Modern Nutrition in Health and Disease 9th edition (January 1999): by Maurice E. Shils (Editor), James A. Olson (Editor), Moshe Shike (Editor), A. Catherine
Ross (Editor) By Lippincott, Williams & Wilkins
By OkDoKeY
Modern Nutrition in Health and Disease
Contents
Editors
Preface
Acknowledgments
Contributors
PART I. SPECIFIC DIETARY COMPONENTS
Section A. Major Dietary Constituents and Energy Needs
Chapter 1. Defining the Essentiality of Nutrients
ALFRED E. HARPER
Chapter 2. Proteins and Amino Acids
DWIGHT E. MATTHEWS
Chapter 3. Carbohydrates
ROY J. LEVIN
Chapter 4. Lipids, Sterols, and Their Metabolites
PETER J.H. JONES AND STANLEY KUBOW
Chapter 5. Energy Needs: Assessment and Requirements in Humans
ERIC T. POEHLMAN AND EDWARD S. HORTON
Section B. Minerals
Chapter 6. Electrolytes, Water, and Acid-Base Balance
MAN S. OH AND JAIME URIBARRI
Chapter 7. Calcium
CONNIE M. WEAVER AND ROBERT P. HEANEY
Chapter 8. Phosphorus
JAMES P. KNOCHEL
Chapter 9. Magnesium
MAURICE E. SHILS
Chapter 10. Iron in Medicine and Nutrition

JAMES E. LEKLEM
Chapter 25. Pantothenic Acid
NORA PLESOFSKY-VIG
Chapter 26. Folic Acid
VICTOR HERBERT
Chapter 27. Vitamin B
12
“Cobalamin”
DONALD G. WEIR AND JOHN M. SCOTT
Chapter 28. Biotin
DONALD M. MOCK
Chapter 29. Vitamin C
ROBERT A. JACOB
Section D. Signs Of Clinical Deficiencies
Chapter 30. Clinical Manifestations of Human Vitamin and Mineral Disorders: A Resumé
DONALD S. McLAREN
Section E. Organic Compounds with Nutritional Relevance
Chapter 31. Carnitine
CHARLES J. REBOUCHE
Chapter 32. Choline and Phosphatidylcholine
STEVEN H. ZEISEL
Chapter 33. Carotenoids
JAMES ALLEN OLSON
Chapter 34. Homocysteine, Cysteine, and Taurine
MARTHA H. STIPANUK
Chapter 35. Glutamine and Arginine
STEVE F. ABCOUWER AND WILEY W. SOUBA
PART II. NUTRITION IN INTEGRATED BIOLOGIC SYSTEMS
Section A. Tutorials in Physiologic Regulation
Chapter 36. Nutritional Regulation of Gene Expression

WILLIAM J. McGANITY, EARL B. DAWSON, AND JAMES W. VAN HOOK
Chapter 51. Nutritional Requirements During Infancy
WILLIAM C. HEIRD
Chapter 52. Diet, Nutrition, and Adolescence
FELIX P. HEALD AND ELIZABETH J. GONG
Chapter 53. Nutrition in the Elderly
LYNNE M. AUSMAN AND ROBERT M. RUSSELL
PART III. DIETARY AND NUTRITIONAL ASSESSMENT OF THE INDIVIDUAL
Chapter 54. Clinical Nutrition Assessment of Infants and Children
VIRGINIA A. STALLINGS AND ELLEN B. FUNG
Chapter 55. Clinical and Functional Assessment of Adults
JEANETTE M. NEWTON AND CHARLES H. HALSTED
Chapter 56. Nutritional Assessment of Malnutrition by Anthropometric Methods
STEVEN B. HEYMSFIELD, RICHARD N. BAUMGARTNER, AND SHEAU-FANG PAN
Chapter 57. Laboratory Tests for Assessing Nutritional Status
NANCY W. ALCOCK
Chapter 58. Dietary Assessment
JOHANNA DWYER
PART IV. PREVENTION AND MANAGEMENT OF DISEASE
Section A. Pediatric and Adolescent Disorders
Chapter 59. Protein-Energy Malnutrition
BENJAMIN TORUN AND FRANCISCO CHEW
Chapter 60. Malnutrition among Children in the United States: The Impact of Poverty
ROBERT KARP
Chapter 61. Nutritional Support of Inherited Metabolic Disease
LOUIS J. ELSAS II AND PHYLLIS B. ACOSTA
Chapter 62. Inherited Metabolic Disease: Defects of b-Oxidation
JERRY VOCKLEY
Chapter 63. Childhood Obesity
WILLIAM H. DIETZ

CHARLES HUGHES AND PATRICIA KOSTKA
Section D. Prevention and Management of Cancer
Chapter 78. Molecular Basis of Human Neoplasia
PAUL D. SAVAGE
Chapter 79. Diet, Nutrition, and the Prevention of Cancer
WALTER C. WILLETT
Chapter 80. Carcinogens in Foods
TAKASHI SUGIMURA AND KEIJI WAKABAYASHI
Chapter 81. Chemoprevention of Cancer
DIANE F. BIRT, JAMES D. SHULL, AND ANN L. YAKTINE
Chapter 82. Nutritional Support of the Cancer Patient
MAURICE E. SHILS AND MOSHE SHIKE
Section E. Prevention and Management of Skeletal and Joint Disorders
Chapter 83. Bone Biology in Health and Disease
ROBERT P. HEANEY
Chapter 84. Nutrition and Diet in Rheumatic Diseases
CLAUDIO GALPERIN, BRUCE J. GERMAN, AND M. ERIC GERSHWIN
Chapter 85. Osteoporosis
ELIZABETH A. KRALL AND BESS DAWSON-HUGHES
Section F. Other Systemic Diseases and Disorders
Chapter 86. Nutritional Management of Diabetes Mellitus
JAMES W. ANDERSON
Chapter 87. Obesity
F. XAVIER PI-SUNYER
Chapter 88. Nutritional Aspects of Hematologic Disorders
ISRAEL CHANARIN
Chapter 89. Renal Disorders and Nutrition
JOEL D. KOPPLE
Chapter 90. Nutrition, Respiratory Function, and Disease
MARGARET M. JOHNSON, ROBERT CHIN, JR., AND EDWARD F. HAPONIK

Chapter 104. Dietary Goals and Guidelines: National and International Perspectives
A. STEWART TRUSWELL
Chapter 105. Nutrition Monitoring in the United States
MARIE FANELLI KUCZMARSKI AND ROBERT J. KUCZMARSKI
Chapter 106. Nutritional Implications of Vegetarian Diets
PATRICIA K. JOHNSTON
Chapter 107. International Priorities for Clinical and Therapeutic Nutrition in the Context of Public Health Realities
NOEL W. SOLOMONS
Chapter 108. Social and Cultural Influences on Food Consumption and Nutritional Status
SARA A. QUANDT
Chapter 109. Fads, Frauds, and Quackery
STEPHEN BARRETT AND VICTOR D. HERBERT
Chapter 110. Alternative Nutrition Therapies
VICTOR D. HERBERT AND STEPHEN BARRETT
PART VI. ADEQUACY, SAFETY, AND OVERSIGHT OF THE FOOD SUPPLY
Chapter 111. Food Processing: Nutrition, Safety, and Quality Balances
ALEXA W. WILLIAMS AND JOHN W. ERDMAN, JR.
Chapter 112. Designing Functional Foods
WAYNE R. BIDLACK AND WEI WANG
Chapter 113. Food Additives, Contaminants, and Natural Toxins
JOHN N. HATHCOCK AND JEANNE I. RADER
Chapter 114. Risk Assessment of Environmental Chemicals in Food
A. M. FAN AND R. S. TOMAR
Chapter 115. Food Labeling, Health Claims, and Dietary Supplement Legislation
ALLAN L. FORBES AND STEPHEN H. McNAMARA
PART VII. APPENDIX
ABBY S. BLOCH AND MAURICE E. SHILS
Appendix Contents
Section I. Conversion Factors, Weights and Measures, and Metabolic Water Formation
Section II. National and International Recommended Dietary Reference Values

Department of Internal Medicine
University of Kentucky
Chief, Endocrine
Metabolic Section
VA Medical Center
Lexington, Kentucky
AFTAB A. ANSARI, Ph.D.
Department of Pathology
Emory University School of Medicine
Atlanta, Georgia
LYNNE M. AUSMAN, D.Sc.
Scientist
Jean Mayer USDA Human Nutrition Research Center on Aging
Tufts University
Boston, Massachusetts
Professor, School of Nutrition Science and Policy
Tufts University
Medford, Massachusetts
STEPHEN BARRETT, M.D.
Consumer Advocate
Member, Board of Directors
National Council Against Health Fraud, Inc.
Allentown, Pennsylvania
RICHARD BAUMGARTNER, Ph.D.
Associate Professor
Division of Epidemiology
Department of Medicine
University of New Mexico
Albuquerque, New Mexico
GEORGE H. BEATON, Ph.D.

New York City, New York
IRWIN G. BRODSKY, M.D., M.P.H.
Assistant Professor of Medicine and Nutrition
Department of Medicine
Endocrinology and Metabolism Section
University of Illinois at Chicago
Chicago, Illinois
REX O. BROWN, Pharm.D., BCNSP, FACN
Professor
Department of Clinical Pharmacy
University of Tennessee
Nutrition Support Pharmacist
Department of Pharmacy
Regional Medical Center at Memphis
University of Tennessee Medical Center
Memphis, Tennessee
RAYMOND F. BURK, M.D.
Professor of Medicine
Director
Division of Gastroenterology
Department of Medicine
Vanderbilt University
Nashville, Tennessee
DANIEL CERVANTES-LAUREAN, M.D.
Pulmonary-Critical Care Medicine Branch
National Heart, Lung, and Blood Institute
National Institutes of Health
Bethesda, Maryland
ISRAEL CHANARIN, M.D., F.R.C.Path.
Formerly, Chief

Associate Professor
Chief
Pediatric Surgical Critical Care
College of Physicians and Surgeons of Columbia University
Harlem Hospital Center
New York City, New York
ROBERT J. COUSINS, Ph.D.
Boston Family Professor of Nutrition
Food Science and Human Nutrition Department and Center for Nutritional Sciences
University of Florida
Gainesville, Florida
EARL B. DAWSON, Ph.D.
Associate Professor
Department of Obstetrics and Gynecology
University of Texas Medical Branch
Galveston, Texas
BESS DAWSON-HUGHES, M.D.
Chief
Calcium and Bone Metabolism Laboratory
Jean Mayer USDA Human Nutrition Research Center on Aging
Associate Professor of Medicine
Tufts University
Boston, Massachusetts
DOMINICK P. DEPAOLA, D.D.S., Ph.D.
President and Dean
College of Dentistry
Texas A&M University
Dallas, Texas
Current address:
President and Chief Executive Officer, Forsyth Dental Center

JOHN W. ERDMAN, Jr., M.D.
Professor
Department of Food Science and Human Nutrition
Director of Nutritional Sciences
University of Illinois
Urbana, Illinois
DAVID ERLIJ, M.D., Ph.D.
Professor of Physiology
State University of New York Health Science Center at Brooklyn
Brooklyn, New York
MARY P. FAINE, M.S., R.D.
Associate Professor and Director of Nutrition Education
Department of Prosthodontics
School of Dentistry
University of Washington
Seattle, Washington
VIRGIL F. FAIRBANKS, M.D.
Consultant
Mayo Clinic
Professor of Medicine and Laboratory Medicine
Mayo Clinic and Mayo Foundation
Rochester, Minnesota
ANNA M. FAN, Ph.D.
Chief
Pesticide and Environmental Toxicology Section
Office of Environmental Health Hazard Assessment
California Environmental Protection Agency
Berkeley, California
LAWRENCE FEINMAN, M.D.
Associate Professor

University of Rochester
Rochester, New York
ELLEN B. FUNG, Ph.D.
Postdoctoral Fellow
Division of Gastroenterology and Nutrition
Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania
ROBERT A. GABBAY, M.D., Ph.D.
Instructor
Harvard Medical School
Endocrine Division
Beth Israel Deaconess Medical Center
Boston, Massachusetts
CLAUDIO GALPERIN, M.D.
Postdoctoral Scholar
Division of Rheumatology/Allergy and Clinical Immunology
University of California at Davis
Davis, California
Current address:
Rua Albuquerque Lins
Säo Paulo, Brazil
J. BRUCE GERMAN, Ph.D.
The John Kinsella Endowed Chair of Food Science
University of California at Davis
Davis, California
M. ERIC GERSHWIN, M.D.
The Jack and Donald Chia Professor of Medicine
Chief
Division of Rheumatology/Allergy and Clinical Immunology
University of California at Davis

Wake Forest University School of Medicine
Winston-Salem, North Carolina
ALFRED E. HARPER, Ph.D.
Professor Emeritus
Department of Nutritional Sciences
Biochemistry
University of Wisconsin
Madison, Wisconsin
ROGER C. HARRIS, Ph.D.
Senior Research Fellow
Royal Veterinary College
University of London
London, England
JOHN N. HATHCOCK, Ph.D.
Director
Nutritional and Regulatory Science
Council for Responsible Nutrition
Washington, DC
FELIX P. HEALD, M.D.
Professor Emeritus of Pediatrics
University of Maryland School of Medicine
Baltimore, Maryland
ROBERT P. HEANEY, M.D.
John A. Creighton University Professor
Creighton University
Omaha, Nebraska
WILLIAM C. HEIRD, M.D.
Professor
Children’s Nutrition Research Center
Department of Pediatrics

Section of Endocrinology, Diabetes, and Metabolism in the Department of Medicine
Boston University School of Medicine
Boston, Massachusetts
EDWARD S. HORTON, M.D.
Professor
Department of Medicine
Harvard Medical School
Medical Director, Joslin Diabetes Center
Boston, Massachusetts
CHARLES HUGHES, M.D.
Professor of Medicine
Medical College of Wisconsin
Department of Cardiology
Department of Veteran Affairs
Clement J. Zablocki Medical Center
Milwaukee, Wisconsin
ERIC HULTMAN, M.D., Ph.D.
Professor Emeritus
Department of Medical Laboratory Sciences and Technology
Karolinska Institute, Division of Clinical Chemistry
Huddinge Hospital
Huddinge, Sweden
DIANE M. HUSE, R.D., M.S.
Assistant Professor of Nutrition
Mayo Medical School
Clinical Dietitian, Mayo Clinic
Rochester, Minnesota
ROBERT A. JACOB, Ph.D.
Research Chemist
USDA Western Research Center

Director
School of Dietetics and Human Nutrition
McGill University
Montreal, Quebec
ROBERT KARP, M.D.
Medical Director
Pediatric Resource Center of Kings County Hospital Center
Professor of Pediatrics
State University of New York Health Science Center at Brooklyn
Brooklyn, New York
CARL L. KEEN, Ph.D.
Professor and Chair
Department of Nutrition
University of California at Davis
Davis, California
DARLENE G. KELLY, M.D., Ph.D.
Assistant Professor
Mayo Medical School
Consultant in Gastroenterology
Department of Internal Medicine
Mayo Foundation
Rochester, Minnesota
GERALD T. KEUSCH, M.D.
Professor of Medicine
Tufts University School of Medicine
New England Medical Center
Boston, Massachusetts
JANET C. KING, Ph.D.
Professor
Department of Nutritional Sciences

Clement J. Zablocki Medical Center
Milwaukee, Wisconsin
JANE M. KOTCHEN, M.D., M.P.H.
Professor
Department of Epidemiology/Medicine
Medical College of Wisconsin
Milwaukee, Wisconsin
THEODORE A. KOTCHEN, M.D.
Professor and Chairman
Department of Medicine
Medical College of Wisconsin
Milwaukee, Wisconsin
ELIZABETH A. KRALL, Ph.D.
Assistant Professor
School of Nutrition
Scientist II
Jean Mayer USDA Human Nutrition Research Center on Aging
Tufts University
Boston, Massachusetts
STANLEY KUBOW, Ph.D.
Associate Professor
School of Dietetics and Human Nutrition
McGill University
Montreal, Quebec
MARIE FANELLI KUCZMARSKI, Ph.D., R.D., L.D.
Associate Professor
Department of Nutrition and Dietetics
University of Delaware
Newark, Delaware
ROBERT J. KUCZMARSKI, Dr.P.H., R.D., L.D.

New York City, New York
Chief, Section of Liver Disease and Nutrition
Director, Alcohol Research and Treatment Center and GI-Liver-Nutrition Training Program
Veterans Affairs Medical Center
Bronx, New York
STEPHEN F. LOWRY, M.D., F.A.C.S.
Professor of Surgery
Cornell University Medical College
New York City, New York
Current address:
Professor and Chairman, Department of Surgery
University of Medicine and Dentistry of New Jersey
New Brunswick, New Jersey
ALEXANDER R. LUCAS, M.D.
Professor of Psychiatry
Mayo Medical School
Division of Child and Adolescent Psychiatry
Mayo Clinic
Rochester, Minnesota
RICHARD D. MATTES, R.D., M.P.H., Ph.D.
Professor
Department of Foods and Nutrition
Purdue University
Lafayette, Indiana
Adjunct Associate Professor of Medicine, Division of Endocrinology and Metabolism
Indiana University School of Medicine
Indianapolis, Indiana
DWIGHT E. MATTHEWS, Ph.D.
Professor of Medicine and Chemistry
University of Vermont

Director, Department of Clinical Nutrition
Arkansas Children’s Hospital
Little Rock, Arkansas
JOEL MOSS, M.D., Ph.D.
Chief
Pulmonary-Critical Care Medicine Branch
National Heart, Lung, and Blood Institute
National Institutes of Health
Bethesda, Maryland
JEANETTE M. NEWTON, M.D.
Fellow in Clinical Nutrition
University of California at Davis
Davis, California
FORREST H. NIELSEN, Ph.D.
Director and Research Nutritionist
Grand Forks Human Nutrition Research Center
United States Department of Agriculture
Grand Forks, North Dakota
MAN S. OH, M.D.
Professor of Medicine
Health Sciences Center at Brooklyn
State University of New York
Brooklyn, New York
JAMES A. OLSON, Ph.D.
Distinguished Professor of Liberal Arts and Sciences
Department of Biochemistry and Biophysics
Iowa State University
Ames, Iowa
ROBERT E. OLSON, M.D., Ph.D.
Professor Emeritus of Medicine

Professor of Medicine
Division of Pharmacology and Metabolic Research
University of Vermont
Burlington, Vermont
SARA A. QUANDT, Ph.D.
Associate Professor
Department of Public Health Sciences
Wake Forest University School of Medicine
Adjunct Associate Professor, Department of Anthropology
Wake Forest University
Winston-Salem, North Carolina
JEANNE I. RADER, Ph.D.
Director
Division of Science and Applied Technology
Department of Food Labeling
Center for Food Safety and Applied Nutrition
United States Food and Drug Administration
Washington, DC
MASSIMO RAIMONDO, M.D.
Resident
Division of Gastroenterology
Department of Internal Medicine
Mayo Clinic
Rochester, Minnesota
CHARLES J. REBOUCHE, Ph.D.
Associate Professor
Department of Pediatrics
University of Iowa
Iowa City, Iowa
A. CATHARINE ROSS, Ph.D.

Fellow
Division of Gastroenterology
Mayo Clinic
Rochester, Minnesota
JOHN M. SCOTT, D.Sc.
Professor of Experimental Nutrition
Department of Biochemistry
Trinity College
Dublin, Ireland
CLAY F. SEMENKOVICH, M.D.
Associate Professor
Departments of Medicine and Cell Biology and Physiology
Washington University School of Medicine
St. Louis, Missouri
MOSHE SHIKE, M.D.
Director of Clinical Nutrition
Memorial Sloan-Kettering Cancer Center
Professor of Medicine
Cornell University Medical College
New York City, New York
MAURICE E. SHILS, M.D., Sc.D.
Professor Emeritus of Medicine
Cornell University Medical College
Consultant Emeritus (Nutrition)
Memorial Sloan-Kettering Cancer Center
New York City, New York
Adjunct Professor (Nutrition), Retired
Department of Public Health Sciences
Wake Forest University School of Medicine
Winston-Salem, North Carolina

Massachusetts General Hospital
Professor of Surgery
Harvard Medical School
Boston, Massachusetts
VIRGINIA A. STALLINGS, M.D.
Chief
Nutrition Section
Division of Gastroenterology and Nutrition
Department of Pediatrics
Childrens Hospital of Philadelphia
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania
WILLIAM F. STENSON, M.D.
Professor of Medicine
Department of Medicine
Washington University School of Medicine
St. Louis, Missouri
MARTHA H. STIPANUK, Ph.D.
Professor
Division of Nutritional Sciences
Cornell University
Ithaca, New York
BARBARA J. STOECKER, Ph.D.
Professor and Head
Department of Nutritional Sciences
Oklahoma State University
Stillwater, Oklahoma
TAKASHI SUGIMURA, M.D.
President Emeritus
National Cancer Center

A. STEWART TRUSWELL, M.D., F.R.C.P., F.R.A.C.P., F.F.P.H.M.
Professor of Human Nutrition
Department of Biochemistry
University of Sydney
Sydney, Australia
JUDITH R. TURNLUND, Ph.D.
Research Leader
Western Human Nutrition Research Center
United States Department of Agriculture
San Francisco, California
PENNY S. TURTEL, M.D.
Associate Attending
Department of Medicine
Monmouth Medical Center
Monmouth, New Jersey
JAIME URIBARRI, M.D.
Associate Professor of Medicine
Mount Sinai Medical School
New York City, New York
VIRGINIA UTERMOHLEN, M.D.
Associate Professor
Division of Nutritional Sciences
Cornell University
Ithaca, New York
JAMES W. VAN HOOK, M.D.
Assistant Professor of Obstetrics and Gynecology
Department of Obstetrics and Gynecology
University of Texas Medical Branch
Galveston, Texas
JERRY VOCKLEY, M.D., Ph.D.

Research Assistant
Department of Food Science and Human Nutrition
University of Illinois
Urbana, Illinois
DOUGLAS W. WILMORE, M.D.
Frank Sawyer Professor of Surgery
Harvard Medical School
Department of Surgery
Brigham and Women’s Hospital
Boston, Massachusetts
THOMAS M. S. WOLEVER, M.D., Ph.D.
Associate Professor
Department of Nutrition Sciences
University of Toronto
Toronto, Ontario, Canada
LUCAS WOLF, M.D.
Fellow in Geographic Medicine and Infectious Diseases
Tufts University School of Medicine
New England Medical Center
Boston, Massachusetts
ANN M. YAKTINE, M.S.
Graduate Assistant
Eppley Institute for Research in Cancer
Department of Biochemistry and Molecular Biology
College of Medicine
University of Nebraska Medical Center
Omaha, Nebraska
STEVEN YOSHIDA, Ph.D.
Postdoctoral Scholar
Division of Rheumatology, Allergy and Clinical Immunology

Professor of Medicine
Cornell University Medical College
New York City, New York
A. CATHARINE ROSS, Ph.D.
Professor and Head
Department of Veterinary Science
Professor
Nutrition Department
College of Health and Human Development
The Pennsylvania State University
University Park, Pennsylvania
Preface
The immediate predecessor of Modern Nutrition in Health and Disease was Dietotherapy, published in 1945 and edited by Drs. Michael Wohl and Robert Goodhart.
With the same editors, its successor, the first edition of Modern Nutrition in Health and Disease, appeared in 1955. Its original objective has remained in succeeding
editions: to serve as a comprehensive authoritative text and reference source reviewing the history, scientific base, and practice of nutrition for students, practitioners,
and educators. The broad scope of nutritional sciences has relevance to all basic and applied biologic sciences, medicine, dentistry, dietetics, nursing, pharmacy,
public health, and public policy.
This edition has 115 chapters and multiple sections of an Appendix, updated by 169 authors in 10 countries and from many scientific disciplines. To these authors we
express our deep appreciation.
Thirty-five chapters review specific dietary components in depth; 18 others are concerned with the role of nutrition in integrated biologic systems; 5 review aspects of
nutrition assessment; 41 cover a variety of clinical disorders; and 13 discuss public health and policy issues.
Thirty-six new chapters have been introduced designed to provide better understanding of the role of nutrition in integrated biologic systems and in other areas.
These include general and specific aspects of molecular biology and genetics, ion channels, transmembrane signaling, and other topics–all in tutorial form. The
matter of essential and conditionally essential nutrients is reviewed historically in the opening chapter and considered in separate chapters on individual essential
nutrients and in those on taurine, homocysteine, glutamine, arginine, choline, and carnitine.
There are added chapters on nutritional issues in pediatrics, cardiovascular disorders, gastroenterology, cancer, hematology, and rheumatology. In the field of public
health, new chapters address vegetarian diets, anthropology, “alternative” nutritional therapies, nutritional priorities in less industrialized countries, and risk
assessment of nutrition-related environmental chemicals.
An extensive Appendix includes dietary reference recommendations from various national (including the new 1997 and 1998 U.S. Dietary Reference Intakes) and
international agencies, multiple anthropometric tables, nutrient and nonnutrient contents of foods and beverages, numerous therapeutic diets and exchange lists, and


Establishing the Concept
Nutritional Classification of Food Constituents

Criteria of Essentiality

Classification According to Essentiality

The Concept of Conditional Essentiality
Modification of Essential Nutrient Needs
Health Benefits Not Related to Nutritional Essentiality

Chapter References

Selected Readings
THE CONCEPT OF NUTRITIONAL ESSENTIALITY
The concept of nutritional essentiality was firmly established less than 100 years ago. It arose from observations that certain diseases observed in human populations
consuming poor diets could be prevented by including other foods in the diet and that failure of animals fed on diets composed of purified components or restricted to
one or a few foodstuffs to grow and survive could similarly be corrected by including another food or an extract of the food in the diet. The food constituents that were
found to prevent these problems were classified as indispensable (or essential) nutrients. Nutrients that could be deleted from the diet without causing growth failure
or specific signs of disease were classified as dispensable (or nonessential).
This classification of nutrients served well through the 1950s as the basis of recommendations for treating dietary deficiency diseases, offering dietary advice to the
public, and establishing food regulations and policy. As information about nutrients accrued, however, some essential nutrients were found to be synthesized from
precursors, interactions among some nutrients in the diet were found to influence the need for others, and later, in some conditions, such as prematurity, certain
pathologic states, and genetic defects, the ability of the body to synthesize several nutrients not ordinarily required was found to be so impaired that a dietary source
was needed. As a result, the system of classifying nutrients simply as indispensable or dispensable has been modified to include a category of conditional essentiality
(1).
Recently, associations observed between the risk of developing certain chronic and degenerative diseases and the consumption of some dispensable nutrients and
nonnutrient components of foods, as well as the beneficial effects sometimes observed with high intakes of some essential nutrients, have raised questions about the
adequacy of the present system of nutritional classification of food constituents ( 2, 3, 4, 5 and 6). In this chapter evolution of the concept of nutritional essentiality is

these foods must contain small amounts of unknown substances essential for life. Their observations, nonetheless, did not stimulate a vigorous search for essential
nutrients in foods, probably because of the skepticism of prominent scientists. Von Bunge, in whose laboratories Lunin and Socin worked, attributed inadequacies of
purified diets to mineral imbalances or failure to supply minerals as organic complexes. Voit, a colleague of Liebig, assumed that purified diets would be adequate if
they could be made palatable.
During the early 1880s, Takaki, director general of the Japanese Navy, noted that about 30% of Japanese sailors developed beriberi, although this disease was not
prevalent among British sailors, whose rations were higher in protein. When evaporated milk and meat were included in the rations of the Japanese Navy, the
incidence of beriberi declined remarkably. He concluded correctly that beriberi was a dietary deficiency disease, but incorrectly that it was caused by an inadequate
intake of protein. In the 1890s, Eijkman, an army physician in the Dutch East Indies who was concerned with the high incidence of beriberi in the prisons in Java
(Indonesia), where polished rice was a staple, discovered that chickens fed on a military hospital diet consisting mainly of polished rice developed a neurologic
disease resembling beriberi, whereas those fed rice with the pericarp intact remained healthy. He proposed that accumulation of starch in the intestine favored
formation of a substance that acted as a nerve poison and that rice hulls contained an antidote.
Grijns extended Eijkman's investigations and showed through feeding trials with chickens that the protective substance in rice hulls could be extracted with water. In
1901, he concluded that beriberi was caused by the absence from polished rice of an essential nutrient present mainly in the hulls. He provided, for the first time, a
clear concept of a dietary deficiency disease, but the broad implications of his discovery were not appreciated. The authors of a British report ( 8) noted that facts
brought to light by research done between 1880 and 1901 had “little or no effect on orthodox views and teaching concerning human nutrition.” Another 15 years of
research was required before the concept that foods contained a variety of unidentified essential nutrients gained widespread acceptance.
Establishing the Concept
The first evidence of essentiality of a specific organic molecule was the discovery by Willcock and Hopkins ( 12) in 1906 that a supplement of the amino acid
tryptophan prolonged the survival of mice fed on a diet in which the protein source was the tryptophan-deficient protein zein. The following year, Holst and Frölich in
Norway reported that guinea pigs fed on dry diets with no fresh vegetables developed a disease resembling scurvy, which was prevented by feeding them fresh
vegetables or citrus juices. This was further evidence that foods contained unidentified substances that protected against specific diseases ( 9, 10).
Also, in 1907, Hart and associates at Wisconsin initiated a direct test of the validity of Liebig's hypothesis that the nutritive value of foods and feeds could be
predicted from measurements of their gross composition by chemical analysis. They fed heifers on different rations designed to contain essentially the same amounts
of major nutrients and minerals, each composed of a single plant source—wheat, oats, or corn—using all parts of the plant. The study lasted 3 years and included two
reproductive periods. Animals that ate the wheat plant ration failed to thrive and did not produce viable calves; those fed the corn plant ration grew well and
reproduced successfully. The results of this study, published in 1911, demonstrated that Liebig's hypothesis was untenable and stimulated intensive investigation in
the United States of nutritional defects in diets ( 13).
In experiments undertaken between 1909 and 1913 to compare the nutritional value of proteins, Osborne and Mendel at Yale had initially been unable to obtain
satisfactory rates of growth of rats fed on purified diets. They solved this problem by including a protein-free milk preparation in the diets. They then demonstrated that
proteins from different sources differed in nutritive value and discovered that lysine, sulfur-containing amino acids, and histidine were essential for the rat ( 14).

dietary intakes (RDIs) or allowances (RDAs) are listed in Table 1.1.
Table 1.1 Nutrients Essential for Humans
Classification According to Essentiality
As knowledge of nutritional needs expanded, nutrients were classified according to their essentiality. This type of classification was applied initially to amino acids. In
the early 1920s, Mendel used the term indispensable for amino acids that are not synthesized in the body. The term nonessential was used widely for those that are
not required in the diet. This term was not considered satisfactory because these amino acids, although not required in the diet, are physiologically essential. Block
and Bolling used the term indispensable for organic nutrients with carbon skeletons that are not synthesized in the body, and dispensable, which does not carry the
broad implication of the term nonessential, for those with carbon skeletons that can be synthesized (15, 16).
Nutritional essentiality is characteristic of the species, not the nutrient. Arginine is required by cats and birds but not by humans. Also, it is not synthesized by the
young of most species in amounts sufficient for rapid growth. It may, therefore, be either dispensable or indispensable depending on the species and stage of growth.
Ascorbic acid (vitamin C), which is required by humans and guinea pigs, is not required by most species.
The Concept of Conditional Essentiality
Snyderman (17) found that premature infants, in whom many enzymes of amino acid metabolism develop late during gestation, required cystine and tyrosine (which
are dispensable for most full-term infants) to ensure nitrogen retention and maintain their normal plasma levels. Cystine and tyrosine were thus essential for
premature infants. Rudman and associates (18, 19) subsequently proposed the term conditionally essential for nutrients not ordinarily required in the diet but which
must be supplied exogenously to specific populations that do not synthesize them in adequate amounts. They applied the term initially to dispensable nutrients
needed by seriously ill patients maintained on total parenteral nutrition (TPN). The term now is used for similar needs that result from developmental immaturity,
pathologic states, or genetic defects.
Developmental Immaturity. Cystine and tyrosine, as mentioned above, are conditionally essential for premature infants ( 17). McCormick (3) has suggested that
because preterm infants lack the enzymes for elongation and desaturation of linoleic and a-linolenic acids, elongated derivatives of these fatty acids, which are
precursors of eicosanoids and membrane phospholipids, should be considered conditionally essential for them.
Damage to the cones of the eye and decline in weight gain of infant monkeys fed a taurine-free diet were prevented by supplements of taurine. In premature infants
maintained on TPN without taurine, plasma taurine concentration declined, and the b-wave of the electroretinogram was attenuated. Gaull ( 20) suggests that taurine
becomes conditionally essential for children maintained on TPN because they cannot synthesize enough to meet the body's need.
Plasma and tissue carnitine concentrations are lower in newborn infants than in adults, but this condition has not been associated with any physiologic defect. In
infants maintained on TPN without carnitine, however, plasma and tissue carnitine levels are low, and in one study, this was associated with impaired fat metabolism
and reduced nitrogen retention, both corrected by carnitine supplementation. Hoppel ( 21) concluded from a comprehensive review of the evidence that carnitine may
be conditionally essential for premature infants maintained on TPN but is not conditionally essential for adults.
Pathologic States. Some patients with cirrhosis of the liver require supplements of cysteine and tyrosine to maintain nitrogen balance and normal plasma levels of
these amino acids. Plasma taurine concentration also declines in adults with low plasma cystine levels. Insufficient synthesis of these nutrients in cirrhotic patients

conversion differs for different species. The cat has an absolute requirement for niacin, but the rat converts tryptophan to niacin very efficiently. Human requirements
for niacin are expressed as niacin-equivalents: 60 mg of dietary tryptophan equals 1 mg of niacin. b-Carotene, and to a lesser extent other carotenoids, are precursors
of retinol (vitamin A). Human requirements for vitamin A are expressed as retinol-equivalents: 1 µg retinol-equivalent equals 1 µg of retinol or 6 µg of b-carotene.
These are examples of interactions that alter the dietary need for essential nutrients ( 24). They are not examples of conditional essentiality.
Imbalances and Disproportions of Nutrients. High proportions of some nutrients in the diet can influence the need for others. This phenomenon was first
recognized when additions of amino acids that stimulated growth of young rats fed on diets low in tryptophan and niacin were found to precipitate niacin
deficiency—an example of a vitamin deficiency induced by an amino acid imbalance. With diets that contain adequate niacin but are low in tryptophan, amino acid
disproportions increased the need for tryptophan and depressed growth ( 25). Many examples of this type of imbalance, involving a variety of amino acids, have been
observed in young animals. The growth-depressing effects result from depressed food intake mediated through alterations in brain neurotransmitter concentrations
(26).
Dietary imbalances can also increase needs for some mineral elements ( 23, 27). Disproportionate amounts of molybdenum and sulfate in the diet increase the dietary
need for copper and precipitate copper deficiency in animals consuming an otherwise adequate amount of copper. Extra manganese in the diets of sheep or pigs
increases the need for iron to prevent anemia, and excess iron reduces the absorption of manganese. The presence in the diet of phytic acid, which binds zinc as well
as other multivalent cations, impairs zinc absorption and increases the need for zinc. Thus, phytic acid can precipitate zinc deficiency in both humans and animals.
Dietary needs for some essential nutrients are influenced by the proportions of macronutrients in the diet. The need for vitamin E in the diet increases as the amount
of fat rich in polyunsaturated fatty acids is increased ( 28). Thiamin functions mainly as part of the cofactor for decarboxylation of the a-ketoacids arising from
metabolism of carbohydrates and branched-chain amino acids; hence, the need for thiamin depends upon the relative proportions of fat, carbohydrate, and protein in
the diet. Fat has long been known to exert a “thiamin-sparing” effect ( 29).
Genetic Defects
Individuals with genetic defects that limit conversion of a vitamin to its coenzyme form develop severe deficiency diseases. Defects in the utilization of biotin,
cobalamin, folate, niacin, pyridoxine, and thiamin are known. Effects of some of these diseases are relieved by large doses of the vitamin, but the degree of response
varies with the disease and among patients with the same defect (30). Intakes required to relieve or correct these conditions are well above the RDA. In the genetic
disease acrodermatitis enteropathica, which impairs zinc absorption, the need for zinc is three to four times the RDI level (see Chapter 11).
Drug-Nutrient Interactions
Many types of drug-nutrient interactions increase the need for a nutrient. The drug may cause malabsorption, act as a vitamin antagonist, or impair mineral absorption
(see Chapter 99). These and other conditions that alter the amounts of essential nutrients needed because of either interactions among dietary constituents or
impairment of a metabolic function are not examples of conditional essentiality.
HEALTH BENEFITS NOT RELATED TO NUTRITIONAL ESSENTIALITY
For several decades after the concept of nutritional essentiality was established in the early 1900s, foods were primarily considered to be sources of essential
nutrients required for critical physiologic functions that, if impaired by dietary deficiencies, caused specific diseases. Except for the debilitating effects of malnutrition,

classifying fiber as an essential nutrient, but some forms of fiber that are transformed in the gastrointestinal tract into products that can be oxidized to yield energy fit
the definition of nutrients. Without question it is a food constituent that provides a desirable health benefit when ingested in moderate amounts ( 33). Fiber is
discussed with carbohydrates in RDI publications and with plant foods in dietary guidelines. A recommendation for inclusion of fiber in diets is appropriate, but
recommended intakes should not be considered as RDIs, which are reference values for intakes of essential nutrients.
To develop a separate category of food constituents of this type (substances with desirable effects on health that are different from effects attributable to the
physiologic functions of essential nutrients), specific criteria must be established to identify those to be included. Establishing appropriate criteria for assessing the
validity of health claims for a category of food constituents that will include a variety of unrelated substances with different types of effects, many of which apply to
only segments of the population, will be more complex than establishing criteria for assessing the validity of claims for essentiality of food constituents. The latter
criteria apply uniformly to all substances proposed for inclusion and can be measured objectively. Assessing the effects of food constituents on health or in preventing
disease involves a greater element of judgment and is more subjective than evaluating the essentiality of nutrients. Thus, claims for such effects must be evaluated
especially critically.
In establishing criteria for assessing claims for desirable health benefits, consideration must be given to the need for subcategories of substances having different
effects. Susceptibility to chronic and degenerative diseases is highly variable and may be influenced by many factors, including genetic differences among individuals
or between populations, lifestyle, and diet-genetic interactions that can influence expression of genetic traits. Among questions that require answers are, Does the
effect result from alteration of a basic mechanism that prevents a disease from developing or is it due to modulation of the disease process? Does the benefit apply to
the entire population or only to individuals at risk? This has been a source of controversy in relation to dietary recommendations for reducing the risk of developing
heart disease (34). The effects of dietary constituents on immunocompetence should be analyzed in a similar manner: Are they of general significance or of
consequence only if the immune system is impaired? When is stimulation of the immune system beneficial and when might it have adverse effects?
An immense number of plant constituents with anticarcinogenic actions are currently under investigation. These constituents differ in both their effects on cells and the
stage of tumor development at which they act, and some have both adverse and beneficial effects (35). A number of subcategories would seem to be needed for
which specific criteria will be required.
Pharmacologic Effects of Nutrients. Nutrients that function in large doses as drugs fall logically into a separate category of pharmacologic agents ( 36). Nicotinic
acid in large doses is used to lower serum cholesterol. This represents use of a nutrient as a drug (see Chapter 23). The effect is unrelated to its function as a vitamin
required for oxidation of energy-yielding nutrients and can be achieved only by quantities that far exceed nutritional requirements or usual dietary amounts. Use of
tryptophan as a sleep inducer (37) and of continuous intravenous infusions of magnesium in the treatment of preeclampsia or myocardial infarction fall into this
category (38). Essential nutrients that fit this pattern are functioning as pharmacologic agents not as nutritional supplements, as are substances, such as aspirin or
quinine, originally isolated from plants, that are used as medicines.
With the current state of knowledge, it is undoubtedly premature to try to resolve definitively the problems encountered in classifying food constituents that have
desirable effects on health or have been implicated in disease prevention. Such actions are not related to the physiologic functions of essential nutrients.
Nonetheless, even though solutions proposed at this stage must be considered tentative, an orderly resolution of questions relating to health effects of food