohydrates into fat and thereby promote weight gain. The Zone Diet claims go beyond
the promise of weight loss via insulin regulation into the realms of disease prevention.
The Zone Diet author argues that a high carbohydrate, low fat diet promotes an imbalance
in “bad” eicosanoid production that can lead to the development of such diseases as
arthritis and coronary heart disease. However, there is no significant body of evidence to
support the author’s claims.28, 29
Putting fad diets aside, an approach to weight management that recognizes overweight
obesity as a chronic condition and incorporates the elements of a healthy diet, exercise,
and behavior modification, is more likely to be successful over time, and particularly in
the maintenance of weight loss.30
Protein Intake — Health Issues

The average American diet is very liberal with respect to protein intake. The RDA for
protein for women aged 19 to 24 is 46 grams, and for men of the same age the RDA is 58
grams.7 In contrast, the average protein intake in grams for adults over 20 in the U.S. is
63.8 grams for women and 94.9 grams for men. Some concern has been expressed over
the long term health consequences of excessive protein intake. There is some evidence in
humans that a lifetime on a high animal protein diet (typical American diet pattern) can
aggravate existing renal problems,31 may increase the risk for cancer of the kidney,32 and
can accelerate adult bone loss.33, 34 Lastly, higher animal protein intake is associated with
higher than desirable levels of total fat and saturated fat intake.
A primary, albeit not exclusive source of protein in the American diet is meat. The U.S.
Food Guide Pyramid recommends between 5 and 7 ounces of cooked lean meat or equiv-
alent in meat alternatives per day. To be consistent with the Dietary Guidelines to reduce
total fat and saturated fat in the diet, it would be helpful to consume lower-fat types of
meat and perhaps a greater amount of some forms of meat alternatives such as soybean
products. However, Americans derive the majority of their protein from meat. The 1994-
96 CSFII indicated that for adult males over 20 years of age, the average daily intake of
meat and meat alternatives was 6.4 ounces, and for women the total was 3.9. With respect
to total intake, men were consuming sufficient amounts of meat and meat alternatives
when compared to the recommended 5 to 7 ounces. Women, on the other hand, fell below
the minimum 5 ounces recommended in the U.S. Food Guide Pyramid. With that in mind,
data from the CSFII indicate that regardless of meat servings, protein intake is meeting
RDA requirements. Consequently, the source of protein may be an important consider-
ation. The ratio of meat to meat alternatives is skewed heavily in favor of meat (beef, pork,
lamb, and veal). For men, of the average 6.4 ounces of lean meat and meat alternatives
consumed daily, 2.7 ounces are derived from lean meat and another 1.0 ounce from the
higher fat sources of frankfurter and lunch meat. Consequently, 3.7 of the 6.4 ounces, or
58%, was from meat. Only 1.5 ounces and 0.5 ounce, respectively, were contributed by
poultry and fish. For women, 1.4 ounces of meat and 0.5 ounces of frankfurter and lunch
meat were consumed on a daily average. This accounts for 49% of the total meat or meat
alternative consumption. For women, poultry contributed 1.1 ounce and fish 0.4 ounce
towards the total meat and meat alternative intake. Some data suggest that an increase in
fish and consequently in omega-3-fatty acid intake may be warranted.
Protein Supplements
Protein supplements are quite common among athletes and physically active adults as
part of their strength training regimens.35 Bucci argues that while there is very little
research that documents the benefits of protein supplementation, high protein diets are
safe.35 However, the amount recommended for endurance athletes is 70 gm/day, and for
strength athletes 112 to 178 gm. The lower range of these recommendations is clearly
within the normal intake of American men. This argues against the need for further protein
supplementation.
Amino Acid Supplements

Individual amino acid supplements have been promoted on the market periodically.
Again, a target audience has often been the athlete or physically active adult, with promises
of enhanced performance. There is a dearth of research that can support such claims.35 In
addition, in 1992 a scientific panel convened to address the safety of amino acid supple-
ments concluded that there is little research on which to support making amino acid
supplement recommendations, and some amino acid supplementation (serine and proline)
can have adverse health effects. Consequently, the panel concluded that no level of amino
acid supplementation may be considered safe at this time.36
Fat Intake Issues — Amount and Type of Fat

The adult American diet is slightly over the 30% of total energy that is recommended.
Data from the 1994-96 CSFII reveals that approximately 25% of the total energy intake is
contributed by discretionary fats as cream, butter, margarine, cream cheese, oil, lard, meat
drippings, cocoa, and chocolate. Based on the average energy intake of adult males,
discretionary fat contributes 614 kcals per day, and for females 412 kcals per day. By cutting
back on discretionary fat intake, American adults could conceivably lose 0.8 to 1.0 lb per
week. This would be helpful in dealing with the adult obesity rates in the U.S. Simple
changes in discretionary fat intake could be helpful. For example:
• Substituting mustard for mayonnaise on sandwiches = 5 gm (45 kcals) fat savings

• Ordering hamburger rather than a cheeseburger = 9 gm fat savings (81 kcals)
• Using salt and pepper instead of sour cream on a baked potato = 3 gm fat savings
(27 kcals)
Americans consume more saturated fat than is desirable. In addition, approximately 5%

of the total fat intake in the American diet is contributed from trans-fatty acids.37 Biochem-
ically, trans-fatty acids act similarly to saturated fatty acids, raising LDL levels and decreas-
ing HDL levels.38 While their effect is not as great as saturated fat, they may contribute
to a lipid intake pattern that raises the risk for coronary heart disease.39 Trans-fatty acids
are formed as a result of the hydrogenation process and are found in such food items as
margarine, shortening, commercial frying fats, and many high-fat baked and snack foods.
Trans-fatty acids also occur naturally in milk and butter as a result of the fatty acids
synthesized by rumen flora in the rumen. Concern over trans-fatty acid intake has led
some consumers to question whether they should forgo margarine and return to butter.
Research suggests that saturated fat, as in butter, still exerts a greater negative effect on
a person’s lipid profile than do trans-fatty acids. However, use of less hydrogenated forms
such as tub rather than stick margarine may be beneficial.
Carbohydrate Intake Issues

Two issues arise with respect to the carbohydrate intake of American adults — low fiber
intake and high sugar intake. Low fiber intake is associated with a higher incidence of
such chronic diseases as heart disease,40 cancer,41 and diabetes.42 At least partial explanation
for the low fiber intake is related to the low fruit and vegetable intake associated with the
typical American diet. Data from the 1994-96 CSFII indicated that for adult males the
average total servings (based on the Food Guide Pyramid serving recommendations) of
vegetables per day was four. For females the average was three servings. For both men
and women, one-third of the vegetable servings were accounted for by white potatoes.
Average servings of fruit per day for both men and women was 1.5. This is just under the
minimum Food Guide Pyramid recommendation for two servings per day. Another con-
tributing factor to the low fiber intake is the lack of whole grain foods in the diet. Adult
men consumed on average 8 servings of grain products per day, which is approximately
mid-range of the 6 to 11 servings of grain products recommended by the Food Guide
Pyramid. Women averaged six servings from grain products. However, for both men and
women, only one of these servings was from whole grain products. The health benefits
of a higher fiber diet are addressed in other relevant sections of this handbook.
The other carbohydrate intake issue is the consumption of refined sugar, which contrib-
utes calories but little other nutritive value to the diet. The 1994-96 CSFII data revealed
that approximately 14% of the average energy intake for adult males was from added
sugars. For women, the caloric contribution from added sugars was slightly higher at
approximately 15%. Foods such as breads, cakes, soft drinks, jam, and ice cream were
contributing to the discretionary sugar intake. In 1994 to 1996, soft drink consumption
out-paced milk and coffee, and approximately 75% of the soft drink consumption is of
the sugar-sweetened variety.43 During the last decade, consumption of snack foods such
as cakes, cookies, pastries, and pies has increased 15%, likely contributing to the high
intake of discretionary sugar.43 These data are in contrast to the importance consumers
report they place on a diet moderate in sugar intake. A majority (slightly over 50%) of
adults surveyed in the 1994-96 CSFII indicated it was very important to consume a diet
moderate in sugar.
Summary
Counseling the normal healthy American adult should focus on dietary intake patterns
that promote health and reduce risk for chronic disease, i.e., diet recommendations should
follow the U.S. Dietary Guidelines. Therefore, consistent with the 2000 edition of the U.S.
Dietary Guidelines, the focus on nutrition counseling should be:
Aim for fitness.

• Aim for a healthy weight:
1. Calculate the appropriate weight for the individual.
2. Consider the fat distribution pattern and take a more aggressive posture
with individuals whose body fat distribution is more “apple” than “pear”
shaped and hence places them at higher health risk.
3. For individuals whose body weight is inappropriate, initiate counseling
to assist in weight reduction. This may include calculation of appropriate
caloric intake, recommendations of sources of caloric intake from the
macro-nutrients of protein, fat, and carbohydrate, appropriate portion
sizes to control caloric intake, and increases in physical activity (second
dietary guideline, see below).
• Be physically active each day.
Build a healthy base.

• Let the pyramid guide your food choices. Based on current consumption
patterns, the average adult can likely benefit from nutrition counseling that:
1. Recommends greater restraint with respect to servings of discretionary
fats, sweets, and alcohol from the top portion of the pyramid.
2.Recommends somewhat higher intake of fish and meat alternatives such

as soy products and a continued reduction of ounces of high fat meats
like frankfurters and luncheon meats.
• Eat a variety of grains daily, especially whole grains. Current carbohydrate
consumption patterns indicate that the average adult American should be
counseled to:
1. Increase his/her consumption of whole grain products.
2. Use greater restraint with respect to his/her consumption of less nutrient
dense refined sugar.
• Eat a variety of fruits and vegetables daily. Variety as well as an increase in
quantity is appropriate when counseling adults. Data indicate that the most
common vegetable is the potato. Greater variety of both fruits and vegetables
will help contribute a wider range of nutrients and other phytochemicals that
might be more appropriate for health promotion.
• Keep food safe to eat. Food safety is as important as nutrient intake with
respect to health maintenance. Attention in counseling should be given to
insuring the individual’s understanding of safe food handling and food prep-
aration techniques.
Choose sensibly.
• Choose a diet low in saturated fat and cholesterol and moderate in total fat.
Over-consumption of discretionary fat is common with adult Americans.
Counseling that helps identify small dietary changes that can be made to
reduce total fat, saturated fat and cholesterol intake is appropriate.
• Choose beverages and foods that limit your intake of sugars. Nutrition coun-
seling for adults should help clients identify sources of sugars in their diet,
particularly the sugar contribution that might be coming from soft drinks.
Not only are soft drinks widely promoted in the American culture, but pop-
ular serving sizes range from 8 to 16 to as high as 32 ounces.
• Choose and prepare foods with less salt. The concerns of a high salt intake
are dealt with in other sections of this handbook, which also indicate the need
to help adults recognize foods that are contributing to an excessive salt intake.
• If you drink alcoholic beverages, do so in moderation. The average American
adult needs to be cognizant of his/her caloric intake. Low nutrient dense
alcohol calories may be inconsistent with the caloric intake needed to achieve/
maintain a healthy weight. This fact needs to be discussed in a nutrition
counseling session.
References
1. United States Department of Health and Human Services, Public Health Service, No. 88-50210,
Surgeon General’s Report on Nutrition and Health. United States Government Printing Office,
Washington DC, 1988.
2. Dietary Guidelines for Americans 2000, www.ars.usda.gov/dgac
3. US Senate, Select Committee on Nutrition and Human Needs, US Senate, December 1977,
95th Congress — 1st Session.
4. United States Department of Agriculture, United States Department of Health and Human
Services, Nutrition and Your Health. Dietary Guidelines for Americans. Home and Garden Bulletin
No. 232, Washington, DC, 1980.
5. United States Department of Agriculture, The Food Guide Pyramid. Home and Garden Bulletin
No. 252.a, United States Printing Office, Washington, DC, 1992.
6. Kant, A.K., Block, G., Schatzkin, A., et al., JADA 91: 1526; 1991.
7. Food and Nutrition Board, National Research Council, Recommended Dietary Allowances, 10th
ed., National Academy Press, Washington, DC, 1989.
8. Food and Nutrition Board, Institute of Medicine, Dietary Reference Intakes for Calcium, Phospho-
rus, Magnesium, Vitamin D and Fluoride, National Academy Press, Washington, DC, 1997.
9. Food and Nutrition Board, Institute of Medicine, Dietary Reference Intakes for Thiamin, Riboflavin,
Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy
10. Food and Drug Administration, Focus on Food Labeling. Special Issue of FDA Consumer Mag-
azine, May 1993, DHHS Publication No. (FDA) 93-2262, United States Government Printing
Office, Washington, DC, 1993.
11. _________________ Nutrition Reviews, 49: 291; 1991.
12. _________________ American Cancer Society, Nutrition and Prevention,
www2.cancer.org/Prevention/index.cfm?prevention=importance.
13. Wardlaw, G. Contemporary Nutrition: Issues and Insights. 3rd ed., Brown and Benchmark, Mad-
ison, WI, 1997.
14. Shetty, P.S., Henry, C.J.K., Black, A.E., Prentice, A.M.., Eur J Clin Nutr, 1006: 11S; 1996.
15. Boyle, M.A., Morris, D.H., Community Nutrition in Action: An Entrepreneurial Approach, 2nd
ed., Wadsworth Publishing, Belmont, CA, 1999, p. 112.
16. Federation of American Societies for Experimental Biology, Third Report on Nutrition Moni-
toring in the United States, Vol. 1, United States Government Printing Office, Washington DC,
1995.
17. Centers for Disease Control and Prevention, National Diabetes Fact Sheet: National Estimate and
General Information on Diabetes in the United States, United States Department of Health and
Human Services, Centers for Disease Control and Prevention, Atlanta, GA, Nov. 1, 1977.
18. McGinnis, J.M., Foege, W.H., JAMA, 270: 2207; 1993.
19. National Institutes of Health, National Heart, Lung and Blood Institute, Clinical guidelines
on the identification, evaluation, and treatment of overweight and obesity in adults — the
evidence report, Ob Res, 6: 51S, 1998.
20. Colditz G.A., Wolf, A.M., In: Progress in Obesity Research, (Anderson, A.H., Bouchard, C., Lau,
D., Leiter, L., Mendelson, R., Eds) John Libbey & Co., 7th International Congress on Obesity,
1996.
21. Centers for Disease Control and Prevention, Update: prevalence of overweight among chil-
dren, adolescents and adults, United States, 1988-94, Mortality and Morbidity Weekly Report,
46(9), 199-202, 1997b.
22. Foreyt, J., Goodrick, K., The Lancet, 346: 134; 1995.
23. American Dietetics Association, Position of the American Dietetic Association: Weight man-
agement. JADA, 97: 71; 1997.
24. National Institutes of Health, Methods for voluntary weight loss and control, Technology Assess-
ment Conference, Bethesda, MD, 1992.
25. The Low-Carb, High-Protein Craze, Am Inst Cancer Res Newsl, Vol. 67, Spring 2000.
26. American Dietetic Association, Position of the American Dietetic Association: Very-low-calorie
weight loss diets, JADA, 90: 722; 1990.
27. Kendall, A., Levitski, D.A., Strupp, B.J., Lissner, L., Amer J Clin Nutr, 53: 1124; 1991.
28. U.C. Berkeley Wellness Letter, June, 1998.
29. Liebman, B., Nutrition Action Health Letter, July/August, 1996.
30. Rippe, J.M., Crossley, S., Ringer, R., Obesity as a chronic disease: modern medical and lifestyle
management, JADA, 98: 2: S9; 1998.
31. Ahmed, F.E., JADA, 91: 1266; 1991.
32. Chow, W.H., Gridley, G., McLaughlin, J.K., Mandel, J.S., et al., J Natl Cancer Inst, 86: 1131; 1994.
33. Hu, J., Zhao, X.H., Parpia, B., Am J Clin Nutr, 58: 398; 1993.
34. Hegsted, D.M., J Nutr, 116: 2316; 1986.
35. Bucci, L., Nutrients as Ergogenic Aids for Sports and Exercise, CRC Press, Boca Raton, 1993.
36. Anderson, S.A., Raiten, D.J., Eds, Safety of Amino Acids Used as Supplements, Federation of
American Societies for Experimental Biology, Bethesda, MD, 1992.
37. Emken, E.A., Amer J Clin Nutr, 62: 659S; 1995.
38. Katan, M.B., Zock, P.L., Ann Rev Nutr 15: 473; 1995.
39. Shapiro, S., Amer J Clin Nutr, 66: 1011S; 1997.
40. Jenkins, D.J.A., New Engl J Med, 329: 21; 1993.
41. Munster, I.P., de Boer, H.M., Jansen, M.C., et al., Amer J Clin Nutr, 59: 626; 1994.
42. Salmeron, J., Manson, J.E., Stampfer, M.J., Coldizt, G.A., et al., JAMA, 277: 472; 1997.
43. Frazao, E., Ed, America’s Eating Habits, Economic Research Service Report. Agriculture Infor-
mation Bulletin No. 750. Washington, DC, 1999.
10
Nutrition in the Later Years
Elaine B. Feldman
Introduction
This section incorporates some nutritional concepts that are described in more detail in
the sections on cardiovascular disease, cancer, skeletal disorders, neuropsychiatric disor-
ders (cognitive), and the adult diet. Information will be provided on the varying problems
of the successful and healthy free-living older adults and domiciled elderly, the very old
(>85 years), and the old old (centenarians).
Background
The elderly are the fastest growing segment of the U.S. population (see below). It is
projected that the number of institutionalized elderly will triple in the next few decades,
and the number of people over 85 years of age (the very old) as a percent of the total
population will quadruple. The nutritional needs and problems of these groups differ
from those of their younger cohorts. Specific changes in lifestyle and physiology influence
nutritional status. The prevalence of chronic disease increases with age, and the treatment
of these diseases with drugs and diet have an additional impact on nutritional status.
Dietary recommendations need to be designed for these people in order to obtain their
compliance. Surveys have shown that in people over age 75, malnutrition affects 15% of
outpatients, 50% of hospitalized patients, and 85% of institutionalized patients.1
The Biology of Aging

Aging is characterized by a gradual, cumulative loss in metabolic control. Homeostatic
mechanisms that control body function gradually become less efficient. Physiologically
0-8493-2705-9/01/$0.00+$1.50
and biochemically, senescence occurs not in an orderly fashion but at unexpected times
and with unanticipated events. Some of these events are predictable, but some are not.
For example, the loss of ovarian function is predictable but its timing is not. There is
considerable individual variation in the loss of menses among women. Some of the age-
related loss in metabolic control can be explained by age-related accumulations of DNA
mutations in both the nuclear and mitochondrial genome. Some of these mutations are
diet responsive while others are not.
With age there are changes in DNA (base substitutions, deletions, aberrant repair) that
result in functional loss in the activity of the gene product(s) the DNA encodes. Changes
in the DNA (as well as some of the gene products) are biomarkers of aging.2 Studies in
animals have shown that lifelong food restriction results in a delay in the appearance of
DNA aberrations as well as a delay in the changes in the activities of key enzymes.
Food–restricted animals live longer than non-restricted animals that are kept under the
same conditions, fed the same qualitative diet, and are of the same gender and genetic
makeup.3 The extrapolation of these findings in rats and mice to humans is questionable
because of the nature of the experimental conditions used. The animals are genetically
similar and they are protected from infectious agents. They are reared under conditions
of carefully regulated environments that are temperature, humidity, and light controlled.
The food is carefully prepared to contain all the needed nutrients, with the only constraint
being the reduction in the energy supply. Humans do not exist under these conditions.
They are randomly exposed to environmental insults, their food is seldom consistent from
one day to the next, and their genetic backgrounds are highly variable. As social creatures
we do not live singly in cages; we experience wars, economic duress, social upheavals,
and so forth. Nonetheless, some of the observations in animals have been also made in
humans. For example, normal aging in humans is characterized by an accumulation of
deletions in mitochondrial DNA in various tissues.4 This may result from free radical
attack on the genome, and may be ameliorated by antioxidants.5
Age has a profound effect on membrane saturation and fluidity.6 An age-related decline
in membrane-associated reactions or pathways occurs, independent of changes in the diet
or the hormonal milieu. The efficiency of oxidative phosphorylation declines with age
(Table 10.1). Mitochondrial damage and loss of function occurs, in part related to increased
formation of superoxide and other free radicals.
With age, the efficiency of transmission of hormone and secondary messenger commu-
nications decreases (Table 10.2). This is due to numerous structural and functional changes
in the endocrine glands, a decline in gene expression, and in the accuracy and efficiency
of protein synthesis. The hormones affected regulate the metabolism of carbohydrates,
lipid, and protein. The progressive changes in the mitochondria and in gene expression
lead to progressive loss in the tight control of intermediary metabolism (Table 10.1). This
is coupled with age-related changes in the endocrine and central nervous systems.
Mortality and Aging Statistics

The leading causes of death in the U.S. in 1980 and 1996 are listed in Table 10.3.7 Over
this period the three leading causes of death remain: cardiovascular, neoplastic, and
cerebrovascular disease. Chronic obstructive pulmonary disease currently exceeds injuries,
followed by diabetes mellitus, human immunodeficiency virus (HIV) infection (not listed
in 1980), suicide, and chronic liver diseases. Table 10.4 lists the death rates for 1996.8 Many
Nutrition in the Later Years 321
TABLE 10.1
Effects of Age on Intermediary Metabolism and Its Control
Pathway Control Points Effects of Agea
Glycolysis Transport of glucose into the cell (mobile glucose transporter) ↓
Glucokinase ↓
Phosphofructokinase ↓
α-Glycerophosphate shuttle
Redox state, phosphorylation state
Pentose phosphate shunt Glucose-6-phosphate dehydrogenase ↓
6-phosphogluconate dehydrogenase ↓
Glycogenesis Stimulated by insulin and glucose ND
High-phosphorylation state (ratio of ATP to ADP) ND
Glycogenolysis Stimulated by catecholamines ND
Lipogenesis Stimulated by insulin
Acetyl-CoA carboxylase
High-phosphorylation state
Malate citrate shuttle ↓
Gluconeogenesis Stimulated by epinephrine
Malate aspartate shuttle ↓
Redox state ↑
Phosphoenopyruvate carboxykinase ↓
Pyruvate kinase
Cholesterogenesis HMG CoA reductase
Ureogenesis Carbamyl phosphate synthesis ↑,↓
ATP ND
Citric acid cycle All three shuttles
Phosphorylation state ↓
Lipolysis Lipoprotein lipase ↓
Respiration ADP influx into the mitochondria ↓
Ca2+ flux
Shuttle activities ↓
Substrate transporters ↓
Oxidative phosphorylation ADP-ATP exchange ↓
Ca2+ ion
Protein synthesis Accuracy of gene transcription ↓
Availability of amino acids ↓
ATP ↓
a ↑ — increased as the animal ages; ↓ — decreased as the animal ages; ND — no data.
From Berdanier, C.D., Advanced Nutrition: Macronutrients, 2nd ed., CRC Press, Boca Raton, 2000, pg. 252. With
permission.
TABLE 10.2
Hormone Changes with Age
Hormone Age Effects
Serum thyroxine (T4) ↓
Serum triiodothyronine (T1) ↓
Thyroid-binding globulin No change or ↑
Thyroid-stimulating hormone ↓
Insulin ↑ followed by ↓
ACTH ↓
Epinephrine ↓
Glucagon ↓
Growth hormone ↓
Estrogen ↓
Testosterone ↓
Cortisol (glucocorticoids) ↓
Pancreatic polypeptide ↑
Note: ↑ — increase; ↓ — decrease.
From Berdanier, C.D., Advanced Nutrition: Macronutrients, 2nd
ed., CRC Press, Boca Raton, 2000, pg. 250. With permission.
TABLE 10.3
Leading Causes of Death and Numbers of Deaths, According to Sex and
Race, United States, 1996
Sex, Race, and
Rank Order Cause of Death Deaths
All Persons
All causes 2,314,690

1 Diseases of heart 733,381
2 Malignant neoplasms 539,633
3 Cerebrovascular diseases 159,942
4 Chronic obstructive pulmonary diseases 106,027
5 Unintentional injuries 94,948
6 Pneumonia and influenza 83,727
7 Diabetes mellitus 61,767
8 Human immunodeficiency virus infection 31,130
9 Suicide 30,903
10 Chronic liver disease and cirrhosis 26,047
Male

9 Suicide 24,998
Female

8 Alzheimer’s disease 14,426
9 Nephritis, nephrotic syndrome, and nephrosis 12,662
10 Septicemia 12,177
White

8 Suicide 27,856
10 Alzheimer’s disease 20,198

Leading Causes of Death and Numbers of Deaths, According to Sex and
Race, United States, 1996
Sex, Race, and
Rank Order Cause of Death Deaths
Black
All causes 282,089

7 Homicide and legal intervention 9,983
10 Certain conditions originating in the perinatal period 4,711
Data based on the National Vital Statistics System, taken from Table 33, Health, United
States, 1998, page 212.
TABLE 10.4
Leading Causes of Death in the United States, Death Rates and
Age-Adjusted Death Rates, 1996
% of Total Rate/100,000 Age-Adjusted
Rank1 Cause of Death Deaths Population Rate
1 Heart diseases 31.6 276.6 134.6
2 Cancers 23.4 205.2 129.1
3 Stroke 6.9 60.5 26.5
4 Lung diseases 4.5 40.0 21.0
5 Accidents2 4.0 35.4 30.1
6 Pneumonia and flu 3.5 31.1 12.6
7 Diabetes mellitus 2.6 23.2 13.6
8 AIDS 1.4 12.3 11.6
9 Suicide 1.3 — 10.8
10 Liver disease 1.1 11.6 7.5
11 Renal diseases 1.1 9.5 4.3
12 Infections 0.9 9.2 4.1
1 Based on the total number of deaths in 1996 (2,322,421). These 12 causes account
for 82.3% of the total.
2 The preferred term is unintentional death. It includes motor vehicle-related deaths.
Taken from Morbidity and Mortality Weekly Report, U.S. Department of Health and
Human Services, Vol. 46, Oct. 10, 1997.
of these disorders are nutrition-related in their etiology or treatment, and are discussed
in individual sections in this handbook.
These mortality statistics are relatively similar for men and women, with striking differ-
ences seen only in the higher prevalence of Alzheimer’s disease, renal disease, and septi-
cemia appearing for women, and HIV, suicide, and liver disease replacing these in men.
Life expectancy at birth is expected to exceed 80 years in the first century of this
millennium, up from 49 years in 1900. The proportion of people in the U.S. over age 65
increased by 89% between 1960 and 1990, and over age 84 by 232%. The number of
centenarians in the U.S. has increased eightfold from 1950 (4447) 1990 (35,808).9
Lifestyle and Socioeconomic Changes Affecting the Nutritional Status of

the Elderly
Changes with aging include:10
• Reduced income with retirement

• Insufficient funds for purchase of food
• Skipping meals
• Illness and increased medical expenses
• Loss of mobility
• Diminished acuity in sensory perceptions (hearing, vision, taste)
• Inability to drive to doctor’s appointments or to the grocery store
• Inability to prepare or store food
• Loss of balance
• Diminished self-esteem
• Social isolation
Diseases that are common in the elderly and impact on their nutritional status include:
• Senile dementia of the Alzheimer’s type, with cognitive impairment and memory
loss
• Arthritis, with limited mobility of joints, and deformities
• Osteopenia, with fractures and deformities
• Parkinson’s disease, with rigidity and tremor
• Dental and oral health problems — problems with chewing
• Gastrointestinal disorders — swallowing difficulties
• Neoplasms, with hypercatabolism, anorexia, and cachexia
• Diabetes mellitus, with restrictive diets and medication interactions
• Renal insufficiency, with restrictive diets and dialysis treatment
• Paralysis, limiting mobility
• Depression, leading to anorexia
Some deterioration in mental function may be attributable to malnutrition of protein,

energy, and vitamins and/or minerals, either primary or secondary to disease. These
aspects are discussed in the sections on the nutrients and the diseases.
A survey of the elderly in South Carolina in 199010 showed that 20% skip meals, 33%
live alone, 45% use multiple prescription medications. Half of those over 85 years of age
are dependent or disabled; 10% over age 65 are cognitively impaired, with 25% so impaired
over age 85. Indicators of poor nutritional status were:
• <80% of desirable weight for age

• <10th percentile for triceps skinfold thickness or midarm muscle circumference
• Weight loss >5%/month or 10% loss in 6 months; involuntary weight loss
210
Systolic
Black women
185
Mean Blood Pressure, mm HG Black men
160
White women
135
White men
110
115
100
Diastolic
85
70
15 25 35 45 55 65 75
Age, years
FIGURE 10.1
The change in blood pressure with age. The ordinate represents mean blood pressure, with the upper curves
depicting systolic blood pressure and the lower curves diastolic pressure. The circles represent black women,
the triangles represent black men, the filled circles represent white women, and the squares represent white
men. From Feldman, E.B., Nutrition in the Middle and Later Years, Wright-PSG, Littleton, MA, 1983. Data are
adapted from Hames, C.G., Postgrad Med, 56: 110; 1974, with permission.
• Osteoporosis
• Anemia
Pathophysiology of Aging
The changes with aging and old age that may be nutrition related and/or diet responsive
include:
• Blood pressure (Figure 10.1)11,12 — Both systolic and diastolic blood pressure
increase with age, so beyond age 50 half of the population has hypertension. In
the Southeast, this is especially prevalent in African-American women.12 A vari-
ety of nutrients affect blood pressure, including energy, sodium, potassium,
calcium, magnesium, selenium, lipids, protein, and vitamin C. Consumption of
fruits and vegetables (10 servings a day) lowered blood pressure significantly.13
While the role of sodium has been questioned, recent trials show a beneficial
effect of sodium restriction even in the presence of other successful non-phar-
macologic interventions.14
• Blood lipids — Genetics and lifestyle (diet, exercise) interact to influence the
concentration and composition of blood lipids and lipoproteins. To date, there
is no convincing evidence that risk factors for cardiovascular disease differ in
the elderly, although their impact may differ because of changes in vasculature.
Neither homocysteine levels in relation to age nor the regulation of homocysteine

by B vitamins have been adequately studied.15 Stroke is more common in older
adults, and nutrients that affect thrombosis and blood clotting are important in
the management of these risk factors. (See section on Cardiovascular Risk.)
• The incidence of cancer and the decline in the immune system with aging may
be influenced by many nutrients. Whether advice about diet (plant-based, avoid-
ance of certain foods/nutrients or cooking methods) is equally applicable to the
elderly is not known. (See section on Cancer Prevention.)
• Bone density — Bone density declines with aging in women and men, beginning
in women around the perimenopausal years, and decades later in men. Bone
mineralization is related to the intakes of calcium, vitamin D, and other nutrients,
as well as to activity level and alcohol intake. Evaluation with appropriate tests
should be part of the geriatric assessment. Women, especially, should be encour-
aged to achieve a maximum bone density through adequate intake of calcium
and physical activity. The greater the bone density at peak, the less serious the
effect of estrogen loss that is associated with decreased bone density. Problems
with bone and cartilage are being addressed with dietary supplements like
glucosamine that are under evaluation. Fish oils and polyunsaturated fatty acids
also may be of benefit in various types of arthritis.16
• Significant memory loss is not a necessary accompaniment of aging. Nutritional
interventions in patients with senile dementia of the Alzheimer type may either
ameliorate or slow the progress of the disease, or, more likely, improve the
patient’s general nutritional status and function.
• The immune system shows impairment, particularly of cellular immunity, and
may be improved with B6, vitamin E, or selenium.17
The Geriatric Assessment

Nutrition screening should be part of the geriatric assessment.18 The clinical nutritional
assessment of adults is detailed in the Assessment section. The elderly are a heterogeneous
population, so no assumptions should be made about individuals.
Particular attention should be paid to the intake of medications. Polypharmacy is com-
mon in the elderly and may lead to drug-nutrient interactions that affect the efficacy and
safety of the medication as well as the nutritional status of the patient. Among these are:
• Thiazide diuretics for the management of hypertension. These drugs increase

the loss of potassium.
• Antidepressants used for mood management. These drugs may induce dry
mouth, altered taste, nausea, vomiting, constipation, and/or reduced appetite.
• Chronic antacids and laxative use (preoccupation with need to have a daily
bowel movement) can result in chronic diarrhea and electrolyte imbalance.
• Anti-inflammatory preparations used to relieve muscle or joint pain. These drugs
may induce iron-deficiency anemia.
• An annual involuntary weight loss of 4% is a cutpoint that affects 13% of indi-
viduals over age 65 whose 2-year mortality is doubled versus weight-stable
individuals.1
The RDAs for the Elderly

The most recent revisions of the Recommended Dietary Allowances, including the new
Dietary Reference Intake values, have added a category for the elderly. Values have been
set for males and females for calcium, phosphorus, magnesium, vitamin D, fluoride,
thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and
choline. Values for vitamin D have been increased because of concern about deficient
intake, decreased metabolism, and the prevalence of bone disease in the elderly (see section
on Skeletal Diseases). More recently, values were set for vitamins C and E and selenium
for those over 70 years of age (Table of DRIs). The remaining RDAs and the recommen-
dations for intake of essential nutrients dating from 1989 (vitamin A, macronutrients, some
trace minerals) are under revision and may set new values for males and females >70
years of age.
A Food Pyramid for those over 70 years of age has been developed by Tufts University
nutritionists (Figure 10.2). In contrast to the original Food Pyramid (Section 11), the need
for water forms the base of the pyramid for the elderly, while the number of servings in
the various food groups has been modified downward, and supplements of calcium,
vitamin D, and vitamin B12 are recommended.19
Body Composition and Aging

Changes in body composition with aging (Figure 10.3) include an increase in the percent
of body fat and a decrease in lean body mass.20 These changes are associated with an age-
related decline in metabolic rate and with a quantitatively greater decline in energy
expenditure from physical activity21 (Figure 10.4).
The fat mass in untrained older men (age 69) was significantly higher than in younger
subjects (age 31) and correlated negatively with plasma IGF-1 levels. Older trained sub-
jects had a similar fat mass to untrained younger subjects. The lean body mass (skeletal
muscle) was lower in older than in younger untrained men, but older trained men did
not differ from similarly trained younger men.22 Investigators have experimented with
the use of growth hormone to lessen age-related changes in body composition, with
encouraging results.23 A study in men age 61 to 81 years showed that injections of human
growth hormone given over 6 months increased low levels of IGF-1 to the higher levels
of the youthful. Lean body mass increased 9%, and fat mass decreased 14%. Data, how-
ever, are inadequate to recommend a costly and potentially toxic therapy that is admin-
istered by injection.
Nutrient Requirements and Aging

For many nutrients, requirements in the older adult relate more to gender and body size
than age. Important changes (increased or decreased need) in a number of nutrients,
however, include energy, vitamins B12, D, and calcium.1
Calcium, vitamin D,
vitamin B-12
SUPPLEMENTS
Fats, Oils, and Sweets
USE SPARINGLY
Milk, Yogurt, and Meat, Poultry, Fish, Dry

Cheese Group Beans, Eggs, and Nut Group
3 SERVINGS ƒ+ ≥ 2 SERVINGS
Vegetable ƒ+ Fruit Group

Group ≥ 2 SERVINGS
≥ 3 SERVINGS ƒ+
ƒ+
ƒ+ ƒ+
ƒ+ Bread, Fortified
ƒ+ Cereal, Rice, and
ƒ+ Pasta Group
≥ 6 SERVINGS
ƒ+ ƒ+ ƒ+
Water
≥ 8 SERVINGS
H2O H2O H2O H2O H2O H2O H2O H2O
• Fat (naturally occurring and added)

Sugars (added)
ƒ+ Fiber (should be present)
These symbols show fat, added sugars and fiber in foods.
FIGURE 10.2
The Food Pyramid modified for adults 70 years of age and older. From Russell, R.M., Rasmussen, H., and
Lichtenstein, A.H. J. Nutr. 129: 156; 1999, with permission.
Energy
The decrease with age in the whole body basal metabolic rate (Figure 10.4) is especially
pronounced in the cells of the brain, skeletal muscle, and heart that are major contributors
to the resting energy expenditure. In combination with the decline in physical activity,
overall energy consumption declines on average 10% per decade after age 60. In men
between age 28 and 80, energy intake declines by 600 kcal.21 Women have a lower metabolic
rate than men, independent of body size. The resting metabolic rate in women declines
Fat 20%
36%
Cell
Mass
47%
36%
Bone
6%
Mineral 4%
Other 27% 24%
Age Age
25 70
FIGURE 10.3
The age-related change in body composition in men. From Feldman, E.B., Essentials of Clinical Nutrition, F.A.
Davis, Philadelphia, 1988, with permission.
4% per decade between age 50 and 80, with an increased downward slope after menopause
compared to a nonsignificant decline before age 50.24
The decline in basal/resting metabolic rate can be lessened somewhat by increased
physical activity (Figure 10.5). A combination of strength training and moderate aerobic
exercise, e.g., 30 minutes/day or walking 10 to 12 miles per week, can increase the resting
metabolic rate by 10%.25
Voluntary expenditure can increase significantly with physical activity. An increase in
energy expenditure by physical activity in an exercise program will have beneficial effects,
improving glucose uptake and metabolism by tissues (Figure 10.6), thereby normalizing
glucose tolerance.26 Studies used the insulin clamp technique and showed no difference
in glucose uptake in healthy persons age 21 to 53 years, with significantly lower values
in persons over 54 years of age. The relative drop in muscle mass in older subjects may
be responsible for this difference.
Fat stores in older men and women can be reduced towards those of younger individuals
(Figure 10.7) with an increase in lean body mass.27 Studies showed that the proportion of
body fat was significantly less in 67-year-olds who exercised regularly than in age-matched
sedentary controls. The loss of aerobic capacity with aging can be attenuated by 50% with
a regular exercise program (Figure 10.8).27 The maximal aerobic capacity of physically
active older subjects was significantly greater than that of persons of comparable age and
3000
2400
Kilocalories/Day
1800
1200
600
28 40 50 60 70 80
Age (Years)
FIGURE 10.4
Energy expenditure and aging. The solid line represents energy expenditure in men, the dashed line indicates
basal expenditure in men, the dotted line shows energy expended for activity in men. The resting metabolic
rate in women is the dot/dash line. The resting metabolic rate in kcal/minute is the ordinate and age in years
is the abscissa. Adapted from Feldman, E.B., In: Essentials of Clinical Nutrition, F.A. Davis, Philadelphia, 1988,
ch. 9 and Rudman, D., Feller, A.G., Nagrai, H.S., et al. N Engl J Med, 323: 11; 1991.
Baseline 1.03 +- 0.12
Light n = 7 (for all)

Exercise 1.04 +- 0.12
Moderate
1.13 +- 0.14
Exercise
0.9 1.0 1.1 1.2

RMR (kcal/min)
FIGURE 10.5
Exercise and the resting metabolic rate in older persons. The length of the top bar represents the resting metabolic
rate in kcalories/minute. The upper bar is the control, the middle bar shows effects of light exercise, and the
lowest bar shows the effect of moderate exercise. Adapted from Poehlman, E.T., Gardner, A.W., Goran, M.I.,
Betabolism, 41: 041; 1992.
300
Insulin-Stimulated Glucose Uptake 250
200
mL/m/min
150
100
50
0
21-34 35-54 > 55
Age (years)
FIGURE 10.6
The effect of age on glucose uptake. The height of the bar represents the mean insulin-stimulated glucose uptake.
The error bars represent 2.5 standard deviations from the mean. The lesser glucose uptake in those over age 55
differs significantly from the other two age groups (p<0.01). Adapted from Rosenthal, M., Doberne, L., Greenfield,
M., et al. J. Am. Geriatr. Soc. 30: 562; 1982.
BMI who did not exercise regularly, and was similar to that of young subjects who did
not exercise regularly.
An exercise program is important to prevent or limit obesity, diabetes mellitus, and
increases in blood pressure, lessen bone loss, and provide a favorable blood lipid profile,
increasing HDL-cholesterol and decreasing triglycerides.
To compensate for decreased energy requirements and prevent excessive weight gain,
overweight, and obesity, the energy intake of the elderly usually needs to decrease. Older
subjects who limit their energy intake, however, must consume more nutrient-dense foods
in order to meet protein and micronutrient needs. They should limit their intakes of
energy-dense foods such as fats and sweets, and take in adequate amounts of protein-rich
foods. A one-a-day multivitamin supplement designed for older adults may be indicated
when decreased energy intake is prescribed.
Vitamin B12
Vitamin B12 status in the elderly is impaired by achlorhydria and bacterial overgrowth
that binds this vitamin, inhibiting absorption. Achlorhydria affects 10 to 30% of the geri-
atric population, and associated atrophic gastritis further decreases the absorption of
vitamin B12 from food. The absorption of synthetic B12 is not adversely affected. This has
led some nutritionists to recommend markedly increasing the level of oral intake for older
adults from the RDA of 2.6 to 25 µg/day. This increased amount may be found in some
Age 34
p < 0.05
Age 68, not trained
Age 67, trained
0 10 20 30
Body Fat (%)
FIGURE 10.7
The effect of aging and physical training on body fat. The length of the top bar indicates values for % body fat
in young people, the middle bar represents these values in old people, not physically trained, and the bar at
the bottom represents the values in old people who are physically trained. Young people differ significantly
from old untrained, and old physically trained differ from old untrained. Adapted from Hollenbeck, C. et al. J.
Am. Geriatr. Soc. 33: 273; 1985.
vitamin supplements formulated for the older age group. The body’s handling of vitamin
B12 is reviewed in the section on Anemia.
Vitamin D
Vitamin D status in the elderly is impaired by multiple factors that decrease:
• Dietary intake
• Exposure to the sun
• Skin synthesis
• Hepatic and renal hydroxylation
• Receptors in the gastrointestinal tract
• Absorption
Skin synthesis of vitamin D by the elderly is only 30-40% of that of children and young
adults.28 The resulting decreases in vitamin D stores in the body lead to an increase in
parathyroid hormone and an increase in bone remodeling and bone loss. These factors
are discussed in the section on Skeletal Disorders.
Age 34
p < 0.001
Age 68, not trained
p < 0.05
Age 67, trained
.VO2 max (mL/kg/min)

0 10 30 50
FIGURE 10.8
The effect of aging and physical training on aerobic capacity. The length of the top bar indicates values for
maximum oxygen consumption in young people. The middle bar represents these values in old persons not
physically trained, and lowest the bar represents the values in old people who are physically trained. Young
people differ significantly from old untrained, and old physically trained differ from old untrained. Adapted
from Hollenbeck, C. et al. J. Am. Geriatr. Soc. 33: 273; 1985.
Multivitamin/Mineral Supplement
A daily multivitamin supplement suitable for the older age group may be indicated to
meet general micronutrient needs (vitamins, minerals). This is especially true for small,
old people, and whenever energy intake to meet energy expenditure is less than 1300
kcal/day.
Anorexia in the Elderly

Anorexia and weight loss are common in the elderly, especially in patients suffering from
medical or mental illness.29 With normal aging, men and women may decrease their energy
intake as they are less active physically and as their resting metabolic rate declines (Figure
10.4). The feeding drive (hunger) may decrease, and satiety may occur more readily. This
physiological change with aging, however, may be the precursor of pathological anorexia
and weight loss that most commonly is due to depression. Physiological and disease-
related anorexia may be mediated by changes in a variety of hormones or cytokines. In
order to prevent cachexia, with resultant morbidity and mortality, early recognition by
nutritional screening, and aggressive management is needed. Management can include
the use of enteral supplements and, if necessary, tube feedings or parenteral nutrition.
The underlying medical or psychiatric disorder must also be diagnosed and treated.
Various interventions have been proposed to improve appetite and metabolism in the
elderly. Among these is the use of growth hormone supplements. Growth hormone has
been shown to have some favorable effects on function, yet it is not without risk and is
quite expensive.23
Other studies in men comparing subjects with average ages 24 and 70 years showed
that aging may be associated with a significant impairment in the ability to control food
intake following overeating or undereating. These findings may explain the vulnerability
of older persons to unexplained weight loss.30
Nutritional Deficiencies in the Elderly

Various recent surveys have shown that 40% of the aged have intakes lower than two-
thirds of the RDA for energy and that intakes of calcium, iron, vitamins A, E, and D, water
soluble vitamins, and zinc are low.1 Deficient intakes are especially prevalent in some
ethnic groups and older individuals with low income. Osteopenia and iron deficiency
anemia are common, and are discussed in the respective sections of this handbook.
Homebound and Institutionalized Elderly

Malnutrition is common in elderly nursing home residents. Of special concern are intakes
of calcium, vitamin A, thiamin, riboflavin, and iron. Recommendations to decrease this
prevalence include improving the eating environment, searching for early signs of under-
nutrition, finding treatable causes of poor food intake (depression, dental problems) with
appropriate modifications of the diet, and controlling infection.31 Predictors or mortality
within six months were low levels of hemoglobin, cholesterol, and albumin. Socialization
improves eating behavior. Spacing meals at five-hour intervals, using multiple smaller
meals and snacks, providing a good breakfast, having food at the proper temperature,
and attention to adequate light all can improve food intake and meal enjoyment.32
Congregate and home delivery feeding programs are crucial for homebound elderly.
Water is a major concern in nursing home subjects. Thirst mechanisms are impaired in
many elderly, and water needs to be provided and intake insured, especially in hot climates
and in hot weather.
Patients should not be over-sedated and should be encouraged to be active, even if bed-
or chair-bound. A study of frail, institutionalized 90-year-olds showed that high-resistance
weight training lead to significant gains in muscle strength, size, and functional mobility.33
The Hospitalized Patient

The severity of nutritional deficits correlates with increased risk of subsequent morbid
events in the hospitalized elderly.34 Risk factors for malnutrition in hospitalized elderly
patients should be evaluated promptly on or after admission. These risk factors include
a history of inadequate food intake or unexplained, rapid weight loss, body weight or
other anthropometric measurements that show depletion, and low serum albumin.
With acute illness, food and water intake may cease. In the presence of hypercatabolism
from diseases, especially inflammatory or infectious disease, nutrient needs are increased.
Injuries or surgery may have similar effects. The elderly have fewer nutritional reserves,
especially if they are already undernourished; attention to feeding is vital. Any deficits
may be enhanced by the food deprivation resulting from tests or treatments that withhold
meals.
A study in a veterans’ hospital of non-terminally ill hospitalized patients indicated that
many elderly patients were maintained on inadequate energy intakes that may have
contributed to an eightfold increased risk of mortality in this group. These patients with
low nutrient intake also exhibited significantly lower serum cholesterol and serum albu-
min levels on discharge than other patients.33 The investigators recommend that greater
efforts should be made to prevent the development of protein–energy undernutrition
during hospitalization. Caregivers should be aware that the food may be unpalatable or
unacceptable by some ethnic groups, and this adds to the difficulty of adequate patient
nourishment. Illness or medication-related nausea, vomiting, or diarrhea will exacerbate
these difficulties.
Enteral supplements or total enteral or parenteral nutrition should be considered when
appropriate. An energy-rich, protein-rich beverage (one to two 8-oz servings daily) can
improve the outcome of patients with hip fracture and chronic obstructive pulmonary
disease, and be associated with diminished falling in frail elderly. Consultation with a
dietitian can help immeasurably.
Conclusion
The older population differs from younger adults not only by age but also by health status.
The elderly group is not a homogeneous population, and their many different health and
social problems impact their nutritional status.35 Optimal nutrient intake not only meets
their needs but prevents some chronic diseases and ameliorates others. Attention must be
paid to environmental, psychological, and pathophysiological parameters in evaluating
nutritional status and interventions. While there is no panacea for the aged, nor a “fountain
of youth,” much can be done to recognize their nutritional needs and improve their
nutritional health.
References
1. Ausman LA, Russell RM. In: Modern Nutrition in Health and Disease (Shils ME, Olson JO, Shike
M, Ross AC, Eds), 9th ed., Williams & Wilkens, Baltimore, 1999, ch. 53.
2. Berdanier CD. In: Encyclopedia of Gerontology (Birren JE, Ed), Vol 2, Academic Press, New York,
1996, pg 135.
3. Wei EC. In: Nutrients and Gene Expression: Clinical Aspects (Berdanier CD, Ed) CRC Press, Boca
Raton, 1996, pg 165.
4. Masoro EJ. Exptl Gerontology 30: 291; 1995.
5. Carr AC, Frei B. Am J Clin Nutr 69: 1086; 1999.
6. Berdanier CD. In: Fatty Acids in Foods and Their Health Implications (Chow CK, Ed) 2nd ed,
Marcel Dekker, New York, pg 569.
7. Health United States, 1998.
8. Morbidity and Mortality Weekly Report, US Department Health and Human Services, Vol. 46,
October 10, 1997.
9. Berdanier CD. Advanced Nutrition: Macronutrients, 2nd ed., CRC Press, Boca Raton, 2000.
10. White P. Nutrition Today 26:142; 1991.
11. Feldman EB. In Nutrition in the Middle and Later Years (Wright-PSG, Ed), Littleton, MA, 1983,
ch. 6.
12. Hames CG. Postgrad Med 56: 110; 1974.
13. Appel LJ, Moore TJ, Obarzanek E, et al. N Eng J Med 338: 1117; 1997.
14. Whelton PK, Appel L, Espeland MA, et al. JAMA 279: 839; 1998.
15. Selhub J, Jaques PF, Bostom AG, et al. N Eng J Med 331: 286; 1995.
16. James MJ, Cleland LG. Sem Arth Rheum 27: 85; 1997.
17. Bogden JD, Bendich A, Kemp FW, et al. Am J Clin Nutr 60: 137; 1994.
18. Fogt EJ, Bell SJ, Blackburn GL. In: Geriatric Nutrition, a Comprehensive Review (Morley JE, Glick
Z, Rubenstein LZ, Eds), 2nd ed., Raven Press, New York, 1995, ch. 5.
19. Russell RM, Rasmussen H, Lichtenstein AH. J Nutr 129: 156; 1999.
20. Feldman EB. In: Essentials of Clinical Nutrition, FA Davis, Philadelphia, 1988, ch. 9.
21. Munro HN. Br Med Bull 37: 84; 1981.
22. Horber FF, Kohler SA, Lippuner K, Jaeger P. Eur J Clin Invest 26: 279; 1996.
23. Rudman D, Feller AG, Nagrai HS, et al. N Eng J Med, 323: 11; 1991.
24. Poehlman ET, Goran MI, Gardner AW, et al. Am J Physiol 264: E450; 1993.
25. Poehlman ET, Gardner AW, Goran MI. Metabolism, 41: 041, 1992.
26. Rosenthal M, Doberne L, Greenfield M, et al. J Am Geriatr Soc 30: 562; 1982.
27. Hollenbeck C, Haskell W, Rosenthal M, Reaven GM, J Am Geriatr Soc 33: 273; 1985.
28. Holick MF, Matsuoka LY, Wortsman J. Lancet 2: 1104; 1989.
29. Morley JE. Drugs & Aging 8: 134; 1996.
30. Roberts S, Fuss P, Heyman MB, et al. JAMA 272: 1601; 1994.
31. Rudman D, Feller AG. J Am Geriatr Soc 37: 173; 1989.
32. Thomas DR, Verdery RB, Gardner L, et al. J Parent Ent Nutr 15: 400; 1991.
33. Fiatarone MA, Marks EC, Ryan ND, et al. JAMA 263: 3029; 1990.
34. Sullivan DH, Sun S, Walls R. JAMA 281: 2013; 1999.
35. Feldman EB. Am J Clin Nutr 58: 1; 1993.
Part V
Human Nutritional
Status Assessment
11
Dietary Guidelines, Food Guidance, and Dietary
Quality
Eileen Kennedy
The 1969 White House Conference on Food, Nutrition, and Health1 was instrumental in
the development of the first set of U.S. dietary guidelines. Specific recommendations
emerged out of this conference advocating that the government examine the links between
diet and chronic disease. The 1969 conference was followed in 1977 by the release of the
U.S. Senate Dietary Goals;2 these dietary goals for the first time summarized specific
recommendations for diet-related goals for the American public.
The Dietary Guidelines for Americans are the cornerstone of federal nutrition policy in
the U.S. Nutrition programs use the Dietary Guidelines as the basis of the nutrition
standards; thus programs such as Food Stamps, School Lunch/School Breakfast, and
Women, Infants, and Children (WIC) use the dietary guidelines in developing program
services. In addition, all nutrition education programs at the federal level must have
messages consistent with the Dietary Guidelines. As a result, the impact of the Dietary
Guidelines is broad. It is estimated that one of every five Americans participates in at least
one federal nutrition program.
History of the Dietary Guidelines for Americans

The Dietary Guidelines attempt to answer the question, “what should Americans eat
to stay healthy?” Specifically, the Dietary Guidelines provide advice for healthy Amer-
icans age two years and over about food choices that promote health and reduce the
risk of disease.
The Dietary Guidelines were first developed in 19803 and have been updated every five
years since then — 1985, 1990, 1995, and the most recent, Dietary Guidelines 2000.4-7 The
National Nutrition Monitoring and Related Research Act of 19908 requires the Secretary of
Agriculture and the Secretary of Health and Human Services to jointly publish a report
every five years entitled “The Dietary Guidelines for Americans.” The report must (1)
contain nutrition and dietary information and guidelines for the general public, (2) be
based on the preponderance of scientific and medical knowledge current at the time of
publication, and (3) be prompted by each federal agency in carrying out federal food,
nutrition, or health programs. The 1995 Dietary Guidelines were the first to be statutorily
mandated by the U.S. Congress.
0-8493-2705-9/01/$0.00+$1.50
Since 1985, the United States Department of Agriculture (USDA) and the Department
of Health and Human Services (HHS) have used essentially the same process to prepare
the Dietary Guidelines. An external Dietary Guidelines Advisory Committee (DGAC) has
been appointed by the two secretaries to review and revise the Dietary Guidelines as
necessary. The members of the DGAC are widely recognized nutrition and medical
experts. A series of open public meetings are held to review and discuss the guidelines.
Upon completion of the DGAC process, a technical report is sent to the two secretaries
and reviewed within the two departments. In addition, in 1995 and 2000, consumer
research was conducted9-10 to test consumer reaction to specific design and content ele-
ments of the technical report. The consumer research is also used as one element in
promoting the Dietary Guidelines.
Dietary Guidelines for Americans

From 1980 to 1995, the Dietary Guidelines have been relatively stable (Table 11.1), main-
taining seven guidelines. However, the 1995 guidelines reflected some exciting and impor-
tant changes. The 1995 guidelines,6 more than ever before, put an emphasis on total diet;
the wording moved away from individual foods in the direction of a total diet based on
variety, moderation, and proportionality. The concept of total diet is reflected symbolically
through the graphic of the 1995 Dietary Guidelines bulletin that links all seven guidelines
together, anchored around “Eat a Variety of Food.”
In the 1995 guideline on variety, the bulletin6 stresses a total diet rather than an indi-
vidual food approach to healthy eating. The recommendation is to choose foods from each
of the five major food groups in the Food Guide Pyramid. Also, an emphasis is placed on
TABLE 11.1
Dietary Guidelines for Americans, 1980 to 2000
1980 7 Guidelines 1985 7 Guidelines 1990 7 Guidelines 1995 7 Guidelines
Eat a variety of foods. Eat a variety of foods. Eat a variety of foods. Eat a variety of foods.
Maintain ideal weight Maintain desirable Maintain healthy weight Balance the food you eat
weight with physical activity —
maintain or improve
your weight
Avoid too much fat, Avoid too much fat, Choose a diet low in fat,
saturated fat, and saturated fat, and saturated fat, and
cholesterol cholesterol cholesterol
Eat foods with adequate Eat foods with adequate Choose a diet with plenty Choose a diet with plenty
starch and fiber starch and fiber of grain products, of grain products,
vegetables, and fruits vegetables, and fruits
Choose a diet low in fat,
saturated fat, and
cholesterol
Avoid too much sugar Avoid too much sugar Use sugars only in Choose a diet moderate
moderation in sugars
Avoid too much sodium Avoid too much sodium Use salt and sodium only Choose a diet moderate
in moderation in salt and sodium
If you drink alcohol, do If you drink alcohol If you drink alcoholic If you drink alcoholic
so in moderation beverages, do so in beverages, do so in beverages, do so in
moderation moderation moderation
Dietary Guidelines, Food Guidance, and Dietary Quality 341
foods from the base of the pyramid (grains) to form the center of the plate, accompanied
by food from other food groups.
For the first time, the Dietary Guidelines in 1995 recognized that with careful planning,
a vegetarian diet can be consistent with the Dietary Guidelines and the Recommended
Dietary Allowances.11 The guidelines also present a clear message that food sources of
nutrients are preferred to supplements. This “food first” strategy is reinforced by a dis-
cussion of other healthful substances present in food but not in dietary supplements.
However, the 1995 guidelines do provide specific examples of situations where dietary
supplements may be needed.
The 1995 guidelines also more forcefully moved in the direction of providing a discus-
sion of the direct link between diet and health. Weight gain with age was discouraged for
adults. Weight maintenance is encouraged as a first step to achieving a healthy weight.
The benefits of physical activity are emphasized, and for the first time, a statement was
included on the benefits of moderate alcohol consumption in reducing the risk of heart
disease. On this later point, both HHS and USDA were clear that the alcohol guideline
was not intended to recommend that people start drinking.
In the 1995 guidelines there was also direct reference to nutrition education tools that
could be used to promote the Dietary Guidelines. The guidelines explain how consumers
can use the “three crown jewels” to build a healthy diet — the Dietary Guidelines, the
Food Guide Pyramid,12 and the Nutrition Facts Label.
The Dietary Guidelines 2000, released by President Clinton in May 2000,7 break with
the tradition of seven guidelines and now incorporate ten guidelines. Not only do the
Dietary Guidelines 2000 continue to emphasize a total diet approach, they also emphasize
a healthy lifestyle approach. This is reflected clearly in three concepts that are used as
organizing principals for the 2000 Guidelines aim for fitness, build a healthy base, and
choose sensibly.
Three new guidelines have been added to the Dietary Guidelines 2000 (Table 11.2). There
is now a separate guideline for physical activity which states, “be physically active every
TABLE 11.2
U.S. Dietary Guidelines 2000 and Countries having Similar Guidelines
U.S. Dietary Guidelines 20007 Countries Having Similar Guidelines13
Aim for a healthy weight Australia, Canada, China, Japan, Korea, Malaysia, The
Netherlands, New Zealand, Philippines, Singapore,
Thailand, United Kingdom
Let the Pyramid guide your food choices Variety: Australia, Canada, China, France, Germany,
Hungary, Indonesia, Korea, Malaysia, New Zealand,
Philippines, Singapore, South Africa, Sri Lanka,
Thailand, United Kingdom, Japan Five Steps to Healthy
Eating: India
Eat a variety of grains daily, especially whole grains Australia, Canada, Denmark, Germany, Hungary
(choose potatoes over rice), India, Malaysia, Norway,
Singapore, South Africa (starchy foods), Thailand
Choose a diet that is low in saturated fat, and Australia (but low fat diets not suitable for children),
cholesterol, and moderate in total fat Canada, Japan, The Netherlands, New Zealand,
Singapore, South Africa
Choose and prepare foods with less salt Australia, Canada, China, Denmark, Germany,
Hungary, India, Japan, Korea, Malaysia, The
Netherlands, Singapore, South Africa, Thailand
If you drink alcoholic beverages, do so in moderation Canada, China, France, Germany, Indonesia (avoid),
Hungary (forbidden for pregnant women and
children), Korea, The Netherlands, New Zealand,
Singapore, South Africa, United Kingdom
day.” In addition to help in maintaining a healthy weight, this guideline discusses other
health benefits of physical activity. Specific quantitative recommendations are given for
amount of physical activity for adults (30 minutes or more) and children (60 minutes or
more) per day. For the first time ever, there is a guideline on food safety. Again, this
reinforces components of a healthy diet and healthy lifestyle. Finally, there is a separate
guideline for fruits and vegetables.
The consumer research conducted as part of the Dietary Guidelines 2000 process10
influenced the development of the guidelines. One clear message is that consumers
preferred simple, action-oriented guidelines. Thus, the guidelines are much more direct
and action oriented as evidenced by “aim for a healthy weight” and “keep foods safe
to eat.”
The guidelines are more consumer friendly, and emphasize practical ways in which the
consumers can put the concepts into practice. To that end, a section entitled “Advice for
Today” is included at the end of each individual guideline and includes suggestions on
key ways to operationalize the guidelines. The consumer research on the 2000 Dietary
Guidelines 10 indicated that consumers particularly appreciated sections such as “Advice
for Today.”
Comparison with Other Dietary Guidelines

A large number of countries — both industrialized and developing — have authoritative
sets of dietary guidelines.13 Despite vastly different geographical and sociocultural con-
texts, six elements are common to the sets of dietary guidelines (Table 11.2).
A guideline on variety is common; it is often the core element of the different sets of
dietary guidelines, and is used to reflect the concepts of dietary diversity. The variety
guidelines range from general statements such as, “Eat a variety of foods” to very specific
quantifications, such as that as found in the Japanese guideline: “Obtain well-balanced
nutrition with a variety of foods; eat 30 foodstuffs a day.”
Many of the country-specific dietary guidelines emphasize limiting or moderating total
fat and saturated fat intake. Where there is a quantification of limits, this is most commonly
a diet containing no more than 30% of total energy from fat and less than 10% of energy
from saturated fat.
Countries typically also include a weight guidelines, clearly emphasizing maintaining
or achieving a healthy weight; in the French guideline this is more specific, indicating that
individuals should weigh themselves monthly.13 Most of the dietary guidelines worldwide
promote a plant-based diet as the building block of healthful eating. To that end, many
countries emphasize grains as the basis of good diet. Reduction of salt and/or sodium is
emphasized in a number of the sets of dietary guidelines.
Finally, the issue of alcohol consumption is addressed in many sets of dietary guide-
lines. There is always a level of caution related to the role of alcohol as part of a healthy
diet. The most recent 2000 Dietary Guidelines for Americans, for example, indicates
that the benefits of alcohol in reducing the risk of heart disease can be achieved in other
ways: maintaining a healthy weight, cessation of smoking, increasing physical activity,
and reducing the level of fat and saturated fat in the diet. Indeed, countries like
Venezuela go even further, and specify that “alcoholic beverages are not part of a healthy
diet.”14
Comparison of U.S. Dietary Guidelines with Disease-Specific Guidelines

A number of professional associations have developed sets of dietary guidelines. Table
11.3 compares the U.S. Dietary Guidelines 20007 with guidelines of the American Heart
Association (AHA)15 and American Cancer Society (ACS).16 Clearly the AHA and ACS
have somewhat different objectives in developing their specific sets of guidelines. The
AHA guidelines put forward recommendations for a healthful diet which, if followed,
reduce the risk of heart disease. Similarly, recommendations from the ACA are for dietary
guidelines which reduce the risk of cancer. Given the somewhat differing objectives,
there is a remarkable degree of similarly in the three sets of guidelines (Table 11.3). Here
again, the USDA/HHS, the AHA, and the ACA each recommend dietary guidelines
related to weight, total fat/saturated fat, salt, and alcohol in moderation as the basis of
a healthful diet.
Future Directions
Many countries have been successful in developing and promoting food-based Dietary
Guidelines. In most cases these guidelines are intended for individuals ages two and older.
In the U.S., the Dietary Guidelines from their inception in 1980 have been intended for
individuals ages two and older. There is a clear gap in dietary guidelines for children ages
two and younger.
A limited number of countries have some parts of their food-based guidelines devoted
to children less than two years of age. In most cases the advice for children under two
years of age relates to a discussion of breastfeeding. Australia, for example, states: “encour-
age and support breastfeeding.” Similar wording is found in guidelines from the Philip-
pines and Singapore.
Most industrialized countries rely on national pediatric associations to guide the broad
policy recommendations for infant feeding and/or feeding practices for the first two years
of life. In almost all cases, advice from pediatric associations stresses that human milk is
the preferred form of infant feeding.17
In devising food-based dietary guidelines for children under two, there would be a clear
need to segment this group of children by age groups; birth to 6 months, 6 to 12 months,
and 13 to 24 months. The dietary issues addressed across these three age groups would
differ.
Dietary Guidance
In the preceeding segment the development of the U.S. Dietary Guidelines was traced.
The United States Department of Agriculture (USDA) has a long, rich history of providing
science-based nutrition information and education for the general public (Table 11.4). The
Organic Act of 1862 not only created USDA but also mandated that the department,
“acquire and diffuse among people useful information on subjects connected to agricul-
ture.” This led to some of the pioneering work of W.O. Atwater, who in the 1890s began
identifying the links between food composition, dietary intake, and health. This seminal
344
TABLE 11.3
Comparison of Three Sets of Dietary Recommendations
Recommendation DGA AHA ACS
Include a variety of foods in the diet; Yes, include food from five major food Yes, echo DGA recommendations: Yes, with emphasis on grains, especially
emphasis on a plant-based diet. groups: bread, cereal, rice, and pasta; grains, fruits, and vegetables should whole grains, fruits, vegetables, and
vegetables, fruits, meat, poultry, fish, supply 55 to 60 percent of total beans as an alternative to meat.
dry beans, eggs, and nuts; and milk, kcalories.
yogurt, and cheese. Also provide
information on good food sources of
nutrients.
Encourages maintenance of a healthy Yes, defined as Body Mass Index (BMI) Yes, healthy weight not specifically Yes, refers to DGA definition of BMI of
weight including importance of of 19 to 25. Recommend gaining no defined. Weight gain in adulthood not 19 to 25. Recommend moderate activity
physical activity. more than 10 pounds after achieving specifically addressed. Regular physical for 30 minutes/day on most, if not all
adult height. Recommend moderate activity encouraged. days.
activity for 30 minutes/day on most, if

not all days.
Limit fat intake. Yes, recommend choosing a diet with no Yes, recommend choosing a diet with no Yes, do not give quantitative limits.
more than 30 percent of calories from more than 30 percent of kcalories from Recommend limiting consumption of
total fat and less than 10 percent of total fat, less than 10 percent of kcalories meats, especially high-fat meats.
kcalories from saturated fat. Refers to from saturated fat, and less than 300 mg
Daily Value of 300 mg/day cholesterol cholesterol/day. Limit intake of omega-
on food labels, without making specific 5 polyunsaturated fatty acids to no
recommendation. Briefly discusses use more than 10 percent of total kcalories.
of omega-3 and trans fatty acids. Recommend limiting trans fatty acids
but do not give quantitative limit.
Limit salt and sodium consumption. Yes, refer to Daily Value on food labels Yes, limit salt to 6g/day (equivalent to Not specifically addressed.
of 2400 mg of sodium/day without 2400 mg of sodium).
making specific recommendation.
Moderate intake of sugars. Yes, no quantitative limitations given. Yes, no quantitative limitations given. Not specifically addressed.
Limit consumption of alcoholic Yes, includes caveat to limit to 1 drink/ Yes, echo DGA recommendations. Yes, refer to DGA recommendations.
beverages. day for women, if you drink at all. Also
includes list of those who should not
drink at all including children and
pregnant women.
TABLE 11.4
History of USDA Food Guidance
1860s 1862 USDA formed
1870s
1880s
1890s 1890 W. O. Atwater — human nutrition research
1900s 1902 Atwater — Variety, Balance, and Moderation
1910s 1914 Cooperative Extension Service
1916 Caroline Hunt — First food guide
1920s
1930s 1933 Food Plans at 4 Cost Levels
1940s 1941 National Nutrition Conference for Defense
1946 School Lunch Program began
1950s 1956 Basic Four Food Guide
1960s 1964 Food Stamp Program began
1969 White House Conference on Food, Nutrition, and Health
1970s 1970 EFNEP began
1971 FNIC formed at NAL
1975 WIC began (WIC pilot projects authorized in 1972)
1977 Food and Agriculture Act of 1977, NET began; USDA named “lead” agency for nutrition research,
extension, and teaching
1980s 1980 Dietary Guidelines for Americans first issued
1982 JSHNR defines “nutrition education research”
1986 USDA Comprehensive Plan for HN Research and Education
1990s 1990 National Nutrition Monitoring and Related Research Act
1990 Nutrition Labeling and Education Act/NEFLE
1992 Food Guide Pyramid
1994 Nutrition and Food Safety Education Task Force
1995 Dietary Guidelines for Americans, 4th edition
2000 May, 2000 National Nutrition Summit
science led to the development of the USDA food guides. Dissemination of the food guides
was facilitated by the 1914 Smith-Lever Act which created the Cooperative Extension
Service and specified that the Extension Service provide people with, “useful and practical
information on subjects relating to agriculture and home economics.”
In the 1930s the USDA began developing family food plans at four separate cost levels.
The food plans continue to be used with the best known — the Thrifty Food Plan —
serving as the nutritional basis of benefits of the Food Stamp Program. Former Secretary
of Agriculture Henry Wallace once commented, “the lack of common-sense knowledge of
nutrition even among the many well to-do people in the U.S. is appalling.”
In 1941 the first set of Recommended Dietary Allowances was released at the National
Nutrition Conference for Defense; at this conference USDA scientists noted that consumers
spent enough money on food but did not obtain an adequate diet. As a result, the USDA
was urged to develop nutrition education and media-type materials to promote good
nutrition for the American public. This emphasis on nutrition education continued in the
1950s and 1960s, culminating with the 1969 White House Conference on Food, Nutrition,
and Health.18,19 The 1969 conference reinforced the need for aggressive nutrition promotion
activities for all Americans, with a special emphasis on reaching low income populations.
Throughout the 1970s, federal agencies increased funding for nutrition programs and
nutrition education activities.20 New programs were created, including the Special Sup-
plemental Food Program for Women, Infants, and Children (WIC), School Breakfast, and
other programs such as Food Stamps and School Lunch were expanded nationwide.
Fats, Oils & Sweets KEY

Fat (naturally occuring and added)
USE SPARINGLY
Sugars (added)
These symbols show fats and added sugar in foods
Milk, Yogurt & Meat, Poultry, Fish, Dry Beans,

Cheese Group Eggs & Nuts Group
Vegetable Group Fruit Group

Bread, Cereal
Rice & Pasta
Group
6-11
SERVINGS
FIGURE 11.1
Food Guide Pyramid: a guide to daily food choices.
The 1977 Food and Agriculture Act named USDA as the lead agency for nutrition
research, extension, and teaching. In 1980 USDA and HHS released the first Dietary
Guidelines for Americans.21 Throughout the 1980s and into the 1990s USDA placed a
renewed emphasis on developing comprehensive, coordinated efforts to promote nutrition
for all Americans.
Food Guide USDA Pyramid

The release of the 1980 Dietary Guidelines for Americans provided the impetus for the
development of a new food guide that would allow consumers to put the dietary guide-
lines into action. Work throughout the 1980s and into the early 1990s culminated in the
now well-known 1992 USDA Food Guide Pyramid.22 The Pyramid has been a popular
success, recognized by the majority of Americans. The Pyramid builds on the extensive
experience with food guidance systems within USDA. The three essential concepts under-
lying the Food Guide Pyramid are variety, balance, and moderation. Different visuals were
tested with consumers to assess which graphic portrayal most effectively communicated
the underlying concepts of balance, variety, and moderation. The graphics were tested
first with adults with at least a high school education; consumer testing was expanded
later to include children and low-literacy and low-income adults. The Pyramid shape
emerged as the most effective graphic, communicating the concepts of variety, balance,
and moderation (Figure 11.1).
The USDA Pyramid communicates a wealth of information with little accompanying
text. Very complex information is presented in the Pyramid visual. As a result, many
consumers are not aware that a more detailed publication on the Food Guide Pyramid
exists.22 This publication discusses the differing energy needs of individuals illustrated at
1600, 2200, and 2800 kcalories. Within the Food Guide Pyramid Bulletin (USDA, 1992)
there is an in-depth discussion of “How to Make the Pyramid Work for You.” Topics such
as what constitutes a serving, different types of fats, and how to use the Pyramid to make
low-fat selections are also included in the Pyramid Bulletin.
The Pyramid graphic shown in Figure 11.1 communicates not only balance, variety, and
moderation but provides the basis of a healthful diet. The number and amounts of foods
recommended in the Pyramid are based on three factors:
• Recommended Dietary Allowances for age and gender groups

• Dietary Guidelines for Americans
• Americans’ typical consumption patterns
The advice provided in the Food Guide Pyramid is designed to provide dietary guidance
that ensures nutritional adequacy — defined as the RDAs and Dietary Guidelines — within
the framework of typical consumption patterns. Thus, while ostensibly an infinite number
of food combinations could be used to ensure nutritional adequacy, the five major food
groups emphasized in the USDA Pyramid anchor the food selections to current consump-
tion patterns.
A proliferation of pyramids has emerged since the USDA version was published in 1992.
However, all of the Pyramids, whether Asian, Mediterranean, or vegetarian, are based on
the same building blocks — grains, vegetables, and fruits.23-25 The similarities in the various
pyramids are more dominant than the differences.
In addition, in 1999, USDA released a children’s version of the Food Guide Pyramid
targeted at children ages two to six years. Here again, the concepts of balance, variety,
and moderation underpin the children’s graphic (Figure 11.2). The specific icons used in
the food groups are based on foods typically consumed by children. Worth noting are the
age-specific recommendations for serving sizes at the bottom of the graphic as well as the
deliberate inclusion of exercise icons.
The year 2000 Dietary Guidelines for Americans26 for the first time include the Food
Guide Pyramid as part of a specific guideline; “Let the Pyramid Guide Your Food Choices”
is the first guideline put forward to build a healthy base. One key reason for including
the Pyramid as a direct part of the Dietary Guidelines is the wide-ranging familarity of
consumers with the Pyramid and the messages embedded within. The USDA Food Guide
Pyramid and the Children’s Food Guide Pyramid will continue to be essential parts of
the nutrition education and nutrition promotion efforts within the USDA.
Diet Quality Measures

Since the early 1900s, the major areas of concern in public health nutrition have shifted
form problems of nutritional deficiency to problems of excesses and imbalances. Problems
of relative overconsumption are, on average, more prevalent today than problems of
underconsumption. The successive sets of U.S. Dietary Guidelines that have emerged since
1980 have emphasized the links between diet and a range of chronic diseases. An extensive
body of scientific literature exists to document the association between diets high in total
fat, saturated fat, and low in fiber and complex carbohydrate with coronary heart disease,
stroke, diabetes, and certain forms of cancer.
While extensive research has been conducted to link the typical American diet to a range
of chronic diseases, less research has been done on methods of measuring diet quality.
Until recently, most of the diet quality measures focused on individual nutrients; most
Guide P Y R A M I D
F O O D
A Daily Guide for
2-to 6-Year-Olds
U.S. Department of Agriculture USDA is an equal opportunity provider and employer.

Center for Nutrition Policy and Promotion
January 2000
Program Aid 1651
W H AT C O U N T S A S O N E S E R V I N G ?
GRAIN GROUP FRUIT GROUP MEAT GROUP
1 slice of bread 1 piece of fruit or melon wedge 2 to 3 ounces of cooked lean
1/2 cup of cooked rice or pasta 3/4 cup of juice meat, poultry, or fish.
FOOD IS FUN and learning about food 1/2 cup of cooked cereal
1 ounce of ready-to-eat cereal

1/2 cup of canned fruit
1/4 cup of dried fruit 1/2 cup of cooked dry beans,
or 1 egg counts as 1 ounce of lean

is fun, too. Eating foods from the Food VEGETABLE GROUP MILD GROUP meat. 2 tablespoons of peanut
1/2 cup of chopped raw butter count as 1 ounce of meat.
Guide Pyramid and being physically or cooked vegetables
1 cup of milk or yogurt
2 ounces of cheese
1 cup of raw leafy vegetables
active will help you grow healthy and FATS AND SWEETS
Limit calories from these.
strong.
Four- to 6-year-olds can eat these serving sizes. Offer 2- to 3-year-olds less, except for milk.
Two- to 6-year-old children need a total of 2 servings from the milk group each day.
E AT a variety of FOODS AND ENJOY!

FIGURE 11.2
Food Guide Pyramid for Young Children.
TABLE 11.5
Components of the Healthy Eating Index and Scoring System
Score Criteria for Maximum Criteria for Minimum
Ranges1 Score of 10 Score of 0
Grain consumption 0–10 6–11 servings2 0 servings
Vegetable consumption 0–10 3–5 servings2 0 servings
Fruit consumption 0–10 2–4 servings2 0 servings
Milk consumption 0–10 2–3 servings2 0 servings
Meat consumption 0–10 2–3 servings2 0 servings
Total fat intake 0–10 30% or less energy 45% or more energy
from fat from fat
Saturated fat intake 0–10 Less than 10% energy 15% or more energy
from saturated fat from saturated fat
Cholesterol intake 0–10 300 mg or less 450 mg or more
Sodium intake 0–10 2400 mg or less 4800 mg or more
Food variety 0–10 8 or more different 3 or fewer different
items in a day items in a day
1 People with consumption or intakes between the maximum and minimum ranges or
amounts were assigned scores proportionately.
2 Number of servings depends on Recommended Energy Allowance.
often these measures were based on measures such as mean percent of the Recommended
Dietary Allowances.27,28
Despite the U.S. Dietary Guidelines’ emphasis on a total diet, indices based on the
dietary guidelines have tended to be selective in the components included.29,30 Few assess-
ment indices have been developed to assess overall diet quality. In an effort to measure
how well American diets conform to recommended healthy eating patterns, USDA devel-
oped the Healthy Eating Index (HEI) in 1995.
Healthy Eating Index Structure

The Healthy Eating Index (HEI) was designed to measure various aspects of a healthful
diet. As shown in Table 11.5; the HEI is a ten-component index; components one through
five measure the degree to which a person’s diet conforms to the Food Guide Pyramid’s
serving recommendations for the five major food groups of grains, vegetables, fruits,
milk, and meat. The number of recommended servings for each food group varies with
the individual’s age, gender, physiological status, and energy requirements. The use of
food groups rather than nutrients was meant to provide consumers with an easier stan-
dard against which to judge their dietary patterns. In addition, there may be as yet
unknown components in foods that would not be picked up by measuring simply the
nutrients in foods.
Components 6 to 9 measure various aspects of the dietary guidelines, including total
fat, saturated fat, cholesterol, and sodium, respectively. Component 10 provides a measure
of dietary variety. Despite general agreement that dietary variety is important, it is sur-
prising how few studies have attempted to quantify the concept of variety.30,31 The HEI
counted the total number of different foods that contribute substantially to meeting one
or more of the five food group requirements. Foods were counted only if they were eaten
in amounts sufficient to contribute at least a half serving in any of the food groups. Identical
foods eaten on separate occasions were aggregated before imposing the one-half serving
cutoff point. Foods that were similar, such as different forms of potatoes or two different
forms of white bread, were counted only once in the variety category.
Each of the ten components has a score ranging from zero to ten; cutoffs for scoring the
minimum and maximum scores are shown in Table 11.5. Thus, the HEI can vary from one
to 100.
What Are Americans Eating?

The HEI was applied to nationally representative data derived from the Continuing Survey
of Food Intake by Individuals (CSFII) for two time periods, 1989 to 1990 and 1994 to 1996.
The combined score for 1989 to 1990 was 63.9,23 contrasted with 63.6, 63.5, and 63.8 for
1994, 1995, and 1996 respectively.25 Clearly there were not wide variations in the average
HEI across this seven-year period.
In addition, the distribution of the average HEI scores did not vary dramatically over
the period of 1989 to 1996. Throughout this time period, the majority of individual scores
fell in the 51 to 80% range, a category defined as “needs improvement.” Only about 11 to
12% of individuals fell in the “good diet” category at any point in time; conversely,
approximately 18% of individuals were classified in the “poor diet” category. Scores for
the individual HEI components varied with the average score, with the fruit category
consistently being the lowest, and the cholesterol score doing best.
The HEI score varied with some economic and demographic factors.23,25 Females had
slightly higher scores than males, and persons in the younger and older groups scored
higher than adults in the 19 to 50 age category. Children two to three years had the highest
HEI score. Children in this age category scored particularly high on the fruit and dairy
component of the HEI when compared with older children, suggesting that changes in
dietary habits may play an important role as children age.
Throughout the seven-year period we see a pattern of increasing HEI with increase in
income. However the effect of increases in education are more dramatic than the effect of
income on increases in HEI. One interpretation is that higher education may enable
individuals to translate dietary guidance into improved food patterns.
The scientific rigor of the HEI depends on its ability to accurately measure diet quality.
Research has documented that the average HEI in 1989 and 1990 correlated with a range
of nutrients and energy intake.23 For most nutrients, the likelihood of falling below 75%
of the RDA for a selected nutrient decreased as the HEI score increased. For example, only
47% of persons with an HEI of 50 or less had vitamin C intake greater than 75% of the
RDA, compared to approximately 91% of people scoring 80 or more on the HEI. The data
would suggest that as the HEI increases, levels of nutrient intake also increase.
Interestingly, the correlation of the HEI with overall energy intake was modest, suggest-
ing that simply consuming larger quantities of food will not by itself result in a better diet.
Finally, the HEI was compared to individuals’ self-rating of their diets.6 Persons who
rated their diets as excellent or good had a significantly higher probability of having an
HEI classified as a “good diet.” Conversely, individuals who self-rated their diet as fair
or poor had an HEI more likely to be classified as “needs improvement.”
Policy Implications
The Food Guide Pyramid and the Dietary Guidelines for Americans provide a standard
against which to evaluate the total diet. However, neither the Pyramid nor the Dietary
Guidelines provide a method for easily assessing total diet. The development of the USDA
Healthy Eating Index provided an easy to use, single summary measure of diet quality.
The HEI provides a method for monitoring diet quality over time using national survey
data. In addition, the HEI has the potential to serve as a tool for individuals to self-evaluate
diet quality.
The data from both 1989 to 1990 and 1994 to 1996 indicate that improvements need to
be made in the dietary patterns of most Americans. The data obtained from applying the
HEI to nationally representative surveys can be one tool to help focus our national nutri-
tion promotion interventions.
Summary
Worldwide major improvements in public health will be accomplished by improvement
in dietary patterns. Food-based dietary guidelines have been developed in a broad range
of countries. A move toward consensus on food-based dietary guidelines is a practical
way to develop core elements of global dietary guidelines that can be effectively promoted
by individual countries as well as international health organizations.
References
1. Office of the President, Proceedings of White House Conference on Food, Nutrition and
Health. White House, Washington, DC, 1970.
2. US Senate Select Committee on Nutrition and Human Needs. Dietary Goals for the United States
(2nd ed.), 1977.
3. US Department of Agriculture and US Department of Health and Human Services. Nutrition
and Your Health: Dietary Guidelines for Americans. Home and Garden Bulletin No. 232, 1980.
and Your Health: Dietary Guidelines for Americans (2nd ed.). Home and Garden Bulletin No. 232,
1985.
and Your Health: Dietary Guidelines for Americans (3rd ed.). Home and Garden Bulletin No. 232,
1990.
and Your Health: Dietary Guidelines for Americans (4th ed.). Home and Garden Bulletin No. 232,
1995.
7. US Department of Agriculture, US Department of Health and Human Services, Nutrition and
Your Health: Dietary Guidelines for Americans (5th ed.). Home and Garden Bulletin No. 232, 39
pp, May 2000.
8. US Congress, Public Law 101-445, 7U.S.C.5341, Library of Congress, Washington DC, 1990.
9. Prospect Associates. Dietary Guidelines Focus Group Report, Final Report, Washington, DC,
Nov 1995.
10. Systems Assessment & Research, Inc; Report to USDA of the Initial Focus Groups on Nutrition
and Your Health: Dietary Guidelines for Americans (4th ed.), Lanham, MD, September 1999.
11. National Research Council, National Academy of Sciences. Recommended Dietary Allowances
(10th ed.), Washington, DC, National Academy Press, 1989a.
12. US Department of Agriculture, The Food Guide Pyramid, Home and Garden Bulletin No. 252,
1992.
13. Modern Nutrition in Health and Disease (9th ed.), Williams & Wilkins, Baltimore, MD, 1990.
14. Peng M, Molina V. Food Dietary Guidelines and Health-Based Promotion in Latin America, Pan
American Health Organization, Washington, DC, April 1999.
15. Krauss RM, Deckelbaum RJ, Ernst N, et al. Dietary guidelines for healthy American adults, a
statement for health professionals from the Nutrition Committee, American Heart Association,
Circulation, 94:1795; 1996.
16. American Cancer Society Advisory Committee on Diet, Nutrition, and Cancer Prevention.
Guidelines on diet, nutrition, and cancer prevention: reducing the risk of cancer with healthy
food choices and physical activity, CA Cancer J Clin 1996; 46: 325-341.
17. American Academy of Pediatrics, Breastfeeding and the Use of Human Milk, Pediatrics. 100(6):
1035-1039.
18. Healthy People: The Surgeon General’s Report on Health Promotion and Disease Prevention, Wash-
ington, DC; US Dept of Health, Education, and Welfare, 1979; 177. DHHW (PHS) publication
79-55071.
19. The Surgeon General’s Report on Nutrition and Health, Washington, DC: US Dept of Health and
Human Services; 1988. DHHS (PHS) publication 88-50210.
20. Healthy People 2000: National Health Promotion and Disease Prevention Objectives, Washington,
DC; US Dept of Health and Human Services; 1991. DHHS (PHS) publication 91-60213.
21. Nutrition and Your Health: Dietary Guidelines for Americans, Washington, DC; US Dept of Agri-
culture/Dept of Health and Human Services; 1980. Home and Garden Bulletin No. 328.
22. Food Guide Pyramid, Washington, DC: US Dept of Agriculture, Human Nutrition Information
Service; 1992. Home and Garden Bulletin No. 252.
23. Kennedy E, Ohls J, Carlson S, Fleming K. JADA 95: 1103; 1995.
24. Kennedy E. Oct, 1998. Building on the pyramid — where do we go from here? Nutrition Today
11: 183-185.
25. Kennedy E, Bowman S, Lino M, Gerrior S, Basiotis PP. 1999. Diet Quality of Americans,
Chapter 5. In: America’s Eating Habits. Frazao E, Ed. Economic Research Service, Washington,
DC.
26. USDA/HHS. May, 2000. Nutrition and Your Health: Dietary Guidelines for Americans, 5th
ed. Home and Garden Bulletin No. 232, Washington, DC.
27. Guthrie HA, Scheer JC. JADA 78: 240; 1981.
28. Block GA. Am J Epidemiol 115: 402; 1982.
29. Patterson RE, Haines RS, Popkin BM. JADA 94: 57; 1994.
30. Kent AK, Schatzkin A, Harris TU, et al. Am J Clin Nutr 57: 434; 1993.
31. Krebs-Smith S, Smieiklas-Wright H, Guthrie HA, Krubs-Smith J. JADA 87: 807; 1987.
Other References
USDA, Center for Nutrition Policy and Promotion. October, 1996. The State of Nutrition Education
in USDA: A Report to the Secretary. USDA: Washington, D.C.
Childrens Food Guide Pyramid, 1999.
2705_frame_C12 Page 353 Thursday, September 20, 2001 9:16 AM
12
Dietary Guidelines in Three Regions of the World
Johanna Dwyer, Odilia I. Bermudez, Leh Chii Chwang, Karin Koehn,

and Chin-Ling Chen*
Introduction and Overview

Dietary guidelines are “recommendations for achieving appropriate diets, and healthy
lifestyles.”1 This section examines the similarities and differences, strengths and weak-
nesses of dietary guidelines from three regions of the world, concluding with some rec-
ommendations for crafting future guidelines.
Effective guidelines have several elements in common. They are designed to address
and mitigate the major diet-related nutrition problems of the population. As these prob-
lems change over time, the focus of dietary guidance must also shift. Effective guidelines
are evidence based, and the strength of supportive evidence is strong. Eating habits,
cultural beliefs, and food supplies available are considered. The messages conveyed are
tested prior to their finalization to ensure that the guidelines can be communicated effec-
tively. Successful guidelines are integrated with other nutritional guidance of a public
health nature. They are recognized as only one of a group of essential components of
effective food and nutrition policies. Other factors include access to a variety of safe and
affordable foods from available resources. Ideally, successful guidelines are promulgated
simultaneously with ways to measure their effectiveness.
In this section we examine guidelines from regions representing different culinary
approaches, food customs, and economies. English-speaking North America and Oceania
are highly industrialized, affluent countries. Several Asian and Latin American countries
that vary in degree of urbanization and standards of living are also examined.
The United States, Canada, Australia, and New Zealand

In English-speaking North America and Oceania, diseases of affluence (i.e., obesity, heart
disease, and certain cancers) are common and therefore these issues are given attention.
* This material is based upon work supported by the U.S. Department of Agriculture, under Agreement No. 58-
1950-9-001. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of
the authors and do not necessarily reflect the views of the U.S. Department of Agriculture. We thank Smita Ghosh
for her help in editing the manuscript.
0-8493-2705-9/01/$0.00+$1.50
All of these affluent countries share similar dietary patterns and nutrition-related prob-
lems, including a diet excessive in calories, fat, salt, sugars, and alcohol, and too low in
fruits, vegetables, and whole grains. Their guidelines have addressed excessive as well as
inadequate food consumption, weight, and physical activity since they were first formu-
lated in the late 1970s and early 1980s.
Each of these countries has an ethnically diverse population. In the U.S., according to
1990 census data, 12% of the population was African American and 9% were of Hispanic
origin.2 The Aboriginal and Torres Strait Islander people comprise only about 2% of the
Australian population, but they often live under impoverished, overcrowded conditions
that put them at nutritional risk,3 and they have a high prevalence of android pattern obesity,
which is associated with many health problems.4 In New Zealand, 13% of the population
belong to the rapidly growing Maori minority, and another 5% are Pacific Islanders.5 Some
of these minority groups have increased risks of chronic degenerative diseases as they move
away from traditional customs to modern diets and lifestyles. The information accompa-
nying the Australian and New Zealand dietary guidelines refers to these special problems,
although the dietary guidelines are targeted to the general population.
Formulation of Dietary Guidelines for the United States, Canada, Australia,

and New Zealand
Table 12.1 shows the approaches used in the development of the dietary guidelines in
these countries. All used experts and scientists, and each of the guidelines was endorsed
by a relevant government agency. In the U.S., the National Nutrition Monitoring and
Related Research Act required that the Dietary Guidelines for Americans be updated every
five years and be reviewed by the Departments of Health and Human Services and
Agriculture. The law has expired but revisions continue on the same timetable, led by
relevant government agencies. Other U.S. federal food guidance for the general public is
required to be consistent with these guidelines.
All four countries address their guidelines to both the general population and health
professionals or other policy makers. New guidelines usually follow the precedents estab-
lished in earlier versions (see Table 12.1). Some changes simply involve different wording.
For example, the American guideline regarding sugar has evolved from “Avoid too much
sugar” in 19806 to “Use sugars only in moderation” in 19907 and “Choose a diet moderate
in sugars” in 1995,8 to the current “Choose beverages and foods that limit your intake of
sugars.”9 Other changes are more innovative. In 1992 Australia added guidelines for two
specific nutrients: calcium and iron. The U.S. added a new guideline on food safety in 2000.
Australia and New Zealand have specific guidelines for infants, toddlers, school-age
children, adolescents, and the elderly that also address other health recommendations.
New Zealand also has dietary guidelines for pregnant or breastfeeding women.
As described in Table 12.1, the U.S., Canada, and Australia all have pictorial represen-
tations or graphics for their dietary recommendations. The U.S. has a food guide pyramid
graphic that incorporates some of its guidelines.10 Canada uses a rainbow graphic to
depict the components of a healthy diet. Australia has two graphics — a pyramid and a
plate.
Similarities and Differences among Dietary Guidelines in the United States, Canada,
Australia, and New Zealand
Table 12.2 shows that all of these countries have recommendations for certain nutrients
and also for groups of foods, such as fruits/vegetables, grains, dairy, and meats. Food
TABLE 12.1
Development of Dietary Guidelines in the United States, Canada, Australia, and New Zealand
United States Canada Australia New Zealand
Title of guideline Dietary Guidelines for Americans Canada’s Guidelines for Healthy Australian Dietary Guidelines Food and Nutrition Guidelines
Eating
Year 1995, 2000 1991 1992 1991
Endorsing unit Departments of Agriculture, Department of National Health National Health and Medical Nutrition Task Force at the
Health, and Human Services and Welfare Research Council Ministry of Health
Approaches* 1-5, 7 1-5, 7 1-5 1-5
Target audiences** G, H, P, N G, H, P, N G, H, P G, H, P
Graphic representation Pyramid Rainbow Pyramid None
* 1 = Experts, scientists views; 2 = Review of former guidelines; 3 = From food groups; 4 = From consumption/nutrition survey; 5 = Definition of nutritional objectives;
6 = Economic data; 7 = Consumer focus groups.
** G = General population; H = Health professionals; P = Policy makers; N = Nutrition education of schoolchildren.
355
356
TABLE 12.2
Dietary Guidelines of the United States, Canada, Australia and New Zealand
United States 2000 Canada Australia New Zealand
1. Aim for a healthy weight 1. Enjoy a variety of foods 1. Enjoy a wide variety of nutritious 1. Eat a variety of foods from each of
2. Be physically active each day 2. Emphasize cereals, breads, other foods the four major food groups each day
3. Let the pyramid guide your food grain products, vegetables and fruits 2. Eat plenty of bread and cereals 2. Prepare meals with minimal added
choices 3. Choose lower-fat dairy products, (preferably whole grain), vegetables fat (especially saturated fat), salt,
4. Build a healthy base leaner meats, and foods prepared (including legumes), and fruits and sugar
5. Choose a variety of grains daily, with little or no fat 3. Eat a diet that is low in fat, and in 3. Choose prepared foods, drinks and
especially whole grains 4. Achieve and maintain a healthy particular, low in saturated fat snacks that are low in fat (especially
6. Choose a variety of fruits and body weight by enjoying regular 4. Maintain a healthy body weight by saturated fat), salt, and sugar
vegetables daily physical activity and healthy eating balancing physical activity and food 4. Maintain a healthy body weight by
7. Keep food safe to eat 5. Limit salt, alcohol, and caffeine intake regular physical activity and by
8. Choose a diet that is low in saturated 5. If you drink alcohol, limit your healthy eating
fat and cholesterol and moderate in intake 5. Drink plenty of liquids each day
total fat 6. Eat only moderate amounts of 6. If drinking alcohol, do so in
9. Choose sensibly sugars and foods containing added moderation
10. Choose beverages and foods that sugars
limit your intake of sugars 7. Choose low salt foods and use salt
11. Choose and prepare foods with less sparingly
salt 8. Encourage and support breast-
12. If you drink alcoholic beverages, do feeding
so in moderation 9. Eat foods containing calcium; this is
particularly important for girls and
women
10. Eat foods containing iron; this is
particularly important for girls and
women, vegetarians and athletes
Dietary Guidelines in Three Regions of the World 357
based guidelines are easier than nutrient based guidelines for the consumer to implement,
since human beings eat foods, not specific nutrients.
In all of these countries, heart disease, hypertension, diabetes with its complications,
and cancer are the leading causes of death.4,9,11-13 Obesity is prevalent and increases the
severity of many of these diseases.13,14
The core messages in all of these dietary guidelines are similar: eat a variety of foods
and include physical activity to achieve/maintain a healthy weight (Table 12.2). All of
these countries have recommendations on limiting fat, salt, and alcohol and increasing
fruits, vegetables, and whole grains. The U.S., Canada, and New Zealand all suggest
limiting alcoholic beverages to less than two drinks per day for men and one for women.
Australia has a higher limit — less than four drinks for men and two for women per day.
The background and supporting information accompanying the Dietary Guidelines
provides the rationale for quantitative suggestions for intakes of specific nutrients.4,9,15,16
All of these countries suggest that 50 to 55% of total calories should come from carbohy-
drates. The U.S., Canada, and Australia recommend less than 30% of total calories from
fat and less than 10% from saturated fat. New Zealand is more liberal, suggesting no more
than 30 to 35% of kcalories from fat and 12% from saturated fat.
There are some differences in the guidelines. In the most recent U.S. guidelines (2000),
food safety is addressed. Australia includes a guideline specifically to encourage and
support breastfeeding, and it also has two other nutrient-specific guidelines, “eat foods
containing calcium” and “eat foods containing iron.”4 The calcium and iron guidelines are
emphasized for both girls and women, and iron is also stressed for vegetarians and athletes.
Most of the guidelines other than alcohol for the U.S. and Canada are for all healthy
individuals over age two years. The fat guideline in Canada is not applicable until a child
reaches age five.
Other health recommendations included in New Zealand’s guidelines are non-smoking
related, especially for adolescents, and pregnant and breastfeeding women. The elderly,
who may suffer from isolation and therefore poor nutrition, are encouraged to “make
mealtime a social time.” Australia encourages its elderly to eat at least three meals per
day. Elderly people and pregnant women are especially vulnerable to risks associated
with foodborne illnesses. Australia’s food safety guidelines address food safety in the
elderly (care for your food: prepare and store it correctly), and the New Zealand guidelines
discuss Listeria in the information specifically directed to pregnant women.
Latin America
Dietary guidelines were first formulated in Latin America in the late 1980s.17 Guidelines
from Chile, Guatemala, Mexico, Panama, and Venezuela are provided as examples of
dietary guidelines in the region.
Latin America is a region with great inequalities in the distribution of welfare, and also
large variations in the nutritional health of its population groups. There has been a shift
from dietary deficiency disease to problems of dietary excess in many countries of the
region over the past two decades. In Chile, the prevalence of protein–calorie malnutrition
in children is declining rapidly. However, the prevalence of chronic degenerative diseases
associated with imbalances in food intake and sedentary lifestyles is rising.18 In contrast,
in Guatemala, Mexico, and Panama, poverty-related undernutrition and dietary deficiency
diseases are still prevalent, especially among children and women of reproductive age in
rural areas. At the same time, the prevalence of diet-related chronic diseases is rising.
Venezuela is an oil-exporting country, but it still has large economic inequalities and
grapples with poverty-related malnutrition as well as dietary excess.
In most Latin American countries, food consumption patterns are influenced by those
of the U.S. Changing cultural and economic influences, rural–urban migration, greater
availability of processed foods, and advertising also affect food consumption.19 Both
over- and undernutrition result.20 The development of poor ghettos in metropolitan areas,
short lactation periods, low wages, and low maternal educational levels is associated
with undernutrition in young children. The interactions of urbanization, sedentary life-
styles, lack of nutrition education, and excessive consumption of cheap foods low in
nutritional value lead to diseases of overconsumption such as obesity, diabetes, and
cardiovascular disease.20
Formulation of the Dietary Guidelines in Latin America
Most of the Latin American countries are in the implementation stage in formulating
dietary guidelines.21 The dietary guidelines for the Mexican population were issued by
the Mexican Institute of Nutrition.22 Venezuela issued dietary guidelines in the late 1980s
that were later revised and updated.23 The dietary guidelines have been implemented in
many ways. For example, they have been incorporated into Venezuelan kindergarten,
elementary, and secondary school curricula.23-25
Table 12.3 contains details about the dietary guidelines development process. Four of
the countries have dietary guidelines for the general population. Some also have guide-
lines for specific population groups (Chile, Panama, and Venezuela) or target certain
groups on specific concerns (Guatemala for food safety among the poor). Governmental
or quasi-governmental organizations develop and promulgate the guidelines based on
the views and opinions of experts and scientists. Some also use background data on food
consumption surveys (Chile, Mexico, Panama) and economic data (Venezuela, Mexico).
Most of the countries also refer to food groups in their dietary guidelines.18,22,23,26,27
Four of the countries also use graphic representations of food groups and supporting
messages (see Table 12.3). Chile, Mexico, and Panama adapted the food guide pyramid
used in the U.S. Guatemala summarized its food groups and dietary guidelines in a family
pot, or “crockpot” graphic. Venezuela has no graphic but the government has produced
an extensive set of educational materials directed at different target groups.24,25
Similarities and Differences among Latin American Dietary

Guidelines
Table 12.4 summarizes the dietary guidelines for the Latin America. The number of
guidelines range from 6 in Panama to 12 in Venezuela; Venezuela also has issued 40
educational messages to facilitate implementation of the guidelines. Mexico has ten dietary
guidelines — each one contains several additional messages.
In general, the guidelines are focused on foods, and provide general guidance. Variety
is mentioned in all guidelines. Guatemala, Mexico, and Venezuela discuss economic dis-
parities in supporting documents. For example, Guatemala recommends that those with
limited resources eat meats, eggs, and dairy products at least once or twice a week, while
Venezuela urges prudence in the management of financial resources (see Table 12.4).
TABLE 12.3
Development of Dietary Guidelines in Latin American Countries
Chile Guatemala Mexico Panama Venezuela
Title of guideline Food Guidelines for Chile Food Guidelines for Food Guidelines — Food Guidelines for Food Guidelines for
Guatemala Mexico Panama Venezuela
Year 1997 1998 1993 1995 1991
Endorsing unit Ministry of Health, the Food Guidelines National Nutrition Ministry of Health CAVENDES Foundation,
Food Technology and National Committee Institute National Institute of

Nutrition Institute, and (inter-institutional) Nutrition, several
the Nutrition Center at universities

the University of Chile
Approaches* 1, 3, 4 1, 3, 6 1, 3, 4, 5, 6 1, 3, 4, 5 1, 2, 5, 6
Target audiences** G, P, N G G G, P G, P, N
Graphic representation Pyramid Family pot Pyramid Pyramid None
Other guidelines For school age children Food safety None For the first year of age For the preschooler,
and the elderly school age children, and
the elderly
6 = Economic data
** G = General population; H = Health professionals; P = Policy makers; N = Nutrition education of schoolchildren.
359
360
TABLE 12.4
Dietary Guidelines of Selected Latin American Countries
Chile Guatemala Mexico Panama Venezuela
1. Eat different types of foods 1. Include grains, cereals, or 1. Avoid monotony by 1. Eat a variety of foods 1. Eat a variety of foods every
throughout the day potatoes at each meal consuming a wide variety 2. Eat sufficient grains, roots, day
2. Increase consumption of because they are nutritious, of foods; select different vegetables, and fruits 2. Eat just enough to maintain
fruits, vegetables, and tasty, and have low cost foods each day and at each 3. Select a diet low in a proper weight
green vegetables 2. Eat vegetables and greens meal, choosing among saturated fat, cholesterol, 3. Eat preferably with your
3. Prefer vegetable oil and every day to benefit your those available at the and oil family
limit animal fats body market and following the 4. Eat sugar and sweets in 4. Practice good hygiene
4. For meat, prefer fish and 3. Every day, eat any type of proportions recommended moderation when handling food
poultry fruit, because they are by the food guide pyramid 5. Eat sat and sodium in 5. Manage your money well
5. Increase consumption of healthy, easy to digest, and 2. Include at least two moderation when selecting and
low fat milk nutritious servings of fruits and 6. Maintain a healthy weight purchasing food
6. Reduce salt intake 4. If you eat tortilla and beans vegetables at every meal 6. Breast milk is the best food
7. Moderate sugar every day, eat one spoonful 3. Eat variety of grains and for children under 6 months
consumption of beans with each tortilla grain products, preferably of age
to make it more nutritious whole grains, at every meal, 7. Eat only moderate
5. At least twice a week eat mixing cereals and legumes quantities of food of animal
one egg or one piece of 4. Include a moderate serving origin
cheese, or drink one glass of of animal products at every 8. Use vegetable oils in
milk, to complement your meal, choosing those with preparing meals and avoid
diet the least fat excess animal fat
6. At least once per week, eat 5. Limit consumption of fats, 9. Get the fiber your body
a serving of liver (beef) or including cooking oils and needs from the vegetable
meat to strengthen your fatty foods, to less than 30% products you eat daily
body of daily energy intake; limit 10. Consume salt in
7. To stay healthy, eat a variety saturated fats, of animal moderation
of foods as indicated in the origin, to less than 10% of 11. Water is essential for life,
household pot total energy; reduce and drinking water helps to
cholesterol intake to less preserve your health
than 300 mg per day 12. Alcoholic beverages are not
part of a healthy diet
6. Reduce consumption of salt
and sugar, starting by not
using salt at the table and
reducing sugars in liquids
(coffee, tea, or juices)
7. Restrict consumption of
products with excess of
additives (colorants,
flavorings, etc.); avoid
alcohol and do not smoke
8. Breastfeed children from
birth and start
complementary food at the
fourth month of age
9. Avoid obesity by
monitoring weight
according to the suggested
weight for stature

10. Increase physical activity,
walk briskly or practice any
other type of aerobic

exercise for about 20-30
minutes, 4 or 5 times a week
361
Some countries incorporate specific concerns about food consumption (Table 12.4).
Guatemala emphasizes the importance of hand washing, and keeping food and water
well covered. Venezuela has a guideline emphasizing good hygiene in handling food.
Guidelines directed to over-consumption are included by all the countries. These include
specific recommendations to increase physical activity (Mexico), maintain a healthy weight
(Mexico, Panama), or to moderate or reduce the use of fats and sugars (Chile, Mexico,
Panama, and Venezuela). Chronic disease risks are also addressed. These include recom-
mendations for moderate use of salt (Chile and Venezuela) or sodium (Panama), limiting
consumption of fats and sugars (Chile, Mexico, Panama, Venezuela), saturated fats (Mex-
ico, Panama), and cholesterol (Mexico, Panama). Other guidelines are directed to limiting
specific foods or nutrients, or to increase other more nutrient-rich foods (fruits, vegetables,
whole grains) (See Table 12.4).
The Latin American guidelines focus mostly on foods, not specific nutrients (Table 12.4).
However, Panama recommends moderation in the use of sodium along with salt. Guate-
mala, a country with low literacy rates, also emphasizes nutrients but in simple, short
messages; it singles out energy, protein (both animal and vegetable), vitamins A and C,
calcium, iron, and zinc, as well as fiber. This emphasis reflects Guatemala’s goals of
preventing both dietary deficiencies and excesses. Venezuela’s guidelines have little
emphasis on specific foods (Table 12.4).
All of the Latin American countries include advice on consuming fruits, vegetables, and
grains daily. Guatemala specifically mentions beans and tortillas. Other countries (Chile,
Mexico, and Venezuela) mention the need for limiting fat. Salt restriction is mentioned in
Mexico, Venezuela, and Panama. Both Mexico and Venezuela have a guideline limiting
alcohol. Chile and Guatemala include a guideline on use of dairy products; Chile focuses
on low-fat milk products; Guatemala urges at least one to two servings of whole fat milk
products, since much of the population is poor and does not consume milk. Mexico and
Venezuela have specific guidelines stressing the importance of breastfeeding. Panama has
special dietary guidelines for infants, recommending exclusive breastfeeding during the
first six months of life, and complementary feeding thereafter.27
Conclusions about Dietary Guidelines in Latin America

Dietary guidelines for Latin American countries reflect the diversity in socioeconomic
situations and nutritional problems in the region, and each country’s unique perspectives.
They offer the general public, service providers, and policy makers actionable recommen-
dations for improving nutrition and health status. Some of these countries have already
identified barriers that limit the use of the dietary guidelines (Chile, Venezuela). Others,
such as Mexico, still need to evaluate the applicability of their guidelines to the eating
practices of the diverse Mexican population. Dietary guidelines in Guatemala were
directed to the poor; problems associated with over-consumption of foods and sedentary
lifestyles still need to be addressed.
Asian Countries
Introduction
Asia’s diversity is reflected in the many nutritional problems that were evident in the ten
countries we reviewed. Until the mid 1950s, poverty-related malnutrition was the major
problem. The primary concern was to ensure adequate energy intakes and prevention or
control of dietary deficiency diseases.28,29 Today, nutrition problems in Asia cover the entire
spectrum from deficiency disease to excess.
Asian dietary guidelines focus on reducing or preventing both chronic deficiency and
chronic degenerative diseases, since both problems are often prevalent.1,30,31 Presently,
India still has high rates of protein–energy malnutrition among some groups. In coun-
tries such as Korea, Japan, Taiwan, and Singapore, protein–energy malnutrition has
declined dramatically in the past three decades.29,31,32 Countries such as Thailand and
China have low rates of protein–energy malnutrition, but micronutrient deficiencies
(iron, iodine, vitamin A, and riboflavin) are still common.33-36 Indonesia and the Philip-
pines face persistent problems of undernutrition and deficiency disease among the poor
coupled with emerging problems of overnutrition and increased chronic degenerative
disease, particularly among the affluent.28,35,37 Filipino guidelines for more affluent pop-
ulations focus on chronic degenerative diseases and avoiding excess,38 whereas their
guidelines for the relatively less affluent population emphasize achieving sufficiency of
nutrient intakes.37
Formulation of the Dietary Guidelines in Asia
Table 12.5 shows the various approaches used in developing dietary guidelines in Asia.
The guidelines are all intended to provide nutrition education and dietary guidance to
the general public in terms that are understandable to most consumers. They are also
often used to help officials in the health, agricultural, and education sectors in program
planning. All of the countries surveyed rely on government agencies and/or professional
societies to develop and endorse their official guidelines.37 Some countries (the Philippines,
Korea, and Japan) formulate guidelines based on findings from national nutrition or food
consumption surveys. Others develop their dietary guidelines based on what experts deem
appropriate.
Graphics have been adopted by many Asian countries to help the public visualize these
dietary guidelines and food guides. These include pyramids (India, Malaysia, Singapore),
pagodas (Korea and China), a plum flower (Taiwan), the “Big 6” for the six food groups
(Japan), and a six-sided star (Philippines). Another pyramid is also available for the more
affluent Filipinos.38
Similarities and Differences among Asian Dietary Guidelines
Table 12.6 presents information on representative dietary guidelines from the Asian
region. Most of the guidelines are general, and are food- rather than nutrient-based.
The exception is Singapore, which has guidelines that are quantitative and nutrient-
specific.39 There are common core food-based messages in all the guidelines; these
include: choose a diet composed of a wide variety of foods, eat enough food to meet
bodily needs and maintain or improve body weight, select foods that are safe to eat,
and enjoy your food.
The guidelines also vary with respect to number and relative emphasis on balance,
adequacy, moderation, and restriction. Although all the Asian dietary guidelines recom-
mend eating a variety of foods, they differ on how they suggest achieving a varied pattern
(see Table 12.6). Some include recommendations for frequency of consumption. Eating
breakfast daily is recommended in the Indonesian guidelines, and having regular meals
is recommended in the Korean guidelines.35,40 Other guidelines recommend specific
364
TABLE 12.5
Development of Dietary Guidelines in Asian Countries
India Indonesia Philippines Malaysia Thailand
Title of guideline Dietary Guideline for 13 Core Messages for a Nutritional Guidelines for Proposed Dietary The Thai Dietary
affluent Indians; Dietary Balanced Diet Filipinos Guidelines for Malaysia Guidelines for Better
Guideline for relatively Health
poor Indians
Year 1988 1995 1990 1996 1995
Endorsing unit Indian Council of Medical National Development Dept. of Science and Ministry of Health The Division of Nutrition,
Research (Expert and Planning Technology (National Department of Health,
Committee) Coordinating Board Guidelines Committee) Ministry of Public
Health
Approaches* 1-6 1 1-5 1, 2 , 3 1
Target audiences** N G G, H G, H G
Graphic representation Pyramid None Pyramid, Pyramid None
6-sided star
Korea Japan Taiwan China Singapore
Title of guideline National Dietary Guidelines for Health Dietary Guidelines for the Chinese Dietary Guidelines for a Healthy
Guidelines Promotion: Dietary Population Guidelines for Chinese Diet
Guidelines Residents
Year 1990 1985 1995 1997 1993
Endorsing unit Korean Nutrition Ministry of Health and Department of Health Chinese Nutrition Society National Advisory
Society/ Ministry of Welfare Committee on Food &
Health and Welfare Nutrition, Ministry of
Health
Approaches* 1, 2, 4 1, 2, 3, 5 1 1 1
Target audiences** G G, H G G G
Graphic representation Pagoda Numeral 6 Plum flower Pagoda Pyramid
6 = Economic data.
** G = General population; H = Health professionals; P = Policy makers; N = Nutrition education of school children.
TABLE 12.6
Dietary Guidelines of Selected Asian Countries
India Affluent India Relatively Poor Indonesia Philippines Malaysia
1. Overall energy should be 1. Diet should be the least 1. Eat a wide variety of foods 1. Eat a variety of foods 1. Enjoy a variety of foods
restricted to levels expensive and conform to 2. Consume foods that 2. Keep ideal body weight 2. Maintain healthy body
commensurate with traditional and cultural provide sufficient energy 3. Consume enough protein weight by balancing food
sedentary occupations so practices as closely as 3. Obtain about half of total 4. Keep fat consumption at intake with regular
that obesity is avoided possible energy requirements from 20% of energy intake physical activity
2. Give preference to 2. Energy derived from complex CHO-rich foods 5. Drink milk every day 3. Eat plenty of rice and other
undermilled over highly cereals should not exceed 4. Obtain not more than a 6. Reduce salt intake cereal products, fruits, and
refined and polished cereals 75% of the total energy quarter of total energy 7. Keep in good dental health vegetables
3. Include green leafy requirement intake from fats or oils 8. Moderate alcohol and 4. Minimize fat in food
vegetables in the diet 3. Some pulses should be 5. Use only iodized salt caffeine consumption preparation and choose
4. Restrict daily edible fat eaten along with the high- 6. Consume iron-rich foods 9. Keep harmony between foods low in fat and
intake to less than 40g, total cereal diet, with at least 7. Breastfeed your baby diet and daily life cholesterol
fat intake to less than 20% 150 ml of milk and 150 g of exclusively for four months 10. Enjoy meals 5. Choose foods low in salt
of total calories, and intake vegetables per day 8. Have breakfast every day and sugar
of ghee (clarified butter) to 4. Energy from fat and oil 9. Drink adequate quantities 6. Drink plenty of water daily
special occasions only should not exceed 10%, and of fluids that are free of 7. Practice breastfeeding
5. Restrict intake of sugar and that from refined contaminants
sweets carbohydrate (sugar or 10. Take adequate exercise
6. Avoid high-salt intake, jaggery) should not exceed 11. Avoid drinking alcoholic
especially for those prone to 5% of total calories drinks
hypertension 12. Consume foods prepared
hygienically
13. Read the labels of packaged
foods
Thailand Korea Japan China Singapore
1. Eat sufficient and 1. Eat a variety of foods 1. Obtain well-balanced 1. Eat a variety of foods 1. Eat a variety of foods
appropriate cereals or 2. Keep ideal body weight nutrition with a variety of 2. Eat appropriate quantity of 2. Maintain desirable body
whole grain cereal products 3. Consume enough protein foods (30 foods a day); take foods weight
2. Eat fish, lean meat, legumes, 4. Keep fat consumption at staple food, main dish, and 3. Moderate oil and fat 3. Restrict total fat intake to
and their products 20% of energy intake side dishes together 4. Eat moderately polished 20-30% of total energy
5. Drink milk every day cereals intake
365
366

Dietary Guidelines of Selected Asian Countries
Thailand Korea Japan China Singapore
3. Be mindful of fat intake of 6. Reduce salt intake 2. Take energy corresponding 5. Limit salt intake 4. Modify composition of fat
below 30% of total energy 7. Keep in good dental health to daily activity 6. Eat fewer sweets in the diet to 1/3
intake and make sure that 8. Moderate alcohol and 3. Consider the amount and 7. Limit alcohol balance food polyunsaturated, 1/3
low cholesterol foods are caffeine consumption quality of fats and oils distribution through three monounsaturated, and 1/3
chosen 9. Keep harmony between consumed: avoid too much; meals saturated
4. Eat a variety of fruits and diet and daily life eat more vegetable oils than 5. Reduce cholesterol intake
vegetables to ensure 10. Enjoy meals animal fat to less than 300 mg/day
adequate vitamins and fiber 4. Avoid too much salt — not 6. Maintain intake of complex
supplies more than 10 g a day carbohydrates at about 50%
5. Eat sweets and sugars only 5. Happy eating makes for total energy intake
in moderation happy family life; sit down 7. Reduce salt intake to less
6. Restrict salt intake and eat together and talk; than 4.5 g a day (1800 mg
7. Recognize and eat well treasure family taste and Na)
prepared food which is free home cooking 8. Reduce intake of salt-cured,
of microorganisms and preserved, and smoked
food contaminants foods
8. Avoid or restrict alcohol 9. Reduce intake of refined
consumption and processed sugar to less
than 10% of energy
10. Increase intake of fruit and
vegetables and whole-grain
cereal products
11. For those who drink
alcohol, have no more than
2-3 standard drinks (about
40 g alcohol) per day
12. Encourage breastfeeding in
infants until at least 6
months of age
amounts of different kinds of foods. For example, to assure a well-balanced diet, the
Japanese guidelines recommend eating thirty or more different kinds of foods daily.41
Japanese guidelines also suggest balancing main and side dishes around staple foods.
Malaysia recommends choosing foods from each of the food groups daily.42 The Filipino
and Chinese guidelines also focus on achieving dietary adequacy, emphasizing food rather
than nutrient-based interventions.
Table 12.6 describes the guidelines with respect to nutrients. Virtually all emphasize
ensuring adequacy of energy/calorie intake. Korea mentions achieving and maintain-
ing energy balance by balancing intake and expenditure.35 Most guidelines stress
increased intakes of fruits, vegetables, cereal, and dairy food to promote fiber, vitamin,
and mineral intakes and geting enough food. Some also indicate the proportion of
foods that should be consumed in relation to total energy intake. For example, the
Indian guidelines for the low-income population recommend that less than 75% of
kcalories should come from cereals.43 In countries where deficiencies of vitamins and
minerals have been identified as public health problems, the guidelines reflect this and
emphasize food sources rich in those nutrients. For example, calcium is mentioned
specifically in some guidelines; a specific calcium-rich food (milk) is mentioned in the
Taiwanese, Chinese, and Korean guidelines, and fish and seaweed in the Japanese
guidelines. In Indonesia, people are advised to “consume iron-rich foods, and use only
iodized salt.”40 The Filipino guidelines recommend choosing “foods fortified with
nutrients.”37 The guidelines for less affluent Indians and Indonesians recommend eating
enough food.40,43
The guidelines for more affluent countries such as Taiwan, Singapore, Korea, Japan
(and also for the more affluent members of the populations in Indonesia and India)
emphasize moderation in fat, saturated fat, and/or simple sugars. The major difference
between the various guidelines in Asia is in the amounts and the relative balance
suggested between dietary constituents. The Asian guidelines on moderation in fat and
salt intake vary greatly. Some simply say to avoid excess, or to limit/restrict the use of
fat (see guidelines for India, Malaysia, Taiwan, China), while others specify the type of
fat to be consumed. For example, the Japanese guidelines recommend use of vegetable
oil instead of animal fat, and in the Indian guidelines, ghee (clarified fat, very high in
saturated fat) is recommended but only for special occasions for affluent Indians. China,
Taiwan, and Singapore are three countries with similar ethnic origins and dietary patterns
that share similar dietary guidelines recommending reducing intake of salt and salt-
cured foods. Singapore is the most specific, recommending eating less than 5 grams of
salt or 2000 mg of sodium per day.39 General recommendations on limiting salt intake
are present in other guidelines throughout the region. The Japanese guidelines recom-
mend eating less than 10 grams of salt per day. Neither Malaysia nor the Philippines
mention salt.39
The majority of the guidelines stress common nonfood-related healthy behaviors such
as not smoking, dental hygiene, stress management, weight control, and physical activity.
Asian dietary guidelines also specify the settings (places or environments) or other cir-
cumstances surrounding food and eating (Table 12.6). Most countries in this region also
acknowledge the impacts of lifestyle changes on health, and emphasize attaining a healthy
body weight to prevent diet-related disease. The Indonesian guideline recommends con-
suming “foods to provide sufficient energy.”40 Some of these differences in emphasis
reflect the vastly different levels of affluence within and between countries in Asia. For
example, India has two sets of guidelines. One is for the poor and emphasizes nutrient
adequacy and avoiding dietary deficiency diseases. The other Indian guideline is for
affluent individuals and emphasizes energy balance, restricting energy intakes to levels
“commensurate with sedentary occupation, so that obesity is avoided,” coupled with

moderation and restriction of fat, saturated fat, and sugar to reduce chronic degenerative
disease.43
Asian guidelines also recognize that eating is more than just “refueling” or nourishment
from the physiological standpoint. They recognize that food provides pleasure and has
strong links to family, tradition, and culture. Enjoyment of meals is therefore a concern in
all countries, but is especially evident in the Japanese and Korean guidelines. In Japan,
dietary guidelines that promote family values are included; citizens are advised to “make
all activities pertaining to food pleasurable ones.” Another Japanese guideline states “enjoy
cooking and use mealtimes as occasions for family communication.”44,45 In Korea, eating
is viewed as a way of keeping harmony between diet and other aspects of daily life, and
this is stated in the guidelines (see Table 12.6).35
Conclusions about Dietary Guidelines in Asian Countries

Dietary guidelines for the Asian countries are all directed at the general population. Many
countries, including Malaysia, Indonesia, China, and Japan, also have specific guidelines
focusing on different ages, sexes, and conditions, such as infants, and pregnant and
lactating women.33,39,44,45 Specific foods are recommended for these population groups. For
example, breastfeeding in early infancy is a common recommendation in the dietary
guidelines of many Asian countries. Human breast milk is recognized as the best food for
infants. Encouragement of breastfeeding and recognition of breast milk’s unique proper-
ties are included in the guidelines.41,58 The duration of exclusive breastfeeding ranges from
four months (Indonesia) to four to six months (Philippines), and six months in Singapore.
Another difference is age of weaning, with introduction of other foods in addition to breast
milk. For example, it is recommended at four to six months in the Philippines, but the
Malaysian guidelines recommend weaning at no earlier than five to six months, with
breastfeeding continuing for up to two years.
Some dietary guidelines are common to all Asian countries. One is to eat clean and safe
foods; such recommendations are especially important in areas where the climate is very
hot and foods are easily spoiled. The hygienic messages range from “consume food that
is hygienically prepared” in Malaysia to “eat clean and safe food to prevent foodborne
disease in the family” in the Philippines. Similar guidelines are provided in both the
Taiwan and the People’s Republic of China’s guidelines. “Drink more boiled water” is
mentioned in Taiwan, and the guideline for Mainland China is “avoiding unsanitary and
spoiled foods.”30,44,46
Conclusions
Dietary guidelines in the future must continue to take into account local dietary patterns,
cultural traditions, and food availability. Guidelines are most effective when they indicate
what aspects of diet need to be addressed to promote nutritional health in both the poor
and rich. In some countries where disparities in incomes are very large, two sets of
guidelines may be necessary.
Dietary guidelines should be flexible so that they can be used by people with different
lifestyles as well as by people of different ages, and with different population groups
(pregnant, lactating, infants, children, and elderly persons). Different guidelines may be
needed for urban and rural populations or for other special groups such as ethnic minor-
ities in some countries.
Messages delivered to the public in dietary guidelines should provide advice on the
selection of a nutritionally balanced diet and encourage other suitable lifestyle behaviors
to promote health in target groups. It is difficult to include all without making the guide-
lines so long that their communicability is compromised. Therefore, other ancillary forms
of nutrition education are also needed. Graphics allow people to put dietary guidelines
and other recommendations about food consumption into action.
Nutrition education using dietary guidelines is only one ingredient for ensuring suffi-
cient knowledge to choose a healthful diet. Motivation and opportunities to change nutri-
tion and health behaviors in favorable directions are also necessary. Knowledge, science,
technology, culture, and food sources all change with the times, and so do foodways.
Therefore, it is necessary to review guidelines periodically and make appropriate modi-
fications, i.e., every five or ten years.
In conclusion, dietary guidelines can serve multiple purposes. These include providing
useful information to the public policy maker; serving as communication tools to nutrition
and health professionals, as guides to the food industry in product formulation, and as
instructional objectives for those involved in the provision of food, nutrition, and health
education. Food is not the only factor that can influence health. Most health problems in
modern society are multifactorial in origin. However, people can help themselves by
establishing healthy dietary habits and paying attention to other factors (such as physical
activity, not smoking, decreasing stress, and improving work environments). Such mea-
sures increase the chances for a long and active life. What individuals and families under-
stand, accept, and do in their day-to-day lives matters the most in implementing healthy
lifestyles. The Dietary Guidelines help people to ensure their nutritional health.
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Health and Human Services and the Secretary of Agriculture, National Technical Information
Service, 2000. Spingfield: Department of Agriculture, US Department of Health, 2000.
10. Food and Nutrition Information Center. Food guide pyramid information.
At: http://www. nla.usda.gov/fnic/etext, accessed March 20, 2000.
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At: http://www.cdc.gov/cancer/nper/register.htm, accessed March 22, 2000.
12. CDC. 1999. Chronic diseases conditions.
At: http://www.cdc.gov/nccdphp/major.htm, accessed March 22, 2000.
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14. Health Canada on-line. Nature and dimensions of nutrition related problems, 1999.
At: http://www.hc-sc.gc.ca, accessed March 15, 2000.
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16. Department of National Health and Welfare. Canada’s Guidelines for Healthy Eating. Ottawa:
Department of Health and Welfare, 1990.
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America. Basis for Their Development. JM Bengoa BT, M Behar, and N Scrimshaw, Eds. Caracas,
Venezuela: Arch Latinoam Nutr, 1987: pg 373-426.
18. Chilean Ministry of Health, Institute of Nutrition and Food Technology, Nutrition Center at
the University of Chile. Guias de alimentacion para la poblacion Chilena. Santiago, Chile:
Ministry of Health, 1997: pg 164.
19. Tagle MA. In: Nutritional goals and food guides in Latin America. Basis for their development.
JM Bengoa BT, M Behar, and N Scrimshaw, Eds. Caracas, Venezuela: Arch Latinoam Nutr 1987:
pg 750-765.
20. Valiente S, Abala C, Avila B, Monckeberg F. In: Nutritional goals and food guides in Latin
America. Basis for their development. JM Bengoa BT, M Behar, and N Scrimshaw, Eds. Caracas,
Venezuela: Arch Latinoam Nutr 1987: pg 445-465.
21. Peña M, Molina V. Food based dietary guidelines and health promotion in Latin America.
Washington, DC: Pan American Health Organization and Institute of Nutrition of Central
America and Panama, 1999: pg 31.
22. Chavez MMd, Chavez A, Rios E, Madrigal H. Guías de alimentación: Consejos practicos para
alcanzar y mantener un buen estado de nutricion y salud. Mexico, DF: Salvador Zubiran
National Institute of Nutrition, 1993: pg 58.
23. Instituto Nacional de Nutrición, Fundación Cavendes. Guías de Alimentación para Venezuela.
Caracas, Venezuela: Fundación Cavendes, 1991: pg 88.
24. Ministerio de la Familia, Fundación Cavendes. Guías de Alimentación en el Niño Menor de
seis Años. Orientacion Normativa. Caracas, Venezuela: Fundación Cavendes, 1997: pg 44.
25. Ministerio de la Familia, Fundación Cavendes. Guías de Alimentación para Venezuela del
Niño Menor de seis Años. Manual para hogares y multihogares de cuidado diario. Caracas,
Venezuela: Fundación Cavendes, 1996: pg 131.
26. Guatemala NCoDG. Guías alimentarias para Guatemala: Los siete pasos para una alimenta-
cion sana. Guatemala: Dietary Guidelines National Committee, 1998: pg 44.
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Ministry of Health, 1995: pg 40.
28. Florentino RF. In: Dietary Guidelines in Asian Countries: Towards a Food-Based Approach,
proceedings of a seminar and workshop on national dietary guidelines. Florentino RF, Ed.
Meeting National Needs of Asian Countries in the 21st Century. Singapore: International Life
Sciences Institution Press, 1996: pg 32.
29. Karyadi D, Karyadi E. In: Dietary Guidelines in Asian Countries: Towards a Food Based
Approach, proceedings of a seminar and workshop on national dietary guidelines. Florentino
RF, Ed. Meeting National Needs of Asian Countries in the 21st Century. Singapore: International
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(1994). Newsletter, Japan Dietetic Association. Tokyo, 1995: 2 pages.
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pines, Quezon City: ASEAN-New Zealand IILP Project 5, 1997: pg 97.
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New Zealand IILP Project 5, 1997: 28 pages.
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13
Healthy People — Goals and Interpretations*
Margaret Tate and Matthew P. Van Tine
Overview
In the 1970s, the United States Department of Health and Human Services began the
process of defining specific goals to improve the health of Americans. The first publication,
Healthy People: The Surgeon General’s Report on Health Promotion and Disease Prevention,1 was
released in 1979. This preventive health initiative is now entering its third decade with
the January 2000 release of Healthy People 2010.2
Healthy People: The Surgeon General’s Report on Health Promotion and Disease Prevention
outlined goals for the nation to reduce premature death and preserve independence for
older adults. In 1980, Promoting Health/Preventing Disease: Objectives for the Nation was
released.3 This report delineated 15 priority areas and 226 objectives for the country to
achieve over the next decade. These objectives were organized under the general heading
of prevention services, health protection, and health promotion.
Healthy People 2000: National Health Promotion and Disease Prevention Objectives4 was
released in 1990. This report expanded on the 1980 objectives. Two new focus areas, cancer
and HIV, were also added. Healthy People 2000 consisted of the following three goals:
• Increase the span of healthy life for Americans

• Reduce health disparities among Americans
• Achieve access to preventive services for all Americans
The report was comprised of 22 priority areas organized under the general headings of
health promotion, health prevention services, and surveillance and data systems. The
report also organized the appropriate objectives in four areas according to age (children,
adolescent and young adults, adults and older adults) and special at–risk population
groups (low income, minorities, and people with disabilities).
In 1995, Healthy People 2000 Midcourse Review and 1995 Revisions5 was released. This
report evaluated the nation’s progress on the 2000 objectives and resulted in changes in
* Special thanks to Judy Moreland, Judy Nowak, Sharon Sass, and Geri Tebo for their help in developing this
manuscript.
0-8493-2705-9/01/$0.00+$1.50
TABLE 13.1
Healthy People 2010 Focus Areas
1. Access to quality health services
2. Arthritis, osteoporosis, and chronic back conditions
3. Cancer
4. Chronic kidney disease
5. Diabetes
6. Disability and secondary conditions
7. Educational and community-based programs
8. Environmental health
9. Family planning
10. Food safety
11. Health communications
12. Heart diseases and stroke
13. HIV
14. Immunization and infectious disease
15. Injury and violence prevention
16. Maternal, infant, and child health
17. Medical product safety
18. Mental health and mental disorders
19. Nutrition and overweight
20. Occupational safety and health
21. Oral health
22. Physical activity and fitness
23. Public health infrastructure
24. Respiratory diseases
25. Sexually transmitted diseases
26. Substance abuse
27. Tobacco use
28. Vision and hearing
U.S. Department of Health and Human Services, Healthy
People 2010 2nd ed., Government Printing Office, Super-
intendent of Documents, Washington, DC, January 2000.
some objectives, as well as incorporation of new objectives. Forty-seven sentinel objectives

were selected to track the nation’s success in meeting the objectives. At the midpoint
review, 33 of the sentinel objectives were moving in the right direction, nine were moving
in the wrong direction, and two had not changed. Data was not available on the remaining
three objectives.
Healthy People 2010, released in January 2000, provides the nation with its third ten-year
blueprint for a healthier population. Over 350 national membership organizations and
270 state and local health agencies contributed to the development of this report.
Healthy People 2010 is organized around the following two goals:
• Increase quality and years of healthy life — defined as “a personal sense of

physical and mental health and the ability to react to factors in the physical and
social environments.”2
• Eliminate health disparities — defined as “eliminate disparities among different
segments of the population. These include differences that occur by gender, race
or ethnicity, education or income, disability, living in rural localities, or sexual
orientation.”2
The two-volume report consists of 467 objectives organized in 28 focus areas. These
focus areas are listed in Table 13.1.
Healthy People — Goals and Interpretations 375
TABLE 13.2
Leading Health Indicators
Physical activity
Overweight and obesity
Tobacco use
Substance abue
Responsible sexual behavior
Mental health
Injury and violence
Environmental quality
Immunization
Access to health care
U.S. Department of Health and Human Services, Healthy
People 2010 2nd ed., Government Printing Office, Super-
intendent of Documents, Washington, DC, January 2000.
A new addition to Healthy People 2010 is the identification of leading health indicators
(Table 13.2). These represent major public health concerns in the U.S. They are divided
into two groups: lifestyle challenges and system enhancement challenges.6 The lifestyle
challenges are physical activity, overweight and obesity, tobacco use, substance abuse, and
responsible sexual behavior. The system challenges are mental health, injury and violence,
environmental quality, immunizations, and access to health care. Specific objectives will
be used to track progress toward improving the leading health indicators.
Nutrition has been one of the focus areas since the beginning of the Healthy People
initiative. In Healthy People 2010, the goal of the nutrition and overweight focus area is to
promote health and reduce chronic disease associated with diet and weight. There are 18
objectives listed in the nutrition section, with 33 other nutrition-related objectives listed
in other focus areas.
Table 13.3 delineates the primary nutriton-related objectives from Healthy People 2000
and Healthy People 2010. The table is organized around the Healthy People 2000 objectives.
The first column lists the nutrition objectives from Section 2 as well as key nutrition-related
objectives from other Healthy People 2000 focus areas. The objectives from the nutrition
section are bolded. The information in italic print was added at the midcourse review. The
second column is the baseline data that was used to evaluate the objectives, and the third
column is the source of that data. The fourth column, Outcome, evaluates the success in
meeting the Healthy People 2000 objective. The fifth column lists the corresponding Healthy
People 2010 objectives, if available. It also lists any new objectives. Again, the objectives
from the nutrition section (Section 19) are bolded. The last two columns list the baseline
data, and data sources for Healthy People 2010. The baseline data rates used in Healthy
People 2010 were age-adjusted to the year 2000, whereas the rates used in Healthy People
2000 were age-adjusted to the 1940 population or are crude rates. If an objective does not
have baseline data or a known data source, it is listed as a developmental objective.
Table 13.4 provides the full names for the abbreviations used in the data source columns.
The information presented in the chart is taken directly from the references indicated in
the footnotes.
Healthy People is truly one of this country’s most significant public health initiatives.
It is a valuable tool to help Americans promote health and prevent disease, disability, and
premature death. To be successful, we must continue to work together to put Healthy
People into practice.
TABLE 13.3
Summary of Healthy People 2000 and 2010 Objectives
376
Healthy People Healthy People

2000 Objectives Baseline Data Source Outcome 2010 Objectives Baseline Data Source
2.1 Reduce coronary Age-adjusted baseline: NVSS, CDC (4) In 1996, the death rate 12-1 Reduce coronary 208 coronary heart NVSS, CDC, NCHS (2)
heart disease deaths to 135/100,000 in 1987. (4) from coronary heart heart disease deaths. disease deaths/100,000
no more than 100/ disease (CHD) was 105 Target: 166/100,000 population (age-
100,000 people. (4) deaths/100,000 people. (2) adjusted) in 1998. (2)
population. (8)
2.2 Reverse the rise in Age-adjusted baseline: NVSS, CDC (4) In 1997, the age adjusted 3-1 Reduce the overall 201.4 cancer deaths/ NVSS, CDC, NCHS (2)
cancer deaths to 133/100,000 in 1987. (4) cancer death rate was cancer death rate. 100,000 population
achieve a rate of no 125 deaths/100,000 Target: 158.7 cancer (age-adjusted) in 1998.
more than 130/100,000 population deaths/100,000 (2)
people. (4) (preliminary data). (8) population. (2)
2.3 Reduce overweight 26% for people age 20 NHANES, CDC; In 1994, the prevalence of 19-1 Increase the 42% of adults age 20 NHANES, CDC,
to a prevalence of no through 74 in 1976-80, Hispanic HANES, overweight was 35% proportion of adults years and older were at NCHS (2)
more than 20% among 24% for men and 27% CDC; IHS; NHIS, CDC for people 20-74 years who are at a healthy a healthy weight
people age 20 and for women; 15% for (4) and 24% for weight. Target: 60%. (2) (defined as a body mass
older and no more than adolescents age 12 adolescents 12-19 years. index (BMI) equal to or
15% among through 19 in 1976-80. This is a substantial greater than 18.5 and
adolescents through (4) increase over the 1976- less than 25) in 1988-94.
19. (4) 80 baseline data. (8) (2)
19-2 Reduce the 23% of adults age 20 NHANES, CDC,
proportion of adults years and older were NCHS (2)
who are obese. Target: identified as obese
15%. (2) (defined as a BMI of 30
or more) in 1988-94. (2)
1988-94 baseline for NHANES, CDC,
19-3 Reduce the children age 6-11: 11%; NCHS (2)
proportion of children age 12-19: 10%; age 6-
and adolescents who 19: 11%. (2)
are overweight or
obese. Target: age 6-11
years: 5%; age 12-19
years: 5%; age 6-19
years: 5%. (2)
2.4 Reduce growth Up to 16% among low- Pediatric Nutrition The target to reduce 19-4 Reduce growth 8% of low-income PNSS, CDC, NCCDPHP
retardation among income children in Surveillance System, growth retardation to retardation among children under age 5 (2)
low-income children 1988, depending on age CDC (4) less than 10% for all low-income children years were growth
age 5 and younger to and race/ethnicity. (4) low-income children under age 5 years. retarded in 1997
less than 10%. (4) age 5 years and under Target: 5%. (2) (defined as height-
has been met, although forage below the 5th
the target for African- percentile in the age-
American children gender appropriate
under 1 year has not. (7) population using the
1977 NCHS/CDC
growth charts). (2)

2.5 Reduce dietary fat 36% of calories from total NHANES, CDC; CSFII, 34% of calories from total 19-8 Increase the 36% of persons age 2 CFSII, USDA (2)
intake to an average of fat and 13% from USDA (4) fat and 12% from proportion of persons years and older
30% of calories or less saturated fat for people saturated fat for people age 2 years and older consumed less than
and average saturated age 20 through 74 in age 20 through 74 from who consume less than 10% of calories from
fat intake to less than 1976-80; 36% and 13% the 1994 NHANES; 34% 10% of calories from saturated fat in 1994-96.
10% of calories among for women age 19 met the goal for fat and saturated fat. Target: (2)
people age 2 and older. through 50 in 1985. (4) 36% met the goal for 75%. (2)
(4) In addition, Baseline (for the saturated fat based on 19-9 Increase the 33% of persons age 2
increase to at least 50% midcourse) addition for the 3-day dietary data proportion of persons years and older CSFII, USDA (2)
the proportion of people age 2 and older: from 1989-91 CSFII. (8) age 2 years and older consumed no more
people age 2 and older 21% met the goal for fat who consume no more than 30% of daily
who meet the Dietary and 21% met the goal than 30% of calories calories from fat in
Guidelines' average for saturated fat based from fat. Target: 75%. 1994-96. (2)
daily goal of no more on 2-day dietary data (2)
than 30% of calories from the 1989-91
from fat, and increase NHANES; 22% met the
to at least 50% the goal for fat and 21%
proportion of people met the goal for
age 2 and older who saturated fat based on
meet the average daily the 3-day dietary data
goal of less than 10% of from 1989-91 CSFII. (5)
calories from saturated

Healthy People — Goals and Interpretations
fat. (5)
2.6 Increase complex 2 1/2 servings of CSFII, USDA (1) 4.7 servings of 19-5 Increase the 28% of persons age 2 CSFII, USDA (2)
carbohydrate and vegetables and fruits vegetables and fruits proportion of persons years and older
fiber-containing foods and 3 servings of grain and 6.9 servings of age 2 years and older consumed at least 2
in the diets of adults to products for women grain products for who consume at least 2 daily servings of fruit in
5 or more daily age 19 through 50 in people age 2 and over; daily servings of fruit. 1994-96. (2)
servings for vegetables 1985. (4) Baseline for 35% met the goal for Target: 75%. (2)
(including legumes) the midcourse fruits and vegetables 19-6 Increase the 3% of persons age 2 years CSFII, USDA (2)
and fruits, and to 6 or addition): 29% met the and 52% met the goal proportion of persons and older consumed at
more daily servings for goal for fruits and for grain products for age 2 years and older least 3 daily servings of
grain products. (4) In vegetables and 40% met people age 2 and older who consume at least 3 vegetables, with at least
addition, increase to at the goal for grain in 1989-91. (8) daily servings of one-third of these
least 50% the products for people age vegetables, with at servings being dark
proportion of people 2 and older based on 3- least one-third being green or deep yellow
age 2 and older who day dietary data in dark green or deep vegetables in 1994-96.
meet the Dietary 1989-91. (5) yellow vegetables. (2)
Guidelines' average Target: 50%. (2) 7% of persons age 2 years
daily goal of 5 or more 19-7 Increase the and older consumed at CSFII, USDA (2)
servings of vegetables/ proportion of persons least 6 daily servings of
fruits, and increase to age 2 years and older grain products, with at
at least 50% the who consume at least 6 least 3 being whole
proportion who meet daily servings of grain grains in 1994-96. (2)
the goal of 6 or more products, with at least
grain products. (5) 3 being whole grains.
Target: 50%. (2)
377
378

2.7 Increase to at least 30% of overweight NHIS, CDC (4) In 1995, 15% of the No corresponding
50% the proportion of women and 25% of overweight women and objective.
overweight people age overweight men for 19% of the overweight
12 and older who have people age 18 and older men age 18 and older
adopted sound dietary in 1985. (4) have adopted sound
practices combined dietary practices
with regular physical combined with
activity to attain an physical activity to
appropriate body attain an appropriate
weight. (4) body weight. (8)
2.8 Increase calcium 7% of women and 14% of CSFII, USDA (4) 15% of people 11-24 19-11 Increase the 46% of persons age 2 NHANES, CDC, NCHS
intake so at least 50% men age 19 through 24 years and 13% proportion of persons years and older were at (2)
of youth age 12 and 24% of pregnant pregnant and lactating age 2 years and older or above approximated
through 24 and 50% of and lactating women females consumed an who meet dietary mean calcium
pregnant and lactating consumed 3 or more average of 3 or more recommendations for requirements (based on
women consume 3 or servings, and 15% of servings daily, and 47% calcium. Target: 75%. consideration of
more servings daily of women and 23% of men of children 2-10 years (2) calcium from foods,
foods rich in calcium, age 25 through 50 and 21% people 25 dietary supplements,
and at least 50% of consumed 2 or more years and over and antacids) in 1988-
people age 25 and servings in 1985-86. (4) consumed 2 or more 94. (2)
older consume 2 or servings in 1996. (8)
more servings daily. (4)
2.9 Decrease salt and 54% of women age 19 CSFII, USDA; Health In 1995, 19% of people 18 19-10 Increase the 21% of persons age 2 NHANES, CDC, NCHS
sodium intake so at through 50 who served and Diet Survey, FDA years and over proportion of persons years and older (2)
least 65% of home as the main meal (4) regularly purchase age 2 years and older consumed 2400 mg of
meal preparers prepare preparer did not use foods with reduced salt who consume 2,400 mg sodium or less daily
foods without adding salt in food and sodium content, or less of sodium daily. (from foods, dietary
salt, at least 80% of preparation, and 68% of 58% rarely or never use (2) supplements, tap
people avoid using salt women age 19 through salt at the table. (8) water, and salt use at
at the table, and at least 50 did not use salt at the the table) in 1988-94. (2)
40% of adults regularly table in 1985; 20% of all
purchase foods people age 18 and older
modified or lower in regularly purchased
sodium. (4) foods with reduced salt
and sodium content in
1988. (4)
2.10 Reduce iron 9% among children age 1 NHANES, CDC; Alaska 6% among children age 19-12 Reduce iron 1988-94 baseline: NHANES, CDC, NCHS;
deficiency to less than through 2, 4% for Native Children, CDC 1-4 years; 9% for deficiency among children age 1-2 years: NCHS (2)
3% among children children age 3 through 1988; PNSS, CDC (4) children age 1-2 years; young children and 9%; Children age 3-4
age 1 through 4 and 4, 5% for women age 20 4% for children age 3-4 females of years: 4%; Non-
among women of through 44 in 1976-80. years; 8% for females childbearing age. pregnant females age
childbearing age. (4) (4) age 20-44 years were Target for children age 12 to 49 years: 11%. (2)
anemic in 1988-94. (8) 1-2 years: 5%; Children
age 3-4 years: 1%; Non-
pregnant females age
12-49 years: 7%. (2)
19-13 Reduce anemia
among low-income 29% of low-income PNSS, CDC, NCCDPHP
pregnant females in pregnant females in (2)
their third trimester. their third trimester
Target: 20%. (2) were anemic (defined
as hemoglobin <11.0 g/
19-14 (Developmental) dL) in 1996. (2)
Reduce iron deficiency Potential Data Source:
among pregnant NHANES, CDC, NCHS
females. (2) (2)
2.11 Increase to at least 54% at discharge from Ross Laboratories 62% in early postpartum 16-19 Increase the 1998 baseline: in early Mothers' Survey, Abbott
75% the proportion of birth site and 21% at 5 Mothers Survey; PNSS, period and 26% at 6 proportion of mothers postpartum period: Laboratories Inc., Ross
mothers who to 6 months in 1988. (4) CDC (4) months in 1997. (8) who breastfeed their 64%; at 6 months: 29%; Products Division (2)
breastfeed their babies babies. Target: in early at 1 year: 16%. (2)
in the early postpartum period:
postpartum period and 75%; at 6 months: 50%;
to at least 50% the at 1 year: 25%. (2)
proportion who
continue
breastfeeding until
their babies are 5 to 6
months old. (4)
2.12 Increase to at least 55% for parents and NHIS, CDC (8) No data beyond No corresponding
75% the proportion of caregivers of children 6- baseline. (7) objective.
parents and caregivers 23 months in 1988. (5)
who use feeding
practices that prevent
baby bottle tooth
decay. (4)
379
380

2.13 Increase to at least 74% used labels to make Health and Diet Survey, In 1995, 75% of the No corresponding
85% the proportion of food selections in 1988. FDA (4) people 18 years and objective.
people age 18 and (4) over reported using
older who use food food labels. (8)
labels to make
nutritious food
selections. (4)
2.14 Achieve useful and 60% of sales of processed Food Label and Package In 1995, 96% of pro- No corresponding
informative nutrition foods regulated by Survey, FDA (4) cessed foods had objective.
labeling for virtually FDA had nutrition nutrition labeling. In

all processed foods labeling in 1988; 1996, 73% of fresh
and at least 40% of baseline data on fresh produce and 71% of
fresh meats, poultry, and carry-away foods fresh seafood had
fish, fruits, vegetables, unavailable. (4) nutrition labeling. (8)
baked goods, and
ready-to-eat carry-
away foods. (4)
2.15 Increase to at least 2500 items reduced in fat Nielsen Company In 1991, 5618 reduced fat No corresponding
5000 brand items the in 1986. (4) National Scantrack (4) and saturated fat food objective.
availability of products were
processed food available. (8)
products that are
reduced in fat and
saturated fat. (4)
2.16 Increase to at least About 70% of fast food Survey of Chain In 1990, 75% of large- No corresponding
90% the proportion of and family restaurant Operators, National chain restaurants objective.
restaurants and chains with 350 or more Restaurant Association offering at least one
institutional food units had at least one (4) low-fat, low-calorie
service operations that low-fat, low-calorie item. (8)
offer identifiable low- item on their menu in
fat, low-calorie food 1989. (4)
choices, consistent
with the Dietary
Guidelines for
Americans. (4)
2.17 Increase to at least 1% of schools offered 1992 School Nutrition There were no new data 19-15 (Developmental) Potential Data Source:
90% the proportion of lunches that provided Dietary Assessment beyond the baseline to Increase the CSFII, USDA (2)
school lunch and an average of 30% or Study; SHPPS, CDC, measure this objective. proportion of children
breakfast services and less of calories from NCCDPHP (8) (7) and adolescents age 6
child care food services total fat, and less than to 19 years whose
with menus that are 1% offered lunches that intake of meals and
consistent with the provided an average of snacks at schools
nutrition principles in less than 1% of calories contributes
the Dietary Guidelines from saturated fat. Of proportionally to good
for Americans. (4) the schools partici- overall dietary quality.
pating in the USDA (2)
school breakfast
program, 44% offered
breakfasts that
provided an average of
30% or less of calories
from total fat, and 4%
offered breakfasts that
provided an average of
less than 10% of calories
from saturated fat in
1992. (5)
2.18 Increase to at least 48% in 1991. (8) NHIS, CDC (8) 50% in 1995. (8) No corresponding
80% the receipt of objective.
home food services by
people age 65 and
older who have
difficulty in preparing
their own meals or are
otherwise in need of
home-delivered meals.
(4)
381
382

2.19 Increase to at least 60% of states in 1991. (5) National Survey of The proportion of States 7-2 Increase the Summary objective SHPPS, CDC,
75% the proportion of School Health that required nutrition proportion of middle, baseline: 28%; NCCDPHP (2)
the nation's schools Education Activities, education increased junior high, and senior unhealthy dietary
that provide nutrition CDC, NCCDPHP (8) from 60% in 1990 to high schools that patterns baseline: 78%
education from 69% in 1994. (8) provide comprehensive in 1994. (2)
preschool through 12th school health education
grade, preferably as to prevent health
part of quality school problems in the

healthy education (4) following areas:
unintentional injury;
violence; suicide;
tobacco use and
addiction; alcohol or
other drug use;
unintended pregnancy;
HIV/AIDS, and STD
infection; unhealthy
dietary patterns;
inadequate physical
activity; and
environmental health.
Summary objective
target: 70%; Unhealthy
dietary patterns target:
95%. (2)
2.20 Increase to at least 17% offered nutrition NWHPS, ODPHP (4) The proportion of 19-16 Increase the pro- 55% of worksites with 50 NWHPS, AWHP (2)
50% the proportion of education activities and worksites with 50 or portion of worksites or more employees
worksites with 50 or 15% offered weight more employees that that offer nutrition or offered nutrition or
more employees that control activities in offer programs for weight management weight management
offer nutrition 1985. (4) employees increased classes or counseling. classes or counseling at
education and/or from 17% in 1985 to Target: 85%. (2) the worksite or through
weight management 31% in 1992. (8) their health plans in
programs for 1998-1999. (2)
employees. (4)
2.21 Increase to at least Physicians provided diet Lewis 1988 (4) There were no new data 19-17 Increase the Counseling or education NAMCS, CDC, NCHS
75% the proportion of counseling for an beyond the baseline to proportion of on diet and nutrition (2)
primary care providers estimated 40-50% of measure this objective. physician office visits was ordered or
who provide nutrition patients in 1988. (4) (7) made by patients with provided for 42% of
assessment and a diagnosis of physician visits that
counseling and/or cardiovascular disease, were related to the
referral to qualified diabetes, or diagnosis of cardio-
nutritionists or hyperlipidemia that vascular disease,
dietitians. (4) include counseling or diabetes, or hyper-
education related to lipidemia in 1997. (2)
diet and nutrition.
Target: 75%. (2)
2.22 Reduce stroke Age-adjusted baseline: NVSS, CDC (4) In 1996, the age adjusted 12-7 Reduce stroke 60 deaths from stroke/ NVSS, CDC, NCHS (2)
deaths to no more than 30.3/100,000 in 1987. death rate from stroke deaths. Target: 48 100,000 population in
20/100,000 people. (5) (5) was 26.4/100,000. (8) deaths/100,000 1998. (2)
population. (2)
2.23 Reduce colorectal 14.4/100,000 in 1987. (5) NVSS, CDC (4) In 1996, the age adjusted 3-5 Reduce the colorectal 21.1 colorectal cancer NVSS, CDC, NCHS (2)
cancer deaths to no death rate was for cancer death rate. deaths/100,000 pop-
more than 13.2/100,000 colorectal cancer 16.3 Target: 13.9 deaths/ ulation in 1998. (2)
people. (5) death/100,000 100,000 population. (2)

population. (8)
2.24 Reduce diabetes to 1986-88, the indence was NHIS, CDC; IHS; In 1994-96, the incidence 5-3 Reduce the overall 40 overall cases (new and NHIS, CDC, NCHS (2)
an incidence of no 2.9/1,000; the Hispanic HANES, CDC of diabetes was 3.1/ rate of diabetes that is existing) of diabetes/
more than 2.5/1,000 prevalance was 28/ (4) 1,000 population and clinically diagnosed. 1,000 population (age-
people and a 1,000. (5) the prevalence was 31/ Target: 25 overall adjusted) in 1997. (2)
prevalence of no more 1,000 population. (8) cases/1,000
than 25/1,000 people. population. (2)
(5)
2.25 Reduce the 27% for people age 20-74 NHANES, CDC (4) The prevalence of high 12-14 Reduce the 21% of adults age 20 NHANES, CDC, NCHS
prevalence of blood in 1976-80, 29% for blood cholesterol was proportion of adults years and older had (2)
cholesterol levels of women and 25% for 19% among people 20- with high total blood total blood cholesterol
240 mg/dL or greater to men. (5) 74 years in 1988-94. (8) cholesterol levels. levels of 240 mg/dL or
no more than 20% Target: 17%. (2) greater in 1988-94. (2)
among adults. (5)
2.26 Increase to at least 11% controlled among NHANES, CDC; 1982-88 In 1991, the control rate 12-10 Increase the 18% of adults age 18 NHANES, CDC, NCHS
50% the proportion of people age 18-74 in Seven State Survey, among people 18-74 proportion of adults years and older with (2)
people with high 1976-80; an estimated NIH (4) years with high blood with high blood high blood pressure
blood pressure whose 24% for people age 18 pressure was 29%. (8) pressure whose blood had it under control in
blood pressure is and older in 1982-84. (5) pressure is under 1988-94. (2)
under control. (5) control. Target: 50%. (2)
383
384

2.27 Reduce the mean 213 mg/dL among NHANES, CDC (4) Average total serum 12-13 Reduce the mean 206 mg/dL was the NHANES, CDC, NCHS
serum cholesterol people age 20-74 in cholesterol for people total blood cholesterol mean total blood (2)
among adults to no 1976-80, 211 mg/dL for 20-74 years was 203 levels among adults. cholesterol level for
more than 200 mg/dL. men and 215 mg/dL for mg/dL in 1988-94. (8) Target: 199 mg/dL. (2) adults age 20 years and
(5) women. (5) older in 1988-94. (2)
19-18 Increase food 88% of all US households Current Population
security among US were food secure in Survey, US Dept of
households and in so 1995. (2) Commerce, Bureau of
doing reduce hunger. the Census; National
Target: 94%. (2) Food and Nutrition
Survey, (beginning in
2001) DHHS and USDA
(2)
4.8 Reduce alcohol 2.54 gallons of ethanol in NIAAA, ADAMHA (4) In 1994, 2.21 gallons 26-12 Reduce average 2.19 gallons of ethanol/ AEDS, NIH, NIAAA (2)
consumption by people 1987 (4) alcohol/person age 14 annual alcohol person age 14 years and
14 and older to an years and older were consumption. Target: 2 older were consumed
annual average of no consumed. (8) gallon. (2) in 1996. (2)
more than 2 gallons of
ethanol/person. (4)
12.1 Reduce infections Salmonella species:18/ NCID, CDC (4) In 1996, Salmonella 10-1 Reduce infections In 1997, the case/100,000 Foodborne Disease
caused by key 100,000; Campylobacter species: 15/100,000; caused by key population was Network (FoodNet),
foodborne pathogens to jejuni: 50/100,000; Campylobacter jejuni: foodborne pathogens. Campylobacter species: CDC, NCID; FDA,
incidences of no more Escherichia coli: 24/100,000; Escherichia Target (cases/100,000): 24.6; Escherichia coli: CFSAN; FSIS, OPHS
than: Salmonella species: 0157:H7: 8/100,000; coli: 0157:H7: 3/ Campylobacter species: 0157-H7:2.1; Listeria and state agencies.
16/100,000 Listeria monocytogenes: 100,000; Listeria 12.3; Escherichia coli monocytogenes: 0.5; Potential data sources:
Campylobacter jejuni: 0.7/ 100,000. (4) monocytogenes: 0.5/ 0157-H7: 1.0; Listeria Salmonella species: 13.7. NNDSS, CDC, NCID
25/100,000; Escherichia 100,000. (8) monocytogenes: 0.25; (2) (2)
coli: 0157:H7: 4/ Salmonella species: 6.8;
100,000; Listeria Cyclospora cayetanensis:
monocytogenes: 0,5/ developmental;
100,000. (4) Postdiarrheal
hemolytic uremic
syndrome:
developmental;
Congenital Toxoplasma
gondii: developmental.
(2)
12.2 Reduce outbreaks of 77 Outbreaks in 1989. (4) NCID, CDC (4) In 1996, there were 50 10-2 Reduce outbreaks of The number of outbreaks Foodborne Disease
infections due to outbreaks due to infections caused by in 1997: Escherichia coli Outbreak Surveillance
Salmonella enteritidious Salmonella enteritidious. key foodborne bacteria. 0157-H7-22; Salmonella System, CDC, NCID (2)
to fewer than 25 (8) Target (number of serotype Enteridis-44.
outbreaks yearly. (4) outbreaks/year): (2)
Escherichia coli 0157-
H7:11; Salmonella
serotype Enteridis: 22.
(2)
12.3 Increase to at least For refrigeration of Food Safety Survey, For refrigeration of 10-5 Increase the 72% of consumers Food Safety Survey,
75% the proportion of perishable foods, 70%; FDA; Diet-Health perishable foods, 72% proportion of followed key food FDA: FSIS, USDA (2)
households in which for washing cutting Knowledge Survey, (in 1993); for washing consumers who follow safety practices in 1998.
principal food boards with soap, 66%; USDA (4) cutting boards with key food safety (2)
preparers routinely and for washing soap, 71% (in 1997); practices. Target: 79%.
refrain from leaving utensils with soap, 55%, washing utensils with (2)
perishable food out of in 1988. (4) soap, no data beyond
the refrigerator for over the baseline. (8)
2 hours and wash
cutting boards and
utensils with soap after
contact with raw meat

and poultry. (4)
14.1 Reduce the infant 10.1/1000 live births in NVSS, CDC: Linked In 1996, the infant 16-1 Reduce fetal and In 1997, (per 1000 live NVSS, CDC, NCHS (2)
mortality rate to no 1987. (4) Birth and Infant Death mortality rate was 7.3/ infant deaths. Target births plus fetal deaths)
more than 7/1000 live Data Set, CDC (4) 1,000 live births. (8) (per 1000 live births 6.8 for 20 or more
births. (4) plus fetal deaths): 4.1 at weeks of gestation; 7.5
20 or more weeks of during the perinatal
gestation; 4.5 during period. (2)
the perinatal period. (2)
14.5 Reduce low birth 6.9 and 1.2%, NVSS, CDC (4) 7.4% and 1.4% 16-10. Reduce low birth 1998 baseline: 7.6% for NVSS, CDC, NCHS (2)
weight to an incidence respectively, in 1987. (4) respectively, in 1996. (8) weight (LBW) and very LBW 1.4% for VLBW.
of no more than 5% of low birth weight (2)
live births and very low (VLBW). Target: 5.0%
birth weight to no more for LBW Target: 0.9%
than 1% of live births. for VLBW. (2)
(4)
14.6 Increase to at least 68% of married females National Natality In 1990, 75% of mothers 16-12. (Developmental) Potential data sources:
85% the proportion of who had a full-term Survey, CDC, National achieved the minimum Increase the proportion NVSS, CDC, NCHS (2)
mothers who achieve live birth and prenatal Maternal and Infant recommended weight of mothers who achieve
the minimum care in 1980. (8) Health Survey, CDC, gain during their a recommended weight
recommended weight NCHS (8) pregnancies. (8) gain during their
gain during their pregnancies. (2)
pregnancies. (4)
385
386

15.5 Increase to at least 79% of aware NHIS, CDC (4) In 1994, 71% of people 18 12-11 Increase the 72% of adults age 18 NHIS, CDC, NCHS (2)
90% the proportion of hypertensives age 18 years and over with proportion of adults years and older with
people with high blood and older were taking high blood pressure with high blood high blood pressure
pressure who are action to control their were using medication pressure who are were taking action to
taking action to help blood pressure in 1985. and diet. (8) taking action (for control it in 1998. (2)
control their blood (4) example, losing weight,
pressure. (4) increasing physical
activity, and reducing
sodium intake) to help

control their blood
pressure. Target: 95%
(2)
15.8 Increase to at least 11% of all people age 18 Health and Diet Survey, 60% of all people age 18 No corresponding
60% the proportion of and older, and thus an FDA (4) Cholesterol and older with high objective.
adults with high blood estimated 30% of Awareness Survey, blood cholesterol were
cholesterol who are people with high blood NHLBI, NIH. (8) aware that their blood
aware of their condition cholesterol were aware cholesterol was high in
and are taking action to that their blood 1995. (8)
reduce their blood cholesterol was high in
cholesterol to 1988. (4)
recommended levels.
(4)
15.15 Increase to at least In 1986, the median Cholesterol Awareness In 1995, the median No corresponding
75% the proportion of cholesterol level when Survey, NIH, NHLBI cholesterol level when objective.
primary care providers diet therapy was (8) diet therapy was
who initiate diet and, if initiated: 240-259 mg/ initiated: 200-219 mg/
necessary, drug therapy dL; median cholesterol dL; median cholesterol
at levels of blood level when drug level when drug
cholesterol consistent therapy was initiated: therapy was initiated:
with current 300-319 mg/dL. (8) 240-259 mg/dL. (8)
management
guidelines for patients
with high blood
cholesterol. (4)
15.16 Increase to at least 16.5% offered high blood NWHPS, ODPHP (4) In 1992, 29% offered high No corresponding
50% proportion of pressure activities and blood pressure objective.
worksites with 50 or 16.8% offered nutrition activities; 31% offered
more employees that education activities in nutrition education
offer high blood 1985. (4) activities; 32% offered
pressure and/or blood pressure
cholesterol education screening. (8)
and control activities to
their employees. (4)
2-9. Reduce the overall 10% of adults age 50 NHANES, CDC, NCHS
number of cases of years and older had (2)
osteoporosis Target: osteoporosis as
8%. (2) measured by low total
femur bone mineral
density (BMD) in 1988-
94. (2)
16.3 Reduce breast 22.9 breast cancer NVSS, CDC (4) 20.2 breast cancer death/ 3-3 Reduce the breast 27.7 breast cancer NVSS, CDC, NCHS (2)
cancer deaths to no deaths/100,000 females 100,000 females in 1997. cancer death rate. deaths/100,000 females
more than 20.6/100,000 in 1987. (4) (8) Target: 22.2 deaths/ in 1998. (2)
women. (4) 100,000 females. (2)

4-3 Increase the 45% of newly diagnosed USRDS, NIH, NIDDK (2)
proportion of treated patients with treated
chronic kidney failure chronic kidney failure
patients who have received counseling on
received counseling on nutrition, treatment
nutrition, treatment choices, and
choices, and cardiovascular care in
cardiovascular care 12 1996. (2)
months before the start
of renal replacement
therapy. Target: 60%. (2)
5-1 Increase the 40% of persons with NHIS, CDC, NCHS (2)
proportion of persons diabetes received
with diabetes who formal diabetes
receive formal diabetes education in 1998. (2)
education. Target: 60%.
(2)
5-2 Prevent diabetes. 3.1 new cases of NHIS, CDC, NCHS (2)
Target: 2.5 new cases/ diabetes/1000 persons
1,000 persons/year. (2) (3-year average) in
1994-96. (2)
387
388

7-11 Increase the 44% for nutrition and NHIS, CDC, NCHS (2)
proportion of local overweight in 1996-97.
health departments (2)
that have established
culturally appropriate
and linguistically
competent community
health promotion and
disease prevention
programs for racial and
ethnic minority
populations. Target:
nutrition and
overweight - 50%. (2)
10-4 (Developmental) Potential data Source:

Reduce deaths from NVSS, CDC, NCHS (2)
anaphylaxis caused by
food allergies. (2)
12-9 Reduce the 28% of adults age 20 NHANES, CDC, NCHS

proportion of adults years and older had (2)
with high blood high blood pressure in
pressure. Target: 16%. 1988-94. (2)
(2)
16-15 Reduce the 6 new cases of spina NBDPN, CDC, NCEH

occurrence of spina bifida or another NTD/ (2)
bifida and other neural 10,000 live births in
tube defects (NTDs). 1996. (2)
Target: 3 new cases/
10,000 live births. (2)
16-16 Increase the 21% for the consumption NHANES, CDC, NCHS
proportion of of folic acid; 161 ng/ml (2)
pregnancies begun for the median RBC
with an optimum folic folate level In 1991-94.
acid level. Target: 80% (2)
for consumption of at
least 400 µg of folic acid
each day from fortified
foods or dietary
supplements by non-
pregnant women age 15
to 44; 220 ng/ml for
median red blood cell
(RBC) folate level
among non-pregnant
women age 15 to 44. (2)
16-17 Increase abstinence Increase in reported National Household

from alcohol, cigarettes, abstinence in past Survey on Drug Abuse;
and illicit drugs among month from substances SAMHSA; NVSS, CDC,
pregnant women. by pregnant women: NCHS (2)
Target: Increase in 86% for alcohol; 99% for

reported abstinence in binge drinking; 87% for

past month from cigarette smoking; 98%
substances by pregnant for illicit drugs in 1996-
women: 94% for 97. (2)
alcohol; 100% for binge
drinking; 98% for
cigarette smoking; 100%
for illicit drugs. (2)
16-18 (Developmental) Potential data sources:

Reduce the occurrence FASnet, CDC, NCEH
of fetal alcohol (2)
syndrome. (2)
18-5 (Developmental) Potential data sources:

Reduce the relapse Prospective studies of
rates for persons with patients with anorexia
eating discorders nervosa and bulimia
including anorexia nervosa, NIH, NIMH.
nervosa and bulimia (2)
nervosa. (2)
389
TABLE 13.4
Abbreviations for Data Sources
Abbreviation Source
ADAMHA Alcohol, Drug Abuse and Mental Health Administration
AEDS Alcohol Epidemiologic Data System
ASTDHPPE Association of State and Territorial Directors of Health Promotion and Public Health Education
AWHP Association of Worksite Health Promotion
CDC Centers for Disease Control and Prevention
CFSAN Center for Food Safety and Applied Nutrition
CSFII Continuing Survey of Food Intake by Individuals
FASnet Fetal Alcohol Syndrome Network
FDA Food and Drug Administration
FSIS Food Safety and Inspection Survey
IHS Indian Health Service
NAMCS National Ambulatory Medical Care Survey
NBDPN National Birth Defects Prevention Network
NCCDPHP National Center for Chronic Disease Prevention and Health Promotion
NCEH National Center for Environmental Health
NCHS National Center for Health Statistics
NCID National Center for Infectious Disease
NHANES National Health and Nutrition Examination Survey
NHIS National Health Interview Survey
NHLBI National Heart, Lung and Blood Institute
NIAAA National Institute of Alcohol Abuse and Alcoholism
NIDDK National Institute of Diabetes and Digestive and Kidney Disease
NIMH National Institute of Mental Health
NIH National Institute of Health
NNDSS National Notifiable Disease Surveillance System
NVSS National Vital Statistics System
NWHPS National Worksite Health Promotion Survey
ODPHP Office of Disease Prevention and Health Promotion
OPHS Office of Public Health and Science
SAMHSA Substance Abuse and Mental Health Services Administration
SHPPS School Health Policies and Programs Study
USDA United States Department of Agriculture
USRDS U.S. Renal Data System
U.S. Department of Health and Human Services, Healthy People 2010 (conference edition, in two volumes),
Washington, DC, January 2000.
References
1. US Department of Health, Education and Welfare (HEW), Healthy People: the Surgeon General’s
Report on Health Promotion and Disease Prevention, Washington, DC, 1979, Superintendent of
Documents.
2. US Department of Health and Human Services, Healthy People 2010, 2nd ed., Government
Printing Office, Superintendant of Documents, Washington, DC: January 2000.
3. US Department of Health and Human Services, Public Health Service: Promoting Health and
Preventing Disease: Objectives for the Nation, Washington, DC, 1980, U.S. Government Printing
Office.
4. US Department of Health and Human Services, Healthy People 2000: National Health Promotion
and Disease Prevention Objectives, Washington, DC, 1990, U.S. Government Printing Office.
5. US Department of Health and Human Services, Healthy People 2000: Midcourse Review and 1995
Revisions, Washington, DC, 1990, U.S. Government Printing Office.
6. ADA Courier, Chicago, 2000. The American Dietetic Association, 39: 5; 5.
Healthy People — Goals and Interpretations 391
7. US Department of Health and Human Services, Healthy People 2010 Objectives: Draft for Public
Comment, Washington, DC: September, 1998.
8. National Center for Health Statistics. Healthy People 2000 Review, 1998-99, Hyattsville, MD,
Public Health Service.
14
Food Labeling: Foods and Dietary Supplements
Constance J. Geiger
Overview
Definition of Food Labeling
Food labeling consists of the information present on all food packages. Nutrition labeling
is one component of the food label. Other components include the principal display panel,
the information panel, the identity of the food, the list of ingredients, the name and place
of business of the manufacturer, packer, or distributor, as well as any claims made.1
Progression of the Section

This section reviews the regulatory history of food labeling, the required portions of the
nutrition label, labeling of restaurant and fresh foods, definitions of allowed nutrient
content claims, and requirements for allowed health claims and structure/function claims.
Additional resources for food labeling are provided.
History of Food Labeling

Major Food and Nutrition Labeling Laws and Regulations
Food labeling laws progressed from protecting consumers from economic harm (Pure
Food and Drug Act of 1906)2 to reducing consumers’ risk of chronic disease (Nutrition
Labeling and Education Act of 19903 [NLEA]). The NLEA amended the Food, Drug, and
Cosmetic Act of 19384 and required that nutrition information be conveyed to consumers
so they could readily understand the information and its significance in the context of a
total daily diet. The NLEA3 mandated major revisions in the Food and Drug Administra-
tion’s (FDA) food labeling regulations, including requiring nutrition labeling on almost
all processed foods, a revised list of nutrients to be labeled, standardized serving sizes,
0-8493-2705-9/01/$0.00+$1.50
TABLE 14.1
Major Food and Nutrition Labeling Laws/Selected Regulations
Law Primary Provisions
Pure Food and Drug Act, 1906 2 Barred false and misleading statements on food and
drug labels.
Federal Food, Drug, and Cosmetic Act, 1938 Replaced the Pure Food and Drug Act of 1906. Created
distinct food labeling requirements. Required
“common and usual name” of food, ingredient
declarations, net quantity information, name and
address of manufacturer/distributor. Defined
misbranding.4
Fair Packaging and Labeling Act, 1966 Provided FDA with authority to regulate provision of
label information and package size.8
Regulations for enforcement of the Federal Food, Merged existing regulations into one entity. Required
Drug, and Cosmetic Act and the Fair Packaging and nutrition labeling on processed foods that were
Labeling Act fortified or carried claims. Provided for labeling of fat
and cholesterol. Established standards for dietary
supplements. Established regulations for artificially
flavored foods and imitation foods per serving.
Disallowed nutrient claims unless food contained
10% or more of the US RDA. Incorporated label
information: number of servings/container; calories,
protein, carbohydrate, and fat content; percentage of
adult US RDA for protein and seven vitamins and
minerals. Provided for sodium labeling without
requirement for the full nutrition label panel.9-11
Nutrition Labeling and Education Act, 1990 Provided for mandatory nutrition labeling on almost
all food products, expanded required nutrition
information in a new format, created standardized
serving sizes, provided consistent definitions of
nutrient content claims, and defined permissible
health claims.3
Dietary Supplement Health and Education Act, 1994 Defined dietary supplements, provided for nutrition
labeling in a new format, required the name and
quantity of every active ingredient, provided for
structure/functions claims and good manufacturing
practices, encouraged research on dietary
supplements, created two new government entities:
Commission on Dietary Supplement Labels and the
Office of Dietary Supplements.12
FDA Modernization Act, 1997 Expanded procedures by which FDA can authorize
health claims and nutrient content claims, e.g.,
provided for a notification process.13
nutrient content claims, and for the first time, health claims. In the interest of harmony
and uniformity, the U.S. Department of Agriculture’s Food Safety and Information Service
(FSIS) issued similar regulations for meat and poultry products.5 Table 14.1 summarizes
the major laws and selected regulations dealing with food labeling. (For further details,
see Geiger, 19926 and Geiger, 1998.7)
Regulatory Oversight for Labeling

A number of regulatory agencies have jurisdiction over food labeling, including FDA,
USDA, Federal Trade Commission (FTC), and Bureau of Alcohol, Tobacco and Firearms
(BATF). Table 14.2 shows their responsibilities.
Food Labeling: Foods and Dietary Supplements 395
TABLE 14.2
Agencies having Jurisdiction over Food Labeling
Agency Responsibility
FDA Mandatory labeling of most packaged foods except products containing certain amounts of meat and
poultry, and beverages with certain amounts of alcohol. Voluntary labeling of fresh fruits and
vegetables, fresh fish, game, and restaurant foods except those containing certain amounts of meat
and poultry
USDA Mandatory labeling on most processed meat and poultry products, e.g., hot dogs, chicken noodle
soup
FTC Claims made in food advertising
BATF Voluntary labeling of alcoholic beverages
Required Portions of the Food Label

Required sections of the Nutrition Facts Label (see Figure 14.1) are illustrated here. The
nutrition facts information is based on a serving of the product as packaged.
Required Nutrients
The nutrients required to be labeled in the Nutrition Facts Panel are listed in Table 14.3.
If a product is fortified with a certain nutrient or a claim is made about a voluntary
nutrient, then that nutrient also is required to be labeled. Other nutrients (voluntary
nutrients) that may be included on the label are found in Table 14.3.
Serving Size
Standardized serving sizes, known as Reference Amounts Customarily Consumed
(RACCs), are established for many categories of foods. RACCs are based on average
amounts people usually eat at one time, based on USDA survey data. These uniform
serving sizes help consumers compare products. See Table 14.4 for selected RACCs.
Kcalories and Kcalories from Fat

Amount of kcalories and kcalories from fat are required because of public health author-
ities’ concerns with fat in the diet.
Daily Values
The standards for labeling of nutrients are known as Daily Values (DVs). The percent of
DV is listed for certain nutrients on the label so that consumers can determine how a serving
of a food fits into their total daily diet. The DVs include Daily Reference Values (DRVs)
and Reference Daily Intakes (RDIs). DRVs are set for nutrients that previously did not have
label standards, such as fat, cholesterol, and saturated fat (see Table 14.5). DRVs are based
on a daily intake of 2000 kcalories, which is a reasonable reference number for adults and
children over four, and are calculated based on current nutrition recommendations. The
THE NEW LABEL FORMAT
Nutrition Facts New title signals

the new label
Serving Size Ser ving Size 1 Cup (248g)
information S e r v i n g s Pe r C o n t a i n e r 4
in household
and metric Amount: Per Serving
measures
Product-specific Information
Calories 150 Calories from Fat 35 Calorie information

% Daily Value*
To t a l F a t 4 g 6%
S a t u r a t e d Fa t 2 . 5 g 12%
New list of nutrients
Cholesterol 20mg 7%
Sodium 170mg 7% % Daily Values
To t a l C a r b o h y d r a t e 1 7 g 6% (DVs) shows how a
Dietary Fiber 0g 0% food fits into a
2,000 calorie
Sugars 17g reference diet
Protein 13g
Vitamin A 4% • Vitamin C 6%
Calcium 40% • Iron 0%
*Percent Daily Values are based on a 2,000 calorie
Consistent Information,
diet. Your daily values may be higher or lower

depending on your calorie needs:
eg. footnotes
Calories: 2,000 2,500

Total Fat Less than 65g 60g Daily Values (DVs)
Sat Fat Less than 20g 25g footnote
Cholesterol Less than 300mg 300mg
Sodium Less than 2,400mg 2,400mg
Total Carbohydrate 375g 375g
Dietary Fiber 30g 30g
Calories per gram:
Fat 9 • Carbohydrate 4 • Protein 4 Caloric Conversion Guide
THIS LABEL IS ONLY A SAMPLE. EXACT SPECIFICATIONS ARE IN THE CODE OF FEDERAL REGULATIONS.
AMERICAN DIETETIC ASSOCIATION
FIGURE 14.1
Nutrition facts panel (© 1994, American Dietetic Association. Learning the New Food Labels. Used with permission).
TABLE 14.3
Labeling of Nutrients: Required and Voluntary1
Required Nutrients Voluntary Nutrients
Total kcalories kcalories from saturated fat
kcalories from fat kcalories from polyunsaturated fat
Total fat kcalories from monounsaturated fat
Saturated fat Potassium
Cholesterol Soluble fiber
Sodium Insoluble fiber
Total carbohydrate Sugar alcohol
Dietary fiber Other carbohydrates
Sugars Other essential vitamins and minerals
Protein
Vitamin A
Vitamin C
Calcium
Iron
TABLE 14.4
Selected Reference Amounts Customarily Consumed (RACCs)1,a
Category RACC
Bakery products: biscuits, bagels, tortillas, soft pretzels 55 g
Beverages: carbonated and noncarbonated beverages, 240 mL
wine coolers, water; coffee or tea, flavored and
sweetened; juice, fruit drinks
Breads 50 g
Cereals and other grain products Varies from 25 g for dry pasta to 140 g for prepared rice
Cheese 30 g
Eggs 50 g
Fats and oils 1 tbsp
Fruits: fresh, canned, or frozen except watermelon 140 g
Meat: entrees without sauce 85 g cooked; 110 g uncooked
Nuts and seeds 30 g
Soups 245 g
Vegetables; fresh, canned, or frozen 85 g fresh or frozen
95 g for vacuum packed
130 g for canned in liquid
a See 21 CFR 101.12 for details.
TABLE 14.5
DRVs for Adults: Calculations and Values1
Nutrient Derivation/Calculation Label Value
Fat 30% of 2000 kcalories from fat = 600 kcalories/9 kcalories/g 65 g
Saturated fat 10% of kcalories from saturated fat = 200 kcalories/9 kcalories/g 20 g
Carbohydrate 60% of kcalories from carbohydrate = 1200 kcalories/ 4 kcalories/g 300 g
Protein 10% of kcalories from protein = 200 kcalories/ 4 kcalories/g 50 g
Fiber 11.5 g per 1000 kcalories 25 g (rounded up)
Cholesterol NA <300 mg
Sodium NA <2400 mg
Potassium NA 3500 mg
TABLE 14.6
RDIs for Adults and Children over 41
Nutrient RDI
Vitamin A 5000 IU
Vitamin C 60 mg
Calcium 1000 mg
Iron 18 mg
Vitamin D 400 IU
Vitamin E 30 IU
Vitamin K 80 µg
Thiamin 1.5 mg
Riboflavin 1.7 mg
Niacin 20 mg
Vitamin B6 2.0 mg
Folate 400 µg
Vitamin B12 6 µg
Biotin 300 µg
Pantothenic acid 10 mg
Phosphorus 1000 mg
Iodine 150 µg
Magnesium 400 µg
Zinc 15 mg
Selenium 70 µg
Copper 2 mg
Manganese 2 mg
Chromium 120 µg
Molybdenum 75 µg
Chloride 2400 mg
term RDIs replaces the term U.S. Recommended Dietary Allowances (RDAs), but the values
are currently the same as the U.S. RDAs, which represent the highest recommended levels
of the 1968 RDAs (see Table 14.6). The RDI values will be updated when the National
Academy of Sciences completes its latest review of all nutrient recommendations.
A DVs footnote is provided at the bottom of the label to inform consumers of the DVs
for both 2000- and 2500-calorie levels. The calorie information at the bottom of the label
is voluntary (see Figure 14.1).
Substances without DVs

Substances without DVs, such as sugars and soluble and insoluble fiber, are not required
to carry a percent of DV. For dietary supplement labels, substances such as herbs are
separated from the nutrients. The amount of the herb must be listed along with a symbol
referring to the statement “Daily Value not established.”
Labeling of Restaurant Foods and Fresh Foods

Restaurant Foods
Labeling of restaurant foods is voluntary. If a nutrient content claim or health claim is
made, then nutrition labeling becomes mandatory. However, the full Nutrition Facts Label
does not need to appear. Only the amount of the nutrient that is the subject of the claim
needs to be labeled, e.g., “low fat,” contains 3 g of fat.
Fresh Fruits, Vegetables, and Seafood

The FDA recommends that food retailers provide nutrition information for raw fruits,
vegetables, and fish at point of purchase. Charts, brochures, or signs can be used to depict
nutrition information for the 20 most commonly consumed fruits, vegetables, and raw
fish. The FDA provides the data for retailers in the Code of Federal Regulations (21 CFR
101.45 and Appendix C to Part 101).
Meats and Poultry

The USDA recommends that food retailers provide point-of-purchase information for meat
and poultry. As with fresh produce and fish, charts, brochures, or signs can be used to
depict the nutrition information.5
Nutrient Content Claims Allowed for Foods and Dietary Supplements

Overview
The FDA and USDA have issued regulations for uniform definitions for nutrient content
claims. A nutrient content claim characterizes the level of a nutrient in a food, e.g., “high
fiber.” Two types of nutrient content claims can be made: absolute (free, low, good source,
high, lean, extra lean) and comparative (reduced, light, less, more). The regulations estab-
lish the allowed terms and the criteria/requirements for their use (see Tables 14.7, 14.8).1
For additional detail see the Code of Federal Regulations (21 CFR 101.13 and 101.54-101.69).
Health Claims Allowed for Foods and Dietary Supplements

Overview
NLEA allowed health claims to be carried on qualified food products. Prior to this time,
these claims were considered unauthorized drug claims. A health claim describes the
relationship between a food, a nutrient, or other substance in a food, and the risk of a
health-related condition or disease.
Health claims can be made through third-party references, such as the American Heart
Association, symbols such as a heart, statements, and vignettes or descriptions. Regardless
of the manner of presentation, the requirements for the claim must be met in order for a
food or supplement to carry the claim on its product packaging or in its advertising.
Health claims carry general and specific requirements. General requirements include not
exceeding certain amounts of fat (13 g), saturated fat (1 g), cholesterol (40 mg), and sodium
(480 mg). The food must be a “good source” of fiber, protein, vitamin A, vitamin C, calcium,
or iron. The specific requirements for each health claim are listed in the Code of Federal
TABLE 14.7
400
Allowed Nutrient Content Claims with Definitions1, a, b

Vitamins/
Claim Calories Fat Saturated Fat Cholesterol Sodium Fiber Sugar Protein Minerals
“Free,” “no,” Less than 5 kcalories 0.5 g or less 0.5 g or less Less than 2 mg Less than 5 mg NA Less than 0.5 g NA NA
“zero,” cholesterol and 2 g
“without” or less saturated fat
and trans fat
“Very low” NA NA NA NA Less than 35 mg NA NA NA NA
“Low,” 40 kcalories or less 3 g or less 1 g or less 20 mg or less 140 mg or less NA NA NA NA
“contains a cholesterol and 2 g
small amount,” or less saturated fat
“little”
“Reduced” 25% lower in 25% lower in 25% lower in 25% lower in 25% lower in NA 25% lower in NA NA
kcalories than the kcalories than the kcalories than the kcalories than the kcalories than the kcalories than the
comparable food comparable food comparable food comparable food comparable food comparable food
“Light” 1/3 fewer kcalories 50% less fat than the NA NA 50% less sodium NA NA NA NA
than the reference reference food than the reference
foods, only if the food, food also is
reference food low fat and low
contains less than calorie
50% calories from
fat
“Good source,” NA NA NA NA NA 2.5-4.9 g NA 5 g or 10 — 19%
“provides,” more of the DV
“contains”
“High,” NA NA NA NA NA 5 g or NA 10 g or 20% or
“excellent more more more of
source of,” “rich the DV
in”
“More,” “added,” NA NA NA NA NA NA NA 10% 10% more
“enriched,” more of of the DV
“fortified” the DV
(5 g)
a Definitions vary for meal and main dishes.
b
Complete definitions are found in 21 CFR 101.13 and 21 CFR 101.54-101.69.

TABLE 14.8
Other Nutrient Content Claims Definitionsa,b
Claim Definition
% Fat-free Must be “low-fat” or “fat-free.” Must indicate the amount of fat present in
100 g of food
Lean Less than 10 g fat, less than 4 g saturated fat, less than 95 mg cholesterol
per RACC and per 100 g
Extra lean Less than 5 g fat, less than 2 g saturated fat, less than 95 mg cholesterol per
RACC and per 100 g
a Definitions vary for main dish and meal products.
b Complete definitions are found in 21 CFR 101.13 and 21 CFR 101.54-101.69.
Regulations (21 CFR 101.14; 101.70-101.81), except for those authorized through FDAMA
or by the courts.
Current health claims are authorized in three ways: by FDA as a result of NLEA, which
also allowed for petitions for new health claims (12 claims); by notification of FDA through
FDAMA (two claims); or through court action as a result of the Pearson decision (two
claims at time of section submission). FDAMA allowed FDA to authorize a health claim
if a scientific body of the U.S. Government that has official responsibility for human
nutrition research or public health protection publishes a current authoritative statement.
A company or organization must notify FDA at least 120 days prior to the introduction
of the food carrying the claim into interstate commerce. FDAMA health claims, unlike the
other claims, do not allow an opportunity for public comment. If FDA takes no action
within 120 days of the notification, the health claim can be made on the food qualifying
for the claim. The Pearson decision resulted from a lawsuit filed by Durk Pearson, Sandy
Shaw, and the American Preventive Medical Association to allow four previously denied
health claims to be made on dietary supplements. The court decision mandated that FDA
1) reconsider whether to authorize the four previously denied health claims, 2) determine
if the weight of the scientific evidence in support of the claim is greater than that against
it, and 3) if so, then determine if qualifying language would not mislead consumers. FDA
is also required to define significant scientific agreement.
FDA authorized seven claims as a result of NLEA. Since that time, FDA has approved
an additional three claims submitted as petitions, two claims submitted as notifications
through FDAMA, and two claims as a result of the Pearson decision.
The health claim model language and requirements are indicated in three tables: those
resulting from NLEA and petitions (Table 14.9); those not prohibited by FDA through
FDAMA (Table 14.10), and those allowed by court decision that carry extensive qualifying
language (Table 14.11). Again, the requirements for the FDAMA and court-mandated
(Pearson decision) health claims do not appear in the Code of Federal Regulations.
Structure Function Claims

Overview
Structure/function claims can be made on dietary supplements (DSHEA 1994).12 A struc-
ture/function claim is characterized as a statement that describes the role of a nutrient or
dietary ingredient that affects a function or structure of the body, or such claims can
describe how such a substance maintains a structure or function.
TABLE 14.9
402
Health Claims Authorized through the Regulations Implementing NLEA1,7

Can Be Made
Health Claim Model Language Requirements On Qualified
Cancer
Fruits and vegetables and Low fat diets rich in fruits and vegetables (foods that are Food product must be or must contain a fruit or vegetable; Foods
cancer low in fat and may contain dietary fiber, vitamin A, and product is “low fat;” product is a “good source” of at least
vitamin C) may reduce the risk of some types of cancer, one of the following: vitamin A, vitamin C, or fiber
a disease associated with many factors. Broccoli is high in
vitamins A and C and is a good source of dietary fiber
Fiber-containing grain Low fat diets rich in fiber-containing grain products, fruits, Food product must be or must contain a grain product, Foods
products, fruits and and vegetables may reduce the risk of some types of fruit, or vegetable; food product is “low fat,” and is (prior
vegetables and cancer cancer, a disease associated with many risk factors to fortification) a “good source of dietary fiber”
Fat and cancer Development of cancer depends on many factors. A diet Food product is “low fat;” fish and game meats must be Foods
low in total fat may reduce the risk for some cancers “extra lean”
Coronary Heart Disease
Fruits, vegetables and Development of heart disease depends on many factors. Food products contains ≥ 0.6 g soluble fiber; soluble fiber Foods
grain products that Eating a diet low in saturated fat and cholesterol and high is listed on Nutrition Facts Panel. Food product must be
contain fiber, especially in fruits, vegetables, and grain products that contain fiber “low fat,” “low saturated fat,” and “low cholesterol;” food
soluble fiber, and risk of may lower blood cholesterol levels and reduce risk of is, or must contain, a vegetable, fruit, or grain product
coronary heart disease heart disease
Soluble fiber from certain Diets low in saturated fat and cholesterol that include ___ g Food is “low saturated fat,” “low cholesterol,” and “low Foods
foods (oats and psyllium) of soluble fiber per day from (name of food) may reduce fat;” food contains β-glucan soluble fiber from whole oats;
and coronary heart the risk of heart disease. One serving of (name of food) food contains ≥0.75 g whole oat soluble fiber; soluble fiber
disease supplies ___ g of the ___ g necessary per day to have this is listed on the Nutrition Facts Panel;
effect or
Food is “low saturated fat,” “low cholesterol,” and “low
fat”; food contains ≥1.7 g soluble fiber from psyllium husk;
soluble fiber is listed on the Nutrition Facts Panel
Soy protein and coronary Diets low in fat and cholesterol that include 25 g of soy Food contains ≥6.25 g soy protein; food is “low cholesterol,” Foods
heart disease protein a day may reduce the risk of heart disease. One “low saturated fat;” food is “low fat,” unless it is derived
serving of (name of food) provides ___ g of soy protein from or consists of whole soybeans and contains no fat in
addition to the fat naturally present in the whole soybeans
it contains or from which it is produced

Saturated fat and Development of heart disease depends upon many factors, Food must be “low saturated fat,” “low fat,” and “low Foods
cholesterol and coronary but its risk may be reduced by diets low in saturated fat cholesterol;” fish and game meats must be “extra lean”
heart disease and cholesterol and healthy lifestyles
Plant sterols/stanol For plant stanol esters: Food contains 1.7 g of plant stanol esters/RACC (spreads, Foods and dietary
esters and coronary heart Diets low in saturated fat and cholesterol that include two salad dressings, snack bars, and dietary supplements in supplements
disease servings of foods that provide a daily total of at least 3.4 softgel form) or 0.65 g of plant sterol esters/RACC
g of vegetable oil stanol esters in two meals may reduce (spreads and salad dressings); food is “low cholesterol”
the risk of heart disease. A serving of [name of food] and “low saturated fat;” food must not exceed the fat
supplies ___ g of vegetable oil stanol esters disqualifying levels (13 g) of health claims unless it is a
For plant sterol esters: spread or a salad dressing. Those products (spreads or
Foods containing at least 0.65 g per serving of plant sterol salad dressings) exceeding 13 g of fat must carry a
esters, eaten twice a day with meals for a daily total intake disclosure statement referring people to the Nutrition
of at least 1.3 g, as part of a diet low in saturated fat and Facts Panel for information about fat content; food
cholesterol, may reduce the risk of heart disease. A serving contains 10% or more of the DV for vitamin A, vitamin C,
of [name of food] supplies ___ g of vegetable oil sterol iron, calcium, protein, or fiber unless the product is a salad
esters dressing14
Other Health Claims

Food Labeling: Foods and Dietary Supplements
Calcium and osteoporosis Regular exercise and a healthy diet with enough calcium Food or dietary supplement must be “high” in calcium Foods and dietary
help teen and young adult white and Asian women supplements
maintain good bone health and may reduce their high risk
of osteoporosis later in life. Adequate calcium intakes are
important, but daily intakes above 2000 mg are not likely
to provide any additional benefit
Sodium and hypertension Diets low in sodium may reduce the risk of high blood Food must be “low sodium” Foods
pressure, a disease caused by many factors
Sugar alcohols and dental Frequent eating of foods high in sugars and starches as Food must contain less than 0.5 g sugar; sugar alcohol in Foods
caries between-meal snacks can promote tooth decay. The sugar the food shall be sorbitol, isomalt, xylitol, lactitol,
alcohol used to sweeten this food may reduce dental caries hydrogenated glucose syrup, hydrogenated starch
hydrolysates, or a combination
Folic acid and neural tube Healthful diets with adequate folate may reduce a woman’s Food or supplements must be a “good source” of folate; Foods and dietary
defects risk of having a child with a brain or spinal cord defect claim cannot be made on foods that contain more than supplements
100% of the RDI for vitamin A, such as preformed vitamin
A or retinol, or vitamin D
403
TABLE 14.10
Health Claims Allowed to Pass Through FDAMA
404
Can Be Made on
Health Claim Model Language Requirements Qualified
Whole grains and CHD Diets rich in whole grains and other plant foods and low Diets rich in whole grain foods and other plant foods and Foods
in total fat, saturated fat, and cholesterol may help reduce low in total fat, saturated fat, and cholesterol may help
the risk of heart disease and certain cancers reduce the risk of heart disease and certain cancers15
Potassium-containing Diets containing foods that are good sources of potassium Foods contain at least 10% DV for potassium/RACC; food Foods
foods and blood pressure and low in sodium may reduce the risk of high blood is “low sodium,” “low cholesterol,” “low saturated fat”/
and stroke pressure and stroke RACC; potassium is listed on the Nutrition Facts Panel16
TABLE 14.11
Qualified Health Claims Allowed by the Pearson Decision
Can Be Made on
Health Claim Model Language Requirements Qualified
Omega-3 fatty acids and The scientific evidence about whether omega-3 fatty acids Dietary supplement cannot state the daily dietary intake Dietary
CHD may reduce the risk of coronary heart disease is necessary to achieve a claimed effect because the evidence supplements
suggestive, but not conclusive. Studies in the general is not definitive; labeling cannot recommend or suggest
population have looked at diets containing fish and not intakes of more than 2 g per day, preferable 1 g or less17
omega-3 fatty acids, and it is not known whether diets or
omega-3 fatty acids in fish may have a possible effect on
a reduced risk of coronary heart disease. It is not known
what effect omega-3 fatty acids may or may not have on
risk of CHD in the general population
Folic acid, vitamin B6, It is known that diets low in saturated fat and cholesterol Dietary supplement cannot state the daily dietary intake Dietary
vitamin B12 and vascular may reduce the risk of heart disease. The scientific necessary to achieve a claimed effect because the evidence supplements
disease evidence about whether folic acid, vitamin B6, and vitamin is not definitive; products with more than 100% DV
B12 may also reduce the risk of heart disease and other (400 µg) of folic acid must identify the safe upper limit of
vascular disease is suggestive, but not conclusive. Studies 1000 µg in parentheses18
in the general population have generally found that these
vitamins lower homocysteine, an amino acid found in the
blood. It is not known whether elevated levels of
homocysteine may cause vascular disease or whether high
homocysteine levels are caused by other factors. Studies
that will directly evaluate whether reducing homocysteine
may also reduce the risk of vascular disease are not yet
complete
Requirements
The general requirements for structure/function claims are: 1) the statement must be
truthful and not misleading, 2) the manufacturer of the product carrying the claim must
notify the FDA within 30 days of first marketing a dietary supplement, and 3) the dietary
supplement must carry the following disclaimer: “This statement has not been evaluated
by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease.”12
Specific requirements for structure/function claims are not found in the Code of Federal
Regulations. FDA does not approve individual claims.
Resources
Food and Drug Association www.fda.gov
The FDA website provides a wealth of information about FDA regulatory actions and
positions, industry guidance, and consumer education materials. The site provides FDA
organizational structure and a telephone and email directory so that staff contacts can be
made. The “What’s New” section lists FDA’s latest actions. A separate page is devoted to
dietary supplements. Links are provided to other regulatory agencies such as the FTC and
the FSIS.
Food Safety and Inspection Service www.fsis.gov

The USDA’s FSIS is responsible for overseeing labeling of meat and poultry foods. The
agency allows health claims on a case-by-case basis. (USDA requires label approval prior
to use on a product.) FSIS’s website provides regulatory guidelines and current information.
Code of Federal Regulations (CFR) www.access.gpo/nara/cfr/index.html

The CFR codifies all of the general and permanent rules published in the Federal Register
by FDA and FSIS, USDA, FTC, and BATF. The CFR is divided into 50 titles, each repre-
senting an area of federal regulation, e.g., 21 CFR is Food and Drugs and 9 CFR is USDA.
The titles are then divided into chapters that usually bear the name of the responsible
agency. Those most pertinent to the food label include 21 CFR 100-169 (FDA, food labeling),
21 CFR 170-199 (FDA, food additives), and 9 CFR 200 to end (FSIS, food labeling). The
CFR can be accessed online through the FDA website. The CFR is updated once per year.
Federal Register
The Federal Register is one of the most important sources for information on any govern-
ment agency’s activities. Federal government agencies, such as FDA and USDA, publish
regulations in the Federal Register to implement food and dietary supplement laws in
various forms (notice, proposed rule, final rule) on a daily (Monday through Friday) basis.
Once a final rule is published it becomes incorporated into the CFR. The Federal Register
can be accessed through FDA’s website. It can be searched by agency, date, date range,
or topic.
References
1. Food and Drug Administration, US Department of Health and Human Services. Code of
Federal Regulations, Title 21, Parts 100-169. Washington, DC: Superintendent of Documents,
US Government Printing Office, 2000.
2. Federal Food and Drug Act of 1906. 34 USC § 768.
3. Nutrition Labeling and Education Act. P. L. No. 101-535, 104 Stat 2353.
4. Federal Food, Drug and Cosmetic Act of 1938. 52 USC § 1040.
5. US Department of Agriculture, Food Safety and Information Service. Code of Federal Regu-
lations, Title 9, Parts 200 to end. Washington, DC: Superintendent of Documents, US Govern-
ment Printing Office, 2000.
6. Geiger, CJ. Review of nutrition labeling formats. J Amer Diet Assoc 91: 808; 1992.
7. Geiger, CJ. Health claims: history, current regulatory status and consumer research. J Amer
Diet Assoc 98: 1312; 1998.
8. Federal Fair Packaging and Labeling Act 1966. 80 USC § 1966.
9. Food and Drug Administration. Nutrition labeling: proposed criteria for food label informa-
tion panel. Federal Register March 30, 1972; 37(62): 6493-6497.
10. Food and Drug Administration. Nutrition labeling: Federal Register January 19, 1973; 38(13):
2124-2164.
11. Food and Drug Administration. Nutrition labeling: Federal Register March 14, 1973; 38(49):
6950-6975.
12. Dietary Supplement Health and Education Act of 1994. 108 Stat. 4325, 4322.
13. Food and Drug Administration Modernization Act of 1997. 21 USC § 301 note.
14. Food and Drug Administration. Food labeling: health claims; plant sterol/stanol esters and
coronary heart disease; interim final rule. Federal Register September 8, 2000; 65(175): 54686-
54739.
15. General Mills. Whole grain foods authoritative statement claim notification. July 1999. Avail-
able at http://vm.cfsan.fda.gov/
16. Tropicana Products, Inc. Notification for a health claim based on an authoritative statement
for potassium containing foods. Docket No. 00Q-1582. Available at http://vm.cfsan.fda.gov/
17. FDA, Center for Foods Safety and Applied Nutrition. Letter regarding dietary supplement
health claim for omega-3 fatty acids and CHD. October 31, 2000. Available at
http://vm.cfsan.fda.gov/
18. FDA. Center for Foods Safety and Applied Nutrition. Letter regarding dietary supplement
health claim for folic acid, vitamin B6, vitamin B12 and vascular disease. November 28, 2000.
Available at http://vm.cfsan.fda.gov/
15
Nutrition Monitoring in the United States
Karil Bialostosky, Ronette R. Briefel, and Jean Pennington
Nutrition monitoring has been defined as “an ongoing description of nutrition conditions
in the population, with particular attention to subgroups defined in socioeconomic terms,
for purposes of planning, analyzing the effects of policies and programs on nutrition
problems, and predicting future trends.”1 The nutrition monitoring program in the United
States has evolved over the past century to meet data needs for nutrition policy and
nutrition research. This section provides a brief review of the evolution of the nutrition
monitoring program, summarizes the program’s monitoring and surveillance activities
during the past decade, and describes the links between nutrition monitoring, nutrition
research, and nutrition policy.
Goal of the Nutrition Monitoring Program

The name of the National Nutrition Monitoring System (NNMS) was changed to the
National Nutrition Monitoring and Related Research Program (NNMRRP) with the pas-
sage of the National Nutrition Monitoring and Related Research Act of 1990 (P.L. 101-
445).2-5 The goal of the nutrition monitoring program is to have a coordinated, compre-
hensive system that provides information about the dietary and nutritional status of the
U.S. population, conditions that affect the dietary and nutritional status of individuals,
and relationships between diet and health.
The program is composed of interconnected federal and state activities that provide
information about the relationship between food and health. A general conceptual model
representing this relationship is shown in Figure 15.1 and is comprised of five measure-
ment components: nutrition and related health measurements; food and nutrient con-
sumption; knowledge, attitudes, and behavior assessments; food composition and nutrient
data bases; and food supply determinations.
0-8493-2705-9/01/$0.00+$1.50
FOOD
Away-from- House-
Influential
Home Food hold Food
Factors
Acquired Acquired
Nutrient
Imports Requirements
Nutrition and
Consumption Nutrient Nutrient
Food Supply Related Health
by Individuals Intake Utilization Measurements
Food Supplement
Production Use
Food Knowledge,
Composition Attitudes, and
Behavior
HEALTH
FIGURE 15.1
Food and health relationships. Source: Adapted from U.S. Department of Health and Human Services and U.S.
Department of Agriculture. Ten-Year Comprehensive Plan for the National Nutrition Monitoring and Related
Research Program. 1993.
Uses of Nutrition Monitoring Data

The nutrition monitoring program provides information for public policy decisions and
scientific research (Table 15.1). Monitoring and surveillance data are used to identify high-
risk population groups to plan public health intervention programs and target food assis-
tance awareness efforts, establish the national health agenda and evaluate progress
towards achieving national health objectives,6,7 establish guidelines for the prevention,
detection, and management of nutritional conditions,8-14 and evaluate the impact of nutri-
tion initiatives for military feeding systems.15 Data are also used to monitor food produc-
tion and marketing programs and their impact on the food supply.7,16
Nutrition Monitoring in the United States 409
TABLE 15.1
Uses of Nutrition Monitoring Data1
Public Policy
Monitoring and Surveillance
Identify high-risk groups and geographical areas with nutrition related problems
Assess progress toward achieving the nutrition and health objectives in Healthy People 2000 and 20106,7
Recommend guidelines for the prevention, detection, and management of nutrition and health conditions
Evaluate the effectiveness of nutritional initiatives for military feeding systems
Evaluate changes in agricultural policy, food production and marketing, that may affect the nutritional quality
and healthfulness of the U.S. food supply
Develop reference standards for nutritional status
Programmatic
Develop nutrition education and dietary guidance (e.g., Dietary Guidelines for Americans and 5 A Day
Plan and evaluate food assistance programs
Plan and assess nutrition intervention programs and public health programs
Regulatory
Develop food labeling policies

Document the need for and monitor food fortification policies
Establish food safety guidelines
Scientific Research
Establish nutrient requirements through the lifecycle (Recommended Dietary Allowances and Dietary Reference
Intakes)
Study diet-health relationships and the relationship of knowledge and attitudes to dietary and health behavior
Foster and conduct national and international nutrition monitoring research
Conduct food composition analysis
Study the economic aspects of food consumption and food security
1 Adapted from the U.S. Department of Health and Human Services and U.S. Department of Agriculture. Ten-
Year Comprehensive Plan for the National Nutrition and Related Research Program. 1993.
One example of the use of nutrition monitoring data for the development of population
reference standards is the U.S. Growth Charts. Data from the third National Health and
Nutrition Examination Survey (NHANES III) were used to develop the revised U.S.
Growth Charts which were released in 2000.17 The revised standards include charts for
infants through 19 years of age, as well as a new chart for body mass index (BMI) by age.17
The charts are included in the Anthro module of the computer software package EpiInfo,
providing both z-scores and percentiles for each chart. NHANES trend data on anthro-
pometric measures in children have been used by the U.S. Consumer Product Safety
Commission to evaluate the need to revise standards for consumer items such as infant
safety seats.18
Nutrition monitoring data are also used to estimate food insecurity in the U.S. Food
security refers to assured access to nutritionally adequate and safe foods “without resort-
ing to emergency food supplies, scavenging, stealing, and other coping strategies.”19
Efforts spearheaded by the private sector and academia began to pave the way toward a
scientific basis for defining and measuring food insecurity and hunger in the mid-
1980s.20-22 Although national surveys such as NHANES and the USDA’s food consumption
surveys used questions related to a food security construct as early as 1977,23-27 the Ten-
Year Comprehensive Plan for the National Nutrition Monitoring and Related Research
Program called for the development of a standard measure of food insecurity.4 Research
and refinement led to an 18-item food security scale that was first included as a supple-
ment to the 1995 Current Population Survey.23 Using the scale, it is estimated that the
prevalence of food security in U.S. households is approximately 88%.28 A number of
nationally representative surveys of the U.S. population have begun to incorporate this
standard measure, and a number of state and local surveys are including an abbreviated
short form.29 Policy documents like Healthy People 20107 and the U.S. Action Plan on Food
Security30 use the food security measure to assess progress, and the scale can also be used
as a yardstick by which to evaluate federal food and nutrition assistance programs with
respect to welfare reform.
Programmatic uses of nutrition monitoring data include developing and promoting
nutrition education activities and programs such as the Dietary Guidelines for Americans31
and 5 A Day for Better Health,32 public health programs such as the National Cholesterol
Education Program8 and the National High Blood Pressure Education Program,9 and
federally supported food assistance programs such as the Food Stamp Program and the
Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).33,34
Regulatory uses of nutrition monitoring data include developing food fortification,35,36
food safety,16 and food labeling policies to inform consumers.37 Nutrition monitoring data
have been used by regulatory agencies to examine U.S. food fortification policies35,36 and
to provide dietary exposure estimates for nutrient and non-nutrient food components.16
For example, dietary intake and serum data collected in NHANES III were used to assess
folate status and the relationship between serum determinations, diet, and other nutrition
and health variables prior to folate food fortification rulemaking by the Food and Drug
Administration (FDA).36,38
Scientific research uses of nutrition monitoring data range from revising the standards
of human nutrient requirements39-41 to studying the relationship between diet, nutrition,
and health. National data on the population’s dietary intakes and serum nutrient levels
have been used extensively for the investigation of nutrient requirements throughout the
lifecycle and for the development of the Dietary Reference Intakes by the National Acad-
emy of Sciences (NAS).39,40 Continued research to develop nutrition status indicators will
be important for future monitoring efforts.
Nutrition monitoring data are essential to identify food and nutrition research priorities
of significance to public health.6,7,13,14,42,43 National nutrition data have been used for sci-
entific reviews such as The Surgeon General’s Report on Nutrition and Health13 and the
NAS report on Diet and Health: Implications for Reducing Chronic Disease Risk.14 Such
scientific reviews often form the basis for the development of nutrition policies. Other
research is focused on studying the relationships between knowledge and attitudes to
dietary and health behavior, the economic aspects of food consumption and food security,
and food composition analysis.
The increased prevalence of overweight and obesity in the U.S. is the current focus of
public health nutrition efforts. Using standardized international health-based definitions
for men and women aged 20 to 74 years, the age-adjusted prevalence of overweight (BMI
> = 25) was 59%, and obesity (BMI > = 30.0) was 20% in NHANES III (1988-94), compared
to 51 and 12%, respectively, in NHANES II (1976-80).7,44 This increasing trend has also
been observed for adolescents, children, and preschoolers.45,46 Using the 95th percentile of
BMI from NHANES II as the definition of overweight and the 85th to 95th percentile as
the definition of risk for overweight, 11% of children and adolescents were overweight
and another 14% were at risk for overweight during 1988 to 1994.45 The prevalence of
overweight in children and adolescents increased from about 5% in the 1960s and 1970s.45
NHANES III anthropometry data serve as the baseline measures for the Healthy People
2010 weight objectives.7 Future NHANES data will be used to track progress in reducing
the prevalence of overweight and obesity. The NIH Obesity Initiative is aimed at public
health efforts to reduce overweight and foster collaborative research to better understand
the etiology and prevention of obesity.10,47 National and state nutrition monitoring data
on dietary intake, physical activity patterns, weight loss efforts, and consumer knowledge,
attitudes, and behaviors will be important for public health education and research efforts
to reduce the prevalence of overweight and obesity in the U.S.
History of the Nutrition Monitoring Program: Milestones and

Publications
Informally, the nutrition monitoring system had its genesis at the end of the 19th century.
Early studies on food and nutrition were begun by Dr. W. O. Atwater in the 1890s.48 These
small-scale studies aimed to help the working class achieve good diets at a low cost. The
first national survey, the Consumer Purchases Study of 1936-37, provided a comprehensive
picture of household food consumption and indicated that one-third of the nation’s fam-
ilies had diets that were poor by nutritional standards. In the late 1960s, concerns about
the nutritional status of the U.S. population re-emerged as a result of widespread hunger.
Not only was Congress concerned about the extent to which people were affected by
hunger, but also by the Federal government’s inability to document the problem because
of a lack of nutrition monitoring coordination. A 1977 act of congress required the U.S.
Department of Agriculture (USDA) and the U.S. Department of Health, Education, and
Welfare (currently Department of Health and Human Services [HHS]) to develop plans
to coordinate the two largest components of the monitoring program, DHHS’s National
Health and Nutrition Examination Survey and USDA’s Nationwide Food Consumption
Survey (NFCS).49 It also mandated the development of a reporting system to translate the
findings from these two national surveys and other monitoring activities into periodic
reports to Congress on the nutritional status of the American population. A 1986 report,
the first progress report on nutrition monitoring, provided an overview of the dietary and
nutritional status of the population and recommendations for improvements in the mon-
itoring program.50 In 1989, the report was updated by an expert panel.51
In 1988, the Interagency Committee on Nutrition Monitoring (ICNM) was established to
provide a formal mechanism for improving the planning, coordination, and communication
among agencies.52 As a first step, the Directory of Federal Nutrition Monitoring Activities
was published in 1989.53 It was updated and expanded in 1992 to include state surveillance
efforts,54 and in 1998 it became available on the Internet.55 The most recent version was
published on the Internet in 2000.56 The publication is used extensively as a resource for
finding nutrition monitoring data sources, contact persons, and published references.
The National Nutrition Monitoring and Related Research Act of 1990 (P.L. 101-445)3 estab-
lished several mechanisms to ensure the collaboration and coordination of federal agencies
as well as state and local governments involved in nutrition monitoring. Under the act,
the Secretaries of DHHS and USDA have joint responsibility for implementation of the
coordinated program and the transmission of required reports to Congress via the Presi-
dent. The ICNM was formalized and became the Interagency Board for Nutrition Moni-
toring and Related Research (IBNMRR), which currently includes 22 agencies that
contribute to or use national nutrition monitoring data. The IBNMRR serves as the central
coordination point for federal nutrition monitoring activities. The board coordinates the
preparation of the annual budget report on nutrition monitoring and biennial reports on
progress and policy implications of scientific findings to the President and Congress, and
the periodic scientific reports that describe the nutritional and related health status of the
population to Congress. In 1993 and 1995, respectively, the Board published Chartbook I:
Selected Findings from the National Nutrition Monitoring and Related Research Program57
and the Third Report on Nutrition Monitoring in the United States.58
Three staff working groups (Survey Comparability, Food Composition Data, and Fed-
eral-State Relations and Information Dissemination and Exchange [Federal-STRIDE]) were
established under the board to improve communication and coordination among member
agencies on high-priority issues. After the welfare reform law was enacted in 1996, a fourth
group — the Welfare Reform, Nutrition, and Data Needs Working Group — was estab-
lished to determine whether federal surveys and surveillance systems represented by the
IBNMRR could capture the effects of welfare reform on nutrition, hunger, and health
status, identify gaps in data collections, encourage use of comparable data collection
among surveys, serve as a repository on national nutrition survey efforts related to welfare
reform, and foster collaborative research on nutrition and welfare reform. The group has
been quite active and now includes federal as well as non-federal members.
The act also established the National Nutrition Monitoring Advisory Council (NNMAC)
to provide scientific and technical guidance to the IBNMRR. The council includes nine
members (five appointed by the President and four by Congress) with expertise in the
areas of public health, nutrition monitoring research, and food production and distribution.
Finally, the 1990 act called for the development of a Ten-Year Comprehensive Plan.59
The plan includes three primary goals: to provide for a comprehensive National Nutrition
Monitoring and Related Research Program (NMRRP) through continuous and coordinated
data collection, improve the comparability and quality of data across NNMRRP, and
improve the research base for nutrition monitoring. These national goals are comple-
mented by state and local objectives to strengthen data collection capacity, improve the
quality of state and local data, and improve methodologies to enhance comparability of
NNMRRP data across national, state, and local levels. Table 15.2 includes a summary of
the nutrition monitoring program’s history.
TABLE 15.2
Milestones and Publications of the National Nutrition Monitoring and Related Research Program
1977 Food and Agriculture Act (P.L. 95-113) passed
1978 Proposal for a comprehensive nutritional status monitoring system submitted to Congress
1986 First progress report on Nutrition Monitoring in the United States published
1988 Interagency Committee on Nutrition Monitoring formed
1989 Second progress report on Nutrition Monitoring in the United States and The Directory of Federal
Nutrition Monitoring Activities published
1990 National Nutrition Monitoring and Related Research Act (P.L. 101-445) passed
1991 Interagency Board for Nutrition Monitoring and Related Research established through incorporation
and expansion of the ICNM
Proposed Ten-Year Comprehensive Plan for the Nutrition Monitoring and Related Research Program
published for comment
1992 National Nutrition Monitoring Advisory Council formed
The Directory of Federal and State Nutrition Monitoring Activities published
1993 Ten-Year Comprehensive Plan for the National Nutrition Monitoring and Related Research Program
published
Chartbook I: Selected Findings from the National Nutrition Monitoring and Related Research Program
published
1995 Third progress report on Nutrition Monitoring in the U.S. published
1998 The Directory of Federal and State Nutrition Monitoring and Related Research Activities published
2000 The Directory of Federal and State Nutrition Monitoring and Related Research Activities revised and
published
Nutrition Monitoring Measurement Components

The NNMRRP aims to study the relationship between food and health through data
collection in five measurement component areas. Since the 1930s, more than 40 surveys
and surveillance systems have evolved in response to the information needs of federal
agencies and other nutrition monitoring data users. Chronological listings of past nutrition
monitoring surveys and activities have been published.4,5,59-61 Subsumed under each area
is a host of studies, surveys, surveillance programs, and related research. Table 15.3
summarizes the major activities since 1990 by measurement area. Brief descriptions of
surveys and surveillance systems are summarized below and have been described in detail
elsewhere.4,5,53-58,60,62 The Directory of Federal and State Nutrition Monitoring and Related
Research Activities includes additional information. As an Internet publication, each sur-
vey synopsis contained in the directory includes a hypertext link for more information on
each activity (http://www.cdc.gov/nchs/data/direc-99.pdf).
Nutrition and Related Health Measurements

Nutrition and related health data have a wide variety of policy, research, health and
nutrition education, medical care practices, and reference standards applications. The
cornerstone of this NNMRRP measurement component, NHANES, provides national data
on the nutritional status, dietary intake, and numerous health indices of the U.S. popula-
tion.3-5,58,60-64 It also provides national population reference distributions, national preva-
lences of diseases and risk factors, and trends in nutritional and health status over time.
NHANES followup studies allow epidemiologic investigations of the relationships of
nutrition and health to risk of death and disability. The current NHANES (1999+) has a
continuous annual design, and oversampling of Mexican Americans, blacks, older persons,
adolescents, and pregnant females in the first three years.
The National Health Interview Survey provides information about self-reported health
conditions annually and about special nutrition and health topics periodically, such as
vitamin/mineral supplement usage, youth risk behavior, food program participation, diet
and nutrition knowledge, cancer, and disability and food preparation. Other special topical
modules relate to tracking of our nation’s health and nutrition objectives.
Recently, a number of health care provider record-based surveys were merged and
expanded into one integrated survey called the National Health Care Survey. Data on
alternative health care settings, such as ambulatory surgical centers, hospital outpatient
departments, emergency rooms, hospices, and home health agencies, are being collected
through this system. The survey provides information on the availability and utilization
of dietary and nutritional services in these types of agencies. For hospital outpatient visits,
information is obtained about physician-reported hypertension and obesity, and counsel-
ing services for diet, weight reduction, and cholesterol reduction. The survey also provides
information on hospitalizations resulting from nutrition-related diseases.
A number of other surveys and surveillance systems, primarily conducted by the Cen-
ters for Disease Control and Prevention (CDC), also contribute nutrition-related health
information, particularly for low-income pregnant women, infants, and children who
participate in publicly funded health, nutrition, and food assistance programs.62,65,66 These
surveillance systems provide data representative of the population in participating states
and include physical measures such as height, weight, hemoglobin, and hematocrit.
TABLE 15.3
414
Federal Nutrition Monitoring Surveys and Surveillance Activities Since 1990

Date (initiated) Dept. Survey Sample Size and Target U.S. Population
Nutrition and Related Health Measurements
Continuous (1915) HHS National Vital Registration System All births and deaths in the total U.S. population
Annual (1957) HHS National Health Interview Survey (NHIS) Civilian, noninstitutionalized household population (N = 103,477
individuals and N = 39,832 households in 1997)
1985, 1990, 1998 HHS National Health Interview Survey on Health Promotion Civilian, noninstitutionalized household population in the U.S., ages 18+ y
and Disease Prevention (N = 41,104 households in 1990)
1987, 1992 HHS National Health Interview Survey on Cancer Epidemiology Civilian, noninstitutionalized household population ages 18+ y in the U.S.
and Cancer Control (N = 12,000 households in 1992)
1991 HHS 1991 National Health Interview Survey on Health Civilian, noninstitutionalized, household population of the United States,
Promotion and Disease Prevention ages 18+ y (N = 43,732 households)
1992–1993 HHS National Health Interview Survey on Youth Behavior Youth ages 12-21 y (N = 10,645 households)
Supplement
1994 HHS National Health Interview Survey on Disability Civilian, noninstitutionalized household population (N = 107,469
households)
1993, 1995 HHS National Health Interview Survey Civilian, noninstitutionalized household population in U.S., ages 18+ y
Year 2000 Objectives Supplement (N = 17,317 households in 1995)
1990, 1995 (1973) HHS National Survey of Family Growth Women, 15-44 y (N = 10,847 households in 1995)
Continuous (1973) HHS Pregnancy Nutrition Surveillance System (PNSS) Low-income, high-risk pregnant women participating in programs in 18
states, the Navajo Nation, and the Intertribal Council of AZ (N = 599,000
records in 1995)
Continuous (1973) HHS Pediatric Nutrition Surveillance System (PedNSS) Low-income, high-risk children, birth-17 y in participating programs in 43
states and DC, Puerto Rico, and 6 Indian reservations (N = 8,800,000 records
in 1995)
1988–1990 HHS National Maternal and Infant Health Survey Women, hospitals, and prenatal care providers associated with live births
(N = 9953), still births (N = 3309), and infant deaths (N = 5332)
1988–1994 HHS Third National Health and Nutrition Examination Survey U.S. noninstitutionalized, civilian population, 2+ mo; Oversampling of
(NHANES III). Followup study is under consideration blacks and Mexican-Americans, children 0-5 y, and individuals 60+ y
(N = 33,994 individuals interviewed; N = 31,311 individuals examined)
1989–1993 HHS National Health and Nutrition Examination III NHANES III (1988-91) examinees 50+ years (N = 2602 completed NHANES
Supplemental Nutrition Survey of Older Americans III dietary recall (DR) and 1st SNS interview; N = 2519 completed NHANES
III DR and 2nd SNS interview; N = 2261 completed NHANES III DR and
2 SNS interviews)
1990–1991 HHS Survey of Heights and Weights of American Indian School American Indian school children, ages 5-18 y (N = 9464 children in 1990-91
Children school year)
1991–1992 HHS Navajo Health and Nutrition Survey Persons ages 12+ y residing on or near the Navajo reservation in AZ, NM,
and CO (N = 985 examined)
1991–1992 HHS Longitudinal Followup to the National Maternal and Infant Participants of the 1988 NMIHS (N = 9400 mothers of 3 yr olds; N = 1000
Health Survey women who had infant deaths; N = 1000 women who had late fetal deaths
in 1988
1992 HHS NHANES I Epidemiologic Followup Study Individuals examined in NHANES I, 25-74 y at baseline, 1971-74 (N = 9281,
1992 cohort)
Continuous (1992) HHS NHANES II Mortality Followup Survey Individuals examined in NHANES II, 30-74 y at baseline, 1976-80 (N = 9252)
Continuous (1992) HHS Hispanic HANES (HHANES) Mortality Followup Survey Individuals interviewed in HHANES, 20-74 y at baseline, 1982-84 (N = NA)
(in progress)
Annual (1992) HHS National Health Care Survey (integrates: National Home Record-based health care provider surveys including: visits to hospital
and Hospice Care Survey (1992-94; 1996), National emergency and outpatients departments of non-Federal, short-stay, general
Nursing Home Survey (since 1973-74) and Followup and specialty hospitals and ambulatory surgical centers; office visits to non-
(1995, 1997), National Hospital Discharge Survey (since Federal, office-based physicians; and home health agencies and nursing
1965), National Ambulatory Medical Care Survey (since homes (N = 11,396 for 1996 NHHCS; N = 9556 for 1995 NNHS; N = 282,525
1973), National Hospital Ambulatory Medical Care Survey for 1995 NHDS; N = 32,978 for 1996 NAMCS; N = 52,194 for 1996
(1992), and National Survey of Ambulatory Surgery (1994- NHAMCS; N = 125,751 for 1996 NSAS)
96)
Continuous (1992) HHS NHANES III Mortality Followup Survey Individuals interviewed and examined in NHANES III, 20+ y at baseline,
1988-94 (N = NA)
1996–1999 HHS Demonstration Sites for PedNSS and PNSS Low-income, high risk women, infants, and children that participate in
government food assistance programs and participate in PedNSS and PNSS
(N = minimum of 1000 children in WIC for PedNSS; N = minimum of 300
women in WIC for PNSS)
1999+ HHS National Health and Nutrition Examination Survey Civilian, noninstitutionalized individuals. Oversampling of blacks,
Mexican-Americans, adolescents, older persons, and pregnant women in
the first 3 years. (N = NA)
Food and Nutrient Consumption
Continuous (1917) DOD Nutritional Evaluation of Military Feeding Systems and Enlisted personnel of the Army, Navy, Marine Corps, and Air Force
Military Populations (N = 20-240 depending on study focus)
Annual supplement BLS; Current Population Survey, Supplement on Food Security Civilian, noninstitutionalized U.S. population (N = approx. 59,500 for CPS)
(1995) CB;
USDA
415
416
Continuous (1980) DOL Consumer Expenditure Survey Civilian, noninstitutionalized, population and a portion of the
institutionalized population (N = 5000 in quarterly interview survey of
consumer unites; N = 6000 diary surveys of consumer unites kept for 2
consecutive 1-week periods)
Continuous (1983) DOC Survey of Income and Program Participation (SIPP) Civilian, noninstitutionalized population of the U.S. (N = 11,600-36,800
households in a continuous series of panels)
1994, 1996 (1984) USDA Study of WIC Participants and Program Characteristics WIC participants using mail surveys of State and local WIC agencies, record
abstractions at local WIC service sites and, in 1988, interviews with
participants (N = 7,000,000+ individuals in 1996)
1988–1994 HHS NHANES III and Supplemental Nutrition Survey of Older See NHANES III listing above. Individuals ages 50+ y examined in
Americans NHANES III with telephones (See listing above for N)
1989–1991, annual USDA Continuing Survey of Food Intakes by Individuals (CSFII) Females 19-50 y and their children 1-5 y and males 19-50 y residing in
1994–1996, annual (Intake of Pyramid Servings and Servings database 1994- households in 48 conterminous States in 1985-86, individuals of all ages
(1985-1986) 1996) residing in households in 48 conterminous States in 1989-91, and

nationwide in 1994-96; oversampling of individuals in low-income
households; individuals 2+ y from CSFII 1994-96 (N = 15,303 in 1994-96)
1989-91 HHS Strong Heart Dietary Survey American Indian adults ages 45-74 y in SD, OK, and AZ (N = 888)
1991–1992 DOC Development of a National Seafood Consumption Survey Individuals residing in eligible households and recreational/subsistence
Model fishermen (N = —)
1992 USDA School Nutrition Dietary Assessment Study School-age children in grades 1-12 in 48 conterminous States and D.C.
(N = 380 school districts; N = 607 schools; N = 4489 students)
1992 USDA Adult Day Care Program Study Adult day care centers and adults participating in the Child and Adult Care
Food Program (N = 282 CACFP Centers; N = 282 non-CACFP Centers;
N = 942 participating adults)
1994–1995 USDA WIC Infant Feeding Practices Study Nationally representative sample of WIC mothers and infants living in the
48 contiguous States, the District of Columbia and the 33 WIC agencies on
Indian reservations (N = 971)
1995 USDA Early Childhood and Child Care Study Child care sponsors, providers, and children participating in the CACFP (N
= 566 sponsors; N = 1962 providers; N = 1951 households; N = 2174 child-
day observations)
1997–1998 USDA Supplemental Children’s Survey Noninstitutionalized children 0-9 y in households in the U.S.; oversampling
of low-income households (N = approx 5000)
1998 USDA School Nutrition Dietary Assessment Study II School-age children in grades 1-12 in 48 conterminous States and D.C.
(N = approx 1152 schools)
1999+ HHS National Health and Nutrition Examination Survey Civilian, noninstitutionalized individuals. Oversampling of blacks,
Mexican-Americans, adolescents, older persons, and pregnant women in
the first 3 years (N = approx 3200)

Knowledge, Attitudes, and Behavior Assessments
Continuous (1984) HHS Behavioral Risk Factor Surveillance System Individuals 18+ y residing in households with telephones in participating
States (N = approx 2039 per state in all 50 states for 1995)
1990, 1994 (1982) HHS Health and Diet Survey Civilian, noninstitutionalized individuals in households w/telephones,
18+ y (N = 5005 in 1995)
1989–1991 USDA Diet and Health Knowledge Survey Main meal-planner/preparers in households participating in 1989-91 and
1994–1996 1994-96 CSFII (N = 5765 for 1994-96)
Annual (1990) HHS Youth Risk Behavior Survey (YRBS) Youths attending school in grades 9-12 and 12-21 y of age in households in
50 States, D.C., Puerto Rico, and Virgin Islands (N = approx 12,000 for the
National surveys and N = approx 2000 for the State and local surveys)
1990 HHS Cholesterol Awareness Survey — Physicians’ Survey Physicians practicing in the conterminous U.S. (N = 1,604)
1990–1991 HHS Nationwide Survey of Nurses’ and Dietitians’ Knowledge, Registered nurses and registered dietitians currently active in their
Attitudes, and Behavior Regarding Cardiovascular Risk professions (N = 7200 registered nurses; N = 1621 occupational health
Factors nurses oversample; N = 1782 registered dietitians)
1990–1991 HHS Nutrition Label Format Studies Primary food shoppers, ages 18+ y (N = 2676)
1991 HHS Weight Loss Practices Survey Individuals currently trying to lose weight, ages 18+ y, in households with
telephones (N = 1232 current dieters; N = 205 African American
oversample; N = 218 nondieting controls)
1991 HHS 5 A Day for Better Health Baseline Survey Individuals ages 18+ y with telephones (N = approx. 2059)
1992–1993; 1998 HHS Consumer Food Handling Practices and Awareness of Individuals in households w/telephones, 18+ y (N = 1620)
Microbiological Hazards Screener
1993–1994 HHS Infant Feeding Practices Survey New mothers and healthy, full-term infants 0-1 y (N = 1200)
1994–1995 USDA WIC Infant Feeding Practices Survey Prenatal and postnatal women and their infants participating in the WIC
program (N = 971)
Food Composition and Nutrient Databases
Continuous (1892) USDA National Nutrient Data Bank (N = —)

Food Composition Laboratory
Annual (1961) HHS Total Diet Study Representative diets of specific age-sex groups
(N = —)
1991–1993, HHS Food Label and Package Survey (N = 1250 food brands)
1993–1994,
1995–1996 (1977)
417
418

Continuous (1977) USDA Survey Nutrient Data Base for CSFII 1989-91, 1994-96; (N = —)
NHANES III 1988-94
1988–1994 HHS Technical Support Information for the NHANES III, 1988- (N = —)
94 Dietary Interview Data Files
1994–1996 USDA CSFII 1994-96 Technical Support Files (N = —)
Food Coding Database
Recipe Database
Survey Nutrient Database and Related Files
Food Supply Determinations
Annual (1909) DOC Fisheries of the United States (N = —)

Annual (1909) U.S. Food and Nutrition Supply Series: (N = —)
USDA Estimates of Food Available
USDA Estimates of Nutrients
Continuous (1985) USDA A.C. Nielsen SCANTRACK (N = 3000 supermarkets since 1988)
Abbreviations: ARS, Agricultural Research Service; ASPE, Assistant Secretary for Planning and Evaluation; BLS, Bureau of Labor Statistics; CACFP, Child and Adult Care
Food Program; CB, Census Bureau; CDC, Centers for Disease Control and Prevention; DOC, Department of Commerce; DOD, Department of Defense; DOL, Department
of Labor; FDA, Food and Drug Administration; ERS, Economic Research Service; FNS, Food and Nutrition Service; HHS, Department of Health and Human Services; HNIS,
Human Nutrition Information Service*; HRSA, Health Resources Services Administration; IHS, Indian Health Service; NCCDPHP, National Center for Chronic Disease
Prevention and Health Promotion; NCHS, National Center for Health Statistics; NCI, National Cancer Institute; NHLBI, National Heart, Lung, and Blood Institute; NIH,
National Institutes of Health; NA — not applicable; NMFS, National Marine Fisheries Service; NOAA, National Oceanic and Atmospheric Administration; SSA, Social
Security Administration; ASARUM, U.S. Army Research Institute of Environmental Medicine; USDA, U.S. Department of Agriculture.
* HNIS was integrated into ARS in 1994.
— = Not applicable
NA = Not available
The Pediatric Nutrition Surveillance System (PedNSS), sponsored since 1973, is used to
monitor simple key indicators of nutritional status among low-income, high-risk infants
and children who participate in publicly funded health, nutrition, and food assistance
programs.66 Data can be analyzed at individual, clinic, county, state, and national levels.
The Pregnancy Nutrition Surveillance System (PNSS), sponsored since 1978, tracks nutri-
tion-related problems and behavioral risk factors associated with low birth weight among
high-risk prenatal women.66 The PNSS is used to identify preventable nutrition-related
problems and behavioral risk factors to target interventions.
Food and Nutrient Consumption

Food consumption measurements include estimates of individuals’ intakes of foods and
beverages (nonalcoholic and alcoholic) and nutritional supplements. Both CSFII and
NHANES provide national estimates of food and nutrient intakes in the general U.S.
population and subgroups. These surveys and the FDA Total Diet Study provide the
potential to assess pesticide levels in diets.
Periodic assessments of food and nutrient consumption of specific population subgroups
not adequately covered in national surveys have been conducted for military populations,
Native Americans, children, and low income populations. A 1996 Supplemental Children’s
Survey was conducted specifically to assess pesticide exposures in the diets of infants and
young children. Since 1995, a yearly supplement to the Current Population Survey (CPS),
conducted by the U.S. Census Bureau, has been devoted to measuring the extent of food
insecurity and hunger among people living in U.S. households.23,28,67
Evaluations of USDA nutrition and food assistance programs are routinely conducted.
The Adult Day Care Program Study and the Early Childhood and Child Care Study each
determined the characteristics and dietary intakes of their participants and the features
of day care centers participating in the Child and Adult Care Food Program. A number
of studies have been conducted to evaluate the nutrition and health effects of participating
in WIC, provide current participant and program characteristics of the WIC program, and
describe the infant feeding practices of WIC participants. The School Nutrition Dietary
Assessment Study assessed the nutrient content of USDA and non-USDA meals offered
in U.S. schools and the contribution of the National School Lunch Program to overall
nutrient intake.68 A follow-up study was conducted to compare changes over time.
Knowledge, Attitudes, and Behavior Assessments

National surveys that measure knowledge, attitudes, and behavior about diet and nutri-
tion and how these relate to health were added to the nutrition monitoring program in
1982. In general, the focus of the Health and Diet Surveys is on people’s awareness of
relationships between diet and risk for chronic disease, and on health-related knowledge
and attitudes. The survey has studied consumer use of food labels, the effectiveness of
the National Cholesterol Education Program, and weight loss practices.69,70 The focus of
the Diet and Health Knowledge Survey initiated by USDA in 1989 is on the relationship
of individuals’ knowledge and attitudes about dietary guidance and food safety to their
food choices and nutrient intakes.
Surveys addressing specific topics such as infant feeding practices, weight loss practices
and progress toward achieving related national health objectives, and cholesterol aware-
ness of health professionals have been periodically conducted to meet specific data needs.
The National Cancer Institute (NCI) conducted the 5 A Day Baseline Survey in collabo-
ration with food industry to assess knowledge, behavior, and attitudes about fruits and
vegetables.71 NCI also conducted the Cancer Prevention Awareness Survey and the
National Knowledge, Attitudes, and Behavior Survey to measure progress on knowledge,
attitudes, and behaviors regarding lifestyle and cancer prevention and risk factors. The
FDA conducted a study to assess consumer food handling practices and awareness of
microbiological hazards, and also conducted a number of studies to evaluate the Nutrition
Facts Label features and usability by consumers.72
The focus of the Behavioral Risk Factor Surveillance System (BRFSS) is on personal
behavior and its relationship to nutritional and health status. BRFSS has been used by
state health departments to plan, initiate, and guide health promotion and disease pre-
vention programs, and to monitor their progress over time.73 The Youth Risk Behavior
Survey monitors priority health risk behaviors among adolescents through national, state,
and local surveys.74
Food Composition and Nutrient Databases

FDA’s Total Diet Study provides annual food composition analysis of core foods of the
U.S. food supply, and the Food Label and Package Survey, sponsored by a number of
agencies, is conducted to monitor labeling practices of U.S. food manufacturers.75,76 The
survey also includes a surveillance program to identify levels of accuracy of selected
nutrient declarations compared to values obtained from nutrient analyses of products.
Since 1892, USDA has maintained the National Nutrient Data Bank (NNDB) for the
purpose of deriving representative nutrient values for more than 6000 foods and up to 80
components consumed in the U.S.77 Data are obtained from the food industry, from USDA-
initiated analytical contracts, and from the scientific literature. Values from NNDB are
released electronically as the USDA Nutrient Data Base for Standard Reference (SR). The
SR is updated periodically to reflect changes in the food supply as well as changes in
analytical methodology. The SR nutrient data are used as the core of most nutrient data-
bases developed in the U.S. for special purposes, such as those used in the commercially
available dietary analysis programs.77-79 USDA produces the Survey Nutrient Data Base
(SNDB), which contains data for 28 food components and energy for each food item for
analysis of NHANES and CSFII.80 The database is periodically updated. The National
Food and Nutrient Analysis Program was initiated in 1997 to produce accurate and current
food composition data characterizing the U.S. national food supply. This goal is being
achieved through stratified random sample collection and chemical assay of commonly
eaten foods accounting for the majority of Americans’ nutrient intake. The new data will
be incorporated into the NNDB.
Many individuals are consuming nutrients from dietary supplements. To enable the
estimation of total nutrient intakes and the impact of dietary supplements on nutrition
and health, the National Center for Health Statistics (NCHS) has developed and is main-
taining a database on dietary supplements for use with national surveys.81
Food Supply Determinations

Since the beginning of this century, U.S. food supply estimates have reflected levels of
foods and nutrients available for consumption. These data, updated and published annu-
ally by USDA as the U.S. Food and Nutrient Supply Series, are used to assess the potential
of the U.S. food supply to meet the nutritional needs of the population and changes in
the food supply over time. They are also used to evaluate the effects of technological
alterations and marketing changes on the food supply over time, to study the relationships
between food and nutrient availability and nutrient-disease associations, and to facilitate
management of federal marketing, food assistance, nutrition education, food enrichment
and fortification policy. The Fisheries of the United States Survey has been conducted by
the National Marine Fisheries Service since 1909 to provide annual estimates of fish and
shellfish availability and consumption in the U.S. food system.
Evolution of the Nutrition Monitoring Program

The history of nutrition monitoring in the U.S. is discussed earlier in this section, and
notes significant legislative and other events. The current nutrition monitoring program
is firmly grounded in USDA and HHS nutrition-related studies and surveys that address
pertinent health issues and needs. The future evolution of the program will be based on
these and other identified health issues and needs of the population that relate to diet,
physical activity, lifestyle, and health. The focus of the program may shift as past health
problems are resolved through nutrition education and public policy changes (e.g., food
fortification) and as new diet-related health concerns emerge. The studies and surveys
within the current monitoring program can be adapted to meet changing needs, and new
studies can be added as resources permit. The present and future needs for nutrition
monitoring will be defined and clarified based on nutrition-related studies conducted by
government, academic, medical, clinical, and private institutions.
Improvements to the nutrition monitoring program will result from research that devel-
ops new methodologies and improves existing ones to assess nutrition and health status.
New and improved methods may allow more accurate and efficient assessment of food
and nutrient intake, assessment of physiological measures of nutrient status, and tech-
niques to relate food and nutrient intake to health status. These improvements will result
in more accurate data, and they may result in data that are not comparable to previous
data collected with other methods. These newer data may also shift the focus of the
nutrition monitoring program.
Changes in Health Needs

Speculation about the future evolution of the nutrition monitoring program requires con-
sideration of the factors that may change the health concerns of the population. Some of
the factors are changes in the food supply, in the demographics of the U.S. population,
and in individual dietary and other lifestyle behaviors. Innovation to the food supply may
alter the nutrient content of existing foods or may result in new food products. In either
case, the nutrient intake of the population or of specific population groups may change as
these altered or new foods are consumed. Changes in the food supply may result from
genetic engineering of plants or animals, changes in agricultural practices, and new man-
ufacturing processes or technologies. Within the past several decades there has been
increased access to food from fast-food chains and other restaurants, increased availability
of prepared foods from grocery stores that require only microwave heating prior to con-
sumption, and increased consumption of ethnic dishes. Such changes are likely to continue.
Alterations in the demographics of the U.S. population may affect the mean food and
nutrient intakes from national surveys, because the surveys reflect the food preferences,
patterns, and practices of the population. The number of Hispanics and blacks in the U.S.
population is increasing at a rate faster than the white, non-Hispanic population. The
population is also becoming older as the baby boomers and their children age. Changes
in income levels and income disparities in the population may result in changes in diet
and health outcomes reported from surveys. Income disparities among racial and ethnic
groups and among age and gender categories will continue to be important in identifying
population groups that are more vulnerable to diet and health-related problems.
Modifications in individual dietary and other lifestyle behavior may lead to changes in
health. Consumers are encouraged to follow the Dietary Guidelines for Americans and the
Food Guide Pyramid, to read Nutrition Facts Labels, and to be more physically active. These
nutrition education efforts may help consumers improve their diets and health outcomes.
Consumers may become increasingly knowledgeable of the health effects of overweight
and obesity and make attempts to alter their eating patterns and physical activity to lose
weight. People are also influenced by the nutrition information they receive from other
sources (TV, radio, books, magazines, advertisements). They may begin to take (or alter
their intake of) dietary supplements, increase intake of functional foods, or become inter-
ested in organic produce, herbal products, or botanicals. Such behavior changes could affect
health. Hopefully, consumers will adopt behaviors that will improve their health; however,
it is possible that poor dietary advice may have the opposite effect. It is also possible that
continued sedentary lifestyles and wide access to food will maintain the current problems
of overweight and obesity in the U.S. and the health problems related to them.
Preparing for the Future

In December 1999 the National Academy of Sciences (NAS) organized a public symposium
entitled “Nutrition Monitoring in the U.S.: Preparing for the Next Millennium.” This
session convened nutrition scientists from industry, academia, government, and the public
sector along with policy makers to discuss current efforts to streamline and integrate the
monitoring program and to identify and highlight future diet, nutrition, and health data
needs. Conference participants discussed ways to optimize the utility and relevance of
the nutrition monitoring program for organizations whose activities depend on the avail-
ability and reliability of the data obtained from the program. The National Nutrition
Summit, held in May, 2000 in Washington, D.C., focused on several nutrition monitoring
themes including obesity, physical activity, and food security.
Additional activities in progress to prepare the nutrition monitoring program for the
future include integration of USDA and NHCS nutrition surveys, improving the compa-
rability and quality of survey methods, and providing state and local nutrition-related
data, including data for population subgroups.
Survey Integration
Continuous collection of diet- and nutrition-related data in cross-sectional and longitudi-
nal surveys and surveillance systems is needed to assess the health of the U.S. population
and plan nutrition services and educational programs. Efforts are under way to integrate
and merge the NHANES and the CSFII by 2002. The survey will include a nationally
representative annual sample of black, white, and Mexican-American persons for all
income and low income households, and a common dietary data collection and processing
system. Federal agencies are currently conducting sample design and dietary survey
methodology research, evaluating the extent of seasonal and geographic coverage with
the combined annual survey, and designing and implementing the integrated sample to
better meet nutrition monitoring data needs and develop a “core” (identical) set of demo-
graphic, socioeconomic, nutrition, and health-related program questions that are essential
to estimate and report dietary intakes for the integrated sample. The two departments are
also working to operationalize improvements in sample design, dietary methodologies,
and questionnaires. The framework for the survey’s design will need to provide flexibility
and opportunities for modifications over time.
Comparability and Quality of Methods

An integral part of the coordination of nutrition monitoring activities is the use of stan-
dardized or comparable methodologies for the collection, quality control, analysis, and
reporting of data. Progress has been made in developing indicators for height and weight
to assess growth and overweight, household food security, and folic acid status. Standard-
ized indicators are needed for population descriptors, food security, diet, nutritional, and
related health status, and knowledge, attitudes, and behavior assessments. As these indi-
cators are developed, they will be incorporated into existing and planned surveillance
systems.
Reliable, valid, and cost-effective measures of nutritional status need to be developed
and improved, along with appropriate interpretive criteria. Research is needed on appro-
priate methods (such as questionnaires, interviewing procedures, physical measures, and
biological indicators) for subgroups at increased nutritional risk, practical and efficient
measures of diet, biochemical, and clinical parameters, and applied statistical methodolo-
gies for the collection and interpretation of nutrition monitoring data. Research to develop
and standardize questionnaires for valid and reliable estimators of knowledge, attitudes,
and behavior will aid in the development of public health strategies at federal, state, and
local levels to improve dietary status, promote health, and prevent nutrition-related disease.
State and Local Data

Nutrition monitoring data are needed at the state and local levels, especially as they relate
to welfare reform and other policy changes. Continued improvements to the CDC state
surveillance systems, the use of comparable methodologies, and supplemental data col-
lection for defined populating groups will be central to meeting state and local data needs
in the future. Improvements will be dependent upon the availability of resources to
provide technical assistance and data collection capacity to states.
Data for Population Subgroups

Many surveys of the nutrition monitoring program collect data on population subgroups
such as low-income people and minorities. However, data are still limited for select sub-
groups, such as the homeless, Native Americans, and Asian and Pacific Islanders. NCHS
is exploring an initiative known as community HANES to study specific population sub-
groups for whom national estimates cannot be easily, practically, or cost-effectively made.
The Link between Nutrition Monitoring, Research, and Policy

Research, monitoring, and policy are intertwined by a complex set of interrelationships.
As shown in Figure 15.2, nutrition monitoring is vital to policymaking and research.15,60,82
Monitoring provides information and a database for public policy decision making and
Research Needs for

Data Data
Results Data Nutrition Needed
Needed
for Policymaking for
Decision- Decision-
making making
Nutrition Nutrition
Research Monitoring
Research Results,
Needs for Data
Data for Research
FIGURE 15.2
Overlapping of nutrition monitoring, policy making, and research. Source: Adapted from U.S. Department of
Health and Human Services and U.S. Department of Agriculture. Ten-Year Comprehensive Plan for the National
Nutrition and Related Research Program. 1993.
establishing research priorities.42,63,83-85 Nutrition research provides data for policymaking

and for identifying nutrition monitoring data needs.42,63
The Third Report on Nutrition Monitoring in the United States identified a number of
food components of particular public health concern in the U.S. population: food energy,
total fat, saturated fatty acids, cholesterol, alcohol, iron, calcium, and sodium. The report
also included a range of health issues of particular concern for low-income, high-risk
populations including anemia, low birth weight, overweight, high serum total cholesterol,
hypertension, osteoporosis, low intakes of a number of nutrients (including folate, calcium,
iron, and others), and food insufficiency.58 Based on these findings, the report also provided
recommendations for future nutrition monitoring and nutrition methods research.
To illustrate the link between nutrition monitoring, nutrition research, and nutrition
policy, this section explores a current public health issue identified in the Third Report on
Nutrition Monitoring in the United States: the relationship of calcium intake and
osteoporosis. All dietary components have unique considerations with respect to deter-
mining dietary adequacy and measuring physiological status. The example of calcium
and osteoporosis illustrates some of the challenges of measuring both dietary and phys-
iological status, drawing conclusions about the relationship between dietary intake and
health, and providing guidance to the public to improve health based on the available
data and scientific research.
Dietary Assessment of Calcium Status

Assessment of dietary calcium intake has been routinely included in national food con-
sumption surveys such as NHANES and CSFII. The Adequate Intakes (AIs) for calcium
established by IOM are 500 mg/day for ages 1 to 3 years, 800 mg/day for ages 4 to 8
years, 1300 mg/day for ages 9 to 18 years, 1000 mg/day for ages 19 to 50 years, and 1200
mg/day for ages 51 years and over.58
Mean total (diet, dietary supplements, antacids) intakes of calcium fall short of AIs,
especially for teenage girls, women, and older males (Table 15.4). During 1988 to 1994
mean calcium intakes for females decreased from a peak at 2 to 8 years of age (789 mg/
day) to about 776 mg/day for women 50 years of age and older. Calcium intakes for males
peaked at 9 to 19 years of age (1016 mg/day) and declined to about 851 mg/day for ages
50 years and over.86 In issuing its recommendations, the Institute of Medicine indicated
that there is a great disparity between recommended calcium values and current dietary
TABLE 15.4
Percent of the U.S. Population Meeting the Adequate Intake (AI) for Calcium,
1988–1994
Total Intake
Dietary Intake (Food) (Food + Supplements + Antacids)
Age and Median % Meeting Mean Median % Meeting
Sex Mean (mg) (mg) AI (mg) (mg) AI
Males
2–8 y 868 853 88 875 856 89

9–19 y 1003 989 51 1016 994 52
20–49 y 920 872 60 982 906 64
50+ y 778 717 30 851 762 35
2+ y 895 862 55 945 889 58
Females
2–8 y 780 767 79 789 773 79

9–19 y 728 721 17 746 729 19
20–49 y 657 624 31 759 672 40
50+ y 610 564 13 776 663 27
2+ y 667 637 29 765 696 36
Total
2–8 y 826 820 84 833 824 84

9–19 y 865 857 34 881 865 35
20–49 y 786 728 45 868 785 52
50+ y 685 633 21 809 708 30
2+ y 777 738 41 852 785 47
Source: NHANES III.
patterns.39 Many individuals are not consuming sufficient intakes to meet their require-
ments and reduce the likelihood that they will develop osteoporosis.
Dairy products provide three-fourths of the dietary calcium intake in U.S. diets, and the
dietary intake of calcium parallels what is known about intake of dairy products, i.e., that
milk consumption begins to decline for females in their teenage years and remain low
throughout life (except perhaps during pregnancy and lactation, when women are advised
to drink milk). Milk consumption is also generally low among older men and women.
Monitoring data from the 1987-88 NFCS showed that 50% of dietary calcium came from
milk and milk products, 20% from milk and cheese as ingredients in mixed dishes, and
30% from all other food groups.87 Additional USDA data indicate that between 1909 and
1990 dairy products comprised approximately 75% of calcium intake, indicating that the
major contributing source has not changed a great deal.58
Because information on the use of dietary supplements and antacids was collected in
NHANES III, it is possible to estimate the total intake of calcium from all sources. About
17% of the population reported the use of supplemental calcium in the diet in 1988 to
1994.86 Table 15.4 indicates that these additional non-food sources of calcium in the diet
have little overall impact on the percentage of the population meeting the AI for calcium.
Overall, children ages 2 to 8 years are most likely to meet the recommended adequate
intakes of calcium, with food sources providing the majority of calcium intake. In fact,
just approximately 52% of calcium for children ages 2 to 18 years is derived from milk.
For children 2 to 5 years, milk contributes almost 60% of calcium, for those 6 to 11 years
milk contributes about 54% of calcium, and it contributes 46% of calcium to the diets of
12- to 18-year-olds.88 Other calcium sources for children ages 2 to 18 include cheese (14%),
yeast bread (7%), ice cream/sherbet/frozen yogurt (3%), and cakes/cookies/quickbreads/
donuts (2.3%).
Physiological Assessment of Calcium Status

About 99% of body calcium is in the skeleton, and its primary function is structural, i.e.,
to build and maintain bones and teeth. The remaining body calcium is in blood, extracel-
lular fluid, muscle, and other tissues, where it plays roles in vascular contraction and
vasodilation, muscle contraction, nerve transmission, and glandular secretion. Blood levels
of calcium remain relatively constant even in people with osteoporosis (decreased bone
mass). The calcium is removed from the bone to maintain blood levels. Calcium metabolism
and bone metabolism are highly integrated and correlated. Osteoporosis takes many years
to develop and is usually not diagnosed until later years, such as when a fracture occurs.
Unfortunately, there have not been large-scale survey methods that are both reliable and
cost-efficient for determining physiological calcium status until recently. In NHANES III,
bone density was measured for the first time in a nationally representative sample of
Americans. Among females 50 years of age and older, osteopenia (less than optimal bone
density) at the total femur occurred in 42% of non-Hispanic whites, 37% of Mexican-
Americans, and 28% of non-Hispanic blacks. Prevalence estimates for osteoporosis at the
total femur in these three groups were 17, 12, and 8%, respectively.89 Research is focused
on developing and interpreting biochemical markers related to bone resorption, bone
turnover, and osteoporosis risk.90-92
Relating Dietary and Physiological Data

Significant bone accretion occurs during adolescence and early adulthood. The low dietary
calcium intakes by many adolescents and adults, particularly females, suggest that they are
not getting the calcium they need to maintain optimal bone health and prevent age-related
bone loss. Low peak bone density coupled with inadequate calcium intake in subsequent
years may increase the risk of bone fracture in later years. Osteopenia and osteoporosis are
both associated with inadequate bone mineral, especially calcium. Fractures resulting from
osteoporosis are a major cause of morbidity in post menopausal caucasian females in the
U.S. Osteoporosis develops over several decades of life and may not be apparent until a
fracture occurs. Although loss of bone mineral is related to dietary intake of calcium, there
are also other important considerations with regard to this condition.
The link between dietary calcium intake and bone status (osteoporosis) is not always
direct. Dietary intake of calcium may not be a good predictor of physiological calcium
status in some population groups or individuals because of the following confounding
factors:
Calcium intake:
• Calcium intake collected in national surveys captures only recent (1 to 2 days)
dietary intake, whereas osteoporosis takes several decades to develop.
NHANES III and NHANES 1999+ did include questions about the historical
consumption of milk, although long-term intake is difficult for many people
to report accurately.93,94 In addition, dietary intake surveys tend to underes-
timate total food and energy intake, so that calcium intake from surveys may
be underestimated as well.95
• The use of calcium supplements will increase calcium intake and may affect
bone health.
Intake of other nutrients:
• If energy intake has not been adequate (as with malnutrition or severe diet-
ing), there may not be sufficient protein or sufficient amounts of other nutri-
ents to help build or maintain bone. Bone is a complex tissue with a steady
turnover rate that requires many nutrients. Even if calcium is adequate, the
bone may not form properly if other important nutrients are lacking.
• Excess protein intake, especially from animal sources, may lead to increased
excretion of calcium in the urine. IOM (1997) points out that while dietary
protein intake increases urinary calcium excretion, inadequate protein intakes
(34 g/day) are associated with poor general health and poor recovery from
osteoporotic hip fractures.
• Dietary phylloquinone (vitamin K-1) or phylloquinone status may be associ-
ated with age-related bone loss.96-98
• The effects of caffeine on the skeleton are modest at calcium intakes of 800
mg/day or higher.39
• The Institute of Medicine39 reviewed the relationship between salt intake and
bone health, and concluded that indirect evidence indicates that dietary salt
has a negative effect on the skeleton, although the effect of a change in sodium
intake on bone loss and fracture rates has not been reported. IOM (1997)
concluded that available evidence does not warrant different calcium intake
requirements for individuals according to their salt consumption.
Role of genetics:
• Blacks and Asians experience more lactose intolerance than whites and tend
to eat fewer dairy products than whites. Although blacks and Asians tend to
have lower calcium intakes than whites, they do not necessarily show an
increase in the prevalence of osteoporosis. In the U.S., older persons of north-

ern European origin have the lowest bone densities and highest fracture risks.
About 75% of older blacks have bone densities above the fracture threshold.
Thus, it appears that race or genetic background plays a role in the develop-
ment of osteoporosis.
Physiological status:
• Decreased estrogen production at menopause is associated with accelerated
bone loss, particularly from the lumbar spine, for about five years.99 Estrogen
replacement therapy at menopause is one approach to help prevent bone loss
and osteoporosis in women for whom no contraindications are present.
• Decreased calcium absorption with age is well recognized and may be due
in part to low vitamin D intake. Vitamin D deficiency may play a role in hip
fractures of those over 70 years. Older people often have decreased vitamin
D intake because most dietary vitamin D comes from vitamin D-fortified milk,
a food not preferred by older persons. In addition, older persons have de-
creased conversion of vitamin D to its active form in the skin. This may be
due do decreased vitamin D metabolism, decreased sun exposure (sunlight
is required for the conversion), and/or use of sunscreen (which blocks sun-
light) to prevent skin cancer.
• Pregnancy and lactation, especially repeated pregnancies and periods of lac-
tation, may create an increased body requirement for calcium, which, if not
met, may lead to decreased bone calcium in the mother.
• Some medications interfere with calcium absorption and function.
• Some endocrine disorders may affect calcium balance and status.
• Weight-bearing exercise is very important to maintain bone health. Negative
calcium balance may result from immobilization, illness, or lack of exer-
cise.100,101
Public Nutrition Policy Regarding Calcium

In addition to the national dietary data, which suggest that calcium intakes are below
recommended levels for girls, women, and older adults, and the physiological data regard-
ing the incidence of osteopenia and osteoporosis in the U.S. population, there are also
epidemiological data linking age-related osteopenia to lifetime calcium intake. These data
support the suspected relationship between dietary calcium intake and bone health. The
Third Report on Nutrition Monitoring in the U.S.58 states,
Many Americans are not getting the calcium they need to maintain optimal bone health
and prevent age-related bone loss. Achieving peak bone mass and maintaining bone
mass appear to be related to adequate calcium intake in adolescence and early adult-
hood. Because of the high rates of bone accretion during adolescence, continued mon-
itoring of calcium intake is important.
The report classifies calcium as a “current public health issue” along with food energy,
total fat, saturated fatty acids, cholesterol, alcohol, iron, and sodium and recommends the
“development of interpretive criteria to link monitoring data to functional outcomes or
health outcomes.”
Nutrition monitoring data on calcium intake and calcium-containing foods were used
to make scientific recommendations at the 1994 NIH Consensus Conference on Optimal
Calcium Intake.12 The U.S. policy on calcium is to continue to emphasize the consumption
of dairy products through the Dietary Guidelines for Americans31 and the Food Guide
Pyramid, and to suggest alternatives (fish with bones, green leafy vegetables, legumes,
calcium-fortified orange juice, calcium supplements) for those who do not consume dairy
products (e.g., those who are vegans, lactose intolerant, allergic to milk, those who do not
like dairy products, and those whose cultural diets do not include dairy products). The
Food Guide Pyramid recommendations are for two servings of dairy products per day
for adults 24 years of age and older, and 3 servings per day for children, teenagers, younger
adults, and pregnant and lactating women.
Conclusion
The primary goal of the 1990 Ten-Year Comprehensive Plan, “to establish a comprehensive
nutrition monitoring and related research program by collecting quality data that are
continuous, coordinated, timely, and reliable; using comparable methods for data collec-
tion and reporting of results; conducting relevant research; and efficiently and effectively
disseminating and exchanging information with data users” is still pertinent a decade
later.39 Nutrition monitoring data are needed to inform both research and policy agendas.
It is through this intertwined relationship between monitoring, research, and policy that
we can continue to effect change. Given the competing demands for limited national
resources and resulting budget limitations, however, the goals for the nutrition monitoring
program will continue to be evaluated against other competing national needs. Continued
support is necessary to maintain and expand the nutrition monitoring program in the U.S.
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Alexandria, VA: U.S. Department of Agriculture, Food and Nutrition Service. August, 1998.
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16
Clinical Nutrition Studies: Unique Applications
Marlene M. Most, Valerie Fishell, Amy Binkoski, Stacie Coval, Denise Shaffer Taylor,
Guixiang Zhao, and Penny Kris-Etherton
Nutrition research is the hallmark of establishing nutrient requirements and giving dietary
guidance to promote health and wellbeing throughout life. Over the years it has been an
active area of investigation, leading to the discovery of many important findings that have
provided the basis for dietary guidelines and recommendations. Until recently, resources
describing the design, implementation, and management of clinical nutrition studies were
limited. Because of the growing interest and activities in clinical nutrition research, a
number of important resources are now available that describe key aspects of conducting
clinical nutrition studies. These resources (i.e., books and journal articles) are listed in
Table 16.1. They provide detailed information about all aspects of conducting nutrition
research with human participants. Collectively, they are a wealth of information for all
researchers interested in and actively involved with human nutrition research. Indeed,
these resources are a true “goldmine” to the field for standard studies, including those
that employ either a single- or multicenter model. However, there are many studies that
are uniquely different, presenting what may seem to be insurmountable challenges with
respect to the experimental design, diet design, participant population studied, and feed-
ing model utilized. For the most part, these have not been discussed in detail in the
publications listed in Table 16.1.
Thus, the purpose of this section is to describe unique challenges in human nutrition
research applications and provide guidance about how they can be effectively managed
to maintain tight experimental control. First, we have included a variety of forms that
were developed for different nutrition studies we have conducted that are not available
in other resources. These forms deal with important aspects of conducting a well-con-
trolled feeding study. They can be adapted to other human nutrition studies that vary in
design from more typical protocols. Second, we provide descriptions of studies that
illustrate challenges in the design and conduct of clinical nutrition studies, with notes on
how these were handled.
Forms and Documentation for Assuring Dietary Protocol Compliance

Essential to all controlled feeding studies is recruiting participants who not only meet the
eligibility criteria that have been defined, but are also willing to adhere to all aspects of
0-8493-2705-9/01/$0.00+$1.50
TABLE 16.1
Resources for Information on the Conduct of Clinical Nutrition Studies
Dennis, BH, Ershow, AG, Obarzanek, E, Clevidence, BA. Well-Controlled Diet Studies in Humans. The American
Dietetic Association, Chicago, IL, 1999.
Dennis, BH, Kris-Etherton, PM. Designing and Managing a Small Clinical Trial. In: Research, Successful Approaches,
pp. 151-170. Edited by E. Monsen. The American Dietetic Association, Chicago, IL, 1992.
Dennis, BH, Stewart, P, Hua-Wang, C, Champagne, C, Windhauser, M, Ershow, A, Karmally, W, Phillips, K,
Stewart, K, Van Heel, N, Farhat-Wood, A, Kris-Etherton, PM. Diet design for a multicenter controlled feeding
trial: The DELTA Program. JADA 1998; 98: 766-776.
Obarzanek, E, Moore, TJ. The Dietary Approaches to Stop Hypertension (DASH) Trial. JADA 1999; 8: S1-S104.
the experimental protocol. Hence, they serve as partners in research with the investigative
team. Also important are the day-to-day operations that depend largely on the proper
preparation, delivery, and consumption of the diets and adherence to study protocol by
the participants. For many studies the diets are the treatments, and therefore must be
strictly delivered as set forth by the protocol. Forms to assist with participant selection
and documentation of diet adherence activities are needed to assure quality.
Recruiting Participants
The major goal of recruitment is to enroll the required number of participants necessary
for the study within the projected timeline and within the budget constraints. The recruit-
ment of potential study participants can be accomplished in many ways, and will be
guided by inclusion/exclusion criteria set forth in the study protocol. Reaching the target
study population is key. For example, post-menopausal women would more likely see an
advertisement in a community weekly than, obviously, in a high school newspaper. There-
fore, recruitment tactics focus on the groups that need to be recruited, and are planned
accordingly. The Institutional Review Board (IRB) must clear all recruiting materials before
use to assure that the information is not misleading and the study is accurately represented.
Detailed information about recruiting is available elsewhere (see Table 16.1), but is briefly
discussed below.
Advertisements in the local media are effective recruitment tools. Newspaper advertise-
ments can be general in nature or contain specific information about the study (see
example, Figure 16.1). An advantage of a newspaper advertisement is that it reaches a
large audience, while a disadvantage is that it can be expensive. The ability to target a
specific audience may be somewhat limited unless the newspaper audience is narrow,
such as for business reports or campus newspapers. Radio and television advertisements
also can be expensive and are limited in the amount of information that can be dissemi-
nated about the study. However, it may be possible to obtain free radio and television
advertising by submitting the material as a public service announcement. Local morning
or early evening magazine-format programs often welcome an interview with the study
investigator, who can describe the study and ask for volunteers.
Other recruiting tools include speaking about the study to different local community
organizations, such as the Lions clubs or church groups. Although time consuming, it
targets a specific audience. Health fairs provide a community service as well as a recruit-
ment opportunity. For example, free blood pressure screenings will help identify potential
participants for a study examining blood pressure-lowering diets. Distributing and posting
flyers on bulletin boards in supermarkets, drug stores, or doctors’ offices is an excellent
avenue for communicating the need for study participants. Mass mailings of a brochure,
postcard, or letter describing the study can be sent to a target population. This tends to
Clinical Nutrition Studies: Unique Applications 437
Is Eating Cocoa and Chocolate Good for You??
We are currently recruiting participants for a nutrition study aimed

at determining whether cocoa and chocolate contain antioxidants that
may be good for you.
The study dates are June 1–June 29 and July 12–Aug 10. You must
complete both 4 week periods.
(There is a break from June 29 to July 12th)
You may qualify if you meet all of these criteria:
• You must be healthy and between the ages of 20–67 (male or pre-menopausal
female);
• You must not be a smoker and cannot consume alcohol, coffee, or tea during
the study;
• You must be willing to eat only foods (including cocoa and chocolate) provided
for the study and come to the study center on University Park campus for
breakfast and dinner 5 days/week — food for lunches and the weekend will
be packed for takeout;
• You must not have diabetes mellitus or uncontrolled (> 140/95) high blood
pressure or other serious health conditions;
• You must not be pregnant, nursing, or planning to get pregnant.
All food will be provided during the study along with monetary
compensation. If you are interested in participating in this study, please call
(814) 863-3168, give your name, mention that you are interested in the Cocoa
Study, and give us a number where you can be reached.
FIGURE 16.1
Sample subject recruitment advertisement.
be an effective tool but is labor-intensive and costly for the materials, mailing list, and
postage. Email also can be used for recruitment but, like mass mailings, it sometimes
requires the purchase of the mailing list.
Regardless of the recruitment method used, careful records are required to track the
recruitment progress, and more importantly, to document that the eligibility criteria are
being met.
Screening Potential Participants

Once a person expresses interest and contacts the recruiter, the screening process begins.
The initial contact should be used to exclude those who do not meet the most easily
identifiable criteria (see Telephone interview form, Figure 16.2). Obviously, a smoker who
calls to ask about a study that is recruiting only non-smokers would be excluded quickly
during the telephone screening process. Another example would be the screening of a
post-menopausal woman who is taking hormone replacement therapy (HRT) when the
study protocol excludes women on HRT. These initial exclusions early in the recruiting
process prevent bringing people in for the more expensive clinic visits, and thus prevent
Folate Study Subject ID: ______________

TELEPHONE INTERVIEW FORM Today’s Date: __/__/__
Pennsylvania State University Reviewer’s Initials: ______
Before asking any questions, please read the following paragraph to obtain verbal consent to conduct the
telephone interview:
“We received your message that you are interested in participating in the Folate Study. I would like to ask you
a series of questions about your willingness to participate in the study, your past medical history, and your
current lifestyle behaviors. If you agree to answer these questions, and it is then determined that you meet the
criteria for this study, we will schedule you for a screening visit. Are you willing to answer a series of questions,
which will take about 15 minutes?”
1. Yes (continue with interview)
2. No (thank them for their time and interest)
Full Name w/middle initial ___________________________________________________ DOB _________________

Local address _____________________________________________________________________________________
Home # _______________ Work # _________________
1. Are you a female between the ages of 19–35 years inclusive? Yes No
2. Do you plan to remain in the area for the duration of the Yes No
study?
3. Are there any personal reasons (e.g., family problems, Yes No
vacations, child care difficulties, etc.) that would keep you
from participating in the study?
4. Are there any professional reasons (e.g., job-related travel, Yes No
irregular work schedule, conferences, etc.) that would keep
you from participating in the study?
5. There is a variety of foods in the Folate Study. Are there Yes No
any foods you refuse to eat, are allergic to, or for whatever
reason have to avoid?
*Go to Food List*
Listed are foods included on the diet for this study. I will go through the list — tell me if there is any food you
cannot or would not eat.
FOODS Ok? FOODS Ok?

Turkey breast Penne pasta
Zucchini (fresh) Celery
Green olives Mayo dressing
Potatoes Radishes
Dill pickles Onion
Tuna Sweet relish
Mayonnaise Canned pears
Canned peaches Applesauce
Grapes (fresh) Watermelon (fresh)
Canned pineapple Blueberries
Jello Potato chips
(regular/barbecue)
Banana muffin Cinnamon-apple
muffin
Blueberry muffin Pineapple-orange
muffin
Beef Mashed potatoes w/
gravy
Chicken breast Seasoned rice
(thyme, oregano,
parsley flakes)
FIGURE 16.2
Telephone interview form.
Spaghetti Meatballs &

marinara sauce
Ground turkey Taco seasoning
Cornbread muffin Skim milk
Crackers Pretzels
6. Do you currently smoke? Yes No

a. If No, have you ever smoked before? Yes No
a. 1. If Yes, how long since your last cigarette? __________
7. Are you willing to discontinue your consumption of Yes No
alcohol for the entire 8 weeks of the study?
8. Do you have access to the following appliances at home/
apartment/dorm:
Refrigerator Yes No
Freezer Yes No
Microwave or oven or toaster oven Yes No
*Explain that they will take Sat/Sun meals home on Friday and
will need a place to store/cook their food*
9. It is important to maintain your current body weight for Yes No
the duration of the study. Are you willing to maintain your
current body weight?
Medical and Lifestyle Information

Do you have any of the following medical conditions:
1. Heart disease Yes No
2. Diabetes Yes No
3. High blood pressure (hypertension) treated with Yes No
medication
4. Renal or kidney failure Yes No
5. Gastrointestinal condition such as Crohn’s disease, irritable Yes No
bowel syndrome, ulcer, or history of bowel surgery
6. History of blood clotting disorder Yes No
7. Liver disease such as cirrhosis Yes No
8. Condition that requires the use of steroid medication Yes No
9. Gout requiring treatment Yes No
10. Recent history of depression or mental condition requiring Yes No
medication within the last 6 months
11. Anemia Yes No
12. Sickle cell anemia Yes No
13. Lung disease such as chronic bronchitis or emphysema Yes No
14. Cancer, active within the last 10 years Yes No
15. Thyroid disease or thyroid problem requiring treatment Yes No
such as iodine or surgery, or taking medication for your
thyroid
16. Do you have any other medical condition not previously
mentioned?
If Yes, specify: ___________________________________________ Yes No
a. If Yes, is the subject eligible? Yes No
17. Do you take any type of doctor-prescribed medication? Yes No
If Yes, specify medication and reason: _______________________
________________________________________________________
a. If Yes, is the subject eligible? Yes No
b. If she takes birth control, explain she has to be willing to Yes No
forego its use for the duration of the study (8 weeks) and has
to have a 2-week wash-out period before starting. This means
she has to finish her entire packet of pills and from that last
day she starts the 2-week wash-out period.
FIGURE 16.2
Continued.
18. Do you take any type of self-prescribed medication, Yes No

vitamin, mineral, or other supplement (including garlic or
ginseng?)
If Yes, specify medication/supplement: ___________________
a. If Yes, are you willing to discontinue? _________________ Yes No
19. Are you on a special diet prescribed by a doctor or self- Yes No
prescribed?
If Yes, specify: __________________________________________
_______________________________________________________ Yes No
a. If Yes, is the subject eligible? _________________________
20. Do you exercise more than 8 hours a week or play sports Yes No
regularly?
If Yes, please describe: __________________________________
_______________________________________________________
_______________________________________________________
21. Are you willing to have a pregnancy test 3x during the 8- Yes No
week study?
22. In order to assess folate, red blood cells, and homocysteine, Yes No
blood will be taken at the beginning of the study and once
every week after that. There will be a total of 9 blood draws,
with no more than 2 tubes of blood taken each time. Are
you willing to do this?
Note: This form has to be reviewed by the Study Coordinator
If any of the bolded boxes are marked, the subject is ineligible.

Is the subject eligible? Yes No
a. If Yes, go to Women’s History Form and then schedule
clinic visit.
b. If No, thank subject for his/her time and terminate the
interview.
FIGURE 16.2
Continued.
wasting resources in terms of staff time and money. For those who pass the initial telephone
interview, further screening is required. They will come to the study site for clinical
laboratory tests or other measurements to assure that they are relatively healthy and meet
all the study eligibility criteria.
To assist with identifying whether someone would be able to adequately follow the
dietary protocol, general dietary information may be gathered in questionnaire form
during the study screening visits. The questions identify participants who cannot or will
not eat any foods due to religious reasons, allergies, or severe physical discomfort. A
complete list of study foods or a copy of the study menus in layman’s terms may be
reviewed with potential participants. This information is especially important when par-
ticular foods in the menu cannot be substituted.
Other useful screening information includes whether a person can safely store and
prepare foods to be consumed away from the clinical site, and environmental, family, or
work situations that may make adherence to the protocol difficult (see General dietary
questionnaire, Figure 16.3). For persons whose adherence may appear to be questionable,
a meeting with the study dietitian may help to determine if reasonable provisions can be
made within the protocol requirements, or they may be deemed ineligible. For example,
participants who have lactose intolerance may be allowed to use lactose digestive aids
and be eligible. Someone who does not have adequate facilities in their home to store and
prepare study foods would be ineligible to participate in the study.
The following questions are related to your overall eating environment. Your answers will help the staff
determine ways they can make your participation in the study more enjoyable.
Yes No
1. Do you foresee any problems transporting, storing, refrigerating, and warming your
study foods when you are away from our center?
2. Do you participate in activities where food is served, such as sporting events,
religious gatherings, business meetings, etc.?
3. Will any holidays, birthdays, family reunions, vacations, etc., occur during the period
you are on the study?
4. If you are responsible for preparing meals in your household, will this make it
difficult for you to meet study requirements?
5. Will anyone in your household be affected or inconvenienced by your participation
in this study?
If yes, who are they and how will they be affected?
6. Will your employment (e.g., job transfer) or work hours (e.g., moving to a night
shift) change during the study?
7. Do you, or anyone in your household, work in the food service industry (cafeteria,
bakery, restaurant, etc.)?
If yes, do you eat any meals or snacks at work either as a requirement of your job
or as a matter of convenience?
8. If you have any concerns about the study, please write them in the space provided
below (use the back of this page if you need additional space).
Reviewed by (staff ID): _________
FIGURE 16.3
General dietary questionnaire.
Orientation Session
When taking part in a feeding study, it is important that each participant carefully follow
the dietary protocol. An orientation form that lists these guidelines may be developed and
reviewed immediately prior to the actual study start date during an orientation session.
Helpful information for the form would be instructions to finish all foods and beverages
provided, squeeze condiment packets until empty, use a rubber spatula or bread to clean
the plate, and eat fruit and vegetable peels as appropriate. Reminders to complete the
daily forms, check for accuracy of the meals, and not make substitutions may be listed.
A guideline stating what to do if participants find that they are too full or hungry is useful.
Heating directions for takeout foods could also be included. A list of contact persons with
telephone numbers is imperative for when questions or problems arise. Participants appre-
ciate a copy of the beverage and seasoning guidelines that specify the types and amounts
that may be consumed. If there are restrictions on mints or gum, these should be listed.
Participants must be instructed in the safe handling of foods provided to be consumed
off site. For example, a simple handout may be given that reminds participants to use a
cooler to transport foods for longer than one hour, to refrigerate all perishable foods as
soon as possible, and to not eat suspected spoiled foods, but to notify the staff immediately
to avoid a missed meal.
Assuring Participant Diet Adherence

Participant adherence to the diet protocol is collected, usually on a daily basis (see Daily
checklist, Figure 16.4) by the participant, and is subject to review by study staff. For this
Fat Challenge 2 Pennington Biomedical Research Center

Name _________________________________________ Date ____________________
Please answer all questions below and place an “X” in appropriate column. Please fill in the additional
information requested when necessary. Please return this form each day to the Pennington Metabolic Kitchen.
1. _______ _______ Were there any study foods you did not eat/drink on this day? Reasons include missing,
Yes No spilled, or inedible food, illness or other.
Food/Drink Amount Reason

______________________________ __________________ __________________
______________________________ __________________ __________________
______________________________ __________________ __________________
2. _______ _______ Did you eat or drink any foods that were not provided by the Metabolic Kitchen today?
Yes No If yes, please give the food/drink (be very specific), the amount, and reason consumed.
Food/Drink Amount Reason

______________________________ __________________ __________________
______________________________ __________________ __________________
______________________________ __________________ __________________
3. _______ _______ Did you consume any decaffeinated sugar-free beverages on this day? Record all
Yes No beverages, including those provided by the Metabolic Kitchen.
Food/Drink Amount
______________________________ __________________ oz.
______________________________ __________________
______________________________ __________________
4. Did you eat any of the “unit foods” today? Y _____N _____
How may “unit foods” did you eat? 0 1 2 3 4 5 Other _____
5. _______ _______ Is there anything you would like us to know in relation to your participation in this
Yes No study?
FIGURE 16.4
Daily checklist.
reason, the participants must be encouraged to record honestly and must not feel that
their participation is threatened in any way. The data, which document diet adherence
and deviations, may be used to calculate daily energy and nutrient intakes and to compute
a compliance score. The form, called a daily diary, daily log, or food and beverage intake
form, may gather information for the following broad categories:
• The type and amount of study foods not eaten

• The type and amount of non-study foods eaten
• The type and amount of discretionary or “allowed” food items consumed
• The type and amount of beverages consumed, including coffee, tea, soft drinks,
and alcoholic beverages
• The number of unit foods or calorie adjusters eaten
• Dietary supplements or over-the-counter medications taken
• Feedback regarding concerns or questions related to participation in the study
The forms should provide the participant’s identification number and date for which
diet information is obtained. It may also contain the kcalorie level for the participant, coded
ILSI Subject ID: _________

Weekly Monitoring Form Today’s Date: __/__/__
Pennsylvania State University Reviewer’s Initials: _________
Week 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Blood Draw Date
Date of blood draw 1: ____/____/____ Date of blood draw 2: ____/____/____
1. In the past week has your exercise level changed? Yes No

a. If Yes, was it More Active
Less Active
No Exercise
2. Have you taken any vitamin, mineral, or other supplements in the past week? Yes No
a. If Yes, specify: description amount
______________________________ _________________________
______________________________ _________________________
3. Have you been ill in the past week? Yes No

a. If Yes, describe illness: _______________________________________________________
______________________________________________________________________________
4. If you were ill in the past week, did your eating change as a result? Yes No
a. If Yes, describe: _____________________________________________________________
______________________________________________________________________________
If any of the bolded boxes are checked, please notify Study Coordinator
FIGURE 16.5
Weekly monitoring form.
treatment diet, a field for entering the participant’s weight, and for females, menstruation
information. The information gathered then may be coded by the study staff, either on the
same form or another form, for data entry.
Another form for staff documentation of diet deviations may be used. This would
provide a record of deviations observed during on-site meals or those called in to staff
during times of off-site meals, such as weekends. If any study food or beverage is left on
the meal tray and was unnoticed during the meal tray check, information regarding the
food (i.e., type and amount) is recorded. Similarly, if a participant calls a staff member to
report a deviation for an off-site meal (i.e., missing, lost, or spoiled food), the appropriate
information is recorded. If discrepancies between the kitchen staff observations and infor-
mation reported by the participant are found, the study dietitian should adjudicate those.
In addition, the study protocol may require the participant to return uneaten portions of
study-provided foods. The type and amount of food returned would be recorded on this
form. Additional information may be collected regarding what was done with the food
not consumed. For example, was the food given back to the participant to eat, replaced
at the next meal and eaten, not replaced or not eaten? The data then may be coded for
compliance measures and energy or nutrient calculations.
Usually on a weekly basis, the participant will complete another form that asks about
general health-related items that might influence food intake or study outcomes (see
Weekly monitoring form, Figure 16.5). For example, changes in exercise, any illnesses, and
any medications or supplements taken may be reported. Queries for possible symptoms,
Diet D Menu 1
Date: ____/____/____
Mm dd yy
Day: M T W T F S S Staff Initials 1500 2000 2500 3000 3500
Breakfast
Orange juice 124.0 124.0 124.0 124.0 248.0
Puffed rice cereal 23.0 23.0 23.0 46.0 46.0
White bread 22.7 45.4 90.4 90.4 90.4
Butter 8.0 9.0 15.0 20.0 20.0
Sweets; jellies 0.0 10.0 10.0 10.0 10.0
Jellies, dietetic 14.2 0.0 0.0 0.0 0.0
Milk, whole 245.0 245.0 245.0 490.0 490.0
Lunch
Sandwich package:
*Turkey breast meat 35.0 50.0 56.7 56.7 75.0
*Mayonnaise, regular 4.3 5.0 6.0 9.0 9.0
*Iceberg lettuce 0.0 0.0 0.0 10.0 10.0
*White bread 45.4 45.4 45.4 45.4 90.8
Iceberg lettuce 24.0 24.0 24.0 40.0 40.0
Olive oil 0.0 2.0 2.0 10.0 8.0
Peaches, juice pack 127.6 127.6 127.6 127.6 127.6
Ginger Cookie 14.0 22.0 22.0 22.0 22.0
FIGURE 16.6
Food production form. Foods are indicated in grams for each energy level diet.
such as poor appetite, stuffy nose, fatigue, diarrhea, constipation, nausea, or headache
could also be included as appropriate.
Food Production and Meal Assembly

Used in conjunction with standardized recipes, a food production form is followed for
the preparation and portioning of all menu items (see Food production form, Figure 16.6).
There will be a separate form for each diet and menu. It is usually helpful to color-code
the forms according to diet treatment. An established menu sequence will determine which
menu is to be served on each day of the study. For each menu, the portion sizes for the
various kcalorie levels are listed. The number of participants receiving each kcalorie level
for the corresponding diet is listed in the box above each kcalorie designation so that the
kitchen staff knows how many servings are required. The food is prepared and portioned
according to the list, and then the staff member responsible initials the item in the space
provided. At times, it might be necessary to substitute a food item. Documentation of the
deviation on the food production form or a separate form, to include the type of food and
when it was used may be informative later when detailed diet information is required.
A tray assembly check sheet is valuable for assuring that all participants receive each
menu item (see Tray assembly check sheet, Figure 16.7). Separate sheets may be needed
for each kcalorie level, menu, and diet, and could be color-coded similar to the food
production forms. As the tray is assembled, the item is checked off in the corresponding
box for each participant and initialed by the staff to verify that all food items are provided.
If the food production forms are used to assemble the foods, a tray assembly check sheet
may be used as a quality assurance check. Similar procedures are followed for packed
meals, checking off each item as it is placed in the takeout container.
Diet D Menu 1 1500 Kcal
Date: ____/____/____ Name or I.D. #

Mm dd yy
Day: M T W T F S S
Breakfast
Orange juice
Puffed rice cereal (1 PC)*
White bread (1 slice)
Butter
Dietetic jelly (1/2 oz.)
Whole milk (1 PC)
Staff Initials
Lunch
Turkey sandwich package
Salad
Salad dressing
Peaches (1 PC)
Ginger cookie (1 small)
Staff Initials
Snack
Trail mix
Staff Initials
FIGURE 16.7
Tray assembly check sheet. * PC = portion control.
Another practical form for packed meals and/or snacks is a checklist of the menu items
that participants use to verify that all items have been packed in their takeout containers
(see Packed meal form, Figure 16.8). The form is attached to or placed inside the container,
and the participant is instructed to contact a kitchen staff member if any item on the form
is missing from the container. Menu cards also could be used in place of the form. These,
Diet D Menu 1
Name ______________________ I.D. ________________________ Telephone Contact (___)___-____
Day M T W T F Sa Su Date ___ ___ ___ Packed by __________________ Meal B L D S
(Circle One) mm dd yy
Breakfast Lunch Dinner

Packed Packed Packed
Orange juice Turkey sandwich package Sirloin tips with gravy
Puffed rice cereal (1 box) Salad Corn
White bread (1 slice) Salad dressing Salad
Butter Peaches (1 can) Salad dressing
Dietetic jelly Ginger cookie (1 small) Roll
Milk (1 carton) Butter
Applesauce
Unit Foods Snack

# of Units Packed Packed
__________ Trail mix
__________
FIGURE 16.8
Packed meal form.
when placed on the on-site meal trays, also provide a means for the participant to double-
check the accuracy of the menu items.
Training Dietary/Kitchen Staff

It is imperative that all staff members who will be involved in the preparation and delivery
of research diets understand the strict procedures necessitated by the protocol. For exam-
ple, they must know the acceptable ranges for gram weights when portioning various
food items, how to read the food production forms, and cooking procedures. Those who
will be interacting with the participants must know the dietary guidelines, such as allowed
beverages and seasonings. The development of a training manual is useful so that staff
can periodically review the standard procedures and have a reference available to answer
any questions that may arise during the course of a study. Actual observation and/or a
written test may be utilized to assess staff competencies. In addition, routine quality
control checks are essential, and kitchen staffs who do not consistently meet the rigorous
standards set for delivering the experimental diets must be relieved of this responsibility.
Quality Assurance of Diets

During the regular production of the menus, duplicate meals should be prepared and
collected for monitoring quality assurance and for chemical analysis of target nutrients.
The food should be prepared and weighed following the standard procedures. Ideally, food
preparation staff should not know that these will be used for quality checks, but this may
be difficult to disguise. One way to overcome possible bias is for the staff to prepare a meal
for analysis identical to one prepared for a participant, and the two may be switched prior
to serving. For portion weight checks, as each food for one menu is placed into a container,
the weight of that food item is recorded and compared to what should be present. Any
discrepancies should be noted. The person who made a mistake when weighing the food
or assembling the meal can be identified by looking for his/her initials on the production
sheets. Retraining of that individual may be necessary to alleviate any further errors. Once
the entire menu is in the container it can be blended, and aliquots taken or frozen for later
analysis. When the analysis is completed, the actual nutrient values may be compared to
the expected nutrient values (from the database), especially for those being controlled.
A spot-checking procedure may be employed to monitor the accuracy of meals distrib-
uted to participants. Randomly selected meals and/or food items are checked for com-
pleteness and accuracy. If a problem is found, it is described, a plan of action for correction
of the problem is detailed, and documentation of the action plan or followup is provided.
Again, the person making the mistake should be retrained.
Miscellaneous Forms
The use of a food service sanitary inspection checklist for personnel, food handling,
equipment, storage practices, dishwashing, and department areas is standard. Inspection
of refrigerator and freezer temperatures also should be conducted on a regular basis. In
a research kitchen, regular accuracy checks of the electronic balances should be docu-
mented. Use of a form that lists acceptable ranges is a practical way to indicate whether
to recalibrate a balance. If foods are donated to the study, their expected delivery, date
received, and accuracy may be tracked on a form that also includes a description of the
food items, company, address, contact person, and telephone number.
Exit Interview
At the end of the study, an exit interview may be planned for each individual or for a
group of participants. Information offered could include laboratory data gathered during
the study, health risk assessments, and appropriate educational materials. In addition,
anonymous input from completing participants about their experiences and views is help-
ful for planning future studies. For example, questions asking about favorite foods, disliked
foods, and about the menus in general that were served during the study can provide
information for improving future menus. Factors that made it easy or difficult to follow
the study protocol may be assessed. Additional questions include how study staff treated
participants and whether the subjects would recommend participating in a study to their
friends. This information can be invaluable for improving future studies by increasing
menu acceptability and making study participation a more enjoyable experience.
Unique Study Challenges and Strategies for Addressing Them

Clinical nutrition studies may present challenges at every stage; for example, with menu
development, recruitment of participants, and finally, preparation and delivery of the
experimental diets. Obstacles must be overcome for a successful outcome. For illustration,
studies will be described that have dealt with unique and challenging situations with the
population studied, experimental design employed, and experimental diet(s) fed to study
participants. The conduct of multiple center clinical nutrition trials present their own
challenges, which are discussed elsewhere (see Table 16.1).
Recruitment and Retention

A study was designed to evaluate the effects of diets high in polyunsaturated fatty acids/
n-3 fatty acids (PUFA/n-3FA, accounting for 12% of energy), derived from walnuts and
walnut oil with different levels of n-6/n-3 FA ratios (9:1 vs. 4:1), on multiple risk factors
for cardiovascular disease (CVD). In this crossover study, we recruited 30 males and
females, ages 45 to 65, so that the results could be somewhat generalized to a middle-
aged population. Various study endpoints, including serum cytokines and the release of
TNFα and IL-6 by polymorphonuclear cells, are affected by the menstrual cycle, so this
dictated that premenopausal or postmenopausal females on hormone replacement therapy
(HRT) be excluded to minimize confounding. All participants were to be healthy, over-
weight or mildly obese, having moderate hypercholesterolemia, and taking no medica-
tions. These eligibility criteria made recruitment efforts challenging. First, many people
within this age group were taking nutrient supplements, cholesterol-lowering drugs, or
medications for hypertension, diabetes, or rheumatoid arthritis, so were not eligible for
the study. Second, many have families and it is difficult for one or both parents to come
to the clinical site for breakfast and dinner each weekday for three six-week dietary
periods. Third, postmenopausal women without HRT account for only a small proportion
of this population.
Various recruitment strategies were used such as advertising by posters, in newspapers
and on television, and sending advertising fliers to churches, senior or retired communi-
ties, and to individuals between the ages of 45 to 65. We even agreed to feed a couple in
order to recruit one of them who qualified to be a study participant while the other did
not. To overcome similar problems with recruiting persons in this age group, other clinical
centers provide guest meal passes so that family members or friends may regularly join
the study participants for meals.
Two studies that needed young females presented unique recruiting and retention
situations. Participants with low iron status were required to observe the overloading
effect of an iron supplement. Females, who generally have a lower iron status than males
due to menstruation, were targeted. Therefore, participants were females, ages 19 to 47,
with regular menstrual periods, in good general health and from all ethnic groups. Diffi-
culties in recruiting occurred for several reasons in a college town. During the summer
months the overall student population at the university diminishes greatly, presenting a
problem by reducing the potential participant pool. Also, the prospect of strictly adhering
to a controlled diet during the relaxing summer months provided another hurdle. The
two-week break between diet periods was planned around the July 4 holiday and a
summer arts festival to avoid further recruiting obstacles.
For this study and one that required females 18 to 22 years of age, weight concerns
proved to be a barrier for recruiting. Many young women were trying to lose weight and
did not want to maintain their current weight as required by the study protocols. In
addition, women in this age group tend to be “fat phobic” and careful about their fat
consumption. They were hesitant to consume diets that may have contained more fat than
their usual diets. Therefore, it was important that the fats and oils were discreetly added
to the study diets. This was accomplished by choosing meals such as turkey with dressing
and mashed potatoes or stuffed flounder, which would readily accept the oils and fats
without drawing attention.
Both recruitment and retention of participants were challenged in a study that compared
whole-food diets with formula diets. For recruitment, potential participants sampled the
formula diets. It was emphasized that the formula was all they would consume during two
of the four diet periods. Once enrolled, participant retention became the paramount issue.
One way of maintaining their participation in the study was to conduct a raffle during each
diet period. Raffle items included tickets to a football game, a movie, and a Broadway show
that came to campus. Another way was to prepare a portion of the daily formula as “ice
cream.” The “flavor of the day” was posted, and chocolate and strawberry flavors were
always available. For the participants, this alleviated the boredom from having to always
drink their meals. Many enjoyed telling their friends that they were on an “ice cream diet.”
Providing specialized, prepackaged meals or foods to participants for daily consumption
may make recruiting easier (i.e., more participants are willing to eat prepackaged foods
at home, rather than having all meals served through a metabolic kitchen), yet challenges
still abound as in other clinical nutrition studies. As one site of a year long, multicenter
study testing the effect of a prepackaged meal plan on multiple CVD risk factors, 70 men
and women with hyperlipidemia, hypertension, and/or Type 2 diabetes mellitus were
recruited. Finding participants who met the entry criteria proved to be difficult in a small
college town. Thus, the study was conducted simultaneously in a more urban location 90
miles away, where the university’s medical school is located. Once all of the participants
were recruited, problems arose with the weekly home delivery of the prepackaged, frozen
meals. The food could not be left without a signature, which proved to be an obstacle.
Participants sometimes received meals different than those they ordered, and they became
bored with their limited food selection during the year-long study.
Food Products and Menu Planning

Cocoa powder is a rich source of antioxidants in the form of flavonoids. The Cocoa Study
was conducted to evaluate the effects of a diet high in cocoa powder (22 g/day) and
dark chocolate (16 g/day) on LDL oxidative susceptibility and total antioxidant capacity
of plasma. The study employed a two-period, crossover design. Using a randomized
diet treatment assignment, participants were fed the cocoa powder/dark chocolate diet
(CP/DC) and an Average American Diet (AAD, control) for four weeks each. The cocoa
powder and dark chocolate were incorporated into only one experimental diet, making
it impossible to employ a blinded experimental diet design. Planning a study of chocolate
would appear to be easy, but the cocoa powder and menu development actually pre-
sented some challenges.
First, it was necessary to control for components present in the cocoa powder and dark
chocolate to “isolate” the flavonoids for testing their contribution to a possible antioxidant
benefit. To do this, the cocoa butter present in the dark chocolate was included in a similar
amount in the AAD. Other components included caffeine, theobromine, and fiber, since
cocoa powder and dark chocolate contain these in addition to the flavonoids. The caffeine
was supplemented in the AAD with diet cola, and 431 mg/day of pure theobromine in a
gel capsule was provided. The fiber was equilibrated with bran cereal. In addition, the
diets were designed to be low in non-CP/DC flavonoids. Thus, foods that were limited
or excluded included tea, coffee, wine, onions, apples, beans, soybeans, orange juice, and
grape juice.
Second, there was a fair amount of cocoa powder in the experimental diet, so the
participants were sometimes required to add cocoa powder (about 15 g) to their milk (or
any other menu item). They also could add a non-caloric sweetener to the “chocolate milk”
if they chose to do so. The resulting beverage was notably different from commercially
available chocolate milk and that prepared from chocolate syrups. Nonetheless, it was a
menu item that the participants found acceptable, albeit different from what they were
accustomed to drinking, and they were willing to consume it throughout the study.
Third, the cocoa powder and dark chocolate were incorporated into the diets in different
ways to avoid monotony. The daily allotment of cocoa powder was also baked into cookies,
muffins, and brownies that would be served at meals. This assured that the cocoa powder
and dark chocolate would be consumed throughout the day.
A soy study evaluated the effects of 31 g/day of an isoflavone-rich soy powder (equiv-
alent to 25 g soy protein) on plasma lipids and lipoproteins and vascular reactivity in
hypercholesterolemic but otherwise healthy male and female participants. All participants
were first fed a Step-I (run-in) diet followed by either a Step-I diet plus soy protein or a
Step-I diet with milk protein. Isoflavones are cleared rapidly from the plasma after inges-
tion, so soy-containing menu items were incorporated throughout the day in an attempt
to achieve maximal effects. The barrier to overcome was incorporation of the soy or milk
protein into baked products at an acceptable level without sacrificing the quality and
acceptability of the product. Acknowledging the importance of this, we worked with a
faculty member with expertise in food product design who prepared several great-tasting
soy products for the study. With considerable product development effort it was possible
to employ a blinded study design.
Similar barriers to flavor were overcome in a study that examined the effects of defatted
rice bran on blood lipids and lipoproteins in moderately hypercholesterolemic men and
women. Participants were randomly assigned to a reference diet with typical levels of
dietary fiber (approximately 15 g/day) or one that contained defatted rice bran to increase
dietary fiber to the recommended intake level (30 g/day). Foods were developed with the
intention of incorporating the highest amount of defatted rice bran possible. The defatted
rice bran had a nutty flavor, a somewhat grainy texture, and imparted a brown color to
all the products to which it was added. After much experimentation, we found that one
gram beyond a certain amount would yield an unacceptable food product. Because of the
color, food products that are expected to be brown, such as spice muffins and ginger
cookies, were ideal for the addition of the defatted rice bran.
Folate fortification of foods in the U.S. created some obstacles in menu development for
a study that examined the effects of a low-folate diet with milk (8 oz milk, 3 times/day)
or with no milk (8 oz apple juice, 3 times/day) on folate absorption and blood homocys-
teine levels. For a low-folate diet, it was necessary to purchase foods from countries that
did not fortify their food products. Pasta imported from Italy became a staple in these
menus and was used for lunch salads and dinner items. Foods which are manufactured
for individuals with celiac sprue are naturally low in folate because they are made with
rice flour and corn starch rather than wheat flour. Some of these items included crackers,
pretzels, and a delicious chocolate truffle brownie. The sources of these low-folate foods
were obtained by searching shops that specialize in imported foods. Furthermore, infor-
mation available on the Worldwide Web was immensely helpful to make these menus
appealing. One limitation with the menus was that there was only a four-day rotation
because of the lack of foods that are naturally low in folate. A short menu rotation may
contribute to monotony and boredom, so encouraging adherence may require extra effort.
The Worldwide Web also proved to be useful in finding food items for other studies,
such as one that manipulated the glycemic load of a low-fat, high-carbohydrate diet. The
number of food items with a known glycemic index is relatively low, and therefore limited
the food choices for the menus. Some of the foods are not routinely eaten in the U.S. For
example, chana dal, a dried baby garbanzo bean, is a staple in Indian food and has a
glycemic index of 8 compared to glucose at 100. Locating a source of the chana dal was
made easy by searching various websites. It was used as the carbohydrate source for
several meals for the low glycemic index menus.
Participant Adherence and Protocol Acceptability

High monounsaturated fatty acid (MUFA) diets have been studied extensively in the
context of evaluating their effects on plasma lipids and lipoproteins. Previous studies have
used mainly olive oil as the MUFA source, while other MUFA-rich food sources have not
been evaluated. The peanut study was conducted to evaluate the effects of experimental
diets high in peanuts and peanut products (e.g., peanut butter and peanut oil) that are
rich MUFA sources, on lipid and lipoprotein risk factors for CVD. The greatest challenge
with this study was its duration. Although there were five test diets, six 24-day diet periods
were scheduled. This schedule necessitated that participants commit to the study for a
period of approximately six months.
In a long-term study such as this, it is imperative that special efforts be made to sustain
the commitment of the participants. The participants selected one diet period off to allow
time for vacations, family activities, or celebrations. Despite participants’ initial enthusi-
asm, some found it difficult to complete the study. Nonetheless, providing some sched-
uling flexibility did help with adherence. Incentives for the participants, such as t-shirts,
coffee mugs, and movie tickets were also advantageous in maintaining long-term adher-
ence. Interestingly, as the study progressed, it was increasingly challenging for the staff
to maintain their enthusiasm as well. Theme parties without food (i.e., Halloween night,
Thanksgiving celebration) helped participants and staff members maintain a positive
attitude throughout the study.
Similarly, some flexibility was given in a nine-month study designed to test the hypoth-
esis that replacement of a fat substitute for dietary fat would significantly decrease body
fat relative to a 33% fat diet or a 25% reduced-fat diet. Testing days were scheduled at
three-month intervals. Participants were given a three-day break from eating the study
meals for the Easter, July 4, and Labor Day holidays. In addition, they were allowed to
take a total of seven “vacation” days within the six weeks immediately following the
testing days. As for the previously described study, incentives were provided throughout
the time period for encouragement.
A study designed to achieve weight maintenance after a weight loss phase presented
interesting situations with participant adherence to and acceptability of the protocol.
Participants who were moderately overweight were placed on one of two energy-restricted
diets to achieve a weight loss of two pounds per week. Following a six-week weight loss
period, they were fed the same diets, but with enough energy to maintain their weight.
Despite using a metabolic cart to calculate energy needs, about 20% of the participants
continued to lose weight during the weight maintenance phase. Because of this, periods
longer than four weeks were necessary to establish a stable body weight.
In general, people enjoy participating in controlled weight loss studies, and conse-
quently, adherence is ideal. For this study, the weight loss aspect generally was motivation
enough for the participants, although weekly incentives were provided. The hardest part
of the study was getting the participants to eat all of their food during the weight main-
tenance phase of the study. Most wanted to continue to lose weight and had to be
encouraged to adhere to the study protocol.
Several people enrolled in the weight loss study had unrecognized eating disorders,
making it difficult for them to comply with the protocol, where kcalories were restricted
for a portion of the study and then increased for the remainder of the study. This problem
pointed out the need for a screening questionnaire that would help identify people with
eating disorders so that they would not be enrolled in the study.
In the following series of studies, each of which incorporated a particular food product,
it is important that participants like the food, or at least tolerate it and be willing to eat
large amounts or more “realistic” quantities daily. While efforts are made to incorporate
the food product into a number of tasty products, it would be difficult for participants to
adhere to the experiment diet if they dislike the particular food product or the foods that
serve as a major delivery vehicle (i.e., milk for cocoa powder).
Studies were conducted using chocolate as a vehicle to assess the effects of stearic acid
on plasma lipids, lipoproteins, and platelet function. Our approach was to first evaluate
a large dose of the major fat in chocolate (i.e., cocoa butter) and subsequently assess a
large dose of milk chocolate (i.e., 10 oz/day), as well as the fat mixture found in chocolate
(cocoa butter and dairy butter — 4:1). Our rationale for using large doses was first to
determine if there was any effect of chocolate on the study endpoints of interest. Then,
more realistic intakes that reflect usual consumption practices would be examined. Initially
we needed to assess whether a large dose of chocolate would cause any significant adverse
side effects, such as gastrointestinal distress, headaches, or skin problems. Thus, a small
pilot study evaluated six participants who were fed large amounts of chocolate (10 oz/
day) for approximately one month. Having seen no adverse symptoms, two studies were
conducted to evaluate the effects of cocoa butter and milk chocolate on plasma lipids,
lipoproteins, and platelet function.
A subsequent study evaluated the incorporation of more realistic amounts of milk
chocolate (1 candy bar/day) to a Step-I diet. Moreover, we wanted to mimic real-world
chocolate consumption practices. Since a peak time for consumption of chocolate is in the
mid-afternoon, participants were required to eat their candy bar at that time. They were
required to return the wrapper to the study staff at the dinner meal for adherence assess-
ment and for communicating an important message that participants needed to consume
the chocolate bar as well as follow all aspects of the experimental protocol.
Conclusions
Well-controlled clinical nutrition studies have been invaluable in generating results that
have advanced our understanding of diet–disease relationships and have provided infor-
mation that has formed the basis for making nutrient recommendations. A number of
recent publications have comprehensively described the process of how to conduct well-
controlled feeding studies in humans that employ quality control standards at each step
(Table 1). Inherent to conducting these studies is the associated myriad of challenges, not
discussed in depth in the literature, that need to be resolved in order to conduct successful
studies. This section has presented an overview of these, which relate globally to subject
recruitment and compliance/adherence, and maintenance of subject and staff enthusiasm
during the feeding study. In addition, we have provided a “forms library” that provides
specific forms or a description for virtually every aspect involved in carrying out these
studies. Specific examples from the many clinical studies that we have conducted are
presented herein, and the approaches we implemented to resolve these problems are
described. This information will help readers to overcome the challenges that can arise
during the conduct of a well-controlled feeding study. Avoiding inherent pitfalls in feeding
studies will facilitate conducting high quality clinical nutrition research efficiently and
effectively, and therefore help advance the field.
17
Nutrition Monitoring and Research Studies:
Observational Studies
Suzanne E. Perumean-Chaney and Gary Cutter
Purpose
The purpose of this section is to provide an overview and examples of observational
studies; specifically, cohort observational studies that incorporate nutritional assessment.
After a brief review of the various types of observational studies and their corresponding
purposes, a detailed description of the characteristics, advantages, and disadvantages of
a cohort study is provided. Next, in order to demonstrate the use of the cohort design in
the area of nutrition, a description of six cohort studies that utilized nutritional assessments
is provided. Finally, selected nutrition-related publications from the six cohort examples
are referenced, along with the corresponding measured nutritional variables.
Observational Studies
Epidemiology is classically known as the study of the distribution of disease in popula-
tions; however, this definition expands and often overlaps with other areas of research.
We are concerned with two types of research here: clinical studies and observational
studies. The primary difference between these two types of research is the randomization
of subjects into groups. Clinical studies allow for the randomization of subjects into various
treatment or control groups, whereas observational studies examine the subjects according
to their natural selection into groups.
Observational studies include natural history studies, case-control studies, prevalence
(cross-sectional or population) studies, and cohort (incidence) studies. The research ques-
tion of interest would generally dictate which of the various observational studies would
be used (see Table 17.1). For example, the diagnosis or prevalence of a disease would be
facilitated by using the prevalence study design. Cohort studies provide the opportunity
to observe populations prospectively, thereby enabling observation of incidence rates as
well as prevalence rates. Risk factors and prognosis of a disease can be identified through
several different types of observational studies.
0-8493-2705-9/01/$0.00+$1.50
TABLE 17.1
The Question and Appropriate Design
Question Observational Studies
Diagnosis Prevalence
Prevalence Prevalence
Incidence Cohort
Risk factors Cohort, case/control, prevalence
Prognosis Cohort, natural history
TABLE 17.2
Characteristics of a Cohort or Incidence Study
Characteristic
Selection of a study cohort WITHOUT disease
Follow study cohort over time (prospective)
Measurement of incidence and/or absolute risk (new cases developed in a time period)
Comparison of incidence in those with and without the risk factor (relative risk and attributable risk)
Cohort Studies
As noted in Table 17.1, the purpose of cohort studies is to identify the risk factors associated
with a disease of interest and obtain the incidence of disease1 and/or its prognosis. Overall,
cohort studies allow the development of a disease to be described, and are therefore
typically a favorite among the various types of observational studies.2
The defining characteristics of a cohort study are shown in Table 17.2. The first charac-
teristic is identification of a study cohort who currently does not have the disease of interest.
Any group of individuals who have either been exposed to the same occurrence, live in a
defined geographic area, or have the same risk factors may be identified as a cohort.1-3
When similar risk factors identify a cohort, a second similar cohort without the identified
risk factors and the disease of interest must be obtained for comparison purposes.2
The second characteristic is that the study cohort(s) is followed over time. Because the
study cohort(s) are disease free, the cohort(s) are followed over time to see which indi-
viduals in the cohort(s) actually develop the disease of interest.1-4 The new cases of the
particular disease which developed within a specified time period are then measured to
obtain the incidence and absolute risk of the particular disease. Finally, a comparison
between the incidence in those individuals who had the risk factors and those individuals
who did not produce a relative risk and attributable risk of these risk factors on the
development of the disease of interest.
Advantages and Disadvantages of the Cohort Studies

There are several advantages and disadvantages of using cohort studies over other types
of observational studies (see Table 17.3). With respect to the advantages, cohort studies
make it easier to distinguish cause from association. Because the risk factors are measured
Nutrition Monitoring and Research Studies: Observational Studies 455
TABLE 17.3
Advantages and Disadvantages of a Cohort Study
Advantages Disadvantages
Easier to distinguish cause from association Results are delayed for low incidence or long
Incidence can be obtained incubation
Multiple outcomes can be studied Large number may be needed
Standard questions and measurements can be used Expensive in resources
May lead to identification of variables which can be Losses may bias results
experimentally examined Methods, criteria, and exposure status may change
over time
TABLE 17.4
Factors Associated with Causality
Magnitude of the association’s strength
Ability to show the association’s consistency through replication
Association’s identification of one risk factor to one outcome
Risk factor must precede outcome
Outcome is sensitive to different levels of risk factor
Association’s logical adherence to current theory
Association’s consistency with other information about the outcome
Association’s correspondence to other causal associations
prior to the development of the disease of interest, temporal order is established. Temporal
order is just one of eight factors associated with causality (see Table 17.4)4 and strengthens
a causal conclusion instead of simply an association between risk factors and outcome
often found in other study designs.1,4 On the other hand, the comparison of cohorts based
on risk factors makes the assumption that both cohorts are similar except for the suspected
risk factor. However, such an assumption rarely is completely supported and, hence
restricts causal implications.1
Another important advantage of cohort studies is the ability to obtain the incidence of
a disease which in turn can provide estimates of new incidences that preventive programs
can use to identify programmatic needs and support budgetary plans.4 Further, multiple
outcomes can be studied, and standard questions and measurements can be used to
compare results found in this study to previously completed studies. For example, the
Framingham study5 has provided important information on blood pressure, cholesterol,
diet, eye disease, and a number of other risk factors and outcome measures. Other studies,
such as the Coronary Artery Risk Development in Young Adults (CARDIA)6 have emu-
lated Framingham. In this study, variables were selected for inclusion in the baseline
examination because of their known or suspected relationships to cardiovascular disease.
The availability of multiple endpoints in the same populations further enables one to
study the temporal development of the components and their interrelationships. Finally,
cohort studies may permit the identification of additional variables related to specific
outcome measures which can then be further examined experimentally.3
One of the most obvious disadvantages of the cohort studies is that length has to be
adequate for development of the disease or a surrogate of the disease of interest.1,4 For
example, blood pressure and cardiovascular disease: cardiovascular disease is the ultimate
outcome of interest, but the surrogate, blood pressure, is sufficiently linked to the outcome
to make it a viable outcome in its own right. For these diseases or surrogates with low
incidence or long incubation periods, the results are delayed. With low disease incidence
rates, the sample size for each study cohort may need to be extremely large in order to
make the necessary comparisons.1,4 With both a lengthy process and large sample size,
another disadvantage is the expense associated with conducting the study.4 The length
of the study may also influence the ability to recapture all of the subjects at the end of
the study. This ability to recapture the study participants depends on their geographic
mobility, interest in continuing the study, and death.4 The inability to capture all study
participants may bias the results1,2 by so-called informative censoring. In addition, the
length of the study dictates other potential concerns. Methods, criteria, and exposure
status may change over time. For example, environmental, cultural, or technological
changes may influence the risk factors identified and the measurement of the variables
under study.2,4
Summary of Observational Studies

Observational studies are an important part of epidemiological research, in that diseases
are studied in their natural environments. Of the various types of observational studies,
cohort studies provide the most valuable approach for identifying temporal relationships
between risk factors and outcomes. The primary characteristic of cohort studies is that
they enable the cohort (or a subgroup of them) to be identified disease-free at the beginning
of the study, facilitating study of the incidence of disease. The development of the disease
of interest can then be measured and compared across cohorts. Like all observational
studies, cohort studies have advantages and disadvantages. The primary advantage is the
cohort study’s ability to distinguish cause from association, while the primary disadvan-
tage is the cost in time, money, large sample size, and loss of subjects which can lead to
substantive biases in the inferences.
The remainder of this section focuses on six selected examples of cohort studies that
utilized some form of nutritional assessment (see Table 17.5). Although there are many
cohort studies available and additional cohort studies that include nutritional assessments,
the following examples were selected to provide a wide range of nationally recognized
studies, unique uses of the cohort design, and, most importantly, different methods of
collecting nutritional data. The selected examples include the following:
1. Coronary Artery Risk Development in Young Adults (CARDIA)

2. Framingham Study: Heart and Vascular Disease Program
3. Framingham Offspring and Their Spouse Study
4. The RENO (Relationship of Energy and Nutrition to Obesity) Diet-Heart Study
5. The Nurses’ Health Study
6. The Health Professionals Follow-Up Study
Examples of Cohort Studies Utilizing Nutrition Assessment

Coronary Artery Risk Development in Young Adults (CARDIA)
The purpose of the CARDIA study was to identify risk factors that either contributed to
or protected young adults from coronary heart disease.6 The sample consisted of 5116
black and white men and women from four cities, who were 18 to 30 years of age.6,10
Measurements were taken at baseline (1985 through 1986), at two years (1987 through
1988), and biannually thereafter.7,9,10 Baseline measurements included a sociodemographic
TABLE 17.5
Examples of Cohort Studies Utilizing Nutrition Assessments
Nutrition
Years Intake
Cohort Study Conducted Sample Studied Outcome Measurement
Coronary Artery Baseline: 5116 sampled men and Coronary heart Baseline:
Risk Development 1985-1986 women blacks and disease risk factors Diet History
in Young Adults Year 2: whites 18-30 years old Questionnaire
(CARDIA) 1987-1988 (interview-
administered)
Year 2:
NCI (Block) Food
Frequency
Questionnaire
Framingham Study: 1949-1989 5209 sampled men and Cardiovascular risk Semi-Quantitative
Heart and Vascular women primarily factors Food Frequency
Disease Program whites 30-62 years old Questionnaire
(Willet)
Framingham 1971-1988 5135 sampled men and Cardiovascular risk 24-hr dietary recall
Offspring and Their women primarily factors
Spouse Study whites 12-60 years old
The RENO 1985-1993 508 sampled men and Cardiovascular risk 1. 24-hr dietary recall
(Relationship of women primarily factors 2. 7-Day food record
Energy and whites 20-69 years old 3. NCI (Block) Food
Nutrition to normal/overweight Frequency
Obesity) Diet-Heart Questionnaire
Study
The Nurses’ Study 1976-1996 121,700 sampled female Cancer risk factors Semi-Quantitative
registered nurses Food Frequency
primarily whites 30-55 Questionnaire
years old (Willet)
The Health 1986-1994 51,529 sampled male Heart disease and Semi-Quantitative
Professionals health professionals cancer risk factors Food Frequency
Follow-Up Study primarily whites 40-75 Questionnaire
years old (Willet)
questionnaire, medical (family history, current medical history, use of medications),

anthropometrics (weight, height, skinfolds, and various circumferences), lab work (lipids,
apolipoprotein, insulin, cotinine), blood pressure, lifestyle (treadmill test, questions on
tobacco and marijuana use, nutrition intake), and psychosocial questionnaires (type A/B
personality, life satisfaction, hostility, social support, and job demand or latitude).6
Nutrition intake was assessed with an interview-administered Diet History Question-
naire at baseline and the NCI (Block) Food Frequency Questionnaire at year two.9,10
Reliability and validity of the Diet History Questionnaire were assessed. Reliability was
measured through the correlation between a one-month test-retest method of the Diet
History Questionnaire.7,8
The nutrient intakes and mean caloric intakes of the Diet History Questionnaire were
compared to the same variables derived from 24-hour recalls,7,8 NCI (Block) Food Fre-
quency Questionnaire,9 NHANES II,7 and RDA’s Body Mass Index7 as an assessment of
concurrent validity. For both reliability and validity, the Diet History Questionnaire appears
to be more applicable for whites than for blacks. The relationship between diet and disease
will await the results for this cohort to enter the risk period and show disease development.
Framingham Study: Heart and Vascular Disease Program

The purpose of the Framingham Study was to provide a population-based prospective
examination of the development of cardiovascular disease and its risk factors.11,12 The
sample consisted of 5209 primarily white men and women between the ages of 30 to 62
years, who lived in Framingham, Massachusetts.5,11 Measurements were taken biennially
from 1949 through 1989. Measurements included blood labs, medical history, and a phys-
ical examination.5 Additional assessments of stress, nutrition intake, and physical activity
were added to the study at a later time. The latest nutrition intake was assessed through
the Willet Semi-Quantitative Food Frequency Questionnaire.11
Framingham Offspring and Their Spouse Study

The purpose of the Framingham Offspring and Their Spouse Study was to examine the
impact of genetic and familial influences on the development of cardiovascular disease
and its risk factors.12-14 The sample consisted of 5135 primarily white men and women
who were 12 to 60 years of age.12,13 Subjects were either the offspring or the offsprings’
spouses of the Framingham Study participants.12-14 Measurements were also taken bien-
nially from 1971 through 1988.12,14 Measurements included those similar to the original
study.12 For this study, however, nutrition intake was assessed with 24-hour recalls, one-
fourth of which were collected during the weekend, and the remaining three-fourths of
the subjects were collected during a weekday.13,14
The RENO (Relationship of Energy and Nutrition to Obesity) Diet-Heart Study

The purpose of the RENO Diet-Heart Study was to examine prospectively over a five year
period the behavioral patterns with respect to weight between normal-weight and mildly
to severely obese individuals.15 The sample consisted of 508 healthy primarily white men
and women between the ages of 20 to 69. Subjects were stratified by gender, weight
(overweight and normal weight), and five age decades. Measurements were taken over
an eight year period (1985 through 1993). Measurements included history questionnaires
(weight, activity, health, and demographics), anthropometrics, energy expenditure, labo-
ratory analyses, blood pressure, pulse, weight and dieting measures, activity data (Caltrac
Monitors and activity diary), nutrition intake and attitudes, cancer questionnaire, and
psychosocial questionnaires (general wellbeing, depression, cohesion, locus of control,
hostility inventory, social support, perceived stress).16
Nutrition intake was assessed through several measures. The first nutrition assessment
was the 24-hour dietary recalls measured at years one and five.17 The NCI (Block) Food
Frequency Questionnaire18 was used to measure nutrition intake at years two, three, and
five. Finally, a seven-day food record that collected information about the day, time, loca-
tion, and the amount and type of food eaten was measured at years one, three, and five.19,20
The Nurses’ Health Study

Initially, the purpose of the Nurses’ Health Study was to examine the relationship between
oral contraceptives and breast cancer.21,22 The study was then expanded to examine other
female-related cancers, lung cancer, and life-style factors such as diet and exercise.21,22 The
sample consisted of 121,700 registered female nurses who were 30 to 55 years of age.21,22
Selected from 11 states, nurses were chosen because they were expected to be more
accurate in reporting the incidence of diseases and lifestyle factors, and in addition were
expected to have higher participation and retention rates.21-23
Measurements were requested biennially from 1976 to 1996. Unique to this study, the
study researchers did not have personal contact with the nurse participants; instead, all
contact was maintained through the mail. That is, study participants were required to
mail in their bodily samples, anthropometric information, and the various question-
naires.21-25 Only when a participant was nonresponsive to mailing in measurements were
telephone interviews conducted. Measurements included basic demographics, medical
history including the use of medications, blood and toenail samples, anthropometrics,
lifestyle factors such as diet, exercise, and cigarette smoking, and quality of life and social
support questionnaires.21,22 In order to confirm the presence of a specified outcome (e.g.,
cancer, myocardial infarction, diabetes, or fractures), medical chart reviews were con-
ducted when participants indicated an outcome’s existence.21,23,25 Nutrition intake was
measured with Willett’s semi-quantitative food frequency questionnaire, which assessed
the consumption frequency of specified portions of food within the last year.21,23-25 In 1980,
the food frequency questionnaire identified only 61 common foods,21 while the 1984, 1986,
1990, and 1994 measures were expanded to include 120 common foods, and both vitamin
and mineral supplementations.23
The Health Professionals Follow-Up Study

The purpose of the Health Professionals Follow-Up Study was to examine the relationship
between diet and two chronic diseases: heart disease and cancer.26 The sample consisted
of 51,529 primarily white male health professionals 40 to 75 years of age.25-27 The health
professions included dentists, optometrists, osteopaths, pharmacists, podiatrics, and vet-
erinarians.
Measurements were taken biennially from 1986 through 1994.25-27 Similar to the Nurses’
Health Study, the measures were all self-administered, mailed, and the outcome identifi-
cations were verified through medical chart reviews.25,27-29 The measurements included
demographics, medical history, anthropometrics (height, weight, body mass index),
chronic disease risk factors (heart disease and cancer in particular), and lifestyle factors
such as diet, physical activity, cigarette smoking, and alcohol use.26-30
Nutrition intake was assessed with Willett’s 131-item semi-quantitative food frequency
questionnaire used as the expanded version in the Nurse’s Health Study.25,28 As in the
Nurse’s Health Study, the food frequency questionnaire assessed the consumption fre-
quency of specified portions of food within the last year.25,28,30 Nutrition intake was
assessed in 1986 and 1990.27
Selected nutrition-related publications from the aforementioned studies and their respec-
tive measured nutrient variables are shown in Table 17.6.
Summary
This section has focused on the benefits of the cohort study and has provided examples
of several studies that have used this form of design. There are certainly other forms
that can be utilized to assess the impact of diet on disease or health. The value of
TABLE 17.6
Selected Nutrition-Related Publications from the Six Cohort Examples
Reference Nutrient Variables
Slattery, M.L., Dyer, A., Jacobs, D.R., Jr., Hilner, J.E., Total kcals, macronutrients, and selected
Cann, B.J., Bild, D.E., Liu, K., McDonald, A., Van micronutrients by gender and race.
Horn, L., Hardin, M. (1994). A comparison of two
methods to ascertain dietary intake: The CARDIA
Study. J Clin Epidemiol, 47, 701-711.
Liu, K., Slattery, M., Jacobs, D. Jr., Cutter, G., Total kcals, macronutrients, and selected
McDonald, A., Van Horn, L., Hilner, J.E., Caan, B., micronutrients by gender and race.
Bragg, C., Dyer, A., Havlik, R. (1994). A study of the
reliability and comparative validity of the CARDIA
dietary history. Ethnicity & Disease, 4, 15-27.
Bild, D.E., Sholinsky, P., Smith, D.E., Lewis, C.E., Baseline caloric and fat intake, change in caloric and
Hardin, J.M., Burke, G.L. (1996). Correlates and fat intake at year 2 by gender and race.
predictors of weight loss in young adults: The
CARDIA Study. Int J Obesity, 20, 47-55.
Tucker, K.L., Selhub, J., Wilson, P.W.F., Rosenberg, I.H. Folate intake, ranking of dietary contributors to folate
(1996). Dietary intake pattern relates to plasma folate intake by gender and age (67-95 years old). Folate
and homocysteine concentrations in the Framingham intake through supplements and breakfast cereals,
Heart Study. Hum Clin Nutr, 126, 3025-3031. orange juice, green leafy vegetables.
Posner, B.M., Cupples, L.A., Franz, M.M., Gagnon, Total kcals, macronutrients, and selected
D.R. (1993). Diet and heart disease risk factors in adult micronutrients by gender. Ranking of dietary
American men and women: The Framingham contributors to total fat, saturated fat, cholesterol,
Offspring-Spouse nutrition studies. Int J Epidemiol, 22, calories, carbohydrate, protein, oleic acid, and linoleic
1014-1025. acid.
Posner, B.M., Cupples, L.A., Gagnon, D., Wilson, Total kcals, macronutrients, and selected
P.W.F., Chetwynd, K., Felix, D. (1993). Healthy People micronutrients by gender.
2000: the rationale and potential efficacy of preventive
nutrition in heart disease: The Framingham
Offspring-Spouse study. Arch Intern Med, 153, 1513-
1556.
Dodds, M.P., Silverstein, L.J. (1997). The 24-Hour Total kcals, macronutrients, and selected
Dietary Recall, in S. St. Jeor (Ed.). Obesity Assessment: micronutrients by gender and weight status. Total
Tools, Methods, Interpretations, New York: Chapman kcals, macronutrients, and selected micronutrients by
and Hall. BMI and age.
RENO Diet-Heart Study
Scott, B.J., Reeves, R.B. (1997). Seven Day Food Total kcals, macronutrients, and selected
Records. In S. St. Jeor (Ed.). Obesity Assessment: Tools, micronutrients by gender and weight status.
Methods, Interpretations, New York: Chapman and
Hall.
RENO Diet-Heart Study
Benedict, J.A., Block, G. (1997). Food Frequency Total kcals, macronutrients, and selected
Questionnaires, in S. St. Jeor (Ed.). Obesity Assessment: micronutrients by gender and weight status. Total
Tools, Methods, Interpretations, New York: Chapman kcal, macronutrients, and selected micronutrients by
andHall. BMI and age.
RENO Diet Heart Study
Silverstein, L.J., Scott, B.J., St. Jeor, S.T. (1997). Eating Number of foods per day, caloric density, number of
Patterns, in S. St. Jeor (Ed.). Obesity Assessment: Tools, meals per day and number of eating incidents per
Methods, Interpretations, New York: Chapman and day by age group. Number of foods per day, caloric
Hall. density, eating incidents per day, calories per eating
RENO Diet Heart Study incident, percent fat and total calories by gender and
weight status. Breakfast eating variables by gender
and weight status.

Selected Nutrition-Related Publications from the Six Cohort Examples
Reference Nutrient Variables
Colditz, G.A. (1995). The Nurses’ Health Study: A Selected macronutrients and selected micronutrients
cohort of U.S. women followed since 1976. JAMWA, by breast cancer, CHD/stroke, colon cancer, fracture,
50, 40-63. diabetes, and other diseases. Fruits and vegetables by
CHD/stroke, red meat by colon cancer, and caffeine
by fractures.
Hu, F.B., Stampfer, M.J., Manson, J.E., Ascherio, A., Saturated fat consumption over ten years. Saturated
Colditz, G.A., Speizer, F.E., Hennekens, C.H., Willett, fat top 5 contributors. Saturated fat consumption by
W.C. (1999). Dietary saturated fats and their food coronary heart disease risk factors. Red meat, white
sources in relation to the risk of coronary heart meat, high-fat and low-fat dairy consumption by
disease in women. Am J Clin Nutr, 70, 1001-1008. coronary heart disease.
Liu, S., Willett, W.C., Stampfer, M.J., Hu, F.B., Franz, Selected macronutrients, selected micronutrients, and
M., Sampson, L., Hennekens, C.H., Manson, J.E. selected food sources by glycemic load. Energy-
(2000). A prospective study of dietary glycemic load, adjusted dietary glycemic load by CHD. Energy-
carbohydrate intake, and risk of coronary heart adjusted total carbohydrate, type of carbohydrate and
disease in U.S. women. Am J Clin Nutr, 71, 1455-1461. glycemic index by CHD.
Michels, K.B., Giovannucci, E., Joshipura, K.J., Rosner, Frequency of fruit and vegetable intake by colorectal
B.A., Stampfer, M.J., Fuchs, C.S., Colditz, G.A., cancer age-standardized risk factors. Selected
Speizer, F.E., Willett, W.C. (2000). Prospective study categories of fruit and vegetables by relative risk of
of fruit and vegetable consumption and incidence of colon cancer and rectal cancer. Selected categories of
colon and rectal cancers. J Nat Cancer Inst, 92, 1740- fruits and vegetables stratified by vitamin
1752. supplement useage by relative risk of colon cancer.
The Nurses’ Health Study and The Health
Professionals’ Follow-Up Study
Van Dam, R.M., Huang, Z., Giovannucci, E., Rimm, Demographics related to nutrient intake, energy-
E.B., Hunter, D.J., Colditz, G.A., Stampfer, M.J., adjusted dietary fat intake by relative risk of basal cell
Willett, W.C. (2000). Diet and basal cell carcinoma of carcinoma of the skin, energy-adjusted intake of select
the skin in a prospective cohort of men. Am J Clin micronutrients and relative risk of basal cell
Nutr, 71, 135-141. carcinoma of the skin.
The Health Professionals’ Follow-Up Study
Platz, E.A., Willett, W.C., Colditz, G.A., Rimm, E.B. Mean alcohol intake, mean red meat intake, mean folic
(2000). Proportion of colon cancer risk that might be acid intake by colon cancer risk factors.
preventable in a cohort of middle-aged U.S. men.
Cancer Causes and Control, 11, 579-588.
Giovannucci, E., Rimm, E.B., Colditz, G.A., Stampfer, Fat intake by cancer-free members and by relative risk
M.J., Ascherio, A., Chute, C.C., Willett, W.C. (1993). of prostate cancer. Levels of fat from various animal
A prospective study of dietary fat and risk of prostate sources by relative risk of advanced prostate cancer.
cancer. J Nat Cancer Inst, 85, 1571-1579.
Giovannucci, E., Rimm, E.B., Wolk, A., Ascherio, A., Low and high intake of total calcium, total fructose,
Stampfer, M.J., Colditz, G.A., Willett, W.C. (1998). fruit fructose and non-fruit fructose by age-
Calcium and fructose intake in relation to risk of standardized selected characteristics. Total calcium
prostate cancer. Cancer Res, 58, 442-447. intake and total fructose intake by total, advanced
The Health Professionals’ Follow-Up Study and metastatic prostate cancer.
prospective observational studies relative to cross-sectional studies, where incidence

cannot be estimated, only prevalence, must be weighted against the real difficulty in
obtaining funding for them. Many such studies today are either sponsored by the
government through direct funding via a contract, or as add-ons to multicenter clinical
trials. It is difficult to convince funding sources that observational studies, especially in
disease areas where a good deal of information already exists, are worth the investment.
Thus, sometimes adding components to existing studies such as a clinical trial can be
done to gather prospective information. However, in this type of observation add-on,
care must be taken to consider generalizability due to the eligibility criteria in the
primary study.
References
1. Monsen ER, Cheney CL. J Am Diet Assoc 88: 1047; 1988.
2. Friedman GD. Primer of Epidemiology, McGraw-Hill, New York, 1987.
3. Zolman JF. Biostatistics: Experimental Design and Statistical Inference, Oxford University Press,
New York, 1993.
4. Slome et al. Basic Epidemiological Methods and Biostatistics: A Workbook, Wadsworth Health
Sciences Division, Monterey, 1982.
5. Dawber TR. The Framingham Study: The Epidemiology of Atherosclerotic Disease, Harvard Uni-
versity Press, Cambridge, 1980.
6. Friedman, GD, et al. J Clin Epidemiol 41: 1105; 1988.
7. McDonald A, et al. J Am Diet Assoc 91: 1104; 1991.
8. Liu K, et al. Ethnicity Disease 4: 15; 1994.
9. Slattery ML, et al. J Clin Epidemiol 47: 701; 1994.
10. Bild DE, et al. Int J Obesity 20: 47; 1996.
11. Tucker KL, et al. Hum Clin Nutr 126: 3025; 1996.
12. Kannel WB, et al. Am J Epidemiol 110: 281; 1979.
13. Posner BM, et al. Int J Epidemiol 22: 1014; 1993.
14. Posner BM, et al. Arch Intern Med 153: 1993.
15. St. Jeor ST, Dyer AR. In Obesity Assessment: Tools, Methods, Interpretations, St Jeor ST, Ed,
Chapman and Hall, New York, 1997, ch. 1.
16. St. Jeor ST, Ed, Obesity Assessment: Tools, Methods, Interpretations, Chapman and Hall, New
York, 1997.
17. Dodds MP, Silverstein LJ. In Obesity Assessment: Tools, Methods, Interpretations, St Jeor ST, Ed,
18. Benedict JA, Block G. In Obesity Assessment: Tools, Methods, Interpretations, St Jeor ST, Ed,
19. Scott BJ, Reeves RB. In Obesity Assessment: Tools, Methods, Interpretations, St Jeor ST, Ed, Chap-
man and Hall, New York, 1997, ch. 18.
20. Silverstein LJ, Scott BJ, St Jeor ST. In Obesity Assessment: Tools, Methods, Interpretations, St Jeor
ST, Ed, Chapman and Hall, New York, 1997, ch. 22.
21. Colditz GA. JAMWA 50: 40; 1995.
22. Colditz GA, Coakley E. Int. J. Sports Med 18: S162; 1997.
23. Hu FB, et al. Am J Clin Nutr 70: 1001; 1999.
24. Liu S, et al. Am J Clin Nutr 71: 1455; 2000.
25. Michels KB, et al. J Natl Cancer Inst 92: 1740; 2000.
26. Rimm EB, et al. The Lancet 338: 464; 1991.
27. Van Dam RM, et al. Am J Clin Nutr 71: 135; 2000.
28. Giovannucci E, et al. J Natl Cancer Inst 85: 1571; 1993.
29. Platz EA, et al. Cancer Causes Control 11: 579; 2000.
30. Giovannucci E, et al. Cancer Res 58: 442; 1998.
18
Nutrition Monitoring and Research Studies: Nutrition
Screening Initiative
Ronni Chernoff
The Nutrition Screening Initiative

Screening for Malnutrition
Malnutrition is not a condition that occurs rapidly; it is a chronic condition that develops
slowly over time. It is widely accepted that malnutrition from any etiology is not a positive
factor in health status, and may have a negative impact on other health conditions. There
have been many reports of the health consequences of malnutrition, particularly in hos-
pitalized individuals where poor nutritional status has been associated with increased
lengths of hospital stay, co-morbidities, complications, readmissions, and mortality.1-6 This
is particularly profound because it has been estimated that 85% of noninstitutionalized
older adults have one or more chronic conditions, many of which are related to nutritional
status.7 If it is possible to identify indicators of risk for the development of malnutrition,
and these factors are reversible conditions, then interventions that will alleviate risk can
be instituted before malnutrition becomes overt and worsens chronic conditions.
Nutritional screening is of value if 1) it reliably identifies the existence of risk factors
for malnutrition; 2) it recognizes the existence of poor nutritional status; 3) it contributes
to the avoidance of malnutrition; 4) it will minimize suffering; and 5) the condition of
malnutrition can be reversed.6,8 Reuben et al.8 describe criteria necessary to define the
potential effectiveness of interventions; these criteria are whether or not identification of
malnutrition can be achieved more accurately with screening than without it, and whether
or not individuals who have malnutrition detected early have a better outcome than those
who have malnutrition detected later in the course of their illness.
Rush9 defines the role of nutrition screening in older adults in different terms. He
describes another criteria set for screening including specificity, sensitivity, inexpensive
screening devices, and interventions where health benefit is not sacrificed by not treating
those who are at moderate or low risk. He indicates that screening is appropriate where
there is a relatively small but important proportion of the population that is affected,
where those who are affected can be identified by an easily applied tool, and where there
is an effective intervention.
0-8493-2705-9/01/$0.00+$1.50
Developing a Tool
Keeping these criteria in mind, and looking for a way to make both professional and
volunteer care providers more attentive to the malnutrition risks encountered by older
adults, the Nutrition Screening Initiative (NSI) was established in 1990 as a public aware-
ness tool for use by community and health care workers who have regular contact with
older adults. The tools were developed as a joint venture of the American Dietetic Asso-
ciation, the American Academy of Family Physicians, and the National Council on the
Aging. The premise of the Nutrition Screening Initiative is that if factors associated with
malnutrition risk are identified early, interventions can be instituted that may delay or
avoid the progression of the risk factors towards overt malnutrition.10
The NSI was developed as a nested set of tools that identify risk factors for poor
nutritional status and then diagnose malnutrition. There are three tiers: a checklist, level
II, and level III screens.11 The items on the tools were developed by reviewing the
literature and developing consensus by a technical advisory committee of experts. The
checklist was tested using a follow-up sample from a previous study of nutritional status
in older people.12
The Checklist
The checklist was created as a public awareness screening tool for use by health care and
social services personnel and other providers who work in community-based programs
in which older adults participate. It was conceived and designed to bring awareness to
nutritional issues that may impact on the health status of elderly clients. The checklist is
widely available for reproduction and information collection, and permission to use it in
non-profit settings is not required.11
The checklist was titled “Determine Your Nutritional Health” based on a mnemonic that
contains the risk factors for malnutrition listed on the reverse side of the checklist. (Figures
18.1a and b). The checklist is a one-page questionnaire that can be used in community, long
term care, or acute health settings by volunteers, health aides, or health professionals. The
objective of awareness of potential nutritional problems in older people was easily achieved;
those who have been critical have built their criticisms on the basis of assumptions that
have gone farther than the original intent of the tool or the NSI campaign.13
The items on the checklist were developed using reference literature, expert opinion,
existing databases, and pilot testing.12 Using biochemical or laboratory parameters to
define nutritional status may be misleading because the most commonly used measures,
such as serum proteins, are affected by so many different factors independent of diet or
nutritional status.9
Implementation Strategies
Screening can be conducted in many settings, and by health professionals as well as health
care workers or lay volunteers. Involving interested participants (nurses, aides, admission
clerks, etc.) will increase the likelihood that data collection (weights, heights, completion
of screening instruments) will be more complete.
Modifications that allow the screening tools to be used in different settings and for
unique purposes make this approach and this instrument user friendly, applicable, and
relevant. A tool that is flexible, valid, and reliable and allows different applications in
diverse settings is very valuable. The easier and less time consuming it is to collect data
that give insights into an individual’s nutrition and health status, the more valuable the
Nutrition Monitoring and Research Studies: Nutrition Screening Initiative 465
The warning signs of poor nutritional

health are often overlooked.
Determine
Use this checklist to find out if you Your
or someone you know is at risk.
Nutritional
Read the statements below. Circle the number in
the yes column for those that apply to you or
Health
someone you know. For each yes answer, score the
number in the box. Total your nutritional score.
YES
I have an illness or condition that made me change the kind and/or amount of food I eat. 2
I eat fewer than 2 meals per day. 3
I eat few fruits or vegetables, or milk products. 2
I have 3 or more drinks of beer, liquor, or wine almost every day. 2
I have tooth or mouth problems that make it hard for me to eat. 2
I don't always have enough money to buy the food I need. 4
I eat alone most of the time. 1
I take 3 or more different prescribed or over-the-counter drugs a day. 1
Without wanting to, I have lost or gained 10 pounds in the last 6 months. 2
I am not always physically able to shop, cook, and/or feed myself. 2
TOTAL
Total Your Nutritional Score. If it's - These materials developed and distributed by
the Nutrition Screening Initiative, a project of:
0-2 Good!Recheck your nutritional score in 6 months. AMERICAN ACADEMY

OF FAMILY PHYSICIANS
3-5 You are at moderate nutritional risk. THE AMERICAN

DIETETIC ASSOCIATION
See what can be done to improve your eating habits and
lifestyle. Your office on aging, senior nutrition program, NC NATIONAL COUNCIL
OA ON THE AGING
senior citizens counter, or health department can help.
Recheck your nutritional score in 3 months.
Remember that warning signs
6 You are at high nutritional risk. suggest risk, but do not represent
or Bring this checklist the next time you see your doctor, diagnosis of any condition.
more
dietitian, or other qualified health or social service Turn this page to learn more
professional. Talk with them about any problem you about the warning signs of poor
may have. Ask for help to improve your nutrition health. nutritional health.
FIGURE 18.1
Determine your nutritional health.
The Nutrition Checklist is based on the Warning Signs described below.

Use the word DETERMINE to remind you of the Warning Signs.
DISEASE
Any disease, illness, or chronic condition which causes you to change the way you eat, or makes it hard for
you to eat, puts your nutritional health at risk. Four out of five adults have chronic diseases that are affect-
ed by diet. Confusion or memory loss that keep getting worse is estimated to affect one out of five or more
older adults. This can make it hard to remember what, when, or if you've eaten. Feeling sad or
depressed which happens to about one in eight older adults, can cause big changes in appetite, digestion,
energy level, weight, and well-being.
EATING POORLY
Eating too little and eating too much both lead to poor health. Eating the same foods day after day or not
eating fruit, vegetables, and milk products daily will also cause poor nutritional health. One in five adults
skips meals daily. Only 13% of adults eat the minimum amount of fruit and vegetables needed. One in four
older adults drinks too much alcohol. Many health problems become worse if you drink more than one or
two alcoholic beverages per day.
TOOTH LOSS/MOUTH PAIN

A healthy mouth, teeth, and gums are needed to eat. Missing, loose, or rotten teeth, or dentures which don't
fit well or cause mouth sores make it hard to eat.
ECONOMIC HARDSHIP
As many as 40% of older Americans have incomes of less that $6000 per year. Having less - or choosing to
spend less - than $25 to 30 per week for food makes it very hard to get the foods you need to stay healthy.
REDUCED SOCIAL CONTACT

One-third of all older people live alone. Being with people daily has a positive effect on morale, well-being,
and eating.
MULTIPLE MEDICINES
Many older Americans must take medicines for health problems. Almost half of older Americans take multi-
ple medicines daily. Growing old may change the way we respond to drugs. The more medicines you take,
the greater the chance for side effects such as increased or decreased appetite, change in taste, constipation,
weakness, drowsiness, diarrhea, nausea, and others. Vitamins or minerals when taken in large doses act like
drugs and can cause harm. Alert your doctor to everything you take.
INVOLUNTARY WEIGHT LOSS/GAIN

Losing or gaining a lot of weight when you are not trying to is an important warning sign that must
not be ignored. Being overweight or underweight also increases your chance of poor health.
NEEDS ASSISTANCE IN SELF CARE

Although most older people are able to eat, one of every five has trouble with walking, shopping, and buying and
cooking food, especially as they get older.
ELDER YEARS ABOVE AGE 80

Most older people lead full and productive lives, but as age increases, risk of frailty and health problems
increase. Checking your nutritional health regularly makes good sense.
The Nutrition Screening Initiative, 1010 Wisconsin Avenue, NW, Suite 800, Washington, D.C. 20007
The Nutrition Screening Initiative is funded in part by a grant from Ross Laboratories, a division of Abbott Laboratories.
FIGURE 18.1
Determine your nutritional health. (Continued.)
information. One example is the slight modifications made to the Nutrition Screening
Initiative Checklist for use in a dental office14,15 (Figure 18.2). Dental professionals are in
a unique position to monitor their patients’ nutritional status since many of the conse-
quences of poor nutrition manifest themselves in the oral cavity (bleeding or swollen
gums; pain in mouth, teeth, gums; angular cheilosis; alterations in the surface of the
tongue). Additionally, oral health problems may contribute to the development of inade-
quate nutritional status due to lesions, loose or missing teeth, poorly fitting dentures, dry
mouth, tooth decay or disease, and difficulty in chewing or swallowing.
The warning signs of poor nutritional health are often overlooked. A checklist can help determine
if someone is a nutritional risk:
Read the statements below. Circle the number in the yes column for those that apply to you. For each yes answer,
score the number in the box. Total your nutritional score.
YES
An illness or condition makes me change the kind and/or amount of food I eat. 2
I avoid eating a food group, i.e., meat, dairy, vegetables, and/or fruit. 2
I have two or more drinks of beer, liquor, or wine almost every day 2
I have tooth pain or mouth sores that make it hard to eat or make me avoid certain foods. 2
I snack or drink sweetened beverages two or more times per day between meals. 2
I had three or more new cavities at a recent dental check-up 2
I don’t always have enough money to buy the food I need. 4
I eat alone most of the time. 1
I have a dry mouth, which makes me drink or use gum, hard candy, cough drops, or mints to moisten 1
my mouth two or more times per day.
I take three or more different prescription or over-the-counter drugs daily. 1
Without wanting to, I have lost or gained 10 pounds in the last six months. 2
I am not always physically able to shop, cook, and/or feed myself. 2
TOTAL
Total your nutritional Score. If it is:
0–2 Good! Recheck your nutritional score in 6 months.

3–5 You are at moderate nutritional risk. Try to improve your eating habits and lifestyle.
6 or more You are at high nutritional risk. Talk with your doctor, dental hygienist, or dietitian about any
problems you may have. Ask for help to improve your nutritional health.
FIGURE 18.2
Determine your nutritional health checklist, modified for use in a dental office.
The checklist can also be modified for use in specialized community or clinical settings.
One example is use in a rural community setting as reported by Jensen et al.16 They found
that the checklist items indicating poor appetite, eating problems, low income, eating
alone, and depression were associated with functional limitation.
Implementation Partners
Nurses are essential partners and participants in nutrition screening. They are the best
individuals to gather anthropometric data and health history information. They are well-
positioned to evaluate individuals’ functional status by assessing ability to engage in
activities of daily living (self care) and instrumental activities of daily living (managing
independence). Clinical nurse specialists (CNS) are uniquely positioned to conduct health
and nutrition screenings in clinic settings, particularly to identify risk factors that are
modifiable before nutritional status begins a slippery slope downward. The advantage of
implementing health promotion programs before or concurrently with the emergence of
risk-associated conditions should be apparent.17
Other health practitioners (dentists, social workers, physical therapists, speech pathol-
ogists, etc.) may also use the screening tool for clients who may have risk factors for the
development of malnutrition. Community workers who run senior centers, senior meal
programs, home health agencies, etc. can also use the checklist to help identify clients
who may require more attention to their dietary intake, social circumstance, and chronic
disease management.
Subjective Global Assessment (SGA)

Another tool devised by a group of clinicians in Canada uses a brief set of history and
physical assessment items to make an evaluation of nutritional status.18 The Subjective
Global Assessment (SGA) includes an analysis of weight changes, dietary change, gas-
trointestinal symptoms, functional capacity, medical status, and physical assessment (Fig-
ure 18.3). This tool relies on a subjective rating by using clinical judgment on weight loss,
dietary intake, loss of subcutaneous tissue, functional capacity, fluid retention, and appar-
(Select appropriate category with a checkmark, or enter numerical value where indicated by “#.”)
A. History
1. Weight change
Overall loss in past 6 months: amount = # ____________ kg; % loss = # ____________
Change in past 2 weeks: ____________ increase
____________ no change
____________ decrease
2. Dietary intake change (relative to normal)
____________ No change
____________ Change Duration = # ____________ weeks
Type: ____________ suboptimal solid diet ____________ full liquid diet
____________ hypocaloric liquids ____________ anorexia
3. Gastrointestinal symptoms (that persisted for >2 weeks)
__________ none __________ nausea __________ vomiting __________ diarrhea __________ anorexia
4. Functional capacity
____________ No dysfunction (e.g., full capacity)
____________ Dysfunction Duration = # ____________ weeks
Type: ____________ working suboptimally
____________ ambulatory
____________ bedridden
5. Disease and its relation to nutritional requirements __________________________________________
Primary diagnosis (specify) ____________
Metabolic demand (stress): ____________ no stress ____________ low stress
____________ moderate stress ____________ high stress
B. Physical (for each trait specify: 0 = normal, 1+ = mild, 2+ = moderate, 3+ = severe)
# ____________ loss of subcutaneous fat (triceps, chest)
# ____________ muscle wasting (quadriceps, deltoids)
# ____________ ankle edema
# ____________ sacral edema
# ____________ ascites
C. SGA rating (select one)
____________ A = Well nourished
____________ B = Moderately (or suspected of being) malnourished
____________ C = Severely malnourished
FIGURE 18.3
Features of Subjective Global Assessment (SGA).
ent muscle wasting.8,18 This tool has been successfully adopted and used by physicians
and nurses in clinical settings. It has been tested in the clinical setting with different
assessors, with a high degree of interrater reliability (0.91).19,20 Most of validity reports of
the SGA were conducted on hospitalized subjects with mean ages of 50 years or older,
which may contribute to some questions about its general applicability. However, the
addition of laboratory values to the SGA did not improve its validity.19
Although the SGA is a short tool that can be used successfully by health practitioners,
there are limitations to its use as a screening tool. It requires a trained clinician to admin-
ister, since there is some clinical judgment involved that would not be expected in someone
who is not a health professional. It requires that the individual being assessed is undressed
and able to be turned, which does not lend itself to community-based assessment pro-
grams. Also, its validation has been demonstrated on middle-aged, rather than elderly,
subjects.8
Mini Nutritional Assessment (MNA)

The Mini Nutritional Assessment (MNA) is a tool developed to easily evaluate the nutri-
tional status of frail elderly individuals.21 This instrument was developed to meet a
perceived need to go beyond the DETERMINE checklist developed by the NSI, which
was designed to raise the awareness of potential malnutrition risks, and the SGA, which
was designed for use with hospitalized individuals. The MNA, therefore, was created to
complement the screening tools already described.
The objectives for the MNA were to meet the following criteria:
• Be a reliable instrument
• Define thresholds
• Be used with minimal training
• Be free of rater bias
• Be minimally intrusive to patients
• Be inexpensive
The tool was designed to collect 18 items that combine objective and subjective data. These
data include simple anthropometric measures (height, weight, arm and calf circumfer-
ences, and weight loss), general geriatric assessment items, a brief general dietary assess-
ment, and self-assessment of health and nutrition perception (Figure 18.4).
This tool has been validated in several studies by comparing the scores to the judgments
of trained nutrition clinicians and to a comprehensive nutritional assessment that collected
in-depth data about the nutritional status of the subjects.22 These studies found that the
threshold for well-nourished on this instrument with a 30-point scale was 22 to 24 points;
the threshold for malnutrition was 16 to 18 points on this scale.
The MNA meets its objectives of being a practical, non-invasive tool that contributes to
the rapid evaluation of an elderly subject’s nutritional status, contributing early interven-
tion to correct nutritional deficits. This tool is easily used in a variety of settings including
hospitals, nursing homes, physician offices, or clinics.
MINI NUTRITIONAL ASSESSMENT

MNATM ID#
Last Name: First Name: M.I. Sex: Date:
Age: Weight,kg: Height, cm: Knee Height, cm:
Complete the form by writing the numbers in the boxes. Add the numbers in the boxes and compare the total assessment to the
Malnutrition Indicator Score.
ANTHROPOMETRIC ASSESSMENT
1. Body Mass Index (BMI) (weight in kg) / (height in m)2 Points 12. Selected consumption markers for protein intake Points
a. BMI < 19 = 0 points . At least one serving of dairy products (milk,
b. BMI 19 to < 21 = 1 points cheese, yogurt) per day? yes no
c. BMI 21 to < 23 = 2 points
d. BMI >
_ 23 = 3 points
. Two or more servings of legumes or eggs per week?
yes no
2. Mid-arm circumference (MAC) in cm . Meat, fish, or poultry every day? yes no
a. MAC < 21 = 0.0 points a. if 0 or 1 yes = 0.0 points
b. MAC 21 <_ 22 = 0.5 points b. if 2 yes = 0.5 points
c. MAC > 22 = 1.0 points c. if 3 yes = 1.0 points
3. Calf circumference (CC) in cm 13. Consumes two or more servings of fruits or
a.CC < 31 = 0 points b. CC >
_ 31 = 1 point vegetables per day?
a. no = 0 points b. yes = 1 point
4. Weight loss during last 3 months
a. weight loss greater than 3kg (6.6 lbs) = 0 points 14. Has food intake declined over the past three
b. does not know = 1 point months due to loss of appetite, digestive problems,
c. weight loss between 1and 3 kg chewing or swallowing difficulties?
(2.2 and 6.6 lbs) = 2 points a. severe loss of appetite = 0 points
d. no weight loss = 3 points b. moderate loss of appetite = 1 point
c. no loss of appetite = 2 points
GENERAL ASSESSMENT
15. How much fluid (water, juice, coffee, tea, milk,...)
5. Lives independently (not in a nursing home or hospital)
is consumed per day? (1 cup = 8 oz.)
a. no = 0 points b. yes = 1 point
a. less than 3 cups = 0.0 points
6. Takes more than 3 prescription drugs per day b. 3 to 5 cups = 0.5 points
a. yes = 0 points b. no = 1 point c. more than 5 cups = 1.0 points
7. Has suffered psychological stress or acute 16. Mode of feeding

disease in the past 3 months a. Unable to eat without assistance = 0 points
a. yes = 0 points b. no = 2 points b. self-fed with some difficulty = 1 point
c. self-fed without any problem = 2 points
8. Mobility
a. bed or chair bound = 0 points SELF ASSESSMENT
b. able to get out of bed/chair but does
17. Do they view themselves as having nutritional problems?
not go out = 1 point
a. major malnutrition = 0 points
c. goes out = 2 points
b. does not know or moderate malnutrition = 1 point
9. Neuropsychological problems c. no nutritional problem = 2 points
a. severe dementia or depression = 0 points
18. In comparison with other people of the same age. how
b. mild dementia = 1 point
do they consider their health status?
c. no psychological problems = 2 points
a. not as good = 0.0 points
10. Pressure sores or skin ulcers b. does not know = 0.5 points
a. yes = 0 points b. no = 1 point c. as good = 1.0 points
d. better = 2.0 points
DIETARY ASSESSMENT
ASSESSMENT TOTAL (max.30 points):
11. How many full meals does the patient eat daily?
a. 1 meal = 0 points
MALNUTRITION INDICATOR SCORE
b. 2 meals = 1 point
c. 3 meals = 2 points _ 24 points
> well-nourished
17 to 23.5 points at risk of malnutrition
< 17 points malnourished
FIGURE 18.4
The Mini Nutritional Assessment form.
Nutritional Assessment in Older Adults

The descriptions of the screening tools used to define nutritional status among elderly
people highlight the fact that one of the more difficult determinations in elderly people
is the accurate assessment of their nutritional status. This evaluation is more challenging
in older adults because of the physiologic changes that occur with normal aging. Many
of the commonly used assessment standards are not reliable in this population for a variety
of reasons.23
Anthropometric Measures
Anthropometric measures, including height, weight, and skinfold measures, are usually
important components of a nutritional assessment. These parameters are the ones most
affected by the aging process.24 The most apparent age-related change occurs in height.
Height decreases as people get older due to changes in skeletal integrity, most noticeably
affecting the spinal column. Loss of height may be due to thinning of the vertebrae,
compression of the vertebral discs, development of kyphosis, and the effects of osteoma-
lacia and osteoporosis.25 Loss of height occurs in both males and females, although it may
happen more rapidly to elderly women with osteoporosis. Therefore, stature changes and
body appearance may be altered and, as older people lose their ability to stand erect, the
organs in the thoracic cavity will become displaced and breathing and gastrointestinal
problems may ensue.26,27
Height is difficult to measure in individuals who are unable to stand erect, cannot stand
unaided, cannot stand at all due to neuromuscular disorders, paralysis, or loss of lower
limbs, or are bedbound due to other medical problems. One estimate of stature in these
individuals is to measure their recumbent height or the bone lengths of extremities.23,28
This estimate of stature may not be very reliable, but it provides some estimate of height
to help determine whether body weight is appropriate for height.
Weight is another important anthropometric measure that is altered with advancing age.
Weight changes occur at different rates among elderly people. Use of most standard height
and weight tables is not valid in older people since most reference tables do not include
elderly people in their subject pool, and most are not age-adjusted.
Body mass index (BMI) is a commonly-used measure to evaluate relative weight for
height using a mathematical ratio of weight (in kilograms) divided by height (in square
meters).
Wt (Kg)/Ht (M)2
This formula yields a whole number that should be greater than 21 and less than
approximately 35.10 Nomograms and tables are available that minimize the need for
calculation. There is some controversy among experts regarding the range of acceptable
BMI measures in elderly people.4,29
Skinfold measurements (triceps, biceps, subscapular, suprailiac, thigh) are often
included in a thorough nutritional assessment. However, loss of muscle mass, shifts in
body fat compartments, changes in skin compressibility and elasticity, and lack of
age-adjusted references serve to decrease the reliability of skinfold measures in the assess-
ment of nutritional status in elderly people.30
Biochemical Measures
Biochemical assessment parameters are also affected by advancing age.23 Laboratory mea-
sures may reflect an age-related decline in renal function, fluid imbalances or hydration
status, or the effects of long-term chronic illnesses. Among the commonly used biochemical
markers of nutritional status, serum transferrin is one that is markedly affected by advanc-
ing age. Since tissue iron stores increase with age, circulating serum transferrin levels are
reduced. A lower than normal serum transferrin should be evaluated in relation to other
biochemical measures and serum iron levels, if obtainable.31
The most reliable predictor of nutritional status in elderly people is serum albumin. A
serum albumin below 4.0 g/dl (depending on local laboratory normal ranges) is not usual
in an older person unless the subject is overhydrated, has cancer, renal or hepatic disease,
or is taking medications that may interfere with hepatic function. Recent evidence suggests
that serum albumin is a prognostic indicator of potential infectious complications and
other nosocomial problems in hospitalized, frail, or dependent elderly individuals.32 A
depressed serum albumin seems to be a primary prognostic indicator of rehospitalization,
extended lengths of stay, and other complications associated with protein energy malnu-
trition in elderly people.33,34 Unless there are medical reasons, most biochemical measures
should remain within normal limits.
Serum cholesterol has been considered in the risk for coronary heart disease, but a
depressed serum cholesterol is also associated with poor health status in older people.35
It may be predictive of impending mortality36 and should be evaluated carefully within
the context of other health measures.
Immunologic Assessment
Tests for immunocompetence are often included as part of a nutritional assessment because
malnutrition results in compromised host-defense mechanisms. However, the incidence
of anergy is reported to increase with advanced age, and the response to skin test antigens
appears to peak after longer intervals in older people.37 The value of these tests is limited
in elderly people.
Socioeconomic Status
Social history, economic status, drug history, oral health condition, family and living
situations, and alcohol use should be evaluated along with the physical and physiologic
measures usually assessed.23 It is also useful to assess elderly individuals using instru-
ments that evaluate how well they perform activities of daily living. Available tools assess
the capability of an individual in managing the activities necessary for independence;
these tools add another valuable dimension to the assessment of elderly people.38,39 (See
Tables 18.1 and 18.2.)
Summary
Nutrition monitoring, screening, and assessment in the older adult population pose chal-
lenges to health care professionals due to the heterogeneity of this group. It has been said
that the older we become, the more unique we are. The difficulty in using the tools
TABLE 18.1
Activities of Daily Living
Toileting
Cares for self; no incontinence

Needs to be reminded or needs help with cleanliness; accidents rare
Soiling or wetting at least once a week
No control of bladder or bowels
Feeding
Eats without assistance

Eats with minor assistance or with help with cleanliness
Feeds with assistance or is messy
Requires extensive assistance with feeding
Relies on being fed
Dressing
Independent in dressing and selecting clothing

Dresses and undresses with minor assistance
Requires moderate assistance with dressing and undressing
Needs major assistance with dressing but is helpful
Completely unable to dress and undress oneself
Grooming
Always neatly dressed and well groomed

Grooming adequate; may need minor assistance
Requires assistance in grooming
Needs grooming care but is able to maintain groomed state
Resists grooming
Ambulation
Totally independent
Ambulates in limited geographical area
Ambulates with assistance (cane, wheelchair, walker, railing)
Sits unsupported in chair or wheelchair but needs help with motion
Bedridden
Bathing
Bathes independently
Bathes self with help getting into bath or shower
Washes hands and face but needs help with bathing
Can be bathed with cooperation
Does not bathe and is combative with those trying to help
Adapted from M.P. Lawton, The functional assessment of elderly
people, Journal of the American Geriatrics Society 19: 4465, 1971.
TABLE 18.2
Instrumental Activities of Daily Living
Ability to use telephone
Shopping
Food preparation
Housekeeping
Laundry
Mode of transportation
Responsibility for own medications
Ability to handle finances
Adapted from M.P. Lawton, The functional
assessment of elderly people, Journal of the
American Geriatrics Society 19: 4465, 1971.
discussed here is that people age at different rates and in different ways related to their
health status, their lifestyle, and their genetic inheritance. Although a variety of reasonable
approaches to nutrition assessment and monitoring in the older population exist, it is wise
for the clinician to understand that the definitive tool or definition of malnutrition in older
people has yet to be reported and that there are vast opportunities for research in this area.
References
1. Bienia R, Ratcliff S, Barbour GL, et al. J Am Geriatr Soc 30: 433; 1982.
2. Herrmann FR, Safran C, Levkoff SE, et al. Arch Int Med 152: 125; 1992.
3. Harris T, Cook EF, Garrison R, et al. JAMA 259: 1520; 1988.
4. Galanos AN, Pieper CF, Cornoni-Hunt JC, et al. J Am Geriatr Soc 42: 368; 1994.
5. Epstein AM, Read JL, Hoefer M. Am J Pub Health 77: 993; 1987.
6. MacLellan DL, Van Til LD. Can J Pub Health 89: 342; 1998.
7. Millen B, Levine EL. In: Geriatric Nutrition: A Health Professional’s Handbook, (Chernoff R, Ed).
Gaithersburg, MD: Aspen Publishers, 1999.
8. Reuben DB, Greendale GA, Harrison GG. J Am Geriatr Soc 43: 415; 1995.
9. Rush D. Ann Rev Nutrition 17: 101; 1997.
10. Lipschitz DA, Ham RJ, White JV. Am Fam Phys 45: 601; 1992.
11. Wellman, NS. Nutrition Today (II), 44S; 1994.
12. Posner BM, Jette AM, Smith KW, Miller DR. Am J Pub Health 83: 972; 1993.
13. Rush D. Am J Pub Health 83: 944; 1993.
14. Boyd LD, Dwyer JT. J Dental Hyg 72: 31; 1998.
15. Saunders MJ. Special Care in Dentistry 15: 26; 1995.
16. Jensen GL, Kita K, Fish J, et al. Am J Clin Nutr 66: 819; 1997.
17. Curl PE, Warren JJ. Clin Nurse Spec 11: 153; 1997.
18. Detsky AS, McLaughlin JR, Baker JP, et al. J Parent Enteral Nutr 11: 8; 1987.
19. Detsky AS, Baker JP, Mendelson RA, et al. J Parent Enteral Nutr 8: 153; 1984.
20. Baker JP, Detsky AS, Wesson D, et al. N Engl J Med 306: 969; 1982.
21. Guigoz Y, Vellas B, Garry PJ. Nutr Rev 54: S59; 1996.
22. Guigoz Y, Vellas B, Garry PJ. Facts Res Gerontol 4: 15; 1994.
23. Mitchell CO, Chernoff R. In: Geriatric Nutrition: The Health Professional’s Handbook, 2nd ed.
(Chernoff R, Ed). Gaithersburg MD, Aspen Publishers, 1999.
24. Mitchell CO, Lipschitz DA. Am J Clin Nutr 35: 398; 1982.
25. Chumlea WC, Garry PJ, Hunt WC, et al. Hum Biol 60: 918; 1988.
26. Silverberg SJ, Lindsay R. Med Clin N Am 71: 41; 1987.
27. Heaney RP. In: Nutrition in Women’s Health (Krummel DA, Kris-Etherton PM, Eds) Gaithers-
burg MD, Aspen Publishers, 1996.
28. Martin AD, Carter JEL, Hendy KC, et al. In: Anthropometric Standardization Reference Manual
(Lohman TG, Roche AF, Martorell R, Eds) Champaign IL, Human Kinetics Publishers, 1988.
29. Nutrition Interventions Manual for Professionals Caring for Older Adults. Washington DC,
Nutrition Screening Initiative, 1992.
30. Chumlea WC, Guo SS, Glasser RM, et al. Nutrition, Health and Aging 1: 7; 1997.
31. Fleming DJ, Jacques PF, Dallal GE, et al. Am J Clin Nutr 67: 722; 1998.
32. Finucane P, Rudra T, Hsu R, et al. Gerontology 34: 304; 1988.
33. Ferguson RP, O’Connor P, Crabtree B, et al. J Am Geriatr Soc 41: 545; 1993.
34. Sullivan DH, Walls RC, Lipschitz DA, Am J Clin Nutr 53: 599; 1991.
35. Wilson PWF, Anderson KM, Harris T, et al. J Gerontol Med Sci 49: M252; 1994.
36. Rudman D, Mattson DE, Nagraj HS, et al. J Parent Enteral Nutr 12: 155; 1988.
37. Cohn JR, Buckley CE, Hohl CA, et al. J Am Geriatr Soc 31: 261; 1983.
38. Katz S. J Am Geriatr Soc 31: 721; 1983.
39. Spector WD. In: Quality of Life Assessments in Clinical Trials (Spilker B, Ed) New York, Raven
Press, 1990.
19
Dietary Intake Assessment: Methods for Adults
Helen Smiciklas-Wright, Diane C. Mitchell, and Jenny H. Ledikwe
Introduction
There has been longstanding interest in assessing diets of individuals.1,2 Early in the 20th
century, nutritionists studied food and nutrient intakes in order to provide guidance in
food selection,3,4 to interpret clinical and laboratory findings,5 and to establish dietary
requirements.6,7 Interest in dietary assessment was stimulated in the latter part of the
century with the increasing evidence for the role of diet in promoting health and reducing
chronic disease risk.8-11
Early investigators were concerned with many of the issues that continue to be important
for dietary assessment:
1. Selecting appropriate methods for collecting dietary data5,12-15

2. Assessing the day-to-day variability of intakes by individuals12,16,17
3. Establishing procedures for data analysis18-20
4. Estimating food/food group and nutrient intake5,21
The following statement appears in the National Research Council’s report on diet and
chronic disease: “One of the most difficult tasks in nutrition research is documenting the
actual or habitual food and nutrient intake of individuals or groups.”8 We should not be
surprised that obtaining information about what individuals consume and analyzing for
dietary components is a challenging undertaking. Food intake can be a complex behav-
ior.22 In any day, an individual may consume many different foods, at several eating
occasions, both at home and away from home. Willingness and ability to report what is
consumed can be influenced by social and environmental events and cognitive abili-
ties.23-25 Furthermore, food composition databases must continuously be updated to reflect
an expanding food marketplace and an increasing number of dietary components asso-
ciated with health.26
This section is organized to review the methods most commonly used to assess intakes
by individuals. Attention is given to methodologic validity as well as to the current
emphasis on food pattern analysis, dietary supplements, and functional foods.
0-8493-2705-9/01/$0.00+$1.50
Methods of Dietary Assessment

The common methods for assessing intakes by individuals are food records, recalls, and
food frequencies/diet histories. There have been several reviews of dietary assessment
methods, their appropriate uses, modes of administration, and sources of error.1,27-31 Meth-
ods are generally characterized either by the reference period in which respondents are
asked to provide information (i.e., retrospective and prospective methods)31 or by the time
frame for which data are collected (i.e., quantitative daily and food frequency methods).27,28,30
There is no single optimal dietary assessment method. The objectives of an assessment
should be used as a guide in selecting the most appropriate method. Some 30 years ago,
Christakis advised that the assessment method selected should be no more detailed, no
more cumbersome, and no more expensive than necessary.32 This advice is still sound.31
Assessment protocols, regardless of method, may need to provide highly quantitative and
detailed data on food consumption. This would be the case for research studies such as
clinical trials.33 More qualitative data is likely to be appropriate when food intake infor-
mation is used for dietary guidance and counseling.34
Food Record
Food records, also known as food diaries, provide a prospective account of foods and
beverages consumed in a defined period of time. Generally, records are kept for brief time
periods (one to seven days),28 but they have been kept for up to a month35 and even a
year.36 To be representative of usual intake, multiple days of records are needed.27,37
Food records may be used to meet a variety of objectives. Records are useful for detecting
imbalances in food intake and making dietary change recommendations.38 They are used as
self-management tools in weight loss interventions and may be valuable in predicting suc-
cessful weight loss.39 Food records have been used extensively to calibrate other dietary
assessment methods.40-45 Records are also useful for documenting compliance of an individ-
ual’s food intake with a feeding protocol in studies where adherence to a specific diet regimen
is important.46 Intervention studies may use food records to document effectiveness.47-49
Food portions may be either weighed or estimated depending on the subjects and the
purpose(s) of the assessment.50 While weighing foods will increase the accuracy of the
portion size recorded, it can also increase respondent burden. Sophisticated scales that do
not disclose food weights are available, decreasing respondent recording burden51 but
increasing cost. A variety of portion size aids, listed in Table 19.1, are available when
portion sizes are to be estimated.
While records are usually kept by respondents, they may also be kept by observers.
When food intake is recorded by observation, trained personnel visually estimate dietary
intake.52,53 Observation is particularly useful when circumstances preclude self-reporting
of food intake. Thus, observation has been used in assessing intake of nursing home
residents. The Omnibus Budget Reconciliation Act54 requires that all Medicare and Med-
icaid certified nursing facilities implement a standardized comprehensive assessment,
including a measure of nutrient intake, for all residents. Observers visually estimate the
portion of served items consumed (i.e., from all to none) by a resident.55
When using food records, consideration should be given to the record forms to be used
as well as instructions and training for subjects, particularly regarding portion size. Instruc-
tions should include guidance on completing the record form as well as directives encour-
aging subjects to record foods at the time of consumption and not to alter normal eating
patterns. Table 19.2 provides sample instructions for the administration of a food record.
Dietary Intake Assessment: Methods for Adults 479
TABLE 19.1
Tools for Portion Size Estimation
Type Examples
Household measures Measuring cups and spoons161
Rulers161
Food models Food replicas165
Graduated food models166
Thickness sticks161
Pictures 2-Dimensional portion shape drawings124,161
Portion photos of popular foods167
Portion drawings of popular foods161
Food labels Nutrition facts label
Food package weights
TABLE 19.2
Sample Instructions for the Administration of a Food Record
To help us do the best analysis of your food intake, please follow these instructions.
Maintain Your Usual Eating Pattern. Try not to modify your food intake because you are keeping a record.
Record Everything You Eat or Drink. Be sure to include all snacks and drinks. Also include any vitamin or
mineral supplements and the dosage for each day.
Write Foods Down As Soon As You Eat Them. Three daily record pages are provided for each day; however,
you may not need to use all three. Try to write clearly.
Details are Important!
Completing the food record form
Date. Please record the date at the top of each form.

Name. Please write your name in the space at the top of the form.
Time of Day. Record the time of the day you ate each meal, including AM or PM.
Meal/Where Prepared? Record the name of the meal eaten (i.e., breakfast, lunch, dinner, supper, or snack) and
where the meal was prepared (i.e., at home, at a restaurant).
Food Item. Write the name of each food item eaten.
Description/Preparation. Include information on how each food was prepared.
Amount. Record the amount of each food either by using the poster provided or common household measures.
After records have been completed, they should be reviewed to ensure completion. If
reviewed with the subject, probing questions may be used to clear up ambiguities and
ensure the completeness of the record. This is termed interviewer-assisted food records.
When data from food records are compiled and analyzed, records will need to be coded
using a standard method.
As subject burden can be high for food records, participant willingness and abilities are
considerations when using this method. Literacy is required for completion of records;
therefore, the method may not be appropriate for all individuals. The act of keeping food
records can affect dietary intake,56,57 which may be critical for estimates of usual intake.
Cost is an additional consideration, as reviewing records for completeness, data entry, and
data analysis can be expensive.31
Recall
Dietary recall provides a retrospective record of intake over a defined time period. While
dietary recall may be for any length of time, this method is almost always administered
to cover a 24-hour time period and is generally termed the 24-hour recall.30 Data can be
collected either for the previous day or for the 24 hours preceding the interview. To
estimate the usual intake of individuals, multiple recalls are needed, preferably on random,
nonconsecutive days.36,58 Typically, an individual is asked to recall all foods eaten during
the reference time period, describe the foods, and estimate the quantities consumed.
The 24-hour recall has become a favored way of collecting dietary data,33,47,59 as recalls
can be administered easily and quickly with low respondent burden. Depending on the
objectives of the recall, the amount and depth of information collected will vary. This
method is becoming the gold standard, particularly as methodological improvements60-62
and technological capabilities63,64 increase validity. With the emergence of technological
aids in dietary assessment, it is becoming more common for interviewers to collect intake
data using interactive software, entering intake data directly into a computer as it is
collected.
Recalls may be obtained either in person or by telephone-administered interview.
Because recalls by telephone interview have been shown to be practical, valid, and cost-
effective,63-68 they are becoming an increasingly popular mode of data collection, especially
for research purposes.
Prior to conducting recalls, training of interviewers is important. This is particularly
relevant when more quantitative data are required, increasing the need to use multiple
pass and probing techniques. Figure 19.1 provides a sample probing sequence to elicit
detailed information regarding one specific food (i.e., macaroni and cheese). The complex-
ity of this probing sequence exemplifies the potentially complex nature of probing ques-
tions and the need for good interviewer training. More qualitative food intake data can
be achieved with more limited questions.
The 24-hour recall has been criticized because of accuracy related to portion size esti-
mation and subject memory. Portion size estimation aids are available to facilitate quantity
estimation (Table 19.1). While 24-hour recalls are not designed to affect the “encoding” of
food information, they can incorporate strategies to facilitate memory retrieval. Those
strategies include standardized data collection protocols, structured probes to ensure
standardized collection, and interactive interview systems.29,47 The multiple pass tech-
nique, which will be discussed later in this section, has also been designed to facilitate
memory retrieval.
Food Frequency Questionnaire

Food frequency questionnaires (FFQs) are designed to obtain information about usual
food consumption patterns. They provide estimates on intake over a specified time period,
ranging from as little as a week69 to as much as one year.70 FFQs consist of a list of foods
and frequency-of-use response categories. Questionnaires may also include portion size
response categories. Food lists may be extensive in order to provide estimates of total
intake or they may be focused on foods, groups of foods, or nutrients. Several nutrient
specific FFQs have been developed which allow for the examination of selected nutrients
such as fat,71 vitamin A,72 and vitamin B6.73 While not necessarily appropriate for identi-
fying precise nutrient intake, these instruments can provide a rapid, cost-effective way to
estimate an individual’s usual intake.74
Questionnaires may be abbreviated when used to screen for nutritional risk. Screening
instruments are typically brief, self-administered, and can be scored quickly, providing an
efficient way to monitor eating patterns of individuals. Examples of screening tools include
the instruments developed as part of the Nutrition Screening Initiative, which were
designed to identify older adults who may need nutrition services and to provide diag-
Macaroni & Cheese
What type of macaroni and cheese was it?
Plain
With egg
With frankfurters
How was it prepared?
Canned or frozen
Prepared from a mix
Prepared from a recipe
Dried cheese sauce

What type of fat was used Prepared cheese sauce What type of cheese sauce
in the mix? Unknown type of cheese was in the mix?
What kind of butter Was the butter

was used in the mix? salted or unsalted?
Butter Regular Salted
Margarine Whipped Unsalted
Oil Light Unknown
Shortening Butter/margarine
Lard Unknown
Animal Clarified or butter oil
No fat used
Unknown if fat used
Unknown type of fat used What type of milk
was used in the mix?
How much did

Whole
you eat?
2% fat
AMOUNT
11 2% fat
CONSUMED
1% fat
1 2 % fat
skim, nonfat, or fat-free

lactose reduced (Lactaid)
Unknown
FIGURE 19.1
A sample probing scheme. This scheme could be used with recalls to elicit more information from a respondent
who consumed macaroni and cheese. Bold print indicates respondent’s reply. Probing questions, which are
specific for each response, are italicized. (Adapted from Nutrition Data System for Research [NDS-R] software,
developed by the Nutrition Coordinating Center [NCC], University of Minnesota, Minneapolis, MN.)
nostic information on nutrition status.75,76 Very abbreviated instruments may not be valid
representations of true intake.77
Creating a food frequency questionnaire is an intensive process,78 thus, there is heavy
reliance on instruments that have already been developed. Validity is a critical issue and
is generally determined by calibration with other assessment methods.73,79-84 When using
an FFQ, it is important to ensure that the questionnaire is valid for use in the population
of interest, as the performance of an instrument may vary between subgroups. Question-
naires have been validated in specific populations such as adolescents,85 pregnant
women,42 and low-income black women.86
Several cognitive issues could compromise the validity of an FFQ. Subjects may have
difficulty recalling foods consumed over a lengthy time period. Additionally, participants
may need to perform arithmetic computations to average usual consumption of foods to
fit into the response categories for consumption frequency. The cognitive demands of the
FFQ may be reduced by a new variation in questionnaire administration, termed the
picture sort approach, in which participants sort food cards into categories.87,88
While FFQs generally provide qualitative data, if portion size estimation is included on
the questionnaire, semi-quantitative information can be deduced from these instruments.
In some cases, inclusion of portion size may yield only small differences in data as
compared to FFQs analyzed using only medium portions.89
Diet History
Food frequency questionnaires are sometimes referred to as diet histories. The classic diet
history method was designed to estimate an individual’s usual intake over a relatively
long period of time. Originally developed by Burke,90 the method consists of several
components, including a 24-hour recall and questions about usual eating patterns, a cross-
check questionnaire with a list of foods and questions about likes, dislikes, and usages,
and a three-day food record. This method is not used commonly today. Administration
requires a highly trained dietitian and can be time consuming.
Summary
Several methods have been listed which can be used to assess the usual dietary intake of
adults. Well-designed quality control procedures are particularly important in research
studies to ensure consistency of data across time and subjects.33 Additionally, the advan-
tages and disadvantages of data collection modes (i.e., self- or interviewer-completed)
should be considered (See Table 19.3). The success of any assessment method is based
upon a partnership between the individual respondent and the assessment staff. Care
should be taken to ensure the appropriateness of the method and the level of detail
collected. Respecting participants’ abilities and ensuring that their dignity is not compro-
mised is salient in establishing a successful partnership.
Issues Affecting Validity

In his address at the First International Conference on Dietary Assessment Methods,
Beaton stated, “In the past decade there has been a great deal published about the errors
TABLE 19.3
Self-Completed and Interviewer-Completed Data Collection
Collection Mode Advantages Disadvantages
Self Interviewer training not needed Response rate may be low
Sense of privacy Respondent burden may be high
Data collection time may be reduced Tasks may be misinterpreted
Respondent training needed for more
complete data
Data preparation and entry time may
be high
Interviewer by phone Good Response rate Contact times may be inconvenient
Opportunities for probing Hearing problems for some subjects
Low respondent burden Availability of portion aids
Relatively quick Data collection may be more
Interviewer anonymity expensive for toll calls
Potential for interviewer bias
Interviewer in person Good response rate Contact times may be inconvenient
Opportunities for probing Potential for interviewer bias
Low respondent burden
Respondent interviewer rapport
in dietary data…this is understandable, but unfortunate because it can easily leave the
impression that dietary data are worthless.”91 He reminded his audience that, while dietary
intake data cannot and never will be estimated without error, a serious limitation is not
the errors themselves, but failure to understand the nature of the errors and the consequent
impact on data analysis and interpretation. Several recent reviews have delineated poten-
tial sources of error for different assessment methods.28,31,51 Consideration of strategies to
minimize error is pertinent in yielding accurate intake data, regardless of assessment
method (see Table 19.4).
Recent attention to the accuracy of dietary intake data has focused on the underreport-
ing of energy by 10 to almost 40%.59,92-97 These findings are based on an extensive literature
comparing intakes to energy needs estimated using doubly-labeled water,98 weight main-
tenance data,59 and applying age- and sex-specific equations to estimate energy require-
ments.99 Underreporting has been found to be more common among women99-101 and
older persons99,100,102 as well as overweight,99-101 post-obese,92 and weight-conscious indi-
viduals.99,100 Literacy103 and depression104 have been associated with underreporting. Selec-
tive underreporting has also been associated with certain food types such as fats95,99,105
and sweets.105
While underreporting of energy is common in groups of individuals,59,94,95,99,100,106-108 both
underreporting and overreporting can occur.44,59,100 Individuals who possess characteristics
TABLE 19.4
Benefits Derived from Minimizing Assessment Error
Clinical Setting Research Setting
Improve ability to detect inadequate, imbalanced, or Improve accuracy of nutrient intake estimations
excessive dietary intake
Provide a better basis for nutrition counseling and Decrease attenuation between intake data and
interventions biomarkers
Improve ability to monitor dietary changes Provide a better basis for nutrition education program
Provide a better basis for elucidation of diet-disease
relationships
associated with underreporting may actually report intake accurately or overreport intake.
However, the magnitude of underreporting may be even greater for individuals as error
due to overestimation can reduce underestimation bias in groups.102
Due to the complex nature of intake data and the variability of under and over reporting,
it is unlikely that a single correction factor will be derived that could be applied to self-
reported energy intake.109 The purpose of this section is to review components of assess-
ment that may be modified to reduce sources of error.
Memory
Food recall is a cognitively demanding task. Understanding of dietary recall accuracy is
derived from advances in cognitive psychology.23 Classic work in this area described
memory processes: encoding or learning information, transmission to long-term memory,
and retrieval.110-112 Early studies described strategies for encoding information as well as
strategies for retrieving memories, such as free recall, recognition, and cued recall.
The memory model of cognitive psychology is applicable to dietary recall.25 To accurately
report intake, people must be able to remember what foods were consumed, how the
foods were prepared, and the quantities of foods eaten. This requires the acquisition of
specific food memories and the ability to retrieve these memories. Individuals who pay
little attention to foods consumed, people who have difficulty storing information in
memory, and those who lack the cognitive ability to retrieve food memories may not be
able to accurately recall dietary intake.
Several techniques have been developed to reduce memory-related error in dietary data.
For the 24-hour recall, techniques such as probing (See Figure 19.1),113 encoding strategies,25
memory retrieval cues,25 and a multiple pass system59,62 have been employed to improve
memory. Campbell and Dodd’s113 classic paper showed that probing elicited additional
information with significant impact on total caloric intake. Ervin and Smiciklas-Wright
found that older adults were able to remember more foods when a deeper processing
strategy was used during encoding and a recognition task was used for memory retrieval.25
Record-assisted recalls may be used to help reduce memory-related error in food
records.114,115
Recent work suggests that 24-hour recalls which incorporate a multiple pass technique
into a standardized interview protocol with structured probes can reduce the commonly
observed underestimation of intake for groups of individuals.62 A multiple pass technique
provides respondents several opportunities (i.e., passes) to recall foods eaten using both
free recall and cued (probed recall) strategies.59,62,116,117 As generally administered, the
strategy involves three recall passes: an introductory opening sequence in which a respon-
dent is asked to recall all items eaten, an interactive, structural probe sequence to elicit
food descriptions and amounts, and a final review of the recall. The multiple pass tech-
nique is theoretically sound,117 and when incorporated into a well-structured interactive
interview process may decrease underreporting for groups of individuals.59,62 While these
studies are encouraging for the presentation of group data, there is room for improvement
in assessing individuals’ intakes.59 Little data exists, however, on alternative modes of
administering a multiple pass strategy and the “gains” at each pass.
A multiple pass technique can be facilitated by the use of interactive software.118 This
allows for a greater level of detail and facilitates data collection, but the technology is
generally expensive and is not used commonly in clinical settings. However, written
tools, such as probing guides, may be used to mimic this process when quantitative
analysis is critical.
Portion Sizes
It is well documented that individuals have difficulty estimating amounts of foods and
beverages.61,119-121 There is a tendency toward overestimation of smaller portion sizes and
underestimation of larger portion sizes which can lead to the “flat slope syndrome.”121,122
Portion size estimation aids (Table 19.1) have been shown to reduce portion size estimation
error.123 Estimation aids vary in sophistication and cost. Choice of tools is dictated partially
by feasibility. In a clinical setting, aids such as food replicas, real foods, and food picture
books may be appropriate. For interviews conducted by phone, tools that are compact for
mailing, such as a chart with two-dimensional portions,124 would be more appropriate.
A number of investigators have investigated whether training subjects to “judge” por-
tion sizes improves quantity estimates.61,125-130 These studies suggest that training effects
may be retained for some days after training and may have significant impact on some,
but not all foods. For example, amorphous foods (e.g., salads) are more resistant to training
effects.
Variability of Intake
Day-to-day variation of food intake has been well documented in the literature.36,131,132
Accordingly, assessment of an individual’s total dietary intake, particularly by quantitative
daily methods, at any one time may not yield an accurate measure of usual intake.36
Basiotis et al. found that over 100 days of dietary data may be needed to accurately estimate
an individual’s typical intake for certain nutrients, such as vitamin A.133 To lessen the effect
of day-to-day dietary variation when using 24-hour recalls, assessment should be done
on multiple, random, nonconsecutive days36,58,134 that include both weekend and week-
days. For food records and 24-hour recalls, increasing the number of assessment days will
decrease error related to variation in food intake; however, this must be balanced with
subject tolerability and assessment objectives.
Consumption Frequency
Accurate estimation of how often foods are consumed is particularly important for retro-
spective assessment methods. For food frequency questionnaires, frequency of consump-
tion estimates may contribute more error than portion size estimates.135 The cognitive
demands required to mathematically calculate consumption frequency contribute to the
error involved with this measure. It has been suggested that the precision of food frequency
questionnaires can be increased by not using predefined consumption frequency catego-
ries, such as three to four times per week, instead allowing participants to simply enter
a number to reflect intake.135 Ability to accurately recall the frequency of consumption of
foods deteriorates as the amount of time between intake and assessment increases, yet
longer reference time periods yield more accurate results than questionnaires with shorter
reference periods.136
Response Bias
All assessment methods are subject to response bias. Social desirability may lead some
individuals to selectively omit foods that may be regarded as unacceptable (e.g., alcohol,
high fat foods),23 while others may report eating a healthier diet than that which was
actually consumed.137,138 Self-reported assessment data may also be biased by participation

in a dietary intervention.139
For both interviewer-assisted and self-completed assessment, questions should be
reviewed for face validity to help ensure that participant comprehension of the questions
is appropriate. When using interviewers to collect data, training to avoid leading questions
and verbal and nonverbal cues that may appear to be judgmental can decrease response
bias. Quality control procedures can ensure that interviewer questioning is consistent and
nonbiasing.140,141 Conducting interviews by telephone may reduce bias compared to face-
to-face interviews.63
In regard to particular assessment methods, food frequency questionnaires may be
subject to response bias, as current diet may influence recall of dietary intake in the past,142
especially for individuals with diet-related illnesses.143 Response bias can also be induced
by methods with a high participant burden. For example, the burden of keeping food
records may lead subjects to submit incomplete records, introducing a response bias.144
Techniques that reduce respondent burden, such as interviewer-assisted food records, can
reduce this effect and may improve the quality of data collected.
Data Entry
Data entry is the link between the information provided by a respondent and analysis of
the data. Data entry often requires decisions by coders to adjust information provided to
meet the demands of a specific data analysis program.145 If the respondent provides
incomplete data or the database does not include all diet items, coders must decide on
reasonable substitutions for portion size or food items. Thus, the quality of the data
provided by respondents, the quality of the database, and the default assumptions by
coders can all contribute to variability in the final food and nutrient data descriptions.145
Decisions about amounts of foods eaten may be guided by U.S. Department of Agricul-
ture (USDA) publications on portions commonly consumed in the United States. The
USDA has published several reports on foods commonly eaten and the quantities con-
sumed at an eating occasion.146,147 These reports provide data on amounts eaten by par-
ticipants in nationwide food consumption surveys.
Food Composition Tables

Food composition databases provide values for the nutritional content of foods. Errors in
these databases will introduce systematic biases during data analysis. Further research to
improve the validity of the nutrient values within food composition databases will further
increase the accuracy of any dietary assessment methodology. This topic will be covered
in more detail in Section 23.
Summary
Dietary assessment is a dynamic field, with novel approaches being developed, such as
computer-assisted self-interviews.148 Various techniques to improve validity have been
developed (See Table 19.5), but much work still needs to be done to decrease both sys-
tematic and random errors. Refinement of current methods and the development of new
techniques will improve confidence in the accuracy of dietary data.
TABLE 19.5
Considerations to Reduce Error when Collecting Assessment Data
Potential Food Frequency
Error Sources 24-Hour Recalls Food Records Questionnaire
Memory Multiple pass technique Interviewer assisted records Memory retrieval techniques
Probing questions Encouraging adherence to
Encoding strategies appropriate instructions
Portion size Portion size estimation aids Portion size estimation aids Portion size estimation aids
Subject training Weighing scale Subject training
Interviewer training Subject training
Day-to-day Multiple recall days Multiple days of records N/A
variability Nonconsecutive days of data Include weekdays &
Include weekdays & weekends
weekends Collect data in different
Collect data in different seasons
seasons
Response bias Interviewer training Objective instructions Objective responses for
Clearly worded, open-ended Reduce respondent burden interviewer mode
questions Limit days of data collection
Objective interviewer
responses
Recalls on unannounced,
random days
Data entry Documentation of decisions Strict coding and data entry Strict coding and data entry
Interactive software with rules rules
detailed probes and Interviewer assisted records Computer scannable forms
automatic coding Detailed probing guides and for automatic coding
instructions
Current Issues in Assessment and Analysis

Dietary Quality Scores and Food Pattern Analysis
Historically, dietary quality scores have been a method of interpreting nutrient intakes of
an individual by comparison with a dietary standard such as the Recommended Dietary
Allowances149 or, more recently, the Daily Reference Intakes.150 The nutrient adequacy ratio
(NAR), the amount of a particular nutrient in the diet divided by the dietary standard,
has been commonly used for a number of years.30,151 A mean adequacy ratio (MAR) can
also be calculated and represents the mean of the NAR for several nutrients of interest.30
Another way to examine the quality of an individual’s diet is to calculate the number of
servings from each food group and compare this with food grouping standards such as
the USDA Food Guide Pyramid.152 However, depending on the food group scheme used,
serving sizes and placement of foods into groups may vary considerably. Approaches to
food group analyses also differ.153 For individuals, a behavioral approach, in which food
group changes are based on nutrition education strategies, is more appropriate. This
approach usually defines specific nutritional education programs for health promotion,
such as the National Cancer Institute’s 5 A Day Program.
With the introduction of the USDA Food Guide Pyramid,152 other dietary quality scores
have been developed which take into account not just nutrients or food group servings
alone, but an aggregation of these two assessments into one score. The Healthy Eating
Index score, created by the USDA, takes into account servings from the major food groups
of the Food Guide Pyramid as well as a dietary variety and health risk-related nutrient
intakes.154 This more comprehensive approach, as well as others that have been devel-
oped,155 is becoming an increasingly popular approach to interpretation of the dietary
intakes of groups or individuals. According to a recent article, identifying food patterns
in groups and in individuals might be a better determinant of risk for disease as well as
mortality.156 This is based on the premise that diets are not comprised of single nutrients
or foods but combinations of nutrients and nonnutrient components. The interactions of
all these dietary components make it difficult to determine the effects of single dietary
components. Additionally, dietary behaviors are complex and many different patterns of
intake may be occurring simultaneously, such as decreasing fat intake while increasing
fruits and vegetables.
Any method of assessing an individual’s dietary intake is dependent on the methods
of interpretation. More comprehensive methods of interpretation may facilitate the iden-
tification of more specific patterns of intake and their relationship to disease.
Dietary Supplements
Increased nutrient intakes from supplements have been related to certain disease risk such
as cardiovascular disease (vitamin E), neural tube defects (folate), osteoporosis (calcium),
and cancer (antioxidants such as vitamin C and beta-carotene). Approximately 40 to 50%
of the general population over the age of two years in the U.S. takes a dietary supplement
(see Table 19.6).157,158 These numbers continue to rise especially for more non-traditional
or complementary therapies such as herbal or botanical supplements. Supplement use is
higher in non-Hispanic white females, and increases with age in some segments of the
population.157,159 The supplement intake of special populations such as individuals with
cancer diagnosis are much higher, up to 80% in some studies.159,160 Knowledge of dietary
supplements as well as an understanding of assessment methods is critical to the overall
assessment of nutrient and other dietary components.
Supplement intake data can be assessed in a variety of ways and is usually collected
by questionnaire, including food frequency questionnaires, or as part of intake data such
TABLE 19.6
Categories of Supplements
Category Examples
Vitamins Vitamin C, E, D, B6
(single or multiple formulations)
Minerals Iron, calcium, chromium, zinc
(single or multiple formulations)
Vitamin(s) with mineral(s) Calcium with vitamin D; vitamin E with selenium
Herbs and other botanicals St. John’s Wort, ginkgo biloba, ginseng, saw palmetto
Flavonoids Quercetin, rutin, hesperidin, diadzin
Carotenoids Lycopene, zeaxanthin, lutein, dried carrot extract,
other vegetable extracts
Fatty acids/fish oils, other oils Linoleic acid, omega 3 fatty acids, DHA EPA
Amino acids/nucleic acids/proteins including co- L-glutamine, coenzyme Q-10, bromelain, tryptophan
enzymes, enzymes & hormones
Microbial prepartions/probiotics Lactobacillus acidophilus, B. bifidus, L. bulgaris
Glandular and other organ preparations Dessicated glands such thyroid and adrenal
Miscellaneous Shark cartilage, pycogenol, chrondoitin sulfate
as by 24-hour dietary recall or by food records. When collected by the latter methods it
is important to recognize that the intake of supplements for the day of data collection may
not reflect the pattern of intake over an extended period of time. Detailed questionnaires,
which are better for capturing long-term intake and frequency of intake, are used fre-
quently in research studies, clinical practice, and nutrition monitoring and surveys.161,162
Quantifying supplement intake is a difficult and tedious process. When collecting sup-
plement information, it is important to identify what level of detail is needed to describe
or quantify dietary intakes with dietary supplements. Strategies may include having those
individuals bring in their supplement labels, or photocopy the labels. Other strategies
include having the participants respond to questionnaires that provide lists of single
vitamins and minerals as well as common brand names for multiple formulations. For
herbal and botanical ingredients and other components not typically found in common
formulations, it might be necessary to identify the active components and, above all else,
to obtain brand name and label information.
Functional Foods
According to the Institute of Medicine of the National Academy of Sciences (1994) the
definition of functional foods is “any food or food ingredient that may provide a health
benefit beyond the traditional nutrients it contains.”163 Currently, there is a major research
emphasis to identify physiologically active components, or phytochemicals, and their
potential for decreasing disease risk. Functional foods can consist of foods or food ingre-
dients, including fruits and vegetables to more specialized products such as those contain-
ing soy or phytostanols (i.e., margarines with claims of reducing blood cholesterol levels).
Since many of the phytochemicals in foods are still under investigation, it is premature
to emphasize quantification of single functional food components in dietary assessment.
However, improvements in individual assessment methods will make it possible to quan-
tify and link these components in functional foods with their potential health benefits.
Examples of where individual assessment plays a significant role in providing this linkage
can be found in the literature examining fruit and vegetable intakes. There are now
databases that can accurately quantify the carotenoid content of foods.118,164 As cooking
methods, storage, and exposure to air and water are known to affect the carotenoid content
of fruits and vegetables, the development of these databases has been a challenge. In the
case of assessing carotenoids, for example, it is important to distinguish between pink
and white grapefruit (i.e., pink grapefruit has 3740 mg lycopene, whereas white grapefruit
has 0 mg). This one simple observation in assessing an individual’s intake can have a
significant impact on determining the relationship between dietary carotenoids and blood
carotenoids and the potential role they may have in cancer risk in groups of individuals.
In assessing diets for research purposes it is important to consider the level of detail
required for other components in foods as well. The assessment issues outlined in this
section are the same for assessing functional foods. As more components are identified
and quantification is possible, databases need to be developed that make analysis of
functional foods and their components possible. The knowledge gained in the study of
functional foods will drive the type and level of detail in methodology and database
development.
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20
Validity and Reliability of Dietary Assessment in
School-Age Children
R. Sue McPherson, Deanna M. Hoelscher, Maria Alexander, Kelley S. Scanlon,

and Mary K. Serdula
Introduction
This review of 50 studies examines the validity and/or reliability of dietary assessment
methods used for school-age children during the last three decades, and discusses the
challenges of measuring children’s dietary behaviors. This section is an update from
previously published work of the referenced authors.67 Recommendations on the use of
available assessment methods are discussed and gaps in our knowledge of dietary assess-
ment in children are outlined, along with suggestions for future research.
Review Methodology
The studies included in this review cover a variety of dietary assessment methods includ-
ing the 24-hour recall, food record, food frequency questionnaire, diet history, and obser-
vation. A total of 41 validity and 9 reliability studies used at least one of these
methodologies and met the three review criteria: 1) publication in a peer-reviewed English
journal article between January 1970 and August 2000; 2) inclusion of school children age
5 to 18 years living in an industrialized country; and 3) reporting of specific reliability
and/or validity tests from a minimum sample of 30 children in either the main study
sample or a subsample (denoted by age, gender, or ethnic), after the publishing author’s
exclusions for analyses. Studies were identified by Medline searches using key words and
supplemented by cross-referencing from author reference lists. Studies that did not spe-
cifically use the words validity, reliability, reproducibility, or repeatability in the results or
discussion may not have been identified. The degree of reliability or validity of the
instrument reported was not considered an inclusion factor. Multiple validity or reliability
studies that were included in a single article were considered separately and are repeated
in the descriptions of results.
0-8493-2705-9/01/$0.00+$1.50
TABLE 20.1
Definitions and Explanation of Tables
General
Study entries are listed in ascending order by age.

Multiple validity or reliability studies included in a single journal article are presented as separate entries in the
appropriate table.
Definitions
Adults required — Adults provided all of the intake information or were required to supplement and assist the
child’s report.
Quantitative — Quantity of food consumed was estimated using weights, measures, or food models. Responses
were open-ended.
Semi-quantitative — Quantity of food consumed was estimated using a standard portion size, serving, or a
predetermined amount, and respondent was asked about the number of portions consumed.
Non-quantitative — Quantity of food consumed was not assessed.
Self-administered — Child completed the dietary assessment without assistance.
Group-administered — Child completed the dietary assessment with help from a proctor, teacher, or caregiver in
a group setting.
Interviewer-administered — A trained interviewer elicited the dietary assessment information from the child in a
one-on-one setting.
Results Section
Omission of any of the following components indicates it was not provided in the article or was from a sample
of less than 30 children. Statistical significance of measures is noted with clarifications as to whether significance
testing was shown in the article or only reported via a statement from the publishing authors. The results are
ordered as follows:
Correlations for energy, protein, and total fat between methodologies or administrations.
Range of correlations between methodologies or administrations for the nutrients assessed.
For validity studies: the absolute values and percent difference in energy intake between the validation standard
and the instrument ([instrument-validation standard]/validation standard × 100).
For reliability studies: the absolute values and percent difference in energy intake between the first and follow-
up assessment ([follow-up instrument-first instrument]/follow-up instrument × 100).
Comparison of mean intake of nutrients assessed.
Comparison of foods or food groups consumed.
Comparison of portion size.
Results by age, gender, or ethnicity.
Dietary Assessment Methodologies

The following topics define each dietary method and refer its tables of results of validity
and reliability studies, thereby providing a summary of the current state of each field. The
format of entries in Tables 20.2 through 20.6, which contain the validity and reliability
studies for the various methods, is explained in Table 20.1.
24-Hour Recall (Table 20.2)

The 24-hour recall consists of a structured interview in which a trained nutritionist or
other professional asks the child and/or adult caregiver to list everything the child ate or
TABLE 20.2
Recall Validity Studies Among School-Age Children
Validation
Reference Sample Age/Grade Instrument Standard Design Results
Basch et al. 1990 16 18 Mb 4-7 y Evening Observation Compared mothers’ Energy-adjusted Pearson correlations between recalled evening
28 Fb Adults meal recall; recall of what child meal and observed evening meal were 0.71 for energy, 0.50 for
Latino requiredc quantitative ate at evening meal protein, and 0.52 for total fat. Range of correlations for 18
on the previous day nutrients assessed was –0.10 for phosphorus to 0.82 for iron.
against observation of Recalled energy intake was 9% higher than observed intake (507
the meal. Excerpted vs. 465 kcal/meal). Seven nutrients were significantly
evening meal from overestimated by recalled intake of the meal (significance testing
24-hour recall. not shown). Range of mothers reporting fewer items consumed
as compared to the number of items observed consumed was
between 4 and 30%. 15.5% of reported portion sizes were smaller
and 33.5% of portions were greater than those observed
(significance testing not shown).

Eck et al. 198911 33 M&F 4-9.5 y Lunch recall; Observation Compared mother’s, Pearson correlations between consensus recall of lunch and
Adults quantitative father’s, or both observed lunch were 0.87 for energy, 0.91 for protein as % of
required parents plus child’s kcal and 0.85 for total fat as % of kcal. Range of correlations for
(consensus) recall of 9 nutrients assessed was 0.75 for carbohydrate as % of kcal to
lunch against 0.91 for protein as % of kcal. Pearson correlations between
observation of lunch observed intake and fathers’ recall were 0.83 for energy, 0.79 for
on the previous day. protein as % of kcal and 0.72 for total fat as % of kcal. Pearson
Excerpted lunch meal correlations between observed intake and mother’s recalled
from 24-hour recall. intake were 0.64 for energy, 0.56 for protein as % of kcal and
0.65 for total fat as % of kcal. Recalled energy intake from the
consensus, fathers’ and mothers’ recalls was 2% (558 kcal/meal),
Validity and Reliability of Dietary Assessment in School-Age Children
5% (545 kcal/meal) and 4% (550 kcal/meal) lower than observed

intake (572 kcal/meal), respectively. Only mothers’ recall of
energy from dairy foods/beverages and snacks/desserts were
significantly different from observed intake. There were no
significant differences in mean nutrient intake between any pairs
compared. Qualitative comparison of number of items recalled
revealed that only fathers’ recalls of non-dairy beverages and
snacks/desserts differed significantly from observed intake.
Consensus approach appeared to reduce the tendency to
overreport low intakes and underreport high intakes (flattened
slope phenomenon).
497
498

Validation
Lindquist et al. 17 Mb 6.5-11.6 y Three 24- f
TEE by Compared average of Pearson correlation between average recalled intake and TEE was
200065 13 Fb Adults hour recalls, doubly- 3 child’s parent- 0.32 for energy. Recalled energy intake was 0.5% higher than
17 White required one phone, labeled assisted recalls TEE from doubly-labeled water (7.90 vs 7.86 mJ/day).
13 Black two water against 14-d TEE. Inaccuracy in energy reporting was not predicted by age, gender,
interview ethnicity, social class, or adiposity.
Reynolds et al. 18 M&F 7-8 y Daytime Observation Compared average of Recalled energy intake was 34% lower for 7-8 year olds (1818 vs.
199017 25 M&F 9-10 y recall; non- 3 child’s recalls of 2751 kcal/daytime meals), 21% lower for 9-10 year olds (2291
31 M&F 11-12 y quantitative daytime meals vs. 2887 kcal/ daytime meals) and 17% lower for 11 year olds
against observation of (2643 vs. 3185 kcal/daytime meals) than observed intake.
daytime meals. Children significantly underestimated their energy,
Exchange units of carbohydrate and fat consumption as compared to observers,
foods that were with younger children having larger differences. Exact
developed from the agreement for the 9 exchange groups ranged from 94% for lean
recalls for analyses. fat meat to 17% for the fat group. Girls were significantly more
accurate in reporting medium fat meat exchange units than
boys, 62% versus 50% respectively (significance testing not
shown).
Lytle et al. 19937 49 M&F 3rd Grade 24-hour Observation Compared food Pearson correlations between recalled and observed intakes were
recall record-assisted recalls 0.59 for energy, 0.62 for protein as % of kcal and 0.64 for total
assisted by completed by fat as % of kcal. Range of correlations for the 8 nutrients assessed
food record; children against was 0.41 for polyunsaturated fat as % of kcal to 0.79 for saturated
quantitative observation of school fat as % of kcal. Recalled energy intake was 10% higher than
lunch and breakfast observed intake (1823 vs. 1650 kcal/day). There was an overall
by trained personnel 77.9% agreement in the types of food items recalled and
and of other meals at observed. Food portions were recalled within 10% of observed
home by parents. portions 35% of the time; overestimation occurred 42% and
underestimation occurred 23% of the time.
Van Horn et al. 18 M 8-10 y 24-Hour 1-Day food Compared child’s Pearson correlations between recalled intake and record of intake
19908 14 F recall by record recall of intake were 0.76 for energy, 0.74 for protein as % of kcal and 0.73 for
phone; against parent’s total fat as % of kcal. Range of correlations for the 10 nutrients
quantitative observation recorded assessed was 0.64 for saturated fat as % of kcal to 0.93 for iron.
as a food record. Recalled energy intake was 2% lower than recorded intake (1799
vs. 1836 kcal/day). There were no significant differences
between child and parent reports of nutrient intake (significance
testing not shown).
Todd & Kretsch 30 M&F 8-11 y Breakfast Observation Compared child’s Pearson correlations between recalled lunch and observed lunch
1986a10 Chinese and lunch recall of intake of for Chinese were 0.49 for energy, 0.62 for protein and 0.25 for
31 M&F recall; school breakfast and total fat, and for Hispanics were 0.53 for energy, 0.51 for protein
Hispanic quantitative lunch against and 0.46 for total fat. Range of correlations for the 15 nutrients
observation of school assessed for Chinese was –0.10 for sodium to 0.63 for thiamin,
meals with plate and for Hispanics was 0.34 for niacin to 0.81 for vitamin C.
waste subtracted. Chinese children’s recalled energy intake was 10% lower than
Excerpted breakfast observed intake (686 vs. 765 kcal/2 meals). Chinese children
and lunch meals from recalled consistently less food than consumed, which was
24-hour recall. significantly lower for 4 of the 15 nutrients. Hispanic children’s

recalled energy intake was 6% higher than observed intake (665
vs. 630 kcal/2 meals). Hispanic children recalled intake versus
consumed intake was inconsistent and was significantly higher
for 2 nutrients and lower for 1 of the 15 nutrients assessed. For
Chinese, food item omissions ranged from 4% for milk to 35%
for vegetables. For Hispanics, food item omissions ranged from
0% for juice and milk to 35% for vegetables.
Samuelson 197013 56 M&F 8y Lunch recall; Chemical Compared child’s Spearman correlations between recall of lunch and chemical
43 M&F 13 y quantitative analysis of recall of lunch against analyses of lunch for 8- and 13-year olds for energy were 0.68
food weighed chemical and 0.71, respectively. Correlations for protein of 8- and 13-year
analyses of a double olds were 0.55 and 0.45, respectively. Correlations for total fat
portion of lunch, with of 8- and 13-year olds were 0.61 and 0.69, respectively. Range of
plate waste correlations for the 4 nutrients assessed for 8-year-olds was 0.55
subtracted. Excerpted for protein to 0.68 for energy. Range of correlations for 13-year-
lunch meal from 24- olds was 0.45 for protein to 0.71 for energy. Among 8-year-olds,
hour recall. recalled energy intake was 18% higher than chemical analyses
(472 vs. 399 kcal/meal). Among 13-year-olds, recalled energy
intake was 1% higher than chemical analyses (494 vs. 491 kcal/
meal). Median portion size estimated by child compared to
weighing was not significantly different for 8-year-olds and was
14% lower among 13-year-olds (significance testing not shown).
499
500

Validation
Lytle et al. 199814 238 M 4th Grade Lunch recall; Observation Compared child’s Pearson correlations between recall and observed intake for
248 F quantitative recall of school lunch energy was 0.44. Range of correlations for the 5 nutrients
253 White against observation of assessed was 0.39 for beta-carotene to 0.61 for vitamin C.
146 Asian lunch. Excerpted Recalled energy intake was 14% higher than observed intake
73 Black lunch meal from 24- (600 vs. 526 kcal/meal). There were significant differences
14 Other hour recall. between recalled and observed nutrient intake for all nutrients
except beta-carotene (borderline significant). The highest
correlation was for servings of fruit, 0.65, and lowest for servings
of vegetables, 0.42. No ethnic specific analyses provided.
Baxter et al. 120 M 4th Grade Lunch recall; Observation Compared child’s Average matched food rates from recall of lunch and observation
1997a15 117 F quantitative recall of food items of lunch were 84% and 68% for same day and next day intervals,
58 White from school lunch respectively. Rates for omitted and added (phantom) foods were
179 Black either the same day or significantly lower for the same day (16% vs. 5%) than next day
the following day recalls (32% vs. 13%). Children were least likely to omit
against observation of beverages and main dishes and most likely to omit condiments
that lunch. and miscellaneous foods. There were no significant gender,
ethnic, or time interval differences in the accuracy of recalling
the amount of food consumed (significance testing not shown).
Mullenbach et al. 22 M 6-9th 24-Hour 3-day food Compared adolescents’ Pearson correlations between recall and food records were 0.42
19929 18 F Grade recall by record parent-assisted recall for energy, 0.42 for protein, and 0.33 for total fat. Range of
Adults phone; against adolescents’ correlations for the 19 nutrients assessed was 0.09 for cholesterol
required quantitative parent-assisted 3-day to 0.57 for riboflavin. Recalled energy intake was 12% lower than
food records recorded energy intake (1835 vs. 2097 kcal/day). There were no
completed 2-4 weeks significant differences between recalled and recorded average
prior to recalls. nutrient intake, although the 24-hour recall estimates were all
lower than those from the food record.
a Results of all subgroups not reported due to samples below the N=30 criterion
b Males (M), females (F)
c Adult assistance required for instrument administration
d N/A — not applicable
e FFQ — food frequency questionnaire
f TEE — total energy expenditure
Validity and Reliability of Dietary Assessment in School-Age Children 501
drank during a specified time period, typically the previous day.5 The 24-hour recall is an
estimate of actual intake that incorporates a detailed description of the food, including
brand names, ingredients of mixed dishes, food preparation methods, and portion sizes
consumed. Because of the detail provided, complete nutrient intake can be calculated for
the designated day. When conducted with a random sample population, a single 24-hour
recall is appropriate for estimating group means, but is not a tool to predict individual-
level health outcomes such as serum cholesterol levels. Because of intra-individual vari-
ation in intake, multiple recalls are needed to accurately estimate usual nutrient intake.
Nelson and colleagues have addressed how to calculate the number of days of recording
required to estimate intakes of individual nutrients for children age 2 to 17 years.6 Col-
lection of 24-hour recall data can occur via paper records or with a computer-assisted
program. Prompts for quantification of portion size such as two- or three-dimensional
food models are typically employed.
Food Record (Table 20.3)

Food records are written accounts of actual intake of the food and beverages consumed
during a specified time period, usually three, five, or seven days.5 A single food record is
a measure of actual intake and, like the 24-hour recall, is appropriate for estimating group
means but is not a tool to predict individual-level health outcomes. The work of Nelson
and colleagues can be used to calculate the number of days of records necessary to
determine nutrient intake with precision.6 Respondents record detailed information about
their dietary intake, such as brand names, ingredients of mixed dishes, food preparation
methods, and estimates of amounts consumed. By collecting the information at the time
of consumption, error due to memory loss is reduced, and thus food records often serve
as a validation standard. Prompts for quantification of food portions, such as two- or
three-dimensional food models are frequently used to aid respondents. Audiotaping food
records has been explored as an alternative to handwritten records.8
Food Frequency Questionnaires (Tables 20.4 and 20.5)

Food frequency questionnaires (FFQs) which measure usual food intake are often used
for epidemiological studies, since they are relatively easy to administer, less expensive
than other assessment methods, and easily adapted for population studies. These measures
of usual intake can be used to rank respondents by intake levels and are useful for
predicting health outcomes at both group and individual levels. Respondents are asked
to report frequency of consumption and sometimes portion size for a defined list of foods;
the questionnaire can be self-administered or conducted with individual or group assis-
tance. Respondents report their usual intake over a defined period of time in the past year,
month, or week, although frequency of intake on the previous day has also been assessed.
FFQs can be classified as quantitative, semi-quantitative, or non-quantitative. Data from
non-quantitative FFQs are generally used to assess frequency of consumption of food;
however, these frequencies may also be associated with standard portions to estimate
nutrient amounts. The burden of work for the researcher is on the front end, developing
the food list for inclusion on the FFQ. The appropriateness of the food list for the FFQ
often needs to be population specific to accurately assess usual intake.
Diet History (Table 20.6)

Diet histories assess the past diet of an individual in the form of usual meal patterns, food
intake, and food preparation practices through an extensive interview or questionnaire.5
502
TABLE 20.3
Food Record Validity Studies Among School-Age Children
Validation
Lindquist et al. 17 M b 6.5-11.6 y 3-Day audio- f
TEE by Compared average of Mean recorded energy intake from 3-day audiotaped records was
200065 13 Fb Adults taped food doubly- 3 child’s parent- 14% lower than TEE from doubly-labeled water (6.73 vs. 7.86
17 White requiredc record labeled assisted reports of mJ/day). Age was significantly related to reporting accuracy
13 Black water intake from with underestimation of energy intake from audiotaped food
audiotaped food records increasing with age.
records against 14-d
TEE.
Knuiman et al. 30 M 8-9 y 3-Day lunch Observation Compared child’s Correlations between mean values from recorded and observed
198721 Adults food record; parent-assisted lunch intake were 0.71 for energy, 0.66 for protein, and 0.63 for
required quantitative record of lunch intake total fat. Range of correlations for 14 nutrients (i.e., both absolute
against observation of and density values) assessed was 0.62 for saturated fatty acids
lunch with weighed as % of kcal to 0.92 for polyunsaturated fat as % of kcal. Recorded
duplicate portions. energy intake was 25% higher than observed intake (456 vs. 365
Excerpted lunch meal kcal/meal). Ten nutrients were significantly overestimated by
from 7-day non- recorded intake of lunch as compared to observation.
consecutive food
records collected over
15 days.
Knuiman et al. 68 M 8-9 y 7-Day dinner Chemical Compared mothers’ Correlations between mean values from recorded dinner intake
198721 Adults food record; analysis of record of dinner and chemical analyses of dinner were 0.52 for energy, 0.56 for
required quantitative food intake against protein, and 0.58 for total fat. Range of correlations for the 14
chemical analyses of nutrients (i.e., both absolute and density values) assessed was
duplicate portions of 0.45 for polyunsaturated fat as % of kcal to 0.85 for cholesterol.
dinner. Excerpted Recorded energy intake was 31% higher than chemical analysis
dinner from 7-day of food (647 vs. 495 kcal/meal). Nine nutrients were significantly
non-consecutive food overestimated by mother’s record of dinner as compared to
records collected over chemical analysis of dinner.
15 days.
Van Horn et al. 33 M&F 8-10 y 1-Day food Observation Compared child’s Pearson correlations between child’s and parent’s records were
19908 record report of intake from 0.68 for energy, 0.82 for protein as % of kcal, and 0.82 for total
audiotaped food record fat as % of kcal. Range of correlations for the 10 nutrients
taped; against parent’s assessed was 0.68 for energy to 0.96 for iron. Child’s recorded
quantitative observation recorded energy intake was 2% lower than parents’ recorded energy
as a food record. intake (1882 vs. 1913 kcal/day). There were no significant
differences between child and parent reports of nutrient intake
Bandini et al. 109 Fb 8-12 y 7-Day food TEE by Compared child’s Mean recorded energy intake was 13% lower than TEE from
199719 White, Adults record; doubly adult-assisted food doubly labeled water (7.00 vs. 8.03 mJ/day). Age was
Black, required quantitative labeled record against 14-day significantly related to reporting accuracy with underestimation
Hispanic, water TEE. of energy intake from food records increasing with age. There
other were no significant differences by ethnicity.
Champagne et al. 60 Mb 9-12 y 8-Day food TEE by Compared child’s Mean recorded energy intake was 24% lower than TEE from
1998 a20 58 F Adults record; doubly- parent assisted record doubly labeled water for boys (1953 vs. 2555 kcal/day) and 27%
56 Black required quantitative labeled of intake against TEE. lower for girls (1633 vs. 2232 kcal/day). Mean recorded energy
62 White water intake was 28% lower than TEE from doubly labeled water for
blacks (1678 vs. 2346 kcal/day) and 22% lower for whites (1909
vs. 2441 kcal/day).
Green et al. 199818 14 F 16 y 3-Day food Serum Compared adolescent’s Pearson correlations between recorded folate intake and serum
19 F 17 y record; folate, red report of folate and folate were 0.65, between recorded folate intake and RBC folate
29 F 18 y quantitative blood cell vitamin B12 intake on were 0.50, and between recorded vitamin B12 intake and serum
43 F 19 y (RBC) weighed record B12 were 0.32.
folate, and against serum
serum micronutrient levels
vitamin collected 1 week
B12. before food records.
a
Results of all subgroups not reported due to samples below the N=30 criterion
503
504
TABLE 20.4
Food Frequency Questionnaire (FFQ) Validity Studies Among School-Age Children
Response
Categories Validation
Reference Sample Age/Grade Instrument (Range) Standard Design Results
Blom et al. 13 Mb 2-16 y 36 Items; (sucrose, Unknown (<1/ 7-Day food Compared child’s parent- Spearman correlations between FFQ and food
1989a22 17 F Adults protein, fat, fiber, week to ≥4 record assisted report of intake records for frequency of food groups with
requiredc nitrite, vitamin C) times/day) of foods with high high content of protein and fat were 0.69 and
self-administered; content of sucrose, 0.69, respectively. Range of correlations for 6
referent period not protein, fat, fiber, nitrite, food groups assessed was 0.52 for sucrose to
specified; and vitamin C against 0.76 for vitamin C. Compared to the food
non-quantitative child’s parent- and other record, 2 food groups were significantly
adult-assisted report of overestimated and 3 significantly
intake on 7-day underestimated by the FFQ. Of 34 food items,

consecutive food record 5 were significantly overestimated and 8
completed 6-8 weeks significantly underestimated by the FFQ.
before the FFQ.
Taylor et al. 26 M 3-6 y 35-Items; (calcium) Open-ended 4-Day diet Compared parent’s report The FFQ significantly overestimated mean
199823 41 F Adults self-administered; (never to record of child’s intake of calcium intake by 18% compared to the food
required past year; semi- number of calcium against parent’s record (942 mg vs. 798 mg/day).
quantitative times/month) report of child’s 4-day
diet record.
Kaskoun et al. 22 M 4-6 y <111-Items; self- 9 (<1/month to TEE by Compared parent’s report The FFQ significantly overestimated total
1994a30 23 F Adults administered; past ≥6 times/day) doubly- of child’s energy intake energy intake by 59% compared to TEE (9.12
white & Native required year; semi- labeled water against 14-day TEE vs. 5.74 mJ/day).
American quantitative; adult completed after or at the
portions same time as the FFQ.
Persson et al. 477 Mb&Fb 4&8y 27 Items; interviewer 8 (None to ≥4 7-Day food Compared parent’s report Of the 27 food items, the frequencies of intake
198431 Adults administered; times/day) record of child’s frequency of of 15 were significantly overestimated, and 9
required referent period not intake of foods against were significantly underestimated by the FFQ
specified; non- parent’s report of child’s compared to the food record.
quantitative intake on 7-day food
records. Foods from the
records were translated
into food categories of
the FFQ.
Hammond et al. 150 M&F 5-11 y 35 Items (fat, energy, 10 (None to 7 14-Day food Compared child’s parent- For the 35 foods, the median difference in
199324 Adults fiber); self- days/week) checklists assisted report of days/week consumption between the FFQs
required administered; frequency of intake of and food checklists was: equal to 0 for 17
past month; foods against child’s foods, >0 for 5 foods, and <0 for 13 foods
non-quantitative parent-assisted report of (significance testing not shown). Differences
intake on 14-day food ranged from –1 (cakes, chips) to 1 (green
checklists. Food vegetables). Percentage of responders
checklists consisted of 2 classified by FFQ to within ± 1 day per week
sets of 7-day consecutive of frequencies reported on checklists ranged
food records 1 and 2 from 46.8% for low-fiber cereal to 99.3% for
months after the FFQ, lamb, fish, and liver.
respectively, and
contained the same food
categories as the FFQ.
Byers et al. 43 M 6-10 y 35 Items 9 (None or <1 Serum Compared parent’s report Spearman correlations between serum and
199325 54 F Adults (15 fruits, 20 time/month carotenoids of child’s fruit and dietary nutrients were 0.16 for carotene, 0.39
white & black required vegetables); to ≥6 vitamins A, vegetable intake against for vitamin C, 0.14 for vitamin A, and 0.32 for
self-administered; times/day) C, and E child’s serum vitamin E. Correlations between serum levels
past 3 months; micronutrient levels. of carotene, vitamin C, vitamin A, and

semi-quantitative; vitamin E and frequencies of intake of total
adult portions fruits and vegetables were 0.24, 0.29, 0.14, and
0.17, respectively. There were no differences
by gender or ethnicity (significance testing
not shown).
Bellu et al. 165 Mb 8-10 y 116 Items; Unknown 24-Hour recall Compared parent’s report Mean energy estimates from the FFQ were 27%
199632 158 Fb Adults self-administered; of child’s nutrient intake higher than the 24-hour recall for girls (2156
required past 6 months; against mother’s report vs. 1703 kcal/day) and 25% higher for boys
semi-quantitative; of child’s intake on 24- (2281 vs. 1821 kcal/day). Among girls, of the
“average” portions hour recall. 10 nutrients, the FFQ significantly
overestimated 1 nutrient and significantly

underestimated 2 nutrients. Among boys, 3
nutrients were significantly overestimated
and 1 was significantly underestimated by
the FFQ.
505
506

Response
Arnold et al. 77 F 7-12 y 160 Items; Open-ended 14-Day food Compared child’s parent- Pearson correlations (log-transformed, energy-
199533 Adults self-administered; (none to record assisted report of adjusted) between the first FFQ and the first
required past year (inferred); number of nutrient intake from 2 food record and the second FFQ and second
semi-quantitative; months/year) administrations against food record were 0.13 to 0.22 for energy, 0.20
adult portions child’s parent-assisted to 0.30 for protein, and 0.28 to 0.46 for fat,
report of intake on 14- respectively. Range of correlations for 16
day food records. nutrients assessed was 0.06 for starch to 0.61
Records, consisting of 2 for vitamin B2. For the first FFQ, energy intake
sets of 7-day consecutive was 24% higher than the first food record
food records were (2319 vs. 1861 kcal/day). For the second FFQ,
completed 1 month after energy intake was 16% higher than the
the first FFQ and 6 second food record (2205 vs. 1902 kcal/day).
months later. Both administrations of the FFQ
overestimated intake for all 16 nutrients
compared to the corresponding food records
Baranowski, 1530-1570 3rd Grade 7 Items (3 fruit, 4 10 (None to ≥5 7-Day food Compared child’s report Pearson correlations between FFQ and food
Smith et al. Mb&Fb vegetables); times/day) record of servings of fruits and records for fruits and vegetables, fruits and
199726 black & white group-administered; vegetables against juices, and vegetables were 0.20, 0.24, and
past month; child’s report of intake 0.15, respectively. Total servings of fruits and
semi-quantitative; on 7-day food records. vegetables/week as measured by the FFQ
“serving” portions Foods from the records was 50.9; by food record was 15.9. The FFQ
were abstracted into the significantly overestimated intake of food
FFQ categories by a items in all 7 food categories, both aggregate
dietitian. and individual items (significance testing not
shown).
Bellu et al. 39 M 9-12 y 116 Items; Unknown 14-Day food Compared parent’s report Pearson correlations between FFQ and food
199534 49 F Adults self-administered; record of child’s nutrient intake records were 0.46 for energy, 0.34 for protein,
required past 6 months; semi- against parent’s report of and 0.39 for fat. Range of correlations for 18
quantitative; child’s intake on 14-day nutrients assessed was 0.07 for vitamin A to
“average” portions weighed food records. 0.52 for carbohydrates. FFQ energy intake
Records consisted of 2 was 40% higher than the diet record (2620 vs.
sets of 7-day consecutive 1865 kcal/day). The FFQ significantly
food records at the overestimated 6 nutrients and significantly
beginning of the study underestimated 5 nutrients compared to the
and 6 months later, food records.
respectively, before and
after the FFQ.
Rockett et al. 122 Mb 9-18 y 131 Items Dependent on 24-Hour recall Compared child’s report Pearson correlations (unadjusted log-
199735 139 Fb Youth/Adolescent type of food of nutrient intake (mean transformed values) between FFQs and
96% White Questionnaire; of 2 administrations 1 recalls were 0.35 for energy, 0.30 for protein,
self-administered; year apart) against and 0.41 for fat. Range of correlations for 28
past year; child’s report of intake nutrients assessed was 0.09 for copper to 0.46
semi-quantitative; on three 24-hour recalls. for vitamin C. Deattenuated correlations
child portions Recalls were collected via (adjusted for energy and within-person
telephone by research variation) were 0.43 for protein and 0.57 for
dietitians in the year total fat. Range of deattenuated correlations
between FFQ for 29 nutrients assessed was 0.24 for sodium
administrations. to 0.75 for vitamin C. FFQ energy intake was
1% higher than the recalls (2196 vs. 2169 kcal/
day). Of 31 nutrients assessed, 16 were
overestimated by the FFQ and 8 were
underestimated (significance testing not
shown). Correlations did not show a
consistent pattern by gender or age

507
508

Response
Domel et al. 160-165 M&F 4-5th Grade 45 Items (15 fruit, 30 7 (None or <1/ 22-Day food Compared child’s report Spearman correlations between month 1 FFQ
199427 black & white vegetables); month to record of frequency of fruit and and food records and month 2 FFQ and food
group-administered; several per vegetable intake (mean records were 0.12 and 0.17 for total fruit, –0.04
past month; day) of 2 administrations) and 0.02 for total vegetables, and –0.05 and
semi-quantitative; against child’s report of 0.01 for total fruit and vegetable. Range of
“serving” portions intake on 22 consecutive correlations for 8 fruit/vegetable groupings
days of food records. assessed was –0.05 for total fruit and
Records were collected vegetables to 0.32 for fruit and vegetable
between FFQ juice. Mean daily servings of total fruit and
administrations; foods vegetables were 409% higher for the month 1
from the records were FFQ compared to the corresponding food
abstracted by a dietitian records (11.7 vs. 2.3), and 135% higher for the
into servings of fruit and month 2 FFQ compared to the food records
vegetables. (5.4 vs. 2.3). Both administrations of the
monthly FFQ significantly overestimated
mean daily servings for all 8 fruit/vegetable
groupings compared to the corresponding
food records.
Domel et al. 154-156 Mb&Fb 4-5th Grade 45 Items (15 fruit, 30 5 (None or <1/ 2-Week food Compared child’s report Spearman correlations between week 1 FFQ
199427 black & white vegetables); week to record of frequency of fruit and and food records and week 2 FFQ and food
group-administered; several per vegetable intake (mean records were 0.18 and 0.18 for total fruit, –0.01
past week; day) of 2 administrations) and 0.11 for total vegetable, and 0.00 and 0.05
semi-quantitative; against child’s report of for total fruit and vegetable. Range of
“serving” portions intake on 7-day food correlations for 8 fruit/vegetable groupings
records. Records were assessed was –0.01 for total vegetable to 0.25
collected between FFQ for total legumes and fruit. Mean daily
administrations; foods servings of total fruits and vegetables were
from the records were 295% higher for week 1 FFQs compared to
abstracted by a dietitian the corresponding food record (8.3 vs. 2.1)
into servings of fruit and and 306% higher for week 2 FFQ (7.3 vs. 1.8).
vegetables. Both administrations of the weekly FFQ
significantly overestimated mean daily
servings for all 8 fruit and vegetable
groupings compared to the corresponding
food records.
Koehler et al. 66 M 5-8th Grade 33 Items Yes, not sure, 24-Hour recall Compared child’s Spearman correlations between scores on the
200066 54 F Yesterday’s Food and no reported intake of FFQ and 24-hour recall were 0.71 for low fat
American Choices-YFC; particular foods against foods, 0.35 for high fiber foods, 0.29 for fruits
Indian, non- self-administered; child’s 24-hour recall, and vegetables, and 0.40 for high fat foods.
hispanic- past day; non- both completed on same
white, quanitative day.
Hispanic
Jenner et al. 61 M ~11-12 y 175 Items; group- 6 (None to 14-Day food Compared child’s report Pearson correlations (log-transformed)
198936 57 F administered; every day) record of nutrient intake against between the children’s FFQs and diet records
past week; child’s report of intake were 0.25 for energy, 0.18 for protein, and 0.19
non-quantitative on 14-day diet records. for total fat. Range of correlations for 13
Seven sets of 2 nutrients assessed was 0.11 for
consecutive day records monounsaturated fat to 0.42 for complex
were collected in the 3 carbohydrates. Correlations between the
months following parents’ FFQs and diet records were 0.38 for
administration of the energy, 0.26 for protein and 0.30 for total fat.
FFQ. Nutrient estimates Range of correlations was 0.26 for protein to
from FFQ completed by 0.47 for complex carbohydrates. Children’s
parents were also FFQ energy intakes were 36% higher than
compared to the 14-day diet records (10.9 vs. 8.0 mJ/day). Parents’
diet records. FFQ estimates of children’s energy intake
were 21% higher than the children’s diet
records (9.7 vs. 8.0 mJ/day). All 13 nutrients
were overestimated by both the child and the
parent FFQ (significance testing not shown).
Kinlay et al. 57 Mb 13-17 y 12 Items Dependent on FFQe Compared child’s parent- Spearman correlations between the brief FFQ
199128 48 Fb Adults (fat, saturated fat); type of food assisted report of fat and the FFQ were 0.40 for total fat as % of
required self-administered; intake against child’s kcal and 0.54 for saturated fat as % of kcal.
past week; parent assisted report of
semi-quantitative fat intake on FFQ.

Field et al. 199829 102 M&F 9-12th Grade 27 Items (12 fruit, 15 Unknown Three 24-hour Compared child’s report Spearman correlations between the brief FFQ
50% M vegetables) (<1/month to recalls of fruit and vegetable and mean of three 24-hour recalls were 0.33
50% F Youth/Adolescent ≥2 times/day) intake against child’s for fruit only, 0.29 for fruit juice, 0.33 for fruit
35% White Questionnaire; self- report of intake on 3 and juice, 0.32 for vegetables, and 0.41 for
24% Black administered; nonconsecutive 24-hour fruit (including juice) and vegetables.
15% Hispanic past year; recalls completed 2
semi-quantitative weeks apart. FFQ was
administered 2-4 weeks
after the third recall.
509
510

Response
Field et al. 199829 102 M&F 9-12th Grade 4 Items (2 fruit, 2 Unknown Three 24-hour Compared child’s report Spearman correlations between YRBSS items
50% M vegetable) (none to ≥3 recalls of fruit and vegetable and mean of 24-hour recalls were 0.17 for fruit
50% F Youth Risk Behavior times/day) intake against child’s only, 0.07 for fruit juice, 0.21 for fruit and
35% White Surveillance System reported mean intake of juice, 0.24 for vegetables, and 0.28 for fruit
24% Black Questionnaire fruits and vegetables (including juice) and vegetables.
15% Hispanic (YRBSS); self- calculated with an
administered; past algorithm using 3
day; nonconsecutive 24-hour
semi-quantitative recalls completed 2
weeks apart. YRBSS was
administered 2-4 weeks
after the third recall.
Field et al. 199829 102 M&F 9-12th Grade 6 Items (2 fruit, 4 Unknown Three 24-hour Compared child’s report Spearman correlations between past day
50% M vegetable) (none to ≥3 recalls of fruit and vegetable BRFSS and mean of 24-hour recalls were 0.33
50% F Behavioral Risk times/day) intake against child’s for fruit only, 0.30 for fruit juice, 0.34 for fruit
35% White Factor Surveillance reported mean intake of and juice, 0.14 for vegetables, and 0.30 for
24% Black System fruits and vegetables fruit (including juice) and vegetables.
15% Hispanic Questionnaire calculated with an
(BRFSS); self- algorithm using 2
administered; past nonconsecutive 24-hour
day; recalls completed 4
semi-quantitative weeks apart. BFRSS was
administered halfway
between the two recalls.
Field et al. 199829 100 M&F 9-12th Grade 6 Items (2 fruit, 4 Unknown Three 24-hour Compared child’s report Spearman correlations between past year
50% M vegetable) (none to ≥5 recalls of fruit and vegetable BRFSS and mean of 24-hour recalls were 0.36
50% F BRFSS; times/day) intake against child’s for fruit only, 0.36 for fruit juice, 0.35 for fruit
35% White self-administered; reported mean intake of and juice, 0.33 for vegetables, and 0.43 for
24% Black past year; fruits and vegetables fruit (including juice) and vegetables.
15% Hispanic semi-quantitative calculated with an
algorithm using 3
nonconsecutive 24-hour
recalls completed 4
weeks apart. BFRSS was
administered preceding
the third recall.
Green et al. 14 F 16 y 116 Items; Unknown Serum folate, Compared child’s report Pearson correlations were 0.48 between folate
199818 19 F 17 y self-administered; red blood cell of folate and vitamin B12 intake from the FFQ and serum folate, 0.42
29 F 18 y past year; (RBC) folate, intake against serum between folate intake from the FFQ and RBC
43 F 19 y semi-quantitative and serum micronutrient levels. folate, and 0.25 between vitamin B12 intake
vitamin B12 from the FFQ and serum B12.
Andersen et al. 13 M 11th Grade 190 Items; Dependent on 7-Day food Compared child’s parent Spearman correlations between FFQ and food
199537 36 F Adults group-administered; type of food record assisted report of records were 0.51 for energy, 0.48 for protein,
required past year; nutrient intake against 0.57 for total fat. Range of correlations for 18
semi-quantitative child’s report of intake nutrients assessed was 0.14 for vitamin D to
on 7-day weighed food 0.66 for monounsaturated fat. FFQ energy
records completed 2-3 intake was 24% higher than diet records (10.7
months after FFQ vs. 8.6 mJ/day). The FFQ significantly
administration. Records overestimated 16 of the 18 nutrients. The FFQ
consisted of 4 significantly overestimated intake of 8 of 13
consecutive days, a 1- food items as compared to diet records.
week interval, and 3
consecutive days.
511
512
TABLE 20.5
Food Frequency Questionnaire (FFQ)e Reliability Studies Among School-Age Children
Response
Age/ Categories
Reference Sample Grade Instrument (Range) Design Results
Basch et al. 166 4-7 y ~116 Items; 9 (None or <1/ Compared both 3-month and Pearson correlations (log-transformed) between the 2 FFQs at 3
199439 M&Fb Adults interviewer- month to ≥6/ 1-year test-retest months were 0.53 for energy, 0.49 for protein, and 0.56 for total
Latino requiredc administered; day) reproducibility of nutrient fat. Range of correlations for 12 nutrients assessed at 3 months
past 6 months; estimates from FFQs was -0.06 for sucrose to 0.61 for crude fiber. At 1 year, correlations
semi-quantitative; completed by the parent. were 0.46 for energy, 0.40 for protein, and 0.47 for total fat. Range
child portions of correlations for 12 nutrients assessed at 1 year was 0.06 for
sucrose to 0.57 for polyunsaturated fat.
Arnold et al. 77 F 7-12 y 160 Items; 5 (Open-ended, Compared 6-month test-retest Pearson correlations (log-transformed, energy adjusted) between
199533 Adults self-administered; none to number reproducibility of nutrient the 2 FFQs were 0.60 for energy, 0.51 for protein, and 0.14 for
required past year; of months/ estimates from FFQs total fat. Range of correlations for 16 nutrients assessed was 0.14
semi-quantitative; year) completed by the parent and for total fat to 0.71 for fiber. Mean energy intake was 5% higher
adult portions child. in the first FFQ compared to the second (2319 vs. 2205 kcal/day).
Mean intake of 15 nutrients was higher in the first FFQ compared
to the second; 1 nutrient was lower (significance testing not
shown).
Domel et al. 146 M&F 4-5th 45 Items (15 fruit, 5 (None or <1/ Compared 1-week test-retest Spearman correlations between the 2 FFQs were 0.50 for total fruit,
199427 black & Grade 30 vegetable); week to several reproducibility of fruit and 0.48 for total vegetable, and 0.54 for total fruit and vegetable
white group- per day) vegetable intake from FFQs intake. Range of correlations for 8 fruit and vegetable groupings
administered; completed by the child. assessed was 0.39 for fruit and vegetable juice to 0.54 for total
past week; Order of fruit (15 items) and fruit and vegetables. Mean daily servings of total fruits and
semi-quantitative; vegetables (30 items) was vegetables was 12% higher for Week 1 FFQ compared to Week 2
“serving” portions reversed between first and FFQ (8.3 vs. 7.3). Mean daily servings of 6 fruit and vegetable
second administrations. groupings of 8 assessed were higher for Week 1 FFQ compared
to Week 2 FFQ (significance testing not shown).
Domel et al. 156 M&F 4–5th 45 Items (15 fruit, 7 (None or <1/ Compared 1-month (3.5- Spearman correlations between the 2 FFQs were 0.43 for total fruit,
199427 black & Grade 30 vegetable); month to week) test-retest 0.37 for total vegetable and 0.47 for total fruit and vegetable
white group- several per day) reproducibility of fruit and intake. Range of correlations for 8 fruit and vegetable groupings
administered; vegetable intake from FFQs assessed was 0.28 for fruit and vegetable juice to 0.47 for both
past month; completed by the child. legumes and total fruit and vegetable intake. Mean daily servings
semi-quantitative; Order of fruit (15 items) and of total fruits and vegetables was 54% higher for Month 1 FFQ
“serving” portions vegetables (30 items) was compared to Month 2 FFQ (11.7 vs. 5.4). Mean daily servings of
reversed between first and 8 fruit and vegetable groupings were higher for Month 1 FFQ
second administrations. compared to Month 2 FFQ (significance testing not shown).
Rockett et 75 M 9-18 y 151 Items 9 (None or <1/ Compared 1-year test-retest Pearson correlations (log-transformed, energy-adjusted) between
al. 199538 101 F Youth/ month to ≥6/ reproducibility of nutrient the 2 FFQs were 0.49 for energy, 0.26 for protein, and 0.41 for
3 N/Ad Adolescent day) estimates from FFQs total fat. Range of correlations for 7 nutrients assessed was 0.26
multi- Questionnaire; completed by the child. for protein and iron to 0.58 for calcium. Mean energy intake was
ethnic self-administered; 10% higher in the first FFQ compared to the second (2477 vs.
past year; 2222 kcal/day). Mean intake of 6 nutrients assessed was
semi-quantitative; significantly higher in the first FFQ compared to the second.
adult portions Range of correlations for 8 food groups assessed was 0.39 for
meats to 0.57 for soda. Pearson correlations (log-transformed) for
servings/day were 0.49 for fruits, 0.48 for vegetables, and 0.48
for fruits and vegetables. Of 8 food groups, mean serving
frequencies of 5 were significantly higher in the first FFQ
compared to the second. Reproducibility of nutrient intake was
significantly higher for girls than boys (mean correlation for all
nutrients was 0.44 and 0.34, respectively). There were no
significant differences by age or ethnicity.
Frank et al. 189 M&F 12-17 y 64 Items; 6 (None to >3 Compared 2-week test-retest Two-thirds of the children reported similar responses for the
199240 black & group- times/day) reproducibility of food frequency of consumption of low-fat milk, diet carbonated soft
white administered; intake from FFQs completed drinks and shellfish. Twelve food groups had percent agreement
past week; by the child. of 50% or better (significance testing not shown).
semi-quantitative;
adult portions
Andersen et 53 M 11th 190 items; Dependent on Compared 6-week test-retest Spearman correlations (energy-adjusted) between the 2 FFQs were
al. 199537 50 F Grade group- type of food reproducibility of nutrient 0.87 for energy, 0.86 for protein, and 0.86 for total fat. Range of
Adults administered; estimates from FFQs correlations for 18 nutrients assessed was 0.72 for vitamin C to
required past year; completed by the child and 0.91 for alcohol. Median energy intake was 11% higher in the first
semi-quantitative parent. FFQ compared to the second (12.3 vs. 10.9 mJ/day). Median
intake of 15 nutrients was significantly higher in the first FFQ
compared to the second FFQ. Differences in median correlations
for nutrient intake were not significant between girls and boys
(0.78 vs. 0.74, respectively).
513
The diet history provides a measure of usual intake appropriate for ranking individuals
and predicting health outcomes. In contrast to other methods of dietary assessment, a diet
history is usually more qualitative than quantitative, allowing detailed information about
food preparation, eating habits, and food consumption to be collected by a highly trained
interviewer. This method requires children and/or parents to recall dietary intake from
the past, understand spatial relationships, be able to apply math skills, and have the
stamina to complete the typically one- to two-hour interview. Because of the respondent
burden, diet histories are not often used to assess children’s diets.
Observation (Table 20.6)

Observation is useful for assessing preliterate children (third grade or younger), either in
a lunchroom setting with school meals or in controlled school or group activities. Inten-
sively trained observers unobtrusively watch the children, sometimes many at a time, to
ascertain foods, brand names and portion sizes consumed. A single observation provides
a measure of actual intake that is appropriate for estimating group means and cannot be
used to predict health outcomes. Multiple observations can provide a measure of usual
intake. The recordings are interpreted after the collection process and coded to a nutrient
database to calculate nutrient intake for each child. Observations are often used as the
validation standard for studies among school-age children.
Discussion
Ideally, a comprehensive review of validity and reliability studies such as this one would
direct researchers to the best assessment technique for a particular setting. Unfortunately,
as this report indicates, dietary assessment techniques for children are difficult to evaluate
and generalize because the validation standards against which the instruments have been
compared are frequently beset with shortcomings. These validation standards may have
inconsistent validity, or use a referent period that differs from that used for the instrument.
Heterogeneity of the studies also makes it difficult to draw conclusions; the differences
in study administrations and study populations make comparisons uncertain both within
a type of assessment method and between methods. Noting these challenges to interpre-
tation, the correlations between the validation standard and the dietary assessment tool
were almost always higher for recalls or records than for FFQs.
This review may serve best to facilitate comparison of dietary methods to determine
the most effective data collection instruments to use with particular quantitative or qual-
itative research questions.43-44 The reader may, for example, scan each table for instruments
with higher or lower nutrient correlations with a particular validity standard, instruments
that children can complete without adult assistance, those with no portion size estimation,
and instruments specific to assessing intake of food groups — all by age or grade. Appli-
cations of the dietary assessment methods are summarized in Table 20.7 which provides
advantages and disadvantages for using the dietary assessment methodologies, applicable
study designs, and brief highlights of their validity from this review. Using this series of
tables, the reader can select a dietary assessment tool that is appropriate for specific
research questions.
It is evident that many of the validation standards used in the reviewed articles are
imperfect, especially for children. Food records or recalls were the most common choices
TABLE 20.6
Diet History and Observation Reliability Studies Among School-Age Children
Age/
Reference Sample Grade Instrument Design Results
Rasanen, 1979 41 47 M&Fb 5y Diet history; Compared 7-month test-retest Pearson correlations between the first and second interviews were
50 M&F 9y past year; reproducibility of nutrient 0.59 for energy, 0.60 for protein, and 0.57 for total fat. Range of
37 M&F 13 y interviewer intake from a diet history correlations for 11 nutrients assessed was 0.41 for ascorbic acid
Adults administered; completed by child and to 0.60 for protein. Mean daily energy intake was 27% higher in
requiredc quantitative parent. the first diet history interview as compared to the second
interview (3256 vs. 2573 kcal/day).

Simons-Morton 45 M&F 3-5th Observation; Compared 2 simultaneously Intraclass correlations between paired observers ranged from 0.81-
et al. 199242 Grade lunch only; collected adult observers’ 0.90 for energy and from 0.74-0.88 for fat. Of the 6 nutrients
Adults quantitative estimates of nutrient intake assessed, intraclass correlations were lowest for total fat (0.74-
required and food items from 0.88) and highest for vitamin A (0.96-0.98). Inter-observer percent
observation of lunch. differences in mean energy intake ranged from 0.1%-6.8%.
Overall agreement on food items between observers was 84%;
percent agreement was highest for chips and condiments, and
lowest for desserts. Differences in portion size estimates
accounted for most of the energy and nutrient differences
between observers.
a Results of subgroups not reported due to samples below the N=30 criterion
b males (M), females (F)
c adult assistance required for instrument administration
d N/A — Not applicable
e FFQ — Food frequency questionnaire
515
516
TABLE 20.7
Summary of Reviewed Dietary Assessment Methods for School-Age Children
Energy &
Method and Macro- Energy Intake
Number of Studies Ages Nutrient Compared with Type of Diet Study Design
Reviewed Evaluated Validitya Standardb Measure Applications Advantages Disadvantages
FOOD RECALL 4-14 y Energy –34 to 18% One recall • Cross-sectional • Short administration time • Recall depends on memory
0.23-0.87 measures • Intervention • Defined recall time • Portion size difficult to estimate
Validity — 12 Adult group intake • Monitoring • Intake can be quantified • Trained interviewer required
Reliability — 0 assistance Protein • Clinical • Procedure does not alter habitual • Expensive to collect and code
needed for 0.05-0.82 Multiple recalls • Epidemiologic dietary patterns
<9 y measure • Low respondent burden

Total fat individual or • Can be telephone administered
0.25-0.46 group intake • Procedure can be automated
FOOD RECORD 8-19 y Energy –28 to 31% One record • Cross-sectional • Record does not rely on memory • Recorder must be literate
0.52-0.71 measures • Intervention • Defined record time • High respondent burden
Validity — 7 Adult group intake • Monitoring • Intake can be quantified • Food eaten away from home
Reliability — 0 assistance Protein • Clinical • Training can be group less accurately recalled
needed for 0.56-0.66 Multiple records • Epidemiologic administered • Procedure alters habitual
<9 y measure • Procedure can be automated dietary patterns
Total fat individual or • Validity may decrease as
0.58-0.63 group intake recording days increase
• Expensive to collect and code
FOOD 2-19 y Energy 1 to 59% One FFQ • Cross-sectional • Trained interviewers not needed • Recall depends on memory
FREQUENCY 0.13-0.51 measures usual • Intervention • Interviewer or self-administered • Period of recall imprecise
Adult intake • Monitoring • Relatively inexpensive to collect • Quantification of intake
Validity — 22 assistance Protein • Epidemiologic • Procedure does not alter habitual imprecise because of poor recall
Reliability — 7 needed for 0.18-0.34 dietary habits or use of standard portion sizes
<9 y • Low respondent burden • Specific food descriptions not
Total fat • Total diet or selected foods or obtained
0.19-0.39 nutrients can be assessed
• Can be used to rank according to
nutrient intake
• Procedure can be automated
DIET HISTORY 5-13 y N/A N/A One history • Monitoring • Literacy not required • Recall depends on memory
measures usual • Clinical • Procedure does not alter habitual • Highly trained interviewers
Validity — 0 Adult intake • Epidemiologic dietary habits required
Reliability — 1 assistance • Can obtain highly detailed • Period of recall imprecise
needed for descriptions of foods and • Very high respondent burden
all ages preparation methods • Requires long interview time
• Quantification of intake
imprecise because of poor recall
or use of standard portion sizes
• Expensive to administer
OBSERVATION 8-10 y N/A N/A One observation • Intervention • Literacy not required • Highly trained observers
measures • Monitoring • Procedure does not alter habitual required
Validity — 0 group intake • Epidemiologic dietary habits • Requires long observation
Reliability — 1 • Procedure does not rely on period
Multiple memory • Expensive to administer
observations • Defined observation time
measure • Intake can be quantified
individual or • Multiple days give measure of
group intake individual or group intake

a Pearson correlation
b Calculation of percentage = ([instrument-validation standard]/validation standard)
517
for validation standards here, and information on the validity of these methods in children
is mixed. Recalls both over- and underestimated energy, and food records underestimated
energy intake. Most recall validity studies used observation of the child as the standard,
but the majority of the studies only considered individual meals or daytime intakes to
determine validity of the 24-hour recall. Accurate completion of food records is greatly
dependent on the ability of the child to read and write. Because young children have not
been shown to accurately complete food records independently, caution is suggested when
interpreting studies that use records as the validation standard. The validity of food
records or recalls for measuring long term or usual food intake improves with more days
of recording,5 indicating that multiple records may be needed. Multiple food records/
recalls can introduce compliance issues for children because of the high respondent bur-
den. Since a high degree of cooperation is required from children for food records and
recalls, it is essential for both methods that children be motivated to participate, and in
particular be cognitively able to complete the records.
In evaluating validation studies, the effect of correlated errors between the method
evaluated and the validation standard should be considered. All dietary assessment meth-
ods have inherent errors; for validation studies, it is important that these errors be as
independent as possible.45 For example, if errors between the methods are similar (e.g.,
both methods rely on dietary information from a respondent such as FFQ and recalls),
correlations between the two methods will be artificially inflated. In contrast, errors inher-
ent in physiologic measures (e.g., doubly labeled water measurements or serum micron-
utrients) or observational data do not rely on information provided by respondents, and
would be a more independent comparison to a respondent-based measure.46 Comparisons
of physiologic endpoints, such as blood nutrient levels, to dietary assessment methods
have not been widely used with school-age children and offer other problems, since food
intake may not be directly correlated with physiologic endpoints.
Selecting a validation standard can be a difficult task, because there is often no dietary
assessment tool available with the same referent period as the assessment tool. Thus, a
compromise may be needed in the study design. For example, an FFQ measures usual
food consumption over a period of six months to a year, while a food record generally is
used to measure food consumption on a day-to-day basis. In order to validate an FFQ, it
would be necessary to complete several sets of food records over the referent period for
the FFQ. Clearly, validation studies that use a week of continuous consecutive food records
may not capture seasonal variation in diet. Similarly, a food recall, which is generally used
to measure one complete day of consumption, should be validated by a method that
assesses an entire day, not just a portion of the day.
The problem of referent periods also influences the experimental design for reliability
studies. Because there is much day-to-day variation in diet, re-administration should be
close enough in time to reflect the same referent period. Since some methods reflect diet
over a short span of time (e.g., 1-day records and 24-hour recalls), theoretically the reli-
ability testing should be completed on the same day as the assessment tool, which may
allow memory effects from the first assessment to bias the re-administration. Studies that
examine reliability should alternate administrations in order to eliminate bias as much as
possible. Because FFQs usually include a longer referent period, it is easier to develop
reproducibility studies for this method.
In all the studies reviewed, adult dietary assessment methods were adapted for admin-
istration to a pediatric population. Specific adaptations included incorporating parental
or adult assistance, adjusting portion size information, using shorter referent times, and
administering the instrument in the school setting. Children younger than nine years of
age need adult assistance to provide accurate dietary information because they usually
have limited reading skills and adults control most of the food offered, as well as the
timing and frequency of eating occasions.47-48 This review found that almost all of the
validity and reliability studies among children less then nine years of age, with the
exception of a few of the recall and FFQ studies, included adult participation. This par-
ticipation varied from completion of the form entirely to obtaining only supplemental
information from parents or surrogates, such as childcare providers, or secondary sources
such as school food service observations.
Children generally have difficulty in estimating portion sizes.30,49,50 A recent review of
portion size aids was unable to make guidelines for portion size estimation for children
or adults.51 Both two- and three-dimensional models have been used to enhance children’s
portion size estimation.7-9,11,16,21,39,41-42,52-54 Pictures of food and portions have been incorpo-
rated in assessments to enhance children’s understanding; however, the addition of pic-
tures did not increase accuracy among third-graders.55 Among the newer tools for dietary
assessment are reference books with life-size photographs of portion sizes, which have
been credited as being both easy and accurate.56-59 Training to improve portion size esti-
mation among children has been attempted with significant improvements in estimation;
however, even with training, some errors were reported as high as 100%.60
Semi-quantitative FFQs have not generally used portion sizes adjusted for children’s
level of intake. This may have enhanced the lack of agreement between the FFQ and
validation standard, if the validation standard allowed for collection of specific portions
consumed by the child. These FFQs may have systematically overestimated intake due to
portion size miscalculations.
Because the school provides a natural means of regularly accessing school-age children,
several researchers continue to explore ways of using this setting to collect dietary intake
data. Methods such as using a group workbook to collect 24-hour recall information61
have been developed to expand the number of eating occasions that can be evaluated,
while trying to minimize the respondent burden for multiple records or recalls.
Recommendations
Despite the extensive dietary intake data available to nutritionists, epidemiologists, and
pediatricians, this review identifies methodological concerns associated with the assess-
ment tools currently used to determine dietary intake of school-age children. Generally,
comparisons across studies were limited by differences in instruments, research design,
validation standards, and populations. The paucity of data in many areas also made it
difficult to draw generalized conclusions.
In the last three decades the most extensive body of validation work among children
has occurred with FFQs, with only a limited number of validation studies and even fewer
reliability studies of the other methods among school-age children. In the future, evalua-
tions of dietary assessment techniques for children need to be conducted that give partic-
ular attention to experimental design, careful use of validation standards, and inclusion
of different age, gender, and ethnic subgroups. As with adults, there is no perfect method
of assessing dietary intake in children. Special consideration must be given to the age and
cognitive ability of the child as well as methodological issues associated with nutrient
analyses, food coding, and portion sizes. Both age and cognitive ability relate to the child’s
understanding of the method used and the thought processes that contribute to self-
reporting of food choices.
What needs to be done? Ideally, studies need to examine the validity and reliability of
each dietary assessment method by age, gender, and ethnic subgroup to understand the
best application of each tool. Selection of the measure of truth for validation studies will
be challenging, since there is not always a good choice when the referent periods differ
so markedly between instruments, and the potential effect of correlated errors is consid-
ered. Physiologically based measures, such as doubly labeled water or serum micronutri-
ent concentrations, represent a type of standard with considerable appeal and merit further
study, since these measures are not affected by respondent error. In addition, studies that
compare multiple validation standards for a particular assessment method would allow
comparisons of the validation standards best suited for particular situations. Future stud-
ies need to address the timing of the referent period that best suits the assessment instru-
ment in the design phase.
New approaches and modifications to existing approaches for dietary assessment among
school-age children are needed. The dietary habits of children, especially young children
who are preliterate, are inherently difficult to study. Unfortunately, assessment techniques
that work reasonably well among adult men and women may not be useful for children,
especially those less than nine years of age, who may need assistance from a proxy or
special prompting techniques to estimate portion size. Creative measures must be devel-
oped to better estimate children’s portion sizes and enhance researchers’ ability to capture
details of their dietary intake. Systematic evaluations of children’s ability to estimate
portion size utilizing various approaches by age are needed.
Researchers are urged to investigate how variables such as age, gender, ethnicity, socio-
economic status, and obesity affect the validity of dietary assessment methods. This
review found little research on the effects of age, gender, or ethnicity. Given the multi-
plicity of minority groups in the U.S., there is a need for research to determine whether
group-specific dietary assessment tools are necessary. Other areas, such as the effect of
body size on reporting of dietary intake, require further study. For example, a recent study
suggested that children with central fat distribution had higher rates of underreporting
energy intake than lean or obese children, or those with peripheral fat distribution.20
Another study reported that energy intake was significantly lower in obese children than
non-obese children when compared to doubly labeled water as a percentage of energy
expenditure.62 Underreporting of dietary intake by obese adolescents is consistent with
recent findings that obese adults tend to underreport their dietary intake.62 With the
increasing prevalence of obesity among children and adolescents, it is essential to deter-
mine whether body size differences significantly affect completion of dietary assessment
instruments.64
In summary, much remains to be learned about the dietary intake of American youth.
This review serves as a guide to the state of dietary assessment among school-age children.
Recalls and records generally agreed more with the validation standards than did FFQs.
Administration protocols differed greatly, the recalls and records often represented only
meals or portions of the day, and the FFQ food lists varied from a few items to the total
diet. This review can also serve as a foundation for initiating new studies and as a resource
for developing research questions from the gaps identified in the current methodologies.
The key to advancing the field is to build on our current base of methods, refine techniques
that are useful, and develop new approaches to overcome obstacles that have been iden-
tified in study designs and data collection procedures. In the new millenium we must be
able to accurately assess the dietary intake of our school-age children so that we can
monitor dietary intake trends, make accurate research and policy decisions, and develop
and effectively evaluate nutrition interventions.
Acknowledgment
The authors would like to thank Heidi Nowak for assisting with manuscript preparation.
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21
Methods and Tools for Dietary Intake Assessment in
Individuals vs. Groups
Ruth E. Patterson
Introduction
Dietary intake is an important, modifiable determinant of health and longevity. Compre-
hensive reviews of the literature have consistently concluded that clear, causal links exist
between food intake and major causes of morbidity and mortality, such as coronary heart
disease, cancer, diabetes, and obesity.1-3 In addition, undernutrition continues to be a
substantial health problem in many countries.4
Given the importance of diet in human health, assessment of dietary intake plays a
pivotal role in efforts to improve the health of individuals and populations throughout
the world. Dietary intake data are used for three major purposes:
1. At the individual level, assessment of dietary intake is necessary for determining

a person’s dietary adequacy or risk, assessing adherence to recommended
dietary patterns, and tailoring education and counseling efforts.
2. Dietary intake assessment is an integral part of research studies investigating
how diet determines the health of individuals and populations. Etiologic studies
assess dietary intake as an exposure for association with disease outcomes.
Behavioral research assesses dietary intake (or change in intake) as an outcome
in studies designed to develop and test strategies that encourage adoption of
healthful eating patterns.
3. Finally, at the population level, assessment of dietary intake is necessary to
identify national health priorities and develop public health dietary recommen-
dations. These data are used to determine the success of public health interven-
tions in improving dietary patterns and for identification of population
subgroups at risk or in need of special assistance. Nutrition monitoring also
serves a key role in food assistance programs, fortification initiatives, food safety
evaluations, and food labeling programs.
0-8493-2705-9/01/$0.00+$1.50
It is clear that dietary assessment is a cornerstone of efforts to improve the health of

individuals and groups. However, there are significant concerns about the accuracy and
usefulness of self-reported dietary data. The challenges associated with assessing dietary
intake are well known and have to do with day-to-day variation in intake, respondent
reporting errors and biases, limitations of the assessment instruments, and error in food
composition tables.5 Several different assessment methods and tools have been developed
to address these difficulties, and each method has different strengths and weaknesses with
regard to the type and quality of data produced. In addition, there are significant differ-
ences among these assessment methods in practical matters of respondent burden and
cost. Therefore it is necessary to carefully consider the specific objectives of the dietary
assessment as a precursor to choosing the best or most appropriate method. Perhaps the
first and most important question is whether the data will be used for assessing intake in
individuals or groups.
Here we describe the three major types of dietary assessment methods: 1) food records
and 24-hour dietary recalls, 2) food frequency questionnaires, and 3) brief assessment
instruments. We summarize the scientific and practical advantages and disadvantages of
each of these methods. Then we consider the use of these three dietary assessment methods
for assessing diet in individuals versus groups; when they are used for determination of
an individual’s dietary adequacy for purposes of counseling, research studies of dietary
intake and disease risk, and nutrition monitoring of populations.
Description of the Three Major Dietary Assessment Methods

Food Records and Dietary Recalls (Records/Recalls)
For many years, food records were considered the “gold standard” of dietary assessment
methods. Food records require individuals to record everything consumed over a specified
period of time, usually one to seven days. Respondents are typically asked to carry the
record with them and to record foods as eaten. Some protocols require participants to
weigh and/or measure foods before eating, while less stringent protocols use models and
other aids to instruct respondents on estimating serving sizes. The food consumption
information is entered into a specialized software program for calculation of nutrient
intakes. This data entry step is a time-consuming task and requires trained data technicians
or nutritionists.
A dietary recall is a 20 to 30 minute interview in which the respondent is asked to recall
all foods and beverages consumed over the past 24 hours. These interviews can be con-
ducted in person or by telephone. In some settings, the information is captured on paper
forms and subsequently entered into the software program for nutrient analysis. However,
ideally the interview will be conducted simultaneously with direct data entry into the
software program. The record/recall analysis program provides specific prompts about
foods, preparation methods, and portion sizes; therefore this protocol results in greatly
increased standardization of the information received.
Advantages and Disadvantages of Records/Recalls

Both records and recalls provide the same type of data: detailed information on all foods
and beverages consumed on specified days. In theory, a food record provides a “perfect”
snapshot of intake. In practice, there are significant limitations associated with this method
Methods and Tools for Dietary Intake Assessment in Individuals vs. Groups 525
for assessing food intake. The principal problems are the large respondent burden of
recording food intake and the impact on usual food consumption caused by record keep-
ing. Respondents may alter their normal food choices merely to simplify record keeping
or because they are sensitized to food choices. The latter reason appears more likely among
women,6 restrained eaters,7 obese respondents,8 or participants in a dietary intervention.9
Other sources of error by respondents include mistakes or omissions in describing foods
and assessing portion sizes.
Unannounced, interviewer-administered 24-hour dietary recalls are often recommended
because respondents cannot change what they ate retrospectively.10 One major disadvan-
tage of dietary recalls is that they rely on the respondent’s memory and ability to estimate
portion sizes. In addition, it cannot be verified that social desirability does not influence
self-report of the previous day’s intake. A noteworthy benefit of recalls is that they are
appropriate for low literacy populations.
Both records and recalls are expensive and time-consuming. However, the major scien-
tific issue with records/recalls concerns the issue of day-to-day variability in intake, which
means that several days of records/recalls are required to characterize usual intake. Using
data on variability in intake from food records completed by 194 participants in the Nurses
Health Study, 11 the number of days needed to estimate the mean intakes for individuals
within 10% of “true” means would be 57 days for fat, 117 days for vitamin C, and 67 days
for calcium. For estimating food consumption for individuals, variability can be even
greater. For example, the number of days needed to estimate the following foods within
10% of “true” means would be 55 days for white fish and 217 days for carrots. Unfortu-
nately, research has shown that reported energy intake, nutrient intake, and recorded
numbers of foods decreases with as few as four days of recording dietary intake.12 These
changes may reflect reduced accuracy and completeness of recording intake or actual
changes in dietary intake to reduce the burden of recording intake. In either case, there
are considerable limitations on the usefulness of this methodology for characterizing usual
intake in individuals.
Food Frequency Questionnaires (FFQs)

FFQs were developed for conducting research on dietary intake and chronic diseases such
as heart disease and cancer. Because these diseases develop over 10 or more years, the
biologically relevant exposure is long-term diet consumed many years prior to disease
diagnosis. Therefore, instruments that only capture data on short-term or current intake
(i.e., food records or recalls) are generally of limited usefulness in nutritional epidemiol-
ogy research.
FFQs are designed to capture standardized, quantitative data on current or past, long-
term diet. Although these questionnaires vary, they usually include three sections: 1)
adjustment questions, 2) the food list, and 3) summary questions. Adjustment questions
assess the nutrient content of specific food items. For example, participants are asked what
type of milk they usually drink and are given several options (e.g., whole, skim, soy),
which saves space and reduces participant burden compared to asking for the frequency
of consumption and usual portion sizes of many different types of milk. Adjustment
questions also permit more refined analyses of fat intake by asking about food preparation
practices (e.g., removing skin from chicken) and types of added fats (e.g., use of butter
versus margarine on vegetables).
The main section of an FFQ consists of a food or food group list, with questions on
usual frequency of intake and portion size. To allow for machine scanning of these forms,
frequency responses are typically categorized from “never or less than once per month”
to “2+ per day” for foods and “6+ per day” for beverages. Portion sizes are often assessed
by asking respondents to mark “small,” “medium,” or “large” in comparison to a given
medium portion size. However, some questionnaires only ask about the frequency of
intake of a “usual” portion size (e.g., 3 ounces of meat).
The food list in an FFQ is chosen to capture data on major sources of energy and nutrients
in the population of interest, between-person variability in food intake, and specific sci-
entific hypotheses. The choice of a food list is part data-driven and part scientific judgment.
One data-based approach uses record/recall data to determine the major nutrient sources
in the diet (i.e., the contribution of specific foods to the total population intake of nutrients).
Information on food sources of nutrients in the American population have been
published13,14 but are often unavailable for specific population groups (e.g., Hispanics).
However, a food is only informative if intake varies from person to person such that it
discriminates between respondents. Therefore, another data-based approach to choosing
the food list is to start with a extensive list of foods that is completed by a representative
sample of the larger population. Stepwise regression analysis is performed where the
dependent variable is the nutrient and the independent variable is frequency of consump-
tion of foods.15 In this process the computer algorithm ranks foods by the degree to which
they explain the most between-person variance in nutrient intake, which is reflected in
change in cumulative R2. In addition to these two data-driven methods, items are often
added to a questionnaire because of specific hypotheses (e.g., does consumption of soy
foods reduce breast cancer risk).
A particularly challenging issue in FFQ food lists has to do with assessing intake of
mixed dishes. For example, many FFQs ask about frequency of pizza consumption. How-
ever, from a nutrient perspective there is no accurate way to define “pizza.” Depending
on whether it is meat or vegetarian, thick or thin crust, tomato or pesto sauce, and so
forth, pizza may be either low-fat and high-carbohydrate or extremely high-fat and high-
protein. However, it is unreasonable to ask individuals to disaggregate their pizza into
servings of breads, vegetables, meats, cheese, and added fats. Therefore FFQs typically
strike an uneasy compromise between asking about some mixed dishes (e.g., pizza, ham-
burgers, tacos) while also asking the respondent to provide information on foods contained
in their mixed dishes: “cheese, including cheese added to foods and in cooking.” Unfor-
tunately, asking about both “lasagna” and “cheese in cooking” presents the peril of double
counting. There are little or no data to guide an investigator in making these judgments.
Finally, to save space and reduce respondent burden, similar foods are often grouped
into a single line item (e.g., white bread, bagels, and pita bread). When grouping foods,
important considerations include whether they are nutritionally similar enough to be
grouped and whether the group will make cognitive sense to the respondent. For example,
a food group composed of rice, macaroni, and cooked breakfast cereal may be nutritionally
sensible. However, this question could be difficult to answer because it requires summing
food consumption across different meal occasions.
Finally, FFQ summary questions that ask about usual intake of fruits and vegetables are
often included in the questionnaire because the long lists of these foods needed to capture
micronutrient intake can lead to overreporting of intake.16
Assessing the Reliability and Validity of Food Frequency Questionnaires

Because records and recalls are open-ended, they can (in theory) be applied in a standard-
ized manner across populations with markedly different eating patterns. However, as
noted above, FFQs are closed-ended forms with limited food lists. Because the food list
varies from questionnaire to questionnaire, every FFQ will have different measurement
characteristics. In addition, a questionnaire with appropriate foods and portion sizes for
one population group (e.g., older caucasian men) may be wholly inappropriate for another
subgroup (e.g., teenage African-American females). Finally, given changes in the food
supply over time, such as the introduction of specially manufactured low-fat foods, ques-
tionnaires can become obsolete. Therefore the measurement characteristics (i.e., reliability
and validity) of an FFQ need to be assessed for each new questionnaire and each new
population group assessed.
Reliability generally refers to reproducibility, or whether an instrument will measure an
exposure (e.g., nutrient intake) in the same way twice on the same respondents. Validity,
which is a higher standard, refers to the accuracy of an instrument. Generally a validity
study compares a practical, epidemiologic instrument (e.g., an FFQ) with a more accurate
but more burdensome method (e.g., dietary recalls).
Reliability and validity of an FFQ are typically investigated using measures of bias and
precision. Bias is the degree to which the FFQ accurately assesses mean intakes in a group.
Lack of bias is especially important when the goal is to measure absolute intakes for
comparison to dietary recommendations or some other objective criteria. For example,
when the aim is to estimate how close Americans are to meeting the dietary recommen-
dation to eat five servings of fruits and vegetables per day, it is critical to know whether
the assessment instrument used under- or overestimates fruit and/or vegetable intake.
Precision concerns whether an FFQ accurately ranks individuals from low to high nutrient
intakes, which is typically the information needed to assess associations of dietary intake
with risk of disease. It is important to remember than an instrument can be reliable without
being accurate. That is, it can yield the same nutrient estimates two times and be wrong
(e.g., biased upward) both times. Alternatively, an instrument can be reliable and consis-
tently yield an accurate group mean (e.g., unbiased), but have poor precision such that it
does not accurately rank individuals in the group from low to high in nutrient intake.
A reliability study compares intake estimates from two administrations of the FFQ in
the same group of respondents. If an instrument is reliable, the mean intake estimates
should not vary substantially between the two administrations. In addition, correlation
coefficients between nutrient intakes estimated from two administrations of the FFQ in
the same group of respondents should be high, and are generally in the range of 0.6 to
0.7. Reliability is easy to measure and gives an upper bound as to the accuracy of an
instrument. While a high reliability coefficient does not imply a high validity coefficient,
a low reliability coefficient clearly means poor validity. That is, if an instrument cannot
measure a stable phenomenon (such as usual nutrient intake) the same way twice, it clearly
cannot be accurate.
In a validity study, bias is assessed by comparing the mean estimates from an FFQ to
those from multiple days of records/recalls in the same respondents. This comparison
allows us to determine whether nutrient intake estimates from an FFQ appear to be under-
or overreported in comparison to the criterion measure. Precision is measured as the
correlation coefficients between nutrient intake estimates from the FFQ in comparison to
a criterion measure, and typically range from 0.4 to 0.6. However, lower correlation
coefficients (<0.4) are not unusual for nutrients that are poorly estimated with an FFQ,
such as energy.17 In addition, inclusion of dietary supplement use will often improve
correlation coefficients (>0.8) because supplement use may be more accurately assessed
and/or because supplement doses can be extraordinarily high compared to dietary intake,
and thereby markedly increase the variability in intake for a nutrient. Some studies also
assess precision by ranking nutrient intake estimates, dividing them into categories (e.g.,
quartiles) and comparing these to similar categories calculated from another instrument.
However classifying a continuous exposure into a small number of categories does not
reduce the effects of measurement error, and therefore this analysis does not provide
additional information above correlation coefficients.18
The theory behind these (so-called) validity studies is that the major sources of error
associated with FFQs are independent of those associated with records and recalls, which
avoids spuriously high estimates of validity resulting from correlated errors. The errors
associated with FFQs are the limitations imposed by a fixed list of foods and the respon-
dents’ ability to report usual frequency of food consumption (and usual portion sizes)
over a broad time frame. In contrast, diet records are open-ended, do not depend on
memory, and permit measurement of portion sizes. Errors in food records result from
coding errors and changes in eating habits while keeping the records. Error in recalls
results from estimation of portion sizes, participant memory, and coding errors.
Nonetheless, it is apparent that there are correlated errors between FFQs and records
or recalls. Social desirability could influence how participants record or recall food intake
across all types of dietary assessment instruments.6,9 Participant error in estimating portion
sizes could bias recall and FFQ estimates of intake in similar ways. There are also correlated
errors in nutrient databases. Finally, research using doubly-labeled water to determine
energy requirements have demonstrated significant underreporting of energy intakes from
food records that may vary by participant characteristics.8 It is important to be aware of
the limitations of records and recalls as criterion measures of dietary intake, and cautiously
interpret results based on these measures.
A final note is that an FFQ cannot, in and of itself, be validated. Only individual nutrient
intake estimates can be validated by comparison of a nutrient estimate from the FFQ to
a more accurate measure.
Advantages and Disadvantages of Food Frequency Questionnaires

The major advantage of FFQs is that they attempt to assess usual, long-term diet; either
current or in the past. In addition, they have relatively low respondent burden and are simple
and inexpensive to analyze because they can be self-administered and are machine scannable.
A disadvantage of these questionnaires is that respondents must estimate usual frequency
of consumption of approximately 100 foods and the associated usual portion sizes. These
types of questions (i.e., this cognitive task) can be exceedingly difficult for many respondents,
as evidenced by the prevalence of energy estimates from FFQs well outside the realm of
what is plausible.19 For example, it is not unusual for respondents to report usual energy
intakes that are less than 500 kcals per day or greater than 5000 kcals per day. In addition,
the format of the questionnaire is not user-friendly. Because FFQs are machine scannable,
respondents must indicate their responses by filling in circles in a food-by-frequency matrix
similar to that used in standardized testing. Some population groups may be unfamiliar or
uncomfortable with such data collection methods. As might be hypothesized, validity studies
of FFQs suggest that these forms may be less valid in less educated respondents.20
Another major disadvantage of these questionnaires is related to the close-ended nature
of the form. The limited food list will not be appropriate for all individuals in a population
and as noted above, different forms have different measurement characteristics in different
populations. Therefore data from different FFQs are not directly comparable, nor are data
from the same FFQ used in different populations, or data from the same FFQ used at
different points in time (because of changes in the food supply). Finally, dependent upon
the food list chosen by the investigator, the validity of nutrient intake estimates will vary
from nutrient to nutrient.
Brief Dietary Assessment Instruments

Comprehensive dietary assessments (records/recalls and FFQs) are not always necessary
or practical, which has led to the development of a diverse collection of brief assessment
instruments. These include three general types: 1) ecologic-level measures such as food
disappearance data or household food inventories, 2) short instruments that target a limited
number of foods and/or nutrients, and 3) questionnaires that assess dietary behavior.
Ecologic-Level Measures
One well-known ecologic assessment of dietary intake is per capita food consumption
estimated using national data on the total food supply. Publications from the Food and
Agricultural Organization provide data on a country’s total food supply from which non-
consumption uses (such as exports and livestock feed) are subtracted, after which the total
remaining food available can be divided by the population to obtain the per capita estimate
of intake. These population intakes have been correlated with disease incidence across
countries in provocative hypothesis-generating studies.21-24
Other ecologic measures, such as supermarket sale receipts,25 have been developed and
evaluated. Household food inventories are another example. In one study, the presence
(in the house) of 15 high-fat foods was found to correlate with household members’ dietary
fat intake at 0.42 (p<0.001).26 Individuals with ≤ 4 high-fat foods in their house had a mean
of 32% energy from fat compared to 37% for those with ≥ 8 high-fat foods. Poor household
food availability has also been shown to be significantly associated with greater individual-
level measures of food insecurity.27
Targeted Instruments
Dietary assessment instruments that measure a limited number of foods and/or nutrients
are most useful when the target food/nutrient is not distributed throughout the food
supply. For example, dietary fat is widely distributed in dairy foods, meats, added fats,
desserts, prepared foods, etc. Therefore, short instruments that attempt to estimate fat
intake tend to be biased and imprecise.28,29 Alternatively, intake of the isoflavones genestein
and daidzain, which are largely limited to soy foods, can be captured with a relatively
short instrument (15 foods).30
Behavioral Instruments
The development of diet behavioral instruments was motivated by problems with assess-
ing dietary intervention effectiveness, particularly low-fat interventions. Traditional com-
prehensive instruments, such as records and FFQs, yield fairly imprecise estimates of fat
intake that may not be sensitive to an intervention focused on changing participants’
dietary behavior. One of the best known instruments of this type is the fat-related diet
habits questionnaire.31 This instrument was based on an anthropologic model that
described low-fat dietary change as four types:
1. Avoiding high-fat foods (exclusion)

2. Altering available foods to make them lower in fat (modification)
3. Using new, specially formulated or processed, lower-fat foods instead of their
higher-fat forms (substitution)
4. Using preparation techniques or food ingredients that replace the common
higher-fat alternative (replacement)
Although originally developed for intervention assessment, the diet-habits question-

naire has since been used as a short assessment instrument in other research settings.32,33
Advantages and Disadvantage of Brief Assessment Instruments

The principal advantage of ecologic measures is that they are simple, inexpensive, non-
intrusive, and objective measures of nutritional status. However these environmental
indicators do not provide precise measures of individual intake.
Targeted questionnaires also tend to yield rather imprecise food and/or nutrient esti-
mates. For example, short questionnaires for assessing fruit and vegetable intake have been
extensively used in surveillance and intervention research. The typical approach uses two
summary questions to capture consumption of most fruits and vegetables: “How often
did you eat a serving of fruit (not including juices)?” and “How often did you eat a serving
of vegetables (not including salad and potatoes)?,” to which are added usual consumption
of juice, salad, and potatoes.34 Comparison of this brief measure with food records, food
frequency estimates, and serum carotenoids indicates that this method yields particularly
biased (underestimated) and imprecise measures of vegetable intake, likely because veg-
etables in mixed foods such as casseroles or sandwiches may be forgotten and unreported.16
The major advantage of the behavioral questionnaires is that they are short and simple
(i.e., low respondent burden) and can be easily data-entered and scored. The disadvantage
is that the diet “score” derived from these measures can be difficult to interpret because
it is not comparable to nutrient or food intake measures. In addition, because these
questionnaires have typically been “validated” in relation to records or recalls, which have
many sources of error and bias, the degree to which they accurately reflect dietary intake
is unknown.
Use of Dietary Assessment Methods in Individuals vs. Groups

Determination of an Individual’s Dietary Adequacy for Purposes of Counseling
Records/Recalls
Records and recalls are used in clinical and counseling settings to assess dietary intake
and are often used in a qualitative fashion. That is, respondents are asked to describe a
usual day’s intake and the nutritionist simply “eyeballs” the eating pattern for estimating
dietary adequacy or risk, adherence to a prescribed diet, and/or areas for improving eating
habits. The individualized nature of the interview can allow for probing and personaliza-
tion of the feedback.
Whether these methods are used in a quantitative or qualitative manner, records and
recalls can provide useful and understandable information to a respondent. The respon-
dent can observe that the dietary recommendations are based directly on the food intake
information provided and can use the advice to alter future food choices, food preparation
techniques, or portion sizes. Therefore, on an individual level, records and recalls can
serve an important teaching function. In addition, there is considerable literature indicat-
ing that the act of keeping records (i.e., self-monitoring) is a significant predictor of success
in achieving weight loss or making other dietary changes.29
Food Frequency Questionnaires

FFQs tend to produce imprecise dietary intake estimates because of respondent error and
inappropriate food lists. In addition, the data input (usual frequency of intake and portion
sizes) and nutrient calculation algorithms are a black box to the respondent. Therefore the
respondent cannot easily use this information to make more healthful food choices. For
these reasons, FFQs are not generally useful for assessing an individual’s nutrient intake
for purposes of counseling.
However, data on food consumption from FFQs has been used for individual feedback.
For example, Kristal et al. developed computer programs for tailored feedback to partic-
ipants in a self-help dietary intervention that used FFQ data to provide food-specific
recommendations to reach nutritional goals (e.g., “if you use low-fat mayonnaise instead
of regular mayonnaise you will cut your fat by 28 g per week”).35 Because the feedback
provided to the participants is food based and taken directly from their responses (e.g.,
type of mayonnaise used and frequency consumed), this approach avoids the black box
problems associated with using FFQs to estimate nutrient intake.
Brief Assessment Instruments

These instruments are diverse, and therefore it is difficult to generalize regarding their use.
Ecologic measures are intended to be environmental indicators and therefore are generally
not appropriate for individuals. However, it is clear that some simple targeted instruments
can be very useful for individual counseling. For example, a rather short set of questions
can likely assess usual fruit and vegetable consumption sufficiently for purposes of advis-
ing a respondent whether his/her intake appears to be adequate or inadequate.
Research Studies of Dietary Intake and Disease Risk

Records/Recalls
Records and recalls have limited usefulness in research studies of diet and disease risk
for both scientific and practical reasons. Scientifically, records/recalls only assess current,
short-term diet, and in most etiologic studies usual long-term (and often past) diet is the
exposure of biologic significance. Practically, records and recalls are infeasible because of
costs and respondent burden. However, records and recalls are often used in subsamples
of the parent study for the following purposes:
1. FFQ reliability and validity substudies

2. Evaluating dietary interventions where the goal is to compare mean intakes in
the intervention versus the control group
3. As a check of the main study assessment instrument (such as an FFQ)

As noted above, the major advantage of an FFQ is that it attempts to assess the exposure
of interest in most applications: usual dietary intake in an individual. The main use of
these instruments is to rank study participants from low to high intake of many foods
and nutrients for comparison (on the individual level) with disease risk. However, these
questionnaires produce food and nutrient estimates containing considerable random error
resulting from inadvertently marking the wrong frequency column, skipping questions,
and failures in judgment. These errors introduce noise into nutrient estimates such that
our ability to find the “signal,” such as an association of dietary fat and breast cancer, is
masked or attenuated (i.e., biased toward no association).
However, a more important concern in research studies is systematic error. Systematic
error refers to under- or overreporting of intake across the population, and person-specific
sources of bias. For example, studies indicate that obese women are more likely to under-
estimate dietary intake than normal-weight women.8 Systematic error may result in either
null or spurious associations. Prentice used data from FFQs collected in a low-fat dietary
intervention trial to simulate the effects of random and systematic error on an association
of dietary fat and breast cancer, where the true relative risk (RR) was assumed to be 4.0.36
Assuming only random error exists in the estimate of fat intake, the projected (i.e.,
observed) RR for fat and breast cancer would be 1.4. Assuming both random error and
systematic error exists, the projected RR would be 1.1, similar to that reported in a recent
meta-analysis on dietary fat and breast cancer.37 Data on systematic error from biomarker
studies, combined with these types of statistical simulations, clearly suggest that measures
of self-reported dietary intake may not be adequate to detect many associations of diet
with disease, even when a strong relationship exists. It is important to note that records/
recalls are not exempt from these biases.
Finally, FFQs cannot provide detailed information on specific foods (e.g., brand names)
or eating patterns (e.g., meals per day or consumption of breakfast) that may be important
in some research studies.

Most brief instruments were developed for very specific research applications. The biggest
concern when using a brief instrument is that it is often impossible to anticipate all the
questions regarding diet that may become important by the end of a study. Therefore, the
choice of a brief instrument limits future questions that can be addressed. Nonetheless,
data collection for research purposes is a compromise between what is ideal and what is
practical, and a comprehensive dietary assessment may not always be possible.
Nutrition Monitoring of Populations

Records/Recalls
Records and recalls have proven very useful for nutrition monitoring. A single day’s intake
can provide estimates of the average intake of large groups that are comparable to those
obtained with more burdensome techniques.38 Because these methods are open-ended,
they are especially useful for assessing mean intake across population groups with mark-
edly different eating patterns.
However, a single day’s intake cannot be used to study distributions of dietary intake
because on any one day, an individual’s diet can be unusually high (e.g., a celebratory
meal) or low (e.g., a sick day). These days are not representative of an individual’s intake
even though they may be perfectly recorded. This day-to-day variation in intake is random
and does not bias the mean intake for a group, although this variability does result in an
increased distribution of observed intake (i.e., a wide standard deviation). However, if
multiple measures (per person) are collected on a subsample of the population, it is possible
to obtain an estimate of the within- vs. between-person variance and calculate the “true”
standard deviation around the mean for the population. This procedure allows the inves-
tigator to determine the percent of individuals above (or below) a specified cut-point.15
Although the use of records/recalls in nutrition monitoring appears straightforward,
there is actual considerable subtlety about the data needed to address public health
dietary objectives. For example, assume that a public health objective is to reduce total
fat intake to less than or equal to 30% energy from fat. A critical clarification of this
objective is whether:
1. The population mean intake should be 30% energy from fat, in which case
approximately half of the group will have intakes exceeding that level, or
2. The entire population should have intakes less than or equal to 30% energy from
fat, in which case the group mean will be several percentage points below 30%.
If the public health objective is the first goal listed, then nutrition monitoring can be
appropriately performed with a single 24-hour record/recall for determination of mean
intake in the population. Alternatively, if the public health objective is the second, then
multiple records/recalls (per person) will need to be collected for assessment of intake
distribution in the population to determine the proportion of individuals consuming more
than 30% energy from fat.

FFQs have proven most useful in nutritional epidemiologic studies when the objective is
to rank individuals from low to high intake for a food or nutrient. However, as described
above, FFQs are close-ended forms with limited food lists, and the accuracy of FFQs will
vary considerably across groups with different eating patterns. Therefore when the goal
is to assess mean intakes in population subgroups with markedly different dietary pat-
terns, or to track changes in intake over long periods of time, the FFQ is not the instrument
of choice.

The accuracy of several of these instruments is particularly sensitive to differences in
dietary patterns across population groups. For example, the validity of a fat-related behav-
ioral questionnaire depends entirely on knowledge of those dietary behaviors that influ-
ence fat intake. In populations with different dietary patterns, the instrument would be
useless for assessment of fat intake. Overall, it is useful to remember that brief dietary
assessment instruments are developed for very specific objectives and caution needs to
be taken when applying them to other populations or using them for other purposes.
Summary
Much of what has been presented here is summarized in Tables 21.1 through 21.3. Spe-
cifically, Table 21.1 summarizes the major scientific and practical advantages and disad-
vantages of the major dietary assessment methods. Table 21.2 provides an overview of
the issues regarding use of data from dietary intake assessment methods. Table 21.3 gives
a summary of consideration regarding use of dietary intake assessment in individuals
versus groups.
The use of sophisticated computerized technologies and internet accessibility has the
potential to address many of the practical and logistic limitations of the major dietary
intake assessment methods. For example, a computer screen could provide life-size pic-
tures of foods to help respondents more accurately estimate serving sizes. A user-friendly
computer-administered dietary recall could eliminate the costs associated with this
method of collecting data. A touch-screen FFQ program, with algorithms for limiting
questions to foods eaten with some minimal frequency, could eliminate the unfriendly
format of the questionnaire and tailor the food list. Nonetheless, these practical advances
will not eliminate the scientific problems inherent in dietary self-report. In particular, the
issues of systematic and person-specific biases in self-report can likely only by addressed
by use of objective biomarkers for identification, quantification, and correction of random
and systematic error.39
It is clear from this brief overview that choosing the appropriate dietary assessment
method is a complex decision based on the specific objective, with an eye toward the
competing demands of accuracy and practicality. There is no right or wrong approach, only
the best possible measure given the specific objectives of the assessment. In spite of all the
challenges and limitations of dietary assessment methods, these data will continue to serve
an essential role in efforts to improve the health and longevity of individuals and groups.
TABLE 21.1
Summary of the Major Advantages and Disadvantages of Dietary Assessment Methods
Food Frequency Questionnaire
Characteristics Single Record/Recall Multiple Record/Recalls per Person (FFQ) Brief Assessment Instruments
Brief Description Detailed recording of everything Multiple days (per person) of Measure of usual intake determined Diverse group of short tools
consumed in one day recording of everything consumed from frequencies of consumption of developed to target limited number
about 100 foods (or food groups) of foods, nutrients, and/or dietary
behavior
Scientific Features
Advantages Open-ended format appropriate for (Same as single records/recalls) Captures data on usual, long-term Ideal for studies where
all types of eating patterns 3-4 days of records/recalls have been intake comprehensive assessment is not
Provides detailed information on used to characterize usual intake in Can be used retrospectively needed
foods consumed individuals Some are non-intrusive and therefore
Provides data that are comparable relatively objective
across populations and time Behavioral assessments may be more
Recalls can’t affect (past) food sensitive to dietary interventions
choices than nutrient estimates

Disadvantages* Can only capture information on (Same as single records/recalls) Accurate reporting of usual intake of Typically provide fairly imprecise
current intake, and one day’s intake Because of day to day variability in foods is very difficult for some estimates of nutrient intakes
does not characterize usual intake intake, even 3-4 days of intake only respondents Because of targeted nature of these
Records can change eating behavior roughly approximates usual intake Limited food list will not be instruments, future scientific
Recalls depend on respondent appropriate for all respondents questions on other foods or
memory Different questionnaires are needed nutrients cannot be addressed
for different populations and
therefore do not produce
comparable nutrient estimates
Practical Features
Methods and Tools for Dietary Intake Assessment in Individuals vs. Groups
Advantages Recalls do not require literate (Same as single records/recalls) Fairly low respondent burden Low respondent burden
respondents Once developed, scannable FFQs are Usually simple and inexpensive to
Because recalls are interviewer inexpensive and easy to analyze code and analyze
administered, data can be collected
in a standardized way
Disadvantages Expensive to collect, code, and (Same as single records/recalls) FFQ development costs are
analyze Multiple records or recalls are extremely high
extremely burdensome for
participants
535
* All types of dietary self-report are subjective and are subject to under-reporting and person-specific biases associated with sex, obesity, social desirability, etc.
536
TABLE 21.2
Summary of the Issues Regarding Use of Data from Dietary Intake Assessment Methods
Multiple Record/Recalls Food Frequency Questionnaire
Data Single Record/Recall per Person (FFQ) Brief Assessment Instruments
Appropriate use To estimate absolute mean values As an approximation of usual Ranking individuals from low to Ranking individuals from low to
of data for intakes of foods and nutrients intake in an individual if used high intakes for foods or nutrients high intakes for the specific food
Group means and standard with caution and recognition that or nutrient being targeted
deviations for comparison to there will be considerable
other groups attenuation of associations with

other variables
Inappropriate use Ranking respondents from low to Estimation of absolute nutrient Estimation of absolute intakes for
of data* high intakes intakes for comparison to other nutrients
For determination of the percent of questionnaires or populations
population above (or below) some Just because an FFQ has been
cut-point “validated” does not mean that it
assesses all nutrients with good,
or equal, accuracy
Data not available These methods cannot be used to (Same as single record/recall) Eating pattern information (e.g., (Same as FFQ)
assess dietary intake in the past meals per day).
Detailed information on foods
consumed, such as brand names
* Because of considerable random and systematic error, no forms of dietary self-report data should be regarded as “truth.”
TABLE 21.3
Summary of Considerations Regarding Use of Dietary Intake Assessment in Individuals vs. Groups
Multiple Record/Recalls per Food Frequency Questionnaire
Single Record/Recall Person (FFQ) Brief Assessment Instruments
Individual Assessment
Appropriate Use Qualitative use in clinical setting (Same as single record/recall) To provide feedback regarding Targeted instrument may be
Teaching tool regarding food 3-4 days can be used as an respondent consumption of a food appropriate for individual
composition approximation of usual intake vs. recommended intake counseling for the food or nutrient
For self-monitoring being assessed
Inappropriate Use As estimate of usual intake Nutrient intake estimates too Reliable estimate of absolute
imprecise for individual intakes
counseling
Research Studies
Appropriate Use For comparing mean intakes in (Same as single record/recall) For ranking individuals from low Where costs or logistic realities
control vs. intervention group Validity substudies for comparison to high intakes for determination prohibit use of a comprehensive
As a check of FFQ mean intake of nutrient intake estimates to of associations with disease risk assessment instrument
estimates for a group FFQ
Inappropriate Use When characterization of usual, (Same as single record/recall) For estimation of absolute intakes In cases where there is the potential
long-term diet is the exposure of In study population where When comparable data needed for important, new research
interest respondent burden will result in across markedly different questions to emerge
poor quality data populations
Nutrition Monitoring of Populations
Appropriate Use Nutrition monitoring of group (Same as single record/recall)
means, including trends analyses 3-4 days can approximate usual
Methods and Tools for Dietary Intake Assessment in Individuals vs. Groups
Descriptive data on population intake in individuals

eating patterns
For international comparisons of
food and nutrient intake
Inappropriate Use To determine percentage of For estimation of absolute intakes To estimate absolute intakes
population meeting a dietary For time trends analyses because
recommendation or at risk changing food supply cam make
questionnaires obsolete
537
References
1. National Research Council and Committee on Diet and Health, Diet and Health: Implications
for Reducing Chronic Disease, National Academy Press, Washington, DC, 1989.
2. US Dept of Health and Human Services, Public Health Service, DHHS (PHS) publication 88-
50210, The Surgeon General’s Report on Nutrition and Health, Washington, DC, 1988.
3. World Cancer Research Fund and the American Institute for Cancer Research, Food, Nutrition,
and the Prevention of Cancer: A Global Perspective. Potter J. Ed, American Institute for Cancer
Research, Washington DC, 1997.
4. Torun B, Chew F. In Modern Nutrition in Health and Disease, 8th ed (Shils ME, Olson JA, Shike
M, Eds.), Lea & Febiger, Philadelphia, PA, 1994, pg 950.
5. Patterson RE. In Nutrition in the Prevention and Treatment of Disease, Coulston M, Rock CL,
Monson E, Eds, Academic Press (in press).
6. Hebert JR, Clemow L, Pbert L, et al. Int J Epidemiol 24: 389; 1995.
7. Jansen A. Br J Clin Psychol 35: 381; 1996.
8. Black AE, Prentice AM, Goldberg GR, et al. JADA 93: 572; 1993.
9. Kristal AR, Andrilla CAH, Koepsell TD, et al. JADA 98: 40; 1998.
10. Buzzard IM, Faucett CL, Jeffery RW, et al. JADA 96: 574; 1996.
11. Willet W. Nutritional Epidemiology, Oxford University Press, New York, 1990.
12. Rebro S, Patterson RE, Kristal AR, Chaney C. JADA 98: 1163; 1998.
13. Block G, Dresser CM, Hartman AM, Carrol MD. Am J Epidemiol 122: 13; 1985.
14. Block G, Dresser CM, Hartman AM, Carrol MD. Am J Epidemiol 122: 27; 1985.
15. Willet W. Nutritional Epidemiology. 2nd ed., Oxford University Press, New York, 1998.
16. Kristal AR, Vizenor NC, Patterson RE, et al. Cancer Epidemiol Biomarkers Prev 9: 939; 2000.
17. Patterson RE, Kristal AR, Carter RA, et al. Ann Epidemiol 9: 178; 1999.
18. Armstrong BK, White E, Saracci R. In: Monographs in Epidemiology and Biostatistics, Oxford
University Press, Oxford, 1994.
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20. Kristal AR, Feng Z, Coates RJ, et al. Am J Epidemiol 146: 856; 1997.
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25. Kerr GR, Amante P, Decker M, Callen PW. Am J Clin Nutr 37: 622; 1983.
26. Patterson RE, Kristal AR, Shannon J, et al. Am J Pub Health 87: 272; 1997.
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29. Tinker LF, Patterson RE, Kristal AR, et al. JADA (in press).
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39. Prentice RL, Sugar E, Wang CY, et al. Pub Health Nutr (in press).
22
The Use of Food Frequency Questionnaires in Minority
Populations
Rebecca S. Reeves
Food frequency questionnaires (FFQs) are selected by investigators to assess the usual
food or nutrient intakes of groups or individuals because they are relatively easy to
administer, less expensive than other dietary assessment methods, and can be adapted to
all racial and ethnic populations in the United States.1 Investigators can also modify these
dietary instruments for telephone interviews or self-administered mailed surveys. FFQs
are commonly used in epidemiological studies on diet and disease, but are also chosen
by investigators as the dietary assessment instrument in clinical intervention studies. The
use of these questionnaires in minority populations in the U.S. is increasing for several
reasons: the country is becoming more racially and ethnically diverse,2 government agen-
cies have placed emphasis on including minority population in health-related research,3
and variations in disease incidence and dietary practices within and across ethnic minor-
ities offer important opportunities for examining the role of diet in relation to risk for
chronic disease.4
This section reviews 12 published studies evaluating the validity and/or reliability of
FFQs used in measuring dietary intakes in adult minority populations in the U.S. over
the last 20 years. Also included are selected samples of FFQs and information on obtaining
copies. Recommendations on the use of these FFQs are discussed.
A search of the National Library of Medicine’s (Bethesda, MD) MEDLINE system was
conducted using various terms such as validity, reliability, reproducibility, diet, food frequency
questionnaire, minority, Hispanic, black, Asian, Pacific-islander and native America to identify
articles published between 1980 and 2000. These searches were supplemented by cross-
referencing from author reference lists. Articles were selected that described the evaluation
of any FFQ that assessed the usual daily diet and provided data on the validity and/or
reliability of the instrument in a specific U.S. ethnic minority population or a diverse
population representing at least 40% minority persons. The degree of reliability or validity
of the instrument reported was not considered an inclusion factor. Validity and reliability
studies that were reported in the same article were considered separately and are refer-
enced in different tables. The measures of performance chosen were reliability, comparison
of means (when available), and validity, because these are usually reported to describe
the results of the evaluation of the FFQ. Correlation coefficients were selected as indicators
of reliability and validity because they are commonly used and are more easily summa-
rized. Factors that can influence correlation coefficients are the number of days between
the times the questionnaire is administered (reliability coefficients) and the number of
0-8493-2705-9/01/$0.00+$1.50
days of food records or 24-hour recalls used for the referent period (validity coefficients).
Unadjusted correlation coefficients if available are reported in the tables because of the
considerable variation in the kinds of adjustment procedures that were used in these
studies and the lack of standardization across studies for methods used.
Terms used to describe FFQs in the tables:
• Quantitative — Quantity of food consumed was estimated using weights, mea-

sures, or food models. Responses were open-ended.
• Semi-quantitative — Quantity of food consumed was estimated using a standard
portion size, serving, or a predetermined amount and the respondent was asked
about the number of portions consumed.
• Nonquantitative — Quantity of food was not assessed.
• Self-administered — An adult completed the dietary assessment without assistance.
• Interviewer-administered — A trained interviewer collected the dietary informa-
tion from the adult in a one-on-one setting.
• Diverse studies — Publications that include various combinations of racial or
ethnic groups
• Minority studies — Publications that include only one racial or ethnic group
The twelve studies reviewed for this section were divided into two groups based on
ethnic participation. Within the group labeled Minority studies, two consisted of only
black subjects,5,6 one of Asian,7 and one of Hispanic subjects.8 In the group labeled Diverse,
two studies included black and white subjects,9,10 three studies black, Hispanic, and white
subjects,11,12,13 one study Hispanic and white,14 one study Asian and white,15 and one
recruited Asian, black, Hispanic, and white subjects.16
The review of the validation studies on FFQs was not conclusive. The median correla-
tions (Table 22.1) between questionnaire–based estimates of nutrient intakes and esti-
mates derived from referent methods were not consistent for ethnic groups, but trends
were suggested. The median correlations for black males and females across validation
studies were in the range of 0.23 to 0.46; for Hispanic females, 0.32 to 0.49 except for one
study conducted in Starr County, Texas which reported a median correlation of 0.75; for
white males and females, 0.53, and for Asian males and females, 0.53. If you consider a
measure of ≥0.05 as satisfactory or good, 0.30 to 0.49 as fair, and <0.30 as poor,15 then
these median correlations suggest that black and Hispanic groups do not perform
extremely well on FFQs.
The validation correlations for total energy, total fat, and vitamin A were inconsistent
and in some cases very low across studies. In Table 22.2 the correlation coefficients for
total fat ranged from 0.23 to 0.65, with the higher correlations usually found in the Asian
or white populations. A similar trend was found for energy among the various groups.
The correlation coefficients for Hispanic and black populations were commonly in the
range of 0.24 to 0.43, but in the white and Asian groups the coefficients ranged from 0.41
to 0.61. Values for vitamin A were more inconsistent, ranging from 0.15 to 0.67 across all
groups. The number of days of food records and recalls that are compared against FFQs
can explain some of these low correlations, especially for vitamin A. Many days are
required to provide a precise estimate of vitamin A intake, and in these studies the greatest
number of daily recalls or records collected over one year was 28. Even in this study,
certain subgroup correlations for vitamin A were still 0.23 and 0.29.
The study5 that reported serum nutrient concentrations of carotenoids, vitamin E, lyco-
pene, and lutein as a referent reported correlations that were much lower for smokers
The Use of Food Frequency Questionnaires in Minority Populations 541
TABLE 22.1
Median and Reported Range of Correlation Coefficients
Median and Reported Range
Study Validity Coefficients Reliability Coefficients
Diverse Groups
Baumgartner et al.14 0.50 (0.21–0.57) HF+WF (adjusted value) 0.62 (0.40–0.71) Unadjusted
Hankin et al.15 0.63 (0.58–0.67) Chinese females
0.46 (0.38–0.64) White females
0.56 (0.49–0.60) Filipino females
0.38 (0.29–0.41) Hawaiian females
0.60 (0.23–0.68) Japanese females
0.58 (0.38–0.68) Chinese males
0.45 (0.34–0.64) White males
0.57 (0.21–0.84) Filipino males
0.36 (0.26–0.62) Hawaiian males
0.55 (0.46–0.77) Japanese males
Kristal et al.11 Baseline
0.31 (0.26–0.46) Black females 0.51(0.37–0.60) Black females
0.35 (0.25–0.48) Hispanic females 0.51(0.19–0.75) Hispanic females
Six months (control group)
0.40 (0.29–0.49) Black females
0.37 (–0.01–0.48) Hispanic females
Larkin et al.9 0.43 (0.26–0.62) White males
0.23 (0.09–0.41) Black males
0.44 (0.27–0.57) White females
Liu et al.10 0.64 (0.50–0.86) White males 0.70 (0.60–0.91) White M+F
0.53 (0.13–0.68) White females 0.58 (0.45–0.85) Black M+F
0.42 (0.23–0.67) Black males
Mayer-Davis et al.12 0.58 (0.30–0.77) White females, urban 0.71 (0.43–0.82) White females
0.38 (0.22–0.62) Black females, urban 0.62 (0.26–0.69) Black females
0.57 (0.24–0.68) White females, rural 0.64 (0.25–0.88) White females, rural
0.32 (0.21–0.44) Hispanic females, rural 0.58 (0.33–0.66) Hispanic females, rural
Stram et al.16 Average correlation for amount
0.30 (0.16–0.41) Black M+F
0.48 (0.27–0.62) Hispanic M+F
0.57 (0.48–0.64) White M+F
Suitor et al.13 0.32 (0.12–0.52) All females combined 0.88 (0.80–0.94) All females
Minority Groups
Coates et al.5 0.34 (–0.02–0.45) Nonsmokers

0.08 (–0.02–0.20) Smokers
Forsythe et al.6 0.88 (0.69–0.98) Black females
Lee et al.7 0.46 (0.21–0.66) Chinese females
McPherson et al.8 0.75 (0.53–0.77) Hispanic M+F 0.85 (0.84–0.90) Hispanic M+F
(≤0.02) than for nonsmokers (<0.40). The investigators summarize that their FFQ is rea-
sonably valid for use in a Southern, urban, low-income black population, except for the
analysis of lutein and lycopene.
In most of the studies reviewed, the FFQ overestimated the mean of the referent recall
or records, and in some cases by nontrivial amounts. One explanation for this difference
was, again, the number of days of recalls or records collected for comparison to the FFQ.
Depending on which nutrient is of interest in the study and the time period the participant
542
TABLE 22.2
Food Frequency Questionnaire (FFQ) Validity Studies among Diverse Adult Populations in the U.S.
Reference Sample Instrument Response Categories Validation Standard Design Results
Baumgartner 43 HF (Hispanic) 140 Items; interviewer- Included per month, 4-Day food records Compared subject’s report Pearson correlation coefficients
et al.14 89 NHF administered; open- week or day of past month’s food (log transformed and energy
ended; referent period intake against 4 randomly adjusted); nutrients which
was previous 4 weeks selected nonconsecutive differed significantly by ethnicity
day food records; third between FFQ2 + FFQ3 and food
FFQ taken 6 months after records:
1st FFQ to recall original Protein(g)
month, then compared HF 0.40 NHF 0.35
against subject’s 4 day FR Vitamin A (RE)

HF 0.67 NHF 0.38
Vitamin C (mg)
HF 0.34 NHF 0.64
Calcium (mg)
HF 0.49 NHF 0.58
Hankin et Japanese Hawaiian Cancer 8 (Never or hardly ever Four 1-week food Compared subject’s report Intraclass correlations (log
al.15 29M + 29F Research Center to 2 or more times/day) records at of nutrient intake (FFQ) transformed) between the
Chinese 47 items, semi- approximately 3-month against average of 4, 1 subjects’ reports on FFQs and
29M + 26 F quantitative; intervals week FR collected at 3 average 7 day FR
Filipino administered; covers month intervals during a Total fat:
22 M + 25 F past twelve months; 1-year period. FFQ JapM 0.55, WM 0.34, ChinM 0.39,
Hawaiian color photographs collected at end of 12 FilM 0.60 HawM 0.26
19 M + 28 F showing S, M, L portion month period JapF 0.68, WF 0.58, ChinF 0.67, FilF
Caucasian sizes were used by 0.55, HawF 0.40.
29 M + 26 F subjects to estimate Vitamin A:
intake on FFQ and FR JapM 0.74, WM 0.38, ChinM 0.65,
FilM 0.53, HawM 0.35, JapF 0.23,
WF 0.40, ChinF 0.64, FilF 0.53,
HawF 0.29
Intraclass correlation for total fat
for all males was 0.48 and for all
females 0.60. FFQ overestimated
means of FR by large amounts
but results on the agreement of
the FFQ with FR were generally
satisfactory
Kristal et al 11 555 White F, 271 black F, 100 Items, self- 9 (Never or <once/mo to 4-Day food records Compared subjects; recall FFQ overestimated % of energy
159 Hispanic F administered, semi- 2 or more times/day for collected at baseline of baseline FFQs with the from fat compared with FR.
recruited at three quantitative; covering foods and 6+/day for and 6 months baseline food records and Pearson correlations (log
clinical centers. Because last three months; beverages) at six months, the 6- transformed) between FFQ and 4
Hispanics recruited at portion sizes were S, M, month FFQ with the 6- day FR:
Miami clinic only, their L. FFQ collected at month food records Baseline:
data were compared screening, baseline and Fat (% energy, adjusted)
with WF from same six months. BF — 0.26
clinic; data for WF and Printed in both English WF — 0.49
BF at two other centers and Spanish HF — 0.35
were collapsed and WF — 0.35
compared Saturated fat (% energy adjusted)
BF — 0.32
WF — 0.50
HF — 0.37
WF — 0.56
Beta-carotene (unadjusted)
BF — 0.42
WF — 0.32
HF — 0.26
WF — 0.30
Correlations at baseline were

significantly larger among whites
than blacks and tended to be
larger for whites than Hispanics.
Six Months — Control group
Fat (% energy)
BF — 0.49
WF — 0.52
HF — 0.48
WF — 0.61
Saturated fat (% energy)
BF — 0.47
WF — 0.53
The Use of Food Frequency Questionnaires in Minority Populations
HF — 0.48
WF — 0.68
Beta-carotene (unadjusted)
BF — 0.34
WF — 0.23
HF — 0.27
WF — 0.57
Educational level associated with
poor validity of FFQ and/or FR
measures.
543
544

Larkin et al. 9 43 BM In Michigan FFQ-113 9 (Not in past year to One 24-hr recall + 3-day Compared by sex and Pearson correlation (nonadjusted)
48 BF food items based on more than once a day) food record collected 4 ethnic group (BM, BF, values between FFQ and 16 days
64 WM data from NFCS 77-78; times/yr about 3 WM, WF) report of food of FR:
73 WF semiquantitative; months apart. FR’s intake (4 sets of food Energy:
(40% subjects black) collected food intake administered and record) against the FFQ BM — 0.23
over past 12 months reviewed in subject’s BF — 0.26
home. FFQ WM — 0.41
administered in WF — 0.43
subject’s home about 3 Protein (gm):
months after 4th set of BM — 0.30
records had been BF — 0.40
completed WM — 0.41
WF — 0.36
Total fat (gm):
BM — 0.23
BF — 0.35
WM — 0.44
WF — 0.39
Vitamin A(IU):
BM — 0.15
BF — 0.28
WM — 0.26
WF — 0.27
FFQ showed larger mean nutrient
intakes compared to FR. Black
M+F had lower coefficients
between FFQ and FR than white
M+F
Liu et al. 10 33 BM About 300 items in 20 Open-ended Seven 24-hr food recalls Compared subject’s recall Mean nutrient values for WM are
32 BF categories; Interviewer- collected by phone of last 30 days against similar between 2 methods; for
30 WM administered seven 24-hr food recalls WF values from FFQ are
33 WF quantitative FF based generally higher than recalls
on the Western Electric (VitA significantly different); for
dietary history; referent BM + BF values from history are
period is past month. much higher than recalls (VitA+
Kcal significantly different);
Pearson correlations (log
transformed)
Total Calories:
WM — 0.64
WF — 0.47
BM — 0.43
BF — 0.21
Total Fat: (g)
WM — 0.65
WF — 0.37
BM — 0.36
BF — 0.23
Vitamin A: (IU)
WM — 0.67
WF — 0.62
BM — 0.62
BF — 0.32
545
546

Mayer-Davis 32 WF (urban) 114-Item, interviewer- 9 (Never or <1/month to Eight 24-hr recalls over Compared subject’s report Pearson correlations (log-
et al.12 63 BF (urban) administered FFQ; 2 or more times/day) course of 1 year of frequency of intake transformed) between FFQ2 and
30 WF (rural) modified from NCI- (randomly selected from FFQ2 to average of food recalls were:
61 HF (rural) HHHQ to include days, about every 6 eight 24-hr recalls; Energy:
regional and ethnic weeks) WF (urban) — 0.61
food choices; past year BF (urban) — 0.37
WF (rural) — 0.56
HF (rural) — 0.27
Total fat: (g)
WF (urban) — 0.66
BF (urban) — 0.59
WF (rural) — 0.58
HF (rural) — 0.40
Vitamin A: (IU)
WF (urban) — 0.38
BF (urban) — 0.28
WF (rural) — 0.24
HF (rural) — 0.28
Correlations by educational status:
Total fat: (g)
<12 grade — 0.05
12 grade — 0.59
Total CHO: (g)
<12 grade — 0.19
12 grade — 0.53
Saturated fat: (g)
<12 grade — 0.07
12 grade — 0.63
Vitamin A: (IU)
<12 grade — 0.31
12 grade — 0.21
Stram et al.16 African-Am Based on Hawaiian Unknown; highest Three random 24-hr An initial FFQ was mailed Corrected correlations for the
151BM, 186 BF Cancer Research Center response for food is >2 recalls conducted by to random sample of regression of mean 24-hr recalls
Japanese FFQ; quantitative by times/day; for phone prospective subjects; 3-24 on the 2nd FFQ by ethnic sex/
224 JM, 222 JF placing serving size beverages, 4 times/day hr recalls were collected group for following nutrients:
Hispanics photos beside the by phone after the initial Total kcals:
136 HM, 123 HF amount category; 8 contact; a second FFQ BM — 0.16 BF — 0.17
Caucasians frequency categories was sent 4-6 weeks after JM — 0.34 JF — 0.19
264 WM, 264 WF for food and 9 for the recalls were HM — 0.33 HF — 0.40
beverages completed; the subjects’ WM — 0.48 WF — 0.28
responses on the 2nd FFQ Total Protein: (g)
were compared against BM — 0.17 BF — 0.22
the 24-hr recall values JM — 0.31 JF — 0.25
HM — 0.27 HF — 0.35
WM — 0.51 WF — 0.38
Total Fat: (g)
BM — 0.29 BF — 0.24
JM — 0.41 JF — 0.32
HM — 0.33 HF — 0.57
WM — 0.57 WF — 0.39
Vitamin A: (IU)
BM — 0.30 BF — 0.22
JM — 0.45 JF — 0.49
HM — 0.62 HF — 0.52
WM — 0.59 WF — 0.58
Suitor et al.13 Initially who provided 3 Willett (Harvard Un.) 111 Unknown (recall of past Three 24-hr recalls Compared female’s report Pearson correlation (unadjusted,
diet recalls: items, self-administered 2 weeks) conducted by phone of food intake between log transformed values) between
WF — 54 (edited foods, portion food recalls and FFQ2 FFQ2’s and recalls
BF — 20 size information which were mailed Energy — 0.41
HF — 18 deleted); developed as Protein — 0.33
Subjects who provided a prenatal FFQ Vitamin A — 0.12
FFQ2 and FR = 62 but Calcium — 0.52
no ethnic breakdown
547
548

Coates et al.5 91 BF HHHQ-original 98 item 4 (Times/day, week, Serum carotenoids, Compared female’s FFQ Pearson correlations (log
FFQ revised to include month or year) alpha-tocopherol, responses to 15-ml transformed, unadjusted)
19 ethnic/regional lycopene, crytoxanthin, nonfasting venous blood between FFQ and serum for
foods resulting in 117 lutein/xeaxanthin sample nonsmokers:
item FFQ; past year Alpha-tocopherol (food only) —
0.19
Provitamin A carotenoids — 0.37
Beta-carotene — 0.34
Cryptoxanthin — 0.37
Lycopene — (-0.02)
Lutein — 0.12
Person correlations (log
transformed, unadjusted) for
smokers were:
Alpha-tocopherol — (–0.12)
Provitamin A carotenoids — 0.07
Beta-carotene — 0.11
Cryptoxanthin — 0.18
Lycopene — (–0.02)
Lutein — 0.11
Results suggest that FFQ was
reasonably valid for black
females. Analysis of lycopene
and lutein may not reflect validity
of the assessment of these
nutrients
Forsythe et 80 BF ethnic mix of FFQ-82 items compiled Unknown (weekly Three 24-hr recalls Compared female’s report Paired t-tests examined differences
al.6 African blacks, Asian from Caribbean food intake patterns) of intake against 3, 24-hr between the food recall means
Indians, Caribbean tables, Willett FFQ, recalls, one recall at and the means of the FFQ at time
whites, Guyanese Stower prenatal food prenatal visit and two 1. Most of the 14 nutrients were
Amerindians, and guide, and regional others by phone during significantly different using the
Caribbean Chinese recipes next 7 days. 2nd FFQ two instruments, with the
administered 3 weeks exception of saturated fat,
later vitamin A and caffeine. The
percentage of energy from
protein, CHO, and fat showed no
significant differences on either
method of assessment. Mean
difference scores were computed
between food recalls and time 2
FFQ responses in the subsample.
Significant differences were
found for energy , CHO and
vitamin C and the percentage of
energy from CHO.
The 24-hr recalls did not fully
support the responses provided
on the FFQ’s.
Lee et al.7 74 Chin W 84 Items; interviewer 5 (Day, week, month, One 24-hr recall (typical Compared female’s report Pearson correlations between the
administered; past year or not at all) day during past month) of frequency of intake FFQ and the food recall:
year; portion size asked against the 1-24 recall; Total kcal — 0.05
for foods eaten >1/ Total fat — 0.21
week; 3-dimensional Protein — 0.56
actual size food models Vitamin A — 0.46.
used; type of fat used in Nutrient intakes by FFQ that were
cooking asked significantly higher than 24-hr
recall were total kcal, total fat,
vitamin A, saturated fat,
cholesterol and beta carotene.
Use of only 1-24 hr recall could
explain the modest correlations.

McPherson 33 HM+F 38 Mutually exclusive Unknown Three random Compared subject’s report Pearson correlation coefficients
et al.8 food types; interviewer nonconsecutive food of past month’s food (unadjusted) between FFQ and
administered; referent records intake against 3-24 hr records
period last 4 weeks food records Energy — 0.77
Total fat — 0.76
Cholesterol — 0.61
None of the differences between
nutrients on FFQ1 and FR were
significant.
549
is asked to recall on the FFQ, more than four to seven days may be required to capture
the actual intake of the individual.
The reliability coefficients across all diverse and minority studies were much higher
than the validity coefficients (Table 22.3). The median correlations for black males and
females across studies were in the range of 0.51 to 0.88; for Hispanic females, 0.51 to 0.58
except for one study conducted in Starr County, Texas which reported a median correla-
tion of 0.85; for white males and females, 0.64 to 0.71. These coefficients would suggest
that within minority and diverse populations, the FFQ can usually describe with some
consistency the food or nutrient intakes of individuals when administered at two points
in time.
In most of the studies reviewed, the investigators made suggestions and recommenda-
tions for improving the performance of the FFQ in minority populations. It was repeatedly
mentioned that a “gold standard” referent method was not available, so collecting valid
dietary intake data remains challenging. The need to identify a complete food list on the
FFQ that captures all of the foods in the usual diet of the study population was highly
recommended. Depending on the study, the food list should include foods that will
contribute substantially to the nutrients under investigation. This importance of a food
list capturing the usual intake of study participants was demonstrated in the study con-
ducted in Starr County, Texas. Because of the limited number of overall foods that the
participants consumed, the food list of the FFQ was able to reflect the major sources of
food and nutrient intake of these individuals. Because of this unique situation, the nutrient
values from the FFQ were more likely to agree with the values from the food records.
Several suggestions were made regarding administration of the dietary assessment forms
in minority populations. It is recommended that any staff person who is responsible for
interviewing a subject for any dietary assessment measure, whether the conversation takes
place in person, or over the phone should be of the same ethnic background as the subject.
Educational attainment of participants appeared to be a major determinant of the valid-
ity of the dietary assessment measures in several studies. Agreement between the food
frequency and the criterion measure of 24-hour dietary recalls was substantially compro-
mised among individuals with less than a high school education. This was particularly
true within a Hispanic group of one study. In another study, it was found that increasing
validity with increased education suggested that poor education is a barrier to accurate
completion of the FFQ, the food record, or both. In this same study, low educational levels
did not affect reliability measures. These findings would suggest that special efforts are
needed when using dietary assessment tools with participants of low educational status
or culturally diverse dietary habits. Small group instruction and practice in using the
dietary tools could improve the dietary information collected. Instructing participants by
videotape on completing dietary forms is another method to help improve the accuracy
of information.
This section includes examples of the food frequency questionnaires that have been used
or adapted for studies of minority populations. This is not intended to be a complete list
of all the questionnaires that were used in the 12 studies reviewed, nor is inclusion in this
set of examples an implied endorsement of one instrument. The FFQs included are those
that are widely available. The FFQs in this set were originally selected by an investigator
for modification to his/her population, or the FFQ is the actual instrument used to assess
dietary intake. Readers who are interested in using or adapting these dietary assessment
tools should contact the resource people listed with each tool.
In selecting a food frequency questionnaire, the reader should consider several points:
1. What is the primary purpose of the project or study you are planning to conduct
and how does the food intake data relate to the outcome?
TABLE 22.3
Food Frequency Questionnaire (FFQ) Reliability Studies among Adult Minority Populations in the U.S.
Response Categories
References Sample Instrument (range) Design Results
Baumgartner 43 HF (Hispanic) 140-items; interviewer Included per month, Compared 6-month test- Pearson coefficients (log transformed, adjusted) by
et al.14 89 WF administered; semi- week or day retest reproducibility of ethnic group between the 2 FFQ’s for 2 nutrients:
quantitative; referent nutrient estimates from Saturated fat:
period was previous 4 FFQ2 and FFQ3. HF — 0.57
weeks Reproducibility coefficients WF — 0.77
were not reported by ethnic Retinol:
group except for 2 nutrients HF — 0.50
WF — 0.80
Forsythe et al.5 80 BF ethnic mix of African FFQ- 82 items compiled Unknown (weekly Compared 3 wk test-retest Paired t-tests examined differences between the food
blacks, Asian Indians, from Caribbean food intake patterns) reproducibility of nutrient recall means and the means of the FFQ at time 1. Most
Caribbean whites, tables, Willett FFQ, estimates from FFQs and of the 14 nutrients were significantly different using
Guyanese Amerindians, Stower prenatal food food recalls the two instruments, with the exception of saturated
and Caribbean Chinese guide, and regional fat, Vitamin A and caffeine. The percentage of energy
recipes from protein, CHO, and fat showed no significant
differences on either method of assessment. Mean

difference scores were computed between food recalls
and time 2 FFQ responses in the subsample.
Significant differences were found for energy, CHO
and Vitamin C and the percentage of energy from
CHO
Pearson correlations between the 2 FFQs were:
Energy — 0.91
Protein — 0.97
Total fat — 0.89
Vitamin A — 0.73
Kristal et al.11 555 WF 100 items, self- 9 (never or <once/ Compared 6-month test- Pearson coefficients (log transformed) between the 2
271BF administered, semi- month to 2 or more retest reproducibility of FFQ’s were:
159 H F recruited at three quantitative; last three times/day) selected nutrient estimates Fat (% energy):
clinical centers. Because months; portion sizes from baseline and 6 month BF — 0.37
Hispanics recruited at were S, M, L. FFQ FFQ’s in the control group WF — 0.51
Miami clinic only, their collected at screening, only HF — 0.45
data was compared with baseline and six months Analyses were also stratified WF — 0.34
WF from same clinic; data on level of education Vitamin C (unadjusted):
for WF and BF at two BF — 0.60
other centers were WF — 0.67
collapsed and compared HF — 0.75
WF — 0.44
Beta-carotene (unadjusted):
BF — 0.54
WF — 0.61
HF — 0.62
WF — 0.46
551
Little evidence that reliability was affected by poor

education
552

Food Frequency Questionnaire (FFQ) Reliability Studies among Adult Minority Populations in the U.S.
Response Categories
References Sample Instrument (range) Design Results
Liu et al.10 33 black M About 300 items in 20 Open-ended Compared subject’s history Sex-adjusted partial correlation coefficients (log
32 black F categories; interviewer- of last 30 days against transformed, not calorie adjusted) between the first
30 white M administered; baseline history and last histories
33 white F quantitative history Energy:
based on the Western W M+F — 0.76

Electric dietary history; B M+F — 0.50
referent period is past Total fat: (g)
month W M+F — 0.73
B M+F — 0.56
Protein: (g)
W M+F — 0.70
B M+F — 0.57
Vitamin A: (IU)
W M+F — 0.77
B M+F — 0.74
McPherson et 20 H M+F 38 mutually exclusive food Unknown Compared 1 month test- Absolute nutrient intake from FFQ2 was greater than
al.8 types; interviewer retest reproducibility of those of FFQ3 and FFQ4.
administered; referent nutrient estimates between Pearson coefficients (unadjusted) between FFQ2 and
period last 4 weeks FFQ2 and 3 and FFQ 2 and 4 FFQ3:
Energy:
0.90
Total fat:
0.85
Cholesterol:
0.85
Coefficients (unadjusted) between FFQ2 and FFQ4 were
Energy:
0.84
Total fat:
0.70
Cholesterol:
0.79
Mayer-Davis et 32 WF (Urban) 114-item, 1st FFQ 9 Compared 2-4 year test-retest Pearson coefficients (log transformed, unadjusted)
al.12 63 BF (Urban) interviewer- (never or <1/month to 2 reproducibility of baseline between 2 FFQ’s were:
30 WF (Rural) administered and 2nd or more times/day) FFQ1 with FFQ2 Energy:
61 HF (Rural) was conducted over WF (urban) — 0.81
phone; modified from BF (urban) — 0.64
NCI-HHHQ to include HF (rural) — 0.83
regional and ethnic food WF (rural) — 0.61
choices; past year Total fat: (g)
WF (urban) — 0.81
BF (urban) — 0.69
HF (rural) — 0.87
WF (rural) — 0.63
Vitamin A: (IU)
WF (urban) — 0.67
BF (urban) — 0.26
HF (rural) — 0.63
WF (rural) — 0.53
Reproducibility of FFQ’s was similar across all
subgroups evaluated including educational
attainment
Suitor et al.13 Initially who provided 3 Willett (Harvard Un.) 111 Unknown (recall of past Compared female’s report of Pearson correlation (unadjusted, log transformed
diet recalls: items, self-administered 2 weeks) food intake between values) between FFQ1 and FFQ2:
WF 54 (edited foods, portion baseline FFQ1 which was Energy — 0.92
BF 20 size information deleted); completed in the clinic and Protein — 0.87
HF 18 developed as a prenatal FFQ2 which was mailed. Vitamin A — 0.89
Subjects who provided FFQ Those returning FFQ2 were Calcium — 0.80
FFQ1 and FFQ2 = 43 but unrepresentative of the
no ethnic breakdown original sample
553
2. What length of time are you interested in assessing food intake? 12 months, 3
months?
3. How current is the food list? Does it reflect the current food supply?
4. Does the food list contain foods that contribute significantly to the nutrients you
are interested in assessing?
5. Does the food list reflect the traditional or cultural foods eaten by your population?
6. Is the nutrient software analysis program updated on a regular basis to reflect
the changing composition of our food supply?
7. Can you individualize the food list of the FFQ to your specific population? How
much latitude do you have to modify the existing questionnaire? Can the existing
software be modified to reflect the changes you wish to make?
8. Request a list of the validity and reliability studies that investigators have con-
ducted using the FFQ you are considering. Were these studies conducted with
populations similar to the groups of persons you wish to recruit into your study?
Diet History Questionnaire

Investigators at the National Cancer Institute have developed a new self-administered,
scannable food frequency questionnaire, the Diet History Questionnaire (DHQ). The
instrument was designed with particular attention to cognitive ease, and has been updated
with respect to the food list and nutrient database using national dietary data (USDA’s
1994-96 Continuing Survey of Food II). This instrument is available on the internet and
can be downloaded from the site http://www-dccps.ims.nci.nih.gov/arp. The data anal-
ysis program that accompanies this questionnaire will become available for downloading
from this site in 2001. Validity studies are in progress, but not within minority populations.
At this internet site, information is provided regarding the original Health Habits and
History Questionnaire (HHHQ) developed by Gladys Block and updated in 1987 and
1992. Recommendations are provided for the continued use of this questionnaire and the
software analysis program that accompanies it. Both the questionnaire and the software
can be downloaded from the site.
Harvard University Food Frequency Questionnaire (Willett

Questionnaire)
Several food frequency questionnaires are available from the Harvard School of Public
Health including this current version designed for use in African American populations.
This is a scannable, self-administered FFQ referred to as the “green version.” Validity
studies of this FFQ among black male prostate cancer survivors will be completed very
soon. This questionnaire contains a section on the assessment of vitamin and mineral
intake followed by approximately 174 food items. The assessment period of the FFQ is
the past 12 months, and respondents are asked to average seasonal use of foods over the
entire year. This tool is designed to enhance an individual’s ability to respond more
appropriately to the food items. For example, the response categories are individualized
for each item ranging from never to six or more times per day, and probing questions are
asked regarding specific characteristics of foods consumed. (Resource: Laura Sampson,

M.S., R.D. Harvard School of Public Health — Nutrition, Bldg. #2, Room 335, 665 Hun-
tington Ave., Boston, MA 02115.)
Fred Hutchinson Cancer Research Center Food Frequency Questionnaire

(Kristal Questionnaire)
This questionnaire links answers from an extensive list of food questions to specific food
frequency items to derive more precise nutrient estimates for those items. The FFQ is
machine-readable and is accompanied by a software system to process the questionnaire.
The format has nine frequency categories and small, medium, and large portion sizes. The
food list is composed of 122 foods and is preceded by 19 behavioral questions related to
preparation techniques and types of food selected. Answers to these questions are used
directly in the program to choose more appropriate nutrient composition values for certain
foods in the food list. This questionnaire is available in Spanish. (Resource: Alan R. Kristal,
Dr. P.H., Cancer Prevention Research Unit, Fred Hutchinson Cancer Research Center, 1124
Columbia St. MP 702, Seattle, WA 98104.)
Cancer Research Center of Hawaii’s Dietary Questionnaire (The Hawaii

Cancer Research Survey)
The Cancer Research Center of Hawaii, part of the University of Hawaii, has developed
a variety of quantitative FFQs for use with the multiethnic population of Hawaii. A
questionnaire was recently developed to assess the diets of the five main ethnic groups
in the Hawaii-Los Angeles Multiethnic Cohort Study: Hispanics, African-Americans, Jap-
anese, Hawaiians, and Caucasians. Unlike previous questionnaires, the cohort question-
naire was designed to be self administered. Three-day measured food items were collected
from all ethnic groups in advance and were used to identify food items for inclusion in
the questionnaire. To ensure more accurate specifications of amounts usually consumed,
photographs showing three portion sizes were printed on the questionnaire. A customized,
an in part ethnic-specific, food composition table was developed for the cohort question-
naire. A calibration study comparing questionnaire responses to the three 24-hour recalls
for the same subjects showed highly satisfactory correlations, particularly after the energy
adjustment. For more information about the The Cancer Research Center of Hawaii ques-
tionnaires, please contact Suzanne P. Murphy, Ph.D., R.D., Cancer Research Center of
Hawaii, University of Hawaii, 1236 Lauhala St., Suite 407, Honolulu, HI 96813. Phone:
808-586-2987. Fax: 909-586-2982. Email: Suzanne@crch.hawaii.edu.
New Mexico Women’s Health Study, Epidemiology and Cancer Control

Program, University of New Mexico Health Sciences Center
This FFQ was developed for an adjunct trial to the New Mexico Women’s Health Study,
a population-based case-control study of breast cancer in non-Hispanic and Hispanic
women. The 140-item FFQ was a modified version of a questionnaire developed by the
Human Nutrition Center, University of Texas School of Public Health — Houston for a
Texas Hispanic population. The FFQ was revised to include important food sources of
energy, macronutrients, and vitamins that were identified following an analysis of food
intake recalls. Emphasis was placed on specific rather than grouped food items because
recall is considered better for specific items. Usual portion size, based on two-dimensional
food models, included data on number of servings, type of food model, and thickness of
food. Common serving descriptions were included for each food item and were based
either on food models or defined portion size. This FFQ was translated into Spanish. For
further information contact R. Sue McPherson, Ph.D., Director, Human Nutrition Center,
Associate Profession of Epidemiology and Nutrition, University of Texas — Houston
School of Public Health, 1200 Herman Pressler, Houston, TX 77030. Phone: 713-500-9317.
Insulin Resistance Atherosclerosis Study FFQ, School of Public Health,

University of South Carolina
The Insulin Resistance Atherosclerosis Study (IRAS) provided the opportunity to evaluate
the comparative validity and reproducibility of a FFQ within and across subgroups of
non-Hispanic white, Hispanic, and African-American individuals. The 114-item question-
naire was modified from the National Cancer Institute — Health Habits and History
Questionnaire originally created by Gladys Block, Ph.D. This interviewer-administered
FFQ was modified to include regional and ethnic food choices that were commonly
consumed by the participants of the study. The FFQ contains nine categories of possible
responses ranging from “never or less than once per month” to “two or more times per
day.” Portion sizes are determined simply as “small, medium, or large compared to other
men/women about your age.” At the end of the FFQ, an open-ended question is asked
to describe foods that are usually eaten “at least once per week” that were not listed on
the FFQ. Also, nine additional questions probe for information regarding common food
preparation methods, specific fats used in cooking, and frequency of consumption of fruits
and vegetables. For further information about the IRAS FFQ, contact Mara Z. Vitolins, Dr.
P.H., R.D., Research Assistant Professor, Wake Forest University School of Medicine,
Department of Public Health Sciences, Medical Center Blvd., Winston-Salem, N.C. 27157-
1063. Phone: 336-716-2886. Fax: 336-713-4157. Email: mvitolin@wfubmc.edu.
References
1. Coates RJ, Monteilh CP. Am J Clin Nutr 65: 1108S; 1997.
2. Spencer G. Projections of the Hispanic Population: 1983-2089. US Department of Commerce,
Bureau of Census, (Series P-25), Washington, DC, 1989.
3. National Institutes of Health, NIH guidelines on the inclusion of women and minorities as
subjects in clinical research, Fed Reg 59: 14508; 1994.
4. Hankin JH, Wilkens LR. Am J Clin Nutr 59: 198S; 1994.
5. Coates RJ, Eley JW, Block G, et al. Am J Epidemiol 15: 658; 1991.
6. Forsythe HE, Gage B. Am J Clin Nutr 59: 203S; 1994.
7. Lee MM, Lee F, Ladenla SW, Miike R. Ann Epidemiol 4: 188; 1994.
8. McPherson RS, Kohl HW, Garcia G, et al. Ann Epidemiol 5: 378; 1995.
9. Larkin FA, Metzner HL, Thompson FE, et al. JADA 89: 215; 1989.
10. Liu K, Slattery M, Jacobs D, et al. Ethnicity Dis 4: 15; 1994.
11. Kristal AR, Feng Z, Coates RJ, et al. Am J Epidemiol 146: 856; 1997.
12. Mayer-Davis JE, Vitolins MZ, Carmichael SL, et al. Ann Epidemiol 9: 314; 1999.
13. Suitor C, Gardner J, Willett WC. JADA 89: 1786; 1989.
14. Baumgartner KB, Gilliland FD, Nicholson CS. Ethnicity Dis 8: 81; 1998.
15. Hankin JH, Wilkens LR, Kolonel LN, Yoshizawa CN. Am J Epidemiol 15: 616; 1991.
16. Stram DO, Hankin JH, Wilkens LR. Am J Epidemiol 15: 358; 2000.
23
Computerized Nutrient Analysis Systems
Judith M. Ashley and Sue Grossbauer
Introduction
Since the early 1980s, nutrient analysis software programs have taken advantage of micro-
computer technology to offer an effective and time-efficient method for calculating dietary
intake for a variety of users.1,2 For health professionals, the computerized dietary analyses
can be used as a persuasive tool to provide feedback for clients about current food choices
as well as healthful alternatives. For nutrition educators, the hands-on applications of
dietary analysis programs are an integral part of student education. For researchers and
government agencies, the computerized dietary results are an essential component for
documenting and analyzing the usual food intake of individuals and groups or target
populations. Computerized nutrient analysis software is also important for recipe develop-
ment by chefs and caterers, as well as for label information provided by food manufacturers.
Nutrient analysis systems convert individual food choices entered from a food record or
food frequency to nutrients.3,4 Computerized data processing includes creating a data file
with a food code and an amount consumed for each food item reported. The computer
software then links the nutrient composition of each food, stores that information, and sums
across all foods for each nutrient. Dietary analysis software is provided by a large number
of companies and organizations today. These companies continually update the quality and
scope of their services to stay competitive in the marketplace. However, their computer
programs vary considerably in cost, ease of use, features, and capabilities. For the prospec-
tive user, the choice of software requires careful consideration of needs and available
resources of staff, and financial support for computer hardware and peripherals. Charac-
teristics and general operating features of a number of widely used commercial nutrient
software programs with extensive database development are included in Table 23.1.
Primary Characteristics and Operating Features of Software Programs

Primary features of software nutrient analysis programs include 1) nutrient components
of interest (e.g., macronutrients, fatty acids, amino acids, sugars, antioxidants), 2) national
0-8493-2705-9/01/$0.00+$1.50
TABLE 23.1
Comparison of Features in Five Selected Programs Available Nationwide
560
Current
Total Number of Number of
Product Targeted Unique Foods/Items Diet Operating Cost of Users or Other Important
Company Name(s) End Users* in Database Comparisons** Support*** Requirements Product Installations Features
Computrition, Inc. Nutritional C, H, M 4200, small database N, M CE, U WindowsNT, $495 small N/A Integrated with
Chatsworth, CA Software 20,000+, large 98, and 2000 database foodservice and
818-701-5544 Library database $995 large nutrition
www.computrition.com database management
(single user software systems
system only)
ESHA Research, Inc. The Food C, H, M, R 25,000+, includes the N, FC, FG, M C, CE, U WindowsNT, $599 3200 Menu analysis, recipe
Salem, OR Processor®: Canadian Nutrient 98, and 2000 Educational analysis
800-659-3742 Nutrition File prices Exercise planning
www.esha.com analysis & available
fitness (cost to add
software stations)
First DataBank Nutritionist Pro H, M, R 18,000 N, FC, FG, M C, CE, U WindowsNT, $595 Thousands Professionally
San Bruno, CA Nutritionist Pro Food groups 98, and 2000 designed reports
800-633-3453 (East); Food Labeling using diabetic Ability to create
800-428-4495 (West) exchanges menu templates to
www.firstdatabank.com make data entry
faster
Ability to generate
food labels
Nutrition Coordinating Nutrition Data R 18,000 N, FC, M C, CE, U WindowsNT, $8500 initial, Over 700 Prompts for complete
Center (NCC) System for System 98, and 2000 $2500 installations food descriptions,
University of Minnesota Research generates 12 additional recipe ingredients,
612-626-9450 (NDS-R) standard years and food
www.ncc.umn.edu Academic NDS- reports $690 Academic preparation
R (for teaching $495 Grad- methods
purposes) Pack Interview facilitated
Grad-Pack by multiple-pass
NDS-R (for system
graduate
students)
University of Texas Food Intake R 7320 Comparison C, U DOS $3500 60 Commercial version
School of Public Analysis standards of USDA’s Survey
Health System 3.99 input by the Net, used in the
713-500-9775 individual user Continuing Survey
www.sph.uth.tmc.edu:8 of Food Intakes
052/hnc/software/ (CSFI)
soft.htm
* C = Consumers, H = Health Professionals, M = Medical Centers or Hospitals, R = Research
** N = Nutrients using DRI/RDA, FC = Other Food components, FG = Food Guide Pyramid food groups, M = Meals
*** C = Company Support Included in Cost, CE = Company Support Extra Cost, U = Updates available
Computerized Nutrient Analysis Systems 561
TABLE 23.2
Examples of Dietary Components Available from Computerized Nutrient Analysis
Energy Sources Fiber Fatty Acids
Energy (kilocalories) Total dietary fiber SFA 4:0 to 22:0
Total protein Soluble fiber MUFA 14:1 to 22:1
Total fat Insoluble fiber PUFA 18:2 to 22:6
Total carbohydrate Pectins Trans FA 16:1 to 18:2
Alcohol
Animal protein Vitamins Amino Acids
Vegetable protein Vitamin A RE Tryptophan
% Calories protein Beta-carotene RE Threonine
% Calories fat Retinol Isoleucine
% Calories carbohydrate Alpha-tocopherol RE Leucine
% Calories alcohol Beta-tocopherol RE Lysine
Gamma-tocopherol RE Methionine
Fat and Cholesterol Delta-tocopherol RE Cystine
Cholesterol Vitamin C Phenylalanine
Total sat fatty acids (SFA) Vitamin D Tyrosine
Total mono fatty acids (MUFA) Vitamin K Valine
Total poly fatty acids (PUFA) Thiamin Arginine
Total trans fatty acids (TFA) Riboflavin Histidine
% Cal SFA Niacin Alanine
% Cal MUFA Folate Aspartic acid
% Cal PUFA Vitamin B6 Glutamic acid
Vitamin B12 Glycine
Carbohydrates Pantothenic acid Proline
Starch Biotin Serine
Fructose
Galactose Minerals Other
Glucose Calcium Aspartame
Lactose Chromium Saccharin
Maltose Copper Ash
Sucrose Magnesium Caffeine
Manganese Oxalic acid
Phosphorous Phytic acid
Potassium Sucrose polyester
Selenium 3-methylhistidine
Sodium Water
Zinc
standards or guidelines used for evaluation (e.g., DRI/RDAs, U.S. Dietary Guidelines,
National Cholesterol Education Program), and 3) comparison by food groups, diabetic
exchanges, selected food items, or meal patterns. Many programs begin with client profile
information such as gender, age, height, weight, pregnancy or lactation status for women,
and tracking information (name, address, phone number, case number). With some pro-
gram packages, dietary standards can be tailored to fit a specific client’s needs, such as
calculating energy needs or targeted weight goals. The final presentation of the data may
take the form of two- and three-dimensional pie and bar charts, Food Pyramid or DRI
comparisons, nutrient summaries, or ranking foods in descending or ascending order
based on any nutrient. Data may be collected and averaged for individuals or groups for
a specified period, from days to weeks. Nutrients commonly included in software systems
results are listed in Table 23.2.
Additional features that may be relevant to users include the software program’s ability
to provide food–drug interaction data; to incorporate nutrition support regimens; to incor-
porate a recipe database; to add and/or modify foods, nutrients, and recipes; to scale and/
or cost recipes; to provide a shopping list; to plan meals and/or provide sample menus;
and to compare a meal with one-third RDA values (for menu planning). The software
may have data export capability (for export into statistical analysis software packages or
word processing programs so that text can be edited, or logos or other graphics added),
support for scannable questionnaires (useful for health surveys, food frequency checklists,
or entering calorie count data from inpatient menus), support for multi-user application,
and interface capability with foodservice management software.
Basic Questions to Ask When Considering Different Software Systems

Depending on the projected use of a nutrient analysis system, many or all of the following
basic questions may apply when evaluating individual programs:
• What are the operating system and hardware requirements? Would this involve an
investment in new equipment and peripherals?
• Who is the target audience of the output? Are consumers, health professionals,
Medical Centers or Hospitals and/or Research included?
• What are the total number and types of foods contained in the database? How many
foods are included? Are baby foods, convenience foods, fast foods, regional
specialties, ethnic specialties, and nutritional supplements included?
• What specific nutrients or food components are in the database? Are only a dozen or
more than 100 nutrients or other components calculated? Can the database be
altered?
• How complete is the database? What is the extent of missing values? When data
for specific nutrients are missing, are they estimated or left as zero (reducing the
usefulness of nutrient reports)? Are missing nutrient values identified on reports,
so that they are not misleading?
• How is the quality of database maintained? As new nutrient data become available,
how often does the software vendor respond?
• What is the ease of inputting for foods and amounts? Are there numeric code, food
name, and search feature options for entering a food? Is online help provided
to distinguish food listings and store frequently used food or meal categories
for ready access? Does flexible entry of portions allow choices by weight, volume,
and/or dimensions?
• Is there an accommodation to support food frequency data? Is this available in a
scannable form?
• Which nutrient standards are used, and are they up to date? Are the latest DRIs used?
Are standards omitted for subpopulations (children, pregnant or lactating
women)?
• What is the variety and quality of on-screen feedback for viewing reports? Can on-
screen reports be used for client counseling? Is the software interactive, allowing
a user to experiment with dietary choices while offering instantaneous feedback
about the bottom-line impact on nutrient intake?
• What is the variety and quality of printed reports? Does the program provide easy-
to-understand graphics (e.g., bar graphs, pie charts) in comparing intake with
designated standards? Are graphical comparisons available with several stan-
dards, such as the Food Pyramid or NCEP, included? Is the report’s final message
well formatted and descriptive?
• Can the reports be customized? Can reports be reformatted or can specific infor-
mation and comments be added?
• Is the report capable of using different measures for comparison? Does the report
include food groups, diabetic food exchanges, glycemic index values?
• Can multiple-day intakes be summarized? Can the report include several days or
weeks for comprehensive analysis?
• What are the formulas used for calculating ideal body weight and energy requirements?
Are current and reasonable standards used?
• Can exercise data be incorporated into caloric requirements? Does the report include
exercise recommendations?
• Can key sources of each nutrient be identified in the food records? Can lists of food
sources of key nutrients be generated?
• What is the quality of software documentation, on-line help, and tutorials? Are they
easy to understand and specific to user needs?
• What is the quality of product support and ongoing maintenance? Is there sufficient
technical support provided to answer user needs?
• What are the system utilities? Are there utilities for backing up valuable data and
reports?
• Finally, what does the complete system, with updates and service, cost? Are there
additional costs to add stations or for multiple users?
Importance of Nutrient Databases

Dietary intake data collected using both food records and food frequency questionnaires
or checklists rely heavily on food databases. Multiple factors affect the accuracy of the
database, including the source of nutrient information, the number of foods and nutrients
in the database, the method of handling missing values, and the frequency of updating
the database. Several published reports have compared nutrient calculations among a
limited number of database systems.5-12 When the database calculations have been com-
pared to a standard13-15 or tested against chemical analyses from a single source,16-18 most
found nutrients to be within 15% of reference values. For example, a recent comparison
from 4 different databases and their deviations from chemically analyzed values of 36
menus showed that the database values for the nutrients examined had relatively good
accuracy: 7 nutrients deviated by values <10%, 5 by 10 to 15%, and only one by 15 to
20%.19 There are several potential reasons for these variations, including:
1. Nutrient variability in the food supply

2. Frequent changes in the nutrient content of processed foods
3. Nutrient information from food labels is permitted to vary from actual nutrient
content by a large margin
4. Estimated or imputed values for missing nutrient information by database devel-
opers is a source of error in nutrient estimates
5. Food substitutions or misidentification of foods entered

6. Constraints of chemically determined nutrient values used for comparison (e.g.,
sample collection, assayed values)
It is important to note that no standardized benchmarks have been established for

comparing nutrient calculation output.
Most nutrient analysis systems in the U.S. contain the USDA National Nutrient Database
(NNDB) complemented by nutrition information from other scientific sources and food
companies.20 The NNDB was developed and implemented in 1985, and includes the most
recent USDA Nutrient Database for Standard Reference and the Primary Nutrient Data
Set for USDA Nationwide Food Surveys. The USDA’s National Nutrient Databank System
(NDBS) is the repository of several types of food information, including food names, food
descriptors, food formulations and recipes, the composition of foods, food yields, nutrient
retentions, factors for deriving energy, protein, and fatty acid values of foods, and weights
for various measures of foods. It currently contains data for over 6200 foods and up to 82
nutrients. The NDBS contains systematic and common food names, source information,
and information about analytical methods. The development of representative food com-
position values involves the acquisition, documentation, evaluation, and aggregation of
food composition data compiled from a wide variety of sources. The USDA does not have
dedicated intramural analytical laboratories to support the NDBS, and limited data are
provided by ongoing research programs. Thus, to meet user needs it is dependent on
other sources including the scientific literature, food industry, academia, other government
agencies, and contracts sponsored by the Nutrient Data Laboratory. The latest 1999 USDA
Nutrient Database, Release #13, includes added food composition data for several hundred
new items and added data on selenium and vitamin D compared to the 1998 Release.21
An online database search program is available on the USDA Nutrient Data Laboratory
home page: www.nal.usda.gov/fnic/foodcomp.
Limitations of Nutrient Analysis Software Reports

Nutrient analysis software has its own unique limitations.4 The calculations of nutrient
intake are not exact because there are too many variables in the analysis, including the
database and the program’s calculation methods. However, these software-related vari-
ables are minor in comparison to the larger human challenges to accuracy. Clients and
subjects tend to give inaccurate reports of actual food intake using both food records and
food frequencies. Data entry is also highly dependent on interpreting and selecting the
right match from the food database.
Individuals may also misinterpret the results. Computer-generated printouts tend to
convey an authoritative tone, often leading to the perception that the reports are more
precise than they really are. Individuals unfamiliar with DRI/RDA comparisons may
easily misinterpret them as minimal nutrient needs, assuming that they should be at 100%
to avoid deficiencies. Even professionals may have difficulty drawing specific conclusions
from the new DRI/RDA comparisons for individuals.
To use nutrient analysis reports effectively, a health professional should provide indi-
vidual counseling, including:
1. Specific comments and/or supplementary resources for interpreting printouts

2. Explanations of the limitations of the analysis

3. Suggestions for ways to improve dietary intake (e.g., list food sources for spec-
ified vitamins or minerals)
4. Specific comments about the appropriateness of different nutrition supplements
5. Other resources for further guidance, as appropriate.
Conclusion
Nutrient or dietary analysis software designed to aid in calculations offers an important
adjunct for improving dietary intake and health for individuals and population. However,
health professionals and consumers alike need to be aware of both the benefits and
limitations of the various systems and reports available.
References
1. Hoover LW. Clin Nutr 6: 198; 1987.
2. Feskanich D, Buzzard IM, Welch BT, et al. JADA 88: 1263; 1988.
3. Byers T, Thompson FE. J Nutr 124: 2245S; 1994.
4. Grossbauer S. In Communicating as Professionals (2nd ed), Chernoff R, Ed, The American Dietetic
Association: Chicago, IL. 1994, pg 56.
5. Adelman MO, Dwyer JT, Woods M, et al. JADA 83: 421; 1983.
6. Hoover LW. JADA 83: 501; 1983.
7. Frank GC, Farris RP, Hyg MS, Berenson GS. JADA 84, 818; 1984.
8. Taylor ML, Kozlowski BW, Baer MT. JADA 85: 1136; 1985.
9. Shanklin D, Endres JM, Sawicki M. JADA 85: 308; 1985.
10. Eck LH, Klesges RC, Hanson CL, et al. JADA 88: 602; 1988.
11. Stumbo PJ. JADA 92: 57; 1992.
12. LaComb RP, Taylor ML, Noble JM. JADA 92: 1391; 1992.
13. Nieman DC, Nieman CN. JADA 87: 930; 1987.
14. Nieman DC, Butterworth DE, Nieman CN, et al. JADA 92: 48; 1992.
15. Lee RD, Nieman DC, Rainwater M. JADA 95: 858; 1995.
16. Pennington JAT, Wilson DB. JADA 90: 375; 1990.
17. Obarzanek E, Reed DB, Bigelow C, et al. Int J Food Sci Nutr 44: 155; 1993.
18. McKeown NM, Rasmujssen HM, Charnley JM, et al. JADA 100: 1201; 2000.
19. McCullough ML, Karanja NM, Lin PH, et al. JADA 99: S45; 1999.
20. Schakel SF, Sievert YA, Buzzard IM. JADA 88: 1268; 1988.
21. US Dept of Agriculture. Agricultural Research Service. 1999. USDA Nutrient Database for
Standard Reference, Release 13. Nutrient Data Laboratory home page,
http://www.nal.usda.gov/fnic/foodcomp.
24
Nutrient Data Analysis Techniques and Strategies
Alan R. Dyer, Kiang Liu, and Christopher T. Sempos
Overview
Analyses of nutrient data pose special challenges to investigators. In such analyses, inves-
tigators need to consider:
1. Possible over- or under-reporting of intakes, leading to “impossible” or extreme

values in the data set
2. How to adjust for total energy intake
3. How to model nutrients, e.g., as continuous or categorical variable
4. How to avoid multicollinearity, particularly when nutrients are expressed in
absolute amounts, e.g., grams/day
5. How to analyze dietary supplement data
6. How to account for large day-to-day variability in intakes, which can lead to
misclassification of individuals with respect to usual intake
The objectives of this section are to examine various approaches to addressing the above
issues; to briefly describe the common types of observational and experimental studies
that collect nutritional data; and to describe the most common methods of analysis used
in the types of studies described.
Quality Control
Whether investigators use a validated food frequency questionnaire or single or multiple
24-hour recalls to collect dietary data, the importance of quality control in such data
collection cannot be overemphasized. The phrase GIGO (garbage in, garbage out) serves
as a stark reminder of the importance of ensuring that dietary data are of the highest
0-8493-2705-9/01/$0.00+$1.50
quality when they are submitted for analysis. No amount of analytic sophistication can
make up for poor quality data.
To improve the quality of collected data, investigators should:
• Develop a Manual of Operations for nutrient data collection

• Train and certify dietary interviewers in collection of data and use of the manual
• Tape interviews with the consent of the participant
• Immediately review a printout of the data collected, including nutrient totals if
the system being used permits
• Develop range limits for important nutrients that result in careful review of the
questionnaire or 24-hour recall with the participant, if limits are exceeded
• Make inquiries to cooks for clarifying information when needed
• Query the participant for a 24-hour recall on whether the amount consumed was
typical, and if atypical, the reason the amount consumed was unusually low or
high, e.g., lower than usual due to illness
• Use food composition data to estimate nutrient composition for foods not found
in a data base when using 24-hour recalls
• Randomly select tape recordings for repeat completion of questionnaires or re-
entry of data, with assessment of discrepancies and correction of incorrect data
• Develop criteria for re-certifying interviewers based on the randomly selected
recordings
Interviewers may also be requested to indicate whether they believe the participant has
provided reliable data. Persons deemed by the interviewer as not providing reliable data
should be excluded from the analyses.
Prior to conducting analyses, investigators might wish to set limits on total caloric intake
above or below which persons would be excluded. For example, in the Coronary Artery
Risk Development in (young) Adults Study (CARDIA),1 men who reported intake of
>8000 kcals or <800 kcals and women who reported intake of >6000 kcals or <600 kcals
on food frequency questionnaires were excluded from analyses, because values outside
these limits were not considered consistent with a normal lifestyle.2 The INTERMAP study
of macronutrients and blood pressure also established exclusionary cutoffs for caloric
intake obtained from 24-hour recalls.3,4 Food frequency questionnaires generally have
larger standard deviations in total energy intake than 24-hour recalls, and thus are more
likely to have individuals with “impossible” or extreme values.5 Hence, investigators using
food frequency questionnaires need to be particularly attentive to establishing exclusion-
ary cutoffs for total energy intake, such as those used in CARDIA. Investigators using 24-
hour recalls should consider whether or not to exclude persons reporting that their 24-
hour intake was unusual.
Identifying Outliers or Extreme Values

Prior to conducting any analyses, investigators should examine the distribution of each
variable of interest for outliers or extreme values. The procedure Proc Univariate in SAS
is particularly useful in this regard.6 In addition to providing the standard descriptive
Nutrient Data Analysis Techniques and Strategies 569
statistics, e.g., mean, median, standard deviation, range, etc., this procedure also identifies
the five largest and five smallest values for each variable, and the 1st, 5th, 95th, and 99th
percentiles. The user can also request a box plot of the data, which can be very helpful in
identifying extreme values. The box plot helps indicate how discrepant the largest and
smallest values are from the rest of the data.
The fact that a statistical software package identifies values as large or extreme relative
to other values in the distribution should not be taken as prima facie evidence that such
values are invalid or that an error was made in data collection or data entry. Values so
identified should be examined for such problems. However, if the values are biologically
plausible and no error appears to have been made, they should not be arbitrarily excluded
from the analysis. Neter, Wasserman, and Kutner7 suggest that a safe rule is “to discard
an outlier only if there is direct evidence that it represents an error in recording, a mis-
calculation, a malfunctioning piece of equipment, or a similar type of circumstance.” When
outliers are retained in a data set, the investigator needs to take special steps to assess
any influence they may have on the results of the analysis. This can include analyses with
and without the outlying value or values, use of nonparametric statistical methods, e.g.,
the Spearman rank correlation instead of the usual Pearson correlation coefficient, trans-
formations of the data which bring the outlying value closer to the other values, e.g., the
log or square root transformation, specific tests for influential observations,7 or use of
robust regression methods.8
Adjustment for Total Energy Intake

Adjustment for total energy intake is of particular relevance for epidemiologic studies in
which investigators use some form of regression model to examine the associations of
specific nutrients with an outcome variable, e.g., blood pressure or cholesterol in multiple
linear regression, case-control status in logistic regression, or coronary heart disease inci-
dence in Cox proportional hazards regression. Thorough discussions on adjustment for
total energy intake can be found in Willett, Howe, and Kushi,9 or in Willett.10 Only the
major issues addressed by these authors are described here. The rationale for adjusting
for total energy intake is that most nutrients are correlated with total energy intake. This
is because they contribute directly to total energy intake, e.g., total fat or carbohydrate,
or because persons who consume more kcalories also eat more, on average, of all nutrients,
e.g., dietary cholesterol or sodium. For example, in participants of the Multiple Risk Factor
Intervention Trial (MRFIT),11 the baseline correlations of 10 energy contributing nutrients
with total energy intake ranged from 0.29 for alcohol intake to 0.87 for total fat intake.
Among 24 non-energy contributing nutrients, the correlations ranged from 0.05 for retinol
to 0.78 for phosphorus, with a median of 0.52. No nutrient had a negative correlation with
total energy intake. Thus, if total energy intake is positively associated with a dependent
variable, almost all specific nutrients will also be positively associated with that variable.
Hence, in regression analyses involving specific nutrients, there is a need to adjust asso-
ciations with specific nutrients for the potential confounding effects of total energy intake.
The most common methods of adjustment for total energy intake are typically referred
to as the nutrient density method, the standard multivariate method, the residual
method, and the multivariate nutrient density method. 9,10,12 The nutrient density method
has been the traditional method of adjusting for total energy intake. In this approach,
nutrient intake is divided by total energy intake, with energy-contributing nutrients
expressed as percent of kcalories, and non-energy contributing nutrients expressed as

intake per 1000 kcal. The strengths of this approach include ease of calculation, familiarity
by nutritionists, and use in national guidelines.9 For example, the Committee on Diet
and Health of the National Research Council recommends that total fat intake be less
than 30% of total energy intake and that saturated fat intake be less than 10%.13 The
primary problem with the nutrient density method is that it does not completely elim-
inate potential confounding with total energy intake, since nutrients expressed as nutri-
ent density often remain correlated with total energy intake. For example, in the MRFIT,
the correlations of percent kcalories from protein, fat, and carbohydrate intake with total
energy intake at baseline were –0.23, 0.18, and –0.11, respectively.11 However, with these
three nutrients expressed as g/day, the corresponding correlations were 0.73, 0.87, and
0.77 in these men.
In the standard multivariate method, total energy intake is included in the multivariate
regression model along with the nutrient or nutrients of interest. In this model, the
regression coefficient for the nutrient of interest represents the effect of changing the
nutrient by one unit while maintaining a constant total energy intake. For energy-contain-
ing nutrients this can only be accomplished by making changes in other energy-contrib-
uting nutrients equal to the amount of energy contained in one unit of the nutrient of
interest. Similarly, the regression coefficient for total energy intake does not represent the
effect of changing total energy intake by 1 kcal, but the effect of changing energy intake
from all other energy contributing nutrients by 1 kcal. For example, if the nutrient in the
model is total protein intake, then total energy intake represents fat and carbohydrate
intake. In using this approach, estimates of the effect of changing intake of the nutrient
by a specific amount should use variation in the nutrient with total energy intake held
constant, i.e., the nutrient residual (see below) as the basis for the estimates of effect.
Failure to do so can result in estimates of effect based on unrealistic differences in intake
of the nutrient.
In the residual method, the investigator regresses each nutrient of interest on total
energy intake, and then computes a nutrient residual for each individual by subtracting
from the individual’s actual intake of that nutrient, the amount predicted based on his/
her total energy intake. Because the mean of these residuals is equal to zero, it may be
desirable to add a constant to each residual, e.g., the mean intake for the nutrient. The
resulting value does not, however, represent the individual’s actual intake, and in fact
has no “biological” or public policy meaning. The residual method is simply one means
by which investigators can adjust for total energy intake. Nutrient residuals are indepen-
dent of total energy intake. Models that use nutrient residuals can also include total
energy intake. The regression coefficient for a nutrient expressed as a nutrient residual
is identical to the regression coefficient for the nutrient in the standard multivariate
model. However, the regression coefficient for total energy intake will not be identical
to that in the standard multivariate model. In the residual model, the association of total
energy intake with the dependent variable is not adjusted for intake of the specific
nutrient, which could result in an inaccurate estimate of the association of total energy
intake with the dependent variable.
In the multivariate nutrient density model, total energy intake is included in the model
along with nutrient density. This approach addresses the problem of potential confounding
by total energy intake in such analyses. In this model, the regression coefficient for the
nutrient estimates the effect of a 1% difference in energy from the nutrient with total caloric
intake held constant. As noted by Willett et al.,9 a major strength of the multivariate
nutrient density approach is that it separates diet into two components: composition and
total amount.
2705_frame_C24 Page 571 Tuesday, September 25, 2001 11:07 AM
Modeling Nutrient Intake

Investigators typically model nutrient intake as a continuous variable or a series of dummy
variables corresponding to quantiles of the nutrient, e.g., quartiles or quintiles. The advan-
tages of categorizing nutrient intake include reduction of the potential effects of outlying
or extreme values, and elimination of the need to assume a linear relation between the
nutrient of interest and the dependent variable. Categorization is also more informative
to readers since it allows estimation of relative risks in logistic regression and Cox pro-
portional hazards regression for persons in each exposure category relative to a referent
category, and in multiple linear regression the mean difference in the dependent variable
for persons in each exposure category relative to the referent category. The main weakness
in categorizing a continuous variable is that when the relationship is linear, the categori-
zation results in a loss of power. However, regardless of how nutrient intake is modeled
in the definitive analysis, categorization is still an extremely useful tool and should be
part of any analysis plan. This is because categorization allows the investigator to examine
the shape of the relation between the nutrient and the dependent variable, and thus
whether the relation is sufficiently linear to support inclusion of the nutrient as a contin-
uous variable in the regression model.
When nutrient intake is categorized, one defines k-1 dummy variables for each individ-
ual for the k categories of the variable. For example, if nutrient intake is divided into
quartiles, three dummy variables are defined. In defining the dummy variables, it is
necessary to define a referent category. This is the category against which the risks or
means for the other exposure categories are compared. If nutrient intake is divided into
quartiles and the first quartile is to be the referent category, the three dummy variables
corresponding to quartiles 2 to 4 are defined as follows:
1 if intake in second quartile

X1 = 
0 otherwise
1 if intake in third quartile
X2 = 
0 otherwise
1 if intake in fourth quartile
X3 = 
0 otherwise
These definitions produce the following values on each of the variables for individuals in
the first through fourth quartiles:
Quartile of intake X1 X2 X3
1 0 0 0
2 1 0 0
3 0 1 0
4 0 0 1
In defining categories for a nutrient, investigators should adjust for total energy intake
by defining the categories based on nutrient residuals or nutrient densities, rather than
absolute intake.12 While the standard multivariate method and the nutrient residual
method provide identical regression coefficients for the nutrient of interest when the
nutrient is entered as a continuous variable, this is not the case when nutrient intake is
categorized.12 In this case, the standard multivariate method should be avoided. It is also
desirable to model total energy intake as a continuous variable in such analyses rather
than as a second categorical variable, particularly if nutrient density is the variable being
categorized.10,12
Multicollinearity
Multicollinearity in a regression model can occur when highly intercorrelated variables
are entered simultaneously into the model, or when a linear combination of several
variables essentially equals a constant. For example, multicollinearity would occur with
nutrient data if the model included percent of kcalories from total fat, protein, and car-
bohydrate, since the sum of these three variables is often 100 or quite close to 100. Hence,
investigators should not attempt to enter more than two of these variables simultaneously
into a regression model. Similarly, multicollinearity would also occur if these same three
variables were entered into a model as g/day along with total energy intake. In this case,
only three of these four variables should be entered simultaneously. In general, investi-
gators need to ensure that they do not include in the same model variables representing
total intake for a nutrient and all individual components of that intake, e.g., total fat plus
saturated fats, polyunsaturated fats, and monounsaturated fats. However, even if inves-
tigators are careful to ensure that the types of multicollinearity described above do not
occur, multicollinearity can still be a problem when multiple intercorrelated variables are
included in a model, e.g., nutrients that come from the same sources. In this situation it
may be impossible to determine the separate and independent associations of the multiple
variables with the dependent variable. For example, in a study on the associations of
potassium, calcium, protein, and milk intakes with blood pressure, the investigators found
that while potassium had a relatively stronger association with blood pressure than the
other three dietary factors, the high correlations of potassium intake with intakes of the
other three made it impossible to determine the independent association of potassium
intake with blood pressure.14
The use of nutrient residuals and nutrient densities help to reduce the likelihood of
multicollinearity, since energy-adjusted nutrients generally have lower intercorrelations
than nutrients expressed as absolute amounts.10 Methods for assessing and detecting mul-
ticollinearity, as well as remedial measures, can be found in Neter, Wasserman, and Kutner.7
Some investigators may believe that procedures that select variables for inclusion in
regression models based on whether or not the variable is significantly related to the
dependent variable are appropriate approaches for preventing multicollinearity. Such
procedures include forward selection or backward elimination of variables, and stepwise
regression. In forward selection of variables, variables are entered into the model one at
a time, beginning with the variable that has the strongest association with the dependent
variable, followed sequentially by those having the strongest residual associations with
the dependent variable, i.e., after taking into account the association of the entering
variable with the variables previously entered and their associations with the dependent
variable. Variables are entered into the model until no remaining variable would have a
statistically significant association with the dependent variable, if it were to enter the
model next. In backward elimination of variables, all available variables are entered into
the model, and those with the weakest association are sequentially removed until only
variables significantly related to the dependent variable remain. Stepwise regression com-
bines forward selection and backward elimination of variables by removing those that are
no longer significant when a new variable is entered into the model, so that the final model
only contains variables significantly related to the dependent variable.
These variable selection procedures should be avoided for a number of reasons. First,
the final model selected will not necessarily be optimal, e.g., maximize R2. Second, the
hypothesis tests used to determine which variables remain in the model are correlated.8
Third, if a large number of variables is involved, initial entry of all variables may not be
possible if one or more is a linear combination of the other variables. Fourth, stepwise
procedures may not select possible confounders that should be included whether or not
the confounder has a significant association with the dependent variable, e.g., age and
sex, or total energy intake in the multivariate nutrient density approach. Fifth, the results
of these procedures are often not unique, i.e., they yield final models that do not include
the same variables. For example, in a logistic analysis involving the associations of total
energy intake and intakes of protein, fat, and carbohydrate with CHD incidence, McGee,
Reed, and Yano15 found that only carbohydrate intake had a significant association with
CHD incidence if forward selection of variables was used. When backward elimination
was used instead, the final model included fat intake and total energy intake as the only
variables significantly and independently related to CHD incidence.
Dietary Supplements
The use of dietary supplements poses a number of complexities for analyses involving
nutrient intake, which are not easily resolved. The first question that must be addressed
is whether supplement-based intake should be included or excluded. The approach rec-
ommended here is to analyze the data with and without inclusion of the supplement-
based intake, since this is likely to provide the most complete information on the associ-
ation of the nutrient with outcome. It may also be beneficial to treat the intake from
supplements and food-based intake as separate nutrients. Such an approach is likely to
be particularly appropriate if it is difficult to determine the separate and independent
effects of food-based intake of the nutrient, or the separate and independent effects of the
supplement due to its high correlation with supplemental intake of other nutrients, or
where food-based intake and supplement-based intake have very different correlations
with other nutrients. If such an analysis is done, food-based intake should be energy
adjusted using nutrient residuals or nutrient densities, with supplement-based intake not
energy adjusted, except through inclusion of total energy intake in the model. Hence, the
analysis for food-based intake would be based on the residual or nutrient density model,
whereas the analysis for supplement-based intake would follow the standard multivariate
model. If intake is categorized, the categorization of food-based intake should use the
nutrient residuals or nutrient densities, whereas the categories for supplement-based
intake would be based on absolute amounts. The reason for not suggesting that supple-
ment-based intake be adjusted for total energy intake through calculation of nutrient
residuals or nutrient densities is a likely low correlation between total energy intake and
supplement-based intake, particularly if the nutrient does not contribute to energy intake.
If analyses are to be conducted in which food- and supplement-based intakes are com-
bined, the investigator needs to decide whether to simply add the two intakes together
or to add supplement-based intake to the energy-adjusted intake from foods.9 It is unclear

how, or if, results between these two approaches will differ. If the intake from supplements
represents a large proportion of the total intake and thus the correlation between total
intake of the nutrient and total energy intake is low, the easiest and probably best approach
is to simply combine the supplement-based intake with the food-based intake, and then
use the standard multivariate model, whether or not nutrient intake is categorized. If the
supplement-based intake does not represent a large proportion of the total intake, it may
be worthwhile to examine the associations using both approaches, since it is unclear how
the results might differ, of if they will differ in any practical way.
Within-Person Variability in Intake

The goal of examining associations of nutrients with an outcome is to estimate the asso-
ciation of usual intake with that outcome. However, information on nutrient intake col-
lected from a single 24-hour recall is subject to substantial within-person variability due
to day-to-day variability in intake in most individuals. Hence, nutrient intake in a single
24-hour recall often does not reflect the individual’s average or usual intake. This day-to-
day variability in nutrient intake is often referred to as “measurement error.” Measurement
error typically results in underestimation of associations of nutrients with outcomes. For
example, for MRFIT men11 it was estimated that with one 24-hour recall, the association
between a dependent variable and percent of kcalories from total fat would be underes-
timated by 77.7% in simple linear regression.
Error can generally be divided into two types: random and systematic. If error is random,
the average of a large number of repeated measurements approaches the true value, or
for nutrient intake, the individual’s usual intake. To reduce measurement error, studies
will often collect multiple 24-hour recalls. Liu et al16 describe methods for estimating the
number of 24-hour recalls required to achieve a suitable degree of accuracy. In MRFIT
men11 it was estimated that the association between a dependent variable and percent of
kcalories from total fat would be underestimated by 46.7% with four 24-hour recalls,
compared to the 77.7% underestimation with one 24-hour recall.
If error is systematic, for example due to systematic over- or underreporting of intake,
the average of a large number of repeated measurements will not reflect the individual’s
usual intake. Food frequency questionnaires may also have systematic error if specific
foods eaten by an individual are not included in the questionnaire.
Methods are available for correcting or adjusting regression coefficients for measurement
error. However, the assumptions that underlie such corrections can be quite strong and
may not be strictly applicable to nutrient data. In particular, it is typically assumed that
error is random and independent of the true value or usual intake, and that error and
usual intake are normally distributed. However, for nutrient data it is likely that error is
correlated with usual intake. For example, an individual with a usual intake of 3000 kcal
is likely to vary more about his/her usual intake than an individual with a usual intake
of 1000 kcal. Correcting for measurement error should be done with care and caution, and
with attention to the assumptions underlying such corrections. A thorough discussion on
correcting for measurement error in linear regression models is given by Fuller.17 Willett10
and Clayton and Gill18 also discuss measurement error in the context of nutrient data.
Spiegelman, McDermott, and Rosner19 describe the regression calibration method for
adjusting point and interval estimates for measurement error in linear regression, logistic
regression, and Cox proportional hazards regression. The regression calibration method
is appropriate when a gold standard is available in a validation study and a linear
measurement error with a constant variance applies, or when replicate measurements are
available in a reliability study and linear random within-person error can be assumed.
These authors also describe SAS macros that can be used to adjust regression coefficients
in these models when the assumptions underlying use of the regression calibration method
appear appropriate.
Types of Epidemiologic Studies

A discussion of types of epidemiologic studies with particular reference to nutrition can
be found in Sempos, Liu, and Ernst,20 while a more general review of the topic is given
in Hennekens and Buring.21 There are generally two types of epidemiologic studies:
observational and experimental. The main difference between an experimental and an
observational study is the control that the investigator exercises over participants, proce-
dures, and exposures. In an experiment, the investigator controls who enters the study,
what drugs or procedures are given to participants, and how the study is carried out. In
a nutritional intervention study, the investigator would manipulate or attempt to manip-
ulate some or all participants’ dietary intake. An observational study does not involve an
intervention or manipulation. In such a study, the investigator does not control who enters
the study or the factors or drugs to which participants are exposed. Observational studies
of individuals include cross-sectional, case-control, and prospective studies, while studies
of groups are referred to as ecologic studies. In nutritional epidemiologic studies, nutrient
intake is measured but not manipulated, the frequency and pattern of outcomes observed,
and associations between nutrients and outcomes estimated using statistical methods.
In a cross-sectional study the question asked is, “What is the correlation or association
between nutrient intake and the outcome?” Individuals are included in the study without
regard to their status on the outcome or nutrient intake. In these studies, nutrient intake
and the outcome are both measured at the same point in time. For example, INTERMAP
is a cross-sectional study of the associations of macronutrients with blood pressure.3,4 In
this study, each participant had blood pressure measured twice on each of four occasions
and completed a 24-hour recall on each day that blood pressure was measured.
Case-control studies, also referred to as retrospective and case-referent studies, are
designed to answer the question, “Do persons with disease (cases) have different nutrient
intake than persons who have not been diagnosed with the disease (controls)?” For
example, do persons with heart disease consume more dietary cholesterol and saturated
fatty acids than persons without heart disease? In case-control studies, recently diagnosed
persons with the disease and a set of persons without the disease are interviewed con-
cerning their dietary habits. The goal is to determine usual nutrient intake before the onset
of disease.
Prospective studies are also referred to as cohort, incidence, follow-up, and longitudinal
studies. The question asked in prospective studies when a nutrient is thought to be related
to increased risk of disease is, “Do persons with higher intake develop or die from the
disease more frequently or sooner than persons with lower intake?” Alternatively, if a
nutrient is thought to be related to decreased risk of disease, the question asked is, “Do
persons with lower intake develop or die from the disease more frequently or sooner than
persons with higher intake?” For example, are persons who consume more than 50 g/day
of alcohol more likely to have a stroke than persons who consume less alcohol? Persons
found to be disease free at the time of the cross-sectional survey are followed over time
to determine who develops the disease and when the disease occurs.
Ecologic studies compare aggregate data representing entire populations. A common
example of this type of study is one in which disease-specific mortality rates for different
countries are correlated with nutrient measurements based on food disappearance data.22
The INTERSALT study included ecologic analyses on associations of urinary electrolytes
and other factors with blood pressure, as well as cross-sectional analyses on electrolyte-
blood pressure associations within individuals.23,24
Experimental studies involving nutritional interventions include feeding or metabolic
ward studies and randomized clinical trials. Feeding studies involve feeding groups of
individuals precisely measured diets with one or more components varied, with an effect
on a biologic variable then measured. The Keys equation for predicting change in total
cholesterol from changes in intakes of saturated and polyunsaturated fatty acids and
dietary cholesterol was determined from a metabolic ward study.25 A common design for
feeding studies is the crossover design, in which each participant serves as his/her own
control. The randomized clinical trial is a prospective study in which individuals are
randomly assigned to intervention and control groups. After randomization, both groups
are followed over time to assess the efficacy and safety of the intervention. For example,
the trial on the Primary Prevention of Hypertension was a randomized, controlled clinical
trial on the effects of weight loss, reduction in sodium intake, decreased alcohol intake,
and increased exercise on the five-year incidence of hypertension in men and women with
high normal blood pressure.26
Methods for Comparing Groups in Cross-Sectional Studies

Table 24.1 lists methods of analysis that can be used to compare nutrient intake between
two groups, e.g., men and women, or among three or more groups, e.g., African-Ameri-
cans, Hispanics, and whites. For nutrient intake considered as a continuous variable, the
goal of the analysis is to determine whether mean or median intake differs significantly
between or among groups. For such analyses, the table indicates the usual method of
TABLE 24.1
Methods for Comparing Nutrient Intake among Groups in Cross-Sectional Studies
Number of Groups (k)
Description k=2 k>2
Nutrient Intake Continuous
Usual method Two-sample t-test Analysis of variance

Nonparametric alternative Wilcoxon rank-sum test Kruskal-Wallis test
Adjustment for other variables Analysis of covariance or
multiple linear regression
Nutrient Intake Categorical (c categories)
Usual method Chi-square test for 2 x c Chi-square test for k x c

contingency table contingency table
analysis, the nonparametric alternative, and methods that can be used to adjust for poten-
tial confounders of differences between groups, e.g., age or total energy intake. Nonpara-
metric tests make fewer assumptions about the shape of the distributions of variables than
parametric tests such as the two-sample t-test or analysis of variance. In the Wilcoxon
rank-sum test and the Kruskal-Wallis test, the actual observations are replaced by their
ranks in the combined sample of all observations. If nutrient intake is divided into cate-
gories, the goal of the analysis is usually to determine whether the distributions of intake
are homogeneous across groups. The methods listed in Table 24.1 can also be used to
compare nutrient intake at baseline in an experimental study; for example, to determine
whether in a randomized clinical trial randomization has provided comparable groups
with respect to intake of specific nutrients. A useful text on these methods and those
described below is that of Rosner.27
Methods for Comparing Cases and Controls in Case-Control Studies

Table 24.2 lists methods of analysis that can be used to compare nutrient intake between
cases and controls in unmatched and matched case-control studies. Matching is often done
in case-control studies to make cases and controls comparable on variables that could
confound associations of the variable of interest with disease. For unmatched case-control
studies, the methods listed are identical to those for comparing nutrient intake between
two groups in cross-sectional studies. For matched case-control studies, the methods of
analysis need to take into account the matching. Hence, for a simple comparison of means
between cases and controls, the investigator should use a paired t-test rather than a two-
sample t-test, or the Wilcoxon signed-rank test rather than the Wilcoxon rank sum test.
When multiple regression is used to adjust the mean difference between cases and controls
for other variables in matched case-control studies, the investigator needs to ensure that
the dependent and independent variables in the model are defined correctly. In such
studies, the dependent variable is the difference in nutrient intake for each case-control
TABLE 24.2
Methods for Comparing Nutrient Intake between Cases and Controls in Case-Control
Studies
Description Unmatched Matched
Nutrient Intake Continuous
Usual method Two-sample t-test Paired t-test

Nonparametric alternative Wilcoxon rank-sum test Wilcoxon signed-rank test
Adjustment for other variables Analysis of covariance or Multiple linear regression*
multiple linear regression
Nutrient Intake Categorical (c categories)
Usual method Chi-square test for 2 x c McNemar’s test for c = 2

contingency table
* In this model, differences in each variable for the case-control pair are used, with the difference in
the nutrient of interest serving as the dependent variable. The test of significance for the adjusted
mean difference is the test of the hypothesis that the intercept of the model is equal to zero.
TABLE 24.3
Methods for Assessing Associations in Epidemiologic Studies
Dependent Adjusted for
Variable Nutrient Intake Unadjusted Other Variables
Cross-Sectional or Ecologic Study
Continous Continous Pearson correlation Partial correlation

Spearman correlation Linear regression
Linear regression
Continous Categorical Linear regression Linear regression
Dichotomous Continuous, categorical Logistic regression Logistic regression
Unmatched Case-Control Study
Case-control status Continuous, categorical Logistic regression Logistic regression
Matched Case-Control Study
None Continuous, categorical Conditional logistic Conditional logistic

regression regression
Prospective Study
Time to event Categorical Log rank test Cox regression

Cox regression
Time to event Continuous Cox regression Cox regression
pair, while the independent variables are the within-pair differences for the potential
confounding variables. The test of significance for the adjusted mean difference is the test
of the hypothesis that the intercept in the model is equal to zero.
Methods for Assessing Associations in Epidemiologic Studies

Table 24.3 lists methods for assessing associations of nutrient intake with outcome vari-
ables in cross-sectional or ecologic studies, matched and unmatched case-control studies,
and prospective studies. For each type of study, the table indicates methods that can be
used when nutrient intake is modeled as a continuous variable or as a categorical variable.
The table also lists the dependent variable for each type of analysis. For example, in Cox
proportional hazards regression, the dependent variable is the time to some event, e.g.,
death from coronary heart disease. In unmatched case-control studies, the dependent
variable is typically case-control status. Since cross-sectional and ecologic studies can have
both continuous and dichotomous dependent variables, methods are listed for both types
of dependent variable. No dependent variable is listed for conditional logistic regression,
since there is no outcome variable that varies from individual to individual in this model.
In conditional logistic regression, the independent variables are the case-control difference
in each variable, and the model does not include a constant term. A useful text on logistic
and Cox regression methods is that of Kahn and Sempos.28
The Spearman correlation is listed for use in cross-sectional and ecologic studies, since
it is the nonparametric alternative to the Pearson product-moment correlation coefficient.
The Pearson-product moment correlation coefficient should not be used if either nutrient
intake or the second variable has a very skewed distribution, since the assumption
underlying its use is that each variable has a normal distribution for each value of the
other variable.
In analyses involving linear regression, interest focuses on the difference in the mean
of the dependent variable for a one-unit or greater difference in the independent variable.
Hence, the focus is on the regression coefficient. In logistic and Cox regression, interest
focuses on estimates of relative risk. In logistic regression, the relative risk is given by the
odds ratio, and in Cox regression the hazard ratio. In both models, relative risk estimates
are obtained by exponentiation of the regression coefficient or the regression coefficient
times some convenient multiplier. For example, if total energy intake is the dietary variable
of interest, exponentiation of the regression coefficient gives the relative risk of the outcome
for two persons who differ in total energy intake by 1 kcal. Since this is not a particularly
meaningful difference for calculating relative risk, an investigator might multiply the
regression coefficient by 500 to obtain the relative risk of the outcome for two persons
who differ in total energy intake by 500 kcal. When nutrient intake is categorized and
dummy variables are included in the regression model, exponentiation of the regression
coefficient for a dummy variable gives the risk of the outcome for those in the category
corresponding to the dummy variable relative to the referent category, e.g., quartile 4
relative to quartile 1.
In analyses based on Cox regression, true associations between diet and disease may
not be found if there are substantial changes in nutrient intake between the baseline
assessment of diet and the development of disease, or if there are substantial changes in
the rank ordering of study participants with respect to intake over the course of followup.
Analyses of Intervention Studies with Change in Nutrient Intake as

Outcome
In nutritional intervention studies, investigators often wish to examine the effects of the
intervention on intakes of specific nutrients following completion of the intervention.
Investigators can use three approaches to determine whether intake of specific nutrients
changed in an intervention group relative to a control group or among three or more groups:
1. Compare intake among groups at followup, ignoring pre-intervention intake

using the methods for cross-sectional studies in Table 24.1.
2. Compare the change in intake from pre-intervention to followup among groups
using the methods for cross-sectional studies.
3. Compare intake among groups at followup, adjusting for pre-intervention intake
with multiple linear regression or analysis of covariance.
Investigators typically use the second approach for intervention studies, even though
it tends to be less powerful than analysis of covariance. Assumptions in regard to the
analysis of covariance may or may not be met in an intervention study. The first approach
may, however, be preferable to the second, if there are no differences in intake among the
groups compared at the pre-intervention assessment, and the correlation between the pre-
intervention and followup assessments for the nutrient of interest is less than 0.5. Corre-
lations smaller than 0.5 are not uncommon for many nutrients assessed on two occasions.11
Hence, for nutrient intake the best approach may be to ignore pre-intervention intake.
Prior to conducting analyses in nutritional intervention studies, investigators should
examine the correlations of the nutrients from pre-intervention to followup and be pre-
pared to ignore pre-intervention intake in the analyses.
References
1. Slattery ML, et al. J Am Coll Nutr 14: 635; 1995.
2. Goldberg GR, et al. Eur J Clin Nutr 45: 569; 1991.
3. INTERMAP Cooperative Research Group Canad J Cardiol 13: 235B; 1997.
4. INTERMAP Research Group. Canad J Cardiol 13: 80B; 1997.
5. Liu K. Am J Clin Nutr 59: 262S; 1994.
6. SAS Procedures Guide, Release 6.03 Edition. Cary, NC: SAS Institute, 1988.
7. Neter J, Wasserman W, Kutner MH. Applied Linear Regression Models. Homewood, IL: Richard
D. Irwin, Inc., 1983.
8. Ryan TP. Modern Regression Methods. New York, NY: John Wiley & Sons, 1997.
9. Willett WC, Howe GR, Kushi LH. Am J Clin Nutr 65: 1220S; 1997.
10. Willett W. Nutritional Epidemiology. New York, NY: Oxford University Press, 1990.
11. Grandits GA, Bartsch GE, Stamler J. In: Dietary and Nutritional Methods and Findings: The
Multiple Risk Factor Intervention Trial (MRFIT) (Stamler J, et al. Eds.) Am J Clin Nutr 65: 211S;
1997.
12. Brown CC, et al. Am J Epidemiol 129: 323; 1994.
13. National Research Council. Diet and Health: Implications for Reducing Chronic Disease Risk.
Washington, DC: National Academy Press, 1989.
14. Reed D, McGee D, Yano K, Hankin J. Hypertension 7: 405; 1985.
15. McGee D, Reed D, Yano K. J Chron Dis 37: 713; 1984.
16. Liu K, et al. J Chron Dis 31: 399; 1978.
17. Fuller WA. Measurement Error Models. New York, NY: John Wiley & Sons, 1987.
18. Clayton D, Gill C. In: Design Concepts in Nutritional Epidemiology. Margetts BM, Nelson M,
Eds, Oxford, UK: Oxford University Press, 1991, pp. 79-96.
19. Spiegelman D, McDermott A, Rosner B. Am J Clin Nutr 65: 1179S; 1997.
20. Sempos CT, Liu K, Ernst N. Am J Clin Nutr 69: 1S; 1999.
21. Hennekens CH, Buring JE. Epidemiology in Medicine (Mayrent SL, Ed) Boston, MA: Little,
Brown, 1987.
22. Stamler J, Shekelle R. Arch Pathol Lab Med 112: 1032; 1988.
23. The INTERSALT Cooperative Research Group. J Hypertens 4: 781; 1986.
24. The INTERSALT Cooperative Research Group. Br Med J 297: 319; 1988.
25. Keys A, Anderson JT, Grande F. Metabolism 65; 776; 1965.
26. Stamler R, et al. JAMA 262: 1801; 1989.
27. Rosner B. Fundamentals of Biostatistics, 5th ed. Belmont, CA: Duxbury Press, 1999.
28. Kahn HA, Sempos C. Statistical Methods in Epidemiology. New York, NY: Oxford University
Press, 1989.
25
Medical Nutritional Evaluation
Elaine B. Feldman
Introduction
Family physicians, pediatricians, and internists are the usual providers of primary medical
care for adults, with gynecologists increasingly performing that task for women. The
assessment of nutritional status should be carried out in their offices and in hospital
settings.1 The most common reasons for office visits that may require nutritional interven-
tion are problems related to hypertension, diabetes mellitus, degenerative joint disease,
heart disease, asthma, abdominal pain, and pregnancy care, as well as part of a general
medical examination.2
Nutrition science should be applied to many aspects of primary care delivery.1,3,4 The
history, physical examination, and laboratory tests are used to assess nutritional status. As
a result, patients may be categorized as normal, malnourished, or at risk of malnutrition.
Dietary history, anthropometric measurements, and specific physiologic and biochemical
laboratory tests should be appropriately elaborated in patients with malnutrition or at
nutritional risk. These usually require referrals. In order to communicate effectively with
their patients, physicians should know the components of a healthy diet in terms of foods
as well as nutrients and the patterns of consuming food in meals. Details of food compo-
sition, however, are more likely in the knowledge base of dietitians and nutritionists.
The physician should obtain specific information about the patient’s body weight and
its change over time, the patient’s recent meal intake (e.g., foods eaten the previous day),
appetite, food preferences, level of physical activity, special diets, and intake of supple-
ments. Height and weight are vital signs that should be measured accurately under
standardized conditions (not self-reported) in all patients, and body weight should be
measured at followup visits. The complete blood count (CBC) and serum albumin provide
clues to nutritional anemias and protein status. The patient who is starved, or with
gastrointestinal diseases, malabsorption, hepatic and pancreatic disease, renal failure,
trauma, sepsis, cancer, or requiring critical care should be given special attention in
assessing nutritional status and developing nutritional therapy.5 A registered dietitian is
an invaluable resource in assessing dietary intake by dietary recalls, prospective food
records, or food frequency questionnaires.
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The use of dietary supplements of vitamins and minerals is common in our population
to meet nutritional needs, optimize nutritional health, and prevent disease. Over-the-
counter remedies are available and are marketed with little restriction. Since patients often
do not report supplement use to the physician, toxicity or possible drug–nutrient interac-
tions can be overlooked with serious adverse consequences. Unsubstantiated health claims
may lead to problems because of toxicity, adverse interactions with other medications or
foods, and avoidance of orthodox effective remedies.
The health professional should be aware of good food sources for vitamins and minerals
(Section 1, 5-10), appropriate serving sizes, and the facts of nutrient fortification and
enrichment of foods, especially as they evolve into newer modalities for nourishment.
Encouraging patients to read food labels will result in improving their nutrition knowledge
and health (see Section 14). Proper food/nutrient intake lessens the risk of cardiovascular
and cerebrovascular diseases (atherosclerosis, hypertension) and cancer.
In the practice of primary care, a miscellany of special circumstances, when suspected,
may warrant nutritional interventions. While serious nutritional deficiencies have disap-
peared in affluent countries, physicians should be aware of their occurrence in patients
with alcoholism. That diagnosis should be recognized and the substance abuse treated.
Special nutritional needs of women should be addressed. These include replacing iron
loss from menstruation to prevent or treat anemia, ameliorating accelerated menopause-
related calcium loss from bone, and the special needs of pregnant and lactating women
including meeting the periconceptual need for folic acid to prevent neural tube defects,
and recognizing the greater susceptibility of women to obesity and alcoholism because of
their size, body composition, and metabolic/hormonal differences compared to men.
Dementia is increasing as the population ages. More than one-half of cognitive deficiencies
in the elderly are attributable to vascular disease and increasingly result from thromboem-
bolism. Risk of vascular disease is increased by a diet high in saturated fats, low in
antioxidants, vitamin B12, and choline — especially important in the patient in the middle
years. Vegetarians not ingesting any animal products may be at nutritional risk, and
vitamin supplementation may be recommended. Patients who cannot or will not eat
should be evaluated for possible enteral or parenteral nutrition support and referred to a
dietitian or nutrition support team. Caregivers must be wary of dietary fads, most prev-
alent with regard to weight reduction. Finally, all physicians should be educated in the
principles of a health-promoting diet.6
Patient Evaluation
The medical history will provide 80 to 90% of the information leading to a diagnosis.5,7,8
The evaluation of nutritional status will emphasize certain elements of the medical history
and social background that will differ depending on the patient’s gender, age, and the
presenting problem. The usual level of physical activity and the degree of stress should
be noted. It is imperative to distinguish whether any impairment of nutritonal status is
caused by a patient’s disease or is directly related to abnormal intake of nutrients or an
unbalanced diet. Malnutrition resulting from disease can be managed effectively only if
the underlying disease is controlled or cured. For example, is there physiological or
anatomic loss of gastrointestinal function, or is the degree of weight change out of pro-
portion to food intake indicating hyper- or hypometabolism? Does the patient have dia-
betes mellitus? Is there excessive blood loss from menstruation?
Medical Nutritional Evaluation 583
Medical History
The elements of a medical history include the present illness, past medical and surgical
history, family history, a medication list, and review of systems.
Pertinent questions to ask are:
• What is the patient’s usual weight?

• Has there been any recent change in weight?
• If so, how much and over what period of time?
• What are the maximum and minimum weights?
• What was the weight one year ago, five years ago?
A rapid and profound weight loss is probably the single most important clue to malnu-
trition. This leads the history taker into an evaluation of normal or abnormal food and
nutrient intake. Are there
• Change in smell or taste

• Depression, alcoholism
• Dental problems, poor dentition, sore tongue or swallowing difficulties, affecting
appetite or enjoyment of eating
• Poverty, low socioeconomic status, limited access to food
• Special diet prescriptions
• Food idiosyncrasies, (e.g., pica), food fads, excessive use of dietary supplements
• Mechanical problems in eating due to muscle weakness, joint deformities, tremors
• Altered memory or dementia interfering with food and water intake
• Digestion and absorption problems
Medications such as antacids, laxatives, oral contraceptives, anticonvulsants
Parasites
Surgical resection of the gastrointestinal tract
Malabsorption syndromes
• Utilization
Anticonvulsants, oral contraceptives, antimetabolites, isoniazid
Inborn errors of metabolism
• Losses
Blood loss
Diarrhea (change in bowel habits)
Vomiting
Draining wounds, fistulas, ostomies
Burns
Proteinuria, dialysis
• Destruction
Fever, sepsis
Hypermetabolism
Multiple trauma, burns
Constipation, obstipation
• Special requirements
Chronic disease
Recent major surgery
Alcohol abuse
Hormone replacement therapy
Chemotherapy
Immunosuppressive therapy
Behavior
Excessive use of caffeine
Alcohol abuse
Fad diets
Excessive use of dietary supplements
• Miscellaneous
Neurologic symptoms, e.g., numbness, dizziness, weakness
Skin rash, dryness, flaking, hair loss
Socioeconomic History
The psychosocial evaluation should generate information concening the patient’s income
and living conditions. This is especially important in the elderly.
• Does the patient live alone?

• Does he or she have access to shopping?
• Are the facilities for storing and cooking food adequate?
• Does the patient have a history of smoking?
• Are financial resources adequate?
• Are there assistance programs available?
Family History
Many nutritional disorders are familial or inherited. Thus, history of cancer, cardiovascular
disease, metabolic diseases, gastrointestinal or liver disease, obesity, etc., should alert the
examiner in the patient evaluation.
Diet History and Evaluation

An extensive assessment is best done by the professionally trained dietitian, and is required
in patients who have nutritional problems or appear at risk of malnutrition. Nevertheless,
the physician should acquire basic knowledge of the patient’s food intake, meal pattern,
and dietary habits. including use of dietary supplements in order to assess general nutri-
tional adequacy and identify potential problems that may need to be addressed.
The physician has the opportunity to practice preventive nutrition by evaluating the
patient’s energy balance (intake, activity) and the consumption of dietary components
predisposing to vascular disease, cancer, or other chronic diseases.
In the inpatient setting it is important to note the diet prescribed and whether the time
constraints of diagnostic tests or interventional therapies preclude the patient’s eating the
meals that were ordered.
General Physical Examination

Height and weight should be considered vital signs and should be measured and recorded
with careful attention to accuracy and precision. Height should be measured annually,
and weight at most office visits and at regular intervals in the hospitalized patient. The
Body Mass Index (BMI) is a useful parameter for monitoring body size. Table 3.20, Section
3, provides BMIs for a wide variety of body sizes. A body weight that is decreased
profoundly alerts the physician to increasing morbidity or mortality. A weight loss to
<80% of ideal increases chances of infection, while weight loss to 60% of ideal predicts
dying, and few individuals survive a loss of 50% of body weight.9
Observation, inspection, and measurement are the primary tools of the examination.
The physical signs of malnutrition are listed and categorized according to anatomic site
and organ system in Table 25.1.
Finding abnormalities provides leads rather than a diagnosis, and alerts the examiner
to further measurements and laboratory tests. Easily recognized abnormalities indicate
advanced disease.
Laboratory Tests
Some routine laboratory tests can assist in the nutritional assessment and diagnosis. These
include CBC, blood chemistries (glucose, electrolytes, minerals, liver and kidney function
tests), and tests of blood coagulation (Table 25.2).
Hemoglobin levels will show the presence of anemia that may be vitamin-specific or
mineral related, and can indicate chronic disease. The red blood cell size and hemoglobin
content and concentration can provide clues to liver disease, alcoholism, and specific
nutritional deficiencies. While serum albumin is not a sensitive indicator of protein status,
it does provide a clue. Low levels may indicate a limiting amount of substrate for hepatic
protein synthesis. On the other hand, non-nutritional factors may be responsible for
hypoalbuminemia such as expanded extracellular fluid, accelerated protein breakdown,
and impaired liver and kidney function. Albumin levels also may be unreliable indicators
TABLE 25.1
Physical Signs of Malnutrition
System Sign Deficiency/Abnormality
Hair Luster, texture (dull, dry) Protein
Depigmentation (flag sign)
Color (reddening)
Easily plucked
Areas of hair loss (alopecia)
Face Rash, seborrhea Riboflavin
Pallor Iron, folate, B12
Eyes Luster of cornea decreased, Bitot spots, Vitamin A, riboflavin
xerosis, keratomalacia, night blindness Iron, B12, folate
Conjunctival injection Hypercholesterolemia
Conjunctival pallor Wilson’s disease, copper excess
Corneal arcus, eyelid xanthelasma Wernicke’s syndrome, thiamin
Kayser-Fleischer ring
Nystagmus
Lips Cheilosis (swelling), angular stomatitis (fissures) Riboflavin
Tongue Glossitic (smooth, red) B12, folate, riboflavin
Pallor, atrophy Iron
Decreased taste Zinc
Gums Bleeding, hypertrophy Vitamin C
Neck Goiter (enlarged thyroid) Iodine
Skin Rash, edema Protein
Pigmentation or depigmentation Niacin
Flakiness, peeling, dry Protein, zinc
Bleeding Vitamin K
Perifollicular hemorrhage Vitamin C
Hyperkeratoses Vitamin A
Nails Spooning Iron
Brittle Protein
Muscles Atrophy Protein
Weakness Protein, iron, B12, folate
Bones, joints Fractures, deformities, tenderness Vitamin D
Deformities Vitamin C
Heart Enlargement Selenium
Failure Thiamin
Arrhythmias Calcium, magnesium, potassium
Abdomen Ascites Protein
Hepatomegaly Alcohol abuse
Neurologic Mental status/dementia Thiamin, B12, folate, niacin
Cranial nerves Thiamin
Gait, ataxia Thiamin, B12, pyridoxine
Sensory Thiamin
Diminished reflexes Iodine
Tetany Calcium, magnesium
Paralysis Potassium
TABLE 25.2
Laboratory Tests Useful in Clinical Nutritional Assessmenta
Body Compartment/
Laboratory Test Organ System Function
Hemoglobin, hematocrit, red and white blood cell counts and indices, differential Protein, visceral
(calculate total lymphocyte count) Anemia
Urea, creatinine, glucose, sodium, potassium, chloride, carbon dioxide Renal function
Diabetes mellitus
Acid-base balance
Cholesterol, triglycerides, lipoproteins Lipid disorders
Total protein, albumin, uric acid Liver, kidney function
Calcium, phosphate, magnesium, bilirubin, alkaline phosphatase Minerals, skeleton
Aminotransferases, iron, ferritin Liver function
Anemia
Transferrin, transthyretin, retinol-binding protein Iron
Protein, visceral
Prothrombin time, partial thromboplastin time Vitamin K, blood clotting
a Adapted from Feldman, E.B. In Laboratory Medicine; the Selection and Interpretation of Clinical Laboratory Studies.
Noe, D.A., Rock, R.C., Eds. Williams & Wilkins. Baltimore, 1993, ch. 10.
of protein status in the postoperative or acutely injured patient. Some enzyme tests are
indicators of nutritional cofactor status, e.g., alkaline phosphatase and zinc, or aminotrans-
ferase for Vitamin B6.
Nutrition Diagnosis and Prescription

The initial nutritional assessment will use information from the history, physical exami-
nation, and laboratory tests that may be supplemented by consultation with a dietitian,
a clinical nutrition specialist, or other medical specialists or subspecialists. The patient’s
route of feeding, energy intake, and proportion and amount of macronutrients will be
prescribed. The needs to replete or restrict and to supplement will be decided.
A single, ideal prognostic indicator of nutritional risk remains elusive. Rather, multiple
parameters must be determined and interpreted in the light of the patient’s medical status.
One example of a global assessment7 utilizes elements from the history (weight change,
dietary intake change, persistent gastrointestinal symptoms, functional capacity, diseases)
and the physical examination (subcutaneous fat, muscle bulk and tone, edema, ascites) to
categorize patients as in good nutritional status, with moderate or suspected malnutrition,
or with severe malnutrition.
Educating Physicians in Nutrition

Nutrition plays an important role in the etiology, prevention, or treatment of many chronic
diseases. Thus, an appropriate knowledge of nutrition principles should be part of the
education and training of physicians, especially those in primary care.4,10 Family medicine
specialists have developed guidelines for incorporating nutrition into their medical edu-
cation and residency training programs.11-13 The current guidelines are presented in Table
25.3 and can be accessed on the Web site of the American Academy of Family Physicians,
www.afp.org.
TABLE 25.3
Recommended Nutrition Guidelines for Family Practicea
Develop Attitudes that Recognize
Nutrition is a major part of wellness, disease prevention and treatment of disease

Poor nutrition can cause disease
Family, ethnic and religious attitudes affect nutrition behavior
Socioeconomic factors are important in nutritional excess and deficiency
Different nutritional considerations at different times are required in the life cycle
Nutritionists and dietitians are important in the area of the patient’s nutritional status, education and disease
prevention
Develop Knowledge Of
Basic nutritional requirements/recommended allowances and intakes

Nutritional content of food and the food pyramid
Nutritional information from public and private sources
The role of qualified nutritional professionals as consultants
The changing nutritional requirements of infancy, childhood, adolescence, pregnancy, lactation, menopause,
aging
Nutritional requirements of disease processes and exercise
Clinical effects of dietary fat, carbohydrate, proteins, and fiber
Basic concepts of vegetarianism
The role of nutrition in the treatment and prevention of disease: hypertension, heart, dental, gastrointestinal,
liver and renal diseases, diabetes, alcoholism, anemia, cancer
Signs and symptoms of nutrient deficiencies
Breast feeding and formula feeding
Use of vitamin and mineral supplements
Weight reduction and dieting
Food and drug interactions
Allergies and food intolerance
Eating disorders
Refeeding syndromes
Nutrition quackery
Develop Skills In
Assessing nutritional status during the history and physical examinations

Assessing nutritional status and needs of hospitalized patients
Ordering laboratory and metabolic studies to detect nutritional deficiencies and assess adequacy of the nutrition
provided
Counseling patients and family about specific nutritional needs related to their life cycle stage and disease
process, the role of diet in preventing disease, safe weight reduction and dieting, including health benefits
Educating patients about food marketing and nutritional quackery
Prescribing and managing oral supplementation, tube feeding, peripheral nutrition, and total parenteral nutrition
Preventing and managing refeeding syndromes
Recognizing and appropriately referring patients with disordered eating habits
a Adapted from Physician’s Curriculum in Clinical Nutrition. STFM, Kansas City, 1995.
References
1. Feldman EB. In Laboratory Medicine; the Selection and Interpretation of Clinical Laboratory Studies.
Noe DA, Rock RC, Eds, Williams & Wilkins, Baltimore, 1993, ch 10.
2. Kolasa KM. Eur J Clin Nutr 53: S89; 1999.
3. Feldman EB. Southern Med J 88: 204; 1995.
4. Feldman EB. Nutrition 16: 649; 2000.
5. Feldman EB. In Essentials of Clinical Nutrition. FA Davis, Philadelphia, 1988, ch 3.

6. Nutrition Screening Initiative. Incorporating Nutrition Screening and Interventions into Medical
Practice. A Monograph for Physicians. 1010 Wisconsin Ave, NW Suite 800, Washington DC 20007.
The Nutrition Screening Initiative, 1994.
7. Newton JM, Halsted CH. In Modern Nutrition in Health and Disease, Shils ME, Olson JA, Shike
M, Ross, AC, Eds, 9th ed, Williams & Wilkins, Baltimore, 1999, ch 55.
8. Owen GM. In Nutrition Assessment, a Comprehensive Guide for Planning Intervention, Simko MD,
Cowell C, Gilbride JA, Eds, 2nd ed, Aspen Publishers, Inc., Gaithersburg, MD, 1995, chap 6.
10. Feldman EB. Am J Clin Nutr 54: 618; 1991.
11. Society for Teachers of Family Medicine Working Group on Nutrition Education, Physician’s
Curriculum in Clinical Nutrition. STFM, Kansas City, 1995.
12. American Academy of Family Physicians (AAFP) Recommended Core Educational Guidelines on
Nutrition for Family Practice Residents. American Academy Family Physicians, Kansas City,
1989, revised 1995.
13. Society for Teachers of Family Medicine. Physicians Guide to Outpatient Nutrition, in press.
26
Assessment of Lipids and Lipoproteins
Elaine B. Feldman
Introduction
The circulating lipids include free cholesterol, cholesterol esterified with long-chain fatty
acids, triacylglycerols (triglycerides, TG), phospholipids, and unesterified or free fatty
acids. Lipids are transported in the blood plasma in the form of lipoproteins. The lipo-
proteins include:
• Chylomicrons
• Very low-density lipoproteins (VLDL)
• Intermediate-density lipoproteins (IDL, beta-VLDL)
• Low-density lipoproteins (LDL)
• High-density lipoproteins (HDL)
The chemical and physical properties of the lipoproteins1 are shown in Table 26.1. This
section summarizes biological factors influencing lipid and lipoprotein levels, describes
methodology for assays in common clinical use in laboratories or health care facilities,
and provides data on the range of normal values.
Cholesterol
Cholesterol is synthesized by all animal cells (endogenous) and by no plants. It also is
derived from animal products in the diet (exogenous). Food sources are listed in Table
51.6 in Section 51. Circulating cholesterol levels vary with age, increasing in men from
puberty to the fifth decade of life, and in women until the seventh decade2 (Table 26.2).
Levels in women are lower than in men from age 30 to 50. Mean cholesterol levels vary
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592
TABLE 26.1
Plasma Lipoproteins in Humansa
Chemical Composition, %
Surface Core
Particle Diameter Flotation Electrophoretic Major Cholesterol
Class (nm) Density Mobility Apoproteins Proteins Phospholipids Cholesterol Esters Tryglycerides
Chylomicrons 80–500 <0.95 α2 B, E, A-1 2 7 2 3 86
A-IV, C
VLDL 30–80 0.95–1.006 pre-β B, E, C 8 18 7 12 55
IDL 25–35 1.006–1.019 slow B, E 19 19 9 29 23
pre-β
LDL 18–28 1.019–1.063 β B 22 22 8 42 6
HDL2 9–12 1.063–1.125 α1 A-I, A-II 40 33 5 17 5
HDL3 5–9 1.125–1.210 α1 A-I, A-II 55 25 4 13 3
Note: VLDL, Very low-density lipoprotein; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein; HDL, high-density lipoprotein.
a Modified from Feldman, E.B. Essentials of Clinical Nutrition, F.A. Davis, Philadelphia, 1988, p. 433.
Assessment of Lipids and Lipoproteins 593
TABLE 26.2
Average Levels of Circulating Lipidsa,b
Total C LDL C HDL C TG
Age, yr mmol/L mg/dl mmol/L mg/dl mmol/L mg/dl mmol/L mg/dl
White Men
15–19 3.95 152 2.42 93 1.20 46 0.77 68

20–24 4.13 159 2.63 101 1.17 45 0.88 78
25–29 4.58 176 3.02 116 1.14 44 0.99 88
30–34 4.94 190 3.22 124 1.17 45 1.15 102
35–39 5.04 194 3.41 131 1.12 43 1.23 109
40–44 5.30 204 3.51 135 1.12 43 1.39 123
45–49 5.46 210 3.67 141 1.17 45 1.34 119
50–54 5.49 211 3.72 143 1.14 44 1.45 128
55–59 5.56 214 3.77 145 1.20 46 1.32 117
60–64 5.59 215 3.72 143 1.27 49 1.25 111
65–69 5.54 213 3.80 146 1.27 49 1.22 108
70+ 5.56 214 3.69 142 1.25 48 1.30 115
White Women
15–19 4.08 157 2.42 93 1.33 51 0.72 64

20–24 4.29 165 2.65 102 1.33 51 0.90 80
25–29 4.6 178 2.81 108 1.43 55 0.86 76
30–34 4.63 178 2.83 109 1.43 55 0.82 73
35–39 4.84 186 3.02 116 1.38 53 0.94 83
40–44 5.02 193 3.17 122 1.46 56 0.77 68
45–49 5.30 204 3.30 127 1.51 58 1.06 94
50–54 5.56 214 3.48 134 1.61 62 1.16 103
55–59 5.95 229 3.77 145 1.56 60 1.25 111
60–64 5.88 226 3.87 149 1.59 61 1.18 105
65–69 6.06 233 3.93 151 1.61 62 1.33 118
70+ 5.88 226 3.82 147 1.56 60 1.24 110
a See Table 26.1 for abbreviations of lipoproteins; C, cholesterol; TG, triglycerides.
b Adapted from Lipid Research Clinics Program, JAMA 251, 351, 1984.
between 4.2 and 6 mmol/L, depending on age and gender. Population levels have been
declining over recent decades. About two-thirds of the plasma cholesterol is transported
as LDL and levels of LDL cholesterol parallel those of total cholesterol (Table 26.2). HDL
transports about one-quarter of the plasma cholesterol, with levels averaging about 1.17
mmol in men, and are 0.23 to 0.44 mmol higher in women (Table 26.2). Table 26.3 provides
data on the upper limits of normal for LDL- and HDL-cholaterol. Table 26.4 provides
data on mean values for lipids and lipoproteins in men and women from NHANES III
data.3
Cholesterol assays and the reference method4-7 are provided in Table 26.5. Clinical
laboratories are automated for the lipid analyses. Specific methods are provided as kits
by the manufacturer of the analytical instrument in use. Desktop methodologies also are
available for outpatient facilities (physicians’ offices, clinics) but are not as accurate or
precise as the commercial or hospital laboratory procedures. The latter are regulated and
supervised by accrediting organizations such as the College of American Pathologists, and
laboratories are regulated by the government (CLIA).
TABLE 26.3
Levels of Circulating Lipids Warranting Attentiona,b
LDLC HDLC TG
75th percentile 25th percentile 90th percentile
Age, yr mmol/L mg/dl mmol/L mg/dl mmol/L mg/dl
White Men
15–19 2.83 109 1.01 39 1.41 125
20–24 3.07 118 0.99 38 1.64 146
25–29 3.59 138 0.96 37 1.92 171
30–34 3.74 144 0.99 38 2.41 214
35–39 4.00 154 0.94 36 2.81 250
40–44 4.08 157 0.94 36 2.84 252
45–49 4.24 163 0.99 38 2.84 252
50–54 4.21 162 0.94 36 2.74 244
55–59 4.37 168 0.99 38 2.36 210
60–64 4.29 165 1.07 41 2.17 193
70+ 4.26 164 1.04 40 2.27 202
White Women
15–19 2.89 111 1.12 43 1.26 112
20–24 2.07 118 1.14 44 1.52 135
25–29 3.28 126 1.22 47 1.54 137
30–34 3.33 128 1.20 46 1.58 140
35–39 3.61 139 1.14 44 1.91 170
40–44 3.80 146 1.25 58 1.81 161
45–49 3.90 150 1.22 47 2.02 180
50–54 4.16 160 1.30 50 2.14 190
55–59 4.37 168 1.30 50 2.6 229
60–64 4.37 168 1.33 51 2.36 210
65–69 4.78 184 1.27 49 2.49 221
70+ 4.42 170 1.25 48 2.13 189
a See Table 26.1 for abbreviations.
b Adapted from Lipid Research Clinics Program, JAMA 251, 351, 1984.
Triacylglycerols (TG)
Circulating TG levels average about 1.13 mmol/L in young adults after overnight fasting.
Levels increase from 50 to 75% with age, and are lower in women compared to men.
(Tables 26.2 and 26.3). Median TG values range from 0.90 to 1.47 mmol/L. TG levels are
labile, varying by up to 50% daily depending on the recent diet. In the fasting state, TG
are transported in the VLDL, whereas chylomicrons transport newly absorbed fat. Upper
limits of normal for TG are given in Table 26.3.
Triacylglycerol assays and reference method9-11 are listed in Table 26.5.
Lipoproteins
Lipoprotein assays12-15 are given in Table 26.5.
TABLE 26.4
Lipid Levels U.S. NHANES III Populationa,b
Lipid Level (mg/dL) Mean ± SD (mg/dL)
Mean total cholesterol 225 ± 45
Men 218 ± 42
Women 237 ± 47
Mean LDL-C 142 ± 37
Men 139 ± 35
Women 147 ± 40
Mean HDL-C 50 ± 16
Men 47 ± 14
Women 56 ± 17
Median TG 140 ± 120
Men 137 ± 129
Women 144 ± 108
Mean total-C/HDL-C 4.9 ± 2.1
Men 5.1 ± 1.7
Women 4.7 ± 2.6
Mean LDL-C/HDL-C 3.1 ± 1.5
Men 3.2 ± 1.2
Women 2.9 ± 1.9
Apolipoprotein A1 147 ± 27
Men 139 ± 23
Women 158 ± 29
Apolipoprotein B 116 ± 26
Men 115 ± 24
Women 119 ± 27
a See Table 26.1 for abbrevations.
b DHHS NCHS. Third National Health and Nutrition Examina-
tions Survey, 1988-94, NHANES III, Hyattsville, MD, 1996.
Chylomicrons
These particles originate in the small intestine when fat is absorbed, and are absent in
plasma from fasting subjects. They are visibly present in blood when TG levels exceed
7.90 mmol/L, and the refrigerated plasma may appear turbid (Figure 52.8, Section 52). At
higher TG levels the standing plasma will show a creamy top layer. Chylomicrons are
transported into the lymphatic system, delivered into the blood, and removed by the
action of the enzyme lipoprotein lipase (LPL) to produce remnant particles that are taken
up by specifc receptors in the liver. (Figure 26.1). The composition of chylomicrons is listed
in Table 26.1.
VLDL
These particles are produced in the liver and result from in vivo synthesis from carbohy-
drate precursors or from free fatty acids mobilized from adipose tissue and delivered to
the liver. VLDL composition is given in Table 26.1. The standing plasma begins to appear
diffusely turbid when TG levels exceed 2.25 mmol/L (Figure 52.8, Section 52). Lipoprotein
lipase action produces VLDL remnants, or IDL, that are rapidly removed from the blood
by receptors in the liver (Figure 26.1). An assay for VLDL remnants that has been
developed for research studies12 is under consideration by laboratory manufacturers for
clinical applications.
596
TABLE 26.5
Tests for Plasma Lipids, Lipoproteins, and Lipolytic Enzymes
Assay Principle of Method Reference Method Clinical/Usual Method Performance Criteria
Total cholesterol Chemical Abell-Kendall5 CV ≤3%
Spectrophotometric Bias <3%
Modified Liebermann-Burchard4a,b
Automated enzymatic Allain6
Colorimetric Rautela7
Triacylglycerol (TG) Glycerol assay Van Handel-Zilversmit8 CV <5%
Spectrophotometric Bias <5%
Automated enzymatic
Spectrophotometric Sampson9
Hagen10
Rautela11
VLDL
VLDL remnant Ultracentrifugation Nakajima12

LDL-calculate TC-{HDL-C + TG/5} Friedewald13 CV <4%
Bias <4%
LDL ultracentrifuge C in d<1.006 – HDL-C Beta-quant Havel-Eder-Bragdon14
LDL direct Precipitation of chylomicrons, VLDL IDL, HDL by McNamara15
antibodies to apo-E and apo A-I
Lp(a) ELISA Marcovina17
HDL Heparin-Mn or dextran-Mg precipitation of VLDL, LDL; Burstein19 CV <4%
analyze C in supernatant Warnick20 Bias <5%
Apo A-I Immunoassay Not available Albers24 CV 6%
Apo B Immunoassay Not available Warnick25
Phospholipids Lipid phosphorus (lipid extract) Bartlett26
Free fatty acids Titration of extracted plasma Dole-Meinertz27
Fatty acid composition Gas-liquid chromatography of fatty acid methyl esters Nelson28
Lipoprotein lipase (LPL) Hydrolysis of radioactive lipid emulsion by post-heparin Olivecrona30 3-5% accuracy
plasma Plasma pool
Hepatic lipase (HL) Antiserum to HL Huttunen31 Values lower in women
NaCl inhibition of LPL
Lecithin-cholesterol acyl Double antibody radioimmunoassay Albers32
transferase (LCAT)
Note: CV = coefficient of variation.
Extrahepatic
NORMAL
LIVER
LDL
VLDL
IDL
LPL
FIGURE 26.1
Production of lipoproteins, delivery into blood, and removal by tissues. See Table 26.1 for abbreviations. LPL =
lipoprotein lipase.
IDL
This TG-rich particle is relatively enriched in the proportion of cholesterol esters compared
to its precursor VLDL (Table 26.1). The atherogenic beta-VLDL is a related cholesterol-
rich particle with interactions with the LDL and remnant receptors (Figure 26.1). This
particle is evanescent in the plasma of healthy normolipidemic subjects.
LDL
This particle is the main transporter of cholesterol in the blood and is considered the most
atherogenic lipoprotein. The LDL cholesterol level reflects changes in lipoprotein compo-
sition. LDL delivers cholesterol to cells and is taken up by specific cell surface receptors
(Figure 26.2). LDL assays are listed in Table 26.5. LDL cholesterol may be calculated as:
LDL = [Total cholesterol] – [HDL-cholesterol] – [TG/5]13

FIGURE 26.2
The generation of HDL and the interrelations of the lipoproteins, their production, and removal. ABC 1 = ATP-
binding-cassette transporter. SRB 1 = Scavenger receptor binder. Adapted from Young S. G., and Fielding C. J.,
Nature Genetics, 22, 316, 1999.
Alternatively, LDL can be measured by ultracentrifugation (beta-quantification, or beta-

quant)14 or directly, using an immunologic procedure15 (Table 26.5).
LDL particle size is variable, ranging from large and buoyant to small and dense (Table
26.6). The small dense particle, oxidative changes in LDL, and the presence of a variant
of LDL, Lp(a), raise the atherogenicity of LDL. Lp(a) levels range from undetectable to
1000 mg/L. The risk of atherosclerosis increases as values exceed 300 mg/L. The Lp (a)
assay17 is listed in Table 26.5.
HDL
The HDL particle is generated by the transfer of surface lipids from TG-rich lipoproteins
during lipolysis18 (Figure 26.2). The HDL2 and HDL3 particles differ in size and compo-
sition, and particles vary in their content of the specific apolipoproteins, apo A-I and A-II
(Tables 26.1 and 26.6). HDL is protective against atherosclerosis, enhancing removal mech-
anisms by reverse cholesterol transport. Methods of assay19, 20 are described in Table 26.5.
Standardization of Assays
Blood samples for assays of serum or plasma lipids and lipoproteins should be obtained
under standardized conditions of a stable diet, avoiding alcohol, and in the morning after
an overnight fast. Serum and plasma values differ as do values of cholesterol when the
TABLE 26.6
Lipoprotein Subclassesa
Association with
Particle Diameter nm Risk of CVD
VLDL 1 Large 80 Higher
2 Medium 70 Intermediate
3 Small 60 Lower
IDL 1 Large 40 Higher
2 Small
LDL I Large 30 Lower
II a
II b
III a Medium Intermediate
III b
IV a Small Higher
IV b 20
HDL 2 b Large 10 Negative risk
2a 9
3a Small 8 Positive risk
3b 7
3c 6
a See Table 26.1 for abbreviations.
subject is supine, sitting, or standing. A recent meal has minor effects on cholesterol and
predominantly cholesterol-containing lipoproteins (LDL, HDL), but has a major influence
on levels of TG and TG-containing lipoproteins (VLDL). Optimally, determinations should
be carried out on plasma samples obtained by using EDTA as anticoagulant and prepared
and stored carefully. The biological variation of cholesterol, within the normal range,
approximates 16%.21 Laboratory accuracy and precision should be standardized with
reference materials or reference laboratories.22 Because of variability, more than one sample
of plasma or serum lipids should be drawn, with an interval of several weeks of unchanged
lifestyle, and analyzed in order to evaluate lipid status or therapy.23
A simple clue to lipid/lipoprotein values is provided by the standing plasma test (Figure
52.8, Section 52). Plasma is refrigerated overnight and examined for turbidity. Hypercho-
lesterolemia does not cause the plasma to become cloudy, whereas elevated TG, either as
VLDL, remnants, or chylomicrons will produce diffuse turbidity with or without a creamy
supernatant layer (see Section 52).
Apoproteins
The apolipoproteins or apoproteins determine the metabolic fate of the lipoprotein parti-
cles and the solubility of lipoprotein lipids in plasma. They include:
• Apo A-I
• Apo A-II
• Apo A-IV
• Apo B-100
• Apo B-48
• Apo C-I
• Apo C-II
• Apo C-III
• Apo-D
• Apo E-2
• Apo E-3 {E-phenotype: E2/2, 2/3, 2/4, 3/3, 3/4, 4/4}
• Apo E-4
• Apo-F
• Apo-G
• Apo-H
• Apo-J
• Apo (a)
Their distribution among the lipoproteins is shown in Table 26.1.

The assay methods available in some clinical laboratories24,25 are provided in Table 26.5.
The mean values in plasma are provided in Table 26.7. The apoprotein level indicates the
number of lipoprotein particles in plasma (i.e., concentration). The apoprotein composition
and levels are determined in some genetic and lipid laboratories using electrophoretic and
immunologic methods.
Other Lipid Assays
• Phospholipids are determined by measuring lipid phosphorus after lipid

extraction.26
• Free fatty acids in plasma can be analyzed, usually in relation to metabolic
abnormalities, such as diabetes mellitus, and related to values of glucose and
insulin. The assay is listed in Table 26.5.27
• The fatty acid composition of plasma lipids, and separated and isolated free fatty
acids, cholesterol esters, phospholipids, or TG can be quantified.28 This may be
useful in the diagnosis of essential fatty acid deficiency and some inborn errors
of metabolism.
• Fecal fat can be measured as free fatty acids or TG fatty acids in order to test for
malabsorption syndromes.29
Regulators of Lipid Metabolism

Enzymes, receptors, and transporters involved in the regulation of lipid and lipoprotein
metabolism are listed in Section 52, Table 52.1. Their values are determined primarily in
lipid research laboratories rather than as part of the usual clinical lipid profile for patient
TABLE 26.7
Average Levels of Apoproteins in Plasma (mg/L)a,b
Apoprotein Mean ± SD
A-I 1,200 ± 200 (men)
1,350 ± 250 (women)
A-II 330 ± 50 (men)
360 ± 60 (women)
B 1,000 ± 200
C-I 70 ± 20
C-II 40 ± 20
C-III 130 ± 50
D 60 ± 10
E 50 ± 20
a SD = standard deviations.
b From Albers, in Eleventh International Congress of Clinical
Chemistry. Keuser, E., Giabal, F., Muller, M. M., et al.,
Eds., Walter de Greyter, Berlin, 1982, with permission.
assessment. Methods for the determination of post-heparin lipolytic activity, lipoprotein

lipase,30 hepatic lipase,31 and lecithin:cholesterol acyltransferase32 are listed in Table 26.5.
References
1. Feldman EB. Essentials of Clinical Nutrition FA Davis, Philadelphia, 1988.
2. Lipid Research Clinics Program, JAMA 251, 351, 1984.
3. NHANES III, JAMA 269, 3000, 1993.
4a. Liebermann C. Ber Deut Chem Ges 18, 1803, 1885.
4b. Burchard H. Chem Zentraalbl 610, 25, 1890.
5. Abell LL, Levy BB, Brodie BB, Kendall FE. J Biol Chem 195, 357, 1952.
6. Allain CC, Pool NS, Chan CSG, et al. Clin Chem 20, 470, 1974.
7. Rautela SS, Liedtke RJ. Clin Chem 24, 108, 1978.
8. Van Handel E, Zilversmit DB. J Lab Clin Med 50P, 152, 1957.
9. Sampson EG, Demers LM, Kreig AF. Clin Chem 21, 1983, 1975.
10. Hagen JR, Hagen PB. Can J Biochem Physiol 40, 1129, 1962.
11. Rautela SS. Clin Chem 20, 857, 1974.
12. Nakajima K, Sato T, Tamura A, et al. Clin Chim Acta 223, 53, 1993.
13. Friedewald WT, Levy RI, Fredrickson DS. Clin Chem 18, 499, 1972.
14. Havel RJ, Eder HA, Bragdon JH. J Clin Invest 34, 1345, 1955.
15. McNamara JR, Cole TG, Contols JH, et al. Clin Chem 46, 232, 1995.
16. Krauss RM, Burke DJ. J Lipid Res 12, 97, 1983.
17. Marcovina SM, Albers JJ, Gabel B, et al. Clin Chem 41, 246, 1995.
18. Young SG, Fielding CJ. Nature Genetics 22, 316, 1999.
19. Burstein M, Scholnick HR, Mortin R. J Lipid Research 11, 283, 1970.
20. Warnick GR. Clin Chem 28, 1379, 1982.

21. Cooper GR, Myers GL, Smith SJ, Schlant RC. JAMA 267, 1652, 1992.
22. Handbook of Lipoprotein Testing, Ed. Rifai N, Warnick GR, Dominiczak MH. AACC Press,
Washington, DC, 1997.
23. Smith SJ, Cooper GR, Myers GL, Sampson EJ. Clin Chem 39, 1012, 1993.
24. Albers JJ. The determination of apoproteins and their diagnostic value in clinical chemistry.
11th International Congress of Clinical Chemistry, Kaiser E, Gabal F, Muller MM, et al, Eds.,
Walter de Gruyter, Berlin, 1982.
25. Warnick GR, Cheung MC, Albers JJ. Clin Chem 25, 596, 1979.
26. Bartlett GR. J Biol Chem 223, 466, 1959.
27. Dole VP, Meinertz H. J Biol Chem 231, 2959, 1960.
28. Blood Lipids and Lipoproteins Quantitation, Composition and Metabolism, Nelson GH, Ed., Wiley
Interscience, NY, 1972.
29. Van de Kamer JH, Huinink HTB, Weijers HA. J Biol Chem 177, 347, 1949.
30. Bengtsson-Oivecrona O, Olivecrona T. Assay of lipoprotein lipase. In Lipoprotein Analysis. A
Practical Approach, Skinner RE, Converse CA, Eds., Oxford University Press, Oxford, 1992, p
169.
31. Huttunen Y, Enholm C, Kinnunen PKJ, Nikkila EA. Clin Chim Acta 63, 335, 1975.
32. Albers JJ, Chen C-H, Lacco AG. Methods in Enzymology 129, 763, 1986.
27
Genetics of Energy and Nutrient Intake
Treva Rice, Louis Pérusse, and Claude Bouchard
Introduction
The study of the role of genetic variation on energy intake and nutrient intake is broad
and has considerable public health implications. Genetic differences influence behavioral
and biological affectors of food intake. They are also thought to impact on several nutri-
tionally influenced risk factors (e.g., dyslipoproteinemia) and morbid conditions (e.g.,
diabetes). These issues have been the topic of much research in the past few decades, as
evidenced by the multiple review articles cited in this section. In the behavioral domain,
the questions are relatively simple. Do genes determine eating behaviors such as how
much one eats, preferences for certain types of foods, and frequency or pattern of eating?
The current research suggests that there is resemblance among family members for these
behaviors, although it is unclear if they are determined by genes, shared environments,
or both.1 In the physiological domain the questions center on the physical and hormonal
mechanisms leading to such things as taste preferences, hunger, and satiety. For instance,
taste receptors are clearly genetically determined, although the gene(s) may not be all
identified yet,2 and a growing number of genes encoding hormones and proteins that
regulate hunger and satiety have been identified recently.3
The genetics of energy and nutrition intake invoke complex issues from the fields of
genetic and molecular epidemiology, involving both genetic and environmental interac-
tions. Gene-gene (GxG) interactions occur when the effect of one gene is modified by or
depends on the effects of another. For example, leptin is a hormone involved in the
signaling between adipose tissue and the hypothalamus. The gene (LEP) that synthesizes
leptin has been identified and mapped to chromosome 7. However, multiple factors
influence the circulating levels of leptin, and some of these (such as insulin levels) have
their own genetic determinants. Thus, the measurable levels of circulating leptin can be
influenced by interactions with other genes.
Another complex issue from genetic and molecular epidemiology involves gene-envi-
ronment interactions (GxE). In this situation, energy and nutrient intake are considered
environmental factors which impact on other traits that may have a profound interest
from a public health perspective. For example, the exposure of individuals with certain
0-8493-2705-9/01/$0.00+$1.50
genetic mutations to high-fat/cholesterol environments may predispose them to develop

disease, while other individuals with alternative gene forms promoting genetic protection
remain free of disease in the same high-risk environment. Such gene-diet interaction
questions have been addressed in the fields of genetic and molecular epidemiology and
constitute the major focus of this review.
This section does not claim to extensively review every topic relating to the genetics of
energy and nutrient intake. Rather, an attempt is made to give an overview of the breadth
of the problem, some interesting findings, and suggestions for further study. A short
review of genetic and molecular epidemiology methods is followed by overviews of the
familial factors underlying the behavioral aspects of macronutrient intake, and gene-diet
interaction effects on risk factors for coronary disease.
Genetic and Molecular Epidemiology

Before investigating the complex issues of GxE interactions, it must first be established that
the trait of interest is heritable, or that it runs in families. Familial resemblance for a trait
arises when members within families are more similar than are unrelated pairs of individ-
uals and may be estimated in terms of correlations (or covariances) among family members.
Methods for estimating familial resemblance range from relatively simple to very com-
plex.4,5 However, the cause of the familial resemblance may be due to shared genes, shared
environments, or both. In the case where the gene is not known, or not measured, familial
resemblance is indexed by comparing the degree of phenotypic (trait) sharing among family
members of varying degrees of relatedness. For example, sibling, parent-offspring and
dizygotic (DZ) twins share 50% of their genes in common, monozygotic (MZ) twins share
100% of their genes in common, and spouse pairs share few or no genes in common if there
is random mating for the trait under study. Depending on cohabitation effects, all of these
relative pairs may share some degree of family environments.
Maximal heritability quantifies the strength of the familial resemblance. It represents
the percentage of variance in a trait that is due to all additive familial effects, and can
include both genetic and familial environmental sources. Depending on the complexity
of the study design, this may be partitioned into separate estimates of genetic versus
cultural (familial environmental) heritabilities. Each of the genetic and familial environ-
mental sources may be partitioned further. For example, complex traits (phenotypes) may
be due to one or more genes with moderate to major effects (oligogenic), many genes each
having small effects (polygenic), and/or familial environments that are specific to certain
relative pairs such as sibling, twin, or spouse.
In addition to these main effects of genes and familial environments, there may be
interactions among these factors such as gene-gene (epistasis) and GxE. These effects are
generally non-additive and thus may not be identified in heritability studies described
above. Of major interest in this review are GxEs that arise when the phenotypic expression
of a trait corresponding to a particular genotype depends, in part, on exposure to particular
environmental factors. For example, GxE may occur if the fat mass response to dietary
intervention depends on (or is modified by) an individual’s genotype. In the hypothetical
case of Figure 27.1, an absence of GxE is depicted in panel (a), where the body fat response
to increasing fat intake is consistent across genotypes, with a simple mean shift by geno-
type. In contrast, GxE is present in panel (b), where some genotypes show very different
patterns of fat mass accumulation with increasing levels of energy intake.
Genetics of Energy and Nutrient Intake 605
+ 3 + 3
pe e
oty typ
Fat Mass Response
n o
Ge n
Ge
p e2
n oty pe
2
Ge ty
G eno
e1
o typ
G en Genotype 1
(a) (b)
+ +
Energy Intake
FIGURE 27.1
Hypothetical example of three genotypes plotted by energy intake (X-axis) and fat mass (Y-axis) values. In panel
(a), there is no gene-diet interaction since the lines depicting the responses by genotype are parallel. In panel
(b), gene by diet interaction is demonstrated, since there is a differential response in fat mass due to energy
intake as a function of the genotype. That is, the genotypes respond differently.
Two major approaches are used to study GxE, unmeasured genotype (genetic epidemi-
ology) and measured genotype (molecular epidemiology), as recently reviewed by Pérusse
and Bouchard.6 The twin methodology is a very useful unmeasured genotype approach
for testing GxE. One important assumption underlying the twin method is that MZ and
DZ twins have equal environmental covariances. Variances can be tested for significant
differences across twin types using classical analysis of variance approaches. If the vari-
ances are different prior to but not after adjustment for pertinent environmental covariates,
then there is indirect evidence of GxE interaction. Alternatively, the twins can be stratified
according to degree of environmental sharing, and heritability estimates may be compared
across the strata.
The above twin method is cross-sectional and therefore an indirect assessment of the
GxE effects. Another unmeasured genotype approach that more directly indexes GxE is
the twin intervention study, where MZ pairs (who share 100% of their genes in common)
are challenged under standardized treatments (environments). A comparison of the
within- and between-pair variances of the response to treatment provides an indication
of whether genetic factors underlie the response. That is, a greater variability between-
than within-pairs suggests a greater correlated response to environmental challenge for
the same genotype.
The second major approach for detecting GxE involves measured genotypes,6 with the
preponderance of evidence for measured gene-nutrition interactions arising from inter-
vention studies. This method is usually applied to association analysis of candidate genes.
However, it can be applied to association or linkage analysis of candidate genes or genome
scan data.7 Linkage studies seek identification of loci that cosegregate with the trait (e.g.,
dietary response) within families, while association studies seek identification of particular
variants that are associated with the response at the population level. In other words,
linkage analysis is often useful in localizing gene effects but requires family data, while
association analysis can provide information about the functional variants that ultimately
give rise to the observed phenotypic variability and may be applied to family or individual
data. These complementary methods provide the means to probe the genome and describe
the complex genetic etiologies underlying the responses to interventions. In association
analysis of candidate genes, the phenotypic responses to intervention are compared among
groups stratified by genotypes. If individuals with a particular allele form tend to respond
to the intervention differently than do individuals with alternative allele forms, then there
is evidence of GxEs. GxG interactions are simply incorporated in association analysis by
including the main effects of multiple candidate genes, as well as the interaction terms
between them.
Although association analysis may be applied to either individual or family data, the
dependencies among related individuals should be considered, since failure to adjust for
nonindependence can inflate the association evidence. Methods for dealing with this
problem range from complex, such as bootstrapping8 where the model is repeatedly fit to
subsets of the data, to relatively simple, such as sandwich estimators.9,10 The sandwich
method asymptotically yields the same parameter estimates as ordinary least squares or
regression methods, but the standard errors (and consequently hypothesis tests) are
adjusted for the dependencies.
Familial Factors Underlying Macronutrient Intake

In the last few decades, the familial factors underlying macro- and micronutrient intake
have been characterized. These studies differed in many respects, making direct compar-
isons difficult. For example, study designs (twin vs. family), statistical methods of analysis
and how macronutrient intake was measured (diaries ranging from 3 to 9 days, 24-hour
recall) and reported (absolute vs. percent of kcalories, and adjusted vs. unadjusted for
covariates) varied.1,11 The major conclusion drawn from a review of these studies is that
there is familial resemblance, although the source of the resemblance is unclear. For
example, deCastro,12 using a twin design, reported that additive genetic effects accounted
for 40 to 65% of the variance for each macronutrient examined, and that there was no
contribution from familial environmental sources. On the other hand, two family studies
13,14 suggested that most of the resemblance (30 to 50% of the variance) was due to familial
environmental factors. An early study, involving the largest sample sizes reported to date,15
reflects the most probable answer to the question of genetic vs. environmental determi-
nation of food intake: people who live together come to resemble each other whether they
are genetically related or not. This conclusion is based on the fact that correlations between
genetically unrelated pairs of individuals who live together are as large as those for
genetically related cohabitating individuals. Similar conclusions were drawn from both
twin12,16 and family studies.13,14,17,18
The magnitude of the familial effect for macronutrient intake generally centers between
30 to 50% in family studies, with higher estimates derived from many twin studies.
However, as shown in Table 27.1, there is a considerable range in estimates across studies.
Moreover, resemblance tends to be higher for nutrients expressed in percent of total caloric
intake as compared to absolute amounts, both across studies and within studies that
indexed both types of measures.13,19 This suggests that the familial effect may be specific
to food selection or preference (nutrient concentrations) rather than for amount of foods
consumed. Results from twin studies 20,21 and from animal models showing differences in
TABLE 27.1
Range of Heritability Estimates (%) for Macronutrients*
Macronutrient Genetic Cultural Combined
Total kcalories 0–78 23–45 24–51
Absolute values
Protein 0–70 26–41 8
Total fat 0–56 26–50 9–24
Saturated fat 50–60 10–27
Monounsaturated fats 33–41
Polyunsaturated fats 10–40 3
Saturated/unsaturated ratio 3–12
Total carbohydrates 0–68 20–26 31–36
Simple carbohydrates 12–60 8–20
Complex carbohydrates 22–62 55–56
Sodium 10–71
Dietary Na/K 20–68
Urinary Na/K 18–53
Percent of total kcalories
Protein 10–70 25–61 61
Total fat 18–48 8–51 27–54
Saturated fat 10–70
Monounsaturated fats 50
Polyunsaturated fats 47
Total carbohydrates 15–67 12–47 52
Dietary cholesterol 66
Sodium 51
Potassium 24
Calcium 52
* Estimates extracted from References 12-14, 16-19, 102.
macronutrient selection among various mouse strains22 also suggest that food preferences
are partly explained by genetic factors. From this review it appears likely that there are
substantial familial effects underlying nutrient intake, but whether this effect is due to
genetic, familial environmental, or both factors is unclear.
Gene-Diet Interactions
While an appropriate diet is recommended for reducing the risks of many common
diseases, it is well known that there is a great deal of variability in people’s responses to
dietary change. For example, atherogenic diets may carry little risk for some people, but
for others dietary changes generally have a good outcome. While the causes for this
heterogeneity across people are not completely understood, there is convincing evidence
that genes play a role. Phenylketonuria (PKU), an inborn error of metabolism causing an
accumulation of phenylalanine in the blood leading to mental retardation, is a classic
example. Restriction of dietary phenylananine in individuals who are homozygous for
the mutation reduces the phenylalanine accumulation and mental retardation.
The following summary of gene-diet interactions is organized around two general topics:
1) adiposity and 2) lipids and lipoproteins. A summary of some of the genes that may
interact with dietary intake to influence these phenotypic domains is given in Table 27.2.
Most of the molecular work investigating specific genes has centered on the latter domain.
608
TABLE 27.2
Summary of Measured Gene-Diet Interactions
Cytogenic
Gene* Location* Intervention** Response Phenotype Study
MTHFR 1p36.32 Cross-sectional, folate Homocysteine Jing Ma et al., 199692
TNFR2 1p36.23 High fat Wt, insulin, leptin in mice Schreyer et al., 199839
Cross-section, diet-treated diabetic vs nondiabetic BMI, leptin Fernandez-Real et al., 200040
Dob1 1p35-1p31 High fat Mice bred for diet response West et al., 1994a, 1994b29,30
LEPR 1p22.3 Overfeeding Fasting insulin, leptin, HDL-c Ukkola et al., 2000b46
HSD3B1 1p12 Aging (longitudinal) Skinfold sum Vohl et al., 1994103
APOB 2p22.3 Crossover, high vs low saturated fat and cholesterol CH, LDL-c Friedlander et al., 200059
Crossover, saturated vs monounsaturated fat ApoAI, LDL-c, ApoB, HDL-c Dreon et al., 1994; 199588,89
Crossover, high saturated vs NCEP vs high monounsaturated TG Lopez-Miranda et al., 200083
IRS1 2q36.3 Optifast wt loss program: diet, exercise, and support group Wt loss Benecke et al., 200038
Dob2 3p21 High fat Mice bred for diet response West et al., 1994a, 1994b29,30
PPARG 3p25.2 Aging (longitudinal) obese vs lean BMI change Ek et al., 199949
FABP2 4q26 Crossover, insoluble vs soluble fiber Total cholesterol, LDL-c, ApoB Hegele et al., 199745
UCP1 4q28.2 Low kcalorie Wt and BMI loss Fumeron et al., 1996104
Low kcalorie + exercise Wt loss Kogure et al., 199844
GRL 5q31.3 Overfeeding Wt, AVF, SBP, CH Ukkola et al., 2000a36
ADRB2 5q32 Overfeeding Wt, leptin, SF8, OGTT insulin area, abdominal Ukkola et al., 2000c37
total fat
Crossover, saturated vs monounsaturated fats TG López-Miranda et al., 200083
LEP 7q31.33 Low kcalorie Leptin Mammes et al., 199845

Low kcalorie Wt loss Oksanen et al., 1997105
LPL 8p21.3 Low kcalorie TG, VLDL-tg, ApoB Jemaa et al., 199774
Crossover, high saturated vs low saturated and high CH Humphries et al., 199675
polyunsaturated
Crossover, high vs low saturated fat and cholesterol TG, HDL-c Friedlander et al., 200059
ADRB3 8p11.22 Aging morbid obese vs normal wt Wt gain Nagase et al., 199753
Wt gain Clément et al., 199554
Optifast wt loss program: diet, exercise, and support group Wt loss Benecke et al., 200038
Dob3 8q23-q24 High fat Mice bred for diet response West et al., 1994a, 1994b29,30
Dob1 9p13 High fat Mice bred for diet response West et al., 1994a, 1994b29,30
UCP3 11q14.1 Cross-sectional, morbidly obese vs nonobese BMI, max BMI, Wt, diabetes Otabe et al., 199943
APOCIII 11q23.2 Crossover, saturated vs monounsaturated fats CH, LDL-c, Apo B López-Miranda et al., 199782
APOAI 11q23.2 Crossover, saturated vs monounsaturated fats LDL-c López-Miranda et al., 199478
APOAIV 11q23.2 Reduced fat HDL-c, TG Dreon et al., 1994; 199588,89
High cholesterol LDL-c McCombs et al., 199479
Crossover, NCEP vs average LDL-c, HDL-c, TG Mata et al., 199480
Crossover, saturated vs monounsaturated fats CH, LDL-c, Apo B Jansen et al., 199781
CETP 16q21 Cross-sectional, alcohol HDL-c Fumeron et al., 199596

Genetics of Energy and Nutrient Intake
LDLR 19p13.2 Fiber ApoB, total cholesterol, LDL-c Hegele et al., 199384
APOE 19q13.32 Reduced fat LDL particle size Dreon et al., 1994; 199588,89
Crossover, low vs high cholesterol HDL-c, CETP Martin et al., 199386
Crossover, low vs high fat HDL-c subclasses and LDL particle size Williams et al., 199587
* MTHFR = 5,10-methylenetetrahydrofolate reductase (NADPH); TNFR2 = tumor necrosis factor alpha, receptor 2; Dob1 = Dietary obese; HSD3B1 = hydroxy-delta-5-steroid
dehydrogenase, 3 beta- and steroid delta-isomerase 1; APOB = apolipoprotein B; IRS1 = insulin receptor substrate 1; Dob2 = Dietary obese; PPARG = peroxisome proliferative
activated receptor, gamma; FABP2 = fatty acid binding protein 2; UCP1 = uncoupling protein 1; GRL = glucocorticoid receptor locus; ADRB2 = beta 2 adrenergic receptor;
LEP = leptin; LPL = lipoprotein lipase; ADRB3 = beta 3 adrenergic receptor; Dob3 = Dietary obese; Dob1 = Dietary obese; UCP3 = uncoupling protein 3; APOCIII =
apolipoprotein C-III; APOAI = apolipoprotein A-I; APOAIV = apolipoprotein A-IV; CETP = cholesteryl ester transfer protein, plasma; LDLR = low-density lipoprotein
receptor; APOE = apolipoprotein E.
** Cross-sectional = different subjects across groups; Crossover = same subjects with repeated measured across groups; NCEP = National Cholesterol Education Program diet
(total fat < 30%, saturated fat < 10%, cholesterol intake < 300 mg/d)
609
Regarding the twin intervention method, one series of studies dominates the literature.
This was an overfeeding experiment involving MZ twin pairs. In the long-term experi-
ment, 12 pairs of male MZ twins were submitted to a 1000 kcal surplus diet 6 days a week
for a period of 100 days.23 The nutrient content of the diet was 50% carbohydrate, 35%
lipid, and 15% protein. During the course of the protocol the excess energy intake was
84,000 kcal. In the short-term experiment, 6 pairs of male MZ twins were given the same
protocol for a period of 22 consecutive days24 In both the long-term and short-term
experiments, a variety of physical and metabolic measurements spanning the phenotypic
domains listed above were measured before and after the dietary interventions. Genetic
epidemiology results from both the long-term and short-term studies have been reported
in several publications and provide evidence for GxE interaction. More recently, associa-
tion studies of the responses to overfeeding for a few candidate genes have been reported.
Adiposity
It is not surprising that overfeeding has an adverse effect on adiposity. In general, an
increase in caloric intake leads to an increase in adiposity, and this effect appears to be
more pronounced in some individuals, depending on genotypes. Evidence for these con-
clusions arises from several sources using different study designs.6,25-27
More direct evidence of GxE on adiposity was obtained in both the short-term24 and
long-term23 MZ intervention experiments. In the long-term intervention experiment, there
was a mean increase in body mass of 8.1 kg, with a threefold difference between the lowest
and highest gainers, ranging from 4 to 12 kg.23 The variability in response for weight was
at least three times greater (F-ratio of 3.4) between unrelated individuals than within twin
pairs, suggesting a significant genotype–overfeeding interaction. Similar magnitudes of
results were found for body mass index (BMI), percent body fat, fat mass measured with
underwater weighing, and subcutaneous fat measured by summing across six skinfolds.
Moreover, the variance was six times greater between than within pairs for abdominal
visceral fat (measured with computed tomography scan) after adjusting for total fat mass.
These findings indicate that some individuals tend to store fat predominantly in selected
fat depots in response to caloric surplus primarily as a result of genetic factors. In another
MZ twin intervention study,28 the opposite dietary treatment was conducted. Fourteen
pairs of female MZ twins were strictly supervised for 28 days on a very low calorie diet.
The diet provided for 1.6 MJ/day and included 37 g protein, 50 g carbohydrates, and 3.8 g
fat. Significant diet-induced reductions were seen for several measures of body composi-
tion, including weight, BMI, percent fat, fat mass, abdominal fat, and several skinfold
measures. Moreover, the variance was 11 to 17 times higher among unrelated individuals
than between twin pairs, suggesting a significant GxE interaction effect. Together, these
twin studies suggest that the changes in body composition due to dietary intervention
(both overfeeding and underfeeding) are due in part to the genotype.
Some of the evidence for gene-diet interactions on adiposity comes from the measured
genotype approach. Given the obvious connection between food intake and obesity, there
is nevertheless a paucity of measured gene-by-diet interaction studies of obesity. West
et al. provided early evidence of gene-diet interaction on obesity in mice.29,30 Nine strains
of mice were selectively bred for their responses to a high-fat diet; there was a sixfold
difference in adiposity gain between strains that were sensitive (AKR/J) and resistant
(SWR/J) to weight gain. Three dietary obese loci (Dob1, Dob2, and Dob3) were found
to underlie these differences, and they have been mapped to syntenic human chromo-
somes on 1p35-p31 and 9p13 for Dob1, 3p21 for Dob2, and 8q23-q24 for Dob3. No studies
were found reporting linkage or association of these genes to dietary responses in
humans. However, linkage of nearby anonymous markers (D1S476, D1S200, D1S193,
D1S197 on chromosome 1 and D8S592 and D8S556 on chromosome 8) with several

adiposity measures (BMI, sum of skinfolds, fat mass, percent fat, and leptin) has been
reported.31,32
The lipoprotein lipase (LPL) gene has been implicated in gene-diet interactions in several
reports. LPL plays a role in the regulation of plasma lipoprotein composition and concen-
trations, and in partitioning triglycerides between the adipose tissue for storage and the
skeletal muscle for oxidation, and is thus an obvious candidate. Overexpression of LPL
in skeletal muscle of transgenic mice was shown to protect against diet-induced obesity.33
While no studies were found linking the changes in adiposity following dietary interven-
tion with LPL in humans, it has been related to lipid responses (reviewed below). More-
over, the Hind III polymorphism was shown to modulate the relation between visceral
fat and plasma triglycerides,34 providing evidence of pleiotropy (i.e., a single gene impact-
ing on multiple traits).
The glucocorticoid receptor locus (GRL) is also involved in the regulation of LPL activity
and lipolysis, and glucocorticoids are insulin antagonists.35 The Bcl I variant of the GRL
locus was associated with the overfeeding response in weight and abdominal visceral fat
in the MZ twin overfeeding study.36 Individuals homozygous for the 2.3 kb allele had a
greater increase in response to overfeeding. A similar result was noted for plasma total,
LDL cholesterol, and systolic blood pressure responses in the same report, suggesting
pleiotropy and that the GRL locus has an impact on the overall atherogenic profile response
to overfeeding.
Another genetic factor related to lipolysis is the adrenergic system. Adrenergic receptors
(ADR) can stimulate (B1, B2, B3) or inhibit (A2) lipolysis by modulating triglyceride
breakdown in the adipocytes. Data from the MZ overfeeding study was used to investigate
the effects of ADRA2, ADRB2, and ADRB3 polymorphisms on adiposity and fat distribu-
tion responses to overfeeding.37 Results indicate a significant GxE effect for ADRB2 on
weight, plasma leptin, sum of skinfolds, and insulin area under the OGTT (oral glucose
tolerance test) curve. Greater weight gain in response to overfeeding occurred in
Glu27Glu/Gln27Gln than Gln27Gln carriers of the ADRB2 gene. As with the LPL and
GRL loci, ADRB2 impacted the response to overfeeding for multiple traits (i.e., pleiotropy).
There were too few subjects with the rare alleles for the ADRA2 and ADRB3 loci in this
study for a comprehensive investigation. However, in another study the response in obese
women to a weight loss program was investigated for rare mutations at both the ADRB3
(Trp64Arg) and IRS1 (Gly972Arg) loci.38 Carriers of both rare mutations lost less weight
and had a higher frequency of type 2 diabetes than noncarriers. Thus, there is evidence
of both pleiotropy (i.e., these loci affect both body composition and insulin levels) and
oligogenic effects (i.e., multiple genes affect body composition) between these two genes.
Pleiotropy was also observed for the tumor necrosis factor alpha receptor, which may
play a key role in the metabolic syndrome involving both diabetes and obesity. TNFA is
expressed in adipose and muscle tissues and blocks the action of insulin. In a study of
mice lacking one of the TNF receptors (TNFR2), weight, insulin, and leptin level responses
to diet were all modulated by the TNFR genotype.39 Although this marker has not been
reported in gene-diet studies of humans, the presence of the A2 allele was seen to predis-
pose subjects to obesity, higher leptin levels, and insulin resistance.40 It is interesting to
note that the TNFR2 locus is closely linked to the Dob1 (dietary obese) locus on chromo-
some 1p (Table 27.2).
The above findings for TNFR2, ADRB2, and ADRB3 suggest that each impacts on both
adiposity and insulin responses to diet. Insulin is a lipogenic hormone regulating tran-
scription of lipogenic genes, and can act directly or in conjunction with glucose metabo-
lites. In animals, insulin inhibits food intake via receptors in the hypothalamus. The insulin
response to diet was examined in the long-term MZ twin overfeeding experiment, in
which an OGTT was administered.41 The between-pair variance in response to overfeeding

was 2.5 to 5 times higher than the within-pair variance for measures of fasting insulin and
glucose and insulin sensitivity from the OGTT, suggesting gene-diet interactions. Thus,
some individuals are more prone than others to modify their insulin and glucose levels
and perhaps insulin sensitivity in response to overfeeding.
The number of studies looking for the genes underlying adiposity is currently in a rapid
growth stage. For example, 48 different candidate genes have been associated with obesity-
related phenotypes in the past few years, as recently reviewed by Pérusse et al.42 Of these,
at least seven candidates (HSD3B1, IRS1, PPARG, UCP1, LEP, ADRB3, and UCP3) were
associated with changes in adiposity over time, although only four these (LEP, UCP1, UCP3,
and IRS1) were investigated for responses to dietary intervention. All of these markers are
good candidates for GxE interactions. The uncoupling proteins have a role in releasing
stored energy as heat. UCP3, which is abundant in skeletal muscle tissue, was recently
associated with weight change in the morbidly obese during diet therapy.43 The G poly-
morphism of the UCP1 gene was also associated with weight loss after a treatment program
that included a low-calorie diet and exercise in obese Japanese women.44 Leptin is a hor-
mone secreted primarily by adipose tissue and is generally considered to act as a satiety
signal in a feedback loop with the brain. Several mutations in the LEP gene were associated
with plasma leptin responses to dietary intervention in one study.45 Those authors con-
cluded that LEP may be a gene regulating the variability of responses to nutritional envi-
ronments rather than for obesity per se. In the long-term MZ twin overfeeding experiment,
the Gln223Arg variant of the leptin receptor (LEPR) was associated with several metabolic
variables,46 including plasma leptin, insulin, and HDL-c, but not body composition mea-
sures. The insulin receptor substrate 1 (IRS1) gene has a role in controlling cellular growth
and metabolism, and was associated with longitudinal changes in BMI.47 As previously
outlined, rare mutations at both the IRS1 and ADRB3 loci led to less weight loss and higher
type 2 diabetes in response to a weight loss program in obese women.38
The remaining markers listed above are also good candidates in gene-diet interaction
effects on obesity, although few reports regarding gene-diet interactions were found. For
example, the peroxisome proliferator-activated receptors (PPARs) are expressed in adipose
tissue, and the gamma subtype (PPARG) has been implicated in adipose cell function,
including lipid composition of the membrane and sensitivity to insulin.48 PPARG was
linked to longitudinal changes in BMI.49 The adrenergic system (discussed above) has a
role in regulating energy balance through thermogenesis and lipid mobilization in adipose
tissue. The beta 3 adrenergic receptor (ADRB3) is thought to play a minor role in cate-
cholamine-induced lipolysis. However, reports of linkage or association of ADRB3 to
obesity and weight changes in humans have been inconsistent.50-54
Lipids, Lipoproteins, and Apolipoproteins

The lipid, lipoprotein, and apolipoprotein response to dietary intervention is the most
extensively studied area of those reviewed in this section. A great deal of evidence55-59
suggests that plasma lipid level responses are under genetic control. Individual differences
in the plasma lipid profile response to dietary fats and cholesterols are found in several
species, including mouse,60 rat,61 and monkey.62,63 Some individuals are quite sensitive to
changes (high-responders) and others are relatively insensitive (low-responders), as con-
firmed in a meta-analysis of 27 studies.64 For example, early evidence of environmental
(including dietary) effects on total cholesterol (CH), high density lipoprotein-cholesterol
(HDL-c), HDL-c subfraction 2 (HDL2-c), and low density lipoprotein-cholesterol (LDL-c)
using the twin design was reported by O’Connell et al.65 Heritability estimates, although
remaining significant, were decreased after adjusting for environmental factors, and by
stratifying the sample based on nutritional variables. In another study of children with
elevated LDL-c levels, the effect of a nutrition-education program was investigated.66
Greater reductions in plasma total and LDL-c were observed in children with less family
history of coronary heart disease.
Evidence for gene-diet interactions on HDL-c subfractions (HDL1-c, HDL2-c, and HDL3-
c) were also reported in a baboon population.67 The baboons were measured under a basal
diet and again after being fed a high cholesterol and saturated fat challenge diet. The
results suggested that there were both pleiotropic effects (i.e., the same gene(s) influencing
multiple traits) and GxE interactions. The authors concluded that although a similar set
of genes influenced the variation in each of the three subfractions under both diet condi-
tions, the expression of the genes influencing HDL1-c and HDL2-c were altered by the
high-fat diet (i.e., a GxE interaction).
Additional evidence of GxE effects come from the short-term MZ twin overfeeding
intervention study. Plasma responses in CH, triglycerides (TG), LDL-c, HDL-c, and the
HDL-c/CH ratio were investigated.68 Although overfeeding induced significant changes
only in CH and LDL-c, there were large interindividual differences in the responses of all
of these variables. GxE interactions were detected for TG, HDL-c, and HDL-c/CH. It was
noted that TG changes were negatively correlated with HDL changes, and that the corre-
lated responses may be related to the susceptibility to develop hypertriglyceridemia, which
is known to be under genetic control and related to changes in insulin concentrations.
Much of the evidence for GxE interactions on lipids, lipoproteins, and apolipoproteins
involve the measured gene approach.59,69-71 Genetic variations in several apolipoprotein
genes (A-I, A-IV, B, CIII, E), the LDL receptor (LDLR) and LDL subclasses (patterns A and
B) have been implicated in the dietary response of lipids.
The LPL gene discussed above, involved in partitioning exogeneous triglycerides
between storage and oxidation, has been associated with plasma lipid levels and CHD
risk.72,73 In humans, several mutations have been implicated in the gene-diet interaction.
For example, the Hind III polymorphism was associated with variability in plasma cho-
lesterol, LDL-c, LDL-triglyceride, and Apo B responses to diet.70,74,75 The N291S mutation
showed a significant effect on TG and HDL-c responses to diet.59 Other evidence from a
MZ twin study (non-intervention) suggests GxE involvement of the Ser447Ter mutation.76
Intrapair variances were different across twin types for CH, TG, and HDL-c levels,
although the environmental source using this method is not specified. The authors sug-
gested that this LPL variant acts as a restrictive variability gene, so that individuals without
the mutation are more susceptible to fluctuations in plasma cholesterol and HDL-c.
Several of the apolipoprotein genes have been implicated in gene-diet interactions.71,77
The APO A-I, A-IV, and C-III complex of genes is involved in lipid metabolism. A mutation
in the A-I gene promoter region (G → A) was associated with the plasma LDL-c response
to a high monounsaturated fat diet.78 Apo A-IV is an intestinal glycoprotein with two
allele forms (A-IV-1 and A-IV-2); its synthesis is stimulated by dietary lipids and it may
act centrally to inhibit food intake. Although conflicting reports are found, individuals
homozygous for the A-IV-1 allele generally have lower HDL-c and higher TG.71 In a
crossover intervention study, subjects consumed a low-cholesterol diet for two weeks,
then three weeks of a high-cholesterol diet.79 In the high-cholesterol diet condition, plasma
LDL-c increased more in the A-IV-1 group than the A-IV-2 group, with no change in HDL-c
or TG levels for either genotype. Similar results were found in men (but not women) in
another report combining data from three intervention studies.80 In another study,81 an
A → T mutation in position 347 affected the total CH, LDL-c, and Apo B responses to a
high fat diet. Lipid changes due to dietary intervention were found to be similar for the
Apo C-III gene. For example, the SstI polymorphism interacted with diet to produce
genotype-dependent responses in total CH, LDL-c, and Apo B levels.82 Thus, for this cluster
of apolipoprotein genes located on chromosome 11q within 1 cM of each other, there is

consistent evidence of a gene-diet interaction effect on LDL-c, although the results for
HDL-c and TG are not as clear.
The APOB gene is involved in the synthesis and secretion of chylomicrons and very
low density lipoprotein (VLDL), and is a ligand for the interaction of LDL-c with the LDL
receptor. Several variants have been associated with lipid responses to dietary interven-
tion. While there are inconsistencies in the literature, genetic variations at both the Mspl
and XbaI RFLPs have been reported to influence the plasma Apo A-I, LDL-c, Apo B, and
HDL-c71 and TG83 responses to dietary fat and cholesterol. Moreover, an insertion/deletion
polymorphism of the APOB gene was related to the lipoprotein response to increases in
dietary fiber.84
Several studies investigated the role of APOE polymorphisms in the response of plasma
LDL-c levels to dietary interventions.85 Apo E is a protein associated with several lipopro-
teins, mediates the lipoprotein interaction with specific cell surface receptors, and has an
important role in CH and TG metabolism. APOE has three common isoforms (E2, E3, and
E4), with E3 the most common. APOE represents the most widely studied candidate, and
although there are conflicting results in the literature,55,71,85 most conclude that carriers of
the E4 variant respond well to dietary intervention. Several possible explanations were
suggested for the differences across studies; for example, expression of the response in
absolute versus fractional levels. Since individuals with the E4 phenotype usually have
higher initial plasma LDL-c levels, there is likely to be a larger absolute change, while the
fractional change may be consistent across APOE phenotypes. Additional factors leading
to inconsistencies across studies include low sample sizes leading to reduced power for
testing hypotheses, and the sex ratio of subjects, since dietary responsiveness differs
between sexes. Other factors include whether the intervention protocol reduced dietary
fat, cholesterol, or fiber.86,87 For example, a meta analysis of 16 studies showed that a greater
lipid response in carriers of the E4 allele was only found when the dietary modification
reduced total fat intake, irrespective of dietary cholesterol.70 In another study, the increase
in dietary fiber was associated with greater reductions in LDL-c in carriers of the E2 allele.
Other studies also suggest a difference in the APOE gene association with plasma LDL-c
response, depending on LDL particle size.88,89 That is, the diet-induced change in LDL-c
levels may not be due to reduced particle number but rather to a shift from larger
cholesterol-rich LDL particles to smaller, denser LDL particles.
The LDL particles vary in size, density and lipid content. Subjects with small, dense LDL
particles (subclass pattern B) exhibit higher levels of TG and Apo B and lower levels of
HDL-c compared to subjects with a predominance of larger LDL particles (pattern A).
Population studies have shown that about 30 to 35% of adult men exhibit the more
atherogenic pattern B which is associated with a threefold higher risk of myocardial
infarction. This lipoprotein phenotype is under strong genetic determination, with herita-
bility levels of about 50% and evidence of a major gene effect.90 The plasma lipoprotein
response to changes in dietary fat in relation to the LDL subclass pattern was investigated
in a dietary crossover experiment.88,89 In this study, 105 men were randomly assigned to
either a high fat (46%) or low fat (24%) diet for six weeks and then switched to the alternate
diet for an additional six weeks. Subjects were categorized as pattern A (n=87) or pattern
B (n=18), and the lipoprotein responses were analyzed as the changes from the high- to
low-fat diets. After this dietary intervention, pattern B subjects exhibited a threefold greater
reduction in LDL-c compared to pattern A subjects, while only men with pattern B exhib-
ited a reduction in Apo B levels. These group differences were independent of BMI, Apo
E phenotype, and plasma lipid levels. The decrease of LDL-c observed in pattern A subjects
was due primarily to a shift in LDL particle mass from larger to smaller cholesterol-
depleted LDL, without a change in LDL particle number. This shift in LDL distribution
with the low fat diet induced expression of pattern B phenotype in 36 of the 87 pattern A
subjects who did not express it on a high fat diet. Thus, in response to a low fat diet 41%
of the pattern A subjects exhibited the more atherogenic pattern B lipoprotein profile. The
results of this study provide a good example of genotype-diet interaction and show that
dietary recommendations may not be equally good for every individual in the population.
LDLR mediate cholesterol uptake and are located on cells of many tissues. LDLR poly-
morphisms within the exon have been related to reductions in plasma concentrations of
ApoB, total, and LDL cholesterol response to dietary fiber,84 but not to the response of
LDL-c concentrations to dietary fatty acids.91
MTHFR is an enzyme involved in folate production and in remethylation of homocys-
teine. Elevated levels of homocysteine are due to enzymatic deficiencies or to low intake
of vitamins B6, B12, and folic acid, and are risk factors for coronary heart disease. Gene-
diet interactions on homocysteine levels have been reported.92 A MTHFR polymorphism
was associated with increased homocysteine levels, but only in men with low folate intake.
Thus, low folate intake may increase the risk of hyperhomocysteinemia in subjects with
the MTHFR mutation. The MTHFR locus is closely linked to both the TNFR2 and Dob1
loci involved with adiposity responses to dietary intervention.
The FABP2 gene produces the intestinal fatty acid binding protein. It plays a role in
absorption and intracellular transport of saturated and unsaturated long chain fatty
acids.93,94 The FABP2 T54 allele has been associated with insulin resistance and an athero-
genic metabolic profile. In a crossover study of the effects of dietary soluble and insoluble
fiber, the T54 allele was associated with a significant decrease in total and LDL cholesterol
and Apo B during a period when the diet was high in soluble fiber.95
Finally, the cholesteryl ester transfer protein (CETP) gene mediates the transfer of cho-
lesteryl ester from HDL-c to triglyceride-rich lipoproteins. It also has a role in reverse
cholesterol transport and in the catabolism of HDL-c. CETP isoforms were associated
HDL-c levels and risk for myocardial infarction, but only in subjects who drank 25 g/day
of alcohol.96 Thus, there is evidence of a gene-alcohol interaction effect on HDL-c levels.
Gene-Gene (GxG) Interactions

Interactions between genes also have a role in determining the susceptibility to diseases.
Gene-gene interactions occur when the impact of a gene is mediated by genetic variation
at another gene locus. For example, it has been suggested that variation in total CH and
LDL-c is influenced by interactions between the linked LDLR and APOE genes.97 The
cholesterol-raising and lowering effects of the E4 and E2 alleles, respectively, were seen
only in individuals with a particular LDLR genotype. These two genes are located about
40 cM apart on chromosome 19p13.2-p13.32. Another example of GxG was reported by
Helbecque et al.98 A significant interaction between the VLDL receptor genotype (VLDLR)
and the Apo E phenotype was found for plasma TG levels. Interactions among GRL, LPL,
and ADRA299 were also reported. GRL and ADRA2 interactions were detected for LDL-
c levels, while GRL and LPL interactions were found for HDL-c levels. Interestingly, none
of the main effects were significant. This is a classical example of GxG interaction, where
there is no association in the presence of either locus separately, but jointly they have an
effect. Although the exact mechanism is not clear, the interaction may influence rates of
lipolysis and release of free fatty acids (FFA) from adipose tissue.
Other examples of GxG interactions are found in the body composition domain. For
example, indirect evidence for two pleiotropic loci affecting fat mass and BMI was
reported by Borecki et al.100 using segregation analysis. One locus apparently affected
extreme overweight, while the other influenced variation only in the “normal” range.
Evidence for multiple loci affecting body composition has also been explored using the
measured gene approach. Since each of the LPL, GRL, and ADRA2 loci had similar effects
on several correlated body composition traits, the hypothesis of GxG interaction was
investigated.101 Previous studies had reported that the ADRA2 Dra I variant and the GRL
Bcl I variant were each associated with abdominal fat. When the three candidates (GRL,
ADRA2, and LPL) were considered simultaneously, significant interactions on overall and
abdominal adiposity were observed that accounted for a small but significant percentage
of the variance.
Only one study was found investigating GxG interactions for responses to dietary inter-
vention, involving the APO A-I and A-IV loci.81 Male subjects were fed three consecutive
diets, each lasting for four weeks, which differed in amounts of saturated and monoun-
saturated fats. The G → A mutation in APOAI and the 347Thr/Ser mutation in APOAIV
were examined. Each locus showed a gene-diet interaction effect on responses in total
cholesterol, LDL-c, and Apo B levels. However, the GxG effect on the response was not
significant, resulting in a simple additive effect of the two loci on the lipid responses.
Conclusions
This section is not intended to be an exhaustive summary of the genetics of nutrition.
Rather, we have attempted to show the broad scope of behavioral and physiological factors
underlying the genetics of nutrition. The general findings may be summarized as follows.
First, there are familial factors underlying food intake and preferences. However, whether
this effect is due to genes, familial environments, or some combination of both is not clear.
Second, it is obvious that nutrition plays an important role in the development of certain
diseases leading to morbidity and mortality such as obesity, dyslipidemia, and diabetes,
and that genes underlie this effect to some extent. Third, there are multiple complex
etiologies that lead to increased risk for these diseases.
A great deal of work remains to be done on several fronts. First, very little was found
regarding gene-diet interactions for many of the peptides and hormones3 that have been
implicated in food intake. Some of these include cholecsytokinin (CCK), glucagon-like
peptide 1, agouti-related peptide, CART, corticotropin releasing factor (CRF), pro-opiomel-
anocortin (POMC), opioids, neuropeptide Y (NPY), and others. These inhibit food intake,
while others stimulate appetite and thus may contribute significantly to the responses to
energy intake. More extensive candidate genotyping of existing intervention data would
be helpful in this regard. Second, it is highly unlikely that the genes identified to date are
the only ones affecting the traits discussed here, even in the lipid domain, for which much
is already known. While candidate gene studies are useful in confirming the effects of
these known genes, linkage analysis of genome scan data are needed in order to locate
novel chromosomal regions that may lead to identification of new genes. In this regard,
large-scale diet intervention studies of family data are needed. While this may be imprac-
tical in human populations, genome scans from intervention studies of closely related
species such as the baboons are feasible. Third, in addition to gene-diet interactions,
models that incorporate the possibility of other complex etiologies such as pleiotropy and
oligogenic and epistatic actions are needed. Since candidate genes for lipids (e.g., LPL)
may also influence other traits such as diabetes and obesity, we should not limit our
candidate gene investigations to one type of trait. This field is ripe for an explosion of
studies that probe the genome and describe the complex genetic etiologies underlying
responses to nutrition. It is obvious that nutrition plays a large role in several traits of
public health interest such as those involved in the metabolic syndrome and discussed
here. An understanding of the factors involved in this syndrome should take nutritional
factors into account.
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28
Documentation to Improve Medical Assessment Access
and Reimbursement
Jessica A. Krenkel
Introduction
Nutrition and nutrition-related medical diagnoses are the basis for medical assessment
and the administration of patient nutrition care. Standards of nutrition care are directed
to quality treatment but reimbursement issues drive treatment access, and reimbursement
is being closely tied to outcomes and costs versus benefits. The recent emphasis on evi-
dence-based medicine and outcomes has stimulated the collection of data to reinforce the
cost benefit for professional nutrition services, usually provided by a registered dietitian.
Registered dietitians are currently the single identifiable group with the standardized
education, clinical training, continuing education, and national credentialing requirements
necessary to be directly reimbursed as a provider of nutrition therapy. Professional services
may include counseling for preventing disease (primary prevention), for detecting asymp-
tomatic disease or risk factors at early, treatable stages (secondary prevention), for disease
treatment (tertiary prevention), and to promote normal growth and development.1 The
approach taken by the National Institute of Medicine (IOM) in making recommendations
for future Medicare coverage included two nutrition service categories or levels: nutrition
therapy and basic education or advice.2 Nutrition therapy was identified by the IOM to
include the assessment of nutritional status, evaluation of nutritional needs, intervention
that ranges from counseling on diet prescriptions to the provision of enteral and parenteral
nutrition, and follow-up care as appropriate. Since nutrition therapy is an intensive
approach to the management of chronic diseases and requires significantly more training
in food and nutrition science than is commonly provided in the curriculum of other health
professions, the registered dietitian is the most common reimbursable provider, while basic
nutrition could be provided by many health professionals.
The American Dietetic Association (ADA) uses the designation medical nutrition ther-
apy (MNT) for assessment and interventions to treat illness and injury based on clinical
research and experience. MNT involves the assessment and analysis of medical and diet
history, blood chemistry lab values, and anthropometric measurements. Components of
MNT include: 1) Diet modification and counseling and 2) specialized nutrition therapies
0-8493-2705-9/01/$0.00+$1.50
TABLE 28.1
Nutrition Diagnoses
260 Failure to thrive, kwashiorkor
261 Marasmus
263.8 Hypoalbuminemia with malnutrition
262-263.9 Mixed protein-kcalorie malnutrition and
263.0, 263.1 Malnutrition of mild to moderate degree
269.9 Nutritional deficiencies, unspecified
278 Obesity
281.9 Anemia, nutritional
646.1 Obesity/Pregnancy
646.8 Weight Loss/Pregnancy
733.1 Failure to thrive, child
783.1 Abnormal weight gain
783.2 Abnormal weight loss
733.0 Anorexia
307.1 Anorexia nervosa
783.6 Bulimia
307.50 Eating disorder, NOS
such as medical foods through food intake, enteral nutrition delivered via tube, or parental
nutrition delivered via intravenous infusion.3
Nutrition Diagnosis
Medical diagnoses are officially coded by the International Classification of Diseases,
Ninth Revision, Clinical Modification, ICD-9-CM, codes.4 The codes identify the reasons
services, equipment, or supplies are ordered. Diseases and injuries are arranged into 17
groups with 3 to 5 numeric descriptors. These include only a few codes specific to a
nutrition diagnosis (Table 28.1) but many that are nutrition-related (Table 28.2) and there-
fore may require medical nutrition therapy as part of the treatment. A clinical modification
of ICD-10-CM has been developed as a replacement for ICD-9-CM but has not been
implemented yet.
There are 24 disease management protocols for the most common nutrition-related
diagnoses provided by the ADA publication, Medical Nutrition Therapy across the Con-
tinuum of Care.5 When coding the diagnosis for reimbursement, the code of choice should
agree with the M.D.-identified diagnosis. For example, the ICD-9-CM codes for diabetes
are very specific for complications and control (250.01 — diabetes mellitus without men-
tion of complication, type 1; 250.02 — diabetes mellitus without mention of complication,
type 2, uncontrolled). Familiar nutrition diagnoses are the codes related to malnutrition:
failure to thrive, kwashiorkor (260), marasmus (261), hypoalbuminemia with malnutrition
(263.8), mixed protein-calorie malnutrition (262-263.9), and malnutrition of mild to mod-
erate degree (263, 263.1). There are suggestions for further clarification of malnutrition
and weight loss diagnoses by describing body compartments: wasting (involuntary
weight loss), cachexia (involuntary loss of body cell mass or fat-free mass when this
compartment is reduced by little or no weight loss), and sarcopenia (involuntary loss of
muscle mass). An increased degree of specificity for malnutrition may have value to
increase the perception of nutrition as medical treatment for the future and to focus
treatment on identified patient needs. Submitting codes to the American Medical
Documentation to Improve Medical Assessment Access and Reimbursement 623
TABLE 28.2
Nutrition-Related ICD-9 Diagnosis Code Examples
042 AIDS/HIV
693.1 Allergies — food related
626 Amenorrhea
429.2 ASCVD
239.6 Breast cancer
579.0 Celiac sprue
574 Cholelithiasis
558.9 Colitis/Ileitis
558.10 Colon cancer
428 Congestive heart failure
564 Constipation
555.9 Crohn’s disease
250 Diabetes mellitus
250.91 Diabetes mellitus, I, complications
250.01 Diabetes mellitus, I, uncomplicated
250.90 Diabetes mellitus, II, complications
250.0 Diabetes mellitus, II, uncomplicated
648.8 Diabetes, gestational
251.0 Diabetic ketoacidosis
558.9 Diarrhea
271 Disorders of lipid metabolism
562.10 Diverticulitis
536.8 Dyspepsia
535.5 Gastritis
553.3 Hiatal hernia
272.03 Hypercholesterolemia
643.0 Hyperemesis gravidarum
272.1 Hyperglycemia
272.3 Hyperlipidemia
275.42 Hypercalcemia
276.7 Hyperkalemia
276.0 Hypernatremia
252.0 Hyperparathyroidism
275.41 Hypocalcemia
250.80 Hypoglycemia, diabetic, unspecified
251.2 Hypoglycemia, nondiabetic, unspecified
276.8 Hypokalemia
276.1 Hyponatremia
272.4 Hyperlipidemia
401-405 Hypertension
564.1 Irritable bowel
271.3 Lactose intolerance
579.9 Malabsorption syndrome
581.9 Nephrotic syndrome
733 Osteoporosis
239 Stomach cancer
Association and participating in the development of diagnosis codes related to nutrition

are new roles for nutrition professionals. Whether the diagnosis codes or the more specific
descriptors would improve reimbursement and outcomes is unknown. Ways to diagnose
nutrition problems or diseases are only one part of a multidimensional concept needed
for clinical nutrition practice today.
Care Standards
Clinical practice tools including practice guidelines, protocols, clinical pathways, care
maps, and algorithms integrate clinical expertise and scientific evidence to reduce frag-
mentation of care, and to guide nutrition practice and nutrition-related diagnoses. The
development of these tools begins with the most costly and frequent medical conditions.
Professional organizations, insurance companies, government agencies, accrediting orga-
nizations, and corporation policies and procedures may establish standards of practice.
Standards of practice are gaining importance for justifying treatment approaches for
patients and for providing legal justification for time, billing, and counseling content.
Professional organizations that provide standards of practice include the American
Dietetic Association, American Society for Parenteral and Enteral Nutrition, American
Public Health Association, American Diabetic Association, and other professional associ-
ations and practice groups. Government agencies provide standards for various practice
settings, which are published in the Federal Register. Additionally, interpretive guidelines
and survey procedures provide additional sources for practice expectations. The Health
Care Financing Administration (HCFA), with responsibility for Medicare, influences
healthcare facility standards as well as the reimbursement system for private and public
health plans. Additionally, the Agency for Health Care Policy and Research (AHCPR) was
created by the U.S. Congress to enhance the quality, appropriateness, and effectiveness of
clinical practice guidelines.6 Accrediting organizations such as the Joint Commission on
Accreditation of Healthcare Organizations (JCAHO), dictate expectations for quality nutri-
tion care for many types of facilities. Corporations have relied on many published stan-
dards of practice to establish contracts, competencies, and policies and procedures for
nutrition practitioners. Employer or professional liability may be determined by adherence
to practice standards. Lawsuits related to practice guidelines in the medical profession
have not permitted a lower standard for different rural communities, geographical areas,
or resource availability, and this would be predicted to be the case for nutrition practice
standards as well. Whether established practice guidelines will foster increased lawsuits
against practitioners who fail to follow recommendations is unknown.7
Medical Assessment Access

Access to quality health care is important in order to eliminate health disparities and
increase the quality and years of healthy life for all Americans.1 Recent major changes in
the U.S. health care system include welfare reform, an emphasis on market forces, the use
of case management, and altered payment and delivery systems. Adequate access to
nutrition care may increase use of these services and improve health outcomes. Conse-
TABLE 28.3
Major Classifications and Models of Managed Care Systems
Classification/Model Characteristics
Health maintenance A managed care organization that provides or arranges for specific health care
organization (HMO) services for plan members for a fixed, prepaid premium or dollar amount.
Staff model The HMO owns and operates all facilities needed for the care of plan members
and directly hires providers to work in HMO facilities. Closed panel with tight
control over practice and benefits.
Group model The HMO contracts with physician groups to care for plan members instead of
directly employing these physicians. These physician groups are managed
independently from the HMO and are paid at negotiated, capitated rates.
Network model The HMO contracts with several single- or multispecialty physician groups.
Independent practice The HMO contracts directly with individual, independent physicians, who are
association (IPA) paid on a capitated basis. These physicians work in their own offices and serve
both HMO and non-HMO patients.
Mixed-model A combination of the above four distinct HMO models and fee-for-service plans
to accommodate the different preferences of providers and health plan members.
Preferred provider The HMO contracts with individual providers or networks of providers to
organization (PPO) provide health care, such as nutrition services or dental care, for plan members
at discounted fee-for-service rates. Plan members are not matched with
gatekeepers and can go to specialists without referrals.
Point-of-service (POS) plan Plan members are coupled with primary care providers but can seek care directly
from other providers for higher copayments.
quently, measures of nutrition access across a continuum of care are an important way to
evaluate quality of care.
A significant measure of the trend of decreased access is the proportion of people who
have health insurance. In 1997, 85% of persons under 65 years of age had health insurance.
Health insurance may be either private or public health plans.8 Private insurance includes
fee-for-service (FFS) plans, single-service hospital plans, or coverage by managed care
organizations. Managed care is divided into three major classifications (See Table 28.3):
health maintenance organizations (HMOs), preferred provider organizations (PPOs), and
point-of-service (POS) plans.9,10 Public insurance includes Medicaid or other public assis-
tance, Aid for Families with Dependent Children (AFDC), Supplemental Security Income
(SSI), Indian Health Service, Medicare, or military health plan coverage.
Medicare Part A (hospital insurance) covers inpatient hospital, home care, and hospice
services, skilled nursing facility care, and end-stage renal disease services. Medicare is
managed by the Health Care Financing Administration (HCFA) which contracts with 46
fiscal intermediaries who are private insurance companies to process claims. Under Medi-
care Part A there are no payments specifically for dietitian services, as facility reimburse-
ment is related to complexity of care for different diagnoses and conditions. For hospitals,
the HCFA classification scheme is called Diagnosis Related Groups (DRGs), while for
skilled nursing facilities the classifications are called Resource Utilization Group (RUGs).
The DRGs and RUGs provide the basis for a Prospective Payment System (PPS) or “bun-
dled” approach for hospitals since 1983, skilled nursing facilities since 1998, and home
health agencies as of October 2000.11
Medicare Part B (medical insurance) provides coverage for outpatient physician and
hospital services, laboratory services, durable medical equipment, and other medical
services. Part B professional services are administered by 33 carriers. Part B equipment
and supplies are administered by four regional durable medical equipment carriers
(DMERCs).11 While there is not a benefit for nutrition counseling under Part B, this is the
focus of current legislative efforts by the ADA.
Medicare Part C (Medicare + Choice) offers alternate health plan options in addition to
the traditional fee-for-service plan. Medicaid is a federal–state matching entitlement pro-
gram for certain individuals and families with low income and resources. State participation
in the Medicaid program is optional as long as the state has a similar program for this
population. Each state has varying coverage of nutrition services for Medicaid recipients.11
Although lack of health insurance is clearly a major factor impeding access to care,
having health insurance does not guarantee that health care will be accessible or affordable.
Managed care has become the dominant form of healthcare delivery in the U.S. replacing
the traditional FFS or indemnity system.12 Managed care shifts financial risk from employ-
ers, insurance companies, and self-paying patients to healthcare systems and providers.
Providers are paid set or predetermined fees under capitation and bundled fee systems
regardless of services ultimately rendered. Managed care attempts to control costs by
preventing duplication of services, restricting choices of providers, and increasing effi-
ciency. Access to service is provided by precertification, utilization review, and credential-
ing. Gatekeepers to the system vary, but the case manager has a key role in complex
medical cases. Educating case managers to showcase the benefits of medical nutrition
therapy, improved patient care, and cost containment is essential for improved nutrition
service access. Nutrition professionals potentially impact preventive services, screening
programs, health risk assessments, and case management if they become more knowl-
edgeable about how the systems operate.
Reimbursement for some care settings over others causes an uneven distribution of
access to service. Access sites should include the entire continuum of care: acute care,
ambulatory care, home care, skilled nursing, and long-term care. While nutrition counsel-
ing is generally more effective outside the hospital setting, coverage for nutrition therapy
in ambulatory settings is at best inconsistent, but most often nonexistent.2 This lack of
access is a significant barrier to improved patient outcomes associated with nutrition care.
Outcomes
Analysis of the effectiveness of the practice guidelines for medical nutrition therapy is a
focus of outcomes research. The outcomes determine reimbursement for clinical practice
in our health care system as evidence-based medicine is becoming a controlling factor in
determining the distribution of healthcare dollars.13 The outcome is the result of a process
of healthcare that weighs options as to cost and effects. The two major categories of
outcomes are health and cost. Outcomes data provide health care payers information on
the effectiveness of care to help them “1) reduce health care costs, 2) prioritize care and
make reimbursement decisions, 3) establish guidelines, and 4) make purchasing deci-
sions.”14 Decisions such as which tests to run first, or whether to try enteral or parenteral
feeding, require knowledge of the evidence which supports nutrition decisions. Accep-
tance of clinical nutrition by the plan practitioners may be enhanced by the realization
that cost-effective medical practice is optimized by wider application of nutrition princi-
ples to health maintenance and patient care.15
Health outcomes include clinical outcomes such as lab results and length of stay, func-
tional outcomes such as quality of life, and general outcomes such as patient satisfaction
and interventions.14 Clinical research, as well as continuous quality improvement (CQI)
or other in-house quality measurements, utilize health outcomes to determine results.16
These need to be coupled with the cost outcomes of cost-effectiveness, cost-benefit, and
charges. Cost-effectiveness is a ratio measure of the number of dollars spent for the
TABLE 28.4
Types of Outcomes
Clinical Outcomes
Primary Secondary
Anatomic or Anthropometric — weight, height, % body fat, etc. Morbidity
Physiologic — Mortality
Biochemical labs, such as albumin, hemoglobin, cytokines Length of stay
Healing, such as pressure ulcers, wounds, burns Rates of infection
Metabolic rate Re-admissions
Study or Disease Specific Drug utilization
Such as stool analysis in cystic fibrosis, or residuals in enteral feeding studies Number of doctor visits
Home health care nursing visits
General Outcomes Functional Outcomes
Patient satisfaction and expectations Quality of life

Learning outcomes — enrollment, knowledge, behavioral change, Activities of daily living
improvements Mental/emotional health
Interventions — type, frequency or usage, acceptance by patient, timeliness Family interaction
Acceptance of recommendations — M.D., interdisciplinary team, patient Self-assessed health care status
Meal, food, nutrient intake Pain
Economic Outcomes
Costs — cost-benefit, cost-effectiveness

Revenue
Reimbursement
improvement in an outcome (e.g., dollars spent for a therapy/HbA1c improvement),

whereas cost-benefit is a ratio of the dollars spent on a therapy or program service to the
number of dollars saved by implementing the program. In Congress, a cost-benefit (COB
score) estimates the cost of legislation over a five-year period.17 Medicare reimbursement
is being considered for diseases where there are estimates for economically significant
benefits to beneficiaries and reduced Medicare program health care expenditures. A lack
of systems to track quality and cost of nutrition care has resulted in increased involvement
of the ADA in collecting outcome data.24 National outcome data for a larger range of
medical conditions and preventive care will allow providers and administrators to identify
nutrition services and populations that are in need of improved delivery and funding.
Quantification of patient satisfaction and quality of life is difficult, but these outcomes
are of importance to the National Committee on Quality Assurance (NCQA) that accredits
health maintenance organizations. The NCQA publishes a Health Plan Employer Data
Information Set (HEDIS). The 3.0 version had 8 domains with 71 total performance mea-
sures to help employers and consumers compare managed care organizations.18 Patient
satisfaction is domain 3, and increased satisfaction has been associated with positive
clinical outcomes.19
Reimbursement
The value of the dietitian is determined by income generation and by contribution to the
goals of the organization in the private and public sectors of society. A lack of reimburse-
ment is a specific barrier to more consistent delivery of diet counseling and to employment
of nutrition professionals.
Reimbursement issues have become a barrier for clinical nutrition in hospitals, clinics,
and educational and other settings that have begun to operate their clinics with more of
a business approach. Reimbursement has been poor to variable, with a wide range of
experience expressed nationwide. The Health Care Financing Team at ADA has encour-
aged registered dietitians to develop skill understanding medical nutrition therapy coding
and the coverage issues that surround reimbursement.20 Recent efforts by ADA offer
potential for increased reimbursement. The ADA has had three MNT current procedural
terminology (CPT) codes accepted by the American Medical Association and published
in the 2001 CPT Code.21 Under HCFA’s coding system, CPT codes are considered Level I
HCPCS codes (acronym for HCFA’s Common Procedure Coding System). These represent
levels of service for individual new (97802) and established (97803) patients and group
(97804) that may be used in the private sector (e.g., with third party payers); however,
they have not been assigned relative value units (RVU). The RVUs will determine possible
payment for MNT levels of service by Medicare and HCFA. The RVU represent a fair and
reasonable fee structure based on geographical location, work required/resources con-
sumed to perform service, other operating expenses, and other related factors. The AMA
Health Care Professional Advisory Committee (HCPAC) has not accepted ADA’s recom-
mended work values which were based on practitioner data collected in March 2000, due
to their unfamiliarity with the content and complexity of nutrition services. ADA has
notified the AMA and HCFA that the Association will extend development of codes by
seeking additional codes and reformatting the present codes to separate the tasks of
assessment and intervention. Similar problems have occurred with the codes and RVUs
being used for diabetes counseling, as the time needs and complexity are unfamiliar to
the AMA. The acceptance of AMA codes and RVU for nutrition provider services is crucial
in obtaining reimbursement from Medicare. Medicare decisions set precedents often fol-
lowed by insurance companies, and add to the credibility of nutrition professionals as
providers. The CPT codes and RVUs specific for recognized nutrition providers would be
expected to become the basis of reimbursement for Medicare and insurance companies.22
Recent bills before congressional committees, the Medical Nutrition Therapy Act of 1999
(H.R. 1187/S.660) and the Medicare Wellness Act of 2000 (S.2225/H.R. 3887), which include
some preventive services for Medicare beneficiaries, demonstrate a climate of change for
Medicare reimbursement. The Medical Nutrition Therapy Act provides coverage for med-
ical nutrition therapy under Medicare Part B furnished by registered dietitians and qual-
ified nutrition professionals. A compromise is being considered that would be a five-year
demonstration project for Medicare coverage of diabetes and renal disease.23 The major
reforms, including prescription drugs, will delay consideration of the controversial Medi-
care Wellness Act until at least 2001. These bills have gained momentum due to the study
of the National Academy of Sciences Institute of Medicine, The Role of Nutrition in
Maintaining Health in the Nations Elderly: Evaluating Coverage of Nutrition Services for
the Medicare Population, which recommends that medical nutrition therapy — with phy-
sician referral — be a covered benefit under the Medicare program.2
Presently, numerous CPT codes are used for clinical nutrition services.10,24,25 Codes and
reimbursement vary from state to state, among the various payors, and in different care
settings, but commonly used codes include physician codes for new patients (99201 series),
established patient or follow-up (99211 series), and consultation codes (99241 series). There
is considerable controversy about the use of these codes by non-physician providers with
and without “incident to” a physician billing. “Incident to” a physician billing requires
supervision by the physician and billing under his tax ID, and is primarily used in states
without dietitian licensure. Legal opinion has questioned the use of this billing practice
by non-physicians for Medicare patients except at the lowest level of service and pay-
ment.26 Health insurance companies with provider agreements continue to accept “inci-
dent to” billing. Hospital-based outpatient clinics bill under the hospital tax ID instead of
the physician or the licensed dietitian certified provider ID.
Other codes such as the new MNT codes (97802, 97803, and 97804), or preventive medicine
codes (99381, 99391, and 99401 series) are available but may often have low reimbursement,
as the RVU are minimal to none. Group counseling for preventive counseling (99411 and
99412) is seldom reimbursed, and also has RVU minimal to none. There has been some
progress with the use of G-codes (G0108, G0109) for diabetes counseling, but numerous
criteria must be met to bill when using these codes, including the need for services to be
provided “incident to” a physician’s services and under the physician’s supervision. The
G codes are provisional codes for a new benefit.10 The HCPCS Level II manual includes a
series of temporary national non-Medicare S codes and descriptors: S9465 — Diabetic
management program, dietitian visit, S9470 — Nutritional counseling, dietitian visit.27
Articles and previously published information about which codes to use may not meet
legal challenge and claims of fraud, as there has not been an easily understandable
definition of how dietitians should use the codes. “Practice” does not mean that Medicare
will accept the coding if investigated. This has recently been emphasized with Medicare’s
vigorous monitoring for fraud and abuse, 28 although thus far dietitians have not faced
prosecution. Requests for clarification from Medicare are often verbal, and there has been
resistance to putting interpretations in writing that are not in the published standards.
These numerous inconsistencies and the increasing legal environment emphasize the need
to have professional organizations such as the ADA involved in coding issues and sup-
porting bills to clarify services.
Contracts with insurance companies and health maintenance organizations may closely
follow Medicare guidelines or may be negotiated for acceptable codes and reimburse-
ment/billing rates. Working with the clinic personnel responsible for these contracts has
been beneficial compared to spending time calling each company to get approval for
individual patients or to become a provider. The provider forms for dietitians are usually
the same as for physicians, but many of the questions are not applicable, and dietitians
are not credentialed the same as physicians, especially in states without licensure. Nutri-
tion provider or credentialing information for contracts and provider agreements varies
between health insurance companies, and within the same company there may be different
benefits, interpretations, and provider agreements by region. A negative complication to
payment for nutrition services is the idea of health insurance companies approving pro-
fessionals for “access.” The nutrition professionals on the list are recommended but the
health insurance company does not provide payment, and the insured have to self-pay.
The billing level does not reflect the reimbursement level. It is important to have a set
fee for any code that is being used, no matter what the reimbursement level. If rates are
set at the expected level of payment the reimbursement will most likely be disappointing,
as most schedules are discounted by payors. Published fees cannot be varied for different
payors, but the fee schedule can be discounted at a set amount for ability to pay or cash
payment. A good practice is to keep track of all patients seen, diagnosis, referring physi-
cian, and charges or amount billed for future use. Certainly the collectibles are only part
of services billed, and nutrition services should be documented to justify diagnosis codes
used on reimbursement claims and provide support for medical necessity.10,11
Key staff in insurance, billing, or information systems can help track billing and code
results and develop procedures to maximize reimbursement. Private practice nutrition
professionals may want to contract out insurance and billing tasks until they become more
familiar with these systems. Claim forms and processing are integral to reimbursement.
Physician offices and some individual certified hospital providers submit claims using
HCFA-1500 and electronic filing. Hospital clinics typically use the HCFA 1450 (UB-92)
form for hospital-employed providers, and most hospital outpatient programs use HCFA
1450 form.
Data on the payor mix is important for assessing contracts, marketing, and reimburse-
ment potential. Cost data analysis helps evaluate if your claims are 80 or 30 cents on the
dollar. A streamlined approach to analysis in a large center with many payors would be
to start with Medicare and the other top four payors.29 Reimbursement may not always
cover costs, but this is important information for decision making and to lobby for changes
in rates. Knowing ahead of time that the dietitian costs are not being covered, such as in
capitated contracts, allows time to present evidence to clinic or facility administrators that
consults are saving physician time or preventing hospitalization and therefore reducing
overall costs.
Conclusion
Medical assessment of nutrition contributes to the diagnosis and interventions that
improve the quality of health care for patients. Access to nutrition care by the patient and
reimbursement of the nutrition professional are inexorably tied to quality outcomes with
cost effectiveness. Nutrition professionals need to actively communicate that medical
assessment and nutrition care are essential components of quality health care with a low
cost versus substantial benefit worthy of healthcare dollars.
Terminology
Capitated Fee — A fixed sum of money per enrollee, paid in advance, for a specified
period of time.
Continuum of care — The array of health services and care settings that address
health promotion, disease prevention, and the diagnosis, treatment, management,
and rehabilitation of disease, injury and disability. Included are primary care and
specialized clinical services provided in community and primary care settings,
hospitals, trauma centers, and rehabilitation and long-term care facilities.
Managed care — According to the Institute of Medicine, “a set of techniques used
by or on behalf of purchasers of health care benefits to manage health care costs
by influencing decisionmaking through case-by-case assessments of the appro-
priateness of care prior to its provision.”
Primary care — According to the Institute of Medicine, “The provision of integrated,
accessible health care services by clinicians who are accountable for addressing
a large majority of personal health care needs, developing a sustained partner-
ship with patients, and practicing in the context of family and community.”
Primary prevention — Measures such as health care services, medical tests, coun-
seling, and health education designed to prevent the onset of a targeted condi-
tion. Routine immunization of healthy individuals is an example of primary
prevention.
Secondary prevention — Measures such as health care services designed to identify

and treat individuals who have a disease or risk factors for a disease but who
are not yet experiencing symptoms of disease. Pap tests and high blood pressure
screening are examples of secondary prevention.
Tertiary prevention — Preventive health care measures or services that are part of
the treatment and management of persons with clinical illnesses. Examples of
tertiary prevention include cholesterol reduction for patients with coronary heart
disease and insulin therapy to prevent complications of diabetes.
Providers — Those providing health care — both individuals (physicians and other
health care providers) and the entities that employ them (hospitals, outpatient
clinics, physician practices, durable medical equipment suppliers).
Payors — Those assuming the financial risk of health claim losses and/or admin-
istering reimbursement for health care claims.
References
1. US Department of Health and Human Services, Office of Public Health and Science, Healthy
People 2010, National Institute of Medicine, Washington, DC, 2000.
2. National Academy of Science’s Institute of Medicine Committee on Nutrition Services for
Medicare Beneficiaries, The Role of Nutrition in Maintaining Health in the Nation’s Elderly:
Evaluating Coverage of Nutrition Services for the Medicare Population, National Academy
3. What is medical nutrition therapy? www.eatright.com/gov/mnt/html, November 30, 2000.
4. US Department of Health and Human Services. International Classification of Diseases, 9th
Revision, Clinical Modification, 6th ed, DHHS Publication No (PHS), 96-1260, US Department
of Health and Human Services, Public Health Service, Health Care Financing Administration,
5. The American Dietetic Association, Medical Nutrition Therapy Across the Continuum of Care, 2nd
ed, The American Dietetic Association and Morrison Healthcare, Chicago, 1998.
6. Rodriguez DJ. Support Line, 21(5), 8, 1999.
7. CDC, National Center for Health Statistics. National Health Interview Survey. Hyattsville,
MD: National Center for Health Statistics, unpublished data, 1999.
8. Donaldson MS, Yordy KD, Kohr KN (Eds.) Institute of Medicine. Primary Care: America’s Health
in a New Era, National Academy Press, Washington, DC, 1996.
9. Ransom SB, Pinsky WW. Clinical Resource and Quality Management, American College of
Physician Executives, Tampa, FL, 1999.
10. American Association of Diabetes Educators, Reimbursement Primer, American Association of
Diabetes Educators and Roche Diagnostics Corporation, Alexandria, VA, 2000.
11. The Medicare program and nutrition services, www.eatright.com/gov/mntcoverrage.html,
December 12, 2000.
12. Kohn L, Corrigan J, Donaldson M. To Err is Human: Building a Safer Health System, Com-
mittee on Quality Healthcare in America, Institute of Medicine, Washington, DC, 1999.
13. US Preventive Services Task Force. Guide to Clinical Preventive Services, 2nd ed, US Depart-
ment of Health and Human Services, Washington, DC, 1995.
14. Voss AC. The Consultant Dietitian, 23: 1; 1999.
15. Halsted CH. Am J Clin Nutr 67: 192; 1998.
16. Byham-Gray LD. Today’s Dietitian April, 31, 2000.
17. Andrews M, Karras, C. STAT Line VII(3): 1; 2000.
18. Committee on Performance Measurement. Health Plan Employer Data and Information Set.
HEDIS 3.0. Washington, DC: National Committee on Quality Assurance; 1997.
19. Clearly PD, McNeil BJ. Inquiry 25: 25; 1988.

20. Larson E. JADA 100: 881; 2000.
21. American Medical Association. CPT 2001: Current Procedural Terminology, Professional Edition,
American Medical Association, Chicago, 2000.
22. American Dietetic Association, Courier, 39(4): 1; 2000.
23. Congressional Negotiations Underway on MNT in Balanced Budget Act Revisions — Action
Alert, Pulse@eatright.org, October 4, 2000.
24. Hodorowicz MA. Money Matters in Managed Care: How to Increase Reimbursement Success in a
Hospital-Based Outpatient Medical Nutrition Therapy Clinic, Lifestyle Nutrition Education and
Counseling; Palos Heights, IL, 1999.
25. Stollman L. Nutrition Entrepreneur’s Guide to Reimbursement Success: A Publication of the Nutrition
Entrepreneurs Dietetic Practice Group, 2nd ed, The American Dietetic Association, Chicago, 1999.
26. How to code for diabetes education services in physician offices without ADA recognition,
Diabetes Education Reimbursement and Policy Report, II(2), October, 2000.
Reimbursement@aadenet.org/gov_frame.html.
27. American Medical Association, HCPCS 2000: Medicare’s National Level II Codes, 12th ed, Amer-
ican Medical Association, Dover, DE, 1999.
28. Smith D. Medicare Nursing Home Enteral Reimbursement Manual: Fraud and Abuse, 5th ed, Ross
Products Division, Columbus, OH, 2000.
29. Maleski PA. Diabetes care center: how to go from a cost center to a profit center, Diabetes
Education Reimbursement and Policy Report, II(1), September, 2000.
29
Body Composition Assessment
Mammals, including man, consist of water, protein, fat, and mineral matter. The assess-
ment of this composition can be direct or indirect. Few studies exist on the direct assess-
ment of body composition of man. Analyses of bodies donated for medical research have
been published.1,2 A total of eight such analyses are available. They were done using
gravimetric analysis methods, with discrete tissue samples held to be representative of
the whole body. Gravimetric methods are those that directly measure the water content
of the sample as the difference in sample weight before and after drying. Fat content is
difference in tissue weight before and after solvent extraction of the sample. Mineral
content (ash content) is the weight of the sample after combustion in a muffle furnace.
Protein content is the amount of nitrogen in the sample multiplied by 6.25 under the
assumption that most samples are 16% protein. The results of these studies are shown in
Table 29.1.
Direct body composition methods are unwieldy for large animals. There is considerable
sampling error because of difficulty in preparing a homogeneous body mixture for sam-
pling. In some instances dissection data (Table 29.2) have been accumulated.3 Direct
analysis is possible for small species, i.e., rodents, but even with these species there are
difficulties attributed to the preparation of a whole body homogenate and sampling errors
associated with nonhomogeniety.
The indirect methods for assessing body composition are more practical. These are listed
in Table 29.3. These methods do not require the death of the donor, and can be used at
intervals to determine whether a given treatment has an effect on certain body compo-
nents. For example, bone mass and density (the mineral component of the body) can be
assessed using an instrument called a dual energy x-ray absorptiometry (DXA). This
machine passes an x-ray through the body and compares the strength of the excitement
of the electrons with a known excitement base. The difference in signal strength is attrib-
uted to the density of the bone through which the x-ray passes. Changes (losses) in bone
mass/density can occur with age, especially in females. Interventions that interfere with
this age-related loss are desirable and can be documented using DXA. For example, Deng
TABLE 29.1
Proximate Body Composition of Adult Humans
% Water 50–70
% Fat 4–27
% Protein 14–23
% Mineral 4.6–6
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TABLE 29.2
Size and Body Composition of Adult Men and Women
Men Women
Age 57 ± 22 76 ± 15
Height (cm) 170 ± 9 158 ± 6
Weight (kg) 64 ± 14 57 ± 11
Skin (kg) 3.9 ± 1.1 3.2 ± 0.6
Adipose (kg) 13.0 ± 7.3 20.8 ± 10.0
Muscle (kg) 25.3 ± 6.7 16.4 ± 3.8
Bone (kg) 10.2 ± 1.5 7.6 ± 1.3
Residual (kg) 11.6 ± 3.5 9.3 ± 5.5
Body mass index (kg/m2) 21.9 ± 3.7 23.2 ± 4.6
Source: Clarys JP, Martin AD, Martell-Jones MJ, et al. Am J Hum
Biol 11: 167; 1999 (with permission).
TABLE 29.3
Indirect Methods for Determining Body Composition
Total body water: dilution of heavy water
Muscle mass: dilution of labeled creatine
Lean body mass: body content of K40 (requires use of whole body counter)
% Body fat: specific gravity (weight of body in air versus under water)
2.118 − 1.354 − 078
% Body fat, calculated: × (% total body water/body weight)
density
% fat = (5.548 – 5.044)/specific gravity
% fat = 100 – total body water/0.732
et al.4 have reported that the effectiveness of hormone replacement therapy is associated
with vitamin D and estrogen receptor genotypes. They documented this association with
periodic DXA determinations of bone mass.
Body fat content can be calculated using either DXA or computer-assisted tomography.5
Investigators have used this technology and compared it with the measurement of skinfold
thickness, and have found a good correlation. Skinfold thicknesses are measured using
calipers at designated places in the body. The most frequent are the skinfold under the
upper arm, the fold over the iliac crest, and the abdominal fold. Using equations (Table
29.4), body fat stores can be estimated.
The body minus its fat store is defined as the lean body mass. This is an arbitrary
designation that assumes that the fat store is not metabolically active, but it is not a correct
assumption from a metabolic point of view. The adipose tissue is a very active tissue,
TABLE 29.4
General Formulas for Calculating Body Fatness from Skinfold Measurements
Males:
% Body Fat = 29.288 × 10–2(X) – 5 × 10–4(X)2 + 15.845 × 10–2 (Age)
Females:
% Body Fat = 29.699 X 10–2(X) – 43 × 10–5(X)2 + 29.63 × 10–3(Age) + 1.4072

X = sum of abdomen, suprailiac, triceps, and thigh skinfolds; age is in years.
Source: Jackson, A. S. and Pollack, M. L. 1985. Phys Sports Med 13: 76-90 (with permission).
Body Composition Assessment 635
having a role in the control of energy balance and a role in the food intake regulatory
system. However, from the body composition point of view, these roles are ignored. Lean
body mass (LBM) can be estimated if one assumes that the fat-free body has a water
content of 72%. The total body water can be measured using heavy water (deuterium) as
a diluent. This water distributes itself throughout the total body and through the appli-
cation of the formula C1V1 = C2V 2 the total body water can be calculated. C1 is the
concentration of the deuterium in the infusate; V1 is the volume of the infusate. C2 is the
concentration of deuterium in the volume of blood withdrawn after a fixed interval
(usually 30 minutes). One then solves for V2, which is the volume of the total body water.
The LBM is then calculated:
LBM = total body water/0.72
The details of body composition measurement have been published, and the reader is
referred to these sources for further information.6-8
References
1. Forbes RM, Cooper AR, Nitchell HH. J Biol Chem 203: 359; 1953.
2. Forbes RM, Mitchell HH, Cooper AR. J Biol Chem 223: 969; 1956.
3. Clarys JP, Martin AD, Marfell-Jones MJ, et al. Am J Hum Biol 11: 167; 1999.
4. Deng H-W, Li J, Li J-l, et al. Hum Genet 103: 576; 1998.
5. Malina RM, Koziell S, Bielicki T. Am J Hum Biol 11: 189; 1999.
6. Jebb SA, Elia M. Int J Obesity 17: 611; 1993.
7. Withers RT, Laforgia J, Heymsfield SB. Am J Hum Biol 11: 175; 1999.
8. Lee RD, Nieman DC. Nutritional Assessment WCB Brown & Benchmark, Madison WI, 1993;
pg 121.
30
The How and Why of Body Composition Assessment
Marta D. Van Loan
Introduction
When it comes to body composition assessment and availability of methods, exercise
specialists, health practitioners, and clinicians must consider the demographic character-
istics of their clients. Age, ethnicity, sex, degree of adiposity, and physical activity are a
few important factors in the selection of appropriate methods and instruments for obtain-
ing the most accurate results. Many methods rely on prediction equations developed from
validation groups with specific characteristics. When these instruments and equations are
used on individuals or groups with characteristics different from those of the validation
group, the accuracy of the results may be questioned. It is also important when selecting
a body composition method to assess the relative worth of the method in terms of the
criterion or reference method used to evaluate the technique of choice. Acceptable refer-
ence or criteria methods include hydrodensitometry (underwater weighing), hydrometry
(isotope dilution), or dual energy x-ray absorptiometry (DXA). These reference methods,
however, are not without errors and assumptions, and cannot be considered “gold stan-
dards” for in vivo body composition assessment.
Reference methods typically focus on the body as a two-compartment system consisting
of the fat-free mass (FFM) and fat mass (FM), and can be of limited use for individuals
whose fat-free mass density and hydration levels differ from the assumed values for this
model. Methods that have been validated against the reference two-compartment model
will systemically underestimate body fatness for American Indian women, black men and
women, and Hispanic women, because the average density of the FFM in these groups
exceeds the assumed value of 1.1 g/cc. This can be avoided, however, if one uses methods
that have been validated against a multi-compartment model which makes corrections
for differences in the hydration level and bone mineral content of the FFM.
Not all body composition assessment is done for the purpose of determining FFM or
FM. Other reasons may include but are not limited to determination of 1) osteoporosis
risk for older women, 2) fluid balance in individuals with renal disease or other disorders,
or 3) monitoring changes in FFM during medical treatment such as AIDS-associated
wasting. In this section a variety of body composition methods will be reviewed and
evaluated regarding their uses, applications, and limitations.
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Ultrasound
Principles
Ultrasound for the assessment of subcutaneous adipose tissue thickness (SAT) was intro-
duced by Booth et al. in 1966.1 The ultrasound method, as its name implies, uses high
frequency sound waves produced by piezoelectrical crystals in a transducer or probe. The
sound waves are “injected” into the skin by placing the transducer over the area of interest.
As the waves pass through the skin they are reflected back or “bounce back” to the
transducer probe when the waves hit different tissue interfaces. When the reflected sound
waves hit the transducer they create a pressure stress on the transducer which is converted
to an electrical signal. A-mode ultrasound instruments (no longer in use) measure the
delay from when the sound was “injected” into the skin until it “bounced” back to the
transducer probe. SAT thickness was then calculated based on the assumption that the
speed of ultrasound transmission through different tissue layers was a constant 1500 m/
sec. Measurements with the A-mode ultrasound had limited precision and were compro-
mised by the occurrence of numerous echos from connective tissue layers within the SAT.
This was especially problematic over the abdomen, the region of most interest.
B-mode and Subcutaneous Adipose Tissue Thickness (SAT)

B-mode ultrasound was an advancement which constructed cross-sectional images of the
tissue thickness from the reflected sound waves. These instruments provide images in
which measurement of the SAT thickness, muscle thickness, and abdominal depth can be
estimated using calipers to measure the thickness of the different tissue layers. Addition-
ally, in the case of pregnancy, images are provided which obstetricians use to assess fetal
development. For SAT measurements a frequency of 5 MHZ is used with an 85 mm
transducer and a wavelength between 0.3 and 1.5 mm. The cross-sectional images can be
saved or “frozen” to allow close examination and assessment of tissue thickness using
electronic calipers that digitally mark the boundaries of the tissue of interest. A monitor
is often used so that images can be enlarged for better viewing and improved accuracy
when placing electronic markers on the tissue edges. In addition, the ultrasound operator
can adjust the black and gray scale levels to allow for brighter images and ease of mea-
surement, especially for abdominal scans of obese individuals and estimation of SAT.
Precision of B-mode ultrasound and calipers is about equal, but ultrasound has a slight
advantage in that a printed hard copy of the image exists which allows for reexamination
if needed. When assessment of body composition of obese individuals is of interest,
skinfold calipers do not always have the necessary range of measurement; often the
subcutaneous layer of adipose tissue is larger than the width that calipers are capable of
opening. This problem does not exist with ultrasound measurements; however, ultrasound
does have two drawbacks: 1) it is moderately expensive, and 2) it lacks portability for use
in field studies.
Ultrasound measurement for SAT in the limbs and trunk has been reported as excellent,
with technical errors of less than 0.2 mm and coefficients of reliability as high as 91 to
98% for most sites.2,3 When making B-mode ultrasound measurement of SAT, ultrasound
gel is applied to the skin surface, to the transducer, and to a bag of gel placed on the skin
to separate the transducer from the skin. The transducer is held at a 90° angle to the skin
surface and with just enough pressure to ensure good contact between the transducer, the
bag of gel, and the skin. Blurred images can be the result of the transducer not aligned at
The How and Why of Body Composition Assessment 639
right angles to the skin surface. To make SAT measurements, the right and left sides of
the transducer are matched with the corresponding sides of the subject, but measurements
of the limb and paraspinal sites are made with the transducer parallel to the limbs and
trunk. Similarly, ultrasound measurements over the suprailiac are made with the trans-
ducer in a direction toward the pubis symphysis. Variations in the alignment of the
transducer are necessary to match the direction of the skinfold measurements.
The use of B-mode ultrasound for the measurement of SAT is similar to that of skinfold
measurements for the estimation of body fat.4 Studies using B-mode ultrasound report
mixed results. Equations to estimate body density from ultrasound measurements of SAT
were reported by Abe et al.5 with an error of 0.0006 g/cc for men and women, as well as
an equation to predict FFM from the muscle thickness measurement of the ultrasound
image. The equations for predicting FFM had errors of 4.4 kg for men and 2.5 kg for women.
Ultrasound for Assessment of Bone Mineral Density

In recent years, ultrasound equipment has been designed for assessment of bone mineral
density of the heel. These instruments measure the velocity or transmission of the speed
of sound (SOS) through the os calcis bone in the heel. The attenuation of the signal at
specific frequencies is related to the density of the bone. One advantage of ultrasound of
the heel, unlike the forearm or hand, is that it is a weight-bearing bone and consists of a
significant amount of trabecular bone. Additionally, ultrasound of the trabecular bone of
the os calcis has little interference from overlying soft tissue. Ultrasound measurements
of the heel provide three basic measurement units: 1) SOS, 2) stiffness, and 3) broadband
ultrasound attenuation (BUA). When done correctly, ultrasound measurements of the heel
are predictive of failure loads of both the proximal femur and vertebra.6 Instruments vary
somewhat among manufacturers; some instruments require the use of a gel as a conductive
medium while others use a small amount of water (100 cc). Additionally, some instruments
require the use of a “shim” under the foot so that all feet, regardless of size, are positioned
in the same location relative to the source of the ultrasound wave. Instruments also vary
in that some have a fixed transducer with a water bath while others have contact ultra-
sound devices with moving transducers. The precision error of the fixed transducer ultra-
sound appears to be about half that of the moving transducer;7 therefore, contact
ultrasounds may be appropriate for determining individuals at risk for osteoporosis, but
they lack enough precision to monitor bone loss or the response to intervention or therapy.
Bioelectrical Impedance Analysis (BIA), Multiple Frequency Impedance

(MF-BIA), and Bioimpedance Spectroscopy (BIS)
BIA Theory and Assumptions
The use of BIA for the assessment of body composition has become very popular during
the past decade because it is noninvasive, reliable, and easy to use. This technique relies
on differences in electrical properties of the FFM and the FM. Impedance (Z) is the resistance
of a conductor to the flow of an alternating current and is composed of two components,
resistance (R) and reactance (Xc). Resistance is the opposite of conduction, and reactance
is the storage of an electrical charge by a condenser for a brief moment. So, impedance is
defined as the square root of the sum of the squares of resistance and reactance:
Z = R 2 + Xc 2 (30.1)
In biological systems, cell membranes function as condensers, and briefly retain some
of the electrical charge. This practice is of little or no consequence for single frequency
BIA but is of some importance for MF-BIA use and will be addressed further in the MF-
BIA section.
In the BIA literature, Z and R are used interchangeably because the reactance component
in biological systems is relatively small. The impedance of the lean body is a function of
the specific resistivity of the lean tissue, the cross-sectional area of the tissue, and the
length of the conductor. This relationship is expressed in the following equation:
Z = ρ L/A (30.2)
where Z is impedance in ohms (Ω), ρ is volume resistivity in ohms* centimeters (Ω × cm),

L is conductor length in centimeters squared (cm2), and A is cross-sectional area. Multi-
plying both sides of the equation by L/L gives:
Z = ρL2/AL (30.3)
where AL is equal to volume (V). Substituting gives:
Z = ρL2/V (30.4)
In biological systems, electrical conduction is related to water and electrolyte distribution

in the conductor. Since FFM contains virtually all the water and electrolytes in the body,
conductivity is much greater in the FFM than the FM. Nyboer8 demonstrated that electri-
cally determined biological volumes were inversely related to Z, R, and Xc. Xc is a small
component compared to R, and since R is a better predictor of Z than Xc, the expression
for the determination of V has become:
V = ρL2/R (30.5)
A simple compartment model would consist of cells in extracellular fluid. The electrolytes
within the intra- and extracellular fluid are highly conductive, while the cell membranes
act as an insulating layer of proteins and lipids. This model is present in Figure 30.1 as
parallel conductive paths where RE and RI represent the resistance of the intra- and
extracellular compartments, and CM is the capacitance of the cell membrane.
Because the human body consists of multiple body parts with differing shapes, sizes,
and geometry as well as differing electrical characteristics, the principles of BIA do not
completely apply. However, the empirical relationship in Eq. 30.5 has been validated and
is used extensively for body composition assessment.
Multiple Frequency BIA (MF-BIA) Theory and Assumptions

The theory behind MF-BIA is not different from that of BIA in terms of the body water
and electrolyte content being means by which electrical current is conducted through the
body. The one difference with MF-BIA is that at least two different frequencies are used.
The theory is that low frequency current can not pass through the cell membrane due to
its capacitance. Therefore, low frequency currents are conducted only through the extra-
cellular fluid (ECF) compartment of the body. Conversely, high frequency current (≥50
FIGURE 30.1
A circuit equivalent model for conduction of an electrical current through the body, where RE represents the
resistance of the extracellular fluid, RI is the resistance of the intracellular fluid, and CM is the capacitance of the
cell membrane.
kHz) is capable of passing through the cell membrane, and thus is conducted through the
total body water compartment of the body. So, MF-BIA has the potential for distinguishing
ECF from total body water (TBW) and, by difference, estimating intracellular fluid, as
shown in Figure 30.2.
This approach, however, still depends on the development of prediction equations using
standard laboratory methods such as isotope dilution for TBW and tracer dilution for ECF.
Again, these prediction equations will vary based on the sample studied, the physical
characteristics of the sample subjects, and whether the individuals represent a “normal”
healthy population or a specific clinical population. There are numerous clinical conditions
for which accurate estimation of fluid compartments can provide valuable information.
Bio-impedance Spectroscopy (BIS) Theory and Assumptions

The basic principle of BIS is similar to MF-BIA in that low frequency current is conducted
primarily through the ECF space, while high frequency current is conducted through
TBW. The difference of these two fluid compartments allows for the estimation of intra-
cellular fluid, which can be considered the same as body cell mass (BCM). The basic
difference between MF-BIA and BIS is that BIS typically operates at 20 to 50 different
frequencies ranging from about 5 kHz to 1 mHz. For each of these frequencies, measure-
ments of resistance, reactance, impedance, and phase are recorded. The values derived
from these measurements when plotted form a curve called an impedance locus, as seen
in Figure 30.3.
The mathematical model to describe this plot is called the Cole-Cole Model.9 This model
produces a semicircular relationship between resistance and reactance with a depressed
FIGURE 30.2
Conduction of low and high frequency currents through the extracellular fluid and the total body water
compartments, respectively.
FIGURE 30.3
Cole-Cole Model of an impedance locus plot with resistance vs. reactance at increasing frequencies.
center. In the BIS technique, this modeling is essentially the only way of independently
analyzing the components of a heterogeneous material, such as the human body.
The prediction of fluid volumes must be adjusted for the mixture effect of having
materials of differing conductive capacity within the fluid being measured. This is done
using mixture theory,10,11 which adjusts for the nonlinear relationship between R and water
volume in a mixed medium system. The mixture effects are greatest at low frequency
because the conductive volume, presumably ECF, is a smaller proportion of the total
volume. Hanai10 developed an equation to describe the effect on the conductivity of a
conducting material having nonconductivity entities in suspension, and hypothesized that
the theory could be applied to tissues with non-conductivity materials ranging from 10 to
90%. This theory requires that at low frequencies, the ECF be considered the conductive
medium, with all other materials as nonconductive. At high frequencies, the combined
fluid compartments of extra- and intracellular fluids are the conductive medium and all
other materials nonconductive.11 This approach has been used successfully by a number
of investigators to monitor changes in ECF, TBW, and FFM under a variety of conditions.12-15
BIA Measurement Procedures

All single frequency BIA instruments are essentially the same, consisting of an alternating
electrical current source, cables and electrodes for introducing the current into the body,
and a device for measuring the impedance and reactance. Although two electrodes have
been used for making BIA measurements, this practice is not common because the two-
electrode configuration requires the use of needle electrodes inserted into the subcutane-
ous layer of the skin to overcome the skin impedance. The most commonly used approach
includes a four- (tetrapolar) electrode arrangement with electrodes placed on the dorsal
surfaces of the hand, wrist, ankle, and foot. This configuration allows for the introduction
of the current into the body through the more distal electrodes (hand and foot), while the
measurement of the impedance to the current is taken from the proximal electrodes (wrist
and ankle). A variety of four-electrode single frequency instruments is available, and most
operate at a fixed frequency of 50 kHz, but amplitudes may differ between manufacturers.
The two most commonly used devices are the RJL model 101 or 103, and the Valhalla
Scientific 1990B, which operate at currents of 800 and 500 µA, respectively.16 Additional
BIA devices include hand-held BIA models17 as well as models that look like bathroom
scales, on which one stands while barefoot. Although all these instruments measure
resistance and reactance, the values among the devices are not always in agreement;16
therefore, one must be careful when picking a prediction equation for body composition
assessment to use equations developed for a specific instrument.
Measurement devices for MF-BIA are not all alike. Some instruments use three frequen-
cies set at 5, 50, and 100 kHz while others use two frequencies set at either 5 and 50 kHz
or 5 and 100 kHz. Again, use of any prediction equations from MF-BIA devices should
be matched with the instrument used when the prediction equation was developed.
Few commercially available BIS instruments use Cole-Cole model as the method for
measuring fluid compartment. The two most often cited instruments are the 4000B or
Hydra-4000 by Xitron Technologies, Inc. (San Diego, CA) and the SEAC (Brisbane, Aus-
tralia). Both of these instruments have been reported to give acceptable results.
BIA Precision and Accuracy

Reliability (getting the same answer when repeat measurements are made on an individual
at a given time) of most instruments is very good, but can be influenced by skin preparation
prior to electrode placement, electrode placement, and test conditions. Variation from day
to day in weight-stable individuals is good, and has been reported to vary by 3 to 10 ohms
or 1 to 2%.16,18 Precision when measuring electronic resistors of known resistance is excel-
lent, and is reported to be less than 0.5%. Other factors that can effect the accuracy of
measurement include time of measurement relative to food consumption, strenuous exer-
cise, alcohol consumption, or other conditions resulting in dehydration. Recommended
guidelines for impedance testing have been standardized, and are outlined in a report
from the National Institutes of Health (NIH).19 Standardized measurement procedures for
single-frequency BIA also apply to MF-BIA and BIS.
BIA Application
Bioelectrical Impedance Analysis (BIA)
Research studies on the validation of BIA for the assessment of FFM and FM are extensive,
and are beyond the limits of this section. However, a brief overview of research with BIA
for the general population, ethnic groups, and children is in order. One of the early studies
which demonstrated the application of a tetrapolar arrangement of electrodes for the
assessment of body composition was that of Lukaski. 20 Lukaski found that the impedance
index, height squared divided by resistance, (HT2/R) was the single best predictor of body
weight, FFM, TBW, and total body potassium (TBK). Numerous other research studies
have documented a strong relationship between the impedance index (HT2/R) or R and
FFM, or components thereof. The single largest set of published BIA data for body com-
position assessment was reported by Segal et al. 21 and consisted of 1567 adults (1069 men,
498 women) ages 17 to 62 years. In this study hydrodensitometry was used as the criterion
method for determination of FFM and FM. Data from four laboratories were pooled and
prediction equations developed for the estimation of lean body mass (LBM) based on
body fatness; over or under 20% fat for men and over or under 30% for women. Initial
fatness level was determined by the sum of four skinfold measurements. Prediction errors
ranged from 1.97 kg LBM for women to 2.47 and 3.03 kg LBM for normal weight and
obese men, respectively. Because the sample size was so large, the Segal study has proven
to be robust and has been successfully cross-validated by other researchers.22,23
The use of BIA for the prediction of TBW and FFM of children has also been studied
by numerous investigators. Typical of these results are the findings of Davies and Preece24
and Houtkooper et al.25 The research conducted by Davies and Preece24 included 26
children and adolescents in whom TBW measurements were made as an indicator of FFM.
Results included the development of a prediction equation for TBW. TBW was highly
correlated (r = 0.97) with the impedance index (HT2/R), and had a prediction error of 1.67
liters. Research by Houtkooper and colleagues25 included an original sample of 94 children,
with cross-validation samples of 68, 25, and 38 from three other research laboratories. The
final prediction equation for children age 10 to 19 years included 225 boys and girls, and
used the impedance index and weight to predict FFM with an R2 = 0.95 and a standard
error of estimate of 2.1 kg.
Prediction equations for use of BIA with different ethnic groups includes white, black,
and Asian adults,26 Hispanic women,23 and West Indians,27 to name a few. The Hispanic
women who were studied were 20 to 39 years of age and had an average body fat of 27%
and a FFM of 43.5 kg. The investigators compared six different BIA prediction equations
in the literature and found that the Segal equations21 and equations published by Lohman
et al.28 and Gray et al.29 gave results comparable to those obtained from hydrodensitometry.
The study by Wang et al.26 included 778 healthy adult men and women ranging from 18
to 94 years and from three ethnic groups: whites 371, blacks 182, and Asians 225. Again,
strong correlations were obtained between the HT2/R and measurements of TBW, FFM,
and TBK. The research conducted on the West Indian volunteers included men, women,
and children ranging in age from 8 to 20 years. The BIA equation used was included in
the standard software package that accompanies the instrument (RJL, Model 103). The
investigators found that the body fat estimates provided by the BIA were similar to those
obtained from hydrodensitometry, and the errors were lower than previously reported.
They concluded that the equations provided in the RJL instrument were appropriate for
a West Indian population residing in the West Indies.
MF-BIA Application
A variety of studies have been conducted to examine the use of MF-BIA for estimation of
body fluid compartments and body composition. An early report by Segal et al.30 used a
trifrequency instrument (TVI-10, Daniger Medical Technology, Columbus, OH) with fre-
quencies of 5, 50, and 100 kHz. Segal and co-workers found a strong relationship between
ECF and HT2/R at 5 kHz, and between TBW and HT2/R at 100 kHz. The prediction
equations developed from this study had an error of estimate of 1.94 and 2.64 L for ECF
and TBW, respectively. Similarly, Van Loan and Mayclin31 also studied multiple frequencies
in an attempt to predict ECF. Using the Xitron-4000 impedance analyzer (Xitron Technol-
ogies Inc., San Diego, CA) they measured R, Xc, Z, and phase angle at 25 frequencies
ranging from 1 kHz to 1.35 mHz. They found that the same frequency that was the best
predictor of TBW was also the best predictor of ECF. In this particular study the impedance
index at a frequency of 224 ohms was the best predictor of both ECF and TBW. In both of
these investigations healthy research volunteers were used. In healthy individuals, where
fluid balance is maintained by normal physiological mechanisms, TBW and ECF are
intricately linked. Therefore, if ECF either increases or decreases, then TBW will also
increase or decrease. In other words, a frequency that is found to accurately predict ECF
will also predict TBW, as in the case of the Van Loan and Mayclin study. In a study with
MF-BIA for predicting water compartments in patients with non-ascitic liver cirrhosis,
Borghi et al.32 used equations developed by Segal et al.30 and Deurenberg et al.33 These
equations used low frequency impedance for the prediction of ECF and a high frequency
current for estimation of TBW. Although the Segal and Deurenberg equations used different
low frequency currents for the prediction of ECF (5 and 1 kHz, respectively), results from
the two equations were similar to each other and to standard laboratory dilution methods.
Likewise, the Segal and Deurenberg equations measured the impedance index at a fre-
quency of 100 kHz for the prediction of TBW and achieved results similar to those obtained
from laboratory dilution techniques. Although the MF-BIA technique appears to give
results equivalent to those obtained from standard laboratory techniques for the prediction
of ECF and TBW, there is a shortcoming. Because multiple regression prediction equations
are used to make estimations for groups, estimates for ECF and TBW compartments on
an individual basis have an error associated with them. Multiple regression analysis results
in smaller individuals being regressed upward toward the group average while larger
individuals are regressed downward toward the group average. Thus, at the low end of
the spectrum the result is an over-prediction of the value, be it ECF, TBW or FFM, while
at the upper end an under-prediction occurs. So, to get the best results possible the user
must be aware of the various prediction equations in the scientific literature and select the
equation that best represents the sample being studied.
BIS Application
More and more studies are available in the scientific literature in which BIS was the
technique by which fluid compartments or FFM were estimated. Four such studies will
be briefly reviewed. Van Loan et al.13 were the first to successfully report the use of BIS
in humans for the assessment of ECF, TBW, ICF, and FFM. Using the Cole-Cole modeling
technique and the Hanai mixture theory, results reported by Van Loan and co-workers
were not different from those obtained by standard laboratory methods. Group averages
for ECF and FFM were identical (14.6 and 45.5 L, respectively), while group averages for
TBW and ICF differed by only 0.1 L or 100 ml. Never before had such close agreement
between a noninvasive bioimpedance method and standard laboratory methods been
reported. A similar experiment was conducted by Cornish et al.34 in healthy adults using
the BIS technique and an SEAC analyzer (Brisbane, Australia). The results of Cornish and
colleagues demonstrated that the estimation was only slightly better than results obtained
by single-frequency BIA and anthropometric measurements. The variability associated
with the SEAC’s estimation of TBW and ECF was 5.2 and 10%, respectively. The difference
between findings reported by Van Loan et al.13 and those of Cornish may be due to different
BIS instruments, instrument sensitivity, variability in the standard techniques for assessing
TBW and ECF, test conditions, etc.; it’s difficult to say. However, the data suggest that
better accuracy was obtained using the Xitron Technologies, Inc. BIS device. Van Loan et
al.14 also used the BIS technique to monitor fluid changes in a group of women prior to
conception, during pregnancy, and postpartum. At 34 to 36 weeks of conception, when
fluid volume is at a maximum, BIS results for ECF and TBW were within about 1 L of
values obtained by standard lab methods; they were about 5% different for ECF and 1%
different for TBW. More recently, Van Loan and co-workers15 reported on the nitrogen
accretion of lean tissue in AIDS-wasted patients using BIS. Based on classic nitrogen
balance techniques, cumulative nitrogen retention over a 12-week period was 5 kg. At 6
weeks, nitrogen retention was 2.5 kg; BIS results indicated an accretion of 2.8 kg; by 12
weeks cumulative accretion by nitrogen balance methods was 5.0 kg, and by BIS was
5.3 kg. These data, in conjunction with other studies, demonstrate that the BIS technique,
using Cole-Cole modeling and Hanai mixture theory, can accurately assess changes in
TBW, ECF, and lean tissue accretion.
Dual Energy X-Ray Absorptiometry (DXA)

Basic Principles and History
Absorptiometry requires a photon or energy source and a detector or counting device.
Early researchers used radionuclide sources such as 125I or 153Gd, but now x-rays are used
to generate the photon energy. Each nuclide source has a characteristic photon energy
spectrum and a half-life of decay. As photons travel through the target tissue, interactions
take place that reduce the beam intensity. This reduction in beam intensity is referred to
as attenuation. Attenuation occurs as photons are either absorbed or scattered when
passing through tissue. It occurs by two main interactions in vivo: Compton scattering and
photoelectric effects. Attenuation of photons passing through a homogenous substance is
a function of photon intensity, mass attenuation coefficient (µm), and mass per unit area
(M). With the DXA method, M represents total mass of the system’s volume element. For
heterogeneous absorbers, like human tissue, transmitted photon intensity is related to the
substance’s fractional mass. Basically, attenuation decreases as photon energy increases
and is greater for substances with larger µms. When photons of two different energies pass
through an absorber, attenuation at the lower energy level can be expressed as a ratio (R)
to attenuation observed at the higher energy level.35 All elements have a characteristic µm
at specific energy levels. For example, hydrogen, with an atomic number of 1, has a µm of
0.3458 at 40 keV (kilelectron Volts) and a µm of 0.3175 at 70 keV, giving a R value of 1.0891.
Elements with higher atomic numbers have larger R values. Thus elements found in soft
tissue, like Na, K, Cl, have higher atomic numbers and larger R values. There are, however,
other elements in vivo with even higher numbers, such as Ca, found primarily in bone.
Thus, it is the R value which allows for the distinction between soft tissue, lower attenu-
ation coefficients, and bone with higher attenuation coefficients. So, the R value of an
unknown element can be used to identify the element because of the known and specific
R values for each element. DXA measurements assume that the body is composed of two
basic compartments, bone and soft tissue. Again, based on attenuation coefficients, soft
tissue can be further divided into two compartments, fat or lean. Therefore, it is the R
value that is used to determine the amount of bone and soft tissue and also the amount
of fat and lean within the soft tissue.
Early devices for the assessment of bone mineral content (BMC) and density (BMD)
used radioisotopes and were either single photon (SPA) or dual photon absorptiometers
(DPA). SPA used iodine-125 (125I) as the photon source (Figure 30.4). This instrument
allowed for the measurement of BMD, BMC, and bone width in the distal end of the radius
and ulna. Cameron and Sorenson36 and Mazess and co-workers37 conducted research
which provided the foundation for validation, standardization, and comparative data for
this early technique.
The second phase of method development for BMD and BMC measurements was the
development of DPA using gadolinium –153 (153Gd) as the photon source. The use of DPA
advanced the technology from a single energy emission to an isotope with gamma emis-
FIGURE 30.4
Single photon absorptiometer using radionuclide source from 125I. Measurement of bone mineral content, bone
width, and bone density is being made of the 1/3 distal radius and ulna of the forearm. Material around the
forearm is “tissue equivalent” material to equalize the size among different individual forearms.
sions at two energy levels, 44 and 100 keV.38,39 This method now included a measurement
surface large enough for an individual to recline and have measurements taken of the
total body, lumbar spine, and femur. In addition to the measurements of BMD and BMC,
this technique now allowed for the assessment of total body composition.40,41 As with all
techniques, this method is not without its limitations. First, the constant decay of the
radioisotope over time resulted in a lack of precision in the BMD measurement for the
same individual and a constant correction of the attenuation coefficient for soft tissue
because of the decaying radionuclide. Another method was needed that was not depen-
dent upon a radioisotope as the energy source for the measurement technique.
Dual energy x-ray absorptiometry (DXA) was the third wave in the development of
this technique for the assessment of bone parameters as well as body composition param-
eters. DXA consists of an x-ray tube, as the replacement for previously used radioisotopes,
and a filter to split the x-ray beam into two distinct low and high energy levels. The use
of two energy levels allows for greater precision in the measurement and estimation of
soft tissue composition, and therefore, greater precision in the measurement of BMC and
BMD. This technical advance resulted in the use of DXA for both bone metabolism studies
and body composition studies. Thus, use of DXA allows for the estimation of numerous
parameters for bone: total body bone mineral content and density (TBBMC or TBBMD)
plus specific sites such as lumbar spine (Figure 30.5) and proximal femur BMC and BMD.
Numerous estimates for body composition can also be made, including total body soft
tissue mass (STM), which consists of lean tissue mass (LTM) and fat mass (FM) (STM =
LTM + FM). Additionally, soft tissue masses can be examined over different regions of
the body.
Measurement of Bone Mineral Mass and Soft Tissue Mass

Estimation of bone mineral mass (g) or bone mineral content (g/cm) can be obtained as
well as bone area (cm). BMD is estimated from these basic units. Since the DXA is only a
two-dimensional scan, actual density can not be determined; rather, bone mineral content
of a given area is measured and adjusted for the width of the bone area, giving g/cm2.
This approach, however, has been validated against neutron activation analysis for the
determination of total body calcium, and has provided the foundation for acceptance of
the DXA estimate of bone mineral content.38 In addition, some animal research has been
done in which chemical analysis of pig carcasses served as the reference by which DXA
was validated. Svendsen et al.42 found good agreement between Lunar DPX (3.2 software)
and fat content with pigs ranging from 35 to 95 kg in body weight. The standard error of
estimate between the DXA estimate and chemical analysis was 2.9%. A similar comparison,
chemical versus instrument, with a Hologic QDR-1000/W and pediatric software (version
6.01) used on small piglets was not as promising;43 the estimates of lean mass were within
6%, bone mineral content was underestimated by 30%, and fat was overestimated by 100%.
In larger piglets (average weight 6 kg) there was good agreement for lean tissue and bone
mineral, but fat was still overestimated by 36%. Since this early work, however, DXA
manufacturers have continued to upgrade instrumentation and software.
The DXA methodology for the measurement of BMC and BMD has its limitations. Jebb
and colleagues44,45 reported that estimates of BMD were affected by tissue depth or thick-
ness, with an increasing error when measuring BMD in tissue greater than 20 cm in depth.
Results reported by Van Loan and co-workers examined how DXA estimates of BMD
and BMC change when body weight changes.46 They observed that when body weight
declined as a result of a weight loss intervention, the DXA measurement of bone area
(BA) changed, presumably because bone edge detection was now easier with less soft
FIGURE 30.5
Image of the spine from a dual energy x-ray absorptiometer (DXA).
tissue attenuation. The net result was a change in the calculation of BMD without a
corresponding change in the BMC. In weight-stable individuals, measurement of soft
tissue composition has been reported to be similar to reference techniques. One such report
was that of Van Loan and Mayclin,47 who compared DXA estimates of body fat and lean
masses to those determined using a four-compartment model for body composition assess-
ment. DXA body composition assessment was in agreement with the results obtained
using this model. These results have been confirmed by others.48 In addition, DXA has
reportedly been useful in the determination of intraabdominal adipose tissue (IAAT).
Treuth and colleagues 49 derived a prediction equation for estimating IAAT using DXA
scans analyzing the upper trunk, lower trunk, and pelvis regions. Anthropometric vari-
ables such as waist circumference and sagittal diameter were also made. These variables
were used in a multiple regression equation to predict the IAAT mass based on images
from computed tomography. This equation can be used in women of varying ages and
body composition.
Equipment
Commercially available DXA instruments have been manufactured primarily by three
companies in the U.S.: Lunar Corp., Madison, WI; Hologic, Waltham, MA; and Norland,
Fort Atkinson, WI. The basis of the measurements for all three instruments is the mass
attenuation ratio (R) discussed above. However, all three instruments do not provide the
same result. Tothill50 reported significant differences among the instruments in the estimate
of percent body fat. When anthropometric models were tested, no differences were
observed between manufacturers; however, there was significant differences in percent
body fat between pairs of instruments when research volunteers were tested, varying 2.6
to 6.3%. Differences in regional body composition indicated trunk percent fat was under-
estimated by Hologic compared to Lunar and Norland, and standard deviations of 4%

suggested inadequate agreement between instruments. Tothill and co-workers concluded
that differences in body fat estimates among the instruments were great enough to preclude
interchanging of instruments on individual subjects and within clinical investigations.
Research reported by Van Loan et al.51 not only found differences in the body composition
assessment between Lunar and Hologic instruments but also found significant differences
in the BMC and BMD values for the two devices. Some of these differences may be due
to physical variations among the instruments. The Hologic model QDR 1000 uses photon
energies at 45 and 100 keV, the Lunar model DPX uses 38 and 70 keV, and the Norland
XR model has energy levels set at 44 and 100 keV. Differences may also be due to variations
in scan areas, pixel area, and calibration procedures. In the ensuing years, DXA technology
has moved from the collimated pencil beam approach of the above three instruments to
a fan beam mode, with the x-ray fan sweeping the measurement area. This fan beam
approach is touted as providing better resolution and precision, shorter scan times, and
less radiation exposure compared to the pencil beam mode. Research by Faulkner et al.52
included cross-validation of Hologic instruments using pencil beam modes QDR-1000W,
QDR-2000, and fan beam modes. They determined that results from the three instruments
were comparable and had low standard errors of estimate. However, research in this area
is limited and requires further investigation to determine how pencil beam and fan beam
results compared with a given company and between the different companies.
Accuracy of DXA
A variety of DXA issues have been discussed here regarding the accuracy of DXA in
measuring different body compartments. The basic tenet has been that DXA does provide
an accurate measure of BMC compared to neutron activation. Several studies have shown
that DXA estimates of soft tissue lean and fat compartments are equivalent to results
obtained from reference methods when used in weight-stable individuals; however, con-
cerns do arise when using the DXA technique for determining BMD in larger individuals,
especially when these individuals engage in a weight loss intervention. DXA has been
shown to be a valuable tool in the estimation of IAAT. Despite these positive outcomes,
all DXA instruments are not “created equal.” Several studies have demonstrated that
differences exist in soft tissue and bone parameters between manufacturers and between
software versions within a given manufacturer. Therefore, one must use caution when
using this technique to monitor individuals longitudinally. In summary, DXA can be used
as a component in multiple-compartment body composition assessment by using just the
BMC values. It can also be used separately as a stand-alone technique for the estimation
of bone mineral, lean tissue, and fat mass. A significant amount of research has been done
to suggest that pencil beam DXA may be viewed as a reference method; however, the
newer fan beam mode of operation has not yet been thoroughly examined. More research
is needed to validate the results using this new approach and determine what, if any,
differences exist between the fan beam mode and the pencil beam mode of operation.
Computed Tomography
Basic Principles
Computed tomography (CT) is another x-ray device used commonly in medical diagnosis.
However, in the 1980s several studies indicated that the technique could be used for the
determination of body composition because images of adipose tissue, muscle, and bone
could be obtained with this technique.53 In this technique, like the DXA, attenuation of an
x-ray signal is the process by which different tissues are distinguished. Many people are
familiar with the “large tunnel” of a CT scanner. Within the structure of the tunnel is an
x-ray tube and detectors. The detectors and x-ray tube are placed opposite one another
so that the detectors can rapidly measure the x-ray attenuation as the x-ray photons pass
through the individual. For a CT scan, the patient lies on a moveable table which positions
the patient in the tube at the appropriate position for the needed image. For example, a
brain CT scan would require specific positioning of the head within the CT tunnel. Once
properly positioned, the x-ray tube rotates around the table while the detectors collect the
necessary attenuation data. A computer then generates an image based on the specific
attenuation coefficient characteristics of the different tissues, thus allowing for the separate
imaging of bone, adipose tissue, and lean tissue. The differences in the attenuation coef-
ficients allow CT to be used for body composition assessment.54,55 The CT attenuation
score, referred to as Hounsfield units (HU) depends on the level of absorption of the
emitted x-ray, and may range from –1000 HU for air to +1000 HU for bone. Research by
Sjöström56 demonstrated that the attenuation score for adipose tissue (AT) was between
–190 and –30 HU.
Accuracy
CT scans are expensive, and this cost has no doubt limited the number and extent of
validation studies. One study, however, conducted by Rössner et al.54 compared direct
adipose tissue thicknesses from cadavers to CT images from 21 cross-sectional abdominal
images and found a significant relationship between the two methods for total adipose
tissue (r = 0.94) and intraabdominal adipose tissue (r = 0.83). Work by Ross and colleagues
on rats demonstrated a relationship between CT images and chemical analysis of lipids
(r = 0.98).57 Validation and accuracy check with this technique are very limited due
primarily to the need for cadaver analysis of humans or chemical analysis of animals.
Body Composition and Visceral Adipose Tissue (VAT) by CT

Whole body composition using CT was investigated by Tokunaga et al.58 using multiple
scans. First, the area within the scan was measured, and then the area between adjacent
scans was measured. Total volume was then calculated. Second, adipose tissue within the
scan area was measured, providing a determination of total adipose tissue within the
region. More extensive work by Sjöström and Kvist59 using 22 scans from head to foot
found that CT estimates of adipose tissue volume were highly correlated to body fat
estimates from tritium dilution, hydrodensitometer, and whole body potassium counting.
These two studies support the use of CT scans for assessment of total body fat as well as
lean tissue that does not rely upon assumptions regarding the constancy of body com-
partments. This method, however, does involve a significant amount of radiation exposure,
requires highly trained technical staff, instrumentation is expensive, and it is not readily
available for body composition studies. Consequently, researchers have tried to limit the
number of scans needed for accurate estimates of abdominal adipose tissue. Després and
co-workers60 demonstrated that the adipose tissue mass in a cross-sectional scan at the
level of lumbar L4-L5 vertebrae was correlated to the total adipose tissue mass in both
men and women. As a result of this work and the work of others, it has been determined
that a single abdominal scan does provide an acceptable estimate of total abdominal
adipose tissue mass.
A major focus of researchers using CT technology for the estimation of adipose tissue
is the association between body fat and chronic disease. More specifically, determination
of at risk individuals for diabetes mellitus, cardiovascular diseases, and elevated plasma
lipid profiles, to name a few, can be improved using CT scans. Investigations61,62 have
shown that obesity with increased levels of VAT was associated with a higher glycemic
response even with hyperinsulinemia, suggesting insulin resistance. VAT was also corre-
lated with glucose tolerance and plasma insulin levels in both men and women. These
relationships were independent of total body fat. Furthermore, obese subjects will smaller
amounts of VAT showed only marginally higher plasma insulin levels compared to control
subjects. It appears that the assessment of total body fat alone can be a misleading indicator
of individuals at risk, and that the more important concern is the amount of adipose tissue
that is sequestered intraabdominally.
Magnetic Resonance Imaging (MRI)

Basic Principles, Acquisition, and Quantification
MRI involves an interaction between the magnet field, generated by the MRI instrument,
and the nucleus of the hydrogen atom. Hydrogen is the most abundant element in bio-
logical systems, and the proton in the hydrogen nucleus acts like a tiny magnet with a
nonzero magnet moment. Typically, an individual is positioned on a moving table and
placed inside the magnetic field. The magnetic field of the MRI instruments is about 10,000
times stronger than the magnetic field of the Earth, and is used to align the hydrogen
protons in a known direction, at which time a pulsed radio frequency (RF) is applied to
the body part within the magnetic field. The hydrogen protons absorb the energy of the
RF and change alignment or directional orientation, like a spinning gyroscope falling out
of position. Once the RF is turned off, the protons release the absorbed energy and
gradually return to their normal position or orientation. The released energy also gives
off an RF signal which is detected. The RF signal from the released energy that is used to
develop the MR images using computer software.
Proton density and the rate at which the absorbed energy is released, referred to as
relaxation time, differs among the different body tissues. The dark and light contrasts in
an MR image are due to the different time parameters associated with the energy release:
1) the time to repeat (TR), and 2) the time to echo (TE) the RF pulse. Variation in the RF
pulse sequence results in manipulation of the TR and TE times. One such variation in the
pulse sequence is called spin-echo, and adjusts the TR parameter for maximum contrast
between adipose tissue and muscle tissue. It is the spin-echo sequence that is routinely
used to assess adipose tissue. All of this takes time, which can be a limitation of this
technique for body composition assessment. The average time needed for abdominal MRI
is about eight minutes, and then the image may include motion artifacts from breathing
and even cardiac contractions (see Figure 30.6). Consequently, new MRI techniques have
included the development of TR and TE so that images can be obtained in a matter of
seconds while an individual holds his breath. These faster techniques are known as FLASH
(Fast and Low Angle Shot) or GRASS (Gradient Recalled Acquisition at Steady State). The
accuracy of these faster techniques has not been thoroughly investigated, but they do allow
for a shorter time period for data acquisition and thus less movement artifact in the image.
Quantification of the tissue masses from the MR image requires a variety of steps. The
image is divided into squares comprising several hundred rows and columns. Each square
FIGURE 30.6
Magnetic resonance image of the abdominal cavity of an individual. Lighter images around the perimeter
represent skin and subcutaneous adipose tissue. Lighter images within the body cavity are visceral adipose
tissue depots. The adipose tissue mass can be quantified by digital analysis of the individual image pixels.
is referred to as a pixel. Pixel values in an MRI are dependent upon 1) the excitation pulse
used, 2) the proton density, and 3) tissue relaxation times, which may vary among indi-
viduals. Additionally, signal intensity may vary within the same tissue in a single acqui-
sition. This is referred to as “ghosting,” and can result in tissue being excluded from the
analysis. This phenomenon has been improved in recent years. However, changes in signal
intensity do require that software programs allow for visual verification and, when nec-
essary, adjustments to include all appropriate tissue. Therefore, adipose tissue quantifica-
tion cannot be done by simply setting an adipose tissue threshold and using software to
count pixels either above or below the designated threshold without manual verification
and correction.
Accuracy
Foster and co-workers63 first reported that MRI could measure adipose tissue and adjacent
muscle tissue. This work was confirmed by carcass and cadaver analysis in which direct
measurements were made of the tissues. Work by Abate et al.64 demonstrated that MRI
measurement of adipose tissue in humans was similar to direct measurement of visceral
and subcutaneous adipose tissue on cadavers. Similar supporting documentation for the
accuracy of MRI has been done by comparing MRI to CT scan results.55 In general, the
relationship between CT and MRI for the assessment of adipose tissue is good, with
correlations ranging from 0.79 for SAT to 0.98 for VAT, and 0.99 for total adipose tissue.
MRI for Body Composition

Unlike CT scans, MR images do not involve a radiation dose, thus making them more
appealing to research volunteers as a method for body composition assessment. MR
images, however, like CT scan, are expensive and generally require multiple scans in order
to obtain adipose tissue distribution information. The number of researchers who have
used MRI is limited. Two different research teams used multiple MRI images over the
entire body. Fowler and colleagues65 acquired 28 images from head to foot, while Ross
and co-workers66 obtained 40+ images from head to foot to determine adipose tissue and
lean tissue distribution in both males and females. Fowler demonstrated that as few as
four MR images could be used, while Ross showed that one image at the level of L4-L5
lumbar vertebrae could be used to predict total adipose tissue volume. MRI has also been
shown to discriminate between visceral and subcutaneous adipose tissue. Measurement
of VAT has been shown to be strongly correlated with complications associated with
obesity. Although MRI has promise as a “reference” method for adipose tissue composi-
tion, more research is needed relative to its accuracy for tissues other than VAT and SAT.
Like CT, the need for highly qualified technical personnel to obtain the images, and the
cost of instrumentation make this technique beyond the reach of most researchers and
clinicians for body composition assessment.
Summary
The techniques discussed in this section are high tech methods, and may not be suitable
for all situations. So, how does one decide which method to use, especially when costs
and technical expertise vary widely among the methods? Appropriate questions might
include the following:
Do I need the information for research or clinical diagnosis?

If for research, do I need greater accuracy and precision to see changes in small
groups of people or are large group trends sufficient?
Will individuals come to the test facility or is the work done in a “field” setting?
For either research or clinical intervention, what body composition parameter(s)
do I need to know?
• Fat Mass
• FFM
• Bone Mass (BMC or BMD)
• Fluid Volumes
• Adipose tissue distribution
What level of technical expertise is needed to get accurate results?

• Does the procedure require highly trained staff and/or licensed staff?
• Can I get my staff adequately trained with minimal difficulty?
• Can I get my staff licensed with minimal expense?
How much will it cost?
• Do I have to contract with a medical facility to do the measurement?
• Can I purchase the instrument and collect the data myself?
More often than not, time and money will be overriding factors in consideration of a
body composition methodology. Thankfully, all the methods discussed in this section do
provide reliable and accurate results when used appropriately.
References
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31
Frame Size, Circumferences, and Skinfolds
Barbara J. Scott
Introduction
Numerous studies conducted over the past 70 years provide a large body of knowledge
and evidence that simple methods of quantifying body size and proportions can be used
in many settings to predict body composition and regional fat distribution. This section
discusses the strengths, weaknesses, and potential best applications of three field anthro-
pometric methods: frame size, skin folds, and circumferences. These methods have been
widely studied and are commonly used because they yield valid and reliable results when
applied correctly and because they are noninvasive, inexpensive, portable, and relatively
simple to perform.
Applications to Practice
Important applications for the measurement and analysis of body composition and body
dimensions using the above methods include:
• Evaluating how individuals or groups are faring in general or in response to

changing economic or political situations (new leadership, prolonged drought
or famine, war, decreased expenditures for health services, increase in number
of individuals or families living in poverty, increased cost of food) (surveillance)
• Monitoring individual response to specific therapeutic interventions (surgery,
medication, chemotherapy)
• Making comparisons of actual with “ideal” (weight for height, waist-to-hip ratio,
level of body fatness)
• Formulating exercise or dietary programs/regimens
• Providing prognostic indicators in certain disease states linked to body compo-
sition (diabetes, certain types of cancer, osteoporosis, cystic fibrosis, HIV/AIDS)
• Providing periodic feedback regarding achievement of goals resulting from life-
style modifications (diet, exercise, smoking cessation)
0-8493-2705-9/01/$0.00+$1.50
• Assessing level of potential risk for chronic disease (cardiovascular, cancer, dia-
betes, osteoporosis) and monitoring relative risk over time
The method chosen depends most often on practical considerations of availability of

equipment, staff (number and expertise of personnel), time, and facilities. The degree of
accuracy or precision needed based on the sample size and purpose for which the infor-
mation is being collected must also be considered. For example, less precision may be
accepted if the purpose is risk assessment or monitoring changes with initiation of an
exercise program than if the information is needed for establishing health policy or making
clinical decisions about treatment or disease prognosis.
Application to Different Populations

Many variables have been found to affect the validity of measurements of body compo-
sition, including age, gender, ethnicity, measurement site selection, weight status, and
health status.1 Therefore, it is imperative that the methods selected are those best suited
to the persons or population being studied. Depending on the setting and application, it
may be necessary to use different methods, different anatomical sites, or to apply different
equations to the same methods.
Reference Methods: AKA “Gold Standards”

Many different methods have been employed over the past seven decades to measure
the composition of the human body,2 and new technologic developments and findings
from validation studies both inform and complicate decisions about which method(s) to
select for a given purpose. A primary consideration in the selection of a method is whether
it can provide valid information for the specific application and population being studied.
Many different tests have been employed to compare body composition from experimen-
tal methods with those from the “gold standard” including: analysis of variance (exam-
ining differences), correlation coefficients (examining similarities), standard error,
coefficient of variation (examining the size of the standard deviation relative to the mean),
level of bias (difference between “gold standard” and experimental measure), regression
analyses to examine unique and additive contributions of different measures in improv-
ing the predictive power of body composition equations, and intra- and interobserver
variance.
There is no absolutely perfect method to measure and find the true value for body
composition in living humans. Thus, indirect methods, most commonly hydrodensitro-
metry (underwater weighing) and dual-energy x-ray absorptiometry (DXA), have been
used as the “gold standards” against which the majority of measures of frame size,
circumferences, and skinfolds have been evaluated.3 The validation studies using under-
water weighing were based on a two-compartment model that divides body composition
into fat and fat-free components and assumes constant densities for these tissues that are
not universally applicable. The more recent availability of DXA technology has provided
a three-compartment method free of assumptions about tissue densities but dependent
on assumptions of software used with the equipment. Differing results from comparisons
of these two methods (ranging from close agreement to significantly higher or lower
values) probably reflect differences in the subjects studied (ethnicity, age, level of activity,
gender, etc). Therefore, even though it is not clear which method yields a “true” value, it
appears that more investigators are leaning toward using DXA as the new standard
Frame Size, Circumferences, and Skinfolds 659
TABLE 31.1
Data Quality and Anthropometric Measurement Error7,8
Goal of Quality
Measurement Terminology, Definitions, and Causes or Contributing Factors
Repeated measures Reliability: Differences between measures on a single subject (within subject
give the same value variability) are not caused by errors in measurement (site or technique) or
physiologic variation.
Imprecision: Different results are obtained for a single subject when measurements
are done either by one person (intra-observer differences) or two or more persons
(interobserver differences) and reflect measurement errors.
Undependability: Different results are due to physiologic factors (such as differences
over the course of a day in weight [due to weight of food eaten or fullness of the
bladder] or height [due to compression of the spine]).
Unreliability: The sum of errors due to imprecision and undependability.
Measurement represents Inaccuracy: A systematic bias is present due to instrument errors or errors of
a “true” value measurement technique.
Validity: Measurement is as close to the true value as it is possible to determine.
because it is more acceptable and easier for the subjects, and because it does not rely on
assumptions about bone mineral content. More recent studies suggest the simultaneous
use of multiple methods is best suited to measuring or accurately examining different
body compartments to establish and/or validate field methods on diverse populations.4
Measurement Error
Once the field method has been selected as appropriate to the purpose or study at hand,
adherence to guidelines for achieving acceptable levels of measurement error5,6 are needed
to evaluate the quality of data collected. (See Table 31.1).
Guidelines for training and certification of measurers direct a repeated-measures pro-
tocol where the trainee and trainer measure the same subjects until the difference between
them is very small. However, the definition of “small difference” is constrained to some
extent by the technique itself (how precise can it be), equipment (how exactly can it be
calibrated, how fine is the scale), and by the magnitude of the potential size of the
measurement itself (measured in many centimeters, such as height versus in few millime-
ters, such as some skinfolds).
Some targets for difference to be achieved to certify competency have been proposed
(Table 31.2).9 Given the limits of what accuracy level is possible, investigators must also
be aware of the proportion of the total measurement represented by the acceptable
difference.10
TABLE 31.2
Recommendations for Evaluating Measurement Differences
between Trainer and Trainee
Difference between Trainer and Trainee
Measurement Good Fair Poor Gross Error
Height (length) (cm) 0–0.5 0.6–0.9 1.0–1.9 2.0 or >

Weight (kg) 0–0.1 0.2 0.3–0.4 0.5 or >
Arm circumference (cm) 0–0.5 0.6–0.9 1.0–1.9 2.0 or >
Skinfolds (any) (mm) 0–0.9 1.0–1.9 2.0–4.9 5.0 or >
Methods
Even though literally hundreds of anthropometric studies have been done comparing
methods and developing predictive equations,11 there is neither clear evidence nor scien-
tific consensus as to which methods, sites, or equations should be used. Thus, the best
practice is to select a method with a preponderance of supporting evidence for the specific
setting, population, and application, use good equipment, train staff well, understand the
limitations, and be able to interpret the results within these limitations. Specific instruc-
tions for taking measurements or locating anatomical sites will not be covered in this
section as detailed anthropometric manuals are available.12,13
Once a method and/or site of measurement has been selected as appropriate to the
purpose for which the information is needed, the next steps include the logistics of
selecting, calibrating, and using equipment, and training and certifying staff in the mea-
surement procedures.
Frame Size
It seems intuitive that fat weight is unhealthy, and that persons with larger frames can
weigh more and still be healthy. While there is general agreement that frame is a valid
consideration in the assessment of weight for height, identifying an exact method for
classifying frame size has been problematic.14 The literature includes a variety of different
concepts of frame size: body type and body proportions (length of trunk relative to total
height), bone and skeletal size and thickness, and muscularity. There are two general
schools of thought, one that frame is primarily a skeletal concept, and the other that it
encompasses the fat-free mass (everything that is not fat including bone and muscle). Most
researchers agree that a valid measure of frame must be independent of body fatness,
while others believe that it must also be somewhat independent of height to be of value
in the assessment of weight. However, studies have shown varying degrees of correlation
of different measures of skeletal size and dimension with height (the linear dimension of
the skeleton) and correlation of measures of both bone and muscle with body weight and
fatness. Therefore, additional criterion for validity of frame size measures have been
proposed:
1. The correlation of the measure with fat free mass (FFM) should be greater than
the correlation of height alone with FFM
2. The measure should have little or no association with body fat beyond that
accounted for by the association of FFM with fat15
Other studies have proposed more generalized methods or observations for classifying
frame according to body type or morphology. The categories of leptomorph, metromorph,
and pyenomorph16 follow the idea that the human body is like a cylinder, and its mass is
determined by height, breadth, and depth.
The main purpose for assessing frame size is to evaluate weight and recommend an
optimal weight that would be associated with the best present state of health and longest
life expectancy. One of the first proposed common uses of frame size was with weight
tables published by the Metropolitan Life Insurance Company in 1954, based on mortality
rates of insured adults in the U.S. and Canada.17 These early tables suggested “ideal”
TABLE 31.3
Approximation of Frame Size by 1983 Metropolitan Height and Weight Tables
Women Men
Height (inches) Elbow Breadth Height (inches) Elbow Breadth
in 1” heels (inches) in 1” heels (inches)
58–59” (4’10”–4’11”) 2 1 4
/ –2 1 2
/” 62–63” (5’2”–5’3”) 2 1/2–2 7/8”
60–63” (5’0”–5’3”) 2 1 4
/ –2 1 2
/” 64–67” (5’4”–5’7”) 2 5/8–2 7/8”
64–67” (5’4”–5’7”) 2 3/8–2 5/8” 68–71” (5’8”–5’11”) 2 3/4–3”
68–71” (5’8”–5’11”) 2 3/8–2 5/8” 72–75” (6’–6’3”) 2 3/4–3 1/8”
72” (6’0”) 2 1/2–2 3/4” 76” (6’4”) 2 7/8–3 1/4”
TABLE 31.4
Frame Size by Elbow Breadth by Gender and Age
Age Males Females
(years) Small Frame Medium Frame Large Frame Small Frame Medium Frame Large Frame
18–24 ≤ 6.6 > 6.6 and <7.7 ≥7.7 ≤5.6 > 5.6 and <6.5 ≥6.5
25–34 ≤ 6.7 > 6.7 and <7.9 ≥7.9 ≤5.7 > 5.7 and <6.8 ≥6.8
35–44 ≤ 6.7 > 6.7 and <8.0 ≥8.0 ≤5.7 > 5.7 and <7.1 ≥7.1
45–54 ≤ 6.7 >6.7 and <8.1 ≥8.1 ≤5.7 > 5.7 and <7.2 ≥7.2
55–64 ≤ 6.7 > 6.7 and <8.1 ≥8.1 ≤5.8 > 5.8 and <7.2 ≥7.2
65–74 ≤ 6.7 > 6.7 and <8.1 ≥8.1 ≤5.8 > 5.8 and <7.2 ≥7.2
Source: Frisancho, A.R., Am. J. Clin. Nutr., 40: 808; 1984.
weights by gender and by ranges of height and frame size (small, medium, and large),
but provided no method or instructions for assessing frame.18 The tables were updated
in 1983 and provided instructions for measuring elbow breadth and applying cutoffs for
classifying frame size using data from the U.S. National Health and Nutrition Examination
Survey (HANES, 1971-75) that were to result in approximately 50% of persons falling in
medium frame and 25% in small and large frame categories, respectively (see Table 31.3).19
When these cutoffs were subsequently tested on a large Canadian sample (n = 12,348
males and 6957 females), they were found to classify only a small percent of the sample
as having large frames, thereby increasing the probability of misclassification into incorrect
frame size categories and consequent unrealistic weight recommendations.20
Practical evaluation of measures of frame size is complicated by several factors including
a lack of national reference standards for any measure except elbow breadth (see Table
31.4). Because frame size can not be directly measured by any single parameter, there is
no “gold standard” by which to judge proposed surrogate measures, nor is there consensus
on how to assign cut points for small, medium, or large frame or a standard upon which
to base expectations of how frame size is (should be) distributed in a normal population.
Different conceptualizations include:
• Distribution by percentiles:
Terciles (equal numbers in each of three frame categories)
Distribution by quartiles where the lowest and highest quartiles constitute
the small and large frame categories, respectively, with the middle two
quartiles combined to indicate medium frame
Distribution by varying “border values” defined at the 15th, 20th , or 25th
and 75th, 80th , or 85th percentiles for small and large frame
• Defining cut-points by standard deviations with medium frame falling within

plus or minus one standard deviation of the mean and those with small and
large frames falling below or above these values.
Many different skeletal measurements, including segmental lengths, breadths, circum-

ferences, and radiographs have been examined for assessing frame size. (See Table 31.5)
These include:
• Wrist and arm circumference

• Elbow, knee, shoulder, chest, hip, wrist and ankle breadths
• Combination measurements:
Ratio of wrist circumference to height,
Frame index ( [elbow breadth (mm)/height (cm)] × 100)
Regression of the sum of bitochanteric and biacromial breadths (large calipers)
on height; and
Ratio of sitting to standing height.
Circumferences
Circumference measurements have been widely examined because they are relatively easy
to perform, inexpensive, noninvasive, and require only a tape measure and minimal
training of personnel. Primary applications include:
• Monitoring brain growth in children

• Monitoring effectiveness of treatments (including physical exercise) to measure
reduction or increase in selected body areas
• As a marker of protein-energy malnutrition
• Estimation of the relative proportion of body weight from fat versus lean both
as an independent measure and as a measure of frame size
• Describing body shape or the relative distribution of body weight using ratios
such as waist to hip or head to chest (children)
Techniques for taking circumference measures are relatively simple. However, signifi-
cant errors can result from improper positioning or placement of the tape and from
differences in tension applied. In general, the tape is placed perpendicular to the long axis
of the body, but exceptions include the head and neck, where the measurement is made
at the widest and narrowest points, respectively. In almost all cases except the head, the
tension on the tape is just enough to place it snug against the skin without causing an
indentation. However, if the purpose of the circumference is to estimate frame size (or
skeletal size), it is not entirely clear whether the tape should be pulled more tightly to get
as close to the bone as possible. Equipment includes a flexible, nonstretchable, relatively
narrow (0.7 cm) tape measure that has metric measures on one side and English on the
other. Special anthropometric tapes are available, such as those already interlocked to slip
over the arm or head, with arrows to make reading the measurement or finding the
midpoint of the back of the arm easier. Detailed instructions for technique for measurement
TABLE 31.5
Selected Validation Studies of Determinants of Frame Size (FS)
Frame Size Measure Subjectsa Methods and Criterionb,d Results
Bony chest breadth 21 n = 2201, , Scotland. a. Bony chest breadth measured by a. Correlation of bony chest breadth to wt > correlation of ht to wt
x-ray b. Wt ↑ about 3.7 kg per each cm ↑ in bony chest breadth
b. Criterion tested: 1, 3, and sig ↑ c. Wt ↑ about 12 kg per FS (S → M → L)
in wt with ↑ in FS d. Wt: bony chest breadth ratio correlated with FFM
Ratio of height (cm) to wrist 100 and adult patients at a. Wrist measured distal to styloid a. Method for assigning frame size not stated. It appears that some
circumference (cm)23 a university medical center, process at wrist crease on right sort or “normal” distribution was applied, but no other criteria
USA arm of validity were tested.
b. Frame size (S, M, L) assigned b. FS assigned by Ht:wrist ratio:
using this ratio by gender S > 10.4; M 9.6-10.4; L < 9.6;
S > 11.0; M 10.1-11.0; L < 10.1
Elbow and bitrochanteric n = 16,494 ; age range: 18 to a. Criterion tested: 1, 3, and 4 a. Correlation coefficients of weight, elbow, bitrochanteric breadth
breadths24 74; and ; black and b. Body fat determined by sum of to log-transformed sum of skinfold values done by gender by 3
white; USA NHANES 1971- triceps and subscapular age groups by race demonstrate lowest correlation with elbow
1974. skinfolds breadth.

b. Categories of SML FS established for elbow breadths with cut
points at the 15th and 85th percentiles (values given by gender,
race, and age group) demonstrate significant gender differences
and some racial differences.
c. Greater differences were observed for mean weights of subjects
when they were categorized by FS (S, M, L) versus height (short,
medium, tall) demonstrating that FS is more effective in weight
discrimination
Elbow breadth21 n = 21,752; “adults” age range: Based on this large data set, a. Values of elbow breadth for S, M, L FS are given for males and
25-54; “elderly” age 55-74; percentiles of weight, skinfolds females by age. (See Table 31.4)
and ; multiracial; USA (triceps, and subscapular), and b. These standards can be used to identify persons who are at risk
NHANES I and II. bone-free upper arm muscle were of being undernourished or overfat.
developed by height, gender, and
FS (using elbow breadth) for two
age groups
Height (H) and sum of mean age = 22; n = 113 , 182 a. Criterion: 3,5 a. Criterion satisfied.
biacromial (A) and ; H; university students; Ht b. Bivariate model developed b. For differences in wt between FS primarily due to differences
bitochanteric (T) (HAT and Wt representative of US based on height (H) and sum of in FFM
method) population for this age biacromial (A) and bitochanteric c. For there was small but sig. increase in FM per FS but no
Body fatness estimated by group; Caucasian, USA. (T) breadths increase in FFM per FS
hydrostatic weighing25 c. Boundaries for FS (S, L) set by d. FS equations: ht (8.239) + (A + T); ht (10.357) + (A + T)
gender using mean ht ± 1 sd e. HAT FS boundaries: S <1459.3; M 1459.4-1591.9; L > 1592.0;
663
S <1661.9; M 1662.0-1850.7; L >1850.8

664

Selected Validation Studies of Determinants of Frame Size (FS)
Frame Size Measure Subjectsa Methods and Criterionb,d Results
Wrist, biacromial, elbow, hip, n = 225 and 215 ; age a. Criterion: 5-6 a. All bone breadth measures were shown to be associated with
knee, and ankle breadths range =18-59; b. Differences in lean weight FFM.
Body fatness estimated by Canada, Quebec City, French between FS categories (assigned b. Biacromial, elbow, hip, and knee did not meet criterion 6.
hydrostatic weighing15 descent. Tended to be leaner by terciles) > differences in % c. Both criterion satisfied for wrist and ankle breadths. (Data not
than either Canadian or US body fat shown for FS cut points.)
reference populations.
Actual FS (AFS)c n = 17; × age = 20.9 ± 1.4; H; a. Criterion: 1-5 and correlation a. Lack of agreement in assigning FS between methods 2-5.
Body composition ; Caucasian; UK with proposed measure AFS b. Criterion satisfied: ankle breadth and elbow breadth 1-5; AFS and
determined by JP, Br26 hand length 1-3 and 5; HAT 1-3; chest breadth 1-4; wrist breadth
2,3; height:wrist 3.
c. Additional correlations: ht → wt r = 0.68 (s); ht → FFM r = 0.70
(s); FFM → FM r = 0.20 (ns)

Frame index5,27 n = 21,648 ; 21,391 Developed: a. Graph of median curves for frame-specific BMI by age (18-64)
(sample size planned for a. Percentile curves for weight, demonstrate important differences with age and gender and
96% statistical confidence); height, BMI by gender and age consistently higher BMI with for larger frame.
age range = 18-70; Germany b. Three categories of frame index b. Graph of median curves for frame-specific % BD by age (18-64)
using 20th and 80th percentiles also demonstrate age and gender differences and consistently
as border values higher body fat with larger FS.
c. Median values for BMI and % BF c. Values used for cut points for frame index (at the 20th and 80th
by gender and age for each FS percentiles by gender and age) are not given for this sample.
However, those published by Frisancho (derived from US
NHANES data) could be used for other studies.
Biacromial, bi-iliocristal, n = 2512 a. Criterion of effectiveness, a. All 4 breadth frame measures were positively associated with BF
wrist, and knee diameters age range = 45-59 improvement in correlation of (range of r = 0.16 [wrist] – 0.45) and height (range of r = 0.32 –
and sitting height South Wales BMI with body fatness when 0.43). (Correlation of sitting height with BF or total ht not
Body composition: DW28 BMI is adjusted for FS reported.)
b. Adjusting BMI for FS did not improve the association of BMI with
BF.
c. Correlations of the BMI adjusted for FS by wrist and sitting height
(both r = 0.74) were essentially the same as for BMI alone (r = 0.76).
d. Correlations of the BMI adjusted for FS by biacromial, bi-iliocristal
and knee diameters (range of r = 0.60 – 0.66) were lower than for
BMI alone (r = 0.76), indicating a possible inflating effect of
subcutaneous fat on these diameter measures.
Elbow breadth and n = 42 ; 38 a. Criterion tested: 3, measures a. Criterion 3 met for but not .
height:wrist ratio age range = 18-55; USA result in normal distribution of b. Both measures resulted in a FS distribution highly skewed to
Body composition: BIA-Lu29 FS, and produce the same FS in small frame (53-73% of subjects) with 0-3% in large frame.
an individual c. These two FS measures produced the same FS in 69% of the
subjects.
Arm and wrist n = 300 (71 and 229 ); a. Criterion tested: 3 and a. Distribution of FS designation varied by determinant but was not
circumferences; ankle, elbow mean age = 72.6 ± 5.1; H; agreement across methods in influenced by age.
and wrist breadths; Caucasian; Midwest, USA classifying FS b. Visual assessment and elbow breadth19 classified about 75% of
subscapular skinfolds; frame subjects as medium frame. Elbow breadth21 and Frame Index 25
index 2; ht and wt; visual resulted in more even distribution of FS.
assessment.30 c. Association with “fatness” (subscapular skinfold) was noted for
women with elbow breadth and for men with height:wrist.
d. Ankle and wrist breadth had lowest correlations with subscapular
skinfold, but lack of population-based standards limits their
application.
Wrist and knee width used as n = 120, matched for age, a. Measured % BF compared by a. % BF differences observed between groups for the same BMI, with
FS measures; ht and wt; gender, and BMI. China matched BMI between ethnic % BF ↑ with ↑ FS.
sitting ht (Singapore and Beijing groups b. % BF calculated vs. measured not different for Beijing Chinese
Slenderness index (ht/wrist + Chinese) and Netherlands b. % BF calculated from BMI and Dutch.
knee width) (Caucasian) compared to measured c. % BF calculated underpredicted true value by 4% in Singapore
% BF measured by UWW and c. Skeletal mass calculated from ht, Chinese.
BIA.31 wrist, and knee width d. Differences in FS are at least partially responsible for differences
in relationship of BMI → % BF among different ethnic groups.
a Footnotes: Subjects (all information provided in the original reference is given): n = number of subjects; age in years; health status: H = healthy; gender: = male; = female.
b Criterion applied: 1 = highly correlated with weight; 2 = highly correlated with fat free mass (FFM); 3 = minimally correlated with body fatness; 4 = minimally correlated
with height; 5 = correlation with FFM is greater than the correlation of height alone with FFM; 6 = little or no association with body fat beyond that accounted for by the
association of FFM with fat.
c In this study, the authors propose a reference measure “actual FS” comprised on the sum of a battery of 22 different skeletal measures (11 breadths, 9 lengths, and 2
depths) as described in text of Logman et al.12
d Methods for determing body composition: UWW = underwater weighing; BIA = bioelectrical impendance analysis; JP = regression equations of Jackson and Pollack;32,33
Br = formula of Brozek et al.;34 DW = regression equation of Durnin and Wormersley;35 BIA-Lu = bioelectrical impedance analysis using the equations of Lukaski et al.36
e Abbreviations: FS = frame size; S, M, L= small, medium, large; ht = height; wt = weight; FFM = fat free mass; FM = fat mass; % BF = percent body fat; r = correlation
coefficient; sig = statistically significant; ns = not statistically significant; sd = standard deviation.
665
of the head, neck, chest, waist, abdomen, hips or buttocks, thigh, calf, ankle, forearm, and
wrist are described by Callaway et al., who recommend intra- and intermeasurer limits
of agreement of 0.2 cm for relatively small sites (calf, ankle, wrist, head, arm, forearm)
and 1.0 for the large sites (waist, abdomen, buttocks, chest).37
One of the most commonly measured and clinically practical anthropometric methods
is the arm muscle area. This method was originally developed for use in the field for the
evaluation of undernourished children.38 Arm circumference and tricep skinfold measure-
ment can be used to compare an individual to a reference population39 and estimate the
relative proportion of fat and muscle40 or to estimate the severity of undernutrition in
seriously ill hospitalized patients.41 The use of arm circumference has importance when
either undernutrition or overnutrition are of concern, and it can be easily used in the field,
hospital, or community setting. Similarly, head circumference is a common measurement
for infants in the first two to three years of life and can be plotted on standard growth
charts to be compared with population norms.
Because of some of the difficulties of applying traditional height-weight tables to indi-
viduals who are either very lean or very fat and because of the practicality of doing
circumference measurements, various researchers have evaluated the validity of using
circumferences to estimate body composition and physical fitness (see Table 31.6). Using
underwater weighing as the “gold standard,” tables have been developed to estimate
percent body fat within 2.5 to 4% for women and men using the following circumferences:
Young Women Older Women Young Men Older Men

(ages 17–26) (ages 27–50) (ages 17–26) (ages 27–50)
Abdomen Abdomen Right upper arm Buttocks
Right thigh Right thigh Abdomen Abdomen
Right forearm Right calf Right forearm Right forearm
Source: Katch, F.I. and McArdle, W.D. in Nutrition, Weight Control, and
Exercise, Lea & Febiger, Philadelphia, 1988.
The U.S. Navy requires personnel to pass certain physical fitness screening tests includ-
ing having an appropriate weight for height. In this setting it is quite important to use a
method that provides more specific information than traditional height-weight indices in
differentiating individuals who have excess lean weight from those individuals with excess
fat. Because of the large numbers of potential recruits and enlisted personnel being mea-
sured, practicality is also very important. Equations using circumference measures have
been used to estimate percent body fat and body density since the early 1980s.
Skinfold Measurements
The skinfold (sometimes referred to as fatfold) technique is performed by pinching the
skin and underlying fat at a given location between the thumb and forefinger, pulling the
fold slightly away from the body, placing calipers on the fold, and measuring its thickness.
Some skinfold sites are relatively easy to locate and measure, while others are not. Many
individual factors can affect the accuracy of skinfold measurements:
• Degree of leaness or fatness

• Muscle tone (including presence of muscle wasting)
• Changes with growth
• Younger or older age (as they affect accuracy of assumptions about tissue com-
position, muscle tone, skinfold compressibility, and elasticity)
TABLE 31.6
Selected Validation Studies of Circumference Measures
Circumference Site(s) Subjectsa Methods Results
Waist, hip 43 n = 18 and 22 , BMI IAF measured by MRI, and central In obese , DXA, waist and hip were equally well correlated with IAF
≥30; Scotland. abdominal fat measured by DXA. (r = 0.74, 0.75, 0.70, respectively)
In obese , only DXA was moderately correlated with IAF (r = 0.46)
Neck, abdomen, thigh44 n = 5710 and 477 , Navy % BF estimated from standardized Estimates of percent body fat derived from these circumference
personnel, USA Navy equations for men {% Body Fat measurements and equations correlated better with performance on the
= (0.740 × abdomen) – (1.249 × neck) Navy’s physical fitness tests than did commonly used weight-height
+ 0.528a indices
2. Body Density = –[.19077 × Log10
(abdomen – neck)] + [.15456 × Log10
(height)] + 1.0324; Percent body fat =
[(4.95/body density) – 4.5] × 100a} and
women {% Body Fat = (1.051 × Biceps)
– (1.522 × forearm) – (0.879 × neck) +
(0.326 × abdomen) + (0.597 × thigh) +

0.707a}
% BF estimates correlated with 3
measures of physical fitness
Waist, hip48 n = 32,978; age range = 25- Identification of obesity compared by Sensitivity was lowest in populations with fewer overweight individuals
64; participants in 19 cut points for waist circumference at and highest in populations with more overweight. Use of waist cut points
and 18 populations 2 levels (1. ≥ 94 cm; ≥ 80 cm; 2. vs BMI or WHR cut points would correctly identify most people without
participating in a WHO ≥ 102 cm; ≥ 88 cm) vs cut points obesity but miss some with obesity. Optimal screening cutoff points for
MONICA project. for BMI (≥ 25 kg/m2) and WHR ( ≥ waist circumference may be population specific.
0.95; ≥ 0.80).
Waist, hip umbilical49 n = 91, ; age range 20-54; % BF by DXA compared with %BF Comparability and precision of % BF estimates from predictive equations
BMI: 18-34 kg/m2 from predictive equations. can be improved by adjusting for umbilical circumference and BMI.
Waist, hip50 n = 385 (140 and 245 % BF by DXA and BIA. BF distribution % BF < % vs &, upper body obesity > % vs & even in older age;
); mean age = 80 (range by skinfolds. Strong age adjusted correlations among obesity measures (BMI, %BF
= 65-96); USA. [DXA & BIA], skinfolds) were observed for both % and &;
Weak associations among measures of upper body obesity differed by
gender .
a Subjects (all information provided in the original reference is given): n = number of subjects; × age = mean age (years); gender: = male; = female.
b Methods for determining intra-abdominal fat: MRI = magnetic resonance imaging.
c Methods for determining body composition: UWW = underwater weighing; DXA = dual energy x-ray absorptiometry; DD = deuterium dilution; TBK = total body
potassium; BIA = bioelectrical impedance analysis; SKF = JP = regression equation of Jackson and Pollack;32,33 Br = formula of Brozek et al.;34 DW = regression equation
of Durnin and Wormersley;35 BIA-Lu = bioelectrical impedance analysis using the equations of Lukaski, et al.36
d
667
Abbreviations: IAF = intraabdominal fat; WHR = waist to hip ratio; ht = height; wt = weight; BMI = body mass index; ffm = fat free mass; fm = fat mass; % BF = percent
body fat; r = correlation coefficient; sig = statistically significant; ns = not statistically significant; sd = standard deviation.
• Subject cooperation (small children may be frightened or uncooperative)

• Ethnicity
• Health status (bedridden vs. ambulatory)
• Hydration status
Use of this method relies on two main assumptions: 1) skinfolds provide good measures
of subcutaneous fat; and 2) there is a good relationship between subcutaneous fat and
total body fat. The ability to predict total body fat varies by site, with some sites highly
correlated with total fat and others relatively independent of total fat. Studies show that
the relationship between subcutaneous and total body fat (ranging from 20 to 70%) is
affected by age, gender, degree of fatness, and race.51-53 Thus, it is important to review the
literature carefully and select sites and predictive equations that have been validated for
the population being measured and provide sufficient precision for the desired application.
Guidelines for skinfold measurement technique, location of measurement sites, and
information on reliability of measurement at the various sites have been published.54
Considerable supervised practice is required before an individual can take accurate skin-
fold measurements. Training by an experienced person should be conducted, and mea-
sures practiced until consistency is achieved between the expert and trainee and by the
trainee on within-subject repeated measures. Experts agree on the importance of using
standardized techniques in both locating the site and using calipers to take the measure-
ment, yet some argue that in light of the many biologic variables affecting body compo-
sition, technical errors in skinfold measurement are of comparatively little importance.55
Nonetheless, given a standard level of training and care in measurement, high levels of
reliability can be achieved (see Table 31.7).
Many different models of skinfold calipers are available, but only those designed to
maintain a constant tension (10 g/mm) between the jaws should be used. However, even
with the higher quality calipers, there is a difference in the pressure exerted by the jaws
and therefore in the degree of compression of the skinfold.56 Differences in compression
have also been attributed to differences in caliper jaw surface area such that calipers with
smaller surface area and lighter spring tension (such as the Lange) give larger values than
TABLE 31.7
Reliability of Selected Skinfold Measurement Sites
Site Intermeasurer Error Intrameasurer Error
Subscapular SEM: 0.88 to 1.53 mm SEM: 0.88 to 1.16 mm
Midaxillary SEM: ± 0.36; 1.47 mm (children); ± 0.64 mm SEM: Children: ± 0.95 mm
(adults) Adults: ± 1.0,1.22, 2.08 mm
Pectoral (chest) R: .9, .93, .97; SEM: 2.1 mm R: .91 to .97 mm; SEM: ± 1-2 mm
Abdominal R: .979; SEM: 0.89 mm
Suprailiac SEM: 1.53 mm (children); 1.7 mm (adults) R: .97; SEM: 0.3-1.0 mm
Thigh R: > .9, .97, .975; SEM: ± 2.1, ± 2.4, 3-4 mm R: .91, .98, .985; SEM: 0.5-0.7 mm, 1-2 mm
Medial calf R: .94, .98, .99; SEM: 1.0-1.5 mm
Tricep SEM: 0.8-1.89 mm SEM: 0.4-0.8 mm
Bicep SEM: ± 1.9 mm SEM: 0.2-0.6, ± 1.9 mm
a Information in this table has been summarized from Harrison GG, Buskirk ER, Carter JEL, et al. Skinfold
Thickness and Measurement Technique. In: Lohman TG, Roche AF, Martorell R. Anthropometric Standard-
ization Reference Manual. (1988) Champaign, IL: Human Kinetics. pp 55-80. This chapter includes the
specific citations for the reliability studies.
b Abbreviations used: SEM: Standard error of measurement; R: reliability coefficient.
c Multiple error estimates represent differing results from different studies.
calipers with larger surface area and tighter spring tension (Holtain and Harpenden).57
Because of these differences attributable to the calipers themselves, it is important to
calibrate often,58 and to consistently use the same equipment in order to compare data
within or across subjects.
Importance of Frame Size, Skinfolds, and Circumferences to Disease Risk

A variety of approaches have been employed to better understand the validity of using
these field measurements for the assessment of risk for the most prevalent and serious
diseases: heart disease, diabetes, cancer, and osteoporosis. Major interest has been in
evaluating these measures for their ability to measure, estimate, or predict:
• Total fat or percent body fat

• Fat or weight patterning or distribution
• Skeletal size or density
• Biochemical markers such as lipids and insulin sensitivity/resistance
• Health outcomes such as elevated blood pressure, morbidity or mortality (cancer,
diabetes, coronary artery disease, myocardial infarction)
The preponderance of studies relating anthropometric measures to disease have been

in the area of cardiovascular disease (CVD) in an attempt to identify potentially modifiable
body factors and to understand potential markers for and predictors of disease. An
extensive summary of studies done in men illustrates the methodological and statistical
difficulties that are encountered when assessing the relationship between CVD and var-
ious body measurements.59 In general, studies have not shown a consistent relationship
between obesity and CVD using a variety of measures (weight for height, relative weight,
total body fat, etc.). The strength of association between central fat distribution and CVD
is stronger than that of body fat alone, yet a large percent (30 to 50%) of the variation
remains unexplained. Potential sources of difficulty in conducting these studies include
inability to identify adequate surrogates for obesity, confounding effects of cigarette
smoking or subclinical disease, short followup periods, and inadequate methodology for
identifying subgroups of obese persons who are at risk. For example, several studies
suggest that persons who have undesirable patterns of body fat distribution that develop
early in life may be at increased risk.60,61 While one study of three distinct populations
found a consistent direct association between abdominal obesity as measured by waist
circumference and waist:hip ratio and dyslipidemia,62 others have found the sagittal
abdominal diameter to be a better predictor of risk than BMI, waist circumference, or
waist-to-hip ratio.63,64
Several studies evaluating the ability of simple anthropometric measures to identify
those at risk for low bone mass and fractures have found a strong association between
weight and bone mineral density (BMD), while others have not. (See Table 31.8). Possible
factors affecting the relationship between body weight and/or size and bone mineral
density include simple mechanical loading (a larger and heavier body will need a stronger
skeletal support), the influence of endogenous sex steroids, and possibly muscularity
(either directly by its contribution to total body weight or indirectly by its association with
increased activity). For these reasons, anthropometric measures related to gender-related
weight distribution (central versus lower body), FS, and measures of muscularity/adipos-
ity have been investigated for their value in estimating BMD.
TABLE 31.8
670
Selected Studies Examining the Relationships between Anthropometric Measures and Bone Mass or Bone Mineral Density
Anthropometric Measures Subjects Methods Results
a. Frame: biacromial, biiliac, n = 342; mean age = Correlation of anthropometric a. For all skeletal sites one frame measure (biacromial width [BW]), one
bicofemoral, bicohumeral, and 44.1 (range = 25- measures to: skinfold (subscapular[SSF]) and one circumference (calf[CC]) provided
wrist breadths; 79); ; USA a. Measured (photon the strongest correlations.
b. Skinfold: triceps, biceps, forearm, absorptiometry) bone mineral b. The greater trochanter was more strongly correlated with all
subscapula, suprailium, calf, density (g/cm2) at the radius, anthropometric measures than any other skeletal site.
abdomen, thigh; femoral neck, Ward’s triangle, c. After inclusion of age, BW, SSF, and muscularity in multiple regression
c. Circumferences: calf, waist, trochanter, lumbar spine model, BW was a significant predictor for all sites except the radius,
upper arm, abdomen b. Constructed summary bone and SSF and muscularity were significant for all sites.
d. Height and weight65 density score (radius, spine, d. Neither height nor weight contributed significantly to the model after
femoral neck) BW, SSF, and CC or muscularity were included.
Muscle mass (termed e. Despite the strength of the associations, none of the models accounted
“muscularity”) estimated from for more than 40-45% of the variability in bone mass at any site and
circumferences and skinfoldsa therefore are not adequate to predict bone mass for individuals.
Multiple regression models f. No measures of distribution of body fat were significantly associated
constructed to test the usefulness with bone mass.
of measures in predicting bone g. Cross-sectional data not adequate to address questions of rates of bone
mass. loss.
a. Elbow breadth n = 6705; Bone mineral density (BMD) a. Weight was the major determinant of BMD at all sites, explaining 6-
b. Height, weight and BMI mean age = 71.2 ± 5, measured by single-photon 20% of the variability. (Weight explained more of the variability at
c. Waist:Hip ratio67 Non-black, USA (proximal and distal radius and direct weight bearing sites — proximal femur and os calcis.) Effect of
calcaneus) and dual-energy x-ray weight on BMD did not seem to vary with age. (Age had independent
absorptiometry (lumbar spine and significant effect on BMD decline.)
proximal femur) b. Although the measures of BMI, elbow breadth, height, and waist:hip
Adiposity measured by bioelectrical ratio resulted in statistically significant (P<0.001) improvements in fit
impedance of the model, they added very little explanatory power over weight
alone.
c. A modest proportion of the weight effect was explained by adiposity
(36-63% at weight bearing sites and 8-12% at forearm sites).
d. These data suggest that both mechanical loading and metabolic
mechanisms affect BMD.
Waist:Hip ratio, wt, BMI, arm n = 1873 (97% Bone mineral content (BMC) and Body wt., BMI, arm muscle and fat sig > in N than either OPN or OPR
muscle and fat area post-menopausal), density (BMD) evaluated by DXA groups.
Italy as normal (N), osteopenic (OPN) or WHR not different between groups.
osteoporotic (OPR) Wt and age sig predictors of BMC and BMD but high levels of variation
in BMC for the same level of wt (under, normal, over) negate its
usefulness as a predictive indicator.

Conclusion
Even though there is an extensive body of literature examining the validity of using
measures of frame size, circumferences, or skinfolds to predict disease risk or disease
outcomes, conclusive findings and consensus on which measures are best remain elusive.
Nonetheless, the ability of researchers to build on the lessons learned from these early
studies and apply emerging new technologies give reason for optimism about reaching
the goal of using simple, inexpensive techniques to improve individual and public health.
References
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32
Height, Weight, and Body Mass Index (BMI)
in Childhood
Christine L. Williams and Mary Horlick
Introduction
In childhood, height (stature) and weight are the two most frequently used measures of
growth and nutritional status. In addition, indices of weight-for-height, especially BMI,
are used as a proxy for body fatness or obesity. Since growth is the most sensitive indicator
of overall health in childhood, it is essential that accurate measurements be made on a
regular basis during routine health supervision of children and adolescents to identify
and address significant deviations in a timely manner.
Pediatric health professionals take two basic anthropometric measurements on each
child: recumbent length (for children under two years of age) or standing height (for children
over two years of age) and weight. From these two measurements, body mass index (BMI)
can be derived from a reference chart or calculated by formula. This section will focus on
these three measures: height (or length), weight, and BMI. For each measurement the
following aspects will be discussed: definition, normal patterns of change, measurement
techniques, and interpretation of values using reference growth charts. Since most prac-
ticing pediatricians in the U.S., as well as other health professionals who care for children,
record their measurements in inches and pounds, these units will be used in the discussion.
Height
Description
Height, or stature, is a linear measure from the base on which the child is standing, to the
firm top of the child’s head. Height is measured in children over two years of age. It is
measured with the child standing with erect posture, and without shoes. From birth to
two years of age, the infant or toddler’s stature is measured as recumbent length. This is
the total length of the child from the bottom of the feet (positioned at a 90-degree angle)
to the top of the head. Recumbent length is slightly greater than standing height measured
in the same individual.
0-8493-2705-9/01/$0.00+$1.50
Normal Patterns of Linear Growth in Childhood

Normal changes in height (or length): during the first year of life, babies increase in
recumbent length about 10 inches on average, from about 20 inches long at birth to 30
inches by their first birthday. During the second year of life their length increases by 4 to
5 inches, or about 1/4 inch per month. After age 2 years, height is measured in the standing
position. Growth continues at a slower but steady rate of about 2 1/2 inches per year until
about the age of 11 in girls and 13 in boys, when the growth spurt associated with puberty
and adolescence usually begins. Puberty is characterized by a greater rate of growth,
culminating in a peak height velocity (inches grown per year) comparable to the rate of
growth during the second year of life. The peak height velocity for girls is about 2 1/2 to
4 1/2 inches/year, and for boys is about 3 to 5 inches/year. For both boys and girls,
however, puberty and the pubertal “growth spurt” may occur several years earlier or later
than average and still be within a normal range. Normal growth stops when the growing
ends of the bones fuse, which usually occurs between 14 and 16 years of age for girls, and
between 16 and 18 years of age for boys.
Normal Growth Rates During Childhood and Adolescence

Growth Rate (per year)
Age Inches (in) Centimeters (cm)
0–1 year 7–10 18–25
1–2 years 4–5 10–13
2 years to puberty 2–2 1/2 5–6
Girls: pubertal growth spurt 2 1/2–4 1/2 6–11
Boys: pubertal growth spurt 3–5 7–13
Measuring Length
The stature of subjects less than two years of age is measured as recumbent length. This
is done most accurately with a measuring “box” or “board” that has an inflexible headpiece
against which the top of the head is positioned, and a moveable footboard against which
the feet are placed at a 90-degree angle. If possible, the child should be relaxed, the legs
should be fully extended, and the head should be positioned so that a line connecting the
outer margin of the eyes with the ears is at a 90-degree angle with the bottom of the
measuring box. Recumbent length is measured from the top of the head to the bottom of
the feet. It should be measured to the nearest quarter inch and recorded in the child’s
chart. Measurement of recumbent length on an examining table without a “box” should
also be from the top of the head to the bottom of the feet, which are positioned at a 90-
degree angle. It is recommended that the same examiner measure the child at each visit
to minimize inter-examiner variability.
Because recumbent length is slightly greater than standing height, it is recommended
that measurements of both length and height be obtained for two visits between two and
three years of age. With these simultaneous recumbent length and standing height values,
measurement discrepancy can be distinguished from actual change in growth rate.
Measuring Height
The height of subjects older than two years of age is measured, without shoes, with a
stadiometer. A stadiometer consists of a measuring tape affixed to a vertical surface, such
as a wall or a rigid free-standing measuring device, and a movable block, attached to the
Height, Weight, and Body Mass Index (BMI) in Childhood 675
vertical surface at a right angle, that can be brought down to the crown of the head. In the
absence of a stadiometer, height can be measured on a platform scale, but this is less
accurate than the stadiometer. In either case, the subject should stand with heels together
and back as straight as possible; the heels, buttocks, shoulders, and head should touch the
wall or the vertical surface of the measuring device. The weight of the subject is distributed
evenly on both feet and the head is positioned in the horizontal plane. The arms hang
freely by the sides with the palms facing the thighs. The subject should be asked to inhale
deeply and maintain a fully erect position. The examiner positions the movable block until
it touches the head; applying sufficient pressure to compress the hair. The height marker
is read while pressing firmly on the headpiece. The number on the height bar immediately
behind the indicator line of the height marker is read. The examiner’s eyes should look
directly at the indicator line at about the same height in order to avoid parallax in reading
the measurement. The height is measured to the nearest quarter inch, and then recorded
on the child’s chart. It is recommended that a second reading be taken to check accuracy.
Height has diurnal variation. Children are tallest in the morning, and shrink as much
as a centimeter during the course of a day as the fibrous intervertebral cartilaginous disks
are compressed. Diurnal variation in height is completely due to changes in the height of
the vertebral column, and full height is regained when the child lies down flat for about
30 minutes.
Interpretation of Height Measurements

Depending on the statural genes that a child inherits from their parents, children tend to
gravitate toward a specific percentile or channel of the standard height (or length) charts
during the first two to three years of life. Thereafter, most children track close to that
percentile or channel, maintaining a stable position relative to their peers.
Children who track consistently along the lowest height percentiles may have familial
short stature in which the parents are short and the child has simply inherited the same
statural genes. Other short children may have constitutionally delayed growth characterized
by a slower rate of growth in the first two or three years of life, followed by normal growth
velocity that tracks along a height percentile or channel lower than expected for the family.
These children often have later onset of puberty and its accompanying growth spurt, as
well as a parent who followed a similar pattern of growth as a child. Final adult height
is generally appropriate for parental height expectations.
Children whose linear growth decelerates and shifts gradually downward to a lower
percentile deserve medical evaluation. Poor linear growth may reflect inadequate nutri-
tion, an underlying disease affecting a major organ system, or a genetic abnormality.
Children whose linear growth accelerates and shifts upward to a higher percentile also
deserve medical evaluation. Increased rate of linear growth may reflect overnutrition,
early or precocious onset of puberty, or another endocrine or genetic abnormality.
Reference Charts for Height (and Length)

Growth charts are simple grids which are used to plot out a child’s height according to age
and sex. Pediatric health professionals should measure and plot height on a growth chart
at every visit, at least every six months before school age, and annually thereafter. Growth
charts are derived from the heights of large numbers of healthy children of all ages, sepa-
rating the wide range of normal heights into percentiles by statistical techniques. The spaces
between the percentile lines are called channels. Age in years is plotted along the horizontal
axis at the bottom of the chart and height in inches (or centimeters) is plotted along the
vertical axis on the left of the chart. The 50th percentile, representing the average height for
a given age, is drawn as a heavy line. Growth charts are commonly drawn for values
between the 5th and 95th or 3rd and 97th percentiles of the population distribution values.
The Center for Disease Control (CDC) has published Growth Charts for boys and girls,
for birth to 36 months of age and for ages 2 to 20 years. These include charts for plotting
linear growth including Length-for-Age (age 2 years of age and under), Height-for-Age
(age 2 years and older), Weight-for-Length, and Weight-for-Height. These charts may be
downloaded from the CDC internet website: http://www.cdc.gov/growthcharts.
Weight
Description
Body weight is a measure of body mass, which is a composite of each contributing tissue
(e.g., fat, muscle, bone, etc). Although weight should ideally be measured without clothing,
this is often impractical. Most commonly, weight is measured with the child in underwear
only, or in light indoor clothing, without shoes.
Normal Patterns of Weight Gain in Childhood

Newborn infants commonly double their birth weight by six months of age, and triple it
by their first birthday. Boys on average increase from 8 pounds at birth to 23 pounds at
1 year; while girls on average increase from slightly less than 8 pounds at birth to about
21 pounds at age 1 year. From 1 to 2 years of age, toddlers who are tracking along the
50th pecentile for weight gain about 5 to 6 pounds, or about 1/2 pound per month, and
during the third year of life weight gain averages about 4 pounds. Children tracking along
higher percentile zones will gain more, and those tracking on the lower percentiles gain
proportionately less.
Measurement Techniques
Weight should be measured in the clinical setting using a standard balance beam scale
with moveable weight or with an instrument of equivalent accuracy. It is recommended
that the scale be calibrated at least monthly using standard weights. It is preferable to
weigh the child without clothing, or in light indoor clothing, but at least the child’s shoes
and heavy outer clothing should be removed. With older children, heavy belts should be
removed and their pockets should be emptied. The beam of the platform scale must be
graduated so that it can be read from both sides. The subject stands still over the center
of the platform with body weight evenly distributed between both feet. Weight is recorded
to the nearest quarter pound.
Weight, like height, has diurnal variation. In contrast to height, however, weight is lowest
in the morning after emptying the bladder, and increases gradually through the day,
depending on diet and physical activity.
Interpretation of Weight Measurements

Body weight and patterns of weight gain and adiposity in childhood are the result of gene-
environment interactions. A child’s genotype reflects the genes inherited from his or her
parents. The phenotype expressed, however, with respect to body weight and fatness, is
also heavily influenced by environmental factors such as diet and physical activity. Most
children will gravitate toward a specific percentile curve of the standard weight charts
during the first few years of life. However, with the increasing prevalence of childhood
obesity in the U.S., it is not uncommon for children’s weights to gradually cross upward
across percentiles, rather than maintain a consistent percentile position relative to their
peers. It is recommended that body weight, height, and calculated BMI values all be mon-
itored carefully during routine health supervision, so that children and adolescents who
begin to deviate from normal growth patterns may receive further evaluation and treatment.
Children’s weight percentiles may be similar to their height percentiles, or may be
somewhat above or below, and still be “normal” or healthy if the BMI is below the 85th
percentile for age.
Healthy children who consistently track along the lower weight percentiles throughout
childhood are considered normal if their weight is proportionate to their height (close to
the same percentile) and consistent with parental heights and weights.
Children whose weight gain decelerates and shifts gradually downward to a lower
percentile, or who actually lose weight (with the exception of overweight children on
medically supervised diets), should be medically evaluated to determine the cause. Poor
weight gain or unexplained weight loss may reflect inadequate nutrition, an eating dis-
order, an underlying disease affecting a major organ system, or depression or other
psychological problems.
Overweight children who are placed on a medically supervised diet to slow down the
rate of weight gain or to lose weight should be carefully monitored so adequate intake of
essential nutrients is assured through a balanced calorie-controlled diet, and caloric intake
is adequate to maintain linear growth throughout treatment.
Reference Charts for Weight

Weight charts are available to plot out a child’s weight according to age and gender,
similar to height charts. Weight charts are also constructed from the weights of large
numbers of healthy children of all ages, separating the wide ranges of weights into
percentiles by statistical techniques. As for the height charts, the spaces between percentile
lines are called channels. Age in years is plotted along the horizontal axis at the bottom
of the chart and weight in pounds (or kilograms) is plotted along the vertical axis on the
left of the chart. The 50th percentile, representing the average weight for a given age, is
drawn as a heavy line. Weight charts most commonly provide percentile channels between
the 5th and 95th percentile, but are also available now for a distribution between the 3rd
and 97th percentiles.
The CDC has published Growth Charts for boys and girls for birth to 36 months of
age and for ages 2 to 20 years. These include charts for plotting weight, weight-for-
age, and weight-for-height. These charts may be downloaded from the CDC website:
http://www.cdc.gov/growthcharts.
Body Mass Index (BMI)

Body Mass Index
Body Mass Index, or BMI (wt/ht2) provides a guideline based on weight and height to
determine underweight or overweight status. BMI is not an exact measure of fatness
because levels of fatness vary among children at a given BMI. This is true because BMI
reflects (1) frame size, (2) leg length, and (3) amount of lean and fat tissue. Although BMI
correlates less well with the percent of body weight that is fat than other more direct
measures of fat such as triceps skinfold thickness or other body composition techniques,
the readily available weight and height data make BMI a more useful tool for assessment
of overweight or underweight.
BMI in children and adolescents compares well to laboratory measurements of body
fat. Children and adolescents with a BMI-for-age above the 95th percentile are classified
as overweight. BMI values above the 95th percentile, applied as a definition of overweight
in children and adolescents
1. Reflects adiposity
2. Is consistent across age groups
3. Is predictive of morbidity
The percentage of children and adolescents who are overweight in the U.S. has more
than doubled in the past 30 years, and the sharpest increase has occurred in the last 20
years, since the late 1970s. For 6 to 17 year old youth, about 12.5% (or 5.3 million) are
overweight (BMI >95th percentile reference value).
The rationale for proposing a pediatric BMI classification is based on studies indicating
that BMI is related to health risks. Overweight children are likely to become overweight
adults, with risk increasing with severity and duration of the problem. Sixty percent of
youth with a BMI-for-age above the 95th percentile have at least one risk factor for cardio-
vascular disease, while twenty percent have two or more risk factors. High blood pressure,
abnormal blood lipid levels (elevated total cholesterol, LDL-cholesterol, and/or triglycer-
ides; low HDL-cholesterol), insulin resistance, and Type II diabetes mellitus are some of
the risk factors observed in overweight children and adolescents. Overweight children are
also at increased risk for a wide range of other medical and psychological problems.
Normal Patterns of BMI during Childhood and Adolescence

For U.S. children, BMI increases rapidly during the first year of life and then declines to
its lowest value on average between four and six years of age. After reaching this nadir,
BMI again begins a slow increase throughout the rest of childhood and adolescence. The
upward shift of the BMI curve, after reaching the lowest point, has been termed “adiposity
rebound.” Studies suggest that children who begin their adiposity rebound at younger
ages are at greater risk for being overweight as older adolescents and young adults.
Measurement of BMI
BMI, also known as the weight-height index or Quetelet index, is calculated as the quotient
of weight divided by height squared:
The English formula (in inches and pounds) is as follows:
Weight in pounds ÷ Height in inches ÷ Height in inches × 703 = BMI
The Metric formula (in meters and kilograms) is as follows:
Weight in kilograms ÷ Height in meters ÷ Height in meters = BMI

Interpretation of BMI Values

Interpretation of BMI depends on the sex and age of the child, since boys and girls differ
in their body fatness as they mature. Therefore BMI is plotted on age and sex-specific charts.
Established cutoff points are used to identify children and adolescents who are underweight
or overweight. BMI values which should raise clinical concern are the following:
Underweight BMI-for-Age <5th percentile

“At-Risk” of Overweight BMI-for-Age 85th–95th percentile
Overweight BMI-for-Age ≥95th percentile
Reference Charts for Body Mass Index (BMI)

The CDC has published BMI-for-age charts; one chart for boys ages 2 to 20 years, and
another chart for girls 2 to 20 years of age. These charts may be downloaded from the
CDC internet website: http://www.cdc.gov/nccdphp/dnpa/bmi/bmi-for-age.htm. At
the same site, a CDC “Table for Calculated Body Mass Index Values for Selected Heights
and Weights for Ages 2 to 20 Years” may also be downloaded. Clinicians can avoid having
to calculate BMI values by using this extensive set of tables covering heights from 29 to
78 inches and weights from 18 to 250 pounds.
kg lb lb
40 40
18 97th
95th
17
38
Weight-for-age percentiles: 38
90th
36 Boys, birth to 36 months 36
16
34 75th 34
15
32 32
50th
14
30 30
25th
13
28 28
10th
12 5th
26 3rd 26
11 24 24
10 22 22
9 20 20
18 18
8
16 16
7
14 14
6
12 12
5
10 10
4
8 8
3
6 6
2
4 4
kg lb lb
Birth 3 6 9 12 15 18 21 24 27 30 33 36
Age (months)
FIGURE 32.1
Weight-for-age percentiles, boys, birth to 36 months, CDC growth charts: United States. Source: Developed by
the National Center for Health Statistics in collaboration with the National Center for Chronic Disease Prevention
and Health Promotion (2000).
kg lb lb
40 40
18 97th
95th
17
38
Weight-for-age percentiles: 38
36 Girls, birth to 36 months 90th 36

16
34 34
15
75th
32 32
14
50th
30 30
13
25th
28 28
12 10th
26 26
5th
3rd
11 24 24
10 22 22
9 20 20
18 18
8
16 16
7
14 14
6
12 12
5
10 10
4
8 8
3
6 6
2
4 4
kg lb lb
Birth 3 6 9 12 15 18 21 24 27 30 33 36
Age (months)
CDC
CENTERS FOR DISEASE CONTR
AND PREVENTION
CONTROL
FIGURE 32.2
Weight-for-age percentiles, girls, birth to 36 months, CDC growth charts: United States. Source: Developed by
cm in in
42 42
105
41 97th 41
40 Length-for-age percentiles: 95th

90th 40
100
39
Boys, birth to 36 months 75th 39
38 50th 38
95
37 25th 37
36 10th 36
90 5th
35 3rd 35
34 34
85
33 33
32 32
80
31 31
30 30
75
29 29
28 28
70
27 27
26 26
65
25 25
24 24
60
23 23
22 22
55
21 21
20 20
50
19 19
18 18
45
17 17
cm in in
Birth 3 6 9 12 15 18 21 24 27 30 33 36
Age (months)
CDC
AND PREVENTION
CONTROL
FIGURE 32.3
Length-for-age percentiles, boys, birth to 36 months, CDC growth charts: United States. Source: Developed by
cm in in
42 42
105
41 41
97th
40 Length-for-age percentiles: 95th 40
90th
100
39 Girls, birth to 36 months 39
75th
38 38
95 50th
37 37
25th
36 36
90 10th
35 5th 35
3rd
34 34
85
33 33
32 32
80
31 31
30 30
75
29 29
28 28
70
27 27
26 26
65
25 25
24 24
60
23 23
22 22
55
21 21
20 20
50
19 19
18 18
45
17 17
cm in in
Birth 3 6 9 12 15 18 21 24 27 30 33 36
Age (months)
CDC
AND PREVENTION
CONTROL
FIGURE 32.4
Length-for-age percentiles, girls, birth to 36 months, CDC growth charts: United States. Source: Developed by
kg lb lb
23
50 50
22 48 48
Weight-for-length percentiles:
21 46
Boys, birth to 36 months 46
20 44 44
97th
19 42 42
95th
40 90th 40
18
38 75th 38
17
36 50th 36
16
34 25th 34
15 10th
32 5th 32
14 3rd
30 30
13
28 28
12 26 26
11 24 24
10 22 22
9 20 20
18 18
8
16 16
7
14 14
6
12 12
5
10 10
4
8 8
3
6 6
2 4 4
1 2 2
kg lb lb
in 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
cm 45 50 55 60 65 70 75 80 85 90 95 100
Length
CDC
AND PREVENTION
CONTROL
OL
FIGURE 32.5
Weight-for-length percentiles, boys, birth to 36 months, CDC growth charts: United States. Source: Developed
by the National Center for Health Statistics in collaboration with the National Center for Chronic Disease
Prevention and Health Promotion (2000).
kg lb lb
23
50 50
22 48 48
21
Weight-for-length percentiles:
46 46
Girls, birth to 36 months
20 44 97th 44
19 42 95th 42
40 90th 40
18
38 38
17 75th
36 50th 36
16
34 25th 34
15
10th
32 32
5th
14 3rd
30 30
13
28 28
12 26 26
11 24 24
10 22 22
9 20 20
18 18
8
16 16
7
14 14
6
12 12
5
10 10
4
8 8
3
6 6
2 4 4
1 2 2
kg lb lb
in 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
cm 45 50 55 60 65 70 75 80 85 90 95 100
Length
CDC
AND PREVENTION
CONTROL
OL
FIGURE 32.6
Weight-for-length percentiles, girls, birth to 36 months, CDC growth charts: United States. Source: Developed
kg lb lb
105 230
230
97th
100 220 220
95 210 Weight-for-age percentiles: 95th

210
90 200
Boys, 2 to 20 years 200
90th
190 190
85
180 180
80 75th
170 170
75
160 160
50th
70
150 150
65
140 25th 140
60
130 10th 130
5th
55 120 120
3rd
50 110 110
45 100 100
90 90
40
80 80
35
70 70
30
60 60
25
50 50
20
40 40
15
30 30
10
20 20
kg lb lb
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Age (years)
CDC
AND PREVENTION
CONTROL
OL
FIGURE 32.7
Weight-for-age percentiles, boys, 2 - to 20 years, CDC growth charts: United States. Source: Developed by the
National Center for Health Statistics in collaboration with the National Center for Chronic Disease Prevention
kg lb lb
105 230 230
100 220 220
95 210 Weight-for-age percentiles: 210
200
Girls, 2 to 20 years 200
90
97th
190 190
85
95th
180 180
80
170 170
75 90th
160 160
70
150 150
75th
65
140 140
60
130 130
50th
55 120 120
25th
50 110 110
10th
5th
45 100 3rd 100
90 90
40
80 80
35
70 70
30
60 60
25
50 50
20
40 40
15
30 30
10
20 20
kg lb lb
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Age (years)
CDC
AND PREVENTION
CONTROL
OL
FIGURE 32.8
Weight-for-age percentiles, girls, 2 to 20 years, CDC growth charts: United States. Source: Developed by the
cm in in
200
78 78
195
76 76
190 Stature-for-age percentiles: 97th
74 95th 74
185
Boys, 2 to 20 years 90th
72 72
75th
180
70 70
50th
175
68 68
25th
170
66 10th 66
165 5th
64 3rd 64
160
62 62
155
60 60
150
58 58
145
56 56
140
54 54
135
52 52
130
50 50
125
48 48
120
46 46
115
44 44
110
42 42
105
40 40
100
38 38
95
36 36
90
34 34
85
32 32
80
30 30
75
cm in in
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Age (years)
CDC
AND PREVENTION
CONTROL
OL
FIGURE 32.9
Stature-for-age percentiles, boys, 2 to 20 years, CDC growth charts: United States. Source: Developed by the
cm in in
200
78 78
195
76 76
190
74
Stature-for-age percentiles: 74
185
72
Girls, 2 to 20 years 72
180
70 70
175 97th
68 95th 68
90th
170
66 75th 66
165
64 50th 64
160 25th
62 62
155 10th
60 5th 60
3rd
150
58 58
145
56 56
140
54 54
135
52 52
130
50 50
125
48 48
120
46 46
115
44 44
110
42 42
105
40 40
100
38 38
95
36 36
90
34 34
85
32 32
80
75 30 30
cm in in
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Age (years)
CDC
AND PREVENTION
CONTROL
OL
FIGURE 32.10
Stature-for-age percentiles, girls, 2 to 20 years, CDC growth charts: United States. Source: Developed by the
kg lb lb
76 76
34
33
72 72
32
Weight-for-stature percentiles: Boys
31 68 68
30
97th
29 64 64
28 95th
60 60
27
90th
26
56 85th 56
25
24 75th
52 52
23
50th
22
48 48
25th
21
10th
5th
20 44 3rd 44
19
18 40 40
17
36 36
16
15
32 32
14
13
28 28
12
11 24 24
10
9 20 20
8
kg lb lb
in 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
cm 80 85 90 95 100 105 110 115 120

Stature
CDC
AND PREVENTION
CONTROL
OL
FIGURE 32.11
Weight-for-stature percentiles, boys, CDC growth charts: United States. Source: Developed by the National
Center for Health Statistics in collaboration with the National Center for Chronic Disease Prevention and Health
Promotion (2000).
kg lb lb
76 76
34
33
72 72
32
Weight-for-stature percentiles: Girls
31 68 68
30
97th
29 64 64
28 95th
60 60
27
90th
26
56 85th 56
25
75th
24
52 52
23
50th
22
48 48
25th
21
10th
20 44 5th 44
3rd
19
40 40
18
17
36 36
16
15
32 32
14
13
28 28
12
11 24 24
10
9 20 20
8
kg lb lb
in 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
cm 80 85 90 95 100 105 110 115 120

Stature
CDC
AND PREVENTION
CONTROL
OL
FIGURE 32.12
Weight-for-stature percentiles, girls, CDC growth charts: United States. Source: Developed by the National Center
for Health Statistics in collaboration with the National Center for Chronic Disease Prevention and Health
Promotion (2000).
BMI BMI
34 Body mass index-for-age percentiles: 34
Boys, 2 to 20 years
97th
32 32
95th
30 30
90th
28 28
85th
26 26
75th
24 24
50th
22 22
25th
20 10th 20
5th
3rd
18 18
16 16
14 14
12 12
kg/m2 kg/m2
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Age (years)
CDC CENTERS FOR DISEASE CONTR

AND PREVENTION
CONTROL
FIGURE 32.13
Body mass index-for-age percentiles, boys, 2 to 20 years, CDC growth charts: United States. Source: Developed
BMI BMI
97th
Body mass index-for-age percentiles:
34 34
Girls, 2 to 20 years
32 95th 32
30 30
90th
28 28
85th
26 26
75th
24 24
22 22
50th
20 20
25th
10th
18 5th 18
3rd
16 16
14 14
12 12
kg/m2 kg/m2
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Age (years)
CDC CENTERS FOR DISEASE CONTR

AND PREVENTION
CONTROL
OL
FIGURE 32.14
Body mass index-for-age percentiles, girls, 2 to 20 years, CDC growth charts: United States. Source: Developed
Sources of Further Information

Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, et al. CDC growth charts: United States. Advance
data from vital statistics; no. 314. National Center for Health Statistics. 2000.
Whitaker RC, Pepe MS, Wright JA, Seidel KD, Dietz WH. Early adiposity rebound and the risk of
adult obesity. Pediatrics 998;101(5). http://www.pediatrics.org/cgi/content,/full/101-3/e5.
Himes JH, Deitz WH. Guidelines for overweight in adolescent preventive services: recommendations
from an expert committee. Am J Clin Nutr 1994; 59: 307-316.
Pietrobelli A, Faith M, Allison DB, Gallagher D, Chiumello G, Heymsfeld SB. Body Mass Index as
a measure of adiposity among children and adolescents: a validation study. J Ped 1998; 132:
204-210.
Lazarus R, et al. BMI in screening for adiposity in children and adolescents: systematic evaluation
using receiver operating curves. Am J Clin Nutr 1996; 63: 500-506.
Freedman DS, et al. The relation of overweight to cardiovascular risk factors among children and
adolescents: the Bogalusa Heart Study. Pediatrics 1999; 103: 1175-1182.
Guo SS, et al. The predictive value of childhood BMI values for overweight at age 35 years. Am J
Clin Nutr 1994: 59: 810-819.
Dietz WH, Bellizzi MC. Introduction: the use of BMI to assess obesity in children. Am J Clin Nutr
1999; 70: 123-5S.
Guo SS, Chumlea WC. Tracking of BMI in children in relation to overweight in adulthood. Am J
Clin Nutr 1999; 70: 145-148S.
Barlow SE, Dietz, WH. Obesity evaluation and treatment: expert committee rcommendations. J Ped
1998; 102(3): 29E.
Gutin B, Basch C, Shea S, et al. Blood pressure, fitness, and fatness in 5- and 6-year-old children.
JAMA 1990; 264: 1123-1127.
Shear CL, Freedman DS, Burke GL, et al. Body fat patterning and blood pressure in children and
young adults — the Bogalusa Heart Study. Hypertension 1987; 9: 236-244.
Rames LK, Clark WR, Connor WE, et al. Normal blood pressures and the evaluation of sustained
blood pressure elevation in childhood: the Muscatine study. Pediatrics 1978; 61: 245-251.
Deschamps L, Desleuz JF, Machinot S, et al. Effects of diet and weight loss on plasma glucose,
Insulin, and free fatty acids in obese children. Ped Res 1978; 12: 757-760.
Parra A, Schultz RS, Graystone JE, et al. Correlative studies in obese children and adolescents
concerning body composition and plasma insulin and growth hormone levels. Ped Res 1971;
5: 606-613.
Tracy W, De NC, Harper JR. Obesity and respiratory infection in infants and young children. BMJ
1971; 1: 16-18.
Gam SM. Continuities and changes in fatness from infancy through adulthood. Curr Prob Ped 1985;
15: 1-47.
Kelsey JL, Acheson RM, Keggi KJ. The body build of patients with slipped capital femoral epiphysis.
Am J Dis Child 1972; 124: 276-281.
Dietz WH. Health consequences of obesity in youth: childhood predictors of adult disease. Pediatrics
1998; 101: 518-525.
Morrison JA, Payne G, Barton BA, Khoury PR, Crawford P. Mother-daughter correlations of obesity
and cardiovascular disease risk factors in black and white households: the NHLBI Growth
and Health Study. AJPH 1994; 84: 1761-1767.
Guo SS, Khoury PR, Sprecker B. Prediction of fat-free mass in black and white preadolescent girls
from anthropometry and impedance. Am J Hum Biol 1993; 5: 735-745.
33
Anthropometric Assessment: Height, Weight, Body
Mass Index (Adults)
George A. Bray
Historical Perspective
Quetelet
Lambert-Adolf-Jacques Quetelet is credited with the concept of the body mass index (BMI).1
The proposal was made in a monograph in 1835 on the development of the human body.
As Freudenthal says, “With Quetelet’s work in 1835 a new era in statistics began … The
work gave a description of the average man as both a static and dynamic phenomenon.”2
It was Quetelet who introduced the concept of quantitation in measurement of the human
being, thus providing a framework for progess in epidemiology and statistics. Quetelet,
with his mathematical background, took statistical methods into new arenas. He was a
pioneer in the application of statistics to human biology, anthropology, and criminology.
Quetelet was interested in the underlying factors that determined the distribution of
such events as births, marriages, deaths, and the prevalence of various types of crime. In
his work he noted the seasonal distribution of births, deaths, and marriages. He also noted
a seasonal distribution of crime, and that crimes against property appeared more fre-
quently in cold months while crimes against the person were more common in the summer.
Commenting on the constancy of crimes from year to year, he said, “Thus we pass from
one year to another with the sad perspective of seeing the same crimes reproduced in the
same order and calling down the same punishments in the same proportions. Sad condi-
tion of humanity …”.1 Fortunately, the human being has been able to change this apparent
constancy by education, laws, and better government. Much of the work in the volume
Sur l’Homme deals with means and distributions of the measurements he made. It was
not until a later publication in 1845 in the Bulletin de la Commission de Statistique (de Belgique)
that he dealt with the concept of the binomial distribution in detail. In his work, Quetelet
devoted a significant amount of space to the issues of height and weight. The concept of
the “average man” originated with Quetelet, and is one of his seminal contributions. To
quote from Chapter 2 of his work, Quetelet says:
If man increased equally in all his dimensions, his weight at different ages would be as
the cube of his height. Now, this is not what we really observe. The increase in weight
0-8493-2705-9/01/$0.00+$1.50
is slower, except during the first year after birth; then the proportion which we have
just pointed out is pretty regularly observed. But after this period, and until near the
age of puberty, the weight increases nearly as the square of the height. The development
of the weight again becomes very rapid at the time of puberty, and almost stops at the
25th year. In general, we do not err much when we assume that, during development,
the square of weight at different ages are as the fifth powers of the height; which
naturally leads to this conclusion, in supposing the specific gravity constant, that the
transverse growth of man is less than the vertical.
However, if we compare two individuals who are fully developed and well-formed with
each other, to ascertain the relations existing between the weight and stature, we shall
find that the weight of developed persons, of different heights, is nearly as the square
of the stature. Whence it naturally follows, that a transverse section, giving both the
breadth and thickness, is just proportioned to the height of the individual. We further-
more conclude that, proportion still being attended, width predominates in individuals
of small stature.1
These two paragraphs succinctly summarize the concept of the body mass according to
Quetelet, and the rationale on which he developed his concept.
Life Insurance
Nearly 70 years after Quetelet, the life insurance industry in the United States began to
weigh in on the importance of excess weight as a risk for early death.3 It was also noted
that a central distribution of weight was important. The 1922 Statistical Bulletin of the
Metropolitan Life Insurance Company4 says:
It is generally recognized that weight of the human body in relation to its height plays
a part in determining the health and longevity of the individual. It is only recently,
however, that the long experience of the insurance companies has made possible the
crystallization of this impression into a series of definite propositions. We know now,
for example, that overweight is a serious impairment among insured lives, the gravity
increasing with the excess in weight over the average for the height and age. But, even
this statement has its exceptions because, at younger ages, a limited amount of over-
weight is apparently an advantage. Such persons have uniformly lower death rates from
tuberculosis. It is after the age of 35 that overweight, even in relatively small amounts,
begins to be dangerous. The seriousness increases with advancing age and with the
amount of overweight.
From this point forward until the last decade of the 20th century, there were “weight
tables” of appropriate, desirable, or ideal weight proposed by the life insurance industry.
The Framingham Study, which was the first American effort at a long-term population-
based evaluation of health risks, used the Metropolitan Life Insurance Table of 1959 as
the basis for comparing the weights of people living in Framingham with some standard.
The term came to be called the Metropolitan Relative Weight, which was the weight for
height of an individual to the expected weight for height from the Metropolitan Life
Insurance Table median frame grouping.
Various Indices
Several indices relating height to weight were proposed in the middle of the 20th century.
The BMI, or what might be appropriately called the Quetelet Index (QI), was compared
Anthropometric Assessment: Height, Weight, Body Mass Index (Adults) 697
against several other indices by Keys et al.5 They evaluated three indices of weight and
height: the Wt/Ht, the Wt/[Ht]2 (QI), and the Ht/[Wt]1/3 (Ponderal Index) against skinfold
estimates of fat. Of these three, the QI had a slightly better correlation with fatness than
Wt/Ht. The Ponderal Index was clearly the worst.
Gradual Adoption of the BMI

Benn reopened this question again in 1971.6 He showed that a simple index of weight/
(Ht)p could be derived for each population, in which p was a power where weight had
the lowest relation to height for that population. For most populations this number is
between 1 and 2. The ratio that Quetelet proposed in 1835 had a power of 2 [wt/(Ht)2].
Lee, Kolonel, and Hinds,7 in an effort to apply a weight/height index to a variety of
populations in Hawaii, found different indices useful for ranking the different populations.
However, these authors did not measure fatness, and since all of these weight-to-height
indices are strongly related to weight,8 their data are not helpful in resolving the value of
the QI versus the Benn Index as estimates of fat. Keys et al.5 examined the relationship of
weight-to-height indices in 12 populations. The best correlations with body fat as estimated
from skinfolds were found with [wt/(Ht)2]. He found that the QI had correlations ranging
between .611 and .850 when related to skinfold thickness. In a detailed evaluation of four
large study populations, Garn and Pesick 8 showed a strong correlation between any index
and weight which approximated r = 0.90. In this study, the population-specific indices, as
proposed by Benn [wt/(Ht)2], ranged between 1.18 and 1.83. These population-specific
indices provided no advantage over the Wt/(Ht)2 when related to skinfolds.
Garrow and Webster9 have examined the QI as a measure of fatness in a group of obese
subjects. Fat was measured by three separate techniques including densitometry, measure-
ment of total body water, and measurement of total body potassium using γ-emission
from naturally occurring 40K. As Garrow and Webster point out, there is considerable
variation in estimating fat between the methods that they selected for this study.9 The
accuracy for measuring fat was greater for men than for women by all methods used by
Garrow and Webster. The standard deviations for estimating fat by the QI, however, were
only slightly larger than those for density, body water, and body potassium. The relation-
ship of FAT/(Ht)2 plotted against [wt/(Ht)2] yielded very similar slopes for men (0.715)
and women (0.713). This indicates that men and women of similar height differ in weight
by tissue which is approximately 75% fat and 25% non-fat. In their data analysis there
was an important difference in the fatness between men and women, such that a woman
with 0 (zero) body fat would have a QI of 13.7 kg/m2, whereas a man with 0 body fat
would have a QI of 16.9 kg/m2. Garrow and Webster thus conclude that “Quetelet’s Index
has been underrated as a measure of obesity in adults. It … provides a measure of fatness
not much less accurate than specialized laboratory methods.” As they point out, this index
can be applied over the entire weight range, while such measurements as skinfold thick-
ness are severely limited in obese individuals and nearly useless in very obese individuals.
An additional feature of the QI is the similarity of the mortality and morbidity curves
plotted against QI for men and women. Whether related to excessive deaths or to mor-
bidity from various disease entities, the minimum QI (BMI) is similar for both sexes at
comparable ages. Yet at all ages, the quantity of body fat in women is higher than men
for any given height/weight combination. This implies that the extra fat in women (the
zero fat BMI values noted above) is not associated with increased risk of excess morbidity
or mortality. A similar conclusion, ushering in the era of studies in body fat distribution,1
suggests that for comparable increases in risk indices such as blood pressure, women have
approximately 20 kg more adipose tissue stores of fat than men.2
In summary, the relationship between height and weight [wt/(Ht)2] proposed by Quete-
let in 1835 has stood the test of time. In tribute to his contribution and its validation from
a number of sources, it would be appropriate to refer to it as the Quetelet Index, or QI,
and replace the frequently used body mass index, or BMI, with this new nomenclature.
Measurement of Weight
Recommended Technique
During infancy, a leveled pan scale with a beam and movable weights is used to measure
weight. The pan must be at least 100 cm long so that it can support a 2-year-old infant at
the 95th percentile for recumbent length. A quilt is left on the scale at all times, and the
scale calibrated to zero and across the range of expected weights when only a quilt is on
it, using test objects of known weights. Calibration is performed monthly and whenever
the scales are moved. Similar procedures are used to calibrate the scales used for older
individuals. When the scales are not in use, the beam should be locked in place or the
weights shifted from zero to reduce wear.
The infant, with or without a diaper, is placed on the scales so that the weight is
distributed equally on each side of the center of the pan. Weight is recorded to the
nearest 10 g with the infant lying quietly, which may require patience. When an infant
is restless, it is possible to weigh the mother when holding the infant and then weigh
the mother without the infant, but this procedure is unreliable, partly because the
mother’s weight will be recorded to the nearest 100 g. It is better to postpone the
measurement and try later. The measurement is repeated three times, and the average
recorded after excluding any clearly erroneous value. If a diaper is worn, the weight of
the diaper is subtracted from the observed weight, because most reference data for
infants are based on nude weights.
In a clinic, the measured weight is recorded in tabular form in addition to being plotted.
This plotting is done while the subject is present. Irregularities may be noted in the serial
data for a subject or there may be major discrepancies between the percentile levels for
highly correlated variables. When this occurs, the measurer checks the accuracy of the
plotting and remeasures the subject if the plotting is correct.
A subject able to stand without support is weighed using a leveled platform scale with
a beam and moveable weights or an electronic balance. The beam on the scale must be
graduated so that it can be read from both sides and the scale positioned so that the measurer
can stand behind the beam, facing the subject, and can move the beam weights without
reaching around the subject. The movable tare is arranged so that a screwdriver is needed
to shift it. The subject stands still over the center of the platform with the body weight
evenly distributed between both feet. Light indoor clothing can be worn, excluding shoes,
long trousers, and sweater. It is better to standardize the clothing, for example, a disposable
paper gown. The weight of this clothing is not subtracted from the observed weight when
the recommended reference data are used. Weight is recorded to the nearest 100 g.*
Handicapped subjects, other than infants, who cannot stand unsupported can be
weighed using a beam chair scale or bed scale. If an adult weighs more than the upper
limit on the beam, a weight can be suspended from the left-hand end of the beam, after
* For electronic scales, the subject stands in the center of the platform in appropriate clothing and the weight is
recorded when stable.
which the measurer must determine how much weight must be placed on the platform
for the scale to record zero when there is no weight on the platform. This weight is added
to the measured value when a scale modified in this fashion is used. In studies to assess
short-term changes, weights must be recorded at times standardized in relation to inges-
tion, micturition, and defecation, but for single weight this is not necessary.
Purpose
Weight is the most commonly recorded anthropometric variable, and generally is mea-
sured with sufficient accuracy. Accuracy can be improved, however, by attention to details
of the measurement technique. Strictly, this measurement is of mass rather than weight,
but the latter term is too well established to be replaced easily. Weight is a composite
measure of total body size. It is important in screening for unusual growth, obesity, and
undernutrition.
Literature
There is general agreement that weight should be measured using a beam scale with
movable weights or a calibrated electronic balance. A pan scale is needed for measure-
ments made during infancy. The use of a spring scale is not recommended, despite its
greater mobility, except in field conditions where there may be no practical alternative.
Automatic scales that print the weight directly onto a permanent record are available but
expensive. The scale should be placed with the platform level and in a position where the
measurer can see the back of the beam without leaning around the subject. Scales with
wheels to facilitate movement from one location to another are not recommended because
they need calibration every time they are moved.
Weight is best measured with the subject nude, which is practical during infancy.10 At
older ages, nude measurements may not be possible.10 If not, standardized light clothing,
for example, a disposable paper gown, should be worn in preference to “light indoor
clothing.”10
There are diurnal variations in weight of about 1 kg in children and 2 kg in adults.
Therefore, recording the time of day at which measurements are made is necessary.10
Usually it is not practical to measure at a fixed time, but a narrow range may be achievable.
Reliability
Intermeasurer differences (M) from the Fels Longitudinal Study are as follows:10
M = 1.2 g (SD = 3.2 g) at 5 to 10 years

M = 1.5 g (SD = 3.6 g) at 10 to 15 years
M = 1.7 g (SD = 3.8 g) at 15 to 20 years
M = 1.5 g (SD = 3.6 g) for adults
In the Health Examination Survey by the National Center for Health Statistics, the
intermeasurer and intrameasurer technical errors were about 1.2 kg, when pairs of mea-
surements were made 2 weeks apart.10 About 10% of the observed error would have been
due to growth.
Measurement of Stature (Standing Height)

Recommended Technique
Measurement of stature requires a vertical board with an attached metric rule and a
horizontal headboard that can be brought into contact with the most superior point on
the head. The combination of these elements is called a stadiometer. Fixed and portable
models are available, and plans for fabrication of a stadiometer by an investigator are
available from the Field Services Branch, Division of Nutrition, Centers for Disease Con-
trol, Atlanta, Georgia 30333.
The subject is barefoot or wears thin socks and little clothing so that the positioning of
the body can be seen. The subject stands on a flat surface that is at a right angle to the
vertical board of the stadiometer. The weight of the subject is distributed evenly on both
feet, and the head is positioned in the Frankford Horizontal Plane. The arms hang freely
by the sides of the trunk, with the palms facing the thighs. The subject places the heels
together, with both heels touching the base of the vertical board. The medial borders of
the feet are at an angle of about 60°. If the subject has knock knees, the feet are separated
so that the medial borders of the knees are in contact but not overlapping. The scapulae
and buttocks are in contact with the vertical board. The heels, buttocks, scapulae, and the
posterior aspect of the cranium of some subjects cannot be placed in one vertical plane
while maintaining a reasonable natural stance. These subjects are positioned so that only
the buttocks and the heels or the cranium are in contact with the vertical board.
The subject is asked to inhale deeply and maintain a fully erect position without altering
the load on the heels. The movable headboard is brought onto the most superior point on
the head with sufficient pressure to compress the hair. The measurement is recorded to
the nearest 0.1 cm, and the time at which the measurement was made is noted.
Recumbent length is measured in place of stature until the age of two years. Between
two and three years, recumbent length or stature can be measured, and the choice made
between these variables must be noted because they differ systematically. Two measurers
are needed to measure stature in children aged two to three years. One measurer places
a hand on the child’s feet to prevent lifting of the heels and keep the heels against the
vertical board, and he or she makes sure that the knees are extended with the other hand.
The second measurer lowers the headboard and observes its level.
When there is lower limb anisomelia (inequality of length), the shorter side is built up
with graduated wooden boards until the pelvis is level, as judged from the iliac crests.
The amount of the buildup is recorded because it can alter the interpretation of weight-stat-
ure relationships.
Purpose
Stature is a major indicator of general body size and bone length. It is important in screening
for disease or malnutrition and in the interpretation of weight. Variations from the normal
range can have social consequences, in addition to their association with disease.
When stature cannot be measured, recumbent length can be substituted and, depending
on the purpose of the study, adjustments for the systematic differences between these highly
correlated measurements may be desirable.10 Arm span may be used in place of stature
when stature cannot be measured and it is not practical to measure recumbent length. The
measurement of arm span is described in the section on segment lengths. Also, stature can
be estimated from knee height, as described in the section on recumbent anthropometry.
Literature
Stature can be measured using a fixed or movable anthropometer. An anthropometer consists
of a vertical graduated rod and a movable rod that is brought onto the head. An anthro-
pometer can be attached to a wall or used in a free-standing mode, utilizing a base plate to
keep the vertical rod properly aligned. Measurements of stature with a movable anthropom-
eter tend to be less than those with a stadiometer.10 It is not recommended that stature be
measured against a wall, but if this must be done, a wall should be chosen that does not
have a baseboard, and the subject should not stand on a carpet. An apparatus that allows
stature to be measured while the subject stands on a platform scale is not recommended.
Some workers do not ask subjects to stretch to the appropriate extent. This is likely to
lead to less reproducible positioning and less reliability than the recommended procedure.
Some workers ask the subjects to assume a position of military attention; this is inappro-
priate for young children and for the elderly. In one alternative technique, a measurer
exerts upward force under the mastoid processes to keep the head at the maximum level
to which it was raised when the subject inhaled deeply. A second measurer lowers the
headboard and observes its level, while a third person records the value. The need for
three measurers reduces the practicality of this technique, but when it is applied the
diurnal variation in stature is reduced.10
Some workers place the head in a “normal” position, with the eyes looking straight
ahead; this is less precise than positioning in the Frankfort Horizontal Plane. Others tilt
the head backwards and forwards and record stature when the head is positioned so that
the maximum value is obtained. It is difficult to apply the latter procedure while the
subject maintains a full inspiration.
It is general practice to place the subject’s heels together, but the angle between the
medial borders has varied from study to study. If these borders are parallel, or nearly so,
many young children and some obese adults are unable to stand erect.
Reliability
Intermeasurer differences (M) for large samples in the Fels Longitudinal Study are as
follows:10
M = 2.4 mm (SD = 2.1 mm) at 5 to 10 years

Comments
BMI and Gender
Women are fatter than men at any BMI. On average, this number is 11-12% higher for the
same BMI and age group. Yet this extra fatness in women is not associated with extra risk
to health. Thus, because the component units of the BMI, height, and weight can be
measured with great reliability compared to total body fat, measuring body fat is not
recommended. Rather, BMI is preferred because it is gender neutral. Table 33.1 shows BMI.
BMI and Ethnic Groups

A recent study compared percent body fat at different ages in men and women of three
ethnic groups (Table 33.2). Ethnic differences are obvious, and imply that using the BMI
to evaluate risk requires an adjustment related to ethnic differences. This is one of many
adjustments to BMI in arriving at the risk from obesity for individuals.11
BMI Curves and Children

BMI curves have been developed for children by the Centers for Disease Control and
Prevention (www.CDC.gov). The principle behind this table for children was to take the
height for BMI 25 and 30 for 18-year-olds and then take corresponding height deviations
at various ages. The BMI of 30 for children is close to the 95th percentile of height for
weight. The BMI of 25 in children is close to the 85th percentile of weight for height in
children.
Misclassification
Since BMI measures height and weight, it is an imperfect tool for evaluating fat. Correlations
of fat with BMI vary from <0.1 to >0.8 depending on initial percent of fat, level of physical
training, and age. Older people tend to lose height, and this elevates the BMI inappropri-
ately. Body builders, Sumo wrestlers, and professional athletes will have high BMI values
for low body fat. However, the purpose and value of the BMI is not to assess athletes, but
to provide a starting point in risk assessment of overweight in sedentary people.
BMI and Central Fat

Body fat and visceral fat are related, but BMI as an index of body fatness cannot assess
central fat. A measure of waist circumference can be a valuable addition in the assessment
of risk. To have a clear picture of the steps in this process, it would be helpful to examine
the natural history of the change in BMI. Figure 33.1 shows the increasing percentage of
the population with a BMI >25 (top line) or >30 (lower line). Both lines rise until age 50
to 60 years. This means that an increasing percentage of the population is moving from
the pre-overweight category with a BMI <25 to overweight or obese. Thus, the natural
history of overweight is a gradual transition of the potentially or pre-overweight into
overweight or clinical overweight categories. In addition, there appears to be about 25%
of the population who will never become overweight. This is shown in Figure 33.1.
Risk Evaluation — Know Your BMI

The BMI is a useful tool in assessing the risk from overweight. In epidemiological studies,
the risk of many diseases increases as BMI increases. This is shown in Figure 33.2, along
with the cut points used for determining overweight and clinical overweight.
The curvilinear relationship shown is for overall mortality. The steepness of the curve
varies for different diseases. For diabetes mellitus there is a very steep relationship. For
TABLE 33.1
Body Mass Index (BMI) Values
Good Weights Overweight Obese
BMI
Height 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
4’10” 91 96 100 105 110 115 119 124 129 134 138 143 148 153 158 162 167 172 177 181 186 191
4’11” 94 99 104 109 114 119 124 128 133 138 143 148 153 158 163 168 173 178 183 188 193 198
5’ 97 102 107 112 118 123 128 133 138 143 148 153 158 163 168 174 179 184 189 194 199 204
5’1” 100 106 111 116 122 127 132 137 143 148 153 158 164 169 174 180 185 190 195 201 206 211
5’2” 104 109 115 120 126 131 136 142 147 153 158 164 169 175 180 186 191 196 202 207 213 218
5’3” 107 113 118 124 130 135 141 146 152 158 163 169 175 180 186 191 197 203 208 214 220 225
5’4” 110 116 122 128 134 140 145 151 157 163 169 174 180 186 192 197 204 209 215 221 227 232
5’5” 114 120 126 132 138 144 150 156 162 169 174 180 186 192 198 204 210 216 222 228 234 240
5’6” 118 124 130 136 142 148 155 161 167 173 179 186 192 198 204 210 216 223 229 235 241 247
5’7” 121 127 134 140 146 153 159 166 172 178 185 191 198 204 211 217 223 230 236 242 249 255
5’8” 125 131 138 144 151 158 164 171 177 184 190 197 203 210 216 223 230 236 243 249 256 262
5’9” 128 135 142 149 155 162 169 176 182 189 196 203 209 216 223 230 236 243 250 257 263 270
5’10” 132 139 146 153 160 167 174 181 188 195 202 209 216 222 229 236 243 250 257 264 271 278
5’11” 136 143 150 157 165 172 179 186 193 200 208 215 222 229 236 243 250 257 265 272 279 286
6’ 140 147 154 162 169 117 184 191 199 206 213 221 228 235 242 250 258 265 272 279 287 294
6’1” 144 151 159 166 174 182 189 197 204 212 219 227 235 242 250 257 265 272 280 288 295 302
Anthropometric Assessment: Height, Weight, Body Mass Index (Adults)
6’2” 148 155 163 171 179 186 194 202 210 218 225 233 241 249 256 264 272 280 287 295 303 311
6’3” 152 160 168 176 184 192 200 208 216 224 232 240 248 256 264 272 279 287 295 303 311 319
6’4” 156 164 172 180 189 197 205 213 221 230 238 246 254 263 271 279 287 295 304 312 320 328
703
TABLE 33.2
Percent Body Fat for Men and Women of Different Ethnic Groups and Three
Age Ranges According to Body Mass Index*
Females (% fat) Males (% fat)
BMI African African
(kg/m2) American Asian Caucasian American Asian Caucasian
Age 20–39
18.5 20 25 21 8 13 8
25 32 35 33 20 23 21
30 38 40 39 26 28 26
Age 40–59
18.5 21 25 23 9 13 11
25 34 36 35 22 24 23
30 39 41 41 27 29 29
Age 60–79
18.5 23 26 25 11 14 13
25 35 36 38 23 24 25
39 41 41 43 29 29 31
* Adapted from Gallagher, D et al. Am J Clin Nutr 2000 Sep; 72(3): 694-701.
Male Female
100 100
Never Overweight
Never Overweight
Pre-overweight
Overweight (%)
Pre-overweight
50 50
Overweight
Overweight
Clinical
Overweight Clinical
Overweight
0 0
Birth 10-19 20-29 30-39 40-49 50-59 69-69 Birth 10-19 20-29 30-39 40-49 50-59 69-69
Age Group Age Group
FIGURE 33.1
The natural history of overweight is a gradual transition of the potentially, pre-overweight into overweight, or
clinical overweight categories. In addition, there appears to be about 25% of the population who will never
become overweight.
300
Digestive & Cardiovascular
Pulmonary Gall Bladder
250 Disease Diabetes Mellitus
200
Mortality Ratio
Clinical
150
Overweight
Overweight
100
Pre-overweight
50 Age at Issue Very Low Moderate High Very

Low Risk Risk Risk High
20-29 Risk Risk
30-39
0
15 20 25 30 35 40
Body Mass Index (Kg/(m)2)
FIGURE 33.2
In epidemiological studies, the risk of many diseases increases as BMI increases. The curvilinear relationship
shown here is for overall mortality. The steepness of the curve varies for different diseases.
this disease, individuals with a BMI of 23 to 24 are already at higher risk than those with
a BMI of 20.
The curvilinear relationship of BMI has a similar shape to that of diastolic blood pressure
and risk of death, or cholesterol concentrations and the risk of death. This is shown for
all three in Figure 33.3. The dashed vertical lines in this figure represent the arbitrary cut
points that separate low from moderate and high risk.
Starting with an accurately determined BMI, a clinician can sort through an algorithm
such as that developed by the National Heart, Lung, and Blood Institute (Figure 33.4).
Using this algorithm points the clinician and patient along the path of effectively evalu-
ating the patient’s BMI. “Know Your BMI” could serve as an effective public health
campaign. If the public began to learn their BMI, it would be incumbent upon health
professionals to be able to guide their patients in its use.
Low Moderate High

Risk Risk Risk
2.5 BMI
2
1.5
0.5
0
20 24 26 28 30.5 35
Body Mass Index
4 Cholesterol
Relative Risk
0
150 170 200 210 220 230 240 250 290
Cholesterol (mg/dL)
5
Diastolic Blood Pressure
4
1
75 80 85 90 95 100 105 110 115 120
Diastolic Blood Pressure
FIGURE 33.3
The curvilinear relationship of BMI has a similar shape to that of diastolic blood pressure and risk of death or
cholesterol concentrations and the risk of death. The dashed vertical lines represent the arbitrary cut points that
separate low from moderate and high risk.
1
Patient Encounter
2
Hx of > 25 BMI?
No
3 BMI Yes
measured in past
2 years?
4 6
BMI > 25 BMI > 30
• Measure weight, 5 or waist 7 or waist
height, and waist Yes circumference Yes
circumference Assess
circumference >88 cm (F) risk factors >88 cm (F)

• Calculate BMI >102 cm (M) 8
>102 cm (M) and >1 risk
factor Clinician and patient
devise goals and
No strategy for weight
No loss and risk factor
14 Yes control
12 Does
Hx of > 25 BMI? Yes
patient want to
lose weight?
No 9 Progress
15 13 Yes
being made/goal
Brief reinforcement/ Advise to maintain No achieved?
Anthropometric Assessment: Height, Weight, Body Mass Index (Adults)
educate on weight weight/ address

management other risk factors No
11 10
16 Maintenance counseling: Assess reasons
Examination
• Diet for failure to lose
Periodic Weight • Behavior modification
Check weight
Treatment • Exercise
FIGURE 33.4
This algorithm developed by the National Heart, Lung, and Blood Institute can point the clinician and patient along the path of effectively evaluating the patient’s BMI.
707
References
1. Quetelet, A. Sur l’homme et le developpement de ses facultes, ou essai de physique sociale;
Paris: Bachelier, 1835.
2. Freudenthal H. In: Dictionary of Scientific Biography (Gillespie CC, Ed). New York: Charles and
Sons; 1975; pg 236.
3. Bray GA. Obes Res 3: 97; 1885.
4. Metropolitan Life Insurance Company. Stat Bull Met Life Ins 1922; 3: 3-4.
5. Keys A, Fidanza F, Karvonen MJ, et al. J Chronic Dis 25: 329; 1972.
6. Benn RT. Brit J Prev Soc Med 25: 42; 1971.
7. Lee J, Kolonel N, Hines MW. Int J Obes 6: 233; 1982.
8. Garn SM, Pesick SD. Am J Clin Nutr 36: 573; 1982.
9. Garrow JS, Webster JD. Int J Obes 9: 147; 1985.
10. Gordon CC, Chumlea WC, Roche AF. In: Anthropometric Standardization Reference Manual.
Champaign, IL: Human Kinetics Books, 1988, pg 3.
11. Gallagher D, Heymsfield SB, Heo M, Jebb SA, Murgatroyd PR, Sakamoto Y. Am J Clin Nutr
2000 Sep;72(3):694-701.
34
Glossary of Terms Used in Energy Assessment
All living things require energy to sustain life. If a plant, that energy comes from the sun.
If an animal, the energy must be provided by the food that is consumed. Warm-blooded
animals are kept warm by their metabolisms. All the reactions that comprise intermediary
metabolism release heat as a byproduct. Some reactions are exogonic; that is, they release
more heat than they consume. Others are endogonic; they consume more energy than
they release. None of the reactions in a living system are 100% efficient. The reaction
produces a product(s) plus heat. This is the heat that sustains the body temperature and
yet also escapes from the body via radiation or evaporation (insensible water loss and
sweating) from the body surface. If a body is neither gaining nor losing weight, the energy
released as heat is equal to that needed by the body to sustain its metabolism. Thus, the
heat that is produced is equal to the total food energy (corrected for digestive loss and
internal energy conversion to mechanical, chemical, and electrical energy) that must be
provided on a daily basis to sustain the body. Altogether, the living system is a heat-
generating system. That heat can be measured directly using a calorimeter or indirectly
by measuring the oxygen consumed and the carbon dioxide produced. Using equations
that relate heat production to the gas exchange (CO2 and O2), the energy used by the body
can be calculated.
The measurement of energy need and energy production has been the subject of nutri-
tional investigation since the time of Lavoisier. A number of terms have evolved that refer
to discrete portions of the energy equation. These are listed in Table 34.1 along with other
terms relevant to energy balance in man and other species.
The standardization of energy terms has been published by the National Academy of
Sciences.1 Nutrition scientists (as well as other scientists interested in energy metabolism)
are encouraged to use these terms.
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TABLE 34.1
Terms of Reference in Energy Metabolism
Anabolism: the totality of reactions that account for the synthesis of the body’s macromolecules; heat is a
byproduct of these reactions.
Android obesity: a form of obesity where fat distribution is mainly in the shoulders and abdomen; sometimes
referred to as the “apple” shape.
Anthropometry: Measurements of body features, i.e., weight, height, etc.
Apparent digested energy (DE): energy of the consumed food (IE) less the energy of the feces (FE); DE = IE – FE.
Archimedes principle: an object’s volume when submerged in water equals the volume of the water it displaces.
If the mass and volume are known, the density can be calculated. This principle is used to determine body
fatness.
Balance: When energy intake (EI) equals energy expenditure (EE), energy balance is zero. When energy intake
exceeds expenditure, balance is positive and weight is gained. When intake is less than expenditure, balance
is negative and weight is lost. (EI = EE; balance = 0)
Basal metabolic rate (BMR): the energy required to sustain life; measured in a resting animal in a thermoneutral
environment (neither sweating nor shivering), at sexual repose, and in the postabsorptive (but not starving)
state. Expressed as heat units/hour/unit body surface or per unit body weight (Kg0.75 ). A less stringent
measurement of this basal energy requirement is the resting metabolic rate (RMR). RMR is measured under
clinical conditions to provide an approximation of the BMR and provide a basis for diet recommendations.
Body cell mass: the metabolically active, energy-requiring mass of the body.
Body density: mass (weight) per unit volume.
Calorie: a unit of heat energy; a calorie is defined as the amount of heat required to raise the temperature of
one gram of water one degree Celsius; this is the physicist’s unit. The nutritionist’s unit is the calorie or
kilocalorie (abbreviated, kcal), and refers to the heat needed to raise the temperature of one kilogram of water
rather than one gram of water. The term kilojoule is the preferred term for expressing the energy need for
living systems because it accounts for not only heat energy but also other forms of energy (mechanical, electrical,
etc.) that living systems use. The kcal can be converted to the kilojoule by multiplying kcal × 4.184.
Calorimetry: the measurement of heat production by the body. This measurement can be either direct (using a
whole body calorimeter) or indirect (using measurements of oxygen consumed and carbon dioxide produced).
Catabolism: the totality of those reactions that reduce macromolecules to usable metabolites, CO2, and water.
Heat is a byproduct of these reactions.
Digestive energy (DE): the energy of food after the energy losses of digestion are subtracted. Similar to apparent
ingestive energy (see above).
Gaseous products of digestion (GE): the energy of combustible gases produced in the digestive tract incident
to fermentation of food by microorganisms. In ruminants, that can account for a substantial energy lost from
the system. In nonruminents this loss is relatively minor.
Gynoid obesity: excess body fat deposited mainly on the hips and thighs; sometimes referred to as the “pear”
form of obesity.
Heat of activity (HjE): the heat produced through muscular activity; an active person can have a very large
percent of their energy need accounted for by HjE. A sedentary person can have the reverse. The energy need
for different activities has been determined, and some of these are listed in Table 34.2. Sometimes TEA (total
energy from activity) is used for this term.
Heat of digestion and absorption (HdE): the heat produced as a result of the action of the digestive enzymes,
and the heat produced when the products of digestion are absorbed. Expressed in heat units (see DE above).
Sometimes DIT (diet-induced thermogenesis) is used.
Heat of fermentation (HfE): the heat produced in the digestive tract as a result of microbial action. Expressed
in heat units (see GE above).
Heat of product formation (HrE): the heat produced in association with metabolic processes of product formation
from absorbed metabolites. In its simplest form, HrE is the heat produced by a biosynthetic pathway. Expressed
as heat units.
Heat of thermal regulation (HcE): the additional heat needed to maintain body temperature when the
environmental temperature falls below or rises above the zone of thermic neutrality. Expressed in heat units.
Sometimes CIT (cold-induced thermogenesis) or BAT (brown fat thermogenesis) is used. It is thought that the
heat generated upon cold exposure emanates primarily from the brown fat depots. There is some argument
about this role of the brown fat.
Heat of waste formation and excretion (HwE): the additional heat production associated with the synthesis
and excretion of waste products. For example, the synthesis and excretion of urea is energetically expensive in
mammals and results in a measurable increase in total heat production. Expressed in heat units.
Glossary of Terms Used in Energy Assessment 711

Terms of Reference in Energy Metabolism
Heat increment (HiE): the increase in heat production following the consumption of food. Includes the heat lost
through digestion and absorption and the heat of fermentation. Expressed as heat units. The heat increment
is usually considered non-useful energy loss, but under special circumstance (cold environments) it helps to
maintain the body temperature.
IBW: ideal body weight.
Indirect calorimetry: the calculation of energy production through the measurement of oxygen consumed. It is
predicated on the relationship of the heat lost when substrates are oxidized to CO2 and water. With this oxidation
via the mitochondrial respiratory chain, some energy is trapped in the high-energy bond of ATP. The rest of
the energy is released as heat. Because there is a relationship between oxygen used and the energy trapped
plus energy released as heat, measuring the oxygen consumed is an indirect measure of heat production. Thus,
at zero energy balance, heat production (oxygen consumed) can predict the energy need of the body at rest or
when actively involved in a variety of tasks. There are several systems available for this measurement. The
closed system uses a reservoir of gases, and the oxygen consumed is measured. The open system measures
the carbon dioxide exhaled without measuring oxygen consumed.
Metabolizable energy (ME): the energy in food minus the energy lost through digestion and absorption, the
energy of undigested residues (FE), and the energy lost through fermentation. ME = IE – (FE + UE + GE).
N-corrected metabolizable energy (MnE): ME adjusted for total nitrogen retained or lost from body tissue. MnE
= ME – (k × TN). For birds or monogastric mammals, gaseous energy is usually not considered. The correction
for mammals is generally k = 7.45 kcal/g/nitrogen retained in body tissue (TN). The factor 8.22 kcal/g TN is
used for birds, representing the energy equivalent of uric acid/g nitrogen.
NPU: net protein use.
NDp cal %: net protein kcalories percent; the percent of the total energy value of the diet provided by protein.
Nutrient density: the nutrient composition of food expressed in terms of nutrient quantity/100 kcal.
Nutritional assessment: measurement of indicators of dietary status and nutrition-related health status of
individuals or populations.
Obesity: excess fat stores; overweight individuals have more than 15 but less than 20% of their body mass as
fat; obese individuals have more than 20% of their body mass as fat. Body fatness may not always be reflected
by the body weight of the individual.
Postprandial: after a meal.
Quantitative computed tomography: an imaging technique consisting of an array of x-ray sources and radiation
detectors aligned opposite each other. As x-ray beams pass through a body they are weakened or attenuated
by the tissues of that body. The signals are then compared with a computer that uses the information to construct
a model of the body and estimate its fatness as well as its composition. This instrument is a very sophisticated
(and expensive) way to determine body fatness.
Respiratory quotient (RQ): ratio of CO2 produced to O2 consumed.
Skinfold thickness: a double fold of skin and underlying tissue that can be used to estimate body fatness.
Thermic effect of food: heat production upon food consumption; sometimes referred to as diet-induced
thermogenesis (DIT).
Thermogenesis: heat production; when stimulated by exposure to cold it is referred to as cold-induced
thermogenesis and represents the extra energy the body generates to maintain body temperature. In rodents
this extra heat is thought to be produced by the brown fat cells. In man there is evidence that both supports
and denies this response of specialized fat cells to cold exposure.
Total heat production (HE): the energy lost from the body as a result of its metabolism. It can be measured
directly or estimated from the gas exchange. The commonly accepted equation for the indirect computation of
heat production from the respiratory exchange is HE (kcal) = 3.866 (liters O2) + 1.200 (liters CO2) – 1.431 (g
urinary nitrogen) – 0.518 (liters CH4).
True digestive energy (TDE): the intake of energy minus the fecal energy of food origin (FiE = FE – FeE – FmE)
minus heat of fermentation and digestive gaseous losses (TDE = IE – FE + FeE + FmE – HfE – GE).
True metabolizable energy (TME): the intake of food energy corrected for fecal loss and urine energy loss (TME
= TDE – UE + UeE).
Urinary energy (UE): the gross energy of the urine. Represents the energy of nonutilized absorbed compounds
from food (UiE), endproducts of metabolic processes (UmE), and endproducts of endogenous origin, i.e.,
creatinine, urea, uric acid, etc.(UeE).
TABLE 34.2
Methods and Equations Used for Calculating Basal Energy Need
Method Equation
1. Heat production, direct calorimetry kcal (kJ)/m2 (surface area)
2. Oxygen consumption; indirect O2 cons./W0.75
3. Heat production; indirect Insensible Water Loss (IWL) = Insensible Weight Loss (IW) + (CO2
exhaled – O2 inhaled)
 100 
Heat production = IWL × 0.58 ×
 25 
4. Energy used; indirect Creatinine N (mg / day)
Basal energy =
0.00482 (W)
5. Estimate (energy need not measured) BMR = 66.4730 + 13.751W + 5.0033L – 6.750A (men)
(Harris Benedict equation)
6. Estimate (energy need not measured) BMR = 655.9055 + 9.563W + 1.8496L – 4.6756A (women)
  L 
BMR = 71.2 W 0.75 1 + 0.004(30 − A) + 0.010 − 43.4  ( men )
  W 0.33 
  L 
BMR = 65.8W 0.75 1 + 0.004(30 − A) + 0.018 (women)
  W 0.33 − 42.1  
Abbreviations are as follows: W = weight in kg; L = height in cm; A = age in years.

See Heshka, S., Feld, K., Yang, M et al. JADA 93: 1031, 1993 for a comparison of various prediction equations.
Reference
1. Subcommittee on Biological Energy, National Research Council, Nutritional Energetics of Do-
mestic Animals Nat. Acad. Press, Washington, DC, 1981.
35
Metabolic Assessment of the Overweight Patient
Shawn C. Franckowiak, Kim M. Forde, and Ross E. Andersen
Introduction
Clinicians often see overweight patients seeking weight loss, and those seeking weight
loss implore advice from nutrition specialists and dietitians on the quantity of calories
they should consume each day. To produce weight loss, a negative energy balance needs
to exist whereby the patient consumes less energy than he or she expends in a day. The
total energy need of a person is expressed as:
Total daily energy needs (TDEE) = BMR + TEF + TEA + energy needed for growth,
reproduction, lactation or healing from injury.
BMR: Basal Metabolic Rate

TEF: Thermic Effect of Feeding
TEA: Thermic Effect of Activity
The total amount of energy a person expends daily during the waking hours is termed
Total Daily Energy Expenditure (TDEE) and is composed of three different components:
the Resting Metabolic Rate (RMR), the Thermic Effect of Feeding (TEF), and the Thermic
Effect of Activity (TEA) (see Figure 35.1). RMR is the energy expenditure needed to sustain
the basic biochemical reactions of the body in a resting state. A resting state is when a
person is fasting (not starving), awake in a thermoneutral environment (not sweating or
shivering), and lies still without any skeletal muscle movement. The TEF is the energy
expenditure attributed to the digestion and absorption of food. The energy needed for the
digestion and absorption of foods is greater than that needed for resting, and therefore is
designated as TEF. It is the difference in energy use between the fed and fasting states.
The TEA is the energy expenditure associated with skeletal muscle movement. TEA is the
most influenced component of TDEE because a person can choose to do variable amounts
of physical activity that ultimately involve skeletal muscle movement. The RMR accounts
for approximately 60 to 75% of TDEE, the TEF constitutes approximately 10%, and the
TEA comprises 15 to 30% of energy expenditure.
0-8493-2705-9/01/$0.00+$1.50
24-Hour Energy Expenditure
kcal
3000
2500 Thermic Effect of

Activity
(TEA) ~15% - 30%
2000
Thermic Effect of
Feeding (TEF) ~10%
1500
Resting Metabolic
1000 Rate (RMR)
~60% - 75%
500
0
FIGURE 35.1
The three major components of the total daily energy expenditure (TDEE). RMR: Resting Metabolic Rate, TEF:
Thermic Effect of Feeding, TEA: Thermic Effect of Activity. Adapted from Poehlman, E.T. Med Sci Sports Exerc,
21; 516, 1989.
Definitions of Energy Units and Components of Metabolism

Before introducing the definition of resting metabolic rate, it is important to define the
energy unit. This is the “kilocalorie” or “kilojoule.” The kilocalorie is the amount of heat
content or energy required to raise the temperature of 1 kg of water 1 degree Celsius at
15 degrees Celsius; it is used in measurements of the heat production of chemical reactions
including those of biological systems.1 At any given time, there are continuous biochemical
reactions consisting of the breakdown of adenosine triphosphate (ATP) to a smaller molec-
ular of adenosine diphosphate (ADP) + ENERGY to serve the functional element of cells.2
This reaction produces the energy that is measurable in kilocalories. The word kilocalorie
may be used to define the amount of energy in the food a person consumes; it can also
quantify the amount of energy a person expends.
Metabolic Assessment of the Overweight Patient 715
RMR is presented as a measure of energy expressed as the amount of kcalories expended

in a day, represented as kcal/d. However, the kilocalorie can also be expressed as the
kilojoule to achieve uniformity of SI unit measuring system.1 One kilocalorie equals 4.184
kilojoules. Although the joule may be a uniform standard unit that scientists use, the
layperson will be better served when measurement of energy intake and expenditure is
presented as kilocalories in order to make the term relevant to food labels and packaging
used in everyday life. Those seeking to lose weight pursue a negative energy balance
whereby they expend more kilocalories than consumed. A negative energy balance can
be achieved by increasing TDEE or decreasing the amount of kcalories consumed during
the weight loss period. Calorie is a word that many people associate with food labels to
define the energy richness of a food item; it is often seen on exercise machinery stating
the quantity of calories expended for a person of a given body weight for each minute of
exercise. When investigating energy balance, it is important to understand the concept
that a kcalorie is a measure of energy, and energy that is expended is measurable using
different techniques. This section will be devoted to defining RMR and several components
that make up TDEE, and it shall provide an overview of the methodology, implementation,
and interpretation of the RMR.
TDEE
TDEE in free-living populations can be measured using doubly-labeled water (2H218O).
Measurement of TDEE by doubly-labeled water involves using stable isotopes of hydrogen
and oxygen. A specimen of urine is collected from the subject at baseline; the administered
dosage of doubly-labeled water is determined by body weight. Although this is the gold
standard for the measurement of TDEE , doubly-labeled water is very costly and is almost
exclusively used by scientists involved in measuring TDEE and various components of
the metabolism for clinical research studies.
Usually, clinicians do not have the option of estimating TDEE by doubly-labeled water.
Therefore, TDEE is typically estimated by measuring the RMR and estimating the energy
expenditure of physical activity. Physical activity patterns may be assessed using acceler-
ometers or by administering a valid questionnaire.
RMR
RMR is one of the three components that comprise total daily energy expenditure.3 RMR
can be defined as the energy required to sustain bodily functions and maintain body
temperature at rest, and is quantitatively the largest component of energy expenditure in
humans. Typically it can account for 60 and 75% of the total daily expenditure.4 RMR is
often used to estimate the daily energy needs of individuals for population-based studies.
It is a useful tool in the clinical management of obesity.4 Researchers have defined RMR
as being different from that of BMR; BMR is the energy expenditure of a person at rest
(not asleep) in a fasting state, at sexual repose in a thermoneutral environment (neither
shivering nor sweating). The RMR is defined as the energy expenditure measured on an
outpatient basis.5 For clinical purposes, the RMR can be assumed to be similar to the BMR.5
It is less expensive and intrusive for the participant.
The RMR is the component of metabolism that is difficult to influence. Clinicians work-
ing with overweight patients will be quick to point out that their overweight clients often
believe that they have a low or sluggish RMR, and consequently feel that this is the reason
for their inability to lose or maintain weight. Often, RMR values are not as low as the
patient believes. RMR measurements are frequently within the normal range for the
patient’s age, gender, height, and weight.
TEF
TEF is occasionally called diet-induced thermogenesis, and accounts for 10% of the TDEE
of a person. TEF represents the energy expenditure associated with the ingestion, diges-
tion, and absorption of food. There is an increase in the metabolic rate when a person has
eaten food. This is why the assessment of RMR typically requires individuals to be fasted
for a minimum of 12 hours prior to the assessment of that component of the metabolism.
TEF can be measured by taking the measurements of a valid RMR assessment and com-
paring these to values attained using the same testing procedures after the ingestion of a
meal of known energy value and composition. The difference between the RMR and the
energy used for digestion and absorption is the TEF (TEF + RMR = energy expended after
a meal is consumed).
TEA
The TEA is the only component of the TDEE that we can directly influence. TEA is the
amount of energy expended as a direct result of voluntary skeletal muscle movement.
TDEE differs between active and sedentary persons. Sedentary persons expend less energy
than active persons, and thus their TEA as a percent of their total energy expenditure is
less than that of active persons.
Techniques for Measuring RMR

RMR can be measured using two different methods: direct calorimetry and indirect calo-
rimetry. Direct calorimetry is the measurement of overall heat liberated by a body mass.
Heat production is proportional to the body surface area available (kilocalories/m2) for
the release of heat by radiation or transvection.
Indirect calorimetry involves measuring oxygen consumption (O2) and carbon dioxide
production (CO2) to determine RMR by using a calculated equation of Weir.6 To produce
measurement values for indirect calorimetry in kilocalories per day, the measurement of
one liter of oxygen consumed generates 3.9 kilocalories, and one liter of carbon dioxide
produced generates 1.1 kilocalorie.7 The original Weir equation involves measurement of
gases that are consumed and produced at rest plus the collection of total 24-hour urine
nitrogen during the same day of measurement. However, a second abbreviated Weir
equation has been developed that is less than 2% measurement error when compared to
the longer equation.6 This equation is below.
Abbreviated Weir Formula:
RMR = [3.9(VO2) + 1.1 (VCO2)]1.44
variables: VO2 = oxygen consumption in mL/min

VCO2 = carbon dioxide production in mL/min
Note: this equation is to determine resting energy expenditure, so for determining
RMR the patient must be in a 12-hour fasted state.
Direct Calorimetry
The measurement of energy need of an adult who is neither gaining nor losing weight
can be made using a whole body calorimeter. This instrument measures the heat released
by the body as a result of its metabolism.7-9 It is a composite value in that it is not only
the result of baseline metabolic reactions that produce heat, but also the heat that results
from the ingestion, digestion, and absorption of foods, plus that which results from
muscular activity. Subjects must remain in the whole body calorimeter for hours at a time
so that sufficient data can be accumulated. This technique is extremely expensive and has
limited clinical potential.7
Indirect Calorimetry
For most, a viable alternative is the indirect calorimeter or metabolic cart. Indirect calorim-
etry measures the gas exchange of an individual.8,10 The gases detected by the metabolic
cart are compared to the environmental conditions of the surrounding room’s gases at
standard temperature, pressure, and humidity (STPD). STPD is a symbol indicating that a
gas volume has been expressed as if it were at standard temperature (0° Celsius), standard
pressure (760 mm Hg absolute), and 0% humidity; under these conditions, a mole of gas
occupies 22.4 liters. The testing environment should be controlled for temperature, baro-
metric pressure, and humidity. Depending on the instrumentation, the measurement con-
ditions are entered prior to beginning the assessment, and correction factors are applied to
standardize the results. The room temperatures should also be kept between 68 and 74°
Fahrenheit. Furthermore, the room should be dimly lit, and spare blankets should be offered
to individuals who may experience coldness when sitting for prolonged periods of time.
The measurement of gas exchange allows for the calculation of the respiratory quotient
(RQ). (RQ = CO2/O2). The RQ reflects cellular metabolism and is a reflection of heat
production (direct calorimetry). The RQ indicates the fuel mixture being oxidized.8 Dif-
ferent fuels such as fats, carbohydrates, and proteins require different amounts of oxygen
for oxidation to CO2 and water. Thus, the RQ varies depending on the ratio of fat to
carbohydrate in the fuel mixture.11 In starvation, the major fuel is fat, and the RQ is 0.70.
Usually a mixture of fuels (carbohydrate and fat) is oxidized. The various substrates and
their RQ values are shown in Table 35.1.
TABLE 35.1
Respiratory Quotient and Energy Content of Various Substrates
Fuel Energy Content Respiratory Quotient
(Substrate) (Kcal · g–1) (RQ)
Carbohydrate 4.1 1.00
Fat 9.3 0.70
Protein 4.3 0.80
Adapted from American College of Sports Medicine. Guidelines for Exer-
cise Testing and Prescription. Malvern, PA: Lea & Febiger, page 14, 1991.
Instrumentation Available
There are two indirect calorimetry systems: open-circuit and closed-circuit systems. Both
techniques require devices to measure the concentration of O2, CO2, gas volume or flow
F out O F o u t CO
F in O 2 2
2
V
F i n CO
2
FIGURE 35.2
Open Circuit technique of Indirect Calorimetry using a canopy hood. From Ferrenini E. Metabolism, 37; 296,
1988. With permission.
Labels: FinO2: Forced Inspiratory Oxygen; FinCO2: Forced Inspiratory Carbon Dioxide; : Gas Flow; FoutO2:
Forced Expiratory Oxygen; FoutCO2: Forced Expiratory Carbon Dioxide.
rate, temperature, and time. In the closed-circuit system, the patient breathes from a
reservoir (a mixture of gases resembling ambient air), and the decrease in oxygen over
time is used to calculate V̇O2. Closed-circuit systems are usually simpler in design and
less costly than open systems. Open-circuit systems are more versatile and can be more
easily used in the clinical setting.7 The patient breathes from a reservoir of air of known
composition in the closed-circuit system; the depletion of oxygen, V̇C O2 and V̇O2 are
calculated.7 In the open-circuit technique (see Figure 35.2), the patient breathes room air
and expires into a gas sampling system which eventually vents the expired air back into
the room. Open-circuit systems are more commonly used to measure RMR in the clinical
setting, since they are more versatile and can be used in a variety of clinical conditions.
The techniques described in this section will therefore focus on the open-circuit indirect
calorimetry system.
Types of Collection Systems

Many types of accessories allow for the collection of consumed and expired gases of the
person being tested, including face masks, mouth pieces, chambers, and ventilated hoods.
Face Masks
Similar to the face masks used by firefighters and military personnel, face masks provide
a sealed environment around the nose and mouth in order to collect all gases. The face
mask has an elastic head harness which encompasses the back of the head. These work
well for collection of gases; however, they may be more awkward for some patients than
other collection systems, and it is important to have several sizes of masks on hand to
optimize fit. Although not as comfortable as some of the other collection devices, the face
mask is very easily used with portable gas analyzers and is useful for field settings or
where exercise-induced energy expenditure is measured.12
Mouthpieces
These are similar to the snorkel that is used to allow breathing underwater. The mouth-
pieces used for RMR measurement are usually identical to mouthpieces used for max-
imal VO2 testing. In order for the mouthpiece to work correctly, the subject being tested
needs to maintain a tight seal around the mouthpiece and have a nose clip sealing off
the nasal passageway. A certain amount of discomfort may be experienced from a static
contraction of the jaw muscles to keep a tight seal around the mouthpiece. Therefore,
this collection system is not often used to assess RMR.
Ventilated (Canopy) Hood

The ventilated hood is the most widely used collection system. It is advantageous for a
number of reasons — it allows for easy spontaneous breathing in apparently healthy
individuals, there is no error associated with facial features such as beard or facial hair of
the test subject, it has been found to be accurate in long term measurement of RMR, and
it is a relatively noninvasive gas collection system. The hood drapes over the entire head
of the subject in a semirecumbent position.
Comparison of Collection Devices

There are advantages and disadvantages for each collection device. In the clinical setting,
the ventilated hood may offer a more relaxed and unobtrusive measurement environment.
However, for patients that may be claustrophobic, the lights of the laboratory may need
to be dimmed to reduce feelings of being confined. The face masks work well for collection
of gases; however, structural differences in the size of the face may make it necessary to
use different sized masks for the variety of structural differences found in patients. Fur-
thermore, face masks are expensive, and for valid measurements a variety of masks is
necessary. Finally, although mouthpieces may seem to have no limitations, they are diffi-
cult for patients when the measurements last for long periods of time. Moreover, a nose
clip must be placed on the nose during measurement to prevent any escape of non-
measured gas, and this can be extremely invasive for the patient as well.
Clinical Applications and Usefulness of RMR

Understanding the energy requirement of an individual can be useful in prescribing a
personal dietary intake. The interpretation of the values attained by RMR measurements
should be done by an experienced clinician. Typically, university hospitals and established
university weight loss centers will have access to metabolic carts to perform RMR assess-
ments. An accurate measure of RMR will allow the clinician to tailor the energy intake of
the individual (and increase overall energy expenditure via the thermic effect of activity)
in order to produce a negative energy balance.
This information may also be important in the estimation of TDEE. The values of RMR
may be multiplied by an activity factor to produce best estimates of TDEE, as outlined in
Table 35.2. It may be helpful get detailed recent exercise histories from patients to help
assess the appropriate level of general activity. Bear in mind that most people overestimate
their activity levels.
TABLE 35.2
Factors for Estimating Total Daily Energy Needs of Activities for
Men and Women (Age 19 to 50)
Activity Factor Energy Expenditure
Level of General Activity (Multiplied by REE†) (Kcal/kg/day)
Very light
Men 1.3 31
Women 1.3 30
Light
Men 1.6 38
Women 1.5 35
Moderate
Men 1.7 41
Women 1.6 37
Heavy
Men 2.1 50
Women 1.9 44
Exceptional
Men 2.4 58
Women 2.2 51
From Food and Nutrition Board, National Research Council, NAS: Recom-
mended Dietary Allowances, 10th ed. Washington, DC. National Academy
Press, 1989, p. 29 (with permission). See Heshka S., Feld K., Yang M.U. et al.
Resting energy expenditure in the obese: A cross-validation and comparison
of prediction equations. J. Am. Diet. Assoc. 93, 1031-1036, 1993 for a compar-
ison of various prediction equations.
† REE = resting energy expenditure.
Helping Patients Gain Weight

RMR values attained from indirect calorimetry can also be used for certain anabolic
circumstances. Often, hospital clinicians will measure RMR in patients suffering from
severe burns or frail, elderly patients as a result of the onset of disease. For these instances,
the values attained at bedside are important in tailoring meal plans to facilitate weight
gain in life-threatening medical situations.
Those individuals seeking to gain weight for performance purposes can also benefit
from accurate measures of RMR. Individuals who seek to increase overall lean body mass
(or fat-free mass) may wish to understand how much energy is required above mainte-
nance to produce a safe rate of weight gain. The values attained from RMR in conjunction
with counseling on an appropriate activity and exercise program may be helpful to
individuals training for body-building or sports performance-related events. Two case
studies depicting the usefulness of values attained from assessment or prediction of RMR
are described below.
Case Studies
Person Seeking Weight Loss
A 40-year-old woman with a height of 5’6” and weight of 185 pounds (BMI of 30 kg/m2)
seeks to lose 20 pounds. This person seeks treatment from a dietician in a hospital that
has no metabolic cart. Therefore, an equation to predict resting metabolic rate will be used.
Using a prediction equation that has a table with value of kcals based on age and gender
multiplied by body surface area,13 the RMR is predicted to be 1498 kcal/d. Furthermore,
the woman participates in 30 minutes of vigorous aerobic exercise 4 days per week.
Therefore, to determine her predicted TDEE, we multiply her RMR by an activity factor
that is equal to a moderately active person. This activity factor is 1.5. Multiplying 1498 by
1.5 yields a TDEE of 2247 kcal/d. To predict a safe rate of weight loss of 1.5 pounds per
week, the energy intake needs to be restricted by 750 kcals per day, equaling a consumption
of approximately 1447 kcal/d (if 3500 kcal equals one pound of weight loss).
Person Seeking Weight Gain

A 20-year-old man who is weight training and agility training over a 15-week period seeks
to gain 15 pounds for the start of fall football season. He is 6’5,” weighs 270 pounds, and
has 18% body fat. Fortunately, he lives near a university hospital that has dieticians who
specialize in sports nutrition and have access to a metabolic cart. When assessed for RMR,
the man has a baseline RMR of 2653 kcal/d. The man’s training habits, which involve two
hours of strength and agility training each day, warrant that his RMR be multiplied by
an activity factor of 1.7. His determined TDEE is therefore 4510 kcal/d. However, he seeks
to gain weight and not remain weight stable. Therefore, in order to predict an average of
1 pound of weight gain per week, the man needs to ingest 500 kcal/d more than his
predicted TDEE. This value is equal to 5010 kcal/d.
Predicting RMR
Often, technology for direct measurement of RMR is not readily available to healthcare
professionals who provide treatment plans based on RMR values. As an alternative,
clinicians frequently use prediction equations to estimate RMR. These prediction equations
have mostly been developed using regression equations to fit functions according to
gender, age, height, weight, and other available clinical variables.14 A majority of these
equations were developed using normal-weight persons who were relatively sedentary.
Unfortunately, this poses a problem when predicting RMR in the obese population, con-
sidering that RMR is directly related to the fat-free mass (FFM) of the individual,15-18 and
the obese person has a larger distribution of adipose tissue and a decreased proportion
of FFM when compared to their normal-weight counterparts.19 Equations are available for
the prediction of RMR for the normal weight and overweight populations (Table 35.3).
Harris-Benedict Equation
For normal-weight individuals (determined by BMI or body composition analysis), the
prediction equation of Harris and Benedict20 offers an appropriate equation:
Men: kcal/d = 66.4730 + 13.751W + 5.0033L – 6.750A

Women: kcal/d = 655.0955 + 9.563W + 1.8496L – 4.6756A
where W = weight (kg); L = height (cm); A = age (years)
These equations were developed in 1919 and are currently widely used by clinicians.
However, given the increased prevalence of overweight in industrialized countries like
the U.S.,21 it may be necessary for the clinician to use prediction equations that have been
validated using overweight persons.
TABLE 35.3
Equations for Estimating Resting Metabolic Rate (RMR) kcal/24 hoursa
Reference Equations Reference
Bernstein et al. W: 7.48(kg) – 0.42(cm) – 3.0(yr) + 844 81
M: 11.0(kg) + 10.2(cm) – 5.8(yr) – 1,032
Cunningham 501.6 + 21.6(LBM); where 82
for W: LBM = [69.8 – 0.26(kg) – 0.12(yr)] × kg/73.2
for M: LBM = [79.5 – 0.24(kg) – 0.15(yr)] × kg/73.2
Harris and Benedict W: 655 + 9.5(kg) + 1.9(cm) – 4.7(yr) 20
M: 66 + 13.8(kg) + 5.0(cm) – 6.8(yr)
Fleischa W/M: kcal’s/m2 of BSA from Fleisch table × [[0.007184 × (kg)]0.425 × 22
(cm)0.725]] × 24
James W: 18 – 30yr: 487 + 14.8(kg) 83
30 – 60yr: 845 + 8.17(kg)
>60yr: 658 + 9.01(kg)
M: 18 – 30yr: 692 + 15.1(kg)
30 – 60yr: 873 + 11.6(kg)
>60yr: 588 + 11.7(kg)
Mifflin et al. W: 9.99(kg) + 6.25(cm) – 4.92(yr) – 161 23
M: 9.99(kg) + 6.25(cm) – 4.92(yr) + 5
Owen et al. W: 795 + 7.18(kg) 84
M: 879 + 10.2(kg)
Pavlou et al. M: –169.1 + 1.02(pRMR) 85
Robertson and Reida W/M: kcals/m2 of BSA from Robertson and Reid table × [[0.007184 13
× (kg)]0.425 × (cm)0.725]] × 24
Key. W = Women, M = Men, pRMR = predicted RMR from the Harris and Benedict equation, athis equation
uses tabled values for kcals/m2. From Heshka S., Feld K., Yang M.U. et al. Resting energy expenditure in
the obese: A cross-validation and comparison of prediction equations. Copyright The American Dietetic
Association. Reprinted with permission from J. Am. Diet. Assoc. 93, 1031-1036, 1993.
Robertson-Reid and Fleisch Equations

Three prediction equations may potentially offer reasonable predictions of RMR for the
overweight patient. The prediction equations of Robertson and Reid13 and the equation
of Fleisch22 have been recommended for obese populations.14 The Robertson and Reid and
Fleisch equations will be presented in this section as viable prediction equations for the
obese patient. The Robertson and Reid equation was derived from the actual measurement
of RMR of 987 men and 1323 women age 3 to 80. The equation requires that the clinician
find a value for heat output (in table form) based on the patient’s age and gender.
Subsequently, this value is multiplied by the body surface area of the person (in m2) to
determine kcal/hr; this number is then multiplied by 24 to yield daily RMR. The basis of
this prediction equation is that there is constant heat output that corresponds to surface
area within people who are the same gender and age:
RMR in kcal/d = heat output in kcal × body surface area in m2 × 24 hours

heat output = value derived for men and women from a table developed
by Robertson and Reid13
body surface area (BSA) = (([0.007184 × (wt in kgs)]0.425 × (ht in cms)0.725))
time = 24
The equation of Fleisch uses the same concept as the Robertson and Reid equation.
However, the values of heat output differ, and Fleisch provides a separate table to calculate
the predicted RMR.22
Mifflin et al. Equation

A third prediction equation for the obese population comes from Mifflin et al.23 This
equation was derived using linear regression analysis on a subset of patients (247 females,
251 males) who had their RMRs measured using indirect calorimetry. In an unpublished
research study at the Johns Hopkins School of Medicine, the equation has provided
predicted RMR values in obese patients at a university weight loss center that are not
different than those produced by actual measurement. The equation is as follows:
Men (kcal/d) = 9.99(kg) + 6.25(cm) – 4.92(years of age) + 5

Women (kcal/d) = 9.99(kg) + 6.25(cm) – 4.92(years of age) – 161
Pretesting Procedures for Measurement of RMR

The testing procedures for determining RMR necessitate that a strict protocol be followed
to ensure that the measurement is accurate. Individuals should be provided with pretesting
requirements for the RMR estimate. The subject should be questioned about his/her
adherence to pretest procedures prior to the test. If one or more of these procedures are
not followed, the individual should be rescheduled at a later date to reduce measurement
error.
Weight Stable
If the subject has experienced recent weight loss, measurement of RMR may not be valid.
Measurement should be avoided if the person being tested is on a weight loss program
or has lost or gained more than one pound in the past week. To reduce error associated
with physiological responses to weight loss, a period of weight stabilization of two weeks
is necessary prior to an RMR assessment.
Well Rested
RMR measurement should be administered as close to the time a person awakes as
possible. Additionally, the individual being tested should get a restful night’s sleep prior
to coming to the clinic or hospital for the RMR assessment. If an individual has had an
uneasy night’s rest prior to RMR assessment, confounding environmental influences may
unduly increase the metabolic expenditure of the individual. Measurement should occur
before 10:00 am; measurements taken in the late morning may be suspect to increased
metabolic activity.
Fasted
Measurements should be taken first thing in the morning after a 12-hour overnight fast.24
A light meal the night before measurement should be encouraged; RMR is the energy
expended at rest in a fasted state, and therefore any lasting effects of food or drink would
contribute additional energy expenditure from diet-induced thermogenesis. Early morn-
ing coffee or tea should be avoided, and only water should be ingested prior to mea-
surement. Clinicians can determine whether the patient is fasting by examining the RQ
values during testing.
Measurement in Relation to Last Exercise Bout

Testing should be performed at least 24 hours after rest from exercise to eliminate any
residual effects from the most recent training session.25 Hence, the person being testing
should be instructed to abstain from programmed exercise for at least one day prior to
measurement of RMR.
Location and Acclimation to the Testing Environment

Studies have shown that there are no differences in measurements of RMR performed
with or without an inpatient overnight stay.5 Therefore, to avoid excessive costs associ-
ated with inpatient stays, an outpatient procedure is usually recommended. Upon arrival
to the lab where the RMR assessment will occur, the subject should be instructed to rest
in a sedentary supine or semirecumbent position for at least 30 minutes prior to the
assessment. During this time, the subject should remain still. The subject should be
asked if they need to void, since it is necessary that they are comfortable during the
entire test. Some laboratories will further acclimatize the individual by placing the
collection system (canopy hood) over him/her to ensure that he/she is comfortable with
the measurement setting.
Analysis
The metabolic cart will often express resting metabolic rate as the mean of multiple minute
measurements. However, the cart will also provide continuous measurements of VO2 and
VCO2. Many researchers suggest that the calculation of RMR be the average of five of these
continuous minute measurements of steady state.18,26 Steady state is 5 minutes of mea-
surement of VO2 and VCO2 that possess an intravariability of 5% or less.26
Table 35.4 is a simple checklist to ensure that the assessment of RMR is valid.
Factors Affecting RMR

A variety of factors have been shown to influence RMR, including genetics, age, gender,
total body weight, fat-free weight, aerobic fitness level, total energy flux through the body,
body and/or environmental temperature, hormonal factors, drugs, and stress.27 Of these
factors, the strongest correlation exists between an individual’s FFM and RMR,27 and
collectively, fat-free mass, age, sex, and physical activity account for 80 to 90% of the
variance in resting metabolic rate.28
Exercise
Since exercise training has been associated with increases in fat-free mass, this is one factor
which can be manipulated to potentiate resting metabolism. Cross-sectional studies have
TABLE 35.4
Checklist for RMR Testing
Pre-Testing Subject Requirements
12 hour fast. Water is allowed ad libitum.

Refrain from strenuous physical activity/exercise for 48 hours prior to testing.
Well Rested. Make sure subject has at least 8 hours of sleep.
Minimize activity the morning of test. Light grooming allowed. Shower the night prior.
Keep food diaries for 48 hours prior to testing. Dinner meal should be <1000 kcals night prior.
Laboratory Requirements
Room should be isolated to reduce any external noise.

Room should be dimly lit, but not dark.
Temperature should be controlled and ideally at 22° to 24° Celsius. Blankets should be used if subject is cold.
The bed or comfortable chair should be semi-recumbent and not flat; having a slight incline of approximately
10 degrees.
Testing Procedures
Monitor subject during testing. Direct subject to avoid any: talking, fidgeting, and sleeping.
Acclimate patient to test. Possibly perform practice test prior to actual procedure.
Rest subject in semi-recumbent position for at least 30 minutes prior to testing.
If able to, use HR monitor to track HR the day before, morning of and during test.
Authors would like to thank Dr. Jack Wilmore for the helpful suggestions for the RMR checklist.
demonstrated that aerobically trained individuals have higher resting metabolic rates for
their metabolic size than their untrained counterparts.29-32
Age
Age is another variable that has been found to have a significant impact on an individual’s
resting metabolism. In fact, the decline in resting metabolic rate is one of the most consistent
physiological changes that occurs with age.33 Recent studies have suggested a curvilinear
reduction in RMR with advancing age that is accelerated beyond middle-age and post-
menopausal years.33 Several studies attribute the age-related decline in RMR primarily to
the loss of fat-free mass that often accompanies aging; however, there remains uncertainty
whether other physiological factors may also contribute to the reduction of RMR.33
Gender
Gender differences in resting metabolism have also been reported, with males having a
higher RMR than females by approximately 50 kcal/day.28 This difference is independent
of the gender difference in fat-free mass, and is consistent across the life span.28 Menopausal
status has also been pinpointed as an influence on RMR in women. Studies have found
lower RMR in postmenopausal women relative to premenopausal women, which was
again primarily attributable to reductions in lean mass and a decline in aerobic fitness.33-35
Environment
Environmental factors also influence RMR, with the resting metabolism of people in
tropical climates typically 5 to 20% higher than that of their counterparts living in more
temperate areas.36 Cold climates also have a significant impact on resting metabolic rate
that is dependent on an individual’s body fat content and the amount and type of clothing
worn.36 During extreme cold stress at rest, metabolic rate can double or triple with shiv-
ering as the body attempts to maintain a stable core temperature.36
Cigarette Smoking
Some studies have documented the influence of such substances as cigarettes, caffeine,
alcohol, and certain medications on resting metabolism. Many lay persons believe that
cigarette smoking may be helpful in maintaining body weight,37 and many smokers are
unwilling to quit because of their fear of weight gain. Over time, studies have demon-
strated that the increase in metabolic rate resulting from cigarette smoking is transient.37
One study found no effect in habitual smokers when assessment of metabolic rate did not
begin until 25 to 30 minutes after smoking. Thus, it is thought that the acute metabolic
effects of cigarettes are not significant beyond 30 minutes after smoking. Yet, given the
typical ~30 minutes between cigarettes for most smokers, RMR may remain slightly
elevated throughout the day as a result of these “acute” effects.37
Caffeine
Caffeine has been identified as a substance that elevates metabolic rate, and caffeine
ingestion has also been shown to increase work performance and promote lipid oxidation
during prolonged exercise.38-40 In a study investigating the influence of caffeine on the
resting metabolic rate of exercise-trained and inactive subjects it was found that metabolic
rate was increased in response to a stimulus of approximately two cups of coffee (300 mg).38
This study also compared regular and non-regular caffeine consumers to investigate the
effects of consumption levels on metabolic response. This investigation confirmed previ-
ous findings that with regular consumption, the physiological and stimulatory effects of
caffeine were not diminished.38
Alcohol
Alcohol is another substance that has been found to influence resting metabolic rate.
Alcohol is decidedly the most commonly consumed psychoactive drug in the U.S., and
because of its energy density, it is widely believed to be a causal factor in the development
and maintenance of obesity.41 However, in a study utilizing data gathered in two national
cross-sectional surveys — the Second National Health and Nutrition Examination Survey
(NHANES II; n = 10929) — and the Behavioral Risk Factor Surveys (BRFS; n = 18388), it
was found that alcohol consumption had a slight negative effect on the body weights of
men, and a profound negative effect on the body weights of women.41,42 This negative
effect was not a result of lowered dietary intake among drinkers. In fact, in controlled
isoenergetic dietary studies, subjects tended to lose weight on alcohol-containing regi-
mens.43,44 This has lead to the hypothesis that alcohol intake may increase resting energy
expenditure.41 Early studies found inconsistent evidence regarding the effects of alcohol
on resting energy expenditure.41,45 However, recent studies have found evidence in support
of the hypothesis that alcohol may increase resting energy expenditure,41,46 although fur-
ther investigations are needed to explain the mechanism by which alcohol suppresses
body weight.41
Medications
Medications are also known to impact resting metabolism. Beta-blocking medications, for
example, are prescribed to several million Americans with cardiovascular disease to treat
conditions such as hypertension and angina.47 Unfortunately, despite their widespread
use in medical practice, beta-blocking medications have many side effects. One such side
effect is the influence on resting energy expenditure. Research indicates that resting energy
expenditure and perhaps the energy needs of individuals treated with beta-blockers are
reduced.47 The magnitude of this reduction in resting metabolic rate has been found to
vary between 8 and 17%.47 One study reported a reduction in resting metabolism of
approximately 17% or 4 kcal/kg/day in a group of healthy subjects taking 80 mg of
propranolol twice daily for 5 days.47 This could result in significant weight gain in a
patient receiving beta-blockers long-term if no changes were made to both dietary and
exercise habits.47
RMR and Weight Loss

America currently has a preoccupation with weight loss and as a result, for many years
scientists have been interested in identifying interventions that might potentiate RMR to
facilitate weight loss in overweight and obese patient populations.27 Factors causing a
decrease in resting metabolic rate would make weight maintenance or weight loss difficult,
or possibly result in weight gain. Conversely, anything that increases resting metabolic
rate would potentially facilitate weight loss and maintenance of the weight lost.48
Energy Restriction and RMR

Over the past decade, there has been a dramatic increase in the prevalence of overweight
and obesity in adults as well as children and adolescents. Using data from the National
Health and Nutrition Examination Survey (NHANES III) it has been reported that more
that 33.4% of U.S. adults are overweight,21,49 representing an increase of 8% over the past
10 years;50,51 paradoxically, dieting has become a way of life for many Americans. In a
study utilizing data from the 1996 state-based Behavioral Risk Factor Surveillance System,
it was reported that 28.8 and 43.6% of men and women, respectively, trying to lose weight
at any given time.52 Researchers have been exploring the consequences of dieting —
particularly those related to changes in the resting metabolic rate.26 Several investigators
have found that a restrictive diet depresses resting metabolic rate, which may contribute
to the regaining of weight often observed after treatment. One such study found that the
RMR of obese individuals decreased during a protein-sparing modified fast, and remained
depressed for two months after treatment despite increased energy consumption to a level
that allowed body weight stabilization.53 Similar findings were reported by Heshka et al.19
in participants of a conservative weight-loss program. It was found that resting metabolic
rate declined to a greater degree than would be expected from loss of lean mass alone.19
Other investigators have found no adverse effects on RMR, and have concluded that any
decline in resting metabolism is fully explained by an anticipated reduction in fat-free
mass accompanying weight loss.26 A study examining the short-term and long-term effects
of very low-calorie diets (VLCDs) observed a 17.3% decrease from baseline of resting
energy expenditure after patients consumed 500 kcal/d for just 2 weeks.54 This reduction
in resting metabolism was associated with a weight reduction of only 5.8%. There was,
however, an observed rebound in RMR accompanying the patients’ return to a 1000 to
1200 kcal/d balanced diet, and the 11% end-of-treatment decline in RMR was paralleled
by a 12% reduction in body weight.54
It appears that RMR declines rapidly in response to energy restriction. Reductions as
great as 30% have been reported in some individuals.27 Very low-energy diets, in particular,
have been found to be associated with substantial short-term reductions in RMR.26 This
decline, however, appears to be attributable primarily to the caloric restriction, and is
largely reversed when dieting is stopped.26 With weight stability, reductions in RMR have
been found to be modest, and are highly related to the changes in fat-free mass.26 It is
thought that physical activity, energy deficit, macronutrient distribution, and rate of
weight loss may be key factors in the retention of fat free mass, and by extension, RMR.
Exercise and RMR

Many effects of exercise are thought to be beneficial to weight loss and weight mainte-
nance. A single bout of exercise produces an increase in energy expenditure, the magnitude
of which is dependent on the intensity, duration, and type of exercise.15 Weight-bearing
activities such as walking, jogging, and cross-country skiing lead to energy expenditure
that is directly related to body weight, and may be of particular benefit to obese individ-
uals.15 Muscle-strengthening exercises may produce an added advantage by maintaining
or increasing muscle mass. Some investigators have proposed a carryover effect of exercise
on metabolic rate; however, if any long-term effect exists, it is thought to only occur after
very vigorous and sustained physical activity.15
Both resistance and endurance training have therefore been proposed as interventions
that might potentiate RMR to facilitate weight loss in overweight and obese patient pop-
ulations. Findings from several cross-sectional studies have indicated that athletes demon-
strate a higher RMR than sedentary individuals, and training studies indicate that sedentary
individuals who are not restricting energy can increase their RMR by beginning a regular
exercise program.4 Despite these findings, the research literature regarding the effects of
resistance and endurance training, separately or in combination, on elevating the RMR is
mixed, and whether exercise training enhances RMR remains a controversial question.25
Resistance Training and RMR

Resistance training is thought to have the potential to increase RMR by increasing fat-free
mass.25 This belief is founded on the significant relation between fat-free mass and RMR.
Heavy resistance training promotes skeletal-muscle development, which could have a
favorable impact on a person’s RMR by increasing the total amount of metabolically active
tissue.27 However, the extent to which resistance training is able to increase RMR has not
been well documented, and studies evaluating the impact of high-intensity resistance
exercise on body composition and other physiological adaptations during weight loss
have reported inconsistent findings. In one longitudinal study comparing the effects of
strength training and aerobic exercise on body composition, body weight, and RMR in
healthy, non-dieting young men, the resistance training was associated with increased
strength and FFM, but body weight and RMR did not change significantly.27 These findings
were corroborated by a similar study with untrained female subjects in which a statistically
significant increase in RMR was not observed despite favorable alterations in body com-
position.18 Further studies of longer duration are needed to determine whether a significant
increase in RMR would be observed with a longer resistance training program.18
Endurance Training and RMR

Physical activity, especially in the form of endurance exercise, significantly affects energy
intake and expenditure, and is therefore a key regulatory component in the energy balance
equation.
After exercise, oxygen consumption decreases rapidly but may remain above resting
levels for several hours or even days after the bout of activity.4 The repair of damaged
muscle tissue and the resynthesis of substrates such as CP, ATP, and glycogen partially
account for the excessive post-exercise oxygen uptake (EPOC) in the exercised muscles,
and may be the cause of the elevated muscle oxygen uptake in recovery. Bullough55
reported that RMR was greater in trained than untrained subjects only when trained
subjects were in a state of recovery from vigorous exercise. Their data indicate that RMR
is influenced by exercise, energy intake, and their interaction, and suggest that higher
RMR in trained versus untrained individuals results from acute effects of high-intensity
exercise rather than from a chronic adaptation to exercise training.
Phelain et al.56 have examined the effects of low- and high-intensity aerobic exercise of
similar energy output on post-exercise energy expenditure and substrate oxidation in fit
eumenorrheic women. They used continuous indirect calorimetry performed during cycle
ergometry exercise and for three hours after low-intensity exercise (500 kcal at 50% VO2
max) or high-intensity exercise (500 kcal at 75% VO2 max). Mean EPOC for the three-hour
post-exercise period for high-intensity exercise (9.0 ± 1.7 L, 41 kcals) was significantly
greater than that for the lower intensity activity (4.8 ± 1.6 L, 22 kcals). Oxygen consumption
(VO2) following the higher intensity exercise remained elevated at the end of the three-hour
post-exercise period, but was not with the low intensity group. Quinn et al.57 reported
that exercise duration increases EPOC significantly, and that a 60-min bout of aerobic
exercise yields approximately twice the EPOC than either 20 or 40 min in trained younger
women. However, Almuzaini et al.58 examined the effects of splitting a 30-min exercise
bout of cycling into two equal sessions versus a single uninterrupted session. They com-
pared the effects of these two exercise trials on EPOC and resting metabolic rate (RMR)
and concluded that dividing a 30-min exercise session into two parts for these individuals
significantly increases magnitude of EPOC but does not affect RMR.
Short and Sedlock59 also found that fit individuals have faster regulation of post-exercise
metabolism when exercising at either the same relative or absolute work rate than their
untrained counterparts. Gillette and colleagues60 also compared strenuous resistive exer-
cise to steady-state endurance exercise of similar estimated energy cost. They found that
the resistance training resulted in a greater excess post-exercise VO2 compared to the aerobic
exercise.
Energy Restriction Combined with Exercise Training: The Effects on RMR

Dietary restriction without exercise does not appear to be an optimal strategy to promote
weight loss and weight maintenance.61 Additionally, in clinical practice, exercise when
used alone has not been viewed as an optimal means of weight reduction.61 This may be
attributed in part to the difficulty many patients have in maintaining an appropriate
program of physical activity.
Ballor and Poehlman62 performed a meta-analysis to examine how exercise training and
gender influence the composition of diet-induced weight loss. They found that diet-plus-
exercise training (DPE) groups did not differ from dietary-restriction-only (DO) groups
with respect to either the amount of body weight lost (mean = –10 ± 1.4 kg) or fat mass
lost (mean = –8 ± 1.1 kg). Exercise training, however, attenuated the amount of body
weight lost as fat-free mass compared to DO for the same sex. The percentage of weight
Men Women
0
Diet alone Diet plus exercise
-2
Changes in RMR (%)
-4
-6
-8
-10
-12
-14
FIGURE 35.3
Changes in resting metabolic rate following interventions of diet plus exercise training or dietary restriction
alone. Data adapted from Ballor, D.L. and Poehlman, E.T. Eur J Appl Physiol, 71; 535-42, 1995.
lost as fat-free mass for DPE subjects was approximately half (P <0.05) of that for DO
subjects of the same sex. The DO males lost 28 ± 4% of weight as fat-free mass, while DPE
males lost 13 ± 6%. The DO females lost 24 ± 2% of their weight from lean mass compared
to the DPE females, who only lost 11 ± 3% of their weight from the FFM. These data
provide evidence that exercise training reduces the amount of fat-free mass lost during
diet-induced weight loss. In addition, gender differences do not seem to exist with respect
to body composition changes of weight reduction.
The decline of RMR in response to energy restriction has been well documented, and
is suspected to decrease the rate of weight loss during periods of energy restriction.63
Exercise is frequently advocated in the treatment of obesity as a means of increasing
energy expenditure and potentially counteracting the negative effects of dietary restric-
tion.16 Several studies based on the addition of a component of exercise to dietary restric-
tion have been published.15,16,49,61,64 Some studies have continued to report similar
decreases in RMR, whereas others have shown an attenuation of the decrement, or an
increase in RMR when an element of exercise was added. Ballor and Poehlman conducted
a meta-analysis to examine the independent and interactive effects of dietary restriction,
endurance exercise training, and gender on RMR.65 Collectively, weight loss was greater
(P <0.05) for men (18 kg) than for women (12 kg). They found no exercise training or
gender effects on RMR during weight loss. Collectively, dietary restriction resulted in a
–0.59 kJ min–1 (approximately –12%) decrease in RMR (P <0.05). When normalized to
body weight, RMR was reduced by less than 2% (P <0.05). These data suggest that exercise
training does not differentially affect RMR during diet-induced weight loss. In addition,
decreases in resting metabolism appear to be proportional to the loss of the metabolically
active tissue (Figure 35.3).
Energy Restriction Combined with Resistance Training: The Effects on RMR

In theory, strength training should attenuate the decline of RMR if it preserves fat free
mass by preventing atrophy of skeletal muscle. Skeletal muscle contributes more than
50% of the fat free mass of the body.64 It is for this reason that resistance training was
initially added to weight-loss programs: to reduce or prevent the loss of muscle during
energy restriction, which, in theory, should attenuate the drop in RMR typically seen with
weight loss.
Few studies have been conducted that combined diet with heavy resistance exercise,
and studies evaluating the impact of high-intensity resistance exercise on body composi-
tion and other physiological adaptations during weight loss have reported inconsistent
findings.61 Conflicting results regarding the impact dietary restriction combined with
resistance training has on lean body mass have been reported. An additional problem in
evaluating the impact of resistance training is the fact that many investigators fail to
examine all the physiological variables of interest simultaneously. Two studies incorpo-
rating strength training during energy restriction found contradictory results. One study
reported an increase in fat free mass (RMR was not measured),64,66 whereas the second
found no effect of strength training on fat free mass or RMR, indicating that there are no
advantages of a resistance training program to maintenance of lean body mass and atten-
uating reductions in resting metabolic rate.64,67 The lack of an effect on fat free mass in
this study may have been attributable to the relatively low energy intake of 522 kcal/d
overriding the potential benefits of strength training.64
In the case of VLCDs, a limited number of studies have combined resistance training
with a VLCD.68 Most studies have found that incorporating resistance training into the
very low energy diet regimen does not attenuate the loss of fat free mass or decrease in
RMR.68 It has, however, been reported that significant muscle hypertrophy is possible in
an individual undergoing severe energy restriction.68,69 Hypertrophy was observed only
in the exercised muscles, and the resistance training was unable to prevent the loss of
overall fat free mass any better than diet alone.68,69 In a study comparing the benefits of
aerobic and resistance training when combined with an 800 kilocalorie liquid diet, it was
found that the addition of an intensive, high-volume resistance training program resulted
in preservation of fat free mass and RMR during weight loss.68
The results of studies examining both moderate and severe dietary energy restriction
have lead to the following hypothesis: there may be a minimum level of dietary intake
necessary for significant muscle hypertrophy to occur with resistance training.68 Research-
ers have reported that a dietary intake of at least 1000 to 1500 kcal/day is required to
attain the positive benefits that exercise training can have on RMR and fat free mass.68,70,71
Further studies are therefore necessary to determine whether a diet adequate in protein,
fiber, and vitamins and minerals, but low in total energy, can help mediate the expected
chronic adaptations to heavy resistance training.61
Caloric Restriction Combined with Endurance Training: The Effects on RMR

Aerobic exercise not only increases energy expenditure, but may also minimize the reduc-
tions in resting energy expenditure (REE) that accompany dieting by potentially increasing
sympathetic nervous system activity.66,70,72 It has also been found to attenuate the loss of
fat-free mass.66,73 In turn, this should prevent reduction in REE. Several studies have been
undertaken to examine the effects of incorporating endurance training into weight loss
regimens, with the hypothesis that its addition would attenuate losses of FFM and, by
extension, reductions in RMR.72 Studies have documented favorable effects of aerobic
activity on REE in participants who consumed diets providing 1200 to 1500 kcal/day.72,74-76
In a study designed to examine the effects of diet and exercise training on resting metabolic
rate, participants were placed on a program combining moderate energy restriction and
supervised aerobic exercise.74 It was found that REE, when adjusted for body weight,
increased 10% in this group of obese women.74 In another study examining the effects of
exercise on weight, body composition, REE, appetite, and mood in obese women, it was
found that participants who consumed diets providing 1200 to 1500 kcal/day and engaged
in aerobic activity experienced favorable changes in REE.72 In addition, the study con-
firmed the findings of previous investigators regarding the effect of aerobic training in
participants consuming VLCDs.77,78 When participants were prescribed a 925 kcal/day
diet, there was no effect of aerobic training on REE. However, when participants termi-
nated their marked dietary energy restriction, a positive effect was observed.72 In contrast,
there have been studies that have found no attenuation of the reduction in RMR in patients
consuming a balanced deficit diet consisting of 1200 to 1500 kcal/day. In a study examining
the physiologic changes after weight reduction with vigorous exercise and moderate
intensity physical activity, there were no differences between groups in decreases in RMR.79
In this study, vigorous aerobic activity did not attenuate reductions in RMR in patients
consuming a self-selected diet.79 There have also been studies which have failed to find
any positive effect on RMR of aerobic training in participants consuming VLCDs. In fact,
one study found that participants who exercised vigorously while consuming 720 kcal/
day had significantly greater reductions in REE than did nonexercising dieters.77 Similar
findings were reported by Heymsfield et al.78 This reduction in REE appears to be a
consequence of compounding the marked caloric deficit introduced by the VLCD with
that introduced by exercise.72 It has therefore been suggested that the most favorable
findings for weight loss are obtained when exercise was combined with diets of 1000 to
1500 kcal/day rather than with VLCDs providing 400 to 800 kcal/day.72
Summary
The research literature regarding the effects of dieting resistance and endurance training,
separately or in combination, on RMR is mixed. (Table 35.5 shows a collection of studies.)
Despite the numerous reported benefits of exercise training, many studies have failed to
show significant benefits of exercise on changes in weight and body composition or RMR.
Consequently, the significance of many of the effects of exercise remains questionable.16
The precise cause of the discrepancy among longitudinal studies investigating the effects
of exercise training on RMR is unknown. There are, however, several factors which have
been suggested as playing a role in the inconsistent findings. The timing of the RMR
measurement in regard to the last bout of exercise training, as well as differences in training
mode, exercise intensity, duration, frequency, and total training load have been highlighted
as potential factors which may account for some of the discrepancies among studies.27
Thus, more rigorous, well-controlled longitudinal studies are needed to elucidate the
impact of exercise training, both resistance and endurance as well as combined strength
and endurance, on RMR.
Despite the equivocal findings regarding the impact of exercise training on resting
metabolic rate of dieting individuals, exercise appears to be the single most important
behavior for long-term weight control in obese individuals.80 In addition to the well-known
benefits of both resistance and endurance training, it has been found, almost universally,
that persons who maintain their weight loss report that they exercise regularly, whereas
weight regainers do not. Exercise should therefore remain a cornerstone in the treatment
of overweight and obesity.
TABLE 35.5
Collection of Some of the Studies Investigating Changes in Physiological Variables Associated
with Treatment
Weight Fat FFM RMR
# of Change Change Change Change
Study Intervention Participants (kg) (kg) (kg) (kcal/day)
Belko et al., 1987 86 diet only 5 –7.78 –5.1 –2.68 –109.9
diet + aerobic 6 –5.70 –4.7 –0.96 –10.0
Broeder et al., control 19 0.3 0.1 0.2 –17.2
199287 strength only 13 0.00 –2.1 2.10 58.5
aerobic only 15 –1.10 –1.4 0.30 30.9
van Dale et al., diet only 6 –12.2 –9.4 –2.80 –533.66
198788 diet + aerobic 6 –13.2 –10.9 –2.30 –371.53
van Dale et al., diet only (no yo-yo) 7 –15.20 –11.9 –3.30 –389.0
198989 diet + aerobic (no yo-yo) 7 –18.90 –15.2 –3.70 –374.0
diet + aerobic (no yo-yo) 6 –19.40 –15.4 –4.00 –302.0
Frey-Hewitt et al., control 41 0.38 –0.27 0.64 27.1
199090 diet only 36 –6.68 –5.52 –1.16 –149.0
aerobic only 44 –4.10 –4.12 0.01 –22.8
Hill et al., 198791 diet only 3 –7.90 –4.48 –3.44 –211.2
diet + aerobic 5 –8.30 –6.13 –2.13 –252.0
Keim et al., 199092 diet + aerobic 5 –13.08 –7.30 –4.70 –139.0
aerobic only 5 –5.61 –3.90 –1.30 18.0
Lennon et al., diet only 22 –6.90 –6.01 –0.89
198574 diet + aerobic (self- 23 –6.70 –6.40 –0.30
selected) 20 –9.70 –8.60 –1.10
diet + aerobic
(prescribed)
Wadden et al., diet (BDD) + aerobic 9 –18.20 –16.3 –0.70 –203.3
199026 diet (VLCD) + aerobic 6 –21.60 –15.6 –1.90 –166.5
Geliebter et al., diet only 22 –9.50 –6.80 –2.70 –88.2
199764 diet + strength 20 –7.80 –6.70 –1.10 –127.2
diet + aerobic 23 –9.60 –7.20 –2.30 –148.9
Pavlou et al., 198915 diet + aerobic 15 –8.30 –6.91 –1.30 1.0
diet only 16 –6.40 –5.47 –0.80 –176.0
Mathieson et al., diet + aerobic (high carb 5 –6.70 na na –333.0
198693 VLCD) 7 –8.00 na na –207.0
diet + aerobic (low carb
VLCD)
Svendson et al., control 20 0.50 0.50 0.60 63.0
199394 diet only 50 –9.50 –7.80 –1.20 –86.25
diet + aerobic 48 –10.30 –9.60 0.00 –45.95
Wilmore et al., aerobic only 77 0.00 –0.60 0.70 16.72
199825
Kraemer et al., control 6 132.0
199761 diet only 8 –6.2 –75.0
diet + aerobic 9 –6.8 –30.0
diet + aerobic + strength 8 –7.0 –143.0
Wadden et al., diet only 29 –14.40 –11.6 –2.80 –106.0
199772 diet + aerobic 31 –17.20 –10.6 –3.20 –46.0
diet + strength 31 –13.70 –14.0 –3.10 –20.0
diet + aerobic + strength 29 –15.20 –13.4 –1.80 –7.0
Racette et al., diet only 13 –8.30 –6.1 –2.2 –129.0
199516 diet + aerobic 10 –10.50 –8.8 –1.7 –129.0
Sum et al., 199495 aerobic + strength 42 –16.10 1.70 –17.8 109.3
Donnelly et al., diet only 26 –20.4 –4.70 –16.1 –138.3
199196 diet + aerobic 16 –21.4 –4.80 –16.6 –158.6
diet + strength 18 –20.9 –4.70 –16.1 –186.9
diet + aerobic + strength 9 –22.9 –4.10 –18.0 –217.0

Collection of Some of the Studies Investigating Changes in Physiological Variables Associated
with Treatment
Weight Fat FFM RMR
# of Change Change Change Change
Study Intervention Participants (kg) (kg) (kg) (kcal/day)
Kraemer et al., control –0.35 –0.80 -4.84 –93
199961 diet only 8 –9.64 –6.68 –80
diet + aerobic 11 –8.99 –7.00 –122
diet + aerobic + strength 10 –9.90 –9.57 –136
Henson et al., diet + aerobic 7 –9.50 –8.59 –1.1 –247.0
198797
Heymsfield et al., diet only 5 –7.0 –4.4 –2.60 –115.2
198978 diet + aerobic 6 –7.5 –5.3 –2.20 –278.4
Bryner et al., 199968 diet + aerobic 10 –18.1 –12.8 –4.1 –210.7
diet + strength 10 –14.4 –14.5 –0.8 63.3
Doucet et al., diet only (phase 1) 10 –11.9 –10.7 –1.2 –304
199998 (men) diet + aerobic (phase 2) 9 –2.0 –3.3 1.3 134
Doucet et al., diet only (phase 1) 7 –7.6 –5.8 –1.8 –148
199998 (women) diet + aerobic (phase 2) 7 –1.2 –2.2 1.0 –199
Franckowiak et al., diet + aerobic 18 –7.03 –5.99 –1.03 –185.4
199979 diet + lifestyle 21 –5.42 –4.71 –0.72 –170.5
Acknowledgment
The authors would like to acknowledge the support from NIH Grant M400-215-2111 RO1
(Dr. Andersen).
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36
Energy Assessment: Physical Activity
M. Joao Almeida and Steven N. Blair
Introduction
Measuring physical activity is one of the most difficult tasks in physical activity research
due to its complexity and the fact that it is based on individual behavior characterized by
daily variability in practices and routines. A recent conference at the Cooper Institute
focused on the Measurement of Physical Activity.1 A major conclusion was that for field
studies there is no single measure able to accurately assess physical activity in all groups
of the population, in all settings, and for all aspects of physical activity. Although some
methods are highly accurate and valid, it may not be feasible to use them in field settings,
as the cost may be prohibitive. Another problem is the lack of a field criterion measure
capable of testing the concurrent validity of current or newly developed methods for
assessing physical activity. Choosing a method to assess physical activity is difficult and
requires finding the balance between objectives of the study or project and the accuracy,
validity, and feasibility of available instruments.
Concepts and Definitions

Physical activity is defined as bodily movement resulting in energy expenditure.2 Total
daily energy expenditure (TEE) has three components: resting metabolic rate (RMR),
thermic effect of food (TEF), and energy expenditure by physical activity. Although RMR
and TEF account for 60 to 80% of TEE, within-subject variability is very small. Physical
activity energy expenditure is the component that can vary greatly from day to day for
every individual; therefore, only activity-related energy expenditure will be considered
in this section. Physical activity includes all types of bodily movement, from complex
sports performance or hard labor in occupational tasks to simply fidgeting. However,
physical activity is commonly characterized by its dimensions such as type, frequency,
0-8493-2705-9/01/$0.00+$1.50
intensity, and duration. Some authors also consider the importance of the circumstances
and purpose of activity3 or its efficiency.4
Although physical activity results in energy expenditure, the latter can remain constant,
whereas the activity may vary immensely; this may result in different physiological effects
and health outcomes for various activities. Energy expenditure varies with body size, so
individuals of different body sizes might be expending different amounts of calories while
performing the same activity. Activity-related energy expenditure is determined by fre-
quency, intensity, and duration and may be expressed in total kilocalories (or kilojoules)
or kilocalories per kilogram of body mass.
• Type is a qualitative parameter of physical activity and can be categorized as:

In adults: occupational physical activity, leisure-time physical activity, or
house and yard work
In children: formal vs. informal activities, or school vs. outside school
activities.
• Intensity of activity can be defined as a qualitative (light, moderate, or vigorous)
or quantitative (specific rate of energy expenditure [METs, Watts, or oxygen
uptake]) variable of activity. Although it can be used as an outcome measure,
intensity is more often used as an independent variable.
• The frequency of physical activity behaviors is usually expressed as bouts or
sessions per day or per week.
• Duration of activity is generally described in minutes, hours, or percentage of
time spent engaging in an activity.
Why it is Important to Assess Physical Activity

Epidemiological studies carried out over the past few decades strongly support a causal
association between low levels of physical activity and increased risk of several chronic
diseases such as cardiovascular disease, type 2 diabetes mellitus, obesity, and some forms
of cancer.5 These relationships have largely been established using self-reported physical
activity, although aerobic fitness is used in some studies.6,7 Reviews of studies examining
the association between physical activity and breast cancer8 and studies of physical activity
determining the characteristics and effects of interventions9 show that inconsistent find-
ings could be related to the lack of precision of some physical activity measures. These
authors emphasized the need to utilize standardized methods, and Melanson and
Freedson10 also emphasized the need for valid, reliable, non-reactive, and precise methods.
Such instruments will facilitate determination of the specific type and amount of habitual
physical activity necessary to gain protective effects against degenerative diseases. Further
evaluation of existing methods and the development of new or alternative methods of
activity assessment are required if we are to improve our understanding of critical activity-
disease relationships.
It also is important to assess physical activity for surveillance purposes. We need to
determine whether individuals of all ages are meeting public health physical activity
recommendations and whether or not patterns are changing over time. Assessing physical
activity will provide valuable information to public health professionals, teachers,
researchers, policymakers, and others responsible for physical activity interventions.
Energy Assessment: Physical Activity 739
Purpose
Many different physical activity assessments are available, and selecting a method for a
particular project can be complicated. The purpose of this section is to provide guidance
and suggestions for this process. Specifically, we will:
• Provide an overview of physical activity assessment issues

• Discuss relevant aspects to be considered when selecting a method for assessing
physical activity
• Review the different methods available and present some advantages and dis-
advantages of each
The techniques available to measure daily physical activity and energy expenditure are
summarized here, and more extensive recent reviews can be found in previous publica-
tions.1,3,10-16 Although some methods estimate total energy expenditure, which is addressed
in a different section of this handbook, we also will discuss them briefly here because they
provide estimates of activity-related energy expenditure. In summary, this section aims
to provide useful and practical information on the assessment of physical activity sum-
marized from recent reviews and relevant published papers.
Important Aspects to Consider in Choosing the Most Appropriate

Measure
Whether evaluating a physical activity intervention program, determining the prevalence
of activity in a population, establishing the associations between physical activity and
health outcomes, or determining whether activity guidelines are being met, it is necessary
to choose an appropriate physical activity assessment method. A perfect method for
assessing physical activity would be accurate, valid, simple, not time consuming, inex-
pensive, and suitable for use in a wide range of study participants. However, such a
method has not yet been developed. Many of the available methods have acceptable
validity and reliability, but all have limitations. Choosing the most appropriate method
or methods depends on various factors.
Purpose of the Assessment

The purpose and objectives of a study or project are the primary factors to consider when
selecting the physical activity assessment method. Depending on these factors, different
measures present advantages and disadvantages that have to be considered. This is anal-
ogous to selecting a dietary assessment instrument, where the choice would be different
if the purpose was to characterize the diet of a population than if the purpose was to
provide information about the habitual dietary pattern of an individual.
We may want to assess physical activity to:
• Estimate the prevalence of activity in a population

• Determine the association between activity and health-related or performance-

related outcomes
• Evaluate the effects of a physical activity intervention program
If the purpose is population surveillance of physical activity, it may be sufficient to

classify individuals into broad activity categories such as sedentary, moderately active,
or highly active. This can be accomplished by relatively simple and inexpensive methods
such as completion of a short questionnaire on general activity patterns. Physical inac-
tivity has been identified as an important public health concern for adults and children;
therefore, assessing sedentary activities is maybe equally as important as measuring
physical activity.
To investigate the relation of activity to health outcomes, additional issues must be
considered. The specific health outcomes of interest often influence the activity assessment
method that is most appropriate. If the health outcome is osteoporosis, specific attention
should be given to weight-bearing and strength-building activities. For cardiovascular
disease or diabetes outcomes, aerobic activity such as walking might be emphasized.
Intervention studies typically involve dozens or hundreds of participants, whereas
population surveillance and epidemiological studies of physical activity and health require
thousands or tens of thousands of participants. The small number of participants in
intervention studies requires detailed information on physical activity to have sufficient
statistical power to detect differences between groups. Another factor to consider in
selecting a physical activity assessment method in an intervention study is the content of
the intervention. If the study will emphasize fitting more walking into daily routines, a
detailed questionnaire on walking times, amounts, intensity, frequency, and duration
would be appropriate. In clinical counseling situations it is often important to assess an
individual’s activity level for the purposes of self-monitoring, goal setting, and evaluating
progress. In this case it is necessary to have data that accurately reflect the person’s activity,
and it is not sufficient to place the participant into a broad activity group. This is analogous
to dietary assessment for individual counseling.
What to Assess — Characteristics of Physical Activity

Specific dimensions of physical activity may have different effects on various health
outcomes. For example, swimming would improve cardiorespiratory fitness but have little
effect on bone density. Weight lifting might improve bone density but not influence colon
cancer prevention. According to Goran and Sun4 it is often important to characterize
physical activity using both quantitative and qualitative methods (i.e., describing aspects
such as type and purpose of physical activity), and quantifying intensity, efficiency, dura-
tion, frequency, and specific energy cost of the activity.
The overall amount or volume of physical activity is generally measured in terms of
the energy expended, and is often expressed in kilocalories. Whole-room calorimetry and
doubly-labeled water (DLW) are valid methods of measuring activity-related energy
expenditure; however, the former cannot be used for assessing physical activity in free-
living conditions, and the latter only allows estimating the daily mean total of energy
expenditure over a number of days. Use of DLW will provide estimates of the specific
energy expenditure of physical activity if one assumes that RMR and TEF remain constant.
There are qualitative and quantitative aspects of physical activity that cannot be measured
by DLW (i.e., type, duration, and frequency of physical activity) which may also be
important in the regulation of energy balance and health.
Movement Pattern (Day, Week, Season, Year)

It may be important to know how the patterns of activity vary at different times. The
majority of health benefits are acquired as chronic adaptations to exercise, which requires
habitual patterns of physical activity to be measured. Adults generally have relatively
regular daily patterns which may only change for different seasons or during holidays.
They may not need to be assessed over longer periods as may be necessary for children.
Climate may influence greatly the type and frequency of activities undertaken. Signifi-
cant differences have been found between weekdays and weekends in type and amount
of activity.
Underlying Mechanism of Effect

There are several health-related dimensions of physical activity such as caloric expendi-
ture, aerobic intensity, weight bearing, flexibility, and strength.17 A similar caloric expen-
diture in different activities may have a different effect on health outcome (i.e., weight
training and swimming). Selecting an activity measure that will accurately assess the
different health-related dimensions is required to find the true associations between phys-
ical activity and health outcomes. This is analogous to selecting different dietary measures
for studies of cardiovascular disease, where saturated fat in the diet may be of prime
importance, and for cancer, where fruit and vegetable intake may be of great interest.
Nature of the Study Population (Age, Gender, Culture)

The nature of the population to be examined is relevant for the choice of method. Methods
developed for adults may not be appropriate for children. One reason for this is that
children appear to have more variation than adults in patterns of activity. Children also
often do not perform activities over extended periods. They may play at one activity for
a few minutes, then abruptly switch to another activity for a few minutes before going
on to something else. This intermittent and frequently changing pattern of activity requires
that children’s physical activity be assessed by using different intervals of assessment and
outcome measures.18 Physical activity has been assessed in children and adolescents by
various methods including self-report by questionnaire or interview and report by proxies
such as parents or teachers. Children have lesser ability than adolescents or adults to recall
their activities accurately, which renders self-report questionnaires in children of limited
value. Objective methods such as heart rate monitors, motion sensors, DLW, and indirect
calorimetry have been used frequently in small-scale studies. A comprehensive approach
to measurement issues in assessing children’s physical activity was presented recently by
Welk et al.18 Points to be considered when selecting a physical activity measurement for
children and adolescents are that seven days of monitoring are required to obtain stable
estimates of overall activity patterns,19 both weekend and weekdays need to be included
in the assessement,20 and motion sensors need to be worn for the entire day or at least for
multiple times over the course of the day.19
Age and gender also need to be considered when selecting a physical activity assessment
method for adults, and socioeconomic factors also may often be important. For example,
activity patterns between female and male executives may be similar, whereas women
who are homemakers with child care responsibilities may have very different activity
patterns than men of the same social class. There has been little work on specific activity
assessment methods for specific racial or ethnic groups, although such work is beginning
to appear.21 It is important to consider the various types of activity that are likely to be
present in a population when planning what assessment method to use. If the study group
is a general population sample, it will probably be necessary to include a wide range of
activities, including occupational, household, caretaking, leisure time, walking or cycling
for transportation to work or on errands, and sports. If the project is to be conducted in
a group of business executives, it is probably reasonable to evaluate leisure time physical
activity in detail, since these are activities that provide most of the energy expenditure
beyond RMR and TEF in this group. For these executives, it is reasonable to give only
limited attention to occupational and household activities.
Physical activity varies with age, with general population data showing a gradual
decline and the highest prevalence of sedentary behavior observed in elderly persons,
especially women.5 However, there may be substantial differences in activity patterns in
retired individuals. For some, most of the activity might be housework and yard work,
for others it might be walking, and perhaps for those living in retirement centers the major
activities might be recreational activities such as golf or dancing. It is not possible to select
a single activity assessment method for use with older individuals, but it is important to
consider the type of older population that will be included in the project.
In summary, the nature of the population to be monitored is important to consider when
selecting a physical activity assessment method. In general, younger persons are more
active than older individuals, men are more active than women, and members of minority
groups tend to be less active than non-Hispanic whites. Nonetheless, it is not possible to
simply select a method based on age, gender, or racial/ethnic group status. Many other
factors such as educational level, health status, geography, climate, and occupational group
must be considered. Ideally, it would be useful to collect some pilot data, perhaps by open-
ended questionnaires, to obtain information on types of activity most often reported by
the target population.
Sample/Population Size
The characteristics or the size of a sample must be taken into account before selecting the
activity measure. A national survey or a large population study is not likely to use labor-
intensive or high-cost techniques. A validation study or clinical trial with a relatively
small sample means that the cost, time, logistical complexity, and other resources per
person can be increased allowing the use of more sophisticated, time-consuming, and
accurate techniques.
Period of Measurement
For instruments that measure activity over periods of time, an important question is the
length of the monitoring period. This may differ for adults as compared with children
and adolescents. According to Janz et al.,22 four or more days of activity monitoring are
needed to achieve satisfactory reliability, although Gretebeck and Montoye23 suggested
that at least five or six days of monitoring are needed to minimize intra-individual vari-
ance. More recently, Trost et al.19 concluded that a seven-day monitoring period was
required for accelerometers to assess usual activity in children and adolescents and account
for apparent differences between weekday and weekend activity behaviors in the same
way as within daily differences.
In addition to considering the length of the monitoring period, it also is necessary to
consider whether multiple periods need to be monitored over the course of a year. It is
obvious that seasonal or climatic effects could have an influence on physical activity, but
this has not been studied adequately. Most epidemiological studies on physical activity
and health have obtained activity measurements at one time point. However, some of
these approaches have asked about activity over periods of various lengths — past week,
past month, past three months, past year, or usual activity. It is not clear whether any
single approach is better than any other, so at this time investigators should simply select
the recall period that seems logical for their specific population.
Cost and Feasibility

Although objective measures are probably more accurate than self-reports for assessing
physical activity, the high cost of these methods does not allow for them to be used in
some studies. For example, the use of methods such as DLW is virtually impossible in
epidemiological studies because of cost, participant burden, and the limited availability
of the isotopes. Motion sensors (reviewed in more detail later) are objective and show
promise, and the cost of such instruments has been decreasing. However, they still may
be too expensive for use in some large studies, and technical support may be required,
which further increases the cost. Many of the objective methods also impart a greater
participant burden than questionnaire approaches. Use of DLW or motion sensors requires
multiple visits to the study laboratory and requires participant cooperation and involve-
ment over longer periods.
Summary
It is not possible to give a few simple guidelines for selecting a physical activity assessment
method, and we have presented several factors that need to be considered when making
a decision. The purpose of the study, type of physical activity that is of interest, nature of
the study group, size and complexity of the study, and the available resources are all
essential elements to be evaluated in order to select the most appropriate method for
measuring physical activity. It is important to spend sufficient time in planning and
selecting an assessment method to avoid later problems.
Methods Available
Extensive research has been carried out on methods for assessing physical activity, which
has resulted in a great number of methods being developed and made available. We review
several categories of activity assessment methods here. Techniques available for assessing
physical activity can be grouped into two broad categories:
• Objective measures — calorimetry, direct observation, physiological markers,

and motion sensors
• Subjective measures — self-report (self-administered questionnaire, interviews,
diaries, or proxy reports)
Objective measures assess activity directly. They have been used in many studies to
assess levels of physical activity in all age groups, and also have been used extensively
to validate self-report measures. Continuing development and refinement of the different
devices are beginning to overcome their high cost and complexity, facilitate their use in
wider samples, and provide easier data entry, manipulation, and analyses. Subjective
methods have been most frequently used in population surveillance and large population
studies. These methods typically result in assigning individuals to one of a few broad
categories of habitual activity — perhaps sedentary, low active, moderately active, or
highly active.
Several recent reviews are available on the different techniques for assessing physical
activity and energy expenditure in both field and laboratory settings.1,3,10-15,24 Some of the
available methods will be discussed here, with particular emphasis on methods that have
been tested for validity and reliability.
Subjective Assessments
Subjective physical activity assessments rely principally on self-report of activity patterns
by the study participant. This information may be obtained by structured interview, self-
completed questionnaires, or diaries. Self-report methods have been widely used in studies
on physical and health outcomes and for population surveillance of physical activity.
Self-report techniques such as physical activity diaries, recall surveys, quantitative his-
tory surveys, and proxy report (e.g., provided by parents, spouses, or teachers) are widely
used to assess typical levels of physical activity. They rely on the subject (or proxy) to
recall activities performed over a period of time that can vary from one day to one year
(more often one week to one month) on the assumption that this period represents the
individual’s typical activity for most of the time. The complexity of the self-report mea-
sures may also vary immensely, in which the subject may be asked a few simple questions
to very detailed information regarding type, frequency, time, duration, intensity, and
perceived exertion. As result, levels of activity are expressed in different scoring systems,
which makes it difficult to interpret and compare among studies.
Self-report methods are useful for adolescents and adults, but are not particularly appro-
priate for children. Self-report methods are unreliable in young children as they do not
have the cognitive ability needed to recall and record type, duration, and intensity of
physical activity, particularly over extended periods of time.25 Furthermore, children seem
to expend energy in diverse contexts and styles, such as those involved in spontaneous
play. This diversity ranges between brief but frequent bouts of vigorous activity to activ-
ities of a longer duration such as walking or biking to school, and this diversity makes
accurate recall difficult. According to Sallis et al.,26 reliability and validity improve with
increasing age, and validity is improved when the recall interval (i.e., time from the
physical activity to the moment of report) is as short as possible. They conclude that recall
instruments should only be used with children 10 years old or older.
Advantages of self-report methods are that they are:
• Useful to assign individuals to broad activity categories, which is appropriate

in epidemiological studies and population surveys
• Relatively inexpensive
• Time efficient and have a low participant burden
• Applicable to mail-back or telephone surveys
Disadvantages of self-report methods are that:
• Accuracy is affected by the individual’s recall errors and incorrect perceptions

of activities
• Validity is limited by the ability of the subject (or proxy) to recall and report
activity behaviors accurately12
• Intensity of activity is difficult to obtain
Interviews
Structured physical activity interviews may facilitate the recall of type, amount, frequency,
duration, and intensity of activity episodes. However, even with this structure and guid-
ance by the interviewer, it is still difficult for participants to recall and report all details
of physical activity participation. A major problem is accurately classifying activity inten-
sity and accurately reporting actual minutes spent in an activity. For example, a person
may report swimming for an hour, when in fact they were at the beach for an hour and
only swam for 10 minutes. When reporting minutes spent in an activity, it is difficult to
know the minimum length of the bout that should be counted. It is reasonably easy to
identify activity bouts of 10 to 15 minutes, but should repeated bouts of five minutes or
two minutes be counted and summed over the course of the day? One of the most widely
used structured interviews is the seven-day physical activity recall, which has been used
in both community surveys and clinical trials.27,28 A major disadvantage with the interview
method for large studies is the increased cost incurred by the interviewers’ time.
Self-Completed Questionnaires
Questionnaires are the most common instruments used in large-scale studies because of
their low cost and ease of administration in large groups of subjects. One problem with
the self-completed questionnaire approach is that study participants often overestimate
the amount of their physical activity. However, even with their limitations, a large body
of evidence from studies on physical activity and health outcomes has been based on self-
completed activity questionnaires. There is good consensus from these studies, with the
clear finding that sedentary individuals are more likely than their more active peers to
develop chronic disease or die prematurely during followup. Thus, the relatively crude
classifications of activity status by the questionnaires appear to be valid for predicting
health outcomes. The various recent reviews of physical activity assessment methods
include a detailed listing of questionnaires.3,24 We encourage investigators to review these
various instruments and select the one that logically appears to be best suited to the specific
purposes and needs of the planned study. Most of the published questionnaires have
acceptable reliability and validity for assigning individuals into broad activity categories.
One of the problems faced by public health officials is surveillance of physical activity
in the population. Issues that can be addressed with a good surveillance system include
trends in population physical activity over time and comparisons of activity in different
regions. Many times it also would be desirable to make cross-national comparisons.
Unfortunately, physical activity surveys in different countries have been performed with
different methods and measurement strategies. In order to help standardize definitions
and physical activity assessments across countries, the World Health Organization and
the U.S. Centers for Disease Control and Prevention have convened an international group
of experts to develop an International Physical Activity Questionnaire (IPAQ). Short and
long versions of the questionnaire have been developed, reviewed, and revised, and are
currently being tested for reliability and validity. Preliminary results of these studies are
now available and are encouraging. The short and long versions of IPAQ can be admin-
istered by interview, self-completed questionnaire (in person or by mail-back survey), or
by a telephone interview. Although the IPAQ may be revised in light of the ongoing
studies, the final version should be available by 2001. Contact information for the Chair
of the International Working Group and the U.S. coordinator is:
• Michael Booth
mikeb@pub.health.su.oa.zu
• Michael Pratt
mxp4@cdc.gov
Diaries
Some investigators have used physical activity diaries to classify study participants.29
According to Bratteby et al.,30 the activity diary method provides a reasonable estimate
of total energy expenditure and physical activity levels in population groups. However,
Sallis concluded that diary measures have strong validity but that the burden on subjects
is high and compliance varies with the population being studied.31 Diaries are not con-
sidered feasible in young children. Physical activity diaries are likely to be most useful
when used in small studies or clinical trials. Participants in these studies are likely to be
more motivated than participants in large population studies to accept the high participant
burden involved in keeping a diary. Diaries are more likely to be successful when used
for relatively short periods of a few days.
Objective Assessments
Several methods of physical activity assessment using objective approaches are available.
These methods tend to require a higher participant burden than the subjective approaches,
and the cost for objective methods is higher, often much higher. Nonetheless, these objec-
tive methods are extremely useful, especially for small and highly controlled clinical trials.
Calorimetry
Calorimetry involves measurement of calories expended. This can be done by directly
measuring heat production by the body, but such methods are costly and are most appli-
cable to a few studies where highly accurate measures of energy expenditure are required.3
Indirect calorimetry is a method that determines energy expenditure from VO2 consump-
tion and VCO2 production, and is frequently used in the laboratory to measure exercise
metabolism. Calorimetry is usually used to validate other physical activity assessment
methods in laboratory settings. Recent advances in instrumentation for portable metabolic
analyzers have made these devices more suitable for field settings to evaluate the metabolic
rate, and thus the energy cost of various free-living activities. These methods are still
intrusive, have a high participant burden, require technically trained laboratory staff, and
are relatively expensive. These approaches can be quite useful to validate other physical
activity assessments in field settings, but have limited applicability in most clinical settings
where activity assessment is desired.
Doubly-Labeled Water
DLW is considered the gold standard for validating other field methods of assessing total
energy expenditure. The measurement of average daily metabolic rate, combined with a
measurement of resting metabolic rate and an estimate of TEF, permits the calculation of
energy expenditure for physical activity under normal daily living conditions.32 This
technique consists of administering an oral dose of 2H218O, after which carbon dioxide
production over time is calculated from the difference in the elimination rates of 2H and
18O, because the 2H label is eliminated from the body only as water, while the 18O label is
eliminated as water and carbon dioxide. Goran et al.33 indicate that studies examining the
validity of the DLW method show the technique to be accurate within 5 to 10% when
compared with data from subjects living in metabolic chambers. Although the DLW
technique is considered the gold standard for validating field methods to assess energy
expenditure, it is notable that it has never been validated in field settings because of the
lack of a suitable reference criterion.3
The advantages of the DLW method are:
• It is unobtrusive and is unlikely to influence daily behaviors

• It allows for determination of energy expenditure in free-living conditions
• It provides an accurate quantification of the energy expenditure of physical
activity over several days
Disadvantages of the DLW method are that:
• It requires specialized equipment and personnel, which makes it expensive

• The isotopes are very expensive and there is limited availability34
• It is necessary to ingest an isotope which may not be accepted by some individuals
• It provides no information about the type, frequency, duration, or intensity of
specific bouts of activity
Therefore, although the method provides an integrated measure of energy expenditure

over time, it does not provide information about how energy expenditure was accom-
plished. For example, total energy expenditure can be increased by small elevations in
activity intensity over many hours or by participating in vigorous intensity activity over
a few minutes, and these two patterns might have very different effects on health or
functional outcomes.
Overall, the DLW method has the potential to be used as the criterion measure to validate
more practical field methods.3 It has already been used to validate some field methods
such as activity diaries,30 heart rate monitoring,35 and accelerometers.32,36
Direct Observation
Direct observation consists of an observer coding the activities (type and intensity) per-
formed by an individual during short periods of time. The observation usually takes place
during specific periods such as playtime at school or physical education classes. It may
be done in real time or by viewing videotapes. Direct observation has been used mainly
to assess physical activity in children. It does not interfere directly with the activities,
assesses multiple dimensions of physical activity, and can include information concerning
contextual variables such as physical and social environments. Although the physical
activity data collected are objective and reliable, times and places available to observe
participants are limited. Thus, observation studies are done more often on preschool37,38
than on school-age children.39 Another disadvantage of direct observation studies is the
fact that they require intensive training and monitoring of observers to maintain quality
control. Direct observation is time-consuming and costly, which may explain its infrequent
use. The method is used primarily with small samples, and also as a criterion measure to
validate other instruments.
Heart Rate Monitoring

Heart rate monitoring is an objective method based on the well-established relationship
between heart rate and metabolic demand; that is, as physical work increases, heart rate
increases to provide increased circulation to the working muscles and the heart. There is
a linear association between heart rate and energy expenditure over much of the heart
rate range. Heart rate monitors are available that provide minute-by-minute recordings
of heart rate over the course of the day, or even several days. This allows for plotting heart
rate over time, and records physical activity at different intensities in short periods of time
(e.g., minute by minute) and continuously over several days.
Heart rate is a common index of activity intensity that has been used in several studies
in both adults and children.22,25,40-43 However, the use of heart rate as an unbiased indicator
of physical activity intensity has been questioned.42,44 Heart rate monitoring provides
useful information about physical activity amount and intensity within individuals, but
is less useful for comparisons between individuals. This is because heart rate for a standard
task, say walking at 3 mph on the level, is strongly influenced by a person’s cardiorespi-
ratory fitness. The fit individual might have a heart rate of 90 beats/minute during this
walk, and the unfit person might have a heart rate of 120 beats/minute. The method can
be used to compare an individual’s activity from day to day, but not to compare multiple
individuals unless the heart rate energy expenditure relationship is calibrated for each
person by laboratory testing.
Riddoch and Boreham15 reviewed 13 studies that used heart rate to assess activity levels
in children, and they concluded that at higher exercise intensities, when heart rates tend
to be high, heart rate monitoring could provide valid estimates of energy expenditure.
However, at lower exercise intensities when fear, excitement, and other emotional states
can significantly affect heart rates, the method was less accurate. Thus, if measurement
of light and moderate intensity activities is intended, heart rate monitoring presents
significant limitations.
In summary, heart rate monitoring is useful to determine whether an individual is
changing his activity patterns from day to day, such as might be expected in a physical
activity intervention study. Heart rate monitoring can be used to compare individuals if
the individual heart rate energy expenditure curves are established, and it is especially
useful for detecting moderately vigorous to vigorous activities. The heart rate monitoring
approach is time consuming, requires close cooperation from study participants, requires
equipment and technical expertise, and is not especially feasible for large population
studies. The method is objective and can provide important information about the intensity
of physical activity, and if summed over the course of the day provides an indication of
overall amount of activity.
Activity Monitors
In the last few years, activity monitors have been increasingly investigated and used in
cross-sectional and intervention studies and to validate other physical activity assessment
instruments. Activity monitors can be simple, such as pedometers or step counters, or
more complex, such as accelerometers.
Pedometers
Pedometers record the number of steps taken, which is provided as total volume during
a period of time, such as one or several days’ activity. Earlier pedometers operated on a
pendulum principle, and there were major problems with reliability and validity of these
instruments. Some more recent pedometers are electronic devices, which are substantially
more accurate than the older pendulum models.
Advantages of the electronic pedometers are that they are:
• Inexpensive, with reliable instruments costing $20 or less

• Small and light in weight, no more than an ounce or two
• Unobtrusive
• Simple to operate
Disadvantages are that they:
• Do not provide chronological information regarding the distribution of steps

over the recording period
• Do not provide data on physical activity intensity
• Do not provide data on pattern of activity over the course of the day
• Are not resistant to tampering
Overall, we find these devices useful for self-monitoring of physical activity in behav-
ioral intervention programs and think that they provide objective data that allows for
assignment to broad activity categories. Ordering information for a frequently used
pedometer that has undergone extensive reliability and feasibility testing is given here.
Yamax DigiWalker
New LifeStyles, 5900 Larson Avenue, Kansas City, MO 64133 USA
Phone: U.S. 888-748-5377, outside U.S. 816-353-1852; Fax 816-353-9808
E-mail teresa@digiwalker.com; Website www.digiwalkerinfo.com
Accelerometers
Accelerometers are motion sensors that detect movement of the body. There has been
extensive research and development of these instruments over the past several years, and
several devices are currently available. Major advantages of accelerometers are:
• Their ability to record and store activity data on a minute-by-minute basis for
extended periods of time under free-living conditions
• The objective measure of total body movement or limb movement respectively
depending on whether they are placed on the torso or on the limbs
• The chronological recording of acceleration allows for evaluation of frequency,
intensity, and duration of body movement; time spent in sedentary activities can
also be determined
• The estimates of total energy expenditure
However, these devices also present limitations such as:
• They cannot be worn during any water activities since they are not developed
to be exposed to water
• They are unable to discriminate the energy cost of activities such as carrying
loads or walking upstairs, and do not distinguish between uphill and downhill
walking or hiking45
• The cost of the equipment and the time needed to download and manipulate
the data for some of these devices are too great for use in large-scale studies
• They have not been validated for the assessment of upper body activities such
as throwing, catching, and lifting
When all things are considered, we think accelerometers offer great potential for physical
activity assessment, especially for smaller studies such as clinical trials or clinical inter-
ventions. Because of the potential of these instruments and the large amount of recent
and ongoing research on accelerometer measurement of physical activity, we will provide
a more extensive review of this approach than we have for other methods presented in
this section.
Accelerometers are available for measurement of movement in a single plane (usually
the vertical plane) or in all three planes. The unidimensional Caltrac is the accelerometer
that has been used most widely in physical activity research.10 A second unidimensional
accelerometer has been developed by Computer Science and Applications (CSA, Shalimar,
FL). Janz et al.22 found correlations of r = 0.50 to 0.74 between the CSA accelerometer and
heart rate telemetry, with higher correlations found for more vigorous activities.
Presently, there are two tridimensional accelerometers, the Tracmor and the TriTrac-R3D
(Hemokinetics, Inc., Madison, WI); however, only the latter is commercially available.
Bouten et al.46 report that tridimensional accelerometers predicted activity-related energy
expenditure better than unidimensional accelerometers when young adults performed
different types of activity (sedentary activities, walking). Tridimensional accelerometers
should more accurately record activities that include extensive horizontal motion, bending,
and twisting. However, some investigators find little difference between unidimensional
and tridimensional accelerometers.
In a study of college students, Matthews and Freedson47 compared results from the
Tritrac accelerometer with self-reports of activity on a three-day log (r = 0.82) and a seven-
day recall (r = 0.77). They concluded that although the Tritrac accelerometer underesti-
mated daily energy expenditure, it provided more accurate results than the Caltrac accel-
erometer. The Tritrac accelerometer correctly classified 84% of the students into two
groups: low active and high active. The ability of the Tritrac accelerometer to measure
activity in one-minute intervals makes it possible to analyze data from specific time
segments and allows determining total time spent at different activity intensities as well
as sustained periods of moderate or vigorous activity.
There have been few investigations using the TriTrac-R3D with children and adolescents.
Results of accelerometer studies may be different in adults than in children, because
children are more likely than adults to expend vertical energy through jumping and
climbing and have more frequent but short bouts of moderate to vigorous activity.48 Welk
and Corbin were among the first to report the use of the Tritrac accelerometer in children.49
In a sample of 35 children (9 to 11 years old), they evaluated the TriTrac-R3D against heart
rate monitoring and the unidimensional Caltrac accelerometer. The TriTrac-R3D was mod-
erately correlated (r = 0.58) with the heart rate monitor and highly correlated (r = 0.88)
with the Caltrac. The correlation of accelerometer data with heart rate was highest during
free play and lowest when activity was more limited or structured.
Ordering information for accelerometers is included here.
• TriTrac-R3D
StayHealthy, Inc, 222 East Huntington Drive, Suite 213, Monrovia, CA 91016
Phone 626-256-6152
Email pbylsma@stayhealthy.com; Website www.stayhealthy.com
• CSA
Computer Science and Applications, Inc., 2 Clifford Drive, Shalimar, FL 32579
Phone 850-651-4991; Fax 850-651-2816
Email csainc@fwb.gulf.net; Website www.csa-ucc.com
Summary
Motion sensors and heart rate monitors overcome problems associated with inaccurate
subject recall of activity and are less costly than direct observation. Objective measure-
ments provided by heart rate monitors and accelerometers can be used across all age
groups as long as their output is provided in raw scores. This is because estimates of
energy expenditure provided by some devices have substantial errors due to the fact that
the population from which the equations were derived is specific and may not represent
the population to be studied. Investigators may need to develop their own energy expen-
diture equations based on their own study group. It is important to remember that these
instruments can be prone to technical problems, are expensive, and they provide no
information concerning specific activities or the context in which activities are performed.12
Although they provide an objective measure of physical activity, accurate assessment relies
on each participant complying to wear the device throughout the monitoring period.
Conclusions
We have reviewed several categories of physical activity assessment methods and discussed
the strengths and weaknesses of each approach. Table 36.1 includes a listing of several
physical activity assessment methods and indications of how each meets various factors
that need to be considered when selecting the most appropriate method. The table combines
information presented in preceding sections and should be a useful summary tool to help
investigators and clinicians make decisions regarding physical activity assessment.
All physical activity assessment methods and instruments have strengths, limitations,
advantages, and disadvantages. Our major recommendation is that the choice of a method
to assess physical activity depends primarily on the purpose of the study and the dimen-
sions to be assessed in order to answer the relevant questions. Other critical factors to be
taken into account include the population to be evaluated, the size of the study group,
and cost and feasibility issues.
Acknowledgments
We thank Melba Morrow for editorial assistance and Stephanie Parker for administrative
assistance. The work reported here was supported in part by grants from the National
Institutes of Health (AG06945 and HL58608).
752
TABLE 36.1
Methods for Assessing Physical Activity
Characteristics of Activity Context in which
Assessed Activity Occurs Population
Format of Units of Period of
Field Measure
Type
Frequency
Intensity
Duration
Total Volume
of Activity
Sedentary
Leisure
Work
Household
Transport
Children
Adolescents
Adults
Older adults
Cost
Sample Size
Instrument Assessment Measurement Measurement
Objective Measures
DLW1-3 Ingestion of a known EE (kj or kcal) 7 to 14 days H S

concentration of
isotopes
Whole-room indirect Re-create free-living EE through A few days H S
calorimeter conditions in a measurement of
confined space heat production
and/or respiratory
gas exchange
Indirect calorimetry Standardized protocols VO2 uptake Minute or less H S
of exercise in a EE intervals
controlled
environment
HR monitor4 Wearing the monitor for Beats/min Intervals of 1 M M
all the measurement minute or less
period for up to
several days
Pedometer Wearing the device for Steps L L
Yamax Digiwalker5 all the measurement
period
Caltrac6,7 Wearing the monitor for Movement counts/ M L
all the measurement kcal
period
CSA8-10 Wearing the monitor for Counts M L
all the measurement
period
TriTrac-R3D11,12 Wearing the monitor for Movement Counts/ M
all the measurement kcal
period
Tracmor13 Wearing the monitor for Counts M
all the measurement
period
Direct Observation14 Observer rates the Minutes of activity H S
activity and intensity
Subjective Measures
7-Day Physical Interview Kcal/kg or kcal/day 7 days L L

Activity Recall
(PAR)15
PAQ-C16 L
Leisure Time Exercise
Energy Assessment: Physical Activity
Quest. (LTEQ)17
PDPAR18,19 After school

Self-administered PA
checklist (SAPAC)20
Child/Adol Activity
Log (CAAL)21
4 x 1 day recalls Interview 1 day repeated M S
four times
Diary22 Can be minutes, kcal, M M
or other measures,
depending on how
diary structured
Cost: L = Low; M = Medium; H = High
Sample size: S = Small (this is typically a few dozen participants); L = Large (can be up to a few 100 participants)
1. Schoeller DA. J Nutr 118:1278; 1988. 2. Schoeller DA. J Nutr 129:1765; 1999. 3. Seale JL, Conway JM, Canary JJ. J Appl Physiol 74:402; 1993. 4. Murayama N, Ohtsuka R. Am
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37
Thermogenesis
Bryan C. Bergman and James O. Hill
Introduction
This section deals with thermogenesis, which we define as energy expenditure (EE) above
resting metabolic rate (RMR) not associated with physical activity. Other sections in this
volume deal with both RMR and physical activity individually, and therefore these subjects
will not be addressed. As defined for discussion in this section, thermogenesis can be
produced from diet, drugs, and cold exposure. This section will discuss factors that may
enhance thermogenesis, followed by a discussion of potential implications of thermogen-
esis in determining total energy expenditure (TEE), and how modulations in thermogen-
esis may influence the obesity epidemic now facing the United States and other countries.
Thermic Effect of Food

The thermic effect of food (TEF) is the acute increase in metabolic rate above resting
metabolic rate after meal ingestion which can last for up to six hours (Figure 37.1). The
TEF has also been called dietary-induced thermogenesis (DIT), but this term is less specific
and could refer to the chronic effect of overfeeding on thermogenesis, which will be
discussed in a later section. Thermic effect of food accounts for approximately 7 to 10%
of daily EE under mixed meal conditions,2,3 and thus could be an important determinant
of daily EE. Factors which influence TEF are controversial, largely because of method-
ological differences between studies and questions about the applicability of laboratory
studies to real-life situations.4 Investigators often do not monitor TEF for sufficient time
to quantitate the full effect of a meal on EE, which may explain much of the disagreement
between studies.1 IT is influenced by many variables, including meal size and frequency,
meal composition, age, gender, obesity, and previous exercise.
0-8493-2705-9/01/$0.00+$1.50
FFM
Meal Size
100
Meal Size
Body Fat
kJ/h above RMR % Body Fat
50
MS2
0 Meal Comp
0 1 2 3 4 5 6
Time in hours
FIGURE 37.1
An illustration of how the TEF (thermic effect of food) curve shifts depending on subject and meal characteristics.
Meal size and fat-free mass (FFM) tend to increase the peak; subject’s body fat and meal size squared (MS 2) tend
to lower the peak; meal size and subject’s body fat tend to move the time of the peak further out. There is some
evidence that increased fat in the meal may decrease the peak. Illustrated curve equation: 175.9 × T x e–T/1.3,
where T is time and e is the base of the natural logarithm. RMR, resting metabolic rate. Reprinted with permission
from: Reed, G. W. and Hill, J. O. Measuring the thermic effect of food. Am J Clin Nutr 63: 164-9, 1996.
Meal Size and Frequency

It should not be surprising that meal size is positively correlated with magnitude of TEF,
due to increased energy requirements necessary to digest, transport, and store the greater
energy load (Figure 37.1).1 Increasing meal size enhances TEF in young women,5 adult
non-obese women,6 and lean and obese men.7,8 The greater the number of kcalories con-
sumed during a meal, the more dramatic the increase in TEF.
The effect of meal frequency on TEF is unclear. Enhanced TEF has been reported when
a meal is consumed in one bolus compared the same meal consumed at 30-minute intervals
over a 3-hour period,9 and is unchanged when a meal is consumed as one meal compared
to two smaller meals.10 The potential absolute change in TEF comparing an isocaloric load
consumed as one meal or several meals is small, and is not likely to significantly affect
daily EE. Thus, any role of meal pattern in overall energy balance is not likely due to
differences in TEF.
Meal Composition
Macronutrient composition of the meal influences the magnitude of TEF. Meals containing
a high percentage of protein invoke a greater TEF compared to isoenergetic meals with a
Thermogenesis 759
high percentage of carbohydrate,11-14 which are more thermogenic than a meal containing
a greater percentage of fat,13,15-17 although there is data to the contrary.6 Additionally, higher
fiber content in isoenergenic- and macronutrient-matched meals may result in enhanced
TEF compared with low fiber meals.18
An important question to consider is whether alterations in TEF can modulate daily EE.
If a high-protein diet increases TEF compared to a high-carbohydrate or high-fat diet, it
is possible that high protein diets may increase daily EE, which may explain some of the
anecdotal success of high-protein diets for weight loss. However, Westerterp et al.17 found
that changes in TEF from alterations in macronutrient content did not significantly affect
daily EE determined by whole room calorimetry. Moreover, others have also reported
isoenergetic high-carbohydrate and low-carbohydrate diets did not change TEE measure
by whole room calorimetry.19,20 Therefore, because TEF is such a small percentage of TEE,
alterations in TEF induced by changes in macronutrient composition do not appear to
increase daily EE, and thus will not enhance weight loss or weight maintenance.
Age, Gender, and Obesity

Effects of age on TEF are unclear, as few studies have examined this directly. From TEF
data on 471 subjects, Tataranni et al.21 reported no overall relationship between the mag-
nitude of TEF and age in men and women, and in women alone, and only a slight negative
relationship between age and TEF in men alone. Moreover, other studies have found
decreased TEF in older, compared to younger men,22 but no relationship between age and
TEF in women.23 While there may be a small decrease in TEF in men but not women with
increasing age, the absolute change in EE is small, and therefore not likely to impact weight
stability in older individuals. More studies are needed to elucidate mechanisms of why
TEF decreases with age in men, but not women.
Gender does not seem to change the magnitude of thermogenesis in response to a
meal.21,24 Potential alterations in TEF with menstrual cycle phase are unclear, as investi-
gators have reported increased TEF during luteal phase,25 decreased TEF during luteal
phase,26 and no change in TEF with menstrual cycle phase.27 Additional studies are needed
to more clearly elucidate whether menstrual cycle phase, or alterations in sex steroid
hormones via utilization of birth control pills, have an effect on TEF.
The role of reduced TEF in the etiology of obesity remains controversial. Some report
that obesity is associated with decreased TEF compared to age-matched control subjects,28-
33 but others report data to the contrary.8,12 Potential factors influencing confounding results
for effects of obesity on TEF have been reviewed by de Jonge and Bray,34 who suggested
that obesity does decrease TEF. Additionally, obese type II diabetic men29 have lower TEF
compared to age-matched obese men, and insulin-resistant lean men exhibit decreased
TEF compare to insulin-sensitive lean men.35 However, when obese subjects lose weight,
TEF is either partially normalized36 or not different from age-matched lean subjects.37,38
These data suggest that alterations in TEF are a result of the obese state and not a
predisposing factor promoting accumulation of adiposity.
Effects of Exercise on TEF

Acute exercise prior to meal ingestion has been reported to increase TEF in normal-weight
men and women,5,39 or not change TEF in lean men.35 The magnitude of enhanced TEF
post exercise is quantitatively small, with enhanced EE of 4.5 kcal/hr for 4 hours reported
by Nichols et al.39 and 5 and 6 kcal/hr for 2 hours reported by Young5 with a 630 and
1260 kcal meal, respectively. Mechanisms for elevations in TEF following exercise are
unclear, as further research is necessary to elucidate mechanisms responsible for
enhanced TEF. Due to the small absolute increase in TEF post exercise, meal consumption
after exercise is not likely to increase whole-body EE or help promote weight loss or
maintenance.
In obese subjects, enhanced post-exercise TEF occurs following an acute one-hour bout
of cycle ergometry.32,35 After exercise, TEF was elevated 3.3 and 7.6 kcal/hr for 3 hours in
insulin-sensitive and non-insulin-sensitive obese men, respectively. While TEF was ele-
vated after exercise in obese men, values were lower than lean men with similar insulin
sensitivity.35 Thus, dampened TEF is a consequence of obesity both at rest and immediately
following exercise.
The literature is also unclear with respect to effects of chronic endurance exercise training
on TEF. Investigators have reported endurance exercise training to both decrease,40 and
increase TEF41 by 30% (4.5 kcal/hr for 2 hrs) in men and rats.42 Additionally, enhanced
TEF has been reported in obese and diabetic men following 12 weeks of cycle ergometer
training.29 While TEF was not normalized compared to age-matched lean subjects, these
data suggest that chronic endurance exercise training may increase TEF. Thus, while most
data suggest that chronic endurance exercise training increases TEF, the absolute change
relative to daily EE is small.
Thermogenesis with Chronic Overfeeding

The previous discussion of TEF has not dealt with potential alterations in RMR with
chronic dietary alterations such as overfeeding. The literature is unclear as to the effect of
overfeeding on RMR. Some investigators have reported enhanced RMR during overfeed-
ing in humans,43-46 while an equal number have not shown an effect.47-51 This confusion
is not due to diet composition, as there does not appear to be a relationship between
macronutrient composition of overfeeding and alterations in RMR.
While the response of RMR to overfeeding is unclear, the effect on TEF is less ambig-
uous. Overfeeding increases TEF due to the greater total amount of food consumed, as
TEF is determined by energy content of the diet.8 However, it is less clear if TEF to a
given energy load is increased during overfeeding. Overfeeding has been reported to
enhance TEF during an isoenergetic meal before and after overfeeding in some,47,51 but
not all studies.49
The notion of “luxoconsumption” originally proposed by Neumann,52 and revisited by
Miller et al.,53 where excess ingested energy is “wasted” to minimize weight gain, has not
been proven. Several investigators have determined all aspects of energy balance during
overfeeding and accounted for the vast majority of ingested energy. They measured
enhanced TEF due to a greater total volume of food consumed, facultative energy require-
ments of excess energy storage, and increased cost of activity due to greater total body
weight.44,49,50 However, 85 to 90% of excess energy consumed is stored and not oxidized.50
Thus, overfeeding may enhance TEF to an isoenergetic challenge, and potentially increase
RMR. However, there is no evidence for “luxoconsumption” in overeating humans, where
excess ingested energy is dissipated as heat and not stored.
Thermogenesis 761
Cold-Induced Thermogenesis
During cold exposure, the first method of maintaining body heat is shunting of blood
from the periphery to the body core to reduce heat loss. As body temperature drops
slightly, shivering is initiated to generate heat through contraction of pilo-erectile muscles
in the skin, followed by involuntary contraction of skeletal muscle. Chronic cold exposure
may lead to cold acclimatization and the development of non-shivering thermogenesis
(NST), where other body tissue begins to produce heat which replaces shivering thermo-
genesis. While NST is well documented in rodents, its role in human thermoregulation
during chronic cold exposure is less clear.
Cold exposure in rats results in increased rates of heat production due, in part, to
increased sympathetic nervous system activity.54 Enhanced norepinephrine release55 and
concentration56 persist for the duration of cold exposure, and serve to increase brown
adipose tissue (BAT) thermogenesis for maintenance of body temperature. BAT is a miton-
chondrially dense specialized tissue for heat generation found in rodents and animals
which hibernate. Heat is generated from uncoupling of oxygen consumption to the phos-
phorylation of ADP to ATP such that oxygen is consumed, but ATP is not produced. The
metabolic energy is released as heat instead of captured in high-energy phosphate bonds.
Norepinephrine is thought to be a vital component to the development of cold tolerance,
as daily injections of norepinephrine improve cold tolerance in animals which had never
before been exposed to cold.57 Acute exposure of rats to cold results in loss of body weight,
and initiation of energetically inefficient shivering thermogenesis for warmth.58 However,
continued exposure results in normalization of weight as animals eat more when shivering
abates due to enhanced activity of BAT for heat production.58,59
Humans, however, respond much differently than rats when exposed to cold. There has
been little evidence to suggest that humans have the capacity for BAT thermogenesis.
Humans have a small amount of BAT, and compared to rodents this tissue is less active.
Thus, compared to rodents, humans exhibit different adaptive mechanisms to tolerate cold
exposure. Following cold acclimatization, humans tolerate lower core body temperature
during cold exposure without enhanced thermogenesis seen in the rat model.59 As a result,
humans acclimatized to cold shiver less during a cold challenge, and adaptive heat pro-
duction is reduced. One study has shown that it is possible to induce NST through chronic
cold exposure in humans;60 however, others have not replicated this result, as shivering
thermogenesis was maintained after cold acclimatization with no evidence for NST.48 Cold
acclimatization is largely an academic question, as it generally does not occur in humans
except under extreme circumstances. Normally, human behavior can be changed to get
out of the cold or alter the microenvironment to prevent a drop in body temperature.61
Over-the-Counter Weight Loss Stimulants

There are numerous products on the market and natural substances in foods and beverages
which may increase whole-body EE. While many products claim to have thermogenic
properties, the extent to which these drugs enhance EE is often tenous. An added difficulty
when assessing thermogenic properties of substances, especially those marketed as an
over-the-counter stimulants, is the large variety of different concentrations available to
the consumer, both between different products and between batches of one individual
product. Additionally, supplements exhibit great variability in drug bioavailability, espe-
cially when the stimulant in question is consumed with other foods and/or drugs. Here
we will attempt to cover the main thermogenic substances on the market, as well as
potential summation or synergy when using these drugs in combination.
Caffeine
Caffeine is a stimulant of EE in both rats and humans. Caffeine ingestion alone has been
reported to increase EE by 3 to 7% for up to three hours.62-64 Dulloo et al.63 reported that
a single 100 mg caffeine dose increased resting metabolic rate by 3 to 4% over 150 minutes
in both lean and post-obese humans. Thus, caffeine ingestion may have utility in enhancing
daily EE for weight loss. However, some investigators have not observed increased EE
with caffeine ingestion alone,65 likely due to small dose administration, as caffeine’s effects
on thermogenesis are dose dependent.66 The mechanism of action of caffeine’s stimulatory
effect on EE may be a result of the energy cost of enhanced lipolysis from phosphodi-
esterase inhibition and/or antagonism of adenosine action.67 In addition to thermogenic
properties of caffeine ingested alone, caffeine also increases TEF when consumed with a
meal in both young and old men and women.68 Additionally, caffeine ingestion with a
meal partially normalizes the attenuated TEF observed in post-obese subjects.63
Not all population groups exhibit similar increases in thermogenesis following caffeine
consumption. Thermogenic effects of caffeine appear to be similar in men and women,68
and in habitual and non-habitual consumers of caffeine.69 However, older men and women
tend to exhibit less of an increase in thermogenesis when compared to young controls.70
Caffeine-stimulated thermogenesis may also be attenuated in endurance-trained subjects
compared to sedentary control subjects.69 Differences in the magnitude of caffeine-induced
thermogenesis in obese compared to lean individuals is unclear. Some investigators
reported less of an effect of caffeine to increase thermogenesis in obese compared to lean
women,71 while others reported no difference in the thermogenic response to caffeine in
lean and obese women.72,73
Following repeated administration of caffeine, Dulloo et al.63 reported that the net
increase in daily EE in post-obese subjects was roughly half that observed in lean controls.
This study found that 100 mg of caffeine ingested at 2-hour intervals for 12 hours promoted
an 11 and 8% increase in EE in lean and post-obese subjects, respectively, during that 12-
hour period, with no effect of caffeine on subsequent 12-hour EE (Figure 37.2).63 Caffeine
administration repeated for 12 hours resulted in an increase in daily EE of 150 kcal/day
in lean, and 79 kcal/day in post-obese subjects. Thus, this study suggested that caffeine
consumption throughout the day may have utility in promoting weight loss or weight
maintenance. However, the effects of caffeine supplementation on weight loss in obese
subjects during an energy-restricted diet were evaluated in a 24-week double-blind trial
by Astrup et al.74 These authors reported no significant difference in weight loss during
200 mg caffeine supplementation administered three times per day compared to placebo
in obese subjects (Figure 37.3). Subjects supplemented with caffeine reported side effects
which included dizziness, headache, and insomnia which abated after eight weeks, with
no effects on systolic or diastolic blood pressure or heart rate. Thus, these data suggest
that caffeine alone in combination with energy restriction offers no benefit for added
weight loss compared to placebo control. Considering the small effect of caffeine to
stimulate thermogenesis, it is not surprising that caffeine ingestion alone does enhance
weight loss via enhanced thermogenesis. However, based on data from Dulloo et al.,63
caffeine supplementation may be needed more times per day than performed by Astrup
Thermogenesis 763
9am to 9pm 9pm to 9am

(0 - 12h) (12 - 24h)
(+11%)
p < 0.02
5.0 (+8% )
p < 0.05 Control
Caffeine
NS
Energy Expenditure ( MJ )
NS
2.5
0
Lean Post - Lean Post -
obese obese
FIGURE 37.2
Energy expenditure compartmented into the first 12-h d period (0 to 12 h) and the subsequent 12-h night period
(12 to 24 h) in lean (n = 5) and postobese (n = 6) subjects during a control study (open bars) and during
administration of caffeine. Vertical bars represent the SEM values. The probability level for significant differences
is for paired data. MG values can be converted to kcal by multiplying them by 239. Reprinted with permission
from: Dulloo, A. G., Geissler, C. A., Horton, T., Collins, A., and Miller, D. S. Normal caffeine consumption:
influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers. Am J Clin
Nutr 49: 44-50, 1989.
et al.74 to significantly increase daily EE. If true, repeated caffeine supplementation for 12
hours during the day may be useful in promoting enhanced EE for weight loss. While not
discussed in this section, caffeine ingestion may be beneficial for assisting weight loss via
appetite suppression, regardless of effects on thermogenesis.
Ephedrine
Ephedrine is a sympathomimetic agent which increases energy expenditure by enhancing
norepinephrine release from sympathetic nerve endings with stimulation of all three beta
receptor subtypes.75 Ephedrine administration alone via intravenous injection has been
reported to increase resting energy expenditure by 16% in dogs76a and 17% in obese
premenopausal women.76 Moreover, chronic oral ephedrine administration in female sub-
jects induced a sustained 10% increase in resting metabolic rate compared to pretreatment
values.77 Similarly, chronic administration of ephedrine alone to mice increased EE by 9%
and induced an 18% decrease in body weight.78 Chronic ephedrine supplementation may
increase the magnitude of enhanced EE compared to acute ephedrine administration.79
FIGURE 37.3
Changes in body weight of diet plus placebo, caffeine (C), ephedrine (E) or E + C. Means ± SEM are presented.
E + C versus placebo: *P<0.04 †P<0.01. Reprinted with permission from: Astrup, A., Breum, L., Toubro, S., Hein,
P., and Quaade, F. The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine,
and placebo in obese subjects on an energy restricted diet. A double blind trial. Int J Obes Relat Metab Disord 16:
269-77, 1992.
These data suggest that chronic ephedrine administration may be a useful adjunct to
promote weight loss in obese individuals.
Despite evidence suggesting ephedrine alone can increase RMR, experimental evidence
is lacking for ephedrine supplementation alone in enhancing weight loss when combined
with energy restriction. Astrup et al.74 reported that ephedrine supplementation of 20 mg
three times per day during energy restriction for 24 weeks did not enhance weight loss
compared to placebo (Figure 37.3). Subjects reported significantly more side effects com-
pared to caffeine-only supplementation, which also did not enhance weight loss, with
symptoms including insomnia, tremor, and dry mouth most prevalent for the first four
weeks of treatment. Additionally, Pasquali et al.80 reported no enhancement of weight loss
with two doses of ephedrine compared to placebo during a three-month intervention.
While evidence suggests ephedrine administration alone does not enhance weight loss
compared to placebo, several studies have investigated ephedrine combined with other
potentially thermogenic agents on RMR and weight loss. A combination of ephedrine and
caffeine administration is more effective in enhancing thermogenesis compared to either
caffeine or ephedrine alone,81 with above additive synergism observed at a dose of 20 mg
ephedrine and 200 mg caffeine.82,83 Additionally, data suggest that addition of ephedrine
and caffeine to an energy-restricted diet enhances weight loss in obese women compared
to caffeine or ephedrine administered separately during isocaloric energy restriction,74 or
compared to energy restriction alone.84 Astrup et al.71 reported supplementation with
ephedrine plus caffeine during a 6-month energy-restricted diet enhanced weight loss by
3.4 kg compared with placebo, caffeine alone, or ephedrine alone (Figure 37.3). Similarly,
Dulloo and Miller81 reported that daily administration of 22 mg ephedrine, 30 mg caffeine,
and 50 mg theophylline to post-obese subjects decreased energy intake by 16% and
increased EE 8%. These data are corroborated by animal studies reporting decreased body
weight during eight weeks of daily ephedrine and caffeine supplementation due to
decreased energy intake and increased EE in monkeys.85 These data suggest that ephedrine
plus caffeine supplementation decreases appetite and enhances TEE, which may be ben-
eficial for weight loss practices in the obese.
Ephedrine supplementation has also been combined with aspirin, which doubled ephe-
drine’s thermogenic action in mice78 and enhanced ephedrine stimulation of TEF in obese,
but not lean women.86 Aspirin acts only to enhance the thermogenic effects of ephedrine,
Thermogenesis 765
as chronic aspirin administration alone had no effect on energy balance in mice.78 However,
addition of aspirin to an ephedrine and caffeine mixture does not further potentiate TEF
induced by ephedrine and caffeine alone in lean and obese women.86 The drug combina-
tion of ephedrine, caffeine, and aspirin taken before meals for two months has been
reported to induce weight loss without controlled energy restriction in a double-blind
experiment in obese humans.87
These data suggest that administration of caffeine and ephedrine in combination, with
or without aspirin, may increase daily EE and enhance weight loss during energy restric-
tion. The increase in metabolic rate is small and may promote weight loss from appetite
suppression when these drugs are used in combination.84,85
Nicotine
Anecdotal evidence suggests that smoking either increases metabolic rate, decreases appe-
tite, or both, as weight gain frequently occurs with smoking cessation. Many investigations
support the former, as resting EE in men has been found to increase 5% for one hour after
smoking 2 cigarettes in 20 minutes (.8 mg nicotine yield),88 3.3% over a 3-hour period after
smoking 4 cigarettes (3.2 mg nicotine yield),62 6.5% over 2 hours following nicotine nasal
spray administration,89 and 6% increase in RMR in male habitual smokers after smoking
2 cigarettes in 20 minutes.90 While an increase in RMR may be advantageous for weight
loss or weight maintenance, the absolute increase in EE from nicotine administration is
not convincing. Collins et al.62 reported the most dramatic increase in RMR (6%) for 3 hours
after smoking 2 cigarettes in 20 minutes. However, the absolute increase in EE was only
an additional 12.5 kcals over the 3-hour period, which is unlikely to promote substantial
weight loss, even if smoking was maintained throughout the day. DIT is not enhanced
following nicotine administration via nasal inhalation at 15 micrograms/kg body weight.89
Additionally, habitual smoking does not appear to influence nicotine-induced thermogen-
esis in men.90 Thus, data are lacking to suggest nicotine administration, either from cigarette
smoking or nasal spray inhalation, may have weight loss effects via enhancement of EE.
Nicotine may be more potent in appetite suppression than in enhancement of EE. Miyata
et al. 91 reported that systemic nicotine infusion decreased body weight in rats via reduc-
tions in energy intake, with the most dramatic effects on reduction in meal number. Gender
differences were not observed for the alterations in meal size and number and body weight
reduction during nicotine administration in rats.92 Increased concentrations of serotonin
and dopamine were found in the lateral hypothalamus following nicotine administration,
which suggested that nicotine may exert anorectic effects in part by alterations in these
brain neurotransmitters. Appetite supressive effects of nicotine are not as clear in humans.
Perkins et al.93 administered nicotine via nasal spray inhalation at three doses and then
monitored subsequent meal size following an overnight fast. Suprisingly, the authors
reported meal caloric intake was increased following nicotine administration in both men
and women compared to placebo controls. However, the same authors reported that
nicotine reduced appetite in men during a subsequent meal test when nicotine was
administered following consumption of a morning meal.94 More studies are needed to
determine if nicotine is an anorectic agent in humans.
Only one study investigated gender differences in thermogenic effects of nicotine, where
nicotine was administered via nasal spray inhalation.89 Nicotine was administered once
every 30 minutes for 2 hours at 20 micrograms nicotine/kg for each dose. Nicotine
increased resting EE in men, but not women. Since nicotine intake is associated with lower
body weights in both men and women, the authors speculated that nicotine exerts anorec-
tic effects in women via more dramatic appetite suppression compared to men.
Obviously, cigarette smoking should not be used to promote weight loss, due to well
documented health risks caused by smoking. However, since smoking cessation should
be a health goal for the population, understanding the expected alterations in appetite
and/or RMR following nicotine withdrawl will be vital to attenuate weight gain often
reported with smoking cessation. The literature suggests that clinicians and health pro-
fessionals may expect a slight decrease in RMR, potentially as dramatic as 6% in chronic
smokers, upon cessation of smoking.62 Assuming that smoking only occurs during waking
hours, 8 hours sleep/night, a caloric equivalent for oxygen of 4.85 kcal/L O2, and RMR
of 3.5 ml/kg/min; a 6% decrease in RMR in a 70 kg individual would be predicted to
decrease EE by only 70 kcal/day. While the accumulation of 70 kcal/day positive energy
balance may promote slight weight gain, this simple calculation suggests that enhanced
appetite following smoking cessation may be more powerful for promoting weight gain,
and thus behavioral therapy may be indicated to help control energy intake.
Prescription Drugs for Weight Loss

Several prescription medications are currently available to physicians to enhance weight
loss. Two of these medications, sibutramine and fenfluramine, are systemic agents which
are putatively thought to only affect appetite. Orlistat, a pancreatic lipase inhibitor, is not
systemic and thus is unlikely to have thermogenic action. The potential thermogenic role
of both sibutramine and fenfluramine for enhancing weight loss is discussed here.
Sibutramine
Sibutramine is a serotonin and norepinephrine reuptake inhibitor95 which enhances weight
loss compared to placebo both with96,97 and without95 behavior modification. However,
thermogenic effects of sibutramine are less clear. Studies in rats suggest that sibutramine
increases resting EE via beta adrenergic stimulation of BAT.98 However, human data
suggests that sibutramine increases resting metabolic rate,99 or does not change RMR or
TEF.96,97 Several investigators have reported that sibutramine attenuates the decline in
RMR that occurs during weight loss.100,101 Thus, effects of sibutramine on thermogenesis
in humans are unclear; however, evidence indicates that sibutramine does decrease appe-
tite and/or increase satiety, which promotes weight loss.99,100
Fenfluramine
Fenfluramine is a serotonin-releasing agent and reuptake inhibitor102 which enhances
weight loss compared to placebo in both rats103 and humans.104-106 Effects of fenfluramine
on thermogenesis are not clear, and there appear to be species differences which further
cloud data interpretation. Investigations on rats suggested fenfluramine promotes a tran-
sient decrease in energy intake, with maintenance of weight loss via enhanced TEF, as
there were no changes in resting energy expenditure.103,107 Others, however, reported that
fenfluramine decreased energy intake throughout the treatment period108 in rats. In
humans, fenfluramine appears to act as an appetite suppressant, with decreased energy
intake compared to placebo reported for treatment groups.105 Most investigators report
unchanged RMR and TEF following fenfluramine treatment in humans.105,109-111 However,
enhanced TEF has been reported in humans following acute administration of fenflu-
Thermogenesis 767
ramine in men.112 Thus, fenfluramine appears to have little, if any, thermogenic action,
with enhancement of weight loss in humans predominately via appetite suppression.
Uncoupling Proteins and Thermogenesis

Uncoupling proteins (UCP) are proteins located in the inner mitochondrial membrane.
These proteins dissipate the proton gradient by allowing proton leaking across the inner
mitochondrial membrane. This results in a disassociation of respiration from ATP produc-
tion, with the result of an increase in heat production.113 Thus, oxygen is consumed and
heat is produced but there is no ATP synthesis. UCP are an exiting area of research, as
they may be potential weight loss drug targets to promote a less efficient metabolism and
subsequent increase in TEE.
The first uncoupling protein, now termed UCP1, was isolated from BAT in 1978 by
Heaton and colleagues,114 subsequently purified by Lin et al.115 in 1980, and molecularly
cloned in 1985.116 UCP1 is only found in BAT, and the inhibition by purine nucleoside di-
and tri-phosphates and stimulation by free fatty acids was initially described in isolated
BAT mitochondria.117 Humans exhibit minimal BAT, therefore alterations in BAT thermo-
genesis cannot explain changes in whole-body energy expenditure or the propagation of
the current obesity epidemic.
Since the discovery of UCP1, proteins with similar homology have been identified. UCP2
is expressed in most tissues, and exhibits 55% homology with UCP1 based on initial
cloning in 1997.118,119 There was considerable excitement over the discovery of UCP3 in
skeletal muscle, BAT, and heart in 1997, as it was thought to be a potential regulator of
thermogenesis which could partly explain susceptibility to, or development of obesity.
However, excitement abated after publications reported UCP2 and 3 mRNA responded
unintuitively following various perturbations, suggesting that UCP2 and 3 are not regu-
lators of thermogenesis in vivo. Fasting increased UCP2 and 3 mRNA expression in
rats120-122 and in lean and obese humans123 during a time when whole-body EE was
decreased,124 suggesting that UCP2 and 3 were not involved in altering thermogenesis in
response to dietary intervention. However, food restriction downregulated UCP3, but not
UCP2 mRNA expression in skeletal muscle.120,121,125,126 Data showing upregulation of UCP3
mRNA in response to conditions associated with enhanced lipid oxidation,120-123 in addi-
tion to results which have shown upregulation of UCP3 mRNA in rats during intralipid
and heparin infusion,127 suggest a role of UCP3 in fat metabolism and not thermogenesis.
It is important to consider that mRNA expression does not necessarily represent alterations
in protein content due to post-transcriptional regulation of the mRNA transcript. Thus,
measures of protein content and activity are necessary to fully elucidate the potential role
of UCP2 and 3 in thermogenesis. However, initial research suggests that they do not
behave similarly to UCP1 in BAT and thus may not determine susceptibility to obesity.
UCP Up-Regulation and Knockout Experiments

Knockout mice for UCP1 cannot maintain body temperature during cold exposure, con-
firming the role of BAT in determining NST.127 Interestingly, UCP1 knockout mice are not
obese, which suggests that UCP1 is not a determinant of obesity.128 Recent reports indicate
that UCP3 knockout mice are also not obese, and they do not show alterations in fatty
acid oxidation, exercise tolerance, or cold-induced thermogenesis.129,130 These knockout
mice do exhibit more tightly coupled mitochondria (state 3/state 4 ratio) as well as reduced
production of reactive oxygen species. Thus, these data suggest that neither UCP1 nor 3
solely determine metabolic rate or body weight regulation.
Thermogenesis and Obesity

There is no strong evidence that alterations in thermogenesis contribute to obesity. Ther-
mogenesis, excluding resting metabolic rate and physical activity, only contributes
roughly 10% to total daily EE. Thermic effect of food is the majority of this 10% of TEE,
which has been reported to be slightly decreased in obese compared to lean subjects in
some,28,29-33,131 but not all studies.8,12 More importantly, it is not known whether alterations
in TEF promoted the obese state, or whether the obese state promotes alterations in TEF.
Insight into this question arises from investigations on subjects before and after weight
reduction. When subjects are studied after weight loss, TEF is either not different from
age-matched lean subjects38 or partially normalized,36 suggesting that decreased TEF is a
result of weight gain, and not a causative factor in the development of obesity. Therefore,
it is unlikely that alterations in thermogenesis can explain the increased prevalence of
obesity today.
Thermogenesis, NEAT, and Alterations in Daily Energy Expenditure

Thermogenesis induced by drugs, food consumption, or cold exposure is of questionable
importance in determining TEE due to their transient nature and the relatively small effect
on increasing whole body oxygen consumption. However, fidgeting behavior has recently
been described and may contribute significantly to enhance whole-body EE.132 Levine et
al.132 quantitated EE during 8 weeks of overfeeding 1000 kcal/day in 16 non-obese men.
They coined the term Nonexercise Activity Thermogenesis (NEAT) to account for EE not
associated with physical activity or TEF. The authors reported that changes in NEAT
predicted resistance to fat gain during overfeeding, while no relationship was observed
between fat gain and changes in TEF or RMR (Figure 37.4). This NEAT exhibited marked
intra-individual variability and may partially explain why some individuals are more
susceptible to obesity than others.
Currently, we don’t have a conclusive idea of what determines the magnitude of NEAT,
or why there is up to tenfold variability in NEAT from person to person.132 However,
NEAT is an interesting avenue for future research which may suggest possible lifestyle
interventions or drug targets which could potentiate NEAT and promote greater whole-
body EE. One should not discount the importance of energy expended by NEAT activities.
Levine et al.133 recently reported on the energetics of gum chewing, a component of NEAT.
The authors reported that gum chewing increased energy expenditure by 11 kcal/hour, a
20% increase over RMR. If gum chewing occurred during the waking hours throughout
Thermogenesis 769
FIGURE 37.4
The relation of the change in (A) basal metabolic rate, (B) postprandial thermogenesis, and (C) activity thermo-
genesis with fat gain after overfeeding (27-33). Exercise levels and the thermic efficiency of exercise were
unchanged with overfeeding, so that changes in activity thermogenesis represent changes in NEAT. Reprinted
with permission from: Levine, J. A., Eberhardt, N. L., and Jensen, M. D. Role of nonexercise activity thermogenesis
in resistance to fat gain in humans [see comments]. Science 283: 212-4, 1999.
the day with no other lifestyle changes, the authors predicted weight loss of up to 5 kg
body weight in one year. Thus, NEAT activities increase EE only slightly, but may have
important implications for long-term energy balance.
Thermic effect of food has the largest influence in dictating changes in whole-body EE
excluding physical activity and NEAT. However, diet composition is the most influential
moderator of TEF, more so than age, gender, or weight.11-17 Thus, differences between
individuals in TEF are mostly due to alterations in macronutrient composition of the diet
(see “Meal Composition” under TEF) and have very small effects on changing whole body
EE. It is therefore unlikely that alterations in TEF are responsible for changes in daily EE
in most people. Rather, the amount of planned physical activity far exceeds any small
increment in thermogenesis induced by drugs, cold, or diet in determining daily EE.
Conclusions
Thermogenesis, as defined in this section, is an increase in whole body EE above RMR
which is not due to physical activity. Meal consumption increases EE, called TEF, which
accounts for up to 10% of daily EE and therefore is the most important element in
determining thermogenesis. Over-the-counter stimulants such as caffeine, ephedrine, and
nicotine are also important in enhancing thermogenesis and reducing appetite, and may
be beneficial in enhancing weight loss during energy restriction. Cold exposure also can
induce thermogenesis to maintain body temperature. But in humans, this process is largely
unimportant except under extraordinary circumstances, as behavior can be changed to
alter our microenvironment to prevent prolonged cold exposure necessary to induce
shivering and non-shivering thermogenesis observed in rodents. Alterations in thermo-
genesis are also unlikely to play a major role in the development of obesity and the growing
problem of obesity around the world, since thermogenesis is a relatively minor determi-
nant of whole-body EE.
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38
Environmental Challenges and Assessment*
Gary D. Foster and Suzanne Phelan
Introduction
Several environmental changes, including advances in technology, research, and educa-
tion, as well as economic improvements have brought about the near disappearance of
many nutritional disorders such as pellagra, beriberi, scurvy, and rickets.1 However, while
these nutritional problems have declined, other nutritional disorders have increased. For
example, the prevalence of overweight and obesity has increased from 43 to 54% of the
U.S. population since 1980 (Figure 38.1).2 Similar increases have occurred in Europe and
other industrialized countries.3
In this section, the major environmental factors that have contributed to the rise in
obesity are examined. In addition, methods of assessing environmental influences at the
population and clinical levels are reviewed.
Etiology of Obesity
Obesity is the result of an energy imbalance in which intake exceeds expenditure. Both
biological and behavioral factors play a role in the development of obesity.4 Research over
the past 15 years has underscored the importance of genetic factors.5,6 However, it is
unlikely that changes in the gene pool could account for the significant increase in obesity
that has occurred since 1980 in both adults and children (Figures 38.1 and 38.2).2,3,7-9 People
of the same genetic makeup who move to industrialized cultures from less industrialized
cultures have a corresponding increase in body weight, suggesting the importance of
environmental factors in the development of obesity.10
Indeed, the environment of industrialized countries has been viewed as so severely
promoting obesity that it has been labeled “toxic.”11,12 In order to combat this toxic envi-
ronment, extreme measures have been proposed, including a tax on high-fat, low-nutrition
foods.13-15 Clearly, the environment of industrialized nations is obesity-promoting.4,16,17 In
* Preparation of this article was supported, in part, by NIH Grant DK-5614.
0-8493-2705-9/01/$0.00+$1.50
60
Prevalence % 50
40
Obesity
30
Overweight
20
10
0
1960-62 1971-74 1976-80 1988-94
NHES I NHANES I NHANES NHANES
II III
FIGURE 38.1
Prevalence of overweight (BMI ≥ 25–29.9 kg/m2) and obesity (BMI ≥ 30 kg/m2) in the U.S. from 1960 to 1994.
NHES = National Health Examination Survey; NHANES = National Health and Nutrition Examination Survey.
Flegal, K.M., et al., Int. J. Obes. Relat. Metab. Disord., 22: 39; 1998, with permission.
16
14
12
10 6-11 y
Percentage %
12-17y
8
6
4
2
0
1963-70 1971-74 1976-80 1988-94
NHES NHANES I NHANES II NHANES III
FIGURE 38.2
Prevalence of overweight and obesity (BMI ≥ 95th percentile) in children and adolescents in the U.S., 1963–1994.
Third Report on Nutrition Monitoring in the United States, U.S. Government Printing Office, Washington, D.C.,
1995, 1–51; Troiano, R.P. et al., Arch. Pediatr. Adolesc. Med., 149: 1085; 1995.
Environmental Challenges and Assessment 775
3900
3800
3700
Food energy (kcal/d)
3600
3500
3400
3300
3200
3100
3000
1909 1945 1946 1965 1970 1980 1994
FIGURE 38.3
Food energy per capita per day in the U.S. USDA Center for Nutrition Policy and Promotion, Washington, D.C.,
1996, 1–10.
order to better understand the environmental influences on obesity, both energy intake
and expenditure must be examined.
Environmental Factors
Energy intake
Despite the increasing prevalence of obesity, U.S. data on food intake suggest only a slight
increase or modest decline in energy intake over the past two to three decades.18,19 Simi-
larly, daily energy intake in England appears to have decreased.20 However, the interpre-
tation of these data is compromised given the consistent inaccuracy of self-reported food
intake.21-23
Several other key indicators suggest that energy consumption may have increased. Data
from the U.S. Department of Agriculture (USDA) indicate that the food supply has
increased substantially over the past century and most significantly over the past few
decades (Figure 38.3). Specifically, the amount of food available for consumption per
capita per day has increased from 3300 kcalories in 1980 to 3800 kcalories in 1994.24
Although these data do not measure energy consumption, other indicators, including
increases in portion sizes and the widespread availability of high-fat, energy-dense foods,
further suggest that increases in energy intake likely account, in part, for the rising
prevalence of obesity.25
Larger Portions and Decreased Costs

Although little empirical data exist examining secular trends in portion sizes, the “super-
sizing” of America is ubiquitous. Whereas once only 8 oz servings of soft drinks were
TABLE 38.1
Typical vs. Recommended Serving Sizes
Typical USDA
Medium baked potato 7 oz 4 oz
Medium bagel 4 oz 2 oz
Medium muffin 6 oz 2 oz
USDA = United States Department of Agriculture
Young, L.R. and Nestle, M., JADA, 98: 458; 1998,
with permission.
available, today 16, 32, and 64 oz drinks can be purchased at convenience stores and
restaurants nationwide.11 A McDonald’s “medium” serving of French fries was re-classi-
fied to “small” in order to make room for a new supersized serving of French fries. In
addition, recommended serving sizes are often much smaller than people’s perceptions.
For example, research participants selected a “medium” bagel that was twice the size of
the recommended USDA serving, and chose a “medium” muffin that was three times the
recommended serving size (Table 38.1).26
Consumption of larger portions is further enhanced by attractive size/quantity dis-
counts. “Value meals” offering larger burgers, fries, and soft drinks for only a small
increase in cost have continued to gain in popularity. Similarly, a 22 oz soft drink at a
movie theatre costs $2.50 while a drink twice the size (i.e., 44 oz) costs only 50 cents more.
In addition, marketing data suggest that supersizing and multiple unit pricing (i.e., “2 for
$1.00” instead of “50 cents each”) translate into greater food consumption.11 In one study,27
subjects poured themselves 20% more bottled water when it came in a two-liter container
than when it came in a one-liter container. Interestingly, when the containers were labeled
“tap water,” participants poured the same amount from each container, suggesting that
consumption is influenced by perceived cost/value. Other research has shown that reduc-
ing the price of health foods increases sales of these items.28,29
High-Fat, Energy-Dense Foods

Of all the nutrients, fat is the most energy dense, providing 9 kcalories per gram compared
to 7 for alcohol and 4 for protein and carbohydrate. Since fat is the most energetically dense
macronutrient, its consumption is likely to increase the risk of subsequent weight gain.30-33
Surprisingly, secular data on food consumption show that the percentage of kcalories
from fat has actually declined steadily over the past 30 years in the U.S.34 and Britain.20
However, other indicators suggest that consumption of high-fat foods is on the rise. For
example, the amount of fats and oils in the food supply has nearly doubled in the U.S.
since 1909 (Figure 38.4).24 In addition, the increased availability of high-fat, energy-dense
food is observable in the proliferation of food courts, service station minimarts, fast food
restaurants, and drive-through windows. Increasingly, fast food restaurants are found in
schools and hospital cafeterias. McDonald’s stated goal is to have no American more than
four minutes from one of their restaurants. Furthermore, an estimated three new
McDonald’s restaurants are opened each day.12
Food retailers spend billions of dollars each year advertising high-fat, energy-dense
foods that bring in the most profit.17 Correspondingly, consumer purchases of high-fat
foods are on the rise. The proportion of money spent at fast-food and other restaurants
has risen from 26.9% in 1974 to 38.2% in 1994.35 A recent study suggests that eating food
away from home, controlling for multiple other factors, is associated with higher weights.36
In addition, home purchases of high-fat, energy-dense foods have risen. Specifically, the
1909 1994
Other
22% Other Grains
23% 25%
Grains
39%
Sugars and
sweeteners
11% Sugars and Meat,
sweeteners poultry and
Fats and 18% fish
oils Meat, 14%
poultry and Fats and
12%
fish oils
16% 20%
FIGURE 38.4
Sources of food energy in the U.S. food supply. USDA Center for Nutrition Policy and Promotion, Washington,
D.C., 1996, 1–10.
1.5
1.4
Fats, oils, prepackaged
foods, frozen meals
1.3
Share Index* (1980 = 1)
1.2
1.1 Cereal and bakery

products
1
Fruits and vegetables
0.9
Meat, poultry, fish
0.8
0.7
0.6
80
82
84
86
88
90
92
19
19
19
19
19
19
19
FIGURE 38.5
Relative changes in amount of home foods purchased, 1980 to 1992. U.S. Bureau of Labor Statistics, Monthly
Labor Review, December: 3–32. * reflects food purchasing habits adjusted for price changes.
proportion of home food purchases of fats, oils, prepackaged foods, and frozen meals has
increased more than any other category of food since the 1980s, even after controlling for
changes in food prices.37 The second largest increase was in cereal and bakery products,
including cookies, cakes, and doughnuts (Figure 38.5). Interestingly, the percentage of
Americans consuming low-fat products has also increased from 19% in 1978 to 76% in
1991.38 The added sugars in low-fat foods and the belief that larger portions are more
acceptable may offset any caloric benefit of consuming low-fat products.39
Summary
The available research, based principally on self-report, does not reveal significant
increases in dietary intake over the past few decades. However, several indicators suggest
that the environment has promoted increased energy intake. Two principal factors appear
to be responsible: 1) increasing portion sizes; and, 2) accessibility to high-fat, energy-dense
foods at affordable prices.
Energy Expenditure
Although about one-fourth of U.S. adults do not engage in any physical activity during
their leisure time, there is little evidence that physical activity levels have changed signif-
icantly over the past decade (Figure 38.6).40 Nonetheless, it is generally accepted that with
the modernization of society, energy expenditure has decreased and is at least partly
responsible for the increasing prevalence of obesity.20,41,42 The decrease in energy expen-
diture is most likely due to changes in activities of daily living.41 While data in the U.S.
are lacking, evidence from Finland and Britain support that decreases in energy spent on
activities of daily living and work have indeed occurred.43
Table 38.2 lists some of the ways time (and energy) is saved each day. While little data
have documented trends in the use of such energy-saving devices, consumer purchases
suggest a proliferation. Automobiles are clearly the preferred mode of travel over walking
in both the U.S. (Figure 38.7)44 and the United Kingdom.45 Purchases of cable television
and videocassette rentals have increased dramatically (Figure 38.8).46 While longitudinal
30
25
Prevalence %
20
No activity
15 Regular, sustained
Regular, vigorous
10
0
85
86
87
88
89
90
91
19
19
19
19
19
19
19
FIGURE 38.6
Trends in leisure-time physical activity of adults age 18+ years. U.S. Department of Health and Human Services,
Washington, D.C., 1996, 88-50210, Government Printing Office.
TABLE 38.2
Energy Savers
Personal computers
Telecommuting
Cellular phones
E-mail/Internet
Shopping by phone
Food delivery services
Phone extensions
Dishwashers
Escalators/Elevators
Cable movies
Drive-thru windows
Computer games
Intercoms
Moving sidewalks
Remote controls
Garage door openers
100
80
Percentage of Trips/Year
60 Other
Bicycle
40 Public Transit
20 Walk
Motor Vehicle
0
1977 1983 1990 1995
Other 3.8 6.5 3 2.4

Bicycle 0.6 0.8 0.7 0.9
Public 2.4 2.2 2 1.8
Transit
Walk 9.3 8.5 7.2 5.5
Motor 83.9 82 87.1 89.3
Vehicle
FIGURE 38.7
Mode of travel in the U.S. from 1977 to 1995. Pickrell, D., and Schimek, P., Nationwide Personal Transportation
Survey, Dept. of Transportation, Washington, D.C., 1998.
50 Cable television
Percentage of households 40
30
20 Rental of videocassettes
10 Videocassette recorders
Telephone answering machines
Computers
0
80
82
84
86
88
90
19
19
19
19
19
19
FIGURE 38.8
Percentage of households reporting expenditures, 1980 to 1990. U.S. Bureau of Labor Statistics, Monthly Labor
Review, May 18–26, 1992.
data on television viewing in the U.S. are lacking, television viewing in England has
increased from 13 hours per week in the 1960s to 26 hours per week today.20 In the U.S.,
television viewing is strongly related to the increasing prevalence of obesity among
children47-49 and to the level of obesity in adults.50,51 Research is needed from other countries
and for other sedentary activities such as video watching and computer work.
Cultural and Social Factors

The increasing prevalence of overweight is also associated with cultural and social factors.
The prevalence of obesity in the U.S. is greatest among non-Hispanic blacks and Mexican-
American women (Figure 38.9).8 This may reflect cultural values and beliefs that limit the
motivation for weight control and effectiveness of weight control programs or specific
behaviors such as lower levels of physical activity.52,53 Recent research also suggests that
metabolic factors play a role, including decreased energy expenditure among obese Afri-
can-American women relative to Caucasian women.54
Obesity is also more common among low-income populations.55 Low-income popula-
tions often experience differential access to health care services56,57 due to cost barriers,
unavailability of health insurance, and discrimination in health care.58,59 Economic status
may also impact families’ nutritional patterns, level of concern about nutrition, and knowl-
edge of foods to purchase and consume.1,60,61
Assessment of Environmental Challenges

A detailed review of measures of food intake and physical activity can be found in Sections
3 and 7 of this book and other comprehensive texts (e.g., St. Jeor, 199762). Therefore, only
a brief review of assessment tools will be provided here.
80
70
Prevalence % 60 Females
50
40
30
Males
20
10
0
Non-Hispanic Non-Hispanic Mexican-
White Black American
FIGURE 38.9
Prevalence of overweight (BMI ≥ 25 kg/m2) in the U.S. by race-ethnic group for men and women age 20–74
years, 1998–1994. Flegal, K.M., et al., Int. J. Obes. Relat. Metab. Disord., 22: 39; 1998, with permission.
Epidemiologic Assessment
Physical Activity
Although physical activity tends to be over-reported,23,40 questionnaires are frequently
used in epidemiologic studies to classify levels of physical activity.63,64 Although several
physical activity measures exist (e.g., diaries, retrospective histories), recall surveys appear
to be the least likely to influence behavior and generally require the least amount of effort
by respondents.40,63 Among the most frequently used measures are the Physical Activity
Recall (PAR)65 and the Paffenbarger.66 The PAR is available in interviewer- and self-
administered versions65 and categorizes activities by their intensity; the Paffenbarger is a
one-page questionnaire that evaluates habitual daily and weekly activity. Measures of
sedentary-promoting behaviors, such as television viewing and computer use, are only
beginning to be utilized and validated. However, sedentary behavior can be simply
assessed by the number of reported minutes per day spent in sedentary behaviors (e.g.,
watching television, using the computer, video games, and driving).
Food Intake
As noted earlier, food intake tends to be underreported, particularly in obese individuals.22
Nonetheless, several methods of assessment exist to measure nutrient intake. The 24-hour
recall has been used in many large-scale studies (e.g., the National Health and Nutrition
Examination Surveys) to assess nutrient intake. The 24-hour recall is typically adminis-
tered by trained interviewers. It takes about 20 minutes to complete, requires no record
keeping on the part of respondents, and, unlike other measures (e.g., food diaries), does
not cause subjects to alter their intake.67 Alternatively, if assessment of subjects’ average,
long-term intake is needed (rather than a more precise measurement of short-term con-
sumption), food frequency questionnaires (FFQ) are an appropriate alternative. FFQ (e.g.,
the Block68) assess the frequency and quantity of habitual consumption of food items listed
on a questionnaire in reference to the past week or month. These are easy to administer
and do not require trained interviewers.
Clinical Assessment
Physical Activity
The questionnaires reviewed above (i.e., PAR65 and the Paffenbarger66) may also be useful
in assessing physical activity in the clinical setting. Alternatively, a few simple questions
may provide a practical and efficient means of assessing physical activity. These include:
“How many minutes do you spend each week in planned physical activity?”; “Approxi-
mately how many city blocks do you walk each day?”; and “How many flights of stairs
do you climb each day?” Television viewing, computer and video game use, and driving
time may also be evaluated in the clinical setting by weekly number of minutes for each
activity. Finally, pedometers, which provide a count of the total number of steps taken
each day, can be very useful in monitoring changes in physical activity.
Food Intake
The most commonly used means to assess energy and nutrient intake in the clinical setting
is the food record. Food records are patients’ daily notations of the type, quantity, and
calories of food and liquid consumed. Patients are instructed to record all meals, drinks,
and snacks immediately after eating. Patients may also record the number of fat grams
consumed, place of consumption, and minutes of television viewing per day. It should
also be noted that food records are commonly used as an intervention tool.69 If a less
reactive and more immediate assessment of intake is required, FFQ or 24-hour recalls may
be used. Restaurant eating can be assessed at the time of the clinic assessment with the
question, “How many times per week, on average, do you eat at restaurants?”.
Assessment Model
The ultimate challenge of environmental assessment is to integrate the multiple factors
that influence obesity. As Figure 38.10 illustrates, food intake and physical activity may
result from a combination of influences (e.g., large portion sizes, use of labor-saving
devices) that interact with cultural and social factors to promote obesity. In this model,
excess food intake may be due to larger portion sizes at restaurants, but other factors must
also be considered. For example, cultural taste preferences and economic status may also
influence restaurant selection. Although distinguishing among the several overlapping
environmental influences can be difficult, an awareness of such interrelationships is critical
for designing public health and clinical interventions aimed at decreasing the prevalence
of obesity.
Summary and Conclusion

In summary, obesity is due to an imbalance of energy intake and expenditure. Both
biological and behavioral factors are implicated. Several environmental changes have
Food Preparation Methods

Beliefs about Nutrition
Value of Exercise
Cultural Factors
Remote Controls Ideals of Beauty

Marketing
Television Viewing High Fat Foods
Automobiles
Bargain Buys
Activity Level Food Intake
Drive-Thrus OBESITY
Computers Large Portion Sizes
Fast Food Restaurants
Cellular Phones
Social Factors
Socioeconomic Status
Economy
Education Food Supply
General Health
Industrialization
FIGURE 38.10
Environmental influences on obesity.
occurred over the past few decades that appear to contribute to the increase in obesity in
industrialized nations. In particular, portion sizes are larger, and high-fat, energy-dense
foods are heavily marketed and readily available at a low cost. In addition, the amount
of energy expended in activities of daily living appears to have declined.
The problem of obesity may be instructive to understanding other nutrition-related
disorders affected by environmental factors, including high cholesterol, hypertension, and
osteoporosis. As in the case of obesity, it is likely that a combination of cultural, societal,
and other environmental forces leads to the development of nutritional problems in the
world today. Clearly, promoting healthy nutrition will require targeting multiple environ-
mental components and encouraging a partnership among various sectors of society,
including the government, food industry, and the media.3
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13. Brownell KD. New York Times, A29, Dec. 15, 1994.
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New York, 1998; pg 105.
15. Ahmad S. U.S. News and World Report, 62-63, 1997.
16. Brownell KD,Wadden TA. In: The Handbook of Eating Disorders: The Physiology, Psychology, and
Treatment of Obesity, Bulimia, and Anorexia, Brownell KD, Foreyt JP, Eds, Basic Books, New
York, 1986.
17. Wadden TA, Brownell KD. In Behavioral Health: A Handbook of Health Education and Disease
Prevention, Matarazzo JB, Miller N, Weiss SM, Herd A, Weiss S, Eds, Wiley, New York, 1984;
pg 608.
18. Ernst N, Obarzanek E, Clark MB. JADA 97: S47; 1997.
19. Federation of American Societies for Experimental Biology, Third Report in Nutrition Monitoring
in the Unites States, US Government Printing Office, Washington, DC, 1995, pg 148.
20. Prentice AM, Jebb SA. Br Med J 311: 437; 1995.
21. Schoeller DA, Fjeld CR. Ann Rev Nutr 11: 355; 1991.
22. Schoeller DA. Metabolism 44: 18; 1995.
23. Lichtman SW, Pisarka K, Berman ER, et al. N Engl J Med, 327: 1893; 1992.
24. US Department of Agriculture’s Center for Nutrition Policy and Promotion, Nutrient Content
of the U.S. Food Supply, 1909-94: A Summary, Washington, DC, 1996, 1-10.
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39
Psychological Tests
Victor R. Pendleton and John P. Foreyt
Psychological factors play a significant role in many nutritional abnormalities. These

factors include mood (depression, anger, anxiety), emotional eating, distorted body image,
low self-esteem, poor self-efficacy, dietary restraint, stress, susceptibility to external cues
to eat, locus of control, and stage of change (see Table 39.1). They contribute to a number
of nutritional abnormalities including obesity, anorexia nervosa, bulimia nervosa, and
binge eating disorder. In this section we discuss instruments that assess psychological
factors relevant to nutritional goals and concerns.
Obesity
Obesity is epidemic in our modern society.1 In the U.S. from 1960 to 1994 the prevalence
of obesity has increased from 10 to 20% in men, and from 15 to 25% in women.2 The
abundance of good tasting, energy-dense food is a significant factor fueling this increasing
prevalence of obesity. Aromas, advertisements, and social gatherings are some of the
environmental cues that trigger eating behavior. An individual’s susceptibility to external
cues to eat, perceptions of ability to control behavior, and feelings of self-efficacy and self-
esteem are factors that interact with the environment to determine behavioral responses.
Despite awareness of the problem of obesity in the U.S., and the chronic and debilitating
conditions related to it, many people do not attempt to change behaviors that contribute
to the problem.1 Of those who do attempt change, the majority fail to maintain their weight
loss goals. Researchers have speculated as to why this is the case. One theory is that, in
general, interventions do not match the way people change. This theory, known as the
Stages of Change or the Transtheoretical Model,3 posits that people move through various
levels of readiness to change, from not interested (precontemplation), to thinking about
it (contemplation), to planning to do it one day (preparation), to making concrete efforts
to change (action), to maintaining successful change (maintenance). The criticism is that
traditional interventions are overwhelmingly action-oriented and offer no help to indi-
viduals in the precontemplation and contemplation stages who might benefit from more
0-8493-2705-9/01/$0.00+$1.50
TABLE 39.1
Psychological Factors Contributing to Nutritional Abnormalities
Depression, anger, anxiety
Emotional eating
Distorted body image
Low self-esteem
Poor self-efficacy
Dietary restraint
Stress
Susceptibility to external cues to eat, locus of control
Stage of change
TABLE 39.2
Psychological Instruments and What They Measure
Body Eating Restricted Locus of Stage of
Mood Image Self-Esteem Self-Efficacy Disorders Eating Control Change
RLCQ X
SCL90-R X
BECK X
FRS X
EDI2 X X
RSE X
ESES X X
BES X X
EDE X
EI X
DEBQ X X
DBS X
SOCA X
URICA X
RLCQ — Recent Life Change Questionnaire; SCL90-R — System Checklist 90 — Revised; BECK — Beck
Depression Inventory; FRS — Figure Rating Scale; EDI2 — Eating Disorders Inventory 2; RSE — Rosenberg
Self-Esteem Scale; ESES — Eating Self-Efficacy Scale; BES — Binge Eating Scale; EDE — Eating Disorders
Examination; EI — Eating Inventory; DEBQ — Dutch Eating Behavior Questionnaire; DBS — Diet Beliefs
Scale; SOCA — Stages of Change Algorithm; URICA — University of Rhode Island Change Assessment Scale
consciousness-raising efforts. Some researchers suggest that this is a contributing factor

to the high relapse rate in traditional weight loss programs.
The ability to measure psychological states and traits may facilitate the planning of
treatment for disordered eating. We have identified instruments that measure these char-
acteristics (Table 39.2) and describe each of them in this section. Each description explains
what the instrument measures, how it measures it, why it is important, administration
and scoring procedures, norms, psychometrics, and availability. Many of the instruments
do not provide norms for obese populations; however, in light of the evidence indicating
no significant differences in levels of psychopathology between obese and non-obese
individuals, the lack of obesity-specific norms may not be a major problem.4
Eating Disorders
Anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) are eating
disorders described in the Diagnostic and Statistical Manual, 4th edition, (DSM-IV) pub-
lished by the American Psychiatric Association (1994). Anorexia nervosa is marked by a
failure to maintain a minimal healthy body weight and a fear of gaining weight. Bulimia
Psychological Tests 789
nervosa is characterized by the uncontrollable eating of unusually large amounts of food

(binge eating) followed by compensatory behavior such as vomiting. Binge eating disor-
der was proposed as an eating disorder for inclusion in the DSM-IV. Although it was not
accepted as a formal disorder, the DSM-IV included research criteria to encourage further
investigation of the condition.5 BED is characterized by recurrent episodes of eating
unusually large amounts of food within discrete periods of time, which are associated
with feelings of being out of control. Three of the following features must also be present
to meet the DSM-IV criteria for BED: rapid eating; eating until uncomfortably full; eating
when not physically hungry; and feelings of embarrassment, disgust, depression, and/
or guilt. Additionally, the behavior must occur at least two days per week for a period
of six months.5
These eating disorders are often comorbid with other psychological abnormalities. For
example, the cardinal features of anorexia nervosa include fear of being out of control and
distorted body image.6 Comorbid major depression or dysthymia has been reported in 50
to 75% of anorexia nervosa patients.7 According to Maxmen and Ward,6 75% of bulimics
develop major depression. Increased rates of anxiety were reported in 43% of bulimics.7
Restrained eating and emotional eating due to stress are believed to be related to binge
eating disorder.8 Large and unplanned changes in body weight are symptoms of depres-
sion.5 Instruments assessing these eating disorders are also described in this section.
Mood
Recent Life Changes Questionnaire (RLCQ)
Overeating has been identified as a compensatory behavior used by some individuals to
cope with stress.9-11 Life events can be a major source of stress. Some individuals experi-
encing high amounts of stress in their lives find it particularly difficult to control their
eating behavior. Rahe12 reported that overweight women experienced more recent stress
than normal controls. The Recent Life Changes Questionnaire (RLCQ)13,14 estimates the
amount of stress experienced by determining the number of significant events that have
recently occurred in the person’s life.
The RLCQ is a popular 74-item questionnaire that quantifies the occurrence of specific
events in the areas of health, work, home/family, personal/social, and finance. It has been
used to assess the relation between stress and general illness susceptibility.13,14 For each
event identified, the RLCQ asks the respondent to give a value on a 100-point scale
representing an appraisal of the degree of stressfulness associated with the event. The
values are added together for a subjective life change unit (SLCU) total. Normative values
(i.e., weights or LCUs) are also available for these 74 items.15
Descriptions of the psychometric properties of the RLCQ are limited. Two studies
address test-retest reliability. Using SLCU values (weights), Rahe16 reported an alpha
correlation of 0.90 for the RLCQ when given one week apart and 0.56 when given eight
months apart. Pearson and Long17 found the alpha reliability of the RLCQ using SLCU
values to be 0.84 (p<.001) over a one-month interval. The RLCQ can be found in Rahe.14
Symptom Checklist 90-R (SCL90-R)

The Symptom Checklist 90-R (SCL90-R)18 is a 90-item self-report instrument designed to
assess current pathology along 9 dimensions: somatization, obsessive-compulsive, inter-
personal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and
psychosis. The scales of particular interest to clinicians are anxiety, hostility, and depression
because they measure characteristics that may be related to abnormal eating behaviors.6
The items describe physical and psychological conditions, and subjects are asked to assess
the degree to which the conditions have affected them over the past seven days. Responses
are selected from a five-point Likert scale that ranges from “not at all” (0) to “extremely”
(4). The subscale scores are determined by averaging the scores of the items comprising
each subscale.
The SCL-90-R has extensive normative data for psychiatric and non-psychiatric popu-
lations, white and non-white subjects, men, women, and adolescents.18 The subscales have
good internal consistency with alpha coefficients ranging from .77 to .90.19 Investigations
yielded Pearson Product Moment Coefficients in the range from .78 to .90, which indicate
good test-retest reliability.19
A weakness of the SCL90-R is a lack of evidence supporting the discriminant validity
of the subscales. The test appears to have the ability to measure general distress; however,
its ability to discriminate between types of distress is not supported. The SCL-90-R is
available from National Computer Systems, Inc. in Minneapolis, Mn. Their email address
is assessment@ncs.com.
Beck Depression Inventory (BDI)

The comorbidity of depression and eating disorders is well documented.20,21 Depressive
symptoms are more severe among obese subjects who also binge eat than among non-
bingers.22 Its assessment in people receiving treatment for these conditions is important
because the depression may have a negative impact on program adherence.23 Intervention
outcome for depressed patients receiving treatment for eating-related disorders may be
improved by treating the depression first.24,25
BDI26 is a 21-item instrument commonly used to measure depression. The items explore
changes in mood, activity level, self-concept, and feelings of self-worth. The BDI has been
used with a broad array of subjects ranging from young adolescents through adults. It is
easy to understand and takes only about 10 minutes to complete.
Each item offers a choice of four self-descriptive statements that range in severity from 0
to 3. The instrument is scored by summing the values of the individual items. The range of
possible scores is from 0 to 63. Cutoff scores for interpretation of the instrument are: 0 to 9
normal; 10 to 18 mild to moderate depression; 19 to 29 moderate to severe depression; and
30 to 63 severe depression.27 Individuals scoring above 16 should receive further screening.
The reliability of the BDI is good. The test-retest reliabilty has been consistently reported
in the range of .60 to .8427 in nonpsychiatric populations. Internal consistency is in the .73
to .92 range.27 The BDI is available from The Psychological Corporation, San Antonio,
Texas. Their email address is customer_service@harcourtbrace.com.
Body Image
Figure Rating Scale (FRS)
The FRS28 is a popular instrument used to assess an individual’s level of dissatisfaction
with physical appearance. Dissatisfaction with aspects of physical appearance is very
common among people suffering with weight and eating problems. Indeed, it is part of
the DSM-IV criteria for diagnosing anorexia and bulimia.5
The instrument consists of a set of nine figures of increasingly larger size. Administration
is done in two parts. First, respondents are asked to select the figure that most closely
resembles their current size. They are then asked to select the figure that most closely
resembles their ideal size. The difference (discrepancy score) between selections represents
their level of body dissatisfaction.
Despite its popularity, little reliability and validity data exist for this instrument. Mea-
surement of internal consistency is not applicable with this type of scale. Two-week test-
retest reliability was .82 for ideal size and .92 for current size in a sample of 34 men, and
.71 for ideal size and .89 for current size in a sample of 58 women.29 In a sample of 146
women, correlations between discrepancy scores and other measures of self-image were
moderate to strong.29 These results suggest that the FRS has adequate validity and good
test-retest reliability. The scale appears in Stunkard, Sorenson, and Schlusinger.28
Eating Disorders Inventory — 2 (EDI2)

The EDI230 is a popular 91-item self-report instrument used to assess eating attitudes and
behaviors along three subscales: drive for thinness, bulimia, and body dissatisfaction.
Measurement of these factors is important because of their relation to serious nutrition-
related conditions such as anorexia and bulimia.
The drive for thinness and the bulimia subscales assess attitudes and behaviors toward
weight and eating, respectively. The body dissatisfaction scale is most related to body
image. It assesses attitudes and behaviors toward the shapes of nine different body parts.
Subjects indicate the degree to which they relate to statements by choosing from six
possible choices ranging from “never” to “always.” The three most pathological responses
are scored 3, 2, and 1 in order of descending severity. The three least pathological responses
are not scored. Scores are computed by summing all responses for each subscale.
Normative data are available for male and female college-age eating-disordered and
non-eating-disordered subjects31 as well as for adolescents. The body dissatisfaction sub-
scale has been found reliable with children as young as eight years old.
In reports on internal consistency, alpha coefficients range from .69 to .93 for the three
scales.31 One-year test-retest reliability in a sample of non-disordered subjects ranged from
.41 to .75.32 Test-retest reliability after a three-week span was above .8 on all scales in a
similar sample.33 The EDI2 is available from Psychological Assessment Resources, Odessa,
FL. Their email address is custserv@parinc.com.
Self-Esteem
Rosenberg Self-Esteem Scale (RSE)
The RSE34 is a ten-item Likert scale that measures global self-esteem. This construct refers
to a person’s general feelings of self-worth. Low self-esteem is related to various eating
disorders35,36 and may confound efforts to correct dysfunctional eating behavior. Identify-
ing and treating low self-esteem may improve outcome in the treatment of some eating
disorders.37
The items are statements of self-perception. Respondents are presented with a choice of
four responses ranging from “strongly agree” to “strongly disagree.” The scale is scored
by assigning a zero to low self-esteem responses and a one to high self-esteem responses.
Individual item scores are summed to arrive at the scale score. A score of 10 indicates
high self-esteem across all items.
The RSE is a mature instrument with norms available from many samples. However,
several scoring approaches have been used, which sometimes makes comparisons tricky.
For example, the aforementioned scoring method is suggested in the RSE available from
the University of Maryland.38 Descriptive statistics for a Guttman-scale version of the RSE
are reported by Wylie.39 In the Guttman-scale version, higher scores represent lower self-
esteem and lower scores represent higher self-esteem. Conversely, Poston et al.40 suggest
that a scoring method resulting in scores ranging from 10 to 40 is the most widely used
method. In this method, lower scores represent lower self-esteem and higher scores rep-
resent higher self-esteem.
The RSE has good internal consistency. Rosenberg34 reported an alpha coefficient of .77
for a sample of 5024 high school juniors and seniors. In a survey of seven studies, Wylie
reported alpha coefficients in the range from .72 to .87.39 Two-week test-retest reliability
for a sample of 28 college students was .85. With a sample of 990 Canadian high school
students, test-retest correlation after a seventh-month interval was .63.39
The RSE is available free of charge for educational and research purposes. It can be
downloaded directly from the University of Maryland website.38 The University of Maryland
website address (URL) for the scale is http://www.bsos.umd.edu/socy/rosenberg.htm.
Self-Efficacy
Eating Self-Efficacy Scale (ESES)
The ESES41 is a self-report instrument designed to measure perceived ability to control
eating behavior in 25 challenging situations. Perceived ability to control eating is evaluated
along two subscales: control in socially acceptable situations and control when experienc-
ing negative affect. For many people, today’s environment is filled with opportunities and
encouragement to consume large quantities of food, and this is especially challenging for
those who eat in response to stress. Understanding a person’s behavioral response in the
presence of gastronomical opportunities and stress is important in the design of programs
to normalize eating.
The ESES is a 25-item Likert scale that presents answers in a 7-point format. Ten of the
items make up the social acceptability subscale and the other 15 make up the negative
affect subscale. Subscale scores are computed by summing the scores of the associated items.
The instrument appears to have good internal consistency across subscales. Alpha coef-
ficients for a sample of 484 female undergraduates were .85 for the negative affect subscale
and .85 for the social acceptability subscale.41 Seven-week test-retest reliability computed
using a sample of 85 female undergraduates was .70.41 The ESES appears in Glynn and
Ruderman.41
Binge Eating Scale (BES)

The BES42 is a 16-item scale designed to assess binge eating in obese subjects. It has also
been used with non-obese populations. Eight items of the BES measure binge eating
behavior and the other eight measure associated feelings and thoughts. Each item consists
of a cluster of self-statements. Respondents are asked to select the statement that most
closely resembles their feelings. Responses are given different weights. The scale score is
computed by summing weighted scores of the 16 items. The BES does not assess all of the
information necessary to make a clinical diagnosis, but does measure behavioral features
and cognitions associated with binge eating. The scale score has been interpreted as an
indication of severity of binge eating.43 The range of potential scores is 0 to 46. The higher
the score, the more severe the binge eating. A score above 27 suggests severe binge eating.
The original work by Gormally et al.42 suggests that the BES has adequate internal
consistency. The scale discriminates well between people with bulimia nervosa (non-
purging) and normal controls.43 The BES has good test-retest reliability.44 The BES, along
with norms and instructions for scoring, appears in Gormally et al.42
Eating Disorders
Eating Disorders Examination (EDE)
The EDE45 is a 62-item semistructured interview that measures the presence of disorders
along four subscales: shape concern, weight concern, eating concern, and dietary restraint.
Shape concern is related to general feelings of dissatisfaction and preoccupation with issues
related to body image. Weight concern relates to the desire to lose weight and the impor-
tance given to it. The eating concern subscale measures fear and guilt about eating as well
as any preoccupation with food. The dietary restraint scale attempts to quantify the degree
to which the subject is guided by strict rules concerning type and quantity of food.
In addition to subscale items, the examination also has diagnostic items used in making
a clinical diagnosis of eating disorders. The EDE was originally developed with individuals
suffering from bulimia and anorexia nervosa. Hence, the examination is useful in deter-
mining specific areas of concern as well as in making formal clinical diagnosis of eating
disorders. It is a mature instrument that underwent many revisions before publication.
The items used in calculating the four subscales are scored using a severity indicator
expressed by a seven-point Likert scale value that ranges from zero to seven. These items
are organized within a set of 23 higher-order categories such as pattern of eating, restraint,
and fear of losing control. The 4 subscales are comprised of these 23 higher order items,
with the restraint scale consisting of 5 items, the eating concern scale 5, the weight concern
scale 5, and the shape concern scale 8. Subscale values are computed by summing the
severity indicators of the related items and then dividing by the number of valid items.
A global score, defined as the sum of the individual subscale scores divided by the number
of valid subscales, may also be computed. The diagnostic items are scored in terms of
frequency; e.g., frequency of binge days over the preceding two months.
The EDE has become the preferred method for the assessment of binge eating. It mea-
sures eating behavior using a 28-day recall method, although some questions extend out
to the previous 3 and 6 months. Even when administered by trained interviewers, requir-
ing subjects to recall what they ate more than 14 days prior is problematic.
The EDE is designed to be administered and scored by trained interviewers familiar
with eating disorders. Administration may take one hour or more when properly admin-
istered. The authors of the instrument recommend that the interviewer first seek to develop
a rapport with the subject. The belief is that good rapport and a feeling of trust facilitates
disclosure and contributes in a positive way to the validity of the process.
The EDE appears to have satisfactory internal consistency. With a sample of 100 eating
disordered patients and 42 controls, Cooper et al.46 reported alpha coefficients ranging
from .68 to .82 for the four subscales. Another study measuring internal consistency in a
sample of 116 eating-disordered people reported alpha coefficients ranging from .68 to
.78.47 In studies of inter-rater reliability, very good correlations were reported across all
items.48,49 The EDE appears in Fairburn and Cooper.45
Restrained Eating
Eating Inventory (EI)
The EI,50 also known as the Three-Factor Eating Questionnaire (TFEQ-R), is a 51-item
self-report instrument that was developed as a measure of behavioral restraint in eating.
Measuring restraint is important in the nutritional context of obesity because severe
caloric restriction may lead to binge eating and increased metabolic efficiency, promoting
weight gain.51,52 Restriction also has nutritional sequelae such as vitamin deficiency and
related morbidity.
The instrument is divided into two parts. The first part consists of 36 true/false ques-
tions. The second part has 14 questions presented in a four-level Likert format with choices
ranging from rarely to always, plus an additional question that is a six-point rating of
perceived self-restraint. Questions ask about cues to eat, ability to control eating, and
willingness to diet. Respondents are asked to indicate how often each statement applies
to their personal behavior patterns.
The questionnaire has three subscales:
1. Cognitive control of eating

2. Disinhibition
3. Susceptibility to hunger
The first subscale is related to one’s awareness of, and ability to cognitively control or
restrain, eating behavior. The second subscale refers to one’s tendency to periodically lose
control of eating, and the third relates to one’s ability to resist cues to eat.
Scoring is described in the Eating Inventory Manual.53 The control sub-scale has 21
questions, the disinhibition subscale has 16, and the hunger subscale has 14. Each question
has a value of zero or one. Individual subscale scores are calculated by summing the scores
of the related questions. Scores above 13, 11, and 10 are considered to be in the clinical
range for the control, disinhibition, and hunger subscales, respectively.
The EI appears to have good construct validity. Food diaries and doubly-labeled water
techniques have been used to assess the construct validity of the subscales. These studies
have shown that high scores on the restraint scale are correlated in the hypothesized
direction with low levels of caloric intake.54,55
The test has good internal consistency (>.80)50 and test-retest reliability of .91 over 2
weeks.56 The inventory appears in Stunkard and Messick (1985).50 The inventory and
related scoring materials are available from The Psychological Corporation, San Antonio,
Texas. Their email address is customer_service@harcourtbrace.com.
Dutch Eating Behavior Questionnaire (DEBQ)

The DEBQ57 is a 33-item self-report instrument that measures eating behavior along three
subscales: restrained eating, emotional eating, and eating in response to external cues. The
diagnostic capabilities of this instrument are useful for identifying overeating triggers
when designing effective behavioral interventions, as well as for the identification of
individuals with restrained eating patterns.
The instrument consists of questions related to eating behavior. Each item is presented
in a five-point Likert response format with possible answers being: never, seldom, sometimes,
often, and very often. Some of the items have an additional not relevant category. Subscale
scores are computed by summing the scores of the related items and dividing by the
number of items. Items scored as not relevant are omitted from the subscale score.
The restraint scale has received most of the research attention. Some norms are available
for the restraint scale.58 In general, they indicate that women have higher restraint scores
than men, and that obese people have higher restraint scores than non-obese. Internal
consistency of the scales was reported in the range from .80 to .95.58 Two-week test-retest
reliability of the restraint scale was .92.56 The DEBQ is published in Van Strien et al.57 and
in Wardle.59
Locus of Control
Dieting Beliefs Scale (DBS)
The DBS60 is a 16-item scale that measures weight-specific locus of control. Weight locus
of control is a method for categorizing beliefs about factors influencing weight. Individuals
with an internal locus of control have the expectancy that they can control, to some extent,
their own weight. An external locus of control implies a more fatalistic orientation marked
by beliefs that weight is determined by factors outside of personal control, e.g., genetics,
environment, and/or social context.
The utility of this instrument is in the planning of treatment for obese and overweight
people. Theoretically, individuals who believe they have control over factors determining
their weight would be expected to have greater success in weight management programs.
Identifying individuals with an external locus of control might be valuable in the process
of treatment planning because it would cue the counselor to be particularly mindful to
avoid interventions that might inadvertently reinforce pre-existing negative expectations.
For example, very modest and frequently measured short term goals may be set for
people with external loci of control in an effort to encourage them toward more positive
expectations.
The 16 items are statements expressing either internal or external locus of control
viewpoints: eight are internal and eight are external. The items are presented in a six-point
Likert format ranging from not at all descriptive of my beliefs (1) to very descriptive of my
beliefs (6). Eight of the items are reverse scored. The instrument is scored in the internal
direction so that high scores indicate more of an internal locus of control.
The DBS has three subscales: internal control, uncontrolled factors, and environmental
factors. The internal control subscale is related to the belief that individuals can control
their weights through internal means such as willpower and effort. The uncontrolled
factors subscale is associated with belief in the importance of factors such as genetics and
fate. The environmental factors subscale is related to beliefs in the importance of context
and social setting. The subscales are scored by summing the scores of the individual items
that make up the scale.
This scale demonstrates moderate internal consistency (Chronbach’s alpha = .69) and
good stability in a sample of undergraduate students.60 The DBS is published in Stotland
and Zuroff.60
Stage of Change
Stages of Change Algorithm (SOCA)
The SOCA61 is a self-report instrument that assesses weight loss activities and intentions.
The instrument is based on the transtheoretical model,62 which conceptualizes change as
a five-stage process. The stages are precontemplation, contemplation, planning, action,
and maintenance. The purpose of the model is to maximize successful behavior change.
The model posits that optimal intervention strategies vary according to a person’s position
in the change process. The purpose of the SOCA is to facilitate treatment planning by
identifying the individual’s position in the process. Persons in the precontemplation stage
may not be at all concerned with their condition. These individuals might benefit from
efforts to raise their awareness and to personalize their risk factors. People in the contem-
plation stage may be concerned but not yet decided on taking action. Such people might
benefit from information regarding possible treatment alternatives. The preparation stage
is characterized by people who have decided to do something about their condition but
who have not yet begun. Encouragement to take action and to make a commitment to
their health may help people in this stage to move to the action stage. Individuals who
are ready to take action, or who have recently begun taking action, may benefit most from
behavioral interventions such as goal setting and self-monitoring. Moral support and
recognition might be best for people in the maintenance stage. The SOCA uses only four
of the stages: precontemplation, contemplation, action, and maintenance. The model is of
particular interest in the context of nutrition because of the refractory nature of dysfunc-
tional eating behavior.
The SOCA consists of four yes/no items. The scoring is simple and the determination
of the person’s stage of change is quickly determined.61 Data describing the reliability of
the SOCA for weight loss are not available. The SOCA was found to be reliable when
applied to similar problems. For example, in their investigation of the processes of change
in smoking-related behavior, Prochaska et al. observed alpha coefficients ranging from .69
to .92, with the majority being above .80.63 The SOCA is published in Rossi et al.61
University of Rhode Island Change Assessment Scale (URICA)

The URICA64,65 is a 32-item Likert scale designed to measure a person’s position in the
four-stage change process: precontemplation, contemplation, action, and maintenance. It
is similar in concept to the SOCA. It is different in that it has 28 more items, and each
stage of change is implemented as a scale. The URICA produces a score for each scale.
When viewed together, the scale scores can be interpreted as a profile. This approach is
richer than the SOCA because it provides a framework that allows attitudes and behaviors
characteristic of different stages of change to coexist in a single individual. Thus, the
URICA may be able to detect gradual shifts from one stage to another. The URICA is
general in format and not specific to any particular problem area. It has been widely used
across an array of problem areas, including a sample of 184 people in a weight control
program.
Items are presented in a five-point format. Scale scores are computed by summing the
responses to the scale items. Good internal consistency is indicated by numerous studies
reporting alpha coefficients ranging from .69 to .89 across all scales.64-66 The general version
of the URICA is published in McConnaughy et al.64 A version designed for use in a weight
control context is available in Rossi et al.61
References
1. Mokdad AH, Serdula MK, Dietz WH, et al. JAMA 282: 1519; 1999.
2. AACE/ACE Obesity Task Force. AACE/ACE Position Statement on the Prevention, Diagnosis
and Treatment of Obesity, Am Assoc Endocrinol Am Coll Endocrinol, 1998.
3. Prochaska JO, Norcross JC, DiClemente CC. Changing for Good: The Revolutionary Program that
Explains the Six Stages of Change and Teaches You How to Free Yourself From Bad Habits. W. Morrow,
New York; 1994.
4. Perri MG, Nezu AM, Viegener BJ. Improving the Long-Term Management of Obesity: Theory,
Research, and Clinical Guidelines. John Wiley & Sons, New York; 1992.
5. Am Psychiatric Assoc Diagnostic and Statistical Manual of Mental Disorders (4th ed). Washington,
DC, 1994.
6. Maxmen JS, Ward NG. Essential Psychopathology and Its Treatment. Norton, New York 1995.
7. Halmi KA, Eckert E, Marchi P, et al. Arch Gen Psychiatry 48: 712; 1991.
8. Polivy J, Herman CP. In: Binge Eating: Nature, Assessment and Treatment. Fairburn CG, Wilson
GT, Eds, Guilford, New York 1993; pg 173.
9. Heatherton TF, Baumeister RF. Psych Bull 110: 86; 1991.
10. Pendleton VR, et al. Eat Disord (in press).
11. Striegel-Moore R. Addict Behav 20: 713; 1995.
12. Rahe RH. In: Obesity Assessment: Tools, Methods, Interpretations. St. Jeor ST, Ed, Chapman &
Hall, New York, 1997; pg 400.
13. Rahe RH. Internat J Psychiat Med 6: 133; 1975.
14. Rahe RH. In: Comprehensive Textbook of Psychiatry, Kaplan HI, Sadock BJ, Eds, Williams &
Wilkins, Baltimore 1995; pg 1545.
15. Miller GD, Harrington ME. In: Obesity Assessment: Tools, Methods, Interpretations. St. Jeor, ST
Ed) Chapman & Hall, New York 1997; pg 457.
16. Rahe RH. Psychosomatic Med 40: 95; 1978.
17. Pearson JE, Long TJ. Eval Counsel Devel 18: 72; 1985.
18. Derogatis LR. Symptom Checklist-90-R Administration, Scoring and Procedures Manual National
Computer Systems, Minneapolis, 1994.
19. Derogatis LR, Cleary PA. J Clin Psychol 33: 891; 1977.
20. Garner DM, Olmstead MP, Davis R, et al. Internat J Eat Disord 9: 1; 1990.
21. Strober M, Katz JL. Internat J Eat Disord 6: 171; 1987.
22. Marcus MD. In: Binge Eating: Nature, Assessment, and Treatment. Fairburn CG, Wilson GT, Eds,
Guilford Press, New York; 1993; pg 77.
23. Webber EM. J Psychol 128: 339; 1994.
24. Clark MM, Niaura R, King TK, Pera V. Addict Behav 21: 509; 1996.
25. Tanco S, Linden W, Earle T. Internat J Eat Disord 23: 325; 1998.
26. Beck AT, Ward C, Mendelson M, et al. Arch Gen Psychiat 4: 53; 1961.
27. Beck AT, Steer RA, Garbin MG. Clin Psychol Rev 8: 77; 1988.
28. Stunkard A, Sorenson T, Schlusinger F. In: The Genetics of Neurological and Psychiatric Disorders.
Kety S, Rowland LP, Sidman RL, Matthysse SW, Eds, Raven, New York, 1983; pg 115.
29. Thompson JK, Atalbe MN. Internat J Eat Disord 10: 615; 1991.
30. Garner DM, Olmnsted MP, Polivy J. Internat J Eat Disord 2: 15; 1983.
31. Garner DM. Eating Disorder Inventory-2 Manual Psychological Assessment Resources Inc, Odes-
sa, FL; 1991.
32. Crowther JH, Lilly RS, Crawford PA, et al. Am Psychol Assoc Nat Convention, Boston; 1990.
33. Wear RW, Pratz O, Internat J Eat Disord 6: 767; 1987.
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1965.
35. Herman CP, Polivy J. In: The Psychobiology of Bulimia. Pirke K, Vandereycken W, Ploog D, Eds,
Springer-Verlag, Munich; 1988.
36. Polivy J, Heatherton TF, Herman CP. J Abnormal Psychol 97: 354; 1988.
37. Fairburn CG, Marcus MD, Wilson GT. In: Binge Eating: Nature, Assessment, and Treatment.
Fairburn CG, Wilson GT, Eds, Guilford, New York 1993; pg 361.
38. Rosenberg M. The Rosenburg Self-Esteem Scale University of Maryland, College Park, 1965.
39. Wylie RC Measures of Self-Concept University of Nebraska Press, Lincoln, 1989.
40. Poston WSC, Goodrick GK, Foreyt JP. In: Obesity Assessment: Tools, Methods, Interpretations. St.
Jeor ST, Ed, Chapman & Hall, New York, 1997; 425.
41. Glynn SM, Ruderman AJ. Cognitive Therapy Res 10: 403; 1986.
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Guilford, New York, 1993; pg 227.
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GT, Eds, Guilford, New York, 1993; pg 317.
46. Cooper Z, Cooper PJ, Fairburn CG. Br J Psychiat 154: 807; 1989.
47. Beumont PJ, Kopec-Schrader EM, Touyz SW. Aus N Zea J Psychiat 27: 506; 1993.
48. Cooper Z, Fairburn CG. Internat J Eat Disord 6: 1; 1987.
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50. Stunkard AJ, Messick S. J Psychosomat Res 29: 71; 1985.
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52. Polivy JH, Herman CP. Am Psychol 40: 193; 1985.
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54. Tuschi RL, Platte P, Laessie RG, et al. Am J Clin Nutr 52: 81; 1990.
55. Laessie RG, Tuschi RJ, Kotthaus BC, Pirke KM. J Abnormal Psychol 98: 504; 1990.
56. Allison DB, Kalinsky LB, Gorman BS. Psychol Assess 4: 391; 1992.
57. Van Strien T, Frijters JE, Bergers GP, Defares PB. Internat J Eat Disord 5: 295; 1986.
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Related Problems. Allison DB, Ed, Sage, London 1995; pg 149.
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60. Stotland S Zuroff, DC. J Personal Assess 54: 191; 1990.
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Behaviors and Weight Related Problems. Allison DB, Ed, Sage, London 1995; pg 387.
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Part VI
Modified Diets
40
Vegetarian Diets in Health Promotion and Disease
Prevention
Claudia S. Plaisted and Kelly M. Adams
Overview/Introduction
Vegetarianism is rapidly growing in popularity. Technically defined, vegetarians are indi-
viduals who do not eat any meat, poultry, or seafood.1,2 Estimates on the number of
vegetarians in the United States vary greatly according to the definition of vegetarianism
provided in the survey. True vegetarians make up about 1% of the population, representing
approximately two million people, according to a 1997 poll.3 A higher percentage of
teenagers than adults follow a vegetarian diet — almost 2%.3
Vegetarian dietary patterns can represent an exceptionally healthy way of eating. They
are typically rich in vitamins, minerals, phytochemicals, and fiber while often also low in
fat, saturated fat, and cholesterol.1,4 However, each individual diet will need to be assessed
for its nutritional adequacy. This section provides some guidance in characterizing vege-
tarian dietary patterns, health benefits, and concerns as well as identifying sources of
various nutrients that may be marginal in many vegetarian diets.
Characteristics of Vegetarian Eating Styles

When working with someone who follows a vegetarian diet, it is important to ask him a
variety of questions about his usual dietary patterns. Many people consider themselves
to be vegetarian if they eat non-flesh foods several days a week. Others claim to be
vegetarians when they consume fish or poultry. Table 40.1 lists the types of vegetarian
diets and describes what foods fall into each category.
In popular culture, many diets incorporate principles of vegetarianism and may repre-
sent more restrictive ways of eating, as described in Table 40.2. For the purposes of this
section, “vegetarian” will refer to an individual following a lacto and/or ovo or vegan
dietary pattern.
0-8493-2705-9/01/$0.00+$1.50
TABLE 40.1
Types of Vegetarian Diets
Vegan Consumes nuts, fruits, grains, legumes, and vegetables. Does not consume animal-
based food products, including eggs, dairy products, red meats, poultry, or seafood.
Some vegetarians may avoid foods with animal processing (honey, sugar, vinegar,
wine, beer).
Lacto-Vegetarian Consumes milk and other dairy products, nuts, fruits, grains, legumes, and vegetables.
Does not consume eggs, red meats, poultry, or seafood.
Ovo-Vegetarian Consumes eggs, nuts, fruits, grains, legumes, and vegetables. Does not consume milk
or dairy, red meats, poultry, or seafood.
Lacto-Ovo Vegetarian Consumes milk and other dairy products, eggs, nuts, fruits, grains, legumes, and
vegetables. Does not consume red meats, poultry, or seafood.
Pollo-Vegetariana Not technically considered a vegetarian type of diet, although often referred to as
“vegetarian” in popular culture. Consumes milk and other dairy products, eggs, nuts,
fruits, grains, legumes, vegetables, and poultry.
Peche-Vegetarian also Not technically considered a vegetarian type of diet, although often referred to as
called pesco- and “vegetarian” in popular culture. Consumes milk and other dairy products, eggs, nuts,
pecto-vegetariana fruits, grains, legumes, vegetables, and seafood.
Omnivore Consumes from a wide variety of foods, including meats, grains, fruits, vegetables,
legumes and dairy products. Individuals who consume red meats (beef, pork, lamb,
etc.), poultry, seafood, or any still or once living non-plant-based matter are not
vegetarians.
a This is not technically a vegetarian diet, although it is often referred to as such.
TABLE 40.2
Types of Popular Diets Incorporating Various Principles of Vegetarianisma
Fad diets Popular weight loss diets often incorporate various principles of vegetarianism,
although not generally in nutritious, balanced ways. The cabbage soup diet is an
example, which is based on consuming only a vegetable soup based on cabbage as a
weight-loss technique.
Fruitarian Consumes botanical fruits (including nuts and seeds); avoids meats, poultry, seafood,
dairy, eggs, and vegetables. May avoid legumes.
Macrobiotic Largely based on grains and in-season foods, including vegetables (except those of the
nightshade family), sea vegetables, soups, and beans. Nuts and seeds are not
consumed on a daily basis; fruits are included with the exception of tropical fruits.
Seafood is sometimes included as well. Asian foods contribute significantly to food
choices. This is an example of a diet following a food-combining philosophy.
Natural hygiene or Generally raw vegetables, fruits, whole grains or sprouted grains (in some cases may
raw foods diet be cooked), sprouted or non-sprouted legumes, nuts, and seeds. Some individuals
may consume raw dairy products. There is great variation in this diet plan: many
followers do consume cooked foods, and some consume meat as well. This is an
example of a diet following a food-combining philosophy, but has many variations
among followers.
a Many variations exist on each of these types of diets. This is not intended as a comprehensive listing.
Individuals following restrictive diets are more susceptible to dietary deficiencies and
imbalances.1,2 Table 40.3 describes the nutrients that may be of concern in many vegetarian
diets.
Health Benefits and Risks of Vegetarianism

Most health risks associated with a vegetarian diet are found with strict vegetarianism
(veganism) only, not with the more liberal forms of intake found in lacto-vegetarians, ovo-
Vegetarian Diets in Health Promotion and Disease Prevention 803
TABLE 40.3
Nutrients Potentially at Risk in Vegetarian Diets; Dietary Reference Intakes (DRIs), Functions and
Sources2,27-29
DRI: adult value
Vitamin/ 19–50 yr old,
Mineral non-pregnant Function Good Sources in Vegetarian Diet
Vitamins
Vitamin B12 M: 2.4 µg Works with folic acid to make red Dairy products, eggs, fortified
F: 2.4 µg blood cells; important in cereals, fortified soy products/
maintaining healthy nerve fibers; meat substitutes, fortified
helps the body use fat and protein. nutritional yeast.
Vitamin D Adequate Intake Promotes absorption of calcium Fortified milk; made in body
(AI): and phosphorus and helps deposit when skin is exposed to sunlight.
M: 5 µg them in bones and teeth.
F: 5 µg
Riboflavin (B2) M: 1.3 mg Helps the body release energy from Fortified dairy products, fortified
F: 1.1 mg protein, fat, and carbohydrates. breads and cereals, tomatoes,
lima beans, raisins, avocado,
beans, and legumes.
Minerals
Calcium AI: Used to build bones and teeth and Dairy products, broccoli, mustard
M: 1000 mg keep them strong; important in and turnip greens.
F: 1000 mg muscle contraction and blood
clotting.
Irona M: 8 mg Carries oxygen in the body, both as Whole-grain and enriched cereals,
F: 18 mg a part of hemoglobin (in the some dried fruits, soybeans.
blood), and myoglobin (in the
muscles).
Zinc M: 11 mg Assists in wound healing, blood Plant and animal proteins.
F: 8 mg formation, and general growth
and maintenance of all tissues;
component of many enzymes.
Manganeseb AI: Found in most of body’s organs and Whole grains, cereal products, tea,
M: 2.3 mg tissues, particularly in bones, liver, some fruits and vegetables.
F: 1.8 mg and kidneys. Serves as a cofactor
in many metabolic processes.
Deficiency not seen in human
populations.
Iodine 150 µg/d Constituent of thyroid hormones Fortified in salt, found widely in
(regulation of metabolic rate, body processed foods and grains
temperature, growth, where soil concentration is
reproduction, making body cells, adequate.
muscle function, nerve growth).
Copperc 900 µg Necessary for the formation of Nuts, legumes, whole grains.
hemoglobin; keeps bones, blood
vessels, and nerves healthy.
Selenium 55 µg Antioxidant functions, role in Eggs, whole grains, legumes,
eicosanoid metabolism, regulation brazil nuts.
of arachadonic acid and lipid
peroxidation, some hormone
conversions.
Macronutrients and Other Dietary Components
Protein RDA: Building of nearly all body tissues, Dairy products, legumes, meat
Male: 63 g particularly muscle tissue, energy. analog products often made
Female: 50 g from soy; whole grains and
or 0.8 gm/kg vegetables are poorer sources.

Nutrients Potentially at Risk in Vegetarian Diets; Dietary Reference Intakes (DRIs), Functions and
Sources2,27-29
DRI: adult value
Vitamin/ 19–50 yr old,
Mineral non-pregnant Function Good Sources in Vegetarian Diet
Omega-3 fatty Optimal intake One is called linolenic acid. Energy Fats and oils (bean, nut, and grain
acids estimated at 1-2 source, cell wall structure, may oils), nuts and seeds (butternuts,
g/d; fatty acids play a role in disease prevention. walnuts, soybean kernels),
should make Fats also play a role in the soybeans, flax seeds, and flax
up at least 3% absorption and transport of fat- seed oil.
of day’s energy soluble vitamins. Linolenic acid
intake. cannot be made by the body.
Omega-3 series fatty acids can be
found in grains, seeds, nuts, and
soybeans, and the body can
manufacture eicosapentaenoic
acid (EPA) and docosahexaenoic
acid (DHA) from these precursors.
a There is some evidence that vegetarian diets tend to be quite high in iron and that iron deficiency anemia is
no more common among vegetarians than in meat eaters.1
b Manganese is not necessarily at risk for deficiency in vegetarians. Some research has indicated that vegetarians
have a higher intake of this nutrient; however, bioavailability may be a concern.14,17
c Copper is not necessarily at risk for deficiency in vegetarians. Some research has indicated that vegetarians
have a higher intake of this nutrient; however, bioavailability may be a concern.14,17
vegetarians, or lacto-ovo vegetarians.1,5,6 Table 40.4 lists the health risks of vegetarianism,
most of which are related to the potential for nutrient deficiencies found with this type
of diet. These health risks are not unique to vegetarians, however, as they can be quite
common in people following an imbalanced omnivorous diet.
Many vegetarians follow a dietary pattern that reduces their risks for common chronic
diseases, as noted in Tables 40.5 and 40.6.4 New vegetarians, in particular, however, may
rely heavily on dairy products which may actually increase risk for cardiovascular disease.
Other practical concerns for new vegetarians are found in Table 40.7.
Table 40.8 compares the typical dietary intake of vegans and lacto-ovo vegetarians with
omnivores; the health risks/outcomes associated with specific kinds of vegetarian diets
are mentioned in Table 40.9. The nutrients of special concern will vary depending on the
TABLE 40.4
Health Risks of Vegetarianism1,5,7,13,22-26,30,31
Dietary Factor Risk
Calcium Low calcium intake in vegan or macrobiotic diet can lead to low bone mineral density.
Iodine A strict vegan consuming no iodized salt or processed food products can develop
goiter.
Vitamin B12 In strict vegans or in the offspring of vegan mothers only, deficiency can lead to anemia,
or in far more severe cases, neuropathy.
Energy Impaired growth can result in infants and children with inadequate energy intake or
those weaned to “homemade” formulas.
Docosahexaenoic acid Greatest concern for fetus and young infants. DHA is needed for neural and retinal
(DHA) development.
Dairy products Limited evidence exists linking high consumption of dairy products to diabetes (type
1) primarily in infants and children, and to ovarian cancer in adults with galactose-
1-phosphate uridyltransferase defects.
TABLE 40.5
Health Benefits of Vegetarianism1,2,4,10-13,19,32-34
Lower Risk Of
Cancer (particularly colon and lung)

Obesity
Heart disease
Type 2 diabetes
Hypertension
Constipation and hemorrhoids
Kidney stones
Gallstones
Potential Lower Risk For (Limited Evidence Suggesting)
Arthritis
Gout
Dementia
Tooth decay
Duodenal ulcers
TABLE 40.6
Protective Factors in the Typical Lacto-Ovo Vegetarian Diet1,4,10,18,20
Higher fiber
Lower fat, saturated fat, and cholesterol
Higher folate intake
Higher intake of antioxidants
Higher intake of phytochemicals
Lower intake of total and animal protein
TABLE 40.7
Practical Concerns about Vegetarianism
New vegetarians or those who are vegetarian for philosophical (as opposed to health) reasons may rely heavily
on the use of dairy products and eggs.
Whole milk cheeses, 2% and higher fat content milk, eggs and whole milk yogurts are rich in fat, saturated fat,
and in some cases cholesterol. These can contribute to higher risks for cardiovascular disease in particular, and
should be evaluated.
Some adolescents with eating disorders may use vegetarianism as a rationalization for avoiding foods or entire
food groups.
TABLE 40.8
Nutrient Differences between Omnivore, Lacto-Ovo and Vegan Dietary Patterns1,2,33
Dietary
Component Vegan Lacto-ovo Omnivore
Total fat ~30% fat 30-36% fat 34-38% fat
Saturated fat Generally low saturated fat Generally moderate Generally higher saturated
intake saturated fat intake fat intake
P/S ratio High P/S Mod P/S Poor P/S
Cholesterol 0 mg 150-300 mg 400 mg
Fiber (g/d range) Generally 50-100% higher Generally 50-100% higher Generally low (range:
than omnivores and higher than omnivores (range: 3.5-33.8 g/d)
than lacto-ovo vegetarians. 5.2-74.4 g/d)
(range: 16.1-55.3 g/d)

Nutrient Differences between Omnivore, Lacto-Ovo and Vegan Dietary Patterns1,2,33
Dietary
Component Vegan Lacto-ovo Omnivore
Carbohydrate (% 50-65% 50-55% <50%
total kcalories)
Protein 10-12% of calories (none 12-14% of calories (~1/2 14-18% of calories (~2/3
from animal sources) from animal sources) from animal sources)
Cholesterol levels 4.29 4.88 5.31
(mmol/L)
Folate 170-385 214-455 252-471
(mcg/d ranges)
Blood pressure 112.5/65.3 111.8/68.8 120.8/76.4
TABLE 40.9
Health Risks of Individuals Following Various Types of Vegetarian Diets1,2,33
Type of Nutrients at
Vegetarian Diet Health Risk Profile Greatest Risk
Vegan Low risk of obesity, heart disease, cancer, hypertension, and diabetes. Vitamin B12
Vegans may have a lower health risk than lacto-ovo vegetarians due to Vitamin D
the typical lower fat and higher fiber content than either lacto-ovo or Calcium
non-vegetarians. Zinc
Energy
Potentially Iron
Lacto-vegetarian Generally low risk of obesity, heart disease, cancer, hypertension, and Zinc
diabetes. Unskilled or new vegetarian may rely heavily on whole-milk Potentially Iron
based products, thus consuming high fat, saturated fat, and cholesterol
intakes which could increase the risk of cardiovascular-related diseases.
Ovo-vegetarian Generally low risk of obesity, heart disease, cancer, hypertension, and Zinc
diabetes. Unskilled or new vegetarian may rely heavily on eggs and Potentially Iron
egg-based products, thus consuming high fat, saturated fat, and
cholesterol intakes which could increase the risk of cardiovascular-
related diseases.
Lacto-ovo Generally low risk of obesity, heart disease, cancer, hypertension, and Zinc
vegetarian diabetes. Unskilled or new vegetarian may rely heavily on whole-milk Potentially Iron
or egg-based products, thus consuming high fat, saturated fat, and
cholesterol intakes which could increase the risk of cardiovascular-
related diseases.
type of vegetarian diet followed. As discussed in Table 40.10, some nutrients are more
critical during specific developmental phases; deficiency of a particular nutrient at a
particular stage of the life cycle can have dramatic consequences.5,7-9
Energy and Macronutrients in the Vegetarian Diet

A common misconception about a vegetarian diet concerns protein. Many new vegetarians
are frequently confronted with the question: “So how do you get your protein?” Individ-
uals following a lacto-ovo vegetarian diet rarely have to worry about protein. Even vegans
eating a reasonably balanced diet with adequate kcalories can easily meet their protein
needs.1,4 In reality, it is much more likely that the individual is suffering from a dietary
TABLE 40.10
Critical Periods of Importance for Selected Nutrients2,25,27
Nutrient Critical Periods during Lifecycle
Vitamin B12 Throughout, particularly critical during pregnancy, infancy, and childhood
Riboflavin (B2) Pregnancy, periods of growth
Vitamin D Childhood and pre-puberty, pregnancy, elderly
Calcium Childhood and pre-puberty, elderly
Iron Infancy, childhood, adolescence, pregnancy, adulthood (women particularly)
Zinc Puberty, pregnancy, elderly
Iodine Adolescence, pregnancy, lactation
Protein Infancy, childhood, adolescence, pregnancy
Omega-3 fatty acids Pregnancy, infancy
(especially DHA)
Energy Periods of growth, especially toddlers/preschoolers, due to small stomach capacity
TABLE 40.11
Definitions Related to Protein Complementation2
Complete protein Contains all essential amino acids in ample amounts; amino acid pattern is very similar
to humans
Incomplete protein May be low in one or more amino acids; amino acid pattern is very different from
humans
Limiting amino acid The essential amino acid(s) that are in the smallest supply in the food
Essential amino acid Cannot be synthesized by the human body. Include: Arginine, Histidine, Isoleucine,
Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine
TABLE 40.12
Limiting Essential Amino Acids and Vegan Sources1,2
Food Limiting Amino Acids Vegan Sources of the Limiting Amino Acids
Legumes Methionine, Cysteine Grains, nuts, seeds, soybeans
Cereals/grains Lysine, Threonine Legumes
Nuts and seeds Lysine Legumes
Peanuts Methionine, Lysine, Threonine Legumes, grains, nuts, seeds, soybeans
Vegetables Methionine Grains, nuts, and seeds, soybeans
Corn Tryptophan, Lysine, Threonine Legumes, sesame and sunflower seeds, soybeans
deficiency of a micronutrient, such as calcium or zinc, than a protein deficiency. Energy

and protein can be of concern in some adult vegetarian diets, particularly if the individual
follows severe dietary restrictions, and in children.8
Tables 40.11 through 40.13 provide information about essential and non-essential amino
acids and protein complementation. In the 1970s, carefully complementing proteins at
each meal was thought to be the only way for vegetarians to avoid protein deficiency. We
now know that it is not necessary to combine proteins at each meal,1,4 yet it is important
to understand the terminology related to the body’s protein needs and the principles of
complementation.
Table 40.14 compares average protein intakes in the U.S., while Tables 40.15 and 40.16
provide information about protein and nutrient- and energy-dense food sources. As an
arbitrary guideline, foods with 2 g or less of protein were not included. Information about
nutrient- and energy-dense foods can be useful for young children who may fill up quickly
on a bulky vegetarian diet without meeting their kcalorie and nutrient needs.9
TABLE 40.13
Guidelines for Protein Complementation1,2
Type of
Vegetarian Diet Guidelines for Complementationa
Lacto-ovo Dairy and eggs provide complete protein, as do other animal products.
Vegan A vegan diet that contains a variety of grains, legumes, vegetables, seeds, and nuts over the
course of a day in amounts to meet a person’s calorie needs will provide adequate amino
acids in appropriate amounts. Soybeans match human needs for essential amino acids as
precisely as animal foods, and are thus a complete protein.
Any It is not necessary to combine proteins in each meal. Young children, however, may need to
have the complementary proteins consumed within a few hours of each other.
a All proteins except gelatin provide all of the amino acids. Some protein sources have relatively low levels of
some amino acids, so a large amount of that food would need to be consumed if it were the only source of
those “limiting” amino acids.1
TABLE 40.14
Protein Intakes in the United States1
Type of Diet Percent of Calories from Protein Sufficient to Meet RDA?
Typical U.S. diet 14–18% Yes
Lacto-ovo vegetarians 12–14% Yes, provided adequate calories are consumed
Vegans 10–12% Yes, provided adequate calories are consumed
TABLE 40.15
Protein: Vegetarian Sources and Amounts27,35,36
Adult RDA: Males 63 g/day Females 50 g/daya
Food Portion Size Protein (g) Kcal
Cereals/Grains
Quinoa 0.5 cup 11.1 318

Millet, cooked 1 cup 8.4 286
Wheat germ, toasted 0.25 cup 8.4 111
Bagel, plain 1 bagel 7.5 195
Couscous, cooked 1 cup 6.8 200
Macaroni, enriched, cooked 1 cup 6.7 197
Pita, whole wheat 1 pita 6.3 170
Grape-Nuts, Post 0.5 cup 6.0 200
Oatmeal Crisp, almond, General Mills 1 cup 6.0 220
Oatmeal, old fashioned, Quaker 0.5 cup dry 5.5 148
Oat bran, raw 0.33 cup 5.4 76
Brown rice, medium grain, cooked 1 cup 4.5 218
English muffin, plain 1 muffin 4.4 134
Barley, pearled, cooked 1 cup 3.5 193
Whole wheat bread 1 slice 2.7 69
Corn grits, instant, white, enriched 1 oz. packet dry 2.4 96
Vegetables
Peas, green, canned 0.5 cup 3.8 59

Corn, yellow, boiled 0.5 cup 2.7 89
Broccoli, boiled 0.5 cup 2.3 22

Protein: Vegetarian Sources and Amounts27,35,36
Adult RDA: Males 63 g/day Females 50 g/daya
Food Portion Size Protein (g) Kcal
Fruits
Prunes, dried 10 prunes 2.2 201
Dairy/Soymilk
Cottage cheese, 1% fat 1 cup 28.0 164
Yogurt, lowfat (1.5% milk fat), plain, Breyers 1 cup 11.0 130
Simple Pleasures, chocolate 0.5 cup 8.9 134
Gruyere cheese 1 oz. 8.5 117
Milk, low fat (1%) 1 cup 8.0 102
Cheddar cheese 1 oz. 7.1 114
Soymilk 1 cup 6.6 79
American processed cheese 1 oz. 6.3 106
Pudding, all flavors, from instant mix Jell-O brand 0.5 cup 4.0 155
Frozen yogurt, soft serve 0.5 cup 2.9 115
Ice cream, vanilla, regular (10% fat) 0.5 cup 2.3 133
Beans/Legumes
Soybean nuts, roasted 0.5 cup 30.3 405
Lentils, boiled 1 cup 17.9 230
Lima beans, boiled 1 cup 14.7 216
Kidney beans, canned 1 cup 13.3 207
Garbanzo beans, canned 1 cup 11.9 286
Soy Products/Meat Substitutes
Tofu, raw, firm 0.5 cup 19.9 183
Tempeh 0.5 cup 15.7 165
Pepperoni from meat substitute 16 slices 14.0 70
Better ‘n Burger, Morningstar Farms 1 patty 11.3 75
Soybeans, green, boiled 0.5 cup 11.1 127
Ground meatless, frozen, Morningstar Farms 0.5 cup 10.3 60
Meatless deli turkey 3 slices 9.0 40
Nuts/Seeds
Peanut butter, chunk style/crunchy 2 T 7.7 188
Sunflower seeds, dried 1 oz. 6.2 160
Almonds, blanched 1 oz. 6.0 174
Sesame butter (tahini) 2 T 5.0 174
Cashews, dry roasted 1 oz. 4.3 163
Eggs
Egg substitute, frozen 0.25 cup 6.8 96
Egg, chicken, whole, fresh/frozen 1 large 6.2 75
Egg, chicken, yolk fresh 1 large 2.8 61
Mixed Foods
Frozen French bread pizza, vegetarian 6 oz. pizza 17.0 270
Shells & cheese, from mix 1 cup 16.0 360
Burritos w/ beans 2 burritos 14.1 447
Biscuit w/ egg 1 item 11.1 316
Potato, baked, w/ sour cream & chives 1 potato 6.7 393
a Taking into account the lower digestibility and amino acid profile, a reasonable RDA for
vegans is approximately 10% more protein than omnivores.1
TABLE 40.16
Vegetarian Sources of Energy-Dense, Nutrient-Dense Foods35,36
Food Portion Size Kcal
Cereals/Grains
Granola, low-fat 1 cup 422

Quinoa 0.5 cup 318
Millet, cooked 1 cup 286
Pancakes, Bisquick, blueberry 3 each 220
Oatmeal Crisp 1 cup 210
Grape-Nuts, Post 0.5 cup 200
Macaroni, enriched, cooked 1 cup 197
Bagel, plain 1 bagel 195
Raisin bran, dry 1 cup 175
Corn muffin (2.5 x 2.25 inch) 1 muffin 174
Pita, whole wheat 1 pita (6.5 in diameter) 170
Banana nut muffin, from mix 1 muffin 160
Oat bran muffin 1 muffin 154
Vegetables
Tater Tots, frozen, heated 4 oz. 204

Potatoes, mashed from granules 1 cup 166
Fruits
Avocado, California, raw 0.5 medium 153

Raisins, golden, seedless 0.66 cup 302
Mixed fruit, dried, diced, Delmonte 0.66 cup 220
Dairy/Soymilk
Milkshake, thick vanilla 1 cup 256

Yogurt, flavored, lowfat, 1% milkfat, Breyers 1 cup 251
Ricotta cheese, part-skim 0.5 cup 171
Cottage cheese (1% fat) 1 cup 164
Pudding, all flavors, from instant mix Jell-O 0.5 cup 155
Milk, whole 1 cup 150
Yogurt, lowfat (1.5 % milk fat), plain, Breyers 1 cup 130
Cheddar cheese 1 oz. 114
Milk, low fat (1%) 1 cup 102
Soymilk 1 cup 79
Beans/Legumes
Soybean, dried, boiled, mature 1 cup 298

Garbanzo beans, canned 1 cup 286
Lentils, boiled 1 cup 230
Soybean nuts (roasted) 0.5 cup 405

Tempeh 1 cup 330
Soyburger w/ cheese 1 each 316
Chicken nuggets, meatless 5 pieces 245
Frankfurter, meatless 1 each 102
Nuts/Seeds
Peanut butter, chunky style 2T 188

Almonds, blanched 1 oz. 174

Vegetarian Sources of Energy-Dense, Nutrient-Dense Foods35,36
Food Portion Size Kcal
Sesame butter (tahini) 2T 174
Sunflower seeds, dried 1 oz. 160
Mixed Foods
Egg salad 1 cup 586

Burritos, w/ beans 2 burritos 447
Potato, baked, w/ sour cream and chives 1 potato 393
Shells & cheese, from mix 1 cup 360
Peanut butter and jam sandwich on wheat 1 each 344
Cheese enchilada 1 item 320
Biscuit w/ egg 1 item 316
Lasagna, no meat, recipe 1 piece 298
Chili, meatless, canned 0.66 cup 190
Trail mix, regular 0.25 cup 150
Vegetable soup 1 cup 145
Pizza, cheese 1/8 of 12-inch 140
Pasta with marinara sauce 1 cup 180-450
Micronutrients in the Vegetarian Diet

Although vegetarian dietary patterns can be extremely healthful,1,10,11-13 certain micronu-
trients can be challenging to obtain in sufficient quantities, depending on the specific
dietary restrictions the individual follows. Tables 40.17 through 40.28 provide information
about sources of micronutrients that can be of concern for some vegetarian individu-
als.1,4-7,11,13-17 As a guideline, foods with less than 5 to 10% of the recommended amount of
that particular nutrient per serving were not included in the tables.
Bioavailability of minerals can influence the amount available for absorption. Tables
40.24 and 40.28 list factors that may enhance or inhibit the absorption of iron and zinc.
Non-Nutritive and Other Important Factors in the Vegetarian Diet

Typical vegetarian diets are rich in many beneficial non-nutritive factors such as dietary
fiber and phytochemicals.18-20 Tables 40.29 and 40.30 provide information about sources
of these beneficial but non-nutritive factors.
Omega-3 fatty acids are a type of polyunsaturated fatty acid thought to reduce the risk
of cardiovascular disease through their effects on triglyceride levels and platelet aggrega-
tion.2,21 One type of omega-3 fatty acid, alpha-linolenic acid, is an essential fatty acid and
must be consumed in the diet to prevent deficiency. Two other types of omega-3 fatty
acids are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty
acids may be of concern to vegetarians because although alpha-linolenic acid is found in
many plant foods, EPA and DHA are not.1 For healthy adults this is not usually a concern,
because the body has the ability to manufacture EPA and DHA from alpha-linolenic acid,
TABLE 40.17
Riboflavin:a Vegetarian Sources and Amounts28,35,36
Adult RDA: Males 1.3 mg/day Females 1.1 mg/day
Food Portion Size Riboflavin (mg) Kcal
Cerealsbc/Grains
Raisin bran 1 cup (2.1 oz.) 0.678 175

Bran flakes 0.66 cup (1 oz.) 0.43 91.5
Corn flakes, Kellogg’s 1 cup (1 oz.) 0.375 90
Bagel, plain 1 bagel (3.5 inch) 0.22 195
Sesame breadsticks 2 sticks 0.22 120
Pita, white 1 pita (6.5 inch diameter) 0.20 165
Lasagna noodles 2 oz. dry 0.20 210
Cornbread, homemade from low-fat milk 1 slice 0.19 173
Corn muffin (2.5 x 2.25 inch) 1 muffin 0.19 174
English muffin, wheat 1 muffin 0.17 127
English muffin, plain 1 muffin 0.16 134
Muffin, blueberry, homemade (2.75 x 2 inch) 1 muffin 0.16 163.5
Macaroni, enriched, cooked 1 cup 0.14 197
Wild rice, cooked 1 cup 0.14 166
Rye bread 1 slice 0.11 83
Vegetables
Mushrooms, boiled 0.5 cup 0.23 21

Tomato puree, canned 1 cup 0.14 100
Sweet potatoes, baked, with skin 1 medium 0.14 117
Tomato, red, sun-dried 0.5 cup 0.13 69.5
Garden cress, boiled 0.5 cup 0.11 16
Fruits
Raisins, golden seedless 0.66 cup 0.19 302

Banana 1 medium 0.11 105
Raspberries, raw 1 cup 0.11 60
Avocado, Calif. raw 0.5 medium 0.105 153
Dairy/Soymilk
Yogurt, plain, lowfat 1 cup 0.493 209

Milk, whole 1 cup 0.395 150
Milk, nonfat 1 cup 0.34 86
Feta cheese 1 oz. 0.24 75
Ricotta cheese, part-skim 0.5 cup 0.23 171
Cheddar cheese, reduced fat 1 oz. 0.14 80
Goat cheese, soft 1 oz. 0.11 76
Beans/Legumes
Soybeans, boiled 1 cup 0.49 298

Kidney beans, canned 1 cup 0.18 207
Great northern beans, canned 1 cup 0.16 299
Pinto beans, boiled 1 cup 0.16 234
Lentils, boiled 1 cup 0.14 230

Riboflavin:a Vegetarian Sources and Amounts28,35,36
Adult RDA: Males 1.3 mg/day Females 1.1 mg/day
Food Portion Size Riboflavin (mg) Kcal
Chicken nuggets, meatless 5 pieces 0.30 245

Vegetarian burger, grilled, Morningstar Farms 1 patty 0.24 140
Breakfast links, Morningstar Farms 2 links 0.22 63
Nuts/Seeds
Almonds, dry roasted 1 oz. 0.17 166
Eggs
Egg, chicken, boiled 1 large 0.298 89.9

Egg substitute, frozen 0.25 cup 0.188 52.8
Mixed Foods
Bean burrito 2 each 0.61 447

Cheese enchilada 1 each 0.42 319
Egg omelet w/ onion, pepper, tomato, mushroom 1 each 0.344 125
Vegetarian chili, fat-free w/black beans, Health Valley 5 oz. 0.255 70
Beverages
Coffee substitute w/ milk 0.75 cup 0.298 120
Miscellaneous
Brewers yeast 1T 0.342 22.6

a Also called vitamin B2.
b Most fortified breakfast cereals contain 0.43-0.51 mg per serving.
c Many “100% Natural” breakfast cereals are not enriched and contain 0.03-0.12 mg per serving.
although vegetarians still have lower levels of blood DHA.1,22 The fetus and young infant
have a dramatically reduced ability to perform this conversion.23 Because DHA is needed
for brain and retinal development, some pregnant or breastfeeding vegetarian women
may need to reduce their intake of linoleic acid (an omega-6 fatty acid) relative to their
intake of alpha-linolenic acid to increase DHA levels, or they may choose to try DHA-
enriched eggs or DHA supplements derived from microalgae, although the safety of this
has not been established.22-26 Table 40.31 lists vegetarian dietary sources of the omega-3
fatty acid alpha-linolenic acid.
The Effects of Cooking, Storage, and Processing on the Critical Nutrients

Cooking, storage, and processing methods can influence the amount of a nutrient present
in a food. Table 40.32 presents the effects of cooking, storage, and processing on the
nutrients that may be of concern in a vegetarian diet.
TABLE 40.18
Vitamin B12: Vegetarian Sources and Amounts28,35,36
Adult RDA: 2.4 µg/day
Food Portion Size Vitamin B12 (µg) Kcal
Cerealsa/Grains
Total, wheat 1 cup 7.00 116

Waffle, whole grain 2 each 3.11 154
Bran flakes 1 cup 2.49 152
Granola, lowfat 0.33 cup 1.50 120
Kix 1.5 cup 1.50 110
Corn flakes, dry 1 cup 1.27 92.9
Waffle, frozen, toasted 1 each 0.882 92.4
Dairy/Soymilkb
Soymilk, Edensoy Extra 1 cup 3.0 130

Milk, skim 1 cup 0.93 86
Yogurt, flavored, lowfat 1% milkfat, Breyers 1 cup 0.90 251
Yogurt, whole, plain 1 cup 0.84 139
Yogurt, nonfat, flavored w/ aspartame, Light ‘n Lively 1 cup 0.60 70
Free 70 Cal
Buttermilk, cultured 1 cup 0.54 99
Feta cheese 1 oz. 0.479 74.8
Swiss cheese 1 oz. 0.476 107
Havarti cheese 1 oz. 0.357 105
American processed cheese food 1 oz. 0.235 68.9
Soy Products/Meat Substitutesc
Breakfast links 2 each 3.41 63

Soyburger w/cheese 1 each 1.72 316
Soyburger 1 each 1.70 142
Tempeh 1 cup 1.66 330
Breakfast patties 1 each 1.49 68
Chicken, meatless, breaded, fried patty 1 piece 0.95 177
Eggs
Egg, chicken, boiled 1 large 0.56 78
Mixed Foods
Spinach soufflé 1 cup 1.37 219

Cheese pizza 1 piece (1/8 of 0.53 223
a 15-inch pie)
Miscellaneous
Fortified nutritional yeast (Red Star T6635) 1T 4.0 40

a Some commercial cereals are not fortified with vitamin B12; check labels carefully.
b Subject to fortification; unfortified soymilk contains no vitamin B12.
c Subject to fortification; check labels of individual products carefully.
TABLE 40.19
Vitamin D: Vegetarian Sources and Amounts28,35-37
Adult Adequate Intake: 5 µg cholecalciferol (200 IU per day)
Food Portion Size Vitamin D (IU)a Kcal
Cereals/Grains
Raisin Bran 1 cup (2.1 oz.) 56 175

Corn Pops 1 cup 50 110
Lucky Charms 1 cup 44.8 125
Corn flakes 1 cup (1 oz.) 44 90
Wheat bran muffin from recipe w/ 2% milk 1 muffin (57 g) 25.1 161
Waffles, plain, recipe 1 each (75 g) 23.5 218
Vegetables
Mushrooms, boiled 0.5 cup 59.3 21.1
Dairy/Soymilk
Soymilk, Soy Moo, fat free, Health Valley 1 cup 100 110
Milk, nonfat 1 cup 98 85.5
Pudding, vanilla, instant, w/ whole milk 0.5 cup 49.0 162
Eggs
Egg, chicken, boiled 1 large 26 78

Egg yolk, cooked 1 each 24.6 59.2
Mixed Foods
Soup, tomato bisque, with milk 1 cup 49.2 198

Egg salad 0.5 cup 38.5 293
Egg omelet w/ mushroom 1 each (69 g) 36.4 91.2
Fats/Oils/Dressings
Margarine, hard, hydrogenated soybeanb 1 tsp. 19.9 29.8
Desserts
Egg custard pie, frozen, baked 1 piece (105 g) 40.1 221

Chocolate-filled crepe 1 each (78 g) 28.1 119
Coffee cake, from mix 1 piece (72 g) 22.2 229
a 1 IU vitamin D = 0.025 µg cholecalciferol.
b Subject to fortification; check labels.
TABLE 40.20
Calcium: Vegetarian Sources and Amounts28,30,35,36
Adult AI: Males 1000 mg/day Females 1000 mg/day
Food Portion size Calcium (mg) Kcal
Cereals/Grains
Calcium fortified cereal bars 1 bar (37 g) 200 140
Vegetables
Collards, frozen, boiled 0.5 cup 179 31
Kale, frozen, boiled 1 cup 179 39
Turnip greens, canned 0.5 cup 138 16
Squash, acorn, baked 1 cup 90.2 115
Okra, boiled 0.5 cup 88 34
Squash, butternut, baked 1 cup 84 82
Broccoli, cooked 1 cup 72 44
Peas, green, cooked, from frozen 0.5 cup 19.2 62.4
Fruits
Calcium-fortified orange juice 8 oz 300 120
Dairy/Soymilk
Soy milk, fortified 8 oz (1 cup) 400 110
Malted milk, chocolate (Ovaltine) 8 oz 384 225
Evaporated milk, skim 4 oz 372 100
Evaporated milk, whole 4 oz 329 169
Goat’s milk 8 oz (1 cup) 327 168
Yogurt, tofu yogurt, frozen 8 oz 309 254
Cow’s milk, skim 8 oz (1 cup) 302 86
Cow’s milk, 1/2% 8 oz (1 cup) 300 90
Cow’s milk, 1% 8 oz (1 cup) 300 102
Yogurt, fat-free 8 oz 300 100
Yogurt, lowfat 8 oz 300 200
Yogurt, regular 8 oz 300 250
Cow’s milk, 2% 8 oz (1 cup) 297 121
Cow’s milk, whole 8 oz 290 150
Swiss cheese 1 oz 272 107
Cheddar cheese 1 oz 204 114
American cheese 1 oz 174 106
Mozzarella cheese, part skim 1 oz 183 72
Feta cheese 1 oz 140 75
Soy milk, non-fortified 8 oz (1 cup) 79.3 150
Cottage cheese, 1% fat 0.5 cup 69 82
Beans/Legumes
Great northern beans 0.5 cup 60 105
Tofu, raw, firm 0.5 cup 258 183
Tempeh 1 cup 154 330
Nuts/Seeds
Almonds, dried 1 oz (about 24 nuts) 75 167
Desserts
Custard, 2% milk 1 cup 394 298
Sherbet, orange 1 cup 264 104
Soft serve ice cream, French vanilla 1 cup 226 370
Frozen yogurt, soft serve 1 cup 212 230
Ice cream, vanilla, regular, 10% fat 1 cup 168 226
Miscellaneous
Blackstrap molasses 1 Tbsp 172 47
TABLE 40.21
Copper:a Vegetarian Sources and Amountsb 27,35,36
Adult RDA: 900 µg/day
Food Portion Size Copper (mg) Kcal
Cereals/Grains
100% Bran 1c 1.04 178

Granola, lowfat, Kellogg’s 0.5 c 0.655 211
Vegetables
Potatoes, baked, stuffed w/cheese 1 ea (254 g) 0.671 373

Vegetable juice cocktail, V-8 1c 0.484 46.0
Potatoes, Baked, w/skin 1 ea (122 g) 0.372 133
Fruits
Avocado, California 1 ea 0.460 306

Prunes, dehydrated, cooked 0.5 c 0.286 158
Dairy/Soy Milk
Soy milk 1c 0.288 79.2
Beans/Legumes
Beans, adzuki, canned, sweetened 0.5 c 0.384 344

Garbanzo beans, boiled 0.5 c 0.289 135
Tempeh 1c 1.11 330

Scallops, meatless, breaded, fried 0.5 c 0.819 257
Luncheon slice, meatless 1 piece (67 g) 0.608 188
Soyburger w/cheese 1 ea 0.559 316
Tofu, raw, firm, calcium sulfate 0.5 c 0.476 183
Nuts & Seeds
Cashew, dry roasted 0.25 c 0.76 197

Sunflower seeds, toasted 0.25 c 0.61 208
a Severe copper deficiency is rare in humans with no dietary deficiency
documented. Generally this is only seen with extended supplemental feed-
ing/total nutrition through manufactured nutrition such as total parenteral
nutrition, or impaired utilization.36
b High zinc intake (from supplements) can cause copper deficiency.2
TABLE 40.22
Iodine: Vegetarian Sources and Amounts27,35,36
Adult RDA 150 µg males and females
Food Portion Size Iodine (µg) Kcal
Cereals/Grains
Rice, white, enriched, cooked, long grain 0.5 c (82.5 g) 52 81

Bread, cornbread, homemade 1 piece (65 g) 44.2 176
Fruit-flavored, sweetened 1.1 oz (32 g) 41 120
Roll, white 2 rolls (38 g) 31 100
Muffin, blueberry/plain 1 ea (50g) 28.5 150
Tortilla, flour, 7-8” diam 1 ea (35 g) 26.3 114
Corn flakes 1 oz (28 g) 26 102
Bread, white 1 slice (28.4 g) 25.8 76.4
Pancakes, from mix, 4” 1ea (38 g) 21 74
Crisped rice 1 oz (28 g) 18.5 111
Noodles, egg, enriched, boiled 1 c (160 g) 17.6 213
Bread, whole wheat 1 slice (28 g) 17.6 69
Bread, rye, American 1 slice (32 g) 15.7 83
Vegetables
Potato, boiled w/peel 1 ea (202g) 62.6 220

Fruit cocktail, heavy syrup, canned 0.5 c (128 g) 42.24 93
Potato, scalloped, homemade 0.5 c (122 g) 37.8 105
Navy beans, boiled 0.5 c (91 g) 35.5 129
Lima beans, baby, frozen, boiled 0.5 c (90 g) 27.9 95
Orange breakfast drink (from dry) 1 cup 27.3 114
Prunes, heavy syrup 5 ea (86 gm) 25.8 90
Cowpeas/blackeye peas 0.5 c (85 g) 22.1 112
Dairy/Soymilk
Yogurt, lowfat, plain 1 cup 87.2 155

Buttermilk, skim, cultured 1 cup 60.0 99.0
2% fat milk 1 cup 56.6 137
Cottage cheese 1% fat 1 cup 56.5 164
Nonfat milk 1 cup 56.4 85.5
Whole milk, 3.3% 1 cup 56.1 150
Fruit yogurt, lowfat 1 cup 45.3 250
Eggs
Fried in margarine 1 ea (46 g) 29 91.5

Scrambled, w/milk, in margarine 1 large, (61 g) 25.6 101
Soft-boiled 1 ea (50 g) 24 78
Mixed Foods
Grilled cheese on wheat 1 ea (118 g) 28.9 392

Macaroni & cheese, box mix 0.5 c 17.3 199
Condiments/Seasonings
Salt, Morton lite salt mixture 1 tsp 119 0

TABLE 40.23
Iron: Nonheme Sources in the Vegetarian Diet27,35,36,38
Adult RDA: Male 8 mg/Female: 18 mg
Available Iron (mg)
Food Portion Size Total Iron (mg) (where info available) Kcals
Cereals/Grains
Raisin Bran, dry 0.75 cup Range: 18.54 to 3.7 0.19 200
Quinoa 1 cup 13.4 — 576
Corn flakes, dry 0.75 cup 6.5 0.32 90
Oatmeal, instant, fortified 0.5 cup 4.2 0.21 145
Special K 0.75 cup 3.4 — 75
Bran muffin 1 med 2.4 0.12
Oatmeal, instant, regular 1 cup 1.59 —- 145
Shredded Wheat, dry 1 oz 1.2 0.06 102
Bagel, enriched 1/2, 3.5” diameter 1.2 0.06 154
Vegetables
Potato, baked, skin 1 med 2.8 0.14 220

Asparagus, pieces, canned 0.5 cup 2.21 — 23
Peas, cooked 0.5 cup 1.3 0.06 59
Spinach, boiled 0.5 cup 3.21 — 21
Fruits
Prune juice 8 oz 3.02 — 182

Figs, dried 5 ea (93.5 g) 2.1 — 239
Raisins 2/3 c (100 g) 2.08 — 300
Prunes, dried 5 ea (42 g) 1.04 — 100
Beans/Legumes
Split pea & carrot soup 7.5 oz 4.5 — 90

Lentil & carrot soup 7.5 oz 4.5 — 90
Black bean and carrot soup 7.5 oz 4.5 — 70
Kidney beans, boiled 0.5 cup 2.6 0.13 112
Navy beans, canned 0.5 cup 2.44 — 148
Chickpeas, boiled 0.5 cup 2.4 0.12 134
Soybeans, green, boiled 0.5 cup 2.25 — 127
Pinto beans, boiled 0.5 cup 2.23 — 117
Lima beans, cooked 0.5 cup 2.09 — 104
Pinto beans, canned 0.5 cup 1.94 — 93.6
Kidney beans, canned 0.5 cup 1.6 0.08 103
Chickpeas, canned 0.5 cup 1.6 0.08 143
Tofu, raw, regular, ~4 oz 6.65 0.32 94

Chili, made with meat 0.67 cup 5.59 — 186
substitute
Garden burger 3.4 oz 2.89 — 186
Scallops, meatless, breaded, .5 cup 1.77 — 257
fried
Soyburger 1 each 1.49 — 142
Breakfast patties 1 each 1.42 — 97.3

Iron: Nonheme Sources in the Vegetarian Diet27,35,36,38
Adult RDA: Male 8 mg/Female: 18 mg
Available Iron (mg)
Food Portion Size Total Iron (mg) (where info available) Kcals
—
Nuts/Seeds
Pumpkin seed kernel, roasted .25 cup 8.45 — 296

Sunflower seeds, kernels, dry .25 cup 2.44 — 205
Cashew, dry roasted .25 cup 2.1 — 197
Coconut milk, canned .25 cup 1.9 — 111
Almonds, dried, whole .25 cup 1.3 — 209
Mixed nuts, dry roasted .25 cup 1.27 — 204
w/peanuts
Miscellaneous
Molasses, blackstrap 1 Tbsp 3.5 — 47
TABLE 40.24
Iron: Absorption Enhancers and Inhibitors1,2,38
Effect on Iron
Class of Inhibitors Examples Found in Absorption
Polyphenols Tannic acid, gallic acid, Coffee, tea, red wines, Coffee-35-40%
and catechin certain spices, fruits, Tea-60%
and vegetables Red wine-50%
Phytates Substances that form Whole grains, bran, soy
insoluble complexes products
with nonheme iron
EDTA (ethylenediamine- Food additive used as Used broadly Possibly up to 50% in
tetraacetic acid) sodium EDTA, calcium some cases
EDTA (prevents color
changes and oxidation
in foods)
Calcium Calcium chloride Additive to bread Possibly up to 30-50% in
(naturally occurring products, potential some cases found with
sources of calcium in effect of other forms of calcium chloride
self selected diets did calcium fortification
not show an inhibitory
effect; however there is
a potential effect of
other forms of calcium)
Fiber Insoluble fibers, Phytate Whole grains Possibly 30-50%
content may be
responsible
Effect on Iron
Class of Enhancersa Examples Found in Absorption
Organic acids Malic, ascorbic, citric, Found widely in foods Enhances absorption
and bile acids
Amino acids Some amino acids such as Protein foods, also found Enhances absorption
cysteine widely in vegetables
and grains
a The presence of these acids with a meal will significantly improve iron absorption and in some cases potentially
overcome the inhibitory effects of other components in foods.
TABLE 40.25
Manganese:a Vegetarian Sources and Amounts27,35,36
Adult AI: Male 2.3 mg/Female 1.8 mg
Food Portion Size Manganese (mg) Kcal
Cereals/Grains
100% Bran 1c 5.96 178

Most cereal 1c 3.63 175
Grape Nuts 1c 2.65 389
Bran Chex 1c 2.53 156
All-Bran 0.33 c 2.39 70.7
Raisin Bran 1c 2.16 175
Noodles, cooked, spinach 1c 2.1 182
Noodles, cooked, macaroni, whole wheat 1c 1.93 174
Rice flour, brown 0.25 c 1.59 144
Noodles, cooked, lasagna, whole wheat 2 ea 1.52 136
Wheat Chex 1c 1.34 169
Vegetables
Lima beans, boiled 0.5 c 1.07 105
Fruits
Pineapple, chunks 1c 2.56 76.0

Blackberries 1c 1.86 74.9
Tofu, raw, firm, w/Nigari 0.5 c 1.49 181

Tempeh 0.5 c 1.19 165
a Manganese is not necessarily at risk for deficiency in vegetarians. Some research has
indicated that vegetarians have a higher intake of this nutrient; however, bioavail-
ability may be a concern.14,17
TABLE 40.26
Selenium:a Vegetarian Sources and Amounts27,35,36,39
Food Portion Size Selenium (µg) Kcal
Cereals/Grains
Special K, Kellogg’s 1 cup 54.9 100

Bagel, plain, toasted 1 each 22.7 195
Granola, lowfat 1 cup 22.5 422
Pita pocket, 100% whole wheat, toasted 1 each 20.2 120
Barley, whole, cooked 0.5 cup 18.2 135
Pita pocket, white 1 each 18 165
Egg noodles, cooked 0.5 cup 17.4 107
Spaghetti/macaroni, enriched, cooked 0.5 cup 14.9 98.5
Puffed wheat 1 cup 14.8 44.4
Whole wheat bread 1 slice 12.8 86.1
Oatmeal, instant, prepared 0.5 cup 12.68 159
Buns, hamburger-style 1 each 12.5 129
English muffin, plain 1 each 11.5 134
Cheerios 1.25 cup 10.6 111
Matzo, whole wheat 1 each 9.89 99.5

Selenium:a Vegetarian Sources and Amounts27,35,36,39
Food Portion Size Selenium (µg) Kcal
Brown rice, long grain 0.5 cup 9.6 108.5
Vegetables
Brussels sprouts, boiled 1 cup 21.1 60.8

Cucumbers, slices with peel 0.5 cup 6.19 6.76
Mushrooms, raw 5 pieces 14.3 32.4
Fruits
Grapes, Thompson seedless 0.5 cup 7.7 57

Applesauce, canned 0.5 cup 6.5 52.5
Dairy/Soymilk
Cottage cheese, 1% 1 cup 13.6 164

Yogurt, fruit, lowfat (12 g protein/8 oz.) 1 cup 8.09 155
Milk, nonfat 1 cup 5.15 85.5
Frozen yogurt, chocolate, nonfat 1 cup 5.02 208
Beans/Legumes
Black beans, dry, boiled 1 cup 13.7 227

Lima beans, cooked 1 cup 8.19 229
Great northern beans, cooked 1 cup 7.26 209
Chickpeas, boiled 1 cup 6.10 269
Tofu 0.5 1.79 94.2
Nuts/Seeds
Brazil nuts, dried 0.25 cup 1036 230

Sunflower seeds, kernels, dry 0.25 cup 21.4 205
Cashew, dry roasted, unsalted 0.25 cup 8 197
Eggs
Egg, hard cooked 1 each 10.7 77.5

Egg yolk, cooked 1 each 7.50 59.2
Egg white, cooked 1 each 5.88 16.6
Mixed Foods
Lasagna, no meat, recipe 1 piece (218 g) 29.9 298

Avocado & cheese sandwich on wheat bread 1 each 25.2 456
Peanut butter and jam sandwich on wheat 1 each 24.3 344
Pizza, cheese 1/8 of 15-inch (120 g) 20.0 268
Bean burrito 1 each 14.1 223.5
Cucumber & vinegar salad 1 cup 11.1 47.8
Desserts
Coffee cake, from mix 1 piece (72 g) 11.0 229

Carrot cake, w/ cream cheese icing, recipe 1 piece (112 g) 9.91 488
a Selenium content of foods can vary widely, according to the selenium content of the soil.39
TABLE 40.27
Zinc: Vegetarian Sources and Amounts27,35,36,40
Adult RDA: Males 11 mg/Females 8 mg
Food Portion size Zinc (mg)a,b Kcal
Cereals/Grains
Just Right 1 cup 22.8 152

Product 19, Kellogg’s 1 cup 15 100
Complete bran 1 cup 8.07 195
100% Bran 1 cup 5.74 178
Raisin bran, dry 1 cup 5.71 175
Bran flakes 1 cup 5.15 127
Cap’n Crunch 1 cup 4.00 156
Quinoa 1 cup 3.4 576
Muffin, wheat bran, from recipe with 2% milk 1 each (57 g) 1.57 161
Noodle, spaghetti, spinach, cooked 1 cup 1.53 182
Bagel, oat bran 1 each 1.42 173
Pancakes, Aunt Jemima, blueberry 3 each (106 g) 1 246
Vegetables
Palm hearts, cooked 1 cup 5.45 150
Dairy/Soymilk

Frozen, nonfat, chocolate yogurt 1 cup 2.18 208
Edam/ball cheese 1 oz. 1.07 101
Buttermilk, cultured 1 cup 1.03 99
Beans/Legumes
Adzuki, cooked 1 cup 4.07 294

Lentils, cooked 1 cup 2.52 230
Blackeye peas, boiled from dry 1 cup 2.22 198
Soybean, dried, boiled 1 cup 2.0 298
Kidney beans, red, cooked 1 cup 1.89 225
Chickpeas, canned 0.5 cup 1.28 143
Natto 1 cup 5.32 371

Miso 0.5 cup 4.60 284
Tempeh 1 cup 3.02 330
Chili with meat substitute 0.66 cup 1.67 186
Meatless scallops, breaded, fried 0.5 cup 1.24 257
Luncheon slice, meatless 1 piece 1.07 188
Nuts/Seeds
Pumpkin seeds, kernel, dry roasted 0.25 cup 2.58 187

Cashew, dry roasted, 0.25 cup 1.9 197
Almonds, dry roasted 0.25 cup 1.7 203
Sunflower seeds, kernels, dry roasted 0.25 cup 1.7 186
Sesame butter/tahini from unroasted kernels 1T 1.58 91.1
Peanuts, dry roasted 0.25 cup 1.2 214
Peanut butter, natural 2T 1.06 187

Zinc: Vegetarian Sources and Amounts27,35,36,40
Adult RDA: Males 11 mg/Females 8 mg
Food Portion size Zinc (mg)a,b Kcal
Eggs
Egg substitute 0.5 cup 1.6 74
Mixed Foods
Cheese enchilada 1 each 2.51 319

Avocado & cheese sandwich on wheat bread 1 each 1.83 456
Pizza, cheese 1/8 of 15-inch 1.56 268
Desserts
Nutrigrain bar, fruit filled 1 each 1.5 150

Pecan pie, 1/8 of a 9” pie 1 piece (122 g) 1.26 503
Trail mix, regular 0.25 cup 1.21 173
Doughnut, eggless, carob-coated, raised 1 piece (78 g) 1.14 285
a Zinc content of foods is influenced by genetic breeding and fertilizer and soil conditions.
b Bioavailability is greater from animal than plant sources.40
TABLE 40.28
Zinc: Absorption Enhancers and Inhibitors1,2,40
Possible Absorption Possible Absorption
Enhancersa Sources Inhibitorsb Sources
Yeast (acts by reducing Fermented bread dough Phytates Whole grains (rye, barley,
phytates) oatmeal, wheat), soy
products
Animal protein Animal products Oxalate Spinach, Swiss chard, leek,
kale, collard greens, okra,
rhubarb, raspberries,
coffee, chocolate, tea,
peanuts, pecans
Histidine Amino acid widely Fiber Whole grains, fruits,
distributed in foods vegetables, legumes
containing protein
Albumin Widely distributed in foods Non-heme iron Legumes, fortified cereals,
containing protein, egg leafy greens
white
Copper Legumes, whole grains,
nuts, seeds, vegetables
Calcium supplements Over-the-counter
supplements,
multivitamins, some
antacids
High iron intakes
relative to zinc intake
a Yeast is the only non-controversial zinc absorption enhancer.
b Phytates are the only non-controversial zinc absorption inhibitor.
TABLE 40.29
Fiber: Types, Functions, and Sources1,2,36
Type of Fiber Fiber Type Food Sources Function
Cellulose Insoluble Whole wheat flour, bran, cabbage, Increases stool bulk and water
peas, green beans, broccoli, absorption, decreases transit time
cucumbers, peppers, apples, through the GI system
carrots
Hemicellulose Insoluble Bran cereals, whole grains, brussels
sprouts, greens, beet root
Lignin Insoluble Breakfast cereals, bran, older
vegetables, strawberries, eggplant,
pears, green beans, radishes
Gums Soluble Oatmeal, oat products, dried beans, Binds to bile acids and certain lipids to
oat bran, barley help lower blood cholesterol levels,
metabolized to short chain fatty acids
in gut which may play a role in
signaling hepatic slowed cholesterol
production
Pectin Soluble Squash, apples, citrus fruits,
cauliflower, cabbage, dried peas
and beans, carrots, strawberries
TABLE 40.30
Common Phytochemicalsa in Foods18
Chemical Names Sources Proposed Mechanism of Action
Sulforaphane Isothiocyanates found in broccoli, cauliflower, Activates phase II enzymes in liver
cress, cabbages, radishes (removes carcinogens from cells)
Flavonoids Citrus fruits and berries Blocks the cancer-promotion process
Monoterpenes Perillyl alcohol in cherries May inhibit the growth of early cancers
(polyphenols) Limonene in citrus
Ellagic acid in strawberries & blueberries
Genistein Soybeans, tofu Prevents the formation of capillaries
required to nourish tumors
Indoles Cruciferous vegetables (broccoli, cauliflower, Increase immunity, facilitate excretion of
cress, cabbages, radishes) toxins
Saponins Kidney beans, chickpeas, soybeans, lentils May prevent cancer cells from
multiplying
Lycopene Tomatoes May fight lung cancer
a More than 10,000 phytochemicals are thought to exist. This table represents only a partial listing.
General Vitamin and Mineral Deficiency and Toxicity Symptoms

It is important for practitioners to be aware of the symptoms of nutrient deficiencies in
any patient. As a group, vegetarians tend to be more health-conscious and knowledgeable
about nutrition than the general public.1 Some vegetarians choose megadoses of vitamins
or minerals to combat real or perceived threats to their health. Therefore, toxicity may be
more of a risk than a nutrient deficiency. Table 40.33 presents deficiency and toxicity
symptoms of the nutrients potentially deficient in a vegetarian diet.
TABLE 40.31
Omega-3 Fatty Acids: Vegetarian Sources and Amounts2,29,41
Reasonable intake: 0.5%-1% of total calorie intake
(represents 1.1-2.2 g on a 2000 kcal diet)
Alpha-linolenic
Food Portion Size Acid (18:3) (mg) Kcal
Cereals/Grains
Oats, germ 0.25 cup 0.4 119
Wheat germ 0.25 cup 0.2 104
Barley, bran 0.25 cup 0.1 115
Vegetables
Soybeans, green, raw 0.5 cup 4.1 188
Kale, raw, chopped 1 cup 0.13 21
Broccoli, raw, chopped 1 cup 0.1 24
Cauliflower, raw 1 cup 0.1 26
Fruits
Avocados, California, raw 1 medium 0.173 306
Dairy/Soymilk
Cheese, Roquefort 1 oz. 0.2 105
Beans/Legumes
Soybeans, dry 0.5 cup 1.5 387
Beans, pinto, boiled 1 cup 0.2 234
Nuts/Seeds
Butternuts (dried) 1 oz. 2.4 174
Walnuts, dried, English/Persian 1 oz. 1.9 182
Fats/Oils/Dressings
Linseed oil 1T 7.5 124
Flax seed 1T 2.2 124
Canola oil (rapeseed oil) 1T 1.6 124
Walnut oil 1T 1.5 124
Salad dressing, comm., mayonnaise, soybean 2T 1.38 116
Soybean oil 1T 1.0 124
Wheat germ oil 1T 1.0 124
Salad dressing, comm., Italian, regular 2T 1.0 140
TABLE 40.32
Effects of Cooking, Storage, and Processing on the Critical Nutrients2
Nutrient Cooking Storage Processing
Riboflavin Stable to heat Destroyed by light and —
irradiation
Vitamin B12 Some losses (30%) Stable Small losses (10%)
Copper Increased content using water Canning with copper adds —
from copper pipes content to the food
Iron Cooking in iron vessels — —
increases iron content of foods
Omega 3 fatty acids Stable in baking; unstable if May go rancid with prolonged —
(a polyunsaturated smoking point is reached storage
fatty acid)
TABLE 40.33
General Vitamin and Mineral Deficiency and Toxicity Symptoms2,14,27,37
Vitamin/Minerala Deficiency Symptomsb Toxicity Symptomsc
Vitamins
Vitamin D Children — rickets Excessive bone and soft tissue calcification

Adults — osteomalacia (lung, kidney, kidney stones, tympanic
membrane)
Hypercalcemia with symptoms of
headache, weakness, nausea and
vomiting, constipation, polyuria,
polydipsia
In infants: retarded growth,
gastrointestinal upsets, and mental
retardation
Vitamin B12 Pernicious (megaloblastic) anemia Physiological stores substantial (~2000 µg).
Smooth red tongue Stores and enterohepatic recycling may
Fatigue prevent deficiency symptoms for several
Skin hypersensitivity (numbness, tingling years (~5) in the absence of intake
and burning of the feet, stiffness and None known up to 100 µg/d. No known
generalized weakness of the legs) benefit to high doses
Degeneration of peripheral nerves
progressing to paralysis
Other (glossitis, hypospermia)
Riboflavin Anemia (normocytic, normochromic) None known
(vitamin B2) Neuropathy
Purple/magenta tongue
General B-vitamin deficiency symptoms
(soreness and burning of lips, mouth, and
tongue)
Cheilosis, glossitis, angular stomatitis,
seborrheic dermatitis of nasolabial fold,
vestibule of the nose, and sometimes the
ears and eyelids, scrotum, and vulva
Minerals
Calcium Bone deformities including osteoporosis, Hypercalcemia of soft tissues and bone
tetany, hypertension (children and adults)
Poor iron and zinc absorption (of particular
concern during pregnancy)
Iron Hypochromic, microcytic anemia Seen at 100 mg intake
Seen across populations, particularly in Constipation
women, children, and those from low Liver toxicity
socioeconomic status Infections
Fatigue Hemochromatosis
Spoon-shaped nails Potential increased risk for heart disease
and myocardial infarction
Zinc Growth retardation resulting in short Toxicity is rare (300 mg/d)
stature, mild anemia, low plasma zinc Continuous supplementation with high
levels, and delayed sexual maturation dose zinc can interfere with copper
Possible in diets very rich in fiber and absorption
phytate, which chelates the zinc in the Supplementation of 50 mg/c may decrease
intestine, thus preventing absorption HDL
Poor taste acuity, poor wound healing, night Zinc sulfate at 2 g/d can result in nausea,
blindness, baldness, and skin lesions have vomiting, diarrhea, dizziness
also been reported Iron and copper losses in urine with doses
as low as 25 mg/day and if large doses
(10-15× the RDA) are taken for even short
periods of time

General Vitamin and Mineral Deficiency and Toxicity Symptoms2,14,27,37
Vitamin/Minerala Deficiency Symptomsb Toxicity Symptomsc
Copper Severe copper deficiency: rare in humans Rare — seen in genetic diseases such as
Adults: neutropenia and microcytic anemia Wilson’s disease (genetic deficiency in
Children: neutropenia and leukopenia liver synthesis of ceruloplasmin)
Decrease in serum copper and
ceruloplasmin levels followed by failure of
iron absorption leading to microcytic,
hemochromic anemia
Neutropenia, leukopenia, and bone
demineralization are later symptoms
Deficiencies have not been reported in
otherwise healthy humans consuming a
varied diet.
a Absorption of some nutrients is affected by concentration of others; intestinal absorption of some nutrients
is competitive.
b Deficiency can result from inadequate provision in the diet or via inadequate absorption.
c Toxicity is typically from overuse of nutritional supplements, although in some cases can be the cause of
improper food fortification procedures (such as milk vitamin D fortification problems that arose in 1992).
Sample Meal Plans

Tables 40.34 through 40.37 present sample meal plans for adults and children following
a lacto-ovo or vegan diet. These menus provide the Recommended Dietary Allowances
(RDA) for energy and protein while presenting an appropriate macronutrient breakdown.
TABLE 40.34
Sample Meal Plan for Lacto-Ovo Vegetarian Adult35,36
Kcals: 2218; Carbohydrate: 374 g (67.35%); Protein: 100 g (18.%); Fat: 55 g (22.29%)
Raisin Bran (1 cup, 2.15 oz) Whole wheat bread, 2 slices Bean burrito
Milk, 1% fat, .75 cup (for cereal) Griller veg. burger patty, 1 each Black beans, 1 cup
Milk, 1% fat, 1 cup (beverage) Mustard Corn tortilla, 2 each, 6”
Orange juice, 1 cup Tomato, sliced, 1/2 tomato Rice, brown, 1 cup
Banana, 1 med Jack cheese, 1 oz Salsa, 2 Tbsp
Apple, 1 med Sour cream, 1 Tbsp
Cheddar cheese, 1 oz
Green salad, 2 cups
Vinegar & oil dressing (1 tsp olive oil)
Broccoli, 1 cup
Milk, 1% fat, 1 cup
Snack
Cereal bar, raspberry

Dried apricots, 10 halves
TABLE 40.35
Sample Meal Plan for Vegan Adult35,36
Kcals: 2217; Carbohydrate: 350g (63%); Protein: 90g (16%); Fat: 62g (25%)
Raisin Bran (1 cup, 2.15 oz) Whole wheat bread, 2 slices Bean Burrito
Soy milk, 1% fat, 1 cup (for cereal) Griller veg. burger patty Black beans, 1 cup
Soy milk, 1% fat, 1 cup (beverage) (Morningstar Farms), 1 each, Corn tortilla, 2 each, 6”
Orange juice, 1 cup, Ca fortified cooked Rice, brown, 1 cup
Banana, 1 med Mustard Salsa, 2 Tbsp
Tomato, sliced, 1/2 tomato Walnuts, ground, .5 oz
Almonds, slivered, blanched, 1 oz Green salad, 2 cups
Apple, 1 med Vinegar & oil dressing (1 tsp olive
oil)
Broccoli, 1 cup
Soy milk, 1 cup
Snack
Cereal Bar, raspberry

Dried Apricots, 10 halves
TABLE 40.36
Sample Meal Plan for Vegan Child Age 4 to 635,36
Kcals: 1864; Carbohydrate: 283 g (60.8%); Protein: 68 g (14.5%); Fat: 62 g (30%)
1 packet instant oatmeal 0.5 cup hummus spread made from veggie hot dog on bun
8 oz soymilk fortified with calcium chickpeas and sesame butter 0.5 cup mashed potatoes
and vitamin B12 2 slices whole wheat bread 0.5 cup cooked “creamed” spinach
1 banana 6 oz. 100% orange pineapple 0.5 cup applesauce
banana juice 8 oz soymilk
carrot sticks
2 molasses cookies
Snack Snack
4 oz fortified soymilk 1.5 oz (approx. 0.25 cup) trail mix

4 graham crackers 4 oz fortified soymilk
TABLE 40.37
Sample Meal Plan for Lacto-Ovo Vegetarian Child Age 4 to 635,36
Kcals: 1794; Carbohydrate: 255 g (57%); Protein: 63 g (14%); Fat: 63 g (31.5%)
1 cup Honey Nut Cheerios with 4 0.5 cup homemade macaroni and burrito with salsa and sour cream,
oz milk on cereal cheese made with vegetarian chili
4 oz 1% milk to drink celery sticks and 2 Tbsp peanut 0.5 cup rice
orange slices butter 4 oz 1% milk
2 fruit cookies 0.5 cup green salad with broccoli
0.5 cup applesauce
Snack Snack
1.5 oz cheese fruit smoothie made with juice,

5 Ritz crackers frozen yogurt, and fruit
4 oz 1% milk
Summary
In summary, the term “vegetarianism” may mean different things to different people.
Before making or accepting generalizations about vegetarianism, it is important to define
the term. A person following a vegetarian lifestyle can have significantly lower risks of
many chronic diseases, such as heart disease or cancer, than an omnivore does. However,
some nutrients are more difficult to easily obtain from a vegetarian diet and may be a
concern for deficiency, especially in children or during other critical life-cycle periods.
References
1. Messina M, Messina V. The Dietitian’s Guide to Vegetarian Diets: Issues and Applications, Aspen
Publishers, Gaithersburg, 1996.
2. Mahan LK, Escott-Stump S. Krause’s Food, Nutrition, and Diet Therapy, 9th ed, WB Saunders,
Philadelphia, 1996.
3. Miller GD, Jarvis JK, McBean LD. Handbook of Dairy Foods and Nutrition, 2nd ed, CRC Press,
Boca Raton, 2000 pg 252.
4. Messina VK, Burke KI. J Am Diet Assoc 97: 1317; 1997.
5. Parsons TJ, Van Dusseldorp M, van der Vliet M, et al. J Bone Mineral Res 12: 1486; 1997.
6. Draper A, Lewis J, Malhotra N, Wheeler E. Br J Nutr 69: 3; 1993.
7. Remer T, Neubert A, Manz F. Br J Nutr 81: 45; 1999.
8. Sanders TA. Pediatr Clin N Am 42: 955; 1995.
9. Sanders TA, Reddy S. Am J Clin Nutr 59: 1176S; 1994.
10. Alexander H, Lockwood LP, Harris MA, Melby DL. J Am Coll Nutr 18: 127; 1999.
11. Craig WJ Am J Clin Nutr 59: 1233S; 1994.
12. Burr ML, Butland BK. Am J Clin Nutr 48: 840; 1988.
13. Harman SK, Parnell WR. NZ Med J 111: 91; 1998.
14. Gibson RS. Am J Clin Nutr 59: 1223S; 1994.
15. Nieman DC, Underwood BC, Sherman KM, et al. J Am Diet Assoc 89: 1763; 1989.
16. Donovan UM, Gibson RS. J Adol Health 18: 292; 1996.
17. Kadrabova J, Madaric A, Kovacikova Z, Ginter E. Biol Trace Element Res 50: 13; 1995.
18. Craig WJ. J Am Diet Assoc 97: 199S; 1997.
19. Tham DM, Gardner CD, Haskell WL. J Clin Endocrinol Metab 83: 2223; 1998.
20. Bingham SA, Atkinson C, Liggins J, et al. Br J Nutr 79: 393; 1998.
21. Uauy-Dagach R, Valenzuela A. Nutr Rev 54: 102S; 1996.
22. Sanders TAB. Am J Clin Nutr 70: 555S; 1999.
23. Gordon N. Brain Devel 19: 165; 1997.
24. Gibson RA, Neumann MA, Makrides M. Lipids 31: 177S; 1996.
25. Kretchmer N, Beard JL, Carlson S. Am J Clin Nutr 63: 997S; 1996.
26. Conquer JA, Holub BJ. Vegetarian Nutrition: An Internation Journal, 1-2: 42; 1997.
27. National Research Council, Recommended Dietary Allowances, 10th ed, National Academy Press,
28. Yates AA, Schlicker SA, Suitor CW. J Am diet Assoc 98: 699; 1998.
29. Health and Welfare Canada. Nutriton Recommendations: The Report of the Scientific Review Com-
mittee, Authority of the Minister of Health and Welfare, Ottawa, 1990.
30. Drezner MK, Hoben KP. Eating Well, Living Well with Osteoporosis. Viking Press, New York,
1996.
31. Thaler SM, Teitelbaum I, Berl T. Am J Kidney Dis 31: 1028; 1998.
32. Toohey ML, Harris MA, DeWitt W, et al. J Am Coll Nutr 17: 407; 1998.
33. Thorogood M, Carter R, Benfield L, et al. Br Med J 295: 351; 1987.
34. Key TJA, Thorogood M, Appleby PN, Burr ML. Br Med J 313: 775; 1996.
35. Pennington JAT. Bowes & Church’s Food Values of portions Commonly Used, 17 ed, Lippincott-
Raven, Philadelphia, 1998.
36. Hands ES. Food Finder: Food Sources of Vitamins and Minerals, ESHA Research, Salem, 1995.
37. Holick MF, Shao Q, Liu WW, Chen TC. N Engl J Med 326: 1178; 1992.
38. Morris DH. Iron in Human Nutrition, 2nd ed, National Cattlemen’s Beef Association, 1998.
39. Holben DH, Smith AM. J Am Diet Assoc 99: 836; 1999.
40. McBean LD. Zinc in Human Nutrition, National Cattlemen’s Beef Association, 1997.
41. United States Department of Agriculture, Agricultural Research Service, Nutrient Data Lab-
oratory, USDA Nutrient Database for Standard Reference, Release 13,
www.nal.usda.gov/fnic/foodcomp/.
41
Allergic Disorders
Scott H. Sicherer
Definition of Food Allergy

Because individuals ingest food throughout the day, potentially any malady could be
falsely associated with eating. In fact, surveys of adults have shown that 18 to 22% believe
that they have a food allergy,1-3 and 28% of parents suspect a food allergy in their infants
and young children.4 However, true food allergy affects 6 to 8% of children4 and approx-
imately 2% of adults.3-5 The discrepancy between suspected and true allergy is due, in
part, to the manner in which food allergy is defined. Technically, a food allergy is an
adverse immune response toward protein in food.6 This is in contrast to a larger number of
non-immune mediated adverse reactions to food. These non-immune-mediated reactions
include those caused by toxins in foods that would affect anyone ingesting the tainted
food, and those caused by a particular condition of the affected individual (food intolerance).
Examples of food intolerance/reactions to toxins are listed in Table 41.1.
Pathophysiology of Food Allergic Reactions

A vast number of potentially immunoreactive food proteins pass through the gut, but the
normal response to these foreign proteins is tolerance. That is, the immune system recog-
nizes these proteins (antigens), but does not process these proteins in a manner that results
in adverse reactions. In fact, approximately 2% of ingested food enters the blood stream
in an immunologically intact form,7 but causes no symptoms in the normal individual. It
remains unclear why some individuals develop food allergies, but a genetic predisposition
toward allergic responses plays a role.8 For those individuals predisposed to food allergies,
food allergens can elicit specific responses in several ways.
The most common immunologic basis for food allergic responses involves the gener-
ation of proteins, IgE antibodies, that mediate immediate food hypersensitivity reac-
tions.9,10 When a protein enters the intestine, immune cells termed antigen presenting
cells (APC) process the protein (usually a glycoprotein) and present a small portion of
0-8493-2705-9/01/$0.00+$1.50
TABLE 41.1
Examples of Food Intolerance/Toxic Reactions (Non-Immunologic, Adverse Reactions to
Food)21,140,141
Disorder/Sensitivity Pathophysiology/Symptoms
Lactase deficiency (lactose intolerance) Bloating, diarrhea from inability to digest the lactose in cow’s milk;
may be dose-related
Tyramine sensitivity Tyramine in hard cheeses, wine may trigger migraine headache
Scombroid fish poisoning Oral pruritus, flushing, vomiting, hives from histamine released from
spoiled dark meat fish (tuna, Mahi-Mahi)
Caffeine Pharmacologic effects of jitteriness, heart palpitations
Myristicin Hallucinogen in nutmeg
Gallbladder disease Pain following ingestion of fatty foods
the protein to T-cells that specifically recognize the protein fragment (Figure 41.1). Cel-
lular interactions between the APC and T-cell may direct the T-cell toward allergic
responses (termed Th-2 responses). The sensitized T-cells replicate and then interact with
B-cells in the context of further exposure to the food antigen, leading these B-cells to
produce IgE antibodies that specifically bind a portion of the food protein (epitope).
These IgE antibodies bind to specific receptors found on mast cells in body tissues and
basophils in the bloodstream. The mast cells and basophils have preformed mediators
(e.g., histamine) that, when released from the cell, cause tissue swelling (edema from
capillary leakage of fluid) and pruritus. When the mast cell or basophil armed with the
food-specific IgE antibody comes in contact with the particular allergenic protein, the
IgE antibodies attach to the protein and crosslink, resulting in release of the mediators
and the onset of the food-allergic reaction.
Intestine
Immunologically intact
food protein
Lymphoid compartment
APC
Cross-linking of IgE,
release of mediators B cell Naïve T cell
IgE antibodies
Memory T cell
High affinity IgE receptors

Preformed mediators (histamine)
Tumor necrosis factor alpha
Mast cell (tissue) IL-4
or Basophil (bloodstream) IL-5
FIGURE 41.1
APC-antigen presenting cells, IL-interleukin. See text for details.
Allergic Disorders 835
TABLE 41.2
Foods Responsible for the Majority (85 to 90%) of
Significant Allergic Reactions3,5,12,13
Infants/Young Children Older Children/Adults
Egg Peanut
Cow’s milk Tree nuts
Soy bean Shellfish
Peanut Fish
Wheat
Fish
Tree nuts (walnut, Brazil, hazel,
almond, cashew, etc.)
Shellfish
A second way in which the immune system may react adversely toward a food protein
does not involve the generation of IgE antibody (non-IgE-mediated). In this case the T-
cell may, through direct interaction with specific receptors on the cells, elaborate mediators
(cytokines) with direct effects. An example is the release of tumor necrosis factor alpha
that causes gut edema in certain forms of cow’s milk allergy.11 Further research is under
way to better delineate the mechanisms of non-IgE-mediated food allergy.
Food Allergens
Many studies have indicated that a rather short list of foods accounts for the majority
(85 to 90%) of food-allergic reactions: chicken egg, cow’s milk, wheat, soybean, peanut,
tree nuts, fish, and shellfish.3,12-15 However, virtually any food protein could elicit an
allergic response. Many of the allergenic food proteins have been characterized and are
generally heat-stable, water-soluble glycoproteins from 10 to 70 kd in size.16,17 For many
of these proteins, the particular allergenic epitopes that bind IgE or T-cell receptors have
been mapped.
Epidemiology
Population-based studies utilizing oral food challenges to confirm reactivity have deter-
mined that food allergy affects 6 to 8% of young children4 and almost 2% of adults.3 The
foods causing significant allergic reactions in different age groups are listed in Table 41.2.
Most children outgrow their sensitivity to milk, egg, soy, and wheat, but allergy to peanut,
tree nuts (e.g., walnut, cashew, Brazil nut, etc.), fish, and shellfish account for the majority
of significant food allergies in adults, and are foods for which tolerance rarely develops.12,18
Peanut and tree nut allergy alone affects 1.3% of the general population of the U.S.19
Allergic reactions to food dyes and additives are comparatively rare, affecting up to 0.23%
of the population.20 Food allergy is a cause of a number of particular illnesses, as shown
in Table 41.3.
TABLE 41.3
Epidemiologic Role of Food Allergy in Various Disorders
Prevalence of Food Allergy as a
Disorder Cause of the Disorder
Anaphylaxis95,96,142 34-52%
Asthmatic children91 6%
Asthmatic adults92 <1%
Atopic dermatitis (moderate-severe) in children30 37%
Atopic dermatitis in adults34 Rare
Acute urticaria143 20%
Chronic urticaria144 1.4%
Infantile refractory reflux145 42%
Childhood refractory constipation73 68%
Food Allergic Disorders

Food allergic disorders affect the skin and the gastrointestinal and respiratory tracts.21
The pathophysiologic basis of the disorders may be IgE-mediated, non-IgE-mediated, or
combined. In general, disorders with acute onset occurring within minutes to an hour
after food ingestion are mediated by IgE antibody, while those that are more chronic and
occur hours after ingestion are not IgE-mediated. Particular food allergic disorders are
discussed below.
Disorders Affecting the Skin

Acute Urticaria
Urticaria, or hives, are characterized by pruritic, transient, erythematous raised lesions
with central clearing and a surrounding area of erythema. The rash should leave no
residual lesions after resolution. Hives may sometimes be accompanied by localized
swellng (angioedema). Although there are many causes of acute urticaria, food allergy
accounts for up to 20% of episodes.22 The immediate onset of hives is mediated by specific
IgE to food protein. Lesions usually occur within an hour of ingestion or skin contact with
the causal food.23
Chronic Urticaria
This disorder of longstanding hives lasting over six weeks is rarely associated with food
allergy. Only 1.4% of chronic/persistent urticaria is caused by food allergy, so a search for
a causative food in the initial evaluation of this illness is often futile.24
Contact Urticaria
In some cases, topical exposure to a food (e.g., on the skin of the face) can cause a local
reaction either through irritation or through specific immune mechanisms.25
Atopic Dermatitis (AD)

This rash usually begins in early infancy. It is characterized by a typical distribution on
the extensor surfaces and faces of infants, or creases in older children and adults, with
extreme pruritis and a chronic and relapsing course.26 Atopic dermatitis is frequently
associated with allergic disorders (asthma, allergic rhinitis) and with a family history of
allergy.27 Evidence suggests that, particularly in children, IgE-mediated food allergy plays
a pathogenic role,27 although non-IgE-mediated food allergy has also been implicated.28
Clinical studies utilizing double-blind, placebo-controlled food challenges (DBPCFCs)
have shown a prevalence rate of food allergy in 33 to 37% of children with moderate to
severe AD.29,30 Studies of dietary elimination have repeatedly shown improvement in AD
symptoms.12,31,32 The more severe the rash, the more likely that food allergy is associated;33
however, AD is rarely associated with food allergy in adults.34,35
Dermatitis Herpetiformis (DH)

DH is a chronic papulovesicular skin disorder with lesions distributed over the extensor
surfaces of the elbows, knees, and buttocks.36 Immunohistologic examination of the
lesions reveals the deposition of granular IgA antibody at the dermoepidermal junction.37
The disorder is associated with a specific non-IgE-mediated immune response to gluten
(a protein found in grains such as wheat, barley, and rye). Although related to celiac
disease, there may be no associated gastrointestinal complaints; however, up to 72% may
show villus atrophy on intestinal biopsy.37 The rash abates with elimination of gluten
from the diet.
Disorders Affecting the Gastrointestinal Tract

Immediate Gastrointestinal Hypersensitivity
In this syndrome, ingestion of the causal protein results in immediate (minutes to up to
one to two hours) gastrointestinal symptoms that may include nausea, vomiting, abdom-
inal pain, and diarrhea. Considered here as a distinct syndrome, it is more commonly
associated with reactions in other organ systems, such as during systemic anaphylaxis in
patients with other atopic diseases. For example, children with atopic dermatitis under-
going oral food challenges with foods to which they have specific IgE antibody will
sometimes manifest only gastrointestinal symptoms.13,38
Oral Allergy Syndrome

Symptoms include pruritus and angioedema of the lips, tongue, and palate, and are of
rapid onset, typically while eating certain fresh fruits and vegetables.39 The reaction occurs
primarily in adults with pollen allergy (hay fever) sensitized to crossreacting proteins in
particular fruits and vegetables as shown in Table 41.4. Up to 71% of adults with pollen
allergy experience these symptoms.40 The proteins are labile, and cooked forms of the
fruits and vegetables generally do not induce symptoms.
Dietary Protein-Induced Proctitis/Proctocolitis of Infancy

Food allergy is the most common cause of rectal bleeding due to colitis in infants.41 Infants
with this disorder are typically healthy, but have streaks of blood mixed with mucus in
their stool. The most common causal food is cow’s milk or soy, and even breastfed infants
can develop this reaction from small amounts of protein passed through breast milk in
mothers ingesting the causal protein.42 Although peripheral eosinophilia and positive
radioallergosorbent tests (RASTs; serum tests to determine specific IgE antibody) to milk
have been reported, they are not consistent findings.41,43-45 In cow’s milk- or soy formula-
fed infants, substitution with a protein hydrolysate formula generally leads to cessation
TABLE 41.4
Cross-Reactions Due to Proteins Shared by Pollens and Foods Leading
to Symptoms of the Oral Allergy Syndrome39,146,147,150
Birch Pollen Ragweed Pollen Grass Pollen
Apple Melons Peach
Carrot Potato
Cherry Tomato
Apricot Cherry
Plum
Celery
of obvious bleeding within 72 hours. The majority of infants who develop this condition
while ingesting protein hydrolysate formulas will experience resolution of bleeding with
substitution of an amino acid-based formula.46
Dietary (Food) Protein-Induced Enteropathy

This disorder affects primarily infants and young children and is characterized by failure
to thrive, diarrhea, emesis, and hypoproteinemia usually related to an immunologic reac-
tion to cow’s milk protein.47-50 The syndrome may also occur following infectious gastro-
enteritis in infants.48,51 Patchy villous atrophy with cellular infiltrate on biopsy is
characteristic. Diagnosis is based upon the combined findings from endoscopy/biopsy,
allergen elimination, and challenge. While this syndrome resembles celiac disease, reso-
lution generally occurs in one to two years.48
Dietary (Food) Protein-Induced Enterocolitis Syndrome (FPIES)

FPIES as defined by Powell52,53 describes a symptom complex of profuse vomiting and
diarrhea diagnosed in infancy during chronic ingestion of the causal food protein —
usually cow’s milk or soy. Since both the small and large bowel are involved, the term
enterocolitis is used. When the causal protein is reintroduced acutely after a period of
avoidance with resolution of symptoms, symptoms characteristically develop after a delay
of two hours, with profuse vomiting and later diarrhea.53,54 There is also an accompanying
increase in the peripheral polymorphonuclear leukocyte count and, in some cases, severe
acidosis and dehydration.54,55 Confirmation of the allergy included a negative search for
other causes, improvement when not ingesting the causal protein, and a positive oral
challenge resulting in the characteristic symptoms/signs. Approximately 50% of the
infants react to both cow’s milk and soy. Sensitivity to milk is lost in 60% and to soy in
25% of the patients after two years from the time of presentation.54,56 Treatment with a
hydrolyzed cow’s milk formula is advised, although some patients may react to the
residual peptides in these formulas, requiring an amino acid-based formula.57
Allergic Eosinophilic Gastroenteritis (AEG)/Allergic Eosinophilic Esophagitis (AEE)

These disorders are characterized by infiltration of the esophagus (AEE), gastric, and/or
intestinal walls (AEG) with eosinophils, peripheral eosinophilia (in 50 to 75%) and absence
of vasculitis.58 Patients with AEG present with postprandial nausea, abdominal pain,
vomiting, diarrhea, protein-losing enteropathy, and weight loss, and depending upon the
obstruction ascites can also develop.59,60 Those with AEE may present with symptoms of
severe reflux disease.61 The diagnosis rests upon biopsy showing eosinophilic infiltration,
although there may be patchy disease and infiltration may be missed.62 Formal trials of
food elimination in adults have had mixed success, but large groups have not been
evaluated for depth of infiltration and abdominal bloating,60,63,64 and those studied clearly
represent a heterogeneous group. In children with AEE, significant success from dietary
elimination has been achieved.61 AEE was associated with positive tests for food-specific
IgE antibody in some of the children, but most with this disorder do not have IgE-mediated
food allergy.
Celiac Disease
Celiac disease is a dietary protein enteropathy characterized by an extensive loss of absorp-
tive villi and hyperplasia of the crypts leading to malabsorption, chronic diarrhea, steat-
orrhea, abdominal distention, flatulence, and weight loss or failure to thrive. As the disease
represents an immune response to a food protein, it may be considered a food allergic
disorder.65 Patients with celiac disease are sensitive to gliadin, the alcohol-soluble portion
of gluten found in wheat, oat, rye, and barley. Endoscopy typically reveals total villous
atrophy and extensive cellular infiltrate. The prevalence of Celiac disease has been reported
between 1:3700 and 1:300.66 Chronic ingestion of gluten-containing grains in Celiac patients
is associated with increased risk of malignancy, especially T-cell lymphoma.67
Other Disorders Possibly Associated with Food Allergy

Gastroesophageal Reflux (GER)
GER has been associated with cow’s milk allergy (CMA) in infants. Forget and Arenda68
demonstrated that infants who appear to have GER but do not respond to medical therapy
may have CMA. Cavataio, Iacono, and colleagues69-71 have investigated these issues in
several prospective controlled trials. They have demonstrated that up to 42% of infants
under one year of age with GER also have CMA.
Constipation
Constipation has also been associated with cow’s milk allergy in young children.72,73
Investigators have demonstrated the presence of eosinophilic proctitis in children with
chronic constipation, resolution of constipation after withdrawal of cow’s milk from the
diet (and substitution with soy-based formula), and recurrence upon reintroduction of
cow’s milk.
Occult Blood Loss from the Gastrointestinal Tract/Iron Deficiency Anemia

Ingestion of whole cow’s milk by infants less than six months of age may lead to occult
blood loss from the gastrointestinal tract and iron deficiency anemia.74 The use of infant
formulas generally results in resolution of symptoms.
Infantile Colic
There is limited evidence that infantile colic is associated with food (cow’s milk) allergy
in a subset of patients (sometimes on an IgE-mediated basis), but more studies are needed
to define the relationship.75-77
Inflammatory Bowel Disease

A role for food allergy in inflammatory bowel disease has been suggested because elemental
diets have been shown to induce remission in Crohn’s disease. 78,79 However, meta-analyses
of elemental diets for Crohn’s disease have demonstrated that they are inferior to steroids
at inducing and maintaining remission, despite their popularity in some countries.80-82
TABLE 41.5
Gastrointestinal Diseases Associated with Food Allergy
Disorder Age Onset Duration Symptoms/Features Foods
Food protein- 1 day-9 months Usually 1-3 years Vomiting, diarrhea, Cow’s milk, soybean,
induced failure to thrive, (rare grains,
enterocolitis villus injury, poultry)
syndrome 53,54 dehydration,
acidosis
Enteropathy 15,48 2-18 months Usually 1-3 years Failure to thrive, Cow’s milk, soy
edema, diarrhea,
villus injury,
malabsorption
Celiac disease152 Any Lifelong Villus injury, Gluten
malabsorption
Proctocolitis 42 Infants 1 year Bloody stools Cow’s milk, soybean
Allergic eosinophilic Any Long-lived Vomiting, abdominal Multiple foods
gastroenteritis/ pain, diarrhea,
esophagitis59,61 eosinophilic
infiltration of gut
Irritable Bowel Syndrome

The relationship of irritable bowel syndrome to food allergy has not been systematically
studied.83-85 A summary of the gastrointestinal diseases associated with food allergy is
given in Table 41.5.
Disorders Affecting the Respiratory Tract

Allergic Rhinitis
Symptoms of congestion, rhinorrhea, and nasal pruritus are usually associated with hyper-
sensitivity to airborne allergens, not foods. Rarely, isolated nasal symptoms may occur as
a result of an IgE-mediated allergy to ingested food proteins.86 The prevalence of this
illness, even among patients referred to allergy clinics, appears to be under 1%. On the
other hand, 25 to 80% of patients with documented IgE-mediated food allergy experience
nasal symptoms during oral food challenges that result in systemic symptoms.86 In contrast
to immune-mediated rhinitis, gustatory rhinitis refers to rhinorrhea caused by spicy foods.
This reaction is mediated by neurologic mechanisms.87
Asthma
Lower airway symptoms of wheezing, cough, and dyspnea induced by lower airway
inflammation and bronchoconstriction can be related to food allergy. Reactions may occur
based upon IgE-mediated reactions from ingestion of the causative food or from inhalation
of vapors released during cooking or in occupational settings.88-90 The prevalence of food-
related asthma in the general population is unknown, but studies utilizing DBPCFCs
report a prevalence of 5.7% among children with asthma,91 11% among children with
atopic dermatitis,88 and 24% among children with a history of food-induced wheezing.89
The prevalence of food-induced wheezing among adults with asthma is under 2%.92
Heiner’s Syndrome
This is a rare, non-IgE-mediated adverse pulmonary response to food, affecting infants.
The disorder is characterized by an immune reaction to cow’s milk proteins with precip-
TABLE 41.6
Symptoms Occurring in Anaphylaxis14,15,94,96
Organ System Symptoms
Respiratory Throat tightness, wheezing, repetitive coughing, nasal
congestion rhinitis, hypoxia/cyanosis
Gastrointestinal Obstructive tongue edema, nausea, vomiting, diarrhea,
abdominal pain, oral pruritus, lip edema
Skin Pruritus, urticaria, angioedema, morbiliform rash
Cardiovascular Hypotension, syncope, dysrhythmia
Other Sense of “impending doom,” uterine contractions
itating antibodies (IgG) to cow’s milk protein resulting in pulmonary infiltrates, pulmo-
nary hemosiderosis, anemia, failure to thrive, and recurrent pneumonias.93 Elimination of
cow’s milk protein is curative.
Multisystem Disorders
Anaphylaxis
Clinically, anaphylaxis refers to a dramatic, severe multi-organ systemic allergic reaction
associated with IgE-mediated hypersensitivity that may be life-threatening. Anaphylaxis
has been defined technically as an immediate, systemic reaction caused by rapid, IgE-
mediated immune release of potent mediators from mast cells and basophils.94 Food is
the most common cause of out-of-hospital anaphylaxis.95-97 Symptoms may affect the skin,
respiratory tract, and gastrointestinal tract (Table 41.6). Symptoms can be severe, progres-
sive, and potentially fatal. Fatal food-induced anaphylaxis appears to be more common
among teenage patients with underlying asthma.14,15 In addition, patients who experi-
enced fatal or near fatal anaphylaxis were unaware that they had ingested the incrimi-
nated food, had almost immediate symptoms, had a delay in receiving adrenaline, and
in about half of the cases there was a period of quiescence prior to a respiratory decom-
pensation.14 The foods most often responsible for food-induced anaphylaxis are peanut,
tree nuts, and shellfish.14,15,98,99
Food-Associated, Exercise-Induced Anaphylaxis

This uncommon disorder refers to patients who are able to ingest a particular food or
exercise without a reaction. However, when exercise follows the ingestion of a particular
food, anaphylaxis results.100-102 In some cases, exercise after any meal results in a reaction.
Treatment depends upon elimination of the causal food for 12 hours prior to exercise.
Disorders not Clearly Related to Food Allergy

Patients may relate a variety of ailments to food allergy (headaches, seizures, behavioral
disorders, fatigue, arthritis, etc.), but many of these are either false associations or adverse
reactions that are not immunologic in nature. Food allergy may play a role in a minority of
patients with migraine headaches,103 although the pharmacologic activity of certain chemi-
cals that are found in some foods (i.e., tyramine in cheeses) is more often responsible. The
role of food allergy in childhood behavioral disorders is also controversial. Although a small
subset of patients with behavioral disorders may be affected by food dyes, there is no
convincing evidence that food allergy plays a direct role in these disorders,104,105 and children
are not allergic to “sugar.” On the other hand, for individuals with these ailments who also
have bona fide allergies, treatment to relieve symptoms of asthma, atopic dermatitis, and
hay fever should be pursued in parallel to treatment directed at the unrelated disorder.
Diagnostic Approach to Food Allergic Disorders

The diagnosis of food allergy often rests simply upon a history of an acute onset of typical
symptoms, such as hives and wheezing, following the isolated ingestion of a suspected
food, with confirmatory laboratory studies indicating the presence of specific IgE antibody
to the suspected food. However, the diagnosis is more complicated when multiple foods
are implicated or when chronic diseases such as asthma106 or atopic dermatitis107 are
evaluated. The diagnosis of food allergy and identification of the particular foods respon-
sible is also problematic when reactions are not mediated by IgE antibody, as is the case
with a number of gastrointestinal food allergies.54 In these latter circumstances, well-
devised elimination diets followed by physician-supervised oral food challenges are crit-
ical in the identification and proper treatment of these disorders.
General Approach to Diagnosis

The history and physical examination must review general medical concerns to exclude
nonimmunologic adverse reactions to foods or to consider other allergic causes for symp-
toms (e.g., cat allergy causing asthma). In relation to foods, a careful history should focus
upon the symptoms attributed to food ingestion (type, acute versus chronic), the food(s)
involved, consistency of reactions, quantity of food required to elicit symptoms, timing
between ingestion and onset of symptoms, the most recent reaction/patterns of reactivity,
and any ancillary associated activity that may play a role (i.e., exercise, alcohol ingestion).
The information gathered is used to determine the best mode of diagnosis, or may lead
to dismissal of the problem based upon the history alone.
For acute reactions after isolated ingestion of a particular food, such as acute urticaria
or anaphylaxis, the history may clearly implicate a particular food, and a positive test for
specific IgE antibody would be confirmatory. If the ingestion was of mixed foods and the
causal food was uncertain (e.g., fruit salad), the history may help to eliminate some of the
foods (those frequently ingested without symptoms), and specific tests for IgE may help
to further narrow the possibilities. In chronic disorders such as atopic dermatitis or asthma,
it is more difficult to pinpoint causal food(s).107 The approach to diagnosis in these chronic
disorders usually requires elimination diets and oral food challenges to confirm suspected
associations. This is particularly the case for the non-IgE-mediated reactions or those
attributed to food dyes/preservatives in which ancillary laboratory testing is not helpful.
Tests for Specific IGE Antibody

In the evaluation of IgE-mediated food allergy, specific tests can help to identify or exclude
responsible foods. One method to determine the presence of specific IgE antibody is prick-
puncture skin testing. While the patient is not taking antihistamines, a device such as a
bifurcated needle or lancet is used to puncture the skin through a glycerinated extract of
a food and appropriate positive (histamine) and negative (saline-glycerine) controls. A
local wheal and flare response indicates the presence of food-specific IgE antibody (a
wheal >3 mm is considered positive). Prick skin tests are most valuable when they are
negative, since the negative predictive value of the tests is very high (over 95%).108,109
Unfortunately, the positive predictive value is on the order of only 50%.108,109 Thus, a
positive skin test in isolation cannot be considered proof of clinically relevant hypersen-
sitivity. Intradermal allergy skin tests with food extracts give an unacceptably high false-
positive rate, have been associated with systemic reactions including fatal anaphylactic
reactions, and should not be used.109 An additional issue is that the protein in commercial
extracts of some fruits and vegetables are prone to degradation, so fresh extracts of these
foods are more reliable110 and the “prick-prick” manner of testing may be indicated, where
the probe is used to first pierce the food being tested (to obtain liquid) and then the skin
of the patient.
RASTs
In vitro tests for specific IgE (RASTs) are also helpful in the evaluation of IgE-mediated
food allergy.111 Unlike skin tests, RASTs can be used while the patient is taking antihista-
mines and does not depend on having an area of rash-free skin for testing. Like skin tests,
a negative result is very reliable in ruling out an IgE-mediated reaction to a particular
food, but a positive result has low specificity. Recent studies have been evaluating
improved RASTs that may have added predictive value for clinical reactivity.111-113
In addition to the high false positive rate of tests for food-specific IgE antibodies, several
other issues complicate interpretation. It is not uncommon for patients to have positive
skin tests and RASTs to several members of a botanical family or animal species. This
usually represents immunologic cross-reactivity but may not represent clinical reactivity.
For example, most peanut-allergic patients will have positive skin tests to at least a few
of the other members of the legume family, but only 5% will have clinical reactions to
more than one legume.114 Further testing with oral challenges, if the history does not
resolve the issue, would be required. More importantly, the foods selected for testing
should be carefully selected to include only those suspected to be at issue in order to avoid
false positive tests that inappropriately lead to questions about foods that have been
previously tolerated. Lastly, one should be wary of tests such as measurement of IgG4
antibody, provocation-neutralization, cytotoxicity, applied kinesiology, among other
unproved methods.115
Food Elimination Diets

As an adjunct to testing, the first step in proving a cause-and-effect relationship with a
particular illness and food allergy (whether IgE-mediated or not) is to show resolution of
symptoms with elimination of the suspected food(s). In many cases, one or several foods
are eliminated, which may be the obvious course of action when an isolated food ingestion
(i.e., peanut) causes a sudden acute reaction and there is a positive test for IgE to the food.
This would also represent a therapeutic intervention. However, eliminating one or a few
suspected foods from the diet when the diagnosis is not so clear (asthma, atopic dermatitis,
chronic urticaria) can be a crucial step in determining whether food is causal in the disease
process. If symptoms persist, the eliminated food(s) is (are) excluded as a cause of symp-
toms. Alternatively, and as is more likely the case for evaluating chronic disorders without
acute reactions, eliminating a large number of foods suspected to cause a chronic problem
(usually including those that are common causes of food-allergic reactions as described
above) and giving a list of “allowed foods” may be the preferred approach. The primary
disadvantage of this approach is that if symptoms persist, the cause could still be attributed
to foods left in the diet. Thus, a third type of elimination diet is an elemental diet in which
calories are obtained from a hydrolyzed formula, or preferably from an amino acid-based
formula. A variation is to include a few foods likely to be tolerated (but, again this adds
the possibility that persistent symptoms are caused by these foods). This diet is extremely
difficult to maintain in patients beyond infancy. In extreme cases, nasogastric feeding of
the amino acid-based formula can be achieved, although some patients can tolerate the
taste of these formulas with the use of flavoring agents provided by the manufacturers.
This diet may be required when the diets mentioned above fail to resolve symptoms, but
suspicion for food-related illness remains high. It is also required in disorders associated
with multiple food allergies such as allergic eosinophilic gastroenteritis. With AEG, pro-
longed dietary elimination for three to six weeks is sometimes needed to determine
whether resolution of symptoms will occur.61
Food Challenges
An oral food challenge is performed by feeding the patient the suspected food under
physician observation. There are several settings in which physician-supervised oral food
challenges are required for diagnosis of food-allergic disease (Table 41.7). Because food
challenges may elicit severe reactions, they are usually conducted under physician super-
vision, with emergency medications to treat anaphylaxis immediately available.116 Chal-
lenges can be performed “openly” with the patient ingesting the food in its native form,
“single-blind” with the food masked and the patient unaware if they are receiving the
test food, or as DBPCFCs where neither patient nor physician knows which challenges
contain the food being tested. While open and single-blind challenges are open to patient
or observer bias, the DBPCFC is considered the gold standard for diagnosis, since bias
is removed.116
In all of these challenges, the food is given in gradually increasing amounts that may
be individualized both in dose and timing, depending on the patient’s history. For most
IgE-mediated reactions, experts suggest giving 8 to 10 grams of the dry food or 100 ml of
wet food (double amount for meat/fish) at 10 to 15 minute intervals over about 90 minutes
followed by a larger, meal-size portion of food a few hours later.116 Starting doses may be
a minute amount applied to the inner lip followed by 1% of the total challenge, followed
by gradually increasing amounts (4, 10, 20%, etc.). However, challenges may be individ-
TABLE 41.7
Indications for Performing Physician-Supervised Oral Food Challenges
To confirm a food allergy when history is unclear and tests not confirmatory
To exclude a food allergy
To monitor for development of tolerance
ualized to parallel the clinical history (i.e., feeding over consecutive days for chronic
disorders with delayed symptoms). Similarly, higher risk challenges may start at extremely
low doses with very gradual increases over longer time intervals.
Symptoms are recorded and frequent assessments are made during the challenge for
symptoms affecting the skin, gastrointestinal tract, and/or respiratory tract. Challenges
are terminated when a reaction becomes apparent, and emergency medications are given
as needed. Generally, antihistamines are given at the earliest sign of a reaction, with
epinephrine and other treatments given if there is progression of symptoms or any poten-
tially life-threatening symptoms.
The practical issues in preparing food challenges include palatability and masking foods
in appropriate vehicles, with placebos for DBPCFCs. In many cases, dry forms of the food
(flour, powdered egg whites, etc.) can be hidden in puddings or liquids. Bulkier foods
may be hidden in pancakes or ground beef. Flavoring agents such as mint can be added
for further masking. Hiding the food in opaque capsules is a convenient method to
administer blinded challenges for patients who are able to ingest these capsules.
Non-IgE-mediated reactions (e.g., AEG, enterocolitis, etc.) are more difficult to diagnose
since there are no specific laboratory tests to identify particular foods that may be respon-
sible for these illnesses. In many cases, a biopsy may be needed (e.g., AEG) to establish
an initial diagnosis. Elimination diets with gradual reintroduction of foods and supervised
oral food challenges are often needed to identify whether diet plays a role in the disorder,
and to identify the causal food(s). Specific challenge protocols have been advised for food-
induced enterocolitis syndrome.53 Oral challenges can be used to evaluate reactions to
food additives (coloring and flavoring agents and preservatives) or virtually any complaint
associated with foods. When used to evaluate behavioral disorders or other complaints
not convincingly associated with food allergy, DBPCFCs are advised to avoid bias.
Treatment of Food Allergy

The mainstay of treatment for food allergy is dietary elimination of the offending food.
The elimination of particular dietary food proteins is not a simple task. Table 41.8 lists a
variety of possible pitfalls in dietary management of food allergy. A primary issue in
avoidance is the ambiguity of food labeling practices. In a cow’s milk-free diet, for
example, patients must be instructed to not only avoid all cow’s milk products, but also
to read ingredient labels for key words which may indicate the presence of cow’s milk
protein. Terms such as casein, whey, lactalbumin, caramel color, “natural flavoring,” and
nougat may, for example, signify the presence of cow’s milk protein. In many cases, the
allergic individual must query companies for further product information, although prod-
uct labeling is improving. Patients and parents must also be made aware that the food
protein, as opposed to sugar or fat, is the ingredient being eliminated. For example,
lactose-free cow’s milk contains cow’s milk protein, and many egg substitutes contain
chicken egg proteins. Conversely, peanut and soy oil do not generally contain the food
protein, unless the processing method is one in which the protein is not completely
eliminated (as with cold pressed or “extruded” oil). Lay organizations such as The Food
Allergy Network (800-929-4040; www.foodallergy.org) assist families and physicians in
the difficult task of eliminating the allergenic foods. When multiple foods are eliminated
from the diet, it is prudent to enlist the aid of a dietitian in formulating a nutritionally
balanced diet.
TABLE 41.8
Pitfalls in Dietary Allergen Avoidance
Pitfall Examples
Unfamiliar terms on food labels Various terms indicating particular food proteins such as casein (milk),
whey (milk), ovalbumin (egg)
Ambiguous terms on food labels “Natural flavoring” may indicate cow’s milk
Religious labels “Pareve” may indicate non-dairy but does not guarantee absence of milk
protein
Cross-contamination In processing lines (e.g., milk protein found in juice boxes) or in the home
setting (shared utensils)
Ingredient switching Large size of a product may have different ingredients than a small size,
despite similar packaging design
Hidden ingredients Egg white to make a pretzel shiny, peanut butter to seal the end of egg rolls,
peanut butter to thicken sauces
In addition to elimination of the offending food, an emergency plan must be in place

to treat reactions caused by accidental ingestion. Injectable epinephrine and oral antihis-
tamine should be readily available and administered without delay to treat patients at
risk for severe reactions.15,94,117 Caregivers must be familiarized with indications for the
use and method of administration of these medications.
Natural History
Most children outgrow their allergies to milk, egg, wheat, and soy by age three years.18
However, patients allergic to peanuts, tree nuts, fish, and shellfish are much less likely to
lose their clinical reactivity,14,96,118,121 and these sensitivities may persist into adulthood.
Approximately one-third of children with AD and food allergy “lost” (or “outgrew”) their
clinical reactivity over one to three years with strict adherence to dietary elimination,
believed to have aided in a more timely recovery.12 Elevated concentrations of food-specific
IgE may indicate a lower likelihood of developing tolerance in the subsequent few
years.113,122 However, tests for food-specific IgE antibody (prick skin tests, RAST) remain
positive for years after the food allergy has resolved and cannot be followed as the sole
indicator of tolerance.12 Thus, it is recommended that patients with chronic disease such
as atopic dermatitis be rechallenged intermittently (e.g., egg: every two to three years;
milk, soy, wheat: every one to two years; peanuts, nuts, fish, and shellfish: if tolerance is
suspected; other foods every one to two years) to determine whether their food allergy
persists, so that restriction diets may be discontinued as soon as possible.
Prevention of Food Allergy

Dietary modification with the goal of allergy prevention has been attempted during preg-
nancy, lactation, and early feeding of infants who are at risk for atopic disease based upon
strong family histories of allergy. In several series, infants from atopic families whose
mothers excluded highly allergenic foods from their diets during lactation had significantly
less AD and food allergy compared to infants whose mothers’ diets were unrestricted.123,126
However, the differences may not may not extend beyond early childhood.126,127
The delayed introduction of solid foods has also been associated with reduction in
allergic disease. In a study of 1265 unselected neonates, the effect of solid food introduction
was evaluated over a ten-year period.128,129 A significant linear relationship was found
between the number of solid foods introduced into the diet by four months of age and
subsequent AD, with a threefold increase in recurrent eczema at ten years of age in infants
receiving four or more solid foods compared to infants receiving no solid foods prior to
four months of age. A prospective, nonrandomized study comparing breastfed infants
who first received solid foods at three or six months of age revealed reduced AD and food
allergy at one year of age in the group avoiding solids for the six-month period,130 but no
significant difference in these parameters at five years.131 Since these series did not ran-
domize patients, the studies must be considered suggestive until further randomized trials
confirm the findings.
Future Therapies
Currently, strict avoidance of causal foods and treatment of accidental ingestion is the
only available therapy for food allergy. Immunotherapy (“allergy shots”) has not proven
practical for treatment132 except in the case of the oral allergy syndrome, in which immu-
notherapy with the pollens responsible for the cross-reactivity may provide relief.133
Toward a goal of more definitive therapies for food allergic disorders, a multitude of
experimental therapies is under investigation.
Humanized anti-IgE antibodies for injection into patients have been developed that are
able to bind and remove free-floating IgE antibodies from the bloodstream and may reduce
or abolish allergic responses. Anti-IgE may, therefore, provide treatment for many IgE-
mediated allergic disorders (not just food allergy). More allergen-specific novel therapies
include vaccination with proteins altered such that the epitopes that bind IgE are removed
while areas of the protein are left intact so that T-cells can still mount a response leading,
potentially, to tolerance.134-137 Another approach to induce tolerance to specific food aller-
gens is vaccination with DNA sequences that code for the production of food aller-
gens,138,139 and the use of immune modulators (cytokines, specific DNA sequences) that
can direct the immune system away from allergic responses and toward tolerance of the
proteins. It is hoped that these novel approaches will provide relief from chronic disease
and prevent anaphylaxis for food allergic individuals.
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42
Enteral Nutrition
Introduction
Historically, enteral feeding can be traced back to ancient Egypt and Greece, where nutrient
enemas were used when patients were unable to take oral nutrition. Various combinations
of wine, milk, broth, grains, and raw eggs were used with limited success.1 Rectal delivery
of nutrients was continued up until the early 1900s despite lack of supportive benefit. In
fact, President James Garfield was given nutrient enemas every 4 hours for 79 days
following his attempted assassination until his death.1
The first reports of nutrient provision through feeding tubes into the esophagus were
in 1598, when an enteral feeding tube was fashioned from eel skin. In 1790 John Hunter
initiated the modern era of gastrointestinal (GI) access with his reports of tube feeding
the stomach.1 Up until this time, nutrient mixtures were delivered by gravity force limiting
flow rate consistency. The first stomach pump was invented in the 18th century, allowing
for consistent enteral nutrient delivery as well as gastric irrigation and emptying.1 Tubes
remained very primitive and uncomfortable until rubber was developed, thus leading to
the evolution of the currently available selections. In 1910 Max Einhorn began feeding
the duodenum through a rubber tube when gastric access was not feasible, claiming that
rectal feeding was unacceptable.1 The implementation of orojejunal tube feeding in sur-
gical patients implemented by Ravdin and Stengel followed in 1939. In 1950 the use of
polyethylene tubes was described with gastric and jejunal tubes 27 inches and 6 feet in
length, respectively. With these tubes came the introduction of the feeding pump to deliver
the formulation.1
Experimentation with the enteral formulations began in the early 1900s with the intro-
duction of the chemically defined or “elemental” diet. The late 1950s through the 1970s
marked the space age and the beginning of space diet research. These chemically defined
diets were investigated in both animals and healthy humans to produce a low residue
diet that would decrease fecal output during space travel. In the late 1960s chemically
defined diets were first reported being used in critically ill surgical patients.1 Since that
time, enteral formulations have undergone extensive modification and now exist for nearly
every metabolic disease state.
0-8493-2705-9/01/$0.00+$1.50
TABLE 42.1
Immune Benefits of Enteral Feeding
Improved mucosal integrity
Enhanced glycemic control
Normalization of GI flora
Preserved GALT
All epithelial surfaces benefit
common mucosal immune hypothesis
Increased secretory IgA
GI: gastrointestinal; GALT: Gut associated lymphoid tissue
Rationale and Benefits

In most major patient care centers enteral nutrition is the preferred route of nutrient
delivery. Parenteral nutrition is substituted only if safe access is unavailable or unsuccess-
ful. Extensive review of the numerous benefits of enteral nutrition is beyond the scope of
this section and is only briefly addressed. Available reviews provide more extensive
background in these areas.2-5
One proposed benefit of enteral nutrition is that it is more physiologic than parenteral
nutrition. The gut and the liver process enteral nutrients prior to their release into systemic
circulation (first pass). When compared to parenteral nutrition, enteral nutrition positively
influences nitrogen balance,6,7 serum protein levels,5,8,9 and the metabolic response to
stress.2-5,10,11
Another benefit of enteral nutrition is its affect on the immune system (Table 42.1). The
lack of GI stimulation by enteral nutrients may promote gut mucosal atrophy. This may lead
to increased intestinal permeability potentially leaving the gut vulnerable to bacterial trans-
location. Enteral nutrition provides maintenance of the gut-associated lymphoid tissue,12,13
maintenance of the normal GI flora,14-16 and a lowering of infectious complications.13,17-19
Enteral nutrition is generally less expensive than parenteral nutrition.20,21 The lower total
cost includes factors such as the cost of enteral formulations, cost of equipment used for
formula preparation and administration, and cost of personnel specialists. The delivery of
enteral nutrition has been shown to be safe in stable as well as in most critical patients.17-19,22
Indications/Contraindications
Enteral nutrition is indicated for patients with access to an adequately functional GI tract
and whose oral nutrient intake is insufficient to meet estimated needs. Specific conditions
for which enteral nutrition is indicated are found in Table 42.2. Although enteral nutrition
is the preferred route of nutrient delivery, it is not innocuous and there are some contrain-
dications to its use (Table 42.3). It is not always clear when enteral nutrition will be
tolerated. If the individual’s needs are not met enterally, parenteral nutrition may be
implemented for either full nutrient provision or concurrently with the enteral delivery
to provide the balance of nutrients not tolerated.
Enteral Access
Route of administration and type of access for tube feedings are usually determined by
the expected length of therapy (Figure 42.1), risk of aspiration (Table 42.4), and local
Enteral Nutrition 853
TABLE 42.2
Enteral Feeding Indications
Hypermetabolism Oncologic Disease
Postoperative major surgery Chemotherapy

Trauma Radiotherapy
Sepsis Neoplasms
Burns
Organ Transplantation
Neurologic Disease Psychiatric Disease
Cerebrovascular accident Anorexia nervosa

Dysphagia Severe depression
Head trauma
Demyelinating disease Organ System Failure
Neoplasm
Respiratory failure
Gastrointestinal Disease (ventilator dependence)
Renal failure
Short bowel syndrome (if remaining bowel has Cardiac failure (cardiac cachexia)
sufficient absorptive capacity ~50-100 cm and Hepatic failure
intact ileocecal valve) Multiple organ system failure
Inflammatory bowel disease Comatose state
Enterocutaneous fistula (<800 mL output/day)
Pancreatitis
TABLE 42.3
Enteral Feeding Contraindications
Bowel obstruction
Persistent intolerance (e.g., emesis, diarrhea)
Hemodynamic instability
Major upper GI bleeds
Ileus
Unable to safely access
Relative Contraindications
Significant bowel wall edema

Nutrient infusion proximal to recent GI anastamosis
High output fistula (>800 mL/day)
expertise. Nasoenteric or oroenteric tubes are generally used when therapy is anticipated
to be of short duration (i.e., <4 weeks) or for interim access before the placement of a long-
term device. Long-term access requires a percutaneous or surgically placed feeding tube.
Nasoenteric Access
Multiple methods exist for gaining enteral access (Table 42.5), all of which carry various
degrees of expertise, risk, and expense. The nasoenteric tube is the most commonly used
method of enteral access. It can be inserted into the stomach, duodenum, or jejunum. Since
these tubes have low complication rates, are relatively inexpensive, and are easy to place,
they are used most often for short-term use. The most common complications are tube
malposition and dislodgement.
Need for Enteral Nutrition
< 4 weeks > 4 weeks
Nasoenteric Tube Long-term tube

NGT
NJT
PEG
Candidate (?)
Yes No
Surgical
PEG
Tube
Laparoscopy
Candidate (?)
Yes No
Laparoscopic FT Open FT
FIGURE 42.1
Enteral access decision tree.
TABLE 42.4
Risk Factors for Aspiration
Altered mental status with inability to protect airway
Swallowing dysfunction
Central (CVA)
Local (vagal disruption, trauma)
History of aspiration
Severe gastroesophageal reflux
Gastric outlet obstruction
Gastroparesis
Patient position restrictions (supine versus semirecumbent)
It is often desirable to place tubes beyond the pylorus in patients with delayed gastric
emptying or absent gag reflex to potentially decrease the risk of aspiration. Positioning
a nasoenteric tube into the small bowel is much more difficult than positioning into the
stomach. Transpyloric tubes can be placed intraoperatively, at bedside, or with endoscopic
or fluoroscopic guidance. Intraoperative placement of a nasoenteric tube involves manual
manipulation during the surgery; however, this is not common practice, as it requires
open laparotomy. Spontaneous placement of a nasoenteric tubes involves advancing the
tube into the stomach and allowing it to migrate independently into the small bowel.
This technique is not very successful in hospitalized patients, especially the critically ill,
due to motility derangements. Several bedside manual methods using special placement
techniques, weighted versus non-weighted tubes, pH sensor tubes, prokinetic agents,
TABLE 42.5
Methods of GI Access
Nasoenteric Feeding Tubes Percutaneous Feeding Tubes
Spontaneous Passage Percutaneous Endoscopic

Bedside — prokinetic agent Gastric (PEG)
Active Passage Gastric/Jejunal (PEG/J)
Bedside — assisted Direct Jejunal (DPEJ)
Endoscopic
Laparoscopic
Fluoroscopic
Operative Gastrostomy
Jejunostomy
Surgical
Gastrostomy
Jejunostomy
magnets, and bioelectrical detection devices have been reported, all with similar success
rates (~85%).23-29
Do to lack of universal success in manual placement of nasoenteric tubes, fluoroscopic
or endoscopic guidance is often sought. If portable equipment is not available, both of
these techniques require patient transport to the endoscopy or radiology suite, which may
not be feasible for critically ill patients. Fluoroscopic techniques of nasoenteric tube
placement involve manipulation of the tube with a long guide wire. Endoscopic tech-
niques include use of a guide wire as well as a “drag” method. In the drag method, a
gastrically placed tube is grasped with a snare or biopsy forceps and dragged with the
endoscope into the duodenum or farther, and then released. All risks of endoscopy
accompany these methods including dental injury, pharyngeal or esophageal injury, gas-
tric bleeding, perforation, and risk of aspiration with the use of intravenous sedation.30
Both fluoroscopic and endoscopic placement methods are ~85 to 95% successful in obtain-
ing postpyloric feeding tube placement. Although placement of postpyloric feeding tubes
using endoscopic, fluoroscopic, and manual techniques may be successful, these tubes
are frequently dislodged. Repeated tube insertion increases risk and costs of these access
methods. For this reason, patients requiring long-term enteral nutrition should receive
more permanent access.
Gastrostomy
Gastrostomy is the most common method for long-term enteral access since it eliminates
nasal irritation, psychological stress, and requirement for an infusion pump, as complex
formulas may be given as boluses. Gastric tubes, due to their large diameter, can serve
many other functions besides feeding, including gastric decompression, gastric pH mon-
itoring, and medication delivery. Insertion can be via laparatomy, laparoscopy, endoscopy,
or fluoroscopy.
Permanent gastric placement can be obtained either by surgical procedures (laparotomy
or laparoscopically) or by nonoperative procedures. Percutaneous endoscopic gastrostomy
(PEG) is the most popular nonoperative procedure for obtaining permanent gastric access.
Gauderer et al.31 first described the procedure in 1980, and despite some modifications,
the basic technique used by most endoscopists is similar. Compared to surgically placed
tubes, PEGs are less costly, have decreased procedure-related morbidity and mortality,
usually do not require general anesthesia, and allow enteral feeding to be initiated
TABLE 42.6
PEG Indications and Contraindications
Indications Contraindications
Long-term access (>4 weeks) No stomach

Decompression Unable to scope
Swallowing dysfunction Hemodynamic instability
Neurologic event precluding swallowing Coagulation disorders
Tracheoesophageal fistula Obstruction
Portal hypertension, esophageal varicies, ascites
Relative Contraindications
Peritoneal dialysis
Prior upper abdominal procedures
Pregnancy
Morbid obesity
quickly.30-36 Indications as well as contraindications for a PEG are described in Table 42.6.
Complications of PEGs include dislodgment, bleeding, tube site infection, intra-abdominal
leak, site leak, and persistent gastric fistula.30
Jejunostomy
The advantage of percutaneous tubes is less apparent when small bowel feeding is
required, owing to the high failure rate of PEG tubes with a jejunal extension (PEG/J).
While a PEG/J tube is beneficial in the acute care setting when a critically ill patient
requiring long-term access is intolerant of gastric feeds, they are not very practical for
long-term use. Long-term failure of the jejunal extension is attributed to its small lumen
leading to frequent clogging, as well as separation of the inner PEJ tube from the outer
gastrostomy tube.37 For these reasons as well as the expertise required to place the
jejunal extension, surgical placement of jejunal tubes is often preferred for long-term
jejunal access.
Several choices are available for intraoperative feeding jejunostomy placement. The
needle catheter jejunostomy (NCJ) is a quick and easy method that involves inserting a
small catheter into the lumen of the jejunum proximal to the ligament of Treitz. The
advantage of an NCJ is that nutrients can be administered almost immediately and the
catheter can easily be removed when it is no longer needed. Unfortunately, the small
lumen of the catheter occludes more readily than larger-bore feeding tubes. Catheters
originally designed for other uses have been adapted for jejunal feeding, with the red
rubber catheter most frequently used.
Jejunal access has also been obtained by direct percutanous endoscopic jejunostomy
placement (DPEJ).38 This method is similar to PEG placement except that the endoscope
is passed through the duodenum, past the ligament of Treitz, into a loop of jejunum
adjacent to the abdominal wall. A regular pull-through PEG tube is used for access. This
procedure is technically more difficult than a PEG due to the peristaltic action and
narrow lumen of the jejunum, but this procedure has many advantages over a PEG/J
such as a decrease in clogging due to the use of a larger diameter tube, and decreased
migration or kinking. As this is a fairly new procedure, data on long-term complications
are lacking.
Enteral Formulas
The increase in the use of enteral over parenteral nutrition in the past few decades has
led to a rapid expansion in the number of commercially available enteral nutrition prod-
ucts. These products do not currently require Food and Drug Administration (FDA)
approval for their proposed clinical implications, and fall under the category of food
supplements. Nearly every major enteral formula company in the United States today
carries a similar line of products. These formulas can be categorized as oral supplements,
standard tube feedings, high-protein tube feedings, and disease-specific products. Table
42.7 provides an overview of these categories, specifying the types of macronutrients and
physical properties of the select formulas. Since these products do not require the rigorous
FDA examination prior to their marketing, it is left up to the experienced nutritionist to
decipher the product indications. The optimal selection and administration of a formula
requires a thorough knowledge of normal and abnormal digestive and absorptive phys-
iology and formula composition. The physical form and quantity of each nutrient may
determine the extent of absorption of and tolerance to the formula (e.g., long-chain versus
medium-chain triglyceride). The following discussion provides an overview of select
macronutrients found in these products, with related supportive research as available.
Macronutrients
Carbohydrate
Among formulas, the two main differences in carbohydrate composition are form and
concentration. The form, ranging from starch to simple glucose, contributes to the char-
acteristics of osmolality, sweetness, and digestibility. In general, the larger carbohydrate
molecules (e.g., starch) exert less osmotic pressure, taste less sweet, and require more
digestion than shorter ones (e.g., maltodextrin, sucrose, corn syrup solids). In the critical
care setting, optimal carbohydrate delivery should be at a level to allow maximal protein
sparing while minimizing hyperglycemia. Currently 4 to 6 mg/kg/min appears to meet
these criteria during states of hypermetabolism.
Fiber
It has been claimed that fiber is beneficial in the control of a myriad of gastrointestinal
disorders, as well as treatment of hyperlipidemia and control of blood glucose. Fiber-
containing formulas have 5 to 14 gm of total dietary fiber per liter. The form of fiber used
is primarily insoluble fiber (e.g., soy fiber), but some formulas also contain extra-soluble
fiber (e.g., guars, pectins). The insoluble fiber is beneficial with regard to colonic function
and bowel regulation. The soluble fibers may slow gastric emptying and decrease the rise
in postprandial blood glucose levels as well as bind bile acids and dietary cholesterol,
thus lowering serum cholesterol levels. The soluble fibers are also substrates for bacterial
fermentation in the colon, yielding short-chain fatty acids (SCFA), carbon dioxide, meth-
ane, hydrogen, and water. SCFAs are known to be the primary fuel for the colonocyte. It
is believed that SCFAs are required to maintain optimal colonocyte function. In patients
requiring long-term tube feeding, a fiber-containing formula may help to regulate GI
motility. Because of the higher viscosity of these formulas, the use of larger bore tubes (10
Fr or greater) or an infusion pump is suggested.
858
TABLE 42.7
Overview of Select Enteral Formulas
% Calories Caloric Product
Formula Protein % Calories Carbohydrate from % Calories Density mL for 100% mOsm/kg Names (Select
Category Sources from Protein Sources Carbohydrate Fat Sources from Fat (Calories/mL) NPC:g N RDI % Free Water Water Number)
Oral supple- Sodium & cal- 14-24 Corn syrup, 47-64 Corn oil, cano- 21-39 1.0-2.0 78-154:1 946-2000 73-85 480-870 Ensure,
ments cium casein- sugar, su- la oil, soy oil, Ensure Plus,
ates, soy crose, malto- sunflower Sustacal,
protein iso- dextrin oil, safflower Sustacal with
late oil Fiber,
Resource Plus,
NuBasics,
Sustacal Plus
Standard tube Sodium & cal- 13-18 Corn syrup, 45-57 Soy oil, corn 29-39 1.0-1.5 116-167:1 830-1890 77-85 270-500 Isocal,
feedings cium casein- maltodextrin oil, canola IsoSource HN,
ates, soy oil, MCT, saf- Nutren 1.0,
protein iso- flower oil Nutren 1.5,
lates Osmolite,
Osmolite HN,
Comply
Standard tube Sodium & cal- 14-18 Corn syrup, 44-57 Canola oil, 29-37 1.0-1.2 110-149:1 933-1500 78-85 300-500 Fibersource,
feedings cium casein- maltodex- soybean oil, Jevity,
with fiber ates, soy trin, corn corn oil, Jevity Plus,
protein iso- syrup solids, MCT ProBalance,
late soy fiber, Ultracal,
guar gum, Nutren 1.0
oat fiber, FOS with Fiber
High protein Sodium and 22-25 Hydrolyzed 38-52 Canola oil, 23-40 1.0-1.5 75-91:1 1000-2000 78-85 300-490 IsoSource
tube feed- calcium cornstarch, MCT, soy- VHN, Re-
ings caseinates maltodex- bean oil, saf- plete with Fi-
trin, sucrose, flower oil ber, Promote,
fructose, oat Protain XL,
fiber, soy fi- TraumaCal
ber
Elemental & Free amino ac- 12-25 Hydrolyzed 36-82 Soybean oil, 3-39 1.0-1.5 67-175:1 1150-2000 76-86 270-650 Vivonex
semi-ele- ids, soy hy- cornstarch, safflower oil, T.E.N., Cru-
mental drolysates, maltodex- canola oil, cial,
hydrolyzed trin, sucrose, MCT sun- Peptamen,
whey, hydro- modified flower oil Perative,
lyzed casein, cornstarch Reablin,
hydrolyzed AlitraQ, San-
soy dosource
Peptide,
Enteral Nutrition
Subdue,
Optimental
Pulmonary Sodium and 17-20 Hydrolyzed 27-40 Canola oil, 40-55 1.5 102-125:1 933-1420 76-79 330-650 Nutrivent,
calcium cornstarch, soybean oil, Pulmocare,
caseinates corn syrup, MCT, corn Respalor,
sucrose, mal- oil, safflower Novasource
todextrin, oil, sardine Pulmonary,
sugar oil, borage Oxepa
oil
Renal Sodium & cal- 7-15 Corn syrup, 40-58 Corn oil, saf- 35-45 2.0 140-340:1 947-1000 70-71 570-700 Nepro,
cium casein- sucrose, fruc- flower oil, Magnacal Re-
ates, Whey- tose, malto- canola oil, nal, Nova-
L-amino ac- dextrin, MCT source Renal
ids sugar RenalCal

Diabetic Sodium & cal- 16-24 Maltodextrin, 34-40 Sunflower oil, 40-49 1.0-1.06 79-125:1 1000-1890 or 85 355-450 Glucerna,
cium casein- hydrolyzed soybean oil, N/A Glytrol,
ates, beef, cornstarch, canola oil, Choice dm,
milk protein, fructose, su- MCT, saf- Diabeti-
soy protein crose, guar flower oil Source, Re-
isolate gum, vegeta- source
bles, fruits, Diabetic
soy fiber
Immune Mod- Sodium & cal- 22-32 Hydrolyzed 38-53 Canola oil, 20-40 1.0-1.5 52-71:1 1250-2000 78-86 375-550 Impact,
ulated cium casein- cornstarch, structured Impact 1.5
ates, L- maltodex- lipids: sun- ImmunAid,
Arginine, L- trin, soy fiber flower oil Crucial
glutamine, and menha-
BCAA den fish oil,
MCT
Hepatic L-amino ac- 11-15 Sucrose, mal- 57-77 Soybean oil, 12-28 1.2-1.5 148-209:1 N/A-1000 76-82 560-690 NutriHep,
ids, Whey todextrin, MCT, canola Hepatic Aid II
modified oil, corn oil,
cornstarch lecithin
859
Fructooligosaccharides
Fructooligosaccharides (FOS) are undigestible sugars that occur naturally in food (e.g.
onions, blueberries). These sugars consist of a sucrose molecule linked to one, two, or
three additional fructose units. Gastric acid or digestive enzymes do not degrade FOS.
These oligosaccharides appear to remain intact in the small intestine and pass into the
colon unaltered, where they are fermented by colonic microorganisms (e.g., bifidobacteria)
to lactate and SCFAs. It is suggested that the proliferation of bifidobacteria species and the
presence of FOS with the consequent production of the fermented byproducts acetate and
lactate, produce an environment undesirable for some pathogenic bacteria such as Clostrid-
ium difficile by lowering the colonic pH.14,16 A few enteral formulations now contain FOS,
but proposed benefits remain to be elucidated.
Fat
The major sources of fat in standard lactose-free formulas are corn, soy, safflower, and
canola oils, lecithin, and medium-chain triacylglycerol (MCT). In addition to their impor-
tance as a concentrated caloric source (9 kcalories/gm), fat is required for essential fatty
acids, and serves as a carrier for the fat-soluble vitamins. Fat also enhances the flavor and
palatability of a formula without increasing osmolality. Long-chain triacylglycerol (LCT)
is a rich source of essential fatty acids, linoleic and linolenic acid. The estimated daily
requirement for essential fatty acids is 3 to 4% of total kcalories. However, due to LCT
route of absorption via the lymphatic system, their limited utilization during hyperme-
tabolism, and their immunosuppressive effects when given in large quantities, many
formulas now combine LCT with MCT.
MCTs are 6 to 12 carbons long and are prepared from palm kernel or coconut oil. MCT
is advantageous because it is more rapidly hydrolyzed and water soluble than LCT,
requires little or no pancreatic lipase or bile salts for absorption, and can be transported
directly into portal venous circulation where it crosses the mitochondrial membrane and
can be oxidized independent of carnitine.39 MCTs are generally well tolerated by the
enteral route but can be associated with some GI symptoms such as nausea, vomiting,
and diarrhea. As they produce ketones, they should not be used in patients who are
prone to high ketone levels.39 Since they do not contain essential fatty acids (EFA), most
enteral formulas that contain MCT also provide some LCT in order to meet the require-
ment for EFA.
Recent metabolic research has led to the incorporation of omega-3 fatty acids (linolenic)
into enteral formulas. Numerous reports using various in vivo and in vitro models suggest
that the slight structural difference between omega-3 and omega-6 fatty acids strongly
favors anti-inflammatory, antithrombotic, antiarrhythmic, hypolipidemic, and antiathero-
sclerotic effects.40-42
Structured lipids are a chemical mixture of LCTs and MCTs incorporated onto the same
glycerol molecule. They differ from the more simple random physical mixtures of LCT
and MCT. Structured lipids may offer the advantages of both types of fats. Structured
lipids have been shown to decrease infection and improve survival by producing less
inflammatory and immunosuppressive eicosanoids as compared with conventional tria-
cylglycerols.39 Enteral formulas, particularly the immune-modulated category, are begin-
ning to include structured lipids as a source of fat.
Protein
Protein contained in enteral formulas may be in the form of intact protein (e.g., lactalbu-
min, casein, caseinates), partially hydrolyzed protein (e.g., oligopeptides, di- or tripep-
tides), or crystalline L-amino acids. Intact protein and protein hydrolysates (≥4 amino acid
residues) require further luminal digestion by pancreatic or brush border enzymes into
peptides (di- or tripeptides) and free amino acids, which are then absorbed primarily in
the proximal small bowel. The peptide transport mechanisms are felt to be responsible
for absorption of the majority of nitrogen, with the single amino acid carriers playing a
minority role in protein absorption. Intact proteins do not add appreciably to the osmo-
lality of the formula, unlike hydrolyzed or crystalline amino acids. The higher the per-
centage of hydrolyzed protein or free amino acids, the greater the solution osmolality will
be. A knowledge of the source and form of protein is essential when prescribing diets for
patients with defects in either protein digestion (e.g., pancreatic insufficiency) or absorp-
tion (e.g., short bowel syndrome).
Stress and other forms of injury may alter protein metabolism. In times of decreased
absorptive surface area, ischemic injury, or malabsorption, provision of enteral formulas
containing hydrolyzed protein or free amino acids has been suggested. At present, no
clear consistent clinical data support the use of solutions in which protein is in the form
of free amino acids or hydrolysates. This may be due to the fact that the small bowel has
a very adaptive absorptive mucosa, even when a large percentage of the small bowel
mucosa is nonfunctional or resected. Although patients with maldigestion and/or malab-
sorption may benefit from a peptide-based enteral formula, the higher cost of these
formulas and lack of clinical supportive data discourage routine use in patients with
normal GI physiology.
Glutamine
Glutamine is the most abundant amino acid in the body and in normal situations is
considered a non-essential amino acid. It can be synthesized in many tissues of the body,
predominantly skeletal muscle, and is the primary fuel for rapidly dividing tissues such
as the small bowel. Glutamine serves many purposes including maintenance of acid-base
status as a precursor of urinary ammonia, as a primary fuel source for enterocytes, as a
fuel source for lymphocytes and macrophages, and as a precursor for nucleotide synthe-
sis.43,44 Glutamine is also a precursor for glutathione, an important antioxidant that may
be protective in a variety of circumstances. During catabolic illness, glutamine uptake by
the small intestine and immunologically active cells may exceed glutamine synthesis and
release from skeletal muscle, making glutamine conditionally essential.43
Limited human data exist regarding the use of enteral glutamine supplementation. In
animal models, supplemental glutamine has been shown to enhance intestinal adaptation
after massive small bowel resection, to attenuate intestinal and pancreatic atrophy, and to
prevent hepatic steatosis associated with parenteral and elemental enteral feeding.43
Glutamine appears to maintain GI tract mucosal thickness, maintain DNA and protein
content, reduce bacteremia and mortality after chemotherapy, and reduce bacteremia and
mortality following sepsis or endotoxemia.43,44
In humans with surgical stress, glutamine-supplemented parenteral nutrition appears
to maintain nitrogen balance and the intracellular glutamine pool in skeletal muscle.43 In
critically ill patients, glutamine supplementation may attenuate villous atrophy and
increased intestinal mucosal permeability associated with parenteral nutrition.45
Parenteral nutrition supplemented with glutamine has also resulted in fewer infections,
improved nitrogen balance, and significantly shorter mean hospital length of stay in bone
marrow transplantation patients.46 Glutamine supplementation may also play a role in
protecting the GI tract against chemotherapy-induced toxicity. Oral glutamine supple-
mentation reduced the severity and decreased the duration of stomatitis that occurred
during chemotherapy.47
While a large volume of animal data supports the beneficial effects of glutamine in a
variety of experimental models, the benefit of enteral glutamine supplementation in crit-
ically ill human patients is less clear. Well-designed clinical trials with clearly defined
endpoints and adequate statistical power are needed to assess whether the animal effects
translate into a reduction in hospital stay and mortality rate in humans.
Arginine
Arginine is classified as a nonessential amino acid in normal situations, since the body
synthesizes adequate arginine for normal maintenance of tissue metabolism. During inju-
ries such as trauma or stress an increase in urinary nitrogen, excreted largely as urea,
represents the end-products of increased tissue catabolism and reprioritized protein syn-
thesis. As the activity of the urea cycle increases, so does the demand for arginine.
Studies indicate that supplemental dietary arginine is beneficial for accelerated wound
healing, enhanced immune response, and positive nitrogen balance.43 The exact mecha-
nism for these benefits is unknown but may in part result from arginine’s role as a potent
stimulant of growth hormone, glucagon, prolactin, and insulin release.43 Arginine is also
a precursor for nitric oxide, a highly reactive molecule synthesized from arginine by the
action of nitric oxide synthase resulting in the formation of nitric oxide and citrulline.48
Nitric oxide is a ubiquitous molecule with important roles in the maintenance of vascular
tone, coagulation, the immune system, and the GI tract, and has been implicated as a
factor in disease states as diverse as sepsis, hypertension, and cirrhosis.48
In animal models, arginine supplementation has been associated with improved wound
healing, with increased wound tensile strength and collagen deposition.49 Arginine-sup-
plemented rats also had improved thymic function as assessed by thymic weight, the total
number of thymic lymphocytes in each thymus, and the mitogenic reactivity of thymic
lymphocytes to phytohemagglutinin and concanavalin A.48 Animal arginine supplemen-
tation resulted in improved survival in burns, and with intraperitoneal bacterial challenge.
Multiple human clinical trials have been conducted comparing the use of various enteral
formulations that contain arginine as well as other supplemental nutrients (e.g., glutamine,
omega-3 fatty acids, nucleotides) to a standard nonsupplemented formula. Results of these
trials have found the supplemented formula groups to have various improved outcomes
such as decreased number and severity of septic complications,50-53 decreased antibiotic
use,50 and decreased hospital and intensive care unit stay.50, 54
While supplemental arginine has been shown to improve survival in various animal
models and to improve a number of in vitro measures of immune function, the benefit of
arginine supplementation alone in critically ill humans is uncertain.
Other Nutrients
Vitamins and Minerals
Most nutritionally complete commercial formulas contain adequate vitamins and minerals
when a sufficient volume of formula to meet energy and macronutrient needs is provided.
Some disease-specific formulas are nutritionally incomplete in relation to vitamin and
mineral content (e.g., hepatic formulas). Liquid vitamin and mineral supplements may be
indicated for patients receiving nutritionally incomplete or diluted formulas for prolonged
periods of time. Fat-soluble vitamin supplementation such as vitamin K may be indicated
for patients with fat malabsorption or for patients with vitamin K deficiency; most com-
mercial formulas include vitamin K.
Water
A large percentage of all enteral formulas is free water. The quantity of water in enteral
formulas is often described as water content or moisture content. The quantity of water is
usually reported in milliliters of water either per 1000 mL of formula or per liter of formula.
Most enteral formulas contain water in the general range of 690 to 860 mL per 1000 mL
of enteral formula. This must be considered when making fluid recommendations.
Physical Properties
Osmolality
Osmolality is the function of size and quantity of ionic and molecular particles (protein,
carbohydrate, electrolytes, and minerals) within a given volume. The unit of measure for
osmolality is mOsm/kg of water versus the unit of measure for osmolarity, which is
mOsm/L. Osmolality is considered the preferred term to use in reference to enteral
formulas.
Osmolality is important because of its role in maintaining the balance between intra-
cellular and extracellular fluids. Several factors affect the osmolality of enteral formulas.
The primary factor is nutrient hydrolysis. The smaller the chain length of carbohydrates
and proteins, the greater will be the formulation’s osmolality. Hence, formulas containing
increased amounts of simple sugars or free amino acids and/or di- and tripeptides will
have a greater osmolality than those containing starch and longer-chain intact proteins.
Lipids contribute minimally to the osmolality of an enteral formula with the exception of
MCT, owing to their water solubility. Because of dissociation properties and small size,
minerals and electrolytes also increase the osmolality.
GI tolerance (e.g., gastric retention, abdominal distention, diarrhea, nausea, and vomit-
ing) is influenced by the osmolality of enteral formulas. Generally, the greater the osmolality,
the greater the likelihood of GI intolerance. Administering hypertonic formulas at a slow,
continuous rate initially (10 to 20 cc/h) with a gradual titration to the final volume while
monitoring for GI complications can reduce the incidence of GI intolerance and allow these
formulas to be administered at full strength. What may be more important than the osmo-
lality of the enteral formula is the osmotic contribution from liquid medications either
infused with the enteral formula or bolused through the feeding tube. The average osmo-
lality range of commercially prepared liquid medications is reported to be 450 to
10,950 mOsm/kg. The osmolality of enteral formulas ranges from 270 to 700 mOsm/kg.
Hydrogen Ion Concentration (pH)

Gastric motility is reportedly slowed with solutions with a pH lower than 3.5. The pH
level of most commercial formulas is >3.5. Feeding tube occlusion can be caused in part
by the pH of the enteral formula. Most intact protein formulas coagulate when acidified
to a pH of less than 5.0.
kcalorie-Nutrient Density
The kcalorie density of enteral formulas is generally 1.0, 1.5, or 2.0 kcalories per milliliter.
This is important as it not only determines how many kcalories, but also the other macro-
and micronutrients that the patient receives. As a formula becomes more nutrient dense,
it contains less free water.
Caloric density often affects the patient’s tolerance for tube feeding. Delayed gastric
emptying frequently occurs in patients who are given concentrated formulas. High fat
formulas contribute to this, being potent inhibitors of gastric emptying. Since the patient’s
nutrient needs are met by a decreased volume of this class of formula, free water supple-
mentation should be given to ensure that fluid requirements are met, and to prevent
dehydration and constipation. Generally, these products are best tolerated as voluntary
oral supplements and not as tube feeding.
Non-Protein Calorie to Gram of Nitrogen Ration (npc:gm N)

In general, the average healthy adult requires a non-protein calorie to gram of nitrogen
(npc:gm N) ratio of 150-250:1. In a catabolic state, the body catabolizes lean body mass as
a nitrogen and energy source. To minimize this process, it is recommended to provide a
npc:gm N of 100-150:1. This protein content of enteral formulas becomes extremely impor-
tant in patients who require wound healing due to trauma, burns, metabolic stress, infec-
tion, and increased wound healing requirements.
Renal Solute Load

Renal solute load refers to the constituents in the formula that must be excreted by the
kidneys. Major contributors to renal solute load in enteral formulas are protein, sodium,
potassium, and chloride. There is an obligatory water loss for each unit of solute. Therefore,
as a formula becomes more concentrated or its renal solute load increases, the patient will
require more water.39 Pediatric and geriatric patients, as well as those with diarrhea,
emesis, fistulas, or fevers, should be monitored closely for hydration status.
Disease-Specific Formulations
Most patients can tolerate enteral nutrition safely with a standard enteral formula and do
not require specialty enteral formulations. Specialty enteral formulas have an increased
cost that often may not be reimbursable; however, factors such as severe hypercatabolism,
renal or hepatic failure, pulmonary insufficiency, or malnutrition may alter nutrient metab-
olism and may thereby warrant an enteral formulation tailored to the specific disease
process. Determining the location of enteral nutrient delivery, mode of delivery, and the
patient’s overall current clinical condition as well as past medical history is necessary for
appropriate cost-effective formula selection.
Renal Formulas
The clinical status of patients with renal failure is diverse; therefore, prescribed nutrient
intake may vary greatly among patients and should depend on individual nutritional
status, catabolic rate, residual glomerular filtration rate, and intensity of dialysis or hemo-
filtration therapy. Formulas for renal insufficiency do not clearly distinguish the difference
between patients with acute failure and those with chronic renal failure.
Renal enteral formulas were first developed as oral supplements; therefore, they tend
to be hyperosmolar secondary to their large simple sugar content for flavor enhancement.
This hypertonicity often causes GI complications if these formulas are tube fed. The simple
sugar content can also be problematic, causing impaired glycemic control in patients who
are hypermetabolic, insulin resistant, or diabetic. The goal of feeding patients with renal
failure is to provide optimal nutrients without compromising their medical condition
through the accumulation of nitrogenous compounds, electrolytes, and fluid. Hence, renal
formulas are all calorically rich, providing 2 kcalories per milliliter and containing low-
to-moderate amounts of protein, electrolytes, and various minerals. Essential amino acid
(EAA) formulas were developed to decrease urea toxicity. However, previously presumed
nonessential amino acids (NEAAs) are probably conditionally essential (e.g., arginine,
glutamine, histidine) during metabolic stress. Recent guidelines recommend the use of
EAAs and NEAAs for enhanced protein synthesis, correction of low plasma NEAA values,
provision of nonspecific nitrogen via NEAAs, and enhanced protein synthesis.55,56 Nutri-
ents should be provided as needed. The development of fluid and electrolyte disorders
or accumulation of metabolic waste products should not be minimized solely by nutrient
restriction, but also by adjusting the intensity of dialysis treatment as tolerated.57 Many
patients with stable levels of creatinine, blood urea nitrogen, and electrolytes with or
without dialysis can be fed with standard complete enteral formulas.
Pulmonary Formulas
Respiratory insufficiency and ventilator dependence can have a major impact on the
feeding of critically ill patients. Often these patients do not receive their full nutritional
needs due to the increased work of breathing, carbon dioxide retention, and fluid and
electrolyte restrictions. This reduced nutrient intake results in loss of lean body tissue (e.g.,
intercostals, diaphragm) and malnutrition that in turn leads to fatigue and further diffi-
culty with weaning from the ventilator.
Lipid oxidation is known to produce less carbon dioxide than oxidation of either glucose
or protein. This has been the basis for the development of high fat (~45 to 55% of kcalories)
and calorically concentrated (1.5 kcalories per milliliter) enteral formulas. Originally these
products consisted of 100% long-chain triacylglycerol, which can suppress the immune
system as well as cause malabsorption. Pulmonary formulas now contain a variety of
lipids including MCT, omega-6 and omega-3 fatty acids, and more recently, γ-linolenic
acid (GLA).
Animal research has shown that omega-3 fatty acids produce reduced amounts of
proinflammatory eicosanoids relative to animals fed omega-6 fatty acids.58 In another
study, animals fed diets enriched by GLA, as borage oil, were found to have higher
inflammatory exudate cellular levels of GLA and dihomogamma-linolenic acid (DGLA)
with reduced levels of prostaglandin E2 (PGE2) and leukotrienes,59 suggesting that GLA
modulates inflammatory status in a manner similar to that of omega-3 fatty acids. In
another animal study, authors concluded that dietary fish oil and fish and borage oil as
compared with corn oil may ameliorate endotoxin-induced acute lung injury by suppress-
ing the levels of proinflammatory eicosanoids in bronchoalveolar lavage fluid, and reduce
pulmonary neutrophil accumulation.60 More clinical trials are necessary to determine these
claims and patient indications.
Aside from the previously mentioned studies with pulmonary patients, previous
research evaluating the use of pulmonary enteral formulas has not demonstrated a clear
benefit in providing a high-fat, reduced-carbohydrate nutrient prescription for the patient
with compromised pulmonary function.61 The excessive carbohydrate associated with
overfeeding can result in a significant rise in pCO2 and respiratory quotient that influences
respiratory function. Close attention should be made to the avoidance of overfeeding by
providing energy intakes from 1.2 to 1.5 times the predicted resting energy expenditure
or by measuring energy expenditure via indirect calorimetry.61
There are potential detrimental effects in using a high-fat, low-carbohydrate enteral
formula. It is well known that high-fat diets can impair gastric emptying.62 Delayed
gastric emptying can result in increased gastric residual volumes and increased risk of
aspiration. Carbohydrate is the primary energy source during vigorous muscle exercise,
as required during ventilator weaning. During vigorous exercise, depleted muscle gly-
cogen stores may limit muscle endurance and strength. Nutritional support for the
pulmonary compromised patient requires a balanced energy mix so that prompt replen-
ishment of respiratory muscle glycogen can occur.61 Pulmonary formulas, with their low
carbohydrate levels, are a potential disadvantage to fully support muscle glycogen reple-
tion during ventilator weaning.
Literature and clinical practice demonstrate that by not calorically overfeeding pulmo-
nary compromised patients, especially if they are septic, nutritional goals may be met
with a standard enteral product (~30% kcalories as fat).56,61
Diabetic Formulas
Nutrition is an integral component in the management of diabetes mellitus (DM). Whether
during critical illness or long-term support, it can be extremely challenging. Over the past
several years, enteral formulas have been developed emphasizing glycemic control for
patients with DM. These formulations contain high fat- low-carbohydrate nutrient ratios,
with actual ingredients varying among the manufacturers (see Table 42.7). The carbohy-
drate sources include fructose and fiber to assist in glycemic management. Some fat sources
have been modified to contain a higher ratio of monounsaturated fatty acids than saturated
fatty acids to better meet the 1994 guidelines of the American Diabetes Association.
A few individual outcome studies have been conducted to determine any benefit of
providing these formulations to gain optimal glycemic control.63,64 Overall, the recommen-
dation is to begin by administering a standard, fiber-containing enteral formula with
moderate carbohydrate and fat content. Blood glucose levels will vary based on the
patient’s diabetes history, metabolic stress level, and nutrient delivery method. Blood
glucose levels should be monitored closely with appropriate insulin management, espe-
cially if feeding regimens are altered or interrupted. If metabolically stable diabetic patients
do not exhibit desired glycemic control with a standard formula, then a diabetic enteral
formula may be beneficial.
Hepatic Failure Formulas

The specialized formulas for patients with cirrhosis and hepatic failure are designed to
correct the abnormal amino acid profile associated with hepatic encephalopathy. In certain
instances of hepatic failure, amino acid metabolism is altered, resulting in increased plasma
aromatic amino acids (AAA) with a significant change in the branched-chain amino acid
(BCAA)-to-AAA ratio. This change results in altered blood-brain barrier transport, with
resultant hepatic encephalopathy. Specialized enteral formulas for hepatic enchephalop-
athy have been designed to reduce the availability of AAAs and decrease their passage
through the blood-brain barrier. Therefore, these formulas contain low quantities of AAAs
and methionine and high quantities of BCAAs.
In metabolically stressed, malnourished cirrhotic patients with encephalopathy, the effec-
tiveness of the BCAA-enriched formulas may lie in correcting malnutrition by increasing
nitrogen intake without aggravating the encephalopathy. However, some life-threatening
derangement in liver failure, such as portal hypertension and esophageal varices, are
unaffected by nutritional repletion. Therefore, these formulas should be provided only in
malnourished patients with liver failure and concomitant encephalopathy who have failed
to respond to conventional medical therapy, and in whom a potentially dangerous higher
level of nitrogen intake is required to induce anabolism.56 Due to the incidence of associated
fluid and electrolyte abnormalities, these formulas are calorically concentrated and contain
minimal amounts of electrolytes, with some formulations failing to provide 100% of the
U.S. recommended daily intake. Therefore, patients receiving these formulations should
be monitored closely to ensure that no further associated nutrient deficiencies occur.
Immune-Modulated Formulas
Over the past several decades, predominantly animal models have shown that certain
individual nutrients demonstrate immune benefits. These nutrients include arginine,
glutamine, omega-3 fatty acids, and nucleotides. Because of this, several enteral formula
manufacturers have developed immune-modulated enteral formulas to potentially
improve clinical outcomes in high-risk or critically ill patients. These products all vary in
the amounts of these nutrients they contain. More recently, several human studies have
been conducted to determine if critically ill or other immune-compromised individuals
experience positive outcomes as a result of receiving these formulations. Results of these
studies vary; they have been scrutinized for several variables, including lack of feeding
comparisons, lack of homogeneous study population comparisons, and the manner in
which the data were analyzed. Outcomes from the studies also vary, with some showing
no benefits regarding the immune formulas and others showing reduced rates of infection,
antibiotic use, incidence of intra-abdominal abscesses, and reduced intensive care unit
and hospital length of stay.40
Overall, the literature suggests that these immune-modulated formulas may be benefi-
cial for some patients. In patients who had undergone complicated GI surgery, sustained
severe trauma, or had complicated ICU stays, immune formulas were linked with
decreased incidence of infections and hospital length of stay, but were not shown to reduce
mortality in severely injured and immune-compromised patients.65 More research is nec-
essary to determine the optimal patient populations and duration of therapy for which
these formulas may be appropriate.
Methods of Administration
The method for enteral tube feeding is limited to the type and site of enteral feeding
access. The formula delivery method selected for the patient also depends on the patient’s
hemodynamic stability, gastric emptying rate, GI tolerance to tube feeding, type of formula
selected, nutrient needs, patient mobility, and ease of administration. The main methods
of tube feeding are by continuous, intermittent, or bolus delivery. Each institution should
have an established protocol for the initiation and advancement of enteral feedings.
Bolus Feeding
Bolus feedings involve the delivery of larger amounts of formula over short periods of
time, usually five minutes or less. The bolus method should only be used with gastric
delivery. The stomach can act as a reservoir to handle relatively large volumes of formula
(e.g., 400 mL) over a short time as opposed to the small intestine. The feedings are usually
administered via a gastrostomy tube, owing to the large lumen, but they can also be given
through a small-bore nasogastric tube. Usually a syringe or bulb is used to push 200 to
500 mL of formula into the feeding tube several times a day. A patient should demonstrate
adequate gastric emptying and the ability to protect his/her airway (i.e., an intact gag
reflex) prior to initiating bolus feedings, especially in the critical care setting, to decrease
the risk of aspiration. The ability to absorb nutrients using this type of feeding depends
on the access site and the functional capability of the gut.
Bolus feedings are considered the most physiologic method of administration since the
gut can rest between feedings and allow for normal hormonal fluctuations. They are the
easiest to administer since a pump is not required. Bolus feedings also allow for increased
patient mobility, since they are delivered intermittently and do not require a pump. For
these reasons, this method of feeding is most desirable for stable patients who are going
home or to an extended care facility with tube feedings.
Intermittent Feedings
This method of feeding requires the formula to be infused over a 20- to 30-minute period.
A feeding container and gravity drip is usually used for this method. Intermittent feedings
are less likely to cause GI side effects than bolus feeding, since the formula is administered
over a longer interval. Depending on the volume delivered, this method may be used for
gastric as well as small bowel formula delivery.
Continuous Feedings
Continuous formula delivery is usually the enteral delivery method best tolerated. Con-
tinuous feedings are delivered slowly over 12 to 24 hours, typically with an infusion pump.
In order to avoid accidental bolus delivery, continuous infusion is preferred over gravity,
as a constant infusion rate can be sustained. Postpyloric feedings require continuous
infusion. The small bowel does not act as a reservoir for large volumes of fluid within a
short time, and GI complications usually arise if feedings are delivered in this manner.
Initiation and progression of continuous feedings should be individualized and based
upon the patient’s clinical condition and feeding tolerance. Typically, feedings may be
initiated at 10 to 50 mL/hour, with the lower range for the critically ill. Progression of tube
feedings may range from 10 to 25 mL/hour every 4 to 24 hours, depending on the patient’s
tolerance, until the desired goal rate is achieved. As a patient is beginning to transition to
oral intake, the tube feedings may be cycled to allow for appetite stimulation, or to allow
for bowel rest and time away from the pump. The feedings may be administered at night
and held during the day to allow for patient mobility and an opportunity to eat.
Enteral Feeding Complications

Although enteral nutrition is the preferred route of nutrient provision in those individuals
unable to consume adequate nutrients orally, it is not without complications. Compared
to parenteral nutrition, enteral nutrition complications are less serious. Most of the com-
plications with enteral nutrition are minor; however there are a few that may be serious.
Most complications can be prevented, or at least made less severe. Appropriate patient
assessment for needs and risks, proper feeding route and formula selection, in addition
to appropriate monitoring of the enteral nutrition feeding regimen can increase the success
of enteral feeding. The most common complications can be categorized as mechanical,
metabolic, and gastrointestinal. Table 42.8 lists some of the common complications; their
possible causes, and suggested corrective measures.
Monitoring
It is very important to continuously monitor patients for signs of formula intolerance,
hydration and electrolyte status, and nutritional status. Physical indicators that should be
TABLE 42.8
Common Complications Associated with Enteral Feeding66,67
Complication Possible Causes Suggested Corrective Measures
Mechanical
Obstructed feeding tube Formula viscosity excessive for feeding Use less viscous formula or larger bore
tube tube
Obstruction from crushed medications Flush tube before and after feeding
administered through tube Give medications as elixir or assure
medications are crushed thoroughly
Flush tube before and after delivering
each medication
Coagulation of formula protein in tube Flush feeding tube only with warm
when in contact with acidic medium water
(medication, flushing solution) Avoid flushing with sodas, coffee, juices
or any other acidic medium
Metabolic
Hyperglycemia Metabolic stress, sepsis, trauma Treat origin of stress and provide insulin
Diabetes as needed
Avoid excessive carbohydrate delivery
Give appropriate insulin dose
Elevated or depressed Excessive or inadequate electrolytes in Change formula
serum electrolytes the formula
Refeeding syndrome Monitor electrolytes closely (e.g.,
potassium, magnesium, phosphorus)
and replace as indicated
Initiate carbohydrate gradually, not
increasing amount provided until
electrolytes and blood glucose levels
stabilized
Dehydration Osmotic diarrhea caused by rapid Infuse formula slowly
infusion of hypertonic formula Change to isotonic formula or dilute
with water
Excessive protein, electrolytes, or both Reduce protein, electrolytes or increase
fluid provision
Inadequate free water provision Assure patient receives adequate free
water, especially if provided calorically
dense formula
Overhydration Excessive fluid intake Assess fluid intake; monitor daily fluid
intake and output
Rapid refeeding in malnourished patient Monitor serum electrolytes, body weight
Increased extracellular mass catabolism daily; weight change >0.2 kg/d reflects
causing loss of body cell mass with decrease or increase of extracellular
subsequent potassium loss fluid
Cardiac, hepatic, or renal insufficiency Use calorically dense formula to
decrease free water if needed
Diuretic therapy
Gradual weight loss Inadequate calories Assure patient is receiving prescribed
amount of calories
Assure to monitor patient over time as
nutrient requirements may change due
to metabolic alterations
Excessive weight gain Excess calories Decrease calories provided, change
formula or decrease volume per day
Visceral protein Inadequate protein or calories Increase protein and/or calorie
depletion provision

Common Complications Associated with Enteral Feeding66,67
Complication Possible Causes Suggested Corrective Measures
Essential fatty acid Inadequate EFA intake Include at least 4% of kcal needs as EFA
(EFA) deficiency Prolonged use of low fat formula
Gastrointestinal
Nausea and vomiting Improper tube location Reposition or replace feeding tube
Excessive formula volume or rate Decrease rate of infusion or volume
infusion infused
Very cold formula Administer formula at room
temperature
High osmolality formula infused Change to isotonic formula or dilute
with water prior to infusing
High fat formula infused Change to lower fat formula
Smell of enteral formulas Add flavorings to formula; use
polymeric as have less offensive odor
Diarrhea Too rapid infusion Decrease rate of infusion
Lactose intolerance Use lactose-free formula
Bolus feedings into small bowel Only provide continuous or slow gravity
feedings into small bowel
High osmolality formula infused Change to isotonic formula or dilute
with water prior to infusing
Hyperosmolar medication delivery Change medications or dilute with
water to make isotonic prior to delivery
Altered GI anatomy or short gut Change to hydrolyzed or free amino acid
formula with MCT oil
Vomiting and diarrhea Contamination Check sanitation of formula and
equipment; assure proper handling
techniques
Abdominal distention, Rapid bolus or intermittent infusion of Administer formula at room
bloating, cramping, gas cold formula temperature
Rapid infusion via syringe Infuse continuously at low rate and
gradually increase to goal
Nutrient malabsorption Use hydrolyzed formula, MCT
containing, lactose free
Rapid administration of MCT Administer MCT gradually as tolerated
Constipation Lack of fiber Use fiber containing formula or add
stool softener
Inadequate free water Increase free water intake
Fecal impaction, GI obstruction Rectal exam, digital disimpaction
Inadequate physical activity Increase ambulation if able
Aspiration or gastric Altered gastric motility, diabetic Assure post-pyloric nutrient delivery
retention gastroparesis, altered gag reflex, altered with continuous infusion
mental status Add prokinetic agent if changed feeding
position does not help
Head of bed <30 degrees Elevate head of bed to >30 degrees if
possible
Displaced feeding tube Verify feeding tube placement and
replace as needed
Ileus or hemodynamic instability If small bowel feedings not tolerated
then hold feedings and initiate TPN for
prolonged intolerance
Medications that may slow gastric Evaluate medications and change if
motility (e.g., opiates, anticholinergics) feasible
Gastric or vagotomy surgery
TABLE 42.9
Example Monitoring Protocol for Enteral Feeding
During Initiation and
Advancement of
Feedings Until Stable at Long-term Enteral
Parameters Goal Rate Stable at Goal Rate Support — Stable
Body weight Daily 1-2 times per week Monthly
Fluid intake/output Daily Daily Daily
Bowel function
Glucose Daily unless abnormal 2-3 times per week; Every 6 months; unless
then every 1 to 8 hours unless diabetic, then diabetic, then daily
until stable daily
Electrolytes Daily 2-3 times per week Every 3-6 months
Blood urea nitrogen
Creatinine
Magnesium
Phosphorus
Calcium
Liver function tests 1-2 times per week 1-2 times per month Every 3-6 months
Triglyceride
Visceral proteins 1-2 times per week Weekly Every 3-6 months
(prealbumin,
transferrin)
Gastric residuals Every 4-6 hours If < 200 mL, then N/A unless
(for gastric feeds only) discontinue gastroparesis, then
every 4-6 hours
From Ideno, K.T. In: Nutrition Support Dietetics Core Curriculum, Gottschlich, M.M., Matarese, L.E., Shronts, E.P.,
Eds., ASPEN, Silver Spring, 1993, 71. With permission.
monitored include incidence of vomiting, stool frequency, diarrhea, abdominal cramps,

bloating, signs of edema or dehydration, and weight changes. In addition, several labo-
ratory parameters should be monitored daily with the initiation of enteral feeding and
tapered as the patient stabilizes and demonstrates tolerance (Table 42.9).
Summary
Enteral feeding is the preferred method of providing nutrition in those who cannot con-
sume adequate nutrients orally. Enteral feeding has many advantages over parenteral
nutrition, including preservation of the structure and function of the GI tract, more efficient
nutrient utilization, fewer infections and metabolic complications, greater ease of admin-
istration, and lower cost. In order for enteral nutrition to be successful, patient assessment
for the optimal access site, appropriate formula selection, nutrient requirements, monitor-
ing, and trouble-shooting complications are required.
References
1. McCamish M, Bounous G, Geraghty M. In: Clinical Nutrition: Enteral and Tubefeeding (Rombeau
J, Rolandelli R, Eds) WB Saunders, Philadelphia, 1997, 1.
2. King BK, Kudsk KA, Li J, et al. Ann Surg 229: 272; 1999.
3. Kudsk KA. Ann Surg 215: 503; 1992.
4. Minard G, Kudsk KA. World J Surg 22: 213; 1998.
5. Suchner U, Senftleben U, Eckart T. Nutrition 12:13; 1996.
6. Hindmarsh JT, Clark RG. Br J Surg 60: 589; 1973.
7. Rowlands BJ, Giddings AB, Johnston AB, et al. Br J Anaesth 49: 781; 1977.
8. Peterson VM, Moore EE, Jones TN, et al. Surgery 104: 199; 1988.
9. Kudsk KA, Minard G, Wojtysiak SL, et al. Surgery 116: 516; 1994.
10. McArdle AH, Palmason C, Morency I, et al. Surgery 90: 616; 1981.
11. Bennegard K, Lindmark L, Wickstrom I, et al. Am J Clin Nutr 40: 752; 1984.
12. Swank GM, Deitch W. J Surgery 20: 411; 1996.
13. Kudsk KA. Nutrition 14: 541; 1998.
14. Bengmark S. Curr Opinion Clin Nutr 2: 83; 1999.
15. Cunningham-Rundles S, Ho Lin D. Nutrition 14: 573; 1998.
16. Bengmark S. J Parent Enter Nutr 19: 410; 1995.
17. Moore FA, Feliciano DV, Andrassy RJ, et al. Ann Surg 216: 172; 1992.
18. Kudsk KA, Croce MA, Fabian TC, et al. Ann Surg 215: 503; 1992.
19. Moore FA, Moore EE, Jones TN, et al. J Trauma 29: 916; 1989.
20. Trice S, Melnik G, Page C. Nutr Clin Prac 12: 114; 1997.
21. Lipman TO. J Parent Enteral Nutr 22: 167; 1998.
22. Adams S, Dellinger EP, Wertz MJ, et al. J Trauma 26: 882; 1986.
23. Zaloga GP. Chest 100: 1643; 1991.
24. Thurlow PM. J Parent Enteral Nutr 10: 104; 1986.
25. Heiselman DE, Vidovich RR, Milkovich G, et al. J Parent Enteral Nutr 17: 562; 1993.
26. Levenson R, Turner WW, Dyson A, et al. J Parent Enteral Nutr 12: 135; 1988.
27. Lord LM, Weiser-Maimone A, Pulhamus M, et al. J Parent Enteral Nutr 17: 271; 1993.
28. Kittinger JW, Sandler RS, Heizer WD. J Parent Enteral Nutr 11: 33; 1987.
29. Cresci G, Grace M, Park M, et al. Nutr Clin Pract 14:101; 1999.
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EP, Eds, ASPEN, Silver Spring, MD, 1993, p. 71.
43
Introduction
Parenteral nutrition can be considered one of the 20th century’s medical breakthroughs.
Its discovery and first implementation in the 1960s greatly enhanced clinical medicine by
providing a means for complete and safe feeding of patients with nonfunctional gas-
trointestinal (GI) tracts. Experimentation with intravenous feeding can be traced as far
back as the 1600s, when sharpened quills were used to administer a mixture of milk and
wine into the veins of dogs.1 The 1800s brought the administration of saline, and by the
1930s 5% dextrose and protein hydrolysates were being infused intravenously.2 Several
factors limited the safe infusion of nutrients intravenously. One factor was the large
volumes that were provided, usually more than 3 liters per day.2 These volumes were
generally not tolerated by patients for long periods of time, and often resulted in pulmo-
nary edema. Another factor was the attempt to deliver hyperosmolar solutions peripher-
ally, which was the common practice in the early years. Dextrose solutions greater than
10% concentration were not tolerated, and resulted in thrombosis. Lastly, volume and the
osmolality restrictions resulted in caloric delivery limitations. This all led to experimen-
tation with alternate fuel substrates, alcohol and fat, due to their increased caloric provision
of 7 and 9 kcalories per gram, respectively. Research quickly revealed that alcohol was
not going to be the answer, as it resulted in hepatoxicity and other side effects when
delivered in large amounts.1 Intravenous fat delivery was an enticing alternative due to
its high caloric load and decreased osmolality. Initially, provision of intravenous fat was
achieved with cottonseed oil in the 1950s. However, it was removed from the market, as
it was associated with jaundice, fever, and bleeding.3 Research continued in Europe, where
emulsions made from soybean oil were successfully administered.2
Great advancement came in 1967, when cannulating the subclavian vein was introduced
to administer intravenous nutrients. Wilmore and Dudrick4 first reported successful pro-
vision of centrally administered nutrition to an infant with intestinal atresia. In the 1970s
advancements continued with the use of crystalline amino acids rather than protein
hydrolysates, recommendations for standard amounts of vitamins and minerals, and the
reintroduction of lipids in the United States.1 After the 1970s, the focus turned to fine-
tuning the parenteral solutions with the development of specialized amino acid sources
0-8493-2705-9/01/$0.00+$1.50
TABLE 43.1
Development of Total Parenteral Nutrition (TPN) Guidelines
Organization Year
American Society for Parenteral and Enteral Nutrition 1986, 1993
American College of Physicians 1987, 1989
American Gastroenterology Association 1989
U.S. Dept of Health and Human Services 1990
TABLE 43.2
Indications for TPN5-8
Clinical Situation Consensus
Short bowel syndrome Inability to absorb adequate nutrients orally
<60 cm small bowel may require indefinite use
Severe pancreatitis Recommended if enteral nutrition causes abdominal pain, ascites, or
elevated amylase/lipase
Increased fistula output with enteral feedings
Intravenous lipids are considered safe if serum triglyceride levels are
<400 mg/dl
Enterocutaneous fistula Fistula that exhibits increased output with enteral nutrition
Intractable diarrhea or vomiting Recommended for losses greater than 500-1000 ml/day with inability to
maintain adequate nutritional status
Bowel obstruction, ileus With obstruction and malnutrition awaiting surgery >7 days
Prolonged ileus >5-7 days with poor nutritional status
Perioperative support Preoperative support is indicated for severely malnourished patients with
expected postoperative NPO status >10 days
For those with postoperative complications rendering NPO >10 days
Inflammatory bowel If enteral nutrition not tolerated or if precluded by GI fistulas
Critical care Unable to gain enteral access, instability, abdominal distention with
prolonged reflux of enteral feedings, expected to remain NPO >7 days
Eating disorders Severe malnutrition and inability to tolerate enteral feeding for psychological
reasons
Pregnancy Safe in pregnancy; hyperemesis gravidarum
for disease states, approval of total nutrient admixtures by the Food and Drug Adminis-
tration, and development of new access devices and delivery systems.1
Rationale for Use of Parenteral Nutrition

Parenteral nutrition was first developed to provide nutrition to those unable to take
complete nutrition via the GI tract due to an inability to digest or absorb nutrients. A
nonfunctioning GI tract and failure to tolerate enteral nutrition still remain the primary
reasons for parenteral nutrition. Certain accompanying conditions also need consideration,
such as a patient being nutritionally at risk, and projected inability to consume anything
by mouth for at least 7 to 14 days.5 Over the past two decades several organizations have
developed practice guidelines to identify the appropriate use for parenteral nutrition
(Table 43.1). Situations that indicate the need for parenteral nutrition include short bowel
syndrome and malabsorption, bowel obstruction, severe pancreatitis, intractable diarrhea
or vomiting, prolonged ileus, and high-output GI fistulas (Table 43.2).5-8
Comparison of Parenteral and Enteral Nutrition

While parenteral nutrition can be lifesaving when used appropriately, it may also poten-
tiate adverse clinical outcomes. The GI tract not only functions to digest and absorb
Parenteral Nutrition 877
TABLE 43.3
Factors that Contribute to Increased Gut Permeability
Absence of enteral stimulation
Broad spectrum antibiotics
H2-receptor blockers
Decreased GI hormone secretion
nutrients, but also serves as a large immunologic organ in the body by acting as a protective
barrier against intraluminal toxins and bacteria. Approximately 50% of the body’s immu-
noglobulin-producing cells line the GI tract, with 80% of the body’s manufactured immu-
noglobulin being secreted across the GI tract.9 During severe physiologic stress gut
ischemia can occur, leading to mucosal damage and disruption of the barrier function and
ultimately passage of bacteria and toxins into the bloodstream.10 In addition, common
clinical practices as well as physiologic changes during acute stress can lend to bacterial
overgrowth in the proximal GI tract and impact the gut’s protective barrier (Table 43.3).
Whether or not bacterial translocation occurring in animals and humans during acute
stress is clinically significant remains debatable. Animal studies support the statement
that enteral rather than parenteral nutrition maintains gut integrity and immune respon-
siveness, and prevents bacterial translocation.11-15 However, there was no significant dif-
ference in overall outcome in an acute pancreatitis model,11 but in animals with induced
bacterial pneumonia, those that received total parenteral nutrition (TPN) had a higher
mortality rate.15 There is no hard evidence to support the statement that parenteral nutri-
tion results in clinically significant bacterial translocation in humans.16,17
Despite this lack of evidence, other disadvantages of parenteral nutrition exist. The
metabolic response to intravenous glucose differs from oral glucose. This may be due to
the fact that the liver retains a large portion of glucose when provided orally, resulting in
less systemic hyperglycemia and hyperinsulinemia.18 A meta-analysis comparing enteral
and parenteral nutrition also concluded that plasma glucose concentrations are lower
during enteral than parenteral nutrition.19 Plasma glucose and insulin concentrations,
glucose oxidation, CO2 production, and minute ventilation increase in proportion to the
proportion of kcalories administered in TPN.20 Prolonged infusion of high rates of glucose
(>4 mg/kg/min) results in de novo lipogenesis in the majority of critically ill patients.20
Furthermore, TPN is associated with increased septic morbidity16,19,21,22 and increased
cost16, 23 when compared with enteral nutrition in trauma patients.
Vascular Access
Peripheral
Prior to initiating parenteral nutrition, vascular access is obtained. Determination of
venous access is based upon the duration of therapy, patient limitations, and availability
of equipment and facilities. Central or peripheral veins may be used for the provision of
parenteral nutrition. Peripheral access with conventional needles uses the small veins of
the extremities — typically the hands and forearms. These small veins are easily sclerosed
by hypertonic parenteral solutions. Therefore, to minimize phlebitis and thrombosis of
the veins, it is recommended that peripheral parenteral solutions (PPN) consist of osmo-
lalities ≤900 mOsm/L.5 Even with appropriate PPN, intravenous sites may need frequent
changing to maintain venous patency.1 The increased fluid requirement necessary to
TABLE 43.4
Typical PPN Order
Usual Concentration gm/L or
Macronutrient in PPN Solution mEq/L Kcal/L mOsmol/L
Dextrose (6%) 5-10% 60* 240 150
Amino acids (3%) 3-5% 30* 120 300
Lipid (20%) 30-60% (of kcal) 20* 200 300
Sodium 35+ — 70
Potassium 30+ — 60
Magnesium 5+ — 5
Calcium — 7
Total 560 892
* gm/L; + mEq/L
TABLE 43.5
Indications for Peripheral Parenteral Nutrition
Indication Example
Patient expected to be NPO 5-7 days Postoperative ileus
Inadequate GI function expected for 5-7 days Hyperemesis gravidarum
Transitioning to an oral diet or tube feeding Patient with Crohn’s disease flare
Central venous access is contraindicated Coagulopathy, sepsis, venous thrombosis
Malnourished patients expected to be NPO Preoperative small bowel obstruction
for several days
Patients with nutrient requirements that can Obese patient with good venous access, small
be met with PPN or elderly people
minimize the PPN solution’s osmolality limits nutrient provision as well as the clinical
utility of PPN (Table 43.4).
PPN solutions vary considerably among institutions. Some may only use dextrose with
electrolytes, vitamins, and minerals while others may include lipids and amino acids to
increase the kcalories and minimize catabolism. PPN formulations composed of carbohy-
drate, amino acids, and lipid generally provide 1000 to 1500 kcal/day . However, PPN
may be useful when the long term plan for nutrition is uncertain and the patient requires
interim nutrition intervention in which the GI tract is nonfunctional, such as with pro-
longed ileus or hyperemesis gravidarum (Table 43.5).
Central
Central venous access refers to the large veins in the trunk. The primary indications for
central venous access include chemotherapy, antibiotic administration, risk of tissue necro-
sis with vesicant medications, and provision of TPN due to its pH and increased osmolality.
Access is obtained with specialized catheters, with the distal tip placed into the vena cava
or right atrial area. The most common venipuncture sites include the subclavian, jugular,
femoral, cephalic, and basilic veins (Table 43.6). Several varieties of central venous cath-
eters are available, the most common being polyurethane and silicone (Table 43.7). Most
catheters are available in a variety of French sizes, lengths, and number of portals or
lumens. Multilumen versions provide for simultaneous infusion of TPN with multiple or
incompatible drugs.
Physiologic, functional, psychological, and social factors all need consideration prior to
determining the type and location of catheter placement (Table 43.8). If the patient is in
the acute care setting and unlikely to be discharged with TPN, the physiologic factors are
TABLE 43.6
Central Venous Catheter Placement24,25
Method Vessels Description
Percutaneous approach Subclavian a. Venipuncture and passage of a
a. Modified Seldinger technique Internal & external jugular guidewire through the needle
Antecubital followed by removal of the
needle and catheter placement
over the guidewire
b. Peel-away introducer sheath b. Catheter passes through the
and tissue dilator introducer into the vein and
introducer tears longitudinally,
leaving the catheter in place
Cutdown Cephalic Surgical dissection, isolation of the
External & internal jugular vessel, and catheter placement
Tunneled 6 cm catheter segment is tunneled
through the subcutaneous tissues
between the venipuncture site
and the skin exit site
Implanted ports A reservoir with a silicone disk and
attached silicone tube is
implanted under the clavicle in a
subcutaneous pocket
TABLE 43.7
Central Venous Catheter Characteristics
Material Description
Silicone elastomer Known as Silastic (Dow Corning)
Biomaterial for longterm indwelling devices
Increased elasticity and flexibility for minimal damage to intima
Resistant to hydrolytic enzymes; hydrophobic surface resists bacterial adherence
Considered chemically inert in blood
Guide wire or peel-away introducer needed for insertion due to soft texture
Polyurethane Increased flexibility and strength; resistance to hydrolytic enzymes
Decreased incidence of inflammatory changes and thrombophlebitis with short
term use
Anticoagulation required with long term use for thrombosis prevention
Polyvinyl chloride Stiff material
Increased rate of thrombogenicity
Infrequently used
Polyethylene High tensile strength
Minimal irritation if used for short duration
Associated with platelet adherance and fibrous capsule formation with long
duration
Polytetrafluoroethylene Known as Teflon; stable; demonstrates nonadhesive, antifriction properties;
resistant to degradative enzymes
Smooth and hydrophobic catheter surface
Not suitable for long term use due to rigidity which causes irritation and thrombosis
formation
Hydrogel Hydrophilic polymers designed for biological use
Absorbs water up to 90% of the catheter’s dry weight without dissolving
Most inert and nonthrombogenic of biomaterials
Material lacks durability unless copolymerized with other monomers
Coated/bonded catheters Antimicrobial impregnated catheters: catherters with the cationic surfactant
tridodecylmethylammonium chloride facilitate bonding of anionic antibiotics to
both the internal and external catheter surfaces
Antiseptic-coated catheters: polyurethane catheters bonded with silver sulfadiazine
and chlorhexidine to the external surface
From Krzywda, E.A. and Edmiston, C.E. ASPEN Practice Manual, 1998. With permission.
TABLE 43.8
Patient Factors for Vascular Access Device Selection
Patient Factor Considerations
Physiologic Vein physiology
Hypercoagulable states
Diabetes
Clotting abnormalities
Skin disorders and conditions
Previous surgical procedures in the thorax or vascular system
Morbid obesity
Surgical risk
Known allergies to vascular materials
Functional Impaired vision, dexterity
Developmental disabilities
Frailty
Psychological Needle phobia (not ideal candidates for implanted ports)
Body image issues (implanted port less disturbing than tunneled)
Previous experience with vascular access devices
Social Support system for line and catheter care
Financial implications
From Evans, M. Nutr. Clin. Prac. 14: 172; 1999. With permission.
of primary concern. However, if a patient is to receive parenteral nutrition in an alternate

care setting, practitioners should consider the other listed factors for optimal patient
compliance.24
Parenteral Nutrient Components

Parenteral nutrient solutions are complex formulations that usually contain the macronu-
trients, carbohydrate, protein, and fat for energy provision, as well as electrolytes, trace
elements, vitamins, water, and occasionally medications. These components need to be
individualized for patients based upon their primary diagnosis, chronic diseases, fluid
and electrolyte balance, acid-base status, and specific nutrition goals.26
Carbohydrate
Carbohydrate serves as the primary energy source in parenteral solutions. The amount of
carbohydrate provided is based upon the patient’s individual nutrient requirements and
glucose oxidation rate. Although the exact requirement is individualized, guidelines are
available. A minimum of 100 gm per day is often used as the obligate need for the central
nervous system, white blood cells, red blood cells, and renal medulla.26 The maximum
rate of glucose oxidation in adults is 4 to 7 mg/kg/min,5 or 400 to 700 gm for a 70-kg
person, with the lower range suggested for critically ill patients secondary to endogenous
glucose production. Excessive carbohydrate provision is associated with hyperglycemia,
excessive carbon dioxide production, and hepatic steatosis.26
Carbohydrate is provided almost exclusively as dextrose monohydrate in parenteral
solutions. Each gram of hydrated dextrose provides 3.4 kcal/gram. Commercial dextrose
preparations are available in concentrations from 5 to 70% (Table 43.9). Dextrose solutions
have an acidic pH (3.5 to 5.5) and are stable after autoclave sterilization.26 Sterilization
TABLE 43.9
Intravenous Dextrose Solutions
Dextrose
Concentration Carbohydrate Calories Osmolarity
% (gm/L) (kcal/L) (mOsm/L)
5 50 170 250
10 100 340 500
20 200 680 1000
30 300 1020 1500
50 500 1700 2500
70 700 2380 3500
also increases the shelf life of dextrose solutions so that they can be stored for extended
periods at room temperature.
Glycerol is a simple organic compound consisting of the elements carbon, hydrogen,
and oxygen. Glycerol yields 4.3 kcal/gram when oxidized to carbon dioxide and water,
and does not require insulin for cellular uptake. When provided in low concentrations
(3%) with amino acids, it has been found to be protein sparing.27 Because of these advan-
tages, glycerol is used an alternative source of calories in some parenteral formulations,
primarily in PPN.
Fat
Since its introduction in Europe in the mid-1960s, intravenous fat emulsions have been
extensively used as a nutrient source in parenteral nutrition. The aqueous fat emulsions
available in the U.S. as of 1999 consist of long-chain triacylglycerols (TAG) manufactured
from soybean and safflower oil. Therefore, the lipid emulsions not only provide a source
of kcalories but also essential fatty acids. These products contain egg yolk phospholipid
as an emulsifying agent and glycerin, which make the products nearly isotonic. The
glycerol raises the caloric concentration of the 10% emulsion to 1.1 kcal/mL and the 20%
emulsion to 2.0 kcal/mL. The phospholipid may contribute to the phosphorus intake of
patients who receive large amounts of lipids (>500 mL/day). Combinations of long-chain
and medium-chain TAG emulsions have been available in Europe for several years.
Most patients tolerate daily infusion of lipids provided as an intermittent or continuous
infusion, often as part of a total nutrient admixture (TNA). Continuous delivery with a
moderate dose is favored over intermittent infusion due to decreased fluctuations in serum
TAG levels and improved fat oxidation.28 The requirement of a test dose is usually elim-
inated with continuous delivery, as the administration rate tends to be less than that with
the test dose. Patients should still be monitored for fever, chills, headache, and back pain
during the first dose of intravenous lipid. Absolute contraindications to intravenous fat
emulsions include pathologic hyperlipidemia, lipoid nephrosis, severe egg allergy, and
acute pancreatitis associated with severe hypertriglyceridemia.26 Caution should be taken
in delivery to patients with severe liver disease, adult respiratory distress syndrome, or
severe metabolic stress. If serum TAG levels are greater than 500 mg/dL, lipids should
be held with only the minimal requirements for essential fatty acids (EFA) provided to
avoid further metabolic complications.
Lipid requirements are met by providing at least 4% of energy as EFA or approximately
10% of energy as a commercial lipid emulsion from safflower oil1 to prevent EFA deficiency.
Since lipid emulsions vary in their composition of EFA depending on the oil source, the
minimum amount provided is based upon the EFA content rather than a percentage of
total energy. Recommendations for optimal lipid delivery have evolved over the years. It
once was common practice to provide 50 to 70% of energy as lipid due to its concentrated
energy source and decreased volume. However, over the years concerns that long-chain
triglycerides impair neutraphil function, endotoxin clearance, and complement synthesis
have resulted in the recommendation to limit lipid administration to 1 gm/kg per day29
or 25 to 30% of total energy.30
Protein
The primary function of protein in parenteral nutrition is to provide nitrogen to maintain
nitrogen balance to help minimize loss of lean body mass and protein degradation for
gluconeogenesis. The protein utilized for parenteral nutrition is primarily in the form of
crystalline amino acids. Parenteral amino acid products can be divided into standard and
modified. Standard amino acid products are suitable for the majority of patients. They
contain a balanced or physiologic mixture of essential and nonessential amino acids in
which the ratios are based on FAO/WHO recommendations for optimal proportions of
essential amino acids. Standard formulations are available in a range of concentrations
from 3 to 15%. Most institutions stock 10 and 15% concentrations, since more dilute
solutions can be made readily by adding sterile water with an automated compounder.
Modified amino acid solutions are designed for patients with disease- or age-specific
amino acid requirements. Formulations are marketed for adults with hepatic failure, renal
dysfunction, metabolic stress, and for neonates with special requirements for growth and
development. These modified formulations are significantly more costly than the standard
formulations and may not always prove as cost-effective; therefore, strict criteria should
be established for their use.
Patients with hepatic failure develop multiple metabolic abnormalities including elec-
trolyte disturbances and alterations in amino acid metabolism. In severe liver disease,
hepatic encephalopathy can occur which is associated with decreased branched chain
amino acid (BCAA) serum levels and elevated aromatic amino acid (AAA) and methionine
serum levels. Patients with hepatic disease without encephalopathy may be provided with
moderate levels of standard amino acids with close monitoring of their mental status.
When hepatic encephalopathy is severe (≥Grade II), a modified hepatic protein formulation
may be beneficial. These formulations have high concentrations of BCAA (~45% of protein)
and low concentrations of AAA and methionine. Improvement in hepatic encephalopathy
and lower mortality have been found in some patients who received this formulation.31
Modified formulations are marketed for patients with renal failure. These formulas
contain mainly essential amino acids, and were designed on the premise that endogenous
urea could be used to synthesize nonessential amino acids. This hypothesis has been
challenged, thus questioning the usefulness of these formulas. Prospective, randomized,
controlled studies have demonstrated that standard amino acids are as effective as mod-
ified amino acids in patients who have renal failure and who require parenteral nutri-
tion.32,33 Thus, patients with severe renal failure may be given standard amino acids as
part of parenteral nutrition in most clinical situations.24
A parenteral formulation with an enhanced BCAA formulation is marketed for patients
with metabolic stress such as that caused by trauma, burns, and sepsis. Metabolic stress
causes an efflux of amino acids from skeletal muscle and the gut to the liver for gluco-
neogenesis and support of acute phase protein synthesis.34 Metabolically stressed patients
have also been shown to have increased serum levels of AAA and decreased BCAA levels.
Therefore, the rationale of using a high BCAA formula in these patients is to provide the
preferential fuel to the body and normalize the patient’s amino acid patterns. Multiple
studies have evaluated the benefits of high BCAA formulations in metabolic stress. Some
studies have shown positive benefits when using these formulations, such as nitrogen
retention, improved visceral protein levels, and reversal of skin test anergy, but there were
no differences in morbidity or mortality.35-37 Other studies have failed to exhibit significant
outcome advantages of BCAAs over standard amino acid formulas in metabolic stress.38-40
Therefore, since the cost-effectiveness of high BCAA solutions has not been clearly dem-
onstrated, initiation of nutrition support with a standard amino acid solution is recom-
mended in patients with metabolic stress.5
Protein requirements are based upon the patient’s clinical condition. For normal healthy
adults the recommendation is for 0.8 gm/kg per day.41 In the critically ill population, a
range of 1.5 to 2.0 gm/kg/day is appropriate.5 For patients with renal or hepatic disease,
protein recommendations vary according to the disease stage and its intervention. For
those with renal disease on peritoneal dialysis, 1.2 to 1.5 gm/kg/day of ideal body weight
is recommended for maintenance or repletion. For hemodialysis, 1.1 to 1.4 gm/kg of ideal
body weight per day is recommended for maintenance or repletion.42 For patients with
uncomplicated hepatic dysfunction, 0.8 to 1.5 gm/kg dry weight is suggested; for end-
stage liver disease with encephalopathy, 0.5 to 0.7 gm/kg; if a high BCAA formula is used,
then 0.8 to 1.2 gm/kg/day is suggested.43
Electrolytes
Electrolytes are essential nutrients that perform many critical physiologic functions. Elec-
trolytes are added to parenteral solutions based upon individual need. The amount added
daily varies based upon the patient’s weight, disease state, renal and hepatic function,
nutrition status, pharmacotherapy, acid-base status, and overall electrolyte balance. Extra-
renal electrolyte losses may be a result of diarrhea, ostomy output, vomiting, fistulas, or
nasogastric suctioning. As patients become anabolic during parenteral nutrient delivery
they may experience increased requirements for the major intracellular electrolytes (potas-
sium, phosphorus, and magnesium). During refeeding of undernourished patients, these
electrolytes should be monitored frequently and replenished accordingly.
Small adjustments in electrolyte intake can affect patient morbidity and mortality and
therefore need careful monitoring. General recommendations for electrolyte provision are
provided in Table 43.10. Electrolyte products are commercially available (Table 43.11), and
the composition of the parenteral solution is dependent upon the compatibility of each
electrolyte with the other components of the admixture. For calcium provision, calcium
gluconate is the preferred form for parenteral formulations due to its stability in solution
and decreased chance of dissociating and forming a precipitate with phosphorus. Whether
to provide an electrolyte as a chloride or an acetate salt depends on the patient’s acid-
base status. Generally, acid-base balance is maintained with providing chloride and acetate
TABLE 43.10
Parenteral Electrolyte Recommendations
Sodium 60-150 mEq/d
Potassium 70-150 mEq/d
Phosphorus 20-30 mmol/d
Magnesium 15-20 mEq/d
Calcium 10-20 mmol
Chloride Equal to Na+ to prevent acid-base disturbances
From Skipper, A. In: Contemporary Nutrition Support Practice. W.B.
Saunders, Philadelphia, 1998, p. 227. With permission.
TABLE 43.11
Commercially Available Electrolyte Formulations25,26
Sodium chloride Magnesium sulfate
Sodium acetate Magnesium chloride
Sodium phosphate Calcium chloride
Sodium lactate Calcium gluconate
Potassium chloride
Potassium acetate
Potassium phosphate
Potassium lactate
in a 1:1 ratio. If a patient has altered acid-base status with skewed electrolyte levels, then
the chloride:acetate ratio can be adjusted to facilitate correction. Acetate and chloride are
also present in the base amino acid solutions in various amounts, and should be considered
when attempting electrolyte homeostasis.
Electrolytes increase the osmolarity of the parenteral solution; however, large amounts
can be added to solutions with amino acids and dextrose without affecting the stability.
When lipids are added to the parenteral solutions caution is needed when adding elec-
trolytes, as there are limitations and hazards.1 An insoluble precipitate can form when
there are excess cations in the parenteral solutions, as with calcium and phosphate, which
may not be visualized in total nutrient admixtures. Crystal formation in the lungs with
subsequent death was reported in patients as a result of precipitate formation in TPN
solutions.44 The solubility of calcium and phosphorus varies with the volume of the
solution, its pH, the type of calcium preparation, the temperature at which the solutions
are stored, and the order of admixture.1 Solutions can be prepared with a range of calcium
and phosphorus contents as long as the product of calcium (in mEq) and phosphorus (in
mmols) is less than 200.45
Vitamins and Trace Elements

Vitamins are typically added to every parenteral formulation in doses consistent with the
American Medical Association Nutrition Advisory Group’s recommendations.46 Guide-
lines are established for the 12 essential vitamins (Table 43.12). Most institutions use a
TABLE 43.12
AMA Recommendations for Parenteral Vitamin Intake
Vitamin Amount
Vitamin A 3,300 IU
Vitamin D 200 IU
Vitamin E 10 IU
Vitamin C (ascorbic acid) 100 mg
Folacin 400 µg
Niacin 40 mg
Riboflavin 3.6 mg
Thiamine 3 mg
Vitamin B6 (pyridoxine) 4 mg
Vitamin B12 (cyanocobalamin) 5 µg
Pantothenic acid 15 mg
Biotin 60 µg
Adapted from Multivitamin preparations for parenteral use.
A statement by the Nutrition Advisory Group. J Parenter En-
teral Nutr 3: 258, 1979.
TABLE 43.13
AMA Recommendations for Parenteral
Mineral Intake
Element Amount
Zinc 2.5-4 mg/day
Copper 0.5-1.5 mg/day
Manganese 150-180 µg/day
Chromium 10-15 µg/day
Selenium* 40-80 µg/day
* Suggested intake.
Adapted from Guidelines for essential trace
element preparations for parenteral use: A
statement by the Nutrition Advisory Group.
J Parenter Enteral Nutr 3: 263, 1979.
commercially available multiple-entity product which contains 12 essential vitamins for

adults. The multivitamin preparations for adults do not contain vitamin K because it
antagonizes the effects of warfarin in patients receiving this medication. In adults, vitamin
K may be administered by adding 1 to 2 mg/day to the parenteral solution or by giving
5 to 10 mg/week intramuscularly or subcutaneously.26 Individual vitamin preparations
are also available and are used to supplement the multivitamin doses when a deficiency
state exists, or with increased needs due to disease or medical condition.
Trace minerals are essential to normal metabolism and growth, and serve as metabolic
cofactors essential for the proper functioning of several enzyme systems. Although the
requirements are minute, deficiency states can develop rapidly secondary to increased
metabolic demands or excessive losses. Most clinicians add these micronutrients daily;
however, there are clinical conditions necessitating trace mineral restriction and therefore
adjustments in the daily intakes.
The Nutrition Advisory Group of the American Medical Association has also published
guidelines for four trace elements known to be important in human nutrition.47 The
suggested amounts of zinc, copper, manganese, and chromium for adults are listed in
Table 43.13. Since the original recommendations, it has become more evident that selenium
also is essential, and many clinicians add this element to the parenteral solution daily
along with the other four.26 Most institutions use a commercially available multiple-entity
product, but there are also single-entity mineral solutions available for use during times
of increased requirements or when certain minerals are contraindicated. Zinc requirements
are increased during metabolic stress due to increased urinary losses, and with excessive
GI losses as with diarrhea and increased ostomy output. Manganese and copper are
excreted through the biliary tract, whereas zinc, chromium, and selenium are excreted via
the kidney. Therefore, copper and manganese should be restricted or withheld from
parenteral nutrition in patients with cholestatic liver disease.26 Selenium depletion has
been found in patients receiving long-term TPN, as well as with thermal injury, acquired
immunodeficiency syndrome, liver failure, and critical illness.26,47
Other Additives
Many patients receiving TPN are also receiving multiple medications, leading to the desire
to add the medications to the TPN solutions. Using TPN as a drug delivery vehicle is very
tempting, as it may allow for continuous medication infusion in addition to minimizing
fluid volume delivery by eliminating the need for a separate dilutent for each medication
TABLE 43.14
Medications Compatible with Parenteral Solutions
Albumina Cyanocobalamin Hydromorphone Nafcillin
Amikacin Cyclophosphamide Imipenem-cilastatin Neostigmine
Aminophyllinea Cytarabine Insulin, regulara Netilmicin
Azlocillin Digoxina Iron dextran Oxacillina
Caffeine Dipyridamole Isoproterenola Oxytocin
Carbenicillina,b Dobutamine Kanamycina Penicillin Ga
Cefamandolea Dopaminea Lidocainea Phenobarbital
Cefazolina Doxycycline Meperidinea Phytonadionea
Cefoperazone Erythromycina Metaraminol Piperacillin
Cefotaxime Famotidinea Methicillina Polymyxin B
Cefoxitina Fluorouracilb Methotrexate Ranitidinea,b
Ceftazidine Folic Acid Methyldopa Tetracycline
Ceftriazone Furosemidea Methylprednisolone Ticarcillina,b
Cephalothina,b Ganciclovir Metoclopramidea Tobramycina
Chloramphenicola Gentamicina Mezlocillin Vancomycin
Chlorpromazine Heparina Miconazole
Cimetidinea Hydralazine Morphine
Clindamycina Hydrochloric acid Moxalactam
a Compatible with total nutrient admixtures (TNA)
b Some data suggest incompatibility under certain conditions. Visual compatibility
only; tested with parenteral nutrition solution without electrolytes; drug may
chelate with divalent cations and cause precipitation.
From Strausburg, K. Parenteral nutrition admixture. ASPEN Practice Manual, 1998.
With permission.
administered. However, scrutiny is needed prior to adding medications to the TPN solu-
tion, as there is potential for drug-drug and drug-nutrient interactions. Issues needing
consideration include medication compatibility with TPN constituents, the effect of pH
changes on TPN compatibility and drug effectiveness, whether the infusion schedule of
the TPN is appropriate to achieve therapeutic levels of the drug, and the potential for
interactions among the drugs if more than one is added.1 The complexity of these issues
usually leads to consultation with a pharmacist experienced in TPN compounding and
compatibility, reference to the institution’s policy and procedure manual, or contact with
the drug manufacturers. Medications most frequently added to TPN include albumin,
aminophylline, cimetidine, famotidine, ranitidine, heparin, hydrochloric acid, and regular
insulin.1 Table 43.14 list medications compatible with TPN solutions, and Table 43.15 lists
those medications which are incompatible with TPN solutions.
Insulin
Even with care to avoid excess carbohydrate delivery, patients receiving TPN often become
hyperglycemic. One method of achieving desired blood glucose control with continuous
TPN infusions is by adding regular insulin to the TPN solution. A few studies have
suggested that absorbance of insulin to glass bottles, polyvinyl chloride bags, and tubing
occurs,49,50 with the greatest loss occurring during the first hour of infusion.51 So, when
adding insulin to TPN solutions to optimize blood glucose control, it is important to
remember that the patient may have an increased insulin requirement due to absorbance.
Histamine H2-Receptor Blockers

Stress ulcer prophylaxis with the addition of H2-receptor blockers to avoid stress ulcers
is common practice with patients on TPN who are not receiving any gastric nutrients.
TABLE 43.15
Medications Incompatible with Parenteral Solutions
Amphotericin B Methyldopaa
Amikacina Metronidazole (with NaHCO3)
Ampicillinb Phenytoina
Cephradine Tetracyclinea,c
Iron dextrana,d
a Incompatible with total nutrient admixtures (TNA)
b Some visual compatibility data suggest compatibility un-
der certain conditions
c Compatible with lipid alone; however, may chelate with
divalent cations of TNAs
d Visually incompatible with TNAs when reconstituted
with 5% dextrose in water; visually compatible when re-
constituted with normal saline solution
From Strausberg, K. Parenteral nutrition admixture. ASPEN
Practice Manual, 1998. With permission.
This may be achieved by adding the H2-receptor blockers to the TPN solution. Famotidine
(20 and 40 mg/L) and ranitidine hydrochloride have been shown to be stable in parenteral
nutrition solutions and three-in-one admixtures.52-56
Heparin
In order to reduce the complications of catheter occlusion related to fibrin formation
around the catheter tip, heparin may be added to the TPN solution. Adding up to 1000
units of heparin per liter reduces the incidence of catheter occlusion without exhibiting
anticoagulant effects on serum.1 Larger amounts of heparin may be used for peripheral
parenteral nutrition.
Methods of Administration
Serious complications with TPN may develop if careful initiation and monitoring are not
followed. TPN solutions may be infused continuously over a 24-hour period, or cycled
over shorter time intervals. If a patient is critically ill or just beginning to receive TPN, it
is suggested to infuse it over a 24-hour period until patient tolerance is demonstrated.
TPN should not be initiated at goal levels of nutrients, as many patients may not tolerate
this prescription. Proportional increases in carbohydrate-dependent electrolytes such as
magnesium and phosphorus, in protein-dependent electrolytes such as potassium, and
in volume-dependent electrolytes such as sodium should be made as the macronutrients
are increased.
For patients with diabetes mellitus, stress hyperglycemia, steroids, or risk for refeeding
syndrome, dextrose should be restricted initially to approximately 100 to 150 gm/day. For
other patients with normal glucose tolerance, dextrose may be initiated at 200 to 250 gm/
day. If after 24 hours serum glucose levels are acceptable, then the dextrose may be
advanced to goal over the next 24 to 48 hours as indicated. Capillary glucose measurements
should be obtained three to four times daily until the values are normal for two consec-
tutive days. Regular insulin may be administered according to a sliding scale.1 A contin-
uous intravenous insulin infusion may be substituted for sliding scale if serum glucose
levels are consistently elevated beyond suggested levels. Insulin may also be added to the
TPN solution; however, one needs to remember that providing insulin in this manner
confines the delivery over the time period of the TPN mixture, and if the hyperglycemia
resolves then the TPN bag must be discontinued to avoid inadvertent hypoglycemia. For
patients requiring insulin prior to TPN institution, approximately half of the established
insulin requirement may be included as regular insulin in the initial bag of TPN formula.1
If blood glucose levels are less than 200 mg/dL, approximately two-thirds of the previous
day’s subcutaneous insulin dose may be added to the TPN as regular insulin. Regardless
of the method of insulin delivery, the goal is to consistently maintain blood glucose levels
between 120 and 200 mg/dl.5
Lipids may be infused for up to 24 hours, and may reduce the effect of lipids on the
reticuloendothelial system.29 Lipids can be given with the first TPN infusion unless serum
triacylglycerol levels are elevated. It is suggested to maintain triacylglycerol levels at
≤400 mg/dL while lipids are being infused.1 If triacylglycerol levels exceed the recom-
mended level, lipids should be held until levels normalize. As this occurs, patients may
be provided with lipids in amounts to prevent essential fatty acid deficiency. For persistent
or severe hypertriacylglycerolemia or for patients with egg allergy, oral or topical safflower
oil can be administered to alleviate the symptoms of essential fatty acid deficiency.58
Critically ill patients may also be receiving significant amounts of lipid from lipid-based
medications, which may predispose them to hypertriacylglycerolemia prior to TPN infu-
sion. The amount of lipid from medications should be considered in the final TPN for-
mulation to avoid providing excess long-chain triacylglycerol.
Although parenteral nutrition is usually provided over a 24-hour continuous rate, it
may also be delivered in a cyclic pattern. Cyclic TPN has been suggested for patients who
are stable and receiving TPN for an extended duration. During TPN, circulating insulin
levels remain elevated, reducing the amount of carbohydrate that enters the cell, thus
favoring hepatic lipogenesis.1 Cyclic TPN also allows for some time off of the TPN pump,
allowing for patient mobility, and therefore it is usually utilized with ambulatory patients.
For individuals with limited vascular access, cyclic infusion may be required in order to
administer necessary medications or blood products. Conversion from 24-hour continuous
infusion to cyclic infusion can be accomplished in two to three days. The largest concern
is with the initiation and discontinuation of the carbohydrate infusion and potential for
hyperglycemia and rebound hypoglycemia. Another concern is with the increased volume
delivery over a shorter time frame. Most stable patients can tolerate cyclic TPN over 8 to
14 hours.
Parenteral Nutrition Discontinuation

Eventually in all patients, the goal is to transition from TPN to enteral nutrition — either
tube feeding or oral intake. Prior to discontinuing TPN, assurance that the patient is
consuming and absorbing adequate nutrients enterally is imperative. This is usually
assessed by diet histories and kcalorie counts. TPN should be decreased as the enteral
intake and tolerance improves to avoid overfeeding. TPN may be discontinued once the
patient is tolerating approximately 65 to 75% of goal nutrients. For patients who are eating,
TPN may be reduced and stopped over a 24- to 48-hour period. If TPN is inadvertently
but abruptly discontinued in patients who are not eating, all insulin should be stopped
and blood glucose levels should be monitored for 30 minutes after discontinuation of
TPN. Based upon the blood glucose levels, appropriate therapy should be implemented.1
Lastly, if the TPN was used as a vehicle for medication or electrolyte administration, an
alternate plan should be made once it is discontinued. Attempting to switch medications
to the enteral route is usually employed. Consultation with a pharmacist can help facilitate
this transition.
Complications of Parenteral Nutrition

Complications of parenteral nutrition have been widely reported. However, TPN can be
safe with minimal complications when it is managed and monitored by a multidisciplinary
team of trained professionals. The type of complications that may arise are diverse and
include mechanical, infectious, and metabolic.
Mechanical complications of catheter insertion (Table 43.16) include pneumothorax,
hydrothorax, and great vessel injury. The catheter malposition may result in venous
thrombosis, causing head, neck, or arm swelling, or possibly a pulmonary emobolus. To
minimize morbidity, obtaining a chest radiograph before using a new central line for TPN
TABLE 43.16
Mechanical Complications of Parenteral Nutrition
Complication Possible Cause Symptoms Treatment Prevention
Pneumothorax Catheter placement Tachycardia, Large Experienced
by inexperienced dyspnea, pneumothorax personnel to place
personnel persistent cough, may require chest catheter
diaphoresis tube placement
Catheter Pulling catheter Cardiac Surgical removal of Avoid withdrawing
embolization back through arrhythmias catheter tip catheter through
needle used for insertion needle
insertion
Air embolism Air is inspired Cyanosis, Immediately place Experienced
while line is tachypnea, patient on left side personnel to place
interrupted and hypotension, and lower head of catheter
uncapped churning heart bed to keep air in
murmur apex of the right
ventricle until it is
reabsorbed
Venous thrombosis Mechanical trauma Swelling or pain in Anticoagulation Silicone catheter,
to vein, one or both arms therapy with adding heparin to
hypotension, or shoulders or urokinase or TPN, low dose
hyperosmolar neck streptokinase; warfarin therapy
solution, hyper- catheter removal
coagulopathy,
sepsis
Catheter occlusion Hypotension, Increasing need for Anticoagulation Larger diameter
failure to maintain greater pressure to therapy with catheter, routine
line patency, maintain urokinase or catheter flushing,
formation of fibrin continuous streptokinase monitor solution
sheath outside the infusion rate for a precipitate
catheter, solution
precipitates
Phlebitis Peripheral Redness, swelling, Change peripheral Maintain
administration of pain at peripheral line site, begin osmolarity of
hypertonic site central TPN if peripheral
solution necessary solution ≤ 900
mOsm/kg
Catheter-related Inappropriate Unexplained fever, Remove catheter Follow strict
sepsis technique of line chills, red, and replace at protocols for line
placement, poor indurated area another site placement and
catheter care, around catheter care
contaminated site
solution
From Skipper, A. In: Contemporary Nutrition Support Practice. W.B. Saunders, Philadelphia, 1998: p. 227. With
permission.
is important to ensure correct line placement and absence of internal injuries that may
have occurred during insertion.
Catheter-related infections can carry a high mortality rate and increased medical costs
for a single event. A catheter infection rate of less than 3% is desirable.5 Appropriate use
of aseptic technique by trained personnel is essential to maintain an acceptable catheter
infection rate. Nursing protocols should be established for dressing changes and line
manipulation. Dressings should be changed every 48 hours and should include local
sterilizing ointment and an occlusive dressing. Since gram-positive catheter-related sepsis
may be treated with antibiotics, removal of the catheter is not always necessary. Catheter
removal is usually necessary with gram-negative organisms.
With close monitoring of TPN, avoidance of metabolic complications (Table 43.17) is
possible. Refeeding syndrome may be defined as a constellation of fluid, micronutrient,
electrolyte, and vitamin imbalances that occur within the first few days after refeeding a
starved patient. Refeeding syndrome may involve hemolytic anemia, respiratory distress,
paresthesias, tetany, and cardiac arrythmias.59 Typical biochemical findings include
hypokalemia, hypophosphatemia, and hypomagnesemia. Proposed risk factors for refeed-
ing include alcoholism, anorexia nervosa, marasmus, rapid refeeding, and excessive dex-
trose infusion. In order to prevent the syndrome from occurring it is suggested to replete
serum potassium, phosphorus, and magnesium concentrations prior to beginning TPN;
limit initial carbohydrate to 150 gm/day, fluid to 800 mL, and sodium intake to no more
than 20 mEq/day in at-risk patients; include adequate amounts of potassium, magnesium,
phosphorus, and vitamins in the TPN solution; and increase carbohydrate-dependent
minerals in proportion to increases in carbohydrate when TPN is advanced.59
Hyperglycemia (nonfasting blood glucose >220 mg/dL) is a common metabolic com-
plication of TPN. Risk factors include metabolic stress, medications, obesity, diabetes, and
excess dextrose administration. Careful glucose monitoring, especially in the first few days
of TPN administration, can help guide advancement of dextrose to goal. Administration
of dextrose in amounts less than the maximum glucose oxidation rate (4 to 7 mg/kg/min)
and initiating dextrose in reduced amounts (100 to 150 gm/day) in at-risk patients may
help minimize the occurrence of hyperglycemia.5
Patients receiving TPN may also experience fluid and electrolyte abnormalities (Table
43.17). The etiology of the abnormalities may be related to several factors including the
patient’s medical condition and treatment, medications, or excessive or inadequate free
water provision. Fluid balance and electrolyte status should be monitored closely (Table
43.18), with corrections in abnormalities made accordingly.
Summary
Parenteral nutrition has been a major medical advancement over the past several decades.
Its institution has saved lives of many people who may have otherwise died of malnutrition.
The next several decades will most likely bring more advances in the technology and science
of parenteral nutrition. With careful selection, implementation, and monitoring, parenteral
nutrition is a medical vehicle for nutritional supplementation of numerous diseases.
TABLE 43.17
Metabolic Complications of Parenteral Nutrition
Complication Possible Cause Treatment
Hypovolemia Inadequate fluid provision, Increase fluid delivery
overdiuresis
Hypervolemia Excess fluid delivery, renal Fluid restriction, diruetics, dialysis
dysfunction, congestive heart
failure, hepatic failure
Hypokalemia Refeeding syndrome, inadequate Increase intravenous or parenteral
potassium provision, increased potassium
losses
Hyperkalemia Renal dysfuntion, too much Decrease potassium intake,
potassium provision, metabolic potassium binders, dialysis in
acidosis, potassium-sparing drugs extreme cases
Hyponatremia Excessive fluid provision, nephritis, Restrict fluid intake, increase sodium
adrenal insufficiency, dilutional intake as indicated clinically
states
Hypernatremia Inadequate free water provision, Decrease sodium intake, replete free
excessive sodium intake, excessive water deficit
water losses
Hypoglycemia Abrupt discontinuation of parenteral Dextrose delivery
nutrition, insulin overdose
Hyperglycemia Rapid infusion of large dextrose load, Insulin, reduce dextrose delivery
sepsis, pancreatitis, steroids,
diabetes, elderly
Hypertriglyceridemia Inability to clear lipid provision, Decrease lipid volume provided,
sepsis, multisystem organ failure, increase infusion time, hold lipids
medications altering fat absorption, up to 14 days to normalize level
history of hyperlipidemia
Hypocalcemia Decrease vitamin D intake, Calcium supplementation
hypoparathyroidism, citrate binding
of calcium due to excessive blood
transfusion, hypoalbuminemia
Hypercalcemia Renal failure, tumor lysis syndrome, Isotonic saline, inorganic phosphate
bone cancer, excess vitamin D supplementation, corticosteroids,
delivery, prolonged immobilization, mithramycin
stress hyperparathyroidism
Hypomagnesemia Refeeding syndrome, alcoholism, Magnesium supplementation
diruetic use, increased losses,
medications, diabetic ketoacidosis,
chemotherapy
Hypermagnesemia Excessive magnesium provision, Decrease magnesium provision
renal insufficiency
Hypophosphatemia Refeeding syndrome, alcoholism, Phosphate supplementation,
phophate-binding antacids, dextrose discontinue phosphate-binding
infusion, overfeeding, secondary antacids, avoid overfeeding, initiate
hyperparathyroidism, insulin dextrose delivery cautiously
therapy
Hyperphosphatemia Renal dysfunction, excessive Decrease phosphate delivery,
provision phosphate binders
Prerenal azotemia Dehydration, excessive protein Increase fluid intake, decrease protein
provision, inadequate nonprotein delivery, increase non-protein
calorie provision with mobilization calories
of own protein stores
Essential fatty acid deficiency Inadequate polyunsaturated long- Lipid administration
chain fatty acid provision
From Skipper, A. In: Contemporary Nutrition Support Practice. W.B. Saunders, Philadelphia, 1998: p. 227. With
permission.
TABLE 43.18
Suggested Monitoring of TPN
Parameter Baseline Level Acute Patients Stable Patients
Electrolytes, BUN, Cr Yes Daily 1-2 × week
Chemistry Panel Yes Daily until stable, then 2- Weekly
Ca2+, PO4–, Mg2+ 3 × week
LFTs Yes 2 × week Weekly-monthly
Triacylglycerol Yes Weekly unless abnormal Weekly-monthly
then 2 × week
Capillary glucose 2-3 × day 3 × day until consistently 2 × day until consistently
< 200 mg/dl < 200 mg/dl
Intake and output Yes Daily Daily or by physical exam
Weight If available Daily Monthly
CBC with differential Yes Weekly Weekly
PT, PTT Yes Weekly Weekly
BUN: blood urea nitrogen; PT: prothrombin time;
PTT: partial thromboplastin time; CBC: complete blood count;
LFT: liver function test; Cr: creatinine
References
1. Skipper A In: Contemporary Nutrition Support Practice. WB Saunders, Philadelphia, 1998: p. 227.
2. Rhoads JE, Dudrick SJ. In: Clinical Nutrition: Parenteral Nutrition. WB Saunders, Philadelphia,
1993, p. 1.
3. Meyer CE, Fancher JA, Schurr PE, Webster HD. Metabolism 6: 591; 1957.
4. Wilmore DW, Dudrick SJ. JAMA 203: 860; 1968.
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6. American College of Physicians. Ann Intern Med 107: 252; 1987.
7. Sitzman JV, Pitt HA. Dig Dis Sci 34: 489; 1989.
8. Pillar B, Perry S. Nutrition 6: 314; 1990.
9. Levine GN, Derin JJ, Steiger E, Zinno R. Gastroenterology 67: 975; 1974.
10. Deitch EA. Arch Surg 124: 699; 1989.
11. Kotani J, Usami M, Nomura H, et al. Arch Surg 134: 287; 1999.
12. Li J, Kudsk D, Gocinski B, et al. J Trauma 39: 44; 1995.
13. King BK, Li J, Kudsk KA. Arch Surg 132:1303; 1997.
14. DaZhong X, Lu Q, Deitch E. J Parent Enteral Nutr 22: 37; 1998.
15. King B, Kudsk K, Li J, et al. Ann Surg 229: 272; 1999.
16. Lipman T. J Parent Enteral Nutr 22: 167; 1998.
17. Heyland D, MacDonald S, Keefe L, Drover J. JAMA 280: 2013; 1998.
18. Vernet O, Christin L, Schultz Y, et al. Am J Physiol 250: E47; 1986.
19. Moore FA, Feliciano DV, Andrassy RJ, et al. Ann Surg 216: 172; 1992.
20. Tappy L, Schwarz J, Schneiter P, Cayeux C, et al. Crit Care Med 26: 860; 1998.
21. Moore FA, Moore EE, Jones TN, et al. J Trauma 29: 916; 1989.
22. Kudsk K, Croce M, Fabian T, et al. Ann Surg 215: 503; 1992.
23. Trice S, Melnik G, Page C. Nutr Clin Prac 12: 114; 1997.
24. Evans M. Nutr Clin Prac 14: 172; 1999.
25. Krzywda EA, Edmiston CE. ASPEN Practice Manual, 1998.
26. Dickerson R, Brown R, Whithe, K. In: Clinical Nutrition: Parenteral Nutrition. WB Saunders,
Philadelphia, 1993: p. 310.
27. Freeman JB, Fairfull-Smith R, Rodman G, et al. Surgery 156: 625; 1983.
28. Abbott WC, Grakauskas AM, Bistrian BR, et al. Arch Surg 119: 1367; 1984.
29. Seidner DL, Mascioli EA, Istfan NW, et al. J Parent Enteral Nutr 13: 614; 1989.
30. Jensen GL, Mascioli EA, Deidner DL, et al. J Parent Enteral Nutr 14: 467; 1990.
31. Cerra FB, Cheung NK, Fischer JE, et al. J Parent Enteral Nutr 9: 288; 1985.
32. Mirtallo JM, Schneider PJ, Mavko K, et al. J Parent Enteral Nutr 6: 109; 1982.
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34. Chiolero R, Revelly J, Tappy L. Nutrition 13: 45S; 1997.
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40. von Meyenfeldt MF, Soeters PB, Vente JP, et al. Br J Surg 77: 924; 1990.
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Matarese L, Shronts E, Eds, ASPEN, Silver Spring, MD, 1993, pg 311.
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44
Sports — Elite Athletes
Michael F. Bergeron
Good nutrition is crucial in any athlete’s quest to reach peak performance. At all levels of
competition, whether for a local recreational league championship or in preparation for
the Olympics, athletes seem to be constantly searching for ways to improve their perfor-
mance and gain a competitive edge. This often includes trying the latest dietary fad or
nutritional supplements. However, dietary strategies for training and competition should
address the athlete’s need for nutrients as influenced by age, fitness, level of competition
and intensity of training, environment, time of competition, duration of play, amount of
time between competitions, and type of activity. Moreover, an effective diet for the athlete
also includes the same general dietary recommendations as for the non-athlete, and these
are intended to promote good health.
Although a healthy diet and body can clearly contribute to better performance, this
section will not focus on general nutrition guidelines to eating for good health; this is
comprehensively addressed in other sections. This section will review several basic nutri-
tion principles and other current nutrition issues as they relate to athletic performance.
The following recommendations are based on established results from research in adults
competing in certain sports or participating in exercise activities. While there has been
extensive research on nutrition and exercise performance in adults, such studies on chil-
dren and adolescents are lacking.
Much of the following information and guidelines related to preparing for competition,
competition, and recovery are also generally appropriate for training and practice sessions.
The unique metabolic demand characteristics and environmental circumstances associated
with the myriad activities classified as sports makes it nearly impossible to address all
athletes’ nutritional concerns for achieving peak performance. Individual preferences also
play a role. Therefore, this section focuses on selected general nutritional aspects that are
applicable for a variety of athletes, especially those who engage in long-duration, endur-
ance-based events.
A Balanced Diet
The primary dietary concern for all athletes should be to generally avoid the known
nutritional risk factors associated with health problems and to follow nutritional guide-
lines that will help promote good health. A diet that provides excess or deficient energy,
0-8493-2705-9/01/$0.00+$1.50
saturated fat, or alcohol or chronic vitamin and/or mineral deficiencies or excesses should
be avoided by anyone interested in good health or good athletic performance. A good
diet is one that supports normal growth and development, regulates metabolism, main-
tains normal menstrual status, and provides adequate energy during training and com-
petition. By following any of the various scientifically based food guides, such as the
United States Food Guide Pyramid,1 athletes, coaches, and parents can achieve appropriate
variety, proportions, and balance in their daily dietary planning such that an adequate
regular intake of all the essential nutrients is not left to chance.
Carbohydrates
Bread, cereal, rice, pasta, fruits, and vegetables are all good primary sources of carbohy-
drate that should be regularly included in any athlete’s diet. Sport drinks and sport bars
are also effective in helping to meet the athlete’s carbohydrate needs. It is generally
recommended that 55 to 70% of an athlete’s daily energy comes from carbohydrates.
However, this recommendation may not always be appropriate or practical, particularly
if the daily total energy requirement is very high. A better guideline for the athlete in
training or during competition would be to ingest at least 7 grams of carbohydrate per
kilogram of body weight each day, and up to 10 grams of carbohydrate per kilogram if
daily training or competition is intense and lasts for several hours or more.2,3 This is
equivalent to at least 490 grams (or 1960 kcalories) from carbohydrates for a 70-kg person,
and would represent roughly 65% of a 3000-calorie daily diet. This relative amount should
provide enough dietary carbohydrate to adequately replenish muscle and liver glycogen
each day under most circumstances.
Before they are absorbed into the blood, dietary carbohydrates are reduced by digestion
to single sugar units (the monosaccharides: glucose, fructose, and galactose). Glucose is
the body’s primary fuel for energy. Fructose (the very sweet sugar of fruit which is also
found in soft drinks and some sport drinks) and galactose (part of lactose or milk sugar)
are converted to glucose prior to use as an energy source. Foods that elicit a large and
rapid rise in blood glucose are categorized as having a high glycemic index.4 These foods
(Table 44.1) provide a rapid and readily utilizable energy source.5 Other carbohydrate-rich
foods provide glucose at a slower rate due to differences in rates of digestion, absorption,
and metabolism. Fructose, for example, is not actively absorbed by the intestine but is
absorbed via the less efficient facilitated diffusion. Consumption of large quantities of
fructose may slow down fluid absorption and cause a feeling of gastrointestinal distress,
particularly during exercise.6
Fats
The general recommendation for dietary fat intake is 20 to 30% of total daily energy intake.7
Further, saturated fats should account for less than 10% of each day’s energy supply. Not
only is fat needed for many biological functions, fat (as fatty acids) can be an effective
metabolic fuel for working trained muscle. Hence, fat provides considerable energy during
many sport activities.2,8,9 Fortunately, most athletes have enough body fat to support their
Sports — Elite Athletes 897
TABLE 44.1
Glycemic Index (Number in Parentheses) of a Variety of Foods. The index
was calculated using glucose as the reference. Average serving size is
used; data are from Foster-Powel, K., and Brand Miller, J., Am. J. Clin.
Nutr. 62: 871S; 1995.
High Medium Low
Glucose (100) Banana (53) Fructose(23)
Sucrose (65) Orange juice (57) Apple, raw (36)
Honey (73) Potato chips (54) Soy beans (18)
Bagel (white flour) (72) White rice (56) Lentils (29)
Ready-to-eat cereal (70-90) Spaghetti, white (41) Peach, raw (28)
Carrots (71) Bread, mixed grain (45) Ice Cream, rich (27)
Graham crackers (74) Skim milk (32)
Potatoes (83) Yogurt (33)
Raisins (64)
Jelly beans (80)
White bread (70)
Sport drinks, high glucose (70)
performance energy requirement for fat, and fat intake during or just prior to exercise is
not necessary or appropriate.
Some athletes regularly exceed the recommendations for daily fat intake. This may be
for convenience or preference, but, for those involved with extensive competition or
training that carries a recurring high energy demand, it is often a practical means to help
maintain body weight. This practice is fairly common10-13 among many athletes and has
been promoted as being beneficial.14 As long as the daily energy need is met the athlete
is not in chronic positive energy balance, then from a performance point of view, this
periodic use of a high-fat diet is appropriate. From a long-term health perspective, the
risks associated with such a diet with fit, very active athletes have not yet been studied.
Presumably, however, excessive fat intake might adversely affect certain diet-related risk
factors for coronary heart disease, even in a fit population.9,15,16
Protein
The need for extra protein in an athlete’s diet has been a topic of considerable debate. The
general recommendation for daily protein intake has been 0.8 grams of high quality protein
per kilogram of body weight (about 10 to 15% of daily energy intake ).7 However, a growing
body of research17-20 suggests that many athletes may need more protein than non-athletes.
During and immediately after strenuous exercise, there is an increase in protein break-
down. This is followed by an increase in protein synthesis during the recovery period.
This suggests that more dietary protein is needed to maintain body protein mass and/or
to support increases in muscle size and muscle energy-producing components. Current
thought17-20 for endurance athletes suggests an intake of 1.2 to 1.8 grams of protein per
kilogram of body weight per day. Given the strong endurance component and physiolog-
ical demands of many competitive sports, athletes involved in extensive regular training
and competition may require this much protein each day to maintain protein balance.
Body builders and power lifters, for example, could require up to 2.0 grams of protein
per kilogram of body weight each day. Such an increase in dietary protein is likely already
met by the typical diets that athletes usually consume. Unless an athlete is inappropriately
restricting energy, protein supplements are generally not needed — particularly not to the
extent that many resistance training athletes ingest regularly.20-22 There are instances such
as when traveling to competition events (especially abroad, where the foods available may
be unacceptable to the athlete) and when the travel/competition time is extensive, that
sufficient nutrient intake may be challenged or in question. Here, a protein-fortified drink
or an energy bar can be a convenient and effective food source to augment the athlete’s diet.
Carbohydrate and Fat: Primary Energy Sources

Many factors contribute to the energy expenditure of an athlete during competition or
during training. Modestly, 600 to 800 kcalories per hour would not be difficult for many
adults to achieve while engaging in sports such as basketball or tennis — and this could
readily be much higher with activities such as long distance running or marathon swim-
ming. In fact, large, well-trained athletes might expend up to 10,000 kcal in a single day
if the intensity and duration of activity is high.23
During continuous endurance activities and other long-duration sports, the metabolic
emphasis shifts to utilizing more carbohydrate and proportionately less fat, as the intensity
of exercise and overall energy expenditure increase.2,3 This is necessary because carbohy-
drate can supply energy for muscle contraction at a much faster rate than fat. However,
the intermittent nature of many sports reduces the duration of a continuous high demand
for energy within any specific muscle group during and between play. Consequently, even
during intense activities such as singles tennis or basketball, fat is used to supply consid-
erable energy throughout the course of the match or game.24
Importantly, using fat for energy still requires a continual simultaneous breakdown of
glucose. Therefore all athletes, regardless of the intensity of activity, will eventually feel
the effects of depleting glycogen stores if the event is long and carbohydrate is not
consumed during the activity. Carbohydrate sufficiency can be further challenged in hot
environments. As the temperature goes up, the rate of carbohydrate usage can also
increase;27 thus, fatigue can occur more rapidly without regular and adequate carbohy-
drate intake.
During the latter part of competition, protein could become a more significant contrib-
utor in meeting an athlete’s energy demands, especially if the pre-event and during-
competition dietary carbohydrate intake is inadequate.20,28 There are ways to reduce poten-
tial protein utilization for energy through ensuring sufficient carbohydrate intake and
availability. Protein breakdown produces amino acids that in turn are deaminated and
used for energy. This, however, puts an additional burden on the body, because the amino
group must be converted to urea and excreted.
Effects of Endurance Training on Carbohydrate, Fat,

and Protein Utilization
As previously noted, many competitive sports have a significant endurance component.
Regularly participating in these sports or other endurance-enhancing exercise or activities
(such as bicycling or running) will cause many specific changes in an athlete’s body that
will positively affect performance.29,30 A comprehensive discussion of these enhancements
is beyond the scope of this section. However, several adaptations relating to the use of
nutrients for energy during competition are worth noting.
As a result of regular endurance training and the associated increase in muscle mito-
chondrial number and activity, there will be an increase in the muscle enzymes that are
used for glucose oxidation as well as for glucose conversion to glycogen and for glyco-
genolysis.31,32 This, along with other changes that improve the delivery and use of oxygen
in the muscles (e.g. an increase in capillary density), permits a more efficient use of
carbohydrate for energy.2 With endurance training there is also an increase in fatty acid
uptake and oxidation by the muscle fibers, due to the training-induced increase in mito-
chondrial number and an induction of the enzymes involved in this process. These are
important considerations for an athlete who consequently might not have to rely on blood
glucose as much and deplete glycogen stores as readily as a lesser-trained individual —
again, fatigue could be delayed, even during high-intensity competition. At the same
time, these changes could indirectly defer an undesirable increased reliance on protein
for energy as carbohydrate stores are diminished.28 Some research34 shows that training
results in an enhanced ability and tendency to use protein for energy during exercise.
This could supplement the use of glucose and fatty acids as metabolic fuel, and potentially
delay fatigue.
Precompetition Nutrition
The nutritional state of the athlete before competition can have a significant impact on
performance.25,35 Many precompetition nutritional strategies are designed to ensure ade-
quate hydration. Appropriate fat, protein, mineral, and vitamin intake are also important,
but, because of the metabolic nature of most sports, the other primary precompetition
nutritional concern for athletes is adequate carbohydrate intake. How to ensure that
carbohydrate stores are maximized prior to competition is the focus of this section.
Ideally, before competition begins, an athlete’s carbohydrate stores (muscle and liver
glycogen) should be full. The emphasis on precompetition dietary carbohydrates ought
to begin at least by the previous evening. The evening meal is typically when the majority
of daily energy intake occurs. Moreover, a progressive increase over several days in
carbohydrate intake and a concomitant decrease in training duration and intensity just
before the start of an event can optimize an athlete’s glycogen stores prior to competition.2
The immediate precompetition meal is often more of a challenge. Here, the goal is to eat
a well-balanced meal with an emphasis on carbohydrate-rich foods and fluids. The recom-
mended energy intake depends, in part, on the competition schedule. In general, the meal
size should be moderate. By the time competition begins, the athlete’s stomach should be
relatively empty, but without feelings of hunger. Prior to competition (three to four hours)
a variety of nutritious, easily digestible, nondistress-causing (e.g., low fiber) solid foods
can be consumed.2,36 Based on a person’s body weight, a general guideline is to consume
approximately 4 to 5 grams of carbohydrate per kilogram of body weight with this meal.
This means that a 70-kilogram athlete could consume 280 to 350 grams of carbohydrate.
This meal should be low in fat and protein, since too much of either could reduce gastric
emptying time. Various fluids (e.g., water, juice, milk, and sport drinks) can be consumed
with the precompetition meal, so long as alcohol and excessive caffeine are avoided.
The precompetition meal depends on the time of the competition within the context of
the athlete’s usual meal pattern. Whatever meal or combination it is, the athlete should
not completely skip other regularly scheduled meals. For example, if a game, match, or
race is to begin in the early or middle afternoon, a good-sized early breakfast (emphasizing
carbohydrates) should be eaten, followed by a smaller precompetition lunch during the
late morning or midday. Alternatively, if the competition begins 3 to 4 hours after a
precompetition breakfast or lunch, the athlete should eat an additional small (1 to 1.5
grams of carbohydrate per kilogram of body weight), easily digestible carbohydrate snack
about 1 to 1.5 hours prior to the start of the event.2,36 A combination such as 500 ml of a
sport drink along with a sport bar or other solid carbohydrate food works well to “top
off” carbohydrate stores and body water.
A common problem encountered at some events arises when an early morning compe-
tition is scheduled — say, for 8 or 9 a.m. Athletes, parents, and coaches often wonder how
to manage breakfast. In this case, it’s usually best to have a smaller-than-usual breakfast,
again with an emphasis on carbohydrates and easily digestible foods, at least 90 minutes
before competition begins. Commercial high-carbohydrate, low-fat liquid meals work well
here, because they have less bulk and are easily digested and absorbed. Then, during
competition, it will be important to consume a carbohydrate-electrolyte drink throughout,
because the body’s stored carbohydrate levels will be initially somewhat lower at the
outset, and the supplemental carbohydrate will likely have a more readily prominent role
in providing energy and deferring hunger.25
Whether because of scheduling, preference, or precompetition anxiety, many athletes
simply do not consume enough energy before they compete. Inadequate precompetition
energy intake and perhaps partially depleted carbohydrate stores can result in premature
fatigue.36
Another common mistake is to neglect regular fluid and carbohydrate intake during
the precompetition warmup session. Such an oversight, especially if it is compounded by
a warmup that is too long and consists of excessive exercise, might increase the likelihood
that the athlete will begin competition unnecessarily fatigued, dehydrated, and carbohy-
drate-depleted. Thus, it is important that appropriate rates of fluid and carbohydrate
intake be followed during the precompetition warmup as well as during competition. If
carbohydrate is not consumed during the warmup period, a small carbohydrate snack
after warmup could be sufficient; its content and size depends on how much time is
available before competition begins.
Nutrition during Competition

Carbohydrate and fat are the primary energy sources used during sport participation and
training activities.2 Yet, because an athlete’s body fat supply is not going to run out in the
course of competition, carbohydrate and water are the only principal nutrients that need
to be consumed while competing (aside from multi-day or ultra-endurance events).2,25,37-
39 In some situations, salt intake during competition has a more significant role in main-
taining fluid balance, but generally it is not a major dietary concern for most athletes while
they compete.
Even if an athlete eats well prior to competition, after 60 to 90 minutes of intense
exercise, liver and muscle glycogen stores will likely be significantly decreased.2 Further,
the ability to maintain blood glucose and meet the muscles’ demand for energy may be
seriously challenged. Lack of carbohydrate can be prevented by periodically ingesting

carbohydrate during the activity.25 The amount of supplemental carbohydrate depends
on factors such as precompetition dietary status, body weight, environment, and intensity
of exercise or play. The body can generally utilize up to 60 grams per hour.36 This can be
provided by a liter of a carbohydrate-electrolyte drink.25 A number of commercial sport
drinks are designed to rapidly deliver carbohydrate and water to maximize performance.
Carbohydrate-electrolyte sport drinks can provide energy in the form of carbohydrate.
These have been shown to delay the onset of fatigue and perception of effort, increase
voluntary fluid intake, and provide electrolytes which help to maintain mineral and fluid
balance.2,25,36,39-42 Moreover, some carbohydrate-electrolyte drinks may be absorbed a little
faster than water. Any of these factors can be an important contributor to maintaining
performance, especially when competing in a hot environment. In fact, supplemental
energy intake may be more readily beneficial during competition in the heat, since
glycogen utilization tends to occur more rapidly as body temperature rises.27 Further-
more, the positive performance effects of carbohydrate and water ingestion during long-
term exercise are additive.43 In other words, appropriate carbohydrate and water con-
sumption (e.g., as a sport drink) during exercise is better than carbohydrate or water
consumption alone. Those sport drinks designed for consumption during exercise have
a carbohydrate concentration of 5 to 8%. Each liter contains 50 to 80 grams of carbohy-
drate. Research shows that higher carbohydrate concentrations (i.e., >10%) delay emp-
tying of the stomach, which in turn delays water and carbohydrate from getting into the
bloodstream.40,42
During the first hour or so of exercise, liver and muscle glycogen often support most
of the body’s demand for glucose.2 Thus, from a standpoint of providing energy, the
supplemental carbohydrate from a sport drink may not have much of an effect on
performance, especially if an athlete’s carbohydrate stores are fully replenished at the
start of competition. However, it may still be best to drink a carbohydrate-electrolyte
drink (perhaps at a diluted concentration at first) from the onset of exercise, even though
glycogen stores may not be low. This will help to maintain blood glucose levels and
may enhance fluid absorption.36,39 Moreover, ingesting carbohydrate throughout the
early stages of competition might have a sparing effect on some of the body’s carbohy-
drate stores.36
Often, athletes drink more than one liter during each hour of exercise in an attempt to
offset very high rates of fluid loss from sweating. Exclusive use of a sport drink (even if
the carbohydrate content is in the 5 to 8% range) in these situations might not be well
tolerated (and may be detrimental) because of the overall excessive amount of carbohy-
drate that would be ingested. As an alternative, many athletes drink a sport drink and
plain water during competition. This combination permits the desired amount of fluid
replenishment without taking in too much carbohydrate. At first, the emphasis can be on
water consumption. As the competition continues, the athlete can make a progressive
transition toward consuming more carbohydrate when he rehydrates.38 Similarly, eating
too large a snack (such as fruit or a sport bar) during competition, while regularly drinking
a sport drink at the same time, might also delay stomach emptying and fluid delivery,
again, because of the excessive carbohydrate intake. Ingesting a high amount of fructose
(liquid or solid) could also cause gastrointestinal distress, since fructose is absorbed more
slowly from the intestine compared to other carbohydrates in sport drinks, such as glucose,
sucrose, or glucose polymers.25 However, a small, easily digestible, high-glycemic index
snack (e.g., crackers, raisins, jelly beans, etc.) may provide additional needed energy late
in the activity.
Postexercise Nutrition
After exercise, an athlete’s primary nutritional interest should be the restoration of lost
fluid, electrolytes, and carbohydrate.36,37,39,44 How immediate and aggressive this effort
needs to be depends on how much carbohydrate was used (roughly suggested by how
intense and long the activity was), how much sweat was lost, and, most importantly, when
the next competitive activity will begin.
Sometimes, with sports such as tennis, an athlete must compete more than once on a
given day. If the next activity is scheduled to begin shortly after the completion of the
first (e.g., within 1 to 2 hours), rehydration and carbohydrate intake (about 50 to 100 grams
or 1 to 1.5 grams of carbohydrate per kilogram of body weight) should begin immediately
(i.e., within 15 minutes of the end of the match).2,36 High-carbohydrate sport drinks, along
with sport bars, gels, and other carbohydrate-rich foods with a high glycemic index (e.g.,
bagels, crackers, certain ready-to-eat cereals, white bread, and jelly beans), are good
choices. These will facilitate the rapid restoration of muscle glycogen more than high-
fructose foods or meals with an emphasis on low glycemic index carbohydrate sources
(e.g., flavored yogurt, apples, oranges, pasta, and mixed-grain bread).5 Notably, some
research45 suggests that a carbohydrate and protein combination might be better than just
carbohydrate for rapid glycogen resynthesis. If convenience is a priority, certain commer-
cial high-carbohydrate sport drinks and sport bars are available that could provide appro-
priate amounts of carbohydrate and protein for this purpose. Otherwise, various
combinations of breads, cereals, and dairy products, for example, can provide similar
ratios of carbohydrate and protein. During the next activity, regular consumption of
carbohydrate may be necessary at an earlier stage to maintain blood glucose, provide
energy, and defer hunger, since the short between-activity recovery period may not have
been long enough to adequately replenish liver and muscle carbohydrate stores.
When preparing for a second competitive activity that begins four to five hours or more
after the completion of the first, athletes should generally follow the precompetition meal
guidelines described earlier; however, many athletes would rather not eat a large meal
between same-day events, even if there is plenty of time. Thus, if smaller quantities of
food are preferred, 50 to 100 grams of carbohydrate, for example, ingested immediately
after exercise, and again every two hours, can be an effective method for replenishing (at
least partially) one’s carbohydrate stores. Having more time to accomplish this task means
that an athlete can choose from a wider variety of foods (low, medium, and high glycemic
index). However, it is generally a good idea to consume some rapidly absorbed carbohy-
drates and fluid (i.e., high glycemic index) right after exercise, so that glycogen and
hydration status will be more promptly and completely restored for the next activity.5,39
If an athlete is not scheduled to compete again until the next day or later, appropriate
regularly scheduled meals and snacks (according to the above guidelines) should provide
enough of the necessary nutrients to nutritionally recover from the previous exercise and
adequately prepare for the next competition.
Nutrition and Fatigue

From a nutritional standpoint, fatigue during sports and exercise occurs when there is an
inadequate supply of carbohydrate and/or a diminished ability to use all available sources
(i.e., carbohydrate, fat, and protein) to produce energy at a fast enough rate to meet the
body’s muscular demands. At this point, the fatigued athlete can no longer continue
competing at the desired level of intensity.
Following the initiation of exercise, an athlete’s blood glucose level tends to increase in
response to a variety of hormonal influences (i.e., cortisol and glucagon) designed to
mobilize carbohydrate. Without supplemental carbohydrate intake during the rest of the
exercise period, a continued high rate of glucose utilization in the muscles will eventually
lead to a much greater reliance on blood glucose for energy, which will, in turn, quickly
deplete liver glycogen stores. As exercise continues, blood glucose progressively
decreases.2,33,46 Pre-exercise carbohydrate status, of course, plays a role in how readily this
occurs. However, with high-intensity competition and repeated long bouts of muscle
activity combined with progressive dehydration, the active muscles’ use of energy will
be accelerated such that carbohydrate will be utilized at an even faster rate. Eventually,
carbohydrate availability will be diminished to the point that performance will be severely
hindered.36,38 This is why regular carbohydrate and fluid intake during difficult and long
sport and exercise activities is so important, especially in hot environmental conditions.
Moreover, if carbohydrate is not consumed during an extended bout of exercise, there
may be a significant increase in the conversion of protein to glucose in order to meet the
continued demand for energy. This could lead to a lower concentration of the branched-
chain amino acids (BCAA) in the blood, which could act as another contributory factor
in an athlete’s sense of fatigue (see Nutritional Ergogenic Aids in this section).47,48
Fluid Balance
When an athlete is involved with any vigorous physical exercise or sport activity, a
considerable amount of heat is produced, which will cause body temperature to rise. And
although athletes normally have several inherent means for dealing with this (e.g., con-
vection or radiated heat loss), sweating is typically the most effective and utilized method
for dissipating heat during exercise, especially in hot weather. However, long-term, exten-
sive sweating can pose a significant fluid balance challenge for athletes.49
If fluid balance and thermoregulation are not effectively managed during competition
and an athlete progressively dehydrates and becomes overheated, the athlete will fatigue
prematurely and possibly lose the race, game, or match. More severely, heat exhaustion,
heat cramps, or, at worst, heat stroke may ultimately ensue.50
In warm to hot conditions, most adult athletes will lose between 1 and 2.5 liters of sweat
during each hour of intense competition or training.37,39,51,52 Even more impressive, sweat
rates over 3.5 liters per hour have been observed with some well-conditioned, world-class
athletes competing in very hot and humid climates.53 During extended competition or
training sessions, it would therefore not be difficult for many athletes to lose 10 or more
liters of fluid.
The degree to which one sweats depends on a number of factors, including the envi-
ronmental heat stress (i.e., temperature, humidity, and solar radiation) and the intensity
of exercise — as an athlete works harder, sweating rate increases to offset the progressive
rise in core body temperature as a result of a higher metabolic rate.49,54 Acclimatization is
another factor. Athletes who have been training and playing in a hot climate for several
weeks or more (and thus, are acclimatized to the heat) may sweat more compared to those
who are not accustomed to such conditions. The same goes for cardiorespiratory fitness.
Such training can improve sweat gland function and increase plasma volume, which can
help to maintain a higher sweating rate.54 One must keep in mind that a higher sweating
rate is a good adaptation, because it gives an athlete a thermoregulatory advantage,
although, at the same time, more extensive sweating will be a greater challenge to offset
with fluid intake, especially during competition.
Sweat is mostly water, but it also contains a number of other elements found in the
blood, including a variety of minerals in varying concentrations. The major mineral ions
found in sweat are sodium (Na+) and chloride (Cl–), although the concentration varies
with a number of factors. For example, well-conditioned athletes who are fully acclima-
tized to the heat often have sweat sodium concentrations in the range of 5 to 30 mmol
per liter (i.e., 115 to 690 mg of sodium per liter of sweat), whereas heat non-acclimatized
athletes typically lose much more sodium through sweating (e.g., 40 to 100 mmol or 920
to 2300 mg per liter). Still, some athletes can have a relatively high concentration of sodium
in their sweat, no matter how fit or heat acclimatized they are, which again suggests a
strong genetic influence. Sweat sodium and chloride concentrations also vary with sweat-
ing rate. As sweating rate goes up, the concentration of these minerals in sweat usually
increases as well.55-57
Without adequate salt replacement, the cumulative effect of such electrolyte losses can
bring about a progressive sweat-induced sodium deficit after several days of playing or
training in the heat. This can readily lead to incomplete rehydration, poorer performance,
and heat-related muscle cramps,58 and possibly put an athlete at a higher risk for
developing heat exhaustion. In contrast, potassium (K+) and magnesium (Mg2+) sweat
losses, for example, are typically much lower.56 In fact, athletes will generally lose 3 to
10 times as much sodium as potassium during exercise. With regard to calcium and
trace minerals such as iron and zinc, their concentrations in sweat are also very low;
however, repeated extensive sweating can lead to a deficit of one or more of these
elements.59-61 Such deficits will not have a direct effect on fluid balance per se, but a
chronic dietary deficiency of any one of these nutrients (i.e., not enough consumed to
offset sweat and other excretory losses) can clearly have a negative impact on overall
health and performance.
Unfortunately, it is also a challenge, and often impossible, to keep up with extensive
sweating rates over the course of an entire race or match. Therefore, it is critical that
athletes prepare and manage as best they can by following a predetermined and compre-
hensive hydration plan before, during, and after competition.
Heat-related muscle cramps (heat cramps) often occur during prolonged exercise when
there have been previous extensive and repeated fluid and sodium losses. Such is often
the case in a tennis tournament, for example, especially by the time a player reaches a
later round. Drinking plenty of water helps, but to completely restore fluids, the salt lost
through sweating must be replenished as well.62,63 Importantly, any plan for increasing
dietary salt intake should be individually designed and include appropriate and adequate
fluid intake. For most people with normal blood pressure, however, a slightly excessive
salt intake will not likely pose a health threat.64
If sufficient carbohydrates and electrolytes are provided by food, then water alone can
serve as a primary or sole precompetition beverage. However, other fluids such as milk,
juice, and sport drinks can be used as well, and their consumption should be encouraged
as part of a well-balanced dietary plan. Alcohol and excessive tea, coffee, and other
caffeine-containing beverages should be avoided, as they can accelerate fluid loss.65,66 An
athlete should be able to urinate, and the urine should be fairly clear or light-colored. This
can be interpreted as a good indication of adequate precompetition hydration.67 As
previously stated, before competition begins an athlete’s carbohydrate (i.e., glycogen)
stores should be at or near capacity. Besides providing a readily available source of energy,
muscle glycogen also has a fair amount of water stored with it. Thus, by replenishing
carbohydrates (even partially), an athlete can improve hydration status as well.
Ideally, athletes should ingest, during competition, enough fluid, electrolytes, and
carbohydrate to fully support all circulatory, metabolic, and thermoregulatory require-
ments, and to offset all fluid losses so that normal body water status (i.e., euhydration)
is maintained. But even with relatively short periods of competition (e.g., less than 75
minutes), it is not unusual for some athletes to end up with a significant body water
deficit (i.e., a net loss near or greater than 2% of their precompetition body weight).51,56
In fact, because many athletes often begin competition or training dehydrated to some
degree,51,58 a post-exercise body water deficit may be even worse than is indicated solely
by one’s pre- and post-exercise body weight difference. Also, because thirst is not a
rapidly responding indicator of body water loss, there may not be a sufficient stimulus
to consume enough fluid in the exercise or post-exercise period.68 For some athletes, there
could be a fluid deficit of more than 1 liter before thirst is distinctly perceived. During
exercise, sweating rates can readily exceed 1.5 liters per hour. Few athletes can comfort-
ably consume this much fluid to replace such a loss. Moreover, it is likely that such a
high rate of fluid intake would readily exceed maximal gastric emptying and intestinal
absorption rates.39,42
After competition, athletes must rehydrate. Plain water alone will rehydrate an athlete
to a point, but it also readily prompts increased urine production and potentially a
premature elimination of the thirst drive.63 Excessive water intake for several hours or
more can lead to severe problems related to hyponatremia.69,70 Unless adequate sodium
and chloride are replaced, rehydration will remain incomplete. 62,63 Fluid ingestion after
prolonged exercise needs to be greater than the volume of fluid that was lost via sweating,
because during the rehydration process there is still an obligatory production of urine,
whether or not rehydration is complete. 62 Athletes should also keep in mind that alcohol
and caffeine can reduce the rate and amount of postexercise plasma volume restoration
and net fluid retention.62,71
Nutritional Ergogenic Aids

Advocates of today’s growing and seemingly endless selection of nutritional ergogenic
(work-enhancing) aids promote these products with promises such as enhanced energy,
increased strength, power, and lean body mass, more endurance, better performance, and
faster recovery. Because many athletes are constantly in search of anything that will
provide a competitive advantage, it’s understandable why such claims can be so tantaliz-
ing. But do the products work? Are the latest supplements just what some athletes need
to perform better? To date, very few nutritional ergogenic supplements have lived up to
their claims. More importantly, some have been found to actually impede optimal perfor-
mance. On the other hand, as a result of well-controlled experimental studies, certain
products have shown some promise as being effective ergogenic aids. Too often, however,
the purported benefits of new supplements are based on unsubstantiated claims or testi-
monials, poor research or research findings taken out of context, or simply misinformation.
Several currently popular and well-studied nutritional ergogenic aids are discussed here,
with particular mention of their appropriateness for most sports.
Creatine
Creatine monohydrate has become one of the most popular “performance-enhancing”
nutritional supplements in use today, and for good reason. Supportive preliminary evi-
dence associated with creatine supplementation includes increased one-repetition maxi-
mum performance (i.e., how much weight a person can lift one time, such as with a bench
press or squat) and peak power, as well as enhanced rowing performance and repetitive
sprint performance in experimental swimming, running, and cycling bouts of exercise. In
addition, many studies have demonstrated increases in body weight.72
Does such laboratory data mean that creatine supplementation will enhance perfor-
mance during sports? Will the same effects be shown with highly trained and conditioned
athletes as have been demonstrated with moderately trained or untrained individuals? Is
creatine supplementation appropriate for the physiological demands of many sports? Are
the observed weight gains actual gains in muscle or mostly fluid retention? And what
about the long-term effects and health risks associated with continued supplementation?
The answers to these questions are not known at this point.
Creatine is a natural compound made by the body from two amino acids, arginine and
glycine. It is also present in fish, meat, and other animal products. During very brief,
explosive-type exercise, the muscles’ capacity to adequately meet the high demand for
energy is largely dependent on the availability of phosphocreatine (PC), a high-energy
compound found in muscle. It has been thought that by increasing the amount of creatine
in the muscles, more PC will be readily available to provide energy at a faster rate during
very high-intensity exercise.
Reports of increased muscle creatine and PC levels, enhanced performance, and desir-
able changes in body composition have been inconsistent and remain somewhat equivocal.
Regarding potential gains in muscle protein, proven and more effective ways exist to gain
the necessary lean body mass required for most sports. And, importantly, the long-term
consequences and health risks associated with continued creatine supplementation have
not yet been comprehensively examined. Potential negative effects on the kidneys, heart,
liver, fluid balance, and thermoregulatory capacity, for example, should be carefully stud-
ied. Lastly, given the specific loading patterns and metabolic demands on individual
muscle groups during many types of sport activities, the muscle creatine and PC levels
are probably (without supplementation) already more than adequate in most well-condi-
tioned athletes. At present, creatine supplementation for most athletes does not appear to
be justified.
A recent consensus statement written for the American College of Sports Medicine on
oral creatine supplementation provides a comprehensive review of the current creatine
literature as well as a critical evaluation of its potential health effects and clinical appli-
cation.72
Medium-Chain Tryglycerides
To increase the availability and oxidation of fats during exercise in an attempt to spare
carbohydrate and improve performance, several dietary fat supplements have been sug-
gested for athletes.9 From this category, medium-chain tryglycerides (MCTs) are one of
the ergogenic aids used by athletes today because of the professed ability of MCTs to
enhance energy levels, fat metabolism, and endurance.73 Once ingested, MCTs leave the
stomach and are absorbed from the intestine in much the same way as are other triglyc-
erides.48 Thus far, MCTs or other fat-loading techniques have not been shown to affect the
rate of carbohydrate oxidation or improve performance. There have also been a number
of reports of gastrointestinal complaints and problems associated with MCT ingestion.48
Therefore, despite the need for fat in an athlete’s diet and the important role of fat in
providing energy during competition for many sports, fat loading prior to play or fat
supplementation during competition are not currently validated or recommended proce-
dures for most athletes.
Sodium Bicarbonate
During very high-intensity exercise, there is an increasing concentration of hydrogen ions
(H+) in the muscle cells as a result of a continuous rapid production of lactic acid. A high
level of H+ will rapidly lead to fatigue. Unless there is something to offset the growing
concentration of H+, there will soon be a decrease in muscle force output, a lower produc-
tion of energy, and a resultant decrease in performance, even in the presence of adequate
carbohydrate supplies. Fortunately, sodium bicarbonate, which is naturally present in the
body, buffers a portion of the H+ associated with the accumulating lactic acid during
anaerobic exercise. This helps to delay fatigue. Would augmented sodium bicarbonate
levels do a better job in delaying the onset of fatigue during high-intensity exercise by
helping to buffer more lactic acid? Probably. Will ingested bicarbonate enhance an athlete’s
overall performance during all sports? Probably not.74,75
The intermittent nature and overall moderate intensity of many sports precludes the
necessity for a great reliance on anaerobic carbohydrate metabolism during competition.
Consequently, lactic acid production is seldom very high.46 Thus, sodium bicarbonate
supplementation would not be very helpful for such activities, since these athletes do not
need to compensate for a large accumulation of H+. It likely rarely occurs. On the other
hand, certain sports that are characterized by high lactic acid production may be better
tolerated with an enhanced capacity to neutralize the accompanying decrease in pH within
the intracellular environment of the active muscles. Ingestion of buffering agents such as
sodium bicarbonate may provide a performance advantage during these activities.75
Branched-Chain Amino Acids

When carbohydrate is in short supply, there is a greater reliance on protein for energy.
This can lead to lower circulating levels of the branched-chain amino acids (BCAA); i.e.,
leucine, isoleucine, and valine. Moreover, during prolonged exercise, there is an increase
in the concentration of free fatty acids in the blood, which leads to higher levels of free
tryptophan (another amino acid). The resultant effect will be a higher free tryp-
tophan:BCAA ratio. This is thought to be an important factor in the development of
fatigue, especially during endurance activities. When free tryptophan enters the brain it
is converted to serotonin; high amounts of this neurotransmitter may be associated with
fatigue.48,76 Many athletes could conceivably be susceptible to fatigue related to lowered
BCAA levels and increased free tryptophan, particularly during lengthy competitions.47
Would BCAA supplementation help to alleviate this situation by maintaining higher levels
of BCAA in the blood? As one might expect, some researchers have shown improved
performance with BCAA supplementation, and others have demonstrated no change in
performance.48,76 Although BCAA might in theory be helpful in delaying the onset of
fatigue during long periods of exercise or competition, especially if carbohydrate stores
are significantly diminished, adequate carbohydrate intake prior to and during competi-
tion could achieve the same effect by reducing the amount of free fatty acids released and
minimizing any potential increase in the free tryptophan:BCAA ratio. Furthermore, BCAA
supplementation could lead to higher levels of ammonia in the blood, which would
accelerate fatigue.76

Vitamin and mineral supplements are widely used by athletes, often in great excess, not
only to maintain health, but also with the hope that performance will be enhanced as
well.77 Likewise, selected mineral supplementation such as increased chromium, vana-
dium, and boron intake has been purported to increase muscle mass, despite a lack of
research evidence.21
B-complex vitamin supplements are particularly popular, likely because of their impor-
tant role as coenzymes in helping carbohydrate and fat to be used for energy. Logically,
it seems that B-complex supplementation would be, in theory, helpful in enhancing the
utilization of these nutrients during many sports and exercise activities. However, despite
the essential role of these and other vitamins in a variety of physiological processes,
including energy metabolism, unless an athlete has a vitamin deficiency, vitamin supple-
mentation will not enhance athletic performance. In fact, excessive intake of the fat-soluble
vitamins (A, D, E, and K) can have a toxic effect. Although extra water-soluble vitamin
(B-complex and C) intake will mostly end up being excreted in urine, excessive intake of
these vitamins can have toxic effects as well. Additional vitamin C and E intake, however,
might be worth considering. Both of these vitamins have been shown to have beneficial
antioxidant and other health-related properties. Moreover, there is evidence that athletes
may need more vitamin C compared to those who do not exercise regularly, and additional
vitamin E intake may reduce exercise-related muscle tissue damage.77
Minerals are necessary for growth, metabolism, and a variety of other physiological
processes. Like vitamins, an athlete’s mineral requirements generally can be easily met by
a well-balanced diet, although certain minerals may need special attention with some
people. These typically include calcium and iron, and sometimes zinc. In addition, exces-
sive and repeated sweating may cause a progressive sodium deficit.55-58 Calcium and iron
deficits can be encouraged by inadequate energy intake (which often includes low intake
of protein and dairy products), other dietary influences, and excessive sweating. In
women, menstrual bleeding can further challenge iron status. But, unless an athlete is
restricting energy intake, mineral status is usually not a problem. As a guide, all athletes
should regularly eat foods rich in calcium and iron (e.g., meat, chicken, fish, milk, yogurt,
dark, leafy green vegetables, whole-grain breads and fortified cereals, etc.); this will likely
ensure adequate intake of these and most other minerals. Importantly, arbitrary excessive
mineral supplementation can also have deleterious effects on health and can interfere with
the absorption of other minerals.77
For many athletes, it is sometimes a challenge to maintain a well-balanced diet, especially

when traveling and competing.78 Therefore, to prevent a potential vitamin or mineral
deficiency, it is safe and probably prudent to regularly take a one-a-day multi-vitamin/
mineral supplement that provides no more than 100% of the Recommended Dietary
Allowance (RDA)7 for any one vitamin or mineral. Slightly higher amounts of vitamins
C and E can be supplemented, although it is probably better to obtain these through careful
food selection (e.g., fruits, vegetables, legumes).
Summary
Proper nutrition is important in any athlete’s quest to reach peak performance. When
integrated with proper training and adequate rest, a well-balanced diet, coupled with a
dietary strategy that optimizes hydration status and fuel availability in the pre-competi-
tion, and recovery periods will greatly enhance an athlete’s opportunity to be a regular
winner anywhere he or she competes. Table 44.2 summarizes the key performance-related
competition points for the elite athlete.
TABLE 44.2
Nutrition-Related Problems and Recommendations for the Elite Athlete
Water
Many athletes begin play or training dehydrated to some degree.

During training or competition, sweat losses can be extensive — 1-2.5 liters per hour or more!
Any water deficit can have a negative effect on an athlete’s performance and wellbeing. A progressive water
deficit (from sweating and inadequate fluid intake) can cause:
Increased cardiovascular strain
Decreased temperature regulation capacity
Decreased strength, endurance, and mental capacity
Many athletes do not rehydrate adequately after training or competition.
Recommendations
Drink plenty of fluids (e.g., water, juice, milk, sport drinks) throughout the day.
Drink regularly during training and competition — typically, older adolescents and adults can comfortably
consume up to 48 ounces (~1.4 liters) per hour.
After training or competition, drink about 150% of any remaining fluid deficit.
Electrolytes
Athletes lose far more sodium and chloride (salt) from sweating than any other electrolyte.
Sodium and chloride losses are greater with higher sweating rates.
Sodium and chloride losses (via sweating) tend to be less when an athlete is acclimatized to the heat.
Sodium deficits can lead to incomplete rehydration and muscle cramps.
To completely rehydrate, an athlete must replace the sodium and chloride that was lost through sweating.
Excessive rapid water consumption, combined with a large sweat-induced sodium deficit, can lead to
hyponatremia.
Recommendations
When an athlete competes or trains in a hot environment, adding salt to the diet (or eating high-salt foods) can
help to prevent a sodium deficit and maintain/restore hydration. Good sodium and chloride sources include:
Salt: 1/4 teaspoon (or 1.5 grams) has 590 mg of sodium
Salted pretzels

Nutrition-Related Problems and Recommendations for the Elite Athlete
Tomato juice
Salted sport drinks (or Pedialyte)
Soup, cheese, tomato sauce, pizza, and many processed foods
Carbohydrates
Adequate carbohydrate intake is crucial to optimal performance in most sports.

Carbohydrate utilization is greater as intensity of exercise increases and when an athlete competes or trains in
the heat.
Even if an athlete eats well prior to competition, after 60 to 90 minutes of intense exercise, glycogen stores will
likely be significantly decreased and the ability to maintain blood glucose and meet the muscles’ demand for
energy may be seriously challenged, which could lead to fatigue.
Recommendations
Generally, 7 to 10 grams of carbohydrate per kilogram of body weight (~500 to 700 grams per day for a 155 lb
athlete) is appropriate for periods of intense training or competition.
Athletes should consume about 30 to 60 grams of carbohydrate per hour during training and competition.
Foods and sport drinks with a high glycemic index can be particularly effective for providing rapid carbohydrate
energy or restoration during and after competition or training.
Lastly, all athletes differ in what foods and which nutritional strategies they can tolerate and that will enhance
their performance. New foods, drinks, or other dietary protocols should be experimented with well prior to
any important event.
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25. Hargreaves M. Sport Science Exchange (Gatorade Sport Science Institute), 12, 1999.
26. Maughan RJ, Greenhaff PL, Leiper JB, et al. J Sports Sci 15: 265; 1997.
27. Hargreaves M, Angus D, Howlett K, et al. Med Sci Sports Exerc 28: 58S; 1996.
28. Tarnopolsky M. In Perspectives in Exercise Science and Sports Medicine Volume 12: The Metabolic
Basis of Performance in Exercise and Sport. Lamb DR, Murray R, Eds, Cooper, Carmel, IN, 1999,
ch. 4.
29. Bassett, Jr, DR, Howley ET. Med Sci Sports Exerc 32: 70; 2000.
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IN, 1999, ch. 1.
31. Holloszy JO. Exerc Sport Sci Rev 1: 45; 1973.
32. Holloszy JO, Coyle EF. J Appl Physiol 56: 831; 1984.
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IN, 1999, ch. 5.
34. Henriksson J. J Experimental Biol 160: 149; 1991.
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37. American College of Sports Medicine, Position stand on exercise and fluid replacement, Med
Sci Sports Exerc 28: i-vii; 1996.
38. Dennis SC, Noakes TD, Hawley JA. J Sports Sci 15: 305; 1997.
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Performance. Lamb DR, Murray R, Eds, Cooper, Carmel, IN, 1997, ch. 4.
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49. Sawka MN. Med Sci Sports Exerc 24: 657; 1992.
50. Armstrong LE, Maresh CM. Med Exerc Nutr Health 2: 125; 1993.
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52. Sawka MN, Pandolf KB. In Perspectives in Exercise Science and Sports Medicine Volume 3: Fluid
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Thermoregulation. Gisolfi CV, Lamb DR, Nadel ER, Eds, Benchmark, Carmel, IN, 1993, ch. 2.
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C, Stanish WD, Micheli LJ, Eds, Oxford University Press, Oxford, UK, 1998.
57. Wenger CB. In Human Performance Physiology and Environmental Medicine at Terrestrial Extremes.
Pandolf KB, Sawka MN, Gonzalez RR, Eds, Benchmark, Indianapolis, 1988, ch. 4.
58. Bergeron MF. Int J Sport Nutr 6: 62; 1996.

59. Bergeron MF, Volpe SL, Gelinas Y. Clin. Chem 44(Suppl.): A167; 1998.
60. Clarkson PM, Haymes EM. Med Sci Sports Exerc 27: 831; 1995.
61. Tipton K, Green NR, Haymes EM, Waller M. Int J Sport Nutr 3: 261; 1993.
62. Maughan RJ, Leiper JB, Shirreffs SM. Br J Sports Med 31: 175; 1997.
63. Nose H, Mack GW, Shi X, Nadel ER. J Appl Physiol 65: 325; 1988.
64. Taubes G. Science 281: 898; 1998.
65. Wilcox AR. In: Sport Science Exchange (Gatorade Sport Science Institute), 3; 1990.
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68. Greenleaf JE. Med Sci Sports Exerc 24: 645; 1992.
69. Speedy DB, Noakes TD, Rogers IR, et al. Med Sci Sports Exerc 31: 809; 1999.
70. Vrijens DM, Rehrer NJ. J Appl Physiol 86: 1847; 1999.
71. Wemple RD, Lamb DR, McKeever KH. Int J Sports Med 18: 40; 1997.
72. The American College of Sports Medicine Roundtable on the physiological and health effects
of oral creatine supplementation, Med Sci Sports Exerc 32: 706; 2000.
73. Lambert EV, Hawley JA, Goedecke J, et al. J Sports Sci 15: 315; 1997.
74. Heigenhauser GJF, Jones NL. In Perspectives in Exercise Science and Sports Medicine Volume 4:
Ergogenics — Enhancement of Performance in Exercise and Sport. Lamb DR, Williams MH, Eds,
Brown & Benchmark, Carmel, IN, 1991, ch. 5.
75. Horswill CA. Int J Sport Nutr 5: 111S; 1995.
76. Davis JM. Int J Sport Nutr 5: 29S; 1995.
77. Lukaski HC. In: Perspectives in Exercise Science and Sports Medicine Volume 12: The Metabolic
Basis of Performance in Exercise and Sport. Lamb, DR, Murray R, Eds, Cooper, Carmel, IN, 1999,
ch. 7.
78. Nelson Steen S. Sport Science Exchange (Gatorade Sport Science Institute), 11; 1998.
Part VII
Clinical Nutrition
45
Alcohol: Its Metabolism and Interaction with
Nutrients
Charles S. Lieber
Respective Role of Alcohol and Nutrition in Organ Damage of the

Alcoholic
Ethanol is not only a psychoactive drug. Besides its pharmacologic action, it has a con-
siderable energy value (7.1 kcal/g). Therefore, substantial use of alcohol has profound
effects on nutritional status.1 Such consumption may cause primary malnutrition by dis-
placing other nutrients in the diet because of the high energy content of the alcoholic
beverages (Figure 45.1) or because of associated socioeconomic and medical disorders.
Secondary malnutrition may result from either maldigestion or malabsorption of nutrients
caused by gastrointestinal complications associated with alcoholism, involving especially
the pancreas and the small intestine. These effects include malabsorption of thiamine and
folate as well as maldigestion and malabsorption secondary to alcohol-induced pancreatic
insufficiency and intestinal lactase deficiency.2 Alcohol also promotes nutrient degradation
or impaired activation. Such primary and secondary malnutrition can affect virtually all
nutrients (vide infra). At the tissue level, alcohol replaces various normal substrates, with
the liver being the most seriously affected organ and malnutrition being incriminated as
a primary etiologic factor of liver dysfunction.
Theories of the exclusively nutritional origin of alcoholic liver disease were supported
by Best, the prominent codiscoverer of insulin who wrote that “there is no more evidence
of a specific toxic effect of pure ethyl alcohol upon liver cells than there is for one due to
sugar.”3 This notion was based largely on experimental work in rats given ethanol in
drinking water.3 Under these conditions, no liver lesions developed unless the diet was
deficient in proteins, methionine, or choline. Deficiency alone sufficed to produce the liver
lesions. However, with the technique of alcohol administration in drinking water, ethanol
consumption usually does not exceed 10 to 25% of the total energy intake of the animal,
because rats have an aversion for alcohol. A comparable amount of alcohol resulted in
negligible ethanol concentrations in the blood.4 Thus, administration of alcohol in drinking
water to rodents is not a suitable model for the human disease. When ethanol was
incorporated into a totally liquid diet,4,5 the aversion for alcohol was overcome, because
0-8493-2705-9/01/$0.00+$1.50
Impaired
activation,
utilization, and
detoxification
Direct toxic effects
Ethanol
Increased “Empty” calorie Maldigestion

degradation Malabsorption
Malnutrition
FIGURE 45.1
Organ damage in the alcoholic. Interaction of direct toxicity of ethanol on various organs with malnutrition
secondary to dietary deficiencies, maldigestion, and malabsorption, as well as impaired hepatic activation or
increased degradation of nutrients. (From Lieber CS, N Engl J Med 333: 1058; 1995, with permission.)
in order to eat or drink, the animals had no choice but to take the alcohol along with
whatever diet was given. With this technique, the quantity of ethanol consumed was
increased to 36% of total energy, an amount relevant to alcohol intake in man. It was found
that even with nutritionally adequate diets, isoenergetic replacement of sucrose or other
carbohydrates by ethanol consistently produced a 5- to 10-fold increase in hepatic triglyc-
erides.4-6 Furthermore, isoenergetic replacement of carbohydrate by fat instead of ethanol
did not produce steatosis.4 With this liquid-diet technique, alcohol was also shown to be
capable of producing cirrhosis in nonhuman primates, even when there was an adequate
diet.7 In addition, the hepatotoxicity of ethanol was established by controlled clinical
investigations which showed that even in the absence of dietary deficiencies, alcohol can
produce fatty liver and ultrastructural lesions in humans.4,5
Some dietary deficiencies were found to exacerbate the effects of alcohol, and judicious
supplementations were shown to have beneficial effects. When protein deficiency is
present, the deficiency may potentiate the effect of ethanol. In rats, a combination of
ethanol and a diet deficient in both protein and lipotropic factors leads to more pronounced
hepatic steatosis than with either factor alone.8 Indeed, protein deficiency impairs lipo-
protein secretion, which can be expected to markedly potentiate hepatic lipid accumulation
secondary to the direct effects of alcohol resulting from its metabolism in the liver. How-
ever, the effect of protein deficiency has not been clearly delineated in human adults. In
Alcohol: Its Metabolism and Interaction with Nutrients 917
children, protein deficiency leads to hepatic steatosis, one of the manifestations of kwash-
iorkor, but this condition does not progress to cirrhosis. In adolescent baboons, protein
restriction to 7% of total energy did not result in conspicuous liver injury (even after 19
months) either by biochemical analysis or by light- and electron-microscopic examination.
Significant steatosis was observed only when the protein intake was reduced to 4% of
total energy.9 On the other hand, an excess of protein (25% of total energy or 2.5 times the
recommended amount) did not prevent alcohol from producing fat accumulation in
human volunteers.10 Thus, in humans, ethanol is capable of producing striking changes
in liver lipids even in the presence of a protein-enriched diet, an effect linked to the
metabolism of ethanol.
The hepatocyte contains three main pathways for ethanol metabolism, each located in
a different subcellular compartment:
1. The alcohol dehydrogenase (ADH) pathway of the cytosol or the soluble fraction
of the cell
2. The microsomal ethanol oxidizing system located in the endoplasmic reticulum
3. Catalase located in the peroxisomes1
Each of these pathways produces specific metabolic and toxic disturbance, and all three
result in the production of acetaldehyde, a highly toxic metabolite.
The Alcohol Dehydrogenase (ADH) Pathway and Associated Metabolic

Disorders of Carbohydrates, Uric Acid, and Lipids
ADH Isozymes
ADH has a broad substrate specificity which includes dehydrogenation of steroids,
oxidation of the intermediary alcohols of the shunt pathway of mevalonate metabolism,
and ω-oxidation of fatty acids;11 these processes may act as the “physiologic” substrates
for ADH.
Human liver ADH is a zinc metalloenzyme with five classes of multiple molecular forms
which arise from the association of eight different types of subunits, α,β1,β2,β3,γ1,γ2, π,
and χ, into active dimeric molecules. A genetic model accounts for this multiplicity as
products of five gene loci, ADH1 through ADH5.12 There are three types of subunit, α, β,
and γ in class I. Polymorphism occurs at two loci, ADH2 and ADH3, which encode the β
and γ subunits. Class II isozymes migrate more anodically than class I isozymes and,
unlike the latter, which generally have low Km values for ethanol, class II (or π) ADH has
a relatively high Km (34 mM) and a relative insensitivity to 4-methylpyrazole inhibition.
Class III (χADH) does not participate in the oxidation of ethanol in the liver because of
its very low affinity for that substrate. More recently, a new isoenzyme of ADH has been
purified from human stomach, so-called σ- or µ-ADH (class IV).
Metabolic Effects of Excessive ADH-Mediated Hepatic NADH Generation

The oxidation of ethanol via the ADH pathway results in the production of acetaldehyde
with loss of H which reduces nicotinamide adenine dinucleotide (NAD) to nicotinamide
adenine dinucleotide — reduced form (NADH). The large amounts of reducing equiva-
lents generated overwhelm the hepatocyte’s ability to maintain redox homeostasis, and a
number of metabolic disorders ensue (Figure 45.2),1 including hypoglycemia and hyper-
lactacidemia. The latter contributes to the acidosis and also reduces the capacity of the
kidney to excrete uric acid, leading to secondary hyperuricemia, which is aggravated by
the alcohol-induced ketosis and acetate-mediated enhanced ATP breakdown and purine
generation.13 Hyperuricemia explains, at least in part, the common clinical observation
that excessive consumption of alcoholic beverages commonly aggravates or precipitates
gouty attacks. The increased NADH also promotes fatty acid synthesis and opposes lipid
oxidation with, as a net result, fat accumulation.14
The effects of ethanol were reproduced in vitro by an alternate NADH-generating system
(sorbitol-fructose) and were blocked by an H+ acceptor (methylene blue).14,15 The preventive
effect of methylene blue against ethanol-induced fat accumulation was recently confirmed.16
Extrahepatic ADH
The human gastric mucosa possesses several ADH isoenzymes,17 one of which (class IV
ADH or σ-ADH) is not present in the liver. This enzyme has now been purified,18 its full-
length cDNA obtained, the complete amino acid sequence deduced,19,20 and its gene cloned
and localized to chromosome 4.21 Gastric ADH is responsible for a large portion of ethanol
metabolism found in cultured rat22 and human23 gastric cells. Its in vivo effect is reflected
by the first pass metabolism (FPM) of ethanol, namely the fact that for a given dose of
ethanol, blood levels are usually higher after IV than after oral administration.24,25 While
the relative contribution of gastric and hepatic ethanol metabolism to FPM is still the
subject of debate,26-28 the role of gastric ethanol metabolism in this FPM has been estab-
lished experimentally.29,30 Furthermore, FPM is partly lost in the alcoholic,31 together with
decreased gastric ADH activity. Moreover, FPM disappears after gastrectomy.32 σ-ADH is
also absent or markedly decreased in activity in a large percentage of Japanese subjects,33
and their FPM is reduced correspondingly34 in keeping with a predominant role for σ-
ADH in human FPM. Thus, the FPM represents some kind of protective barrier against
the systemic effects of ethanol, including attenuation of liver damage.35,36
Pathogenic Role of ADH Polymorphism

Individual differences in the rate of ethanol metabolism may be genetically controlled.
Furthermore, genetic factors influence the severity of alcohol-induced liver disease.
Indeed, the frequency of an alcohol dehydrogenase 3 allele has been found to differ in
patients with alcohol-related end-organ damage (including cirrhosis) and matched con-
trols, suggesting that genetically determined differences in alcohol metabolism may
explain differences in the susceptibility to alcohol-related disease (possibly through the
enhanced generation of toxic metabolites),37 but this hypothesis has been questioned.38
Microsomal Ethanol Oxidizing System (MEOS)

This new pathway has been the subject of extensive research, reviewed in detail else-
where.39,40 Such a system was demonstrated in liver microsomes in vitro and found to be
inducible by chronic alcohol feeding in vivo,41 and was named the microsomal ethanol
oxidizing system.41,42
The key enzyme of the MEOS is the ethanol-inducible cytochrome P4502E1 (CYP2E1)
which is increased 4- to 10-fold in liver biopsies of recently drinking subjects,43 with a
corresponding rise in mRNA.44 This induction contributes to the metabolic tolerance to
Ethanol (CH3CH2OH)
Physical Dependence?
Organelle Immunologic
Dysfunction? Stimulation? Toxicity Secondary Malnutrition Vitamins
Proteins
Hypoxic Damage
Primary
MEMBRANE ALTERATIONS Fatty Liver
Usable Energy & Hyperlipemia
MICROSOMAL
ADH Hypoproteinemia
CYTOCHROME P-450 INDUCTION O2 Metabolic Hypoglycemia
Derangements Hypoglucuronidation
- 2E1 Hyperlactacidemia
OH. + O2
GSH Depletion MEOS Acetaldehyde NADH Hyperuricemia

Lipid Peroxidation (CH3CHO) Increased Collagen
Activation of Hepatotoxins Synthesis
and Carcinogens Acetate
Covalent Binding to Protein
Acetone Metabolism Microtubular Impairment
(+ Protein Retention and Hepatocyte Swelling)
Alcohol: Its Metabolism and Interaction with Nutrients
ATP Degradation Lipid Peroxidation

Impaired Lipolysis Adverse Pyridoxine Depletion
4A1
Effects Increased Collagen Synthesis
Increased Ω hydroxylation, peroxisomal Inhibition of DNA Repair
β-oxidation, L-FABP & FA esterification Stimulation of Immunologic Reactivity
Hyperglycemia?
Accelerated metabolism of drugs, Impairment of Mitochondrial Electron Transport Chain
enhanced degradation of testosterone
& retinoids; energy wastage
FIGURE 45.2
Hepatic, nutritional, and metabolic abnormalities after ethanol abuse. Malnutrition, whether primary or secondary, can be differentiated from metabolic changes or direct
toxicity, resulting partly from ADH-mediated redox changes, effects secondary to microsomal induction, or acetaldehyde production. (From Lieber CS, J Stud Alcohol 59: 9;
1998, with permission.)
919
ethanol that develops in the alcoholic (in addition to the central nervous tolerance), with
other cytochromes P450 (CYP1A2, CYP3A4) possibly also involved.45
In addition to tolerance to ethanol, alcoholics tend to display tolerance to various other
drugs. Indeed, it has been shown that the rate of drug clearance from the blood is enhanced
in alcoholics. Of course, this could be caused by a variety of factors other than ethanol,
such as the congeners and the use of other drugs so commonly associated with alcoholism.
Controlled studies showed, however, that administration of pure ethanol with non-defi-
cient diets either to rats or man (under metabolic ward conditions) resulted in a striking
increase in the rate of blood clearance of meprobamate, pentobarbital,46 and various other
drugs.1 The metabolic tolerance persists several days to weeks after cessation of alcohol
abuse, and the duration of recovery varies depending on the drug considered.47
Experimentally, this effect of chronic ethanol consumption is modulated, in part, by the
dietary content in carbohydrates,48 lipids,49 and proteins.50 It is now recognized that CYP2E1,
in addition to its ethanol oxidizing activity, catalyzes fatty acid ω-1 and ω-2 hydroxyla-
tions.51-53 Furthermore, acetone is both an inducer and a substrate of CYP2E154-56 (Figure
45.3). Excess ketones and fatty acid commonly accompany diabetes and morbid obesity,
conditions associated with non-alcoholic steatohepatitis (NASH). Experimentally, obese,
overfed rats also exhibit substantially higher microsomal ethanol oxidation, acetaminophen
activation, and p-nitrophenol hydroxylation (monooxygenase activities catalyzed by
CYP2E1).57 These diabetic rats are experimental models relevant to NASH, and indeed the
hepatopathology of NASH appears to be due, at least in part, to excess CYP2E1 induction.58
Clinically, a most important feature of CYP2E1 is not only ethanol oxidation, but also
its extraordinary capacity to convert many xenobiotics to highly toxic metabolites, thereby
explaining the increased vulnerability of the alcoholic. These agents include industrial
solvents (e.g., bromobenzene, vinylidene chloride), anesthetic agents (e.g., enflurane,59 meth-
oxyflurane), commonly used medications (e.g., isoniazid, phenylbutazone), illicit drugs
(e.g., cocaine) and over-the-counter analgesics (e.g., acetaminophen),60 all of which are
substrates for, and/or inducers of CYP2E1. The effects of acetaminophen, ethanol, and
fasting are synergistic,61 because all three deplete the level of reduced glutathione (GSH),
OH-Products
Detoxification
Glucose
_ . .
Activation to toxins, carcinogens
O2 , OH and other free radicals
CYP2E1
+
NADPH
O2
Ketones
Fatty Acids Xenobiotics (including ethanol)

FIGURE 45.3
Physiologic and toxic roles of CYP2E1, the main cytochrome P450 of the microsomal ethanol oxidizing system
(MEOS). Many endogenous and xenobiotic compounds are substrates for CYP2E1 and induce its activity through
various mechanisms, resulting in an array of beneficial as well as harmful effects. (From Lieber CS, Alcohol: Clin
Exp Res 23: 991; 1999, with permission.)
a scavenger of toxic free radicals. Rats fed ethanol chronically have increased rates of GSH
turnover,62 and ethanol produces an enhanced loss from the liver.63 The selective loss of
the compound from liver mitochondria64 contributes to the striking alcohol-induced oxi-
dant stress and impairment of this organelle.
CYP2E1 also generates several species of active oxygen (Figures 45.2, 45.3) which, in
concert with a decrease in the level of GSH, promote injury by inactivation of enzymes and
peroxidation of lipids. In patients with cirrhosis, hepatic depletion of α-tocopherol,65 a major
antioxidant, potentiates this effect. GSH offers one of the mechanisms for the scavenging
of toxic free radicals. Replenishment of GSH can be achieved by administration of precursors
of cysteine (one of the amino acids of this tripeptide) such as acetylcysteine or S-adenosyl-
L-methionine (SAMe).66,67 Experimentally, CYP2E1 has also been downregulated by poly-
enylphosphatidylcholine (PPC),68 a potentially beneficial therapeutic approach.
Nutritional Status of Alcoholics

Overall Assessment
Alcoholics hospitalized for medical complications of alcohol intoxication (such as states
of acute intoxication and withdrawal) have the most severe malnutrition. These alcoholics
have inadequate dietary protein,69 signs of protein malnutrition,70,71 and anthropometric
measurements indicative of impaired nutrition: their height-to-weight ratio is lower,72
muscle mass estimated by the creatinine-height index is reduced,71,72 and triceps skin folds
are thinner.71-73 Continued drinking results in weight loss, whereas abstinence results in
weight gain74,75 in patients with and without liver disease.74
Many patients who drink to excess are either not malnourished or are less malnourished
than the hospitalized group. Women drinking one or more drinks per day weighed on
average 2.3 kg less than nondrinkers, and they and their male counterparts continued on
a more stable weight over the next ten years than the nondrinkers, whose weight rose.76
Other surveys, however, found that alcohol intake, especially when accompanied by high
fat intake and sedentary behavior,77 favors truncal obesity, particularly in women.78 Those
with moderate alcohol intake,79 even those admitted to hospital for alcohol rehabilitation
rather than for medical problems,80 often hardly differ nutritionally from controls (matched
for socioeconomic status and health history), except that females have a lower level of
thiamin excretion than control patients following a thiamin load test.80
The wide range in nutritional status of our alcoholic population surely reflects, in part,
differences in what they eat. Moderate alcohol intake, with alcohol accounting for 16% of
total kcalories (alcohol included), is associated with slightly increased total energy intake.81
Although ethanol is rich in energy (7.1 kcal/g), chronic consumption does not produce
the expected gain in body weight.82 This energy deficit can be attributed, in part, to
damaged mitochondria and the resulting poor coupling of oxidation of fat with energy
production, as well as to microsomal pathways that oxidize ethanol without conserving
chemical energy (Figure 45.2). Thus, perhaps because of these energy considerations, this
group with higher total caloric intake has no weight gain, despite physical activity levels
comparable to those of the non-alcohol consuming population. This level of alcohol intake,
and even slightly higher levels (23%)83 is associated with a substitution of alcohol for
carbohydrate in the diet. In those individuals consuming more than 30% of total kcalories
as alcohol, significant decreases in protein and fat intake occur, too, and the consumption
of vitamins A, C, and thiamin may descend below the recommended daily allowances.81
Calcium, iron, and fiber intake are also lowered.83
The mechanisms underlying the altered pattern of food intake are under debate. Sup-
pression of appetite has been postulated.84 Depressed consciousness during inebriation,
hangover, and gastroduodenitis due to ethanol, partly explain the decreased food intake.
The contribution of subtle nutritional alterations produced by ethanol to the pathogenesis
of ethanol-induced or other disease states, including alcoholism, is largely unchartered.
Specific Nutrients
Vitamin C
The vitamin C status of alcoholic patients admitted to a hospital is lower than that of
nonalcoholics as measured by serum ascorbic acid, peripheral leukocyte ascorbic acid, or
urinary ascorbic acid after an oral challenge.85 In addition to a lower mean ascorbic acid
level, some 25% of patients with Laennec’s cirrhosis had serum ascorbic acid levels below
the range of healthy controls.85 Ascorbic acid status is low in alcoholic patients with and
without liver disease. When alcohol intake exceeds 30% of total kcalories, vitamin C
generally falls below recommended dietary allowances.86 The clinical significance is
unknown for patients who have low ascorbic acid levels but who are not clearly scorbutic.
Vitamin D
Alcoholics have illnesses related to abnormalities of calcium, phosphorus, and vitamin D
homeostasis. They have decreases in bone density87 and bone mass,88 increased suscepti-
bility to fractures,89 and increased osteonecrosis.90 Low blood calcium, phosphorus, mag-
nesium, and low, normal, or high vitamin D3 levels have been reported, indicating disturbed
calcium metabolism.88 In patients with alcoholic liver disease, vitamin D deficiency prob-
ably derives from too little vitamin D substrate, which results from poor dietary intake,
malabsorption due to cholestasis or pancreatic insufficiency, and insufficient sunlight.
Vitamin K
Vitamin K deficiency in alcoholism may arise when there is an interruption of fat absorp-
tion due to pancreatic insufficiency, biliary obstruction, or intestinal mucosal abnormality
secondary to folic acid deficiency. Dietary vitamin K inadequacy is not a likely cause of
clinical deficiency unless there is concomitant sterilization of the large gut, a reliable source
of the vitamin.
Folic Acid
Alcoholics tend to have low folic acid status when they are drinking heavily and their
folic acid intake is reduced. For example, a group of unselected alcoholics showed a 37.5%
incidence of low serum folate levels and a 17.6% incidence of low red blood cell folate
levels.74
In pigs fed ethanol for 11 months, folic acid absorption is normal but jejunal folate
hydrolase, an early enzyme of folate polyglutamate breakdown, is decreased.91,92 In vitro
preparations of rat intestine absorb folate less well when exposed to a variety of alcohols.93
Malnourished alcoholics without liver disease also absorb folic acid less well compared
to their better-nourished counterparts.94 Folic acid absorption, usually increased by partial
starvation, is less increased in rats when alcohol is ingested.95 It has not been clearly shown,
however, that either protein deficiency or alcohol94,95 decreases folate absorption in vivo.
Thus, it is still unclear what aspects of malnutrition adversely affect folate absorption and
under what clinical circumstances alcohol may interfere with folate absorption.
Alcohol accelerates the production of megaloblastic anemia in patients with depleted
folate stores96 and suppresses the hematologic response to folic acid in folic acid-depleted
patients.97 Alcohol also has other effects on folate metabolism but their significance is not
clear: alcohol given acutely causes a decrease in serum folate, which is partly explained
by increased urinary excretion;98 alcohol administered chronically to monkeys decreased
hepatic folate levels, partly because of the inability of the liver to retain folate,99 and
perhaps partly because of increased urinary and fecal losses.100
Vitamin B12
Alcoholics do not commonly have vitamin B12 deficiency. Their serum levels are usually
normal even when they are deficient in folate, whether they have cirrhosis101,102 or not.94,95
This is probably due to large body stores of vitamin B12. Pancreatic insufficiency, however,
results in decreased vitamin B12 absorption as measured by the Schilling test. In this
circumstance there is insufficient luminal protease activity and alkalinity, which normally
serve to release vitamin B12 from the “r’’ protein secreted by salivary glands, intestines,
and possibly the stomach.103 Alcohol ingestion has also been shown to decrease vitamin
B12 absorption in volunteers after several weeks of intake.104 The alcohol effect may be in
the ileum, because co-administration of intrinsic factor or pancreatin does not correct the
Schilling test results. It is controversial whether the binding of intrinsic factor-vitamin B12
complex to ileal sites is abnormal.105,106
Riboflavin
When there is a general lack of B vitamin intake, riboflavin deficiency may be encoun-
tered.107 In one study, deficiency was found in 50% of a small group of patients with
medical complications severe enough to warrant hospital admission.108 Although none of
the patients exhibited classic signs of riboflavin deficiency, they had an abnormal activity
coefficient (AC) that returned to normal 2 to 7 days after intramuscular replacement with
5 mg riboflavin daily. Activity coefficient is measured as the ratio of erythrocyte glu-
tathione reductase activity upon addition of flavin adenine dinucleotide to the activity
with no additions. Riboflavin deficiency could be induced readily by alcohol feeding to
the Syrian hamster; the most severe deficiency was seen in animals also restricted in
riboflavin intake.109 Riboflavin and pyridoxine storage in the liver is adversely affected by
alcohol, at least in experimental animals.
Vitamin E and Selenium

Vitamin E deficiency is not a recognized complication of alcoholism, although patients
with chronic alcoholic pancreatitis have a lower vitamin E-to-total plasma lipid ratio.110
When rodents were fed ethanol repeatedly in one study, their hepatic vitamin E levels,
measured as α-tocopherol, were low;111 this was accompanied by increased hepatic lipid
peroxidation when alcohol was combined with a low-vitamin E diet.112 The mechanism
of hepatic vitamin E depletion by ethanol is probably enhanced oxidation of α-tocopherol
to α-tocopherol quinone in liver microsomes.112 Alcohol-induced liver injury may be medi-
ated, in part, by stress on cellular antioxidant mechanisms interrelated with vitamin E
and selenium. Considering the findings in humans with fat malabsorption or severe
cholestasis, and the evidence of vitamin E depletion by chronic alcohol feeding of exper-
imental animals, it would seem that there is great potential for vitamin E deficiency in
chronic alcoholics who combine low vitamin E intake with steatorrhea from chronic
pancreatitis or prolonged cholestasis.
Magnesium
Acute doses of ethanol cause magnesium loss in the urine,113 and alcoholism is associated
with magnesium deficiency.114 Alcoholics have low blood magnesium and low body-
exchangeable magnesium; symptoms in alcoholics resemble those in patients with mag-
nesium deficiency of other causes; upon withdrawal from alcohol, magnesium balance is
positive. Hypocalcemia in alcoholics in the setting of magnesium deficiency has been
ascribed, in part, to impaired parathyroid hormone (PTH) secretion as well as renal and
skeletal resistance to PTH,115 and the hypocalcemia may only be responsive to magnesium
repletion. Hospitalized alcoholics with normal serum total magnesium had significantly
lower serum ionized magnesium.116
Iron
There may be either deficiency or excess of iron in the body. Alcoholics may be iron-
deficient as a result of the several gastrointestinal lesions to which they are prone and that
may bleed.
Hepatic iron content was found to be increased in autopsy studies of most patients with
early alcoholic cirrhosis.117 In most alcoholics, however, the iron content of the liver is
normal or only modestly elevated, although there may be stainable iron in reticuloendo-
thelial cells, possibly because of bouts of hemolysis. It is unclear whether increased intes-
tinal absorption of iron because of alcohol118 or hepatic uptake of iron from plasma in
established alcoholic liver disease119 contributes significantly to increased hepatic iron
levels. There is usually little difficulty in distinguishing the hepatic iron increases of
alcoholic liver disease from the much higher amounts characteristic of genetic hemochro-
matosis, using a measure of absolute iron content per gram of liver with upward adjust-
ments for age.120 The contribution that hepatic iron may make to liver damage via its role
in lipid peroxidation121 (in conjunction with the effects of alcohol) and its possible role in
promoting fibrogenesis122 are of great potential significance.
Zinc
Patients have low plasma zinc,123 low liver zinc,124 and increased urinary zinc levels.124,125
Acute ethanol ingestion, however, does not cause zincuria.126 The low zinc content of
chronic alcoholics with cirrhosis is attributed to decreased intake and absorption as well
as increased urinary excretion. Many Americans have a diet marginal in zinc.127 Alcoholics
fall into several of those groups with marginal intake. It is interesting that zinc absorption
has been shown to be low in alcoholic cirrhotics but not in patients with cirrhosis of other
causes,128 although cirrhosis of varied etiologies is characterized by low serum zinc.129
Currently, the therapeutic use of zinc in alcoholism is restricted to the treatment of night
blindness not responsive to vitamin A.
Copper
Hepatic copper content is increased in advanced alcoholic cirrhosis.117 Serum copper
content has been reported to be elevated in alcoholics independent of the stage of liver
disease,130 but others have reported normal levels.131
Trace Metals
Nickel levels are consistently high in alcoholic liver disease; manganese and chromium
are unchanged.117 Intracellular shifts in trace metals have been described upon acute
administration of alcohol.132 Versieck et al. reported increased serum molybdenum in
patients with acute liver disease;133 increased levels were not seen in those patients with
cirrhosis. The clinical significance of trace metal changes is still obscure, except for the
cardiotoxicity ascribed to alcoholic beverages with high cobalt content.
Effects of Ethanol on Digestion and Absorption

Diarrhea frequently occurs in alcoholics. In the heavy drinker, diarrhea may occur for a
variety of reasons including ethanol-exacerbated lactase deficiency, especially in blacks.2
Alcohol consumption is also associated with motility changes. In the jejunum, ethanol
decreases type I (impeding) waves, while in the ileum it increases type III (propulsive)
waves. Another major complication is alcoholic pancreatitis. Intestinal malabsorption may
also be secondary to folic acid deficiency (vide supra).
Steatorrhea is commonly due to folic acid deficiency and luminal bile salt deficiency.
Intraluminal bile salts are decreased by acute ethanol administration.134 In rodents, long-
term ethanol administration delays the half-time excretion of cholic and chenodeoxycholic
acids by decreasing the daily excretion and expanding the pool size slightly.135 Alcoholic
cirrhotic patients may have bile low in deoxycholic acid, possibly due to impaired con-
version of cholate to deoxycholate by bacteria.136
Hospitalized alcoholics were reported to have impaired thiamin absorption compared
to control patients when tested by radioactive thiamin excretion,137 a test also affected by
steps not related to absorption. However, folic acid deficiency was not adequately excluded
as a cause of thiamin malabsorption in these studies. Refined testing revealed reduced
thiamin absorption due to alcohol in a minority of subjects.138 Jejunal perfusion studies
did not show an effect of 5% alcohol on thiamin absorption in man.139 Thus, whereas
human thiamin absorption may not be affected by alcohol, it is clearly impaired in rodents.
Alcohol also interferes with riboflavin absorption in rodents, but this has not been
studied in humans. Alcohol impairs folic acid absorption in malnourished humans, but
the mechanism is unclear (vide supra).
Effect of Alcohol on Nutrient Activation

Thiamine and Pyridoxine
Thiamin deficiency in alcoholics causes Wernicke-Korsakoff syndrome and beriberi heart
disease, and probably contributes to polyneuropathy. There has been no confirmation of
an inborn error of transketolase affinity for its cofactor thiamine pyrophosphate in Wer-
nicke-Korsakoff syndrome as was once claimed.
Neurologic, hematologic, and dermatologic disorders can be caused in part by pyridox-
ine deficiency. Pyridoxine deficiency, as measured by low plasma pyridoxal-5’-phosphate
(PLP), was reported in over 50% of alcoholics without hematologic findings or abnormal
liver function tests.140,141 Inadequate intake may partly explain low PLP, but increased
destruction and reduced formation may also contribute. PLP is more rapidly destroyed
in erythrocytes in the presence of acetaldehyde, the product of ethanol oxidation, perhaps
by displacement of PLP from protein and consequent exposure to phosphatase.140,142 Stud-
ies showed that chronic ethanol feeding lowered hepatic content of PLP by decreasing net
synthesis from pyridoxine.143-145 The acetaldehyde produced on alcohol oxidation was
thought to enhance hydrolysis of PLP by cellular phosphatases.140
Methionine and S-Adenosylmethionine (SAMe)

Methionine deficiency has been described and its supplementation has been considered
for the treatment of liver diseases, especially the alcoholic variety, but excess methionine
was shown to have some adverse effects,146 including a decrease in hepatic ATP.147 Fur-
thermore, whereas in some patients with alcoholic liver disease, circulating methionine
levels are normal,148 elevated levels were observed in others.149-151 Kinsell et al.152 found a
delay in the clearance of plasma methionine after its systemic administration to patients
with liver damage. Similarly, Horowitz et al.153 reported that the blood clearance of
methionine after an oral load of this amino acid was slowed. Since about half the methion-
ine is metabolized by the liver, these observations suggested impaired hepatic metabolism
of this amino acid in patients with alcoholic liver disease. Indeed, for most of its functions,
methionine must be activated to S-adenosylmethionine (SAMe), and in cirrhotic livers
Duce et al.154 reported a decrease in the activity of SAMe synthetase, the enzyme involved,
also called methionine adenosyltransferase (Figure 45.4).
Various mechanisms of inactivation of SAMe synthetase have been reviewed
recently.155 One factor that may have contributed to the defect is relative hypoxia, with
nitric oxide-mediated inactivation and transcriptional arrest.156 In addition, long-term
alcohol consumption was found to be associated with enhanced methionine utilization
and depletion.157 As a consequence, SAMe depletion as well as its decreased availability
could be expected, and indeed, long-term ethanol consumption under controlled condi-
tions by nonhuman primates was associated with a significant depletion of hepatic
SAMe.66 Potentially, such SAMe depletion may have a number of adverse effects. SAMe
is the principal methylating agent in various transmethylation reactions which are impor-
tant to nucleic acid and protein synthesis. Hirata and Axelrod158 and Hirata et al.159 also
demonstrated the importance of methylation to cell membrane function with regard to
membrane fluidity and the transport of metabolites and transmission of signals across
membranes. Thus, depletion of SAMe, by impairing methyltransferase activity, may
promote the membrane injury which has been documented in alcohol-induced liver
damage.160 Furthermore, SAMe plays a key role in the synthesis of polyamines and
provides a source of cysteine for glutathione production (Figure 45.4). Thus, the defi-
ciency in methionine activation and in SAMe production resulting from the decrease in
the activity of the corresponding synthetase results in a number of adverse effects,
including inadequate cysteine and GSH production, especially when aggravated by
associated folate, B6, or B12 deficiencies (Figure 45.4). The consequences of this enzymic
defect can be alleviated by providing SAMe, the product of the reaction. SAMe is
unstable, but the synthesis of a stable salt allowed for replenishment of SAMe through
ingestion of this compound: blood levels of SAMe increased after oral administration in
rodents161 and man.162 It has been claimed that the liver does not take up SAMe from
the bloodstream,163 but results in baboons66 clearly showed hepatic uptake of exogenous
SAMe. The effective use of SAMe for transmethylation and transsulfuration has also
been demonstrated in vivo.164
METABOLITES
LIPID
PEROXIDATION
α_AMINO_n_BUTYRIC ACID
ETHANOL FREE
1 2 RADICALS GSH
ADH MICROSOMES α_KETOBUTYRIC ACID
ACETALDEHYDE CYSTEINE
METHIONINE d
c
a SERINE CYSTATHIONINE
S-ADENOSYL_METHIONINE HOMOCYSTEINE
3 PHOSPHATIDYLCHOLINE 4
b
PHOSPHATIDYLETHANOLAMINE
FIGURE 45.4
Lipid peroxidation and other consequences of alcoholic liver disease and/or increased free radical generation
and acetaldehyde production by ethanol-induced microsomes, with sites of possible therapeutic interventions.
Metabolic blocks caused by liver disease (a,b), folate (c), B12 (c) or B6 (d) deficiencies are illustrated, with
corresponding depletions in S-adenosylmethionine, phosphatidylcholine, and glutathione (GSH). New thera-
peutic approaches include 1) downregulation of microsomal enzyme induction especially of CYP2E1, 2) decrease
of free radicals with antioxidants, 3) replenishment of S-adenosylmethionine, and 4) phosphatidylcholine. (From
Lieber CS. J Hepatology. 32: 113; 2000, with permission.)
Clinical trials revealed that SAMe treatment is beneficial in intrahepatic cholestasis,165

including recurrent intrahepatic cholestasis and jaundice caused by androgens or estro-
gens. It was also used successfully in severe cholestasis of pregnancy166 with few, if any,
untoward effects. Oral administration of 1200 mg/day of SAMe for 6 months also resulted
in a significant increase of hepatic GSH in patients with alcoholic as well as non-alcoholic
liver disease.167
The most impressive therapeutic success was achieved in a recent long-term random-
ized, placebo-controlled, double-blind, multicenter clinical trial of SAMe in patients with
alcoholic liver cirrhosis in whom SAMe significantly improved survival or delayed liver
transplantation.168
Phosphatidylcholine (PC)
In the presence of liver disease, the activity of phosphatidylethanolamine methyltrans-
ferase is depressed,154 with significant pathologic effects. This enzymatic block can again
be bypassed through the administration of the product of that reaction, in this case PC169
(Figure 45.4). This is emerging as potentially important approach to the treatment of liver
disease. Indeed, feeding of a mixture rich in polyunsaturated PCs (PPC), especially dili-
noleoylphosphatidylcholine (DLPC), which has a high bioavailability, exerted a remark-
able protection against alcohol-induced fibrosis and cirrhosis.170
PPC contains choline, but in amounts present in PPC, choline had no protective action
against the fibrogenic effects of ethanol in the baboon.171 In primates in general, choline
plays a lesser role as a dietary nutrient than in rodents, in part because of lesser choline
oxidase activity. In fact, as reviewed elsewhere,172 choline becomes essential for human
nutrition only in severely restricted feeding situations. The decreased phospholipid meth-
yltransferase activity in cirrhotic livers154 is not simply secondary to the cirrhosis, but may
in fact be a primary defect related to alcohol, as suggested by the observation that the
enzyme activity is already decreased prior to development of cirrhosis.169 Another mech-
anism whereby ethanol may affect phospholipids is increased lipid peroxidation as
reflected by increased F2-isoprostanes,171 which could explain the associated decrease of
arachidonic acid in phospholipids.173
One concern was that PPC and DLPC, because of their polyunsaturated nature, may
aggravate the oxidative stress, but the opposite was found, both in vitro and in vivo. In
alcohol-fed baboons, PPC not only prevented septal fibrosis and cirrhosis170 but also
resulted in a total protection against oxidative stress, as determined by normalization of
4-hydroxynonenal, F2-isoprostanes and GSH levels.174 In patients with hepatitis C, PPC
improved the transaminase levels, but the effect on liver fibrosis was not assessed.175
However, a clinical trial on alcoholic fibrosis is presently ongoing in the U.S.
Toxic Interaction of Alcohol with Nutrients

Adverse Interaction with Retinol
In addition to the classic aspects of vitamin A deficiency due to either poor dietary intake
or severe liver disease, direct effects of alcohol on vitamin A metabolism and resulting
alterations in hepatic vitamin A levels have been elucidated.176
Depletion of Hepatic Vitamin A by Ethanol, its Mechanism and Pathological

Consequences
Alcoholic liver disease is associated with severely decreased hepatic vitamin A levels
(Figure 45.5), even when liver injury is moderate (fatty liver) and when blood values of
vitamin A, retinol binding protein (RBP), and prealbumin are still unaffected.
Malnutrition, when present, can of course contribute to hepatic vitamin A depletion,
but the patients with low liver vitamin A in the study of Leo and Lieber177 appeared well
nourished, which suggested a more direct effect of alcohol. Under strictly controlled
conditions, chronic ethanol consumption was found to decrease hepatic vitamin A in
baboons pair-fed a nutritionally adequate liquid diet containing 50% of total energy either
as ethanol or isocaloric carbohydrate. In these baboons, fatty liver developed after 4
months of ethanol feeding, with a 59% decrease in hepatic vitamin A levels, and fibrosis
or cirrhosis appeared after 24 to 84 months with a 95% decrease in hepatic vitamin A
concentrations.178 Similarly, hepatic vitamin A levels of rats fed ethanol (36% of total
energy) were decreased after 3 weeks (by 42%) and continued to decline up to 9 weeks.
In contrast, serum vitamin A and RBP levels were not significantly changed. When dietary
vitamin A was increased fivefold, hepatic vitamin A nevertheless decreased in ethanol-
fed rats relative to the corresponding controls, and sometimes even compared to the rats
given five times less vitamin A (without ethanol).178 To avoid the confounding effect of
dietary vitamin A, it was virtually eliminated in some experiments. Under those condi-
tions, the depletion rate of vitamin A from endogenous hepatic storage was observed to
be 2.5 times faster in ethanol-fed rats than in controls.
900
800
700
LIVER VITAMIN A (µg/g wet weight)
500
400
300
200
100
0
<0.001 <0.001 <0.001 <0.001
Normal Persistent Fatty Alcoholic Cirrhosis
Liver Hepatitis Liver Hepatitis
Autopsy liver
Diabetes
FIGURE 45.5
Hepatic vitamin A levels in subjects with normal livers, chronic persistent hepatitis, and various stages of
alcoholic injury (Data from Leo MA, Lieber CS, N Engl J Med 307: 597; 1982).
When dietary vitamin A intake was virtually eliminated, the difference in hepatic storage
between ethanol-fed rats and controls was much greater than could be accounted for by
the total vitamin A intake. Thus, malabsorption was not the only reason for the depletion
of hepatic vitamin A. Two possible mechanisms other than malabsorption can be invoked:
increased mobilization of vitamin A from the liver, and enhanced catabolism of vitamin
A in the liver or in other organs. There is experimental evidence for both.178-180
The various pathways involved in hepatic vitamin A metabolism have been reviewed.181
Drugs that induce the cytochromes P450 in liver microsomes were shown to result in a
depletion of hepatic vitamin A.182 A similar effect was observed after administration of
ethanol177,178 and other xenobiotics that are known to interact with liver microsomes,
including carcinogens.183 The hepatic depletion was strikingly exacerbated when ethanol
and drugs were combined,184 which mimicks a common clinical occurrence.
Retinoic acid has been shown to be degraded in microsomes of hamsters185 and rats.180,186
In both species, the reported activity was very low compared to the degree of hepatic
vitamin A depletion. These observations prompted the search for alternate pathways of
retinol metabolism, and two new pathways of retinol metabolism were described: rat
liver microsomes, when fortified with NADPH, converted retinol to polar metabolites,
including 4-hydroxyretinol.186 This activity was also demonstrated in a reconstituted
monooxygenase system containing purified forms of rat cytochromes P-450,187 including
P4502B1 (a phenobarbital-inducible isozyme). More recently, it has been shown that other
cytochromes (such as P450 CYP 1A1) also catalyze the conversion of retinal to retinoic
acid.188 In addition, a new microsomal NAD+-dependent retinol dehydrogenase was
described.189 The classic pathway for the conversion of retinol to retinal in the liver
involves a cytosolic NAD-dependent retinol dehydrogenase (CRD), believed to be similar,
if not identical, to the liver cytosolic alcohol dehydrogenase (ADH, alcohol: NAD– oxi-
doreductase, EC 1.1.1.1). The observation that a strain of deermice lacks this enzyme
without apparent adverse effects190 prompted a search for an alternate pathway for the
production of retinal, the precursor of retinoic acid. Evidence was obtained for the exist-
ence of a NAD-dependent microsomal retinol dehydrogenase (MRD)189 which can convert
retinol to retinal using NAD, and retinal to retinol using NADH as cofactors. The activity
of the retinol189 as well as the retinal191 dehydrogenases is inducible by chronic alcohol
consumption, thereby contributing to hepatic vitamin A depletion. Finally, metabolism
of retinol and retinoic acid was also demonstrated with human liver microsomes and
purified cytochrome P-4502C8.191
In patients with severe as well as moderate depletion of hepatic vitamin A, multivesicular
lysosome-like organelles were detected in increased numbers.192 That a low hepatic vitamin
A concentration contributes to these lesions was also verified experimentally in rats.193
Hepatic vitamin A depletion plays a key role in hepatic fibrosis, and both hepatocytes
and stellate cells are involved. Hepatic stellate cells are the principal storage site of vitamin
A. The activation of stellate cells into myofibroblast-like cells, which then synthesize
collagen, is associated with a decrease in vitamin A storage in these cells.194 Retinoic acid,
and to a lesser extent retinol, were shown to reduce stellate cell proliferation and collagen
production in culture.194-196 Conversely, lack of retinoids could promote fibrosis in these
tissues, especially in the liver, consistent with the associated activation of stellate cells.194
Paradoxically, however, vitamin A excess may also promote fibrosis (vide infra).
Concomitant ethanol consumption and vitamin A deficiency resulted in an increased
severity of squamous metaplasia of the trachea.197,198 This potentiation of vitamin A defi-
ciency by alcohol may predispose the tracheal epithelium to neoplastic transformation.
A relatively high risk of squamous cell carcinoma of the lung was found in a Norwegian
population that drank large amounts of alcohol and had a low dietary intake of vitamin
A.199 Furthermore, a positive association of alcohol consumption with lung cancer has
been reported in Japanese men in Hawaii.200 In addition, ethanol-induced vitamin A
depletion is associated with decreased detoxification of xenobiotics, including carcinogens
such as nitrosodimethylamine,201 thereby playing a role in chemical carcinogenesis (vide
supra). Recent data also suggest that functional downregulation of retinoic acid receptors,
by inhibiting biosynthesis of retinoic acid and upregulating activator protein-1 (c-Jun and
c-Fos) gene expression, may be important mechanisms for causing malignant transforma-
tion by ethanol.202
In addition to promoting vitamin A depletion, ethanol may interfere more directly with
retinoic acid synthesis, since both were shown in vitro to serve as substrates for the same
enzymes.203 Specifically, one of the mechanisms by which ethanol induces gastrointestinal
cancer may be an inhibition of ADH-catalyzed gastrointestinal retinoic acid synthesis
which is needed for epithelial differentiation. Indeed, class I ADH (ADH-I) and class IV
ADH (ADH-IV) function as retinol dehydrogenases in vitro and are abundantly distributed
along the GI tract.204 Deficiency of retinoic acids can produce birth defects and, as discussed
above, ethanol promotes deficiency of retinoids. Duester203,205 and Pullarkat206 implicated
competitive inhibition by ethanol of the biosynthesis of retinoic acid from retinol, since
class I alcohol dehydrogenase (E.C. 1.1.1.1) can contribute to the biosynthesis of retinoic
acid from retinol. Indeed, this group identified one human ADH isozyme that exists in
the affected embryonic tissues to act as a retinol dehydrogenase catalyzing the synthesis
of retinoic acid. Ethanol did, in fact, reduce RA levels in cultured mouse embryos.207
However, other results208 failed to verify, in conceptal tissues, that competitive inhibition
of the conversion of retinol to retinoic acid is a significant factor in ethanol-induced
embryotoxicity. More recently, Kedishvili et al.209 characterized an ADH enzyme (ADH-
F) that oxidizes all-trans-retinol and steroid alcohols in fetal tissues.
Abnormalities Associated with Excess Vitamin A

Vitamin A deficiency promotes carcinogenesis (vide supra), but paradoxically, vitamin A
excess may have a similar effect: Tuyns et al.210 and DeCarli et al211 noted that foods
providing large amounts of retinol increase the risk of cancer of the esophagus, and in an
epidemiologic study the increased cancer risk associated with the use of cigarettes and
alcohol was enhanced upon ingestion of foods containing retinol.212 Other food constitu-
ents could also play a role in that regard.
The teratogenic potential of excessive intake of retinoid has been clearly demonstrated
in experimental animals,213 with corresponding data evolving in humans: teratogenicity
of 13-cis-retinoic acid, used to treat cystic acne, has been established in epidemiological
studies.214 In addition, among babies born to women who took more than 10,000 IU of
preformed vitamin A per day as supplements, about 1 infant in 57 had a malformation.215
However, some caution in the interpretation of these data is still indicated.216 Furthermore,
acetaldehyde can cross the placenta217 and may also contribute to the development of the
fetal alcohol syndrome, the most prevalent cause of preventable congenital abnormality.218
Therefore, in addition to potentiating the teratogenicity of vitamin A deficiency, alcohol
can be expected to aggravate that of vitamin A excess, and this was indeed verified
experimentally.219
An excess of vitamin A is also known to be hepatotoxic.220,221 The smallest daily sup-
plement of vitamin A reported to be associated with liver cirrhosis is 7500 µg RE (25,000
IU) taken for 6 years.222 These supplements fall well within common therapeutic dosages
and amounts used prophylactically with over-the-counter preparations by the population
at large.
Potentiation of vitamin A hepatotoxicity by ethanol was first demonstrated in rats fed
diets for two months with either normal or fivefold increased vitamin A content, both
with and without ethanol.223 Whereas under these conditions ethanol alone produced only
modest changes and vitamin A supplementation at the dose used had no adverse effect,
the combination resulted in striking lesions, with giant mitochondria containing paracrys-
talline filamentous inclusions and depression of oxygen consumption in state 3 respiration
with five different substrates. The potentiation of vitamin A toxicity by ethanol was also
seen in patients treated with 10,000 IU vitamin A per day for sexual dysfunction attrib-
utable to excess alcohol consumption.224 In addition to giant mitochondria, filamentous
or crystalline-like inclusions were seen in the liver mitochondria of patients with hyper-
vitaminosis A.225,226 The potentiation of vitamin A toxicity by ethanol was most dramati-
cally documented in another study in which rats were given a combination of vitamin A
supplementation and ethanol for up to nine months.227 There was striking hepatic inflam-
mation and necrosis, accompanied by a rise in the serum level of liver enzymes (glutamic
dehydrogenase and AST).
Since retinol, retinal, and retinoic acid can be further metabolized by liver microsomes,
particularly when the latter system is induced by chronic ethanol consumption,180,186,187,189
one can postulate that some of these metabolites produced in increased amounts (possibly
by some specific forms of cytochrome P-450) might also participate in the enhanced
toxicity, but at the present time direct experimental evidence to support such a hypothesis
is lacking.
Adverse Interactions of Ethanol with β-Carotene

In contrast with retinoids, carotenoids were not known to produce toxic manifestations,
even when ingested chronically in large amounts.228 Therefore, it made sense to assess
whether carotenoids may serve as effective (but less toxic) substitutes for retinol, especially
in alcoholic liver injury which has been attributed, in part, to oxidative stress, and since
β-carotene is an antioxidant. It was not known, however, whether β-carotene can actually
offset alcohol-induced lipid peroxidation.
Effects of Alcohol on β-Carotene Concentrations

Studies in man revealed that for a given β-carotene intake, there is a correlation between
alcohol consumption and plasma β-carotene concentration.229 Thus, whereas in general,
alcoholics have low plasma β-carotene levels,229,230 presumably reflecting low intake, alco-
hol per se might in fact increase blood levels in man.229 There was also an increase in
women with a dose as low as two drinks a day.231 Furthermore, there was an increase in
non-human primates studied under strictly controlled conditions.232 Indeed, in baboons
fed ethanol chronically, liver β-carotene was increased, in contrast with vitamin A, which
was depleted. Similarly, plasma β-carotene levels were elevated in these ethanol-fed
baboons, with a striking delay in the clearance from the blood after a β-carotene load.
Whereas β-carotene administration increased hepatic vitamin A in control baboons, this
effect was much less evident in alcohol-fed animals. The combination of an increase in β-
carotene and a relative lack of a corresponding rise in vitamin A suggests a blockage in
the conversion of β-carotene to vitamin A by ethanol.
β-Carotene, Alcohol, Oxidative Stress, and Liver Injury

In the baboon, the administration of ethanol together with β-carotene resulted in a more
striking hepatic injury than with either compound alone,232 with increased activity of liver
enzymes in the plasma, an inflammatory response in the liver and, at the ultrastructural
level, striking autophagic vacuoles and alterations of the endoplasmic reticulum and the
mitochondria.233 The ethanol-induced oxidative stress, assessed by an increase in hepatic
4-hydroxynonenal and F2-isoprostanes (measured by gas chromatography-mass spectrom-
etry), was not improved despite a concomitant rise in hepatic antioxidants (β-carotene
and vitamin E).
Extrahepatic Side Effects

Cardiovascular Complications
There was no evidence of lower mortality from cardiovascular disease or other causes
following β-carotene supplementation.234 Similarly, the study of Hennekens et al.235 ruled
out the possibility that there was even a slight reduction in the incidence of mortality from
cardiovascular disease with supplementation of 50 mg β-carotene on every other day, for
an average of 12 years. Recent results even suggest that β-carotene participates as a pro-
oxidant in the oxidative degradation of low density lipoprotein (LDL), and that increased
LDL β-carotene may cancel the protective qualities of α-tocopherol.236
In the Alpha-Tocopherol, Beta-Carotene and Cancer Prevention (ATBC) Study237 and the
Beta-Carotene and Retinol Efficacy Trial (CARET),238 it was noted that in smokers, β-
carotene supplementation increased death from coronary heart disease.
Interaction with Cancer

Two epidemiologic investigations, namely both the ATBC237 and the CARET238 studies,
revealed that β-carotene supplementation increases the incidence of pulmonary cancer in
smokers. Because heavy smokers are commonly heavy drinkers, we raised the possibility
that alcohol abuse was contributory,239 since alcohol is known to act as a carcinogen and
to exacerbate the carcinogenicity of other xenobiotics, especially those of tobacco smoke.240
Why this should be aggravated by β-carotene is not clear, but β-carotene was found in rat
lung to produce a powerful booster effect on phase I carcinogen-bioactivating enzymes,
including activators of polycyclic aromatic hydrocarbons (PAHs).241,242 In addition, since
pulmonary cells are exposed to relatively high oxygen pressures, and because β-carotene
loses its antioxidant activity and shows an autocatalytic, pro-oxidant effect at these higher
pressures,243 such an interaction is at least plausible and deserves further study, especially
since recent studies showed that β-carotene protects against oxidative damage in HT29
cells at low concentrations but rapidly loses this capacity at higher doses,244 and that β-
carotene enhances hydrogen peroxide-induced DNA damage in human hepatocellular
HepG2 cells.245 Furthermore, the more recent publications of the ATBC and CARET studies
showed that the increased incidence of pulmonary cancer was related to the amount of
alcohol consumed by the participants.246-248
Concentrations of carotenoids, retinoids, and tocopherols were also determined in the
homogenate of macroscopically normal-appearing oropharygeal mucosa from chronic
alcoholics and control patients. All the alcoholics except one had oropharyngeal cancer.
No significant difference was found in tissue levels of carotenoids and tocopherols between
alcoholics and controls. Furthermore, in 7 of 11 controls, retinol was undetectable in the
oropharyngeal mucosa, while in the alcoholics only 2 out of 10 had unmeasurable retinol
levels.249 These results did not support the concept that ethanol-associated oropharyngeal
carcinogenesis is due, at least in part, to local deficiencies in retinoids, carotenoids, or α-
tocopherol.
Contrasting with the investigations showing a lack of beneficial effects of β-carotene
supplementation (reviewed above), β-carotene was found to inhibit rat liver chromosomal
aberrations and DNA chain break after a single injection of diethylnitrosamine.250 Further-
more, a study of nonmelanocytic skin cancer showed that a high intake of vegetables and
other β-carotene-containing foods is protective for nonmelanocytic skin cancers.251 Con-
versely, Menkes et al.252 showed an association between low levels of serum β-carotene
and the risk of squamous cell carcinoma of the lung. However, the latter two observations
do not necessarily prove a causal link, since the beneficial effects may be associated with
active nutrients other than β-carotene.
Therapeutic Window of Retinoids and Carotenoids

As already mentioned, vitamin A deficiency aggravates alcohol-induced liver injury, fetal-
alcohol syndrome, and carcinogenesis. Vitamin A deficiency results not only from a poor
dietary intake, but may also derive from direct effects of ethanol on the breakdown of
retinol in the liver. Supplementation of vitamin A in the heavy drinker may thus be
indicated, but is complicated by the intrinsic hepatotoxicity of large amounts of vitamin
A, which is strikingly potentiated by concomitant alcohol use. β-carotene is a precursor
and a nontoxic substitute for retinol, but ethanol interferes with its conversion to vitamin
A, and even moderate alcohol intake can result in increased levels of β-carotene when the
latter is given in commonly used dosage for supplementation. Side effects observed under
these conditions include hepatotoxicity, promotion of pulmonary cancer, and possibly
cardiovascular complications. Thus, detrimental effects result from deficiency as well as
from excess of retinoids and carotenoids, and paradoxically, both have similar adverse
effects in terms of fibrosis, carcinogenesis, and possibly embryotoxicity. Treatment efforts
therefore must carefully respect the resulting narrow therapeutic window, especially for
drinkers in whom alcohol narrows this therapeutic window even further by promoting
the depletion of retinoids and potentiating their toxicity.
Effects of Ethanol on the Metabolism of Proteins

As reviewed elsewhere,253 ethanol given in single doses causes impaired hepatic amino
acid uptake, decreased leucine oxidation,254 increased serum branched chain amino acids,
and impaired synthesis of lipoproteins, albumin,255-258 and fibrinogen.254 Given chronically,
ethanol causes impaired protein secretion from the liver, probably related to alterations
in microtubules and retention of proteins in enlarged hepatocytes.259 It promotes protein
catabolism in the heart260 and gastrointestinal tract.261
Effects of Dietary Factors on Ethanol Metabolism

Low-protein diets reduce hepatic ADH in rats262 and lower ethanol oxidation rates in rats262
and man.263 Prolonged fasting also decreases ethanol oxidation rates as shown in isolated
rat liver cells. A mechanism for lowered metabolism of ethanol during fasting is the lack
of available metabolites to shuttle reducing equivalents from ethanol oxidation into mito-
chondria.264 For a given alcohol intake, malnourished alcoholics may develop higher blood
alcohol levels and sustain them longer than normally nourished individuals.265
In rats, MEOS activity in the liver showed greater induction by alcohol on a normal
than a low-fat diet, although induction of CYP2E1 was the same.266
Nutritional Therapy in Alcoholism

Individuals consuming over 30% of total kcalories as alcohol have a high probability of
ingesting less than the recommended daily amounts of carbohydrate, protein, fat, vitamins
A, C, and B (especially thiamin), and minerals such as calcium and iron (vide supra). It is
sensible to recommend a complete diet comparable to that of nonalcoholics to forestall
deficiency syndromes, although this does not suffice to prevent some organ damage due
to the direct toxicity of alcohol (e.g., alcoholic liver disease).
Damage due to lack of thiamin is serious but treatable with a great margin of safety;
therefore thiamin deficiency should be presumed and, if not definitely disproved,
parenteral therapy with 50 mg of thiamin per day should be given until similar doses can
be taken by mouth. Riboflavin and pyridoxine should be routinely administered at the
dosages usually contained in standard multivitamin preparations. Adequate folic acid
replacement can be accomplished with the usual hospital diet. Additional replacement is
optional unless deficiency is severe. Vitamin A replacement should only be given for well-
documented deficiency, and to patients whose abstinence from alcohol is assured.
Zinc replacement is indicated only for night blindness unresponsive to vitamin A

replacement. Magnesium replacement is recommended for symptomatic patients with low
serum magnesium. Iron deficiency that has been clearly diagnosed may be corrected orally.
The nutritional management of acute and chronic liver disease due to alcoholism should
include feeding programs to achieve protein replenishment without promoting hepatic
encephalopathy, as reviewed elsewhere.1
Acute pancreatitis may require withholding oral feeding for prolonged periods, during
which time venous alimentation must be given. Chronic pancreatic exocrine insufficiency
is treated by dietary manipulation (including decreases in fat) with oral pancreatic
enzymes at mealtime. In addition to defining feeding programs to reverse malnutrition,
the nutritional management of liver disease due to alcoholism must take into account that,
because of the alcohol-induced disease process, some of the nutritional requirements
change. This is exemplified by methionine which normally is one of the essential amino
acids for humans, but needs to be activated to SAMe, a process impaired by the disease.
Thus, SAMe rather than methionine is the compound to be used for supplementation in
the presence of significant liver disease, and a resulting prolonged survival has now been
documented16 (vide supra). Similarly, because of an impairment in phosphatidylethanola-
mine methyltransferase activity, supplementation with phosphatidylcholine, particularly
the highly bioavailable DLPC, may be useful for prevention and treatment (vide supra).
Acknowledgment
Modified from Annual Review of Nutrition, Lieber, C.S. 20: 395; 3000 (with permission).
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46
Anemias
Linda K. Hendricks and Abdullah Kutlar
Introduction
Hematopoiesis is the process whereby mature blood cells (red cells, white cells, and
platelets) are produced from the pluripotent hematopoietic stem cells in the bone marrow.
The process involves the proliferation and differentiation of stem cells into different
lineages (megakaryocytic, erythroid, lymphoid, granulocytic/marophage) with the ulti-
mate production of mature blood cells. This process is influenced by many complex factors
including the bone marrow microenvironment, an elaborate network of cytokines and
hematopoietic growth factors, and an adequate supply of nutrients, vitamins, and some
trace elements (Table 46.1). Erythropoiesis refers to the production of red blood cells whose
major function is oxygen transport and delivery. A decrease in red blood cell mass and
oxygen-carrying capacity results in anemia.
This section will provide an overview of the classification and pathogenesis of anemia,
and will primarily focus on a detailed discussion of nutritional deficiencies leading to
various types of anemia.
Anemia: Definition and Classification

Anemia is best defined as a reduction in the oxygen-carrying capacity of blood. Since this
function is carried out by hemoglobin (Hb) in the red blood cells, measurement of Hb
provides an accurate, reproducible means of detecting anemia. The normal values for Hb
for different age groups as well as for adult men and women are shown in Table 46.2.
Initial laboratory approach to anemia is summarized in Table 46.3.
Anemias can be classified morphologically and functionally. The morphologic classifi-
cation is based upon the mean corpuscular volume (MCV), average volume of the red cell
(Table 46.4). The diameter of a red cell is close to the size of the nucleus of a normal
lymphocyte, approximately 7 µm (Color Figure 46.1*). Normal red cells are formed in the
shape of two biconcave discs that are flexible and change shape according to a variety of
* Color figures follow page 992.
0-8493-2705-9/01/$0.00+$1.50
TABLE 46.1
Nutrients Important for Normal Red Blood Cell (RBC) Production
Protein/Calories
Vitamin B12 (cobalamin)
Folate
Iron
Vitamin B6 (pyridoxine)
Riboflavin
Nicotinic acid
Ascorbic acid
Vitamin A (retinol)
Vitamin E (α-tocopherol)
Copper
TABLE 46.2
Criteria for Anemia and Normal MCV Values
Hgb (g/dl) Hct (%) MCV (fl)
Infants
1-3 days <14.5 <45 95-108

One month <10 <31 85-104
Two months <9 <28 77-96
0.5-2 years <11 <33 70-78
Children
2-6 years <11.5 <34 75-81

6-12 years <11.5 <35 77-86
12-18 yrs
Female <12 <36 78-90
Male <13 <37 78-88
Women <12 <37 80-90
Men <14 <40 80-90
MCV = Mean Corpuscular Volume
TABLE 46.3
Initial Laboratory Data in the Evaluation of Anemia
CBC (complete blood count)
White count and differential
Platelet count
Hemoglobin and hematocrit
MCV (mean cell volume)
Reticulocyte count
Red cell morphology on peripheral blood smear
factors. The amount of volume inside the cell membrane is the MCV. The normal MCV
of a red cell is 80 to 100 fl. When evaluating either the MCV or the Hb of an individual,
it is important to consider the patient’s age and sex.
The functional classification takes the pathogenesis of anemia into consideration. Thus,
anemias can be hypoproliferative (bone marrow or stem cell defects, decreased stimulation
of erythropoiesis), or result from maturation defects (nuclear or cytoplasmic) or from blood
loss or destruction (hemorrhage, hemolysis, and sequestration) (Table 46.5).
Anemias 943
TABLE 46.4
Classification of Anemias by Morphology
Low MCV (Microcytic) High MCV (Macrocytic) Normal MCV (Normocytic)
Fe deficiency Nonmegaloblastic Bone marrow failure
Thalassemia Liver disease Aplastic anemia
Sideroblastic anemia Hypothyroidism Red cell aplasia (acquired
Chronic disease Reticulocytosis and congenital)
Lead poisoning Aplastic anemia Marrow infiltration
Protein deficiency Chronic renal failure
Megaloblastic Endocrine abnormalities
Vitamin B12 deficiency Hypothyroidism
Folate deficiency Adrenal insufficiency
Myelodysplastic syndromes HIV
Chronic disease
Drug Induced
Chemotherapeutic agents
Nitrous oxide (laughing gas)
FIGURE 46.1
(See Color Figure 46.1) A normal peripheral blood smear.
Normal Erythropoiesis
A good understanding of normal erythropoiesis will enable one to better understand and
appreciate the pathogenesis of different types of anemias (Color Figure 46.2). The earliest
red cell precursor, the proerythroblast, is very large (12 to 20 µm) with a large nucleus.
The nucleus contains DNA necessary for cell division, and the cytoplasm contains RNA
necessary for hemoglobin synthesis. As the cells divide and mature, the nucleus becomes
very small and condensed. Eventually the nucleus is extruded and the mature red cell
remaining is only the cytoplasm full of hemoglobin. The normal red cell is smaller than
the precursor cells and is pink-colored from the hemoglobin.
Perturbations of either the nuclear (DNA) or cytoplasmic (RNA and hemoglobin) mat-
uration leads to anemia. The nucleus of the red cell precursor utilizes cobalamin (vitamin
B12) and folate in the synthesis of DNA. When either of these nutrients is sparse the nucleus
cannot divide or mature normally, despite normal cytoplasmic development. The red cells
formed are large (macrocytic). The bone marrow reveals red cell precursors that are
megaloblastic, that is, large with fine, sparse nuclear chromatin. Other nucleated bone
marrow cells are also affected such as the white cells, resulting in hypersegmented neu-
trophils in the peripheral blood (Color Figure 46.3).
In the cytoplasm, hemoglobin synthesis proceeds normally as long as both heme and
globin are manufactured normally. Defective heme synthesis can occur by two mecha-
TABLE 46.5
Functional Causes of Anemia
Blood loss
Gastrointestinal bleeding
Menses/Menorrhagia
Internal bleeding
Decreased production of red blood cells
Nutritional deficiencies
Primary bone marrow failure
(myelodysplastic syndromes, leukemias, infiltrative processes)
Secondary bone marrow failure
(drugs, toxins, metabolic processes, infections)
Increased destruction of red blood cells
Immune hemolytic anemia
Mechanical hemolysis
(heart valve, microangiopathic hemolytic anemia, TTP, DIC)
Hereditary hemolysis
hemoglobinopathies
enzyme defects (G6PD, pyruvate kinase)
membrane defects
Acquired membrane defects
paroxysmal nocturnal hemoglobinuria
spur cell anemia
Infection related hemolysis
Clostridia, malaria, babesiosis
Splenic sequestration
Increased plasma volume
Pregnancy
Red Blood Cell Development
Basophilic Polychromatic Orthochromic

Pronormoblast Normoblast Normoblast Normoblast Reticulocyte
Normal
B12
Folate
Deficiency
Iron
Deficiency
FIGURE 46.2
(See Color Figure 46.2) Erythropoiesis as it is affected by states of iron deficiency and vitamin B12 or folate
deficiency.
Anemias 945
FIGURE 46.3
(See Color Figure 46.3) Macrocytic RBCs. Red blood cells that are larger than normal (macrocytic) and white
blood cells that have nuclei with multiple segments (hypersegmented neutrophils) are characteristic of a vitamin
B12 deficiency anemia.
FIGURE 46.4
(See Color Figure 46.4) Microcytic RBCs. Red blood cells that are smaller than normal and have pale features
(microcytic and hypochromic) are characteristic of Fe deficiency anemia.
nisms: faulty iron metabolism (iron deficiency anemia) or defective porphyrin metabolism
(sideroblastic anemia). A deletion in or defect of the genes encoding globin (thalassemia)
causes defective globin synthesis. All of these anemias are characterized by small red cells,
microcytosis, because the nucleus divides and matures normally (Color Figure 46.4).
The Reticulocyte
The normal red blood cell (RBC) lives about 120 days in the peripheral blood: when the
senescent RBC are destroyed they have to be replaced by new RBCs to maintain RBC
homeostasis. A newly produced, young RBC still has residual RNA and mitochondria in
the cytoplasm and is slightly larger than a normal red cell, appearing a little bluish on the
peripheral blood smear. This is called a reticulocyte. A special stain is performed using new
methylene blue, which stains the residual RNA, making a reticulocyte easy to identify and
count in the blood (Color Figure 46.5). The reticulocyte count is the number of reticulocytes
counted in 1000 red cells, reported as a percentage. A reticulocyte lives normally two days
before it matures into a fully developed RBC. In a normal person with normal red cells and
normal bone marrow the reticulocyte count will range from 0.5 to 1.5% (1/120 of RBCs
replaced daily). Thus, the reticulocyte count is a sensitive method to detect how rigorous
the bone marrow is producing new RBCs. Two corrections need to be made after the
reticulocyte percentage is obtained before a conclusion can be drawn about the bone marrow.
One, if a patient has decreased numbers of red cells to begin with, then a reticulocyte
count of 0.5 to 1.5% would not be considered an appropriate bone marrow response.
FIGURE 46.5
(See Color Figure 46.5) Reticulocytes. The appearance of young, newly produced red blood cells, reticulocytes,
as seen in the peripheral blood smear that has been stained with new methylene blue.
Because of the fewer number of RBCs present, a reticulocyte percentage within that range
would actually reflect a much smaller absolute reticulocyte number; i.e., two percent of a
hundred cells is less than two percent of a thousand cells. The bone marrow should be
producing more reticulocytes in the setting of anemia. Thus, when reticulocytes are
counted it is important to take into account the degree of anemia present to avoid a
misleading “normal” percentage of reticulocytes. Dividing the patient’s hematocrit or
hemoglobin by the normal hematocrit or hemoglobin does this. This gives us the fraction
of normal red cells the patient has. That fraction is then multiplied by the reticulocyte
count giving us the corrected reticulocyte count.
Second, the faster the bone marrow is producing reticulocytes, the younger they are
when they are released into the peripheral blood. When the reticulocytes are counted on
the special stain, both older reticulocytes and younger reticulocytes are counted. Therefore,
adjustments for this can be made when calculating a patient’s reticulocyte index (Color
Figure 46.6). The corrected reticulocyte count is divided by the number of days the
reticulocyte lives in the peripheral blood. This number, of course, depends on the degree
of anemia. The more severely anemic someone is, the earlier the reticulocyte is pushed
into the peripheral blood and the longer it stays as a reticulocyte in the blood. (The usual
number used in the setting of anemia, however, is two.) After these two corrections have
been made to the reticulocyte count, then one has a fair estimate of how well the bone
marrow is able to make new RBCs. In the case of nutritionally caused anemias, the
reticulocyte index will invariably be low (Table 46.6).
Erythropoietin
Erythropoietin, a glycoprotein hormone produced in the kidney in response to tissue
hypoxia, is the major regulator of erythropoiesis. In cases of renal failure the erythropoietin
level may be low, causing anemia, usually normocytic. Measuring the erythropoietin level
may be a useful step in the evaluation of anemia; however, in cases of nutritionally
deficient anemia the level is normal or elevated and is not, therefore, routinely measured.
Symptoms of Anemia
Patients with anemia will often present with similar symptoms regardless of the cause.
Low RBCs decrease the oxygen-carrying capacity of the blood, producing generalized
symptoms (Table 46.7). The severity of the symptoms, however, is directly related to how
rapidly the anemia develops. Anemias that develop rapidly such as in acute bleeding,
Anemias 947
Understanding the Reticulocyte Index
2 1/2 days
2 days in blood
1 1/2 days in blood
1 day in blood
BLOOD in blood
BONE 1 1/2 days
MARROW 2 days
2 1/2 days maturing maturing in
3 days
maturing in bone bone marrow
maturing
in bone in bone marrow
marrow marrow
Hct 45 Hct 35 Hct 25 Hct 15

Normal Mildly anemic Moderately anemic Severely anemic
Patient Hct
Reticulocyte Index = X retic % measured Normal = 0.8-4%
Normal Hct
maturation time in blood (depending on Hct)

(1=normal; 1.5,2,2.5 depending on Hct)
FIGURE 46.6
Understanding the reticulocyte index.
TABLE 46.6
Categorizing Anemias by Reticulocyte Count
Low Reticulocytes High Reticulocytes
Decreased production: Acute blood loss
Fe deficiency Splenic seqestration
B12 deficiency Increased destruction
Folate deficiency (hemolysis)
TABLE 46.7
Symptoms of Anemia
Dyspnea with exertion
Dizziness
Lightheadedness
Throbbing headaches
Tinnitus
Palpitations
Syncope
Fatigue
Disrupted sleep patterns
Decreased libido
Mood disturbances
Difficulty concentrating
TABLE 46.8
Physical Findings in Anemia
Pallor of skin
Pallor of mucous membranes
Mild to moderate tachycardia
Widened pulse pressure
Systolic ejection murmur
Venous hums
Mild peripheral edema
will be more symptomatic than anemias that progress slowly over months to years. The
heart must increase the rate of blood flow to the body to compensate for anemia. This
may precipitate palpitations, shortness of breath, and throbbing headaches. Syncope
occurs with severe anemia due to decreased oxygenation of the brain in the upright
position. Often patients with chronic anemia such as those with sickle cell disease will
maintain a hemoglobin level much lower than normal and have few symptoms, due to
compensation by the body.
Physical Findings
Anemia causes general physical findings independent of the cause of the anemia (Table
46.8). These findings are due to the decrease in hemoglobin; skin and mucous membranes
may be pale and the heart rate may be increased. As in symptoms, the physical findings
may be influenced by the chronicity of the anemia.
Vitamin B 12 Deficiency
Mechanism of Anemia
Erythropoiesis depends on proper nuclear (DNA) and cytoplasmic (RNA and hemoglobin)
maturation. Vitamin B12 (or cobalamin) is important in DNA synthesis. When vitamin B12
is not available, the conversion of homocysteine to methionine is impaired. DNA is not
synthesized properly and megaloblastic anemia ensues.
Etiology of Vitamin B12 Deficiency

The most common cause of vitamin B12 deficiency is not the dietary lack of vitamin B12 but
the inability to absorb the vitamin from food due to a condition known as pernicious anemia.
Normally, vitamin B12 is released from food in the acidic environment of the stomach and
is bound to intrinsic factor formed by the parietal cells of the stomach that allow absorption
in the ileum. In pernicious anemia, the stomach does not make intrinsic factor, and the
vitamin cannot be absorbed. Pernicious anemia is more commonly seen in people of North-
ern European descent, but can be seen in all racial groups. Women are affected more than
men are. A family history of pernicious anemia may indicate increased risk.
Other causes of vitamin B12 deficiency are related to the absorption mechanism (Table
46.9). For example, antibodies to intrinsic factor or to the parietal cells of the stomach may
inhibit proper function. Gastrectomy will result in lack of intrinsic factor. Conditions that
Anemias 949
TABLE 46.9
Causes of Vitamin B12 Deficiency
Pernicious anemia (most common cause)
Gastrectomy
Zollinger Ellison syndrome
Intestinal causes
Ileal resection or disease
Blind loop syndrome
Fish tapeworm
Pancreatic insufficiency
Strict vegetarianism (those who exclude meats, eggs, and milk)
TABLE 46.10
Clinical Features of B12 Deficiency
Megaloblastic anemia
Pallor/icterus
Sore tongue or mouth
Gastrointestinal symptoms
Neurologic symptoms
Finger and toe paresthesias
Disturbance of vibration and position sense
Spastic ataxia — subacute combined degeneration
Somnolence, impairment of taste, smell, vision
Dementia, psychosis, “megaloblastic madness”
Well nourished, generally
interfere with the binding of intrinsic factor to the ileum include Crohn’s disease, ileal
resection, and tropical sprue. The fish tapeworm, Diphyllobothrium latum, competes for
vitamin B12 and can be a cause of deficiency in infected patients. If pancreatic enzymes
are not sufficient to aid in the binding of B12 to intrinsic factor, the absorption will be
impaired. Only very rarely is dietary deficiency of vitamin B12 seen in the United States.
Those cases are usually seen in very strict vegans, those who exclude meats, eggs, and
milk from their diets. The deficiency develops slowly over many years.
The Clinical Features of B12 Deficiency

Full-blown cases of deficiency present with megaloblastic anemia. Sore tongue or mouth
and gastrointestinal complaints can occur. Neurologic effects can be devastating (Table
46.10). Demyelination of nerves leads to axonal degeneration and highly variable clinical
symptoms. Subacute combined degeneration of the spinal cord and cerebral abnormalities
include symptoms of finger and toe paresthesias, disturbance of vibration and position
sense, spastic ataxia, impairment of taste, smell, vision, and even psychosis often referred
to as “megaloblastic madness.” Importantly, the anemia and neurologic effects are not
always seen together. A patient could have severe megaloblastic anemia with no neuro-
logic effects, and vice versa. The mechanism of neurologic effects is poorly understood.
Unfortunately, treatment with vitamin B12 does not always correct the neurologic effects
despite correction of the anemia.
The Hematologic Effects of B12 Deficiency

The nuclear maturation defect results in a macrocytic anemia (Table 46.11). The mean cell
volume is usually greater than 110 fl and can vary depending on the degree of deficiency.
TABLE 46.11
Laboratory Features of B12 Deficiency
Hematologic
Megaloblastic anemia (MCV>110)
Leukopenia and thrombocytopenia
Bone marrow
Megaloblastic appearance
Ineffective erythropoiesis
Biochemical
Serum B12 level is decreased, i.e., <223 pg/ml
Methylmalonic acid is elevated, i.e., >0.4 µmol/L
Homocysteine is elevated, i.e., >14 µm
Marked increase in LDH, i.e., >3000 units/ml (normal 260 U/ml)
Serum folate levels may be elevated
Schilling Test
In vitamin B12 deficiency the red cell precursors in the bone marrow are large with
immature nuclei, megaloblastic. Ineffective erythropoiesis (destruction of RBC precursors
in the marrow) can be quite significant and is responsible for the elevated indirect bilirubin
level and high lactate dehydrogenase (LDH). In fact, up to 90% of the red cells may actually
be destroyed in the bone marrow before being released to the peripheral blood as com-
pared to the 10 to 15% seen in normal subjects. Furthermore, the white cell and platelet
lineages are affected, and the hematologic picture is often one of pancytopenia.
The Laboratory Diagnosis of B12 Deficiency

The serum vitamin B12 level reflects the vitamin stores in the body and is the standard
method in determining vitamin B12 deficiency usually ranging from 200 to 1000 pg/ml.
Some conditions such as folic acid deficiency, pregnancy, oral contraceptive use, multiple
myeloma, and possibly antibiotic therapy can cause falsely low vitamin B12 levels. Because
it is important to differentiate true B12 deficiency from folic acid deficiency, the serum
methylmalonic acid level and serum homocysteine level can be measured (Table 46.12).
While the homocysteine level may be elevated in both vitamin B12 deficiency and folate
deficiency due to interruption of the formation of succinyl CoA, methylmalonic acid will
be elevated only in vitamin B12 deficiency because it utilizes vitamin B12 to form methion-
ine, a process not dependent on folate.
TABLE 46.12
The Laboratory Difference between Negative Nutritional Balance
and True Folate and B12 Deficiency
Serum RBC Serum Serum Serum
Lab Value Folate Folate B12 HCYS MMA
Condition
Negative folate balance ⇓ NL NL NL NL
Folate deficiency ⇓ ⇓ NL ⇑ NL
Negative B12 balance NL NL NL NL NL
B12 deficiency NL/⇑ NL/⇓ ⇓ ⇑ ⇑
Combined deficiency ⇓/NL ⇓ ⇓ ⇑ ⇑
HCYS = Homocysteine
MMA = Methylmalonic acid
Anemias 951
TABLE 46.13
Treatment of B12 Deficiency
Standard dose is 1000 µg intramuscularly
Anemia only: 1000 µg daily for a week, then weekly until Hgb normalizes; maintenance dose is 1000 µg monthly
Neurologic deficits: 1000 µg daily for two weeks, then weekly until Hgb normalizes followed by twice a month
for 6 months, then monthly for life
If injections are not an option, oral dose is 1000 µg daily
For the rare case of decreased oral intake from malnutrition, replacement of 50 µg daily is adequate
The Schilling Test

Once vitamin B12 deficiency is diagnosed, the cause can be determined by the Schilling
Test. The test will differentiate between dietary deficiency, absence of intrinsic factor, and
ileal malabsorption. The test consists of two parts: the first part involves administering
radiolabeled cobalamin orally to the patient. The urine is collected for 24 hours and
radioactivity is measured. If at least 7.5% of the oral dose is excreted in the urine, this
means that the patient was able to absorb the vitamin and subsequently excrete the unused
amount in the urine. However, if less than 7.5% of radiolabeled cobalamin is excreted in
the urine, this means that the vitamin was not absorbed adequately. These patients go on
to part two of the test: patients are given the radiolabeled cobalamin orally again. This
time they are also given intrinsic factor. The urine collection is repeated. If the excretion
is above 7.5% this time, this means that the addition of intrinsic factor corrected the
absorption and the patient has pernicious anemia. If the urine excretion is still less than
7.5%, this points to a problem with absorption such as sprue or intrinsic factor receptor
abnormalities. Before the test, all patients are given a dose of unlabeled vitamin B12
intramuscularly to saturate the cobalamin receptors in the tissues and plasma. This way,
the body will absorb and then excrete the unused radiolabeled cobalamin and the test
will be valid.
Nutritional Requirements of Vitamin B12 and Treatment

The normal total body pool of vitamin B12 is 3000 µgs. The daily dietary requirement is
approximately 1 µg. The recommended daily allowance is 2 µg, and the average daily diet
contains 5 to 15 µg a day (ranging from 1 to 100 µg a day). Thus it is very difficult to
become vitamin B12 deficient based on poor diet alone. When deficiency is present the
treatment requires only 1 µg of B12 a day; however, in the setting of neurologic deficiencies,
higher doses are often given. The standard maintenance dose is 100 µg intramuscularly
each month after an initial loading dose is given (Table 46.13).
Folate Deficiency
Mechanism of Anemia
Like vitamin B12, folate is utilized in the synthesis of DNA in the nucleus. The deficiency
of folate causes megaloblastic anemia due to the arrested nuclear maturation. The main
function of folate in the biochemistry of hematopoiesis is the transfer of carbon groups to
various compounds. The most important compounds formed by this carbon donation are
TABLE 46.14
Causes of Folate Deficiency
Decreased nutritional intake
Poverty
Old age
Alcoholism/ cirrhosis
Children on synthetic diets
Goat’s milk anemia
Premature infants
Hemodialysis
Hyperalimentation
Nontropical sprue (gluten-sensitive enteropathy)
Tropical sprue
Congenital folate malabsorption
Other small intestine disease
Pregnancy
Increased cell turnover (chronic hemolysis, exfoliative dermatitis)
Drug induced
Alcohol
Trimethoprim and Pyrimethamine
Methotrexate
Sulfasalazine
Oral contraceptives
Anticonvulsants
the purines, dTMP and methionine. As explained above, methionine formation also
requires vitamin B12. Without vitamin B12, methionine is not formed and the prospective
folate cannot be recycled, causing a “folate trap.” Thus, vitamin B12 deficiency can also
give a laboratory picture of folate deficiency.
Etiology of Folate Deficiency

Unlike vitamin B12 deficiency, nutritional factors play the major role in folate deficiency
(Table 46.14). This is seen most commonly in the elderly, the poor, or in alcoholics. Financial
reasons, poor nutritional education, and excessive alcohol consumption prohibiting good
dietary habits all contribute to the development of folate deficiency. States such as preg-
nancy or hemolysis, which increase the requirements of folate, will often precipitate a
folate deficiency. Drugs can interfere with the recycling of folate by interfering with
enzymes necessary to transfer carbon groups to folate. These include methotrexate, some
anticonvulsants, and oral contraceptives. Malabsorption of folate, while unusual, is seen
in cases of sprue. Bacterial overgrowth in the intestine may utilize the folate before it can
be absorbed, such as in blind loop syndrome.
Clinical Features of Folate Deficiency

Unlike patients with vitamin B12 deficiency, patients with folate deficiency are more apt
to appear malnourished. While the neurologic deficits described above due to vitamin B12
deficiency are not seen in folate deficiency, patients with folate deficiency commonly
complain of poor sleep, irritability, and depression, and may appear to have a blunted
affect (Table 46.15). Folate-deficient patients may also have other nutrient deficiencies such
as vitamins A, D, and K, and protein/calorie malnutrition. These concomitant deficiencies
may contribute to skin pigmentation changes, sores at the corners of the mouth (angular
cheilosis), and pallor such as lemon-tinted skin.
Anemias 953
TABLE 46.15
Clinical Features of Folate Deficiency
Blunted affect/ mask-like facies
Depression
Irritability
Forgetfulness
Sleep deprivation
Weight loss from underlying GI disease
Diffuse blotchy brownish skin pigmentation in nail beds/ skin creases
Poor nutritional state
Pallor/icterus from anemia
TABLE 46.16
Laboratory Diagnosis of Folate Deficiency
Red blood cell folate level is reduced
Serum folate level may be reduced but this is not specific; it may also be elevated,
depending on the recent folate intake
Serum B12 level is normal
The Hematologic Effects of Folate Deficiency

Macrocytosis and megaloblastosis due to folate deficiency are essentially identical to that
seen in vitamin B12 deficiency.
The Laboratory Diagnosis of Folate Deficiency

The serum folate level reflects only the recent dietary intake of folate and does not provide
an accurate assessment of folate stores (Table 46.16). The RBC folate level is low in true
folate deficiency. The serum folate level will fall early in dietary restriction, and in true
deficiency the red cell folate levels will fall. In vitamin B12 deficiency, the folate is trapped
in the unconjugated form as described above, leading to a loss of folate in the RBC. Thus,
vitamin B12 deficiency may give a falsely low RBC folate value, but the serum folate will
be normal to increased. Serum homocysteine, the precursor to methionine, will be elevated
in folate deficiency as it is in B12 deficiency. The methylmalonic acid, however, will be
normal in folate deficiency.
Nutritional Requirements of Folate and Treatment

The total body pool of folate stores is 5 to 10 mg. The daily dietary requirement is 50 µg/
day and the recommended daily allowance is 200 µg/day for men and 180 µg/day for
women. The average daily diet contains 225 µg/day of folate. Foods rich in folate include
green leafy vegetables, liver, kidney, fruits, dairy products, and cereals. Because the most
common cause of folate deficiency is decreased nutritional intake, treatment is folate
supplementation given in one-mg tablets daily (Tables 46.17 and 46.18).
TABLE 46.17
Treatment of Folate Deficiency
Dose is 1-5 mg orally, daily
Pregnancy maintenance dose is 1 mg daily
TABLE 46.18
Causes for Treatment Failure
Wrong diagnosis
Additional vitamin and/or mineral deficiency (concomitant B12
and folate, for example)
Additional iron deficiency
Additional hemoglobinopathy (sickle cell disease or thalassemia)
Associated anemia of chronic disease
Hypothyroidism
TABLE 46.19
Who Should Receive Prophylaxis for B12 and Folate Deficiency?
Vitamin B12
Infants of mothers with pernicious anemia

Strict vegetarians
Patients who have had total gastrectomy
Folate
ALL women considering pregnancy (0.4 mg/day orally)

Pregnant women
Breastfeeding women
Premature infants
Chronic hemolytic states/ hyperproliferative states
Patients receiving methotrexate for a rheumatologic condition
Certain individuals with hyperhomocysteinemia
Prophylactic Administration of Folate and Vitamin B12

Some patients can be at risk for either folate deficiency or vitamin B12 deficiency. These
patients should receive supplementation prophylactically (Table 46.19). For vitamin B12,
these patients include those with gastrectomy, very strict vegetarians, and infants born to
mothers with pernicious anemia, because of the possibility of placental transfer of parietal
cell or intrinsic factor antibodies. Folate prophylaxis should be given to pregnant women
and women considering pregnancy to prevent neural tube defects. Breastfeeding women
and premature infants should also receive folate. Patients with chronic hemolytic states
such as sickle cell disease should receive folate as well as patients receiving chronic meth-
otrexate for rheumatologic conditions, as the methotrexate inhibits dihydrofolate reductase,
creating a form of “folate trap.” Certain individuals with hyperhomocysteinemia may
benefit from prophylactic folate administration, because a concomitant folate deficiency
would create an exacerbation of the homocysteinemia due to the inhibition of methionine
synthesis. Elevated homocysteine levels increase the risk of coronary artery disease.
Iron Deficiency Anemia

Mechanism of Anemia
Every cell in the body requires iron. The cells utilize iron in oxidative metabolism, growth,
and cellular proliferation as well as in oxygen transport. The major portion of body iron
Anemias 955
is found in hemoglobin. Heme is the component of hemoglobin that binds the iron, thus
other heme-containing compounds including myoglobin and enzymes also contain iron.
Hemoglobin accounts for 85% of all the heme-containing compounds in the body. Iron
exists in the body bound to proteins, both in storage and in heme compounds and enzymes
(Hb, myoglobin, and cytochrome). Unbound iron is toxic, primarily by generating reactive
oxygen species.
Iron is absorbed from the duodenum and transported via transferrin to tissues such as
RBC precursors. When not immediately utilized, the iron is stored mostly in the liver in
the form of ferritin. During erythropoiesis iron is incorporated in the hemoglobin, where
it functions as the transporter of oxygen. When senescent red cells are destroyed in the
reticuloendothelial system, macrophages of the spleen and liver take up the iron and
recycle it to transferrin to be transported back to the bone marrow.
While vitamin B12 and folate are used in DNA synthesis in red cell precursors, iron is
utilized in cytoplasmic hemoglobin synthesis. Heme requires adequate iron and porphyrin
metabolism for formation. Defective porphyrin metabolism (sideroblastic anemia) some-
times responds to pyridoxine treatment; however, the cause of anemia is not due to a
nutritional deficiency of pyridoxine but to inherent enzyme mutations disrupting normal
porphyrin metabolism. Thus, sideroblastic anemia is beyond the scope of this section.
Deficiency of iron creates a cytoplasmic maturation defect while the nuclear maturation
proceeds normally. The result is small (microcytic) cells with poorly hemoglobinized
cytoplasm (hypochromia).
Etiology of Iron Deficiency

Iron deficiency is the most common nutritional deficiency in the U.S. In the late 1800s
young menstruating females were considered fashionable if they were pale and chlorotic,
a state of iron deficiency, though at the time the diagnosis of iron deficiency was not
known. The loss of iron through chronic blood loss such as menses in a young female is
the classic cause of iron deficiency. Any time iron is removed from the recycling process
and lost from the body, iron deficiency can ensue (Table 46.20). Other conditions that
remove iron include pregnancy and lactation. Increased iron requirements occur during
periods of rapid growth such as in childhood. Adult men or menopausal women who are
proven to have iron deficiency must be evaluated for blood loss, such as occurs in occult
colon cancer, for example. Dietary causes of iron deficiency are unusual in developed
countries except among infants, adolescents, and pregnant women, where the iron require-
ments are increased and the diet often compromised. The average adult man consumes
more than adequate iron daily to make up for the normal iron loss. Therefore, in the U.S.,
iron deficiency seen in a patient not falling under one of these categories should be
thoroughly evaluated for blood loss and not just merely treated.
TABLE 46.20
Causes of Iron Deficiency Anemia
Gastrointestinal bleed
Genitourinary bleed
Menses
Repeated blood donation
Growth
Pregnancy and lactation
Poor diets
Intestinal malabsorption
Hookworm/intestinal parasites
Gastric surgery
TABLE 46.21
Clinical Features of Iron Deficiency
Symptoms of anemia
Pagophagia (heavy ice consumption)
Koilonychia (brittle spoon nails)
Blue sclera
glossitis
Angular stomatitis
Postcricoid esophageal web/stricture
(Plummer-Vinson syndrome)
Gastric atrophy
Impaired immunity
Decreased exercise tolerance
Neuropsychological abnormalities
The Clinical Features of Iron Deficiency

Children who develop iron deficiency may demonstrate irritability, memory loss, and
learning difficulties. In adults, iron deficiency can develop slowly, and very low levels of
hemoglobin may be attained before symptoms of anemia develop (Table 46.21). It is not
unusual for a woman to present with hemoglobin of 2 or 3 g/dl with only moderate
symptoms of fatigue or shortness of breath. Blood transfusion in these patients can be
dangerous and should be performed very carefully, and only with one or two units to
avoid congestive heart failure or stroke from rapid increase in intravascular volume and
red cell numbers. Iron deficiency anemia may cause brittle “spoon” nails (koilonychia),
blue-tinted sclera, and a painful tongue (glossitis). Immunity may be impaired due to the
lack of iron needed by white blood cells and the enzymes used in host defense.
Pica is a fascinating manifestation of iron deficiency whereby the appetite is altered and
patients crave unusual things to eat. Classic examples include starch, ice, or clay consump-
tion. Pica in most cases is the symptom of iron deficiency and not the cause. However,
clay inhibits the absorption of iron and may perpetuate the condition. Furthermore, exces-
sive consumption of these items provides for a poor diet in general, thus exacerbating
iron deficiency. In some cultures, pica is practiced as a norm, and in those cases iron
deficiency may be the result of and not the cause of pica.
The Hematologic Effects of Iron Deficiency

As mentioned, the perturbation of cytoplasmic maturation during erythropoiesis
(decreased Hb synthesis due to Fe deficiency) leads to small, underhemoglobinized red
cells (microcytosis and hypochromia). In fact, the MCV can be as low as 50 fl in severe
cases. The reticulocyte index is low. Often cells of various shapes and sizes are released
from the bone marrow. Platelets may increase in iron deficiency and can even exceed one
million (normal being 150 to 400 thousand.) If concurrent folate or vitamin B12 deficiency
exists, then the red cells may not demonstrate the microcytosis as expected due to the
concomitant macrocytosis. However, if folate or vitamin B12 is replaced the cells will
become small.
The Laboratory Diagnosis of Fe Deficiency

Ferritin is the storage compartment for iron in the body; therefore, serum ferritin levels
reflect the state of body Fe stores. A ferritin level of less than 12 µg/dl is diagnostic of
Anemias 957
TABLE 46.22
Laboratory Features of Iron Deficiency
Hematologic
Microcytic anemia
Thrombocytosis
Bone marrow
Normal nuclear maturation
Cytoplasmic abnormalities
Absent iron stores on iron stain
Biochemical
Ferritin level is decreased
Total iron binding capacity is elevated
Iron saturation and serum iron are decreased
iron deficiency. Other laboratory features such as the transferrin level (or the iron-binding
capacity), the serum iron level, and the transferrin saturation are summarized in Table
46.22. If iron stores are low the iron binding capacity will, of course, be elevated reflecting
the vacant binding sites. The transferrin saturation will be decreased. The degree of iron
deficiency present and the resultant hematologic effects is an important concept. By the
time microcytosis is evident, the red cell hemoglobin content is decreased. Before that
stage, however, the body stores of iron will be decreased but the red cell amount of iron
will be maintained. This is why a patient may demonstrate a low ferritin, an elevated
TIBC, and decreased iron saturation, yet have no evidence of anemia. These patients will
develop symptoms of anemia in time if the iron loss is not corrected.
Ferritin is also an acute phase reactant. Thus, conditions such as renal failure, infection,
liver disease, acute or chronic inflammatory states will lead to elevated ferritin levels. In
these cases it may be necessary to ascertain iron stores directly with a bone marrow
aspirate. The bone marrow should demonstrate iron in the interstitium when stained with
an iron stain. If no iron is demonstrated in the marrow, the patient definitely has iron
depletion. Iron deficiency anemia, however, is only diagnosed by the RBC iron studies.
Nutritional Requirements of Iron and Treatment

Adult men have 50 mg of iron per kilogram of body weight; women have 35 mg/kg. The
minimal daily requirement is 1 mg for men and 2 mg for menstruating women. The
recommended daily allowance is 12 mg/d for men and 15 mg/d for women. The average
daily diet contains 6 mg of iron per 1000 kcal of food consumed (10 to 30 mg/day). Foods
rich in iron include red meat. Remember the conditions that increase iron requirements
such as pregnancy, childhood, and chronic blood loss. In pregnancy the daily requirement
may increase to 5-6 mg. For infants the daily requirement is 0.5 mg, and for children 1 mg.
Oral iron replacement is sufficient in the majority of cases of iron deficiency anemia
(Table 46.23). The usual dose is 60 mg of elemental iron administered as 325 mg of iron
sulfate three times a day. The best available is in the ferrous form and heme iron as in red
meat. The reticulocyte response will peak at day 8 to 10 after initiation of treatment, and
the hemoglobin should normalize over 6 to 10 weeks. An improved sense of wellbeing
may occur as soon as day 2 or 3 of treatment, however. Often patients complain of
gastrointestinal side effects of oral iron (Table 46.24). These include constipation, diarrhea,
epigastric discomfort, and nausea. Taking the iron with food can ameliorate the symptoms,
though this decreases the absorption as much as 50%. Alternatively, smaller amounts may
be given or different preparations tried. Some other iron formulations (iron-sorbitol) may
be better tolerated in terms of gastrointestinal side effects. On very rare occasions it may
TABLE 46.23
Treatment of Iron Deficiency
Oral
150-200 mg elemental iron a day given in 3 divided doses on empty stomach

(Children’s dose is 3 mg iron/ kilogram body weight per day in 3 divided doses)
Ferrous sulfate is best absorbed and least expensive. One tablet of 325 mg ferrous sulfate contains 60-70 mg of
elemental iron. This given 3 times a day is a good standard treatment for adults. Hemoglobin should rise
approximately 2 grams/dl every 3 weeks. Treatment should continue for 4-6 months after obtaining normal
hemoglobin.
Intravenous
Iron dextran with dose depending on body weight and degree of anemia is the most widely used preparation.
This is a one-time dose calculated from a chart included in the product insert. This solution of ferric
oxyhydroxide and low-molecular-weight dextran contains 50 mg of elemental iron per ml. An average dose
for a 70 kg patient with hemoglobin of 7 g/dl would be 40 ml of iron dextran (2000 mg of elemental iron.)
TABLE 46.24
Possible Side Effects of Iron Therapy
Oral
Constipation
Diarrhea
Nausea
Epigastric discomfort
Vomiting
Intravenous
Anaphylactic reaction (rare)

Fever
Urticaria
Adenopathy
Myalgias
Arthralgias
Phlebitis
Pain at injection site
be necessary to administer intravenous or intramuscular iron. This can be associated with

some untoward side effects, but will eliminate the need for oral iron. Oral iron therapy
should be continued for six months once the hemoglobin is normalized. Parenteral iron
need only be given once. It should be kept in mind that if the cause of the iron deficiency
is blood loss and this continues iron deficiency may recur in the future, and chronic iron
replacement may be indicated (Table 46.25).
Anemias 959
TABLE 46.25
Nutritional Information on B12, Folate, and Iron
B12 Folate Iron
Total body pool 3000 µg 5-10 mg Men: 50 mg/kg
Women: 35 mg/kg
Minimal daily adult 0.3-1.2 µg/day 50 µg/day 10-20 mg/day
Requirement (dietary)
Recommended dietary allowance 2 µg/day Men: 200 µg/day Men: 12 mg/d
(RDA) Women: 180 µg/day Women: 15mg/d
Average daily diet 5-15 µg/day 225 µg/day 6 mg/1000 kcal
(range 1-100 µg/d) (10-30 mg/d)
Prevalence of deficiency 0.2% of population 8% of men in NA 2% adult men
10-13% of women 8% women
Source foods Animal origin Green leafy vegs. Red meat
liver, kidney, liver, kidney
mollusks, muscle, fruits, breakfast cereals,
eggs, cheese, milk dairy, tea
Multivitamins Multivitamins
Time to develop blood signs after 5-6 years 3 weeks Years
abstinence of nutrient
Additional Sources of Information

1. Wintrobe MM. Clinical Hematology, Lippincott Williams & Wilkins, Philadelphia, 1999.
2. Israels LG, Israels ED. Mechanisms in Hematology, Core Health Services Inc., Ontario, 1998.
3. Hoffman R. Hematology, Churchill Livingstone, New York, 1995.
4. Hercberg S, Galan P. Nutritional anemias, Clinical Haematology, Vol. 5, Fleming AF, Ed, Bailliere
Tindall, London, 1992, pp 143-168.
5. Hughes-Jones NC, Wickramasinghe SN. Lecture Notes on Haematology, Blackwell Science,
London, 1996.
6. Foucar K. Bone Marrow Pathology, ASCP Press, Chicago, 1995.
7. Jandl JH. Blood, Little, Brown, Boston, 1987.
8. Duffy TP. Normochromic, normocytic anemias, Cecil Textbook of Medicine, 20th ed, Bennett JC,
Plum F, Eds, WB Saunders, Philadelphia, 1996, p 837.
9. Duffy TP. Microcytic and hypochromic anemias, Cecil Textbook of Medicine, 20th ed, Bennett
JC, Plum F, Eds, WB Saunders, Philadelphia, 1996, p 839.
10. Allen RH, Megaloblastic anemias, Cecil Textbook of Medicine, 20th ed, Bennett JC, Plum F, Eds,
WB Saunders, Philadelphia, 1996, p 843.
47
Nutritional Treatment of Blood Pressure:
Nonpharmacologic Therapy
L. Michael Prisant
Blood pressure is a continuous variable, like temperature and heart rate.1 The level of
blood pressure gradually increases from birth to age 18 years. The dividing line between
a normal and an abnormal blood pressure is arbitrary. However, there is a continuous
relationship between the level of blood pressure and various cardiovascular events, includ-
ing myocardial infarction, strokes, congestive heart failure, renal failure, and mortality.
An optimal blood pressure is a systolic blood pressure less than 120 mmHg and diastolic
blood pressure less than 80 mmHg. Hypertension is defined by the average of multiple
measurements with either a systolic blood pressure ≥140 mmHg or a diastolic blood
pressure ≥90 mmHg.
The hallmark of hypertension is an elevated systemic vascular resistance. Hypertension
may be caused by various adrenal tumors producing cortisol, aldosterone, and norepi-
nephrine, hyperthyroidism, hypothyroidism, hyperparathyroidism with increased par-
athormone and calcium, acromegaly with increased growth hormone, renal failure, renal
artery stenosis resulting in renal ischemia and increased renin, and various drugs that
cause salt and water retention, increase renin, or activate the sympathetic nervous system.
The majority of patients with arterial hypertension do not have a known cause.
Why the prevalence of essential hypertension increases with aging and what causes it
remain an enigma. It is likely that what is called essential hypertension may be the result
of diverse causes. Multiple factors alter the level of blood pressure. The sympathetic
nervous system is important for modifying the tone of blood vessels. Circulating renin,
angiotensin, aldosterone, norepinephrine, and endothelin are vasoconstrictors. The kidney
is necessary to regulate sodium excretion and volume. Endothelial damage due to abnor-
mal lipids, glucose intolerance, tobacco use, hyperhomocystinemia, hyperinsulinemia, and
circulating vasoconstrictors is less responsive to local endogenous vasodilators such as
nitric oxide. Essential hypertension is not a homogenous disease state; it is likely a poly-
genic trait.
Hypertension affects 24% of the U.S. adult population. Since essential hypertension
accounts for 90 to 95% of all causes and the prevalence increases with each decade of life,
there is an interest in the role of nutrients and foods for both the etiology and treatment
of hypertension. A primary preventive approach is advocated by some epidemiologists
and researchers.
0-8493-2705-9/01/$0.00+$1.50
Nutrients and Blood Pressure

Sodium
A large body of data relates salt intake to the level of blood pressure. In a study of
chimpanzees that normally eat a fruit and vegetable diet (low sodium and high potassium
intake), half had salt (up to 15 g/d) added gradually to their diet over 20 months.2 Sodium
chloride resulted in a blood pressure increase of 33/10 mmHg, which could be reversed
within six months of removing sodium chloride from the diet. Similar studies have con-
vinced the medical community that salt may be responsible for the higher prevalence of
hypertension in modern society compared to more primitive communities. However,
sodium may not be the sole culprit. Studies suggest that the chloride anion with sodium
is necessary for an increase in blood pressure, since giving sodium with other anions does
not increase blood pressure.3,4
The INTERSALT (International Study of Salt and Blood Pressure) Cooperative group
examined 10,079 men and women aged 20 to 59 by urine sodium excretion and blood
pressure at 52 centers throughout the world.5 The average intake of sodium was 100 to
200 mmol (6 to 12g NaCl or 2.5 to 5g sodium). The relationship of sodium excretion and
systolic blood pressure correlated positively in 33 of 52 centers after correcting for age,
gender, body mass index (BMI), alcohol consumption, and urine potassium excretion, but
was significant in only eight centers. Negative correlations were observed in 19 centers.
For the entire cohort, the adjusted effect of sodium for systolic blood pressure was 2.17
mmHg per 100 mmol 24 hour sodium excretion (p<0.001). There was not a significant
adjusted effect for diastolic blood pressure. Among the centers with a low BMI (21.8 kg/
m2) and a low sodium intake (26.7 mmol), the mean prevalence of hypertension was 1.7%.
For the sites with a low BMI (22.2 kg/m2) but with a high sodium intake (187.7 mmol),
the prevalence of hypertension was 11.9%.6 Alternatively, the Scottish Heart Health Study
of 7354 men and women aged 40 to 59 years reported a weak positive correlation of
urinary sodium excretion and either systolic or diastolic blood pressure.7 The correlation
was not significant after adjustment for age, BMI, alcohol consumption, and urinary
potassium excretion.
The implication of INTERSALT is that if the population reduces daily sodium intake by
100 mmol or 1 teaspoon of salt per day, systolic blood pressure would decrease 2 to 3
mmHg.6 This could have the potential to reduce coronary deaths by 4 to 5%, stroke deaths
6 to 8%, and total mortality by 3 to 4%. The impact would be greater over a lifetime for
a whole population, reducing total, coronary, and stroke mortality by 13, 16, and 23%,
respectively. The public policy sodium intake goal is 6 g per day.8
Not every person’s blood pressure increases with salt. Salt-sensitivity refers to those
individuals whose blood pressure increases with increased salt intake and decreases with
reduced salt intake. Up to 50% of hypertensives may be salt sensitive. The blood pressure
response to sodium chloride is determined by genetic and environmental factors. African
Americans, obese patients, low-renin hypertensives, chronic renal insufficiency patients,
and the elderly may benefit more than other groups by reducing sodium intake.
To assess the impact of sodium chloride on blood pressure, trials have been conducted
either by restricting or supplementing sodium to the diet. Sodium supplementation trials
are conducted less commonly (Table 47.1).9 In the Study of Sodium and Blood Pressure,
normotensive subjects participated in a trial, using a placebo or 96 mEq sodium capsules
in 4-week treatment periods separated by a 2-week washout period.9 Overnight urinary
sodium excretion decreased 51 mEq/8 hr from baseline to 9 mEq/8 hr after the low sodium
Nutritional Treatment of Blood Pressure: Nonpharmacologic Therapy 963
TABLE 47.1
Randomized Double-Blind Trials of Sodium Supplementation
Sodium Effect
Group on Pressure ∆
Differences Systolic/∆
in Na+ Excretion Diastolic
Author, Year Study Group Design n (mEq/24 hr) (mmHg)
Australian National Hypertensive Parallel 103 43 +4.8/+2.8
Committee, 1989
Dodson, 1989 Hypertensive Parallel 9 76 +9.7/+5.1
Type 2 Diabetes
McCarron, 1997 Hypertensive Crossover 99 55 +4.9/+2.9
MacGregor, 1982 Hypertensive Crossover 19 146 +10/+5
MacGregor, 1989 Hypertensive Crossover 20
High intake 141 +16/+9
Moderate intake 59 +8/+4
Mascioli, 1991 Normotensive Crossover 48 60 +3.6/+2.3
Palmer, 1989 Elderly Crossover 7 — +11.0/+8.6
Watt, 1983 Hypertensive Crossover 18 56 +0.5/+0.4
Updated and modified from Mascioli et al., Hypertension 17: 121; 1991.
diet run-in period, before treatment periods were initiated. Differences in systolic and
diastolic blood pressure between sodium and placebo treatment periods were significant.
Sodium excretion increased +20.4 mEq/8 hr (p < 0.001). An increase of systolic and diastolic
blood pressure with the salt capsules was experienced by 65 and 69% of study participants.
A number of meta-analyses have sought to summarize the impact of sodium restriction
on blood pressure.10-15 One meta-analysis of 2635 subjects with 32 randomized trials on
sodium reduction required random allocation, no confounding variables, an objective
measure of a change in sodium intake (i.e., urine sodium excretion), and no adolescents,14
updating an earlier analysis by the same authors.11 The individual studies are listed in
Tables 47.2 and 47.3. The largest meta-analysis of 4294 subjects included 58 trials of
hypertensive and 56 trials of normotensive persons.15 The mean reduction of blood pres-
sure by sodium restriction in hypertensive individuals was –3.9/–1.9 mmHg (p <0.001 for
both) and in normotensives was –1.2/–0.26 mmHg (p <0.001 for systolic only). Tables 47.4
and 47.5 provide a comprehensive list of the trials used in that meta-analysis. The authors
conclude that the cumulative blood pressure-lowering effect of individual sodium restric-
tion trials in both normotensive and hypertensive populations has been stable since 1985.
Future trials are unlikely to change the average treatment effect noted above.
The reduction of sodium intake for primary prevention as well as nonpharmacologic
treatment of hypertension has become controversial in recent years.16-18 In one study, 2937
hypertensive men provided 24-hour urine collections for sodium determination off med-
ication for 3 to 4 weeks.16 After 3.8 years of average followup, 117 cardiovascular events
(including 55 myocardial infarctions) occurred. There was an inverse relationship between
baseline urinary sodium excretion and myocardial infarction rate. A recent meta-analysis
indicated that renin, aldosterone, norepinephrine, total cholesterol, and low-density lipo-
protein cholesterol increases with sodium restriction.15 Other hazards of moderate sodium
restriction suggested include a potential increase in blood pressure in 15% of patients,
increased sympathetic activity and sleep disturbances, the potential of simultaneous
restriction of grain products, meat, poultry, and fish, and dairy products (which contain
50% of sodium intake), decreased iodine intake, decreased susceptibility of the elderly to
respond to blood loss or heat stress, the potential for fetal growth retardation during
pregnancy, and unknown effects of alternative food preservatives.19
964
TABLE 47.2
Descriptive Summary of Sodium-Reduction Trials in Normotensive Subjects*
Duration ∆ Urinary Na (No)¶ Changes in ∆ Systolic ∆ Diastolic
Author , Year n (mo) Blinding mmol/24 h Confounders mm Hg mm Hg
Crossover Trials
Skrabal, 1981 20 0.5 NR –170 Wt (K) –2.7 –3.0

Cooper, 1984 113 2 BP obs –68 Wt, (K) –0.6 –1.4
Watt, 1985 (H) 35 1 DB –74 (Wt), K –1.4 1.2
Watt, 1985 (L) 31 1 DB –60 (Wt), K –0.5 1.4
Teow, 1985 9 0.5 BP obs –210 (Wt), K –0.6 –2.7
Myers, 1989 172 1 BP obs –130 (Wt), (K) –3.5† –1.9†
Hargreaves, 1989 8 0.5 DB –106 (Wt), (K) –6 .0† –3.0†
Mascioli, 1991 48 1 DB –20.2/8h NR –3.6† –2.3†
Parallel Trials‡
Puska , 1983 19, 19‡ 0.5 BP obs –117 Wt, K, Alc, (P:S) –1.5 –1.1
HPT, 1990 174, 177 36 BP obs (RZ) –16 (Wt), K 0.1 0.2
Cobiac, 1992 26, 28 1 DB –71 (Wt), (K) –1.7 0.8
TOHP, 1992 327, 417 18 BP obs (RZ) –44 (Wt), (K), (Ca), –1.7† –0.9†
(mg), (alc), (fat)
Nestel, 993 (Females) 15, 15 6 DB –94 (Wt), (K) –6.0† –2.0†
Nestel, 993 (Males) 17, 19 6 DB –76 (Wt), (K) –2.0† –1.0†
* NR, not reported; Wt, body weight; K, potassium excretion; BP obs, observers blinded; H, high blood pressure; L, low blood
pressure; DB, double blind; Alc, alcohol intake; P:S, ratio of polyunsaturated to saturated fat; HPT, Hypertension Prevention
Trial; RZ, random zero manometer; TOHP, Trials of Hypertension Prevention Collaborative; Ca, calcium intake; Mg, magnesium
intake; fat, fat intake.
† p < 0.05.
‡ values are the number of subjects in the sodium-reduction treatment and control groups, respectively.
¶ Parentheses denote controlled factors; no parentheses denotes possible confounders
Modified from Cutler.11 Reproduced with permission from Am J Clin Nutr, 1997; 65(2):643S-651S. Copyright Am. J. Clin. Nutr.,
American Society for Clinical Nutrition.
TABLE 47.3
Descriptive Summary of Sodium-Reduction Trials in Hypertensive Subjects*
Duration ∆ Urinary Na (No)¶ Changes in ∆ Systolic ∆ Diastolic
Author , Year n (mo) Blinding mmol/24 h Confounders mm Hg mm Hg
Crossover Trials
Parijs,1973 15 1 NR –98 (Wt) –6.7 3.2
MacGregor, 1982 19 1 DB –76 Wt, (K) –10.0† –5.0†
Watt,1983 18 1 DB –56 (Wt), (K) 0.5 –0.3
Richards, 1984 12 1–1.5 NR –105 (Wt), K –5.2 –1.8
Grobbee, 1987 40 1.5 DB –72 (Wt), (K) –0.8 –0.8
MacGregor, 1989 20 1 DB –82 (Wt), (K) –8 .0† –5.0†
Dodson,1989 9 1 DB –76 (Wt), (K) 9.7† –5.1
ANHMRC,1989 88 2 DB –67 (K) –2.6† –2.1†
Benetos, 1992 20 1 DB –78 (Wt), (K), (Ca) –6.5† –3.7†
Parallel Trials‡
Morgan, 1978 31, 31‡ 24 BP obs –27 NR –1.5† –6.9†
Morgan,1981 6, 6 2 BP obs –98 K NR –6.02

Morgan, 1981 6, 6 2 BP obs –78 K NR –4.0
Costa, 1981 20, 21 12 NR NR§ NR –18.3† –5.9†
Silman, 1983 10, 15 12 BP obs (RZ) –53 (Wt), (K) –8.7 –6.3
Puska, 1983 15, 19 1.5 BP obs –117 Wt, K, Alc, (P:S) 1.8 0.5
Fagerberg, 1984 15, 15 2.3 NR –89 (Wt), (K), (Alc) –13.3† –6.7†
Maxwell,1984 18, 12 3 NR –171 Wt –2.0 2.0
Erwteman,1984 44, 50 6 BP obs (RZ) –58 NR –2.7 –3.4†
Chalmers,1986 48, 52 3 NR –54 (K) –5.1† –4.2†
Logan,1986 37, 38 6 BP obs –32 Wt, (K) –1.1 –0.2
Dodson, 1989 17, 17 3 BP obs –59 (Wt). (K) –13.0† –1.8
Nutritional Treatment of Blood Pressure: Nonpharmacologic Therapy
ANHMRC, 1989 50, 53 2 DB –71 (Alc) –5.5† –2.8†

Sciarrone, 1992 46, 45 2 DB –84 (Wt), (K) –6 .0† –1.0
Parker,1990, low EtOH, 16, 15 1 DB –80 (Wt), (Alc), (K), (Ca), (Mg) 2.2 0.5
Parker ,1990, norm EtOH 15, 13 1 DB –52 (Wt), (Alc), (K), (Ca), (Mg) –0.1 0.8
* NR, not reported; Wt, body weight; DB, double blind; K, potassium intake/excretion: ANHMRC, Australian National Health and Medical Research Council;
Ca, calcium intake/excretion; BP obs, observers blinded: RZ, random zero manometer; Alc, alcohol intake; P:S, ratio of polyunsaturated to saturated fatty
acid; Mg, magnesium excretion.
† p < 0.05.
‡ n values given for each study are the number of subjects in the sodium-reduction treatment and control groups, respectively.
§ –23% intracellular Na.
¶ Parentheses denote controlled factors; no parentheses denotes possible confounders
Modified from Cutler.11 Reproduced with permission from Am J Clin Nutr, 1997; 65(2): 643S-651S. Copyright Am. J. Clin. Nutr., American Society for Clinical
965
Nutrition.
966
TABLE 47.4
Characteristics of Trials of Sodium Restriction and Blood Pressure in Normotensive Populations*
Cum Effect Effect Cum. Cum Z Z
Author, Year Design Dur. N Age NU SR SR SBP DBP SBP DBP SBP DBP
Sullivan, 1980 Op, CO 4 27 29 1 146 146 –7.1 –1.1 –7.1 –1.1 –2.2 –0.4
Skrabal, 1981 Op, CO 14 20 23 1 150 147 2.7 3.0 –2.7 0.7 –1.0 0.4
Myers, 1982 Op, CO 14 136 39 1 130 133 3.3 2.7 2.4 2.4 1.1 2.2
Puska, 1983 SB, P 72 38 40 3 90 123 1.5 2.1 2.4 2.2 1.1 2.2
Cooper, 1984 SB, CO 24 59 16 1 55 111 1.4 3.4 2.0 3.5 1.6 3.0
Cooper, 1984 SB, CO 24 54 16 1 72 107 –0.3 –0.7 1.3 2.7 1.3 2.6
Skrabal, 1984 Op, CO 14 30 23 1 137 109 –1.4 –0.8 1.2 2.3 1.0 2.2
Skrabal, 1984 Op, CO 14 22 23 1 167 113 7.7 4.6 1.5 2.4 1.9 2.7
Skrabal, 1985 SB, CO 14 34 23 1 144 115 0.1 0.6 0.9 1.9 1.9 2.8
Skrabal, 1985 SB, CO 14 28 23 1 163 118 5.8 3.3 1.4 2.0 3.3 3.9
Watt, 1985 DB, CO 28 31 23 4 60 114 0.5 –1.4 1.3 1.4 3.4 3.3
Watt, 1985 DB, CO 28 35 22 4 75 111 1.4 –1.2 1.3 0.9 3.7 2.8
Teow, 986 Op, CO 14 9 25 1 200 112 0.6 2.7 1.3 0.9 3.6 2.9
Richards, 1986 SB, CO 4 8 36 4 181 114 2.0 –7.0 1.3 0.9 3.5 2.2
Fuchs, 1987 Op, CO 9 6 20 3 99 113 5.8 –3.0 1.3 0.8 3.6 1.9
Fuchs, 1987 Op, CO 9 11 20 3 93 111 1.1 –1.0 1.3 0.8 3.5 1.8
El Ashry, 1987 SB, CO 14 13 24 1 222 111 0.0 4.0 1.3 0.8 3.4 1.9
El Ashry, 1987 SB, CO 14 13 27 1 232 115 0.0 1.0 1.3 0.8 3.3 1.9
Lawton, 1988 Op, CO 6 13 24 1 313 119 2.0 –2.0 1.3 0.8 3.3 1.7
Hargreaves, 1989 DB, CO 14 8 23 2 106 119 6.0 3.0 1.3 0.8 3.4 1.7
Mtabaji, 1990 Op, P 7 30 • 1 272 121 9.0 9.0 1.4 1.0 4.0 2.3
Friberg, 1990 Op, CO 13 10 33 3 117 120 0.0 1.0 1.4 1.0 4.0 2.4
Dimsdale, 1990 Op, CO 5 19 34 2 183 129 –1.4 –4.1 1.2 0.5 3.7 1.6
Dimsdale, 1990 Op, CO 5 23 34 2 178 132 –1.0 –4.4 1.2 0.3 3.6 1.0
HPT, 1990 SB, P 1100 228 40 1 23 125 –0.3 –0.1 1.1 0.3 3.5 0.9
Sharma, 1990 SB, CO 7 15 24 2 192 127 0.9 3.7 1.1 0.3 3.4 1.1
Schmid, 1990 SB, CO 7 9 32 1 190 128 3.0 0.0 1.1 0.3 3.5 1.0
Bruun, 1990 Op, CO 4 10 46 1 341 131 5.0 1.0 1.1 0.3 3.6 1.1
Ruppert, 1991 SB, CO 7 98 35 3 275 179 –0.3 –0.3 1.1 0.3 3.5 1.0
Ruppert, 1991 SB, CO 7 24 36 3 275 190 –6.0 –6.0 0.9 0.1 2.9 0.4
Ruppert, 1991 SB, CO 7 25 46 3 262 198 7.5 7.5 1.0 0.2 3.3 0.9
Sharma, 1991 SB, CO 6 13 25 3 246 198 3.0 –0.5 1.1 0.2 3.6 0.9
Sharma, 1991 SB, CO 6 10 24 3 247 198 6.4 5.9 1.1 0.2 3.7 1.1
Mascioli, 1991 DB, CO 28 48 52 5 70 197 3.6 2.3 1.3 0.4 4.3 1.5
Steegers, 1991 SB, P 140 36 27 5 63 195 –2.0 –2.0 1.3 0.4 4.1 1.4
Cobiac, 1992 DB, P 28 52 66 2 75 194 3.1 2.8 1.3 0.4 4.3 1.8
Cobiac, 1992 DB, P 28 54 67 2 73 192 2.7 –0.6 1.3 0.4 4.4 1.7
TOHP, 1992 SB, P 550 744 43 3 47 135 1.7 0.9 1.4 0.4 4.7 2.0
Burnier, 1993 Op, CO 6 16 29 1 186 136 1.0 –0.5 1.4 0.4 4.7 1.9
Burnier, 1993 Op, CO 6 7 29 1 218 137 1.0 –1.2 1.4 0.4 4.7 1.8
Ruppert, 1993 SB, CO 7 30 46 3 270 146 12.6 5.6 1.4 0.4 5.1 2.3
Ruppert, 1993 SB, CO 7 108 36 3 275 160 1.4 –1.2 1.4 0.4 5.2 2.1
Ruppert, 1993 SB, CO 7 25 35 3 280 165 –5.9 –8.0 1.4 0.3 4.9 1.5
Sharma, 1993 SB, CO 7 16 24 3 224 166 0.8 0.5 1.4 0.3 4.9 1.5
Fliser, 1993 SB, CO 8 8 25 2 190 167 1.3 1.3 1.4 0.3 4.9 1.5
Fliser, 1993 SB, CO 8 8 26 2 181 167 0.6 0.6 1.4 0.3 4.8 1.5
Nestel, 1993 DB, P 42 72 66 4 56 166 2.0 1.0 1.4 0.3 4.9 1.6
Nestel, 1993 DB, P 42 60 65 4 73 165 6.0 2.0 1.4 0.4 5.1 1.7
Donovan, 1993 SB, CO 5 8 36 1 152 164 2.0 –1.0 1.4 0.4 5.1 1.6
Grey, 1996 DB, CO 7 34 23 1 133 164 –1.0 –1.0 1.4 0.3 5.0 1.5
Feldmann, 1996 DB, CO 7 5 27 1 176 164 –5.0 –5.0 1.2 0.2 4.5 1.1
Schorr, 1996 DB, CO 28 16 64 2 61 162 1.0 0.0 1.2 0.2 4.4 1.0
Miller, 1997 Op, CO 7 12 23 2 182 163 1.0 1.0 1.2 0.2 4.5 1.1
Miller, 1997 Op, CO 7 10 • 2 194 163 –1.0 –1.0 1.2 0.2 4.4 1.1
Schorr, 1997 SB, CO 7 27 25 7 208 163 5.6 5.6 1.3 0.3 4.6 1.3
Schorr, 1997 SB, CO 7 76 25 7 208 165 –2.8 –2.8 1.2 0.3 4.5 1.2
* Dur.: duration of intervention, days; Op: open; SB: single blind; DB: double blind; P: parallel; CO: cross–over; N: number of
persons in trial; Age: mean age of persons in trial; NU: number of urine collections per person per treatment period; SR: sodium
reduction, mmol/24–h; Cum: cumulative; CI: 95% confidence interval of previous column. SBP: systolic blood pressure; DBP:
diastolic blood pressure; Z: summary statistic; •: no data.
Personal Communication from NA Graudal of unpublished data from his manuscript.15
967
968
TABLE 47.5
Characteristics of Trials of Sodium Restriction in Hypertensive Populations*
Cum Effect Effect Cum. Cum Z Z
Author, Year Design Dur. N Age NU SR SR SBP DBP SBP DBP SBP DBP
Parijs, 1973 Op, CO 28 15 41 1 98 98 6.7 –3.2 6.7 –3.2 1.6 –1.2
Mark, 1975 Op, CO 10 6 28 1 305 216 13.1 7.7 9.8 –0.1 2.7 0.4
Morgan, 1978 SB, P 90 62 60 2 23 114 1.0 2.0 6.2 1.2 2.6 0.9
Sullivan, 1980 Op, CO 4 19 27 1 153 121 –1.2 1.2 4.6 1.2 2.2 0.9
Morgan, 1981 SB, P 56 12 38 2 67 106 • 4.0 • 1.9 • 1.1
Morgan, 1981 SB, P 56 12 40 2 92 104 • 8.0 • 3.0 • 1.7
Ambrosioni, 1982 SB, CO 42 25 23 6 60 91 2.2 0.4 3.9 2.6 1.3 1.7
MacGregor, 1982 DB, CO 28 19 49 2 76 89 10.0 5.0 5.4 3.0 2.0 2.2
Beard, 1982 Op, P 84 90 48 3 124 95 5.2 3.4 5.4 3.0 2.2 2.5
Watt, 1983 DB, CO 28 18 52 4 56 92 0.5 0.3 3.6 2.0 2.3 2.5
Silman, 1983 Op, P 90 28 55 4 63 91 –3.5 –0.5 3.5 1.9 2.1 2.4
Puska, 1983 SB, P 72 34 40 3 90 91 –1.8 –0.5 3.3 1.8 2.0 2.3
Koolen, 1984 Op, CO 14 20 41 2 213 97 6.5 4.9 3.4 1.9 2.2 2.5
Richards, 1984 SB, CO 28 12 36 2 100 97 4.0 3.0 3.4 2.0 2.4 2.7
Erwteman, 1984 SB, P 28 94 46 4 58 91 2.7 2.5 3.3 2.0 2.5 2.9
Maxwell, 1984 Op, P 84 30 46 4 161 92 2.0 –2.0 3.3 1.9 2.5 2.8
Fagerberg, 1984 Op, P 63 30 51 4 99 92 3.7 3.1 3.3 2.0 2.6 2.9
Resnick, 1985 Op, CO 5 12 • 1 190 96 3.0 1.0 3.3 1.9 2.7 2.9
Logan, 1986 Op, P 180 86 47 1 43 92 1.1 0.2 3.1 1.9 2.8 2.9
Chalmers, 1986 SB, P 84 100 53 6 70 91 4.8 4.2 3.3 2.3 3.0 3.5
Grobbee, 1987 DB, CO 42 40 24 4 72 88 0.8 0.8 3.1 2.3 3.0 3.5
MacGregor, 1987 DB, CO 30 15 52 2 100 88 13.0 9.0 3.6 2.4 3.6 3.9
Kurtz, 1987 DB, CO 7 5 58 2 217 91 16.0 8.4 4.7 2.6 4.6 4.3
Morgan, 1987 SB, P 60 20 58 5 57 90 6.0 4.0 4.7 2.6 4.5 4.4
Morgan, 1988 SB, CO 14 16 63 1 50 89 3.0 4.0 4.5 2.7 4.7 4.6
Lawton, 1988 Op, CO 6 9 25 1 328 91 1.0 –4.0 4.4 2.6 4.7 4.4
Shore, 1988 SB, CO 5 6 • 5 97 91 9.0 5.6 4.5 2.6 4.8 4.4
ANHMRC, 1989 Op, P 48 103 58 4 63 89 5.5 2.9 4.6 2.7 5.2 4.8
MacGregor, 1989 DB, CO 30 20 57 2 150 91 16.0 9.0 4.8 2.8 5.6 5.2
Dodson, 1989 SB, P 90 34 62 3 44 90 13.0 1.8 4.8 2.8 5.8 5.2
Dimsdale, 1990 Op, CO 5 16 34 2 178 93 6.4 –2.0 4.9 2.7 6.0 5.0
Dimsdale, 1990 Op, CO 5 17 34 2 198 98 0.1 –0.8 4.6 2.6 6.0 4.9
Parker, 1990 DB, P 28 31 50 4 73 97 –1.9 0.1 4.3 2.4 5.8 4.9
Parker, 1990 DB, P 28 28 54 4 49 97 –1.9 –1.8 4.1 2.4 5.6 4.7
Schmid, 1990 SB, CO 7 9 36 1 181 99 6.0 1.9 4.1 2.4 5.7 4.7
Bruun, 1990 Op, CO 4 12 47 1 331 103 8.0 4.0 4.2 2.4 5.8 4.8
Egan, 1991 DB, CO 7 27 39 1 194 106 1.1 1.1 3.9 2.3 5.9 4.8
Carney, 1991 DB, CO 42 11 54 4 102 106 1.0 –1.0 3.9 2.3 5.8 4.8
Singer, 1991 DB, CO 30 21 54 2 91 106 9.0 3.0 4.0 2.3 6.1 4.9
Sciarrone, 1992 DB, P 56 91 54 1 82 104 5.8 0.4 4.0 2.2 6.4 4.9
Benetos, 1992 DB, CO 28 20 42 1 78 103 6.5 3.7 4.1 2.3 6.5 5.1
Del Rio, 1993 DB, CO 14 30 49 1 151 106 1.4 0.5 4.0 2.2 6.5 5.1
Ruilope, 1993 DB, P 21 19 • 1 69 106 4.0 4.0 4.0 2.3 6.4 5.1
Redon-Mas, 1993 Op, P 28 418 55 1 104 105 –1.0 –1.9 3.5 1.6 6.3 4.7
Fotherby, 1993 DB, CO 35 17 73 2 79 105 8.0 0.0 3.6 1.5 6.5 4.7
Buckley, 1994 SB, CO 5 12 49 1 296 106 8.7 8.7 3.7 1.6 6.8 5.0
Jula, 1994 Op, P 365 76 44 3 57 105 6.7 3.8 3.7 1.7 6.9 5.2
Zoccali, 1994 SB, CO 7 15 45 1 163 106 14.0 8.0 3.8 1.7 7.2 5.6
Weir, 1995 SB, CO 14 11 60 5 146 106 9.0 7.0 3.8 1.8 7.2 5.7
Weir, 1995 SB, CO 14 11 60 5 127 106 –4.0 –5.0 3.8 1.7 7.1 5.5
Overlack, 1995 DB, CO 7 11 61 3 240 109 9.9 9.9 3.9 1.8 7.4 5.8
Overlack, 1995 DB, CO 7 27 40 3 249 114 0.8 0.8 3.8 1.8 7.3 5.8
Overlack, 1995 DB, CO 7 8 43 3 234 115 –6.0 –6.0 3.7 1.7 7.1 5.6
Ferri, 1996 DB, CO 14 61 47 2 264 120 7.4 3.5 3.9 1.8 7.6 5.9
Feldmann, 1996 DB, CO 7 8 27 1 178 120 –2.0 –2.0 3.8 1.8 7.4 5.7
Mühlhauser, 1996 DB, P 28 16 36 4 107 120 2.0 0.0 3.8 1.8 7.2 5.5
McCarron, 1997 DB, CO 28 99 52 1 56 119 4.9 2.9 3.8 1.8 7.4 5.7
Cappuccio, 1997 DB, CO 30 47 67 2 83 118 7.3 3.2 3.9 1.9 7.7 6.0
* Dur.: duration of intervention, days; Op: open; SB: single blind; DB: double blind; P: parallel; CO: cross-over; N: number of
persons in trial; Age: mean age of persons in trial; NU: number of urine collections per person per treatment period; SR:
sodium reduction, mmol/24-h; Cum: cumulative; CI: 95% confidence interval of previous column. SBP: systolic blood pressure;
DBP: diastolic blood pressure; Z: summary statistic; •: no data.
Personal Communication from NA Graudal of unpublished data from his manuscript.15
969
Potassium
Intracellular potassium is the major cation responsible for establishing the membrane
potential. The blood pressure of normotensives increases with potassium depletion.20
Observational studies suggest an inverse relationship between potassium intake and blood
pressure.21 Often there is an inverse relationship with dietary potassium and sodium or
a positive relationship between urinary Na+/K+ ratio and blood pressure.5, 21 In the
Scottish Heart Health Study, the relationship between blood pressure and the urinary
Na+/K+ ratio was stronger than the relationship between excretion of either sodium or
potassium individually and blood pressure.7 After adjusting for age, gender, BMI, ethanol
intake, and urinary sodium intake, it was observed in the INTERSALT study that the
systolic blood pressure was 2.7 mmHg lower for each 60 mmol/d higher excretion of
potassium.5 Since African Americans have a lower intake of potassium due to decreased
consumption of fresh fruits and vegetables, this may explain the higher prevalence of
hypertension in blacks compared to whites.21-24 Potassium supplementation (80 mmol/d)
compared to placebo reduced systolic and diastolic blood pressure (–6.9/–2.5 mmHg)
significantly in African Americans consuming a diet low in potassium for 21 days.25
Explanations for the hypotensive effects of potassium include direct vasodilatation, a direct
natriuretic effect, altered baroreceptor function, increased urinary kallikrein, or suppres-
sion of the renin-angiotensin-aldosterone axis or sympathetic nervous system.8
Studies using the Dahl salt-sensitive rat show a protective effect of potassium supple-
mentation, reducing mortality by 93% in the hypertensive rats.26 In a 12-year prospective
population study of 859 older persons, the relative risks of stroke-associated mortality in
the lowest tertile of potassium intake, as compared with that in the top two tertiles
combined, were 2.6 (p = 0.16) in men and 4.8 (p = 0.01) in women.27 A 10-mmol increase
in daily potassium decreased stroke-associated mortality by 40% (p <0.001) in a multi-
variate analysis. In the Health Professionals Follow-up Study, a multivariate analysis
demonstrated the greater the potassium intake, the lower the relative risk of stroke (p =
0.007) (Figure 47.1).28 Furthermore, use of potassium supplements, especially among men
1
1
0.9 0.85
0.78 0.76
0.8
0.7 0.62
0.6
Relative Risk
0.5
of Stroke
0.4
0.3
0.2
0.1
0
2.4 3.0 3.3 3.6 4.3
Median Intake of Potassium (g/d) for Each Quintiles
FIGURE 47.1
Multivariate adjusted relative risk of stroke of 43,738 United States men, 40 to 75 years by quintile of potassium
intake: adjusted for age, total energy intake, smoking, alcohol consumption, history of hypertension and hyper-
cholesterolemia, family history of premature myocardial infarction, profession, body mass index, and physical
activity (p = 0.007 for trend). Derived from Ascherio.28
taking diuretics, was also inversely related to the risk of stroke. However, after further
adjustment for fiber and magnesium intake, the relative risk of stroke was no longer
statistically significant.
The largest meta-analysis (see Tables 47.6 and 47.7) observed a significant reduction in
both systolic and diastolic blood pressure (–4.44/–2.45 mmHg, p <0.01 for both) for oral
potassium supplementation.29 There was a greater decrease in blood pressure (–4.91/–2.71
mmHg, p <0.01 for both) when trials were examined that achieved a net change in urinary
potassium ≥20mmol/d. If trials excluded concomitant antihypertensive drugs, the change
in blood pressure was –4.85/–2.71 mmHg, p <0.01 for both). The change in blood pressure
was lower for normotensives (–1.8/–1.0 mmHg) compared with hypertensives (–4.4/–2.5
mmHg). The change for systolic blood pressure among black subjects was greater than
white subjects (–5.6 mmHg versus –2.0 mmHg, p = 0.03); however, the change for diastolic
blood pressure was not significant (–3.0 mmHg versus –1.1 mmHg, p = 0.19).
Interestingly, there was no overall association between 24-hour urinary potassium excre-
tion and change in systolic or diastolic blood pressure; however, the higher the urinary
sodium excretion at followup (see Figure 47.2), the greater the decline in both systolic
(p <0.001) and diastolic blood pressure (p <0.001).29 This explains the lack of benefit seen
in a study that combined sodium restriction and potassium supplementation in patients.30
This randomized, placebo-controlled, double-blind trial of 287 men assessed the effect of
96 mmol of microcrystalline potassium chloride or placebo on a sodium-restricted diet.
After the withdrawal of their antihypertensive medication at 12 weeks, there was no
significant difference in either systolic or diastolic blood pressure between the two groups
at any point in time up to an average of 2.2 years.30
Calcium
Most body calcium is found in the skeleton. Calcium is important for its role in smooth
muscle relaxation and contraction, especially the vascular smooth muscle that alters
peripheral vascular resistance directly. An inverse relationship between water hardness
and blood pressure has stimulated an interest in the role of calcium supplementation on
blood pressure.31 Paradoxically, data from the first Health and Nutrition Examination
Survey found that daily calcium intake was lower in 1012 hypertensive vs. 8541 normo-
tensive persons (608 mg vs. 722 mg, p <0.01).32 However, it was not associated with blood
pressure when age and BMI were controlled. For 58,218 female nurses with a calcium
intake of at least 800 mg/day, the reduction in the risk of hypertension was 22% when
compared with an intake of less than 400 mg/day.33 In men, calcium was inversely
associated with baseline blood pressure but not with change in blood pressure; further-
more, intake of calcium in men was not inversely associated with an increased risk of
stroke.28,34 Other observational studies have reported both positive and negative correla-
tions with blood pressure, but many studies did not adjust for weight and alcohol, vitamin
D, sodium, and other nutrient intake, and are based on dietary recall.35 Also, it has been
suggested that calcium supplementation is important in African Americans, since intake
of dairy products is especially low and the prevalence of hypertension much higher than
in caucasians. In addition, sodium excretion and calcium intake interact in salt-sensitive
individuals: increased ingested calcium facilitates sodium excretion.36 Calcium supple-
mentation is associated with controversy because of the association of hyperparathyroid-
ism and hypertension, the pressor effect of hypercalcemia in normotensives, and the direct
relationship of calcium and blood pressure.37 However, responders to calcium supplemen-
tation may be a subset of hypertensives with a low renin level, high parathormone level,
and low ionized calcium.36
TABLE 47.6
Participant and Study Design Characteristics in 33 Potassium Supplementation Trials
Study
No. of Age, y Age, y % % % AntiHTN Study Duration,
Author, Year Subjects Mean Range Male White HTN† Medication Design* wk
Skrabal, 1981
(a) 20 ... 21-25 100 ... 0 No XO 2
(b) 20 ... 21-25 100 … 0 No XO 2
MacGregor, 1982 23 45 26-66 52 78 100 No XD 4

Khaw and Thom, 1982 20 ... 22-35 100 ... 0 No XD 2
Richards, 1984 12 ... 19-52 67 ... 100 No XO 4-6
Smith, 1985 20 53 30-66 55 90 100 No XD 4

Kaplan, 1985 16 49 35-66 38 19 100 Yes‡ XD 6
Zoccali, 1985 19 38 26-53 53 100 100 No XD 2
Bulpitt, 1985 33 55 ... 45 ... 100 Yes‡ PO 12
Matlou, 1986 32 51 34-62 0 0 100 No XS 6
Barden, 1986 44 32 18-55 0 ... 0 No XD 4
Poulter and Sever ,1986 19 ... 18-47 100 0 0 No XD 2
Chalmers, 1986
(a) 107 52 ... 85 ... 100 No PO 12
(b) 105 52 ... 86 ... 100 No PO 12
Grobbee, 1987 40 24 18-28 85 ... 100 No XD 6
Siani, 1987 37 45 21-61 62 ... 100 No PD 15
Svetkey, 1987 101 51 ... 74 88 100 No PD 8
Medical Research Council, 1987 484 ... 35-64 56 ... 100 Yes‡ PS 24
Grimm, 1988 312 58 45-68 100 ... 100 Yes‡ PD 12
Cushman and Langford, 1988 58 54 26-69 100 47 100 No PD 10
Obell, 1989 48 41 23-56 44 0 100 No PD 16
Krishna, 1989 10 ... 20-40 100 100 0 No XD 10d
Hypertension Prevention Trial, 391 39 25-49 64 83 0 No PO 3y
1990
Mullen and O’Connor, 1990
(a) 24 25 22-31 100 9 0 No XD 2
(b) 24 25 22-31 100 92 0 No XD 2
Patki, 1990 37 50 ... 22 ... 100 No XD 8
Valdes, 1991 24 50 ... 54 100 No XD 4
Barden ,1991 37 32 ... 0 0 No XD 4d
Overlack, 1991 12 37 25-59 67 ... 100 No XS 8
Smith, 1992 22 67 _ 60 57 71 100 No XD 4d
Fotherby and Potter, 1992 18 75 66-79 28 ... 100 No XD 4
Whelton, 1995 353 43 30-54 72 86 0 No PD 24
Brancati, 1996 87 48 27-65 36 0 0 No PD 3
* XO indicates crossover open; XS, crossover single blind; XD, crossover double blind; PO, parallel open; PS, parallel
single blind; PD, parallel double blind; and ellipses, no data.
† HTN indicates hypertensive, BP indicates blood pressure; SBP, systolic BP; and DBP, diastolic BP. Sitting BP was used
in the studies by Khaw and Thom, Matlou, Poulter and Sever, Chalmers, Svetkey, Grimm, Hypertension Prevention
Trial, Barden, and Overlack.
‡ Study participants were treated with thiazide or thiazide-like diuretics (hydrochlorothiazide [25-75 mg/d] or chlo-
rthalidone [50 mg/d] and in addition, clonidine [0.1 mg twice daily] in 1 subject [Kaplan]; bendrofluazide [2.5-10
mg/d], cyclopenthiazide [25-50 mg/d], hydrochlorothiazide [25 mg/d], furosemide [40-80 mg/d], and chlorthalidone
[50-100 mg/d] [Bulpitt]) ; bendrofluazide [5-10 mg/d] [Medical Research Council]; chlorthalidone or hydrochlorothi-
azide [84%], β-blockers [43%], other medications, e.g., reserpine [6%], hydralazine [6%], and methyldopa [5%] [doses
not specified] [Grimm]).
Table Modified from Whelton, PK.29 Reproduced with permission from May 28, 1997 JAMA 277(20):1624-32. Copyright
1997, American Medical Association.
TABLE 47.6
Participant and Study Design Characteristics in 33 Potassium Supplementation Trials
Baseline Supine Baseline Urinary Baseline
BP, mm Hg† Electrolytes, mmol/d K+
Intervention Control SBP/DBP K+/Na+ mmol/L
200 mmol K from diet, 200 mmol 80 mmol KCl, 200 mmol NaCl ... .../... 4.7
NaCl
200 mmol K from diet, 50 mmol 80 mmol KCI,50 mmol NaCl ... …/... 4.6
NaCl
64 mmol KCl Placebo 154/99 68/152 4.0
64 mmol KCl Placebo 118/74 73/138 ...
200 mmol K from diet, 180 mmol 60 mmol KCI,180 mmol NaCl 140-180/90-105 .../... 3.8
NaCl
64 mmol KCI, 70 mmol NaCl Placebo,70 mmol NaCl 163/103 72/68 3.9
60 mmol KCI Placebo 131/96 46/166 3.0
100 mmol KCI Placebo 154/96 .../... 3.8
64 mmol KCl Usual care 150/95 66/... 3.7
65 mmol KCl Placebo 154/105 62/172 3.8
80 mmol KCl Placebo 118/71 50/131 ...
64 mmol KCl Placebo 113/69 39/123 ...
100 mmol K from diet Normal diet 150/95 71/155 ...

100 mmol K from diet, low Na Low Na 152/95 68/148 ...
72 mmol KCI, low Na Placebo, low Na 143/78 71/141 3.8
48 mmol KCI Placebo 145/92 60/190 4.4
120 mmol KCI Placebo 145/95 .../... 4.4
17-34 mmol KCl Usual care 161/98 .../... 4.2
96 mmol KCI, low Na Placebo, low Na 124/80 79/166 4.2
80 mmol KCl Placebo 150/95 52/176 ...
64 mmol KCl Placebo 174/100 59/171 4.0
90 mmol KCI 10 mmol KCl 120/77 70/164 3.2
100 mmol K from diet, low Na Low Na 124/82 64/161 ...
75 mmol KCI Placebo 117/69 77/153 4.2
75 mmol K citrate Placebo 117/69 77/153 4.2
60 mmol KCl Placebo 155/100 62/196 3.6

64 mmol KCl Placebo 147/96 57/155 3.8
80 mmol KCl Placebo 105/63 53/105 ...
120 mmol K citrate and Placebo 150/100 62/169 4.4
bicarbonate
120 mmol KCI Placebo 152/87 70/192 3.9
60 mmol KCI Placebo 187/96 63/115 4.2
60 mmol KCI Placebo 122/81 59/153 ...
80 mmol KCl Placebo 125/78 47/147 ...
Reproduced with permission from May 28, 1997 JAMA 277(20):1624-32. Copyright 1997, American Medical Association.
TABLE 47.7
Urinary Electrolyte Excretion, Body Weight, and Blood Pressure during Followup in 33 Potassium
Supplementation Trials*
Mean Net Urinary Sodium Mean Net Mean Net Change,
Change in Urinary Excretion during Change in Blood Pressure,
Electrolytes, mmol/d Followup, in Body mm Hg
Author, Year K+/Na+ mmol/d Weight, kg Systolic/Diastolic
Skrabal, 1981
(a) 44/-55 155 -0.9 -1.7/-4.5
(b) 107/-12 28 -0.2 0.4/-0.5
MacGregor, 1982 56/29 169 -0.2 -7.0/-4.0
Khaw and Thom, 1982 52/9 164 ... -1.1/-2.4
Richards, 1984 129/5 200 0.8 -1.9/-1.0
Smith, 1985 50/7 80 0.1 -2.0/0
Kaplan, 1985 46/1 168 0.8 -5.6/-5.8
Zoccali, 1985 81/13 195 ... -1.0/-3.0
Bulpitt et at, 1985 40/10 149 1.2 2.3/4.8
Matlou et at, 1986 62/35 165 -0.4 -7.0/-3.0
Barden et at, 1986 68/5 130 ... -1.4/-1.4
Poulter and Sever, 1986 38/1 114 -0.1 -1.2/2.0
Chalmers et at, 1986
(a) 22/7 150 ... -3.9/-3.1
(b) 12/25 79 ... -1.0/1.6
Grobbee, 1987 57/12 69 0.4 -2.5/-0.6
Siani, 1987 30/6 189 ... -14.0/-10.5
Svetkey, 1987 .../... ... ... 6.3/-2.5
Medical Research Council, 1987 .../... ... ... 0.8/-0.7
Grimm, 1988 80/-9 114 ... 0.7/1.4
Cushman and Langford, 1988 36/177 177 ... .../-0.1
Obel, 1989 39/... 172 ... -41.0/-17.0
Krishna, 1989 47/44 144 -0.6 5.5/-7.4
Hypertension Prevention Trial, 0/-6 155 0.2 -1.3/-0.9
1990
Mullen and O’Connor, 1990
(a) 23/-12 141 -0.1 0/3.0
(b) 34/-15 138 -0.2 -2.0/2.0
Patki, 1990 22/-14 184 ... -12.1/-13.1
Valdes, 1991 68/19 166 -1 -6.3/-3.0
Barden, 1991 72/15 120 ... -1.7/-0.6
Overlack, 1991 105/-13 156 0 2.8/3.0
Smith et at, 1992 109/29 221 0.2 -4.3/-1.7
Fotherby and Potter, 1992 39/13 136 -0.7 -10.0/-6.0
Whelton, 1995 42/6 144 ... -0.3/0.1
Brancati, 1996 70/20 141 -0.1 -6.9/-2.5
* Ellipses indicate no data.
Table Modified from Whelton PK, He J, Cutler JA, et al. Reproduced with permission from May 28, 1997 JAMA
277(20):1624-32. Copyright 1997, American Medical Association.
In a randomized, double-blind study of 48 hypertensive persons and 32 normotensive

persons, 1000 mg per day of calcium or placebo was given for 8 weeks.38 Supine blood
pressure decreased significantly 3.8/2.3 mmHg in the hypertensive subjects; 25, 23, and
13% of subjects achieved a blood pressure goal of systolic <140 mmHg, diastolic <90
mmHg and both systolic <140 mmHg and diastolic <90 mmHg, respectively. Calcium did
not lower blood pressure in the normotensives. 44% of hypertensive and 19% of normo-
tensive subjects lowered their standing systolic blood pressure >10 mmHg. There have
been at least 67 randomized trials of calcium supplements in nonpregnant study popula-
1 0.1
0
-1
-2 -1.2 -1.4
Mean -3 -2.1
Net Change - 4
(mmHg) - 5 Systolic Blood Pressure
-4.7
-6 Diastolic Blood Pressure
-7
-8 -7.3
-9
<140 140-164 ≥ 165
Urinary Sodium During Follow-up
(mmol/d)
FIGURE 47.2
Effect of potassium supplementation on net blood pressure reduction according to urinary sodium excretion
during followup: the greater the sodium excretion, the greater the blood pressure reduction with potassium
supplementation (p <0.001 for both systolic and diastolic blood pressure). Derived from Whelton PK, He J, Cutler
JA, et al. JAMA 277: 1624, 1997. With permission.
tions. There have been several meta-analyses to assess the effect of dietary and nondietary
interventions on blood pressure.35,39-43 A larger effect of calcium supplementation on sys-
tolic blood pressure was observed with increasing age and among women.41 The subgroup
of hypertensive subjects had a greater reduction in blood pressure than the normotensives
(–4.30/–1.50 mmHg versus –0.27/–0.33 mmHg).42 The change in systolic and diastolic
blood pressure was significant for the hypertensives, but not the normotensives.42 The
largest meta-analysis (see Tables 47.8 and 47.9) shows a reduction of blood pressure of
–1.44/–0.84 mmHg (p <0.001 for each).43 There was no difference in the change in blood
pressure comparing 33 nondietary trials (–1.09/–0.87 mmHg) and the 9 dietary trials
(–2.01/–1.09 mmHg). The authors concluded that the small reduction in blood pressure
of calcium supplements does not merit its use in mild hypertension, and further suggest
that the use of calcium must weigh the benefits of reducing cardiovascular disease and
increasing bone density versus the risk of nephrolithiasis.
Despite this modest benefit in nonpregnant subjects, a meta-analysis (see Tables 47.10
and 47.11) of calcium supplementation in pregnancy observed a blood pressure reduction
of –5.40/–3.44 mmHg and a decrease in the rate of preeclampsia (odds ratio = 0.38 [95%
CI: 0.22 to 0.65]).44 Since the publication of the meta-analysis, the National Institutes of
Health sponsored trial, Calcium for Preeclampsia Prevention, has been completed.45 This
placebo-controlled, randomized, multicenter trial assigned 4589 nulliparous women 13 to
21 weeks pregnant to 2 g of calcium carbonate or placebo. There was no benefit in the
rate of preeclampsia (6.9 versus 7.3%), the prevalence of gestational hypertension (15.3
versus 17.3%), or pregnancy-associated proteinuria (3.4 versus 3.3%) in the calcium (n =
2295) and placebo (n = 2294) groups.
Magnesium
Magnesium is a divalent intracellular cation. The adult body contains about 25 g distrib-
uted between the skeleton (60%) and soft tissues (40%).46 It serves as a cofactor for many
enzyme systems. Intracellular calcium increases and blood pressure rises as magnesium
depletion occurs in rats. The hypotensive effect of magnesium is observed best when given
TABLE 47.8
Randomized Controlled Trials Examining the Relationship of Calcium and Blood Pressure
No. of
Subjects Elemental Study
Author, Year, (Intervention/ Quality Calcium Calcium Duration
Study Design Control) Score* Formulation (mg/day) (weeks)
Nondietary Interventions
Belizan, 1983 30/27 4 Calcium gluconate 1000 22

Sunderrajan, 1984cx 17/17 0 Calcium carbonate 1000 4
Johnson, 1985 59/56 2 Calcium carbonate 1500 208
McCarron, 1985cx 80/80 3 Calcium carbonate 1000 8
Grobbee, 1986 46/44 4 Calcium citrate 1000 12
Nowson, 1986 31/33 3 Calcium carbonate 1600 8
Resnick, 1986cx, ci 8/8 0 Calcium carbonate 2000 8
Strazzullo, 1986cx, ci 17/17 3 Calcium gluconate 1000 15
Van Berestyn, 1986 29/29 3 Calcium carbonate 1500 6
Cappuccio, 1987cx 18/18 4 Calcium gluconate 1600 4
Lyle, 1987 37/38 4 Calcium carbonate 1500 12
Meese, 1987cx 19/17 3 Calcium carbonate 800 8
Siani, 1987cx 8/8 4 Calcium gluconate 1000 3
Thomsen, 1987 14/14 3 Calcium gluconate 2000 52
Vinson, 1987 4/5 4 Calcium carbonate 500 7
Zoccali, 1987cx, ci 11/11 3 Calcium gluconate 1000 2
Siani, 1988cx 14/14 5 Calcium gluconate 1000 4
Zoccali, 1988cx 21/21 3 Calcium gluconate 1000 8
Orwoll, 1990ci 34/28 3 Calcium carbonate 1000 156
Tanji, 199lcx 28/28 3 Calcium carbonate 1200 12
Cutler, 1992 237/234 6 Calcium carbonate 1000 26
Lyle, 1992 21/21 3 Calcium carbonate 1500 8
Galloe, 1993cx 20/20 4 Calcium gluconate 2000 12
Jespersen, 1993cx 7/7 5 Calcium carbonate 1000 8
Pan, 1993cx 14/15 1 Calcium citrate and placebo 800 11
Vitamin D
Weinberger, 1993cx 46/46 4 Calcium carbonate 1500 8
Petersen, 1994ci 10/10 1 Calcium gluconate 2000 26
Zhou, 1994 30/27 3 Calcium carbonate 1000 14
Gillman, 1995 51/50 4 Calcium citrate malate 600 12
Sacks, 1995ci 34/31 5 Calcium carbonate 1000 26
Lijnen, 1996ci 16/16 5 Calcium gluconate 2000 16
Davis, 1997 17/17 3 Calcium gluconate 1500 4
Sanchez, 1997 10/10 4 Calcium gluconate 1500 8
Dietary Interventions
Margetts, 1986cx, ci 39/39 3 Other dietary manipulation 1076 6

Rouse, 1986 18/18 3 Other dietary manipulation 1177 6
Bierenbaum, 1988cx 50/50 1 Milk/dairy product suppl 1150 26
Morris, 1988 142/139 4 Other dietary manipulation 1500 12
Hakala, 1989 31/37 3 Other dietary manipulation 1163 52
Van Beresteijn, 1990 28/25 3 Milk/dairy product suppl 1180 6
Kynast-Gales, 1992cx 7/7 1 Milk/dairy product suppl 1515 4
McCarron, 1997 274/274 4 Milk/dairy product suppl 1886 10
Appel, 1997 151/154 4 Milk/dairy product suppl 1265 8
cx
, cross-over study; ci, cointervention.
* A quality score of 6 corresponds to the highest quality level
Adapted from Griffith LE, Guyatt GH, Cook RJ, et al. Am J Hypertens 12, 84, 1999. With permission.
TABLE 47.9
Randomized Controlled Trials Studying the Effect of Calcium Supplementation and Blood Pressure
Systolic Systolic Diastolic Diastolic
Position of Mean Mean Mean Mean
Blood Pressure Mean BP at Baseline, Difference, Baseline, Difference,
Author, Year Measurement Study End* mm Hg mmHg (SD) mm Hg mm Hg (SD)
Nondietary Interventions
Belizan, 1983
Women Lateral 1 102 -2.40 (1.03) 68 -4.50 (1.46)
Men Lateral 1 113 -0.80 (1.05) 71 -6.00 (1.94)
Sunderrajan, 1984
Normotensive Sitting 2 NA 1.89 (2.78) NA 1.89 (2.50)
Hypertensive Sitting 2 NA -1.63 (5.93) NA -4.13 (2.50)
Johnson, 1985
Normotensive Sitting 2 120 0.00 (3.01) 74 0.00 (1.67)
Hypertensive Sitting 2 141 -13.0 (6.52) 86 0.00 (2.79)
McCarron, 1985
Normotensive Standing 2 113 1.30 (2.00) 75 1.00 (2.62)
Hypertensive Standing 2 144 -5.60 (2.10) 92 -2.30 (1.40)
Grobbee, 1986 Sitting 1 143 -0.40 (2.27) 83 -2.40 (1.90)
Nowson, 1986
Normotensive Sitting 1 0.00 (2.97) 0.30 (2.33)
Hypertensive Sitting 1 157 1.60 (3.83) 92 1.30 (2.90)
Resnick, 1986
Salt-sensitive Sitting 1 NA NA NA -8.0 (6.0)
Salt-insensitive Sitting 1 NA NA NA 7.0 (6.0)
Strazzullo, 1986 Standing 2 145 -8.60 (4.98) 98 -1.70 (2.56)
Van Berestevn, 1986 Supine 1 115 -1.36 (1.88) 65 0.79 (1.66)
Cappuccio, 1987 Standing 2 156 2.00 (4.17) 112 0.40 (2.64)
Lyle, 1987
White Sitting 1 115 -2.44 (2.00) 75 -1.89 (2.31)
Black Sitting 1 114 -3.63 (3.85) 71 4.02 (5.67)
Meese, 1987 Sitting 2 143 -5.00 (4.21) 95 -2.00 (2.83)
Siani, 1987 Supine 2 154 5.10 (8.01) 96 1.30 (4.10)
Thomsen, 1987 Supine 2 124 -0.50 (6.10) 76 -1.30 (3.78)
Vinson, 1987 Supine 2 114 7.90 (4.93) 74 2.40 (2.05)
Zoccali, 1987 Sitting 1 141 6.45 (3.35) 88 4.64 (2.21)
Siani, 1988 Supine 2 139 2.20 (4.94) 91 0.70 (3.68)
Zoccali, 1988 Sitting 1 142 -2.80 (2.97) 88 -2.80 (2.47)
Orwoll, 1990 Sitting 1 131 2.60 (3.54) 84 3.08 (2.63)
Tanji, 1991 Sitting 1 146 3.00 (4.20) 95 2.00 (2.40)
Cutler, 1992 Sitting 1 126 -0.46 (0.67) 84 0.20 (0.46)
Lyle, 1992 Sitting 1 133 -5.90 (1.99) 87 -7.20 (1.71)
Galloe, 1993 Sitting 1 168 2.20 (4.49) 97 3.30 (2.75)
Jespersen, 1993 Supine 1 148 -0.57 (7.20) 93 -0.86 (3.88)
Pan, 1993 Sitting 1 136 -7.09 (7.89) 72 -0.87 (3.29)
Weinberger, 1993
Normotensive Sitting 2 116 1.00 (3.00) 72 -1.00 (2.64)
Hypertensive Sitting 2 131 -2.00 (5.68) 87 -1.00 (2.92)
Petersen, 1994 Sitting 2 145 4.50 (13.2) 81 -8.20 (5.10)
Zhou, 1994 Sitting 1 158 -14.6 (4.48) 103 -7.11 (2.43)
Gillman, 1995 Sitting 1 102 -2.20 (11.0) 58 -0.80 (7.16)
Sacks, 1995 Sitting 1 NA 3.70 (2.45) NA 3.60 (2.32)
Lijnen, 1996 Supine 1 114 -5.70 (2.18) 73 -3.50 (1.79)
Davis, 1997 Mean 24 h 1 125 -1.72 (1.20) 91 -0.49 (0.35)
ambulatory
Sanchez, 1997 Sitting 1 166 1.60 (1.60) 99 0.40 (1.21)

Randomized Controlled Trials Studying the Effect of Calcium Supplementation and Blood Pressure
Systolic Systolic Diastolic Diastolic
Position of Mean Mean Mean Mean
Blood Pressure Mean BP at Baseline, Difference, Baseline, Difference,
Author, Year Measurement Study End* mm Hg mmHg (SD) mm Hg mm Hg (SD)
Dietary Interventions
Margetts, 1986 Sitting 1 NA -3.50 (1.75) NA -1.20 (1.00)

Rouse, 1986 Sitting 2 NA 1.90 (2.30) NA 2.30 (1.40)
Bierenbaum, 1988 Sitting 2 119 -2.00 (2.19) 79 -1.00 (1.33)
Morris, 1988
Normotensive Standing 1 113 -1.00 (1.04) 77 -0.90 (0.80)
Hypertensive Standing 1 145 -3.60 (1.50) 94 -1.20 (0.86)
Hakala, 1989 Sitting 1 129 3.80 (11.9) 84 3.20 (4.53)
Van Beresteijn, 1990 Supine 1 114 -2.82 (1.83) 63 0.43 (1.89)
Kynast-Gales, 1992 Supine 1 136 -8.29 (8.12) 83 -0.14 (6.15)
McCarron, 1997 Sitting 1 134 -1.80 (0.78) 85 -1.20 (0.46)
Appel, 1997 Sitting 1 131 -2.70 (0.83) 84 -1.90 (0.60)
* For mean blood pressure at study end, 1 indicates change and 2 indicates mean.
Modified from Griffith LE, Guyatt GH, Cook RJ, et al. Am J Hypertens 12, 84, 1999. With permission.
in preeclampsia and toxemia. Magnesium supplementation in 400 normotensive primi-

gravida women given from 13 to 24 weeks gestation did not lower blood pressure or the
incidence of preeclampsia.47 However, among 2138 hypertensive women admitted in labor,
intramuscular magnesium sulfate was superior to phenytoin in preventing eclamptic
seizures (0 versus 0.92%, p = 0.004).48
Magnesium and calcium contribute to water hardness. There is an inverse relationship
between water hardness and blood pressure.49,50 However, epidemiologic studies assessing
the role of magnesium and blood pressure often do not control for potential confounders,
including caloric, ethanol, sodium, potassium, and calcium intake, and use of antihyper-
tensive medication.50 Thus, observational studies using 24-hour dietary recall, food
records, and food frequency questionnaires have not always shown a consistent correla-
tion, but generally show a negative correlation with both systolic and diastolic blood
pressure after adjustment.50 In the Health Professionals Follow-up Study, the relative risk
of a stroke among 43,738 men between the lowest quintile of magnesium intake and
highest quintile, after adjustment for age, BMI, various risk factors, family history, pro-
fession, and physical activity, was 0.62 (p <0.002).28 In the Atherosclerosis Risk in Com-
munities Study of four U.S. communities (n = 15,248 participants), an early report
suggested that low serum and dietary magnesium may be related to the etiology of
hypertension; however, a subsequent report found no association between dietary mag-
nesium intake and incident hypertension.51,52
The mechanism most often cited for the apparent antihypertensive effect of magnesium
is a calcium antagonist property. Other mechanisms include stimulation of vascular pros-
tacyclin release, renal vasodilation, acceleration of the cell membrane sodium pump, and
alterations in vascular responsiveness to vasoactive agents.53 One 1988 analysis concluded
that there were inadequate data from the four randomized, controlled trials to suggest a
hypotensive effect.49 Since that report, there have been a number of trials reported with
mixed results (see Table 47.12). It has been suggested that combinations of cations may
act in concert; however, in a randomized, double-blind, multicenter trial of 125 partici-
pants, there was no hypotensive effect of magnesium in combination with either calcium
or potassium.53 In normotensive women whose reported intake of magnesium was
TABLE 47.10
Randomized Controlled Trials of Calcium Supplementation in Pregnancy
No. of Elemental
Participants, Calcium Calcium
Supplementation/ Calcium Equivalent, Type of Weeks of Treatment Compliance Quality
Author, Year Placebo Formulation mg/d Control Gestation Duration, wk Cointervention Assessed Score†
Trials Providing Data on Treatment Effects of Systolic and Diastolic Blood Pressure
Belizan, 1983 11/14 Calcium Sandoz 2000 Placebo 15 22 NA* NA 3

Marya , 1987 188/182 Unknown calcium 375 Placebo 22 18 No Yes 5
supplement
Villar,1987 25/27 Os-Cal tablets 1500 Placebo 26 14 Yes Yes 0
Lopez-Jaramillo,1989 49/43 Calcium gluconate 2000 Placebo 23 17 No Yes 1

Repke, 1989 16/18 Os-Cal tablets 1500 Placebo 25 10 No Yes 4
Lopez-Jaramillo,1990 22/34 Elemental calcium 2000 Placebo 30 10 No No 4
Belizan, 1991 579/588 Calcium carbonate 2000 Placebo 20 20 No Yes 2
Felix, 1991 14/11 Elemental calcium 2000 Placebo 20 20 No Yes 3
Knight, 1992 10/10 Os-Cal tablets 1000 Normal diet 12 20 Yes Yes 5
Sanchez-Ramos, 1993 36/39 Unknown calcium NA Unknown 22 18 No No 6
supplement
Sanchez-Ramos, 1994 29/34 Calcium carbonate 2000 Placebo 25 15 No Yes 4
Levine, 1997‡ 2294/2295 Calcium carbonate 2000 Placebo 17 21 No Yes 6
Trials Providing Data on Binary Outcomes Exclusively
Montanaro, 1990 84/86 Calcium carbonate 2000 Placebo 24 16 No No 1

Villar and Repke 1990 95/95 Os-Cal tablets‡ 2000 Placebo 23 20 Yes Yes 2
Cong, 1993 50/50 Shen gu capsules Unknown Placebo 22 18 No No 0
* NA indicates not applicable.
† Quality scores range from 0 to 6 with 6 indicating the highest quality score
‡ Calcium for the Preeclampsia Prevention Trial (Not in the original meta-analysis)
Modified from Bucher HC. Reproduced with permission from April 10, 1996 JAMA 275(14):1113-7. Copyright 1996, American Medical Association.
979
TABLE 47.11
Change in Blood Pressure in Randomized Controlled Trials
of Calcium Supplementation in Pregnancy
Mean Difference Mean Difference
In Systolic Blood in Diastolic Blood
Author, Year Pressure, mm Hg Pressure, mm Hg
Belizan, 1983 -5.10 -5.70
Marya, 1987 -6.90 -3.40
Villar, 1987 -4.10 -4.90
Lopez-Jaramillo, 1989 -8.70 -6.60
Repke, 1989 -2.50 -2.77
Lopez-Jaramillo, 1990 -13.10 -11.80
Belizan 1991 -1.70 -0.90
Felix, 1991 -6.30 -5.80
Knight and Keith, 1992
Normotensive -2.70 0.50
Hypertensive +4.8 0
Sanchez-Ramos, 1993 +4.6 -0.82
Sanchez-Ramos, 1994 -4.08 -3.00
Levine, 1997* -0.3 +0.3
* Calcium for the Preeclampsia Prevention Trial (not in the original
meta-analysis)
Modified from Bucher HC. Reproduced with permission from April
10, 1996 JAMA 275(14):1113-7. Copyright 1996, American Medical
Association.
between the 10th and 15th percentiles, 16 weeks’ daily supplement of magnesium 14 mmol
had no significant treatment effect (–0.9/–0.7 mmHg). The administration of magnesium
with potassium did not enhance the effect of potassium alone.54
ω-3 Polyunsaturated Fatty Acids

ω-3 polyunsaturated fatty acids refer to the fish oil, very long chain fatty acids eicosap-
entaenoic (EPA) and docosahexaenoic (DHA) acids. ω-3 polyunsaturated fatty acids are
thought to lower blood pressure by altering the balance of the vasoconstrictor thrombox-
ane A2 and the vasodilator prostacyclin prostaglandin I3, modulating the vasoconstrictor
response to pressors, or decreasing blood viscosity.8
A meta-analysis by Appel identified 40 studies testing the impact of ω-3 polyunsaturated
fatty acids on blood pressure; however, 23 were eliminated because of design, including
concurrent antihypertensive medications, no control group, unhealthy study population,
concurrent use of ω-3 polyunsaturated fatty acids in the control group, or insufficient
data.55 Most trials used a combined dose of 3 g daily of EPA and DHA, which is equal to
6 to 10 capsules of commercial fish oil supplements or two 100 g servings of fish that are
high in ω-3 polyunsaturated fatty acids. The overall change in blood pressure, –1.5/–1.0
mmHg, was significant. For normotensives, the change in blood pressure, –1.0/–0.5
mmHg, was significant for the systolic blood pressure only. However, the decline in blood
pressure, –5.5/–3.5 mmHg, for hypertensives was significant for both systolic and diastolic
blood pressure (p <0.001). Interestingly, the higher the blood pressure, the greater the
reduction (p <0.05); however, this was not a function of the dose of the ω-3 polyunsaturated
fatty acids, duration of treatment, type of intervention (food versus oil capsules), or age
of participants. Side effects summarized include the unpleasant or fishy taste, gastrointes-
TABLE 47.12
Randomized Trials of Magnesium Supplementation
Mean Men, BP Mg Salt, Study Duration, Control Magnesium
Author, Year n Age, Yr % Cohort Meds mmol Mg/d Design Weeks ∆SBP/∆DBP ∆SBP/∆DBP
Itoh, 1997 33 65 33 Mixed ? Hydroxide, 17-23 DB, PR 4 +1/-1 -5/-2
TOHP, 1992‡ 461 43 70 Normotensive No Diglycine, 15 DB, PR 24 -2.9/-2.7 -3.0/-2.9
Sacks, 1998 153 39 0 Normotensive No Lactate, 14 DB, PR 16 +0.4/+0.2 -0.5/-0.5
de Valk, 1998 50 62.5 56 Diabetes (insulin) ? Aspartate, 15 DB, PR 12 -10.4/-0.8 -7.7/-0.3
Purvis, 1994 28 53.8 86 Diabetes (no insulin) ? Chloride, 15.7 DB, CO 6 -7.4/-2.3
Cappuccio, 1985 17 52 53 Hypertensive No Aspartate, 15 DB, CO 4 -3/-3 0/-2

Dyckner, 1983 20 65 33 90% Hypertensive Yes Aspartate, 15 O,PR 24 -0/-4 -12/-8
Ferrara, 1992 14 47.5 57 Hypertensive No Pidolate, 15 DB, PR 24 -17/-4 -7/-7
Henderson, 1986 41 62 ? Hypertensive Yes Oxide, 12.5 DB, PR 24 -3/-1 -4/-3
Kawano, 1998 60 58 57 Hypertensive Some Oxide, 20 CO 8 -3.7/-1.7
Lind, 1991 71 61 52 Hypertensive No Mixed†, 15 DB, PR 24 -2/-4.2 +1/-2
Plum-Wirell, 1994 39 39 62 Hypertensive No Aspartate, 15 DB, CO 8 -0.8/-0.4 -2.4/-0.4
Reyes, 1984 21 57 19 Hypertensive Yes Chloride, 15.8 DB, PR 3 -13/-4 -11/-7
Sanjuliani, 1996 15 36-65 47 Hypertensive No Oxide, 25 DB, CO 3 +1.7/-1.0 -7.6/-3.8
Sibai, 1989 374 18 0 Pregnancy No Aspartate, 15 DB, PR 21 +16/+18 +15/+16
Widman, 1993 17 50 88 Hypertensive No Hydroxide, 15-40 DB, CO 9 -1/0.0 -7.9/-8.2

Wirell, 1994 39 26-69 77 Hypertensive Yes Aspartate, 15 DB, CO 8 +3.2/+2.3 -3.8//-1.7
Witteman, 1994 91 57 0 Hypertensive No Aspartate, 20 DB, PR 24 +0.2/+0.1 -3.3/-2.4
Zemel, 1990 13 ~49 86 Hypertensive No Aspartate, 40 DB, PR 12 -1/+1 +3/+2
† 4.58 mmol Mg lactate + 0.42 Mg Citrate; ‡ TOPH, Trial of Hypertension Prevention (Phase I)
981
tinal symptoms, eructation, loose stool or diarrhea, and obstipation occurring in 28% of
experimental subjects — 13% of the control group (p <0.001).55
Another meta-analysis included 31 of 52 studies that included trials with a placebo
group and a report of pretreatment and post-treatment blood pressures (see Table 47.13).56
Like the previous meta-analysis, hypertensives (–3.4/–2.0 mmHg) had greater blood pres-
sure decline than normotensives (–0.4/–0.7 mmHg), but the dose of the fish oils was higher
in the hypertensive group (5.6 g/d) than the normotensive group (4.2 g/d). There also
was a statistically significant dose-dependent decline in blood pressure: ≤ 3g/d, –1.3/–0.7
mmHg; >3 to 7g/d, –2.9/–1.6 mmHg; and 15g/d, –8.1/–5.8 mmHg. The effect of fish oil
on blood pressure is maximally manifested by 3 to 4 weeks.
Since the completion of these meta-analyses, several new studies have supported their
conclusions. In a double-blind, placebo-controlled trial of parallel design, 59 overweight,
mildly hyperlipidemic men were randomized to 4 g/d of purified EPA, DHA, or olive oil
(placebo) capsules and continued their usual diets for 6 weeks. Fifty-six subjects completed
the study. Only DHA significantly reduced 24-hour and daytime ambulatory blood pres-
sure (p <0.05).57 In 63 overweight hypertensives, combining a daily fish meal with a weight-
reducing regimen led to additive reduction on ambulatory blood pressure and decreased
heart rate.58
Dietary Protein
Cross-sectional studies show that dietary protein intake is inversely related to blood
pressure, although a direct relationship was considered to exist.59 Protein intake was
thought to increase blood pressure due to adverse effects on renal function in partially
nephrectomized rats. The mechanism of action of high dietary protein intake is not clear,
but multicollinearity (multiple nutrient intake that correlated with one another) is a prob-
lem. Amino acid production (e.g., tryptophan, tyrosine, and arginine) may affect hormones
or neurotransmitters that ultimately alter blood pressure. For instance, the sulfonic amino
acid taurine given 6 g for 7 days in 19 young hypertensive subjects decreased blood
pressure –9.0/–4.1 mm Hg compared with to –2.7/–1.2 mmHg in the placebo-treated
subjects in a double-blind, placebo-controlled trial.60 Perhaps other protein metabolites
have natriuretic or diuretic activity.
Human observational studies on protein and blood pressure are displayed in Table 47.14.
These studies show in aggregate that increased protein intake, determined by food records
or recall or by urine studies of sulfate and urea nitrogen, is associated with decreased
blood pressure. The relationship of blood pressure and vegetable protein versus animal
protein is unclear. After adjustment for age, BMI, alcohol consumption, urinary sodium
excretion, dietary intake, and resident area for each one standard deviation higher level
of dietary protein intake (39 g), a 3.55 mmHg lower systolic blood pressure was observed.
Most intervention trials (Table 47.15) have been conducted in normotensive subjects,
were not designed to assess the relationship between protein and blood pressure or
determine a dose relationship, and were not powered adequately or randomized.59,61
Dietary Fiber
Vegetarians and other persons with high fiber intakes have lower average blood pressures
than persons with low fiber intakes do. In the Coronary Artery Risk Development in Young
Adults (CARDIA) Study, fiber intake predicted insulin levels, weight gain, and other
cardiovascular risk factors more potently than did fat consumption.62 High intake of fiber
was associated with lower systolic and diastolic blood pressure in whites but not African-
TABLE 47.13
Characteristics of the 31 Trials used for the Meta-Analysis of Fish Oil and Blood Pressure*
Study Blinding Blinding Study ω-3 Dose Gender Baseline BP Effect
Study, Year Design* Subject Observer§ Length n, Treatment* (g/d)‡ (Age Range) Pressure¶ SBP/DBP¶
Health Subjects
Mortensen, 1983 XO + + 4 20 Fish oil 3.3 Men 120/76 -4.0/-4.0

20 Mixed oil (25-40 y)
Bruckner, 1987 PG + - 3 10 Fish oil 3.9 Men 119/80 +5.0/+1.0
11 Olive oil (19-40 y)
v Houwelingen, 1987
Maastricht PG - + 6 19 Fish 4.7 Men 121/77 +1.1/-0.9
20 Meat (20-45 y)
Tromso PG - + 6 11 Fish 4.7 Men 118/77 +0.1/-0.9

12 Meat (20-45 y)
Zeist PG - + 6 10 Fish 4.7 Men 115/73 -3.7/-3.0
10 Meat (20-45 y)
Flaten, 1990 PG + + 6 27 Fish oil 6.5 Men 119/80 +1.5/+0.8
Ryu, 1990 PG NS† NS 4 10 Fish oil 3 Men 124/73 -4.3/-2.0
10 Wheat germ (20-39 y)
TOHP, 1992 PG + + 24 175 Fish oil 2.4 Men & Women 123/81 -0.2/-0.6
175 Olive oil (30-54y)
Hypertensive Subjects
Norris, 1986 XO + + 6 16 Fish oil NS Men & Women 161/95 -10.0/-2.0

16 Placebo (45-74 y)
Knapp, 1989 PG - - 4 8 Fish oil 3 Men 137/94 -2.6/-0.1
8 Saturated mix (age NS)
Meland, 1989 PG + + 6 20 Fish oil 6 Men 149/101 +1.0/-1.0
20 Mixed oil (26-66 y)
Bonaa, 1990 PG NS NS 10 78 Fish oil 5.1 Men & Women 144/95 -6.4/-2.8
78 Corn oil (34-60 y)
983
984

Characteristics of the 31 Trials used for the Meta-Analysis of Fish Oil and Blood Pressure*
Study Blinding Blinding Study ω-3 Dose Gender Baseline BP Effect
Study, Year Design* Subject Observer§ Length n, Treatment* (g/d)‡ (Age Range) Pressure¶ SBP/DBP¶
Levinson, 1990 PG + + 6 8 Fish oil 15 Men & Women 147/94 -8.0/-9.0
8 Saturated mix (18-75 y)
Wing, 1990 XO + + 8 20 Fish oil 4.5 Men & Women 139/81 +0.6/-0.3
Radack, 1991 PG + + 12 16 Fish oil 2 Men & Women 136/95 -7.2/-6.7
17 Safflower (mean, 46 y)
Margolin, 1991 PG + + 8 22 Fish oil 4.7 Men & Women 164/94 +1.1/+0.1
24 Corn oil (60-80 y)
Morris, 1992 XO + + 6 18 Fish oil 4.8 Men & Women 130/87 -2.4/-1.8
Hypercholesterolemic Subjects
Demke, 1988 PG + + 4 13 Fish oil 1.7 Men & Women 119/74 -3/+1.0
18 Safflower (18-60y)
Bach, 1989 PG + + 5 30 Total 2.5 Men & Women 130/85 -9.0-4.0
saturated (mean, 31 y)
Dart, 1989 XO NS NS 8 21 Fish oil 6 Men & Women 125/77 -5.3/-2.0
21 Olive oil (mean, 46 y)
Wilt, 1989 XO NS NS 12 38 Fish oil 6 Men 124/84 -2.7/-1.8
38 Safflower (mean, 42 y)
Kestin, 1990 PG + + 6 11 Fish oil 3.4 Men 124/75 -5.1/0.0
11 Linoleic (mean, 46 y)
Cobiac, 1991 PG - - 5 12 Fish 4.5 Men 128/79 -0.6/+1.3
13 Fish oil (30-60 y)
6 Saturated mix
Davidson, 1986 PG + + 4 30 Total 6 Age, sex: NS† 142/88 -9.8/-3.2
olive oil
Cardiovascular Disease Subjects
Mehta, 1988 XO + + 4 8 Fish oil 5.4 Men 138/80 -10.0/-4.0

8 Placebo (52-73 y)
Solomon, 1990 PG + + 12 5 Fish oil 4.6 Men & Women 142/87 -16.8/-9.6
5 Olive oil (42-64y)
Gans, 1990 PG + + 16 16 Fish oil 3 Men & Women 148/80 +9.0/+1.0
16 Corn oil (mean, 66 y)
Diabetic Subjects
Haines, 1986 PG - - 6 19 Fish oil 4.6 Men & Women 136/82 +1.0/+1.7
Jensen, 1989 XO + + 8 18 Fish oil 4.6 Men & Women 148/89 -9.0/-4.0
Hendra, 1990 PG + + 6 40 Fish oil 3 Men & Women 143/83 +0.4/-0.6
40 Olive oil (mean, 56 y)
Mixed Sample†
Rogers, 1987 PG + + 4 30 Fish oil 3.3 Men 130/76 -3.1/-5.0

* The number of subjects in each treatment period is listed for crossover studies. XO, Crossover, PG, Parallel Group. The number of subjects in each
treatment group was not reported for Davidson, 1986 and Bach, 1989. Saturated mix is a mixture of saturated and other oils; mixed oil is a mixture of
corn and olive oils.
† NS, not specified. Mixed sample indicates that there were no inclusion criteria for health of the sample.
‡ ω−3 Dose represents eicosapentaenoic acid plus docosahexaenoic acid. The ω−3 dose for Bruckner, 1987, reported as 1.5 g/10 kg body wt, is estimated
based on a mean weight of 85 kg.

¶ Average blood pressure at baseline for active and control groups for parallel group studies and blood pressure during the placebo period for crossover
studies. SBP, systolic blood pressure; DBP, diastolic blood pressure; NS, not specified. Change in BP attributed to fish oil treatment.
§ Blinded to treatment status.
Tabulated from Tables 2 and 3 from Morris.56
985
TABLE 47.14
Observational Studies on Protein and Blood Pressure*
Study Number, Age Protein Measurement Results
Cross-Sectional Studies
Yamori, 1981 1120, NS* Spot urine: sulfate:urea nitrogen ↓ SBP with ↑ animal protein
ratio
Kihara, 1984 1120, 30-70+ y Spot urine: sulfate:urea nitrogen ↓ SBP in men with ↑ animal
ratio protein
Reed, 1981 6496 men, NS Single 24-h recall: g/d ↓ SBP, ↓ DBP with ↑ total protein
Pellum, 1983 61, 22-25 y 3-d food record: g/d ↓ SBP with ↑ total protein
Elliott, 1991 1190, 20-59 y 24-h urine: total nitrogen, urea ↓ SBP with ↑ total and animal
nitrogen, sulfate protein
Dyer, 1992 2325, 20-59 y 24-h urine: total nitrogen, urea ↓ SBP with ↑ total protein
nitrogen
Stamler, 1992 11342 men, 35-57 y Four or five 24-h recalls: % ↓ SBP with ↑ total protein
energy intake
Eliott, 1992 1922, mean age 39 y 7-d weighed food record: g/d, ↓ SBP in women, ↓ DBP in men
% energy intake and women with ↑ total
protein
Liu, 1992 3809, 18-30 y Interviewer-administered food- ↓ DBP in white women, black
frequency questionnaire: % women, and black men with ↑
energy intake vegetable protein only
Zhou, 1989 2672, 35-50 y Three 24-h recalls: percentage ↓ SBP with ↑ animal protein
energy intake only
Zhou, 1994 705, 40-59 y Three 24-h recalls: % energy ↓ SBP, ↓ DBP with ↑ animal
intake protein only
Havlik, 1990 402 male twins, 42-56 y Interviewer-administered ↑ DBP with ↑ total protein
food-frequency questionnaire:
% energy intake, g/d, g/d
adjusted for energy
He, 1995 827 men, mean 31-45 y Three 24-h recalls: % energy ↓ SBP with ↑ total protein
intake
Stamler, 1996 10020, 20-59 y 24-h urine: total nitrogen, urea ↓ SBP, ↓ DBP with ↑ total protein
nitrogen, sulfate
Stamler, 1996 11342 men, 35-57 y Four or five 24-h recalls: % ↓ DBP with ↑ total protein
energy intake
Longitudinal Studies
Liu, 1993 1804 men, 40-56 y Quantitative diet history: % ↓ SBP with ↑ vegetable protein
energy intake only
Liu, 1995† 3809, 18-30 y Interviewer-administered food- No change, with ↑ total, animal,
frequency questionnaire: % or vegetable protein
energy intake
* SBP indicates systolic blood pressure; DBP, diastolic blood pressure; NS, not stated
† Personal communication
Reproduced with permission from May 22/29, 1996 JAMA 275(20):1598-603. Copyright 1996, American Medical
Association.
TABLE 47.15
Human Intervention Studies on Protein and Blood Pressure*
Study Number, Age, Cohort Study Design Results Conclusion
Chapman, 1950 8 men, 31-58 y, Sequential: (1) control, (2) rice-fruit; ↓SBP and ↓DBP, but both NS Compared with rice-fruit diet,
hypertensive protein (3) rice-fruit + 40 g milk (animal) no effect of animal protein on
BP
Hatch, 1954 9, 36-66 y, hypertensive Sequential: (1) low-sodium control; ↓SBP and ↓DBP, but both NS No effect of ↑animal protein on
(2) low-sodium + 30-50 g milk and BP
meat protein
Brussaard, 1981 69, 18-30 y, normotensive Parallel, randomized, each for 4 wk: Casein: ↓SBP and ↑ DBP, but No effect of animal or vegetable
(1) control; (2) casein protein; (3) soy both NS; Soy: ↑ SBP and ↑ DBP, protein on BP
protein but both NS
Sacks , 1981 21, 20-55 y normotensive Sequential: (1) 2 wk control ↑ SBP (p<0.05), ↓DBP (NS) Animal protein ↑ SBP
vegans vegetarian diet; (2) 4 wk 250 g of
added beef
Sacks, 1984 18, 22-41 y, normotensive Crossover, randomized each for 6 wk Compared with low protein, No effect of ↑ vegetable protein
vegans (1) high protein (58 g soy and wheat high protein: ↑ SBP and ↑ DBP, on BP
protein); (2) low protein (7 g rice but both NS
protein)
Sacks, 1984 Study 1 — 19, 14-54 y Study I — Sequential: (1) 3 wk at Study 1 — Low-fat vegetarian Study 1 — No effect of
normotensive baseline (2) 3 mo lactovegetarian protein diet: ↑ SBP and ↑ DBP, vegetarian diet on BP
diet but both NS
Study 2 — 17, 18-24 y, Study 2 — Crossover, randomized, Study 2 — 1 egg/d: ↑ SBP and Study 2 — No effect of eggs on
normotensive vegetarians each for 3 wk: (1) no eggs; (2) 1 egg/ ↑ DBP, but both NS BP
d
Prescott , 1987 50, 18-60 y, normotensive Parallel, randomized, each for 12 wk: Compared with meat protein No difference in BP between
(1) meat protein (93 g of protein) (2) diet, vegetable protein: ↓SBP vegetable and animal protein
vegetable protein (84 g protein) and ↑ DBP, but both NS
Sacks, 1988 13, 21-41 y, normotensive Crossover, randomized, each for 3 Compared with casein protein; No difference in BP between
vegans wk: (1) 27 g casein protein; (2) 27 g soy protein: ↓SBP, and ↓DBP, vegetable and animal protein
soy protein but both NS
Kestin, 1989 26 men, 28-64 y, Crossover, randomized, each for 6 Lactoovovegetarian diet: No No difference in BP between
normotensive wk: (1) lean meat (high animal change in SBP and ↑ DBP, but low-fat animal and low-fat
protein); (2) lactoovovegetarian both NS vegetable protein diet
(high vegetable protein)
* SBP indicates systolic blood pressure; DBP, diastolic blood pressure; BP, blood pressure; and NS, not significant.
Reproduced with permission from May 22/29, 1996 JAMA 275(20):1598-603. Copyright 1996, American Medical Association.
987
Americans. Among 30,681 white male health professionals, only dietary fiber had an
independent inverse association with hypertension after four years of follow up.34 The
relative risk of hypertension was 1.57 times greater for men with a fiber intake of less than
12 g/day versus greater than 24 g/day. In the Health Professionals Follow-up Study
(43,738 men), high intakes of cereal fiber and magnesium were inversely associated with
the risk of all strokes after 8 years.28 Among 827 Chinese men, a 10 g higher intake of
dietary fiber was significantly associated with a reduced systolic and diastolic blood
pressure (–2.2/–2.1 mmHg).63
The explanation for lower blood pressure with fiber is unclear. Suggestions include an
increased intake in dietary potassium and Vitamin C and/or a decreased sodium intake.64
Among controlled studies the average intake of fiber (primarily cereal) was increased by
14 g, resulting in an average reduction of blood pressure of –1.6/–2.0 mmHg.65 Better
studies need to be conducted to understand the relationship of fiber with blood pressure.
Ascorbic Acid (Vitamin C) and Antioxidant Combinations

Ascorbic acid is an antioxidant and a free radical scavenger. Low vitamin C levels might
decrease the production of nitric oxide and increase blood pressure by increasing free
radical formation.66 Other mechanisms include decreased vasodilating prostaglandin for-
mation, modified leukotriene metabolism, altered vascular sodium content, or nutrient
multicollinearity.67 Several studies suggest an inverse relationship between blood pressure
or stroke and vitamin C levels. Differences in nutritional consumption between hyperten-
sives and normotensives are shown in Figure 47.3.68
It has been observed that a low potassium could also explain this association.69 In 722
Eastern Finnish men in the Kuopio Ischaemic Heart Disease Risk Factor Study, both
plasma ascorbic acid and serum selenium concentrations had independent inverse asso-
ciations with the blood pressure.66 However, neither vitamin E nor vitamin C supplements
Cholesterol 1.0%
Linoleic Acid -1.2%
Vitamin C -11.9%
Vitamin A -11.8%
Potassium -7.1%
Sodium -1.3%
Phosphorous -3.4%
Calcium -7.6%
Carbohydrates -2.9%
Protein 1.3%
Fat -1.3%
Calories -0.6%
-16.0% -14.0% -12.0% -10.0% -8.0% -6.0% -4.0% -2.0% 0.0% 2.0%
% of Mean Difference in Nutrient Intake of Hypertensives and Normotensives
FIGURE 47.3
Health and Nutrition Examination Survey I: % mean difference in average nutritional consumption between
hypertensive and normotensive persons, adjusted for age. Derived from McCarron DA, Morris CD, Henry HJ,
Stanton JL. Science 224(4656), 1392, 1984. With permission.
TABLE 47.16
Trials of Ascorbic Acid and Blood Pressure
Patient Blood Pressure (mm Hg)
Study Number Design Duration Intervention Systolic/Diastolic
Osilesi O, 1991 20 Crossover 6 wks 1000 mg/d -6.3 /0.6
Feldman EB, 1992 21 Single Blind 4 wks 1000 mg/d -4.2/-2.9
Lovat LB, 1993 27 Crossover 4 wks 400 mg/d -·2 to -5·3 /-0.2 to -1.9
Ghosh SK,1994 48 Controlled 6 wks 500 mg/d -2.5/-1.2
Duffy SJ, 1999 39 Controlled 4 wks 2000 mg bolus -11/-6
500 mg per day
Table modified from Ness A, Sterne J. Lancet 335(9211), 1271, 2000.
reduced the risk of stroke in the Health Professionals Follow-up Study of 43,738 men.70
In 168 healthy subjects, plasma concentrations of ascorbic acid (but not α-tocopherol,
selenium, or taurine) were significantly inversely related to systolic and diastolic blood
pressure.67 Intravenous vitamin C, thiopronine, and glutathione (all antioxidants) indi-
vidually demonstrated an acute decrease in blood pressure in 20 unmedicated hyperten-
sive and 20 diabetic subjects. 71 Few studies assess the impact of ascorbic acid
supplementation alone. Ascorbic acid — 500 mg twice daily in 21 subjects — lowered
blood pressure 4.2/2.9 mmHg in a pilot study.72 In a double-blind randomized crossover
study, ascorbic acid 200 mg twice daily or placebo for four weeks was given to 27 elderly
hypertensives.73 No significant treatment effect was observed. Following a 2-week run-in
phase, 48 untreated elderly hypertensive subjects in a randomized, double-blind, placebo-
controlled six week study received ascorbic acid 250 mg twice daily or placebo.74 The
change in blood pressure in the vitamin C group was –10.3/–5.9 mmHg, and in the placebo
group –7.7/–4.7 mmHg (p = nonsignificant). In a controlled trial, 20 subjects received
placebo and 19 subjects received a 2 g bolus followed by 500 mg daily of ascorbic acid
for 30 days.75 Systolic blood pressure decreased 13 mmHg (p <0.05); the change in diastolic
blood pressure was not significant. Table 47.16 summarizes several trials of vitamin C
supplementation and blood pressure.76 The effect on systolic blood pressure is consistently
greater than diastolic blood pressure.
Several studies have combined several antioxidants to assess an effect on blood pressure.
In a randomized, placebo-controlled, clinical trial of 297 retired teachers randomly
assigned to 2 to 4 months of the combination of 400 IU/day vitamin E, 500 mg/day vitamin
C, and 6 mg/day β-carotene or placebo, the antioxidant combination capsule had no
significant hypotensive effect.77 In a randomized, double-blind, crossover design placebo-
controlled study of 21 hypertensives and 17 normotensives, participants were assigned to
receive either 8 weeks of placebo followed by 2 weeks washout, then 8 weeks antioxidants
200 mg of zinc sulfate, 500 mg of ascorbic acid, 600 mg of α-tocopherol and 30 mg of β-
carotene daily, or the opposite sequence. Only systolic blood pressure (–5.3 mmHg)
decreased significantly at the end of the antioxidant phase compared with the placebo
phase (+3.7 mmHg) in hypertensive subjects (p <0.01).78
Garlic (Allium Sativum)

Garlic has been reported to decrease blood pressure and attenuate age-related increased
aortic stiffness, which could alter blood pressure rise with aging.79-83 Allicin is believed to
be the component responsible for the medicinal effects of garlic. In rabbits and dogs, garlic
elicits a dose-dependent diuretic-natriuretic response.84,85 In a randomized, placebo-con-
trolled, double-blind trial, 47 subjects with mild hypertension (diastolic blood pressures
from 95 to 104 mmHg) took either garlic powder or a placebo of identical appearance for
12 weeks.79 The supine diastolic blood pressure in the garlic treatment group decreased
13 mmHg after 12 weeks (p < 0.01) compared with no significant changes in the placebo
group. In a double-blind crossover study of 41 moderately hypercholesterolemic men
assessing the effect of aged garlic extract versus placebo on blood lipids, there was a 5.5%
decrease in systolic blood pressure and a modest reduction of diastolic blood pressure.81
Another study of 40 hypercholesterolemic men treated with 900 mg of garlic powder
observed a similar finding.80 In a randomized, double-blind study, 42 healthy adults took
either 300 mg three times a day of standardized garlic powder in tablet form, or placebo
for 12 weeks.86 There was no significant change in blood pressure.
A meta-analysis of 8 trials (415 subjects) using dried garlic powder 600 to 900 mg
observed a decrease for systolic blood pressure of –7.7 (95% CI –11.0 to –4.3) and diastolic
blood pressure of –5.0 (95% CI –7.1 to –2.9) mmHg, which represented the overall pooled
difference in the absolute change (baseline to final measurement) in blood pressure relative
to placebo (see Table 47.17).87 The same analysis for hypertensive subjects reported an
–11.1/–6.5 mmHg decline in blood pressure. The authors observe that blinding may have
been difficult due to the odor of garlic. Furthermore, they emphasize that their quality
assessment of the trials was poor because the authors did not state their technique to
achieve effective randomization. Side effects appear to be rare. A recent randomized,
multicenter, double-blind, placebo-controlled, 12-week parallel treatment study in hyper-
cholesterolemic subjects using garlic powder (Kwai) 300 mg 3 times per day found no
benefits in lowering blood pressure.88 The authors of this paper emphasize that negative
studies tend not to be submitted or published, suggesting that the current literature on
garlic represents a publication bias.87,88 Despite the suggested benefit, more trials need to
be conducted to assess the benefit in hypertensives.
Ethanol
Alcohol consumption increases the risk of the development of hypertension.89,90 The risk
increases above 28 g of ethanol per day (which is equivalent to 24 oz of beer, 10 oz wine,
and 3 oz of distilled spirits).91 The maximum addition to the prevalence of hypertension
of alcohol usage greater than two drinks daily is estimated to be 5 to 7%; however, the
11% risk in men is greater than in women because of greater alcohol intake.92 In another
study, alcohol consumption greater than 20 g per day gradually increases the risk of
hypertension among women.93 The relationship of alcohol intake to blood pressure is
graded and continuous with the effect clearer in men than in women and more consistent
in whites than in blacks (see Figure 47.4).94 The effect of alcohol consumption on systolic
blood pressure is independent of the effects of age, obesity, cigarette smoking, and physical
activity.95 In the INTERSALT Study (n = 10,079), both BMI and heavy alcohol consumption
were significantly and independently correlated with both systolic and diastolic blood
pressure (p <0.001).5 The effect of alcohol consumption on blood pressure is independent
of and additive to BMI and urinary excretion of sodium and potassium.96 The effect of
alcohol on change in blood pressure independent of other risk factors is displayed in
Figure 47.4.94 In the Scottish Health Heart Study, alcohol consumption showed a weak
positive correlation with blood pressure among 7354 men, but the correlation was greater
than for sodium.7
Resting plasma concentrations of norepinephrine, epinephrine, renin activity, angio-
tensin II, aldosterone, and cortisol are similar in drinkers and nondrinkers.97 In a prospec-
tive study of 7735 middle-aged British men, the prevalence of measured hypertension and
TABLE 47.17
Randomized Controlled Trials of Garlic and Blood Pressure*
Dose per Number of Heart
Reference Participants day (mg) Control Blinding Subjects Duration Position Rate Analysis
Kandziora, 1988 Hypertensives 600 Reserpine- Single 40 12 weeks Sup/St UC ITT
diuretic
Kandziora, 1988 Hypertensives 600 Placebo Double 40 12 weeks Sup/St UC ITT
Auer, 1990 Hypertensives 600 Placebo Double 47 12 weeks Sup/St NS NS
Vorberg, 1990 Hyperlipidemics 900 Placebo Double 40 16 weeks Sup NS NS
Kiesewetter, 1991 SWISA 800 Placebo Double 60 4 weeks NS NS NS
Holzgartner, 1992 Hyperlipidemics 900 Bezafibrate Double 94 12 weeks NS UC ITT
Santos, 1993 NS 900 Placebo Double 60 6 months NS NS ORT
Jain, 1993 Hyperlipidemics 900 Placebo Double 42 12 months NS NA NS
* Sup, supine; St, standing; UC, unchanged; ITT intention to treat; NS, not stated; SWISA, subjects with increased spontaneous aggregation;
ORT, on randomized treatment; NA. not available. Crossover study.
Modified from Silagy CA, Neil HA. J Hypertens 12(4), 463, 1994. With permission.
991
White Men
(n=20,171)
10 9.1
9 Systolic
8 Diastolic
Change in 7 5.6 5.6
Blood 6
Pressure 54 3.5
(mmHg) 3 2.8
2 1.6
1
0
1—2 3—5 6—8
Alcohol Consumption (drinks/day)
White Women
(n=23,191)
10
Systolic
8
Diastolic
Change in
6
Blood 4.6
Pressure 4
(mmHg) 2.9 3.1 2.5
2 1.4
0.5
0
1—2 3—5 6—8
Alcohol Consumption (drinks/day)
FIGURE 47.4
The effect of ethanol consumption on the change in blood pressure independent of other factors. Graph derived
from data of Klatsky AL, Friedman GD, Armstrong MA. Circulation 73(4): 628, 1986.
level of blood pressure were significantly higher on Mondays and lower on Fridays than
on other weekdays.98 This suggests a withdrawal effect of weekend ethanol consumption.
Modest alcohol intake has been associated with a protective effect on ischemic heart
disease events. Heavy alcohol intake has been associated with an increased rate of hem-
orrhagic strokes.99,100 However, mild to moderate consumption in men reduced the risk of
ischemic stroke without increasing the risk of hemorrhagic stroke.101
Several trials have been conducted to assess the impact of alcohol in moderation on
blood pressure. These are listed in Table 47.18. Prevention and Treatment of Hypertension
Study (PATHS)91,102 was designed to assess alcohol intake reduction in nondependent
moderate to heavy drinkers. 641 outpatient hypertensive and nonhypertensive veterans
with a diastolic blood pressure of 80 to 99 mmHg were randomized to observation or
behavioral cognitive intervention. To qualify for enrollment, self-reported alcohol intake
had to be ≥294 g/week or ≥21 drinks/week for the preceding six months. The goal of
behavioral cognitive intervention was to reduce alcohol intake to less than 50% of baseline
intake or 14 drinks per week.
For the entire cohort, the average reduction of alcohol intake at 6 and 24 months between
groups was 131 and 124 g/wk (p <0.001 for each). For the 265 hypertensive subjects, the
average reduction at 6 and 24 months was 157 and 135 g/wk (each p <0.001). At 6 and
12 months, this translated to a nonsignificant reduction in blood pressure (i.e., treatment
TABLE 47.18
Randomized Controlled Trials of Alcohol Reduction on Blood Pressure
Age, Years Alcohol Intake Blood Pressure
(Mean ± SD Duration, Baseline BP, Difference, Reduction,
Study, Year n or Range) Weeks mm Hg Drinks†/Day mm Hg p Value
Puddey, 1985 46 35 ± 8 6 133/76 3.7 3.8/1.4 <.001/<.05
Howes, 1985 10 25-41 0.6 120/66 5.7 8/6 <.025/<.001
Puddey, 1987 44 53 ± 16 6 142/84 4.0 5/3 <.001/<.001
Ueshima, 1987 50 46 ± 7 2 148/93 2.6 5.2/2.2 <.005/NS
Wallace, 1988 641 42 ± 20 52 136/82 1.0 2.1/? <.05/NS
Parker, 1990 59 52 ± 11 4 138/85 3.8 5.4/3.2 <.01/<.01
Cox, 1990 72 20-45 4 132/73 3.4 4.1/1.6 <.05/<-05
Maheswaran, 1992 41 40s 8 144/90 3.1 Not reported NS
Puddey, 1992 86 44 18 137/85 3.0 4.8/3.3 <.01/<.01
Ueshima, 1993 54 44 ± 8 3 144/96 1.7 3.6/1.9 <.05/NS
PATHS, 1998‡ 641 57 ± 11 104 140/86 1.3 0.9/0.6 0.16/0.10
† A standard drink is defined as 14 g of ethanol and is contained in a 12-oz glass of beer, a 5-oz glass of table
wine, or 1.5 oz of distilled spirits.
‡ PATHS is Prevention and Treatment of Hypertension Study.
Modified from report of Cushman WC, Cutler JA, Bingham SF, et al. Am J Hypertens 7(9PT1), 814, 1994.
effect) for the entire cohort of –1.0/–0.6 mmHg and –0.9/–0.6 mmHg. For the hypertensive
participants, the nonsignificant treatment effect at 6 and 12 months was –1.9/–0.6 and
–1.6/–0.4 mmHg. There was no significant difference in the incidence of hypertension at
24 months: 16.6% in the intervention group and 21.8% in the control group. Weight
declined more in the intervention group by –0.5 and –1.0 kg at 6 and 24 months.
PATHS was designed to achieve a 2-drink reduction in alcohol between treatments, but
only achieved a reduction of 1.3 drinks per day. Furthermore, it was anticipated that 60%
of the intervention group and 20% of the control group could reduce baseline alcohol
intake to less than 50%; however, at 6 months the level for the control group was 23% and
the intervention group was 44%.
Caffeine
Caffeine may increase peripheral vascular resistance by blocking the adenosine receptors.
There are few randomized, controlled trials assessing the impact of coffee consumption
on blood pressure. A meta-analysis (see Table 47.19) reviewed 36 studies and identified
11 controlled trials with 522 subjects.103 The median duration of the trials was 56 days.
They estimated the overall pooled treatment effect attributable for a median coffee intake
of 5 cups/d as +2.4 mmHg (95% CI +1.0 to +3.7) for systolic blood pressure and +1.2
mmHg (95% CI +0.4 to +2.1) for diastolic blood pressure. Only one of the 11 trials included
a hypertensive cohort. This meta-analysis did not observe a treatment effect on blood
pressure based on treatment duration, the type of coffee (instant or not), whether coffee
was filtered, or the type of coffee control (decaffeinated or no coffee). Age, coffee con-
sumption, and sample size were independently associated with both systolic and diastolic
blood pressure. The systolic and diastolic blood pressure increased 0.8 and 0.5 mmHg per
cup of coffee consumed. A recent study using ambulatory blood pressure monitoring to
study nonsmoking men and women older than 50 years reported a +4.8/+3.0 mmHg
higher 24-hour systolic and diastolic blood pressure comparing 14 hypertensive coffee
drinkers of 5 cups/d for two weeks compared with 13 hypertensive abstainers after a
mandatory period of abstention of caffeine-containing foods for two weeks.104
994
TABLE 47.19
Controlled Studies of Coffee Consumption
Baseline Habitual
No. of Age, y Age, y BP Study Random Study BP, mmHg Intake, Run-time Coffee Coffee No Cups Caffeine
Author, Year Subjects Mean Range % Male Drugs Design* Study Duration SBP/DBP cups/d Time, d Method Filtered of Coffee Content
Ammon, 1983 8 27 20-30 100 No XO, D No 28 d 123/82‡ ... 7 Instant No 504
... 126/85§
Burr, 1989 54 35 18-58 65 No XO, S Yes 28 d 116/69 ... 7 Instant No 5 ...
Bak, 1989a 67 26 18-33 54 No PG, ... Yes 63 d 122/71 5.9 21 Boiled No 5 630
Bak, 1989b 68 26 18-33 54 No PG, ... Yes 63 d 122/71 5.5 21 Boiled Yes 5 670
Van Dusseldorp, 1980 45 38 25-45 49 No XO, D Yes 42 d 124/76 .. 0 Drip Yes 5 435
Rosmarin, 1990 21 36 ... 100 No XO, ... Yes 56 d 115/72 ... 0 Drip Yes 3.6 ...
MacDonald, 1991† 52 47 26-67 44 No XO, D Yes 14 d 134/87¶ ... 0 Instant No 3 ...
Van Dusseldorp, 1992a 43 39 17-57 42 No PG, D Yes 79 d 110/69¶ 5.5 17 Boiled No 6 860
Van Dusseldorp, 1992b 42 39 17-57 42 No PG, D Yes 79 d 110/70¶ 5.5 17 Boiled Yes 6 887
Eggertsen, 1993 23 56 28-74 57 Yes XO, D Yes 14 d 130/80¶ 3.5 14 Instant No 3.5 ...
Superko, 1994 99 46 43-48# 100 No PG, D Yes 56 d 116/74 4.5 0 Drip Yes 4.5 584
* BP indicates blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; XO, crossover; D, double-blind; S, single-blind; and PG, parallel group.
† MacDonald (1991): mean ambulatory BID during caffeinated coffee regimen vs caffeine-free diet.
‡ Regular coffee group.
§ Decaffeinated coffee group.
¶ Ambulatory BP measurements.
# Range of means.
Modified from Jee SH, He J, Whelton PK, et al. Hypertension 33(2), 647, 1999.
Weight Reduction (Caloric Deprivation)

The relationship between obesity and hypertension is well documented. All adults with
a BMI of 25 kg/m2 or greater are at risk for hypertension.105 The impact of weight reduction
as a modality for preventing or reducing blood pressure is addressed in the section on
major nonpharmacologic trials.
Summary
Table 47.20 summarizes the meta-analyses on nonpharmacologic intervention and blood
pressure. The importance of the amount of change in blood pressure varies with the
perspective of the clinician vs. that of the epidemiologist.
TABLE 47.20
Meta-Analysis of Results of Studies on Nonpharmacologic Intervention and Blood
Pressure
Number Systolic Pressure Diastolic Pressure
Author, Year of Trials Nutrient (95% CI) (95% CI)
Jee, 1999103 11 Caffeine +2.4 (+1.0 to +3.7) +1.2 (+0.4 to +2.1)
Normotensives 10 +2.4 (+1.0 to +3.8) +1.2 (+0.4 to +2.1)
Cappuccio, 198939 15 Calcium -0.13 (-0.46 to +0.19) +0.03 (-0.17 to +0.22)
Hypertensives 10 +0.06 (-0.59 to +0.72) +0.03 (-0.21 to +0.27)
Cutler, 199035 19 Calcium -1.8 (-3.0 to -0.6) -0.7 (-1.5 to +0.2)
Normotensives 9 -1.3 (-3.2 to +0.8) -1.3 (-2.6 to -0.1)
Hypertensives 12 -2.1 (-3.6 to -0.6) -0.1 (-1.3 to +1.0)
Allender, 1996 41 22 Calcium -0.89 (-1.74 to -0.05) -0.18 (-0.75 to +0.40)
Normotensives 13 -0.53 (-1.56 to +0.49) -0.28 (-0.99 to +0.42)
Hypertensives 16 -1.68 (-3.18 to -0.18) +0.02 (-0.96 to +1.00)
Buchner, 199642 33 Calcium -1.27 (-2.25 to -0.29) -0.24 (-0.92 to +0.44)
Hypertensives 6 -4.30 (-6.47 to -2.13) -1.50 (-2.77 to -0.23)
Griffith, 199943 42 Calcium -1.44 (-2.20 to -0.68) -0.84 (-1.44 to -0.24)
He, 199665 20 Fiber -1.6 (-2.7 to -0.4) -2.0 (-2.9 to -1.1)
Silagy, 199487 8 Garlic -7.7 (-11.0 to -4.3) -5.0 (-7.1 to -2.9)
Appel, 199355 17 ω-3-Fatty Acids -1.5 (-2.4 to -0.6) -1.0 (-1.6 to -0.4)
Normotensives 11 -1.0 (-2.0 to 0.0) -0.5 (-1.2 to +0.20)
Morris, 199356 31 ω-3- Fatty Acids -3.0 (-4.5 to -1.5) -1.5 (-2.2 to -0.8)
Cappuccio, 1991106 18 Potassium -4.0 (-4.7 to -3.2) -2.4 (-3.0 to -1.8)
Whelton, 199729 32 Potassium -3.11 (-4.31 to -1.91) -1.97 (-3.42 to -0.52)
Normotensives 12 -1.8 (-2.9 to -0.6) -1.0 (-2.1 to 0.0)
Cutler,199111 23 Sodium -2.91 (-3.67 to -2.15) -1.60 (-2.09 to -1.11)
Normotensives 6 -1.70 (-2.68 to -0.72) -0.97 (-1.62 to -0.32)
Midgley, 199613 56 Sodium -0.5 (-1.17 to -0.07) -1.6 (-2.10 to -1.02)
Cutler, 199714 32 Sodium -2.81 (-3.39 to -2.23) -1.52 (-1.90 to -1.14)
Normotensives 12 -1.90 (-2.62 to -1.18) -1.09 (-1.57 to -0.61)
Graudal, 199815 Sodium
Normotensives 56 -1.2 (-1.8 to -0.6) -0.26 (-0.3 to +0.9)
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48
Nutritional Treatment of Blood Pressure:
Major Nonpharmacologic Trials of Prevention
or Treatment of Hypertension
L. Michael Prisant
Major Nonpharmacologic Trials of Prevention or Treatment of

Hypertension
Primary Prevention Trials
Primary Prevention of Hypertension (PPH) Trial
The purpose of PPH was to determine whether intense lifestyle modifications would
reduce the incidence of hypertension and lower blood pressure in the intervention versus
the monitored (control) group.1 “Hypertension-prone” individuals between the ages of 30
to 44 years were screened. Diastolic blood pressure < 90 mmHg was required for enroll-
ment. Greater than 50% above desirable weight, excess alcohol use, diabetes mellitus, and
major cardiovascular diseases precluded participation in the trial. Diastolic blood pressure
≥90 mmHg or initiation of antihypertensive drug therapy was the primary endpoint.
Interventions by nutrition counselors and physicians included either:
The greater of a 4.5 kg decrease or 5% weight loss in overweight subjects

Decreased sodium intake to ≤1800 mg (4.5g NaCl)
Reduced alcohol intake (≤26g)
Increased physical activity (30 minutes for 3 days per week)
The group that did not receive the intervention was monitored. Baseline characteristics
are shown in Table 48.1. The incidence of hypertension was 8.8% of 102 intervention and
19.2% of monitored subjects (p = 0.027) over 5 years. The odds ratio for hypertension
development in the control group was 2.4 (90% CI 1.2-4.8, p <0.027).
0-8493-2705-9/01/$0.00+$1.50
1000
TABLE 48.1
Nonpharmacologic Interventions in High Normal Blood Pressure*
Systolic/ Relative
Mean % % Study Initial Diastolic Risk of
Trial n Age (Yr) Male White Duration Intervention Blood Pressure Change Hypertension*
Primary Prevention of Hypertension 1 201 38 87 82 5 yr ↓calories & NaCl 123/83 -1.3/-1.2 0.46†
↓ethanol
↑physical activity
Hypertension Prevention Trial2 252 38 68 80 3 yr ↓calories 125/83 -2.4/-1.8 0.77
392 39 62 84 3 yr ↓NaCl 124/83 +0.2/+0.1 0.79
255 39 62 82 3 yr ↓calories & NaCl 125/83 -1.0/-1.3 0.95

391 38 63 85 3 yr ↓NaCl & ↑ KCl 124/83 -1.2/-0.7 0.77
Trial of Hypertension Prevention3 564 43 72 79 18 mo ↓calories & 124/84 -2.9/-2.3 0.49†
(Phase 1) ↑physical activity
744 43 72 79 18 mo ↓NaCl 125/84 -1.7/-0.9 0.76
562 43 71 84 18 mo Manage Stress 125/84 -0.5/-0.8 1.07
471 43 68 85 6 mo ↑ Calcium 126/84 -0.5/+0.2 0.91
461 43 68 85 6 mo ↑ Magnesium 125/84 -0.2/-0.1 0.63
351 43 72 87 6 mo ↑ Potassium 122/81 +0.1/-0.4 0.87
350 43 70 86 6 mo ↑ Fish Oil 123/81 -0.2/-0.6 1.11
Trial of Hypertension Prevention4 1191 43 66 79 36 mo ↓calories 127/86 -1.3/-0.9 0.81†
(Phase 2) 1190 43 67 80 36 mo ↓NaCl 128/86 -1.2/-0.7 0.88
1193 43 69 79 36 mo ↓calories & NaCl 127/86 -1.1/-0.6 0.84†
* Defined as diastolic blood pressure of ≥90 mmHg or antihypertensive drug therapy during followup.
† p <0.05.
Modified from Arch Intern Med 1993;153 January 2 :186-208.19 Used with permission and Copyright 1993, American Medical Association.
Nutritional Treatment of Blood Pressure 1001
TABLE 48.2
Hypertension Prevention Trial (HPT): Six-Month Change in Interventions
High BMI Low BMI
Sodium/ Sodium/
Control Kcalories Sodium Calories Control Sodium Potassium
Number of subjects 121 112 109 113 191 173 180
∆SBP/DBP (mmHg) -1.8/-2.5 -6.9†/-5.3‡ -3.6/-3.4 -5.8/-4.0 -2.1/-3.0 -3.8/-3.4 -3.4/-3.7
∆Weight (kg) +0.18 -5.58† -0.04 -3.90 +0.27 +0.00* +0.27
∆Na+Excretion (mmol/8h) -4.5 -4.2 -7.8 -8.4 -3.9 -9.4¶ -11.4
∆K+Excretion (mmol/8h) 0.3 -1.1 0.9 -0.1 -0.1 0.2 1.2
* p = 0.025; † p <0.001; ‡ p <0.01; ¶ p = 0.002.
Derived from Tables 4 and 5 in the report of The Hypertension Prevention Trial, Arch Intern Med 150: 153; 1990.
Hypertension Prevention Trial (HPT)

Men and women between the ages of 25 to 49 years with a diastolic blood pressure ≤89
mmHg were randomized.2 Group and individual dietary counseling was performed. This
primary prevention trial allocated subjects (see Table 48.1) on the basis of body mass index
(BMI) into several interventions. Low BMI (men <25 kg/m2 and women <23 kg/m2 were
randomized to either a control group (n = 70), sodium restriction (n = 70) ≤70 mmol/d
(≤1610 mg/d) or sodium restriction and potassium augmentation (n = 71) ≥100 mmol/d
(3900 mg/d). High BMI individuals were randomized to control (n = 126), caloric restric-
tion (n = 125), sodium restriction (n = 126), sodium and caloric restriction (n = 129), and
sodium restriction and potassium augmentation (n = 124).
The mean change in blood pressure for the interventions is displayed for both systolic
and diastolic blood pressure at six months in Table 48.2. Caloric restriction reduced blood
pressure significantly. Caloric and sodium restriction was a less effective strategy in this
cohort. Sodium restriction with or without caloric restriction or potassium supplementa-
tion had no effect on blood pressure reduction. After three years, weight reduction was
still significant (3.5 kg, p <0.001) and was associated with a significant blood pressure
reduction of –2.4/–1.8 mmHg. After three years, the incidence of hypertension was sig-
nificantly reduced in the low BMI group only (p <0.01), but only marginally so in the high
BMI group (p = 0.066) as shown in Figure 48.1.
Trials of Hypertension Prevention (TOHP), Phase I

The TOHP (Phase I) was designed to assess the effect of various nonpharmacologic
interventions in nonhypertensive subjects to lower blood pressure, and to determine the
long-term impact on preventing the development of hypertension (see Table 48.1).3 The
trial was a multicenter, randomized study that examined three lifestyle interventions —
weight reduction (n = 308), sodium restriction (n = 327), and stress management (n = 242)
— compared to usual care (n = 589), and various nutritional supplements in two stages
with an intervening washout period:
1. 25 mmol or 1g QD of calcium carbonate (n = 237), 15 mmol or 360 mg QD of

magnesium diglycine (n = 227), and placebo (n = 234)
2. 6 g of fish oil containing 3g of ω-3 fatty acids (n = 175), 60 mmol or 4.5 g of
potassium chloride (n = 178), and placebo (n = 175)
Weight reduction used a combination of caloric reduction, exercise increase, and behav-
ioral self-management. Stress management involved teaching slow breathing, progressive
High Body Mass Index Group
38.7%
40.0%
35.0%
31.2%
30.0% 28.2%
26.9%
Rate of 25.0%
Hypertension
20.0%
Treatment or BP
≥ 140/ ≥ 90 mmHg 15.0%
10.0%
5.0%
0.0%
Control Caloric Na+ Restriction Na+/Caloric
(n=124) Reduction (n=119) Reduction
(N=124) (n=125)
Low Body Mass Index Group
40.0%
35.0% 33.5%
30.0%
24.6%
Rate of 25.0% 21.7%
Hypertension
20.0%
Treatment or
≥ 140/ ≥ 90 mmHg 15.0%
10.0%
5.0%
0.0%
Control Na+ Na+
(n=194) Restriction Reduction/K+
(n=187) Increase
(n=189)
FIGURE 48.1
The Hypertension Prevention Trial: three-year rate of elevated blood pressure or treatment for hypertension,
according to BMI and intervention.
muscular relaxation, mental imagery, stretching, and managing stress perceptions, reac-
tions, and situations. The lifestyle modifications lasted 18 months and used blinded mea-
surement of blood pressure as an endpoint. The nutritional supplements were placebo
controlled, doubled blinded, and lasted 6 months.
The primary outcomes are displayed in Table 48.3 and Figure 48.2. Only weight reduc-
tion significantly lowered blood pressure and reduced the development of hypertension
TABLE 48.3
Intervention Outcome, Treatment Effect, and Blood Pressure Effect (Active – Control)
in Trial of Hypertension Prevention, Phase I
Outcome Treatment Blood Pressure
Intervention Effect Effect
18 Months Maximum Followup
Sodium excretion (mmol/24h) -43.86† -1.69†/-0.85*

Weight change (kg) -3.90† -2.90†/-2.28†
Stress score frequency/intensity +2.35†/-0.01 -0.47/-0.82
6 Months Maximum Followup
Magnesium excretion (mmol/24h)/serum (mmol/L) 1.31†/+0.04† -0.20/-0.05

Calcium excretion (mmol/24h) 0.91† -0.46/+0.20
Potassium excretion (mmol/24h) 42.29† +0.06/-0.42
% Eicosapentaenoic/Docosahexaenoic fatty acid 2.90†/2.04† -0.22/-0.62
* p <0.05; † p <0.01.
Derived from Tables 2 and 3 in Trial of Hypertension Prevention, Phase 1, JAMA 267: 1213; 1992.
14.0% 13.3%
12.0% 11.3% Control

10.3%
9.7% Active
10.0%
8.6%
8.0%
Rate 6.5%
( % ) 6.0% 5.6% 5.6% 5.7%
5.1% 5.1% 4.5% 5.1%
4.0% 3.5%
2.0%
0.0%
Sodium Weight Stress Magnesium Calcium Potassium Fish Oil
Reduction Reduction Management (n=461) (n=471) (n=353) (n=350)
(n=744) (n=564) (n=562)
FIGURE 48.2
Trial of Hypertension Prevention, Phase 1. Incidence of hypertension in each lifestyle change and nutritional
supplement group. Only weight reduction significantly reduced incidence of hypertension, relative risk = 0.49
(95% CI, 0.29 to 0.83). Derived from corrected table in JAMA 1992; 267(17): 2330.
at maximal followup at 18 months. Sodium restriction significantly lowered systolic and

diastolic blood pressure, –1.7/–0.9 mmHg, but did not significantly reduce the incidence
of hypertension.
The weight loss goal was 4.5 kg for the participants with 115 to 165% of desirable body
weight that were enrolled. 45% of men and 26% of women in the intervention group
compared with 12% of men and 18% of women in the control group met the weight loss
goal at 18 months. The net change in weight at 18 months was 4.7 kg for men and 1.8 kg
for women (p <0.01). Rather than being related to gender, the treatment effect was related
to the higher baseline weight in males. In fact, the amount of blood pressure change, by
gender related more to the quintile of weight change as shown in Table 48.4.
TABLE 48.4
Trial of Hypertension Prevention, Phase 1: Effect of Weight
Change on Blood Pressure Reduction at 18 Months by Gender
Quintile of Weight Change, kg
<-9.5 -9.5 to <-4.5 -4.5 to <-2.0 -2.0 to <1.0 ≥1.0
∆ Systolic Blood Pressure (mmHg)
Men -9.0 -6.6 -4.8 -3.3 -1.6

Women -5.7 -7.5 -5.0 -0.8 -1.2
∆ Diastolic Blood Pressure (mmHg)
Men -9.4 -6.8 -5.5 -4.2 -2.6

Women -9.1 -7.1 -4.3 -4.9 -4.1
Derived from Figures 3, 4, and 5 in Trial of Hypertension Prevention,
Phase 1, JAMA 267: 1213; 1992.
TABLE 48.5
Baseline Characteristics and Outcomes of Trials of Hypertension Prevention (Phase II)
Sodium
Weight Loss Restriction Combined Usual Care
Number 595 594 597 596
Age, y 43.4 44.2 43.6 43.2
Male, % 63.0 64.8 68.8 68.3
White, % 78.0 81.1 78.4 79.5
Weight, kg 93.4 94.0 93.6 93.6
Baseline sodium excretion, mmol/d 180.9 186.1 179.3 188.0
Baseline blood pressure, mmHg 127.6/86.0 127.7/86.1 127.4/86.0 127.3/85.8
Six Month Followup
Weight change, kg -4.4 -1.1 -4.1 0.1

p <0.001* p <0.001* p <0.006*
Sodium excretion change, mmol/d -18.2 -78.0 -64.3 -27.6
p = 0.48* p <0.001* p = 0.006*
Change in blood pressure, mmHg -6.0/-5.5 -5.1/-4.4 -6.2/-5.6 -2.2/-2.8
p <0.001/<0.001† p <0.001/<0.001† p <0.001/<0.001†
Incidence of hypertension, % 4.2 4.5 2.7 7.3
p = 0.02* p = 0.04* p <0.001*
36 Month Followup
Weight change, kg -0.2 +1.7 -0.3 +1.8

p <0.001* p = 0.92* p <0.001*
Sodium excretion change, mmol/d -9.0 -50.9 -34.1 -10.5
p = 0.79* p <0.001* p <0.001*
Change in blood pressure, mmHg -0.8/-3.2 -0.7/-3.0 -0.5/-3.0 +0.6/-2.4
p = 0.01/0.04† p = 0.02/0.10† p = 0.05/0.19†
Incidence of hypertension, % 31.9 34.4 32.8 39.2
* significance vs. usual care group
† significance of systolic and diastolic blood pressure vs. usual group
Derived from Tables 1 through 4 from The Trials of Hypertension Prevention (Phase II) Prevention Collaborative
Research Group, Arch Intern Med 157: 657; 1997.
Trials of Hypertension Prevention (TOHP II), Phase II

The randomized TOHP II was conducted as a two-by-two factorial design study to assess
the effect of weight reduction, sodium restriction, or both compared to usual care in
lowering blood pressure and preventing the development of hypertension after three to
four years of followup.4 Diastolic blood pressure was required to be 83 to 89 mmHg at
the third screening visit, and weight 110 to 165% of desirable body weight. Intervention
goals for the weight reduction group was weight loss ≥4.5 kg, and for the sodium reduction
group a decrease in sodium intake ≤80 mmol/d. Blinded observers measured blood
pressure. 2382 subjects were recruited.
Baseline and treatment outcomes are displayed in Table 48.5. By 6 months, neither the
weight loss nor sodium restriction goals were met by the groups; however, the net blood
pressure reduction compared to the usual care group was significant (p <0.001 for each
intervention): weight loss, –3.7/–2.7 mmHg; sodium restriction, –2.9/–1.6 mmHg; and the
combination, –4.0/–2.8 mmHg. At 36 months, many of the treatment effects were lost. The
38% incidence of hypertension was similar in all treatment groups, compared to 44% in
the usual care group, and did not appear additive at 36 months. The relative risk of
hypertension (compared with the usual care group) was 0.87 for the weight loss group (p
= 0.06), 0.86 for the sodium reduction group (p = 0.04), and 0.85 for the combined inter-
vention group (p = 0.02).4
Secondary Prevention Trials

Dietary Intervention Study of Hypertension (DISH)
Participants in DISH were former medicated participants of the Hypertension Detection
and Follow-up Program.5 The cohort (n = 496) was grouped into obese (≥120% of ideal
body weight) or nonobese. The obese group was randomized into one of four groups: 1)
continue drug therapy or 2) discontinue drug therapy and a) receive no dietary interven-
tion, the control group, b) decrease sodium intake, or c) lose weight. The nonobese group
was randomized to 1) continue drug therapy or 2) discontinue drug therapy and a) receive
no dietary intervention, the control group, or b) decrease sodium intake.
Demographics and outcomes are shown in Table 48.6. Among overweight persons, 46.3%
lost an average of 5% of weight, or greater than 4.5 kg after 56 weeks. The average weight
TABLE 48.6
Dietary Intervention Study in Hypertension: Demographics and Outcome
Obese Obese Obese Obese Lean Lean Lean
Drug Therapy No Drug Sodium Weight Drug Therapy No Drug Sodium
Control Control Restriction Reduction Control Control Restriction
Number 48 89 101 87 33 70 68
Age (Yr) 59 57 57 56 58 57 56
% Black 75 70 64 62 58 73 56
% Women 69 64 59 68 52 50 47
BP (mmHg) 131/80 128/80 128/81 128/81 126/80 124/80 127/81
∆Weight (kg) -0.46 -0.46 0 -4.0 +0.46 0 +0.46
∆ Urine Na+ -13 -10 -59 0 +2 -5 -44
(mEq/d)
% on no BP 0 35 45 60 0 45 53
Drugs
Derived from Tables 1, 2, and 3 in article by Langford, H.G., et al. JAMA 253: 657; 1985.
TABLE 48.7
Hypertension Control Program: Demographics and Outcome
No BP Drugs No BP Drugs BP Drugs
Nutritional Therapy No Nutritional Therapy No Nutritional Therapy
Number 97 44 48
Age (Yr) 57 55 55
% Female 35 39 38
% Black 11 21 15
BP (mmHg) 122/78 118/77 119/79
∆ Weight (kg)* -1.8‡ +2.0 +2.0
∆ Urinary Na+ (mEq/d) -60‡ +20 -5
∆ Ethanol (g/d)† -12.5 -7.1 -10.2
% Without BP Drugs 39%‡ 5% 0%
* Among obese subjects only; † Among drinkers only; ‡ p <0.001
Derived from tables and manuscript of Stamler, R. et al. JAMA 257: 1484; 1987.
loss in this group was 4.0 kg (p <0.05 versus the no-medication control group). Among
obese and nonobese persons who were sodium restricted, the mean decrease in urine
sodium output was –59 mEq/24 hr and –44 mEq/24 hr (each p <0.05 versus the no-
medication control group) after 56 weeks. The percent not taking antihypertensive med-
ication among obese individuals was 35.3% in the control group, 44.9% in the sodium
restricted group, and 59.5% in weight loss group (p = 0.0015 versus control). In the lean
group, the percent not taking antihypertensive medication was 45% in the control group
and 53.4% in the sodium-restricted group (not significantly different).
The Hypertension Control Program (HCP)

Participants in the HCP were former drug-treated participants of the Hypertension Detec-
tion and Follow-up Program. Subjects (n = 189) were randomized to three groups:
1. Discontinue antihypertensive therapy and reduce overweight, excess salt, and

alcohol
2. Stop medication without nutritional intervention (the control group)
3. Continue drug treatment with no nutritional program
The primary endpoint was the percentage of subjects remaining hypertensive in the
intervention versus the control group.
As shown in Table 48.7, in the nutritional intervention group, weight decreased (p
<0.001) and sodium output increased (p <0.001) significantly after four years. 39% of the
nutritional therapy group were maintained on no drug therapy compared to only 5% of
the control group (p <0.001).
Trial of Antihypertensive Intervention and Management (TAIM)

This multicenter, placebo-controlled trial randomized 787 overweight (110 to 160% ideal
body weight) hypertensive (baseline diastolic pressure 90 to 100 mmHg) men and women
to one of three drugs (placebo, chlorthalidone 25 mg QD, or atenolol 50 mg QD) and three
dietary interventions (usual diet, weight loss, or sodium decrease/potassium increase).6
The weight loss goal was 10% of baseline weight or 4.54 kg, whichever was greater. Sodium
reduction was 52 to 100 mmoles/d and potassium increase 62 to 115 mmoles/d, and
depended on weight. Both weight reduction and electrolyte changes required group nutri-
TABLE 48.8
Trial of Antihypertensive Intervention and Management: Change in Blood
Pressure from Baseline by Treatment Group at Six Months
Usual Diet Weight Loss Low Na+/High K+
Placebo -10.34/-7.96 (n = 90) -11.49/-8.78 (n = 90) -8.66/-7.91 (n = 79)
Chlorthalidone -17.41/-10.78 (n = 87) -21.72/-15.06 (n = 87) -19.51/-12.18 (n = 89)
Atenolol -15.06/-12.43 (n = 87) -18.11/-14.81 (n = 88) -18.29/-12.76 (n = 90)
Derived from Tables 2 and 3 from Langford, H.G. et al. Hypertension 17: 210; 1991.
tional counseling weekly for 10 weeks, and individually thereafter every 6 to 12 weeks.
There was no change in the drugs or their dosages during the first six months of the trial
unless critical diastolic blood pressures were reached (treatment crossovers). Change in
diastolic blood pressure treatment failure (as assessed by the need to increase drug treat-
ment), quality of life, and calculated cardiovascular risk were assessed.
Table 48.8 shows the change in systolic and diastolic blood pressure from baseline to six
months by treatment group. In the weight loss group, the average decrease in weight was
4.5 kg after six months. Weight loss was more effective than usual diet (p = 0.001) or the
low sodium/high potassium diet (p = 0.019) in lowering diastolic blood pressure. Weight
loss in combination with either a diuretic (–4.3 mmHg, p = 0.002), added significantly to
blood pressure reduction compared to usual diet with a diuretic. The combination of weight
loss with a β-blocker (–2.4 mmHg, p = 0.07) did not add to the effect of the drug alone.
45% of the weight loss cohort lost ≥4.5 kg. For patients who were not treatment cross-
overs, placebo and usual diet (n = 71) was associated with a 7 mmHg decrease in blood
pressure and a 0.63 kg change in weight, and was less effective than placebo with >4.5
kg weight loss and diastolic blood pressure decrease of 11.6 mmHg (p <.01). There was a
graded relationship with the amount of weight reduction and blood pressure decrease:
<2.25 kg, –6.9 mmHg; –2.25 to 4.5 kg, –8.9 mmHg; and >4.5 kg, –11.6 mmHg. The change
in diastolic blood pressure inversely correlated with the baseline plasma renin indexed to
the 24-hour urinary sodium in the weight loss diet group.7 In fact, the change in diastolic
blood pressure with >4.5 kg weight change is comparable to low-dose drug therapy as
seen in Table 48.9. After 24 months, there was gradual return of weight toward the
baseline.8 Among the weight-loss diet patients, the least mean change in weight occurred
among atenolol-treated subjects. In fact, among atenolol-treated subjects assigned to usual
diet or electrolyte modification, there was a mean weight gain. The 5-year incidence of
treatment failure was lower in the weight loss group (49.8 per 100 subjects) than in the
usual diet group (56.7 per 100 subjects).9
TABLE 48.9
Trial of Antihypertensive Intervention and
Management: Change in Diastolic Blood Pressure with
>4.5 kg Weight Change — Comparable to Low-Dose
Drug Therapy
Usual Diet ≥4.5 kg Weight Loss
Placebo -7.0 (n = 71) -11.6 (n = 33)*
Chlorthalidone -11.1 (n = 80) -15.3 (n = 53)†
Atenolol -12.4 (n = 79) -18.4 (n = 26)‡
* p <0.01, † p = .002, and ‡ p = 0.0005 compared to usual diet.
Derived from Figures 2 and 3 from Wassertheil-Smoller, S. et
al. Arch Intern Med 152: 131; 1992.
In the low sodium/high potassium group, the average decrease in urinary sodium was
27.4 mmol/d and the average increase in urinary potassium 10.9 mmol/d. The effect on
blood pressure of the low sodium/high potassium diet did not differ from that of the
usual diet (p = 0.347) on blood pressure. The low sodium/high potassium diet did not
further lower diastolic blood pressure, but the baseline urinary sodium excretion was
already relatively low (133 mmol/d). However, in the placebo group, when urinary
sodium excretion ≤70 mEq/d was achieved, systolic and diastolic blood pressure reduction
was greater than in the usual diet group (–23.7/–13.9 mmHg versus –9.6/–7.0 mmHg,
each p <0.005).10
After 3 years, compared to the usual diet, the net difference of urinary sodium excre-
tion reduction was 30 mmol/d and urinary potassium excretion augmentation was
11 mmol/d.11 There was a 41% decrease (p = 0.01) in the risk of treatment failure for
women and 34% decrease (p = 0.03) among less obese patients. After 3.5 years among
patients assigned to low sodium/high potassium diet, treatment failures occurred in
68% of placebo-, 47% of diuretic-, and 35% of β-blocker-assigned subjects.
Quality of life was improved with weight reduction.12 Weight reduction significantly
reduced symptoms of physical problems, especially sexual problems, and improved sat-
isfaction with physical health. Weight loss improved the erectile dysfunction reported with
chlorthalidone and usual diet (12.1 versus 26.2%).13 Weight reduction reduced symptoms
of sexual problems in both men and women significantly. The low sodium/high potassium
diet with placebo was associated with greater fatigue (34.3%) than was either usual diet
(18.1%, p = 0.04) or weight reduction (14.6%, p = 0.009). The electrolyte intervention group
in combination with chlorthalidone (32.0%, p = 0.04) was associated with more sleep
disturbances than chlorthalidone versus usual diet (16%). A nonsignificant (p = 0.07)
similar trend was observed with atenolol.
Overall calculated cardiovascular risk worsened with chlorthalidone therapy in the
usual diet group at six months due to the changes in cholesterol and glucose.14 Those
persons treated with atenolol or weight reduction showed the lowest relative risk.
Trial of Nonpharmacologic Interventions in the Elderly

This was a randomized, multicenter, controlled trial of 975 men and women aged 60 to
80 years with blood pressure of <145/<85 mmHg on a single hypertensive drug.15 Patients
were randomized to treatment based on their body habitus. 585 obese patients either
received usual care, sodium restriction (a dietary intake of less than 80 mmoles per day
as measured by 24-hour urine sodium collection), a weight loss program to achieve a loss
of 4.5 kilograms or greater, or a combination of sodium restriction and weight loss. 390
nonobese patients were randomized to either usual care or sodium restriction.
The mean change in blood pressure prior to attempted medication withdrawal for each
group was: sodium reduction, –3.4/–1.9 mmHg; weight reduction, –4.0/–1.1 mmHg;
combination intervention, –5.3/–3.4 mmHg; and usual care, –0.8/–0.8 mmHg. Sodium
reduction, weight reduction, and the combination intervention lower blood pressure sig-
nificantly more than usual care. After three months of nonpharmacological therapy, anti-
hypertensive medication withdrawal was attempted. After 30 months, 44% of patients in
the combined sodium and weight reduction group were free of a primary endpoint
(sustained blood pressure of 150/90 mmHg or higher, pharmacologic treatment of hyper-
tension, or occurrence a clinical cardiovascular event). Compared to 16% in the usual care
group, 34% of the sodium restriction group and 37% of the weight reduction group did
not have a primary endpoint at 30 months. The sodium-restricted group reduced average
sodium intake about 40 mmoles per day. In the weight loss group, average body weight
decreased by 3.5 kilograms. Sodium restriction was equally effective in the obese and lean
subjects; however, the combined intervention was not more effective than either single
intervention. Predictors of successful long-term withdrawal of pharmacologic treatment
include lower baseline systolic blood pressure, shorter duration of hypertension or drug
treatment, and absence of a history of cardiovascular disease.16
Dietary Approaches to Stop Hypertension (DASH)

The DASH trial was a multicenter, randomized feeding study that sought to assess the
impact of nutrients naturally occurring in food in contrast to nutritional supplements.17
Subjects were required to have a systolic blood pressure less than 160 mmHg and a
diastolic blood pressure 80 to 95 mmHg. Persons consuming greater than 14 alcoholic
beverages per week were excluded from the study. After screening, all subjects completed
a three-week control diet. The control diet included magnesium, potassium, and calcium
at the 25th percentile of consumption, and fiber at the average level of consumption. After
the control period, 459 study participants received either a control diet, a fruit and vege-
table diet, or combination diet for eight weeks. The fruit and vegetable diet provided
magnesium and potassium at the 75th percentile of consumption and was also high in
fiber. The combination diet was high in protein and fiber, provided increased calcium,
magnesium, and potassium to the 75th percentile of consumption, and reduced intake of
total fat, total cholesterol, and saturated fat. The sodium content (~3000 mg per day) was
similar for all three diets, and caloric intake was adjusted so that weight gain did not
occur in the study.
The average age of the subjects was 44 years; 60% were African Americans and 49%
were women. About 14% had a diastolic blood pressure ≥90 mmHg, and 23.5% had a
systolic blood pressure ≥140 mmHg. Change in the diastolic blood pressure was the
primary outcome. The change in blood pressure in the combination group (corrected for
the change in the control group) was –5.5/–3.0 mmHg (p <0.001 for each). The change in
blood pressure among hypertensive subjects was larger than in nonhypertensive subjects
(–11.4/–5.5 mmHg versus –3.5/–2.1 mmHg), and among minority subjects was larger than
nonminority subjects (–6.8/–3.5 mmHg versus –3.0/–2.0 mmHg). The change in blood
pressure in the fruit and vegetable group minus the change in the control group was –2.8/
–1.1 mmHg (p <0.001 for each). Hypertensive subjects had a greater blood pressure
reduction (–7.2/–2.8 mmHg) on the fruit and vegetable diet.
The combination diet demonstrated superiority over the fruits and vegetables in reduc-
ing blood pressure significantly an average of –2.5/–1.9 mmHg more. The combination
diet lowered systolic blood pressure significantly more in African Americans (6.8 mm Hg)
than in whites (3.0 mm Hg), and in hypertensive subjects (11.4 mm Hg) than in nonhy-
pertensive subjects (3.4 mm Hg) (p <0.05 for both).18
Since the DASH trial showed a blood pressure-lowering effect for a diet rich in vegeta-
bles, fruits, grains, low-fat dairy products, fish, poultry, and nuts, a logical question was
whether there was an additional benefit of a low sodium diet. To answer this question,
412 subjects were randomly assigned to either the DASH diet or a control diet.21 Each
person for their assigned diet was rotated in random order at 30-day intervals to a low
(50 mmol/d), intermediate (100 mmol/d) or high (150 mmol/d) sodium intake diet. The
study population included 57% females, 57% blacks, and 41% hypertensives. Since this
was a feeding trial, it was not surprising that urinary excretion of sodium was reduced
according to treatment assignment in both the DASH and control diet groups. The change
in blood pressure in the control diet group from high to intermediate sodium intake was
–2.1/–1.1 mmHg, and from intermediate to low sodium intake –4.6/–2.4 mmHg. The
corresponding values for the DASH diet were –1.3/–0.6 mmHg and –1.7/–1.0 mmHg. All
of these values are statistically significant except for the change in diastolic blood pressure
from high to intermediate sodium intake in the DASH group. The benefit of the DASH
diet over the control diet was confirmed by the change in blood pressure in the high (–5.9/
–2.9 mmHg), intermediate (–5.0/–2.5 mmHg), and low sodium intake (-2.2/-1.0 mmHg)
groups. The greatest benefit was seen in hypertensive subjects, African Americans, and
women. There was a less than additive effect of decreased sodium intake and DASH diet,
but a greater effect than either intervention individually.
Summary
The primary prevention trials prove that sodium restriction and weight reduction are
effective in reducing the rate of development of hypertension. However, the behavioral
changes are difficult to sustain over a 36-month period, and the treatment effects are
modest. Individual strategies of potassium, calcium, magnesium, or fish oil supplemen-
tation are not effective in nonhypertensive subjects in lowering blood pressure or prevent-
ing the development of hypertension.
The secondary prevention trials document a clear benefit for sodium restriction and
weight reduction in controlling blood pressure. However, the combination of weight
reduction and sodium restriction was not additive. Weight loss was additive to diuretic
therapy and improved quality of life, including sexual dysfunction. Although individual
dietary components of potassium, calcium, magnesium, and fish oil supplementation have
not been successful strategies for primary prevention, the DASH feeding study, which
reduced intake of total fat, total cholesterol, and saturated fat, and increased protein, fiber,
fruit, and vegetable intake, demonstrates the potential that can be achieved with nonp-
harmacological interventions rich in these individual components.
References
1. Stamler R, Stamler J, Gosch FC, et al. JAMA, 262: 1801; 1989.
2. Arch Intern Med 150: 153; 1990.
3. JAMA 267: 1213; 1992.
4. Arch Intern Med 157(6): 657; 1997.
5. Langford HG, Blaufox MD, Oberman A, et al. JAMA 253: 657; 1985.
6. Langford HG, Davis BR, Blaufox D, et al. Hypertension 17: 210; 1991.
7. Blaufox MD, Lee HB, Davis B, et al. JAMA 267: 1221; 1992.
8. Davis BR, Oberman A, Blaufox MD, et al. Hypertension 19: 393; 1992.
9. Davis BR, Blaufox MD, Oberman A, et al. Arch Intern Med 153: 1773; 1993.
10. Wassertheil-Smoller S, Blaufox MD, Oberman AS, et al. Arch Intern Med 152(1): 131, 1992.
11. Davis BR, Oberman A, Blaufox MD, et al. Am J Hypertens 7: 926; 1994.
12. Wassertheil-Smoller S, Blaufox MD, Oberman A, et al. Ann Intern Med 114: 613; 1991.
13. Wassertheil-Smoller S, Oberman A, Blaufox MD, et al. Am J Hypertens 5: 37; 1992.
14. Oberman A, Wassertheil-Smoller S, Langford HG, et al. Ann Intern Med 112: 89; 1990.
15. Whelton PK, Appel LJ, Espeland MA, et al. JAMA 279: 839; 1998.
16. Espeland MA, Whelton PK, Kostis JB, et al. Arch Fam Med 8: 228; 1999.
17. Appel LJ, Moore TJ, Obarzanek E, et al. N Engl J Med 336: 1117; 1997.
18. Svetkey LP, Simons-Morton D, Vollmer WM, et al. Arch Intern Med 159: 285; 1999.
19. __________ Arch Intern Med 153: 186; 1993.
20. Stamler R, Stamler J, Grimm R, et al. JAMA 257: 1484; 1987.
21. Sacks FM, Svetkey LP, Vollmer WM, et al. N Engl J Med 344: 3; 2001.
49
Chemoprevention of Cancer in Humans
by Dietary Means
Elizabeth K. Weisburger and Ritva Butrum
This section will attempt to describe succinctly the basis for prevention of cancer by dietary
means. An understanding of the processes involved in carcinogenesis is vital to any efforts
in prevention. Reference 1 provides information on the metabolic activation of chemical
carcinogens to the ultimate forms, which interact with the genetic material of the cell. In
addition, the separate stages in carcinogenesis are described; namely, initiation or the first
step, promotion or enhancement of the process, and progression or increased growth and
expansion of the cancerous cells. Examples of how the different stages can be inhibited
or altered are provided.
Diet or nutrition is an essential part of life, for it furnishes the food elements needed to
sustain life, wards off some disease conditions, and helps insure a reasonable level of well
being. The choices we make for our diets can have an appreciable impact on our health
and vigor. Balanced and varied diets of natural foodstuffs, high in whole-grain products,
fruits, and vegetables, are more likely to enhance our health than diets of highly refined
foods. For a proper balance, various macronutrients, vitamins, minerals, and even non-
nutritive food constituents are necessary, as discussed herewith.
Macronutrients
Carbohydrates
Carbohydrates, either simple sugars or starches, are formed in plants through the process
of photosynthesis from carbon dioxide and water, and thus represent the means by which
the energy from the sun is converted into food. The simple sugars of dietary carbohydrates
are mono- and disaccharides such as glucose, sucrose, and fructose. Oligo and higher
polysaccharides, which include both starch and non-starch polysaccharides constitute the
major portion of dietary fiber. Starch occurs in cereals, legumes, roots, tubers, plantains,
and bananas; it is the energy source for plants, equivalent to liver glycogen in animals.
Starch which is resistant to digestion in the small intestine occurs in whole grains,
legumes, and potatoes, for example. This resistant starch is metabolized by the bacteria in
the large intestine to compounds which are important for both the growth of endogeneous
bacteria and for colonic epithelial cell proliferation. Nonstarch polysaccharides, along with
0-8493-2705-9/01/$0.00+$1.50
lignan from plant cell walls comprise dietary fiber, which plays an important role in
regulation of stool bulk and weight. Dietary fiber is considered to have a preventative
effect against colorectal cancer, since by increasing stool bulk, it dilutes any toxic material.2
Dietary carbohydrates should account for about 40 to 85% of total energy. Diets outside
these guidelines may be lacking in other needed constituents.3 Preferably, dietary carbo-
hydrates should include high fiber sources, since besides decreasing the risk of colorectal
cancer, there may be a preventative action for pancreatic and breast cancer. Conversely,
high starch diets or those high in refined starch may increase risk for stomach cancer.
Thus, the type of dietary carbohydrate can either be beneficial or deleterious with respect
to cancer risk.
Fats
Fats, often maligned as relatively undesirable dietary constituents, are nevertheless essen-
tial components of food. They are necessary building blocks for biological membranes,
have a high nutritive value, are a source of certain essential fatty acids and vitamins,
impart a pleasant feel to foods, solubilize or carry many of the flavor components of foods,
and serve as an energy storage depot. Chemically, fats are composed chiefly of the tri-
esters of long-chain aliphatic carboxylic acids with glycerol, along with minor amounts
of free acids and mono- and diacylglycerols. The composition of fat is affected by the
source — animal or vegetable, growth environment, type of food if from an animal, climate,
and location.
During the digestive process, fats are hydrolyzed by lipases to the respective acids which
serve as an energy source. The major acids from most domestic food animals are stearic,
palmitic, and oleic acids, while plant fats yield more of the unsaturated acids such as oleic,
linoleic, and linolenic. Fish oils, although containing some palmitic and stearic acids, have
varying amounts of other unsaturated fatty acids. As for nomenclature, the double bond
position is determined by counting from the methyl end of the aliphatic chain, using the
notation Ω (omega). Fatty acids from fish contain large amounts of Ω-3 fatty acids; those
from plants contain more of the Ω-6 type. The “shorthand” description of the fatty acid
depicts the number of carbon atoms in the chain and the number, positions, and config-
urations (cis/trans) of the double bonds (see Table 49.1).
The acids derived from fats or oils, besides being energy sources, have a role in enhanc-
ing or promoting, and suppressing or inhibiting, the processes involved with carcinogen-
esis. Generally, oleic acid and the Ω-3 unsaturated acids from fish oils appear to suppress
neoplastic effects, both in experimental and epidemiologic studies. Although epidemio-
logic studies cannot be controlled to the extent of animal studies, they indicate that
populations consuming diets richer in olive oil have a lower breast cancer incidence.4,5 In
some cases, higher fish consumption was associated with possibly decreased risk for
cancer of the larynx, pharynx, liver, colon, endometrium, and kidney.6,7 There are many
confounding factors in such studies, but the indications are that olive and fish oils are
beneficial, while the saturated fats from most meats and some of the Ω-6 unsaturated fats
from many oilseeds may enhance the action of exogenous or endogenous carcinogens.
An additional fatty acid with antimutagenic and anticarcinogenic effects in animal
systems is conjugated linoleic acid (CLA), a mixture of positional isomers of linoleic acid
where the double bonds are in positions 9 and 11 or 10 and 12 along the carbon chain.
Since the bonds can be in the cis or trans configuration, eight isomers are possible. CLA
was originally identified in grilled ground beef, but it has also been found in meat from
other ruminants, and in dairy products such as cheese. In animal experiments, CLA has
been effective as an inhibitor of tumors from application of polycyclic aromatic hydrocar-
bons, in decreasing the action of tumor promoters, decreasing cell proliferation, reducing
Chemoprevention of Cancer in Humans by Dietary Means 1013
TABLE 49.1
Typical Dietary Fatty Acids
Name Melting
Designation Structure Systematic Common Point(°C)
4:0 H3C(CH2)2 COOH Butanoic Butyric acid -7.9
5:0 H3C(CH2)3 COOH Pentanoic Valeric -34.5
6:0 H3C(CH2)4 COOH Hexanoic Caproic -3.9
7:0 H3C(CH2)5 COOH Heptanoic Enanthoic -7.5
8:0 H3C(CH2)6 COOH Octanoic Caprylic 16.3
9:0 H3C(CH2)7 COOH Nonanoic Pelargonic 12.4
10:0 H3C(CH2)8 COOH Decanoic Capric 31.3
12:0 H3C(CH2)10 COOH Dodecanoic Lauric 44.0
14:0 H3C(CH2)12 COOH Tetradecanoic Myristic 54.4
15:0 H3C(CH2)13 COOH Pentadecanoic Pentadecylic 52.1
16:0 H3C(CH2)14 COOH Hexadecanoic Palmitic 62.9
17:0 H3C(CH2)15 COOH Heptadecanoic Margaric 61.3
18:0 H3C(CH2)16 COOH Octadecanoic Stearic 69.6
20:0 H3C(CH2)18 COOH Eicosanoic Arachidic 75.4
22:0 H3C(CH2)20 COOH Docosanoic Behenic 80.0
24:0 H3C(CH2)22 COOH Tetracasonoic Lignoceric 84.2
26:0 H3C(CH2)24 COOH Hexacosanoic Cerotic 87.7
18:1 (9) CH3(CH2)7 CH=CH-(CH2)7 COOH Oleic 13.4
22:1 (13) CH3(CH2)7 CH=CH-(CH2)11 COOH Erucic 34.7
18:2 (9,12) CH3(CH2)4-(CH=CH-CH2)2 (CH2)6 COOH Linoleic -5.0
18:3 (6,9,12) CH3(CH2)4-(CH=CH-CH2)3 (CH2)3 COOH γ-Linoleic
20:4 (5,8,11,14) CH3(CH2)4-(CH=CH-CH2)4 (CH2)2 COOH Arachidonic -49.5
18:1 (tr 9) CH3(CH2)7 CH=CH (CH2)7 COOH Elaidic 46.0
18:3 (9,12,15) CH3-CH2 (CH=CH-CH2)3 (CH2) 6 COOH α-Linolenic -11.0
From CRC Handbook of Chemistry and Physics, D.R. Lide, Ed., 80th ed., 1999-2000.
the activation of heterocyclic amine carcinogens for some organ sites but not others, and
modulating the action of protein kinase C proteins involved in signal transduction.8,9 CLA
was effective at a dietary level of 0.1%, one-hundredfold less than the level of dietary fish
oil needed to inhibit animal tumors. Despite the effectiveness in both animal and cell
culture studies, CLA as such has not been investigated in any sizable population studies.
A controversial aspect of the fatty acid situation relates to trans fatty acids. These
compounds, where the hydrogens are on opposite sides of the carbons in the double
bonds, are linear, akin to the shape of saturated fatty acids. Although trans fatty acids
occur in nature in plants and in milk and meat from ruminants, the main source of dietary
intake is through partial hydrogenation of vegetable oils, which have been used in mar-
garine, salad oils, shortenings, and cooking fats for most of this century. Animal studies
have shown that diets with up to 35% trans fat had no effect on growth or reproduction,
but like natural saturated fats, they increased blood cholesterol levels. Epidemiological
studies are controversial, but they have not shown untoward effects of trans fatty acids
if used prudently.10,11
Thus, monounsaturated dietary fatty acids and perhaps the Ω-3 unsaturated acids found
in fish oils may have a suppressing action against certain human cancers. Nevertheless,
even such advantageous fats should be used prudently.12,13
Protein
Proteins are complex molecules comprising combinations of amino acids. They can be
of plant or animal origin; for example, about 20 to 35% of legumes is protein, 8 to 25%
of nuts and seeds, 8 to 16% of cereals, 10 to 20% of meat and fish, 15% of eggs, 3.5% of
milk, and 13% of vegetables. Proteins are important nutritionally, as they supply the
necessary building blocks for protein biosynthesis in specific organisms, contribute to
the physical properties of food, and are either part of the flavor of food or are the
precursors for flavor components formed during thermal or enzymatic reactions occur-
ring during food processing.
Protein intake usually varies between 10 and 18% of total energy in different countries,
and the composition varies depending whether animal or vegetable proteins are con-
sumed.14 There are no definitive data in humans indicating an association between cancer
risk and protein intake, due to the presence of other macroconstituents in protein sources
and various micronutrients. Dietary use of soy products has been suggestive for a lower
risk of breast and endometrial cancer in Asian women.15-17 Whether this is due to the soy
protein, or more likely, the flavonoids present in soy has not been exactly determined. In
animal studies, however, low protein diets tend to inhibit cancer, probably due to slower
growth, while a high intake tends to enhance cancer development at various sites.
Proteins themselves are hydrolyzed or split by proteases to the individual amino acids,
some of which are essential for mammalian growth and development while others are
not (Table 49.2). Proteins from animal sources (animals, birds, fish, shellfish) are considered
complete proteins since all the essential amino acids are present. Proteins from plant
sources are generally incomplete since one or the other of the essential amino acids is low.
However, combinations of plant proteins can usually supply all the essential amino acids;
for example, corn and beans or rice and beans.
Chemically, some of the amino acids have nonpolar uncharged side chains; others have
uncharged polar side chains, while still others have charged polar side chains (Table 49.2).
These side chains are involved in the reactions and configurations of amino acids and the
proteins from them.
Of all the amino acids, only methionine appears to be involved in physiological processes
which have a chemopreventive action against cancer. As its S-adenosyl derivative or SAM,
it is important, in conjunction with folate, in methylation of nucleic acid bases. Under- or
hypomethylation of these cell constituents has been associated with cancer in animal
studies. In animal experiments, deficiencies of SAM and folate led to tumors in rats and
mice. The data for the folate/SAM effect for decreasing colorectal cancer in humans are
suggestive but not definitive.18,19
Total Energy
Total energy denotes the sum of the kcalories from fats, proteins, and carbohydrates within
the diet of an individual. Energy requirements for each person vary with weight, height,
age, body mass, and physical activity. Persons involved in strenuous physical activity such
as competitive sports or mountain climbing obviously require more kcalories than those
with sedentary lifestyles. However, it is excess total energy that becomes a problem, for the
caloric matter in excess food is converted to fat and stored as such in the body. Fat, besides
being an energy storage depot, also serves as a repository for all lipid-soluble xenobiotics
and leads to greater conversion of endogenous steroids to estrogen. Estrogen, in turn, is a
risk factor associated with breast and endometrial cancers. Higher body mass index is linked
to an increased risk for cancer of the kidney and possibly gallbladder, colon, pancreas, and
prostate. Continued physical activity and a body mass index below average tend to a
decrease in cancer risk. Thus, continued physical activity tends to decrease cancer risk.20
Recommendations on a diet for prevention of cancer emphasize the need to rely on a
low-fat diet, since dietary fat contains more kcalories on a weight basis than other macro-
TABLE 49.2
Amino Acids
Non- Non-polar, Polar, Uncharged Charged
Name Formula Essential essential Uncharged Sidechain Sidechain Sidechain
Alanine (Ala) H2N-CH(CH3) COOH X X
Arginine (Arg) H2N-C(=NH) NH(CH2)3 CH(NH2) COOH X X
Asparagine (Asn) H2N-CH (COOH) CH2 CONH2 X X
Aspartic acid (Asp) H2N-CH (COOH) CH2 COOH X X
Cysteine (Cys) H2N-CH (CH2SH) COOH X X
Glutamic acid (Glu) H2N-CH (COOH) (CH2)2 COOH X X

Glutamine (Gln) H2N-CH (COOH) (CH2) 2 CONH2 X X
Glycine (Gly) H2N-CH2 COOH X X
Histidine (His) H2N-CH (COOH) CH2 (C3N2H3) X (infant) X
Isoleucine (Ile) H2N-CH (COOH) CH(CH3) CH2 CH3 X X
Leucine (Leu) H2N-CH (COOH) CH2 (CHCH2CH3) X X
Chemoprevention of Cancer in Humans by Dietary Means
Lysine (Lys) H2N-CH (COOH) (CH2)4NH2 X X

Methionine (Met) H2N-CH (COOH) (CH2)2 SCH3 X X
Phenylalanine (Phe) H2N CH (COOH) CH2 C6H5 X X
Proline (Pro) HN (CH2)3 CH (COOH) X X
Serine (Ser) H2N-CH (COOH) CH2 OH X X
Threonine (Thr) H2N-CH (COOH) CH (OH) CH3 X X
Tryptophan (Try) H2N-CH (COOH) CH2 C8H6N X X
Tyrosine (Tyr) H2N-CH (COOH) CH2 C6H4 OH X X
Valine (Val) H2N-CH (COOH) CH2 CH (CH3)2 X X
1015
nutrients. However, there is no clear association between dietary fat and cancer in all
cases. In one study, a higher risk of prostate cancer was associated with higher energy
intake, but there was no clear association between fat intake and the cancer risk.21 Con-
versely, in a study of skin cancer patients, reducing the level of dietary fat from 37 to 40%
to about 20% led to a significant reduction in the incidence of new actinic keratosis and
nonmelanoma skin cancer.22
Numerous animal studies have shown an inverse relationship between cancer incidence
and lower body weight due to a calorie-restricted diet.23 Such results may not apply to
humans, but it seems that obesity, a sign of excess total energy, should be avoided by
matching energy intake with expenditure and increasing physical activity.24,25
Vitamins
Vitamin A
Vitamin A or retinol is a fat-soluble vitamin with an unsaturated aliphatic chain. It has a
role in cell differentiation, in the protein metabolism of cells originating from the ectoderm,
and in formation of the chromosphere component of visual cycle chromoproteins. Lack
of retinol causes night blindness and thickening of the skin; conversely, excess vitamin A
is toxic. Except for the occurrence in milk fat, egg yolk, and liver of mammals, most vitamin
A is usually obtained from carotenoids. These precursors to vitamin A occur in vegetables,
mostly green, yellow, and dark green leafy vegetables, and many yellow or orange fruits.26
They are converted to vitamin A in the intestinal tract. Investigations in different animal
species have shown that retinol esters and beta-carotene can inhibit the effects of various
carcinogens through modulating DNA stability and decreasing lipid peroxidation.27
As for humans, there have been many epidemiologic studies of retinol and carotenes,
with conflicting results. There were no protective effects against melanoma of the skin,
suggestive but insufficient evidence for a decreased risk of bladder cancer with higher
dietary retinol, and no consistent protective effect for cancer of the lung, stomach, breast,
and cervix. An IARC (International Agency for Research on Cancer) group concluded that
there is little evidence that vitamin A intake has a substantial cancer-preventive effect.28
The situation differs for dietary carotenoids, where there is evidence for a modest to
weak protective action against lung cancer29-31 and a possible decreased risk for esoph-
ageal,32 stomach, colorectal, breast, and cervical cancers,33-35 as well as an effect against
cancers of the thyroid36 and salivary gland.37 Some epidemiologic surveys showed no such
protective action.38-41 Conversely, supplemental beta-carotene or megadose vitamin sup-
plementation did not lead to any benefit.42
The controversy about carotenoids was heightened when studies of Finnish smokers
receiving supplemental beta-carotene showed a higher death rate from lung cancer in
those receiving additional beta-carotene than in those who did not.43 Likewise, a combi-
nation study of beta-carotene with retinol had a similar trend, leading to termination of
these studies.44
Nevertheless, another carotenoid which is not a vitamin A precursor, namely lycopene,
responsible for the color of tomatoes, has shown a protective action against chemical
carcinogens in animals.45 Furthermore, epidemiologic studies have indicated that con-
sumption of tomato products, along with a modest amount of fat to facilitate absorption,
has been associated with a lower incidence of prostate46 and digestive tract cancers.47
On balance, although dietary supplements do not seem efficacious, obtaining vitamin
A or carotenoids through a diet with high levels of fruits and vegetables seems to afford
modest protection against cancer.
Vitamin B
Vitamin B actually consists of several water-soluble compounds without any apparent
structural similarity. All are necessary for proper physiological function; the requirements
for some are actually filled through synthesis by endogenous intestinal bacteria (Table
49.3). Riboflavin, one of the B vitamins, was shown relatively early to have a chemopre-
ventive action in rats fed a carcinogenic aminoazo dye. In this situation, as part of the
enzyme system that reductively split the dye to two non-effective groups, dietary ribofla-
vin definitely was a preventive agent.48 However, there are no epidemiologic studies that
indicate a connection between riboflavin and the prevention of cancer.
The situation differs for the B6, B12, and Bc vitamins, as these are involved in reactions
of amino acids and one–carbon units. Methionine, an essential amino acid, combines with
adenosine triphosphate to form S-adenosylmethionine (SAM); in turn, SAM transfers
methyl groups to adjacent molecules, thereby regulating expression of genes, preservation
of membranes, and the action of various hormones and neurotransmitters. After the
transfer of the methyl group, methionine becomes homocysteine, which has toxic effects
on the cardiovascular system and the developing fetus. In the presence of B12 and Bc,
homocysteine is remethylated to methionine, with folate being especially important. Vita-
min B6, in turn, is involved by converting homocysteine to glutathione, another protective
body constituent.
Both hypo- and hypermethylation of DNA are markers of the early stages of carcino-
genesis. By maintaining a normal methylation pattern, folic acid may aid in decreasing
cancer risk. For example, high dietary folate intake was weakly associated with decreased
risk of colon cancer.18,19
Vitamin C
Vitamin C has been widely studied, both in animal systems and in epidemiologic trials.
Vitamin C, or ascorbic acid, is involved in biological hydroxylation reactions and formation
of collagen in connective tissues, is important in wound healing, and is necessary for the
prevention of scurvy. Most animals, except for primates and guinea pigs, synthesize their
daily requirements, but for species which do not, the following foods are excellent sources:
citrus fruits, strawberries, currants, cabbages, and potatoes. A great excess of vitamin C
is not especially beneficial, as it is metabolized to oxalic acid, which is harmful to the
kidneys. The recommended daily intake is 175 to 400 mg.
In many animal experiments, vitamin C had a beneficial action against skin or mammary
cancer with dimethylbenz(a)anthracene, benzo(a)pyrene, or against estrogen-induced kid-
ney cancer in hamsters. The most effective action was against formation of N-nitrosamines
in vivo by combined administration of nitrite and a secondary amine; in this case, ascorbic
acid reacts preferentially with nitrite, yielding non-effective compounds. However, in other
cases vitamin C had no beneficial action.49,50
Epidemiologic trials have been less definitive. Most studies have shown some possible
decrease in cancers of many organ systems, but the effects were not dramatic. Thus, the
question of whether any protection was due solely to vitamin C or to a combined action
with other constituents of the diet cannot be answered definitely.38,51
1018
TABLE 49.3
B Vitamins
Vitamin Name Function Dietary Sources Result of Deficiency
B1 Thiamine Component of enzymes catalyzing oxidative Wheat germ, pork Beri-beri
decarboxylation reactions in Krebs cycle.
B2 Riboflavin Occurs in flavin mononucleotides (FMN) and Yeast , liver, egg yolk, milk, Chellosis (cracking of lips)
flavin adenine dinucleotide (FAD), prosthetic fish, green vegetables
groups in flavoproteins which are respiratory
enzymes.
B3 Niacin Component of nicotinamide adenine Wheat germ, yeast, liver Pellagra
dinucleotide (NAD) and its phosphate

derivatives (NADP) which are electron
carriers in respiratory systems.
B5 Pantothenic Acid Constituent of coenzyme A, important in many Animal or plant tissue, Deficiency rare
physiological processes such as fatty acid produced by intestinal
metabolism. bacteria
B6 Pyridoxine Pyridoxine and derivatives, pyridoxal, Fish, meat, poultry, grains, Skin lesions, anemia, muscle
pyridoxamines and their phosphates are co- legumes, potatoes cramps
factors for enzymes involved in metabolism of
proteins and amino acids
B12 Cyanocobalamin Essential growth factor, component of enzyme Animal tissues, produced by Pernicious anemia
involved in reactions of one-carbon units. intestinal bacteria
BC Folic Acid Needed for amino acid metabolism and Yeast extract, green Anemia, spina bifida in fetus
(pteroylglutamic acid) formation of red blood cells; involved in vegetables
reactions of one-carbon units (methylation)
Data from Kingston, R., Supplementary benefits, Chem. Brit., 35, 29, 1999.
Vitamin D
Vitamin D, a fat-soluble vitamin (cholecalciferol; D3), is formed naturally from cholesterol
in the skin through photolysis of 7-dehydrocholesterol under the influence of ultraviolet
light. The active metabolites are the 1, 25-dihydroxy- and 1-α-hydroxy-forms. These are
needed for intestinal resorption of calcium and for its deposition into the organic matrix
of the bones, which then triggers the biosynthesis of calcium-binding proteins. Deficiency
of vitamin D in children leads to increased excretion of calcium and phosphate, thus
impairing bone formation due to inadequate calcification of cartilage and bones — the
disease known as rickets. In adults, deficiency leads to softening and weakening of bones,
or osteomalacia. Some foods, especially milk, are fortified with vitamin D. Biochemically,
vitamin D interacts with the vitamin D receptor, a member of the steroid/thyroid/retinoic
acid family of nuclear receptors, which either induce or repress the expression of specific
genes. In turn, the protein products of these genes include calcium-binding proteins
(calbindins), bone matrix proteins (osteocalcin, osteopontin), digestive enzymes such as
alkaline phosphatase, and vitamin D-metabolizing enzymes.52
The effect of vitamin D is linked to the level of dietary calcium, while therapeutic use
is limited due to the calcemic effect of vitamin D, which causes calcium carbonate or
phosphate disorders in various organs.
Although vitamin D inhibits the growth of breast cancer cells in vitro, the exact mech-
anism has not been delineated; induction of apoptosis has been implicated.53 There is some
evidence from population studies that higher serum vitamin D was associated with lower
risk of breast cancer; likewise vitamin D may possibly reduce the risk of colorectal and
prostate cancer.53-55 As with other protective factors, the effect of vitamin D alone is
relatively small. Animal studies with vitamin D in the chemoprevention of cancer have
been few, and the results were positive in some cases, but not in others.50 However, both
animal and human studies lend support to the concept that increased intake of calcium
and vitamin D can reduce the risk of colon cancer associated with high dietary fat.56
Vitamin E
Vitamin E occurs in vegetable oils, especially the germ oils of cereals as tocopherols; of
all these, d-α-tocopherol has the greatest biological activity. Tocopherols are antioxidants,
and thus retard the oxidation of lipids or stabilize vitamin A, ubiquinones, hormones, and
various enzymes. Vitamin E protects polyunsaturated fatty acids against autooxidation,
protects against the immune response, and decreases the adherence of platelets to blood
vessel walls.57 In experiments using the hamster buccal pouch or other animal systems,
vitamin E had a protective action against chemical carcinogens, but the effect on colon
cancer in model animal systems was inconsistent.50 In humans, vitamin E possibly protects
against cancer of the mouth and pharynx, esophagus, pancreas, stomach, colon and rec-
tum, cervix, and prostate.58 For breast cancer, the epidemiologic results have been incon-
clusive.38,51,59 The mechanism of its action, apart from the antioxidant properties, has not
been elucidated.
Minerals
Calcium
Calcium, one of the more abundant essential minerals of the body, has several roles in
building and maintaining bones and teeth, in blood clotting, and in muscle contraction.
The usual requirement is 500 to 700 mg daily, with more necessary during pregnancy and
lactation, or in osteoporosis patients. The main dietary sources are milk and dairy products,
although some vegetables (watercress, kale, spinach, broccoli) have reasonable levels.
Supplementation of fruit juices with calcium has also become popular.
As for any chemopreventive action against cancer, a number of studies show a beneficial
effect, but conflicts remain. A protective association for pancreatic cancer was noted in
one study,60 and for colorectal cancer, the weight of the evidence points toward an inhib-
itory action, as do some animal tests.61-65 However, conflicting results were also noted.54
Higher intake of calcium may reduce breast cancer risks,51 but the data on prostate cancer
and calcium intake levels are conflicting. 55,66
Thus, for continued good health and body function, sufficient calcium is necessary.
Except for breast and colorectal cancer, the epidemiologic studies are not definitive on
whether calcium protects against other cancers.
Chromium
Chromium is an essential micronutrient for utilization of glucose, since it activates phos-
phoglucomutase and increases insulin activity. The daily intake varies depending on the
region of the country, with most foods containing some chromium; brown sugar is a good
source along with meat and seafood. Average intake is about 80 µg per day.67 Few, if any,
chemopreventive experiments have been done with chromium, since hexavalent chro-
mium has been considered a human carcinogen by the IARC.68 Animal tests with trivalent
chromium were negative, and surveys on chromium levels in diets and cancer incidence
are lacking. Nevertheless, a sufficient supply is needed for good health. Although no long-
term toxicity studies have been done, the use of chromium picolinate as a dietary supple-
ment has increased recently. Chromium thus represents a paradox — it is needed for
proper body function, but it presents a hazard under certain conditions.69
Iodine
Iodine is an essential element for the thyroid gland to biosynthesize the hormones thy-
roxine or tetraiodothyronine and triiodothyronine; the requirement is 100 to 200 µg/day.
A deficiency of iodine is associated with goiter or thyroid enlargement, which in turn is
associated with a higher risk of cancer. Many epidemiologic studies have confirmed such
an effect.1
The opposite, excess intake of iodine (18 to 1000 mg/day) can block uptake of iodine
by the thyroid, leading to elevated thyroid-stimulating hormone (TSH) levels and an
increased risk of thyroid cancer, as confirmed by animal experiments.1 Thus, a proper
balance in iodine uptake is required to maintain thyroid hormone levels and to decrease
the risk of thyroid cancer.
Iron
The essential micronutrient iron is mostly present in the body in the hemoglobin of the
blood and the myoglobin of muscle tissue. Iron also occurs in various oxidative enzymes
such as the P450s, peroxidases, catalases, hydroxylases, and flavine enzymes. The daily
requirement is about 1 to 3 mg, but an intake of about 15 to 25 mg is needed due to poor
absorption of iron. Good sources of iron are egg yolks, liver, wheat germ, lentils, and
spinach.70
Deficiency of iron leads to anemia and has been associated with cancer of the esophagus
and Plummer-Vinson syndrome.71 Conversely, the risk of various other types of cancer
increases in association with higher body iron stores. High serum ferritin levels were
associated with an increased risk of colorectal adenomas or cancer,72 and a high concen-
tration of iron in the liver was linked to a greater risk of liver cancer.73 The suggestion has
been made that high dietary intakes of iron enhance the generation of free radicals, which
are implicated in the initiation or promotion phases of carcinogenesis. As with other
essential micronutrients, a balance between a deficiency and an excess of iron is needed
to maintain good health.
Selenium
Selenium was recognized only about 30 years ago as an essential micronutrient, with a
recommended intake of 75 to 125 µg daily. It is a component of the glutathione peroxidase
system and occurs in organ meats, seafood, and in cereals and seeds at levels proportional
to those in the soil.74 An excess of selenium is toxic, resulting in damaged hooves and hair
in range animals. A deficiency leads to “white muscle disease” in calves and lambs; thus,
a proper balance in selenium levels is needed.
A survey of soil selenium levels in the U.S. versus cancer incidence pointed toward a
decreased risk in high selenium areas. Likewise, animal studies with selenium, mostly as
the selenite salt, have shown an inhibitory action against tumor development in various
organs.75 In humans, the data are often conflicting. High blood levels of selenium were
correlated with esophageal cancer in a Chinese population,76 while in other studies, high
body selenium was protective against stomach cancer. Data for liver and pancreatic cancer
are somewhat conflicting, but overall there was some inhibitory effect. Evidence for a
protective action against colorectal and breast cancer in humans is limited.
Consumption of high-selenium brewer’s yeast did not prevent the appearance of new
skin cancers in patients who already had developed basal cell and squamous cell skin
cancers, but total cancer incidence and deaths were lower in the selenium-using group.77
Furthermore, higher body stores of selenium were associated with reduced risk of
advanced prostate cancer.78 Accordingly, although selenium suppresses most types of
cancer and has a beneficial action, the toxicity of selenium limits the amount that can be
administered, and must be considered.
Zinc
Zinc is an essential trace element, as it is a component of several enzymes, including
alcohol, glutamate, lactate, and malate dehydrogenases, carboxypeptidases, and carbonic
anhydrase. In addition, several other enzymes are activated by zinc. Zinc deficiency causes
serious disorders, but high zinc intake is toxic. A normal diet usually provides the daily
requirement of a little over 10 mg (6 to 22 mg).79
Many animal experiments have shown that dietary zinc deficiency as well as zinc
supplementation can increase the incidence of some carcinogen-induced tumors and
decrease the incidence of others.80 However, there are no definitive epidemiologic studies
that associate human cancers with either a deficiency or an excess of zinc.
Nonnutritive Components
Fiber
Of all the nonnutritive food constituents, dietary fiber has been the one most extensively
investigated in humans. The evidence is suggestive that high dietary fiber decreases the
risk of stomach, pancreatic, and breast cancer, and is protective against colorectal (and
possibly endometrial) cancer,17,3981-83 although contradicting studies are also available.84
Animal studies showing the preventive effects of fiber against intestinal cancer predated
most epidemiologic studies by a decade or more.34,85-87
Several possible reasons exist for the beneficial action of dietary fiber. The fiber may
physically trap or attach to various deleterious substances ranging from carcinogen metab-
olites to certain bile acids, and sweep them out of the intestinal tract. Fiber may also trap
hormonal constituents and thus help decrease breast cancer. Further, some fiber is even-
tually fermented by intestinal bacteria to butyric acid, which regulates cell cycles.88,89
For continued good health and function of the digestive system, a reasonable level of
fiber in the diet is needed. Generally, this can be attained by eating a diet with whole grain
products and fruits and vegetables.
Flavonoids, Isoflavones, and Polyphenols

Flavonoids and isoflavones are present in plants and their various parts in combination
with sugars (glycosides). The common property of many chemopreventive plant products
is the presence of several hydroxyl groups in the molecule; thus the designation as
polyphenols is appropriate for a wide range of these substances.
Many polyphenols from foods have demonstrated preventive effects against chemical
carcinogens in animal experiments. Examples include ellagic acid,90 silymarin from the
artichoke,91 quercetin, found in most plant materials,92 the flavones or epicatechins com-
mon in tea,93 curcumin in tumeric and mustard, caffeic and ferulic acids, resveratrol from
grapes, and lignans derived from plant phenolics through bacterial action in the intestinal
tract. Further, several plant phenolics can inhibit nitrosamine formation in vivo and thus
have a chemopreventive action. The beneficial effects of these polyphenols are difficult to
delineate separately, since they occur in many fruits and vegetables. Epidemiologic studies
definitely associating one or the other dietary polyphenol with a reduction in cancer
incidence are lacking or inconclusive.
That is not the case with the soybean compounds genistein and daidzein, examples of
isoflavones. Various surveys have indicated a lower risk of breast and possibly endometrial
cancer in women who consume soybean products,15,94 while animal studies have confirmed
the chemopreventive action of genistein.95,96 The mechanism probably resides in the weak
estrogenic effect of these compounds which then bind to estrogen receptors, thus blocking
the action of the more potent natural estrogens.16 Plant lignans, which also are beneficial,
appear to bind weakly to estrogen receptors. Furthermore, daidzein sulfoconjugates inhibit
the enzymes involved in estrogen steroid activation.97
An additional benefit of soy, reported recently, was that a soy-based beverage had
suppressed an increase in prostate specific antigen (PSA) in prostate cancer patients.98
Despite these beneficial aspects of soy consumption, soy should be used in moderation.
Soy consumption is associated with a goitrogenic effect, as confirmed by mechanistic
studies in animals.99 Thus, moderation in use is a reasonable policy.
Indole-3-carbinol
Indole-3-carbinol (I3C) was one of the first specific cancer chemopreventive compounds
to be isolated from a cruciferous vegetable, namely Brussels sprouts.100 Many animal
studies have shown its ability to suppress the effects of chemical carcinogens, presumably
through its induction of detoxifying enzymes.101 There is a concern that under certain
conditions it may act as a promoting agent, and possible application of I3C as a chemo-
preventive agent in humans should be approached cautiously.102
Isothiocyanates
Isothiocyanates occur naturally in the form of their glucosinolate conjugates in a variety
of cruciferous vegetables. When the plant cells are damaged by cutting or chewing, the
enzyme myrosinase is released, which causes hydrolysis of the glucosinolates followed
by a rearrangement which affords the isothiocyanates. These are generally responsible for
the sharp taste associated with cruciferous vegetables, mustard, horseradish, and water-
cress. Animal studies with isothiocyanates have shown definitive and often quite specific
inhibition of the action of some carcinogens, largely through suppressing metabolism to
an activated intermediate.103
Epidemiologic studies focused specifically on isothiocyanates are lacking. However, one
trial showed that if confirmed smokers ate watercress, a source of phenethyl isothiocyan-
ate, the oxidative action of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a car-
cinogen present in tobacco smoke, was suppressed and higher urinary levels of a
detoxification product of NNK were observed.104
Another unique isothiocyanate, sulforaphane or 1-isothiocyanate-4-methylsulfinyl-
butane, has been isolated from broccoli.105 Sulforaphorane induces P450 enzymes which
tend to detoxify carcinogens.106 It appears to be still another component of the protective
substances present in cruciferous vegetables.
Methods have recently been developed to quantify the metabolic endproducts of isothio-
cyanates.107,108 This should expedite the further application of these compounds in both
metabolic and epidemiologic studies.109
Sulfides
The chemical background for the numerous sulfides and their selenium analogs occurring
in “Allium” vegetables has been presented in several reviews. The substances involved are
various sulfur derivatives, and in series are: alkyl cysteine-S-oxides, sulfenic acids, and
thiosulfinate esters, which in turn afford alkyl and allyl sulfides and the selenium analogs.110
Animal tests have shown an inhibitory action of garlic and onion constituents, especially
diallyl sulfide, on experimental carcinogenesis of the skin, esophagus, and colon. Epide-
miologic studies have noted the same trend — that Allium vegetables protect against
stomach and colon cancer — but no such action was noted for breast and lung cancer.111
In one animal trial, garlic enriched with selenium had a chemopreventive action against
the effects of a mammary carcinogen.112 However, application of these results to the human
situation will require much further study.
Terpenoids
The terpenoid substances which occur in foods generally are the monoterpenes; examples
include carvone, p-cymene, geraniol, limonene, linalool, nerol, perillyl alcohol, pinene,
and thymol, among others. These substances occur in the essential oils of fruits and plants,
in citrus and other fruits, cherries, certain grapes, mint, dill, and caraway, and are largely
responsible for the pleasant fragrances of the fruits and plants.
The inhibitory action of fruit oil containing a monoterpene on the effect of a potent
chemical carcinogen was noted several decades ago. More recent efforts have confirmed
TABLE 49.4
Cancer Preventive Action of Vitamins
Vitamin Species Organ/Tissue
A Mouse Skin
Rat Mammary gland
Urinary bladder
B (folate) Mouse Lung
Human Colon (weakly)
C Mouse Colon
Lung
Rat Mammary gland
Colon
Liver
Hamster Kidney
D Mouse Skin
Rat Colon
Human Breast
Colon/rectum
Prostate
E Mouse Skin
Colon?
Rat Mammary gland
Stomach
Colon?
Ear duct
Liver
Hamster Buccal pouch
Human Mouth (possibly)
Pharynx (possibly)
Esophagus (possibly)
Pancreas (possibly)
Stomach (possibly)
Colon/rectum (possibly)
Cervix and prostate (possibly)
that d-limonene, the putative active component of sweet orange oil, has several inhibitory
mechanisms.113 It suppresses the activation of nitrosamines114 and azoxymethane,115
induces glutathione-S-transferase, and inhibits oncogene activation by depressing the
isoprenylation of oncogene products. The benefits of consuming citrus fruits may lie not
only in their vitamin C content, but also in the limonene contained therein. Another
monoterpene, perillyl alcohol, also inhibits protein isoprenylation, thus suppressing even-
tual oncogene activation,116 even in human-derived cell lines.117
Although other monoterpenes have not been investigated, it is gratifying to know that
these compounds with a pleasant fragrance are beneficial for health.
The diversity of cancer chemopreventive substances in foods is noteworthy and allows

the individual many choices in devising a healthful diet. The aim should be a varied diet
with moderation in the amounts of any one constituent. Dietary supplements, in which
the active factor has been isolated and administered in a concentrated form, are not as
useful as the actual food. However, Tables 49.4 and 49.5 provide results from both animal
and human studies with vitamins and nonnutritive food components. In an actual diet,
synergism among food constituents may occur with the combination, as in foods, being
better than the individual components. All the more incentive to follow a varied moderate
diet with plenty of fruits, vegetables, and whole-grain products.
TABLE 49.5
Chemopreventive Action of Nonnutritive Principles of Foods
Substance Species Organ/Tissue
Fiber Human Stomach
Pancreas
Breast
Colon/rectum
Endometrium
Rat Colon
Flavonoids, isoflavones, polyphenols Human Breast
Endometrium
Rodents Mammary gland
Skin
Indole-3-carbinol Mouse Forestomach
Rat Mammary gland
Isothiocyanates Mouse Lung
Forestomach
Rat Mammary gland
Sulfides Human Stomach
Colon
Rat Esophagus
Lung
Thyroid
Mouse Forestomach
Lung
Colon
Terpenoids Mouse Forestomach
Lung
Rat Mammary gland
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50
Nutrition and Cancer Treatment
David Heber and Susan Bowerman
Etiology of Malnutrition in the Cancer Patient

Malnutrition is a frequent and serious problem in patients with cancer. Some types of cancers
such as lung, prostate, head and neck, and gastric cancer are more frequently affected, but
the overall incidence of malnutrition ranges between 30 and 87% of different populations
studied.1,2 The advanced starvation state resulting from decreased food intake and hormonal/
metabolic abnormalities characteristic of the interaction between tumor and host has been
called cancer cachexia.3 A retrospective analysis of patient body weight at the beginning of
cooperative chemotherapy trials determined that the presence of a 6% weight loss from usual
body weight was a significant prognostic factor for survival.4 The apparent effect of weight
loss at the time of diagnosis on median survival for certain common cancers was greater than
the impact of chemotherapy. Despite the development of advanced technology and delivery
systems for total parenteral nutrition and continuous enteral nutrition, nutrition therapy alone
has had little impact on this problem. While nutritional rehabilitation can be demonstrated
in selected patients who respond to antineoplastic therapy, the application of parenteral and
enteral nutrition as an adjunct to chemotherapy in cancer patients has not resulted in
increased survival or predictable weight gain.5,6 These observations suggest that decreased
food intake alone cannot account for the progressive weight loss noted in cancer patients.
Metabolic Abnormalities in the Cancer Patient

Since predictable renutrition of the cancer patient has not been possible, a great deal of
research has been conducted concerning specific hormonal and metabolic abnormalities
which could interfere with renutrition. Over the last 15 years, research on the basic patho-
physiology of cancer cachexia has resulted in the definition of several metabolic and hormonal
abnormalities in malnourished cancer patients. These abnormalities are listed in Table 50.1.
Based on these abnormalities, a number of strategies using hormonal and metabolic
agents have been tested. These are listed in Table 50.2. None of the above hormonal or
metabolic strategies tested resulted in predictable weight gain.
0-8493-2705-9/01/$0.00+$1.50
TABLE 50.1
Metabolic Abnormalities in Cancer Patients
Hypogonadism in male cancer patients7
Increased glucose production8,9
Increased protein catabolism10,11
Increased lipolysis and fatty acid oxidation12,13
Insulin resistance14,15
TABLE 50.2
Research Strategies to Counter Metabolic Abnormalities
Hydrazine sulfate to inhibit gluconeogenesis16
Anabolic androgens to counteract metabolic effects of hypogonadism17
Insulin supplementation to counteract apparent insulin resistance18
Based on autopsy studies performed in the 1920s19,20 and animal studies done in the
1950s21 it was postulated that tumors acted to siphon off needed energy and protein from
the host. In the 1970s and 1980s, specific abnormalities of intermediary metabolism were
identified in cancer patients that could account for the common observation that such
patients lost weight even in the face of apparently adequate nutrition. Studies conducted
in a number of laboratories, including our own, have demonstrated that maladaptive
metabolic abnormalities occur frequently in patients with cancer. In 1983, we demonstrated
that adequate energy and protein administered to six patients with active localized head
and neck cancer via forced continuous enteral alimentation under metabolic ward condi-
tions for 29 days failed to lead to significant weight gain.22 The mean nitrogen balance in
these patients is shown in Figure 50.1. The observed failure of these patients to gain weight
despite adequate caloric intake under metabolic ward conditions supports the concept
that malnourished cancer patients are hypermetabolic.
If metabolic abnormalities promote the development of malnutrition or interfere with
renutrition, then there should be some evidence of abnormally increased energy expen-
diture. A number of investigators have used indirect calorimetry and the abbreviated Weir
formula to calculate energy expenditure at rest, and then compared this to the basal energy
expenditure (BEE) determined using the Harris-Benedict formulas. Long et al.23 demon-
strated a mean difference of 2% when this comparison was performed in 20 normal
controls. In 1980, Bozetti et al.24 found that 60% of a group of patients with advanced
cancer had basal metabolic rates increased 20% above predicted. In 1983, Dempsey et al.25
studied energy expenditure in a group of 173 malnourished gastrointestinal (GI) cancer
patients. Fifty-eight percent had abnormal resting energy expenditure (REE) by indirect
calorimetry compared to BEE, but a greater percentage were hypometabolic rather than
hypermetabolic (36 versus 22%). Knox et al.26 studied 200 patients with a variety of cancers
and found abnormal energy metabolism in 59%, but found more hypometabolic than
hypermetabolic individuals (33 versus 26%). Figure 50.2 shows that while standard for-
mulae accurately predict metabolic rate in normal individuals, the measured metabolic
rates in patients with cancer have a much wider distribution.
Lean body mass rather than fat mass correlates with the individual variations observed
in measured REE. The hypothesis that the malnourished cancer patient may be hyper-
metabolic relative to the amount of lean body mass remaining has been examined. Peacock
et al.27 studied resting energy expenditure in non-cachectic patients with sarcomas. These
patients had no prior treatment, had large localized sarcomas, and had no weight loss or
history of decreased food intake. REE corrected for body cell mass (BCM) determined by
total body potassium counting or body surface area was significantly greater in male
Nutrition and Cancer Treatment 1031
11
10
9
8
7
6
Mean Nitrogen Balance (g/24hrs)
5
4
3
2
1
0
-1
-2
-3
-4
-5
10
12
14
16
18
20
22
24
26
4
Day
FIGURE 50.1
Mean nitrogen balance in grams per 24 hours in six patients with head and neck cancer receiving 1.25 × BEE
kcal for 5 days and 2.25 × BEE for 19 days as a continuous enteral infusion. (From Geber, D., Byerley, L.O., Chi,
J., et al. Cancer 58: 1867; 1986. With permission.)
40
Percentage of patients
30
Normals
20
10
Cancer patients
0
60 80 100 120 140 160 180
Measured resting energy expenditure as a percentage
of predicted energy expenditure
FIGURE 50.2
Measured resting energy expenditure as a percentage of predicted energy expenditure. (From Knox, L.S., Crosby,
L.O., Feurer, I.D., et al. Ann Surg 197: 152; 1983.
sarcoma patients compared to controls. This difference was due to both a decrease in
BCM and an increase in REE in these patients before the onset of weight loss. Tumors
have been demonstrated to increase the rate of glucose utilization in a number of tissues.28
Since there are only 1200 kcal stored in the body as liver and muscle glycogen, blood
glucose levels would be expected to fall. This does not occur since there is also an increase
in hepatic glucose production in cachectic and anorectic tumor-bearing animals and
humans. The regulation of protein metabolism is tightly linked to carbohydrate metabo-
lism, since these processes are critical to the normal adaptation to starvation or under-
feeding. During starvation there is a decrease in glucose production, protein synthesis,
and protein catabolism. The decrease in glucose production occurs as fat-derived fuels,
primarily ketone bodies, are used for energy production. While there are 54,000 kcal of
protein stored in the body cell mass, only about half of these are available for energy
production. In fact, depletion below 50% of body protein stores is incompatible with life.
Whole body protein breakdown is increased in lung cancer patients and has been shown
to correlate with the degree of malnutrition such that more malnourished patients have
greater elevations of their whole body protein breakdown rates expressed per kg of body
weight (Figure 50.3).11 The results of metabolic studies in lung cancer patients compared
7.0
6.0
5.0
Protein Turnover (gm/kg/day)
r= 0.69
4.0
3.0
2.0
1.0
0.0
60 70 80 90 100 110 120
% Ideal Body Weight
FIGURE 50.3
Whole-body protein turnover determined by [U-14C] lysine infusion in the fasting state in g/kg/day versus
percentage of ideal body weight for height in non-oat cell lung cancer patients (●) and age-matched healthy
controls (). The correlation coefficient of the linear regression drawn (- - - -) is shown as r (p < 0.05). (From
Heber D, Chlebowski RT, Ishibashi DE, et al. Cancer Res 42: 4815, 1982. With permission.)
TABLE 50.3
Total Body Protein Turnover, Glucose Production, and 3-Methylhistidine
Excretion in the Fasting State on Day 5 of Constant Nitrogen and Kcalorie Intake
in Lung Cancer Patients Compared to Healthy Controls
Protein Turnover Glucose Production 3-Methylhistidine Excretion
Group (g/kg/day) (mg/kg/min) (µmol/g creatinine/day)
Control 2.12 ± 0.38 2.18 ± 0.06 71 ± 8
Lung Cancer 3.15 ± 0.51a,b 2.84 ± 0.16a 106 ± 11a
a p < 0.05 versus control subjects.
b Mean ± S.D.
to healthy controls are shown in Table 50.3. Muscle catabolism, measured by 3-methyl-
histidine excretion, was increased in lung cancer patients compared to that of healthy
controls. Methylhistidine excretion rates did not correlate with weight loss, percentage
of ideal body weight, or age in the lung cancer patients studied. Glucose production rates
were markedly increased in lung cancer patients compared with healthy controls, and
changes in glucose production rates in the cancer patients studied did not correlate with
weight loss, percent of ideal body weight, or age.
Hydrazine sulfate is a non-competitive inhibitor of gluconeogenesis. When this drug is
administered to lung cancer patients not only does whole body glucose production
decrease as expected, but there is also a decrease in whole body protein breakdown rates.29
Increases in glucose production are directly and quantitatively linked to increased protein
breakdown and changes in the circulating levels of individual glucogenic amino acids.
Table 50.4 shows the influence of hydrazine sulfate on lysine flux. At one month, there
TABLE 50.4
Whole Body Lysine Flux in Lung Cancer Patients
Lysine Flux (µmol/h)
Baseline 1 mo
Placebo Group
1 2172 2812
2 1869 2959
3 2373 2674
4 2772 2269
5 2758 3195
6 3542 3585
Mean (SD) 2580 (580) 2920 (450)a,b
Hydrazine Treated
7 2675 1146
8 2522 2119
9 2666 3129
10 1808 1217
11 2264 1438
12 3114 2006
Mean (SD) 2510 (440) 1840 (750)b,c
a p = 0.08; b p < 0.05, paired t-tests with baseline; c p <
0.01 by combined paired t-test both groups
was a significant reduction in the hydrazine group and a nonsignificant increase in the
placebo group.
Both anorexia and abnormal metabolic adaptations to starvation play a role in the
genesis of cancer cachexia. Anorexia has been given less attention than the metabolic
abnormalities of increased glucose production, protein breakdown, and lipolysis. The
tumor-bearing host does not adapt to decreased food intake normally, but studies of
glucoregulatory and thyroid hormones fail to reveal systematic abnormalities other than
insulin resistance which could impair renutrition. The immune response of the host to the
tumor results in the local and perhaps systemic release of cytokines with potent metabolic
effects. In fact, TNF-α has been shown to cause all of the metabolic abnormalities charac-
teristic of cancer cachexia. It is possible that other cytokines may also participate in the
pathogenesis of cancer cachexia. The study of the mechanisms of action of these cytokines
and their interactions with cellular and soluble receptors may lead to improved strategies
for the treatment of this perplexing clinical problem.
Assessment of the Cancer Patient’s Nutritional Status

There are several nutritional assessment factors specific to the cancer patient, and these
are listed in Table 50.5. Involuntary weight loss is a key indicator of undernutrition and
is often a sign associated with a poorer prognosis and survival. The rate of weight loss is
also important. It is accepted that an involuntary weight loss of 10% of the patient’s usual
body weight over a period of 6 months or less indicates undernutrition in patients with
cancer.30 One complicating factor in cancer patients is the development of edema or ascites;
this should be kept in mind when interpreting weight data.
Ideal body weight is the weight associated with optimal survivorship in populations
studied by life insurance companies. A commonly used reference is the 1983 Metropolitan
Life Insurance Tables. With these tables, ideal weight range is calculated on the basis of
height, body frame size, and sex, but no adjustments are made for age. Studies undertaken
at the Gerontology Research Center (GRC), however, indicate that age significantly affects
ideal body weight, while sex differences are not significant.31 For a given height, older
subjects have a higher ideal body weight range than younger individuals. Importantly,
both tables are based on the same database, except that age is introduced as a variable
only by the more recent GRC tables. Since cancer affects both the young and the aged,
with the majority of patients in the older age groups,32 it is more appropriate to utilize
the age-adjusted tables to calculate ideal body weight range. Serious shortcomings still
exist since there is no correction for disease-related changes in height, and no guidelines
are provided in these tables for patients 70 years old or older.
Based on these ranges, we determine whether the patient is above, within, or below the
ideal weight range. Thus, current weight compared to the expected or ideal body weight
TABLE 50.5
Nutritional Assessment Factors in the Cancer Patient
Involuntary weight loss
Comparison to usual, pre-illness, or ideal body weight
Anorexia and decreased food intake
Anthropometric measures
Biochemical and cellular biomarkers
range may help us determine the patient’s nutritional status. An additional variable for
consideration is usual or pre-illness weight. Therefore, both information on percent ideal
weight and percent usual or pre-illness weight should be collected on all patients.There
are healthy individuals who are below their projected weight for many years. From a
clinical standpoint, stable weight and an adequate diet often equate with good nutrition
even if the individual is below the ideal body weight range.
Anorexia and decreased food intake have long been recognized as key causes of under-
nutrition in patients with malignancies.33,34 Anorexia is a treatable symptom of cancer
which, if left untreated, leads to significant patient discomfort in addition to malnutrition.35
This information can be obtained by simply questioning the patient about a subjective
loss of appetite and decrease in food intake. In order to further quantify these changes,
we ask the patient to rate the appetite level from 0 to 7 (0 = no appetite; 1 = very poor; 2
= poor; 3 = fair; 4 = good; 5 = very good; 6 = excellent; 7 = always hungry). We also ask
whether the amount eaten is enough to meet the patient’s needs (0 = not at all; 1 = less
than enough; 2 = enough; 3 = more than enough).
Detailed anthropometric measurements (such as mid-arm circumference and triceps
skin fold) have long been utilized to determine skeletal muscle mass and nutritional
status.36 Although the value of these measurements can be limited if done in the hospital
setting, serial measurements by the same professional in the outpatient clinic can help
assess the patient’s ongoing nutritional state. Problems with these measurements include
interobserver variability and interference by edema or patient positioning. The decision
to do these measurements should be individualized according to the acuteness of the
underlying process, the availability of trained personnel, and intervention goals. It should
be noted that muscle wasting and loss of adipose tissue reserves seen on physical exam-
ination are important but late signs of undernutrition. Ideally, early diagnosis and inter-
vention should be directed at avoiding this advanced stage of undernutrition or cachexia.
The role of laboratory parameters, such as albumin or prealbumin level, transferrin, or
total lymphocyte count, are less well defined in patients with cancer. These and other tests
can be useful to assess protein depletion, but are difficult to interpret in patients with
advanced cancer who often have metastases to visceral sites with organ dysfunction as
well as metabolic and immunologic derangements due to cancer therapy.
Routine chemistry panels include albumin levels, which can be a useful indication of
nutritional state. Albumin has a half-life in the circulation of about three weeks. Hypoal-
buminemia can result from malnutrition but is also associated with liver disease, dissem-
inated malignancies, protein-losing enteropathy, nephrotic syndrome, and conditions
leading to expanded plasma volume such as congestive heart failure.
Prealbumin has a half-life of just under two days, and its level may increase with the
use of steroid hormones and can be decreased by liver disease, disseminated malignancies,
nephrotic syndrome, inflammatory bowel disease, the use of salicylates, or malnutrition.37,38
Transferrin can be measured by the transferrin antigen assay; the iron binding capacity
provides with roughly equivalent results. Transferrin has a half-life of about one week, and
it may increase with storage iron depletion or the use of hormonal agents and decrease with
infection, malignancy, inflammation, liver disease, nephrotic syndrome, or malnutrition.39
Absolute lymphocyte counts can be reduced by malnutrition as well as a variety of other
factors. More sophisticated tests (bioimpedance, total body K, basal metabolic rate [BMR]
and others) are clinical research procedures.40
In many instances, a brief clinical nutritional assessment based on the degree of weight
loss from usual or pre-illness weight, current weight as a percentage of usual and ideal
body weight, and dietary history is sufficient to determine the clinical situation and
consider potential interventions. We therefore reserve the use of anthropometric and
TABLE 50.6
Patient Characteristics in 644 Consecutive Cancer Patients*
Characteristic Percent of Patients
Age — Median (range) in Years: 66 (22-91)
Age <65 45
Age ≥65 55
Sex
Women 53
Men 47
Type of Cancer
Breast 16
Colon/rectum 14
Leukemia/lymphoma 13
Lung/non-small cell 14
Prostate 5
Stomach 4
Head/neck squamous 4
Ovary 3
Kidney/urinary bladder 3
Lung/small cell 2
All others 22
Stage of Cancer
Metastatic 52
Non-metastatic 48
* Seen at Pacific Shores Medical Group and St. Mary Medical
Center, Long Beach, California.
laboratory evaluations to specific individual situations. Interpretations of these evaluations

should be based on an assessment of the clinical context.
A number of associated conditions are prevalent in older patients and can affect their
food intake and nutrition. Mucositis as a side effect of chemotherapy or radiation therapy
is common. Oral pain and dryness, poor dentition, periodontal disease, and ill-fitting
dentures are also common. Other problems requiring consideration are dysphagia, alter-
ation in taste, fatigue, nausea, vomiting, and diarrhea or constipation. Pain and other
symptoms such as dyspnea can also interfere with nutrition. Depression is a well known
cause of weight loss, and depression can worsen due to the stress of coping with cancer.
Feelings of isolation and actual social isolation are not uncommon, especially in those
patients who do not have strong family support. Socioeconomic and living conditions
must be taken into account because they may impact food availability and preparation.
These can all be very serious problems for patients with cancer, and require a multidisci-
plinary effort for proper management.
An understanding of the frequency and severity of malnutrition in cancer patients is
necessary to better plan preventive, diagnostic, and therapeutic approaches, including
the allocation of a variety of resources. To this end and as part of a more comprehensive
effort, we studied nutrition-related clinical variables in 644 consecutive oncology patients
regardless of type, status, or stage of cancer. The characteristics of these patients is shown
in Table 50.6. The majority were seen as outpatients. We divided patients by age (<65
versus ≥65), and we analyzed the entire group as well as the subset of patients who had
TABLE 50.7
Nutritional Variables in 644 Consecutive Cancer Patients*
All Stages Patients with Metastases
Variable (n = 644) (n = 377)
Decreased appetite 54% 59%
Decreased food intake 61% 67%
Underweight 49% 54%
Normal weight 37% 33%
Overweight 14% 13%
Weight loss
Any 74% 76%
Up to 5% 15% 15%
>5 to <10% 22% 20%
10-20% 26% 27%
None 26% 24%
* Seen at Pacific Shores Medical Group and St. Mary Medical Cen-
ter, Long Beach, California.
metastatic disease. Ideal body weight range was calculated using the GRC tables. The
vast majority of patients sustained the weight loss shown within a period of six months
from cancer diagnosis.
As shown in Table 50.7, the incidence of weight loss is very high in all patients, but
particularly in those over the age of 65. Thus, 72% of all patients 65 or older with metastatic
cancer had some degree of weight loss; 56% were underweight, 54% had decreased
appetite, and 61% reported a decrease in food intake. Thirty-eight percent of patients 65
or older with metastatic disease had weight loss of 10% or more of their usual body weight.
These data suggest that undernutrition at various stages is highly prevalent among oncol-
ogy patients, particularly in the older population. Attention to the nutritional status of
patients may afford the clinician opportunities for early diagnosis and intervention.
Nutritional and Adjunctive Pharmacotherapy of Anorexia and Cachexia

Counseling
The benefits of initial and follow-up evaluations and counseling by a registered dietitian,
preferably in the context of a team approach, can be enormous, although difficult to
quantify.17 The main benefits relate to patient satisfaction, nutrition improvement or main-
tenance, compliance with team or institutional management protocols and guidelines, and
a judicious use of risky and expensive treatments. The costs of nutritional counseling are
modest when compared to other interventions. Table 50.8 shows the benefits, methodology
and risks of common nutrition interventions. Nutritional evaluation and counseling, usu-
ally undertaken by a registered dietitian, is a first and important step. Ideally, a dietitian
should be an integral part of the cancer care team.
In addition to assessing the clinical nutritional parameters previously outlined, it is our
practice to first determine, through the dietary history, whether the patient is consuming
a “balanced diet.” The dietitian obtains a 24- to 72-hour recall diet history either verbally
or, preferably, recorded at home. This diet record is then examined to assess the adequacy
of kcalories and protein, utilizing food analysis tables compared to estimated energy and
protein needs. Usually a weight-maintenance diet depends on the BEE, and is calculated
1038
TABLE 50.8
Benefits, Methodology, and Risks of Nutrition Interventions
Benefits Methodology Risks
1. Counseling Patient satisfaction 1 initial and 2 follow-up visits by None
Nutrition maintenance dietitian
Adherence to protocols
2. Food Supplements Nutrition maintenance Limited risks: diarrhea, nausea
a. Home-made Avoid or delay need for more expensive a. Three 8-oz servings = 750 kcal/day a. Diarrhea with lactose intolerance
b. Commercial therapy b. Three 8-oz servings = 750-1080 kcal/ b. Patients may not like taste
day
3. Appetite Stimulants
a. Megestrol acetate oral suspension a. Improved appetite, weight, wellbeing, a. 200 mg/d, 1 month supply a. Impotence, vaginal bleeding, deep
b. Dronabinol quality of life 400 mg/d, 1 month supply vein thrombosis
c. Prednisone b. Improved appetite, no significant 800 mg/d, 1 month supply
weight change b. 2.5 mg/d, 1 month supply b. Euphoria, somnolence, dizziness,
c. Short-term (4 weeks) appetite 5 mg/d, 1 month supply confusion
stimulation (see text) c. 40 mg/d, 1 month supply c. Hypokalemia, muscle weakness,
cushingoid features, hyperglycemia,
immune suppression
4. Enteral nutrition Maintenance of nutrition via enteral Requires nasogastric, gastrostomy, or Aspiration, diarrhea, nausea, bloating,
route when oral route is not possible jejunostomy tube placement infection, bleeding
5. Home parenteral nutrition Maintenance of nutrition when no other Central catheter surgically placed; Catheter-related pneumothorax, sepsis,
alternative is appropriate; no evidence parenteral infusion equipment and thrombosis, bleeding; hepatic
of improved survival in end-stage parenteral formulas: dextrose (20-25% dysfunction, fluid and electrolyte
cancer w/w), crystalline amino acids (2-4% imbalance
w/w), lipid emulsions (500 cc/d →
500 cc/wk)
based on the Harris-Benedict formula15 which, on an average, results in a daily requirement

of 20 to 25 kcal per kg of body weight. The minimum recommended protein need is at
least 0.8 grams per kg/per day.16 These values need to be adjusted according to whether
weight gain is desirable, and to match the metabolic needs of the patient.
One goal of nutrition education and counseling is to have the patient increase consump-
tion of nutrient-dense foods to correct nutritional imbalances and deficiencies in order to
achieve and maintain a desirable weight. Nutrient-dense foods are those with a high
content in kcalories, protein, fat, and vitamins relative to their volume. Liquid supplements
are the most common types of nutritional supplements, and are readily available for
patient consumption. Patients may be anorectic due to illness, or be affected by disabling
factors such as difficulty chewing, inability to prepare foods for themselves, visual diffi-
culties, decreased energy level, or poor access to foods. Nutritional supplements may be
homemade and are usually milk-based or commercially prepared and packaged. Although
somewhat expensive, commercial supplements provide balanced, fortified (vitamin and
mineral enriched) nutrition which require little or no preparation.
Not all cancer patients have the same requirements for nutrition. One major difference
is whether patients are losing weight or have been treated successfully and are trying to
prevent a recurrence through healthful nutrition. In the former case, calorically dense
foods including those with low nutrient density can be used to increase the efficiency of
kcalorie conversion to body fat stores. One limitation of this approach is that malnourished
patients often are limited in their ability to absorb and digest fat due to the effects of
malnutrition or enteritis caused by radiation or chemotherapy. Therefore, overprescription
of high fat foods can in some cases lead to gastrointestinal distress. Foods containing
refined sugar can also be used in these patients, as long as the patient has normal glucose
tolerance. Since diabetes is a not uncommon comorbid condition in cancer patients, this
is a practical consideration. Table 50.9 lists calorically dense foods and strategies for these
types of patients. For patients who have been successfully treated, a preventive diet
covered elsewhere in this text should be used.
Food Supplements
Liquid concentrated food supplements provide high kcalorie and protein, low volume
nutrients, and are reviewed elsewhere.17 Instant breakfast and milk provide an inexpensive
and usually well-tolerated alternative. Commercial products may be more convenient and
better tolerated in those patients with lactose intolerance. Dietitians will help patients
select products on the basis of tolerance and palatability. These products are particularly
helpful when patients can not maintain an adequate intake through a regular diet but are
able to swallow and have a relatively intact GI tract.
Commercially prepared supplements are available in a variety of flavors (including
unflavored) and in a variety of nutrient compositions. Most commercially prepared sup-
plements are available in ready-to-drink eight-ounce cans or boxes and are usually lactose
free, which for the patients is often more acceptable due to the increased incidence of
perceived milk intolerance in this population. When patients have difficulty consuming
adequate volumes of enteral supplement, a high-caloric supplement containing 2 kcal/
ml (e.g., Isocal HCN [Mead Johnson] or Magnacal [Sherwood Medical]) can be used.
Homemade supplements can also be made with commercially available products com-
prising a dry milk base to which whole milk and flavoring is added for a nutrient-dense
TABLE 50.9
Foods Recommended to Increase Kcalorie and Protein Intake of the Patient with Cancer
Food Group Recommendations
Fruits and vegetables Fruit juice added to canned fruit; pureed fruit added to milk, cereals, pudding,
ice cream, gelatin; gelatin made with fruit juice to replace water; tender,
cooked vegetables (mashed white or sweet potatoes, squash, spinach, carrots);
vegetables added to soups and sauces; vegetables in cream or cheese sauces
Grains Hot cereals prepared with milk instead of water; high protein noodles; noodles
or rice in casseroles and soups; breaded and floured meats; bread or rice
pudding; dense breads (i.e., bagels) and dense cereals (granolas, mueslis)
Beverages Milk beverages; shakes made with fruit juices and sherbet when milk is not
tolerated
Milk and calcium equivalents Custards; milkshakes; ice cream; yogurt; cheeses; cheesecake; double-strength
milk (1 quart fluid milk mixed with 1 cup nonfat dry milk powder); cottage
cheese; flavored milk; pudding; commercial eggnog; cream soups; nonfat dry
milk powder added to puddings, soups, sauces and gravies, casseroles and
mixed dishes
Meat and protein equivalents Diced or ground meat; casseroles; smooth peanut butter; cheese; egg and egg
dishes; chopped, diced or puréed meats mixed with soups, sauces, and
gravies; fish, poultry, and vegetable protein meat substitutes; tuna, meat, or
cheese in cream sauces
Fats Margarine or oil added to vegetables, hot cereals, and casseroles; cream used
in place of milk or added to fruits and desserts; sour cream; salad dressings;
mayonnaise mixed with tuna, egg, chicken salad
Sweets Desserts made with dry milk powder, peanut butter, or eggs
beverage. Commercially prepared powdered breakfast drinks (e.g., Ultra Slim-Fast, Instant
Breakfast), to which whole milk is added, is an inexpensive effective supplement when
lactose intolerance is not an issue. These supplements have vitamin, mineral, kcalorie, fat,
carbohydrate, and protein content similar to most commercially prepared supplements.
An eight-ounce supplement varies in nutrient density from 240 to 480 kcals, 7 to 20
grams of protein, 5 to 19 grams of fat and 12 to 25% of the U.S. Recommended Dietary
Allowances (USRDA) for vitamins and minerals.
A nutritional supplement is advisable for patients whose GI tract is functional but who
are unable to obtain adequate nutrition from a regular diet. The volume and choice of
supplement is based on patients’ individual nutrient needs and preferences, and GI tol-
erance. Supplements with fiber, generally soy or oat fiber, are available and may be
beneficial to the patient who has diarrhea or constipation. Nutritional supplements are
generally well accepted and may offer relief to a patient who has difficulties eating solid
food. Tolerability can be enhanced by starting with small quantities and diluting the
supplement with water or ice to decrease osmolality. A patient will usually accept one to
three 8-ounce supplements per day, but there is great individual variability. Patients who
have alterations in taste or nausea may better tolerate an unflavored supplement.
A common concern of patients and families is whether adding vitamins and other
micronutrients to the patient’s diet is beneficial. An analysis of the dietary record for the
recommended number of servings from the Basic Four Food Groups (milk, meat and meat
substitutes, vegetable and fruit, and grain) helps establish whether the minimum vitamin
and mineral requirements are met. A computerized diet analysis program can help to
quickly and accurately assess the nutrient content including vitamins and minerals. When
intake is inadequate, we prescribe a daily multivitamin.
Patients should be provided with practical dietary advice about how to improve daily
caloric intake, and the following are some simple tips to increase food intake:
• Avoid favorite foods after highly emetogenic chemotherapy to prevent the devel-
opment of food aversions.
• Patients should be encouraged to consume any foods regardless of foods being
labelled “non-nutritious,” such as potato chips, nuts, or ice cream.
• Emphasize consumption of “nutrient-dense” foods as part of main meals or
snacks, i.e., peanut butter, cheese, whole milk, and yogurt.
• Avoid the “Why don’t you eat?” complaint. The patient should not be psycho-
logically punished by the cancer care team and/or the family for not eating, but
rather should be supported to overcome anorexia and other problems that lead
to decreased food intake.
• Emphasize the pleasurable as well as social aspects of meals. Encourage patients
to have their meals in a relaxed, friendly, and familiar atmosphere.
• Moderate alcohol intake is usually compatible with treatments and should be
allowed before meals unless contraindicated.
• Avoid odors that can cause nausea. A short walk outside while meals are being
prepared is advisable.
• Encourage food supplements and snacks between meals without being con-
cerned that they may affect intake at meal time.
Patients are often deeply interested in the topic of nutrition as an unproven treatement.
However, many will not bring up this topic unless encouraged and listened to in a non-
judgmental fashion. Open discussion and patient education may help prevent untoward
effects of these diets and introduce nutrition-related issues into the mainstream of
oncology care.
Nutrition Options and Alternative Therapies

A number of alternative therapies are being used by cancer patients in addition to standard
medical oncology therapy,41 as listed in Table 50.10. For this section, the nutrition alterna-
tives will be outlined without reference to acupuncture or other non-nutritional therapies.
Often patients fail to indicate that they are using these nutritional therapies. A number of
potential side effects and concerns, listed in Table 50.11, may arise and need to be
addressed.
Up until recently, most uses of vitamins and herbs were thought to be nontoxic. Recent
animal studies suggest that antioxidants may affect tumor biology. The ATBC and CARET
trials42 in smokers demonstrated an increased incidence of lung cancer following admin-
TABLE 50.10
Alternative Nutritional Therapies Used by Cancer Patients
Multivitamins and single vitamin supplements
Low fat-, high fiber-, soy protein-supplemented diets
Specific macrobiotic diets
Vegetable and grass juicing
Herbal supplements (green tea extract, antioxidants)
Chinese herbal medicine (mushrooms, teas, roots)
TABLE 50.11
Potential Side Effects and Concerns
Vitamin toxicities (e.g. vitamin A >5000 IU per day)
Possible vitamin effects on tumor biology (apoptosis, proliferation)
Vitamin imbalances and conditioned deficiencies
Drug-nutrient interactions
istration of beta-carotene at a dose of 30 mg per day. There were no cancer-stimulatory

effects noted with these doses of beta-carotene in non-smokers in a large heart disease
prevention trial. However, there remains real uncertainty as to the safety of vitamin and
mineral supplementation during chemotherapy or radiation therapy. For the large num-
bers of patients diagnosed today with early cancers of the breast and prostate, vitamin
supplementation is as safe as in the general population once the treatment has been
completed and nutritional intervention may prevent or delay cancer recurrence. However,
the possibility of antioxidant effects on tumor biology or the effectiveness of antitumor
drugs on radiation therapy requires much more research before general recommendations
can be made. At this time, each patient and each oncologist must decide on the advisability
of a given regimen for a given cancer patient based on clinical criteria without the benefit
of a large scientific basis of controlled trials.
References
1. Nixon DW, Heymsfield SB, Cohen A, et al. Am J Med 68: 683; 1980.
2. Shils ME. Cancer Res 37: 2366; 1977
3. Brennan MF. Cancer Res 58: 1867; 1977
4. DeWys D, Begg C, Lavin PT, et al. Am J Med 69: 491; 1980
5. Brennan MF. New Engl J Med 305: 375; 1981.
6. Shike M, Russell DM, Detsky AS, et al. Ann Int Med 101: 303; 1984.
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8. Holroyde CP, Gabuzda T, Putnam R, et al. Cancer Res 35: 3710; 1975.
9. Chlebowski RT, Heber D. Surg Clin North Am 66: 957; 1986.
10. Burt ME, Stein PT, Schwade JG, Brennan MF. Cancer 53: 1246; 1984.
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13. Shaw JHF, Wolfe RR. Ann Surg 205: 368; 1987.
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20. Terepka AR, Waterhouse C. Am J Med 20: 225; 1956.
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22. Heber D, Byerley LO, Chi J, et al. Cancer 58: 1867; 1986.
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24. Bozzetti F, Pagnoni AM, Del Vecchio M. Surg Gynecol Obstet 150: 229; 1980.
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30. Blackburn G, Bistrian B, Maini B, et al. J Parent Eenteral Nutr 1: 11; 1977.
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35. Tchekmedyian NS, Hickman M, Siau J, et al. Oncology 4: 185; 1990.
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51
Cardiovascular Disease Risk — Prevention by Diet
Elaine B. Feldman
Introduction
Coronary heart disease (CHD) is the leading cause of death in both men and women in
developed countries. Mortality rates vary from ~50/100,000 in Japanese women to 436/
100,000 in Scottish men.1 In the U.S. 32% of women and 50% of men will develop CHD,
and CHD is the cause of death in 31% of men and 24% of women. The current concepts
of the role of the diet in the etiology of cardiovascular disease (CVD) relate components
of the diet to the pathogenesis of atherosclerosis. Primarily dietary fats, especially satu-
rated fat and cholesterol, impact on the levels of circulating lipids to raise total and low-
density lipoprotein (LDL) cholesterol that increase CHD risk. Dietary factors increase
triacylglycerol (TG) levels that also increase the risk of CHD and/or decrease high density
lipoprotein (HDL) cholesterol the lipoprotein that lessens CHD risk. Thus, diets that lower
LDL cholesterol and/or TG and/or raise (or do not lower) HDL are protective against
CHD. Other dietary components such as antioxidants (carotenoids, vitamin C, vitamin E)
may lessen the risk of CVD by decreasing oxidized LDL, which is more atherogenic. High
blood levels of homocysteine are atherogenic, and the levels of this amino acid are
decreased by intake of folate, vitamin B6 and vitamin B12. This section will review:
• The background for these hypotheses and associations

• The dietary factors that influence circulating lipids and lipoproteins (Table 51.1)
and their mechanisms of atherogenesis
• The role of some nutrients in vascular biology
• The diet that may best prevent CHD in those without the disease or in individuals
post-myocardial infarction
The Extended Lipid Hypothesis

The fat content and fatty acid composition of the diet were determined to be important
factors in the pathogenesis of atherosclerosis as an inference from the decline in cardio-
0-8493-2705-9/01/$0.00+$1.50
TABLE 51.1
Foods and Nutrients that Affect Cholesterol Levels
Cholesterol-Lowering Cholesterol-Raising
Plant sterols, 3 g/day Saturated fatty acids
Fruits and vegetables, 5 servings/day Trans fatty acids
Soy proteins, 25 g/day Dietary cholesterol
Whole grains
Soluble fiber, 30 g/day
Psyllium
Monounsaturated fatty acids
The Mediterranean diet
N-6 polyunsaturated fatty acids
vascular mortality that was observed during the depression and with World War II.2 Food
was scarce, with a decrease in the consumption of dairy products and eggs, rich sources
of saturated fat and cholesterol. The dietary fat–heart hypothesis was proposed by Keys.3
Epidemiologic studies related CHD rates to the intake of dietary fat, especially saturated
fat (Figure 51.1). A high-fat diet, enriched in saturated fats, was also related to the rise in
serum cholesterol with age. The related cholesterol hypothesis proposes that increasing
serum cholesterol raises the risk of CHD, and that decreasing serum cholesterol levels will
reduce risk.2
The risk of developing CHD is continuous over the range of serum total cholesterol
levels. Cholesterol levels exceeding the 75th percentile are associated with moderate risk
of atherosclerosis, and at >90th percentile with high risk.4 Low-density lipoprotein cho-
lesterol levels similarly can be classified into low, moderate, and high risk.5 Small, dense
LDL particles are associated with a tripling of the risk of myocardial infarction (MI),
compared to the larger, more buoyant LDL particle.6 Elevated lp (a) increases the risk of
700
CHD Deaths/10,000 Men/Decade
500
300
100
4 8 12 16 20 24
% Calories Saturated Fat
FIGURE 51.1
Death rates from CHD and the intake of saturated fat in the Seven Countries Study. The ordinate represents
deaths from coronary heart disease that occurred over a 10-year period per 10,000 men enrolled in the study.
The cohorts are from sites in seven countries: the U.S., Japan, Greece, Italy, Yugoslavia, the Netherlands, Finland.
The regression equation is y = –83 + 25.1x, r + 0.84. Adapted from Keys A. Seven Countries Study — A Multivariate
Study of Death and Coronary Heart Disease, Harvard University Press, Cambridge, 1980.)
Cardiovascular Disease Risk — Prevention by Diet 1047
TABLE 51.2
Factors Affecting HDL Cholesterol Levels
Increased Levels Decreased Levels
Saturated fats Polyunsaturated fat, high
Dietary cholesterol Simple sugars/high carbohydrate diet (short period)
Alcohol <2 drinks/day Some antihypertensive drugs
Long-term aerobic exercise program Physical inactivity
Estrogens Androgens
Progestogens
Anabolic steroids
Female gender Male gender
Obesity
Diabetes mellitus
Cigarette smoking
atherosclerosis,7 although it is unknown whether decreasing levels with any intervention

reduces risk. Elevated lp (a) levels are resistant to treatment other than high doses of
niacin. The smaller lp (a) particles are more atherogenic, may act by promoting LDL
oxidation, and may decrease endothelial-dependent vasodilatation. This additional risk
factor is an indication for more aggressive management of other risk factors. Coronary
events are reduced by 2 to 3% for every 1% decrease in LDL cholesterol.1
HDL cholesterol levels are inversely related to CVD risk.8 Risk is appreciably higher in
subjects with HDL levels < 0.92 mmol/L (35 mg/dl), and decreases when HDL levels are
>1.5 mol/L (60 mg/dl). In addition, the ratio of total cholesterol to HDL cholesterol, or
of LDL:HDL cholesterol, or total to non-HDL cholesterol indicate varying degrees of CVD
risk. Factors influencing HDL cholesterol levels are listed in Table 51.2. Coronary events
are reduced by 3% for every 1% increase in HDL cholesterol.1
TG levels in blood are increased by excess energy intake, fats, carbohydrates, and
alcohol. Whether TG levels are independent risk factors for CHD has been debated over
decades. Recent data have supported the concept that higher TG levels increase risk
independent of HDL levels or other confounding factors of the dyslipidemic syndrome
such as glucose intolerance, hyperinsulinism, obesity, hypertension, etc.9 Results from one
prospective study in Quebec males followed for up to five years suggest that fasting
plasma insulin, apolipoprotein B levels, and LDL particle size may improve risk assess-
ment. Identification of individuals with this cluster of abnormalities may lead to effective
diet and exercise interventions.10 This study supports conclusions from the Physicians’
Health Study that elevated TG levels may help identify individuals at high risk because
of the associated predominance of small, dense LDL particles.11 Data from the Framingham
Offspring Study indicate that elevated levels of fasting insulin are associated with impaired
fibrinolysis and hypercoagulability in individuals with normal or abnormal glucose tol-
erance. This suggests that the risk factors of hyperinsulinemia and glucose intolerance
may be mediated in part by enhanced potential for acute thrombosis.12
A meta-analysis of studies of TG levels and CVD showed that a l mmol/L increase in
TG levels was associated with a 76% increase in CVD risk in women and a 31% increase
in men.13 Current data indicate that TG levels >100 mg/dl raise CVD risk, independent
of the usual accompanying low HDL.14 In the Copenhagen Male Study, fasting hypertrig-
lyceridemia was found to be a stronger predictive risk factor than total cholesterol.15
Levels of circulating apoproteins may be useful in predicting the risk of CVD. Absolute
levels, or changes in lipoprotein particle size or amino acid composition may be better
predictors of CHD than are lipid levels.
A puzzling and as yet unanswered aspect of CHD risk is that the lipid levels of patients
with various clinical symptoms or pathologic signs of atherosclerosis often fall within the
“normal range.” In the most recent National Health and Nutrition Examination Survey
(NHANES III) (Table 26.4), the average level of total cholesterol in the U.S. was 225 mg/
dl, and the average level of LDL cholesterol was 142 mg/dl.16 Patients studied with CHD,
such as in the Framingham Study, have had total cholesterol levels ranging from 200 to
250 mg/dl and LDL cholesterol ranges of 132 to 156 mg/dl.8
Dietary Effects on Serum Lipids and Lipoproteins

Lipids
Diets high in total fat, saturated fat, and cholesterol are atherogenic for many animal
species. Long-chain saturated fatty acids (Figure 51.2) in animal or vegetable fats raise
plasma cholesterol levels and decrease LDL receptor activity.17 Paradoxically, these fats
also raise HDL cholesterol levels. Predominantly monounsaturated liquid vegetable oils
have a cholesterol-lowering effect, lowering LDL cholesterol, but not HDL cholesterol;
some monounsaturated oils have shown a TG-lowering effect.18,19 Polyunsaturated fats of
the n-6 series in liquid vegetable oils decrease LDL cholesterol and increased amounts
lower HDL cholesterol.4 The n-3 series of polyunsaturated fatty acids found in fish (espe-
cially deep-water ocean fatty fish) and fish oil have variable effects on total LDL, and HDL
cholesterol, and lower TG levels.20 Trans-fatty acids produced from some processes of
partial or complete hydrogenation of unsaturated liquid vegetable oils (in the U.S. pre-
dominantly soybean oil) raise LDL cholesterol to a somewhat lesser degree than long-
chain saturated fats or butter, but in contrast, lower HDL cholesterol.21 Investigators
concluded that vegetable shortening and stick margarine have advantages over butter
with respect to LDL cholesterol levels (–5 to 7%), with ingestion of liquid soybean oil or
semiliquid margarine resulting in 11 to 12% lowering of LDL cholesterol in comparison
100
90 Coconut Oil
Palm Kernel Oil
% Saturated Fatty Acids
80
70
Butterfat
60
Beef Tallow
50 Palm Oil
Menhaden Oil
40 Lard
Chicken Fat
30 Cottonseed Oil
Cod Liver Oil
20
Soybean Oil Corn Oil Sunflower Oil
10 Peanut Oil Olive Oil Safflower Oil
0 Canola Oil
FIGURE 51.2
The saturated fatty acid content of various fats and oils.
to butter. Cholesterol is found in the diet only in animal products and is not present in
any plant sources.
Atherosclerosis
Theories of Atherogenesis
Theories of atherogenesis propose that LDL cholesterol is the pathogen, delivering cho-
lesterol to the arterial wall. Endothelial injury initiates proliferation of vascular smooth
muscle cells and conversion of monocytes to macrophages (cholesterol ester-laden foam
cells) and fibroblasts under the influence of growth factors and cytokines.22 Oxidized LDL
accelerates formation of foam cells, atheroma, and the fibrous plaque.23 Plaque rupture
initiates the events of myocardial infarction. CHD progression is related to levels of total
and LDL cholesterol, and decreased levels of HDL cholesterol, especially HDL2, or the
ratio of HDL2 to LDL cholesterol.1,2 Levels of TG >2.28 mmol/L (250 mg/dl) also increase
the risk of MI and warrant intervention; more recent data suggest lowering this level,
perhaps to 0.91 mmol/L (100 mg/dl).13,14 Regression of atherosclerosis occurs when cho-
lesterol ester is mobilized from the superficial layers of plaque. Cholesterol is removed
from plaque when LDL cholesterol levels are reduced to <2.5 mmol/L (95 mg/dl).2 This
level of LDL usually parallels a total cholesterol value <4.6 mmol/L (180 mg/dl).
Current theories of atherogenesis implicate plaque rupture with release of a necrotic
lipid core as the precipitating factor for thrombosis at the site and MI.22 Lipid lowering,
especially of LDL cholesterol, stabilizes the plaque and reduces the risk of MI. Lower lipid
levels may also decrease local concentrations of modified lipoproteins that have proin-
flammatory effects.24 Evaluation of recent cholesterol-lowering clinical trials in the aggre-
gate suggests that with treatment, CVD mortality is decreased by 25% and MI by 50%,
and that a drop of 44% in LDL cholesterol halts progression of coronary atherosclerosis.
The percent drop in LDL correlates 1:1 with the decrease in coronary events.25,26
Atherosclerosis begins in childhood and is strongly associated with LDL cholesterol
levels. A lipid-lowering diet applicable to the general population can be recommended
for children over the age of two years.27
Some mutations that predispose to atherosclerosis by affecting lipid levels and lipopro-
tein concentrations and composition are listed in Table 51.3.
TABLE 51.3
Mutations that Predispose to Atherosclerosis
Heterozygous LPL gene mutation
(May be associated with pattern B LDL)
LDL subclass pattern B (small dense)
Increased apo C-II, C-III or A-II on TG-rich lipoproteins
(Delays clearance and increases atherogenic remnant particles)
? Subtle polymorphisms in ABC-1 gene contribute to reduction in HDL levels
Risk Factors for Atherosclerotic CVD

In addition to the composition and concentration of serum lipids and lipoproteins that
have been associated with risk of CVD, i.e., hypercholesterolemia, high lp (a), other factors
modify risk and may interact with the lipids. These risk factors include:28,29
TABLE 51.4
National Cholesterol Education Program Guidelines, Adult Treatment Panel III, mg/dla
Near/Above Borderline
Factor Optimal Optimal High High Very High
LDL cholesterol <100 100-129 130-159 160-189 >190
Non-HDL cholesterol <130 <160 <190
Total cholesterol Desirable 200-239 >240
<200
HDL cholesterol Low >60
<40 men
<50 women
Triglycerides Normal 150-199 200-499 >500
<150
a Full report available on the NHLBI Web site: http//www.nhlbi.nih.gov/guidelines/cholesterol/
index.htm
Adapted from expert panel on detection, evaluation, and treatment of high blood cholesterol in
adults. JAMA 285: 2486, 2001.
• Cigarette smoking
• Hypertension
• Diabetes mellitus
• Obesity, especially truncal; weight gain 5 kg+ after age 18 (women)
• A sedentary lifestyle (physical inactivity)
• Gender (males at increased risk, females at lower risk)
• Increasing age
• Excessive alcohol
• (Low socioeconomic status)
Obviously, optimal prevention should aim at modifying any or all of these factors that
can be manipulated.
NCEP and Dietary Guidelines

The National Cholesterol Education Program Adult Treatment Plan (NCEP ATP) recom-
mends strategies for identifying and managing subjects at risk for CHD, either primary
prevention in healthy people, or secondary prevention for those with CHD5 (Table 51.4).
Dietary and lifestyle modification is the first intervention, with lipid-lowering drugs
added if target goals are not reached. Diet is more aggressive when lipid levels are higher.
The more potent drug intervention is introduced earlier when lipid levels are very high,
when there are multiple risk factors, or in patients who already have CVD (MI, unstable
angina, stroke).
Diet modifications and the strategies proposed to lessen the risk of CVD and optimize
the lipid and lipoprotein risk factors include:
• Lower total fat from the usual 35% in the American diet to 30% (low fat), or to
<20% (very low fat)
TABLE 51.5
Selected Foods High in Monounsaturated Fatty Acids
Food g/30 g Portion
Canola oil 16.4
Olive oil 20.0
High oleic safflower oil 20.4
High oleic sunflower oil 23.4
Hazelnuts 14.7
Macadamia nuts 16.5
Pistachios 10.1
Pecans 11.4
• Emphasize that the decrease in fat content should mainly reduce saturated fat
(+trans) intake to <10%, or to <7% (Figure 51.1 shows the saturated fatty acid
content of some common fats and oils)
• Decrease saturated fat similarly but not total fat by substituting monounsat-
urated fat for saturated fat (Mediterranean diet)
• Concentrate on the ratio of saturated, monounsaturated, and polyunsaturated
fats to decrease saturates, increase polyunsaturates, and result in a l:l:l proportion
of the three types of long-chain fatty acids
• Consume primarily a plant-based diet and limit meat and dairy products
• Increase whole grains and soluble fiber and limit refined sugars and foods with
a high glycemic index. Dietary fiber has been estimated to lower LDL cholesterol
from 3 to 10%.1.2 Fiber sources include oats, barley, beans, psyllium, pectin, and
guar gum. Gastrointestinal side effects are common. The AHA recommends a
total dietary fiber intake of 25 to 30 g/day from food, about double the current
intake in the U.S.
• Balance energy intake with energy expenditure to prevent or treat obesity which
contributes to the atherogenic lipid pattern
Food sources of saturated fat, monounsaturated fat, and cholesterol are listed in Tables
51.5 through 51.7. The AHA Step 1 and Step 2 diets are described in Table 51.8.
Maximal dietary therapy typically reduced LDL cholesterol by 15 to 25 mg/dL, or about
5 to 10%.5,30,31 Addition of a vigorous exercise program (10 miles/week of brisk walking
or jogging) doubled LDL lowering in contrast to the Step 2 diet while preserving HDL
cholesterol levels.32
Other proposals emphasize increasing the intake of fish and n-3 oils like flaxseed, in
part because of their favorable action on eicosanoids.33-35 Recently, commercial food prod-
ucts have been developed that add cholesterol-lowering plant sterols or their derivatives
(sitosterol, sitostanol) to fats and salad dressings. Studies have shown a reduction in total
cholesterol of 6 to 13% and a 9 to 20% reduction of LDL cholesterol with 3 g/day of stanol
ester in margarine.36 Other dietary components that lower cholesterol or reduce oxidized
cholesterol include 25 g/day of soy protein, perhaps 35 mg/day of the soy isoflavones,37
and antioxidant vitamins (E, C, and carotenoids).38 The amount and type of dietary protein
can affect levels of total and LDL cholesterol, i.e., animal proteins are hypercholesterolemic,
and plant proteins are cholesterol-lowering. This may be attributable to the content of
amino acids lysine and methionine in animal proteins, and arginine in plant proteins.39
Some additional foods that may favorably influence CV risk and lipid/lipoprotein levels
and atherogenicity include garlic (putative lipid lowering) or green tea (antioxidant).40 In
TABLE 51.6
Dietary Sources of Cholesterola
Foodb Cholesterol
Fruits, grains, vegetables 0 mg LOW
Scallops (cooked) 53 mg
Oysters (cooked) 45 mg
Clams (cooked) 65 mg
Fish, lean 65 mg
Chicken, turkey, light meat (without skin) 80 mg
Lobster 85 mg
Beef, lean 90 mg
Chicken, turkey, dark meat (without skin) 95 mg
Crab 100 mg
Shrimp 150 mg
Egg yolk 270 mg
Beef liver 440 mg
Beef kidney 700 mg
a From National Heart, Lung, and Blood Institute, NIH
Publication No. 85-2606, January 1985.
b Seafood, fish, poultry, and meat are cooked, and portion
size is about 3 1/2 oz.
TABLE 51.7
Selected Foods High in Saturated Fatty Acids
Food g/100 g Edible Portion
Beef, roast, chuck, cooked 11.2
Beef, steak, prime rib, cooked 12.8
Ground beef, cooked 9.9
Bologna, beef, regular 13.8
Frankfurter, all beef, Kosher, regular 13.6
Frankfurter, regular, beef and pork 13.7
Salami, hard or dry, pork 16.0
Bacon, regular cut 23.7
Egg, yolk only, cooked 9.6
Cream, half-and-half 32.6
Cream, light, coffee cream 12.0
Parmesan cheese, dry 19.1
American cheese, processed 18.7
Cream cheese, Neufchatel 13.8
Cheddar cheese, natural 21.1
Cheddar cheese, low fat 10.9
Swiss cheese, natural 17.8
Monterey Jack cheese, natural 19.1
Mozzarella cheese, part skim milk 10.9
Brie cheese 15.3
American flavor cheese, low fat 9.8
Coconut oil 86.5
Palm oil 49.3
Palm kernel oil 71.5
Lard 39.2
Butter, regular, salted 50.5
Coconut, fresh 29.7
Adapted from Table A 21-a in Modern Nutrition in Health and
Disease, Shils M.E., Olson J.A., Shike M., Ross, A.C., Eds, 9th ed,
Williams & Wilkins, Baltimore, 1999, p A-121.
TABLE 51.8
Step I and Step II Diets
Nutrient Step I Recommend Step II Recommend
Total fat <30 % of kcalories <30% of kcalories
Saturated fat 8%-10% of kcalories <7% of kcalories
Polyunsaturated fat Up to 10% of kcalories Up to 10% of kcalories
Monounsaturated fat Up to 15% of kcalories Up to 15% of kcalories
Carbohydrate >55% of kcalories >55% of kcalories
Protein ~15% of kcalories ~15% of kcalories
Cholesterol <300 mg/day <200 mg/day
Kcalories Achieve, maintain desirable weight Achieve, maintain desirable weight
addition to effects on blood lipids and LDL oxidation, these nutrients also may influence
factors involved in vascular reactivity, such as nitric oxide and thrombus formation.41
Chinese red yeast rice is another traditional herbal remedy that may be lipid lowering
because of its content of statins and precursors.42
HDL cholesterol levels are raised by moderate intake of alcoholic beverages;43 red wine,
grapes, and grapeseed oil also may contain favorable antioxidants.44 Short-term replace-
ment of usual dietary oil with grapeseed oil in subjects with moderate elevations of LDL
cholesterol and low HDL cholesterol resulted in a 7% lowering and 8% increment respec-
tively (personal communication, D.T. Nash). Similar antioxidants are found in rice bran
oil.45 Ingestion of rice bran oil has resulted in decreases in LDL and increases in HDL
comparable to effects of canola oil. Components of fats and oils that are not the fatty acids,
but perhaps the tocotrienols, plant sterols, or flavonoids may be partially responsible for
an antiatherogenic effect. As vascular biologists derive more scientific data, foods may
influence atherogenesis by mechanisms less dependent on lipid/lipoprotein levels.
Nutritionists debate the importance of limiting dietary cholesterol intake (see Table 51.7
for sources), especially in relation to the established merit of decreased saturated fat.
Examples of some menus and foods for lipid-lowering diets are provided in Table 51.9.
Diet Trials
There has been no large scale long-term trial of the effects of diet on serum lipids and
lipoproteins, or most importantly on cardiovascular risk (morbidity, mortality). Dietary
recommendations are derived by consensus and are modified as new scientific information
is obtained, usually from epidemiologic or animal studies.
Some relevant diet and lifestyle trials include the GISSI (Gruppo Italiano per lo Studio
della Sopravvivenza nell Infarto [Miocardico]) trial that evaluated dietary supplementa-
tion with n-3 polyunsaturated fatty acids and vitamin E in patients after MI.33 Patients
who took 1 g daily of n-3 PUFA (equivalent to about 100 g/day of fatty fish), but not
those who took 300 mg/day of vitamin E, had significant benefit attributable to the 20 to
30% decrease in risk for overall and cardiovascular mortality. The fish oil capsule contained
375 mg DHA ethyl ester and 465 mg EPA ethyl ester. All of these study patients in Italy
were also ingesting a Mediterranean diet and were taking cardiac medications. The inves-
tigators propose the benefit of n-3 PUFA on arrhythmogenesis over the 3 1/2 years of
treatment. A similar protective effect of fatty fish in the secondary prevention of CHD
(29% reduction in overall mortality) has been reported in the Diet and Reinfarction Trial
TABLE 51.9
Step I AHA — Meal Plan
Goals: <30% Fat
<10% Sat. Fat
<300 mg Chol.
Total Fat Sat. Fat Chol.
Food Kcal (g) (g) (mg)
Breakfast
Cantaloupe, pieces, 1 c 56 0.4 0.1 0

Toast, whole wheat, 2 sl 130 2 0.4 0
Margarine, Promise Extra Lite soft, 1 Tb 50 5.6 0.9 0
Milk, 1% Fat, 8 fl. oz 102 2.6 1.6 10
Breakfast subtotal 338 10.6 3 10
Lunch
Grilled chicken sandwich:

Chicken breast w/o skin, boneless, 2 oz 95 2.1 0.6 47
Bun, 1 133 2.2 0.2 0
Mayonnaise, light, 1 Tb 50 5 1 0
Lettuce, 1 leaf 2 0 0 0
Carrot, raw, 1 med 31 0.1 0 0
Pretzels, 1 oz 108 1 0.2 0
Apple, raw w/peel, 1 med 81 0.5 0.1 0
Lunch subtotal 500 10.9 2.1 47
Dinner
Grouper, baked, 4 oz 133 1.4 0.4 52

Rice, 1/2 c cooked 100 0.5 0.1 0
Green peas, 1/2 c 59 0.3 0.1 0
Margarine, Promise Extra Lite, soft, 1 Tb 50 5.6 0.9 0
Dinner roll, 1 85 2.1 0.5 0
Sherbert, 1/2 c 132 1.9 1.1 5
Pineapple, raw, pieces, 1/2 c 37 0.4 0 0
Dinner subtotal 596 12.2 3.1 57
Snacks
Oatbran muffin, 1 med 154 4.2 0.5 0

Milk, 1%, 8 fl. oz 102 2.6 1.6 10
Snacks subtotal 256 6.8 2.1 10
Daily Total 1690 40.5 10.3 124
22% 5%
20% Protein
58% Carbohydrate
(DART).46 The protective effect of fish also was reported in the observational Health
Professionals Study34 and the U.S. Physicians Health Study.35 Diet recommendations devel-
oped and updated by the American Heart Association and the federal government will
be modified in 2000.
Since TG levels are raised by diets high in carbohydrate, especially refined sugars, and
also are sensitive to alcohol and excess kcalories, TG-lowering diets limit sugars, alcohol,
and kcalories, and increase energy expenditure.47
FIGURE 51.3
Homocysteine metabolism is regulated by enzymes dependent on folate and vitamins B6 and B12. + = activation,
– = inhibition. Abbreviations: THF = tetrayhydrofolate; MeTHF = methylene tetrahydrofolate; MTHF = methyl-
tetrahydrofolate; SAM = S-adenosylmethionine; PLP = pyridoxalphosphate (biological active form of vitamin
B6); CS + cystathionine synthase; CL = cystathionine lyase; MS = methionine synthase; MTHFR = methylene
tetrahydrofolate reductase; BHMT = betaine homocysteine methyl transferase.
Other Nutritional Factors and CVD Risk

Homocysteine
An important nutritional risk factor for CVD is the blood homocysteine level, which
increases in relation to deficient intake or metabolism of folate, and vitamins B6 and B12
(see Figure 51.3). Elevated levels of homocysteine may be due to defects in enzymes
catalyzing transsulfuration or remethylation pathways caused by drugs (methotrexate,
phenytoin, theophylline, carbamazepine), deficiency of cofactors or cosubstrates (folate,
B12, B6), impaired renal clearance, hypothyroidism, ovarian, pancreatic or breast cancer, or
increasing age impairing vitamin absorption.
In recent years evidence has accumulated concerning the efficacy of folate (folic acid)
in preventing heart disease. It is arguable whether folate from food sources (poly-
glutamates) is as effective as folic acid supplements (monoglutamate) in risk reduction.
Folate bioavailability from food is 50%, whereas bioavailability from synthetic folic acid
approaches 85% (1.7×).
Dietary folate or folic acid supplements may reduce the risk of cardiovascular disease
in individuals with hyperhomocysteinemia resulting from genetic disorders of methionine
metabolism and/or subclinical deficiencies of the B vitamins folate, B12, and B6. The genetic
disorder is associated with premature cerebral, peripheral, and possibly coronary vascular
disease. Homocyst(e)ine has been proposed as a risk factor for atherosclerotic CHD for
more than 30 years.48 Recent studies have concluded that homocyst(e)ine is an independent
risk factor for coronary heart disease equivalent in importance to hyperlipidemia and
smoking.49,50 It promotes prothrombotic changes in the vascular environment, arterial

narrowing and endothelial cell toxicity, affects platelets and clotting control mechanisms,
and stimulates smooth muscle cell proliferation. Investigators have linked hyperhomocys-
teinemia with premature vascular occlusive diseases: carotid occlusive disease, cerebrovas-
cular disease, CHD, peripheral arterial occlusive disease, and veno-occlusive disease.
Homocysteine may be synergistic for thromboembolic disease with other risk factors, e.g.,
diabetes mellitus, hyperlipidemia, smoking, deficient antithrombin II, protein C, protein
S, or Factor V Leiden.
Normal fasting levels are slightly lower in women (6 to 10 µmol/L) than in men (8 to
12 µmol/L). Risk of CVD is significantly increased when homocysteine levels exceed the
95th percentile (~15.8 nmol/ml). There appears to be a graded effect of the homocysteine
level on risk of CVD, and homocysteine level is a strong predictor of cardiovascular
mortality. Elevated homocysteine may account for 10% of the attributable risk of CHD.
Importantly, elevated blood levels of homocysteine can be normalized with vitamin
supplements (0.2 to 1 mg folic acid, with or without 0.4 mg cyanocobalamin, 10 mg
pyridoxal), potentially decreasing cardiovascular risk. Results of such intervention have
not yet been reported in any prospective large scale randomized placebo-controlled clinical
prevention trial. Whether reduction of plasma homocysteine by diet and/or vitamin
therapy will reduce CVD risk is not known. Thus, at the present time emphasis should
be placed on meeting requirements for folate and vitamins B6 and B12. Screening for fasting
plasma homocysteine may be indicated in patients with premature CVD or with a family
history of premature CVD.

Other nutrients that have been associated with CVD risk include niacin that is lipid
lowering only in pharmacologic doses at minimum 50 times the daily requirement for the
vitamin,51 copper (cholesterol and LDL-lowering),52 and zinc (increasing cholesterol and
LDL).53 Vitamin D may be atherogenic, and retinoids have been shown to raise TG levels.
The possible role of antioxidant vitamins (beta-carotene and carotenoids, vitamin C,
vitamin E) and dietary supplements in reducing CVD risk is under investigation. At
present the dose of vitamin E that may be effective and safe, and the minimum duration
of treatment for protection are unknown. The Canadian Heart Outcome Prevention Eval-
uation Study in patients at high risk for CV events found that treatment with 400 IU daily
of vitamin E for 4.5 years had no apparent effect on cardiovascular outcomes.54
CVD Risk Prevention by Non-Lifestyle Modifications

In recent years successful primary and secondary prevention as well as documented
slowing of progression or regression of atherosclerotic lesions have been achieved by a
variety of modalities established by sound randomized, often double-blind, intervention
trials that have been carried out in the U.S. and abroad.25 Most trials address the lipid risk
factors by use of lipid-lowering medications or ileal bypass. Other modalities include LDL
plasmapheresis.55 Chelation therapy with EDTA is unorthodox therapy that is generally
not recognized as effective or safe. Low-dose aspirin has been shown to reduce the risk of
MI in men, and oral anticoagulants continue to be proposed to reduce the risk of MI and
stroke.41 Some studies have shown a reduction in the risk of stroke as well as cardiovascular
events with the use of statin drugs.56 Of interest and debate is whether the favorable
response is proportional to lowering of cholesterol and LDL, or raising of HDL, or whether

a threshold is achieved for optimal prevention. In some trials, favorable results decreasing
morbidity and mortality occurred too soon to expect them to be related to the degree of
atherosclerosis but were more likely associated with stabilization of plaque. These trials
also have demonstrated favorable effects in patients with lipid levels within the normal
or average range, which is the level found in many patients with CHD. In fact, 20 to 25%
of MIs occur in people with LDL cholesterol levels between 100 and 129 mg/dl.8,57
The first effective and safe cholesterol-lowering drugs were the bile acid-binding resins
cholestyramine and colestipol. The efficacy of resins and the newer statin drugs (HMG
Co A reductase inhibitors) and fibric acid derivatives on lipids and lipoproteins is depicted
in Figure 52.9 of the Hyperlipidemia section. High-dose niacin therapy has also been
administered for several decades, and is included as well. Often these drugs are used in
combination to aggressively treat resistant forms of hyperlipidemia. Adverse effects of
lipid-lowering drugs are observed on the gastrointestinal tract, liver, and muscles. The
diet modifications initiated prior to drug therapy are usually continued during drug
treatment in order to minimize the drug dosage, thereby decreasing adverse events and
cost. If the diet, however, has been shown to be ineffective, then emphasis during drug
treatment might better be placed on controlling body weight and eating a balanced diet.
Clinical Trials, Lifestyle

The studies of the effects on circulating lipids of changes in the content and composition
of the diet are too numerous to cite in this section. Rather, more recent multicenter or large
scale diet trials and three randomized controlled lifestyle intervention trials that address
disease outcomes and/or angiographic endpoints over five years will be discussed.
The Lifestyle Heart Trial in patients with moderate to severe CHD demonstrated that
intensive lifestyle changes lead to regression of coronary atherosclerosis.58,59 The diet
prescribed was a 10% fat, vegetarian diet and moderate aerobic exercise, stress manage-
ment training, smoking cessation, and group support.
The St. Thomas’ Atherosclerosis Regression Study (STARS) in patients with CHD
included one arm of a 27% fat, weight reduction diet supervised by dietitians.60 Dietary
change retarded overall progression and induced regression of CHD.
The diet and exercise trial from Heidelberg in high-risk young men included rigorous
exercise and a 20% fat diet.28 A significant slowing of progression of coronary lesions was
demonstrated.
Despite the demonstrated benefits of the Ornish regimen, other investigators have
reported no benefit in lowering fat some 3 to 5% below the Step 1 diet in hypercholester-
olemic men with and without hypertriglyceridemia followed for one year.61 The Diet
Effects on Lipoproteins and Thrombogenic Activity (DELTA) study at four sites included
women, minorities, and older subjects in a comparison of eight weeks of the Step 1 diet
(6% lower in total fat and saturated fat) and a 3% even lower-fat and saturated fatty acid
diet in contrast to the average American diet (34% fat, 15% saturated fat).31 Confirming
other studies, the significant results were that with the Step 1 diet there was a drop in
total (5%), LDL and HDL cholesterol (7%), apo B (–3%), and apo A-1 (5%), with a 9%
increase in TG and 10% increase in lp (a). Further fat reduction resulted in a significant 4
to 5% fall in total, LDL, and HDL cholesterol and apo A-1, and a 7% increase in lp (a).
The increase in negative risk factors lp (a) and TG raised questions about benefit in
lowering CHD risk. The degree of lipid lowering with diet was similar to that observed
in the earlier diet-lovastatin study30 and continue to be less than earlier predictions from
Keys-Hegsted.1
Lessons from Large-Scale Clinical Trials of Lipid-Lowering Therapy 25,26,65

Many studies using effective lipid-lowering drugs, primarily statins, in primary and
secondary prevention of CHD have yielded an overwhelming body of evidence to confirm
that significant risk reduction can be achieved in about five years of treatment. Interest-
ingly, the benefit is beyond the change in plaque in angiographic studies, but extends to
symptoms of unstable angina and precipitation of acute MI from plaque rupture. Thus,
the conclusion is that lesions are stabilized as a result of effective lipid-lowering treatments
that may affect a number of inflammatory and thrombotic mechanisms. More aggressive
treatment with LDL cholesterol lowered to <100 mg/dl reduces progression still more.
The implication is that all patients with CHD should be treated to lower their cholesterol.
This recommendation also may apply to individuals with very high LDL (>220 mg/dl)
or with LDL levels >160 mg/dl and other risk factors, especially diabetes mellitus.
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2. Grundy S.M. In Modern Nutrition in Health and Disease, Shils ME, Olson JA, Shike M, Ross AC,
Eds, 9th ed, Williams & Wilkins, Baltimore, 1999, ch 75.
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52
Hyperlipidemias and Nutrient-Gene Interactions
Elaine B. Feldman
A variety of factors under genetic control are involved in the production and metabolism
of serum lipids and lipoproteins (Table 52.1).1,2 Nutrients in the diet may affect one or
more steps of gene regulation of lipoproteins, resulting in abnormal lipid or lipoprotein
levels and predisposition to atherosclerosis. The factors affected are listed in Table 52.1.
Examples of effects of diet and lifestyle on genetic mechanisms are included in Table 52.2.1
Hyperlipidemias
These lipid disorders reflect abnormal increase in one or another serum lipid component
and/or lipoprotein carrier (Tables 52.3, 52.4). The abnormalities often are inherited and
are strongly influenced by the diet. Their management requires accurate diagnosis and
evaluation, searching for other diseases that may induce secondary hyperlipidemia.3 The
dietary intervention, if unsuccessful, should be followed by appropriate medication that
normalizes the lipids and lipoproteins in order to prevent complications of atherosclerotic
disease (myocardial infarction, peripheral vascular disease) or pancreatitis.4
These subjects have lipid levels generally above the 90th percentile for their age and sex
(Table 26.3). Blood samples should be obtained after a 12 to 14-hour fast in individuals
ingesting their usual diet. At least three blood samples should be evaluated, two or three
weeks apart. The lipid studies may need to be more elaborate than the usual lipid screen or
profile (see Section 26). Ultracentrifugation of the plasma often is necessary, usually per-
formed in a specialized lipid laboratory. These lipid disorders can be suspected from the
patient’s history, family history, and physical examination. First degree relatives should also
be investigated in order to detect others with the disorder and to characterize the genetics.
Numerous mutations have been associated with the various types of familial hyperli-
poproteinemias (Table 52.4).5 In the future, nutrient modulation of gene expression may
be used as therapy. More than half the variability in serum cholesterol (low density
lipoprotein, LDL cholesterol) among individuals is attributable to genetic variation, pre-
sumably polygenic. Polymorphisms in apo-E or apo-B are examples. The remaining vari-
ability in cholesterol levels may be attributable to the diet, diet-gene interactions, or
postulated genes that control variability of response to the environment. The prevalence
of hyperlipidemias is increased in patients with premature coronary heart disease (CHD),
i.e., <55 years of age.
0-8493-2705-9/02/$0.00+$1.50
TABLE 52.1
Factors Involved in the Formation and Metabolism of Lipoproteins
Type Action
Apoproteins
Apo A-I Anti-atherogenic

Apo A-II Apo A-II-containing lipoproteins are not effectively metabolized by
lipoprotein lipase (defective lipolysis)
Apo B100 Ligand for the LDL receptor
Apo C-I Blocks apo E binding to receptors
Apo C-II Activates lipoprotein lipase (LPL)
Apo C-III Impairs TAG hydrolysis delaying clearance of remnants of
chylomicrons; inhibits LPL; decreases LDL binding to receptors;
displaces apo E from lipoprotein particles
Apo E Ligand for the LDL receptor; interacts with the LDL receptor-related
protein (LRP); enhances lipolysis
Enzymes
Lipoprotein lipase (LPL) Hydrolyzes TAGs to free fatty acids in chylomicrons and VLDL to form
chylomicron remnants and IDL. Excess lipoprotein surface
components are released to form HDL particles
Hepatic lipase (HL) Functions as a phospholipase and TAG hydrolase. Important for
conversion of IDL to LDL. Increased activity leads to LDL pattern B
(small dense) and low HDL
Lecithin:cholesterol acyltransferase Catalyzes the esterification of free cholesterol to cholesterol ester on
(LCAT) plasma lipoproteins
Acyl CoA:cholesterol acyltransferase Catalyzes cholesterol esterification
(ACAT)
Carboxyl ester lipase (CEL)
Receptors
LDL receptor Binds apo B-containing lipoproteins, such as LDL

LDL receptor-related protein (LRP) Takes up chylomicron remnants
Scavenger receptor A (SR-A) Binds LDL modified by oxidation
CD-36, a scavenger receptor on Binds modified LDL
macrophages
Scavenger receptor B1 (SR-B1) Selectively removes cholesterol esters from HDL and apo B-containing
lipoproteins
Peroxisome proliferator-activated Putative HDL receptor takes up HDL particles
receptor-α (PPARα)
VLDL receptor
Transfer Proteins
Cholesterol ester transfer protein Required for normal clearance of HDL. Transfers cholesterol esters
(CETP) synthesized in HDL to the apo B-containing lipoproteins in exchange
for TAG
ATP-binding-cassette transporter 1 Actively transports free cholesterol out of cells and into HDL particles
(ABC-1) transforming lipid-poor A-I particles into nascent HDL particles
Microsomal triglyceride transfer Necessary to generate LDL (VLDL)
protein (MTP)
2705_frame_C52 Page 1063 Friday, August 16, 2002 11:43 AM
Hyperlipidemias and Nutrient-Gene Interactions 1063
TABLE 52.2
Effects of Diet and Lifestyle on Gene Regulation of Lipoprotein Expression
Factor Effect
Cholesterol Decreases expression of the LDL receptor by suppressing transcription of its gene
Regulates H:MG CoA reductase expression by controlling the stability of the
HMG CoA reductase protein (post-translational level)
Polyunsaturated fatty acids Block transcription of the fatty acid synthase gene
Fats Excessive intake induces excessive secretion of apo-B containing lipoproteins by
stabilizing the protein (post-translational)
Affects LDL receptor expression
Increases expression of LPL activity, inducing adipose tissue LPL activity and
suppressing skeletal muscle LPL activity (perhaps via insulin). Post-
translational regulation by glycosylation is possible.
Atherogenic diet Decreases HDL
Decreases the expression of the gene encoding paraoxonase, an enzyme that
protects LDL from oxidation
Exercise Increases muscle LPL activity pre-translationally
Glucose Increases fatty acid synthesis by stabilizing the fatty acid synthase mRNA (post-
transcriptional)
Other Subjects with the E3/E4 phenotype respond to a low fat, low cholesterol diet
intervention with a greater LDL decrease than those with the E3/E3 or E3/E2
phenotype
TABLE 52.3
Classification (Type) of Hyperlipidemia and the Underlying Lipoprotein Abnormality
Type Lipoprotein Abnormality
I Increased exogenous triacylglycerols (TAG) in the form of chylomicrons
IIa Hypercholesterolemia with increase in LDL and normal TAG levels
Iib Hypercholesterolemia combined with mild hypertriglyceridemia (increase in LDL and
VLDL particle number, overproduction of apo-B)
III Remnant hyperlipemia; hypercholesterolemia with hypertriglyceridemia and increase
in IDL
IV Mild to moderate endogenous hyperlipemia; increased VLDL with TAG 2.8-7.9 mmol/
L or 250-700 mg/dl
V Mixed hyperlipemia; moderate to severe hypertriglyceridemia (>11.3 mmol/L or 1000
mg/dl) with mixed VLDL and chylomicrons
Types of Hyperlipidemias
Chylomicronemia (Type I Hyperlipoproteinemia)3-7
Dietary TAGs that are transported as chylomicrons are increased in Type I. This rare
disorder results from a defect in removal of chylomicrons from the blood due to the
presence of a recessive gene that results in deficiency of lipoprotein lipase (LPL, Table
52.4).6 A similar disorder results from the absence or abnormal function of the apo-C II
activator of LPL,7 or from the presence of a circulating inhibitor of LPL. Type I may present
in infants and children. It does not usually predispose to vascular disease, but patients
are at risk of recurrent severe pancreatitis. Signs of lipemia retinalis (Color Figure 52.1*),
eruptive xanthomas (Color Figure 52.2), and hepatosplenomegaly may be present. The
plasma shows a chylomicron creamy layer over a clear infranatant. Plasma TAG levels
usually exceed 17 mmol/L.
* Color figures follow page 992.

TABLE 52.4
Genetic Basis of Familial Hyperlipidemias
Type Abnormality Mutation
Type I Familial lipoprotein lipase deficiency 40 known missense and nonsense mutations of gene
encoding enzyme
Familial lipoprotein lipase inhibitor
Familial apo C-II deficiency 14 defects identified
Familial hepatic lipase deficiency
Type II Familial hypercholesterolemia 400 deletions/point mutations in 5 classes of the LDL gene
Familial defective apo B100 Apo B 3500 mutation impairs binding to the LDL receptor
Polygenic hypercholesterolemia Apo A-I/C-III/A-IV gene clusters
Type Iib Familial combined hyperlipidemia Apo A-I/C-III/A-IV
LCAT
Mn superoxide dismutase linkage
Partial LPL deficiency
Type III Familial dysbetalipoproteinemia Apo E gene polymorphism affects amino acid coding
E2/E2 phenotype
Type IV Familial hypertriglyceridemia (mild) Apo A-I/C-III/A-IV
?Hepatic lipase deficiency
Type V Familial hypertriglyceridemia (severe) Apo A-I/C-III/A-IV
Familial lipoprotein lipase deficiency Apo A-II
Apo C-II deficiency
FIGURE 52.1
(See Color Figure 52.1) Lipemia retinalis visualized in the optical fundus of a patient with chylomicronemia
with TAG levels exceeding 3000 mg/dl.
FIGURE 52.2
(See Color Figure 52.2) Eruptive xanthomas observed in a patient with chylomicronemia.
Hypercholesterolemia (Type IIa and Type IIb Hyperlipoproteinemias)3,4,9

In Type IIa hypercholesterolemia, increased LDL is present with normal levels of TAGs.
Familial hypercholesterolemia (FH) is a single-gene defect of the cell surface receptor that
binds circulating LDL and delivers cholesterol to cells.8 To date, more than 400 mutations
have been characterized in five classes.5,9 In the heterozygote, receptor number or activity
is about half normal. LDL cholesterol does not enter the cell and does not suppress the
activity of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting
step in cholesterol synthesis. Cholesterol synthesis continues and esterified cholesterol
accumulates in the cell, suppressing LDL receptor synthesis. The LDL cholesterol level in
blood doubles (to about 9 mmol/L) and the fractional catabolic rate of LDL is halved. In
the FH homozygote with no receptors, LDL production is greatly enhanced and removal
severely decreased. LDL cholesterol levels average 19 mmol/L.
Signs of FH include lipid deposits such as eyelid xanthelasma (Color Figure 52.3), corneal
arcus (Color Figure 52.4), and tendon and tuberous xanthomas of the skin (Color Figures
52.5, 52.6) that appear in the second or third decade of life. Hypercholesterolemia is present
from birth.10 FH homozygotes may have xanthomas in infancy or early childhood. The
incidence of CHD is increased 25-fold in FH patients and occurs prematurely (before age
50). In FH homozygotes, CHD may be present in infancy and early childhood, with death
occurring by age 21.
Patients with familial defective apo B (Table 52.4) may exhibit a phenotype identical to
FH.5 In Type IIb, hypercholesterolema is combined with hypertriglyceridemia, with LDL
and very low density lipoprotein (VLDL) increased, and overproduction of apo-B. Familial
combined hyperlipidemia (FCH) is the most common hyperlipidemic syndrome in
patients with premature CHD. In this condition, small, dense LDL is overproduced, with
increased levels of apo-B.11-13
Type III Hyperlipoproteinemia (Dysbetalipoproteinemia, Broad-beta or Floating-beta

Disease)14
In this syndrome, hypercholesterolemia is combined with hypertriglyceridemia. Interme-
diate density lipoprotein (IDL) remnants are increased, at times mixed with chylomicrons.
FIGURE 52.3
(See Color Figure 52.3) Eyelid xanthelasma from a woman with familial hypercholesterolemia.
FIGURE 52.4
(See Color Figure 52.4) Corneal arcus observed in a 31-year-old man with familial hypercholesterolemia.
FIGURE 52.5
(See Color Figure 52.5) Xanthomas of the Achilles tendons of a patient with familial hypercholesterolemia.
FIGURE 52.6
(See Color Figure 52.6) Tuberous xanthomas in the skin of the elbows of a teenage girl with familial hypercho-
lesterolemia.
FIGURE 52.7
(See Color Figure 52.7) Yellow linear deposits in the creases of the fingers and palms of the hands of a 33-year-
old man with Type III hyperlipoproteinemia.
The disorder is due to a genetic defect in the apo-E isoforms. The normal E3 is replaced
by one or two E2 proteins that have defective receptor binding. This results in a lesser rate
of removal and increases the circulating level of IDL. Preparative ultracentrifugation
demonstrates increased cholesterol relative to TAG in the VLDL fraction, with more rapid
migration of the lipoprotein on electrophoresis. Apo-E isoforms should be determined (E
phenotype). Patients show planar xanthomas of the palms (Color Figure 52.7) and tuberous
xanthomas as early as the third decade of life. Patients have premature peripheral vascular
disease and CHD.15
Type IV Hyperlipoproteinemia5
Endogenous hypertriglyceridemia is characterized by mild to moderate increase in TAG
levels (3 to 8 mmol/L, 250 to 700 mg/dl), with increase in VLDL.16,17 Both overproduction
and decreased removal of VLDL TAG may be responsible. LDL cholesterol levels are
within the normal range. Usually HDL cholesterol is decreased. These subjects may be at
increased risk of atherosclerosis, and hypertriglyceridemia per se may be an independent
risk factor for cardiovascular disease (CVD).16,17 Patients often have no signs or symptoms
other than the abnormal lipid and lipoprotein values, and may present initially with
cardiovascular events. Underlying mechanisms and genetic defects are multiple.5 See also
atherogenic dyslipidemia, below.
Type V Hyperlipoproteinemia
Moderate to severe increases in TAG levels exceeding 11.3 mmol/L or 1000 mg/dl char-
acterize this disorder, often termed the chylomicronemia syndrome.3,4,6,15 Chylomicrons
appear along with increased levels of VLDL. Patients exhibit eruptive xanthomas and
lipemia retinalis (TAG levels >34 mmol/L, 3000 mg/dl) (Color Figures 52.1, 52.2). They
are at high risk for recurrent episodes of acute pancreatitis, at times resulting in pancreatic
insufficiency. Fifty percent or more of these patients have diabetes mellitus that must be
TABLE 52.5
Metabolic Syndrome Risk Factors
Insulin resistance
Elevated Triaglycerides
Increased dense LDL
Low HDL
Hyperinsulinemia
Glucose intolerance
Hypertension
Prothrombotic state
Truncal obesity
Premature CVD
controlled to effectively lower TAG levels. Alcohol intake or estrogen treatment may
convert a type IV patient to type V, or worsen type V and precipitate pancreatitis.3
Underlying mechanisms and genetic defects are a mixture of those of Type I and Type IV
(Table 52.4).
Dyslipoproteinemia (Atherogenic Dislipidemia)

Some lipidologists have proposed and prefer a simpler classification into subgroups of
hypercholesterolemia, chylomicronemia, or atherogenic dyslipidemia.4 This metabolic syn-
drome encompasses hypertriglyceridemia, small dense LDL, low HDL, insulin resistance,
abdominal obesity, and hypertension (Table 52.5). These patients are at high risk of ath-
erosclerosis.1,7
Evaluation of Patients with Hyperlipidemia

Table 52.6 enumerates the details of the history, physical examination, and laboratory tests
used for the evaluation of subjects who may have one of the hyperlipidemic syndromes
(Color Figure 52.8).
Dietary Management of Hyperlipidemias

Appropriate diet tailored to the lipid abnormality is the initial intervention. Treatment
goals are to normalize lipids, or in patients with vascular disease, to lower these to optimal
levels that promote regression of atherosclerotic disease and stabilize plaque. Lipid levels
should be monitored at six- to eight-week intervals. After a three- to six-month trial of
diet, depending on the response and the severity of the disease, appropriate cholesterol-
and/or triglyceride-lowering medication should be added. The diet is continued (unless
the response is adverse) so that medication dose can be lower, thereby minimizing side
effects and cost. Treatment is lifelong.
Diets to Lower Serum Cholesterol and LDL Cholesterol3,4

Cholesterol lowering is achieved by a diet that regulates kcalories to achieve desirable
weight, and includes an exercise regimen. Depending on the severity of hypercholester-
olemia, total fat should be decreased to 30% or less of energy, with saturated fat reduced
to <10% or <7% of kcalories depending on severity and response, and cholesterol intake
should be 70 to 100 mg/1000 kcal. Consumption of plant based foods, complex carbohy-
drates, and dietary fiber should be increased.
TABLE 52.6
Evaluation of Patient for Hyperlipidemia
History of:
Vascular disease, angina, MI, angioplasty, bypass surgery, claudication

Abdominal pain
Diabetes
Thyroid, hepatic, renal, disease, gout
Smoking habits, exercise, medications
Body weight
Family history of vascular disease, diabetes, gout
Diet history: alcohol, supplement use, amount and type of fat and cholesterol, energy, protein, carbohydrate,
sucrose intakes (best done by a dietitian)
Physical Examination:
Blood pressure, height, and weight

Corneal arcus, xanthelasma, retinopathy, lipemia retinalis
Xanthomas of skin and/or tendons
Dry skin, hair loss
Bruits, murmurs, absent pulses, arrhythmias
Liver, spleen size
Laboratory:
Blood, after 12-14 hour overnight fast, cholesterol, TAG, HDL cholesterol, glucose
Plasma turbidity
Apoproteins, ultracentrifugation, electrophoresis
Post-heparin lipolytic activity
Tests of renal, hepatic, and thyroid function
Electrocardiogram
FIGURE 52.8
(See Color Figure 52.8) The appearance of plasma, refrigerated overnight, from fasting patients. The tubes with
plasma samples are taken from (left to right): a subject with normal lipid levels and clear plasma (similar to a
patient with Type IIa); a patient with chylomicronemia (Type I) with a creamy top layer above a clear infranatant;
a patient with hypercholesterolemia (Type IIa) with clear plasma; a patient with Type III hyperlipoproteinemia
with diffusely turbid plasma; a patient with Type IV hyperlipoproteinemia also showing diffuse turbidity; and
a patient with Type V hyperlipoproteinemia with plasma exhibiting a creamy top layer over a turbid infranatant.
TABLE 52.7
Guidelines of Food Choices and Menu Plans for Patients with Severe
Hypercholesterolemia (FH)a
Very Low-Fat Diet-Meal Plan Goal 10-15% Fat Kcals
Total Fat Sat Fat Chol
Food Kcal (g) (g) (mg)
Breakfast
Orange juice, fresh, 6 fl. oz 84 0 0 0

Banana slices, 1/2 med 52 0.5 0 0
Shredded wheat, spoon size, 1 c 170 0.5 0 0
Milk, fat-free, 8 fl. oz 86 0.4 0.3 4
Breakfast subtotal 392 1.4 0.3 4
Lunch
Turkey sandwich:
Turkey breast, fat-free luncheon meat, 2 oz 52 0.4 0.2 23
Mayonnaise, light, 1 Tb 50 5 1 0
Whole wheat bread, 2 slices 130 2 0.4 0
Sliced tomato, 1/2 med 13 0.2 0 0
Apple, 1 med 81 0.5 0.1 0
Lunch subtotal 326 8.1 0.7 23
Dinner
Pork tenderloin, marinated, 4 oz 140 4 1.5 65

Baked potato, w/skin, 8 oz 220 0.2 0.1 0
Fat-free sour cream, 2 Tb 35 0 0 5
Margarine, Promise Ultra fat free, 1 Tb 5 0 0 0
Broccoli, steamed, 1 c 44 0.6 0 0
Angel food cake, 1/12 130 0 0 0
Strawberries, fresh, 1/2 c 23 0.6 0 0
Whipped topping, fat-free, 2 Tb 15 0 0 0
Dinner subtotal 612 5.4 1.6 70
Snacks
Non-fat vanilla yogurt, 8 fl oz 200 0 0 5

Honeydew melon, cubed pieces, 1c 60 0.2 0 0
Snacks subtotal 298 0.7 0 5
Daily Total 1628 15.6 2.6 102
8.6% 1.4%
19% Protein
72% Carbohydrate
a Prepared by Sandra Leonard, M.S., R.D.
See Table 52.7 for food choices and menu plans for patients with Type II hyperlipidemia
or FH.19,20 Compliance with and response to these changes may lower total and LDL
cholesterol by 10 to 20%.
Diets to Lower Serum TAG3,4

TAG in VLDL are decreased when kcalories are restricted, especially the intake from
refined carbohydrates and alcohol. N-3 fatty acids in fish and fish oils lower TAG.21
Chylomicron TAG are lowered by limiting fat intake severely to 50 g or less daily, or to
less than 20% of kcalories. Patients with Type V who become pregnant may require
TABLE 52.8
Guidelines of Food Choices and Menu Plans for Patients with Severe
Hypertriglyceridemia (Type V)a
Goals: <30% Fat
<10% Sat Fat
low refined sugar
Triglyceride-Lowering Meal Plan low cholesterol
Total Fat Sat Fat Sugar Cholesterol
Food Kcal (g) (g) (g) (mg)
Breakfast
Cheerios, 1 1/2 c 165 3 0 1.5 0

Milk, 1%, 8 fl. oz 102 2.6 1.6 *N/A 10
Blackberries, fresh, 1/2 c 37 0.3 0 *N/A 0
Orange juice, 1/2 c 56 0.2 0 8 0
Breakfast subtotal 360 6.1 1.6 9.5 10
Lunch
Ham and cheese sandwich

Lean ham, 2 oz 69 2.2 0.8 1.8 29
Cheese, cheddar, lowfat, 1 oz 49 2 1.2 0 6
Mustard, 1 Tb 0 0 0 0 0
Whole wheat bread, 2 sl 130 2 0.4 4 0
Peach, fresh, 1 med 37 0.1 0 *N/A 0
Tea, w/sugar substitute 0 0 0 0 0
Lunch subtotal 285 6.3 2.4 5.8 35
Dinner
Pink salmon, broiled, 6 oz 254 7.6 1.2 0 114

Salad:
Romaine, 1 c 8 0.2 0 1.2 0
Tomato, 1/2 med 13 0.2 0 1.7 0
Ranch dressing, light, 2 Tb 100 8.0 1.0 1.0 5
Pasta, cooked, 1/2 c 100 0.5 0 0 0
Marinara sauce, 1/4 c 55 2.5 0.8 4.0 0
Asparagus, 6 spears 22 0.3 0.1 1.4 0
Lemon juice 0 0 0 0 0
Cherries, sweet, fresh, 10 49 0.7 0.1 *N/A 0
Dinner subtotal 601 20 3.2 9.3 119
Snacks
Pear, raw, 1 med 98 0.7 0 *N/A 0

Triscuits, reduced fat, 8 wafers 130 3 0.5 0 0
Snacks subtotal 228 3.7 0.5 0 0
Daily Total 1474 36.1 7.7 24.6 164
22% 4.7%
19% Protein
56% Carbohydrate
* N/A = Not Available
a Provided by Sandra Leonard, M.S., R.D.
placement on diets with the fat content lowered to 20 g/day. Alcohol should be eliminated
from the diet, which also controls kcalories and increases exercise to optimize weight.
Table 52.8 indicates some food choices and menu plans for TAG lowering in patients with
more severe forms of hypertriglyceridemia (Type V). 20 Patients may respond rapidly to
withdrawal of dietary fat, with TAG levels falling by 50%/day.
Diet and Lp(a)22

The only effects of diet on levels of Lp(a) are the decrease observed with trans-fatty acids.
Niacin is the only intervention that lowers Lp(a). Therefore, the advice to individuals with
elevated Lp(a) is to aggressively treat any known risk factors for CHD, especially elevated
levels of LDL cholesterol.
Drug Management of Hyperlipidemias4,23-26

Patients with severe hypercholesterolemia (FH) are unlikely to reach desirable levels in
terms of CHD prevention with diet alone. Therefore the trial of diet should be shortened
and medication added. The diet trial is worthwhile in order to ascertain whether the subject
is diet responsive. Patients with CHD and hypercholesterolemia who are at higher risk
also may be placed on medication after a shortened diet trial period. Drug treatment should
be monitored for efficacy and safety, and medication needs to be taken throughout life.
Drugs to Lower Cholesterol23,24

Drugs that primarily lower total and LDL cholesterol include: the bile acid-binding resins
cholestyramine and colestipol, niacin and the statins (lovastatin, pravastatin, simvastatin,
atorvastatin, fluvastatin, cerivastatin). Relative efficacy of these classes of drugs is depicted
in Figure 52.9. Niacin and statins also increase HDL cholesterol. Side effects with resins
(constipation) and niacin (flushing, hepatotoxicity) are more common and serious than
those encountered with statins (hepatotoxicity, myositis). Drugs may need to be used in
combination in the management of severe hypercholesterolemia. Timing of medication
and efficacy in combination with food vary among these drugs, so that the patient must
be advised appropriately by health caregiver or pharmacist.
Resin Statins Niacin Fibrates

+30
+20
+10
-10
% Change
-20
-30
-40
-50
FIGURE 52.9
The efficacy of various lipid-lowering drugs in treating patients with hypercholesterolemia. Data represent the
percent change in lipoprotein lipid levels from levels obtained from patients ingesting a baseline lipid-lowering diet.
Plasmapheresis has been used successfully for treating severe forms of FH that are
poorly controlled with diet and multiple medications. Liver transplant may improve
patients with homozygous FH.
Drugs Affecting TAG Levels25,26

Fibric acid derivatives (clofibrate, gemfibrozil, fenofibrate) and niacin are potent TAG-
lowering medications that also increase HDL cholesterol. These medications should be
added to the diet early in patients with Type V with severe elevations of TAG in order to
prevent attacks of acute pancreatitis. At times the LDL levels will increase with fibric acid
derivatives as VLDL and chylomicrons decrease, so that a statin may need to be combined
with the initial agent. Side effects of fibric acid derivatives include lithogenic bile and
gallstones, gastrointestinal distress, and myositis. Oral contraceptives, estrogens, or cor-
ticosteroids may raise triglycerides and worsen hypertriglyceridemia. TAG levels should
be monitored carefully in patients with Type V using these drugs.
Additional relevant information may be found in Section 26, that addresses the labora-
tory assessment of lipids and lipoproteins and Section 51, that discusses the role of
nutrition in preventing and modifying cardiovascular risk factors.
References
1. Semenkovich CF. In Modern Nutrition in Health and Disease, 9th ed, Shils ME, Olson JA, Shike
M, Ross AC, Eds, Williams & Wilkins, Baltimore, 1999, ch 74.
2. Havel RJ, Kane JP. In: The Metabolic and Molecular Bases of Inherited Disease, 7th ed, Scriver CL,
Beaudet AL, Sly WS, Valle D, Eds, McGraw Hill, NY, 1995, ch 56.
3. Feldman EB. In: Modern Nutrition in Health and Disease, 8th ed, Shils ME, Olson JA, Shike M,
Eds, Lea & Febiger, Philadelphia, 1993, ch 72.
4. Grundy SM. In: Modern Nutrition in Health and Disease, 9th ed, (Shils ME, Olson JA, Shike M,
Ross AC, Eds, Williams & Wilkins, Baltimore, 1999, ch 75.
5. Humphries SE, Peacock R, Gudnason V. In Lipoproteins in Health and Disease, Betteridge DJ,
Illingworth DR, Shepherd J, Eds, Oxford University Press, NY, 1999.
6. Brunzell JD. In The Metabolic and Molecular Bases of Inherited Disease, 7th ed, Scriver CL, Beaudet
AL, Sly WS, Valle D, Eds, McGraw Hill, NY, 1995, ch 59.
7. Santmarina-Fojo S. Curr Opin Lipidology 3: 186; 1992.
8. Brown MS, Goldstein JL. Science 232: 34; 1986.
9. Goldstein JL, Hobbs HH, Brown MS. In The Metabolic and Molecular Bases of Inherited Disease,
7th ed, Scriver CL, Beaudet AL, Sly WS, Valle D, Eds, McGraw Hill, NY, 1995, ch 62.
10. Sohar E, Bossak, ET, Wang CI, Adlersberg D. Science 123: 461; 1957.
11. Aouizerat BE, Allayee H, Cantor RM, et al. Arterioscler Thromb Vasc Biol 19: 2730; 19XX.
12. Kwiterovich PO, Jr. Curr Opin Lipidology 4: 133; 1993.
13. Campos H, Dreon DM, Krauss RM. J Lipid Res 34: 397; 1993.
14. Mahley RW, Rall SC, Jr. In The Metabolic and Molecular Bases of Inherited Disease, 7th ed, Scriver
CL, Beaudet AL, Sly WS, Valle D, Eds, McGraw Hill, NY, 1995, ch 61.
16. Brewer HB, Jr. Am J Cardiol 83: 3F; 1999.
17. Austin MA, Hokanson HE, Edwards KL, Am J Cardiol 82: 7B; 19XX.
18. Grundy SM. Circulation 95: 1; 1997.
19. Greene JM, Feldman EB. J Am Coll Nutr 10: 443; 1991.
20. Bloch AS, Shils ME. In Modern Nutrition in Health and Disease, 9th ed, Shils ME, Olson JA,
Shike M, Ross AC, Eds, Williams & Wilkins, Baltimore, 1999, pp A167, 170.
21. Harris WS. Curr Opin Lipidology 7: 3; 1996.
22. Nestel P, Noakes M, Belling B, et al. J Lipid Res 33: 1029; 1992.
23. Lipid Research Clinics Program. JAMA 251: 351; 1984.
24. Jones P, Kalonek S, Laurora I, Hunninghake D. for the CURVES Investigators, Am J Cardiol
81: 582; 1998.
25. Knopp RH, Waldaen CE, Rezlaff BM, et al. JAMA 278: 1509; 1997.
26. Goldberg AC, Schonfeld G, Feldman EB, et al. Clin Ther 11: 69; 1989.
53
Nutrition in Diabetes Mellitus
Maria F. Lopes-Virella, Carolyn H. Jenkins, and Marina Mironova
Introduction
Diabetes mellitus is a common metabolic disorder.1,2 The hallmark of diabetes is fasting
and/or post-prandial hyperglycemia. Hyperglycemia results from insulin deficiency or
interference with its action (insulin resistance) or both. Uncontrolled diabetes leads to
widespread metabolic derangement. Sixteen million people in the United States have
diabetes mellitus. The prevalence of diabetes is increasing at an alarming rate in all age
groups, from children to the elderly. The disorder is progressively more common with
advancing age. Fifty percent or more of the population after 80 to 90 years of age has
glucose intolerance or diabetes. It is the sixth leading cause of death due to disease in the
U.S. and decreases the average life expectancy up to 15 years when compared to the
population without diabetes. Diabetes has an enormous social impact, mostly due to its
chronic microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular
complications. Diabetic retinopathy is the leading cause of blindness in the U.S. In people
with diabetes, age 20 to 74 years, there are 12,000 to 24,000 new cases of blindness each
year. Diabetic nephropathy is responsible for a large number of the patients on renal
dialysis and undergoing renal transplantation. In 1996 more than 130,000 people with
diabetes underwent either dialysis or kidney transplantation. Diabetic neuropathy is
present in 60 to 70% of all patients with diabetes. Besides increasing the risk for sudden
death and silent myocardial infarction, diabetic neuropathy leads to impotence, which is
experienced by 50% of men with diabetes. Diabetic neuropathy together with peripheral
vascular disease is responsible for more than 200,000 cases of foot ulcers and 80,000 limb
amputations each year. Finally, diabetes is also responsible for macrovascular complica-
tions including peripheral vascular disease, stroke, and cardiovascular disease. Cardio-
vascular disease is the leading cause of death in diabetes (80% of all patients with diabetes
die of cardiovascular disease). Seventy five percent of the cardiovascular mortality in
diabetes is from coronary heart disease and 25% is from cerebral or peripheral vascular
disease. Coronary heart disease, peripheral vascular disease, and stroke account for nearly
one million hospital admissions each year among patients with diabetes. In women,
diabetes carries yet another burden since it may lead to problems during pregnancy —
mainly congenital malformations in babies born to diabetic mothers. The rate of major
0-8493-2705-9/02/$0.00+$1.50
congenital malformations is 10% compared to 2% in non-diabetic women, and fetal mor-

tality occurs in 3 to 5% of pregnancies.
Classification and Diagnostic Criteria of the Several Subtypes of Diabetes

and Intermediate Syndromes
Classification of Diabetes Mellitus
Type 1 Diabetes
Type 1 diabetes is characterized by pancreatic β-cell destruction, usually leading to abso-
lute insulin deficiency.3,4 Its etiology is likely due to a combination of genetic and envi-
ronment factors. Most type 1 diabetes is an organ-specific autoimmune disease
characterized by T-cell mediated autoimmune destruction of the pancreatic β-cells. In a
few cases there is no evidence of an autoimmune process, and these cases are classified
as idiopathic.
Type 2 Diabetes
Type 2 diabetes is characterized by insulin resistance and an insulin secretory defect.3,4 It
is the most prevalent type of diabetes, and comprises 90% of the population with diabetes.
As with type 1 diabetes, type 2 has both a genetic and an environment component. Type
2 diabetes may range from cases with predominantly insulin resistance and relative insulin
deficiency to cases with a predominantly secretory defect and some degree of insulin
resistance.
Other Specific Types of Diabetes

Genetic defects in β-cell function or in insulin action as well as several diseases of the
exocrine pancreas, endocrinopathies, infections, drugs or chemicals, uncommon forms of
immune-mediated diabetes, and other genetic syndromes that may lead to hyperglycemia
are included under the definition of other specific types of diabetes. A comprehensive list
is included in Table 53.1.
Gestational Diabetes (GDM)

Gestational diabetes is defined by any degree of glucose intolerance that is initially rec-
ognized during pregnancy. The type of treatment required to manage glucose intolerance
in pregnancy and whether or not the glucose intolerance continues after pregnancy does
not affect the diagnosis. Six or more weeks after pregnancy it is necessary to reclassify the
patient and determine whether diabetes, impaired glucose tolerance, impaired fasting
glucose, or normoglycemia is present. About 4% of all pregnancies are complicated by
gestational diabetes, and the diagnosis is commonly made during the third trimester.
At present it is not recommended that all women be screened for gestational diabetes.
Screening should, however, be performed in women if they a) are more than 25 years of
age, b) are overweight, c) have family history of diabetes, or d) are Hispanic, Asian, Afro-
American, or native American. The first test to be performed is a screening test using a
50 g load of glucose. If the screening test is positive, a 100 g diagnostic loading test needs
to be performed.
Nutrition in Diabetes Mellitus 1079
TABLE 53.1
Etiologic Classification of Diabetes Mellitus
I. Type I diabetes* (β-cell destruction, usually leading to absolute insulin deficiency)
A. Immune mediated
B. Idiopathic
II. Type II diabetes* (may range from predominantly insulin resistance with relative insulin deficiency to a
predominantly secretory defect)
III. Other specific types
A. Genetic defects of β-cell function
1. Chromosome 12, HNF-1a (MODY3)
2. Chromosome 7, glucokinase (MODY2)
3. Chromosome 20, HNF-4a (MODY1)
4. Mitochondrial DNA
5. Others
B. Genetic defects in insulin action
1. Type A insulin resistance
2. Leprechaunism
3. Rabson — Mendenhall syndrome
4. Lipoatrophic diabetes
5. Others
C. Diseases of the exocrine pancreas
1. Pancreatitis
2. Trauma/pancreatectomy
3. Neoplasia
4. Cystic fibrosis
5. Hemochromatosis
6. Fibrocalculous pancreatopathy
7. Others
D. Endocrinopathies
1. Acromegaly
2. Cushing’s syndrome
3. Glucagonoma
4. Pheochromocytoma
5. Hyperthyroidism
6. Somatostatinoma
7. Aldosteronoma
8. Others
E. Drug- or chemical-induced
1. Vacor
2. Pentamidine
3. Nicotinic acid
4. Glucocorticoids
5. Thyroid hormone
6. Diazoxide
7. β-adrenergic agonists
8. Thiazides
9. Dilantin
10. α-interferon
11. Others
F. Infections
1. Congenital rubella
2. Cytomegalovirus
3. Others
G. Uncommon forms of immune-mediated diabetes
1. “Stiff-man” syndrome
2. Anti-insulin receptor antibodies
3. Others
H. Other genetic syndromes sometimes associated with diabetes
1. Down’s syndrome

Etiologic Classification of Diabetes Mellitus
2. Klinefelter’s syndrome
3. Turner’s syndrome
4. Wolfram’s syndrome
5. Friedreich’s ataxia
6. Huntington’s chorea
7. Laurence-Moon-Biedl syndrome
8. Myotonic dystrophy
9. Porphyria
10. Prader-Willi syndrome
11. Others
IV. Gestational diabetes mellitus (GDM)
* Patients with any form of diabetes may require insulin treatment at some stage of their disease. Such use of
insulin does not, of itself, classify the patient.
Reprinted with authorization from American Diabetes Association (Diabetes Care 23(1): 6S; 2000).
Impaired Glucose Tolerance and Impaired Fasting Glucose

These two syndromes are usually associated with an intermediate metabolic stage between
normal glucose metabolism and diabetes. Impaired glucose tolerance is associated with
levels of plasma glucose ≥140 mg/dl but <200 mg/dl after an oral load of 75 g of glucose.
Patients with glucose intolerance are often hyperglycemic if challenged with an oral
glucose load, but in normal conditions they may have normal or near-normal plasma
glucose levels and hemoglobin A1c. Impaired fasting glucose corresponds to fasting levels
of plasma glucose ≥110 mg/dl but <126 mg/dl. Neither of these two syndromes is a
disease per se, but they are considered risk factors for the development of macrovascular
disease and diabetes. They are considered as risk factors for macrovascular disease because
both syndromes can be associated with the insulin resistance syndrome, a metabolic
syndrome previously named by Reaven as syndrome X.5 This syndrome includes visceral
obesity, insulin resistance, compensatory hyperinsulinemia, hypertriglyceridemia, low
HDL-cholesterol, hypertension, and the presence of dense LDL. The two syndromes can
also be observed in the disease processes listed in Table 53.1. Interestingly however, a
recent study by Tominaga et al.6 examining the cumulative survival rates from cardiovas-
cular disease in a Japanese population of 2534 individuals with normal glucose tolerance,
impaired glucose tolerance, impaired fasting glucose, or diabetes showed no significant
difference between the survival rates from cardiovascular disease in subjects with normal
glucose tolerance and subjects with impaired fasting glucose, but a significant decrease
in survival in subjects with impaired glucose tolerance and diabetes. They therefore
concluded that impaired glucose tolerance was a risk factor for cardiovascular disease,
but impaired fasting glucose was not.
Diagnostic Criteria
The diagnostic criteria for diabetes, for type 1, type 2, and other specific types of diabetes,
have been modified recently. In the past, the criteria used was that recommended by the
National Diabetes Data Group3 or World Health Organization (WHO);1 the revised criteria
are shown in Table 53.2. For epidemiological studies determining prevalence and/or
incidence of diabetes, the first criterion (fasting plasma glucose >126 mg/dl) can be used,
but it will lead to slightly lower estimates of prevalence/incidence than the combined use
of the fasting plasma glucose and oral glucose tolerance test. That is clearly demonstrated
by the data obtained in NHANES III2 as summarized in Table 53.3. WHO criteria were
TABLE 53.2
Criteria for the Diagnosis of Diabetes Mellitus*
1. Symptoms of diabetes plus casual plasma glucose concentration ≥200 mg/dl (11.1 mmol/l). Casual is defined
as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria,
polydipsia, and unexpected weight loss.
or
2. FPG ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h.
or
3. 2-h PG ≥200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by WHO (2),
using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water.
* In the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria should be
confirmed by repeat testing on a different day. The third measure (OGTT) is not recommended for routine
clinical use.
TABLE 53.3
Estimated Prevalence of Diabetes in the U.S. in Individuals 40 to 74 Years of Age using
Data from the NHANES III
Prevalence (%) of Diabetes by
Glucose Criteria without a Medical Total Diabetes
Diabetes Diagnostic Criteria History of Diabetes* Prevalence (%)#
Medical history of diabetes — 7.92
WHO (2) criteria for diabetes:
FPG ≥140 mg/dl (7.8 mmol/l) or 6.34 14.26
2-h PG ≥200 mg/dl (11.1 mmol/l)
FPG ≥126 mg/dl (7.0 mmol/l) 4.35 12.27
* Diabetes prevalence (by glucose criteria) in those without a medical history of diabetes × (100%-
prevalence of diabetes by medical history).
# First column of data plus 7.92.
Data are from K. Flegal, National Center for Health Statistics, personal communication. Reprinted
with authorization from American Diabetes Association (Diabetes Care 23(1): 11S; 2000).
based on the fact that the prevalence of retinopathy and nephropathy would rise markedly
when the level of glucose 2 h after a standardized glucose load was >200 mg/dl. The
revised criteria are based on results of several studies showing that fasting plasma level
>126 mg/dl, like a 2-h post glucose load of >200 mg/dl, is associated with a marked rise
in the prevalence of vascular complications.4 In other words, levels of glucose ≥126 mg/
dl reflect a serious metabolic disorder associated with the development of serious chronic
diabetic complications.
Impaired fasting glucose is defined by glucose levels ≥110 mg/dl and <126 mg/dl after
an eight-hour fast. Impaired glucose tolerance is defined by a level of glucose ≥140 mg/
dl but <200 mg/dl two hours after a 75 g oral glucose load. The impaired glucose tolerance
criteria will identify more people with impaired glucose homeostasis than the criteria of
impaired fasting glucose.
Criteria for Screening for Diabetes

Screening for type 1 diabetes is not recommended. Type 1 diabetes is commonly an
autoimmune process characterized by a variety of auto-antibodies against intracellular or
TABLE 53.4
Major Risk Factors for Diabetes Mellitus
Family history of diabetes (i.e., parents or siblings with diabetes)
Obesity (i.e., ≥20% over desired body weight or BMI ≥27 kg/m2)
Race/ethnicity (i.e., African-Americans, Hispanic-Americans, Native Americans, Asian-Americans, Pacific
Islanders)
Age ≥45 years
Previously identified IFG or IGT
Hypertension (≥140/90 mm Hg)
HDL cholesterol level ≥35 mg/dl (0.90 mmol/l) and/or a triglyceride level ≥250 mg/dl (2.82/l)
History of GDM or delivery of babies over 9 lb
surface protein epitopes in the β-cell. The markers that may identify patients at risk before
development of the disease are many. However, the levels of the markers that would
permit the diagnosis of high-risk patients are not well established. Furthermore, the
methodology is not easily accessible, and there is no consensus about what to do if high
levels of auto-antibodies are observed. Nowadays, there is no effective and safe treatment
to prevent the development of type 1 diabetes. A number of ongoing clinical trials testing
various ways to prevent the development of type 1 diabetes are being conducted, and it
is possible that in the near future, screening for patients at high risk for developing type
1 diabetes will be justifiable. At present the cost effectiveness and clinical relevance of
such testing is questionable.
Screening for type 2 diabetes is, however, highly recommended. Undiagnosed type 2
diabetes is very common in the U.S. Approximately 50% of patients with type 2 diabetes
are undiagnosed.7 Some epidemiological studies have shown that retinopathy will start
developing seven years prior to making the diagnosis of diabetes.8 Even more worrisome
is the fact that patients with undiagnosed diabetes are at significantly higher risk of
developing premature macrovascular disease.9 The risk of developing type 2 diabetes
increases with age, obesity, and lack of physical activity. Furthermore, diabetes is more
common in certain racial/ethnic groups (Hispanic, Asian, African-Americans, and native
Americans), in women with gestational diabetes, and in individuals with a family history
of diabetes, hypertension, or dyslipidemia. The major risk factors for developing diabetes
are listed in Table 53.4.
The American Diabetes Association (ADA) recommends screening individuals who have
one or more of the risk factors shown in Table 53.4 at three-year intervals. Fasting plasma
glucose measurement or oral glucose tolerance test are adequate to perform screening for
diabetes. Fasting, as mentioned before, represents a period of at least eight hours without
food or beverage other than water. When an oral glucose tolerance test is performed, a
load of 75 g of anhydrous glucose is considered the standard load for adult testing.
Interpretation of the results is crucial, and should be made according to the criteria shown
in Table 53.5. It is important to remember that certain drugs including furosemide, gluco-
corticosteroids, thiazides, estrogen-containing preparations, β-blockers, and nicotinic acid
may induce hyperglycemia. In community screening tests it is sometimes impossible to
use a fasting plasma glucose assay; therefore, a fasting capillary whole blood glucose is
performed due to its convenience and simplicity of measurement. The levels are not,
however, as accurate as those measured in plasma, and they are lower. If the measurement
is made in capillary whole blood, individuals with blood glucose ≥110 mg/dl should be
referred to a physician for further evaluation and testing. Criteria for diagnosis of gesta-
tional diabetes mellitus (GDM) is summarized in Table 53.6.
TABLE 53.5
Criteria for the Diagnosis of Diabetes Mellitus using Glucose Tolerance Results
Normoglycemia Impaired Glucose Metabolism DM*
FPG < 110 mg/dl FPG ≥ 110 mg/dl and < 126 mg/dl FPG ≥ 126 mg/dl
2-h PG† < 140 mg/dl 2-h PG† ≥ 140 mg/dl and < 200 mg/dl 2-h PG† ≥ 200 mg/dl
Symptoms of DM and random plasma
glucose concentration ≥ 200 mg/dl
* A diagnosis of diabetes must be confirmed on a subsequent day by measurement of FPG, 2-h PG or random
plasma glucose (if symptoms are present). The FPG test is greatly preferred because of ease of adminis-
tration, acceptability to patients, and lower cost. Fasting is defined as no caloric intake for at least 8 h.
† This test requires the use of a glucose load containing 75 g anhydrous glucose dissolved in water.
* DM, diabetes mellitus; 2-h PG, 2-h postload glucose.
TABLE 53.6
Screening and Diagnosis Scheme for Gestational Diabetes Mellitus (GDM)*
Plasma Glucose 75-g Oral Glucose Load 100-g Oral Glucose Load
Fasting 95 mg/dl 95 mg/dl
1-h 180 mg/dl 180 mg/dl
2-h 155 mg/dl 155 mg/dl
3-h not done 140 mg/dl
* The diagnosis of GDM requires any two or more plasma glucose values obtained
during the test to meet or exceed the values shown above.
Reprinted with authorization from American Diabetes Association (Diabetes Care 23(1):
78S; 2000).
Diabetic Complications: Microvascular

Retinopathy
Diabetic retinopathy is a specific microvascular complication present in both type 1 and
type 2 diabetes, strongly correlated with the duration of diabetes. After 20 years of diabetes,
nearly all patients with type 1 diabetes and more than 60% of the patients with type 2
diabetes will have some degree of retinopathy.10
Retinopathy can be defined as damage to the retina, a cell layer in the posterior part of
the eye that contains the photoreceptors necessary for vision. It can be classified as mild,
nonproliferative (also called background retinopathy), or moderate to severe non-prolif-
erative retinopathy, characterized by hard exudates and retinal blot hemorrhages. This
type of retinopathy advances to a preproliferative phase when retinal ischemia becomes
more severe. Proliferative retinopathy is the most advanced stage of retinopathy, and is
characterized by the growth of new blood vessels on the retina and posterior surface of
the vitreous. Proliferative retinopathy usually leads to loss of vision due to retinal detach-
ment, and is the leading cause of blindness in persons 30 to 65 years of age. Vision loss
may also occur in patients without proliferative retinopathy when vascular leakage (mac-
ular edema) and/or occlusion occurs in the area of the macula. Maculopathy is more
common in type 2 than type 1 diabetes and is an important cause for decreased visual
acuity in this group of patients.
TABLE 53.7
Screening and Followup of Patients with Diabetes for Retinopathy
Recommended Ophthalmologic Recommended Minimum
Examination* Followup
Type 1 diabetes > 10 years of age Within 3-5 years after onset of Yearly
disease
Type 2 diabetes At the time of diagnosis of diabetes Yearly or more often if retinopathy
is progressing
Diabetic patients during pregnancy Prior to conception if programmed As often as necessary, according to
and during the 1st trimester physician
Patients with macular edema, Immediately after diagnosis of the As often as necessary, according to
severe proliferative retinopathy condition physician
* The ophthalmologic exam recommended is a dilated and comprehensive exam by an ophthalmologist or
optometrist.
Screening
Screening for the presence of retinopathy depends on the rates of progression of diabetic
retinopathy and the risk factors that may alter these rates. Most of the available data is
based on studies on Caucasian populations, and it is not certain whether these data can
be applied to the ethnic groups with the highest incidence of diabetes and complications.
The guidelines for screening and followup of patients with diabetic retinopathy are sum-
marized in Table 53.7.
Influence of Glycemic Control and Treatment of Hypertension and Dyslipidemia

Data from the Diabetes Control and Complications Trial Research Group (DCCT) clearly
show a definitive and direct relationship between glycemic control and diabetic microvas-
cular complications, including retinopathy.11 The DCCT shows that intensive insulin ther-
apy for type 1 diabetes reduced or prevented the progression of diabetic retinopathy by
27% when compared with conventional therapy. Similar results were observed in type 2
diabetes as shown by the U.K. Prospective Diabetes Study Group (UKPDS).12,13 The earlier
that intensive control is started in the course of diabetes, the more effective it is in
preventing the development of retinopathy. Besides poor glycemic control, proteinuria is
also associated with retinopathy. Hypertension is an established risk factor for proteinuria.
Thus, it is important to tightly control hypertension. Finally, maculopathy consists of
edema and/or lipid exudates; since the lipid exudates observed in cases of maculopathy
originate from circulating blood lipids, aggressive treatment of lipid abnormalities is also
important in the prevention of retinopathy/maculopathy.
The main reason that screening for diabetic retinopathy is essential is the well known
efficacy of laser photocoagulation therapy in patients with proliferative retinopathy and
macular edema. The surgery, as well demonstrated in the Early Treatment Diabetic Ret-
inopathy Study and the Diabetic Retinopathy Study, is extremely efficient in preventing
loss of vision, but does not have much impact in reversing visual acuity if already dimin-
ished. Since proliferative retinopathy and macular edema are quite often asymptomatic,
screening is crucial.
Neuropathy
Symptomatic and potentially disabling neuropathy affects nearly 50% of diabetic patients.
Neuropathy can be symmetrical or focal, and often involves the autonomic nervous
TABLE 53.8
Classification of Diabetic Neuropathy
Diabetic Polyneuropathies Diabetic Mononeuropathies
Distal symmetrical Peripheral
Chronic sensorimotor Cranial
Autonomic Radiculopathy
Proximal motor Isolated nerve lesions
Acute sensory
TABLE 53.9
Symptoms and Signs of Diabetic Polyneuropathy
Symptoms Signs
Polyneuropathy Pain and paresthesias most Diminished sensation to touch, temperature,
common at night pain, and vibration; loss of reflexes
Atrophy of intrinsic hand muscles; sensory
impairment
system. The prevalence of symmetrical neuropathy is similar in type 1 and type 2 diabetes,
but the focal forms of neuropathy are more common in the older type 2 diabetic patient.
The classification of neuropathy is made according to the areas affected due to the
relatively poor understanding of the pathogenic mechanisms of this diabetic complica-
tion. Table 53.8 includes the most commonly accepted classification of diabetic neuro-
pathic syndromes.
The cause for mononeuropathies is unknown, but they usually have a sudden onset,
which suggests a vascular component in their pathogenesis. They usually tend to resolve
with time, and although they occur in diabetes they are not the typical neuropathic lesions
of diabetes. Diabetic polyneuropathies are the main problem for diabetic patients, and
they will be discussed in some detail. To assess diabetic neuropathy, history of clinical
symptoms and physical exam, electrodiagnostic studies, quantitative sensory testing, and
autonomic function testing should be performed. Table 53.9 summarizes the clinical signs
and symptoms of diabetic polyneuropathy, and Table 53.10 summarizes the functional
changes associated with autonomic failure. In Table 53.11, adequate diagnostic testing to
assess diabetic neuropathy is summarized.
TABLE 53.10
Functional Changes Associated with Autonomic Failure
Systems
Involved Manifestations
Cardiovascular Resting tachycardia, impaired exercise-induced cardiovascular responses, cardiac
denervation, orthostatic hypotension, heat intolerance, impaired vasodilatation, impaired
venoarteriolar reflex (dependent edema)
Eye Decreased diameter of dark-adapted pupil (dark-adapted miosis)
Gastrointestinal Esophageal enteropathy, gallbladder atony, impaired colonic motility (diarrhea, constipation),
anorectal sphincter dysfunction (incontinence)
Genitourinary Neurogenic vesical dysfunction (decreased bladder sensitivity/incontinence/retention),
sexual dysfunction, (male: penile erectile failure and retrograde ejaculation; female: defective
lubrication)
Sudomotor Anhidrosis/hyperhidrosis (heat intolerance), gustatory sweating
Endocrine Hypoglycemia-associated autonomic failure
TABLE 53.11
Electrodiagnostic Studies, Sensory Testing, and Autonomic Function Testing for the Diagnosis of
Diabetic Neuropathy
Sensory Testing Electrodiagnosis Autonomic Function Testing
Vibration/touch thresholds Motor and sensory nerve conduction R-R variations, orthostasis, Valsalva
Thermal thresholds studies Resting heart rate
Pain thresholds Needle electromyography of extremity QTc, DAPS, NPT, CMG+BST
and paraspinal muscles REPs, QSART, TST
Solid phase gastric motility
Clamped hypoglycemia
Clamped insulin infusion test
Abbreviations: QTc — corrected QT interval on EKG; DAPS — dark-adapted pupil size; NPT — nocturnal
penile tumescence, CMG+BST — cystometrogram+Bethanechol supersensivity test; REPs — reflex-evoked
potentials; QSART — quantitative sudomotor axon reflex test; TST — thermoregulated sweat test.
TABLE 53.12
Definition of Abnormalities in Albumin Excretion
24-h Collection Timed Collection Spot Collection
Normal <30 mg/24 h <20µg/min <30 mg/g creatinine
Microalbuminuria* (incipient nephropathy) 30-300 mg/24 h 20-200 µg/min 30-300 mg/g creatinine
Nephropathy* >300 mg/24 h >200 µg/min >300 mg/g creatinine
* Two out of three urine specimens collected within a 3 to 6 month period should be abnormal before diagnosing
a patient as having incipient nephropathy or nephropathy.
Influence of Glycemic Control

Data from the DCCT and UKPDS clearly show a definitive and direct relationship between
glycemic control and diabetic microvascular complications, including neuropathy.11-13 The
DCCT data showed that intensive insulin therapy when compared with conventional
therapy reduced or prevented the progression of diabetic neuropathy in patients with type
1 diabetes. The UKPDS showed the same results in patients with type 2 diabetes.
Nephropathy
Diabetic nephropathy is characterized by persistent albumin excretion exceeding 300 mg/
24 h, a progressive decline in the glomerular filtration rate, and increased blood pressure.14
The earliest clinical evidence of nephropathy is the increased excretion of albumin in the
urine. This phase of incipient nephropathy is designated as microalbuminuria. The levels
of albumin excretion in the microalbuminuria stage of nephropathy range from 30 to 300
mg/24 h. Table 53.12 summarizes the cutoff levels for diagnostic purposes as well as the
correspondent values in spot urine collections. Measurement of creatinine and albumin
excretion simultaneously in the same urine specimen is necessary when a spot urine is
collected, and it is also recommended in timed specimens to ensure that a proper urine
collection was obtained. Interpretation of microalbuminuria needs to take into consideration
factors such as hyperglycemia, level of exercise preceding the urine collection, uncontrolled
hypertension, urinary tract infections, acute febrile illnesses, and heart failure, since all of
these conditions may lead to increased albuminuria. Diagnosis of nephropathy needs to be
based on data from three urine specimens collected within a three- to six-month period. At
least two of the specimens may be concordant to allow establishment of a valid diagnosis.
About 20 to 30% of patients with type 1 or type 2 diabetes develop nephropathy. A high
percentage of subjects with type 2 diabetes are found to have microalbuminuria shortly
after their initial diagnosis. Two possible reasons are that in many cases diabetes has been
present for many years and not diagnosed, and microalbuminuria in type 2 diabetes is
less specific of diabetic nephropathy, as shown by renal biopsy studies.
Approximately 80% of individuals with type 1 diabetes who develop sustained microal-
buminuria will progress to overt nephropathy over a period of 10 to 15 years. Once overt
nephropathy occurs and if there is no therapeutic intervention, 50% of these patients will
progress to end-stage renal disease in 10 years, and 75% in 20 years. The progression to
overt nephropathy in type 2 diabetes, without therapeutic intervention, is less than in type
1 diabetes (approximately in 20 to 40% of the cases), and only approximately 20% will
progress to end-stage renal disease. A marked racial/ethnic variability exists, however, as
far as progression to end-stage renal disease in type 2 diabetes. Native Americans, Mex-
ican-Americans and African-Americans have a much higher risk of developing end-stage
renal disease than the other populations with type 2 diabetes. In the U.S., diabetic neph-
ropathy is responsible for one third of all cases of end-stage renal disease, and that is a
terrible burden in the country’s economy. Regardless of the fact that subjects with type 1
diabetes are more prone to progress to end-stage renal disease, half of the patients with
diabetes on dialysis have type 2 diabetes due to the higher prevalence of type 2 diabetes
in the population.
Two major risk factors that can be easily intervened upon are involved in the progression
of nephropathy: hypertension and hyperglycemia. The standards of care for hypertension
and hyperglycemia in diabetes will be discussed later in this section.
Influence of Hypertension and Glycemic Control

In type 1 diabetes, hypertension is usually caused by the underlying diabetic nephropathy,
and typically is detected at the time microalbuminuria becomes apparent. In type 2
diabetes, hypertension is present at the time diabetes is diagnosed in one third of the
patients. The hypertension may be related to the underlying diabetic nephropathy, may
be secondary to other diseases, or may be a coexisting disease, “essential hypertension.”
Commonly, subjects with type 2 diabetes, before being diagnosed as having diabetes, have
been found to have an insulin resistance syndrome, which basically comprises a cluster
of problems including hypertension, obesity, dyslipidemia, and glucose intolerance. The
presence of both systolic and diastolic hypertension contributes to the accelerated devel-
opment of diabetic nephropathy, and therefore treating hypertension aggressively in
patients with diabetes is an essential step that cannot be overemphasized.
Hyperglycemia has been shown in recent trials to have a major impact in the develop-
ment of microvascular complications, including nephropathy. Intensive treatment of dia-
betes to obtain near-normal glucose and hemoglobin A1c levels has significantly reduced
the risk of development of microalbuminuria and overt nephropathy.11-13
Influence of Protein Restriction and Treatment of Lipid Disorders

It is well known that microalbuminuria is a marker for increased cardiovascular mortality
and morbidity in patients with either type 1 or type 2 diabetes. In reality, microalbuminuria
is considered as an indicator to screen patients for macrovascular complications (see
Macrovascular Complications). Interestingly, some preliminary evidence also shows that
lowering cholesterol leads to a reduction in the level of proteinuria. More work is needed
to adequately validate this observation. Protein restriction has been shown to be of great
benefit in animal studies to reduce progression of renal disease, including diabetic neph-
ropathy. However, studies in humans are less clear. Several small studies seem to indicate
that patients with overt nephropathy treated with a diet containing protein at 0.7 g/kg of
body weight had mild retardation in the fall of the glomerular filtration rate. A recent
study of patients with renal disease in which 3% had type 2 diabetes failed to show any
benefit of protein restriction. In reality, marked decrease of protein intake in patients with
end-stage renal disease on dialysis showed that the main predictive factor of mortality
was low albumin due to protein-energy malnutrition.
Diabetic Complications: Macrovascular Disease

General Considerations
Macrovascular disease, which includes coronary artery disease (CAD), cerebrovascular
disease, and peripheral vascular disease, is the leading cause of mortality in people with
diabetes. Individuals with diabetes have at least a two- to fourfold increased risk of
cardiovascular events and stroke, and an eightfold increased likelihood of peripheral
vascular disease compared with age-matched subjects without diabetes. The atheroscle-
rotic process in diabetic patients is indistinguishable from that affecting the nondiabetic
population, but begins earlier and is more severe. Most deaths in the diabetic population
are due to complications of CAD. Although diabetic patients have a higher prevalence of
traditional CAD risk factors (i.e., hypertension, dyslipidemia, obesity) compared to people
without diabetes, these risk factors account for less than half the excess mortality associ-
ated with diabetes. Thus, the diagnosis of diabetes is a major independent risk factor for
the development of CAD and adverse outcomes following a myocardial event. Other
abnormalities induced by diabetes such as increased levels of small, dense atherogenic
LDL, oxidized or glycated LDL, increased platelet aggregation, hyperviscosity, endothelial
cell dysfunction, decreased fibrinolysis, and increased clotting factors and fibrinogen are
likely responsible for accelerated atherosclerosis in diabetic patients.
Current Treatment and Prevention Strategies

Current treatment of macrovascular complications includes reduction of cardiovascular risk
factors (obesity, smoking, sedentary lifestyle), with special emphasis on the treatment of
hypertension and dyslipidemia. Diabetic patients with existing or incipient macrovascular
disease in general require multiple modifications of lifestyle and diet, as well as a polyp-
harmaceutical approach to address the optimization of lipid level, blood pressure, and other
disease risk factors. Glycemic control seems also to contribute to a reduction in macrovas-
cular events both in type 1 and type 2 diabetes, but its impact is much less marked than
impact of treatment of cardiovascular risk factors such as dyslipidemia and hypertension.
Treatment of Hypertension
Hypertension accelerates not only atherosclerosis, but also nephropathy and probably
retinopathy. Thus in diabetes, it is important to treat even minimal elevations of blood
pressure that in nondiabetic patients might be dismissed. The normal nocturnal fall in
blood pressure may be lost in diabetic patients, leading to a more sustained hypertension
throughout the day. Initially, nonpharmacologic measures such as weight loss, exercise
training, and sodium restriction should be implemented (see Section 48). If blood pressure
is not lower than 130/85 mmHg, drug therapy is indicated. Among the various therapeutic
options, ACE inhibitors offer special advantages, mainly when there is concomitant renal
disease. Calcium channel blockers and vasodilators have no adverse metabolic effects,
and therefore are good alternatives.
Treatment of Dyslipidemia
Dyslipidemia is common in subjects with diabetes. The more common lipid abnormalities
in diabetes are increased triglycerides and low HDL cholesterol levels. Small, cholesterol-
poor, dense LDL particles are also common in patients with hypertriglyceridemia and the
insulin resistance syndrome. Dense LDL is more readily oxidized and more atherogenic.
Aggressive treatment of dyslipoproteinemia is crucial to prevent the development and/or
progression of macrovascular complications in diabetes.15 Recommendations by the ADA
concerning goals for therapy of hyperlipidemia as well as guidelines for medical nutrition
therapy (MNT), physical activity, and drug treatment have been widely promulgated. Opti-
mal triglyceride levels in diabetes are below 150 mg/dl, as in nondiabetic patients. This level
was recommended by the National Cholesterol Education Program Adult Treatment Panel
III (NCEP0-ATP III) on the recently released guidelines15a and it is lower than the 200 mg/dl
previously recommended by both the NCEP-ATP II and the ADA. HDL-cholesterol levels
above 45 mg/dl are the target in diabetes. According to ADA guidelines and the NCEP-ATP
III guidelines, values below 40 µg/dl for men and above 50 mg/dl are used to define the
metabolic syndrome. Levels of HDL-cholesterol below 40 mg/dl instead of 35 mg/dl are
considered in the new NCEP guidelines a risk factor for CHD. The AFCAPS-Tex CAPS trial
was instrumental in this change since it showed clearly that CHD risk decreases with levels
of HDL-cholesterol above 40 mg/dl. Weight loss, increased physical activity, and good
glycemic control are important measures to lower triglycerides and increase HDL-cholesterol
levels. Increased LDL-cholesterol levels were not considered important in the treatment of
diabetic dyslipidemia until recently. However, in the past decade it became apparent that
lowering LDL-cholesterol levels in diabetes led to a significant reduction in the risk of a
major congestive heart disease (CHD) event. That was clearly shown in several clinical trials
including two major secondary prevention trials: Scandinavian Simvastatin Survival Study16
and CARE trial.17 The results of these trials were instrumental in the establishment of the
guidelines to treat dyslipidemia in diabetes recently published by the ADA, and together
with the results of several studies, among them the East West Study,17a were behind the
change in the NCEP-ATP III guidelines that now considers diabetes as a CHD equivalent.
Optimal LDL-cholesterol levels for adults with diabetes are <100 mg/dl, regardless of their
risk factor profile or presence or absence of established cardiovascular disease.
Indications for Cardiac Testing

Asymptomatic CAD and silent myocardial infarction (MI) are frequent in subjects with
diabetes. Thus, early diagnosis of CAD in patients with diabetes is very important, and
allows earlier implementation of preventive programs aimed at reducing the risk of future
coronary morbidity and mortality, initiation of treatment with anti-ischemic medications
in silent ischemia, and earlier identification of patients in whom revascularization is
appropriate. Indications for cardiac testing are summarized in Table 53.13.
Diabetic Complications: Hypoglycemia

It is well established that glycemic control will prevent specific long-term complications
of diabetes. However, in order to prevent complications intensive treatment of diabetes
is necessary, and unfortunately this may lead to hypoglycemia. It is obvious that even in
optimal conditions, hypoglycemia is the limiting factor in the management of patients
TABLE 53.13
Indications for Cardiac Testing in Diabetic Patients
Testing for CAD is warranted in patients with the following:
1. Typical or atypical cardiac symptoms

2. Resting EKG suggestive of ischemia or infarction
3. Peripheral or carotid occlusive arterial disease
4. Sedentary lifestyle, age ≥ 35 years, and plans to begin a vigorous exercise program
5. Two or more of the risk factors listed below (a-e) in addition to diabetes
a) Total cholesterol ≥ 240 mg/dl, LDL cholesterol ≥ 160 mg/dl, or HDL cholesterol < 35 mg/dl
b) Blood pressure > 140/90 mm Hg
c) Smoking
d) Family history of premature CAD
e) Positive micro/macroalbuminuria test
Reprinted with authorization from American Diabetes Association (Diabetes Care 21: 1551; 1998).
with type 1 diabetes. Hypoglycemia is defined as a blood glucose of ≤60 mg/dl that may
occur with or without symptoms.18 During the course of the DCCT trial and even under
optimal conditions, the incidence of severe hypoglycemia was more than three times
higher in patients on intensive therapy when compared with patients treated with con-
ventional therapy. The effects of hypoglycemia cannot be ignored, since they can be
devastating, particularly on the brain. The first signs of hypoglycemia are shakiness,
sweating, tachycardia, hunger, irritability, and dizziness. These symptoms are followed
by inability to concentrate, confusion, slurred speech, irrational behavior, blurred vision,
and extreme fatigue. Finally, the symptoms of severe hypoglycemia are seizures, unre-
sponsiveness, and loss of consciousness. Symptoms of hypoglycemia may occur at any
time, and therefore patients with diabetes should always be prepared to address them.
The level of glucose that leads to symptoms of hypoglycemia may vary from person to
person and also varies in the same individual under different circumstances. Hypoglyce-
mia is a much less frequent problem for people with type 2 diabetes except in the elderly,
mainly when they have associated diseases that require the use of beta blockers. Hypogly-
cemia usually occurs gradually, and in general is associated with warning signs, including
rapid heart beat, perspiration, shakiness, anxiety, and hunger. However, warning symp-
toms of hypoglycemia may be absent, causing the clinical syndrome of hypoglycemia
unawareness. This syndrome results from excessive insulin in the setting of absent glu-
cagon secretory responses to falling glucose levels. These episodes, in turn, cause reduced
autonomic responses and lead to further decrease of the warning symptoms of hypogly-
cemia. This creates a vicious cycle that can only be broken by avoiding inducing iatrogenic
hypoglycemia. The most common causes of hypoglycemia include: a) skipping, delaying,
or reducing the size of the meals and snacks; b) increased physical activity without
adequately adjusting therapy; c) alcohol intake mainly on an empty stomach; and d)
treatment with excessively high levels of insulin or other antidiabetic medications.
Hypoglycemia occurs mainly when the patient is being treated with insulin or sulphony-
lureas. In theory, biguanidines, thiazolidinediones, and α-glucosidase inhibitors would
not be expected to induce hypoglycemia, since by themselves they will not increase the
level of plasma insulin. However, it is conceivable that any intervention that limits hepatic
glucose production, favors glucose utilization, or both may lead to hypoglycemia, since
increased hepatic glucose production and limited glucose utilization are mechanisms of
defense against a drop in plasma glucose levels. In the elderly, it is not uncommon to have
hypoglycemia episodes, and these may be dangerous since these subjects often live alone.
A recent study examining the risk of sulphonylurea-induced hypoglycemia in elderly type
2 diabetic patients concluded that therapy with sulphonylureas is well tolerated by the
elderly, and that the primary mechanism of protection against hypoglycemia is an increase
in epinephrine secretion.19 That suggests that glucagon secretion in elderly patients is
diminished, and supports the concept that treatment of these patients with sulphonylureas
or insulin when they are also being treated with β-blockers may be dangerous, and close
followup is needed. Oral antidiabetic agents other than sulphonylureas are probably better
candidates for the treatment of these patients if their hyperglycemia is relatively modest.
Although hypoglycemia during treatment with these agents may also occur, it is likely to
be less frequently observed and less severe.
Standards of Medical Care for Diabetic Patients

Standards of medical care for diabetic patients have been markedly influenced by the
results of recent major clinical trials. Some of the trials were specifically designed to
address the importance of intensive glycemic control in subjects with type 1 or type 2
diabetes (DCCT and UKPDS). Some clinical trials, although not designed to specifically
address questions related to diabetic patients, had a sufficiently large number of patients
with type 2 diabetes and glucose intolerance to allow drawing conclusions on the effect
of lipid-lowering therapy in the development of macrovascular complications (CARE, 4S,
AF-CAPS/TEX-CAPS). The data published concerning these trials as well as the technical
reviews of the ADA20 will provide evidence for the standard-of-care measures proposed
by the ADA for the treatment of patients with diabetes.
Standards of diabetes care are expected to provide health care providers taking care of
patients with diabetes the means to establish treatment goals, assess the quality of the
diabetes treatment provided, identify areas where more self management is needed, and
define situations when referral to specialists is necessary. Also, the same standards of
diabetes care should allow patients with diabetes to assess the quality of medical care that
they receive, understand their role in the treatment of their disease, and compare their
treatment outcomes with standard goals.
General Principles
It is accepted that lowering blood glucose levels to normal or near-normal levels will reduce:
• The danger of acute decompensation due to diabetic ketoacydosis or hyperos-

molar hyperglycemic nonketotic syndrome
• The symptoms of blurred vision and symptoms/signs usually accompanying
diabetes (polyuria, polydipsia, weight loss with polyphagia, fatigue) as well as
vaginitis or balanitis
• The development or progression of diabetic retinopathy, nephropathy, and
neuropathy
• Triglycerides leading to a less atherogenic lipid profile
It is also well accepted that lowering lipid levels will result in a decrease in diabetic
macrovascular complications.
Thus, proper standards of diabetes care should include:
• Appropriate frequency of self monitoring of blood glucose

• Adequate medical nutrition therapy
• Regular exercise
• Adequate regimens with insulin and/or oral glucose-lowering agents
• Instructions in the prevention and treatment of hypoglycemia
• Instructions in the prevention and treatment of acute and chronic diabetes com-
plications
• Adequate regimens of lipid-lowering therapy
• Continuing education and reinforcement programs
• Periodic assessment of treatment goals
Specific Goals for Management of Diabetes

An overview of the steps, goals, and treatment needed to obtain optimal care of patients
with diabetes is summarized in Table 53.14.
Special Considirations
Pregnancy
To reduce the risk of fetal malformations and maternal and fetal complications, pregnant
diabetic women require excellent glycemic control. Followup by a multidisciplinary team
including a diabetologist, internist or family physician, obstetrician, and diabetes educator
is essential. Other specialists need to be called upon if necessary. Self-management skills
essential for glycemic control and preparation for pregnancy include:
• Designing an appropriate meal plan, with timing of meals and snacks and an
appropriate physical activity plan
• Self-monitoring blood glucose levels, choosing the time and site for insulin
injections, using therapy with glucagon or carbohydrate intake for treatment of
hypoglycemia, and self-adjusting insulin dosages
• Reducing stress and coping with denial
Before conception, it is essential to have a good laboratory evaluation including HbA1c,

baseline assessment of renal function, thyroid function tests, and lipid profile. Other tests
may need to be added according to medical history and physical exam. Conception should
be deferred until the initial evaluation is completed and specific goals of therapy, including
glucose control and dietary and physical activity adherence, are attained. Since the safety
of oral antidiabetic agents is not well established for the fetus, patients need to be switched
to insulin therapy. The goals for blood glucose are 70 to 100 mg/dl preprandial and <140
or <120 mg/dl respectively one or two hours postprandial. Hypertension, retinopathy,
nephropathy, gastroparesis, and other neuropathies as well as elevated lipid levels need
to be stabilized prior to conception. Pregnancy will exacerbate and accelerate acute and
long-term complications of diabetes. Continuing care by a team of professionals is essential
in the management of pregnant diabetic patients.
Macrovascular Disease
Recommendations listed in Table 53.14 for LDL and HDL cholesterol levels as well as for
triglycerides have a goal of reducing the risk for development of coronary heart disease
TABLE 53.14
Recommended Diabetes Management Guidelines
Parameters to Assess Frequency of Evaluation Goal Action Indicated If: Recommended Treatment
Assessment of Metabolic Control
HbA1c Quarterly ≤7% ≥8% Diet, exercise, oral agents, and/

or insulin
Self-monitoring of blood
glucose:
Preprandial As necessary for glycemic 80-120mg/dL >140 mg/dL Stepped adjustment of
Bedtime control 100-140 mg/dL >160mg/dL medication/diet to obtain

adequate glycemic control
Technique check Annually Proficient Not proficient Referral for teaching
Hypoglycemic episodes Each visit No episodes Episodes occur Change in lifestyle, diet, and/or
drug treatment
Hyperglycemic episodes/ Each visit No episodes Episodes occur Change in lifestyle, diet, and
ketonuria drug treatment
Assessment Macrovascular Complications
Blood pressure Each visit ≤ 130/80 mm Hg > 130/80 mm Hg ACE Inhibitors and off other
antihypertensive medications
Lipid profile: At least yearly. Quarterly or
LDL-Cholesterol more frequently if levels are < 100 mg/dL** >100 mg/dL Stepped approach to lipid
HDL-Cholesterol abnormal >45 mg/dL < 45 mg/dL control with lipid lowering
Triglycerides <150 mg/dL > 150 mg/dL medications, diet, and exercise
Low dosage aspirin for patients
with established
macrovascular disease or
patients with several risk
factors for macrovascular
disease
EKG Annually Normal Abnormal Stress test and/or referral to
cardiology
Ankle/brachial ratio Annually Normal Abnormal Peripheral vascular assessment
and/or referral to vascular
surgery
1093
1094

Recommended Diabetes Management Guidlines
Parameters to Assess Frequency of Evaluation Goal Action Indicated If: Recommended Treatment
Peripheral pulses Each visit Normal Abnormal See above
Assessment of Microvascular Complications
Retinopathy:
Dilated eye exam by eye care Annually Normal Abnormal Referral to ophthamology
specialist Adequate glycemic control
Nephropathy:
Microalbumin Annually or quarterly if < 30 mg/24 h or < 30 mg/g of ≥ 30 mg/24 h or ≥ 30 mg/g of Adequate glycemic control
abnormal creatinine (spot urine) creatinine (spot urine) Adequate treatment with ACE
inhibitors
Adequate treatment of
hyperlipidemia
Referral to nephrology if
necessary
Neuropathy:
Peripheral sensory Annually Intact sensation Abnormal Protective and preventive
education
Adequate glycemic control
Drug treatment for
symptomatic disease
Feet exam Each visit No complications Corns, calluses, ulcers, wounds, Referral to podiatry and/or
infections vascular surgery specialist
Adequate control of lipid
abnormalities and blood
glucose
Treatment of infections if
present
Assessment of Other Complications
Oral/periodontal Each visit Healthy gums/teeth If no routine dental visits and Referral for dental hygiene and
Dental visit and hygiene every hygiene are being performed care
6 months Adequate glycemic control*
Other infection Each visit Absence of infection If infection is present Adequate glycemic control*
Appropriate treatment of
infection and referral to ID if
necessary
Lifestyle Assessment
Exercise Each visit 20-45 minutes on most days < 3 times weekly Exercise counseling related to
type, frequency, duration, and
intensity
Smoking, tobacco use Each visit No use Any use Smoking cessation counseling
Weight Each visit Ideal body weight Patient is over- or underweight For overweight: diet adjustment
for short term-weight lost of

0.2-0.5 kg/week; for long term
weight loss as much as needed
to attain IBW
For underweight: if severe —
consult NST
If mild — assess the reasons for
weight loss and treat
accordingly
Nutrition Each visit Healthy eating daily weight Poor glucose or lipid control or Referral for nutrition
Annual in-depth assessment by control increased weight counseling
RD Metabolic control In-depth nutrition assessment,
plan, and followup by RD
Overall diabetes self- Each visit Healthy diabetes management Early signs of complications Referral to diabetes educator or
management practices Annual in-depth assessment with metabolic control and at and early signs of poor self- formal diabetes education
and self-management update least annual diabetes management of diabetes classes for assessment, plan,
assessment and self- evaluation, and followup by
management education CDE
update
Severe gum disease or any local of systemic infection is associated with higher glucose levels. Treatment of infection improves glycemic control.
1095
TABLE 53.15
Treatment Decisions Based on LDL Cholesterol Levels in Adults
Medical Nutrition Therapy Drug Therapy
Initiation Initiation
Level LDL Goal Level LDL Goal
With CAD, PVD, or CVD >100 ≤100 >100 ≤100
Without CAD, PVD, or CVD >100 ≤100 ≥130 ≤100
Data are given in mg/dl.
Reprinted with authorization from American Diabetes Association (Diabetes Care 23(1):
58S; 2000).
and to stop progression or cause regression in patients with already established macrovas-
cular disease. The goal for LDL cholesterol levels is 100 mg/dl for all diabetics. Lipid-
lowering drug therapy is recommended to be started in patients with established vascular
disease (coronary heart disease, peripheral vascular or cerebrovascular disease) if the levels
of LDL-cholesterol are above 100 mg/dl. In diabetic patients without established macrovas-
cular disease, lipid-lowering drug therapy is recommended for LDL-cholesterol of 130 mg/
dl or above. The recommendations for treatment of elevated LDL-cholesterol are summa-
rized in Table 53.15. Pharmacological therapy should be initiated after behavioral interven-
tions are used. However, in patients with clinical CAD or very high LDL-cholesterol levels
(i.e., ≥200 mg/dl), pharmacological therapy should be initiated at the same time that
behavioral therapy is started. According to the NCEP-ATP III guidelines, diabetes drug
treatment and behavioral modification should be performed simultaneously. The ADA
guidelines recommend that diabetic subjects with clinical CAD and an LDL cholesterol
level of >100 mg/dl be treated with pharmacological agents. For diabetics without pre-
existing CAD, the current ADA recommendations for starting pharmacological therapy are
LDL-cholesterol levels ≥130 mg/dl. Recent clinical trial data strongly suggests that these
goals may become more stringent soon.
A point to consider in diabetic patients is the method used to measure LDL-cholesterol.
Due to the prevalence of dense LDL in these patients, the conventional method to calculate
LDL-cholesterol is inappropriate and the levels determined are in general falsely low.
Increased triglyceride levels are also recognized as a target for intervention. The levels
of triglycerides considered acceptable are <150 mg/dl, and the HDL-cholesterol levels >45
mg/dl. The initial therapy for hypertriglyceridemia is behavioral modification with weight
loss, increased physical activity, and no alcohol consumption. In the case of severe hyper-
triglyceridemia (≥1,000 mg/dl according to the ADA guidelines and ≥500 mg/dl according
to NCEP-ATP III guidelines), severe dietary fat restriction (15 to 20% of kcalories as fat)
in addition to pharmacological therapy is necessary to reduce the risk of pancreatitis.
These patients are hard to manage, and improving glycemic control rather tightly is a
very effective measure for reducing triglyceride levels and should be aggressively used
before the introduction of fibric acid derivatives.
Nutritional Recommendations and Principles for the Dietary Treatment

of Diabetics
Goals of Nutrition Therapy
The goals of medical nutrition therapy are to optimize health, control diabetes, and prevent
or delay complications of diabetes.21 The goals are summarized in Table 53.16. MNT is
TABLE 53.16
Goals of Medical Nutrition Therapy for Diabetes
• Achieve and maintain near-normal blood glucose goals
• Achieve and/or maintain optimal blood lipid levels
• Achieve and/or maintain normal blood pressure
• Prevent, delay or treat nutrition-related complications
• Provide adequate kcalories for achievement of reasonable body weight
• Provide optimal nutrition for maximizing health and for growth, development, pregnancy, and
lactation
individualized for the person with diabetes to integrate the therapy into the daily routine
of living. A registered dietitian completes a nutritional assessment and develops the
individualized meal plan and behavioral interventions with the person with diabetes and
the family.22 The effectiveness of the dietary interventions in helping the person with
diabetes achieve the identified goals should be evaluated routinely until goals are
achieved. If goals are not met, changes in the overall management plan are needed. When
goals are achieved, reassessment, continuing education, and evaluation should occur at
least annually, and more often with changes in lifestyle, to assure optimal control of
diabetes and maintenance of health.
Nutrition Therapy for Different Types of Diabetes

Type 1 Diabetes
The person with type 1 diabetes is typically thin or within recommended weight range.
Prior to diagnosis the patient may have experienced weight loss, frequent urination (poly-
uria), thirst and increased fluid intake (polydipsia), and hunger (polyphagia). The initial
goals of MNT are to replace fluids, normalize blood glucose and lipids, and provide
appropriate kcalories for healthy living. Food, insulin administration, and physical activity
need to be well balanced to obtain optimal control. It is essential that the person with
diabetes coordinates the eating and exercise patterns with the onset of action and the
duration of the insulin. The person with newly diagnosed type 1 diabetes may be over-
whelmed with changes in daily routine; thus, initially the focus is on survival skills for
managing diabetes (Table 53.17) followed by teaching self-management knowledge and
skills which are needed to optimally control diabetes and its complications.23,24 Dietary
changes to optimize health can be made more slowly over time. Figure 53.1 outlines the
TABLE 53.17
Survival Skills for Managing Diabetes
• To acquire an adequate knowledge of:
Basic food and meal guidelines (including when eating out)
Effect of carbohydrates on blood glucose
Amount of carbohydrates taken daily
Carbohydrate food groups, portion sizes, and label information
• To coordinate insulin administration with food intake
• To be able to perform self-monitoring of blood glucose
• To schedule exercise according to food intake and glucose control
• To acquire knowledge of how to treat hypoglycemia:
(in general, 15 grams of carbohydrates should raise blood glucose 50-100 mg/dl in 15 minutes)
• To know that alcohol intake may cause hypoglycemia (by inhibiting gluconeogenesis in liver)
• To know why, when, and how to call the health care provider and/or dietitian
• To have an established plan for recording self-management and returning for continuing care
Integrate insulin with eating and exercise habits
Conventional Intensive
therapy therapy
Synchronize Eat Integrate Adjust insulin

food with consistently, insulin into to compensate
insulin adjust insulin lifestyle for lifestyle
FIGURE 53.1
Nutrition therapy for type 1 diabetes. Reprinted with permission from Maximizing the Role of Nutrition in Diabetes
Management, American Diabetes Association, Alexandria, 1994.
two approaches to nutrition therapy currently recommended by the ADA.25 Blood glucose
levels need to be monitored and insulin doses and/or food intake to control blood glucose
adjusted according to recommended levels (Table 53.14).
Type 2 Diabetes
The person with newly diagnosed type 2 diabetes may have had asymptomatic type 2
diabetes for a number of years prior to diagnosis, and may present with one or more
complications. Most are obese or have increased percentage of body fat distributed pre-
dominately in the abdominal region. The goals of therapy are to achieve and maintain
glucose, lipid, and blood pressure within the recommended range and to achieve a mod-
erate weight loss (5 to 9 pounds) if overweight.26,27 Methods for attaining these goals are
outlined in Figure 53.2. There is no clear answer about which goal should have first
priority; however, the UKPDS researchers found that blood pressure control produced the
most improved outcomes.28 The desired outcomes of medical nutrition therapy for persons
with type 2 diabetes are outlined in Tables 53.14 and 53.16.
Learn new behaviors
Monitor blood glucose, Restrict calories for

Add meds if needed Moderate weight loss
Glucose Control
and
Blood Pressure Control Improve food choices
Increase physical
activity
Modify sodium intake

Modify fat intake Space meals
FIGURE 53.2
Nutrition therapy for type 2 diabetes. Adapted with permission from Maximizing the Role of Nutrition in Diabetes
Management, American Diabetes Association, Alexandria, 1994.
TABLE 53.18
Goals for Medical Nutrition Therapy in GDM
• Optimal nutrition for developing fetus
• Optimal nutrition for mother
• To maintain maternal euglycemia keeping an adequate diet
• Good nutrition patterns taught to the family ‘gatekeeper’
• To develop nutritional patterns that prevent or forestall recurrence of GDM and onset of type 2 diabetes
mellitus
Reprinted with permission from American Diabetes Association: Thomas-Dobersen, D., et al. Clinical Diabetes 1:
172; 1999.
TABLE 53.19
Blood Glucose Goals for Pregnancy
Preexisting Diabetes Gestational
Mellitus Diabetes
Fasting 70-100 mg/dl ≤105 mg/dl
Premeal 70-100 mg/dl 70-105 mg/dl
Postprandial 1 hour ≤140 mg/dl ≤120 mg/dl
Postprandial 2 hour ≤120 mg/dl ≤120 mg/dl
Adapted with permission from Hoeer, J.H., Green-Pastors, J.,
Diabetes Medical Nutrition Therapy, American Diabetes Associa-
tion, Alexandria, ch. 8, 1997.
Diabetes in Pregnancy
The goal of nutrition therapy for diabetes in pregnancy is to produce a healthy baby at
term and maintain optimal health for the mother. If type 1 or type 2 diabetes is diagnosed
prior to pregnancy, counseling is recommended to attain optimal control of diabetes prior
to conception and throughout pregnancy. The pregnant woman is defined as having
gestational diabetes if first diagnosed during the present pregnancy. GDM does not exclude
the possibility that diabetes may have been unrecognized prior to pregnancy; however,
GDM typically occurs around the 24th week of pregnancy. Women diagnosed with GDM
in a prior pregnancy have a 30 to 65% probability of developing GDM in a subsequent
pregnancy. Studies also show that women with GDM have a 22 to 30% probability of
developing type 2 diabetes in 7 to 10 years and a 50 to 60% risk of developing diabetes in
their lifetime. Additionally, the offspring have an increased risk of obesity and GDM.29
The overall goals for medical nutrition therapy are shown in Table 53.18, and blood
glucose goals are shown in Table 53.19. To accomplish these goals, meal patterns, nutrient
composition, and caloric needs are reviewed in Table 53.20, and a typical meal/snack
pattern is shown in Table 53.21.
Nutritional Recommendations
Guidelines for nutrient consumption and other nutrition components such as sweeteners
and cholesterol along with technical reviews of the evidence for the guidelines have been
published by the ADA,30-34 and are summarized in Table 53.22. The energy nutrients can
be converted into blood glucose, and Table 53.23 summarizes their degree of conversion.
Protein and fats have minimal effect on blood glucose except in patients whose diabetes
is poorly controlled, since these nutrients may lead to a rapid increase in gluconeogenesis
and deteriorated glycemic control.32 Many persons with diabetes initially think that only
sugar can increase blood glucose; thus, diabetes education about the effect of nutrients
(especially carbohydrates) is essential to good control.
TABLE 53.20
Summary of Intensive Nutritional Therapy for GDM
Meal Pattern
Three meals plus three or more snacks (2-3 hour intervals)

(breakfast with low carbohydrate content)
ADA exchange pattern individualized
Composition
Nutrition therapy and exercise only (no insulin)

38-45% carbohydrate complex, high fiber, >150 g minimum
(lower level can be used as long as no ketonuria is present)
20-25% protein (1.3 g/kg body weight)
30-40% fat (mono or polyunsaturated emphasized)
Energy Levels
Second trimester, 25-30 kcal/kg IBW prepregnant

Third trimester, 30-35 kcal/kg IBW prepregnant
Weight Gain
Adjust kcalorie level to achieve appropriate weight gain for

prepregnancy BMI category:
Prepregnancy BMI Total gain

Underweight <19.8 28-40 lbs. (12.5-18 kg)
Normal weight 19.8-26 25-35 lbs. (11.5-16 kg)
Overweight >26-29 15-25 lbs. (7-11.5 kg)
Obese >29 Minimum 15 lbs. (7.1 kg)
Reprinted with permission from American Diabetes Association. Gun-
derson, E.P., Diabetes Care 20: 223; 1997.
TABLE 53.21
Intensive Medical Nutrition Therapy for GDM
Total Carbohydrate Carbohydrate
Meal or Snack kcalories (%) (g)
Breakfast 10-15 15-30
A.M. snack 10 15-30
Lunch 20-25 30-60
P.M. snack 15 15-45
Dinner 25 45-60
Bedtime snack 15 30 or more
Daily total 100 150-250
Reprinted with permission from American Diabetes As-
sociation. Gunderson, E.P., Diabetes Care 20: 223; 1997.
Carbohydrate level should vary according to kcalorie
prescription and the individual’s tolerance for carbohy-
drate, which worsens as gestation progresses. The re-
stricted levels listed above are characteristic of late
gestation.
TABLE 53.22
Medical Nutrition Therapy Recommendations
Nutrient Recommendation Comments
Protein
Sources: chicken, fish, meat, eggs, 10-20% of total kcalories should come from protein sources. Research indicates needs are similar for people with or without
milk, tofu, nuts, peanut butter diabetes.
With onset of nephropathy, limit protein to adult RDA (0.8 g/
kg/day).
Some research studies suggest vegetable protein may not be as
harmful to the kidneys as animal protein.

Carbohydrate
Sources: starch (grains, bread, pasta, 80-90% of kcalories are divided between carbohydrate and fats Total carbohydrate intake has greater impact on blood glucose
rice, potato, beans) milk, fruit, based on individual risk factors and needs. Depending on control than source of carbohydrate, i.e., whether complex
vegetables, sugar, honey, jam, nutritional assessment and medical nutritional therapy goals, carbohydrate or sucrose.
molasses, etc. this generally equates to 45-60% of total kcalories from Sucrose and sucrose-containing foods should be consumed
carbohydrate. within the context of a healthful diet. These foods are often high
in total carbohydrate and fat and low in vitamins and minerals.
Sugars and Other Sweeteners
Sources: sucrose, fructose, corn % of kcalories will vary and is individualized based on usual Sucrose and sucrose-containing foods should be consumed
sweeteners such as corn syrup, fruit eating habits, glucose and lipid goals. Sucrose and other within the context of a healthful diet. These foods are often high
juice, or fruit juice concentrate, sugars/sweeteners can be integrated into a healthy eating in total carbohydrate and fat and low in vitamins and minerals.
honey, molasses, dextrose, maltose; pattern for persons with diabetes. Individuals can be taught to substitute sucrose-containing foods
sorbitol, mannitol, xylitol (sugar for other carbohydrate foods in their meal plans.
alcohols)
Nonnutritive sweeteners such as All are approved by the FDA and the FDA determines an
saccharin, aspartame, acesulfame K, acceptable daily intake (ADI) which includes a 100-fold safety
and sucralose factor. Actual intake by persons with diabetes is well below the
ADI.
Fat
Sources: monounsaturated: olive and 60-70% of total kcalories should be divided between Individuals with diabetes should limit total fat to 25-35% of total
canola oils, avocado, nuts monounsaturated fats and carbohydrates. kcalories and <200 mg of dietary cholesterol per day.
polyunsaturated: safflower, Up to 10% of kcalories should be from polyunsaturated fats. If obesity and weight management are the primary issues,
sunflower, corn, and soy oils reduced total fat to reduce total kcalories and increasing
exercise should be recommended.
1101
1102

Medical Nutrition Therapy Recommendations
Nutrient Recommendation Comments
saturated: butter, lard, shortening, Less than 7% of total kcalories should be from saturated fats. Guidelines for reducing cardiovascular risk are emphasized —
animal fats, coconut, and palm oils nobody should exceed 7% of total kcalories from saturated fats.
Depending on nutritional assessment, total fat intake equates to If elevated triglyceride and very low-density lipoprotein
25-35% of total kcalories. cholesterol are the primary concerns, a moderate increase in
monounsaturated fat intake, with <7% of total kcalories from
saturated fat, and a more moderate (slight decrease) in
carbohydrate can be tried. Some studies have shown that a diet
with increased total fat from monounsaturated fats can lower

plasma triglycerides, glucose, and insulin levels more than a
high-carbohydrate diet in some individuals. In individuals with
triglycerides >1000, reduction of all types of dietary fats to
reduce levels of plasma dietary fat in the form of chylomicrons
should be implemented.
Fat replacers
Typically fall into three categories Foods with fat replacers can be substituted in an individual’s Food products that contain <20 kcalories or 5 grams of
based on their nutrient content: meal plan based on the nutrient profile of the food product. carbohydrate per serving have a negligible effect on metabolic
Carbohydrate-based: includes control.
carrageenan, cellulose gum, corn Foods containing 20 kcalories per serving should be limited to
syrup solids, dextrin, guar gum, 3 servings spread throughout the day.
hydrolyzed corn starch,
maltodextrin, modified food starch,
pectin, polydextrose, sugar beet
fiber, tapioca dextrin, xanthan gum.
Protein-based: includes
microparticulated egg white and
milk protein (Simplesse, K-Blazer),
whey protein concentrate
Fat-based: includes caprenin, olestra
(Olean), salatrin (Benefat), and
others.
Dietary cholesterol <200 mg per day MNT typically reduces LDL Cholesterol 15-25 mg/dl (0.40-0.65
mmol/l)
Fiber 10-25 grams of soluble fiber per day — same recommendation Research suggests that in the amounts typically consumed, fiber
as for individuals without diabetes.* intake has very little impact on blood glucose levels.
Sodium Same as for general population: <3000 mg per day. There is an association between hypertension and both IDDM
If hypertensive, individuals should reduce sodium intake to and NIDDM, with an increase for people with NIDDM who
<2400 mg per day. are obese. There is also evidence that individuals with NIDDM
Food selection guidelines: <400 mg sodium per single serving are more salt sensitive.
of food; <800 mg sodium per entree or convenience meal.
Alcohol Abstinence is recommended for those with history of alcohol
1 drink = 12 oz. beer, 5 oz. wine, 1 oz. Insulin users: limit to 2 drinks per day and do not cut back on abuse or alcohol-induced hypertriglyceridemia, and during
80-proof liquor food. pregnancy.
Non-insulin users: substitute alcohol for fat. Drink only with food. Alcohol can lead to hypoglycemia via
inhibition of gluconeogenesis.
Limit for weight loss and elevated triglycerides.
Micronutrients The vitamin and mineral needs of people who are healthy appear Individuals at greatest risk for vitamin/mineral deficiency
to be adequately met by the RDAs, which include a generous include those on weight loss diets, strict vegetarians, the elderly,
safety factor. pregnant or lactating women, those taking medications known

to alter micronutrient metabolism, people with poor glycemic
control (i.e., glycosuria), people with malabsorption disorders,
and people with congestive heart failure or myocardial
infarction.
* Exception in patients with autonomic neuropathy who should not have increased fiber in their diet.
Adapted and expanded from Karlsen, M., Khakpour, D., and Thomson, L.L. Clinical Diabetes 14: 54; 1996.
1103
TABLE 53.23
Energy Nutrients and Their Absorption
% Nutrient Converted Estimated Time
Nutrient Kcalories/Gram to Glucose for Absorption*
Carbohydrate 4 100%
Simple 5-30 min
Complex 1-3 h
Protein 4 50-60% 3-6 h
Fat 9 10% 3-8 h
* The absorption time is affected by the nutrient mix. For example, the sugar
from a candy bar with high fat content is more slowly absorbed than a piece
of candy than contains no fat.
TABLE 53.24
Meal Planning Approaches
Approach Benefits Drawbacks
Food guide pyramid Well known by the general public Little focus on meal spacing
Health food choices Mixes guidelines with meal plan Often perceived as diet
Exchange lists for meal planning Places emphasis on all nutrient Concept difficult to understand by
groups the lay person
Counting plans Good approach for specific Requires committed learner
nutrient intervention
Carbohydrate indications Useful for adequate glucose control Ignores other nutrients
Protein indications Address diabetic nephropathy Ignores other nutrients
Fat indications Address weight or hyperlipidemia Ignores other nutrients
Reprinted with permission from American Diabetes Association. Karlsen, M., Khakpour, D., and Thomson, L.L.
Clincal Diabetes, May/June: 54; 1996.
Food Guides and Planning Food Intake for Persons with Diabetes
Historically, the approaches to planning food intake for persons with diabetes have ranged
from starvation diets (during the pre-insulin era) to high-fat, low-carbohydrate diet plans,
to our present system of more liberalized food intake. Various food guides and methods
for planning food intake have been used. An overview of the meal planning approaches
for providing MNT to persons with diabetes is reviewed in Table 53.24. A meal planning
approach that provides the desired outcomes (decrease of complications and optimal
health and satisfaction) is desirable. Carbohydrate counting is one method that allows
maximum flexibility as well as excellent glycemic control. The different ways to count
carbohydrates are reviewed in Table 53.25.
Food Labeling
Teaching patients with diabetes how to read a food label is especially important to those
who count carbohydrate, fat, or protein in their meal plans. For persons using exchange
TABLE 53.25
Ways to Count Carbohydrates
Premeal or Bolus Dose
Method Description Ease vs. Accuracy Calculation*
Counting carbohydrate Count each serving of Easiest method but also Calculate pre-meal dose
exchanges starch, fruit, and milk as the least accurate units/exchange
(interchanges) one carbohydrate Requires the least math
exchange and consider skill
them equal in
carbohydrate value
Counting food exchanges Add the carbohydrate Easy and fairly accurate Calculate pre-meal dose
values of all exchanges as units/exchange,
that contain counting vegetables as
carbohydrate (including carbohydrates, or
vegetables) to obtain the calculate the bolus by
carbohydrate total for a dividing the total grams
meal of carbohydrate in the
meal by the insulin-to-
carbohydrate ratio
Carbohydrate gram Add carbohydrate gram More time-consuming Calculate pre-meal dose
counting values for all foods than methods 1 and 2 by dividing the total
eaten to obtain the total but also quite accurate. grams of carbohydrate
carbohydrate intake per Requires more math skill in the meal by the
meal to add and divide 2- and insulin-to-carbohydrate
3-digit number ratio
Calculating available Count grams of Most difficult; requires Multiply grams of
glucose carbohydrate for all the most math skill of all protein in meal by 0.6 to
foods eaten, then methods obtain available glucose,
calculate the glucose add to grams of
available from protein carbohydrate; calculate
and add this value to the the dose by dividing this
carbohydrate grams to total by the insulin-to-
obtain the meal total carbohydrate ratio
* Short-acting insulin adminstered before meals to control the meal-related glucose rise. The calibration of
insulin to food intake is recommended for individuals with type 1 diabetes, especially those following
intensive therapy.
lists for meal planning, information about how to use the nutrition information to fit foods
into the exchange lists is helpful (and essential for combination foods). The key question
for the patient to ask is “how does this food, based on the nutritional information, fit into
my food plan for controlling diabetes?”35
Diabetes and Physical Activity

Exercise can be used as a therapeutic tool for controlling diabetes, and the person with
diabetes needs to incorporate exercise into the lifestyle for healthy living with diabetes.
Patient Evaluation before Exercise

The person with diabetes should undergo a medical evaluation with appropriate diag-
nostic studies and should be screened for complications that may be worsened by the
exercise program.36 If complications are present, the patient should have an individual-
ized exercise program prescription that specifies the frequency, intensity, and duration
of exercise, along with specific precautions for minimizing risks. The benefits of physical
activity are many, including cardiovascular fitness and psychological wellbeing. How-
ever, the risks of exercise for the person with diabetes are many, including fluctuations
in blood glucose control, ketosis, lower-extremity injury, and exacerbation of pre-existing
complications.
Exercise Recommendations
For Persons with Cardiovascular Disease
Diabetics at risk or with diagnosed cardiovascular disease should undergo medical eval-
uation of cardiac status and special evaluation for exercise tolerance before participating
in increased physical activities. Supervised cardiovascular risk reduction or rehabilitation
programs often provide the patient and his family with increased support for increasing
physical activities.
Positive effects of regular exercise on reducing blood pressure have been consistently
demonstrated in hyperinsulinemic persons.
For Persons with Peripheral Arterial Disease

Following an evaluation of peripheral arterial disease, the basic treatment is a supervised
exercise program and no smoking, carried out under the supervision of a physician. A
walking program may improve muscle metabolism and collateral circulation for a person
with intermittent claudication. If pain is severe and does not improve, further evaluation
and possible limitation of exercises involving the lower extremities may be considered.
For Persons with Retinopathy

Following a dilated eye exam, if proliferative diabetic retinopathy is present, the person
with diabetes may need to avoid anaerobic exercise and exercise that involves straining,
jarring, or Valsalva maneuvers, and any other activities that increase systolic blood pres-
sure. Medical status dictates the level of risks associated with exercise; however, low-
impact cardiovascular conditioning such as swimming, walking, low-impact aerobics,
stationary cycling, and endurance exercises are low risk.
For Persons with Nephropathy

Specific exercise recommendations have not been developed for persons with nephropa-
thy, but some patients may self-limit exercise based on a reduced capacity for activity.
High-intensity or strenuous exercises should probably be discouraged for persons with
overt nephropathy, but other low intensity-physical activities may increase a sense of
wellbeing and socialization.
For Persons with Neuropathy

Peripheral
For the person who has loss of protective sensation in the feet on testing, weight-bearing
exercises are contraindicated. This includes use of treadmill, prolonged walking, jogging,
and step exercises. Recommended exercises include swimming, bicycling, rowing, chair
and arm exercises, along with other nonweight-bearing exercises.
Autonomic
Autonomic neuropathy increases the risks of exercise-related problems, and certain precau-
tions need to be taken to tailor the exercise prescription to each individual patient following
an in-depth evaluation. Thermoregulation may be difficult, so avoiding exercise in hot or
cold environments, and special attention to adequate hydration are most important.
Exercise and Glycemic Control

Regular exercise activities (30 or more minutes on most days) have demonstrated consis-
tent beneficial effects on carbohydrate metabolism and insulin sensitivity, as well as
enhanced weight loss.
Exercise for Persons with Type 1 Diabetes

Persons with type 1 diabetes, who do not exhibit some of the limiting complications
previously discussed or poor glycemic control, can enjoy all types of exercise.37 The key
is regulating the glycemic response to exercise. The person should avoid exercise if fasting
glucose levels are >250 mg/dl with ketosis present or if glucose levels are >300 mg/dl. If
glucose levels are <100 mg/dl prior to exercise, additional carbohydrates are recom-
mended. Food adjustments for exercise for persons with type 1 diabetes are shown in
Table 53.26. Food and fluids should be readily available for persons with type 1 diabetes
TABLE 53.26
Food Adjustments for Exercise for Persons with Type 1 Diabetes
General Guidelines
Types of Exercise If Blood Suggestion of Food
and Examples Glucose Is: Increase Food Intake By: Exchanges to Use:
Short duration, low-to- <100 mg/dL 10 to 15 g of CHO 1 Fruit or 1 starch
moderate intensity (walking ≥100 mg/dL None
a half mile or leisurely
bicycling for <30 minutes)
Moderate intensity (1 hour of <100 mg/dL 25 to 50 g CHO before 1 Meat sandwich with a milk
tennis, swimming, jogging, exercise, then 10 to 15 g/h or fruit
leisurely bicycling, golfing, of exercise
etc.) 100-180 mg/dL 10 to 15 gm CHO 1 Fruit or 1 starch
180-300 mg/dL None
>300 mg/dL Do not begin exercise until
blood glucose is under
control
Strenuous (about 1-2 hours of <100 mg/dL 50 g CHO, monitor blood 1 Meat sandwich (2 slices of
football, hockey, racquetball, glucose carefully bread) with a milk and fruit
or basketball; strenuous 100-180 mg/dL 25 to 50 g CHO depending Meat sandwich with a milk
bicycling or swimming; on intensity and duration and fruit
shoveling heavy snow) 180-300 mg/dL 10 to 15 g CHO 1 Fruit or 1 starch
>300 mg/dL Do not begin exercise until
blood glucose is under
better control
Self-blood glucose monitoring is essential for all persons to determine their carbohydrate needs. Persons with
type 2 diabetes usually do not need an exercise snack. During periods of exercise, all individuals need to increase
fluid intake.
CHO = carbohydrates.
Adapted with permission from Franz, M.J., and Barry, B., Diabetes and Exercise: Guidelines for Safe and Enjoyable
Activity, American Diabetes Association, Alexandria, 1996, p. 16.
during exercise. If the duration of exercise is 30 minutes or more during peak action time
of insulin and blood glucose is in good control, reduction of insulin is recommended. The
reduction of insulin is based on duration and intensity of exercise, and usually ranges
from 5 to 60% of daily requirements. After exercise, an extra carabohydrate snack may be
necessary. Frequent monitoring of blood glucose and adequate food/fluid intake to pre-
vent hypoglycemia are essential for self-management and maintaining a healthy lifestyle.
Exercise for Persons with Type 2 Diabetes

Many persons with type 2 diabetes may have some of the previously mentioned compli-
cations at diagnosis, and also may have been sedentary for many years. Thus, before
beginning an exercise program, an in-depth physical examination and recommendations
for exercise frequency, intensity, and duration is recommended.38 Beginning with 5 to 10
minute sessions with gradual increases usually is successful and safe. Unless treated with
insulin or glucose-lowering medications, the person with type 2 diabetes does not usually
need additional food before, during, or following exercise, except for exercise that is
intense or of long duration. Recent attention has focused on the useful role of exercise in
preventing or delaying the onset of type 2 diabetes.
Exercise for Older Adults with Diabetes

Exercise for older adults with diabetes is recommended, and may lead to an improved
quality of life and less chronic disease. The same precautions should be taken with older
adults with and without diabetes.
Hospital Admission Guidelines for Persons with Diabetes

If the standard of care is adequate, seldom will a diabetic patient require hospitalization.
According to the guidelines of the ADA, inpatient care may be required in:
• Life-threatening acute metabolic complications of diabetes

• Newly diagnosed diabetes in children and adolescents
• Patients with chronic poor metabolic control that necessitates close monitoring
to determine the problem behind the poor control and changes in therapy
• Patients with severe chronic complications that require intensive treatment either
of diabetes or of conditions that significantly affect diabetes control and further
development of complications
• Uncontrolled or newly discovered insulin-requiring diabetes during pregnancy
• Patients in whom institution of insulin-pump therapy or other intensive insulin
regimens are being contemplated
Translation of Medical Nutrition Therapy for Diabetes to Health Care

Institutions
Today’s recommendations for MNT in health care facilities are based on individualized
needs of the patients with diabetes. One of the approaches frequently used is the “con-
TABLE 53.27
Developing a Consistent Carbohydrate Diabetes Meal Plan Menu for Health Care Facilities
1. Establish the desired kcalorie range.
2. Determine the desired percentages of macronutrients (carbohydrate, protein, saturated fat, total fat).
3. Determine the numbers of CHO choices to be given at each meal, and if included, at bedtime snack.
4. Determine how often to include sucrose-containing desserts and the maximum number of CHO choices to
be allotted to each dessert.
5. Analyze current fat-modified menus for distribution of macronutrients (% carbohydrate, protein, saturated
fat, total fat) to determine if they meet goal ranges of new diabetic menus.
6. Determine how many grams of carbohydrate or CHO choices are in each item in the fat-modified menu (i.e.,
fruits, salads, starches, casseroles, desserts, milk, juices).
7. For nonselective menus, adjust the fat-modified menus to provide the established number of CHO choices,
and include a bedtime snack if desired.
8. For facilities with menu selections, identify the CHO choices for each carbohydrate item, and include
instructions on the menu regarding the number of carbohydrate choices to make at each meal.
9. For long-term care facilities that wish to base their diabetic diet (consistent carbohydrate diet) on regular
menus, use the same process as for fat-modified menus.
Reprinted with permission from Schafer, R.G. Practical Diabetology 16:3, 48; 1997.
sistent carbohydrate diabetes meal plan;” a plan for developing a menu is shown in
Table 53.27.
Acute Health Care Facilities

Approximately one out of seven hospital beds is occupied by a person with diabetes. In
the acute care facility, many of the patients have complex health problems in addition to
diabetes. Thus, the challenge is to maximize health potential and provide foods that are
culturally acceptable to the patient. Each acute care facility has a different meal planning
system that best meets its needs. The consistent carbohydrate menu plan can be used to
improve metabolic control. The ideal meal plan reflects the diabetes nutrition recommen-
dations and does not unnecessarily restrict sucrose.39
Long-Term Health Care Facilities

Since the risk of diabetes increases with age, the patient population in long-term care
includes many individuals with diabetes. Additionally, malnutrition is a recognized
challenge in the older adult population. Food intake should be adequate and not overly
restricted. Regular menus, with consistent amounts of carbohydrate at meals and snacks,
are the recommended approach. Monitoring of blood glucose and hemoglobin A1c should
be used to evaluate glycemic control, with individualized approaches to achieve goals
of MNT.
Self-Management Education for Persons with Diabetes

Diabetes self-management education and continuing nutrition care is essential for meeting
the goals of MNT and diabetes control.23,30 The outpatient and home settings are the ideal
environments. If the patient is hospitalized with multiple other priorities, usually the
concern of the patient and the family is not focused on diabetes self-management educa-
tion. Learning readiness is the cornerstone for self-management education. At discharge
from the inpatient facility, plans are made for continuing education and followup by the
health care team.
Education for Health Care Professionals and Administrators

The role of MNT in helping the team and person with diabetes attain the desired treatment
goals is cost effective and leads to quality health services. One of the roles of the registered
dietitian is to translate nutrition recommendations for the diabetes care team and to
integrate these recommendations into the overall care of the person with diabetes. Team
members should have access to simplified guidelines for patient nutrition care until a
registered dietitian is available.
Third Party Reimbursement for Diabetes Care, Supplies, and Self-

Management Education
Currently, 37 states have enacted diabetes reform laws that improve insurance coverage
for supplies, equipment, and education for people with diabetes. States that have enacted
these laws are listed in Table 53.28.40 MNT counseling is usually included in diabetes
education coverage; however, examination of each state’s reform laws is necessary to
determine the extent of coverage. New Medicare regulations are expected to be released
in 2000, and diabetes advocates and nutrition professionals are working to assure inclu-
sion of MNT in these regulations. Medicaid, a federal–state partnership program for
persons unable to afford health care and private third-party insurance, offers coverage
for MNT in some states. To determine if your state offers coverage, contact the state’s
Medicaid program.
The frequency of dietitian contact with the patient and the essential care processes for
MNT have not been clearly delineated; yet quality health care today requires consistently
applied, evidence-based care that leads to positive outcomes for most patients. In a
research study conducted by the Diabetes Care and Education Practice Group of the ADA,
use of guidelines resulted in changes in dietitian practices and produced greater improve-
ment in patient blood glucose outcomes at three months compared to usual care.41 Self-
management education is critical to successful diabetes management, and medical treat-
ment without self-management education is regarded as substandard and unethical.
Numerous studies have demonstrated that self-management education and MNT improve
outcomes for persons with diabetes.
TABLE 53.28
States that have Enacted Diabetes Reform Laws (as of
January 2000)27
Arizona Iowa Nebraska Rhode Island
Arkansas Kansas Nevada South Carolina
California Kentucky New Hampshire South Dakota
Colorado Louisiana New Jersey Tennessee
Connecticut Maine New Mexico Texas
Florida Maryland New York Vermont
Georgia Minnesota North Carolina Virginia
Illinois Mississippi Oklahoma Washington
Indiana Missouri Pennsylvania West Virginia
Wisconsin
From Maggio, C.A., Pi-Sunyer, F.X. Diabetes Care 20: 1744; 1997.
References
1. World Health Organization: Diabetes Mellitus: Report of a WHO Study Group. Geneva, World
Health Org, 1985 (Tech Rep Ser no 727).
2. Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldshtein DE, Little RR, Wiedmeyer HM,
Byrd-Holt DD. Diabetes Care 21: 518; 1998.
3. National Diabetes Data Group. Diabetes 28: 1039; 1979.
4. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, Diabetes Care 21(1):
5S; 1998.
5. Reaven GM. Diabetes 37: 1595; 1988.
6. Tominaga M, Eguchi H, Manaka H, et al. Diabetes Care 22: 920; 1999.
7. Harris MI, Hadden WC, Knowler WC, Bennett PH. Diabetes 36: 523; 1987.
8. Harris MI. Diabetes Care 16: 642; 1993.
9. Klein R. Diabetes Care 18: 258; 1995.
10. Aiello LP, Gardner TW, King GL, et al. Diabetes Care 21: 143; 1998.
11. The Diabetes Control and Complications Trial Research Group, N Engl J Med 329: 997; 1993.
12. UK Prospective Diabetes Study Group, Lancet 352: 837; 1998.
13. UK Prospective Diabetes Study Group, Lancet 352: 854; 1998.
14. DeFronzo RA. Diabetes Reviews 3: 510; 1995.
15. Haffner SM. Diabetes Care 21: 160; 1998.
15a. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
JAMA 285: 2486, 2001.
16. Pyorala K, Pederson TR, Kjekshus J, et al. Diabetes Care 20: 614; 1997.
17. Sacks FM, Pfeffer MA, Moye LA, et al. N Engl J Med 335: 1001; 1996.
17a. Haffner SM, et al. N Engl J Med 339, 229, 1998.
18. Cryer PE, Fisher JN, Shamoon H. Diabetes Care 17: 734; 1994.
19. Burge MR, Schmitz-Firentino K, Fischett C, et al. JAMA 279: 137; 1998.
20. Weir GC, Nathan DM, Singer DE. Diabetes Care 17: 1514; 1994.
21. Franz MJ, Horton ES, Bantle JP, et al. Diabetes Care 17: 490; 1994.
22. Schafer RG, Bohannon B, Franz M, et al. Diabetes Care 20: 96; 1997.
23. Clement S. Diabetes Care 18: 1204; 1995.
24. Funnell MM, Haas LB. Diabetes Care 18: 100; 1995.
25. American Diabetes Association. Maximizing the role of nutrition in diabetes management, Amer-
ican Diabetes Association, Alexandria, 1994, ch 5, 6.
26. Hoeer JH, Green-Pastors J. Diabetes Medical Nutrition Therapy. American Diabetes Association,
Alexandria, 1997, ch 3.
27. Maggio CA, Pi-Sunyer FX. Diabetes Care 20: 1744; 1997.
28. American Diabetes Association. Diabetes Care 23(1): 27S; 2000.
29. Thomas-Dobersen D. Clinical Diabetes 17: 179; 1999.
30. Franz MJ, Horton ES, Bantle JP, et al. Diabetes Care 17: 490; 1994.
31. Karlsen M, Khakpour D, Thomson LL. Clinical Diabetes 14: 54; 1996.
32. Henry RR. Diabetes Care 17: 1502; 1994.
33. Warshaw H, Franz M, Powers MS. Diabetes Care 19: 1294; 1996.
34. Mooradian AD, Failla M, Hoogwerf B, et al. Diabetes Care 17: 464; 1994.
35. Wheeler ML, Franz M, Heins J, et al. Diabetes Care 17: 489; 1994.
37. Wasserman DH, Zinman B. Diabetes Care 17: 924; 1994.
38. Schneuider SH, Ruderman NB. Diabetes Care 13: 785; 1990.
40. American Diabetes Association. Diabetes Advocate (Newsletter) January, 2000.
41. Kulkarni K, Castle G, Gregory R, et al. J Am Diet Assoc 98: 62; 1998.
54
Nutrition and Oral Medicine
Dominick P. DePaola, Connie Mobley, and Riva Touger-Decker
Introduction
In the Spring of 2000, the Surgeon General of the United States released the first-ever
report on “Oral Health in America.” The intent of this landmark report is to alert the
American people to the full meaning of oral health and its importance to general health
and well being. The report has five major themes:1
1. Oral health means much more than healthy teeth.

2. Oral health is integral to general health.
3. Safe and effective disease prevention measures exist that everyone can adopt to
improve oral health and prevent disease.
4. General health risk factors, such as tobacco use and poor dietary practices, also
affect oral and craniofacial health.
5. There are significant oral health disparities among racial and ethnic minority
population cohorts.
The overlying theme is that the etiology and pathogenesis of diseases and disorders
affecting the craniofacial structures are complex and multifactional, involving an interplay
and interaction among genetic, environmental, and behavioral factors. The major envi-
ronmental factor in this interplay is diet and nutrition during development of the cranio-
facial complex, the maintenance of craniofacial structure integrity, and fending off
subsequent microbial challenge. In fact, the two classic dental diseases, caries and peri-
odontal disease(s), both have vital nutrition and dietary components. Caries is intimately
linked to adequate nutrient intake during development of teeth and salivary glands, and
to the frequent ingestion of fermentable carbohydrates post-eruption. Periodontal disease
is generally considered to be caused by bacterial plaque residing on the tooth structure,
but the inflammatory response can be modulated by adequate systemic nutriture. In terms
of craniofacial disorders, cleft lip and palate — among the most common birth defects
affecting humans — are linked, in part, to adequate folate nutriture during critical periods
in craniofacial development, much the same way that neural tube defects are linked to
0-8493-2705-9/02/$0.00+$1.50
folate nutriture. Importantly, the diet and nutrition relationship to oral, dental, and cran-
iofacial diseases is much more extensive than those classic illustrations. For example,
systemic disease resulting from infectious oral microbes is generally recognized to occur
in patients with immunological and nutritional deficiencies such that individual host
defenses are compromised, allowing oral microbes to gain systemic access.2 In turn, the
oral, dental, and craniofacial tissues are the sites of signs and symptoms of about 120
systemic diseases.1 Additionally, changing demographics suggest that an aging population
will increasingly present medically significant oral problems.1
This section reviews the relationship between nutrition and oral, dental, and craniofacial
diseases and disorders, the nutrient-tissue interplay, and, where appropriate, prevention,
treatment, or intervention strategies using diet and nutrition. The section begins with an
illustration of the burden of oral disease and proceeds to discuss chronic oral infectious
disease (caries, periodontal disease, others); selected systemic diseases; neoplastic diseases;
craniofacial-dental-oral birth defects; and health promotion, health education, and behav-
ioral change.
The Burden of Oral Disease

Dental, oral, and craniofacial diseases and disorders are among the most common of
human maladies, with widespread tooth loss due to caries and periodontal disease. Dental
caries, in particular, disproportionately affects low socioeconomic populations and some
racial/ethnic minorities. Additionally, oral and pharyngeal cancer results in over 12,000
deaths per year and has one of the worst morbidity and mortality rates of any cancer.
Birth defects, particularly cleft lip and/or palate, are highly prevalent, as are a variety of
chronic and disabling diseases and disorders, the oral complications of systemic diseases,
and the oral complications of those interventions and medications consequent to treating
systemic disease. Figure 54.1 illustrates the burden of disease according to the most recent
NIDCR data.1,3
Chronic Oral Infectious Disease

Dental Caries
In spite of a substantial reduction over the last 20 years, dental caries continues to be a
major problem for adults and children worldwide. For example, a 1988 to 1991 survey of
the U.S. population showed that over 45% of children and adolescents in the 5- to 17-year
age group had carious teeth.4 In adults, over 93% had evidence of caries, with an increasing
incidence of root caries with age.5 The impact of dental caries on pain and suffering remains
profound. The Surgeon General’s Report estimates that 51 million school hours are lost
each year to dental related illness, and in adults more than 164 million work hours are
lost each year for dental related illness or treatment.1
The etiology of dental caries is well documented and results from the interplay of dental
plaque present on the tooth surface with ingested fermentable carbohydrates. Many stud-
ies have documented that a demineralization-mineralization equilibrium occurs at the
tooth-plaque-saliva interface, where the equilibrium balance favors demineralization
Birth Defect Edentulism - Total Loss of Teeth Trauma Periodontal Diseases
• Cleft lip/palate births estimated at 1 • 11% of adults 25 and older have lost • 19.8 Million emergency room visits • 90% of people 13 and older show
in 600 for whites and 1 out of 850 for all natural teeth; the rate is 17% for are estimated for craniofacial injuries evidence of periodontal problems
African Americans adults living in poverty each year • Maternal periodontal infection
• 30% of adults 65 and older are • Motor vehicle crashes are leading appears associated with increased
Dental Caries toothless; the rate is 46% for those in cause of unintentional injury deaths risk of spontaneous pre-term birth
• 5-10% of pre-school age children have poverty in children, with majority resulting and low birth weight
early childhood caries; rates are from head injuries • Periodontal infection appears to be a
substantially higher in low income Head and Neck Cancer • 25% of people age 6-50 show risk factor for cardiovascular diseases
Nutrition and Oral Medicine
families and some racial/ethnic • 12,300 deaths and 40,400 new cases evidence of anterior tooth trauma and stroke
minorities per year for oral, pharyngeal and
• 19% of all young children age 2-5 laryngeal cancers combined Pain Oral Complications of Cancer
have untreated caries in primary • Five years after diagnosis, half of all • 22% of adults report some form of Therapy
teeth; the rate is 30% for children patients with oral and pharyngeal orofacial pain in last 6 months • Each year an estimated 490,000
living in poverty cancers survive; less than a third of • 6% of adults report pain symptoms patients undergoing cancer therapy
• 45% of school children and 94% of African American male patients commonly associated with suffer from such complications as
adults have experienced caries in survive that long temporomandibular joint disorders painful mouth ulcers, mucositis,
permanent teeth (TMD) rampant caries, fungal infections,
• 5x more common than asthma and 7x Osteoporosis & Oral Bone Loss • Orofacial pain is a major component impaired taste, and salivary gland
more common than hay fever • Osteoporosis is a major health threat of Bell’s palsy, trigeminal neuralgia, dysfunction
for 28 million Americans, 80% female fibromyalgia, and diabetic
Dental Orthopedics • Oral bone loss is also found in neuropathy Older Adults
• 20% of adults and 18% of children patients with osteoporosis • About 30% of adults 65 years and
have mild to severe malocclusions older are edentulous
requiring orthodontic treatment Salivary Gland Dysfunction • 23% of 65- to 74-year-olds have severe
• Between 1 and 4 million Americans periodontal disease
Candidiasis are estimated to have Sjögren’s • Most older Americans take
• Candidiasis is the most common oral syndrome medications which have oral side
fungal infection in patients with • Cystic fibrosis affects about 30,000 effects, especially dry mouth
immunodeficiency disorders, such as Americans. More than 500
HIV infection prescription and over-the-counter
drugs have xerostomic effects
FIGURE 54.1
The burden of disease. From: NIDCR (www.nih.nidcr.gov) 1999 and Surgeon General’s Report, 2000.
1115
Protective Factors Pathological Factors
Salivary flow and components Reduced salivary function

Proteins, antibacterial components, Bacteria: mutans streptococci,
and agents lactobacilli
Fluoride, calcium, and phosphate Dietary components: frequency
Dietary components: protective carbohydrates
No Caries Caries
FIGURE 54.2
The caries balance: a schematic diagram of the balance between pathological and protective factors in the caries
process. From: Featherstone, J.D.B., J. Amer. Dent. Assoc. 131: 887; 2000. With permission.
when the plaque pH drops, such as when carbohydrates (sugars) are fermented by plaque
bacteria to form organic acids.6 Mineral flows back when the pH is neutralized mostly
due to the presence of salivary buffers and mineral ions, particularly when supplemented
with fluoride.6 Fluoride, when ingested at optimum amounts during tooth development
(about 0.7 to 1.0 ppm), makes the enamel hydroxapatite crystal less soluble. Additionally,
individuals with hyposalivation or xerostomia due to use of specific medications, head
and neck irradiation, or chronic diseases like Sjögren’s syndrome, lack appropriate salivary
buffering capacity and thus have increased risk for caries.7
In a recent review, Featherstone illustrated that caries balance is dependent on the
interaction of protective and pathological factors (Figure 54.2).6 Dental caries represent an
excellent example of how understanding the complex etiological agents of this multifac-
torial disease can have health promotion, intervention, and treatment consequences that
can effect not only the disease itself, but the intricate interactions between health and
nutritional status. As shown in Figure 54.3, the balance between health and disease in the
oral and craniofacial complex is dependent on food choices and dietary patterns interwo-
ven with nutritional and oral health status. Furthermore, there is a synergy between these
two measures of health, (nutriture and oral status) that has a significant impact on general
health and thus individual risk for many contemporary chronic and disabling diseases. If
dietary intake leads to poor nutritional status, chronic disease is more likely to occur in
the presence of additional risk factors that might include other lifestyle, environmental,
and genetic factors.
Periodontal Disease(s)
Periodontal disease is an infection with local and systemic inflammatory effects. The
initiation and progression of periodontal disease is markedly affected by risk factors. The
relationship between nutrition and periodontal disease is multifaceted, where environ-
mental and host risk factors contribute to its pathogenesis. Some of the host factors related
to diet and nutrition include presence of other systemic or chronic disease, lifestage (preg-
Nutrition and Oral Medicine 1117
ORAL Health NUTRITIONAL

Tooth Status
Integrity Status
ORAL
Remineralization FUNCTIONAL
LIMITATIONS
Nutrient
Adequacy
Demineralization
Food Choices
Topical and
Effect Dietary Patterns
Bacteria
Fluoride
Saliva
FIGURE 54.3
Diet and dental health.
nancy, menopause, elderly, etc.), osteoporosis, medications, and nutrition status. The cur-
rent knowledge of nutrition and periodontal disease can be viewed in one of three ways:
1. Known relationships between periodontal disease, nutrition status, and immune

response
2. Relationships of periodontal disease with nutrients that have been demonstrated
in select populations
3. Unknown and yet to be tested relationships between periodontal disease, indi-
vidual nutrients, and select host defense and health status variables
Known relationships include the impact of malnutrition on inflammation and infection,

and the associations between calcium and periodontal disease. A superb overview of the
new paradigm for the pathogenesis of periodontitis was provided recently by Page and
Kornman, and is depicted in Figure 54.4.8
Nutrient deficiencies can compromise the system’s response to inflammation and infec-
tion and increase the kcalories and protein needs necessary for adequate wound healing.9
In this manner, poor nutritional status can impact host response to the inflammatory
process and infection imposed by periodontal disease. A balanced diet along with good
nutrition status is the appropriate nutrition management strategy for nutritional wellbeing
Environmental and
acquired (behavioral)
risk factors
Antibody Cytokines and

prostanoids
Polymorpho- Host immuno- Connective Clinical signs
Microbial nuclear inflammatory tissue and of disease and
challenge neutrophils response bone progression
metabolism
Antigens Matrix
metallo-
proteinases
Lipopoly-
saccharide
virulence
factors
Genetic risk factors
FIGURE 54.4
A new paradigm for the pathobiology of periodontitis. From: Page and Kornman, 1997, Periodontology 2000,
14: 9; 1997, with permission. Reprinted in Surgeon General’s Report.
to reduce risk of malnutrition-associated compromises in immune and inflammatory

responses and wound healing.
Relationships between periodontal disease, osteoporosis, and calcium intake is pre-
sented elsewhere in this section. Krall et al. have demonstrated that osteopenia and bone
loss are associated with oral bone loss.10 Treatments for osteoporosis, including hormone
replacement therapy and biphosphanides, are associated with reduced oral bone and
tooth loss. The relationship between calcium and vitamin D and incidence of periodontal
disease remains to be demonstrated in broader gender- and age-related populations. The
need for adequate calcium in the diet (either with foods and/or supplements) is impor-
tant for prevention and management of osteopenia and osteoporosis as well as for
periodontal disease.
The relationship between various antioxidants and periodontal disease is a developing
area of research. Nishida et al. demonstrated that low dietary intake of vitamin C was
significantly (although “weakly”) associated with periodontal disease in individuals who
currently smoke or have a history of smoking tobacco.11 However, vitamin C has not
been proven efficacious for improving periodontal health or reducing risk of disease in
the general population.11 Several studies have implicated deficiencies in ascorbate and
folate with severity of gingivitis. For example, Leggott demonstrated that depletion of
vitamin C was associated with increased gingival bleeding but no other markers of
periodontal disease.12
The relationship between diabetes and periodontal disease is discussed elsewhere. How-
ever, the potential relationship between obesity and periodontal disease is a new area for
investigation. In a study of obese, healthy Japanese men undergoing evaluation of peri-
odontal status, there was a positive association between degree of obesity, as measured
by body mass index, and incidence of periodontal disease.13 After adjusting for age, sex,
oral hygiene status, and smoking, the relative risk of periodontal disease was 1.3 for each
5% increase in body mass index.13 Although type 2 diabetes is a recognized risk factor for
periodontal disease, there was no association in this study between fasting blood glucose
or glycosolated hemoglobin values and periodontal disease.13 Further research is needed
to explore relationships between obesity and periodontal disease, particularly in individ-
uals with diabetes, a disease in which obesity can further compromise metabolic control.
Changes in oral tissues associated with aging can also impact periodontal status. Alve-
olar bone loses approximately 1% per year after age 30, and tooth mobility occurs more
frequently in the elderly.1 Soft tissue changes include thinning of the surface epithelium
of the mucus membranes and gingival recession. Decreased salivary flow, most often
secondary to medications or disease, is also common. These changes can also impact on
nutrition status and eating ability. If severe, diet intake and nutrition status can suffer.
The combined changes in the oral cavity increase the risk for nutrient intake compromise
and periodontal disease.
Consumption of a balanced diet consistent with the food guide pyramid and inclusive
of fruits, vegetables, grains, and adequate protein will provide sufficient vitamins, minerals,
phytochemicals, and protein for overall and oral health. At this point, no published scien-
tifically sound evidence exists to support the notion that individuals with periodontal
disease need supplemental doses of any individual nutrients or groups of nutrients.
Environmental Oral Health Promotion: Fluoridation

In the early 1900s, Americans could expect to lose their teeth by middle age. With the
discovery of the properties of fluoride and the adjustment of the concentration of fluoride
in the supply of drinking water in the 1940s, this trend was reversed. Community water
fluoridation remains one of the great achievements of public health and health promotion
in the 20th century.14 It is considered an inexpensive means of improving oral health
benefits for all residents of a community. In 1992, 56% of the U.S. population was receiving
fluoridated water at levels equal to or greater than 0.7 parts per million, either from natural
or fluoridated public water systems. Dental caries prevention is effective at 0.7 to 1.2 part
per million.14 Some foods, beverages, and other dental products provide additional sources
of fluoride to individuals.
Since the early days of community water fluoridation, the prevalence of dental caries
in the U.S. has declined in communities with and without fluoridated water. This has been
largely due to the diffusion of fluoridated water to areas without fluoridated water via
food/beverage distribution channels and the widespread use of fluoride toothpaste.15
Although early studies focused mostly on children, water fluoridation also reduces enamel
caries in adults by 20 to 40%, and prevents root surface caries, a condition that particularly
affects older adults.1,16
Health care providers are agents of health promotion at both individual and community
levels. In the absence of a water supply with adequate fluoride to prevent dental caries,
health promotion practices that support primary prevention through fluoride supplemen-
tation are encouraged. The American Dental Association Council on Scientific Affairs17
and the American Academy of Pediatrics18 recommend safe levels of daily fluoride sup-
plementation for children living in unfluoridated communities. Table 54.1 describes the
recommended supplementation schedule. Dietary fluoride supplements are available as
tablets, drops, or lozenges. Supplementation has not been shown to be beneficial during
pregnancy.19,20 Flouridation is an inexpensive means of improving oral health, and benefits
all residents of a community.
TABLE 54.1
Supplemental Fluoride Dosage Schedule (mg/day)a
Concentration of Fluoride in Drinking Water (ppm)
Age < 0.3 0.3 to 0.6 >0.6
6 months to 3 years 0.25 mg 0 0
3 to 6 years 0.50 mg 0.25 mg 0
6 to 16 years 1.00 mg 0.50 mg 0
a ppm = parts per million; 2.2 mg sodium fluoride contains 1 mg fluoride.
From American Dental Association, J. Am. Dent. Assoc. 126: 19S; 1995. With
permission.
Systemic Diseases
General Observations
The oral cavity is the gateway to the rest of the body, and at times reflects systemic as
well as oral health and disease.1 The mechanisms by which oral manifestations occur as
a result of some systemic diseases are not fully known. Systemic diseases which affect the
integrity of the oral cavity, and oral diseases themselves, may impact upon nutrition status,
as well as the converse. Any condition affecting the functional capacity of the oral cavity
(sensory or motor function) and/or the health and integrity of the soft tissue may impact
on diet intake. If the integrity of the oral tissues is compromised due to infection, surgery,
trauma, or medications, nutrient needs are increased. Unfortunately, this is often in the
face of compromised intake due to pain, dysphagia, or anorexia. In these situations,
nutrition status is compromised and the risk of malnutrition is increased. Malnutrition in
turn can compromise wound healing and integrity of the immune system, further increas-
ing the risk of oral infectious disease.
Emerging areas of research in dentistry in the 21st century include the relationships
between oral infections and systemic diseases, and the oral manifestations and complica-
tions of systemic diseases and chronic disabling diseases.2 It is anticipated that when fully
appraised of these oral health–systemic health and nutrition interactions, health care
professionals will be able to work collectively to identify dental and nutrition patient
management strategies.
It is well documented that nutritional status may influence disease progression and
recovery from illness, infection, and surgery. Malnutrition and individual nutrient defi-
ciencies can affect tissue integrity and muscle function. A selected list of chronic diseases
with recognized oral manifestations affecting nutrition status, and diseases with associated
oral infections are listed in Table 54.2. Nutrition status may be affected via two primary
mechanisms, functionally and metabolically, both of which can effect the sense of taste.
Additionally, functional integrity of the oral cavity is critical for optimal smell, mastication,
and swallowing; negative impacts on any of these functions can influence food and fluid
intake, and consequently nutrition status. Metabolic impacts also include altered nutrient
metabolism, typically increased catabolism of protein stores for energy, as well as increased
protein and kcalorie needs due to infection. The end result of either a functional or
metabolic mechanism(s) is often compromised nutrition status, increased risk of secondary
infection, and altered response to disease and treatment. Weight loss of 10% or more,
which can occur as a result of these diseases, increases morbidity and mortality.
TABLE 54.2
Selected Systemic Diseases with Potential Oral
Manifestations Affecting Nutrition Status
Arthropathies Autoimmune disorders
Cancers Chronic orofacial pain
Cardiovascular disease Diabetes
End-stage renal disease HIV infection/AIDS
Inflammatory bowel disease Liver disease
Megaloblastic anemia Oral-facial pain syndromes
Osteoporosis Pulmonary disease
Vesiculobullous diseases Herpes Zoster
TABLE 54.3
Medications with Associated Oral Manifestations
Anticonvulsants Antipsychotics
Antidepressants Corticosteroids
Diuretics Immune suppressing agents
Opiates Serotonin uptake inhibitors
Tricyclic antidepressants Protease inhibitors
Anti-anxiety agents
Medications used to treat chronic diseases may also have oral sequellae that in turn
compromise food intake and nutrition status. Xerostomia may occur independently, as a
consequence of another systemic disease, or as a side effect of medication. More than 400
prescribed and over-the-counter medications are associated with xerostomia.1 Xerostomia
can affect sense of taste and swallowing ability as well as caries risk. Food texture and
temperature may need to be modified for individuals with moderate to severe xerostomia.
Drugs may also alter appetite and nutrient metabolism. Antidepressant medications and
steroids can increase appetite, thus leading to increased risk of weight gain and subsequent
obesity. Steroids increase catabolism of protein and carbohydrate, and lead to calcium
losses. Individuals on long-term steroids are at risk for type 2 diabetes, and require calcium
supplementation and added protein in their diets to reduce risk of osteoporosis and
malnutrition, respectively. Classes of medications with oral manifestations are found in
Table 54.3. Individual drugs are not listed; practitioners should check the Physicians Desk
Reference (PDR) for individual drugs and their associated oral manifestations.
Table 54.4 addresses clinical symptomatology with associated oral clinical and systemic
disorders and nutritional implications. Clinical features may represent one or more local
and systemic diseases. It is imperative that clinicians look beyond the symptom to discern
the actual cause of the symptomatology so as to treat the symptoms and the primary
cause or disease. Although select clinical features may have an associated nutritional
etiology, all other causes must be considered, and treatment aimed at the root cause and
associated symptoms.
HIV-AIDS
As of December 1999, there were 33.6 million individuals with HIV/AIDS.21 Estimates
indicated 5.6 million new cases alone in 1999 and 2.6 million deaths worldwide from
AIDS.21 In the U.S., combination antiretroviral therapies have contributed to a decline in
death due to AIDS as well as a reduction in the incidence of complications. Individuals
with immunosuppressive diseases including HIV infection and AIDS are at increased risk
TABLE 54.4
Abnormal Oral Findings: Associated Local and Systemic Diseases
Associated Nutritional
Clinical Feature Associated Finding Disorders Considerations
Xerostomia Excessive dental caries, Drug-induced xerostomia, Increase fluids, minimize
candidiasis, dysphagia, head and neck irradiation, cariogenic foods, modify
dysgeusia, burning Sjögren’s syndrome, food consistency and
mouth/tongue diabetes flavoring, evaluate
glucose control in diabetes
Burning May be associated with Anemia, diabetes, Determine etiology of
mouth/tongue mucosal erythema/ candidiasis anemia (iron, folate, B12),
atrophy, glossitis check riboflavin, modify
food consistency and
flavoring, evaluate
glucose control
Angular cheilitis Dry, cracked, fissured Dehydration, anemia, ill- Determine etiology
corner of the mouth fitting dentures (drooling)
Candidiasis White and/or red Immunodeficiency, Determine etiology
removable patches on the diabetes
oral mucosa
Difficulty chewing Partial or complete Cranial nerve disorders Determine etiology, referral
edentulism, poor for medical nutrition
occlusion, ill fitting therapy
dentures
Adapted from Touger-Decker R, Sirois D. Support Line 3: 1; 1996.
of oral complications and malnutrition due to the disease and associated metabolic, oral,
GI, immune, psychosocial, and pharmacological sequellae. Macronutrient metabolism is
often altered; women lose more fat tissue, further contributing to malnutrition, while men
tend to lose lean tissue, again contributing to malnutrition and increased needs.21 The
psychological and physiological stress associated with HIV and AIDS contributes to alter-
ations in nutrient intake and subsequent nutrition status.
Poor oral hygiene, malnutrition, and lack of dental care are key factors in the develop-
ment and severity of oral lesions in this population. Candidiasis occurs in 80 to 100% of
HIV patients with AIDS upon onset of the disease.3 Periodontal disease including necro-
tizing ulcerative periodontitis (NUP) is common in patients with HIV. Cancers of the oral
cavity, Kaposi’s sarcoma, and lymphoma may also occur. Thus, oral challenges, combined
with common nutrition problems such as wasting syndrome, visceral and somatic protein
depletion, maldigestion and malabsorption, altered nutrient and energy needs, polyphar-
macy, and reduced oral food intake secondary to anorexia, nausea, or compromised oral
health status further contribute to the malnutrition observed in this population.
The possible causes of anorexia in this population can be seen in Table 54.5. Medical
Nutrition Therapy (MNT) by the Registered Dietician (RD) and physician is warranted to
prevent further nutritional depletion, altered taste perception, odynophagia/dysphagia,
TABLE 54.5
Possible Causes of Anorexia in HIV/AIDS
Polypharmacy Dysgeusia
Odynophagia/dysphagia Nausea/vomiting
Depression Weakness/lethargy
Oral infections/lesions Tooth loss
GI disease Kaposi’s sarcoma
TABLE 54.6
Impact of HIV Infection on Nutrition and Diet in the Upper GI Tract
Location Problem Effect Diet Management
Oral cavity Candidiasis, KS herpes, Pain, infection, lesions, Increase kcalories & protein
stomatitis, apthous ulcers altered ability to eat, saliva; Oral supplements
dysgeusia Caries risk reduction
Xerostomia Caries risk, pain, no Moist, soft foods; non-spicy,
moistening power, food “smooth,” cool/warm, fluids
sticks, dysgeusia Caries risk reduction
Esophagus Candidiasis, herpes, KS, Dysphagia, odynophagia Oral supp 1st, 2nd = NG using
Cryptosporidius silastic feeding tube or PEG
CMV CMV + ulceration Dysphagia, food Percutaneous endoscopic
accumulation gastrostomy
nausea/vomiting, psychosocial considerations, weakness/lethargy, and the expanded use

of other medications.
Wasting syndrome is characteristic of later stages of HIV and is defined as “a greater
than (>)10% unintentional weight loss from usual body weight in the presence of diarrhea
or fever for greater than (>) 30 days that is not attributable to other disease processes.”22
Wasting Syndrome is also defined as “a process of decline characterized by pathological
alterations in body composition, weight loss, fatigue and loss of strength and a decrease
in quality of life.”23 The pathogenesis of wasting can be attributed to several factors
including decreased energy intake, anorexia, GI dysfunction, and deranged metabolism
including increased insulin sensitivity, altered carbohydrate metabolism, and increased
protein turnover. During acute phases of the disease, drugs and medical nutrition therapy
are critical to manage the disease and preserve lean body mass. As individuals progress
to lifelong drug management with combinations of antiretroviral therapies, nutrition status
is challenged by the associated drug side effects. These side effects may include food-drug
interactions, oral lesions, and infection as well as alterations in appetite and intake.
Table 54.6 outlines the impact of HIV infection in the GI tract. Common HIV-associated
oral infectious disorders include those of fungal, viral, and bacterial origin, detailed in
Table 54.7.24 Oropharyngeal fungal infections may cause a burning, painful mouth and
dysphagia. The ulcers found with viral infections such as herpes simplex and cytomega-
TABLE 54.7
Common HIV-Associated Oral Disorders
Infection
Bacterial Linear erythematous gingivitis, necrotizing ulcerative periodontitis, syphilis, caries

Fungal Candida, cryptococcus, histoplasmosis
Viral Herpes simplex, hairy leukoplakia, human papiloma
Neoplasm
Fungal Kaposi’s sarcoma

Viral Non-Hodgkin’s lymphoma
Other
Fungal Parotid disease, xerostomia, apthous ulcers

Viral Pain syndromes, necrotizing stomatitis
Adapted with permission from D. Sirois, Mt. Sinai J. Med. 65: 322; 1998.
TABLE 54.8
Oral Manifestations of Diabetes
Gingivitis Altered taste
Periodontal disease Burning mouth
Reduced saliva (with resultant xerostomia) Increased thirst
Salivary hyperglycemia Neuropathies
Increased risk of infectious disorders and complications
Slowed wound healing
lovirus cause pain and reduced oral intake. Oral and esophageal candidiasis results in
painful chewing, sucking, and swallowing, consequently reducing an already compro-
mised appetite and intake. Kaposi’s sarcoma compromises oral intake and increases nutri-
ent needs. The oral disorders found with HIV and AIDS increase nutrient demands on
the body for healing, and compromise eating ability. MNT is critical to healing and
maintenance of lean body mass. Oral diets with or without nutritional supplements should
be tried first, followed by tube feedings if needed. The dental professional should observe
patients for changes in intake, weight, and overall nutritional wellbeing, and refer indi-
viduals to an RD and/or physician early in the process of disease management.25,26
Diabetes
Over 11 million individuals in the U.S. have diabetes; another 13 million have impaired
glucose tolerance.27 Diabetes is the seventh leading cause of death in the U.S. Oral sequellae
occurring with diabetes are usually a result of poorly controlled diabetes, or hyperglyce-
mia. Oral cell metabolism, immune surveillance, and vascular integrity as well as salivary
chemistry may be altered in individuals with diabetes, particularly when uncontrolled.
Over 90% of individuals over age 13 with diabetes have some periodontal problems
relative to diabetes.28 While there is limited evidence that periodontal infection affects
glycemic control,29 any infection can contribute to adverse alterations in glycemic control.
Other oral manifestations may occur, impacting diet intake and nutrition status. These
can be seen in Table 54.8.
Diabetes, particularly when poorly controlled, is associated with a higher prevalence of
all infections including oral infections, as compared to non-diabetics.28 The susceptibility
to periodontal disease in diabetes is likely directly related to impaired defense mecha-
nisms. Micro- and macrovascular circulation are altered, along with wound healing, col-
lagen metabolism, neutrophil chemotaxis, and proteolysis. Pathologic tissue destruction
contributes to periodontal tissue destruction. Increased salivary glucose increases bacterial
substrate and plaque formation. Microangiopathies, altered vascular permeability, and
metabolic alterations may lead to an altered immune response and precipitate periodontal
disease progression. The oral complications associated with diabetes are often referred to
as the sixth major medical complication of diabetes.
The relationship between oral manifestations in diabetes and diet/nutrition is a complex
two-way street. While uncontrolled diabetes is partly due to poor diet management, oral
manifestations challenge and ultimately compromise eating ability and consequent dietary
intake. Taste in patients with diabetes is often altered due to salivary chemistry, xerostomia,
and/or candidiasis. Management of burning mouth/tongue requires a determination of
the cause. When due to a nutrient deficiency, augmentation of the diet with the appropriate
nutrient(s) or supplements will treat the cause and subsequent symptomatology. When a
physical or biochemical abnormality cannot be found, the symptoms of burning mouth
can be improved using tricyclic antidepressant medications. However, the unfortunate
side effect of tricyclic antidepressants is xerostomia, which may compound any existing
alterations in saliva, and increase risk of candidiasis and dental caries.
Diet management is the cornerstone of diabetes care. Proper diet control, in kcalorie
and macronutrient distribution throughout the day, is critical to glycemic control, partic-
ularly in type 1 diabetes. In both type 1 and type 2 diabetes, a diet consistent with the
food guide pyramid consisting of 50% carbohydrate, 20% protein, and 30% fat is recom-
mended with attainment and maintenance of desirable body weight. In most states, MNT
by an RD with several follow-up visits is a benefit covered by all third party payers and
Medicaid. The oral health professional should work closely with the patient’s physician
and refer patients, as appropriate, to an RD, reinforce the need to adhere to the diabetic
diet, integrate oral hygiene into daily routines, and modify diet consistencies as needed
to manage oral conditions and surgeries.
Crohn’s Disease
Crohn’s disease can present with apthous ulcers, angular stomatitis, and/or glossitis. Oral
lesions present on the lips, gingiva, and buccal mucosa may precede gastrointestinal
symptoms and have a dramatic impact on oral function. The size of the lesion may not
coincide with the intensity of pain reported or degree of compromise in food and fluid
intake. Ability to eat may be hampered by pain; topical anesthetic agents (or a 1:1 mixture
of Milk of Magnesia and Benadryl as a rinse and spit) prior to meals may temporarily
relieve pain and allow more comfort in eating. Pharmacological management is critical;
steroids are often needed. The impact of steroids on nutritional wellbeing has been
addressed in other sections of this handbook.
Autoimmune Disease
Autoimmune diseases such as Pemphigus Vulgaris (PV) increase nutrition risk by virtue
of the oral and facial sequellae of the disease and the medications used to manage it.
Steroids are often used in the management of vesiculobullous diseases of the oral cavity
including PV. PV can impact diet intake and nutrition status by virtue of the disease
process as well as the medications used to manage it. Much like other diseases with oral
lesions, PV affects appetite and eating ability due to associated pain. In addition to the
medications used for the disease, topical anesthetics, as well as a rinse-and-spit 1:1 mixture
of Benadryl and Milk of Magnesia immediately prior to eating, provides a topical coating,
allowing more comfort during mealtime. Other autoimmune diseases including Sjögren’s
Syndrome and rheumatoid arthritis (RA) can affect the oral cavity and subsequent nutri-
tion status. Oral and nutritional implications of select diseases in this category are outlined
in Table 54.9. While diet modifications are addressed, particular attention needs to be paid
to the individual’s stage of disease. During disease exacerbation, eating ability may be
severely compromised and a liquid diet using oral supplements (meal replacement for-
mulas) such as Sustacal or Boost (Mead Johnson) or Ensure+ (Ross) may be required to
meet energy and protein needs. During remission, individuals may be able to liberalize
diets considerably.
Osteoporosis
Osteoporosis is the most common bone disease.30 Osteoporosis is clinically defined as
reduced bone mineral density.30 The majority of individuals with osteoporosis are women
TABLE 54.9
Autoimmune Disorders with Associated Oral and Nutritional Side Effects
Disease Oral Manifestation Nutrition Implications
Rheumatoid arthritis TMJ ankylosis Pain upon eating
Limited mandibular opening Modify diet consistency
Erythema multiforme Oral mucosal lesions, often Pain upon eating
ulcerative Increased needs for healing
Modify diet, often liquid
consistency with straw during
exacerbation
If treated with steroids: increase
calcium, protein
Pemphigus Vulgaris Oral mucosal lesions Eating painful and difficult
If treated with steroids: increase
calcium, protein
Modify diet as needed in
temperature, consistency
Sjögrens syndrome Xerostomia; mucosa dry, Increased fluids with and between
erythematous; fissures; more meals, increase fluidity of foods,
susceptible to trauma; soft, temperate foods, non-spicy
increased risk of caries; fissured
tongue; periodontal disease;
cervical caries
Systemic lupus Ulcerations of mucosa Manage side effects of steroids and
erythematosus medications, diet as per Sjögrens
(80%); however it is a risk for up to 28 million Americans, and is often known as a “silent
killer.”1 One in two caucasian women will have an osteoporotic fracture in their lifetime.30
Nonmodifiable and modifiable causes of osteoporosis are listed in Table 54.10. Since dental
health care professionals see patients on a regular basis and since alveolar boss loss is
associated with osteoporosis, the dental professional is in an ideal situation to access
patients at risk for osteoporosis. Simple screening in the dental office can include asking
patients about calcium intake in the form of dairy products (milk, cheese, yogurt), func-
tional foods or foods fortified with calcium (orange juice, cereal), and calcium supple-
ments. Other individuals at risk for osteoporosis (see Table 54.10) should be referred for
a dexascan to determine risk for or presence of osteopenia or osteoporosis.
Bone loss is a common denominator for both periodontal disease and osteoporosis. The
relationship between the two diseases remains to be fully determined.31 However, an
association between periodontal disease and systemic osteopenia and osteoporosis has
been documented in adults.31,32 The relationship between calcium intake and risk of peri-
odontal disease has also been demonstrated; lowered dietary intakes in adults have been
found to be associated with increased periodontal disease risk.11 While a serum calcium
level may not be associated with actual calcium intake, decreasing levels of intake below
the recommended dietary intakes is associated with increased risk and incidence of
osteoporosis.33 Tezal et al. pose “four possible pathways” for the relationship between
osteoporosis and severity of periodontal disease, including systemic loss of bone mineral
density, modified local tissue response to infection as a result of “systemic factors of bone
remodeling”, genetics, and lifestyle factors.31 The final pathway, lifestyle factor, links the
issues of hygiene, diet, and exercise with local and systemic disease. Osteoporosis has also
been linked to the development of tooth loss, particularly in post-menopausal women.10
Please refer to Section 61 for a thorough description of osteoporosis and other bone
diseases and disorders.
TABLE 54.10
Risk Factors for Osteoporosis
Nonmodifiable
History of fracture as an adult

Caucasian or Asian race
Advanced age
Female gender
Dementia
Poor health/frailty
Prolonged use of glucocorticoids, phenytoin
Estrogen deficiency:
Menopause/early menopause (<age 45) or bilateral ovariectomy; prolonged
premenopausal amenorrhea (>1 year)
Prolonged immobilization, i.e., spinal cord injury
Potentially Modifiable
Current cigarette smoking

Low body weight (<127 lbs)
Low calcium intake (lifelong)
Alcoholism
Impaired eyesight despite adequate correction
Recurrent falls
Inadequate physical activity
Poor health/frailty
End-stage renal disease
From National Osteoporosis Foundation, Physicians Guide to Prevention and
Treatment of Osteoporosis, 1998. With permission.
Neoplastic Diseases: Oral Cancer

Oral cancer develops from a precancerous lesion most commonly on the tongue, lips, and
floor of the mouth. White leukoplakia or reddish erythroplakia are usually induced by
tobacco use alone or in combination with alcohol abuse.34,35 It is the sixth most common
cancer in males living in the U.S. Over 90% of oral cancers are squamous cell carcinomas
— cancers of the epithelial cells. Tobacco components act as promoters of carcinogenesis,
and alcohol may act as a solvent to facilitate penetration of the tobacco carcinogens into
oral tissue.36 Viruses, including the herpes simplex type 1 and human papilloma virus,
have both been implicated in oral cancer. Of the known oncogenes, many have been
implicated in oral and pharyngeal cancer.37 Both disarmament of the cell’s DNA repair
mechanisms and mutation of tumor suppressor genes have been linked to smoking and
alcohol use, and play a major role in oral cancer development. Likewise, nicotine stimu-
lates negative changes in immune cells that can promote tumor growth.
Ecologic and case-control studies have suggested that nutrients may play an important
role in the prevention and management of early oral cancer and precancerous leukoplakia.
Likewise, several studies have shown that smokers have lower plasma levels of vitamin
E, C, beta-carotene, and other antioxidants due to both low intake and increased metabolic
use.38 Total fruits and vegetables, fresh fruits, green leafy vegetables, other vegetables,
total bread and cereals, and whole grain breads and cereals which are excellent sources
of multiple antioxidants have been shown to be associated with decreased risk of oral
cancer.39 More specifically, citrus, dark yellow and other fruits were more consistently
associated with decreased risk than were estimated intake of specific nutrients including
carotene, vitamin C, fiber, folate, thiamine, riboflavin, niacin, vitamin E, and iron. A case-
control study conducted in Italy illustrated that the more a micronutrient, such as vitamin
C, carotene, or vitamin E, was correlated to total vegetable and fruit intake, the stronger
was its protective effect against oral cancer.40 Thus, it appears that total fruit and vegetable
intake may offer greater risk reduction than singular antioxidant nutrients in supplemental
doses. Fioretti et al. reported that even in the absence of tobacco use, if subjects reduced
alcohol and saturated fat intake and increased fruit and carrot consumption, there
appeared to be a favorable effect on oral cancer risk among subjects who participated in
a large case-control study.41
Nutritional care of the patient with oral cancer will vary based on treatment modalities
and side effects that can include changes in weight, sore mouth or throat, xerostomia,
mucositis, dental caries, gingival infection, changes in sense of taste and smell, nausea,
vomiting, and fatigue. Nutritional management strategies will require the services of
oncology health care professionals.
Craniofacial-Oral-Dental Birth Defects

Nearly two infants in every 1000 live births have some type of craniofacial birth defect.42
These defects can occur in isolation or as a component of a larger birth defect syndrome
caused by genetic influences, environmental disturbances, or the interplay between gene
and environment. A number of congenital oral-dental-craniofacial birth defects can be
prevented by reducing risk factors associated with human craniofacial malformations.
Among the common environmental risk factors are alcohol (associated with fetal alcohol
syndrome); smoking (associated with risk of cleft lip with or without cleft palate); anti-
convulsant medications, such as phenytoin and other teratogens (associated with a variety
of birth defects involving the face, teeth, and jaws); retinoic acid analogues (associated
with severe craniofacial and oral clefts and limb defects); and vitamin deficiency, partic-
ularly folate (associated with increased risk of cleft lip with or without cleft palate).42
Available data from the NIDCR revealed that about 20% of craniofacial-oral-dental birth
defects are either genetic or familial.42 The largest majority are caused by the defined risk
factors noted above or unknown causes. From a nutrition perspective, there are a number
of important discoveries that could be applied to oral-dental-craniofacial defects. One
application relates to the preventive effects of micronutrients. A growing body of evidence
strongly suggests that the use of multivitamin supplements and folic acid result in the
prevention of cleft lip and/or cleft palate in much the same way that these micronutrients
work to prevent neural tube defects such spina bifida. As these studies progress, it will
become important to carefully titrate the dose of the micronutrient provided to an expect-
ant woman that will result in a maximum protective effect. This is vital because there is
a possibility that excessive amounts of some nutrients, such as vitamin A or retinoic acid,
can result in the opposite effect; that is, they could be teratogenic.42,43 Retinoic acid-induced
embryopathy includes defects in craniofacial, skeletal, cardiac, thymic, and central nervous
system structures.42,43
The protective molecular mechanism for retinoic acid-induced embryopathy relates to
the binding of retinoic acid to cognate receptors that, in turn, bind to unique regions
within the promoter region of structural and/or regulatory genes.44 Indeed, the expression
of the homeobox gene, Hoxb-1, is highly responsive to vitamin A. Since Hoxb-1 regulates
embryonic axial patterning, excess vitamin A induces altered pattern formation with
apoptosis.44 Thus, folic acid and vitamin A represent excellent examples of the exquisite
sensitivity of embryogenesis, and the craniofacial complex in particular, to nutrients. A
critical message for the oral health practitioner is the necessity to work closely with the
nutritionist and physician to educate prospective and expectant parents regarding nutri-
tion and oral health.
Importantly, following the birth of a “cleft” child, depending on the extent and severity
of clefting, a series of physiological, psychological, medical, dental, and social issues
emerges. The establishment of a craniofacial anomaly or cleft team to manage patients
with clefting and/or other craniofacial defects is ideal. This multidisciplinary team
assesses the child and his/her various medical, nutritional, social, and psychological
needs. Often a nutritionist/dietician is an integral part of such a team, since one of the
major issues to overcome for such children is the ability to ingest adequate amounts of
food and nutrients consistent with increased nutrient requirements of the early develop-
mental years. These nutrition requirements are exacerbated by multiple surgical interven-
tions and the extent of the defects. Therefore, craniofacial anomalies present two challenges
for the health care professional and the nutrition community in particular. One is to
identify women at risk for birth defects and use appropriate interventions to prevent
craniofacial anomalies. The second is to work closely in an interdisciplinary team to
mitigate the effects of the anomaly.
Health Promotion, Health Education, and Behavior Change

Health promotion is a term used to describe not only heath education but also organiza-
tional, economic, and environmental channels that provide support for enabling people
to increase control over and improvement of their health.45,46 Dental nutrition is an integral
part of general health promotion and disease prevention.
According to health promotion theoretical models, personal health practices and behav-
iors that enhance lifestyle lead to reduced morbidity and mortality, improved health status,
and improved quality of life. Frequently, oral diseases in children are associated with
eating difficulty, general health problems, and even lost school time.47 In aging populations
strong associations exist between oral health status and ability to swallow, chew efficiently,
and select a variety of foods.48 Numerous nutrition and dietary practices enhance positive
oral health outcomes throughout the life span. Thus, it is imperative that dietary intake
provide adequate nutrients to support oral health and function.
Nutrition education programs focused on changing dietary behaviors should include
oral health promotion within the Food Guide Pyramid and U.S. Dietary Guidelines mes-
sages.49 Table 54.11 describes global nutrition messages appropriate for inclusion in oral
health promotion programs targeting primary and secondary prevention of dental caries.
Table 54.12 identifies messages appropriate for early childhood caries (ECC) prevention.
Effort has been made to reduce ECC, particularly in high-risk populations that include
minority and low socioeconomic groups. Unfortunately, the nutrition focus has been
limited to infant feeding practices, promoting early weaning with transition from bottle
to cup and the impression that milk sugar (lactose) is the primary culprit. Sucrose, glucose,
and fructose found in fruit juices and drinks as well as sweetened solid foods are probably
the main sugars associated with ECC.55 Due to the casein as well as calcium and phosphate
TABLE 54.11
Global Nutrition Messages Addressing Primary and Secondary Prevention of Dental Caries
Message Rationale
Eat a balanced diet representing moderation and Focus on positive aspects of healthy eating.
variety Fermentable carbohydrates can contribute to dietary
intake and be consumed in moderation.
Combine and sequence foods to encourage chewing Combinations of raw and cooked foods can increase
and saliva production saliva flow. Protein-rich foods combined with cooked
carbohydrates, and dairy foods combined with
fermentable carbohydrates can alter dental plaque
pH. (Rugg-Gunn, 1993)50
Space the frequency of eating or drinking fermentable It may take up to 120 minutes for dental plaque pH to
carbohydrates at least two hours apart return to neutral after exposure to fermentable
carbohydrate. (Edgar, 1996)51
Chew sugarless gum after meals and snacks to increase The Food and Drug Administration authorized the use
saliva of sugar alcohol containing foods to be labeled “does
not promote,” or “useful in not promoting,” or
“expressly for not promoting” dental caries if the food
does not cause a drop in dental plaque pH below 5.7
when a fermentable carbohydrate is present. (U.S.
Food and Drug Administration, 1996)52
Drink water to satisfy thirst and hydration needs A review of fermentable carbohydrate consumption in
the U.S. identified carbonated beverages as the major
contributor to total intake. (Gibney, 1995)53
content, milk formulas (with the exception of some soy-based and protein hydrolyzed
formulas), bovine milk, and human milk may indeed be cariostatic and not a source of
cariogenic substrate in ECC. However, the nursing bottle can effectively block salivary
access to tooth surfaces and may increase the caries-promoting potential of any food that
remains in the mouth.56 Reisine and Douglass have suggested that psychosocial and
behavioral issues related to elements of the environment may be greater modulators of
ECC than the baby bottle.57
Numerous opportunities exist for nutrition messages to be included in oral health
promotion initiatives. Table 54.13 lists a variety of health topics that impact oral health
outcomes and status. With the advent of The Surgeon General’s Report on Oral Health,
attention has been drawn to the need for health care professionals to address oral health
and systemic health as one entity: health!1 This list in Table 54.13 provides insight into the
aforementioned synergy between oral and nutritional status, and offers targeted messages
for health promotion in public health and private practice.
Better understanding of the role of behavioral variables in health and disease, including
the role of prevention, is important in the delivery of messages that promote both nutri-
tional and oral health status. Practices that attempt to translate the scientific discoveries
in nutrition and oral health will provide a basis upon which to plan and execute future
health promotion activities.
TABLE 54.12
Nutrition Messages to Integrate into Parenting Practices for Primary Prevention of ECC
Message Rationale
Birth to 6 Months of Age
Encourage feeding schedules that encourage breast The American Academy of Pediatrics (AAP)
milk and formula consumption on a regular routine encourages breastfeeding on demand in response to
basis rather than continuously on-demand. signs of hunger, described as increased alertness or
activity, mouthing or rooting.
The American Academy of Pediatric Dentistry (AAPD)
recommend that infants not be put to sleep with a
bottle and that nocturnal breastfeeding should be
avoided after the first primary tooth begins to erupt.
Instruct mothers to avoid introduction of food until The AAP recommends breastfeeding exclusively for
the infant doubles the birth weight or weighs at least about the first six months after birth, after which time
13 pounds. iron-enriched solid foods can be added to
complement the breast milk diet. Infants will double
their birth weight or reach 13 pounds at between 4
and 6 months of age, or approximately 5 months.
Hold the infant when bottle and/or breast feeding. This will prevent bottle propping, prolonged exposure
to caries-promoting substrate, and allowing infants
to drink from bottles on a continuing basis.
6 to 12 Months
Promote weaning from the bottle in combination with The AAPD encourages parents to have infants drink
the introduction of a cup and spoon. from a cup prior to their first birthday and be weaned
from the bottle at 12-14 months of age.
Promote introduction of foods to encourage self- The AAPD recommends implementation of oral
feeding and growth and development as well as hygiene measures by the time of eruption of the first
dental health. primary tooth.
1 to 16 Years of Age
Promote snacking habits that support growth and The AAPD endorses the Dietary Guidelines for
development and dental health. Americans that promote variety, a healthy weight, a
diet that includes vegetables, fruits, and grains, and
use of sugars in moderation for children and adults.
Advocate discontinued bottle and breast feeding
practice.
Stress the value of mealtime and the importance of
variety and moderation.
Encourage the beginning of routine dental visits for The AAPD recommends an oral evaluation visit within
the child. six months of the eruption of the first tooth and no
later than twelve months of age.
American Academy of Pediatrics, Pediatrics 11: 1035; 1997.
Journal of The American Academy of Pediatric Dentistry Reference Manual 1996-97. Pediatr. Dent. 18: 25; 1996.
TABLE 54.13
Nutrition Messages for Targeted Oral Health Promotion Topics
Oral Health Promotion Topics Nutrition Messages
Hypomineralized or Children who are malnourished pre-, peri-, or postnatally and/or low
hypoplastic primary teeth and birthweight are more likely to have this condition. (Alvarez 1995, Lai
caries risk 1998)58,59
Craniofacial development Causes are attributed to genetic defects often working in concert with
environmental factors such as alcohol intake and possibly excessive
therapeutic vitamin A. Neural tube defects and risks of cleft lip and palate
may be reduced in children if women support dietary folic acid intake with
additional supplementation to equal 400 µg. (Bonin 1998)60
Bone status Loss of teeth leads to bone atrophy. Localized diseases like periodontal disease
and systemic diseases like osteoporosis may further affect alveolar bone loss.
Promotion of diets adequate in calcium and vitamin D to target these effects
should be discussed in the context of oral health. (Bhaskar 1991)61
Oral soft tissue integrity Nutritional status can enhance the ability of healthy epithelial tissue to
prevent penetration of bacterial endotoxins into gingival tissue. Protein,
vitamins A, C, and E, as well as the B-compex vitamins and zinc will help
to maintain immune system integrity, but there is a paucity of scientific data
to support supplemental use of these nutrients. Prevention of diseases of
the soft tissue related to diseases like periodontal disease and systemic
diabetes may challenge utilization of nutrients and can increase risk of
decreased oral soft tissue integrity. (Touger-Decker 2000)62
Salivary output Saliva and salivary glands provide clues to overall health and disease and
function in the mucosal immune system to protect oral tissue integrity. Saliva
moistens food and lubricates the bolus for swallowing. Fiber intake and
frequency of eating can promote salivary output. Xerostomia (dry mouth)
associated with disease and drug therapies may require medical nutrition
therapy. (Martin 1999)48
Edentulous state Toothless persons or those who wear dentures need to be encouraged to
modify food selection habits and method of preparing foods for easier biting
and chewing. One can still achieve good nutritional status important to the
maintenance of the oral tissue.
Oral cancer prevention Promoting five or more servings a day of fruits and vegetables from a variety
of sources that include both dark green and yellow sources may decrease
risk for oral cancer. Weight management strategies for those interested in
smoking cessation can possibly enhance success and should be explored
when appropriate. (Jones and Mobley 2000)63
Dental erosion Fruit juices, citrus fruits, acid sweet candies and mints, pickles, and cola
drinks can cause loss of tooth enamel. Vomiting and regurgitation associated
with gastroesophageal reflux and eating disorders can also cause this dental
condition. Encourage dietary practices to neutralize the impact of these
products and conditions. (Rugg-Gunn 1993)50
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55
Foodborne Infections and Infestations
Kumar S. Venkitanarayanan and Michael P. Doyle
Introduction
The microbiological safety of foods is a major concern to consumers and to the food
industry. During the last decade, food safety received considerable attention due to the
emergence of several new foodborne pathogens, and the involvement of foods that tradi-
tionally have been considered safe in many foodborne disease outbreaks. Further,
increased globalization of the food supply and consumer demands for preservative-free
convenience foods and ready-to-eat meals highlight the relevance of the microbial safety
of foods. A recently published study by the U.S. Centers for Disease Control and Preven-
tion reported an estimated 76 million cases of foodborne illness which resulted in 325,000
hospitalizations and 5000 deaths in the United States annually.1 Besides the public health
impact, outbreaks of foodborne illness impose major economic losses to both the food
industry and society. The various microbiological hazards associated with foods can be
classified as bacterial, viral, fungal, and parasitic.
Bacterial Foodborne Pathogens (Table 55.1)

Bacteria are a major agent of microbial foodborne illnesses. Bacterial foodborne illnesses
can be classified into foodborne infections resulting from ingestion of foods containing
viable cells of bacterial pathogens, and foodborne intoxications, which result from con-
sumption of foods containing preformed toxins produced by toxigenic bacteria. The var-
ious bacterial pathogens associated with foodborne diseases are discussed below.
Escherichia coli O157:H7

Enterohemorrhagic Escherichia coli O157:H7 emerged in 1982 as a food-borne pathogen
and is now recognized as a major public health concern in the United States. Many food-
0-8493-2705-9/02/$0.00+$1.50
1136
TABLE 55.1
Bacterial Foodborne Pathogens
Biochemical and Estimated No. of Incubation Period,
Growth Sources/ Foodborne Cases Symptoms and
Microorganism Characteristics Reservoirs Vehicles Annually in USA1 Duration Detection Methods Control/Prevention
Escherichia coli Gram negative, facultative Cattle, Raw or undercooked 62,500 3 to 9 days Cultural methods Adequate cooking of beef;
O157:H7 anaerobe, nonspore- humans beef, unpasteurized Severe abdominal cramps, followed by pasteurization of milk
forming, optimum milk and apple juice, watery diarrhea that can confirmatory and apple juice; use of
growth at 37°-40°C, lettuce, alfalfa become bloody, absence biochemical tests102,103 potable water for
inability to grow at ≥ sprouts, water of fever, kidney failure, Latex agglutination drinking; avoid eating
44.5°C in presence of seizures, coma assay104, 105 alfalfa and vegetable
selective agents, inability Duration is days to weeks ELISA106, 107 sprouts; good personal
to ferment sorbitol PCR108 hygiene
within 24 h, does not
produce β-glucuronid-
ase, acid tolerance
Salmonella spp. Gram negative, facultative Cattle, swine, Raw or undercooked 1,340,000 6 to 72 h up to 4 days. Cultural methods Adequate cooking of food;
(non typhoid) anaerobe, oxidase poultry, meat, poultry, eggs, Abdominal cramps, followed by avoid cross-contamina-
negative, catalase humans and milk and diarrhea, fever, chills, confirmatory tion of raw foods of
positive, untreated water headache and vomiting. biochemical tests109, 110 animal origin with
nonsporeforming, Duration is few days to Latex agglutination cooked or ready to eat
growth at 5°-47°C, one week, occasionally assay111 foods; avoid eating raw
optimum growth at up to 3 weeks. ELISA112 or undercooked foods of
37°C, metabolize PCR113, 114 animal origin; use of
nutrients by respiratory potable water; good
and fermentative personal hygiene
pathways
Salmonella enterica Gram negative, facultative Humans Raw milk, shellfish, 660 (> 70% of cases 7 to 28 days Biochemical tests115 Good personal hygiene
serovar Typhi anaerobe, ferment D- raw salads, under acquired abroad) Remittent fever with Latex test116 and food handling
xylose cooked foods stepwise increments ELISA117 practices; proper sewage
over a period of days, PCR118 systems; effective
high temperature of 103 surveillance of known
to 104°F, abdominal pain, carriers
diarrhea, and headache
Duration is up to 3 weeks
Campylobacter jejuni Gram negative, Poultry Raw or undercooked 1,960,000 1 to 11 days, usually 2 to 5 Cultural methods Adequate cooking of
and coli microaerophilic, Swine chicken, pork, and days followed by meat; avoid cross-
nonsporeforming, Cattle beef, and Abdominal pain, diarrhea, confirmatory contamination of raw
optimal growth at 42°C, Sheep unpasteurized milk malaise, headache, fever biochemical tests31, 119 foods of animal origin
CO2 is required for good Wild birds Duration is up to 10 days Immunoassay120 with cooked or ready to
growth, growth optimal PCR121, 122 eat foods; pasteurization
in 3-6% O2, sensitive to of milk
dehydration, survives
best at refrigeration
temperature
Shigella spp. Gram negative, facultative Humans Raw foods and water 89,600 1 to 7 days Cultural methods Good personal hygiene,
anaerobe, nonspore- contaminated with Severe abdominal and followed by including adequate
forming, does not human feces; rectal pain, bloody confirmatory cooking of food,
ferment lactose, growth prepared salads diarrhea with mucus, biochemical tests123 drinking potable water
at 10°-45°C, optimal fever ELISA124
growth at 37°C Dehydration PCR125
Duration is few days to
few weeks
Yersinia Gram negative, facultative Swine is Undercooked or raw 86,700 1 to 11 days, usually 24 to Cultural methods Adequate cooking of pork,
enterocolitica anaerobe, nonspore- principal pork, especially 36 h followed by disinfection of drinking
forming, growth at 0°- reservoir of tongue Severe abdominal pain, confirmatory water, control of Y.
44°C, optimal growth at pathogenic nausea, diarrhea, fever, biochemical tests126 enterocolitica in pigs,
ca. 29°C, growth at pH strains sometimes vomiting PCR127 prevent cross-
4.6-9.0, growth in Duration is usually 2-3 contamination of pig
presence of 5% NaCl but days but may continue viscera, feces, and hair
not 7% NaCl for up to 3 weeks with food and water
Vibrio cholerae Gram negative, facultative Humans, Undercooked or raw 49 1 to 3 days Cultural methods Safe disposal of human
anaerobe, marine seafoods; vegetables Profuse watery diarrhea, followed by sewage, disinfection of
nonsporeforming, waters, fertilized with which can lead to severe confirmatory drinking water, avoid
growth at 18°-42°C with especially contaminated human dehydration, abdominal biochemical tests128, 129 eating raw seafood,
optimal growth at 37°C, brackish feces or irrigated pain, vomiting ELISA130 adequate cooking of food
growth is stimulated in water and with contaminated Duration is up to 7 days PCR131, 132
presence of 3% NaCl, pH estuaries water; water
range for growth is 6-11
Vibrio Gram negative, facultative Coastal Raw or undercooked 5100 9 to 25 hours, up to 3 days, Cultural methods Adequate cooking of
parahaemolyticus anaerobe, nonspore- seawater, fish and seafoods Profuse watery diarrhea, followed by seafood, rapid chilling of
forming, growth in estuarine abdominal pain, confirmatory seafoods, prevent cross-
presence of 8% NaCl, brackish vomiting, fever biochemical tests128, 129 contamination from raw
optimal growth at 37°C waters above Duration is up to 8 days ELISA133 seafoods to other foods
with rapid generation 15°C, marine PCR134 and preparation surfaces
time (ca. 10 minutes), fish, shellfish
growth at 10°C, sensitive
to storage at refrigeration
temperature
1137
1138

Vibrio vulnificus Gram negative, Coastal and Raw seafood, 47 12 h to 3 days, Cultural methods Avoid eating raw seafood,
nonsporeforming, estuarine especially raw Profuse diarrhea with followed by especially raw oysters
optimal growth at 37°C waters oysters blood in feces, confirmatory when have a history of
fulminating septicemia, biochemical tests128,129 liver disease or
hypotension ELISA135 alcoholism
Duration is days to weeks PCR136
Aeromonas Gram negative, facultative Aquatic Untreated water Very few 24 to 48 h Cultural methods Avoid consumption of
hydrophila anaerobe, environment, Abdominal pain, followed by raw seafoods, avoid
nonsporeforming, freshwater vomiting, watery stools, confirmatory long-term storage of
oxidase positive, some fish mild fever biochemical tests137, 138, 139 refrigerated foods,
strains are (especially Duration is days to weeks PCR140, 141 adequate cooking of
psychrotrophic (4°C) Salmonids) foods, disinfection of
optimum growth at ca. drinking water
28°C
Plesiomonas Gram negative, facultative Fresh and Fish, shellfish, oysters, Very few 1 to 2 days Cultural methods Avoid consumption of
shigelloides anaerobe, estuarine shrimp and Abdominal pain, nausea, followed by raw seafoods,
nonsporeforming, waters, fish, untreated water vomiting, diarrhea, confirmatory disinfection of drinking
oxidase positive, some and shellfish chills, headache biochemical tests137, 138 water
strains are Duration is days to weeks
psychrotrophic
Listeria Gram positive, facultative Soil, sewage, Raw milk, soft cheese, 2490 Few days to several weeks Cultural methods Proper sanitation of food
monocytogenes anaerobe, vegetation, pâte, ready-to-eat Flu-like symptoms such as followed by processing equipment
nonsporeforming, water, and cooked meat fever, chills, headache confirmatory and environments,
growth at 2°-45°C, feces of products (poultry, Abdominal pain and biochemical tests142, 143, 144 adequate cooking of
optimal growth at 30°- humans and hot dogs) and cooked diarrhea are present in Immunoassay145 meat and meat products,
35°C, growth in presence animals seafoods (smoked some cases PCR146 prevent recontamination
of 10% NaCl fish), and raw In pregnant women, of cooked products,
vegetables spontaneous abortion proper reheating of
and stillbirth cooked food, avoid
Duration is days to weeks drinking raw milk, avoid
certain high risk foods
(e.g., soft cheeses and
pâtes) by pregnant
women and
immunocompromised
individuals
Staphylococcus Gram positive, facultative Humans (nose, Ham, chicken and egg 185,000 2 to 6 h Cultural methods Good personal hygiene in
aureus anaerobe, throat and salads, cream-filled Abdominal cramps, followed by food preparation and
(staphylococcal nonsporeforming, skin) and pastries nausea, vomiting, confirmatory handling, adequate
enterotoxin) coagulase positive, animals diarrhea, headache, biochemical tests147, 148 cooking of foods, proper
growth at 7°-48°C, chills, and dizziness PCR149, 150 refrigeration of cooked
optimal growth at ca. Duration is up to 2 days Detection of toxin by foods
37°C, toxin production at microslide gel double
aw of 0.86, toxin is heat diffusion test151
stable (can withstand
boiling for 1 h)
Clostridium Gram positive, obligate Soil, dust, Beef, pork, fish, 58 12 to 36 h, can range from Cultural methods Boiling of foods will
botulinum anaerobe, sporeforming, vegetation, vegetables, and few h to 8 days followed by destroy toxin, adequate
(botulinum produce seven potent animals, honey (infant Very severe life confirmatory heat processing of home-
neurotoxin) neurotoxins A-G (only A, birds, insects, botulism) threatening intoxication, biochemical tests152 canned foods, proper
B, E and rarely F and marine headache, fixed and PCR153, 154 refrigeration of vacuum-
associated with human and fresh dilated pupils, vertigo, Detection of toxin by packaged fresh or lightly
illness), proteolytic water blurred or double vision, mouse bioassay155 cooked/smoked foods,
strains grow at 10°-50°C, sediments lack of muscle acid-preserved foods
nonproteolytic strains and the coordination, dry mouth, should be below pH 4.6,
can grow at 3.3°C, spores intestinal difficulty in breathing discard swollen cans,
are resistant to normal tracts of fish Gastrointestinal avoid feeding honey to
cooking temperatures, (type E) symptoms include infants

and survive freezing and abdominal pain, nausea,
drying vomiting, constipation
Duration is days to
months (8 months)
Clostridium Gram positive, anaerobe, Soil, sewage, Cooked meat and 249,000 8 to 24 h Cultural methods Adequate cooking of
perfringens sporeforming, optimum dust, poultry, especially Abdominal pain and followed by foods; cooked food
growth at 37°-47°C, vegetation, roast beef, turkey diarrhea confirmatory should be rapidly cooled
grows slowly below 20°C feces of and gravies Duration is 1 to 2 days biochemical tests68 (<5°C) or held hot
humans and Latex agglutination test156 (>60°C); proper
animals Colony hybridization refrigeration and
assay157 adequate reheating of
PCR156 stored cooked foods
Bacillus cereus Gram positive, facultative Widely Cereals, fried rice, 27,000 Diarrheal syndrome (toxic Cultural methods Adequate cooking of
anaerobe, sporeforming, distributed in potatoes, cooked infection): 8 to 16 h followed by foods; cooked foods
some strains can grow at nature, soil, meat products, milk Abdominal pain, watery confirmatory should be rapidly cooled
4°-6°C; optimum growth dust, and dairy products, diarrhea biochemical tests158 (<5°C) or held hot (60°C);
at 28°-37°C vegetation spices, dried foods Duration is 24 to 36 h ELISA159 avoid leaving cooked
Emetic syndrome PCR160 foods at room
(preformed, heat stable temperature for long
toxin): 1 to 5 h time
Nausea, vomiting,
malaise, sometimes
diarrhea
Duration is 24 to 36 h
1139
1140

Brucella spp. Gram negative, aerobe, Cattle, sheep, Raw milk and 780 Acute form: 3 to 21 days, Cultural methods161 Vaccination of livestock
nonsporeforming, pig, goat products made from infrequently months ELISA162, 163 against Brucella spp.,
optimal growth at 37°C unpasteurized milk Pyrexia, profuse sweats, PCR163 avoid contact with
chills, constipation, infected animals,

weakness, malaise, body eradication of diseased
aches, joint pains, weight animals; pasteurization
loss, anorexia of milk; avoid eating
Chronic form: several unpasteurized dairy
months products
Long history of fever,
inertia, recurrent
depression, sexual
impotence, insomnia
Duration is weeks
Helicobacter pylori Gram negative, Humans, cats Untreated water, Unknown Gastritis, dyspepsia, Cultural methods78 Avoid contact with
microaerophile to foodborne peptic ulcer, gastric ELISA76 infected animals, use of
anaerobe transmission of carcinoma PCR77 chlorinated water for
disease has not been cooking and drinking
proven
Foodborne Infections and Infestations 1141
associated outbreaks are reported each year, with 340 outbreak-associated confirmed cases
reported in 1997.2 A wide variety of foods, including undercooked ground beef, raw milk,
roast beef, venison jerky, salami, yogurt, lettuce, unpasteurized apple juice, cantaloupe,
alfalfa sprouts, and coleslaw, have been implicated as vehicles of E. coli O157:H7 infection.3
In addition, outbreaks involving person-to-person and waterborne transmission have been
reported.3 Cattle have been identified as an important reservoir of E. coli O157:H7,4, 5 with
undercooked ground beef being a major vehicle of foodborne outbreaks.6 A survey per-
formed by the National Animal Monitoring System of the U.S. Department of Agriculture
revealed that 1.6% of feedlot cattle shed E. coli O157:H7 and 0.4% shed E. coli O157
nonmotile bacteria in their feces.7 This is likely an underestimate of the actual percentage
of E. coli O157:H7 harbored by cattle. The use of more sensitive isolation procedures will
likely identify considerably higher carriage rates. E. coli O157:H7 localizes in cattle pri-
marily in the rumen and colon, and is shed in feces.8 E. coli O157:H7 can survive in bovine
feces for many months,9 hence potentially contaminating cattle, food, water, and the
environment. During slaughter and subsequent processing operations, contamination of
carcasses with E. coli O157:H7 from the digesta or feces of cattle can occur. Moreover, fruits
and vegetables grown on soil fertilized with cattle manure or irrigated with water con-
taminated with cattle manure has the potential of being a vehicle of E. coli O157:H7.
Acidification is commonly used in food processing to control growth and survival of
spoilage-causing and pathogenic microorganisms in foods. The U.S. Food and Drug
Administration does not regard foods with pH ≤ 4.6 (high-acid foods) to be microbiolog-
ically hazardous. However, E. coli O157:H7 has been associated with outbreaks attributed
to high-acid foods, including apple juice, mayonnaise, fermented sausage, and yogurt,10
raising concerns about the safety of these foods. Several studies have revealed that many
strains of E. coli O157:H7 are highly tolerant to acidic conditions, being able to survive for
extended periods of time in synthetic gastric juice and in highly acidic foods.10,11 Further,
exposure of E. coli O157:H7 to mild or moderate acidic environments can induce an acid
tolerance response, which enables the pathogen to survive extreme acidic conditions. For
example, acid-adapted cells of E. coli O157:H7 survived longer in apple cider, fermented
sausage, and hydrochloric acid than non-acid adapted cells.12,13 However, E. coli O157:H7
is not unusually heat resistant14 or salt tolerant15 unless cells are preexposed to acid to
become acid adapted. Acid-adapted E. coli O157:H7 cells have been determined to have
increased heat tolerance.
In humans, three important manifestations of illness have been reported in E. coli
O157:H7 infection. These include hemorrhagic colitis, hemolytic uremic syndrome, and
thrombocytopenic purpura.16 Two important factors attributed to the pathogenesis of E.
coli O157:H7 include the ability of the pathogen to adhere to the intestinal mucosa of the
host, and production of Shiga toxin I and/or Shiga toxin II.16 Retrospective analysis of
foods implicated in outbreaks of E. coli O157:H7 infection suggest a low infectious dose
of the pathogen, probably less than a hundred cells.17
Salmonella Species
Salmonella spp. are facultatively anaerobic, gram-negative, rod-shaped bacteria belonging
to the family Enterobacteriaceae. Members of the genus Salmonella have an optimum growth
temperature of 37°C and utilize glucose with the production of acid and gas.18 Salmonella
spp. are widely distributed in nature. They colonize the intestinal tracts of humans,
animals, birds, and reptiles, and are excreted in feces, which contaminate the environment,
water, and foods.19 Many food products, especially foods having contact with animal
feces, including beef, pork, poultry, eggs, milk, fruits, and vegetables, have been associated
with outbreaks of salmonellosis.20 Salmonella spp. can be divided into host-adapted sero-
vars and those without any host preferences. Most of the foodborne serovars are in the
latter group.
The ability of many strains of Salmonella to adapt to extreme environmental conditions
emphasizes the potential risk of these microorganisms as foodborne pathogens. Although
salmonellae optimally grow at 37°C, the genus Salmonella consists of strains which are
capable of growth from 5° to 47°C.21 Salmonella spp. can grow at pH values ranging from
4.5 to 7.0, with optimum growth observed near neutral pH.19 Pre-exposure of Salmonella
to mild acidic environments (pH 5.5 to 6.0) can induce in some strains an acid tolerance
response, which enables the bacteria to survive for extended periods of time exposure to
acidic and other adverse environmental conditions such as heat and low water activity.22,23
However, most Salmonella spp. possess no unusual tolerance to salt and heat. A concen-
tration of 3 to 4% NaCl can inhibit the growth of Salmonella.24 Most salmonellae are
sensitive to heat, hence ordinary pasteurization and cooking temperatures are capable of
killing the pathogen.25
The most common species of Salmonella that cause foodborne salmonellosis in humans
are S. enterica serovar Typhimurium and S. enterica serovar Enteritiditis.26 A wide variety
of foods, including beef, pork, milk, chicken, and turkey have been associated with out-
breaks caused by S. Typhimurium. S. Enteritidis outbreaks, however, are most frequently
associated with consumption of poultry products, especially eggs. During the period from
1985 to 1987, 77% of S. Enteritidis outbreaks in the U.S. was associated with Grade A shell
eggs or foods containing eggs.27 One of the major routes of S. Enteritidis contamination
of intact eggs is through transovarian transmission of the pathogen to the yolk.28
S. enterica serovar Typhi is the causative agent of typhoid (enteric fever), a serious human
disease. Typhoid fever has a long incubation period of 7 to 28 days, and is characterized
by prolonged and spiking fever, abdominal pain, diarrhea, and headache.18 The disease
can be diagnosed by isolation of the pathogen from urine, blood, or stool specimens of
affected individuals. S. typhi is an uncommon cause of foodborne illness in the U.S.
Campylobacter Species
The genus Campylobacter consists of 14 species, however, C. jejuni subsp. jejuni and C. coli
are the dominant foodborne pathogens. C. jejuni is a slender, rod-shaped, microaerophilic
bacterium that requires approximately 3 to 6% oxygen for growth. It can be differentiated
from C. coli by its ability to hydrolyze hippurate.29 C. jejuni is the most common bacterial
agent causing diarrheal disease in humans in the U.S. and many other countries.30 Many
animals including poultry, swine, cattle, sheep, horses, and domestic pets harbor C. jejuni
in their intestinal tracts, hence serving as reservoirs of human infection. Although a
number of vehicles such as beef, pork, eggs, and untreated water have been implicated
in outbreaks of campylobacter enteritis, chicken and unpasteurized milk are reported as
the most commonly involved foods.31 The organism does not survive well in the environ-
ment, being sensitive to drying, highly acidic conditions, and freezing. It is also readily
killed in foods by adequate cooking.32
Usually campylobacter enteritis in humans is a self-limiting illness characterized by
abdominal cramps, diarrhea, headache, and fever lasting up to four days. However, severe
cases, involving bloody diarrhea and abdominal pain mimicking appendicitis, also occur.29
Guillain-Barré syndrome (GBS) is an infrequent sequela to Campylobacter infection in
humans. GBS is characterized by acute neuromuscular paralysis32 and is estimated to occur
in approximately one of every 1000 cases of campylobacter enteritis.33 A few strains of C.
jejuni reportedly produce a heat-labile enterotoxin similar to that produced by Vibrio
cholerae and enterotoxigenic E. coli.29 Some strains of C. jejuni and C. coli also can produce
a cytolethal distending toxin, which causes a rapid and specific cell cycle arrest in HeLa
and Caco-2 cells.30
Shigella Species
The genus Shigella is divided into four major groups: S. dysenteriae (group A), S. flexneri
(group B), S. boydii (group C), and S. sonnei (group D) based on the organism’s somatic
(O) antigen. Humans are the natural reservoir of Shigella spp. The fecal-oral route is the
primary mode of transmission of shigellae, and proper personal hygiene and sanitary
practices of cooks and food handlers can greatly reduce the occurrence of outbreaks of
shigellosis. Most foodborne outbreaks of shigellosis are associated with ingestion of foods
such as salads and water contaminated with human feces containing the pathogen.
Shigellosis is characterized by diarrhea containing bloody mucus, which lasts one to two
weeks. The infectious dose for Shigella infection is low. The ID50 of S. flexneri and S. sonnei
in humans is approximately 5000 microorganisms, and that of S. dysenteriae is a few
hundred cells; hence secondary transmission of Shigella by person-to-person contact fre-
quently occurs in outbreaks of foodborne illness.
Yersinia enterocolitica
Swine have been identified as an important reservoir of Yersinia enterocolitica, in which the
pathogen colonizes primarily the buccal cavity.34 Although pork and pork products are
considered to be the primary vehicles of Y. enterocolitica, a variety of other foods, including
milk, beef, lamb, seafood, and vegetables, has been identified as vehicles of Y. enterocolitica
infection.35 One of the largest outbreaks of yersiniosis in the U.S. was associated with
milk.36 Water has also been a vehicle of several outbreaks of Y. enterocolitica infection.36
Surveys have revealed that Y. enterocolitica is frequently present in foods, having been
isolated from 11% of sandwiches, 15% of chilled foods, and 22% of raw milk in Europe.37
However, most isolates from foods of non-pork origin are nonpathogenic for humans.
Although contaminated foods are a major source of Y. enterocolitica infection, contaminated
blood used in transfusions has resulted in many cases of Y. enterocolitica sepsis.38 Several
serovars of pathogenic Y. enterocolitica have been reported, which include O:3, O:5, O:8,
and O:9,39 with serovar 0:8 being common in the U.S.40
An unusual characteristic of Y. enterocolitica that influences food safety is its ability to
grow at low temperatures, even as low as –1°C.41 Several studies have revealed growth
of Y. enterocolitica in foods stored at refrigeration temperature. Y. enterocolitica grew on
pork, chicken, and beef at 0 to 1°C.42,43 The ability of Y. enterocolitica to grow well at
refrigeration temperature has been exploited for isolating the pathogen from foods, water,
and stool specimens. Such samples are incubated at 4 to 8°C in an enrichment broth for
several days to selectively culture Y. enterocolitica based on its psychrotrophic nature.
Vibrio Species
The genus Vibrio consists of 28 species, of which V. parahaemolyticus, V. vulnificus, and V.
cholerae are the most important foodborne pathogens. Vibrios are associated with estuarine
and marine waters, and their populations in surface waters and in seafoods are higher
during the warm than cold months of the year.44 V. parahaemolyticus is present in coastal
waters of the U.S. and the world. A survey by the U.S. Food and Drug Administration
revealed that 86% of 635 seafood samples contained V. parahaemolyticus, being isolated
from clams, oysters, lobsters, scallops, shrimp, fish, and shellfish.44 An important virulence
characteristic of pathogenic strains of V. parahemolyticus is their ability to produce a ther-

mostable hemolysin (Kanagawa hemolysin).45 Studies in humans on the infectious dose
of pathogenic V. parahemolyticus strains revealed that ingestion of approximately 105 to 107
organisms can cause gastroenteritis.44
V. cholerae serovars O1 and O139, the causative agents of cholera in humans, are a part
of the normal estuarine microflora, and foods such as raw fish, mussels, oysters, and clams
have been associated with outbreaks of cholera.46 Infected humans can serve as short-term
carriers, shedding the pathogen in feces. Cholera is characterized by profuse diarrhea,
potentially fatal in severe cases, and often described as “rice water” diarrhea due to the
presence of prolific amounts of mucus in the stools. Gastroenteritis caused by non-O1 and
non-O139 serovars of V. cholerae is usually mild in nature.
V. vulnificus is the most serious of the vibrios and is responsible for most of the seafood-
associated deaths in the U.S., especially in Florida.44 Although a number of seafoods has
been associated with V. vulnificus infection, raw oysters are the most common vehicle
associated with cases of illness.47 This pathogen causes a fulminating septicemia with a
40 to 50% mortality rate.
Aeromonas hydrophila
Although Aeromonas species have been recognized as pathogens of cold-blooded animals,
their potential to cause human infections, especially foodborne illness, received attention
only recently. A. hydrophila has been isolated from drinking water, fresh and saline waters,
and sewage.48 It also has been isolated from a variety of foods such as fish, oyster, shellfish,
raw milk, ground beef, chicken, and pork.48 Although A. hydrophila is sensitive to highly
acidic conditions and does not possess any unusual thermal resistance, some strains are
psychrotrophic and grow at refrigeration temperature.49 A. hydrophila can grow on a variety
of refrigerated foods, including pork, asparagus, cauliflower, and broccoli.50,51 However,
considering the widespread occurrence of A. hydrophila in water and food and its relatively
infrequent association with human illness, it is likely that most strains of this bacterium
are not pathogenic for humans. A. hydrophila infection in humans is characterized by
watery diarrhea and mild fever. Virulent strains of A. hydrophila produce a 52-kDa polypep-
tide, which possesses enterotoxic, cytotoxic, and hemolytic activities.52
Plesiomonas shigelloides
P. shigelloides has been implicated in several cases of sporadic and epidemic gastroenteri-
tis.53 The pathogen is present in fresh and estuarine waters, and has been isolated from
various aquatic animals.49 Seafoods such as fish, crabs, and oysters have been associated
with cases of P. shigelloides infection. The most common symptoms of P. shigelloides infection
include abdominal pain, nausea, chills, fever, and diarrhea. Potential virulence factors of
P. shigelloides include cytotoxic enterotoxin, invasins, and β-hemolysin.49
Listeria monocytogenes
L. monocytogenes has emerged into a highly significant and fatal foodborne pathogen
throughout the world, especially in the U.S. There is an estimated approximately 2500
cases of listeriosis annually in the U.S., with a mortality rate of ca. 25%.1 A large outbreak
of listeriosis involving more than 100 cases and associated with eating contaminated
turkey frankfurters occurred during 1998-99.54 During this period of time there were more
than 35 recalls of a number of different food products contaminated with listeriae.54 L.

monocytogenes is widespread in nature, occurring in soil, vegetation, and untreated water.
Humans and a wide variety of farm animals, including cattle, sheep, goat, pig, and poultry,
are known sources of L. monocytogenes.55 L. monocytogenes also occurs frequently in food
processing facilities, especially in moist areas such as floor drains, floors, and processing
equipment.56 L. monocytogenes can also grow in biofilms attached to a variety of processing
plant surfaces such as stainless steel, glass, and rubber.57
A wide spectrum of foods, including milk, cheese, beef, pork, chicken, seafoods, fruits,
and vegetables, has been identified as vehicles of L. monocytogenes.55 However, ready-to-
eat cooked foods such as low-acid soft cheese, pâtes, and cooked poultry meat which can
support the growth of listeriae to large populations (>106 cells per gram) when held at
refrigeration temperature for several weeks, have been regarded as high-risk foods.58,59 L.
monocytogenes possesses several characteristics which enable the pathogen to successfully
contaminate, survive, and grow in foods, thereby resulting in outbreaks. These traits
include an ability to grow at refrigeration temperature and in a medium with minimal
nutrients, ability to survive in acidic conditions, e.g., pH 4.2, ability to tolerate up to 10%
sodium chloride, ability to survive incomplete cooking or subminimal pasteurization
treatments, and the ability to survive in biofilms on equipment in food processing plants
and resist superficial cleaning and disinfection treatments.54
Human listeriosis is an uncommon illness with a high mortality rate. Clinical manifes-
tations range from mild influenza-like symptoms to meningitis and meningoencephalitis.
Pregnant females infected with the pathogen may not present symptoms of illness or may
exhibit only mild influenza-like symptoms. However, spontaneous abortion, premature
birth, or stillbirth are frequent sequela to listeriosis in pregnant females.59 Although the
infective dose of L. monocytogenes is not known, published reports indicate that it is likely
more than 100 CFU per gram of food.59 However, the infective dose depends on the age,
condition of health, and immunological status of the host. Important virulence factors of
L. monocytogenes include intracellular invasin and production of listeriolysin O.60
Staphylococcus aureus
Pre-formed, heat stable enterotoxin that can resist boiling for several minutes is the agent
responsible for staphylococcal food poisoning. Humans are the principal reservoir of S.
aureus strains involved in outbreaks of foodborne illness. Colonized humans can be long-
term carriers of S. aureus, and thereby contaminate foods and other humans.61 The organ-
ism commonly resides in the throat and nasal cavity, and on the skin, especially in boils
and carbuncles.61 Protein-rich foods such as ham, poultry, fish, dairy products, custards,
cream-filled bakery products, and salads containing cooked meat, chicken, and potatoes
are the vehicles most frequently associated with S. aureus food poisoning.62 S. aureus is
usually overgrown by competing bacterial flora in raw foods; hence raw foods are not
typical vehicles of staphylococcal food poisoning. Cooking eliminates most of the normal
bacterial flora of raw foods, thereby enabling the growth of S. aureus, which can be
introduced by infected cooks and food handlers into foods after cooking. The incubation
period of staphylococcal food poisoning is very short, with symptoms observed within
two to six hours after eating toxin-contaminated food. Symptoms include nausea, vomit-
ing, diarrhea, and abdominal pain.
S. aureus can grow within a wide range of pH values from 4 to 9.3, with optimum growth
occurring at pH 6 to 7. S. aureus has an exceptional tolerance to sodium chloride, being
able to grow in foods in the presence of 7 to 10% NaCl, with some strains tolerating up
to 20% NaCl.62 S. aureus has the unique ability to grow at a water activity as low as 0.83
to 0.86, which is unusual for a nonhalophilic bacterium.63 S. aureus produces nine different
enterotoxins which are quite heat resistant, losing their serological activity at 121°C but
not at 100°C for several minutes.63
Clostridium botulinum
Foodborne botulism is an intoxication caused by ingestion of foods containing pre-formed
botulinal toxin, which is produced by C. botulinum under anaerobic conditions. There are
seven types of C. botulinum (A, B, C, D, E, F, and G) classified on the basis of the antigenic
specificity of the neurotoxin they produce.64 The organism is present in soil, vegetation,
and sedimentation under water. Type A strains are proteolytic, whereas type E strains are
nonproteolytic.65 Another classification divides C. botulinum into four groups: group 1
(type A strains and proteolytic strains of types B and F), group II (type E strains and
nonproteolytic strains of B and F), group III (type C and D strains), and group IV (type
G strains). Types A, B, E, and F are associated with botulism in humans. Type A C.
botulinum occurs frequently in soils of the western U.S., whereas type B strains are more
often present in the eastern states and in Europe.65 Type E strains are largely associated
with aquatic environments and fish. Foods most often associated with cases of botulism
include fish, meat, honey, and home-canned vegetables.64 Type A cases of botulism in the
U.S. are frequently associated with temperature-abused, home-prepared foods. Proteolytic
type A, B, and F strains produce heat-resistant spores, which pose a safety concern in low-
acid canned foods. In contrast, nonproteolytic type B, E, and F strains produce heat-labile
spores, which are of concern in pasteurized or unheated foods.65 The minimum pH for
growth of group I and group II strains is 4.6 and 5, respectively.64 Group I strains can grow
at a minimum water activity of 0.94, whereas group II strains do not grow below a water
activity of 0.97.66 The proteolytic strains of C. botulinum are generally more resistant to
heat than nonproteolytic strains.
Clostridium perfringens
C. perfringens strains are grouped into five types: A, B, C, D, and E, based on the type(s)
of toxin(s) produced. C. perfringens foodborne illness is almost exclusively associated with
type A isolates of C. perfringens. C. perfringens is commonly present in soil, dust, water,
and in the intestinal tracts of humans and animals.67 It is frequently present in foods; about
50% of raw or frozen meat and poultry contain C. perfringens.68 Spores produced by C.
perfringens are quite heat resistant, and can survive boiling for up to one hour.68 C. perfrin-
gens spores can survive in cooked foods, and if not properly cooled before refrigerated
storage, the spores will germinate and vegetative cells can grow to large populations
during holding at growth temperatures. Large populations of C. perfringens cells (>106/g)
ingested with contaminated food will enter the small intestine, multiply, and sporulate.
During sporulation in the small intestine C. perfringens enterotoxin is produced, which
induces a diarrheal response. Although vegetative cells of C. perfringens are sensitive to
cold temperature and freezing, spores tolerate cold temperature well and can survive in
refrigerated foods.
Bacillus cereus
B. cereus is a spore-forming pathogen present in soil and on vegetation. It is frequently
isolated from foods such as meat, spices, vegetables, dairy products, and cereal grains,
especially fried rice.69 There are two types of foodborne illness caused by B. cereus, i.e., a
diarrheagenic illness and an emetic syndrome.70 The diarrheal syndrome is usually mild
and is characterized by abdominal cramps, nausea, and watery stools. Types of foods
implicated in outbreaks of diarrheal syndrome include cereal food products containing
corn and corn starch, mashed potatoes, vegetables, milk, and cooked meat products. The
emetic syndrome is more severe and acute in nature, characterized by severe vomiting.
Refried or rewarmed boiled rice dishes are frequently implicated in outbreaks of emetic
syndrome.71 The dose of B. cereus required to produce diarrheal illness is estimated at
more than 105 cells/g.72
Brucella Species
Brucella spp. are pathogens in many animals, causing sterility and abortion. In humans,
Brucella is the etiologic agent of undulant fever. The genus Brucella consists of six species,
of which those of principal concern are B. abortus, B. suis, and B. melitensis.73 B. abortus
causes disease in cattle, B. suis in swine, and B. melitensis is the primary pathogen of sheep.
B. melitensis is the most pathogenic species for humans. Human brucellosis is primarily
an occupational disease of veterinarians and meat industry workers. Brucellosis can be
transmitted by aerosols and dust. Foodborne brucellosis can be transmitted to humans by
consumption of meat and milk products from infected farm animals. The most common
food vehicle of brucellosis for humans is unpasteurized milk.73 Meat is a less common
source of foodborne brucellosis because the organisms are destroyed by cooking.
Helicobacter pylori
H. pylori is a human pathogen causing chronic gastritis, gastric ulcer, and gastric carci-
noma.74,75 Although, humans are the primary host of H. pylori, the bacterium has been
isolated from cats.58 H. pylori does not survive well outside its host, but it has been detected
in water and vegetables.76,77 A study on the effect of environmental and substrate factors
on the growth of H. pylori indicated that the pathogen likely lacks the ability to grow in
most foods.78 However, H. pylori may survive for long periods in low-acid environments
under refrigerated conditions. Presently, the mode of transmission of H. pylori in human
infection has not been elucidated, but contaminated water and food are considered poten-
tial vehicles.
Viral Foodborne Pathogens (Table 55.2)

Recent estimates by the Centers for Disease Control and Prevention of the incidence of
foodborne illness in the U.S. indicate that viruses are responsible for approximately 67%
of the total foodborne illnesses of known etiology annually.1 Viruses are obligate intrac-
ellular microorganisms, and most foodborne viruses contain RNA rather than DNA. Since
viruses require a host for multiplication, they cannot grow in foods. Foodborne viruses
are generally enteric in nature, causing illness through ingestion of foods and water
contaminated with human feces. Viruses disseminated through foods also can be spread
by person-to-person contact. Hepatitis A virus, Norwalk-like viruses, and possibly rotavi-
rus are among the most significant of the foodborne viruses.
1148
TABLE 55.2
Viral Foodborne Pathogens
Estimated No. of
Foodborne Cases Incubation Period,
Significant Sources/ Annually in Symptoms and
Microorganism Characteristics Reservoirs Vehicles USA121 Duration Detection Methods Control/Prevention
Hepatitis A virus Single-stranded RNA Humans, Raw or undercooked 4170 15 to 45 days, usually ca. Cultural methods 164, 165 Avoid consumption of
virus, spherical in shape, sewage- shellfish and 25 days Enzyme immunoassay166 raw seafoods,
remains viable for long polluted seafoods harvested Loss of appetite, nausea, PCR167, 168 disinfection of drinking
periods of time in foods waters from sewage- abdominal pain, fever, water, good personal
stored at refrigeration polluted water, jaundice, dark urine, hygiene and food
temperature, virus ready-to-eat foods pale stools handling practices,
multiplies in the gut such as salads Duration is a few weeks to vaccination of
epitheliums before being prepared by infected months professional food

carried by blood to the food handler handlers, safe sewage
liver. Virus is shed in disposal
feces before symptoms of
liver damage become
apparent
Norwalk-like Single-stranded RNA Humans, Raw or undercooked 9,200,000 1 to 2 days Enzyme immunoassay169 Avoid consumption of
viruses (small virus, spherical in shape, sewage- shellfish and Loss of appetite, nausea, PCR168 raw seafoods,
round structured does not multiply in any polluted seafoods harvested abdominal pain, disinfection of drinking
viruses; SRSV) known laboratory host waters from sewage diarrhea, vomiting, water, good personal
polluted water, headache hygiene and food
drinking water Duration is 2 days handling practices,
hygienic sewage
disposal, treatment of
wastewater used for
irrigation
Rotavirus Double-stranded RNA Humans To be determined 39,000 1 to 3 days Cultural methods164, 165 Avoid consumption of
virus, icosahedral in Vomiting, abdominal pain ELISA170 raw seafoods
shape followed by watery PCR171 Avoid drinking of
diarrhea untreated water,
Duration is 6 to 8 days Good personal hygiene
Hepatitis A virus
Hepatitis A virus is a member of the family Picornaviridae and is transmitted by the fecal-
oral route. Raw shellfish harvested from waters contaminated by human sewage is among
the foods most frequently associated with outbreaks of hepatitis A virus.79 Hepatitis A
virus is more resistant to heat and drying than other picornaviruses.79 The incubation
period for onset of symptoms of hepatitis A infection ranges from 15 to 45 days, and
symptoms include nausea, abdominal pain, jaundice, and fever. The virus is shed in feces
by infected humans many days before the onset of symptoms, indicating the importance
of good personal hygienic practices of cooks and food handlers who could otherwise
contaminate food during the period of asymptomatic fecal shedding.
Norwalk-like viruses
Norwalk-like viruses belong to the family Calciviridae, and are often referred to as small,
round structured viruses. Viruses of this type are believed to be the most common cause
of foodborne viral diseases in the U.S. Raw or undercooked shellfish and other seafoods
are common vehicles of Norwalk-like viruses. The incubation period of infection ranges
from 24 to 48 h, and symptoms include nausea, vomiting, and diarrhea. Infected humans
shed the virus in feces for up to a week after symptoms have subsided. Although little
information is available on the stability of these viruses in foods, qualitative studies in
human volunteers indicate that the viruses are infective for up to 3 h when exposed to a
medium at pH 2.2 at room temperature or for 60 minutes at pH 7 at 60°C.80
Rotavirus
Rotavirus is the most common cause of diarrhea in children worldwide, especially in
developing countries. In the U.S., there are an estimated 3.9 million cases of rotavirus
diarrhea each year; however, only 39,000 cases are estimated to be acquired through
contaminated foods.1 Rotavirus infection has an incubation period of one to three days,
and is characterized by fever, vomiting, and diarrhea. The virus is shed in the feces of
infected humans and can survive on vegetables at 4° or 20°C for many days.81 It also has
been shown to survive the process of making soft cheese.81
Fungal Foodborne Pathogens (Table 55.3)

Molds are widely distributed in nature and are an integral part of the microflora of foods.
Although molds are major spoilage agents of many foods, many molds also produce myc-
otoxins of which some are carcinogenic and mutagenic. Mycotoxins are secondary metab-
olites produced by molds usually at the end of their exponential phase of growth. Some of
the principal species of molds which produce mycotoxins in foods are described here.
Aspergillus Species
A. flavus and A. parasiticus are the most important toxigenic foodborne aspergilli. A wide
variety of foods such as nuts, corn, oil seeds, and sorghum are potential vehicles of these
1150
TABLE 55.3
Fungal Foodborne Pathogens
Sources/
Microorganism/ Significant Reservoirs Control/
Toxin Characteristics of Fungi Vehicles of Toxins Toxic Effects Detection Methods Prevention
Aspergillus parasiticus and Growth at 10°-43°C, Environment, Corn, peanuts, Effects of aflatoxin in animals: Cultural methods172, 173, 174 Proper storage of cereal
Aspergillus flavus/ optimal growth at 32°C, soil, vegetation cottonseed Acute: hemorrhage in the ELISA175 products, detoxification of
Aflatoxin produces aflatoxins at gastrointestinal tract, liver PCR176 mycotoxins in cereal
12°-40°C, growth at pH damage, death products by treatment with

3 to 11 Chronic: cirrhosis of liver, liver hydrogen peroxide,
tumors, immunosuppression ammonia
Penicillium expansum/ P. expansum is Environment, P. expansum: Fruits, Effects of patulin: Cultural methods173, 174, 177 Avoid consumption of rotten
Patulin; Penicillium psychrotrophic, capable soil, vegetation especially apples and Gastrointestinal, neurological, Gas chromatography178 apples and pears, proper
citrinum/Citrinin of growth at -2° to -3°C, pears and immunological effects in storage of cereal products
optimal growth at 25°C P. citrinum: Cereals, animals
especially rice, wheat, Citrinin: fatty degeneration and
corn necrosis of kidneys of pigs and
dogs; significance in human
health is unresolved
Fusarium graminearum/ Growth at 5°C but not at Environment, Cereals, especially wheat, Effects of deoxynivolenol: Cultural methods Proper storage of cereal
Deoxynivalernol, 37°C, optimal growth at soil, vegetation barley and corn nausea, vomiting, abdominal followed by products
nivalenol, zearalenone 25°C pain, diarrhea, headache, fever, morphology179, 180
chills, throat irritation PCR181
aspergilli. A. flavus and A. parasiticus produce aflatoxins, which are difuranocoumarin

derivatives.82 The common types of aflatoxins produced are B1, B2, G1, and G2.83 Aflatoxicosis
in animals can be acute or chronic. Acute cases are characterized by severe liver damage,
whereas liver cirrhosis, liver cancer, and teratogenesis occur in chronic toxicity. Chronic
intake of aflatoxins in animals can lead to poor feed conversion and low weight gain.
Penicillium Species
The genus Penicillium consists of more than 150 species, of which nearly 100 produce known
toxins. Three important foodborne toxigenic Penicillium species include P. verrucosum, P.
expansum, and P. citrinum. P. verrucosum is present on grains grown in temperate zones,
and is commonly associated with Scandanavian barley and wheat.84 P. verrucosum produces
Ochratoxin A, which has immunosuppressive and potential carcinogenic properties.84 Och-
ratoxin A also has been associated with nephritis in pigs in Scandanavia.85 P. expansum,
which is frequently associated with fresh fruits, produces patulin, a toxin that produces
immunological, neurological, and gastrointestinal toxic effects in animal models. P. expan-
sum is commonly present in rotten apples and pears, and to a lesser extent in cereals. An
unusual characteristic of P. expansum is its ability to grow at low temperature, i.e., –2° to
–3°C.84 P. citrinin is a widely occurring mold commonly present on rice, wheat, and corn.
P. citrinin produces the metabolite citrinin. Although the toxicological effect of citrinin in
humans is not known, it has been reported to cause renal toxicity in pigs and cats.86
Fusarium graminearum
F. graminearum is a toxigenic mold commonly present in soil and on cereals such as wheat
and corn. It produces a number of mycotoxins, including deoxynevalenol and zearale-
none.87 Ingestion of foods containing deoxynevalenol produces illness termed Scabby
grain intoxication, which is characterized by anorexia, nausea, vomiting, diarrhea, dizzi-
ness, and convulsions. Foods most frequently implicated as vehicles of deoxynevalenol
include cereal grains, wheat, barley, and noodles.
Parasitic Foodborne Pathogens (Table 55.4)

Foods can be vehicles of several types of parasites, including protozoa, roundworms, and
flatworms. Although foodborne transmission of parasites such as Trichinella spiralis and
Taenia solium has been known for many years, the foodborne disease potential of many
protozoan parasites such as Cryptosporidium and Cyclospora has only recently been recog-
nized. Unlike bacteria, parasites do not multiply in foods. Moreover, parasites need at
least one specific host to complete their life cycle. Many of the well-recognized parasites
that can be transmitted to humans through foods are listed below.
Giardia lamblia
G. lamblia is a flagellated protozoan parasite that colonizes the intestinal tract of humans
and animals. It is commonly present in lakes, rivers, and stagnated waters. The life cycle
of G. lamblia includes flagellated trophozoites, which become pear-shaped cysts.88 The
1152
TABLE 55.4
Parasitic Foodborne Pathogens
Estimated No. of Incubation Period,
Significant Sources/ Foodborne Cases Symptoms and Control/
Parasite Characteristics Reservoirs Vehicles Annually in USA1 Duration Detection Methods Prevention
Giardia lamblia Flagellate protozoa, Humans, Drinking water, raw 200,000 4 to 25 days, usually 7 to 10 Immuno- Adequate cooking of
produces oval- animals, fruits and vegetables days fluorescence182 foods, filtration of
shaped cysts ranging especially contaminated with Abdominal cramps, Immunochromato- drinking water, good
from 8 to 20 µm in beavers and cysts, ready-to-eat nausea, abdominal graphy183 personal hygiene and
length and 5 to 12 µm muskrats, water foods such as salads distension, diarrhea PCR184 food handling
in width, cysts contaminated by which can be chronic and practices
contain four nuclei infected food relapsing, fatigue, weight
and are resistant to handlers loss, anorexia
chlorination used to Duration is weeks to years
disinfect water
Entamoeba histolytica Amoeboid protozoa, Humans, dogs, Foods and water Unknown 2 to 4 weeks Microscopic Good personal
anaerobe survives in rats contaminated with Abdominal pain, fever, examination hygiene and food
environment in feces or irrigation vomiting, diarrhea ELISA185 handling practices,
crypted form, cysts water containing blood and PCR185, 186 adequate cooking of
remain viable in feces mucus, weight loss foods, filtration of
for several days and Duration is weeks to water, hygienic
in soil for at least 8 months disposal of sewage
days at 30°C and for water, treatment of
more than 1 month at irrigation water
10°C, relatively
resistant to chlorine
Cryptosporidium Obligate intracellular Humans, wild Contaminated 30,000 2 to 14 days Immunofluorescence Thorough cooking of
parvum coccidian parasite, and domestic drinking and Profuse, watery diarrhea, assay187 food, avoid contact
oocysts are spherical animals, recreational water, abdominal pain, nausea, PCR188 with infected
to oval in shape with especially calves raw milk from vomiting animals, filtration of
an average size of 4.5 infected cattle, fresh Duration is few days to 3 drinking water, good
to 5.0 µm, oocysts are vegetables and other weeks personal hygiene and
resistant to foods contaminated food handling
chlorination used to with feces from practices
disinfect water infected humans and
animals
Cyclospora cayetanesis Obligate intracellular Humans Water, fruits and 14,600 1 week Staining and Good personal
coccidian parasite, vegetables Watery diarrhea, microscopic hygiene, filtration of
oocysts are spherical contaminated with abdominal pain, nausea, examination189 drinking water
in shape with an oocysts vomiting, anorexia, PCR190
average size of 8 to 10 myalgia, weight loss
µm Duration is a few days to 1
month
Toxoplasma gondii Obligate intracellular Cats, farm Raw or undercooked 112,500 5 to 23 days Cell culture and Prevent
coccidian protozoa animals, meat, raw goat milk, Fever, rash, headache, mouse inoculation191 environmental
transplacental raw vegetables muscle pain, swelling of Immunoassay192 contamination with
transmission lymph nodes; PCR191 cat feces, avoid
from infected transplacental infection consumption of raw
mother to fetus may cause abortion meat and milk, safe
Duration is variable disposal of cat feces,
wash hands after
contact with cats
Trichinella spiralis Nematode with no Wild and Raw or undercooked 50 Initial symptoms: Microscopic Adequate cooking of
free living stage in domestic meat of animals 24 to 72 h, examination meat, freezing of
the life cycle, adult animals, containing encysted Systemic symptoms: 8 to 21 ELISA193 meat at -15°C for 30
female worms are 3 especially swine larvae such as swine days PCR194 days or at -35°C,
to 4 mm in length, and horses or horses Initial phase: abdominal preventing
transmissible form is pain, fever, nausea, trichinosis in pigs by
larval cyst which can vomiting, diarrhea not feeding swine
occur in pork muscle Systemic phase: periorbital garbage containing
oedema, eosinophilia, infected meat
myalgia, difficulty in
breathing, thirst, profuse
sweating, chills,
weakness, prostration
Duration is 2 weeks to 3
months
Anisakis spp. Nematode, slender Sea mammals Some undercooked Unknown 4 to 12 h ELISA195 Adequate cooking of
threadlike parasite salt water fish, sushi, Epigastric pain, nausea, PCR196 saltwater fish,
measuring 1.5 to 1.6 herring, sashimi, vomiting, sometimes freezing fish at -23°C
cm in length and 0.1 ceviche hematemesis for 7 days
cm in diameter Duration is variable
Taenia solium Tapeworm, dependent Humans, cattle, Raw or undercooked Unknown Few days to >10 years Detection of eggs or Adequate cooking of
Taenia saginata on the digestive swine beef or pork Nausea, epigastric pain, proglottids in feces beef and pork,
system of the host for nervousness, insomnia, ELISA197 proper disposal of
nutrition anorexia, weight loss, PCR198 sewage and human
digestive disturbances, wastes, freezing of
weakness, dizziness meat at -10°C for 2
Duration is weeks to weeks
months
Diphyllobothrium latum Largest human Saltwater fish, Raw or undercooked Unknown Epigastric pain, nausea, Detection of eggs in Adequate cooking of
tapeworm humans saltwater fish abdominal pain, diarrhea, feces fish, proper disposal
weakness, pernicious of sewage and
anemia human waste
Duration is months to years
1153
cysts contaminate water or food through feces of infected animals or humans. Following
ingestion of cyst-contaminated water or food, the trophozoites reach the small intestine,
where they undergo excystation and multiply by binary fission. New trophozoites subse-
quently become cysts in the distal small intestine, and the encysted trophozoites are shed
in the feces. The symptoms of giardiasis include abdominal pain, abdominal distension,
nausea, vomiting, and diarrhea. Although water and foods contaminated with cysts are
primary vehicles of giardiasis, little is known about the survival characteristics of the cysts
in foods. In most cases of foodborne transmission, infected food handlers transfer the cysts
to foods they prepare.
Entamoeba histolytica
E. histolytica is a protozoan parasite that causes amoebiasis or amoebic dysentery in
humans. Although the parasite survives in the environment and water, humans are the
principal source of amoebiasis. In humans, cysts containing the trophozites are released,
which in turn multiply and are subsequently excreted in the feces as cysts.89 Foods and
water contaminated with the cysts transmit the disease. Since the fecal-oral route is the
principal route of transmission of amoebiasis, personal hygiene of infected food handlers
plays a critical role in preventing foodborne amoebiasis. Human amoebiasis can occur in
two forms: intestinal amoebiasis and amoebic liver abscess, which is usually a sequela to
the intestinal form. Intestinal amoebiasis is characterized by abdominal pain, vomiting,
and watery diarrhea containing mucus and blood. Symptoms of the hepatic form of
amoebiasis include wasting, painful and enlarged liver, weight loss, and anemia.
Cryptosporidium parvum
C. parvum is a protozoan parasite that infects a wide range of animals and humans. C.
parvum is monoexenous in its life cycle, requiring only one host for its development.88
Infected hosts shed in their feces oocysts of the parasite, subsequently contaminating the
environment, food, and water. The life cycle of C. parvum can be summarized as follows.88
Upon ingestion of contaminated water or food, or by inhalation of oocysts, sporozoites
are released by excystation of oocysts into the gastrointestinal or respiratory tract. The
sporozoites enter the epithelial cells and develop into trophozoites, which in turn differ-
entiate into type I and type II meronts. The merozoites from type I meronts invade new
tissues and develop into trophozoites to continue the life cycle. The merozoites from type
II meronts invade infected cells and undergo sexual multiplication to give rise to male
and female gametes. The zygotes resulting from fertilized gametes become infectious by
sporulation, and the sporulated oocysts are excreted in feces.
Cryptosporidiosis is a self-limiting disease with an incubation period of one to two
weeks, and is characterized by profuse, watery diarrhea, abdominal pain, vomiting, and
low-grade fever. Water is the most common source of C. parvum for human infections.58
Oocysts of the pathogen have been detected in fresh vegetables, raw milk, sausage, and
apple cider.58 Infected food handlers can also transfer the oocysts to foods.90, 91 C. parvum
oocysts are sensitive to freezing and freeze-drying. The oocysts lose infectivity in distilled
water stored at 4°C.92 However, the oocysts are quite resistant to chlorine; no loss in
infectivity was observed in water containing 1 to 3% chlorine for up to 18 hours.93 How-
ever, the oocysts are sensitive to ozone, losing more than 90% infectivity in the presence
of 1 ppm ozone for 5 minutes.94
Cyclospora cayetanensis
C. cayetanensis is an emerging foodborne, protozoan pathogen, especially in the U.S. The
parasite was implicated in several foodborne outbreaks in the U.S. during 1996 and 1997.95
C. cayetanensis is spread through infected feces and is transmitted to humans by the fecal-
oral route. Water and foods, especially fruits and vegetables containing oocysts, are com-
mon vehicles of human infection. The symptoms of C. cayetanensis infection in humans
include watery diarrhea, nausea, abdominal pain, vomiting, and weight loss. Presently,
very little information is available on the effects of heat, freezing, and disinfection agents
on Cyclospora oocysts. Preliminary studies revealed that exposure of oocysts to –20°C for
24 h or 60°C for 1 h prevented oocysts from sporulating. Exposing oocysts to 4° or 37°C
for 14 days delayed sporulation.96
Toxoplasma gondii
T. gondii is an obligate intracellular protozoan parasite for which cats are the definitive
hosts. In the intestines of cats, the parasite undergoes sexual reproduction to form oocysts,
which are excreted in feces.97 The oocysts undergo maturation and survive in the envi-
ronment for months. Toxoplasmosis in humans results following ingestion of food or water
contaminated with oocysts. Transmission also occurs from an infected pregnant mother
to child by transplacental transmission.89 Symptoms in healthy adults are usually mild,
and include rash, headache, muscle pain, and swelling of lymph nodes. The oocysts are
sensitive to both heat and cold;98 hence the cysts are killed in properly cooked foods.99
Trichinella spiralis
T. spiralis is a roundworm that primarily infects wild and domestic animals, especially
pigs. Humans contract trichinosis by consumption of raw or undercooked meat containing
larvae of the parasite. Pigs are infected by consuming uncooked scraps of infected pork.
The encysted larvae upon ingestion are liberated from the cyst in the intestine, where they
sexually mature.100 The mature male and female worms copulate in the lumen of the small
intestine, giving rise to a new generation of larvae. The newly born larvae migrate to
various tissues in the body. Those larvae that reach the striated muscles penetrate into the
sarcolemma of the muscle fibers and develop to maturity as encapsulated cysts.100 The
larvae continue their life cycle when raw or undercooked meat, especially pork containing
the larvae, is consumed by humans.
Anisakis Species
Anisakiasis in humans is caused by two foodborne roundworms. These include A. simplex,
whose definitive host is whales, and Pseudoterranova decipiens, which primarily inhabits
seals. The eggs of these roundworms are excreted in feces by their respective hosts. The
eggs then undergo molting in suitable intermediate hosts and subsequently develop into
larvae, which are ingested by fish.101 Humans contract anisakiasis by consumption of raw
or undercooked fish and seafoods containing the larvae. In noninvasive anisakiasis, the
worms released from ingested foods migrate to the pharynx, resulting in “tingling throat
syndrome.”101 The worms are ultimately expelled by coughing. In the invasive form of
anisakiasis, the worms penetrate the intestinal mucosa, causing symptoms that include
epigastric pain, nausea, vomiting, and diarrhea.
Taenia Species
The genus Taenia includes two meatborne pathogenic flat worms, T. saginata (beef tape-
worm) and T. solium (pork tapeworm). The eggs of T. saginata survive in the environment,
including on pastures, and are ingested by cattle in which they hatch into embryos.100 The
embryos migrate to skeletal muscles or the heart, and develop into larvae known as
cysticercus bovis. Humans become infected by consuming raw or undercooked beef con-
taining the larvae. Larvae that are released into the small intestine develop into mature,
adult worms. The symptoms of T. saginata infection in humans include decreased appetite,
headache, dizziness, diarrhea, and weight loss.
In the normal life cycle of T. solium, pigs serve as the intermediate host. Eggs ingested
by pigs develop into embryos in the duodenum, penetrate the intestinal wall, migrate
through the blood and the lymphatic system, and finally reach the skeletal muscles and
myocardium, where they develop into larvae known as cysticercus cellulose. Humans
consuming raw or undercooked pork are infected with the larvae, which develop into
adult worms in the small intestine. The symptoms of T. solium infection in humans include
discomfort, hunger pains, anorexia, and nervous disorders. Worms are passed in the feces.
In the abnormal life cycle of T. solium, humans serve as intermediate hosts in which the
larvae develop in striated muscles and in subcutaneous tissue.
Diphyllobothrium latum
D. latum is commonly referred to as the broad tapeworm because it is the largest human
tapeworm.101 Humans contract diphyllobothriasis by consuming raw or undercooked fish
containing the larval forms called plerocercoids. Upon ingestion, the larvae develop into
mature worms in the intestines. Eggs produced by mature worms are excreted in feces.
If feces containing the eggs contaminate water, the eggs develop into free-swimming larvae
called coricidia. Coricidia are ingested by crustaceans, where they develop into a juvenile
stage known as procercoid. Following ingestion of infected crustaceans by fish, procercoids
develop into plerocercoids to continue the life cycle. Diphyllobothriasis in humans is
characterized by nausea, abdominal pain, diarrhea, weakness, and pernicious anemia.101
Cases of diphyllobothriasis have been associated with eating raw salmon and sushi.
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56
Nutrition and Hollow Organs of the Upper
Gastrointestinal Tract
Nutrition is an integral part of the management of gastrointestinal illness. The following

two sections will elucidate the basic mechanisms of how the hollow organs of the gas-
trointestinal (GI) tract handle and digest food, how illnesses of these organs affect nutri-
tional status, and the role of nutrition in the management of these illnesses. The readers
are referred to a GI textbook for further details on diseases mentioned in these sections.
Neoplasms of the GI tract are not included (see Section 50).
Introduction
The general roles of the various parts of the digestive system are given in Table 56.1.
Diseases of these various parts not only cause damage to individual organs but also disrupt
the harmonious mechanisms that enable adequate handling and digestion of food.
Food enters through the mouth where it is lubricated and broken down into pieces by
mastication. Lubrication serves several purposes including protection of the mouth from
damage by food, ease of transfer of food over surfaces of the GI tract and, formation of a
liquid medium in which chemical reactions of digestion can occur. Mastication is not only
necessary for food breakdown, but also helps to increase the surface area of the food
particles to allow reach by digestive enzymes.
Transport of food through the mouth and the pharynx into the esophagus is accom-
plished by the swallowing reflex. This reflex involves coordinated actions of the tongue,
the soft and hard palates, the pharyngeal muscles, the glottis, the epiglottis, and the upper
esophageal sphincter. It is extremely rapid with a duration less than a second, and is
regulated by both peripheral nerves and a swallowing center in the brain stem.1 The
multiple levels of control of swallowing and the redundancy of the control mechanisms
allow compensating for minor problems.
Once swallowing is initiated voluntarily or involuntarily and the content of the mouth
is pushed back into the pharynx, the swallowing reflex results in closure of the larynx by
the epiglottis and concomitant relaxation of the upper esophageal sphincter (UES) to
enable reception of bolus into the esophagus. Subsequently, the esophageal body, which
has a short segment of striated muscle proximally but mainly is made up of smooth muscle,
0-8493-2705-9/02/$0.00+$1.50
TABLE 56.1
Parts of the Digestive System and Their Functions
Parts Functions
Mouth, salivary glands, Breakdown of food into parts for transport to downstream; lubrication of food
and pharynx pieces for transport; initiation of the digestion of carbohydrates in food
Esophagus Transport and lubrication of food pieces; protection of the airway from food entry
Stomach Storage and trituration of food into small pieces (<1 mm3); initiation of the
digestion of proteins with acid and proteases; initiation of the digestion of fats
Small intestines Breakdown of foods into molecules; and absorption of macro- and micronutrients;
maintenance of water and electrolyte balance
Colon Absorption of water and electrolytes; synthesis of certain vitamins and breakdown
of carbohydrates to short chain fatty acids by bacteria; excretion of waste
propels the bolus downward with peristaltic motion. As the bolus travels through the
distal esophagus, the lower esophageal sphincter (LES) relaxes and food is transported
into the stomach for short-term storage and digestion. The integrity of the entire esoph-
ageal food transfer mechanism is very important to prevent food entering the airway.
Food goes through two functionally distinct compartments in the stomach. The proximal
compartment, consisting of the fundus and upper body, acts as a reservoir. An adequate
capacity in this compartment is achieved through receptive relaxation of the stomach wall,
mediated by inhibition of vagal pathways and hormones such as secretin, gastric inhibitory
peptide, and cholecystokinin (CCK). This relaxation allows for a wide range of storage
volumes up to 1 to 2 liters without significant increases in intragastric pressure. At the same
time, release of acid and digestive enzymes into the reservoir initiates gastric digestion.
The distal and second compartment of the stomach consists of the lower body and
antrum, whose main function is dissolution of food into gastric chyme with particle size
<1 to 2 millimeters prior to exit through the pylorus. This process, termed trituration, is
achieved by the strong propulsive motor activity of the stomach. After initiation of the
electrical signal that is generated by specialized pacemaker cells located in the mid-portion
of the greater curvature, the stomach begins to contract from the mid-body, the contraction
gradually spreads towards the antrum in a peristaltic fashion, and partial closure of the
pyloric channel occurs. The stomach contents are forced backward against the antral walls
and a closed pylorus, with passage of only a small amount of well-ground food into the
duodenum. The shearing physical forces generated in this repetitive propulsion and
retropulsion of gastric contents attain the particle size required of solid foods before
passage into the small intestine.
Antral contractions cause emptying of solid food from the stomach. Liquids exit pro-
portional to the pressure gradient between the duodenum and the stomach. This pressure
gradient increases after completion of a meal when receptive relaxation fades away and
the gastric fundus returns to its normal tone, increasing intragastric pressure. The rate of
emptying from the stomach is also determined by the chemical and physical composition
of the meal, as well as the way the body reacts to the food via the vagus nerve and the
GI hormones. Liquids empty faster than solids; foods with high carbohydrate contents
empty faster than foods that contain fat or are high in fiber. Hypo- or hypertonic fluids,
highly viscous fluids, acid (pH 3.5), chyme with a high caloric density, polypeptides,
oligosaccharides, and fatty acids entering the duodenum, or overdistention of the small
intestine inhibit gastric emptying. If nutrients rapidly enter or bypass the jejunum, rapidly
reaching the ileum and colon, GI transit time is extended via an ileal “brake.” This brake
is mediated through neurohumoral mechanisms and GI hormones, the most important of
which is peptide YY. These mechanisms assure that food is gradually released into the
Nutrition and Hollow Organs of the Upper Gastrointestinal Tract 1165
small intestine, is optimally mixed with pancreatic and biliary secretions, and has adequate
contact time with digestive enzymes and the small intestinal absorptive mucosa.
The small intestine is designed to have a large surface area, by arrangement of its cells
into villi and crypts. The epithelial cells’ lumenal surfaces have fingerlike projections
termed microvilli that collectively make up the brush border. Most intestinal secretions
come from the crypt cells, whereas the major function of the cells of the villi is digestion
and absorption of water and nutrients. The villi, as well as their lining cells, are taller in
the jejunum, and the height of both decreases caudally towards the ileum. Intestinal cells
also become more specialized towards the ileum, where absorption of bile salts and certain
vitamins occurs. Digestion of nutrients is accomplished both by brush border and intralu-
minal enzymes, especially pancreatic exocrine ones. The different types of nutrients and
how they are digested by the various enzymes in the GI tract are shown in Figure 56.1.
After gastric chyme arrives at the small intestine, its acidity is rapidly neutralized by
duodenal secretions and bicarbonate released from the pancreas. This neutralization is
important for establishing a favorable milieu for optimal enzyme action. Furthermore,
large amounts of electrolytes and water are secreted into the jejunal lumen to make chyme
isoosmolar, dilute toxins, and enable mucosal defense mechanisms such as secretory IgA.
Almost simultaneously, motor activity of the intestines changes: propulsive movement
decreases and segmental motor contractility increases. The net effect is stirring of intestinal
contents with slow forward motion, which in turn increases contact of nutrients with
intestinal cells.
During this process, blood flow and lymphatic drainage of the intestine are tightly
regulated. Both flows increase as food, electrolytes, and water are absorbed, rapidly
carrying these away to facilitate further diffusion. This rapid circulation ensures meeting
intestinal oxygen, salt, and water demands, especially during secretion.
The products of digestion get absorbed, utilizing various mechanisms such as passive
diffusion and osmosis, facilitated diffusion, and active transport. The sites of absorption
of different nutrients and the mechanism(s) involved in this process are given in Table
56.2. A small amount of macronutrients leaves the small intestine undigested. Undigested
portions are larger for complex carbohydrates, vary with fat intake, and are minimal for
proteins.
In the colon, bacteria act on the remaining nutrients and fiber, forming short chain fatty
acids and a variety of vitamins. These and large amounts of electrolyte and water are
avidly absorbed by the colon, resulting in a small amount of feces. Together with the
enterohepatic circulation of bile, the absorption of 98% of all GI fluid and electrolytes
makes the GI system one of the most efficient parts of the body. The various GI secretions
are listed in Table 56.3, along with calculation of the net fluid balance.
Nutrition in Selected Diseases of the Upper Gastrointestinal Tract

Gastroesophageal Reflux Disease (GERD)
Definition and Epidemiology
GERD exists in individuals who have symptoms or histopathological changes related to
backflow of gastric contents into the esophagus (see Tables 56.4 and 56.5). There is no gold
standard test to diagnose GERD; its incidence is estimated from either the disease symp-
toms (most frequently heartburn) or from findings of esophageal injury such as
1166
Carbohydrates Fat Protein
Complex Carbohydrates Simple Carbohydrates Triglycerides Cholesterol Hydrochloric acid

(Starch, Glycogen, Dextrin) (Sucrose, Lactose, Maltose) Pepsinogen
(Stomach)
Amylase Lipase and colipase Cholesterol esterase
(Saliva) (Pancreas) (Pancreas)
Large polypeptides and amino acids
+ Bile + Bile Protein
Branched oligosaccharides
Some maltose Trypsinogen

Fatty acids Cholesterol esters Chymotrypsinogen
Alpha-amylase Monoglycerides Procarboxypeptidase
(Panceas) Glycerol (Pancreas)
Monoglyceride lipase
Phospholipase A and B (+Bile) Small polypeptides and amino acids
Maltose and dextrins Lecithinase
(Pancreas)
Disaccharidases Aminopeptidases
(Small bowel brush border) Dipeptidases
Fatty acids, Glycerol, Phosphoric acid (Small bowel brush border &
cytoplasm of absorptive cells)
Glucose, Maltotriose, Fructose, Galactose Smaller polypeptides and amino acids
FIGURE 56.1
Digestion of macronutrients.
TABLE 56.2
Overview of Nutrient Absorption
Nutrient Absorption Site Mechanism of Absorption
Lipids Proximal and distal jejunum, Passive diffusion, facilitated diffusion*
colon
Monosaccharides Proximal and distal jejunum Na-dependent active transport
Amino acids Proximal and distal jejunum Carrier-mediated active transport, simple diffusion
Small peptides Proximal and distal jejunum Na-independent tertiary active transport
Bile salts and Distal ileum Passive absorption, specific active absorption
acids
Vitamin A Duodenum, mid-jejunum Passive diffusion**

Vitamin D Duodenum, mid-jejunum, ileum Passive diffusion**
Vitamin E Duodenum, mid-jejunum Passive diffusion**
Vitamin K1 Duodenum, mid-jejunum, ileum, Carrier-mediated uptake**
colon
Vitamin K2 Duodenum, mid-jejunum, ileum, Passive diffusion**
colon
Ascorbic acid Mid-jejunum, ileum Na-dependent active transport
Vitamin B12 Ileum Intrinsic factor binding, specific receptor med
Vitamin B6 Jejunum Passive diffusion
Thiamine Duodenum, mid-jejunum Na-dependent active transport***
Riboflavin Duodenum, mid-jejunum Na-dependent active transport***
Niacin Duodenum, mid-jejunum Awaits further study
Pantothenic acid Mid-jejunum Na-dependent active transport
Biotin Duodenum, jejunum, colon Na-dependent active transport
Folate Duodenum, mid-jejunum, ileum Specific carrier mediated
Na-dependent active transport
pH-sensitive process
Sodium Colon Ion-specific channel

Carrier mediated coupling sodium and nutrients
Antiport carrier
Chloride Colon Electrogenic diffusion created by Na absorption

Transcellular transport linked to Na via dual antiport
Anion exchangers
Potassium Colon Active transport by K-ATPase pumps
Calcium Duodenum, mid-jejunum, ileum Active transcellular process via specific channels,
colon binding to calbindin and Ca-ATPase
Passive paracellular diffusive process
Phosphorus Duodenum, mid-jejunum Active transport, passive diffusion
Magnesium Duodenum, mid-jejunum, ileum Passive paracellular diffusive process

Transcellular carrier mediated saturable process
Iron Duodenum, mid-jejunum Passive paracellular diffusive process

Nonessential fatty acid stimulated pathway
Intracellular iron binding proteins
Zinc Mid-jejunum Saturable carrier mediated process

Nonsaturable diffusion process
Iodine Stomach Active transport, passive diffusion†
Selenium Duodenum Active transport, passive diffusion†


Overview of Nutrient Absorption
Nutrient Absorption Site Mechanism of Absorption
Copper Stomach, duodenum Unknown††
Molybdenum Stomach, mid-jejunum Unknown††
Chromium Mid-jejunum Unknown††
Manganese Mid-jejunum Unknown††
Fluoride Stomach Unknown††
* linoleic acid uptake occurs by facilitated diffusion
** bile salts are required for solubilization of the vitamins
*** includes hydrolytic acid phosphorilation steps
† some is also transported as amino acid complexes
†† possibly via facilitated diffusion or active diffusion or passive diffusion
TABLE 56.3
Gastrointestinal Secretions
Approximate Volume
Site (in ml)
1. Salivary glands 1500
2. Stomach 2500
3. Liver (as bile) 500
4. Pancreas 1500
5. Small intestine 1000
GI tract secretions(1+2+3+4+5) +7000

Daily oral intake +2500
Absorption –9300
Net excretion in the form of stool 200
TABLE 56.4
Symptoms of GERD
Esophageal Extraesophageal
Heartburn (pyrosis) Hypersalivation
Acid regurgitation Nocturnal choking sensation
Dysphagia Symptoms related to asthma:
Odynophagia Wheezing
Chest pain Shortness of breath
Globus sensation Chronic cough
Nausea/Vomiting Other symptoms of asthma
Symptoms of GI bleeding: Symptoms related to posterior laryngitis:
Coffee ground emesis Chronic hoarseness/Dysphonia
Melena Frequent throat clearing
Chronic cough
Sore throat
Other symptoms of laryngitis
Symptoms related to dental caries
TABLE 56.5
Histopathological Changes Related to GERD
Reflux esophagitis: Destruction of esophageal epithelium: erosions, ulcers, balloon cells in
epithelium
Neutrophilic or eosinophilic infiltration of the mucosa
Large basal zone (>15% of the total epithelial thickness)
Extension of mucosal papillae
Regenerative changes in the epithelium
Barrett’s esophagus: Metaplastic columnar epithelium replacing normal esophageal mucosa
Adenocarcinoma of the esophagus
Peptic strictures
Inflammatory polyps of the esophagus
Pseudodiverticula
Esophageal fistulas
TABLE 56.6
Major Mechanisms Thought to be Involved in the Pathogenesis
of GERD
1. Incompetent lower esophageal sphincter (LES)
a. Increased transient relaxations of LES
b. Hypotensive LES, i.e., decreased LES tone
c. High gastroesophageal pressure gradient
2. Irritant effects of the refluxed material (especially gastric acid and pepsin)
3. Abnormal esophageal clearance/ neutralization of the refluxed material
4. Delayed gastric emptying
5. Increased esophageal sensory perception
esophagitis. Heartburn is very common: 36% of the population experience heartburn at

least once a month.2 Esophagitis is estimated to occur in 3 to 5% of the general population.
Mechanisms
Factors and mechanisms important in GERD pathogenesis are listed in Table 56.6. Current
dietary management of GERD is based on preventing or counteracting these mechanisms.
Effects on Nutritional Status

Uncomplicated GERD occasionally may lead to malnutrition in infants and children,
although this is extremely rare in adults. Scurvy has been reported as a result of long-
term avoidance of foods that contain vitamin C.3 Additionally, megaloblastic anemia has
occurred in association with long-term use of a proton pump inhibitor.4
In cases of significant malnutrition with GERD symptoms, diseases giving rise to similar
symptomatology and complications of GERD need to be sought. Examples include eating
disorders and scleroderma, which are easily overlooked. Complications of GERD are given
in Table 56.7.
Lifestyle Factors That May Affect GERD

Lifestyle factors that may adversely affect the severity or frequency of GERD-related
symptoms are given in Table 56.8.
TABLE 56.7
Major Complications of GERD
1. Acute GI bleeding
2. Chronic GI bleeding with anemia
3. Peptic strictures
4. Esophageal perforation
5. Barrett’s esophagus
6. Adenocarcinoma of the esophagus
TABLE 56.8
Lifestyle Factors That May Adversely
Affect Severity or Frequency of GERD
1. Obesity
2. Smoking
3. Exercise
4. Alcohol consumption
5. Recumbent body position
6. Tight clothing over abdomen
Obesity
GERD is associated with obesity, and the occurrence of GERD is positively correlated with
increasing body mass index (BMI). The frequency and severity of GERD seems to be worse
in obese individuals; a significantly higher number of GERD-related hospitalizations
occurred among the obese in the NHANES study.5 Obese individuals also tend to have a
higher incidence of hiatal hernia that adversely affects LES function and competence.6 In
some obese individuals, LES pressures are lower than controls,7 but this is not a consistent
mechanism of GERD.8 It is postulated that the gastroesophageal pressure gradient (dif-
ference between the pressures in the esophagus and stomach) may play a more important
role. As a result of the mechanical effects of increased intraabdominal fat, this gradient
may be high in many obese patients with GERD. This forces gastric contents towards the
relatively lower pressure esophageal environment and may promote reflux during any
sphincter relaxation. Additionally, obese individuals have a higher incidence of esophageal
motility disturbances8 and cannot clear acid/gastric contents from the esophagus as fast
as non-obese controls.9 Combination of the high gastroesophageal pressure gradient with
decreased clearance may explain the frequency and severity of GERD with obesity.
One study among obese GERD patients who are not medication dependent for symptom
control showed significant symptomatic improvement with weight loss.10 The authors
have anecdotal evidence that even loss of a few pounds may improve symptoms. However,
definitive evidence that relates weight reduction to improvement in GERD is lacking.
Some studies show no benefit, although most of these studies have been undertaken in
individuals who are medication dependent with severely symptomatic disease. Large
amounts of weight loss may be required in the morbidly obese before symptomatic
improvement is evident. Nevertheless, most obese individuals should be encouraged to
lose weight as first line treatment not only for GERD, but also for other health benefits.
Exercise
Exercise such as rowing, cycling, or jogging may cause GERD in healthy volunteers.11
Reflux is further potentiated if the exercise is performed after meals.11-13 There are no
definitive studies of GERD patients in this area.
Tight Clothing
Tight clothing worn over the abdomen and stomach has been postulated to elevate the
gastroesophageal pressure gradient, especially postprandially.14 Therefore, loose-fitting
clothing has been recommended, although no clinical data support this recommendation.
Food and Diet in GERD

Dietary Habits, Body Position after Meals, and GERD
Gastric distention is a potent stimulus for inappropriate transient LES relaxations. Espe-
cially after the first few hours of eating, meal size is the most important determinant of
gastric distention. Therefore, GERD patients are advised to eat smaller meals and drink
liquids between, as opposed to with, meals.
Recumbent body position and sleep both decrease the clearance of refluxed gastric
contents from the esophagus, resulting in prolonged esophageal exposure to acid, pepsin,
etc.15 Such exposure is a major contributor to the severity of esophagitis and stricture
formation. Intraesophageal pH recordings in sleeping GERD patients show that elevation
of the head of the bed significantly improves nocturnal acid clearance times.16-18 Combined
with H2 blocker therapy, use of blocks to raise the head of the bed decreases retrosternal
chest pain better than medication alone.19 This effect is especially prominent for smokers
and alcohol consumers. Thus, GERD patients are advised not to sleep for at least two
hours after eating, to assume an upright body posture while awake, and to elevate the
head of their bed using blocks or a foam wedge.
Meal Types and Foods That May Adversely Affect the GERD Patient
A recent study comparing various different meals suggests that more than one component
or feature of the meal determines induction of GERD.20 Use of spices, caloric density, fat
content, and alcohol consumption with the meal, alone or in combination, may affect
initiation of symptoms.
Various foods that are known to induce GERD, worsen its severity, or adversely affect
healing of esophagitis are given in Table 56.9 together with their mechanisms of action.
Alcohol’s effects on promoting reflux are well documented and may be potentiated in the
presence of fatty meals. Different than other alcoholic beverages, wine is very hypertonic,
acidic, and has high tyramine content. Tyramine competes with histamine for degradation
and may therefore delay the breakdown of the latter, which increases gastric acid secretion.
In a survey of 349 individuals with GERD, wine has been reported to cause reflux in 37%.21
While there is no evidence that meal consistency (solid vs. liquid) affects reflux, osmo-
lality of food may be important. Hyperosmolar versus isoosmolar foods reproduce esoph-
ageal symptoms. Coffee is thought to provoke GERD symptoms because of its high
osmolality and irritant effects on the esophageal mucosa22,23 rather than its effects on LES
pressure and transient LES relaxations, which are variable.
The relationship between fat intake and GERD is unclear. Fat may increase GERD by
decreasing LES pressure24 caused by cholecystokinin (CCK) release, and by slowing gastric
emptying, which in turn is thought to increase the frequency of transient LES relaxations
resulting from a vagovagal reflex originating in stomach mechanoreceptors.25
Survey findings show that fatty foods precipitate symptoms of GERD in 38% of normal
subjects. Earlier studies show that in healthy volunteers, LES pressures decrease after
ingestion of a fatty meal, as opposed to increase with a protein meal. When adjusted for
body position, this effect of fat on LES pressure was present only in recumbency in one
study,26 and only in the upright position in another.27 In a third study, high fat content
(50%) compared to low (10%) made no difference.28 However, nonphysiological fat expo-
TABLE 56.9
Foods That May Worsen GERD
Food Effect(s)
Methylxanthines ↓ LES pressure 2o inhibition of phosphodiesterase → increased cAMP and smooth
(e.g., theophylline in tea) muscle relaxation
Carminatives ↓ LES pressure
(e.g., peppermint) ↑ transient LES relaxations
Chocolate Methylxanthines in it cause ↓ LES pressure
High fat content ↓ gastric emptying
↑ transient LES relaxations
Alcohol ↓ or ↑ LES pressure
↓ esophageal peristalsis → ↓ acid clearance
Caustic effect on mucosa
Adverse effects on protective mucus
↑ gastric acid secretion
↑ number of reflux episodes
↑ nocturnal acid reflux
Citrus juice Directly irritant to the esophageal mucosa
Tomatoes Directly irritant to the esophageal mucosa
↑ transient LES relaxations possibly secondary to salicylate content
Capsaicin Directly irritant to the esophageal mucosa
(found in peppers) ↑ gastric acid and pepsin secretion
Spearmint Directly irritant to the esophageal mucosa
Coffee Directly irritant to the esophageal mucosa
↑ gastric acid secretion
↓ or ↑ LES pressure
(effects worse with concomitant food intake)
(effects vary with brand and treatment prior to consumption)
Onions ↑ transient LES relaxations
↑ acid-pepsin injury possibly through inhibition of arachidonic acid metabolism
(raw ones create worse symptoms compared to cooked)
Milk ↑ gastric acid secretion
sures (100% fat infused into the duodenum) increased the rate of reflux episodes and the
incidence of reflux during transient LES relaxations.29 The discrepancy in results may be
related to variations in composition of the diets used, the small number of patients
involved, and the differences in baseline characteristics of the study subjects.
Results are more consistent for GERD patients. In terms of esophageal acid exposure when
identical protein content, volume, and kcalories are provided to patients, fat does not seem
to matter.27 Recent work confirms that a high fat meal (52%), compared to 24% fat meal in
an isovolumic and isoosmolar balanced one, affects neither the acidity of the esophagus nor
resting LES pressures and the rate of transient LES relaxations three hours postprandially
in healthy subjects and GERD patients.30 However, these studies involve small numbers of
subjects; findings may not apply to various subgroups of patients, and there may not be
enough power to detect significant differences. Nevertheless, based on these results, a low
fat diet cannot be recommended for all patients with GERD. For the individual symptomatic
patient who cannot tolerate fat, avoidance of fatty meals is reasonable.
The type of fat in a meal may also affect GERD. In preterm infants, medium-chain
triglycerides have been shown to significantly increase gastric emptying compared to long-
chain triglycerides. One study investigating reflux rates two hours postprandially has
found no difference with or without medium-chain triglycerides in pediatric formulas.31
In healthy adults, new non-digestible fats (e.g., olestra) do not alter esophageal acid
exposure or delay gastric emptying.32
TABLE 56.10
Summary of Tips for the GERD Patient
1. If overweight, lose weight
2. Try avoiding foods that may worsen GERD (given in Table 56.9)
3. Eat small quantities of food at a time
4. Eat in an upright position
5. Avoid drinking large quantities of liquids with meals
6. Do not recline for at least 2 hours after meals
7. Do not exercise for several hours after meals
8. If night time symptoms are present, try elevating the head of the bed with a wedge
9. If taking proton pump inhibitors, take medication 30 minutes before a meal
Data on other macronutrients and components of diet and GERD are sparse. High
protein meals increased LES pressure in volunteers in one study,24 but a commercially
available amino acid solution infused intravenously or given intragastrically did not
change reflux episodes or transient LES relaxations.33 Oral L-Arginine did not promote
reflux, despite increasing nitric oxide and lowering LES pressures.34 High fiber did not
cause reflux in 20 patients with suspected GERD.35
Gas-containing foods such as carbonated beverages are commonly believed to initiate
reflux episodes through belching. Although no definitive data exists, in one study among
GERD patients, postprandial gas reflux made up 47% of the reflux episodes versus liquid
reflux, which happened 78% of the time. Only 24% of liquid retroflow into the esophagus
was preceded by gas reflux, which suggests that most episodes occur without belching.36
Another reflux-promoting mechanism may be stimulation of gastric acid secretion, as seen
with cola beverages.
Do We Really Need a Certain Diet for GERD? Is There Enough Scientific Evidence for a Particular
Diet?
There is no scientific evidence for a specific diet for all or most GERD patients. While a
combination of lifestyle modifications such as weight loss, bland diet, elevation of the
head of the bed, and antacids has been used in the past, the majority of patients with
chronic symptoms and complications (about 81% in one study) do not respond, and
ultimately require use of medications like H2 blockers and proton pump inhibitors (PPIs),
or surgical therapy. However, this may not apply to numerous individuals with less severe
GERD, who may not even present to physicians. Given the high disease prevalence, the
potential side effects of medications, and the expense of chronic PPI therapy, studies
pertaining to the utility of diet therapies alone or in combination with other lifestyle
modifications in patients with less severe disease are needed urgently. In the meantime,
the authors assert that all patients should be educated about various aspects of diet and
its effects on GERD. Patients should be given a chance to experience and experiment with
the nutritional tips for GERD patients given in Table 56.10. Treatment with a diet consisting
of avoidance of reflux-promoting foods (as in Table 56.9) should be reserved for the
individual patient responding with the most symptomatic relief. The physician should
ascertain that such treatment does not impair the patient’s quality of life, as effective
alternative management exists.
GERD Therapy and Diet

In general, patients with GERD tolerate all foods while on treatment with medications.
Patients who do not symptomatically or histologically improve with standard therapy
may have allergic eosinophilic esophagitis. Most such patients are children,37 for whom
therapy is withdrawal of the offending protein and feeding an elemental diet.
Surgical treatment of GERD may be complicated with dumping syndrome, dysphagia,

and gas-bloat syndrome. Dietary treatment of dumping syndrome is given below. Dietary
treatment of dysphagia and gas-bloat syndrome after fundoplication is based on common
sense and anecdotal evidence. For dysphagia, authors suggest that patients eat soft foods,
eat slowly, and chew food well. For gas-bloat syndrome, the suggestions are the following:
1. to decrease aerophagia: avoid talking and laughing during meals, avoid chewing gum,
hard candy, mints, etc., chew foods well, do not rush through meals or eat on the run; 2.
to decrease intestinal gas production: avoid gas-forming foods such as legumes, beans,
etc., or foods that contain significant amounts of nondigestible materials like sorbitol,
olestra, etc.
Nutritional tips for patients with GERD are summarized in Table 56.10.
The Patient on Enteral Nutrition and GERD

Theoretically, GERD may get worse with nasogastric or nasoenteric feedings as well as
with gastrostomy placement. However, these interventions usually involve sick patients
who may already have GI motility problems as a result of underlying illnesses. Therefore,
worsening of GERD in such settings may not be reflective of these interventions.
Aspiration is the number one complication of enteral feeding via tube placement.
Nasoenteric tubes can promote transient LES relaxations38 and therefore may put patients
at a higher risk of aspiration compared to gastrostomy tubes. Differences between gas-
trostomy and jejunostomy tubes have been evaluated in small or poorly designed studies
without clear documentation of tube position. The American Gastroenterological Associ-
ation recommends reservation of jejunostomy to patients with a history of GERD or
recurrent aspiration secondary to gastrostomy tubes.39
Peptic Ulcer Disease (PUD)

Peptic ulcer disease is characterized by defects in the mucosa that extend through the
muscularis mucosa (i.e., ulcers) in the presence of acid-peptic injury. PUD is common,
with a lifetime prevalence of 5 to 10%. The etiologies for the disease are given in Table 56.11.
Mechanisms
Proposed mechanisms of peptic ulcer pathogenesis are given in Table 56.12. Of these, the
most important is the presence of gastric acid. Many studies have shown that when acid
is eliminated, ulcers do not form. Therefore, the current treatment of PUD is directed at
TABLE 56.11
Causes of PUD
Common Uncommon
Helicobacter pylori Diseases that cause hyperacidity:
Nonsteroidal anti-inflammatory drugs Zollinger Ellison syndrome (gastrinoma)
Stress-related mucosal damage Mastocytosis/Basophilic leukemia
Antral G cell hyperplasia or hyperfunction
Infections of the gastric mucosa:
Cytomegalovirus
Herpes simplex
Vascular diseases:
Chronic radiation injury
Crack cocaine-related injury
Chemotherapy related injury
TABLE 56.12
Major Mechanisms of Tissue Damage and Repair Involved in the Pathogenesis of PUD
1. Epithelial cell injury resulting from:
a. Exogenous irritants like NSAIDs and alcohol
b. Endogenous irritants like acid, pepsin, bile acids, and lysolecithin
c. Breakdown of epithelial defense mechanisms:
i. Weak mucus and bicarbonate layer
ii. Low resistance of the apical cell membrane to acid back diffusion
iii. Inadequate acid clearance intracellularly because of derangements of the Na+/H+ antiporter
iv. Inadequate acid clearance extracellularly because of altered mucosal blood flow
2. Inadequate repair of epithelial injury:
a. Inadequate epithelial cell restitution and growth
b. Inadequate wound healing
decreasing gastric acidity with medications. If H. pylori is present, treatment with antibi-
otics is undertaken to preven recurrence.

PUD may affect nutritional status, especially if complications related to PUD or to the
cause of PUD are present. These are given in Table 56.13. Helicobacter pylori or medication-
induced atrophic gastritis may lead to vitamin B12 deficiency. Repeated blood loss from
bleeding ulcers may cause iron deficiency anemia. Chronic long-standing gastric outlet
obstruction as a result of scarring of the pyloric channel or development of severe dumping
syndrome following surgical treatment of ulcers can cause protein and kcalorie malnutri-
tion. These complications are rare in the U.S.
Diet in PUD
The role of diet in PUD occurrence and treatment has changed tremendously as our
knowledge about the pathogenesis of PUD increased. In the early 1900s, with the rationale
that food buffers stomach acid, Lenhartz39a proposed that frequent small meals might be
of benefit in PUD treatment. Physicians of the day followed with restrictive dietary treat-
ment programs that advocated small quantities of bland food at frequent intervals, in the
hopes that such a feeding regimen would also stimulate less acid secretion and thereby
hasten healing. One PUD treatment consisting of milk, cream, and eggs with subsequent
addition of soft and “nonirritating” foods, the Sippy diet, was formulated by Sippy and
Hurst in 1910.40 This diet and its modifications prevailed in PUD treatment over eight
decades. A 1977 survey by Welsh et al. of 326 hospitals in the U.S. demonstrated that 77%
used a bland diet and 55% routinely or usually gave milk to PUD patients.41 Marked
variations were seen in the composition of these supposedly similar diets.
The benefits of restrictive diets, including the Sippy and its modifications, are refuted
in numerous studies.42-45 First, acidity of the stomach following bland diets and freely
TABLE 56.13
Major Complications Related to PUD
1. Atrophic gastritis
2. Gastric carcinoma related to H. pylori
3. Obstruction, esp. at gastric outlet
4. Hemorrhage (acute or chronic)
5. Perforation
6. Penetration of ulcers
chosen diets do not differ.46 More importantly, controlled studies of radiological ulcer
healing or resolution of clinical symptoms show no improvement on these diets.47,48 The
same is true for ulcer recurrence, which is not different with or without such diets when
patients are followed up to a year or more.47,49 Instead, these diets in the long-term may
be harmful; they can result in nutritional deficiencies such as scurvy.50 Given this evidence,
there is no reason to support the use of a restricted or bland diet for PUD. Further evidence
for and against various dietary interventions are given below.
Small Frequent Feedings

Food-related gastric acid stimulation is prolonged in PUD patients, and therefore it is not
logical to expect adequate acid buffering with any type of meal.51,52 Even though peak
acid secretion may be higher as a result of gastric distention with larger meals, studies
show that mean acid concentration does not differ when patients are fed two-hourly
portions as opposed to four-hourly ones.53
Increased Use of Milk

Milk had been advocated as part of the early diets for PUD (including the Sippy and its
modifications) because of its acid-buffering capacity. However, in a study of a large group
of PUD patients, intragastric milk drip did not improve radiological healing of PUD,
although pain relief was quicker.54 In another study of 65 patients taking equal doses of
cimetidine, endoscopic ulcer healing or pain relief at four weeks was worse in the group
given milk with seasonal fruits as opposed to the group given a regular diet.55
Milk increases gastric acid secretion (about 30% in duodenal ulcer patients)56 and its
capability to neutralize acid is short-lived.57 Whether milk is whole, low-fat, or non-fat
does not make a difference.57 Amino acids released as a result of hydrolysis of milk proteins
stimulate gastrin secretion.56 The relatively high calcium in milk acts as a second messenger
for gastrin and acetylcholine stimulated acid release, and ulcer patients are more sensitive
to such effects of calcium.58
Milk can also be harmful to ulcer patients who consume large amounts of absorbable
antacids concomitantly. These PUD patients may develop acute or chronic milk-alkali
syndrome leading to alkalosis, renal insufficiency/calculi and hypercalcemia.59
Changing the Macronutrient Composition of Diet

Protein stimulates gastric acid more than carbohydrates and fat;60 however, there is also
evidence that high protein may result in lower gastric and duodenal acidity following
meals.61 Whether this effect is due to satiety induced by the high protein is unknown.
Thus, no recommendations concerning the protein content of the meal for PUD can be
made. Although fat in the small intestine inhibits gastric acid secretion,62 there is no
satisfactory evidence that high-fat diets are beneficial to ulcer patients, either. In fact, many
of the bland diets, including the Sippy diet, are high in fat and have been shown to be
harmful by increasing the risk of cardiovascular disease among PUD patients.
Alcohol Consumption
Alcohol ingestion can cause acute erosive gastritis with ulcerations and bleeding. Alcohol
concentrations of at least 8% were required to break the gastric mucosal barrier in one
study,63 while higher levels of 40% or more were needed in another study.64 Alcohol as
low as 5% stimulates gastric acid secretion both through direct stimulation of parietal cells
and through release of antral gastrin, although the effects may vary depending on the
type of beverage consumed.65 Beer, for example, can increase acid independent of its
ethanol content. Intake of alcohol with salicylates may contribute to its irritant effects by
causing back-diffusion of acid and stimulating pepsin secretion. Furthermore, acute alco-
hol ingestion can weaken duodenal defenses against ulcer formation by inhibiting basal
and secretin-stimulated pancreatic fluid and bicarbonate secretion,66-68 which is not entirely
due to alcohol-induced contraction of the sphincter of Oddi.69
Epidemiological studies, however, show no difference in alcohol consumption between
high and low PUD areas throughout different parts of the world, and alcohol intake is
not independently predictive of PUD prevalence in surveys (although most studies were
conducted before testing for H. pylori was implemented.) Indeed, in one prospective study,
alcohol consumption was lower among PUD patients compared to controls. Alcohol does
not adversely affect ulcer healing either. In one study, moderate alcohol consumption
(20g/day or less) promoted healing of duodenal ulcers. An author of this study, Sonnen-
berg, also reported that alcohol in small amounts is protective against NSAID injury, and
hypothesized that alcohol may be similar to mild irritants in that low doses may heighten
mucosal defenses through stimulation of prostaglandin production.70
Caffeine/Coffee/Tea/Carbonated Drinks
Caffeine stimulates both acid and pepsin release, and patients with duodenal ulcer have a
greater and longer response. The effects of coffee and tea, however, exceed what their
caffeine content induces.71 Serum gastrin and gastric acidity (especially in ulcer patients)
is higher than caffeine, and decaffeination diminishes this acid-secretory potency only
minimally.71 In one study, the addition of milk and sugar to tea lessened this effect.72
Whether these translate into clinical significance is unknown. Habitual coffee consumption
in college students was linked to development of PUD in later life. Conversely, a very large
survey of 37,000 subjects failed to show an association between coffee and PUD. Carbonated
beverages similarly stimulate acid production, but this may also be unrelated to caffeine.71
Salt Intake
A large oral load of salt can be an irritant to the gastric mucosa, leading to gastritis.73 In
epidemiological studies, PUD mortality correlates linearly with increasing salt consump-
tion.74 Case control studies also show that gastric ulcer patients have a higher level of salt
intake compared to healthy controls.75
Avoidance of Certain Spices

Application of spices on upper GI mucosa revealed that cinnamon, nutmeg, allspice,
thyme, black pepper, cloves, and paprika cause no endoscopic damage, whereas hot
pepper, chili powder, and mustard lead to edema, erythema, and mucosal breakdown.76
The latter spices also lead to epigastric discomfort in patients.76 Furthermore, peppers
induce supramaximal acid output in duodenal ulcer patients, and have been associated
with gastritis.77 In one study using gastric lavage, both red and black pepper caused higher
levels of gastric cell exfoliation, acid and pepsin secretion, and microbleeding, although
this was not confirmed endoscopically.78 In several others, gastric aspirates after use of
capsaicin (found in red peppers and paprika) and black peppers showed increased DNA
fragment levels, indicating mucosal damage.72 In other studies, peppers increased pro-
duction of mucus with only minimal acid secretory effects. Duodenal ulcer patients on
acid-suppressive therapy eating 3 g of red chili powder had clinical and endoscopic healing
rates similar to patients not eating the spice.42 Authors of this study suggested that direct
installation of spices via tubes in a fasting state in previous studies, as opposed to more
physiological consumption of the spice, might explain the discrepancy between prior
reports of gastric damage and their findings. Concomitant antacid intake may have altered
the effects of the spice in this study. It is also unknown whether chronic consumption of
potentially irritant spices leads to an adaptation response by stimulating gastric defenses,

explaining some of the earlier work showing high levels of mucous production.
Dietary Fiber
Fiber has been postulated to be beneficial for PUD because of its buffering effects, short-
ening of GI transit leading to decreased acid secretion, and binding of irritant bile acids.79
The role of dietary fiber in treatment or prevention of PUD is controversial. Reduction in
clinical and endoscopic ulcer recurrence with high-fiber diets has been shown,80,81 although
epidemiological studies have found elevated incidence of PUD in areas of the world with
high fiber consumption. Low fiber consumption may predispose to PUD, rather than high
fiber having protective effects.82
Supplementation of fiber in the form of pectin has not affected ulcer recurrence.83 Guar
gum may reduce gastric acid; it has not been shown to normalize it.84 Therefore, compo-
nents of the high fiber diet other than fiber itself may be protective.
Fiber given as wheat bran can bind bile acids and may reduce their elevated concentra-
tion in gastric ulcer patients;85 it may be beneficial in biliary reflux-associated ulcerations.

Linoleic acid, an essential fatty acid (EFA) and a major substrate for synthesis of prostag-
landins that are protective for upper GI tract mucosa, has been shown to be deficient in
the diets of duodenal ulcer patients.86 Additionally, Hollander and Tarnawksi have shown
that the declining incidence of PUD parallels a 200% increase in dietary availability of
EFAs.87 They have hypothesized that this association reflects a cause-and-effect relation-
ship and that higher intakes of EFA induce mucosal prostaglandin E synthesis, thereby
conferring protection against mucosal irritants and NSAIDs. Although the epidemiological
evidence for this hypothesis is strong, direct evidence is lacking.
Many dietary factors may be significant in the pathogenesis and treatment of ulcer
disease, but most studies have been conducted before H. pylori was implicated in ulcer
formation. Therefore, some of the evidence, especially the epidemiological, for or against
various interventions may not be applicable to current PUD patients. The available infor-
mation is summarized in Table 56.14. A summary of nutritional tips for patients with PUD
is given in Table 56.15. With the potent antisecretory medications available today, diet
TABLE 56.14
Summary of Evidence on Diet and PUD
Definitely Not Beneficial and Potentially Harmful to PUD Patients
Bland and restrictive diets including the Sippy diet and its modifications
Frequent milk intake
Probably Harmful to PUD Patients
Alcohol
Caffeine
Coffee/Tea
Carbonated beverages
Certain spices
High salt load
Probably Beneficial to PUD Patients
Essential fatty acids

Fiber intake
TABLE 56.15
Summary of Nutritional Tips for PUD Patients
1. Avoid restrictive diets
2. Avoid frequent milk intake
3. Avoid high salt intake
4. Avoid concentrated alcoholic beverages
5. Avoid directly irritant foods and spices such as peppers, chili powder, etc.
6. Take proton pump inhibitors, 30 minutes before a meal
therapy has a limited role in treatment of PUD. Patients with PUD should be allowed to
eat as they desire, with few exceptions.
Food and PUD Medications

Proton pump inhibitors frequently used in the treatment of acid-peptic diseases including
PUD are expensive medications that irreversibly bind and block the hydrogen pump of
the parietal cell. These drugs are rapidly cleared from the bloodstream within a few hours
following intake. Therefore, for utmost efficacy, they should be timed so that effective
concentrations are in the circulation when acid secretion is maximally stimulated. This
usually requires these drugs to be taken about 30 minutes prior to a meal.
Gastroparesis
Abnormally slow emptying of the stomach from causes other than mechanical obstruction is
called gastroparesis. The many causes are given in Table 56.16, with diabetes the most common.
The various factors and medications that affect the rate of gastric emptying are given
in Table 56.17. The mainstay of the dietary treatment of gastroparesis involves avoidance
of the factors that delay emptying (as shown in Table 56.17) while adopting a diet that
exits the stomach easily. No one diet has been shown effective.
In general, dietary fiber usually needs to be decreased, as it may result in bezoar
formation. Koch promotes six smaller meals in order to decrease symptom severity, and
he advocates a three-step nausea and vomiting diet.88 These recommendations need to be
tested to prove their usefulness.
Dietary treatment frequently needs to be combined with prokinetic medications, usually
administered before meals. Oral medications should preferably be in liquid formulations
that are absorbed faster than capsules and tablets, which may lie in the stomach for hours.
As the disease progresses, dietary and medical treatment may not suffice, and refractory
patients may require drainage gastrostomy with jejunal enteral feeding. Although no
controlled studies exist, in one retrospective study, enteral feeding via a jejunostomy
improved overall health status in diabetic patients.89 Nutritional tips for the gastroparetic
patient are summarized in Table 56.18.
Dumping Syndrome
Dumping syndrome is the collection of symptoms triggered by rapid entry of large boluses
of food into the small bowel. The syndrome most often occurs in patients who have had
a vagotomy and/or gastrectomy, frequently done in the past for PUD. The two main types
of the syndrome, the symptoms, and possible mechanisms are given in Table 56.19.
Dietary treatment of early dumping aims to slow emptying of the stomach and decrease
the volume and osmolality of food boluses delivered to the small bowel. For this purpose,
TABLE 56.16
Causes of Gastroparesis
Metabolic and Endocrine:

Diabetes, thyroid disease, uremia, porphyrias, pregnancy, electrolyte imbalance, Addison’s disease
Iatrogenic:
Surgical damage to vagal trunk, drugs, radiation damage to stomach
Neurological:
Intracranial/spinal cord lesions, Guillain-Barré syndrome, acute dysautonomic syndrome, Shy-
Drager syndrome, Parkinson’s disease, seizure disorder, multiple sclerosis, labyrinthitis
Psychogenic:
Anorexia, bulimia, psychological stress
Inflammatory:
Viral gastritis, Chagas disease, Botulinum toxin, celiac sprue
Rheumatologic:
Scleroderma, SLE, PM/DM, amyloidosis
muscular disorders
Paraneoplastic:
Small cell lung cancer, breast cancer
Idiopathic
TABLE 56.17
Factors that Affect the Rate of Gastric Emptying
Factor Fast Emptying Slow Emptying
Luminal:
Consistency of food Liquid Solid
Macronutrient composition Fat Protein Carbohydrate
Fiber content of food Low High
Osmolality in stomach or duodenum Low High (>800 mOsm/L)
Change in temperature of stomach Hot/Cold Body temperature
Gastric distention High Low
Volume in duodenum Low High
pH in duodenum High Low
Drugs: Cholinergic Anticholinergic

Erythromycin
Metoclopropamide
Cisapride
Domperidone
Gastrointestinal hormones: Gastrin Cholecystokinin

Motilin Glucagon
Secretin
patients are advised to avoid consuming liquid and solids simultaneously, stay away from
highly osmolar foods, and eat small meals. Dietary treatment of late dumping syndrome
aims to decrease rapid entry of large amounts of carbohydrates, especially concentrated
simple sugars, into the small intestine. Patients are advised to keep away from concen-
trated sweets such as candy, honey, syrup, etc. These latter recommendations have not
been rigorously tested but are consistent with the pathophysiology of dumping.
TABLE 56.18
Summary of Tips for the Gastroparesis Patient
1. Eat small quantities at a time
2. Eat in upright position
3. Do not recline until several hours after meals
4. Chew every bite of food well
5. Consume a low fat diet
6. Avoid fiber/roughage
7. Eat well-cooked foods
8. Turn foods into liquid/pureed form if unable to tolerate solids
9. Take medications in liquid formulation, 30 minutes before meals
TABLE 56.19
Types of Dumping Syndrome
Timing Following
a Meal Cause Mediators Symptoms*
Early 15-30 min Rapid fluid shift from Release of vasoactive intestinal Flushing
intravascular space to hormones (e.g., VIP, Dizziness
small intestinal lumen neurotensin, motilin, etc.) Nausea
Palpitations
Diaphoresis
Syncope
Late 2-4 h Rapid rise of blood glucose Rapid rise in insulin in
response to glucose
* Symptoms are similar for both early and late dumping.
TABLE 56.20
Summary of Nutritional Tips in Dumping Syndrome
1. Eat small and drink quantities at a time
2. Spread meals throughout the day
3. Avoid drinking liquids with meals, instead drink liquids in between meals
4. Avoid hypertonic foods and concentrated sweets (such as soft drinks, juices, pies, cakes, cookies, candy, etc.)
5. Avoids foods rich in simple carbohydrates, replace with complex carbohydrates
6. Consume high-protein, moderate fat foods
7. Increase fiber intake if tolerated
8. Lie down after meals if possible
Additionally, in order to delay gastric emptying, and especially bind the liquid compo-
nent of the meal, fiber such as guar gum and pectin has been added to meals. Results
with pectin are variable: in small studies it delays gastric emptying in the majority of
patients but may also increase it; therefore, doses may need to be individualized to achieve
a particular viscosity.90,91 In one study, muffins that contain 5 g of pectin failed to alter
symptoms or gastric emptying.92 In open-label studies, addition of 5 g of guar gum to
meals for four weeks symptomatically benefited 8/16 patients with proximal selective
vagotomy-induced dumping, although the effect was minimal in 3 patients.93 Recent work
also suggests that increasing viscosity of the liquid phase of a meal by pectin or guar gum
may stimulate more propulsive forces in the stomach, causing a detrimental effect.94 Most
patients with severe dumping do not respond to the commonly used dietary instructions.
In these refractory patients, octreotide is useful.95
Nutritional tips for patients with dumping syndrome are summarized in Table 56.20.
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57
Nutrition and Hollow Organs of the Lower
Gastrointestinal Tract
Basic principles of nutrition in diseases of the small and large intestines are covered in
this section. Often the disease processes are complex and result in challenges frequently
requiring that nutritional treatment be individualized. Thus, consultation with a nutrition
specialist is usually necessary and highly recommended.
Celiac Sprue (CS)

Celiac sprue (celiac disease, gluten-sensitive enteropathy) is an allergic disease of the small
intestine characterized by malabsorption of nutrients, a specific histological appearance
on biopsy (Table 57.1), and prompt improvement after withdrawal of gluten (a water-
insoluble protein moiety in certain cereal grains) from the diet. The disease is prevalent
in almost every population, with higher numbers among people of northern European
descent. In Europe, the prevalence is estimated to be 0.05 to 0.2%; however, the disease is
underdiagnosed. When U.S. blood donors were screened using antiendomysial antibodies
(AEA), which are serological markers with high specificity for CS, 1 in 250 were positive.
The classic symptoms of the disease are diarrhea, flatulence, weight loss, and fatigue,
although many patients without extensive small bowel damage may not have one or more
of these symptoms. In fact, celiac disease patients may also be asymptomatic in terms of
any GI manifestations, and may present with extraintestinal or malnutrition-related prob-
lems (such as miscarriages, osteoporosis with fractures, skin diseases, etc.) Clinical man-
ifestations of the disease are given in Table 57.2. Patient populations at risk and their
disease prevalence are given in Table 57.3.
Mechanisms
Gluten, the main allergen, is a protein found in wheat. The prolamin fraction of gluten is
an alcoholic extract rich in proline and glutamine residues. This fraction is also termed
gliadin, and certain amino acid sequences occurring in it (proline-serine-glutamine-
0-8493-2705-9/02/$0.00+$1.50
TABLE 57.1
Histological Features of Celiac Sprue (CS)
1. Loss of villi with resultant flat absorptive surface
2. Presence of cuboidal epithelial cells at surface
3. Hyperplasia of crypts, with increased mitotic figures
4. Increased intraepithelial lymphocytes
5. Increased cellularity in lamina propria
TABLE 57.2
Clinical Manifestations/Presentations of Celiac Sprue
Gastrointestinal Extra-Intestinal
Diarrhea Dermatitis herpetiformis
Steatorrhea/Weight loss Amenorrhea/Infertility/Miscarriages
Nausea/Vomiting Anemia (iron or folate deficiency)
GERD Osteoporosis/Osteomalacia
Abdominal pain/Dyspepsia Brittle diabetes
Bloating/Flatulence Dementia
Occult blood in stool Depression
Elevated transaminases Neuropathy
Recurrent pancreatitis Seizures
Hyposplenism
Headaches
Hypoparathyroidism
IgA nephropathy
Malaise/Fatigue
TABLE 57.3
Patient Populations at Risk for CS
At Risk Population Disease Prevalence
Family members of a patient with CS: 5-20%
Monozygotic twins 70-90%
Siblings with HLA DQW2 or HLA DR5/DR7 40%
First degree relatives 10-20%
Autoimmune thyroid disease 4-5%
Diabetes mellitus type I 2-5%
Ig A deficiency 15%
Sjögren’s syndrome 15%
Down’s syndrome 4-5%
glutamine and glutamine-glutamine-glutamine-proline) initiate the allergic reaction in CS.

Many grains such as rye, barley and wheat also contain similar prolamin fractions, and
are therefore toxic to CS patients (Figure 57.1). Taxonomy of common cereal grains and
chemical names for their prolamin fractions are given in Figure 57.1.
In genetically predisposed individuals, the prolamin fractions from cereal grains bind
a tissue autoantigen called tissue transglutaminase.1 The bound complex is believed to
initiate an autoimmune reaction leading to activation of intraepithelial T lymphocytes and
formation of autoantibodies, resulting in destruction of small intestinal epithelial cells and
the interstitium that make up the villus.
Tissue transglutaminase is normally found in the cytoplasm of the small intestinal
epithelial cell, and its main function is to cross-link glutamine residues. In vitro, the enzyme
preferentially acts on gluten, 35% of which is made up of glutamine, and renders it more
susceptible to uptake and processing by the enterocyte. Tissue transglutaminase can also
Family Gramineae
Subfamily Festucoideae Panicoideae
Tribe Triticeae Aveneae Oryzeae
Genus Triticum Secale Hordeuam Avena Oryza Zea

Species WHEAT RYE BARLEY OAT RICE CORN
Name of
prolamin Gliadin Secalin Hordein Avenin
fraction
Toxic in CS Considered toxic in Non-toxic in CS
U.S. but allowed
Nutrition and Hollow Organs of the Lower Gastrointestinal Tract
in certain parts
of Europe
FIGURE 57.1
Taxonomy of grains.
1187
TABLE 57.4
Pathogenetic Factors in Celiac Sprue
1. Dietary gluten
2. Genetic predisposition
a. Association with HLA-DQw2, B8 and DR3
3. Autoimmunity
a. Heightened gut permeability to macromolecules
b. Increased T lymphocytes (esp. γ∆ type) in lamina propria
c. Increased humoral mucosal immune response
d. Tissue transglutaminase
i. Creation of new antigenic epitopes by binding gliadin
ii. Deamidation of glutamine residues in gliadin, causing increased binding to HLA
4. Acute trigger factors
a. Infection with viruses
b. Acute inflammation due to food allergy, etc.
c. Mechanical stress
deamidate glutamyl donor molecules, which can bind to celiac disease-specific HLA-DQ2
better than their non-deamidated counterparts.
How tissue transglutaminase and gluten come into contact is unclear. Postulated mech-
anisms include exposure during mechanical stress, inflammation, infection, or apoptosis.
For example, instigation of tissue injury by infection with adenovirus 12 has been hypoth-
esized to cause release of tissue transglutaminase into the extracellular environment where
it links with gluten. Supporting this hypothesis, Kagnoff et al.2 have shown that a particular
portion of the E1B protein of adenovirus 12 and alpha-gliadin are homologous, and 89%
of patients with CS have evidence of prior exposure to this virus. Others propose that
gluten is inadequately digested and toxic fractions accumulate. Subsequent sampling of
the intestinal milieu leads to presentation of the gliadin peptides on antigen presenting
cells within the cleft of the HLA-DQ2 molecules carried by susceptible individuals. Various
hypotheses and factors important in the pathogenesis of CS are given in Table 57.4.

CS can profoundly affect nutritional status, leading to steatorrhea, weight loss, and many
micronutrient deficiencies, although about half of adult patients present with rather subtle
clinical signs of malnutrition, as the disease can be patchy, and the extent of involvement
of the small intestine varies from person to person. The degree of malnutrition is positively
correlated with the presence of symptoms; asymptomatic patients are less malnourished
than symptomatic ones (31 versus 67%).3 CS patients tend to have lower body fat, bone
mass, and lean body mass compared to healthy controls. Total body fat can even be
decreased significantly in asymptomatic cases with latent sprue.4 Laboratory studies show
that albumin, triglycerides, and hemoglobin are typically below normal. Anemia is fre-
quent in both overt and latent CS, and may be due to iron, folate, or vitamin B12 deficiencies
resulting from malabsorption and/or bacterial overgrowth. Micronutrient problems such
as low calcium, potassium, magnesium, copper, zinc, and selenium, and vitamin K defi-
ciency have been reported. Additionally, vitamin E deficiency has been linked to the
neurological symptoms of CS. Of utmost importance, patients with symptomatic as well
as latent CS may have osteomalacia and/or low bone mineral density5 partly as a result
of vitamin D and calcium deficiency, and these need to be supplemented to prevent
osteoporosis. There is no correlation between clinical or biochemical abnormalities and
bone mineral density, so supplementation with regular screening should be undertaken
in all patients.
Nutrition and Hollow Organs of the Lower Gastrointestinal Tract 1189
Diet in Celiac Sprue

The Gluten-Free Diet
CS patients need to avoid foods that contain certain cereal grains. For medical purposes,
such a diet is termed a gluten-free diet (GFD). In general, the oryzeae or the tripsaceae
such as rice, corn, and maize are safe because the protein fractions of these grains are
significantly different from gliadin, due to their different taxonomy, shown in Figure 57.1.
Basic principles of the GFD are given in Table 57.5.
Caution should be exercised when the word “gluten” is used to select foods, as it has
different meanings to different people. Bakers typically use it to mean the sticky part of
grains, whereas chemists only refer to wheat-derived protein fractions, and use the chem-
ical names given in Figure 57.1 for other cereal grains. Therefore, patients are encouraged
to ask, “Is this food free of wheat, rye, barley, oats, etc., and ingredients derived from
grains?” rather than, “Is this a gluten-free food?.”
Unfortunately, many dietary additives exist in processed foods containing hidden ingre-
dients that are derived from cereal grains; therefore, compliance with a truly GFD diet is
difficult. A simple watch list for some of these ingredients is given in Table 57.5, Item 3.
Chemicals/fillers added to nonfood items such as vitamins and pills may also be sources
of gluten. Moreover, food-processing elements, which need not to be reported on food
labels, may use grains. Hence, patients are encouraged to consult a dietitian experienced
in GFD with questions, as well as to join professional societies such as The Celiac Sprue
Association, U.S.A.
Manifestations of the diseases responsive to GFD are given in Table 57.6. Numerous
studies show that GFD is not only essential in controlling GI symptoms, but also prevents
complications.
Osteopenia and osteoporosis are common, and can result from vitamin D and calcium
malabsorption as well as secondary to hypoparathyroidism from hypomagnesaemia.6
GFD leads to increases in bone mineral density, with the greatest benefit in the first
year of treatment,7-10 but normalization may not occur even on GFD.10 In a study of 65
patients with CS on GFD, up to 50% had a T score of less than –2 on dual energy x-ray
absorptiometry.11
There is a two- to threefold relative increase in the risk of cancer among patients with
CS.12,13 Specifically, T-cell lymphomas of the small intestine, adenocarcinoma of the small
intestine, cancers of the mouth, nasopharynx, and esophagus are more common in CS.
TABLE 57.5
Principles of the Gluten-Free Diet (GFD)
1. Avoid the following grains: wheat, rye, barley, oat, spelt (dinkel), kamut, buckwheat
2. Avoid the following grain based products: bulgar*, couscous*, wheat starch, wheat germ, semolina*, durum*,
bran, oat bran, germ, graham flour
3. Avoid potentially grain based products or additives: malt**, malt flavoring, malt extract, malt syrup, food
starch (edible starch)***, icing sugar****, soy sauce*****, filler+, gum base, oat gum, cereal binding, white
vinegar*****, hydrolyzed vegetable protein or hydrolyzed plant protein
4. Avoid sauces, salad dressings, and fat substitutes as these may typically contain grain-derived products.
5. Avoid grain-based alcohol such as beer or alcoholic extracts of grains.
6. Corn and rice are the only allowable cereal grains.
7. All fresh vegetables and fruits are allowed.
* derived from wheat
** may be derived from barley
*** may be derived from wheat
**** contains 5% wheat starch
***** may contain wheat or barley
+ found frequently in medications and vitamins
TABLE 57.6
Manifestations of CS Responsive to GFD
1. Gastrointestinal symptoms
a. Diarrhea
b. Malbsorption
2. Osteopenia/Osteoporosis
3. Anemia
4. Dermatitis herpetiformis
5. Depression
6. Increased risk of malignancy
7. Amenorrhea/Infertility/Spontaneous abortions
Malignant complications correlate with GFD; in patients who have been on GFD for five
years or more, malignancy risk reverts back to that for the general population.13,14 For
those on a reduced gluten or normal diet, the risk for non-Hodgkin’s lymphoma and
cancers of the mouth, pharynx, and esophagus is 78-fold, and 23-fold higher compared
to the general population.13
The time to respond to GFD clinically varies, depending on the severity of disease. A
prompt improvement in symptoms is expected within days to a few weeks. Patients with
milder disease in biopsies tend to respond sooner than those with villus atrophy, in whom
resolution of symptoms may take up to several months. Still, normalization of biopsy
samples when total villus atrophy is present has been reported incomplete even after two
years.15 Dermatitis herpetiformis takes longer to resolve with GFD than other symptoms
(on average two years), and older patients take longer to respond than younger ones.
What to Do in the Patient Who is Unresponsive to a GFD?

From a dietary standpoint, careful review of the patient’s diet for hidden sources of gluten
is suggested. The most common causes of GI symptoms in such patients are bacterial
overgrowth, development of other autoimmune diseases, and a new onset of microscopic/
collagenous colitis found in 5% of patients with CS. Treatment of bacterial overgrowth
with antibiotics may be beneficial.16 Complications of CS such as development of T-cell
lymphoma, adenocarcinoma, and collagenous sprue should also be investigated.
Exocrine pancreatic insufficiency due to impaired cholecystokinin-pancreozymin release
from abnormal mucosa has been reported, suggesting a beneficial role for pancreatic
enzyme supplements.17,18 In fact, mild to moderate pancreatic insufficiency with subnormal
levels in one or more pancreatic enzymes was found in 29% of patients with CS in one
study, and the presence of insufficiency did not seem to correlate with overall nutritional
status.19 A prospective, double-blind, randomized study of adolescents has shown improve-
ment in anthropometric variables as well as weight gain with enzyme supplementation.20
Searches for dietary antigens other than gliadin have shown usefulness to an elimination
diet in 77% of patients in one study.21 This elimination diet excluded foods containing
natural salicylates, amines and/or glutamine, food colorings, preservatives, monosodium
glutamate, lactose and/or dairy products, soy, and millet-containing foods.
Patients in whom symptoms persists are considered to have “refractory sprue” upon
exclusion of other diagnoses. These patients may benefit from corticosteroids,22 azathio-
prine,23 or cyclosporine.24 Zinc-deficient patients with refractory sprue may respond to
zinc supplements,25 although this issue is controversial.26
Is There a Safe Amount of Gluten that CS Patients May Consume?

The amount of gluten required to initiate CS is unknown. One study suggests that at least
10 g-gluten challenge leads to relapse of disease within seven weeks,27 although there is
no consensus in this regard. Diets recommended by professional societies in the U.S. do

not allow any gluten, whereas the Codex Alimentarius Commission of the Food and
Agricultural Organization of the United Nations (FAO) and the World Health Organization
(WHO) permit a gluten-free label on foods that contain up to 0.3% of protein from toxic
grains. Most of this protein comes from wheat starch or malt.
Wheat starch (that only contains 0.75 mg/100 g gliadin) is not tolerated well, and its
withdrawal from the diet results in marked improvement of intestinal symptoms and
dermatitis herpetiformis.28 In a recent study examining patients who are symptomatic
despite the GFD as defined by FAO/WHO standards, conversion to a no-detectable gluten
diet resulted in complete resolution or reduction of symptoms in 23 and 45% respectively.29
Based on these results, there is no safe amount of gluten in the diet.
Can CS Patients Eat Oats?

Evidence that oats may not be harmful to CS patients dates back to the 1970s, when
Dissanayake, Truelove, and Whitehead administered 40 to 60 g of oats to four CS patients
for one month and showed no damage to the small intestinal mucosa.30 Several investiga-
tors claim that oats, which taxonomically belong to a different subclass in the cereal grains,
the aveneae, do not elicit the immune reaction seen with the ones in the triticeae tribe; oats
have a lower content of proline, which is abundant in the toxic amino acid sequences
(proline-serine-glutamine-glutamine and glutamine-glutamine-glutamine-proline) of pro-
lamin fractions. Also, these sequences occur fewer times per molecule of oat avenin as
opposed to wheat prolamin.31 Whether such lower amounts are enough to elicit the autoim-
mune reaction of CS or whether there is a certain safe level of oat consumption is unclear.
In vitro investigations show that antibodies from sera of patients with CS and dermatitis
herpetiformis can react against oat avenin, but the significance of this finding is question-
able, because similar immunoreactivity against corn has also been demonstrated.32
Two small cohort studies with CS and dermatitis herpetiformis patients have shown no
rise in antibody titers and no clinical or histological deterioration when oats are given 50
g/day and 62.5 g/day, respectively.33,34 In the largest randomized placebo-controlled study
to date, newly diagnosed European patients and ones in remission on GFD were studied
for 12 and 6 months, respectively.35 The patients were not blinded, although the investi-
gators were. Consumption of 50 g of oats daily did not cause any clinical relapse or
histopathological worsening in the established patients with CS, nor did it prevent clinical
or histological healing in newly diagnosed cases. The authors concluded that small to
moderate amounts of oats can be included in a GFD, and may improve poor compliance
with the diet. Despite the well-design of this study, long-term evidence regarding the
safety of oats is lacking. Considering crop rotation and lack of specified mills for oats in
the U.S., addition of oats to GFD cannot be recommended at this time.
Should CS Patients Also Avoid Lactose?

Lactase, the enzyme needed for digestion of lactose, is located at the very tip of the brush
border. As a result of damage to the villi, the levels of lactase are assumed to be lower in
most acutely ill patients with CS. Therefore, most professionals advocate a lactose-free diet
at the beginning of treatment with a GFD until resolution of symptoms. This is especially
true for patients with severe disease, requiring corticosteroids. No controlled studies have
been done examining the utility of a lactose-free diet in CS. Long-term avoidance of lactose
is not appropriate, considering the high incidence of osteopenia among CS patients.
Does Breastfeeding Prevent Occurrence of CS?

The incidence of CS is increased in the relatives of patients. The relative risks for family
members of CS patients are given in Table 57.3. Retrospective studies have shown that
TABLE 57.7
Nutritional Tips for CS Patients
1. Avoid lactose (mainly milk and dairy products) in acute disease
2. Follow a gluten free diet (Table 57.5) at all times:
a. Read food labels
b. Ask about grains in foods and medications
c. Avoid all foods if it is not certain that they do not contain the restricted grains
d. Select plain meats, fresh fruits, and vegetables when eating outside of the home if not sure
e. Record weight and symptoms, and keep a food diary until symptoms resolve on the GFD
3. Avoid foods that initiate/exacerbate symptoms as they may contain hidden sources of grains or other food
allergens
4. Consult an experienced dietitian with questions
5. Report persistent symptoms promptly
6. Join support groups for people with CS
relative risk of CS development is fourfold less in siblings of Italian children with CS if

they are breastfed for over 30 days.36 Similar findings showing a protective effect of
breastfeeding has been confirmed in Tunisian children.37 This effect may be correlated
with duration of breastfeeding, and appears independent of the delays in introduction of
wheat and grain products into an infant’s diet.38 Age at gluten introduction seems to be
a separate factor. Epidemiological evidence links increasing incidence of CS in Sweden,
as opposed to Denmark, to early- and high-level introduction of gluten into infant feed-
ings.39 However, case control studies have not yet confirmed these results.40 Presently, this
topic needs further study. Nutritional tips for CS are given in Table 57.7.
Inflammatory Bowel Disease (IBD)

Inflammatory bowel disease is an idiopathic chronic inflammatory disorder of the gas-
trointestinal system. The two main forms of the disease are Crohn’s disease (CD) and
ulcerative colitis (UC). The main differences of these diseases are shown in Table 57.8.
Mechanisms
Various factors and mechanisms important in the pathogenesis of IBD are listed in Table
57.9. Most recently, certain genetic foci associated with IBD have been discovered, and it
TABLE 57.8
Differences between UC and CD
UC CD
Clinical Bloody diarrhea is main symptom Obstruction, fistulae, perianal disease
may be present
Site of involvement Rectum extending proximally into Any part of the GI tract
colon as a continuum Normal tissue between areas of
involvement (i.e., skip areas)
Small bowel normal 70% small bowel involvement
Only mucosal involvement Involvement of the entire bowel wall
Pathological appearance No granulomas Presence of granulomas
Prognosis/recurrence Can be cured with colectomy Cannot be cured with surgical resection
TABLE 57.9
Factors Important in the Pathogenesis of IBD
1. Genetic predisposition
2. Environmental factors (e.g., smoking, urban lifestyle, etc.)
3. Dietary factors
4. Infectious agents
a. Mycobacteria
b. Measles virus
5. Immune reactivity
6. Psychosocial factors and stress
is hypothesized that environmental factors in susceptible individuals ultimately initiate

the inflammatory process leading to disease. Environmental factors include diet and
dietary antigens as well as the bacterial flora of the intestines.

Malnutrition is common in IBD; however, there is an important difference between CD
and UC. CD usually leads to chronic malnutrition that develops insidiously over long
periods of time, whereas in most cases, UC causes acute reductions in weight during
flareups of disease. Up to 85% of patients hospitalized with IBD and about 23% of out-
patients with CD have protein-energy malnutrition.41 Stable patients with the disease tend
to have a normal fat-free mass but low fat stores.
The causes of malnutrition in patients with IBD are multifactorial, and are given in Table
57.10. There is an increase in the resting metabolic rates in active IBD, but mean increases
are modest (19% in active UC,42 12% in active CD43) when compared to the calculated ones
from the Harris Benedict Equation, or to controls. Total energy expenditures, however,
are comparable to healthy people.44 Most stable outpatients with IBD do not have increased
energy expenditures either.45 One exception is underweight individuals (body weight
<90% of ideal)45,46 who may represent a special subgroup with specific metabolic abnor-
malities different than the rest. Interestingly, stable patients with CD who have decreased
fat stores but a similar fat-free mass to healthy controls or UC patients, have enhanced
utilization of lipids and diet-induced thermogenesis.47,48 A worse subclinical disease might
be the cause in these patients, as increased lipid oxidation is seen with active disease and
its level correlates with disease activity.43
TABLE 57.10
Causes of Malnutrition in IBD Patients
1. Reduced dietary intake
a. Anorexia to avoid symptoms
b. Restricted diets
c. Drug-induced taste alterations
2. Maldigestion and malabsorption
a. Inadequate mucosal surface
b. Bile salt malabsorption from ileal disease
c. Bacterial overgrowth
d. Drug induced
3. Increased requirements
a. Inflammatory catabolism
b. Drug-induced nutrient wasting
4. Exudative protein losses from inflamed intestine or fistulae
TABLE 57.11
Micronutrient Deficiencies in IBD
% Prevalance in:
Micronutrient UC CD
Iron 81 39
Folic acid 35 54-67
Vitamin B12 5 48
Potassium 6-20
Calcium 13
Magnesium 14-33
Vitamin A 26-93 11-50
Vitamin D 35 75
Zinc 40-50
Selenium 35-40
Fecal energy and protein losses in IBD are significant in active IBD, but most patients
compensate by increased food intake. Generally, patients on corticosteroids are also in
positive energy balance, possibly due to the appetite stimulant properties of these drugs.49
Yet, attention should be paid to the provision of adequate protein to meet increased protein
need by the patient with active IBD, especially in malnourished patients who may require
as much as 2 g/kg/day of protein.50
Food intolerances are twice as common among IBD patients as in the general population.51
These intolerances are commonly towards corn, wheat, cereals, cruciferous vegetables, and
milk, although intolerances to foods such as rice or even tap water have been observed.
In patients without obvious malabsorption, food intolerances together with less hunger,
decreased appetite, and fewer sensations of pleasure related to eating lead to significantly
reduced food intakes.52 This is the major cause of weight loss in patients with IBD.52 In
patients without other objective evidence of active inflammation, weight loss should not
be attributed to IBD, but rather close attention should be paid to the patient’s food intake.
Patients with IBD commonly have many micronutrient deficiencies, as shown in Table
57.11. Low levels of zinc and selenium that are cofactors for oxidant-protective enzymes
and low antioxidant vitamins (A, E, and C) have been implicated in worsening of the
disease course as well as contributing to the high rate of carcinogenesis among IBD patients.
Osteopenia, a well-recognized complication of IBD, is widespread among both adult
and pediatric patients53 and may occur independent of steroid use. Both osteopenia and
osteoporosis have been linked to vitamin D and calcium deficiencies, and supplementation
has been beneficial in treatment of these disorders.
Diet in IBD
Diet as a Potential Cause of IBD
Epidemiological evidence suggests that the incidence of Crohn’s disease (CD) has been
increasing over the last half century, while that of ulcerative colitis (UC) is declining,
especially in developed countries. Moreover, migrant populations of Asians into England,
or of European Jews into the U.S., have a much greater increase in the incidence of CD
compared to their counterparts living in their native countries. Assuming that the migrants
and natives have similar genetic pools, the increase has been attributed to environmental
factors. Strikingly, a higher incidence of CD in urban areas as opposed to rural ones further
suggests environmental factors at play. Among these factors, diet is important.
Pre-Illness Diet Factors and Dietary Habits of Patients with IBD

Many studies on dietary factors in the development of IBD and the roles of many types
of food (such as refined sugar, cereals, fiber, and dairy products including milk) have been
undertaken.
In general, patients with IBD tend towards higher intake of sugar compared to con-
trols,54,55 and this trend specifically reaches statistical significance for CD54,55 in most stud-
ies, and for UC in one.56 Fruit, vegetable, and fiber consumption, on the other hand, was
much lower in IBD in these studies. One study in the Japanese population confirmed the
lower intakes of vegetables and fruits among IBD patients, and a Westernized diet
increased the risk for UC.57 These findings among IBD patients are not surprising, as they
may represent an adaptation to the disease process rather than the cause of IBD.
Realizing this pitfall, in some studies only patients who have recent exacerbation of IBD
were questioned about their diets. Such studies also confirmed that there is higher intake
of sugars among CD patients but not UC ones.58-64 In one of these, deleterious effect of
increased intake of sugars was only seen with sucrose, but not with lactose or polysac-
charides.58 IBD patients also consume more fat prior to onset of disease.58 One epidemio-
logical study suggests that IBD is related to increased n-6 polyunsaturated fatty acid and
animal protein intake.65
Does Milk Cause IBD? Should Patients with IBD Avoid Milk?
The role of milk in initiating or worsening IBD is debatable, and whether lactose intoler-
ance is more common in IBD is controversial. Even among IBD patients who are not lactose
malabsorbers, elimination of milk from the diet leads to improvement in diarrhea in 1/5
to 1/4 of the cases with UC, and in 1/3 of the patients with CD.66,67
Although no clear-cut explanation for this exists, morphological changes in small intes-
tinal mucosa are well documented in CD and UC.68,69 The extent to which these changes
are related to decreased food intake or starvation as a result of disease symptoms is
unknown. Nevertheless, in CD, improvements related to a milk-free diet are not attribut-
able to changes in brush border lactase levels.70 In UC, measurements of intestinal lactase
have shown that deficiencies of lactase are real during active disease, but lactase deficit
is not necessarily more frequent in the active phase compared to inactive.71
This raises the question of whether milk itself is an allergen. One group of studies has
searched for humoral immune responses to milk proteins. Antibodies to milk proteins can
be readily detected in sera of IBD patients,72 but their levels may not be increased73,74 nor
are they particularly common.75 Some investigators have correlated antibody response
against milk to disease activity in CD but not in UC.76 However, disruptions of the
intestinal barrier as a result of inflammation can easily lead to such antibody formation,
making it a secondary phenomenon rather than the cause of disease. Other studies have
directly looked at the effects of a milk-free diet. In one, elimination of milk from the diet
decreased relapses of UC when patients were followed up to one year subsequent to
treatment with steroids77 even though strict statistical comparisons between treatment and
control groups were not undertaken. In another small study, 40% of IBD patients without
lactose intolerance improved.66 Allergy to cow milk may play a role in initiating or per-
petuating inflammation in IBD in a subset of patients, although no evidence clearly
establishes milk as an allergen.
Milk may also modify the intestinal flora, causing harm to individuals genetically
susceptible to IBD, or to IBD patients. Supporting this hypothesis, lack of breastfeeding
has been an independent risk factor for childhood CD,78 but not UC.79
Is IBD Caused by Allergy to Foods?

In a subset of patients who respond to elimination diets, IBD may be caused by allergy
to a specific food item. However, such patients constitute a very small minority and may
represent cases with an allergic colitis that is misdiagnosed as IBD. Further studies are
needed to answer this question.
Dietary Treatment for IBD

Energy and Protein Requirements in IBD
The Harris Benedict equation is useful in calculating the energy requirements of IBD
patients. Active disease may increase calculated requirements up to 20%. Fecal losses of
protein are the norm in active disease; therefore, patients should be given or encouraged
to consume at least 1.5 g/kg of protein.
Effects of Diet Counseling

Individualized dietary counseling for six months can lead to significant decreases in the
CD activity index, the need for medications such as prednisone, days spent in the hospital
for acute exacerbations, and number of days lost from work.80 Counseling can also lead
to increased incidence of disease remission, with beneficial effects persisting up to one
year, and is useful in both active and inactive disease.
Unproven Diets
High Fiber Diets that Restrict Sugar or Provide Unrefined Carbohydrates
Investigators have studied the impact of a diet with little or no sugar, rich in unrefined
carbohydrates and fiber on IBD. In one open-label study of CD patients and matched
controls, hospital admissions were significantly fewer and shorter in the treatment group.64
Subjects were given over 30 g of fiber/day on average, with no adverse effects seen in the
patients with strictures. In a larger, better-designed, controlled, multicenter trial with CD,
the diet intervention group did not have a clinically different course than the group
consuming a low-fiber, unrestricted sugar diet.81
Low Residue Diet for Active CD

A study of patients with active nonstenosing CD compared a low-residue diet with an ad-
lib diet.82 There were no differences in the incidence of poor outcomes such as need for
surgery, hospitalization, prolonged bedrest, partial obstruction, or new inflammatory mass.
The Simple Carbohydrate Diet

Patients are resorting to diet therapies because of the many side effects of immunosup-
pressive medications used in treatment of IBD and their lack of effectiveness in a significant
number of cases. There is a growing body of anecdotal evidence towards the efficacy of
various diets used by patients. One very popular example is the simple carbohydrate diet
(SCD) pioneered by Dr. Haas and currently advocated by Elaine Gottschall, whose son
has been afflicted with UC.83 The diet is based on avoidance of all complex sugars and
grains, is gluten-free, and is devoid of all additives/preservatives. With a few exceptions,
only fresh food is allowed, and it is cooked well to promote easy digestion. The principles
of the diet attempt to generate an “elemental carbohydrate diet.” Although elemental diets
work in IBD, polymeric enteral formulas have been found to be just as effective in one-
to-one comparisons. Moreover, many of the elemental formulations do, in fact, contain
polymeric carbohydrates, refuting the possibility that taking in only simple carbohydrates
will be successful. To date, the SCD diet has not been tested scientifically; therefore it
cannot be advocated for general use. If it is proven effective after objective scientific
evaluation, this may be based on features other than its “simple carbohydrates.” For the
patient who wishes to stay on the SCD diet, adequate macro- and micronutrient intake
should be supervised by an experienced dietitian.
Elimination Diets
Report of food intolerances by IBD patients have led to investigations into elimination
diets as a potential therapy. In an uncontrolled trial, 66% of CD patients were able to find
a nutritionally adequate diet after elimination of various foods.84 More than half of these
patients needed elimination of more than one or two foods. The relapse rate was 33% at
the end of the first year on the diets, with annual averages of about 14% within the first
three years. A controlled trial by the same investigators showed that 7/10 patients in the
treatment group remained in remission after three months, as opposed to all patients
relapsing in the control group given an unrefined carbohydrate fiber rich diet.84 Unfortu-
nately, these beneficial results have not been confirmed with better-designed studies to
eliminate bias. In fact, in a study of 42 eligible CD patients put into remission with
elemental diet, 33% dropped out of the study; 19% did not identify food intolerance, and
48% did.85 Among this 48%, food sensitivity was confirmed in half, in open-challenge with
the item, and this was reproducible in only three patients on double-blind challenge. These
findings suggest that elimination diets are of little help in the day-to-day treatment of IBD.
Growth Hormone and High-Protein Diet

The effects of high-protein diet versus glucocorticoids on the course of active CD was
considered in a small study of pediatric patients. No significant dissimilarities between
the two treatment groups in terms of improvement of pediatric Crohn’s Disease activity
index (CDAI) or laboratory parameters at two weeks were observed, although the study
may not have had adequate power to detect any differences. In a followup of 1.3 years,
patients given steroids tended to relapse more than the diet group.86
High-protein diet and growth hormone also have been shown to enhance adaptation
of the small intestine after massive resection87 and to improve protein absorption and
reduce stool output and requirements for hyperalimentation in short bowel syndrome
when used together with glutamine.88 A pilot study of high-protein diet (protein intake
= 2 g/kg/day) in conjunction with growth hormone injections (loading dose 5 mg/day
for one week, maintenance 1.5 mg/day for four months) in moderate-to-severe CD patients
undergoing conventional treatment has been studied in a double-blind and placebo-
controlled fashion. Although the study is limited because of a small number of patients
and does not indicate the percentage of patients entering remission, a significantly lower
score of CDAI was seen in the treatment group.89 This effect may be a result of increased
amino acid uptake and electrolytes, increased intestinal protein synthesis, and/or
decreased intestinal permeability in response to growth hormone. Further studies are
needed before this treatment is applicable in clinical practice.
Fish Oils (Omega-3 fatty acids)

Omega-3 fatty acids such as eicosapentaenoic acid and docosahexanoic acid have been
shown to inhibit production of leukotriene B4, a major neutrophil chemo-attractant in IBD.
In two trials with active UC patients, oral fish oil decreased steroid requirements and
improved histology.90,91 In another study of patients with moderate UC, decrease in disease
activity was seen, although no improvement was noted in histology or leukotriene B4
levels.92 In UC, no beneficial effects of fish oil in maintenance of remission were seen.90,93
In CD, intravenous administration of eicosapentaenoic acid increases the ratio of leu-

kotriene B5: leukotriene B4.94 A one-year study in CD patients has shown reduced rates of
relapse while on high doses of n-3 fatty acids (= 2.7 g/day), given as nine capsules a day.
Compliance can be difficult with this regimen because of the large number of pills, and
because some patients report a fishy odor at this dosage.
Capsaicin
Capsaicin, found in peppers, worsens colitis in IBD animal models by interfering with
sensory neuroimmunomodulation.95 No data exists in humans.
Short Chain Fatty Acids (SCFAs)

SCFAs are produced in the colon by fermentation of fiber or undigested starch by colonic
flora, and represent the primary energy source of colonic cells. Small open-label trials of
butyrate, a SCFA, given as an enema to patients with left-sided UC, have shown rates of
remission similar to treatments with steroids and mesalamine.96-99 The expense and the
pungent smell of SCFA enemas precludes their clinical use; oral precursors of SCFAs are
being developed. In animal studies, pectin increases SCFAs and leads to reduction of
inflammation and enhancement of repair.100
Gut Microflora/Probiotics/Prebiotics
A large body of research indicates that the intestinal flora may be proinflammatory in
IBD. This may explain why antibiotics that alter the flora, such as fluoroquinolones or
metronidazole, or diversion of the fecal stream with an ostomy, are utilized in the treatment
of IBD. The proinflammatory effect of the flora may be a result of expansion of harmful
colonies of normal gut microorganisms in the presence of certain lumenal conditions such
as an acidic pH, etc. Therefore, novel probiotic therapies that administer “good colonies
(non-inflammatory)” of gut bacteria, which compete with “bad colonies,” have been
developed for treatment of IBD. One of these, E. coli strain Niessle 1917 most recently has
been shown to be as effective as conventional treatment with 5-ASA drugs in the main-
tenance of remission in UC.101 Another probiotic preparation containing 5 × 1011 composed
of four strains of lactobacilli, three strains of bifidobacteria and one strain of Streptococcus
salivarius can prevent recurrence of pouchitis, (inflammation of the ileal pouch anasto-
mosed to the rectum in patients who have undergone colectomy for UC), in a nine month
follow-up period.102 A different approach has been the use of prebiotics, nondigestible
food substances that promote only the growth of a defined subset of good bacteria. Certain
foodstuffs or their components have been found to be prebiotics (e.g., fructo-oligosaccha-
rides and oats) that can profoundly influence the gut microflora, favoring expansion of
good organisms like lactobacillus. Although no controlled studies with these substances
exist in humans, a pilot study of patients with IBD has reported increases in favorable
intestinal flora as well as SCFA.103
Medium-Chain Triglycerides (MCTs)

Foods rich in medium-chain triglycerides are readily absorbed, and enhance kcaloric
intakes in malabsorptive states like IBD.
Enteral Nutrition and IBD

Primary Therapy
Many different formulations have been used for enteral nutrition in IBD. Polymeric for-
mulas usually have starches, complex protein, long-chain triglycerides, and MCTs.
Semielemental formulations contain oligosaccharides, peptides, and MCTs. Elemental for-

mulations typically contain predigested nutrients such as amino acids and glucose.
In active CD, comparison of elemental/semielemental diets with corticosteroids have
shown equal efficacy in achieving short term remission (≤ 3 months) in the range of 70 to
80% in individual studies,104-106 but a meta-analysis indicates that steroids may be more
effective.107 Long-term effects of enteral diets are less well known, although percentage of
patients in remission at one year ranges from 9 to 56%.105,106,108 This rate is not significantly
different when elemental diets are compared with polymeric or semi-elemental formula-
tions in most studies.107,109 Elemental diets are poorly tolerated because of their smell/
taste, complications such as diarrhea, and high costs. Therefore, polymeric formulations
should be favored. Furthermore, relapse rates are generally higher with elemental diets
as opposed to conventional therapy;110 therefore, enteral nutrition as primary therapy
should be attempted only in selected cases.
Investigators have found that CD patients with severe disease111 and/or CDAI >450112
and patients with colonic disease together with a fever113 are less likely to respond to
enteral nutrition therapy. In one study, the initial response rates were 38 versus 76% for
CD patients with moderate disease, as opposed to patients with severe inflammation.111
Studies with UC reveal no benefit from enteral nutrition for induction of remission.114
Comparison of hyperalimentation with enteral nutrition in CD has shown no superiority
of parenteral nutrition.41,109,115 Given the multiple potential side effects of parenteral nutri-
tion, enteral therapy should be used whenever possible.
Parenteral Nutrition and IBD

Preoperative
Parenteral nutrition decreases postoperative complications only in severely malnourished
patients with IBD. In one study, therapy duration of at least five days was required to see
any beneficial effect.116
Primary Therapy
Randomized prospective studies have shown a response rate to parenteral nutrition in
the 30 to 50% range in acute UC, but no significant differences over placebo have been
demonstrated.117-120 Furthermore disease-free maintenance rates on total parenteral nutri-
tion (TPN) have been poor, and complications requiring surgery may be higher; therefore,
there is no role for TPN as primary therapy of UC.117-120
In retrospective and prospective analyses in CD, parenteral nutrition can induce remission
in 70 to 100% of patients refractory to conventional treatments,114,115,117,118 but in at least one
prospective study, 60% relapse rate is seen within two years.121 This rate is four times higher
than historical controls treated with surgical resection. Therefore, consideration of parenteral
nutrition is recommended only in patients who are malnourished and have extensive disease
precluding surgical treatment. Given the many complications of parenteral nutrition, this
treatment should be a last resort, after exhaustion of other therapies.
Micronutrients
Antioxidants
Lower levels of antioxidant vitamins such as vitamin A, E, C, and beta-carotene have been
shown in both sera and colonic tissue of patients with IBD when compared to healthy
controls.122,123 In one study, vitamin C level also correlated with disease severity.122 Vitamin
C can especially be low in patients with fistulous tracts.
Animal studies suggest that antioxidant supplementation over and above corrections
for deficiency states may ameliorate colitis; however, no randomized placebo controlled
trials have been performed in humans.
Calcium/Vitamin D
Low levels of vitamin D are found in 75% of patients with CD and 35% of patients with
UC.109 Low levels also correlate with disease activity in undernourished CD patients.124
Of such patients, 45% have osteoporosis.125 Therefore, supplementation of vitamin D and
calcium is essential for the prevention of osteopenia/osteoporosis in IBD. Smoking also
independently increases the rate of osteoporosis, and should be avoided.
Folate
In retrospective analyses, folate supplementation has been shown to reduce incidence of
dysplasia and cancer in patients with UC.126,127 Folate requirements in IBD are increased
due to anemia and medications such as azathioprine, 6-mercaptopurine, and sulfasalazine;
therefore supplementation is recommended in almost all patients.
Zinc
Zinc deficiency is especially common among patients with fistulous disease, and has been
implicated as a cause for poor wound healing in these patients.128
Vitamin B12
Deficiency of vitamin B12 occurs as a result of ileal involvement or resection as well as
bacterial overgrowth in CD. All patients with CD should have supplementation either
nasally or as monthly injections, because oral absorption is inadequate. Recently, sublin-
gual administration of two over-the-counter vitamin nuggets (1000 µg/nugget) daily for
seven to ten days to a small group of patients with B12 deficiency has been reported to be
effective in raising blood levels. This latter route requires further study.
Specific Situations
Obstruction
Patients with intermittent obstruction are advised to consume a low-residue diet, although
no definite data exists.
Fistulae
Postoperative fistulae may respond to TPN, but CD fistulae are less likely to close and
frequently reopen promptly after food intake is resumed.129,130 Similar results are seen with
elemental diet.111,113,131,132 In the era of effective anti-tumor necrosis factor therapies, TPN
cannot be recommended as first-line therapy for fistulae in CD.
Severe Diarrhea and Antidiarrheals/Pectin

Diarrhea can be disabling for patients with IBD, and many require antidiarrheals such as
Loperamide or Lomotil. These agents induce their effects by diminishing GI motility by
binding opioid receptors in the GI tract, and therefore have been implicated in the patho-
genesis of IBD complications such as toxic megacolon. Thus, caution should be exercised
when using these, and for severely symptomatic patients without any obstruction, antid-
iarrheals such as Kaopectate, that bind excess liquid in the lumen, should be tried.
TABLE 57.12
Nutritional Tips for IBD Patients
1. Seek dietary counseling from an experienced dietitian
2. Avoid milk and milk products during active disease
3. Consume 10-20% more kcalories and 50% more protein with active disease
4. Do not avoid fiber, in fact try to increase fiber in diet as long as there is no obstruction in the GI tract
5. Follow a low residue diet if there is partial obstruction in the GI tract, consult with a physician and dietitian
before making dietary changes
6. Prefer fish over other dishes (fish with high fat/fish oils such as catfish, salmon, etc., should be selected)
7. Take a multivitamin supplying 100% of RDA of vitamins and minerals, make sure to have monthly vitamin
B12 injections if having CD
8. During inactive disease, consume foods that are rich in naturally occurring probiotics (such as yogurt
containing lactobacillus)
Extraintestinal Manifestations
Unconfirmed reports suggest associations between resolution of pyoderma gangrenosum
and uveitis with diet therapy.133
Ileal Resection and Kidney Stones

Patients with CD are at increased risk of oxalate kidney stones if their colons are relatively
intact and they have had extensive ileal resections. Such patients should be advised to
follow a low oxalate diet. Patients with a history of oxalate stones should also be treated
with binding resins such as cholestyramine.
Nutritional tips for IBD patients are given in Table 57.12.
Short Bowel Syndrome

Short bowel syndrome (SBS) is a malabsorptive state with a distinct group of symptoms
and signs that occur as a consequence of major reductions in small intestinal absorptive
surface area typically due to intestinal resection(s). Patients usually experience large-
volume diarrhea with salient fluid and electrolyte losses as well as weight loss. The most
important determinant of SBS is the length of the remaining functional small intestine,
and less than 200 cm (6.5 feet) of length invariably is associated with compromised
nutritional status. Less than 100 cm (3 to 3.5 feet) usually requires TPN. Small intestinal
length is variable from person to person, with a range of 330 to 850 cm; therefore, the
length of resected segments is clinically irrelevant. If there is doubt as to the length of the
remaining small intestine, this crucial information can be obtained by doing a small bowel
followthrough, since surgical and radiographic measurements correlate well.134
Although the true incidence and prevalence of SBS is not known, it is estimated that 10
to 20 thousand people in the U.S. require TPN as a result of it. The commonest causes of
SBS are Crohn’s disease, malignancy, radiation enteritis, and ischemic bowel. Others
include jejunoileal bypass operations (used in the past to treat obesity), congenital abnor-
malities such as intestinal atresia, malrotation of the intestines, aganglionosis, and necro-
tizing enterocolitis in childhood.
TABLE 57.13
Factors That Affect the Type of Nutrition Required by SBS Patients
Factors The Effect
Phases of SBS See Table 57.14
Length of remaining small intestine Very short lengths (60-100 cm) worsen severity of SBS
The extent of disease in remaining intestine Impact of even mild disease on nutritional status can be
profound. As disease worsens, the length of functioning small
intestine decreases
Absence of the stomach Loss of timed and slow release of gastric chyme decreases
contact time between food and digestive/absorptive
epithelium, thereby worsening SBS. Lack of stomach acid
facilitates bacterial overgrowth aggravating malabsorption
Absence of the ileocecal valve Leads to bacterial overgrowth enabling passage of colonic
bacteria into the small intestine
Absence of the colon Promotes water and electrolyte losses. Kcaloric losses are more
extensive. Lack of gastrocolic reflex results in rapid transit of
food, enhancing malabsorption
TABLE 57.14
Phases of SBS with Their Characteristics
Phase Duration Main Problems
Postoperative 1-2 weeks High volume/severe diarrhea
Gastric hypersecretion
Related fluid and electrolyte imbalances
Transition 1-3 months Diarrhea with oral intake
Malabsorption:
Increased kcaloric requirements
Micronutrient deficiencies
Social problems
TPN related problems
Adaptation 3 months to 1-2 years Dietary restrictions
Adequacy of oral intake
Complications:
Renal stones
Gallstones
D-Lactic acidosis
Pathophysiology and Types of SBS

The main factors that affect the type of nutrition required by patients are listed in Table
57.13. The phase of SBS (i.e., the elapsed time after intestinal insult or surgery resulting in
SBS) is of utmost importance in the acute management of SBS (Table 57.14). The remaining
factors determine how well a patient will handle enteral nutrition in the long run.
In general, jejunal resections are better tolerated than ileal ones for several reasons:
1. Most of the intestinal fluid secretion that balances the osmotic load of gastric
chyme entering the small bowel occurs in the jejunum. Subsequently, a large
percentage of the proximally secreted water/electrolytes are absorbed distally
in the ileum. Therefore, ileal as opposed to jejunal resections/insults result in
more voluminous diarrhea, with loss of nutrients in stool.
2. GI transit is faster in patients with ileal resections because of the lack of the ileal
brake mechanism, discussed in the first GI section.
3. The ileum has a greater adaptive potential.
With colon: Without colon:

Jejunum anastomosed to colon End-jejunostomy
FIGURE 57.2
Anatomic types of short bowel syndrome.
Most patients with SBS fall into two main categories: those with and those without a
colon. Patients with a colon usually have the majority of their ileum and some of their
jejunum resected, with a resultant jejunocolic anastomosis. Those without a colon usually
have end-jejunostomies (see Figure 57.2). Patients with a colon typically do better, espe-
cially in maintaining fluid and electrolyte balance, and cases with >50 cm of jejunum
remaining may be managed with oral/enteral nutrition instead of TPN.
Diet in SBS
Dietary interventions in SBS should be individualized for each patient, as the needs differ
considerably. Some general recommendations are given in the following paragraphs.
Postoperative Phase
No enteral nutrition is given at this phase because of the osmotic effects of food, and all
patients require TPN. There are massive losses of fluids and electrolytes, and the amount
is highly variable; therefore, careful monitoring of all intake and output as well as daily
laboratory tests must be done. Patients should be given back their entire deficit plus an
extra estimated 300 to 500 cc/day for insensible losses. Preferably, this type of replacement
should be done on an hourly basis and separate from the TPN.
Agents that slow intestinal transit such as parenteral codeine and drugs that reduce the
commonly seen gastric hypersecretion are also helpful in reducing the volume of stool
output. Gastric hypersecretion is usually comparable to the level seen in duodenal ulcer
patients,135 can lead to significant volume losses, especially within the first six months
following surgery,136 and can contribute to malabsorption by inactivating pancreatic lipase
and deconjugating bile salts. Treatment with cimetidine has been shown to improve
absorption.136,137 A study of 13 patients with large-volume ostomy output has shown that
omeprazole can increase water absorption in cases with fecal outputs >2.5 kg/day, but
does not alter absorption of kcalories, macronutrients, or electrolytes.138
Octreotide (50 to 100 µg subcutaneously twice a day) has also been shown useful in
patients with end jejunostomies who have >3 L/day of ostomy output.139 Initial concerns
that octreotide may delay adaptation have not been substantiated in animal studies.140
Transition Phase and Adaptation Phase

Oral Diet
In the transition phase, TPN is continued while patients are first started on isotonic clear
liquids that contain salt and glucose. It is advised to wait until the ostomy output is less
than 2 to 3 L/day before commencement of oral intake. The average sodium concentration
in the ostomy secretions generally varies between 80 to 100 mEq/L, so the initial hydration
solutions should have at least this amount. Alternatively, sodium in the ostomy secretions
can be measured to calculate the concentration in the replacement solution. Patients who
can tolerate these solutions should also be switched to oral antidiarrheals such as Loper-
amide, Lomotil, or tincture of opium. The commonly used dosages given in Table 57.15
are typically high.
Subsequently, patients should be transitioned into an oral diet. In general, patients with
SBS do not tolerate large amounts of food at one time, foods with concentrated carbohy-
drates (especially mono and disaccharides) and high lactose, or foods high in oxalate and
insoluble fiber. Hypotonic fluids such as water, tea, juices, and alcohol also need to be
avoided, especially in patients without a colon, because this type of fluid draws sodium
into the jejunal lumen, causing increased salt and water losses. Additionally, patients
should be advised not to consume foods or supplements with non-absorbable sugars (such
as sorbitol and mannitol) or non-absorbable fat (such as olestra), and to watch out for
hidden diarrheal agents (e.g., polyethylene glycol found in certain mints). It is best to try
small and frequent amounts of solid food until the patient can consume at least 1200 kcal/
day without a significant increase in diarrhea. Once this is achieved, TPN may be gradually
cycled to go on only during the night and then on alternate days, together with slow
advancement of oral intake.
Enteral Feeding
Patients who are not able to take in adequate kcalories via the oral route should be tried
on enteral feedings. There is no consensus on which type of enteral feeding is best for
SBS, but isotonic polymeric formulas are recommended over elemental ones, which are
expensive and poorly tolerated by patients because of their taste, smell, and high osmo-
lality that increases jejunal secretion.
TABLE 57.15
Dosages for Antidiarrheals in SBS
Antidiarrheal Typical Dosage
Loperamide 4-6 mg/4-5 times a day
Lomotil 2.5-5 mg/4 times a day
Tincture of opium 5-10 cc every 4 hours
Codeine phosphate 30 mg/3-4 times a day
TABLE 57.16
Selected Complications of TPN in SBS and Their Prevention/Treatment
Complication Treatment
Line infections Remove catheter completely if fungal infections or Staph.
aureus are the cause (change over a wire is not acceptable)
Staph. aureus requires 2-6 weeks of antibiotics
Staph. epidermidis may be cured 80% of the time with 7-
10 days of iv vancomycin
Bacterial overgrowth Treat with broad spectrum antibitotics (tetracycline,
ciprofloxacin, metronidazole, etc.)
Rotate antibiotics every 4-8 weeks
Liver disease Pursue enteral feedings aggressively
Take care to prevent line infections
Avoid overfeeding with excessive kcalories
Prefer lipid kcalories to high carbohydrate nutrition
Treat bacterial overgrowth
Screen for cholelithiasis
Patients who cannot stop TPN need to be monitored for complications such as feeding
catheter infections, liver disease, bacterial overgrowth, and nutritional deficiencies. Some
of these, together with their treatments, are given in Table 57.16.
Dietary Requirements and the Composition of the Diet in SBS

Energy
Most patients with SBS only absorb 50 to 60% of total energy, with the highest % malab-
sorption in fat and carbohydrates.141 Thus, they need 1.5 to 2 times the amount of food/
energy to maintain weight. For patients not able to increase their intake to this level,
enteral feedings at night or additional TPN is required.
Carbohydrate versus Fat

In normal individuals, about 20% of all carbohydrates consumed exit the small bowel
undigested and are fermented to SCFAs in the colon, where they are absorbed.142,143 In
order to take advantage of this colonic absorption, a well-designed study has compared
the use of a high carbohydrate (60:20:20% of kcalories from carbohydrate: fat: protein)
versus a high fat diet (20:60:20%) in SBS.144 Intakes of the various diets did not affect stool
or ostomy outputs, but consumption of the high carbohydrate diet by patients with a colon
reduced the fecal loss of kcalories by 2 ± 0.2 MJ/day, which may equal up to 20 to 25% of
the daily kcaloric intake of an average patient with SBS. Thus, patients with a colon should
be advised to consume a high carbohydrate (50 to 60% of kcalories) and lower fat (20 to
30% of kcalories) diet. Diets containing more than 60% of energy as carbohydrates may
ultimately overcome the colon’s energy salvage capability of 2.2 MJ/day of SCFAs.145
In patients without a colon, neither high-fat nor high-carbohydrate diet significantly
affects energy or water/electrolyte losses.144 Furthermore, many patients with very short
jejunal segments and high ostomy outputs have been shown not to need or benefit from
any particular diet.146,147 So, restriction of fat in the diet is not recommended, because such
restriction limits palatability of food and deprives patients of valuable concentrated energy.
Long-Chain Fatty Acids (LCFAs) versus MCTs

There is a tendency to use MCTs because of their better absorption in the presence of a
reduced bile acid pool and/or pancreatic insufficiency. MCTs can help reduce ostomy
output148 in some cases, but they also exert a higher osmotic load in the small intestine
and have a lower caloric density compared to LCFAs. Besides, LCFAs are better in inducing
intestinal adaptation;149 thus, a mixture of LCFAs and MCTs seems to be the most logical
approach. A recent study compared the effects of a high fat (56% of kcalories as fat) diet
in SBS. Patients were given fat in the form of LCFAs or a mixture of MCTs and LCFAs
(about 1:1). Only patients with a colon benefited, with an increase in energy absorption
from 46 to 58%.150
Lactose
Although the concentration of lactase in the intestine of SBS patients is unaltered, there
is a reduction in the total quantity of available lactase. Thus, intake of food with high
lactose content (e.g., milk) is discouraged, although many patients are able to tolerate
small quantities of cheese and yogurt well.
Insoluble Fiber
Insoluble fiber such as bran decreases intestinal transit time and should be avoided by
SBS patients.
Micronutrients
Deficiency of divalent cations such as calcium, magnesium, and zinc are typical. Water-
soluble vitamin deficiencies are rare because most are absorbed in the proximal jejunum.
Vitamin B12, which is absorbed in the terminal ileum, and fat-soluble vitamins A, D, E,
and K need to be replaced routinely. A water-soluble form of vitamin A (Aquasol A) may
be tried. Monthly injections of 1000 µg vitamin B12 are necessary.
Bile Acid Replacement

Although the bile acid pool is reduced in patients with SBS, clinicians do not replace it
routinely because of a fear that diarrhea will increase when bile acids are fermented by
bacteria, causing secretion of water and electrolytes. A recent case report contradicts this
and has demonstrated a 40 g/day increase in fat absorption when the patient was given
a natural conjugated bile acid mixture isolated from ox bile or a synthetic bile acid named
cholylsarcosine.151
Common Problems and Complications in SBS

Hypomagnesemia
Patients with end-jejunostomies tend to have hypomagnesemia more often than those
with colons.152 The condition requires parenteral magnesium frequently but oral 1-α-
hydroxycholecalciferol may also be tried.152 Urinary magnesium levels are a better indi-
cator of deficiency than serum levels, which represent only 4% of the total body pool.153
Renal Stones
Risk of oxalate stones is increased, occurring in 25% of all SBS patients with a colon.154
Calcium, which normally binds to oxalate and causes its excretion with feces, actually
binds the malabsorbed fatty acids in the lumen in SBS, leaving oxalate available for
absorption in the colon. Unabsorbed bile acids that enter the colon also stimulate absorp-
tion of oxalate.
Urinary oxalate excretion should be measured in patients with a colon, and oxalate
should be restricted in patients with high levels of excretion. In patients with a history of
stones, restriction of fat in the diet may be considered. Additionally, urinary citrate and
magnesium, which inhibit stone formation, are low and may need to be supplemented.
Gallstones
There is a two- to threefold increased risk of cholesterol gallstones because of the decreased
bile acid pool in SBS. This increased risk is not different for patients with or without a
colon, but risk of calcium bilirubinate stones is higher in patients on TPN because of
gallbladder stasis and low oral intake. Cholecystokinin injections have been tried in dogs155
with good success in preventing gallbladder stasis. Some advocate prophylactic cholecys-
tectomy in SBS.156
Social Problems
Patients with end-jejunostomies and those dependent on TPN frequently have social
problems that require help of psychiatrists and psychologists.
D-Lactic Acidosis
Fermentation of malabsorbed carbohydrates in the colon produces D-lactic acid that can-
not be metabolized by humans. Elevated levels cause an anion-gap metabolic acidosis
with confusion, ataxia, nystagmus, opthalmoplegia, and dysarthria.157 The condition is
more likely when thiamine deficiency is present, and it is treated with nonabsorbable
antibiotics (neomycin or vancomycin) and restriction of carbohydrates (especially mono-
and oligosaccharides) in the diet.158
In summary, nutritional management of SBS is complex, and patients should best be
referred to an experienced multidisciplinary nutrition management team.
Acute Infectious Diarrhea

Acute infectious diarrhea usually does not affect nutritional status, even though it can
result in severe water and electrolyte disturbances. Although no specific diet therapy is
proven to be effective in this disease, patients should be encouraged to drink plenty of
fluids that contain a mixture of glucose and sodium. Absorption of sodium in the intestinal
tract is altered in acute diarrhea, but glucose-coupled sodium transport through the SGLT1
transporter is adequate in most cases to sustain hydration. An ideal mixture of glucose
and sodium is found in the WHO oral rehydration solution (ORS), which can be made
by mixing 20 g glucose, 3.5 g sodium chloride, 2.9 g sodium bicarbonate and 1.5 g
potassium chloride in 1 L water. The commonly advocated sports drinks contain far less
sodium and much more glucose compared to this ORS solution, and should not replace
the latter. Within the last two decades, rice and other cereal-based ORS solutions that take
advantage of other apical membrane sodium-dependent solute-transport transporters
have been discovered. In these solutions, rice or cereal flour replace glucose found in the
original ORS. The rice ORS solution is superior to the glucose-based ORS in decreasing
stool output.159 Most recently, induction of sodium absorption from the colon by short-
chain fatty acids was observed.160 A clinical application of this principle has been tested:
50 g/L amylase-resistant maize starch, which is malabsorbed and fermented to short-chain
fatty acids by colonic flora, was added to the original WHO ORS. In adolescents and
adults with Vibrio Cholerae-induced diarrhea, stool output and duration of diarrhea was
less in patients given the maize starch ORS compared to controls given standard ORS.161
Further studies are needed before the latter is incorporated into common clinical practice.
Although it is rational to advise patients to stay away from hard-to-digest foods such
as red meat, high fiber-containing vegetables (e.g., salads, greens, broccoli, etc.), and lactose,
because of the increased rate of intestinal transit and concurrent malabsorption that occur
in acute diarrhea, there exists no data in this regard. Most recently, an antidiarrheal factor
has been found in rice, suggesting that a rice-based diet may be useful.162 This factor blocks
the secretory response of intestinal crypt cells to cyclic adenosine monophosphate and
targets the cystic fibrosis transmembrane regulator (CFTR) chloride channel.
Clostridium Difficile Colitis and Probiotics

C. difficile colitis is a major cause of antibiotic-associated diarrhea and acute diarrhea in
hospitalized patients. Spores of the bacterium are hard to destroy, and a mean of 20%
(range 5 to 66%) of patients have recurrences despite treatment with effective antibiotics.
Preliminary results of a trial with yogurt enriched in Lactobacillus GG (trial using medicinal
microbiotic yogurt = TUMMY) together with standard antibiotic therapy have been prom-
ising in prevention of recurrence.163 Final results are awaited for further recommendations.
Functional Disorders of the Gastrointestinal Tract (FGIDs)

Functional gastrointestinal disorders (FGIDs) are the most common diseases of the GI
tract, with at least 4.7 million affected individuals in the U.S. They comprise about 20 to
50% of gastroenterology clinic visits and are estimated to cost 8 billion dollars/year to the
healthcare system. Definitions for the different types of FGIDs are established, and are
known as the Rome II criteria.164
Mechanisms
Various factors and mechanisms thought to be important in the pathogenesis of these
disorders are listed in Table 57.17. Currently recommended dietary management is based
on decreasing food allergies, affecting GI motility and lowering intestinal gas production
in an effort to decrease bowel wall distention.

FGIDs usually do not lead to weight loss. If a patient with FGIDs has significant weight
loss, other causes should be sought. Although there are no reports of malnutrition,
patients with FGIDs have many self-reported food intolerances, resulting in avoidance
of various foods. This avoidance may lead to nutritional deficiencies. In one study
comparing nutrient intake using 48-hour dietary recall, women with FGID had lower
mean consumption of kcalories as well as folate, ascorbic acid, and vitamin A, compared
to GERD and IBD patients.165
TABLE 57.17
Factors Important in Pathogenesis of FGIDs
1. Cognitive factors
a. Illness behavior
b. Illness coping strategies
2. Behavioral/Emotional factors
a. Psychosocial stress
b. Physical and/or sexual abuse
c. Anxiety
d. Depression
3. Physiological factors
a. Visceral hyperalgesia
b. Altered intestinal motility
c. Altered neuroendocrine response
4. Environmental factors
a. Dietary allergens
b. Enteric infections
Diet in FGIDs
There is no particular diet for patients with FGIDs, and there is little evidence for dietary
therapies of functional upper digestive tract diseases. Some patients with functional
chest pain may improve with diets similar to ones recommended for GERD patients
(given in the previous GI section, Table 56.10). Others with functional dyspepsia may
benefit from elimination of foods that delay gastric emptying (given in the previous GI
section, Table 56.17).
Fiber for Irritable Bowel Syndrome (IBS)

Types of Dietary Fiber
Dietary fiber is defined as endogenous components of plants that are resistant to digestion
by human enzymes. Fiber consists either of non-starch polysaccharides (e.g., cellulose,
hemicellulose, pectins, and gums) or of non-polysaccharides (e.g., lignins composed of
phenylpropane units). Cellulose is a non-digestible glucose polymer found in the cell walls
of all vegetation, making it the most abundant organic compound in the world. Hemicel-
lulose fibers are cellulose molecules substituted with other sugars, such as xylan, galactan,
mannan, etc. Pectins and gums are composed of arabinose or galactose side chains added
on to a galacturonate backbone; they naturally form gels.
Cellulose and hemicellulose are the major components of bran and whole grains. Lignins
are commonly found in seeds and stems of vegetation. Pectin is part of apples, citrus
fruits, and strawberries, and is widely added to jams and jellies. Gums naturally occur in
oats, legumes, guar, and barley. Structural fibers such as celluloses, lignins, and some
hemicelluloses are water-insoluble. Gums, pectins, psyllium, oat bran, and beans are
water-soluble.
Insoluble fiber mainly adds bulk to stool and increases transit through the colon. Soluble
fibers such as guar and pectin delay gastric emptying and transit through the small
intestine, but speed transit through the colon and lower intraluminal pressures. Soluble
fibers may also bind bile acids and minerals such as calcium and iron.
Bran
Fiber, in the form of bran, for IBS was popularized after Burkitt’s initial work in early
1970s demonstrating that it increases stool weight and decreases intestinal transit time.
Others confirmed these findings,166 and a lack of fiber was implicated for the development
of many GI diseases including diverticular disease, colon cancer, and IBS. Consequently,
studies in the 1970s undertook bran replacement as therapy for IBS, and the results were
positive in some167 but clearly negative in many others.168 Most of these studies had
methodological flaws, and were usually done with small numbers of patients. Neverthe-
less, given the lack of other effective therapies for the disease, bran became the standard
of care.
Evidence over the last two decades contradicts this, and indicates that patients with IBS
consume equal amounts of total fiber but less vegetable fiber compared to healthy con-
trols.169 Fiber replacement in the form of bran is no more effective than placebo,170-172 and
is poorly tolerated in many subjects. In one study, 55% of patients worsened after bran
therapy, with deterioration in bowel habits, abdominal distention, and pain.173 Improve-
ment was seen in only 10%. These findings are corroborated by data from other studies
upon careful review;174 not only may patients worsen initially and not tolerate bran, but
they also may have a high subsequent withdrawal rate.175
Soluble Fiber
Soluble fiber replacement seems to be better tolerated and more effective for IBS in
comparison with bran.176 It has also been used in combination with antispasmodics,
anxiolytics, and antidepressants, and has a synergistic effect in such combinations177 in
some studies. Soluble fiber (such as psyllium, methylcellulose, or calcium polycarbophil)
is most effective for constipation predominant IBS patients, and should be gradually
increased over a period of weeks to avoid bloating and flatulence.
High-Fiber Diets
The role of a high-fiber diet for IBS is debatable, given the above controversies regarding
bran as treatment for IBS. In an open-label trial, the symptoms that have been shown to
benefit most from a high fiber diet are hard stools, constipation, and urgency. In this study,
all patients who were able to consume 30 g or more fiber improved symptomatically.178
In another trial of 14 patients followed for two to three years, 50% improved greatly,
whereas 28.5% had worsening of their symptoms.179 In conclusion, fiber is not ideal therapy
for all patients with IBS, but should be tried especially in patients with constipation-
predominant symptoms.
Food Allergies and IBS

Patients with IBS have many food intolerances, although a small number of these repre-
sent true food allergies. Food intolerances are typically to more than one item and are
not specific, suggesting intolerance to food in general exists, rather than true food sensi-
tivity. Problem foods are identified in 6 to 58% of cases, depending on the study.180 The
most common adverse food reactions, confirmed on double-blind challenge, are to milk,
wheat, eggs, dairy products, corn, peas, tea, coffee, potatoes, nuts, wine, citrus fruits,
tomatoes, chocolate, bananas, tuna fish, celery, and yeast. Some authors believe that these
foods represent foods with a high salicylate content.180 Many adverse reactions to food
are not the classical wheal and flare type, a mere 3% are truly anaphylactoid-like and
cause rash or swelling of the lips or throat,181 and only some of the reactions are able to
be confirmed by skin prick testing.182 Most of the true food allergies in IBS are seen in
patients with other atopic diseases.183,184 Furthermore, most true food allergies on testing
may not be clinically relevant. In a study of IBS patients, food intolerance was identified
in 62.5%; skin prick tests to various foods were positive in 52.3%; but, strikingly, only
13.7% of the patients were symptomatic with foods that they were allergic to on prick
tests.182 These findings argue against undertaking a search for food allergies as part of
the clinical evaluation of IBS patients.
A positive response to elimination diets in IBS ranges from 15 to 71%, but most studies
have methodological flaws.180 Supporting the role of food allergy in IBS, equal improve-
ment of symptoms up to 50% has been noted in both study groups in trials with diet versus
sodium chromoglycate administration for diarrhea-predominant disease.185,186 These find-
ings need to be confirmed in well-designed placebo controlled experiments before they
can be considered clinically applicable, given a high placebo response rate in IBS.
Recently an in vivo colonoscopic allergen provocation (COLAP) test based on wheal and
flare reactions in the colonic mucosa has been developed, and has shown positive reactions
in 77% of patients with food-related symptoms.187 The clinical utility of this test in IBS is
yet to be determined.
In conclusion, a small subgroup of patients with true food allergies is classified as IBS.
These patients tend to have atopy in general, and diarrhea-predominant disease. In
selected patients, a symptom and food diary may be useful as an initial investigation for
food allergy. Foods that lead to symptoms may then be eliminated and rechallenges may
be done. Referral to an allergy specialist may be useful in such cases.
For the majority of cases, however, elimination of certain foods that the individual
patient believes to cause symptoms is adequate therapy. Physicians also need to ensure
that the patient’s self-imposed dietary restrictions do not lead to macro- or micronutrient
deficiencies.
Carbohydrates in IBS
Fructose and Sorbitol
A number of studies show that IBS symptoms are exacerbated in patients after ingesting
fructose and sorbitol mixtures. Fructose is a natural ingredient of fruits, as is sorbitol. The
latter is also a common sweetener in dietetic foods. Ingestion of 10 g of sorbitol, equivalent
of 4 to 5 sugar-free mints or two medium pears, can produce moderate to severe abdominal
discomfort, bloating, and diarrhea in 27% of healthy volunteers.188 Symptoms may last up
to six hours.
A subset of IBS patients has true malabsorption of fructose and sorbitol as assessed by
breath hydrogen production,189,190 although the level of breath hydrogen produced does
not necessarily correlate with the degree of symptoms.191 Whether fructose and sorbitol
malabsorption is more common or more severe among IBS patients compared to healthy
controls is uncertain. In one large study, there was no higher incidence or higher level of
malabsorption.192 Among malabsorbers, symptoms cannot be explained by changes in
jejunal sensitivity and motor function of the small bowel. At present, avoidance of sorbitol
and high intakes of fructose may be considered in selected patients.
Lactose
Subjective lactose intolerance is also increased in IBS, and lactose malabsorption is com-
mon. Most lactose malabsorbers among IBS patients are malabsorbers of fructose and
sorbitol as well. However, elimination of lactose from the diet does not impact on the
disease course or reduce symptoms when assessed objectively in long-term followup.193
In contrast with these findings, many patients subjectively feel that identification of their
lactose malabsorptive state has helped them gain awareness of food-symptom relation-
ships and alleviate their symptoms partially. Treatment with lactase194 or acidophilus milk
have shown no benefit over unaltered milk in IBS patients with and without lactose
malabsorption.
Therapies Directed against Gas Production and Enzyme Therapies

Gas in the upper GI tract is a result of swallowed air and the carbon dioxide generated
by chemical reactions of acid and alkali substances, whereas in the colon, gas forms as a
result of fermentation of nutrients by the bacterial flora. Bloating and gas are common
complaints of patients with IBS, even though the total amount of gas in the intestinal tract
is not increased.195 Rather, IBS patients have a hypersensitivity to the presence of gas,
resulting in discomfort and pain. Therefore, therapies directed against gas seem reasonable
in symptomatic patients.
In order to reduce air in the upper digestive tract, patients may be instructed to eat
smaller quantities, avoid eating on the run, not talk during eating, avoid carbonated
beverages, chewing gum, smoking, and excessive fluid intake with meals. Additionally,
simethicone may be tried despite its questionable efficacy, as it poses no harm to patients
other than their pocketbooks.196
One small study suggests that pancreatic enzyme supplements (30,000 USP lipase-
112,500 USP protease-99,600 USP amylase) may reduce symptomatic bloating, gas, and
fullness without significant decreases in breath hydrogen or methane levels in healthy
subjects in response to a high-fat meal.197 It is unknown whether the marginal symptomatic
benefit in this study can be translated into patients with functional dyspepsia or IBS.
Activated charcoal has been shown to be partially effective in reducing gas in the lower
GI tract.196,198 A preparation called “Beano,” containing the enzyme beanase, has been
reported to reduce flatulence and breath hydrogen produced after ingestion of mashed
black beans, although no studies exist demonstrating its clinical utility in IBS.199
It is commonly recommended that IBS patients avoid known gas-producing foods such
as cabbage, legumes, lentils, beans, and certain cruciferous vegetables such as cauliflower
and broccoli, although such a diet has not been tested, either. Interestingly, King and
colleagues200 have devised an elimination diet that reduces abnormal colonic fermentation.
This diet allows meat and fish except beef, replaces all dairy products with soy products,
eliminates all grains except rice, and restricts yeast, citrus, caffeinated drinks, and tap
water. A pilot study of diarrhea predominant patients on this elimination diet has dem-
onstrated reduction in median symptom scores, compared to controls. Further studies are
needed before such a restrictive diet can be recommended for IBS in general.
Nutritional tips for patients with FGIDs are summarized in Table 57.18.
Diverticular Disease of the Colon

Diverticular disease of the colon is common in Western countries. The incidence increases
with age, but the true incidence is difficult to determine, since most patients remain
asymptomatic. Nonetheless it is rare before age 40, and can be found in up to two-thirds
of patients over the age of 80.201-203 In contrast to Western countries (U.S., Australia, and
European countries) diverticula are less common in South America, and extraordinarily
rare in Africa and rural Asia. Owing to worldwide geographical variability, diverticular
disease of the colon has been termed a disease of Western civilization.
TABLE 57.18
Summary of Nutritional Tips for the IBS Patient
1. If constipation predominant IBS, try soluble fiber supplements
2. If diarrhea predominant disease and atopic patient, keep food diary and seek
help from an allergy specialist
3. Avoid only those foods that cause symptoms every time they are consumed
4. Replace consumption of heavily processed foods, containing preservatives,
additives, food coloring, etc., with a natural balanced diet
5. Seek help from a dietitian to ensure adequate macro- and micronutrient intake
if having to avoid many food items
6. Avoid gas-producing vegetables (e.g., legumes, cruciferous vegetables, etc.)
7. Avoid carbonated and caffeinated beverages
The majority of diverticula are histologically pseudodiverticula, which are herniations

of the mucosa and submucosa through the muscular layer of the colon as opposed to true
diverticula, which involve all layers. The sigmoid colon is the most frequent location for
diverticular disease in the U.S.
Mechanisms
Role of Diet in the Pathogenesis
Dietary fiber deficiency along with the theory of colonic segmentation has been the leading
hypothesis for the etiology of diverticular disease of colon. According to the segmentation
theory, contraction of the colon at the haustral folds causes the colon to act as a series of
“little bladders” instead of a continuous single-chambered lumen.202 Formation of these
segments leads to delayed transport, increased water absorption, and more importantly,
a rise in intraluminal pressure, resulting in mucosal herniation.204
The incidence of diverticula within a society increases following the adoption of a
Western diet that is low in fiber.205 This is supported by animal data as well as epide-
miological studies.205,206 Compared to patients on a diet high in fiber content, those who
consume a low-fiber diet have a threefold increase in the incidence of diverticulosis.207
Consumption of a low-fiber Westernized diet leads to a lower intake of crude cereal
grains, increase in consumption of white flour, refined sugar, conserves, and meat. Lack
of “adequate” dietary fiber decreases stool weight, prolongs transit time, and increases
the colonic intraluminal pressure, all of which predispose to the diverticula formation
in concert with segmentation.202,208 Additionally, a high meat diet changes bacterial
metabolism in the colon, and bacteria may produce a toxic metabolite favoring diver-
ticulosis, which is hypothesized to be a spasmogen, or an agent that weakens the colonic
wall.209
Diet and Diverticulosis

Diet in Prevention of Diverticulosis
Given the importance of fiber in the pathogenesis of diverticula, it is reasonable to
recommend a high-fiber diet in the prevention of diverticular disease. Confirming the
importance of high-fiber diet as a prophylactic measure, the Health Professionals Follow-
up Study, which included over 50 thousand health professionals, showed an inverse
relationship between the amount of dietary fiber intake and the risk of developing symp-
tomatic diverticular disease. Those who consumed more that 32 g/day of fiber had the
greatest benefit.210
Diet in Treatment of Symptomatic Disease

The beneficial effects of dietary fiber on symptomatic uncomplicated diverticular disease
continue to be subject to debate. Two controlled trials that evaluated the impact of fiber
supplementation in patients with uncomplicated diverticulosis showed conflicting
results.211,212 However, this disagreement does not preclude the potential benefits from a
trial of high-fiber diet, which still seems a reasonable approach. The American Society of
Colon and Rectal Surgeons practice guidelines recommend the resumption of a high fiber
diet following the resolution of uncomplicated acute diverticulitis.213 In cases of compli-
cated diverticular disease, the patient should be placed on clear liquid diet or be kept
NPO in order to achieve bowel rest, which remains the mainstay of therapy along with
the antibiotics. There is neither evidence nor scientific basis for avoidance of nuts, popcorn,
or seeds for prevention of symptomatic attacks, even though this recommendation seems
to be common.
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58
Nutrient Metabolism and Support in the Normal
and Diseased Liver
Mark T. DeMeo
Introduction
The liver plays a dual role in nutritional wellbeing. First, it contributes to nutrient assim-
ilation through the synthesis of bile acids. At the time of a meal, as the gallbladder
contracts, bile acids are released into the gut lumen. These bile acids enable lipids to be
absorbed efficiently. Second, the liver plays a major role in substrate metabolism and
allocation. It maintains nutrient blood levels at a constant level despite variations in
substrate availability. It is therefore not surprising that damage to this vital organ has a
tremendous impact on nutritional status.
Role of the Liver in Normal Nutrient Metabolism

Carbohydrates
Certain cells such as neutrophils, erythrocytes, and platelets are obligate utilizers of glu-
cose. Therefore, during periods when glucose is not ingested, such as an overnight fast,
glucose requirements continue. Many organs that use glucose during the fed state use
fatty acids when supplies of glucose are low. It is estimated that carbohydrates account
for 45% of the resting energy expenditure in overnight-fasted humans.1 In this setting, the
liver accounts for about 90% of the glucose released into circulation. Earlier studies sug-
gested that approximately three-quarters of that glucose comes from glycogen, its liver
storage form; however, a more recent study determined that glycogen contributes only
about one-third to hepatic glucose production during the first 22 hours of fasting.2 The
remaining portion comes from gluconeogenesis.1,2 Gluconeogenesis is the formation of
glucose from precursors such as lactate, pyruvate, glycerol, and the gluconeogenic amino
acids (mainly alanine, glutamine, and glycine). Gluconeogenesis is regulated by hormones
and facilitated by a drop in insulin level and a rise in glucagon secretion, characteristic
0-8493-2705-9/02/$0.00+$1.50
Insulin/Glucagon
cAMP Glycogen
+ Glucose-1-P
+
Protein
Kinase
Glucose-6-P Glucose
Fructose-6-P
PFK-2 PFK-1 FDPase
Fructose-1-6-P
F-2,6 P2
Phosphoenopyruvate
PK
Oxaloacetate Pyruvate Lactate

Amino Acids
Mitochondria
AcetylCoA
TCA cycle
Amino Acids
FIGURE 58.1
Hormonal regulation of glucose homeostasis in the liver. During fast, the insulin/glucagon ratio decreases. This
stimulates an increase in cAMP in the hepatocyte. cAMP activates cAMP-dependent protein kinase, which
activates glycogen phosphorylase. This enzyme leads to the breakdown of glycogen and the formation of glucose-
1-phosphate. Protein kinase also inactivates phosphofructokinase-2 (PFK-2). PFK-2 catalyzes the conversion of
Fructose-6-Phosphate to fructose-2, 6-bisphosphate (F-2, 6 P2). F-2, 6 P2 is an important activator of Phosphofruc-
tokinase 1 (PFK-1). The impaired activation of PFK-1 slows glycolysis and favors the conversion of Fructose-1-6-
P to Fructose-6-P and ultimately favors the formation of glucose. Protein kinase also interferes with the conversion
of Phosphoenopyruvate (PEP) to Pyruvate, by blocking the enzyme pyruvate kinase (PK). This favors the forma-
tion of Fructose-1-6-P and ultimately glucose. Glucagon also stimulates gluconeogenesis, in part through carrier
mediated uptake of alanine, the major gluconeogenic amino acid. This and other gluconeogenic amino acids enter
the TCA cycle with the resultant formation of Oxaloacetate (OAA). OAA is converted to PEP and proceeds toward
the formation of Glucose-6-P and ultimately glucose. (Adapted from Brodsky IG. In: Modern Nutrition in Health
and Disease, 9th ed, Shils ME, Olson JA, Shike M, Ross AC, Eds, Williams and Wilkins, Baltimore, 1999, p. 699.)
of the fasted state. The drop in insulin decreases the activity of pyruvate kinase (Figure
58.1). This “blockage” drives the equation back to Glucose 6-phosphate and ultimately
increases hepatic output of glucose.
In the fed state, metabolic and hormonal signals change the liver’s response to carbo-
hydrates. It is estimated that between 25 and 45% of an oral glucose load is taken up by
the liver. This percentage may increase as the carbohydrate load increases.1 Glucose taken
up by the liver is largely used to replenish the glycogen depleted after an overnight fast.
Nutrient Metabolism and Support in the Normal and Diseased Liver 1221
O
CH3 C
S CoA
Fatty acid
Acetyl-CoA synthase (FAS)
CH3 CH2 CH2 C FAS
O O
O
C CH2 C Butyryl group-FAS
O S CoA
Malonyl-CoA
elongases
Butyryl group-FAS 7 Malonyl-CoA Palmitate Saturated Fatty Acids
elongases
desaturases
Unsaturated Fatty Acids
FIGURE 58.2
Fatty acid synthesis. Acetyl-CoA combines with Malonyl-CoA in the presence of the fatty acid synthase complex.
Then through a series of condensation, reduction, dehydration, and translocation steps, a four-carbon, saturated
fatty amyl compound is formed. Seven more cycles take place to form plasmatic acid (C16: 0). Other fatty acids,
both saturated and unsaturated, can be formed using a series of elongates and desaturases.
High postprandial glucose levels stimulate the pancreas to release insulin. This decreases
hepatic glucose production and increases glucose metabolism and storage. Insulin facili-
tates the synthesis of glycogen by stimulating the enzyme glycogen synthase. However,
the liver glycogen concentration also influences synthesis. As the concentration of this
storage form of glucose increases, its rate of formation slows. This phenomenon can occur
in spite of high insulin levels and glucose concentrations, emphasizing the fact that this
is a limited form of energy storage. It should also be noted that glucose is a relatively
poor substrate for glycogen synthesis. Only about 50% of “neoglycogens” come from
ingested glucose, while the remainder is derived from gluconeogenic precursors. Thus,
the amount of carbohydrates presented to the liver could exceed the ability to form
glycogen. Insulin also stimulates glucose oxidation by increasing pyruvate dehydrogenase,
which converts pyruvate to acetyl-CoA. When the acetyl-CoA generated by glycolysis is
not needed for oxidative phosphorylation, it is converted to fatty acids and ultimately to
triglycerides3 (Figure 58.2).
Lipids and Lipoproteins

The liver synthesizes bile acids from cholesterol. The bile acids are secreted in bile and
released in response to a meal. When bile acids are released in sufficient quantities, the
critical micellar concentration, they will form micelles. Micelles have a hydrophilic or
water-soluble surface, and a lipophilic or lipid-soluble core. Most dietary fat is in the form
of triglycerides, which are fatty acids esterified to a glycerol backbone. Triglycerides are
a major source of both stored and available energy. As pancreatic lipase cleaves the fatty
acids from the dietary triglycerides, these water-insoluble molecules are absorbed into the
lipophilic core of the micelle. The micelle provides a conduit through the intestinal
unstirred water layer to the lipid-soluble membranes of the intestinal enterocyte. The fatty
acid diffuses into the lipid-soluble membrane of the enterocyte (Figure 58.3). Medium
chain triglycerides can be absorbed directly into the portal vein and do not need this
“micellar intermediate” to facilitate absorption. The bile acids are largely taken up by
2705_frame_C58 Page 1222 Tuesday, September 25, 2001 12:22 PM
FIGURE 58.3
Fatty acid transport. Co-lipase attaches to the lipid droplet and then binds lipase, the principal enzyme of
triglyceride digestion. Lipase then hydrolyzes the ester bonds of the tryglycerides forming free fatty acids. The
fatty acids are taken up by the lipophilic inner core of the micelle. The outer core of the micelle is hydrophilic,
allowing for this particle to traverse the unstirred water layer of the intestine. The fatty acids in the inner core
of the micelle are placed in approximation to the lipid soluble membrane of the enterocyte, allowing for diffusion
across the enterocyte membrane. (Adapted from Reference 5.)
receptors in the terminal ileum and transported back to the liver via the enterohepatic
circulation. Some unabsorbed bile acids are excreted into the feces.5
In the enterocyte, fatty acids are reesterified into triglycerides and packaged into lipo-
proteins called chylomicrons. Chylomicrons are secreted into the lymphatics, travel
through the thoracic duct to the superior vena cava, and are then circulated to target tissues.
Chylomicrons are part of the exogenous transport system for lipids. The endogenous
system is comprised of three main carriers, VLDL, LDL, and HDL.5,6 Many of the protein
components of these lipoproteins, called apoproteins, are also synthesized in the liver.
The liver can also manufacture triglycerides from fatty acids synthesized by repetitive
additions of two carbon fragments, derived from Acetyl-CoA, to malonyl CoA, or from
non-esterified fatty acids removed from the blood.3 Triglycerides synthesized by the liver
are transported by the lipoprotein LDL to target tissues. Similarly, cholesterol synthesized
in the liver is taken by the LDL carrier to target tissues. Peripheral tissues transport
cholesterol back to the liver for excretion by the gallbladder through the action of HDL.
Amino Acids and Proteins

The liver also plays a major role in amino acid homeostasis. Amino acids serve as building
blocks of proteins and as precursors to many other important biomolecules, such as
purines and pyrimidines. Additionally they can be a source of energy, particularly when
they are present in excess of need for visceral or somatic protein synthesis. Amino acids
are either essential or non-essential. The distinguishing feature between these two types
of amino acids is the ability of the body to synthesize their carbon skeleton. Essential
amino acids have a carbon skeleton that cannot be synthesized de novo and must be
obtained from the diet.
The first step in the catabolic process of most amino acids is the removal of the α-amino
group from the carbon skeleton. This occurs via a pathway known as transamination. In
the liver, most of α-amino groups derived from ingested protein, muscle protein, or protein
from other tissues are separated from the parent carbon skeleton, leaving a ketoacid and
an amino group. This amino group is combined with α-ketogluterate to form glutamate.
Glutamate then undergoes oxidative deamination in the mitochondria, yielding the pro-
tonated form of ammonia (NH4+). The NH4+ is a co-substrate in forming carbamoyl phos-
phatase. It then enters the urea cycle. As ammonia is toxic to animals, the urea cycle
enzymes, also located largely in the liver, allow excretion of this harmful metabolite (Figure
58.4). Transamination can also occur between other amino acids. The presence of transam-
inase enzymes in the liver ensures that the liver is able to conserve essential amino acids
and interconvert nonessential amino acids. Although most amino acid catabolism occurs
in the liver, the three amino acids with branched side chains (leucine, valine, and isoleu-
cine) are particularly noteworthy. They are oxidized as fuels to be used primarily by
extrahepatic tissue, particularly muscle, adipose, kidney, and brain. These extrahepatic
tissues contain a single aminotransferase not present in the liver. This acts on all three
branched chain amino acids (BCAAs) to produce the corresponding α-ketoacid.
Amino acid carbohydrate skeletons can metabolize to pyruvate or intermediates of the
tricarboxylic acid cycle. These can be converted into glucose and are called glucogenic
amino acids. These precursors contribute to a process known as gluconeogenesis. In
humans, gluconeogenesis occurs largely in the liver, and to a much smaller extent in the
renal cortex. Since some tissues in the body are obligate glucose utilizers, this pathway is
extremely important during periods of relative glucose deficiency. It maintains hepatic
glucose output to glucose-utilizing tissues.8,9
The liver absorbs amino acids from plasma to be utilized in protein synthesis. The most
abundant plasma protein secreted by the liver is albumin. Albumin is the most important
regulator of plasma oncotic pressure and is the principal transport protein for many
endogenous and exogenous substances. The liver also produces transport proteins for
lipids (lipoproteins), iron (transferrin), and copper (caeruloplasmin) as well as steroid
hormone-binding proteins, thyroid hormone-binding proteins, and several vitamin-bind-
ing proteins. An equally essential role for the liver is the synthesis of many of the coag-
ulation and fibrinolysis proteins. The liver is also the primary site of synthesis of the
complement system that plays an important role in host defense against infectious agents.
Finally, it is the major site of synthesis of protease inhibitors, inhibitors of coagulation and
fibrinolysis, as well as many other proteins involved in immunomodulation, drug binding,
and other aspects of the acute phase response.10
Impact of Liver Disease on Nutrient Metabolism

Carbohydrates
Damage to the liver can negatively impact glycogen stores. Since the liver is the major
source of glucose production in the fasted state, it would be expected that patients with
liver disease might have low blood glucose levels after an overnight fast or a prolonged
COO COO
+ transamination
H3N-C-H C O
H3N +
R R
Amino Acids from α-Keto
ingested proteins acids
Glutamate α-Ketoglutarate
Hepatocyte
α-Ketoglutarate
Citrulline
Ornithin
Transcarbamylase
Carbamoyl Urea
Glutamate NH4
phosphate
Ornithine cycle
Carbamoyl
phosphate
synthetase I
α-Ketoglutarate
Mitochondria
Urea
FIGURE 58.4
NH3 Metabolism. Amino acids from ingested proteins are transaminated to yield NH3 and α-keto acids. The
amino group is then transferred to α-ketogluterate to form glutamate. Glutamate is transported to the hepatocyte
mitochondria where α-ketogluterate is reformed with the loss of NH4. This ammonium group combines with
HCO3 and 2 ATPs to form carbamoyl phosphate. Carbamoyl phosphate enters the urea cycle, is converted to
urea after a series of reactions. (Adapted from Nelson DL, Cox MM. In: Principals of Biochemistry, 2nd ed,
Lehninger AL, Nelson DL, Cox MM, Eds, Worth Publishers, New York, 1993, pg 506.)
absence of oral intake. However, hypoglycemia is rare in liver disease, usually seen only
in fulminant hepatic failure or in the terminal stages of chronic hepatic insufficiency. This
is probably due to the tremendous reserve capacity of the liver to produce glucose, with
approximately 20% of the hepatic mass needed to maintain normal glucose levels in the
fasted state.1
More commonly, fasting glucose levels in patients with liver disease are normal or high.
Despite high levels of glucagon seen in these patients, increased hepatic glucose production
does not seem to be a contributing factor. Unless there is coexistent diabetes, studies suggest
that hepatic glucose production in liver disease varies from normal to 20-40% lower than
normal. However, diabetic cirrhotics with fasting hyperglycemia displayed increased
hepatic glucose production, which was not appropriately decreased by insulin.4
Since glycogen synthesis is impaired in liver disease and glycogen stores are rapidly
depleted in the fasted state, patients with liver disease more rapidly transition to gluco-
neogeneisis and ketogenesis to fill their glucose and energy needs. It is estimated that
gluconeogenesis accounts for about 67% of hepatic glucose production, with the remainder
coming from glycogenlysis. The rapid switch to a fatty acid/ketone economy for energy
needs is an adaptive response, as it decreases reliance on hepatic glucose production.
Glucose production by the damaged liver may be limited due to decreased glycogen stores
and potentially diminished delivery of gluconeogenic precursors to the liver.1
After glucose ingestion, many patients with liver disease have abnormally elevated
blood glucose concentrations.1 In fact, 60 to 80% of patients with cirrhosis are glucose
intolerant, and 10 to 30% eventually develop frank diabetes.4 In a recent study, non-diabetic
cirrhotics given a mixed meal had elevated blood glucose levels in spite of a fivefold
increase in blood insulin levels.12 It appears that in these glucose-intolerant patients, both
oxidative and nonoxidative glucose disposal is impaired.1,4 The oxidative impairment of
glucose utilization, the less significant of the two abnormalities, is due in part to the
preferential utilization of fatty acids seen in this patient population. The generation of
Acetyl-CoA from the metabolism of fatty acids inhibits pyruvate dehydrogenase resulting
in a diminution of pyruvate oxidation.4 The nonoxidative utilization of glucose is essen-
tially the formation of glycogen. In spite of hyperinsulinemia seen in these patients, they
demonstrate peripheral insulin resistance. As such, glucose uptake by muscle and stimu-
lation of glycogen synthesis is significantly impaired. This accounts for most of the
decreased glucose disposal and consequent glucose intolerance seen in these patients, as
hepatic glucose production is still normal in the basal state and normally suppressed by
insulin.1,4 In contrast, liver disease patients with diabetes not only have abnormalities with
glucose disposal but also are unable to appropriately suppress hepatic glucose suppres-
sion, suggesting a relative lack of insulin. Petrides et al. hypothesized that patients with
liver disease become frankly diabetic when the pancreatic β-cells cannot meet the increased
demand for insulin secretion due to insulin resistance.4
Lipids and Lipoproteins

Since cholesterol is excreted from the body through the biliary tree, the total cholesterol
level tends to rise in obstructive jaundice. However, in severe parenchymal disease, cho-
lesterol ester levels tend to fall. This latter sign is the result of reduced activity of lecithin
cholesterol acyltransferase (LCAT) activity. LCAT is an enzyme synthesized in the liver
that catalyses the transfer of a fatty acid from the 2-position of lecithin to the 3 β-OH
group to form cholesterol ester and lysolecithin. It plays a key role in the turnover of
cholesterol and lecithin. Low levels of this enzyme also alter the lipid composition of
lipoproteins.
Plasma triglycerides are often elevated, both in obstructive, and less often in parenchy-
mal liver disease. Triglycerides are normally cleared by the action of peripheral lipoprotein
lipases (LPL) and hepatic triglyceride lipases (HTLP). The latter enzyme levels are reduced
in liver disease and may account for triglyceride abnormality.6
These changes in lipids may effect membrane lipid content, fluidity, and function. They
may, in part, explain the abnormalities associated with liver disease in platelet aggregation
and in the morphology of red blood cells.6 These changes in the lipid content of cell
membranes effect all cells in the body. The subsequent effects on membrane fluidity and
function have been advanced as a possible contributing factor in the hyporesponsiveness
of cirrhotic myocardium to pharmacologic or psychologic stress.7
After an overnight fast, cirrhotic patients derive a greater proportion of energy from fat
oxidation than do controls. This difference in endogenous energy substrate use has been
attributed to diminished glycogen stores. After ingestion of a mixed meal, fat oxidation
of cirrhotic patients decreases but still remains elevated compared to controls. The
increased reliance on endogenous fat during fasting and the continued high rate of fat
oxidation in spite of ingestion of a mixed meal may account for the reduction in body fat
stores common in this patient population.12
Amino Acids and Proteins

Patients with liver disease often have disturbances in plasma amino acid concentrations,
characterized by increased levels of aromatic amino acids and methionine. This is most
likely a result of the injured liver’s poor utilization of these amino acids as well as
portosystemic shunting.8 Additionally, since the enzymes involved in urea production are
largely localized in the liver, urea synthesis, and hence α-amino nitrogen clearance, is
lower in cirrhotics compared to controls. In patients with severe decompensated liver
disease, the plasma urea level tends to drop and the amount of urea excreted in the urine
is reduced. In patients with well-compensated cirrhosis, urea production rates remains
stable under basal conditions but maximal urea production capacity is significantly
reduced in response to a protein or amino acid load.8,11
Chronic alcohol consumption actually increases the synthesis of albumin and constituent
hepatic proteins but is also associated with a reduced secretion of these proteins from the
liver.10 However, as liver damage increases, there is a decrease in synthesis of albumin
with an apparent significant correlation between its synthesis rate and Childs score (a
scoring system based on clinical and laboratory values that is used to demonstrate the
severity of the underlying liver disease).10 Although the albumin is used in many different
prognostic scoring systems, it should be remembered that the plasma concentration of
albumin is not only dependent on synthesis but also is reliant on the rate of degradation.
Additionally, newly synthesized albumin is secreted into the lymph and ascitic fluid, when
present, which increases the distribution volume and can contribute to hypoalbuminemia.
Therefore, in the acute setting, the serum level of albumin does not purely reflect decreases
in hepatic synthesis.
The liver is also important in maintaining homeostasis. All clotting proteins, coagulation
factors, and inhibitors, and most of the components of the fibrinolytic system are synthe-
sized by hepatocytes except for von Willebrand factor, which is produced by endothelial
cells, and megakaryocytes. Liver damage can lead to decreased levels of the clotting factors
produced in the liver. It is unusual for fibrinogen to be reduced significantly unless there
is concomitant disseminated intravascular coagulation. Overall, liver impairment favors
bleeding due to impaired synthesis of coagulation factors and increased fibrinolytic activ-
ity. However, it also increases susceptibility to intravascular coagulation resulting from
impaired clearance of procoagulant material.13
Nutritional Evaluation in Liver Disease

Energy Expenditure in Liver Disease
There is significant controversy about the ability to accurately predict metabolic rates in
cirrhotic patients. This is partly because hypermetabolism occurs only when a measured
value (indirect or direct calorimetry) is compared to a predicted value. Thus, depending
on the methods of standardization and comparison, (i.e., formula equations versus esti-
mates of lean body tissue), the baseline for comparison differs. Common formula equations
that use age, weight, and height are standardized for normal proportioned individuals.
They do not make allowances for differences in body compartments that may occur in
liver disease. For example, if there is depletion of body fat, a common occurrence in
cirrhotics, there is a relative overrepresentation of metabolically active tissue per unit mass.
If this were the case, formula equations may predict a lower energy expenditure relative
to a measured value. One method to address this potential discrepancy is to correct for
lean body mass by using creatinine secretion. Since the secretion of creatinine roughly
correlates with the presence of lean body tissue, standardization to this value should help
account for discrepancies in somatic protein/fat composition. However, it should be kept
in mind that creatine, the precursor of creatinine, is synthesized in the liver. Thus, signif-
icant liver disease can compromise the urinary recovery of creatinine and result in an
underestimation of the amount of metabolically active tissue. This could subsequently
result in an underestimation of lean body tissue and an overestimation of metabolic rate
when a measured value is compared to a predicted value corrected for fat-free mass.14
Alternatively, fluid retention tends to increase weight or body surface area; formulas
that standardize energy expenditure on these values overestimate the predicted metabolic
rate compared to a measured value.15 More recently, researchers have attempted to mea-
sure fat-free mass, since this a more accurate indicator of metabolically active tissue. They
use this variable in predictive formulas for resting energy expenditure. However, even
with these more complicated formulas, only 50 to 60% of the observed variation between
measured and predicted values can be accounted for.
Most studies have failed to show significant differences in energy expenditure between
cirrhotics and control patients.14,16,17 However, others, such as in a study by Madden, have
demonstrated that the mean measured resting energy expenditure in patients with cirrho-
sis is significantly higher than in controls when adjusted for body weight. Overall, using
multiple predictive formulae, 12% of the patients were considered hypometabolic while
30% were determined to be hypermetabolic. A recent comprehensive study by Müller
found a similar proportion of hypermetabolic patients (33.8%). Unfortunately, neither
author could identify the hypermetabolic patients on the basis of demographic or clinical
variables.18,19 A possible exception to this is primary biliary cirrhosis patients, in whom
worsening disease was associated with increased resting energy expenditure and pro-
longed diet-induced thermogenesis after a meal.20
Müller also demonstrated that increased levels of catecholamines in hypermetabolic
patients could be a contributing factor in increased metabolic rate. He further determined
that for these patients, a propranolol infusion resulted in a pronounced decrease in energy
expenditure.19
Clinically, determining hypermetabolism is important for these patients, as they are
more likely to present malnourished, and this clinical status may be further complicated
by difficulty in nutrient assimilation. Thus, hypermetabolism may further negatively
impact outcome. A study assessing preoperative risk factors in patients undergoing liver
transplantation associated hypermetabolism and diminished body cell mass (<35% of
body weight) with reduced survival after liver transplantation.21 Given the clinical impli-
cations of determining an accurate metabolic rate in cirrhotic patients and the fact that
this rate cannot be accurately determined from formulas and clinical variables, many
authors are advocating that the metabolic rate should be measured in cirrhotic individuals
to accurately determine this value.18,19
Prevalence of Malnutrition in Liver Disease

Protein-calorie malnutrition (PCM) is common in advanced liver disease. A summary of
five studies using a total of 550 subjects demonstrated a range of PCM from 10 to 100%,
depending in part on the criteria used to determine PCM.22 In the Veterans Administration
Cooperative study on alcoholic hepatitis, malnutrition was a ubiquitous finding and
correlated with dietary intake and severity of liver dysfunction.23,24 In hospitalized patients
with less severe alcoholic and nonalcoholic liver disease, the prevalence of PCM ranged
from 30 to 40%. It should be noted that much of the data on malnutrition is derived from
the alcoholic liver disease population. However, a recent study by Sarin et al.24 demon-
strated that malnutrition in patients with alcoholic and nonalcoholic cirrhosis is very
common, and present to the same degree. The patterns of malnutrition appear to be
different depending on the underlying liver disease. Patients with nonalcoholic cirrhosis
demonstrated decreases in both fat and muscle mass, while those with alcoholic liver
disease demonstrated a greater decrease in muscle mass but relative sparing of fat stores.
The authors of the accompanying editorial hypothesize that this discrepancy may be due
to the “precirrhotic nutritional status” of the patient or to toxic effects of alcohol on meal-
stimulated protein secretion. They also speculated that alcohol might lead to changes in
intestinal permeability, which could potentially lead to transmigration of intestinal bacteria
or toxins with resultant release of proteolytic cytokines.25 The authors determined that the
dietary intake of both groups was reduced to a similar degree.24
Nutritional Assessment
The presence of liver disease may affect many of the traditional modalities used to evaluate
the nutritional status of patients. Visceral protein stores can be greatly influenced by acute
and/or extensive damage to the liver. Liver injury can result in decreases in visceral
markers that may be unrelated to the nutritional status of the patient, and may therefore
not improve significantly with nutritional intervention. In fact, serum visceral protein
appears to correlate better with the degree of liver damage than with the nutritional status
of the patient. Chronic liver disease can also cause alterations in cellular immunity and
total lymphocyte count independent of protein malnutrition.22 Furthermore, abnormal
immunologic reactivity, again independent of nutritional status, is a prominent feature of
chronic autoimmune hepatitis, primary biliary cirrhosis, and possibly viral hepatitis.27
From a clinical standpoint, a thorough nutritional evaluation should be performed and
repeated serially. A bedside assessment of somatic protein stores and subcutaneous fat
stores usually provides a reliable nutritional assessment.26 Other important aspects of this
subjective global assessment tool adapted for liver patients included the presence of
encephalopathy, edema, weight change, renal insufficiency, constipation, satiety, and dif-
ficulty chewing. Anthropometric data, specifically the assessment of fat stores by tricep
or subscapular skinfold thickness and the assessment of somatic stores by midarm muscle
circumference or body weight to height, can yield valuable information. Assessments
should be performed by a skilled person, as there can be problems with reproducibility.
Additionally, apparent or subclinical edema can lead to a potential underestimation of the
severity of protein and fat losses.27 The creatinine height index is generally a good indicator
of lean body mass in patients with liver disease. However, it, too, has shortcomings, as
there is frequently associated renal dysfunction which could impair collection. Further-
more, with severe liver disease there can be a decrease in creatinine formation, as its
substrate creatine is synthesized in the liver. Both of these circumstances could result in
underestimation of lean body tissue.
In summary, given the numerous limitations of standard nutritional parameters in
patients with liver disorders, it is preferable to rely on collective information generated
from the use of several parameters used simultaneously and on a serial basis.27
Nutritional Intervention in Liver Disease

Background Data
It is well known that patients with chronic liver disease are usually malnourished, and that
frequently the degree of malnutrition parallels the severity of the liver disease. Reasons for
malnutrition include altered metabolism, malabsorption/maldigestion, anorexia, iatrogenic
restrictions, and poor dietary intake. Though there appears to be a correlation between the
severity of malnutrition and subsequent morbidity and mortality from liver disease, it is
intuitive, though less clear, that nutritional intervention can have an impact. An article by
Patek et al., published in 1948, was one of the earliest to evidence that nutritional inter-
vention could impact the course of liver disease. In this study, 124 patients (89% of whom
had “significant weight loss”) were admitted to the hospital with “hepatic failure.” These
patients were given a diet of approximately 3500 kcals with 140 gms of protein, supple-
mented with a vitamin B complex preparation. The supplemented group was compared
to historic controls. Although the patients’ ability to achieve dietary goals was not men-
tioned, 49% were described as “clinically improved.” This improvement was characterized
by 1) a disappearance of ascites, jaundice, and edema, 2) weight gain and strength, and 3)
improvement in liver function test results. Furthermore, there appeared to be significant
differences in survival between the treated group and historical controls at one and five
years.30 This positive study provided the basis for subsequent studies assessing the impact
of enteral, parenteral, and oral supplementation in patients with liver disease.
Many recent studies have focused on nutritional intervention in alcoholic liver disease.
Acute alcoholic hepatitis is a potentially reversible condition, but is associated with high
mortality. The majority of patients with alcoholic liver disease who require hospitalization
for their disease are moderately to severely malnourished. Malnutrition can contribute to
delayed wound healing, increased risk of infection, increased toxicity of alcohol to the
liver, reduced protein synthesis, and impaired regenerative capacity of the injured liver.28,31
Additionally, both human and animal data suggest that poor nutrition combined with
alcohol is more injurious to the liver than alcohol alone.3,31 These factors imply that
nutritional intervention may be beneficial in this disease.28,31 In an early and much-cited
trial by Galambos, 28 days of peripheral amino acid infusion resulted in significant
improvement in albumin and bilirubin levels in the supplemented group compared to
controls. The supplemented group also showed a trend toward improved survival.33,34
Mendenhall authored a series of landmark articles on alcoholic hepatitis. A nutritional
investigation of patients with alcoholic hepatitis was part of a larger multicentered VA
cooperative study of the effects of steroid therapy in the treatment of this disease. In an
early study, the patients were categorized into mild, moderate, and severe protein calorie
malnutriton (PCM) based on eight parameters that included tests to assess somatic protein
stores, visceral protein stores, and delayed cutaneous hypersensitivity. The investigators
were able to demonstrate that 30-day and 6-month mortality rates correlated with nutri-
tional category. Perhaps equally important was that patients who moved from one nutri-
tional category to another assumed the mortality associated with their new category.35
However, it should be noted that this early observation on nutrition and outcome was a
secondary endpoint.
The same researchers subsequently designed a study to intercede with nutritional sup-
plements while providing patients with anabolic steroids (oxandrolone). Oxandrolone was
used in this population because the researchers believed it would increase anabolism and
liver regeneration. In a group of patients defined as having moderate PCM yet adequate
caloric intake (>2500 kcals), oxandralone significantly decreased mortality compared to

the placebo group. In addition, patients defined as having severe PCM yet adequate caloric
intake had significantly lower 6-month mortality regardless of the use of oxandrolone.
Finally, caloric intake during the first month demonstrated a significant inverse correlation,
with mortality at six months. It should be noted, however, that as the severity of the liver
disease increased, the caloric intake decreased.29 Unfortunately, it is unclear from this
study whether nutritional supplementation, even if the patient accepts and is compliant
with this supplementation, will improve the “nutritional category.” It is possible that other
changes in underlying liver disease also have to occur before nutritional repletion is
realized. However, the authors mentioned that there was a “marginally significant corre-
lation” between percent of basal energy expenditure consumed and the improvement in
PCM during hospitalization.
These authors published another followup article focused solely on the nutritional
indices in this same cohort of patients. The authors were able to identify four nutritional
parameters that seem to effect six-month mortality. They included creatinine height index,
total lymphocyte count, handgrip strength, and prealbumin levels. The authors suggested
that surviving patients tend to improve in most of their measured nutritional parameters,
but it is again unclear that either adequate protein or energy intake significantly influences
these four variables. Nevertheless, the authors conclude that nutritional therapy improves
both prognosis and overall nutritional status. They qualify this statement, however, by
stating that the degree of improvement is dependent on the severity of the PCM.39
A recent study by Cabre et al. assessed the effects of total enteral nutrition and predniso-
lone in the treatment of patients with alcoholic hepatitis. Patients were randomized to receive
either TEN (2000 kcal/d and 72 g protein via a nasoenteral tube) or prednisolone. The latter
group was encouraged to eat a standard hospital diet of approximately 2000 kcals and 1 g/
kg of protein. Although no difference was seen in short term or one-year survival, differences
in the time to death and cause of death were noted. Deaths occurred earlier in the TEN
group (median of seven days). In the prednisolone-treated group, most of the deaths
occurred in the immediate six weeks after the end of the treatment period and were largely
due to infectious complications. The authors speculate that most of the early mortality may
have been caused by inflammatory mediators (thus the early benefit of steroids). The latter
mortality may have been caused by changes in the intestinal barrier (supporting the impor-
tance of enteral nutrition in maintaining the integrity of the gut barrier). The author suggests
that there might be a synergistic effect realized in using both modes of therapy.41
The positive effects of nutritional supplementation are not, however, limited to patients
with alcoholic hepatitis. In an earlier study, Cabre et al. looked at enteral nutrition in
hospitalized cirrhotic patients. The treatment group was given an enteral formula con-
taining 2115 kcal/d with 71 g protein via nasoenteral tube. The control group was offered
a standard low-sodium hospital diet supplying 2200 kcals and 70 to 80 g protein. The
etiology of the cirrhosis was varied (though largely alcoholic) and there were no differ-
ences in Child’s scores. All patients in both groups had severe protein energy malnutrition.
Although the incidence of major complications was similar in both groups, the Child
score improved and mortality fell (47 versus 12%) only in the TEN group. The authors
were unable to explain the discrepancy. They suggested that the GI tract stimulation may
have decreased the catabolic effect of the injury or resulted in decreased bacterial/endo-
toxin translocation.42
In summary, multiple studies using oral, enteral, and parenteral supplementation have
demonstrated only modest improvements in liver function tests and nutritional param-
eters. A decrease in mortality in nutritionally supplemented patients has not been a
consistent or overwhelming finding,34,40,43-45 though other important facts have emerged.
These patients appear to tolerate the protein supplementation, including those with
hepatic encephalopathy. Fluid retention has not been a major problem.34 It should also
be noted that there is no published study demonstrating an adverse effect of nutritional
supplementation. These studies point out that nutritional supplementation, though very
important, is only one of several factors likely to determine the ultimate outcome in liver
disease patients. As this is a factor that can be influenced, at least to some degree, and
there do not seem to be untoward effects when used appropriately, attention to nutrition,
with supplementation when indicated, should be considered a mainstay in the therapy
for these patients.
The use of branched chain amino acids (BCAA) has been advocated in the treatment of
liver disease. It has been suggested that 50 to 60% of patients with chronic liver failure
will tolerate 60 to 80 g/d of a standard amino acid mixture as part of a parenteral nutrition
regimen. The remainder, in particular those with grade III or IV hepatic encephalopathy,
seem to respond better to with modified solutions containing BCAA.54 One rationale for
their use in hepatic encephalopathy concerns the high aromatic amino acid (AA)-to-BCAA
ratio in the blood of patients with decompensated liver disease. This is primarily due to
poor metabolism of AAs by the failing/injured liver. Conversely, BCAAs are deaminated
mainly by skeletal muscle, and so have an alternate pathway for their metabolism. Since
both of these amino acids compete for the same transmembrane transport system in order
to cross the blood brain barrier, the increase in AA/BCAA in the blood favors the transport
of AAs. In the central nervous system these AAs can be metabolized to false neurotrans-
mitters (octopamine and phenylethanolamine) and thus contribute to hepatic encephal-
opathy. Additionally, infusion of BCAAs has been shown to reduce blood ammonia
levels.46 The branch chain amino acids have also been reported to augment protein syn-
thesis in humans. Leucine, or more specifically, its deamination product, βα-keto-isocap-
rioic acid, is thought to have an important role in stimulating protein synthesis and
inhibiting protein degradation.46,47 Thus, it would seem that a BCAA mixture would be
an ideal mode of therapy in patients with liver disease.
Several studies have looked at the use of BCAA in the treatment of hepatic encephalop-
athy. The largest study was by Cerra et al., who concluded that the BCAA-enriched formula
resulted in more rapid and complete recovery from encephalopathy as compared to the
standard treatment of neomycin. The treatment group also showed improvements in nitro-
gen balance and survival. Interestingly, the control group was not given any protein, and
their sole source of kcalories was a 25% dextrose solution. Both the BCAA and dextrose
solutions were started at 1.5 liters and advanced to a maximum of 3 liters over the ensuing
days.48 Unfortunately, the lack of protein in the control group challenges the validity of the
nitrogen balance data and perhaps the mortality differences in these populations.
Overall, studies regarding the use of BCAA in encephalopathy have yielded mixed
results.47,69 A recent meta-analysis by Naylor et al. suggests that BCAA solutions have a
significant and beneficial effect on recovery from hepatic encephalopathy, though the
authors state that analysis is difficult, given the diversity of the studies involved. The
same authors were unable to verify an advantage of BCAA solutions on mortality.54
Another extensive analysis by Eriksson et al. presented a much more skeptical view of
the benefits of BCAA solutions in either acute or chronic encephalopathy. The authors
proposed that problems with data analysis, biased assignment of patients to groups in
regard to etiology of the encephalopathy, and study design disallowed any firm conclusion
that BCAA or their keto analogues were beneficial.55 Thus, though the use of BCAA-
enriched supplements may lead to mild improvement in encephalopathy compared to
standard therapy, other positive effects are not consistently demonstrated. The benefits
do not seem to justify routine use of this enriched formula at the present time.
An exception to this may be the patient with chronic encephalopathy who is intolerant
to increases in protein or standard amino acid solutions. Eriksson’s analysis did concede
that in the setting of chronic encephalopathy in which increases in standard protein

supplements worsened or precipitated encepahalopathy, BCAA mixtures were better tol-
erated. A study by Egberts et al. of this population demonstrated significant improvements
in psychomotor function, attention, and practical intelligence when stable patients were
supplemented with a BCAA-enriched mixture.50 However, the clinical applicability of
these improvements in psychomotor testing has been called into question.55
In vitro studies of isolated hepatocytes suggest that the keto acid analogues of BCAAs
augment protein synthesis.51 However, when the effects of these BCAA solutions were
evaluated in cirrhotic patients, no such augmentation was seen.46,52 In an editorial accom-
panying this paper, Charlton speculated that because the BCAA-enriched infusate lacked
sufficient AAs for protein synthesis, the expected protein synthetic response may have
been dampened. Alternately, he suggests that relative hyperglucagonemia may shunt
amino acids toward gluconeogenesis and thus render them unavailable for protein syn-
thesis. He concluded that these abnormalities may account for the less-than-convincing
“improved outcomes” with BCAA-enriched formulas for patients with liver disease.
Nutritional Recommendations
In multiple diverse populations, malnutrition can negatively impact infection, wound
healing, and organ function. The great majority of patients who present for liver disease
are malnourished, and the severity of their malnutrition has prognostic implications.
However, when studies on nutritional intervention in liver disease are considered, it is
difficult to ascertain whether nutritional intervention can positively impact the course of
the disease. A similar conclusion can be arrived at in most disease states, both acute and
chronic, in which nutritional intervention has been critically assessed. This does not
necessarily mean that nutritional intervention is not important in the individual patient.
The diverse baseline nutritional status in patients (both from a macronutrient as well as
a micronutrient perspective), the differences in insult severity, and the myriad of therapies
and approaches given to the individual patient, explain why there does not appear to be
a guiding light for nutritional intervention. In spite of this, some general recommendations
can be made with regard to energy and protein requirements.
Energy Needs
As discussed previously, difficulties in estimating energy expenditure in cirrhotics have
been attributed to fluid retention, relative changes in body compartments, and other
variables related to metabolic abnormalities in patients with liver disease. Nonetheless,
in stable cirrhotics, various studies have measured energy expenditures ranging from
approximately 1500 to 2100 kcals/d.16,18,19 Thus, though the controversy over whether these
patients are hypermetabolic compared to controls remains unanswered, the absolute
energy requirements in these patients do not appear to be excessive. Furthermore, in the
acute setting, increases in the metabolic rate are influenced by many variables including
the severity of the insult, the presence of infection, and medications that the patient may
be receiving. These latter variables further complicate accurate extrapolation of energy
needs from formula equations. REE, or resting energy expenditure, is measurement of the
body’s daily energy expenditure, not involving activity or caloric intake. REE with indirect
calorimetry remains the most accurate and practical way of estimating total caloric needs.
In the absence of indirect calorimetry, the simplest and most accurate predictive formula
is the Schofield formula. This formula, referenced by Madden et al.,18 varies significantly
by age. In men between the ages of 30 to 60 it is as follows:
(11.48 × wt) – (2.63 × ht) + 877.57
Most interventional studies have used a caloric intake of 2000 to 3000 kcals. In the VA
cooperative study, a level of 2500 kcalories and above was considered adequate therapy.
Alternately, values ranging from 25 kcals/kg/d (stable cirrhotic) to 45 kcals/kg/d (post-
operative cirrhotic) have been proposed.22 Excessive caloric delivery is not beneficial, as
it can create metabolic and respiratory stresses. High caloric delivery may also involve
increasing the fluids given to these usually fluid-restricted patients. Additionally, nutri-
tional repletion is not usually accomplished during hospitalization in the current medical
climate. Energy goals should thus be directed at maintenance without causing metabolic
abnormalities.
Perhaps more important than delivery of a caloric load is the mixture of the kcalories
provided. In an interesting study by Chanda and Mehendale, rats subjected to a hepato-
toxin demonstrated a decrease in hepatocellular regeneration and tissue repair when given
15% glucose in drinking water.56 Conversely, in a similar experiment, rats given palmitic
acid and L-carnitine were protected against similar doses of that hepatotoxin. The authors
suggest that the regenerating liver uses fatty acids as the main source of cellular energy.
The increased demand for cellular energy in the form of ATP needed to support hepato-
cellular division is essentially derived from fatty acid oxidation.57
It is also interesting to note that the two outwardly “negative studies” doing BCAA
supplementation in a test group were compared to a control group on a lipid-based
formula. It is possibile that the lack of efficacy in these studies was due to the lipids
conveying some advantage to the control group, thus decreasing by comparison the
effectiveness of the BCAA solution in the treatment group.
Other interesting animal data suggests that lipids, specifically saturated fatty acids, may
offer protection against alcoholic liver injury. Nanji et al. found that diets enriched with
saturated fatty acids (palm oil) reverse the pathological changes induced by ethanol.
Conversely, omega-3 fatty acids (fish oil) do not improve the severity of alcohol-induced
injury. The authors suggest that the protective effects may be explained in part by differ-
ences in lipid peroxidation. Dietary fat helps to modify the expression of cytochrome p450
2E1, which contributes to NADPH-dependant lipid peroxidation. The animals fed the
diets rich in saturated fatty acids demonstrated less induction of the CYP2E1 enzyme
system.58 Alternately, the protective effect may be through positive changes in eicosanoid
metabolism manifested as an increase in the prostacycline-to-thromboxane B2 ratio. In
previous studies, these authors found that decreases in this ratio preceded the production
of pathologic liver disease.
Saturated fats are probably not the only nutrients that may have a protective effect
against liver disease. Lieber found that baboons maintained on a chronic ethanol-enriched
diet supplemented with polyunsaturated phospholipids (55 to 60% of which was polyun-
saturated phosphatidylcholine [PPC]) were protected against alcohol-induced fibrosis. In
a similar study, the animals were given a purer extract, comprising 94 to 96% phosphati-
dylcholine. The researchers found that these baboons given ethanol for up to eight years
did not develop cirrhosis or septal fibrosis when fed this supplemented diet. Leiber
proposed that the phosphatidylcholine directly affects collagen metabolism and opposes
oxidative stress.3,59,60 Unfortunately, supplementing fat does not appear to be the entire
answer. In a rat model, Lieber also found that in the setting of chronic alcohol consumption,
increased triglycerides in the diet results in increased fat accumulation in the liver.3
Extrapolating from animal data, it would therefore seem that in the setting of alcoholic
liver disease, 25 to 35% of the total kcalories should be derived from a mixture of these
lipids. Thus, it would appear that the type as well as amount of fat are important consid-
erations in supplementing patients with liver disease.
Protein supplementation in the patient with acute liver injury is probably the most con-
troversial aspect of macronutreint nutritional supplementation. These patients usually dem-
onstrate somatic protein wasting and decreases in muscle strength, immune reactivity, and
protein synthesis. These deficiencies may in part be due to diminished protein stores. Also,
repair of injury, extrapolated from other clinical settings, requires adequate protein. Finally,
it has been assumed that liver regeneration is delayed when there is insufficient protein.3
In their studies of nutritional intervention in patients with alcoholic liver disease, Men-
denhall et al. have stated that all patients with alcoholic hepatitis achieved positive nitro-
gen balance with 1.2 g/kg of protein. Additionally, this intake of protein was well tolerated
in spite of severe liver disease. Encephalopathy was observed in 20% of patients, but its
occurrence did not correlate with protein intake.39 In patients with chronic liver disease,
Lieber states that positive nitrogen balance can be attained with a protein intake of 0.74 g/
kg. Thus it appears that the stringent protein restrictions often imposed on hospitalized
patients with liver disease can be eased. Protein provisions in the range of 0.6 to 0.8 g/
kg can usually be safely given during the acute setting, increasing protein delivery as
tolerated to at least 1.2 g/kg. It should be noted that the protein supplemented in Men-
denhall’s study, and the basis of his recommendations, was enriched with BCAA. Although
there have been no definitive studies comparing tolerability of standard amino acid mix-
tures to BCAA, it is possible that an individual patient with acute liver injury may tolerate
a larger quantity of protein if supplemented with BCAA supplementation. Thus, clinical
surveillance is important when increasing protein load in these patients.
Finally, the remainder of patients’ energy needs should be met with carbohydrates. As
discussed previously, insulin resistance is common in patients with cirrhosis, and this
intolerance is further exacerbated in the setting of acute injury. Therefore, providing
carbohydrates to the point of inducing metabolic aberrations is not advisable. Cirrhotics
may further benefit from complex carbohydrates to reduce insulin requirements. Complex
carbohydrates may also be advantageous in the setting of encephalopathy, as they tend
to decrease transit time and and lower colonic pH, both of which serve to decrease
ammonia absorption from the gastrointestinal tract.3
Nutritional Supplements
S-Adenosylmethionine
S-Adenosylmethionine (SAMe) is synthesized by the transfer of an adenosyl group from
ATP to the essential amino acid methionine. SAMe serves primarily as a methyl donor.
These SAMe-dependent methylations are essential for the biosynthesis of a variety of
cellular components including carnitine, phospholipids, proteins, DNA, and RNA, as well
as polyamines needed for cell regeneration.31,61 In addition, it serves as one source of
csyteine for glutathione production (Figure 58.5). Furthermore, it has been shown that
methionine metabolism is impaired in patients with liver disease and that the activity of
SAMe synthase is decreased in human cirrhotic livers.31,62,63
The administration of exogenous SAMe should be effective in liver disease. In baboons,
correction of ethanol-induced hepatic SAMe depletion with oral SAMe supplementation
resulted in a corresponding attenuation of ethanol-induced liver injury.32,64 Thus, supple-
mentation with SAMe dampens the depletion of hepatic glutathione (GSH) stores. Without
supplementation, depletion of GSH leads to inactivation of SAMe synthetase, which would
tend to further reduce GSH stores, thereby predisposing to hepatic injury.32 The studies
that have evaluated SAMe supplementation have demonstrated significant improvements
in subjective symptoms, serum markers of cholestasis, and hepatic GSH levels.32,65,66 More
recently, Mato et al. demonstrated that SAMe supplementation could improve survival or
delay time to transplantation compared to controls. These results demonstrated a positive
Methionine Phosphatidylcholine
ATP
Tetrahydrofolate Pi+PPi Phosphatidylethanolamine
S-Adenosyl-Methionine
Acceptor
Methyl-tetrahydrofolate
Methylated
acceptor
Homocysteine S-Adenosyl-homocysteine
Serine
Cystathionine
Glutathione Cysteine Cystine

FIGURE 58.5
SAMe synthase. S-Adenosyl-L-Methionine (SAMe) is formed in an irreversible reaction that transfers an adenosyl
group from methionine. SAMe is an important donor of methyl groups, and is active in the conversion of creatine
to creatinine and of phosphatidylethanolamine to phosphatidylcholine. SAMe is converted to S-adenosyl-ho-
mocysteine and then to homocysteine. Homocysteine can combine with serine to form csytathionine which can
ultimately be converted to glutathione. (Adapted from Kruszynska YT. In: Oxford Textbook of Clinical Hepatology,
2nd ed, Bircher J, Benhamou J, McIntyre N, Rizzetto M, Rodes J, Eds, Oxford University Press, Oxford, 1999, p.
257 and Lieber CS. In: Modern Nutrition in Health and Disease, 9th ed, Shils ME, Olson JA, Shike M, Ross AC,
Eds, Williams and Wilkins, Baltimore 1999, pg 1177.)
trend in favor of the supplemented group, but achieved significance only when patients
with advanced cirrhotic liver disease (Child C) patients were excluded.31,67
Supplementation with SAMe shows significant promise in the treatment of liver disease
and will undoubtedly be investigated with larger studies in the future.
Zinc
Zinc (Zn) is the most abundant intracellular trace element. It is involved in a multitude
of diverse catalytic, structural, and regulatory functions. Many physiologic functions
require zinc, including protein metabolism, normal immune functioning and wound heal-
ing, neurosensory function such as cognition and taste, and membrane stability.68,69
Hypozincemia is common in various types of liver disease.69 The deficiency is multifac-
torial and is believed to involve poor dietary intake and impaired intestinal absorption
(possibly due to a cytokine-induced intestinal metallothionein, which dampens zinc
absorption). Additionally, there is decreased affinity of albumin for zinc in cirrhotics, which
might influence bioavailability and lead to increased urinary losses of zinc. Finally,
increased cytokine or hormonal concentrations may lead to altered zinc metabolism.69
Zinc deficiency may play a role in increasing plasma ammonia levels. Zinc deficiency
was shown to decrease activity of glutamate dehydrogenase and ornithine transcarbam-
ylase (OTC), enzymes important in normal nitrogen metabolism (Figure 58.4). Urea syn-
thetic capacity is believed to be reduced in zinc-deficient patients due to reduced OTC
activity, as zinc acts as a cofactor in the activity of this enzyme. Zinc supplementation
speeds up the kinetics of nitrogen conversion from amino acids into urea in cirrhotics.11
Zinc deficiency also increases muscle glutamine synthetase and adenosine monophos-
phate deaminase, enzymes that increase ammonia production from aspartate.70
Although zinc deficiency may play a role in some of the altered taste sensations seen
in liver disease, it is unlikely to be a major cause of anorexia in liver disease. It is much
more likely that the anorexia seen in this disease is cytokine mediated.69 Conversely, zinc
deficiency, at least in part, does appear to play a role in immune dysfunction and perhaps
in delayed wound healing. The latter may occur through the effect of zinc on insulin-like
growth factor.69 In regard to protein synthesis, a recent study showed lower serum albumin
levels in children undergoing liver transplantation than in other transplant patients in
whom serum zinc levels were normal. This correlates with the findings by Bates and
McClain, which demonstrated improvement or normalization of serum transport proteins
in zinc-deficient patients on parenteral nutrition when supplemented with zinc.71,72
Selenium
There are at least eleven selenoproteins; the most well known class is the glutathione
peroxidases. These proteins are important participants in the body’s antioxidant defenses.
Selenium concentrations have been reported to be lower in patients with cirrhosis com-
pared to healthy controls. Selenium deficiency could therefore contribute to the morbidity
of cirrhosis. This deficiency could be easily addressed with supplementation. However, a
recent study by Burk et al. reported that, though plasma selenium is indeed depressed in
patients with cirrhosis, the changes noted in plasma selenoproteins of cirrhotics are not
the same as those found in selenium-deficient subjects without liver disease. Functionally,
these patients had an increase in the plasma gluatathione concentration, arguing against
a true selenium deficiency.73,74
Carnitine
Fatty acids are the preferred fuel for patients with cirrhosis. Since carnitine is essential for
the mitochondrial use of long-chain fatty acids for energy production, decreased avail-
ability of this quaternary amine may lead to energy deficiency in cirrhotics. Deficiency
can arise from poor dietary intake or disruption of carnitine biosynthesis, the last step
occurring almost exclusively in the liver. Measured levels of carnitine in patients with
chronic liver disease can be reduced or increased. The literature suggests that plasma and
tissue carnitine levels can be altered in patients with chronic liver disease, depending on
both its cause and progression.75,76
A recent study by Krahenbuhl and Reichen found that patients with chronic liver disease
are normally not carnitine deficient. They also concluded that carnitine metabolism can
be disturbed in subgroups of patients with liver disease. For example, patients with
alcoholic cirrhosis demonstrated increased plasma concentrations. Patients with primary
biliary cirrhosis were able to maintain normal plasma levels of carnitine, but demonstrated
increased renal excretion.76
Conclusion
It is clear that the relationship between nutrition and the liver is intricate and interdepen-
dent. Liver disease can result in anorexia, malabsorption, and abnormalities in nutrient
metabolism leading to a compromise in the nutritional status of the host. This impaired
nutritional status can impact negatively on immune function, compromise the ability of
the liver to limit the extent of hepatic insults, and retard an appropriate response to injury.
Nutritional deficiencies in patients with liver disease can range from subtle abnormalities
to advanced protein calorie malnutrition. Some degree of nutritional compromise is invari-
ably present. In treating patients with liver disease, the recognition and aggressive treat-
ment of these deficiencies is paramount. In milder forms of liver disease, this intervention
may take the form of nutrient and vitamin supplementation. In more advanced liver
disease, aggressive nutritional support, preferably in the form of enteral access and feed-
ing, may be the “controllable” factor that leads to an improved outcome.
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59
Nutrition and the Pancreas: Physiology and
Interventional Strategies
Mark T. De Meo
Introduction
The pancreas plays a major role in nutrient digestion as well as in the control of interme-
diate metabolism. Patients with pancreatic disease will likely have their nutritional homeo-
stasis compromised with both macronutrient and micronutrient deficiencies. This section
will explore the effects of a diseased pancreas on nutritional health and nutritional inter-
ventions that may be beneficial to patients with a diseased or inflamed pancreas.
Normal Pancreatic Function

The exocrine pancreas delivers two main products to the lumen of the duodenum during
the digestive process — digestive enzymes and bicarbonate. The digestive enzymes
secreted by the pancreas are key to the breakdown of ingested macronutrients (carbohy-
drates, proteins, and fats). Table 59.1 demonstrates the various enzymes and their func-
tions. The bicarbonate secreted in pancreatic juice neutralizes the acidic chyme entering
the duodenum from the stomach, and in so doing, increases duodenal pH. This alkaline
environment in the duodenum in turn allows for optimal functioning of the pancreatic
digestive enzymes.
Carbohydrate Digestion
Dietary carbohydrates are an important component of daily caloric intake in adults.
Ingested carbohydrates take three major forms: monosaccarides such as fructose; disaccha-
rides such as lactose and sucrose; and polysaccharides, of which starch is the predominant
form. Monosaccharides are absorbed directly by the normal small bowel mucosa. Disac-
charides require the action of enzymes called disaccharidases, found in the brush border
0-8493-2705-9/02/$0.00+$1.50
TABLE 59.1
Digestive Enzymes Secreted by the Pancreas
Amylase Splits alpha 1-4 glycosidic linkages of dietary polysaccharides
Trypsin Cleaves internal bonds with a preference for positively charged amino acids
Chymotrypsin Cleaves internal bonds with a preference for amino acids with aromatic side groups
Elastase Cleaves internal bonds with a preference for amino acids with aliphatic side chains
Carboxypeptidase A Cleaves carboxy-terminal amino acids
Carboxypeptidase B Cleaves carboxy-terminal amino acids with a preference for peptide bonds after arginine
or lysine residues
Lipase Preferentially hydrolyzes the 1 & 3 position of dietary triglycerides
Colipase Binds to the lipid/aqueous interface between the emulsion and the unstirred water layer
and also binds to lipase; this allows for the approximation of lipase to dietary
triglycerides and facilitates digestion
Phospholipase A2 Cleaves the phospholipid at the 2 position to yield a lysophosphoglyceride and a fatty
acid
Cholesterol esterase Cleaves esterfied fatty acid from cholesterol moiety
From Lowe, M.E. In Physiology of the Gastrointestinal Tract, 3rd ed., Johnson, L.R. et al., Eds., Raven Press, New
York, 1994, p. 1531, with permission.
of mucosal cells lining the small bowel. The disaccharidases break down these small
carbohydrates into their component sugars prior to absorption. Starches are much larger
molecules of repeating glucose molecules joined by either a C1-4 or C1-6 linkage (Figure
59.1). Starches require digestion prior to absorption.
Digestion of starch begins with the release of salivary amylase in the mouth. However,
salivary amylase becomes neutralized quickly by gastric acid. Starch then passes to the
duodenum where α-amylase, secreted by the pancreas, continues the digestive process.
1-4 linkage
amylase
+
amylose maltotriose maltose
1-6 linkage
amylase
amylopectin limit dextrans

Na Monosaccharide
Disaccharide
brush border hydrolases
OR
Enterocyte Na Glucose
Enterocyte
FIGURE 59.1
Mechanism of monosaccharide absorption. Monosaccharides can be absorbed directly by the small bowel
mucosa. Disaccharides are futher metabolized by brush border disaccharidases. Polysaccharides are cleaved by
amylase at the 1-4 but not the 1-6 linkages forming oligosaccharides. These oligosaccharides are cleaved by
brush border enzymes to their constituent monosaccharides.
Nutrition and the Pancreas: Physiology and Interventional Strategies 1241
Pancreatic amylase cleaves the 1-4 glucose linkages but not the 1-6 linkages or the 1-4
linkages juxtaposed to the 1-6 links. This hydrolysis results in the formation of large
oligosaccharides, with an average chain length of about eight glucose units with one or
more 1-6 linkages. These oligosaccharides are hydrolyzed by intestinal brush border
enzymes into their constituent monosaccharides. The resultant monosaccharides are trans-
ported into the mucosal epithelial cell.1,2
Protein Digestion
Protein digestion begins in the stomach with the nonspecific actions of pepsin and hydro-
chloric acid. Enzymes secreted from the pancreas also play a major role in protein diges-
tion. These enzymes are released in the form of zymogens or inactivated enzymes.
Trypsinogen is activated by enterokinase, which is released from the intestinal mucosa.
The active enzyme, trypsin, then activates the proenzyme forms of chymotrypsin, elastase,
and carboxypeptidase A and B. Trypsin, chymotrypsin, and elastase are called endopep-
tidases, as they cleave internal bonds. Interluminal digestion of protein results in the
generation of free amino acids and oligopeptides. Oligopeptides are further hydrolyzed
by the membrane-bound oligopeptidases of the enterocyte brush border.3
Lipid Digestion
Lipid digestion begins in the oral cavity with the secretion of lingual lipase and the
mechanical effects of mastication. In the stomach, gastric lipase is released and mixes with
lingual lipase. In addition, gastric contractions cause a mechanical grinding of the ingested
fat, resulting in the formation of an emulsion. An emulsion is a suspension of enzymatically
partially digested and mechanically disrupted fat droplets in liquid. The emulsion acquires
a coating comprised of phospholipids, bile acids, and triglycerides which serves to stabilize
the fat globule. This stabilized emulsion ultimately passes into the duodenum.
Pancreatic lipase, the principal enzyme of triglyceride digestion, hydrolyzes ester bonds
at the 1 and 3 positions of the glycerol moiety. However, in the presence of bile acids, this
enzymatic process is inefficient. Another enzyme secreted by the pancreas, colipase, avidly
binds to the triglyceride/aqueous interface of the emulsion and also has a binding site
for lipase. Colipase thus ensures the adhesion of lipase to the lipid droplet and increases
the efficiency of the latter enzyme in the digestion of triglycerides. Phospholipase A2 is
also secreted by the pancreas and acts upon ingested phospholipids to yield a fatty acid
and a lysophosphatidylcholine (Figure 59.2). Finally, cholesterol esterase hydrolyzes an
esterafied fatty acid from the parent cholesterol molecule.
Once hydrolyzed, lipid products have to traverse the unstirred water layer of the gut
prior to being absorbed by the mucosal absorptive cell. However, since fat is not water
soluble, fat digestion products have difficulty crossing this water layer. Bile acids, secreted
by the liver, greatly facilitate this diffusion. Bile acids are effective because they have a
hydrophilic (water-soluble) end and one hydrophobic or lipophilic end (water-insoluble
or, conversely, lipid-soluble). These bile acids, when secreted in sufficient quantity, form
micelles, which are small spheres with an outward hydrophilic projection and an inner
lipophilic core. The products of fat digestion pass into the fat-soluble core while the outer
layer remains soluble in the unstirred water layer. This lipid-rich conduit is able to traverse
the unstirred water layer and bring the inner lipid core into proximity with the mucosal
absorptive cell membrane, which is largely comprised of lipids. Once in contact with the
lipid membrane, the micelle core lipids diffuse into the endothelial absorptive cell. This
O
CH2 O C
O
CH O C
O
CH2 O P O CH2 N(CH3)3
O
Phospholipase A2
O
CH2 O C
O
CH O H + HO C
O
CH2 O P O CH2 N(CH3)3
O
FIGURE 59.2
Phospholipase A2 action. Phospholipase A2 hydrolyzes the phospholipid at position 2 to yield a fatty acid, and a
lysophospatidylcholine and a fatty acid. (Adapted from Linscheer WG, Vergroesen AJ. In: Modern Nutrition in
Health and Disease 8th ed, Shils ME, Olson JA, Shike M, Ross AC, Eds, Williams and Wilkins, Baltimore, 1999, pg. 47.)
“shuttling of lipids” from the lumen, where digestion takes place, to the absorptive
enterocyte membrane, greatly facilitates lipid absorption.4,5
Nutritional Implications and Ramifications in Pancreatic Disease

The nutritional status of patients with pancreatitis is in part dependent on the duration
of the disease, the severity of the acute exacerbation, and the underlying etiology of the
pancreatitis.
The two most common etiologies of acute pancreatitis in the Western world are alcohol
and biliary tract disease. The nutritional status of the patient at the time of acute episode
may impact on the clinical course. In a recent study of 99 consecutive patients with acute
pancreatitis, 64% of whom had alcohol as an etiology of their disease, only 15% were
considered underweight (BMI<19) according to their body mass index (BMI) (weight in
kg/height in m2).6 Obesity as opposed to malnutrition appears to be a risk factor for severe
disease, particularly in alcoholics.6,7 Still, a severe acute episode could lead to protracted
inability to take nutrition by mouth, and relative hypermetabolism.8 This can lead to
depletion of nutritional reserves and, depending on the patient’s nutritional status prior
to the acute event, may predispose the patient to infection and compromise his ability to
survive the acute episode. Thus, although obesity may increase the severity of the pre-
senting episode, it is unclear if a patient whose nutritional reserves are compromised will
have a more complicated hospital course.
Alternately, chronic pancreatic patients are generally characterized by an asthenic body

type and a low BMI. The causes for a compromised nutritional status are multifactorial
but mainly include decreased food intake, maldigestion, and malabsorption.
Decreased Food Intake

Many patients with chronic pancreatitis experience abdominal pain, frequently with
accompanying nausea and anorexia. As these symptoms are usually meal related, they
often severely limit oral intake.
Maldigestion
Decreases in enzyme and bicarbonate secretion parallel progressive injury to the pancreas.
Preliminary studies in patients with pancreatic insufficiency suggest that 5 to 10% of
normal postprandial enzyme output by the pancreas is sufficient to maintain normal
digestion.9,10 Maldigestion does not proceed equally among the three macronutrients.
Fat maldigestion is invariably the first to become clinically manifest as nonpancreatic
mechanisms do not perform well in lipid digestion. However, there is some compensation
for fat digestion, such as to the action of small amounts of lingual or gastric lipases.
Given these compensatory mechanisms, an estimated 50% of dietary fat is absorbed.11
The synthesis and secretion of pancreatic lipase is also more impaired in the damaged
pancreas compared to other enzymes. Additionally, lipase is much more sensitive to
inactivation in an acidic milieu. Thus, a corresponding decrease in the production of
bicarbonate by the damaged gland results in a greater deactivation of lipase. Finally,
lipase, once secreted, is more rapidly degraded in the intestinal lumen than the other
pancreatic enzymes.
When fat malabsorption is present, the standard for the diagnosis is the finding of greater
than 7 g of fat per day in stool collected over a three-day period. Prior to obtaining the
specimen, the patient should consume 100 g fat/day for three days and continue on this
diet during the three days of collection.12
Malabsorption
Malabsorption occurs secondary to the effects of chronic pancreatitis on micelle formation.
The failure of the damaged pancreas to secrete sufficient bicarbonate to neutralize the
stomach’s acidic chyme causes precipitation of bile acids. This impairs micelle formation,
which leads to decreased solubility and absorption of ingested fat. A diminished secretion
of pancreatic enzymes lessens the bactericidal effect of these enzymes and can result in
bacterial overgrowth. The bacteria deconjugate bile acids, which leads to impaired micelle
formation, again resulting in malabsorption. Finally, associated complications such as
diabetes and cirrhosis can also impair absorption. The former promotes bacterial over-
growth and the latter impairs synthesis of bile acids. Additionally, when diabetes compli-
cates pancreatitis, the nutrient wasting and relatively high glucagon-to-insulin ratio
promote malnutrition.
Many patients with chronic pancreatitis have low serum albumin and cholesterol. The
latter is in part due to a malabsorption of bile acids which causes increased demand to
form bile acids from cholesterol. Other contributing factors include a decrease in the
consumption of cholesterol-containing food and malabsorption of luminal cholesterol.
Blood fatty acid profiles are also abnormal and can lead to several of the abnormalities
that are seen in this disease. Specifically, the blood levels of linoleic acid and arachidonic
acid are elevated, while those of eicosapentanoic acid and docosahexanoic acid are
increased. There is also a compensatory increase in palmitoleic acid. Polyunsaturated fatty
acids play an important role in vascular endothelial cells and platelets in coagulation and
thrombus formation. Thus, abnormalities in the levels of these lipids may impact on
hemostasis. Finally, the serum concentration of fat-soluble vitamins is low due to poor
intake and malabsorption.13
A recent study found a slightly greater metabolic rate in patients with chronic pancreatitis
compared to a malnourished control group, even when corrected for fat-free mass. There
was also a difference within the chronic pancreatis group between those who were normally
nourished and those who were undernourished, with the latter group being more “hyper-
catabolic.” This increased resting energy expenditure was seen in over 60% of the stable
population with chronic pancreatitis. The authors concluded that the differences were not
readily explained by infection, alcohol use, or nicotine use. They suggested that this unex-
plained metabolic status might contribute to the malnutrition seen in this disease.14
Patients with pancreatic cancer are at particularly high risk for nutritional problems.
They have the highest incidence of weight loss of any group of patients with cancer, with
approximately 80 to 90% losing weight during the course of their illness.15,16 The devel-
opment of cachexia and weight loss, which are poor prognostic variables in this disease,16
is due in part to damage to an organ that is crucial to nutrient digestion as well as
constitutional symptoms such as nausea, depression, and anorexia associated with advanc-
ing disease. Cytokines released by the tumor or by host cells in response to the tumor
lead to anorexia and metabolic dysregulation.
Nutritional Intervention in Pancreatic Disease

Nutritional Intervention in Acute Pancreatitis
Nutritional intervention during an acute episode of pancreatitis is largely determined by
the severity of the initial inflammatory event, the estimated period of time that the patient
will remain without adequate oral intake, and the patient’s underlying nutritional status.
The inflammatory response evoked during an acute episode of pancreatitis is largely
mediated through the release of cytokines and counterregulatory hormones. This response
is teleologically advantageous to the host. Collectively, the acute phase response serves
to clear bacteria from the bloodstream, sequester potentially virulent substances, and limit
“innocent bystander” oxidative damage. Cytokines also stimulate immune cells and signal
them to the appropriate point of engagement, regulating the inflammatory response up
or down as needed. This response has been adapted over time to alert, enforce, and aid
the immune response as well as limit damage to the host in a response directed against
an offending agent. This response, however, can deplete the body’s nutrient resources.
The greater the insult, the greater the use of endogenous substrate. In spite of exogenous
attempts to provide nutritional resources, “autocannibalism” continues, largely unabated.
It is therefore plausible, though unproven, that in the setting of poor endogenous
resources, a prolonged inflammatory state can overwhelm the body’s ability to bring forth
an inflammatory response and can contribute to the demise of the host. Unfortunately,
there is no simple gauge with which to assess the body’s ability to respond appropriately
to the challenge.
Ranson Criteria APACHE-II

At admission Temperature (rectal)
Age >55 Mean arterial pressure
WBC count >16,000/mm3 Heart rate
Glucose > 200 mg/dl Respiratory rate
Lactate dehydrogenase (LDH) > 350 IU/L Oxygenation
Aspartate transaminase (AST) > 250 U/L Arterial pH
Serum sodium
During initial 48 hours Serum potassium
Hematocrit decrease of > 10 mg/dl Serum creatinine
Blood urea nitrogen (BUN) increase of > 5 mg/dl Hematocrit
Calcium < 8 mg/dl WBC count
PaO2 < 60 mm Hg Glasgow coma score
Base deficit > 4 mEq/L
Fluid sequestration > 6 L Age points
Chronic health points
FIGURE 59.3
Ranson criteria and APACHE II severity of pancreatitis. Ranson criteria and the APACHE II severity of disease
classification system are two scoring systems used to judge the severity of acute pancreatitis. In the APACHE
II system, points were given for each of twelve variables (in box) based on the severity of those variables. Points
were also awarded for increasing age, a history of organ dysfunction, immunocompetence, and surgical inter-
ventions. Three or more Ranson criteria or eight or more APACHE II points are considered significant disease.
The inflammatory challenge also brings with it a state of substrate intolerance, partic-
ularly to carbohydrates and less so to lipids, which makes imprudent use of nutritional
support potentially harmful. Additionally, visceral proteins such as albumin, which often
are used as nutritional parameters in epidemiological studies, are affected by the inflam-
matory response and lose value as predictors of substrate exhaustion. Perhaps in the future
we will be guided by readily available tests of immune function that will allow us to
discern when the immune response is faltering from lack of available substrate. However,
currently, we must estimate the severity and duration of the inflammatory response as
well as the underlying nutritional status of the host to determine whether nutritional
intervention will be of benefit.
Approximately 80% of patients admitted to the hospital with acute pancreatitis have
mild disease. These patients are expected to be able to ingest kcalories orally in five to
seven days. From a nutritional perspective, unless there is severe underlying malnutrition
antedating the episode of pancreatitis, there is little need to intervene.
Severe pancreatitis occurs in about 20% of patients, and with prolonged absence of oral
intake nutritional intervention may be necessary. The diagnosis of severe pancreatitis is
suspected on the basis of clinical and laboratory evaluations and can be modified by
imaging criteria. Several criteria, including Ranson and APACHE II scores, have been
established and validated as indicators of severity in acute pancreatitis17-19 (Figure 59.3).
There is one reason for providing nutrition in acute pancreatitis accompanied by a
mitigating circumstance. Nutrition is provided to support the underlying nutritional status
of the host while the patient is beseiged by mediators of the inflammatory process. If there
is a deficiency in endogenous substrate, artificial nutrition will furnish the needed building
blocks to survive the insult. The mitigating circumstance is whether the treatment itself
does more harm, as the therapy may stimulate the inflamed pancreas and aggravate the
underlying problem. Additionally, metabolic aberrations potentially caused by the therapy
may complicate the clinical picture.
Several studies in animals (with and without pancreatitis), healthy humans, and humans
with stable pancreatic fistulas demonstrate little convincing evidence that parenteral nutri-
tion or enteral feeding delivered to the jejunum produce significant pancreatic stimulation.
The more convincing data come from human trials in patients with pancreatitis, in whom
there is no increased rate of pancreas-related complications using either modality.20,21
Unfortunately, only a few randomized controlled studies exist on the benefit of nutri-
tional intervention. In a study by Sax et al., patients with mild pancreatitis (average Ranson
criteria 1 to 2) were randomized to receive either standard hydration or parenteral nutri-
tion.22 The authors found no advantage to using parenteral nutrition with respect to
hospital days or number of pancreatic complications. The authors did find a greater risk
of line infections in this group than in patients with other diseases requiring parenteral
nutrition who were cared for concurrently using the same central line care. The importance
of parenteral nutrition in this study may have been understated, as all the patients had
mild disease.
Another study by Kalfarentzos et al. examined parenteral nutrition in patients with
more severe disease (Ranson criteria 3 or greater). The study was retrospective, and the
groups were divided on the basis of whether patients began parenteral nutrition within
the first 72 hours. The authors stated that the initiation of parenteral nutrition was based
on clinical grounds, but it is not clear what factors initiated the use of TPN and why the
authors chose 72 hours as a reference point. In spite of these potential biases, the authors
showed a statistically significant reduction in local complications and mortality. The
authors also reconfirmed the apparent increased risk of catheter-related complications in
this group of patients (again, compared to concurrent, nonpancreatic disease patients who
were receiving parenteral nutrition).23 Thus, the interpretation of this one prospective
study and several retrospective studies is that parenteral nutrition does not worsen pan-
creatitis and may be of benefit in severe disease, though the data are not convincing.
McClave et al. compared enteral jejunal feedings to parenteral nutrition in patients with
mild pancreatitis, generally of alcoholic etiology. The authors found that the enteral route
was safe and there were no differences in clinical or biochemical resolution of pancreatitis
in their study patients. However, the cost of nutritional intervention in the enteral group
was significantly lower than the parenteral group.24 Kalfarentzos and colleagues also
performed a randomized prospective trial of enteral versus parenteral feeding in severe
acute pancreatitis (APACHE II score 8 to 15). They not only showed that enteral feeding
was safe, they also showed that these patients had a significantly lower septic complication
rate than the parenteral nutrition group. Other morbidities, including the incidence of
infectious pancreatic or peripancreatic necrosis, were also lower in the enteral nutrition
group but did not reach statistical significance, probably because of the small numbers of
patients in the groups.25
Jejunal feeding in patients with pancreatitis is not only safe but also as effective as
parenteral nutrition in supporting the patient. An additional question is whether the
enteral route, by stimulating trophic factors which can potentially maintain the integrity
of the gut as a barrier against bacterial translocation, is beneficial to patient care in ways
that are not realized with parenteral nutrition. The issue of translocation in other predis-
posing states such as trauma and sepsis has been more readily proven in animal models
than in humans.26,27 The proof that this process is clinically significant in humans is less
established.28 The causative bacteria in infected pancreatic necrosis are often of gut origin,
and translocation of bacteria and/or endotoxin can contribute to the inflammatory pro-
cess.29-31 Enteral nutrition in pancreatitis appears to be safe from the available clinical
studies, and it offers cost savings and fewer septic complications. It should be considered
strongly as the treatment of choice in these patients. If it also decreases the incidence of
infected pancreatic necrosis, which is associated with a significantly increased morbidity
and mortality, it moves out of the realm of purely nutritional support and into the realm
of a therapeutic intervention.
A recent study examined the immunoinflammatory response and its relationship to
nutritional outcome with enteral feeding. In addition to finding that enteral nutrition was
associated with decreases in sepsis and multiorgan failure (though not significant), the
authors reported significant decreases in the APACHE II scores for enterally fed patients
(11 to 2) versus parenterally fed patients (12 to 10). They also reported moderate decreases
in c-reactive protein (CRP). Parenterally fed patients had significant increases in IgM
antiendotoxin response, while these levels remained unchanged in enterally fed patients.
These data support enteral feeding as an intervention that will improve disease severity
and clinical outcome by modifying the acute phase response. Moreover, these findings
lend support to the concept that enteral feeding maintains the integrity of the gut as a
barrier against translocation, which can be a contributor to the inflammatory response
seen in this disease.32
As more evidence shows that enteral nutrition is safe and beneficial, it should begin to
supplant parenteral nutrition in the management of pancreatitis. In reality, although these
studies are promising, they are still small in number and the practice of enteral nutrition
is not widespread.
In severe acute disease, the predominant treatment in most hospitals and medical centers
is parenteral nutrition. Knowledge of the appropriate use and the individual components
of the parenteral solution becomes a mainstay in treating patients with severe disease.
Parenteral Nutrition Issues

Which Patients are Candidates for Parenteral Nutrition
Candidates are those who have severe disease (as assessed by severity scores), those who
are malnourished upon admission to the hospital, and those who have complications of
their disease.
Delivery Volume; Total Kcalories; Individual Macronutrients, Micronutrients, and other

Additives
Fluid volume: pancreatitis has been compared to an internal burn, with tremendous
shifts in fluid. Recent data suggest that the level of hemoconcentration seen at
presentation may have prognostic significance in acute pancreatitis. This not only
suggests that relative hypovolemia may contribute to pancreatic damage, but
also underscores the importance of fluid resuscitation. However, since renal,
lung, and cardiac dysfunction can accompany severe pancreatic insult, vigorous
or inadequate use of fluids can be detrimental to the patient. Though fluid
resuscitation is important, total volume replacement is not an essential goal of
parenteral nutrition in a severe, acute setting. At our institution, the volume of
solution is based on providing 20 to 35 cc of fluid per kilogram estimated dry
weight of the patient. Additionally, adjustments are made for the presence of
heart or renal failure, or conversely for the presence of increased fluid loss or
sequestration. Usually only one liter of the solution is infused the first day to
determine the patient’s metabolic response to the infused nutrients. Care should
be taken to ensure against metabolic aberrations. Additional volume for resus-
citation can be delivered through peripheral intravenous fluids.
Kcalories: when estimating the total kcalories provided to the patient, consider that
a significant percentage of patients with pancreatitis are hypermetabolic. How-
ever, the same factor, the inflammatory response, that increases the metabolic
rate in these patients also introduces an element of substrate intolerance. This
intolerance, which is mainly to carbohydrates but is also to a lesser degree to
lipids, is not specific to pancreatitis but is a feature of any significant inflamma-
tory response. Similarly, if renal failure or encephalopathy are present, the pro-
vision of protein also needs careful monitoring. Additionally, the

hypermetabolism seen with an acute insult should be considered dynamic and
can decrease or increase during the hospitalization, roughly paralleling the pa-
tient’s clinical course.
The most reliable indicator of kcaloric needs in the hospital setting is indirect
calorimetry. If this is not available, then formula equations can be used to
estimate needs, although formula equations are less reliable. These equations
were developed in healthy individuals and are secondarily extrapolated to the
severely ill. There may be a significant under- or overestimation of metabolic
needs in the individual patient. The first tenet in treating these patients is to do
no harm. Therefore, although targets for estimating needs may be logically
derived or measured, pushing macronutrient delivery to hyperglycemia or hy-
perlipidemia, especially in the setting of pancreatitis, is clearly not in the pa-
tient’s best interest.
Protein: though amino acids may be the most important macronutrient provided,
there is little data to support an optimal amount. In studies of parenteral nutrition
in pancreatitis, the protein provided ranged from 1 to 2.5 g/kg.22-25,32 In the setting
of renal impairment or encephalopathy, the protein load needs to be conservative
and monitored closely. Conversely, if protein losses seem very high, protein
should move toward the higher end of the range provided there are no intoler-
ances. Initiate a more conservative amount of protein and advance only after the
patient demonstrates stability to the initial protein load.
It is controversial whether protein kcalories should be considered as part of
total kcalories. Parenterally-provided protein is not intended to be a kcaloric
source; yet there is partial metabolism. Thus, including protein in the kcaloric
goal will likely result in an underestimation of kcalories, whereas the opposite
will result if protein is calculated separately. However, as the kcaloric content of
the provided protein is usually modest and since more harm, in the

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HANDBOOK

Elaine B. Feldman, M.D.

William P. Flatt, Ph.D.

Sachiko T. St. Jeor, Ph.D., R.D.

Library of Congress Cataloging-in-Publication Data

QP141 .C774 2001

Visit the CRC Press Web site at www.crcpress.com

© 2002 by CRC Press LLC

No claim to original U.S. Government works

nutrition-related illnesses. In addition, the assessment of human nutritional status is

Carolyn D. Berdanier, Ph.D., is Professor Emerita of Nutrition at the University of Georgia

Kelly Adams Carolyn D. Berdanier

Maria Alexander Michael Bergeron

Paule Barbeau Amy Binkoski

Susan Bowerman Gail A. Cresci

Ritva Butrum Michael P. Doyle

Leh Chii Chwang Leon Ellenbogen

Stacie Coval Elaine B. Feldman

Valerie Fishell Bernard Gutin

Gary D. Foster James O. Hill

Eileen Kennedy Charles S. Lieber

Connie Mobley Allen M. Perelson

Richard S. Rivlin Sachiko T. St. Jeor

Helen Smiciklas-Wright David G. Weismiller

Christine L. Williams Guixiang Zhao

1 Food Constituents ................................................................................................3

2 Metabolic Maps ..................................................................................................99

Figure 2.9 Catabolism of threonine showing its relationship to that of serine

3 Tables of Clinical Significance ....................................................................... 121

Part III Comparative Nutrition

4 Animal Needs and Uses (Comparative Nutrition) ....................................... 163

Part IV Human Nutrient Needs in the Life Cycle

5 Nutrition During Pregnancy and Lactation .................................................. 175

Table 5.2 Nutritional Care at Preconception, Prenatal, and Postnatal

6 Feeding the Premature Infant ......................................................................... 203

References .......................................................................................................... 216

7 Feeding the Term Infant .................................................................................. 219

8 Nutrition for Healthy Children and Adolescents Ages 2 to

Table 8.18 Research Concerning Exposure to Food and Preschool Children’s

9 The Health-Promoting Diet throughout Life: Adults .................................. 299

10 Nutrition in the Later Years ............................................................................ 319

Part V Human Nutritional Status Assessment

11 Dietary Guidelines, Food Guidance, and Diet Quality .............................. 339

Summary ............................................................................................................ 351

12 Dietary Guidelines in Three Regions of the World .................................... 353

13 Healthy People — Goals and Interpretations............................................... 373

14 Food Labeling: Foods and Dietary Supplements ......................................... 393

Nutrient Content Claims Allowed for Foods and Dietary

15 Nutrition Monitoring in the United States................................................... 407

16 Clinical Nutrition Studies: Unique Applications ........................................ 435

17 Nutrition Monitoring and Research Studies: Observational

18 Nutrition Monitoring and Research Studies: Nutrition Screening

Figure 18.1 Determine your nutritional health ............................................ 465

19 Dietary Intake Assessment: Methods for Adults ......................................... 477

20 Validity and Reliability of Dietary Assessment in School-Age

21 Methods and Tools for Dietary Intake Assessment in Individuals vs.

22 The Use of Food Frequency Questionnaires in Minority

23 Computerized Nutrient Analysis Systems .................................................... 559

Table 23.1 Comparison of Features in Five Selected Programs

24 Nutrient Data Analysis Techniques and Strategies ..................................... 567

25 Medical Nutritional Evaluation...................................................................... 581

26 Assessment of Lipids and Lipoproteins ........................................................ 591

27 Genetics of Energy and Nutrient Intake ....................................................... 603