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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
DIETARY REFERENCE INTAKES FOR Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and ZincA Report of the
Panel on Micronutrients,
Subcommittees on Upper Reference Levels of Nutrients and of
Interpretation and Uses of Dietary Reference Intakes, and the
Standing Committee on the Scientific Evaluation of Dietary Reference Intakes
Food and Nutrition Board
Institute of Medicine
NATIONAL ACADEMY PRESS
Washington, D.C.
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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
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, T03; the National Institutes of Health Office of Dietary Supplements; the Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Division of Nutrition and Physical Activity; 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 to date include Daiichi Fine Chemicals, Inc., Kemin Foods, L.C., M&M/Mars, Mead Johnson Nutritionals, Nabisco Foods Group, Natural Source Vitamin E Association, Roche Vitamins Inc., U.S. Borax, and Weider Nutritional Group. 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 A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc : a report of the Panel on Micronutrients … [et al.], 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 0-309-07279-4 (pbk.)—ISBN 0-309-07290-5 (hc.)
1. Trace elements in nutrition. 2. Vitamin A in human nutrition. 3. Vitamin K. 4. Reference Values (Medicine) I. Institute of Medicine (U.S.). Panel on Micronutrients.
QP534 .D54 2002
612.3′924--dc21
2001052139
This report is available for sale from the
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Copyright 2001 by the National Academy of Sciences. All rights reserved.
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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
—Goethe
INSTITUTE OF MEDICINE
Shaping the Future for Health
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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. Wm. 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. Wm. A. Wulf are chairman and vice chairman, respectively, of the National Research Council.
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PANEL ON MICRONUTRIENTS
ROBERT RUSSELL (Chair),
Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts
JOHN L. BEARD,
Department of Nutrition, The Pennsylvania State University, University Park
ROBERT J. COUSINS,
Center for Nutritional Sciences, University of Florida, Gainesville
JOHN T. DUNN,
University of Virginia Health System, Charlottesville
GUYLAINE FERLAND,
Department of Nutrition, University of Montreal, Quebec, Canada
K. MICHAEL HAMBIDGE,
Department of Pediatrics, University of Colorado Health Sciences Center, Denver
SEAN LYNCH,
Veterans Administration Medical Center, Hampton, Virginia
JAMES G. PENLAND,
U.S. Department of Agriculture Human Nutrition Research Center, Grand Forks, North Dakota
A. CATHARINE ROSS,
Department of Nutrition, The Pennsylvania State University, University Park
BARBARA J. STOEKER,
Department of Nutritional Sciences, Oklahoma State University, Stillwater
JOHN W. SUTTIE,
Department of Biochemistry, University of Wisconsin, Madison
JUDITH R. TURNLUND,
U.S. Department of Agriculture Western Human Nutrition Research Center, Davis, California
KEITH P. WEST,
Center for Human Nutrition, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland
STANLEY H. ZLOTKIN,
Departments of Pediatrics and Nutritional Sciences, The Hospital for Sick Children and The University of Toronto, Ontario, Canada
Consultants
LEWIS BRAVERMAN,
School of Medicine, Harvard University, Boston, Massachusetts
FRANCOISE DELANGE,
Department of Pediatrics, Hôpital Saint-Pierre, Brussels, Belgium
Staff
PAULA R. TRUMBO, Study Director
ALICE L. VOROSMARTI, Research Associate
MICHELE RAMSEY, Senior Project Assistant
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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,
Institute for Evaluating Health Risks, 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
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,
Clinical Nutrition Division, the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University and New England Medical Center, Boston, Massachusetts
STEVE L. TAYLOR,
Department of Food Science and Technology and Food Processing Center, University of Nebraska, Lincoln
JOHN A. THOMAS, Retired,
University of Texas Health Science Center at San Antonio
GARY M. WILLIAMS,
Department of Pathology, New York Medical College, Valhalla
Staff
SANDRA SCHLICKER, Study Director
ELISABETH A. REESE, Research Associate
MICHELE RAMSEY, Senior Project Assistant
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SUBCOMMITTEE ON INTERPRETATION AND USES OF DIETARY REFERENCE INTAKES
SUZANNE MURPHY (Chair),
Cancer Research Center of Hawaii, University of Hawaii, Honolulu
LENORE ARAB,
University of North Carolina School of Public Health, Chapel Hill
SUSAN I. BARR,
University of British Columbia, Vancouver
SUSAN T. BORRA,
International Food Information Council, Washington, D.C.
ALICIA CARRIQUIRY,
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,
Cornell University, Ithaca, New York
HARRIET V. KUHNLEIN,
Centre for Indigenous Peoples’ Nutrition and Environment, McGill University, Ste. Anne de Bellevue, Quebec, Canada
Staff
MARY POOS, Study Director
ALICE L. VOROSMARTI, Research Associate
SHELLEY GOLDBERG, Senior Project Assistant
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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, Faculty of Health Sciences, 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,
University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania
SCOTT M. GRUNDY,
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas
SANFORD A. MILLER,
Graduate School of Biomedical Sciences, University of Texas Health Science 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
Consultant
GEORGE BEATON,
GHB Consulting, Willowdale, Ontario, Canada
Staff
ALLISON A. YATES, Study Director
SANDRA SCHLICKER, Senior Program Officer
MARY POOS, Senior Program Officer
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PAULA TRUMBO, Senior Program Officer
ALICE L. VOROSMARTI, Research Associate
KIMBERLY FREITAG, Research Assistant
MICHELE RAMSEY, Senior Project Assistant
GAIL E. SPEARS, Administrative Assistant
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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
FOOD AND NUTRITION BOARD
CUTBERTO GARZA (Chair),
Division of Nutrition, Cornell University, Ithaca, New York
ALFRED H. MERRILL, JR. (Vice Chair),
Department of Biochemistry, Emory Center for Nutrition and Health Sciences, Emory University, Atlanta, Georgia
ROBERT M. RUSSELL (Vice Chair),
Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts
VIRGINIA A. STALLINGS (Vice Chair),
Division of Gastroenterology and Nutrition, The Children’s Hospital of Philadelphia, Pennsylvania
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
JOHANNA T. DWYER,
Frances Stern Nutrition Center, New England Medical Center and Tufts University, Boston, Massachusetts
SCOTT M. GRUNDY,
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas
SHIRIKI KUMANYIKA,
University of Pennsylvania School of Medicine, Philadelphia
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 E. SMITH,
R.E. Smith Consulting, Inc., Newport, Vermont
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
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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
Preface
This report is one in 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 (IOM) working in cooperation with Canadian scientists.
The report establishes a set of reference values for vitamin A, vitamin K, chromium, copper, iodine, iron, manganese, molybdenum, and zinc to replace previously published Recommended Dietary Allowances (RDAs) and Recommended Nutrient Intakes (RNIs) for the United States and Canada. The report also examines data about arsenic, boron, nickel, silicon, and vanadium. Although all reference values are based on data, available data often were scanty or drawn from studies that had limitations in addressing the various questions that confronted the Panel. Thus, although governed by reasoning, informed judgments often were required in setting reference values. The reasoning used is described for each nutrient in Chapters 4 through 13.
Close attention was given to the evidence relating intake of micronutrients to reduction of the risk of chronic disease, and the daily amounts needed to maintain normal status based on biochemical indicators and daily body losses. In addition, a major task of the Panel on Micronutrients, Subcommittee on Upper Reference Levels of Nutrients (UL 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
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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
staff’s constant assistance. Thus, we also recognize and appreciate the contributions of Sandra Schlicker, Mary Poos, Elisabeth Reese, Alice Vorosmarti, Gail Spears, and Michele Ramsey and thank Pat Stephens for editing the manuscript, Jacqueline Dupont for technical review, 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
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Reviewers
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 NRC’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its 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 review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:
Sarah L. Booth, Tufts University
James D. Cook, Kansas University Medical Center
Mark L. Failla, University of North Carolina
Jeanne Freeland-Graves, University of Texas
James K. Friel, Memorial University of Newfoundland
Walter Mertz, Rockville, Maryland
Phylis B. Moser-Veillon, University of Maryland
Robert S. Parker, Cornell University
John B. Stanbury, Massachusetts General Hospital
Clive E. West, Wageningen Agricultural University
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the
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conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Kurt J. Isselbacher, Massachusetts General Hospital and Ronald W. Estabrook, University of Texas Southwestern Medical Center at Dallas. Appointed by the National Research Council and Institute of Medicine, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committees and the institution.
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Contents
SUMMARY
1
What Are Dietary Reference Intakes?,
2
Approach for Setting Dietary Reference Intakes,
7
Nutrient Functions and the Indicators Used to Estimate Requirements,
10
Criteria and Proposed Values for Tolerable Upper Intake Levels,
16
Using Dietary Reference Intakes to Assess Nutrient Intakes of Groups,
19
Consideration of the Risk of Chronic Degenerative Disease,
22
Research Recommendations,
26
1
INTRODUCTION TO DIETARY REFERENCE INTAKES
29
What Are Dietary Reference Intakes?,
29
Categories of Dietary Reference Intakes,
30
Parameters for Dietary Reference Intakes,
36
Summary,
42
References,
42
2
OVERVIEW AND METHODS
44
Methodological Considerations,
45
Estimates of Nutrient Intake,
54
Dietary Intakes in the United States and Canada,
55
Summary,
58
References,
58
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3
A MODEL FOR THE DEVELOPMENT OF TOLERABLE UPPER INTAKE LEVELS
60
Background,
60
A Model for the Derivation of Tolerable Upper Intake Levels,
62
Risk Assessment and Food Safety,
62
Application of the Risk Assessment Model to Nutrients,
67
Steps in the Development of the Tolerable Upper Intake Level,
71
Intake Assessment,
79
Risk Characterization,
79
References,
80
4
VITAMIN A
82
Summary,
82
Background Information,
83
Selection of Indicators for Estimating the Requirement for Vitamin A,
97
Factors Affecting the Vitamin A Requirement,
106
Findings by Life Stage and Gender Group,
110
Intake of Vitamin A,
122
Tolerable Upper Intake Levels,
125
Research Recommendations for Vitamin A,
146
References,
146
5
VITAMIN K
162
Summary,
162
Background Information,
162
Selection of Indicators for Estimating the Requirement for Vitamin K,
165
Factors Affecting the Vitamin K Requirement,
173
Findings by Life Stage and Gender Group,
176
Intake of Vitamin K,
184
Tolerable Upper Intake Levels,
187
Research Recommendations for Vitamin K,
189
References,
189
6
CHROMIUM
197
Summary,
197
Background Information,
197
Selection of Indicators for Estimating the Requirement for Chromium,
202
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Factors Affecting the Chromium Requirement,
204
Findings by Life Stage and Gender Group,
205
Intake of Chromium,
211
Tolerable Upper Intake Levels,
213
Research Recommendations for Chromium,
216
References,
217
7
COPPER
224
Summary,
224
Background Information,
224
Selection of Indicators for Estimating the Requirement for Copper,
229
Factors Affecting the Copper Requirement,
233
Findings by Life Stage and Gender Group,
235
Intake of Copper,
245
Tolerable Upper Intake Levels,
246
Research Recommendations for Copper,
252
References,
252
8
IODINE
258
Summary,
258
Background Information,
258
Selection of Indicators for Estimating the Requirement for Iodine,
262
Factors Affecting the Iodine Requirement,
267
Findings by Life Stage and Gender Group,
268
Intake of Iodine,
277
Tolerable Upper Intake Levels,
278
Research Recommendations for Iodine,
284
References,
284
9
IRON
290
Summary,
290
Background Information,
290
Selection of Indicators for Estimating the Requirement for Iron,
300
Factors Affecting the Iron Requirement,
311
Findings by Life Stage and Gender Group,
316
Intake of Iron,
355
Tolerable Upper Intake Levels,
356
Research Recommendations for Iron,
378
References,
378
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10
MANGANESE
394
Summary,
394
Background Information,
394
Selection of Indicators for Estimating the Requirement for Manganese,
397
Factors Affecting the Manganese Requirement,
401
Findings by Life Stage and Gender Group,
402
Intake of Manganese,
407
Tolerable Upper Intake Levels,
408
Research Recommendations for Manganese,
414
References,
415
11
MOLYBDENUM
420
Summary,
420
Background Information,
420
Selection of Indicators for Estimating the Requirement for Molybdenum,
422
Factors Affecting the Molybdenum Requirement,
424
Findings by Life Stage and Gender Group,
425
Intake of Molybdenum,
432
Tolerable Upper Intake Levels,
433
Research Recommendations for Molybdenum,
439
References,
439
12
ZINC
442
Summary,
442
Background Information,
442
Selection of Indicators for Estimating the Requirement for Zinc,
447
Factors Affecting the Zinc Requirement,
454
Findings by Life Stage and Gender Group,
458
Intake of Zinc,
480
Tolerable Upper Intake Levels,
481
Research Recommendations for Zinc,
488
References,
489
13
ARSENIC, BORON, NICKEL, SILICON, AND VANADIUM
502
Summary,
502
Arsenic,
503
Boron,
510
Nickel,
521
Silicon,
529
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Vanadium,
532
References,
543
14
USES OF DIETARY REFERENCE INTAKES
554
Overview,
554
Assessing Nutrient Intakes of Individuals,
555
Assessing Nutrient Intakes of Groups,
558
Planning Nutrient Intakes of Individuals,
562
Planning Nutrient Intakes of Groups,
563
Nutrient-Specific Considerations,
564
Summary,
576
References,
578
15
A RESEARCH AGENDA
580
Approach,
580
Major Knowledge Gaps,
581
The Research Agenda,
584
APPENDIXES
A
Origin and Framework of the Development of Dietary Reference Intakes,
587
B
Acknowledgments,
591
C
Dietary Intake Data from the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994,
594
D
Dietary Intake Data from the Continuing Survey of Food Intakes By Individuals (CSFII), 1994–1996,
644
E
Dietary Intake Data from the U.S. Food and Drug Administration Total Diet Study, 1991–1997,
654
F
Canadian Dietary Intake Data, 1990,
674
G
Biochemical Indicators for Iron, Vitamin A, and Iodine from the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994,
680
H
Comparison of Vitamin A and Iron Intake and Biochemical Indicators from the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994,
692
I
Iron Intakes and Estimated Percentiles of the Distribution of Iron Requirements from the Continuing Survey of Food Intakes by Individuals (CSFII), 1994–1996,
697
J
Glossary and Acronyms,
704
K
Conversion of Units,
709
L
Options for Dealing with Uncertainties,
710
M
Biographical Sketches of Panel and Subcommittee Members,
715
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INDEX
729
SUMMARY TABLE, Dietary Reference Intakes: Recommended Intakes for Individuals, Vitamins
770
SUMMARY TABLE, Dietary Reference Intakes: Recommended Intakes for Individuals, Elements
772
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DIETARY REFERENCE INTAKES FOR Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
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