NATIONAL ACADEMY PRESS
2101 Constitution Avenue, N.W. Washington, DC 20418
NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This project was funded by the U.S. Department of Health and Human Services Office of Disease Prevention and Health Promotion, Contract No. 282-96-0033; Health Canada; the Institute of Medicine; the Dietary Reference Intakes Private Foundation Fund, including the Dannon Institute and the International Life Sciences Institute; and the Dietary Reference Intakes Corporate Donors' Fund. Contributors to the Fund include Roche Vitamins Inc.; Mead Johnson Nutrition Group; Daiichi Fine Chemicals, Inc.; Kemin Foods, Inc.; M&M Mars; Weider Nutrition Group; Nabisco Foods Group; U.S. Borax; and Natural Source Vitamin E Association. The opinions or conclusions expressed herein do not necessarily reflect those of the funders.
Library of Congress Cataloging-in-Publication Data
Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids : a report of the Panel on Dietary Antioxidants and Related Compounds, Subcommitties on Upper Reference Levels of Nutrients and of Interpretation and Use of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine.
p. ; cm.
Includes bibliographical references and index.
ISBN 0-309-06949-1 (case) – ISBN 0-309-06935-1 (paper)
1. Antioxidants. 2. Reference values (Medicine). 3. Vitamin C. 4. Vitamin E. 5. Carotenoids. I. Institute of Medicine (U.S.). Panel on Dietary Antioxidants and Related Compounds.
[DNLM: 1. Nutritional Requirements. 2. Ascorbic Acid. 3. Carotenoids. 4. Reference Values. 5. Selenium. 6. Vitamin E. QU 145 D56566 2000]
QP801.A66 D53 2000
612.3′9–dc21
00-035521
This report is available for sale from the
National Academy Press
, 2101 Constitution Avenue, N.W., Box 285, Washington, DC 20055; call (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area), or visit the NAP's on-line bookstore at http://www.nap.edu.
For more information about the Institute of Medicine or the Food and Nutrition Board, visit the IOM home page at http://www.iom.edu.
Copyright 2000 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.
THE NATIONAL ACADEMIES
National Academy of Sciences
National Academy of Engineering
Institute of Medicine
National Research Council
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. William A. Wulf is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council.
PANEL ON DIETARY ANTIOXIDANTS AND RELATED COMPOUNDS
NORMAN I. KRINSKY (Chair),
Department of Biochemistry, Tufts University, Boston, Massachusetts
GARY R. BEECHER,
U.S. Department of Agriculture Beltsville Human Nutrition Research Center, Beltsville, Maryland
RAYMOND F. BURK,
Clinical Nutrition Unit, Vanderbilt University Medical Center, Nashville, Tennessee
ALVIN C. CHAN,
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ontario, Canada
JOHN W. ERDMAN, JR.,
Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign
ROBERT A. JACOB,
U.S. Department of Agriculture Western Human Nutrition Research Center, University of California, Davis
ISHWARLAL JIALAL,
Department of Pathology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas
LAURENCE N. KOLONEL,
Cancer Research Center, University of Hawaii, Honolulu
JAMES R. MARSHALL,
Cancer Prevention and Control, Arizona Cancer Center, University of Arizona, Tucson
SUSAN TAYLOR MAYNE,
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut
ROSS L. PRENTICE,
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
KATHLEEN B. SCHWARZ,
Division of Pediatric GI/Nutrition, Johns Hopkins Hospital, Baltimore, Maryland
DANIEL STEINBERG,
Division of Endocrinology and Metabolism, University of California, San Diego
MARET G. TRABER,
Department of Nutrition and Food Management, Oregon State University, Corvallis
Food and Nutrition Board Liaison
CHARLES H. HENNEKENS,
Boca Raton, Florida
Federal Project Steering Committee Liaison
LTC KARL FRIEDL,
U.S. Army Medical Research and Materiel Command, Ft. Detrick, Frederick, Maryland
Staff
SANDRA A. SCHLICKER, Study Director
ELISABETH A. REESE, Research Associate
ALICE L. VOROSMARTI, Research Associate
MICHELE R. RAMSEY, Senior Project Assistant
SUBCOMMITTEE ON UPPER REFERENCE LEVELS OF NUTRIENTS
IAN C. MUNRO (Chair),
CanTox, Inc., Mississauga, Ontario, Canada
GEORGE C. BECKING,
Phoenix OHC, Kingston, Ontario, Canada
RENATE D. KIMBROUGH, Independent Consultant,
Washington, D.C.
RITA B. MESSING,
Division of Environmental Health, Minnesota Department of Health, St. Paul
SANFORD A. MILLER,
Graduate School of Biomedical Sciences, University of Texas Health Sciences Center, San Antonio
SUZANNE P. MURPHY,
Cancer Research Center, University of Hawaii, Honolulu
HARRIS PASTIDES,
School of Public Health, University of South Carolina, Columbia
JOSEPH V. RODRICKS,
The Life Sciences Consultancy LLC, Washington, D.C.
IRWIN H. ROSENBERG,
Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts
STEVE L. TAYLOR,
Department of Food Science and Technology and Food Processing Center, University of Nebraska, Lincoln
JOHN A. THOMAS, Retired,
San Antonio, Texas
GARY M. WILLIAMS,
Department of Pathology, New York Medical College, Valhalla
Staff
SANDRA A. SCHLICKER, Study Director
ELISABETH A. REESE, Research Associate
MICHELE R. RAMSEY, Senior Project Assistant
SUBCOMMITTEE ON INTERPRETATION AND USES OF DIETARY REFERENCE INTAKES
SUZANNE P. MURPHY (Chair),
Cancer Research Center, University of Hawaii, Honolulu
LENORE ARAB,
Departments of Epidemiology and Nutrition, University of North Carolina School of Public Health, Chapel Hill
SUSAN I. BARR,
Department of Nutrition, University of British Columbia, Vancouver, Canada
SUSAN T. BORRA,
International Food Information Council, Washington, D.C.
ALICIA L. CARRIQUIRY,
Department of Statistics, Iowa State University, Ames
BARBARA L. DEVANEY,
Mathematica Policy Research, Princeton, New Jersey
JOHANNA T. DWYER,
Frances Stern Nutrition Center, New England Medical Center and Tufts University, Boston, Massachusetts
JEAN-PIERRE HABICHT,
Division of Nutritional Sciences, Cornell University, Ithaca, New York
HARRIET V. KUHNLEIN,
Centre for Indigenous Peoples' Nutrition and Environment, McGill University, Ste. Anne de Bellevue, Quebec, Canada
Consultant
GEORGE BEATON,
GHB Consulting, Willowdale, Ontario, Canada
Staff
MARY I. POOS, Study Director
ALICE L. VOROSMARTI, Research Associate
MICHELE R. RAMSEY, Senior Project Assistant
STANDING COMMITTEE ON THE SCIENTIFIC EVALUATION OF DIETARY REFERENCE INTAKES
VERNON R. YOUNG (Chair),
Laboratory of Human Nutrition, School of Science, Massachusetts Institute of Technology, Cambridge
JOHN W. ERDMAN, JR. (Vice-Chair),
Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign
LINDSAY H. ALLEN,
Department of Nutrition, University of California, Davis
STEPHANIE A. ATKINSON,
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
ROBERT J. COUSINS,
Center for Nutritional Sciences, University of Florida, Gainesville
JOHANNA T. DWYER,
Frances Stern Nutrition Center, New England Medical Center and Tufts University, Boston, Massachusetts
JOHN D. FERNSTROM,
Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
SCOTT M. GRUNDY,
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas
CHARLES H. HENNEKENS,
Boca Raton, Florida
SANFORD A. MILLER,
Graduate School of Biomedical Sciences, University of Texas Health Sciences Center, San Antonio
WILLIAM M. RAND,
Department of Family Medicine and Community Health, Tufts University School of Medicine, Boston, Massachusetts
U.S. Government Liaison
ELIZABETH CASTRO,
Office of Disease Prevention and Health Promotion, U.S. Department of Health and Human Services, Washington, D.C.
Canadian Government Liaison
PETER W.F. FISCHER,
Nutrition Research Division, Health Protection Branch, Health Canada, Ottawa, Ontario, Canada
Staff
ALLISON A. YATES, Study Director
GAIL E. SPEARS, Administrative Assistant
FOOD AND NUTRITION BOARD
CUTBERTO GARZA (Chair),
Division of Nutrition, Cornell University, Ithaca, New York
LARRY R. BEUCHAT,
Center for Food Safety and Quality Enhancement, University of Georgia, Griffin
BENJAMIN CABALLERO,
Center for Human Nutrition, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland
FERGUS M. CLYDESDALE,
Department of Food Science, University of Massachusetts, Amherst
ROBERT J. COUSINS,
Center for Nutritional Sciences, University of Florida, Gainesville
SCOTT M. GRUNDY,
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas
ALFRED H. MERRILL, JR.,
Department of Biochemistry, Emory Center for Nutrition and Health Sciences, Emory University, Atlanta, Georgia
LYNN PARKER,
Child Nutrition Programs and Nutrition Policy, Food Research and Action Center, Washington, D.C.
ROSS L. PRENTICE,
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
A. CATHARINE ROSS,
Department of Nutrition, The Pennsylvania State University, University Park
ROBERT M. RUSSELL,
Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts
ROBERT E. SMITH,
R.E. Smith Consulting, Inc., Newport, Vermont
VIRGINIA A. STALLINGS,
Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, Pennsylvania
STEVE L. TAYLOR,
Department of Food Science and Technology and Food Processing Center, University of Nebraska, Lincoln
Staff
ALLISON A. YATES, Director
GAIL E. SPEARS, Administrative Assistant
GARY WALKER, Financial Associate
Preface
This report is one of a series that presents a comprehensive set of reference values for nutrient intakes for healthy U.S and Canadian populations. It is a product of the Food and Nutrition Board of the Institute of Medicine working in cooperation with scientists from Canada.
The report establishes a set of reference values for vitamin C, vitamin E, and selenium to replace previously published Recommended Dietary Allowances (RDAs) and Recommended Nutrient Intakes (RNIs) for the United States and Canada and examines data about β-carotene and the other carotenoids (α-carotene, β-cryptoxanthin, lutein, lycopene, and zeaxanthin). Evidence has been reviewed regarding the impact of these compounds on chronic disease along with their roles related to deficiency states. Although the reference values are based on data, the data were often scanty or drawn from studies that had limitations in addressing the various questions that needed to be dealt with in order to develop reference values for these nutrients and food components. Thus, scientific judgment was required in setting the reference values. The reasoning used is described for each nutrient in Chapter 5, Chapter 6, Chapter 7 through Chapter 8.
These compounds, vitamin C, vitamin E, selenium, β-carotene and other carotenoids, have been termed “dietary antioxidants” somewhat loosely by many. There has been intense interest by the public and the media in the possibility that increased intakes of dietary antioxidants protect against chronic disease. Many research programs are under way in this area.
Epidemiological evidence suggests that the consumption of fruits and vegetables reduces the risk of both cancer and cardiovascular disease, and it has been hypothesized that this is due in part to the presence of compounds with antioxidant properties found in these food groups. While dietary antioxidants is a convenient generic title, these compounds are multifunctional, and some of the actions observed in vivo may not represent an antioxidant function, even though the compounds have been frequently classified as antioxidant nutrients.
Although a definition of a dietary antioxidant is provided in this report at the specific request of the federal agencies, the above compounds were evaluated with respect to their role in human nutrition, without limiting the criteria to antioxidant properties or to only those compounds or nutrients which met the definition. Data were reviewed regarding the minimum amount of these compounds required to prevent deficiency diseases, as well as the amounts that might impact on chronic diseases regardless of whether or not the putatively protective mechanisms involved antioxidant properties. Thus, a major task of the Panel on Dietary Antioxidants and Related Compounds, the Subcommittee on Upper Reference Levels of Nutrients (UL Subcommittee), the Subcommittee on Interpretation and Uses of Dietary Reference Intakes (Uses Subcommittee), and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (DRI Committee) was to analyze the evidence on beneficial and adverse effects of various intakes of vitamin C, vitamin E, selenium, and β-carotene in the context of setting Dietary Reference Intakes (DRIs) for these compounds.
Many of the questions raised about requirements for and recommended intakes of these nutrients cannot be answered fully because of inadequacies in the present database. Apart from studies of overt deficiency disease, there is a dearth of studies that address specific effects of inadequate intakes on specific indicators of health status. For these compounds, there is no direct information that permits estimating the amounts required by children, adolescents, lactating women, and the elderly. For β-carotene, data useful for the setting of Tolerable Upper Intake Levels (ULs) are inconsistent and for the other carotenoids data are sparse, precluding reliable estimates of the minimum intake above which there is the risk of adverse effects. For some of these nutrients, there are questions about how much is contained in the food North Americans eat. Thus, another major task of the report was to outline a research agenda to provide a basis for public policy decisions related to rec-
ommended intakes of vitamin C, vitamin E, selenium, and the carotenoids and ways to achieve those intakes.
The process for establishing DRIs is an iterative process and is thus evolving as the conceptual framework is applied to new nutrients and food components. With more experience, the proposed models for establishing reference intakes for use with nutrients and food components that play a role in health will be refined. Also, as new information or new methods of analysis are adopted, these reference values undoubtedly will be reassessed.
Because the project is ongoing as indicated above, many comments were solicited and have been received on the two reports previously published (Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride and Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12,Pantothenic Acid, Biotin, and Choline). Refinements have been included in the general discussion regarding approaches used (Chapter 1, Chapter 2, Chapter 3 through Chapter 4) and in the discussion of uses of DRIs (Chapter 9 in this report). For example, it is now clearly stated that animal data can be used as the critical adverse effect in setting a UL for a nutrient.
Among the comments received to date have been requests for additional guidance in the practical application of DRIs. The Uses Subcommittee, conceptually included since the beginning of the DRI process, was formed subsequent to the release of the first two reports. Although their activities will involve reports specifically addressing the rationale for using DRIs for assessing intake and planning, in this report Chapter 9 addresses some of the major issues that relate to the anticipated uses and applications of reference values.
This report reflects the work of the Food and Nutrition Board's DRI Committee, its expert Panel on Dietary Antioxidants and Related Compounds, UL Subcommittee, and Uses Subcommittee. It is important to acknowledge the support of the government of Canada and Canadian scientists in this initiative, which represents a pioneering first step in the standardization of nutrient reference intakes at least within a major part of one continent. A brief description of the overall project of the DRI Committee and of the panel's task are given in Appendix A. It is hoped that the critical, comprehensive analyses of available information and of knowledge gaps in this initial series of reports will greatly assist the private sector, foundations, universities, government laboratories, and other institutions with the development of a productive research agenda for the next decade.
The DRI Committee, the Panel on Dietary Antioxidants and Related Compounds, the UL Subcommittee, and the Uses Subcommittee wish to extend sincere thanks to the many experts who have assisted with this report by giving presentations, providing written materials, participating in discussions, analyzing data, and other means. Many, but far from all, of these people are named in Appendix B. Special thanks go to staff at the National Center for Health Statistics, the Food Surveys Research Group of the Agricultural Research Service, and the Department of Statistics at Iowa State University for extensive analyses of survey data.
The respective chairs and members of the panel and subcommittees have performed their work under great time pressure. Their dedication made the completion of this report possible. All gave of their time willingly and without financial reward; both the science and practice of nutrition are major beneficiaries.
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council's Report Review Committee. The purpose of this independent review is to provide candid and critical comments to assist the panel and subcommittee members and the Institute of Medicine in making the published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge.
The content of the final report is the responsibility of the Institute of Medicine and the study panel and not the responsibility of the reviewers. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. The panel wishes to thank the following individuals, who are neither officials nor employees of the Institute of Medicine, for their participation in the review of this report: Bruce N. Ames, Ph.D., University of California at Berkeley; Dennis M. Bier, M.D., Baylor College of Medicine; James R. Coughlin, Ph.D., Coughlin & Associates; Barry Halliwell, D.Sc., University of London, Kings College; John E. Halver, Ph.D., University of Washington; Richard J. Havel, M.D., University of California at San Francisco; Orville Levander, Ph.D., U.S. Department of Agriculture; Stanley D. Omaye, Ph.D., University of Nevada; Helmut Sies, M.D., Heinrich-Heine-Universität Düsseldorf; Thressa C. Stadtman, Ph.D., National Institutes of Health; and Walter Willett, M.D., Dr. P.H., Harvard School of Public Health.
The DRI Committee wishes to acknowledge, in particular, the commitment shown by Norman Krinsky, chair of the panel, who steered this difficult project through what at times seemed to some
like “dangerous and uncharted waters.” His ability to keep the effort and the various perspectives moving in a positive direction is very much appreciated. Thanks also are due to DRI Committee members Scott Grundy and John Fernstrom, in-depth internal reviewers for this report.
Special thanks go to the staff of the Food and Nutrition Board and foremost to Sandra Schlicker, who was the study director for the panel and without whose assistance, both intellectual and managerial, this report would neither have been as polished nor as timely in its release.
It is, of course, those at the Food and Nutrition Board who get much of the work completed and so the panel, subcommittees, and the Food and Nutrition Board wish to thank Allison Yates, Director of the Food and Nutrition Board, for constant assistance and it also recognizes, with appreciation, the contributions of Mary Poos, Elisabeth Reese, Alice Vorosmarti, Gail Spears, and Michele Ramsey. We also thank Florence Poillon and Sydne Newberry for editing the manuscript and Mike Edington and Claudia Carl for assistance with publication.
Vernon Young
Chair, Standing Committee on the Scientific Evaluation of Dietary Reference Intakes
Cutberto Garza
Chair, Food and Nutrition Board