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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline
DRI DIETARY REFERENCE INTAKES
FOR Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline
A Report of the
Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients
Food and Nutrition Board
Institute of Medicine
NATIONAL ACADEMY PRESS
Washington, D.C.
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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline
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, T01; the National Institutes of Health Office of Nutrition Supplements, Contract No. N01–OD–4–2139, T024, 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; 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, 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 thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline/a report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients, Food and Nutrition Board, Institute of Medicine.
p. cm.
Includes bibliographical references and index.
ISBN 0-309-06554-2 (pbk.) —ISBN 0-309-06411-2 (case)
1. Vitamin B in human nutrition. 2. Reference values (Medicine) I. Institute of Medicine (U.S.). Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. II. Institute of Medicine (U.S.). Panel on Folate, Other B Vitamins, and Choline. III. Institute of Medicine (U.S.). Subcommittee on Upper Reference Levels of Nutrients.
QP772.V52 D53 2000
612.3′99–dc21
00–028380
Additional copies of this report are available from
National Academy Press,
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For more information about the Institute of Medicine or the Food and Nutrition Board, visit the IOM home page at http://www.nas.edu/iom.
Copyright 1998 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
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“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. 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.
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PANEL ON FOLATE, OTHER B VITAMINS, AND CHOLINE
ROY M.PITKIN (Chair),
Department of Obstetrics and Gynecology, University of California, Los Angeles
(Professor Emeritus)
and Obstetrics & Gynecology
(Editor),
Los Angeles
LINDSAY H.ALLEN,
Department of Nutrition, University of California, Davis
LYNN B.BAILEY,
Food Science and Human Nutrition Department, University of Florida, Gainesville
MERTON BERNFIELD,
Department of Pediatrics, Harvard Medical School, Boston
PHILLIPE De WALS,
Department of Community Health Sciences, University of Sherbrooke, Quebec
RALPH GREEN,
Department of Pathology, University of California at Davis Medical Center, Sacramento
DONALD B.McCORMICK,
Department of Biochemistry, Emory University School of Medicine, Atlanta
ROBERT M.RUSSELL,
Department of Medicine and Nutrition at the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston
BARRY SHANE,
Department of Nutritional Sciences, University of California, Berkeley
STEVEN H.ZEISEL,
Department of Nutrition, University of North Carolina School of Public Health and School of Medicine, Chapel Hill
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, Liaison to the Panel from the Subcommittee on Upper Reference Levels of Nutrients
Staff
CAROL W.SUITOR, Study Director
ELISABETH A.REESE, Research Associate
ALICE L.KULIK, Research Assistant
MICHELE RAMSEY, Project Assistant
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SUBCOMMITTEE ON UPPER REFERENCE LEVELS OF NUTRIENTS
IAN C.MUNRO (Chair),
CanTox, Inc., Mississauga, Ontario
WALTER MERTZ,
Retired, U.S. Department of Agriculture Human Nutrition Research Center, Rockville, Maryland
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,
Department of Nutritional Sciences, University of California, Berkeley
JOSEPH V.RODRICKS,
ENVIRON Corporation, Arlington, Virginia
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
STEVE L.TAYLOR,
Department of Food Science and Technology and Food Processing Center, University of Nebraska, Lincoln
ROBERT H.WASSERMAN,
Department of Physiology, College of Veterinary Medicine, Cornell University, Ithaca
Consultants
SHEILA DUBOIS,
Food Directorate, Health Canada, Ottawa
HERBERT BLUMENTHAL,
Retired, Food and Drug Administration, Washington, D.C.
Staff
SANDRA SCHLICKER, Study Director
ELISABETH A.REESE, Research Associate
GERALDINE KENNEDO, 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
JANET C.KING (Vice-Chair),
University of California, Berkeley, and U.S. Department of Agriculture Western Human Nutrition Research Center, Presidio of San Francisco
LINDSAY H.ALLEN,
Department of Nutrition, University of California, Davis
STEPHANIE A.ATKINSON,
Department of Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario
JOHANNA T.DWYER,
Frances Stern Nutrition Center, New England Medical Center and Tufts University, Boston
JOHN D.FERNSTROM,
Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh
SCOTT M.GRUNDY,
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas
CHARLES H.HENNEKENS,
Department of Medicine, Ambulatory Care and Prevention and Division of Preventive Medicine, Harvard Medical School, Boston
SANFORD A.MILLER,
Graduate School of Biomedical Sciences, University of Texas Health Science Center, San Antonio
U.S. Government Liaison
LINDA MEYERS,
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
Staff
ALLISON A.YATES, Study Director
SANDRA SCHLICKER, Senior Program Officer
CAROL W.SUITOR, Senior Program Officer
ELISABETH A.REESE, Research Associate
ALICE L.KULIK, Research Assistant
GAIL E.SPEARS, Administrative Assistant
GERALDINE KENNEDO, Project Assistant
MICHELE RAMSEY, Project Assistant
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FOOD AND NUTRITION BOARD
CUTBERTO GARZA (Chair),
Division of Nutrition, Cornell University, Ithaca
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
BENJAMIN CABALLERO,
Center for Human Nutrition, Johns Hopkins School of Hygiene and Public Health, Baltimore
ROBERT J.COUSINS,
Center for Nutritional Sciences, University of Florida, Gainesville
FERGUS M.CLYDESDALE,
Department of Food Science, University of Massachusetts, Amherst
MICHAEL P.DOYLE,
Department of Food Science and Technology, Center for Food Safety and Quality Enhancement, University of Georgia, Griffin
JOHANNA T.DWYER,
Frances Stern Nutrition Center, New England Medical Center and Tufts University, Boston
SCOTT M.GRUNDY,
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas
CHARLES H.HENNEKENS,
Department of Medicine, Ambulatory Care and Prevention and Division of Preventive Medicine, Harvard Medical School, Boston
JANET C.KING,
University of California, Berkeley, and U.S. Department of Agriculture Western Human Nutrition Research Center, Presidio of San Francisco
SANFORD A.MILLER,
Graduate School of Biomedical Sciences, University of Texas Health Science Center, San Antonio
ROSS L.PRENTICE,
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle
A.CATHARINE ROSS,
Department of Nutrition, The Pennsylvania State University, University Park
ROBERT E.SMITH,
R.E. Smith Consulting, Inc., Newport, Vermont
VIRGINIA A.STALLINGS,
Division of Gastroenterology and Nutrition, The Children’s Hospital of Philadelphia
VERNON R.YOUNG,
Laboratory of Human Nutrition, School of Science, Massachusetts Institute of Technology, Cambridge
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Ex-Officio Member
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
CARLOS GABRIEL, Financial Associate
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Preface
This report is the second 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 scientists from Canada.
The report establishes a set of reference values for the B vitamins and choline to replace previously published Recommended Dietary Allowances (RDAs) for the United States and Recommended Nutrient Intakes (RNIs) for Canada. It considers evidence concerning the prevention of disease and developmental disorders along with more traditional evidence of sufficient nutrient intake; and examines data about choline, a food component that in the past has not been considered essential in the human diet. Although the reference values are based on data, the data were often scanty or drawn from studies that had limitations in addressing the question. Thus, scientific judgment was required in setting the reference values. The reasoning used is described for each nutrient in Chapters 4 through 12. Evidence concerning the use of these nutrients for the amelioration or cure of disease or disability was not considered because that was beyond the project’s scope of work.
The B vitamins appear second in the series largely because recommendations for folate intake have been a subject of controversy for many years. The RDA for folate has shifted up and down. Recently, low folate intake has been linked with vascular disease and other chronic conditions as well as risk of neural tube defects and other
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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 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 authors and the IOM 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 review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their participation in the review of this report: Frederick C.Battaglia, M.D., University of Colorado Health Sciences Center; Enriqueta C.Bond, Ph.D., Burroughs Wellcome Fund; Patricia K.Crumrine, M.D., Children’s Hospital; Krishnamurti Dakshinamurti, Ph.D., University of Manitoba; Gary Flamm, Ph.D., Flamm Associates; Theresa Glanville, Ph.D., Mount Saint Vincent University; John Hathcock, Ph.D., Council for Responsible Nutrition; James Marshall, Ph.D., Arizona Cancer Center; Deborah O’Connor, Ph.D., Ross Laboratories; Claire Regan, M.S., R.D., Grocery Manufacturers of America; Eric Rimm, Sc.D., Harvard School of Public Health; Killian Robinson, M.D., Cleveland Clinic Foundation; Robert Rucker, Ph.D., University of California-Davis; Robert F.Schilling, M.D., University of Wisconsin; John Scott, Ph.D., Sc.D., M.A., University of Dublin, Trinity College.
Although the individuals listed above have provided many constructive comments and suggestions, responsibility for the final content of this report rests solely with the authoring committee and the IOM.
The DRI Committee wishes to acknowledge, in particular, the commitment shown by Roy Pitkin, chair of the panel, who steered this difficult project through what at times seemed to some of us like dangerous and uncharted waters. His ability to keep the effort and our various biases moving in a positive direction is very much appreciated.
Special thanks go to the staff of the Food and Nutrition Board and foremost to Carol Suitor, 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 initial release. She now moves on to enjoy the peace of her new home in beautiful Vermont and we wish her well. It is, of course
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those at the Food and Nutrition Board who get the real work completed and so the committee wishes to thank Allison Yates, Director of the Food and Nutrition Board, for constant assistance and it also recognizes, with appreciation, the contributions of Sandra Schlicker, Elisabeth Reese, Kimberly Brewer, Alice Kulik, Sheila Moats, Gail Spears, Diane Johnson, Michele Ramsey, and Geraldine Kennedo. We also thank Judith Grumstrup-Scott and Judith Dickson 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
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Contents
SUMMARY
1
What Are Dietary Reference Intakes?,
2
Comparison of Recommended Dietary Allowances and Adequate Intakes,
6
Approach for Setting Dietary Reference Intakes,
6
Criteria and Proposed Values for Tolerable Upper Intake Levels,
12
Using Dietary Reference Intakes to Assess the Nutrient Intake of Groups,
14
How to Meet Recommended Dietary Allowances or Adequate Intakes,
14
Recommendations,
15
1
INTRODUCTION TO DIETARY REFERENCE INTAKES
17
What Are Dietary Reference Intakes?,
17
Categories of Dietary Reference Intakes,
18
Parameters for Dietary Reference Intakes,
23
Summary,
26
References,
26
2
THE B VITAMINS AND CHOLINE: OVERVIEW AND METHODS
27
Overview,
27
Methodological Considerations,
28
Estimates of Laboratory Values,
34
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Estimates of Nutrient Intake,
35
Dietary Intakes in the United States and Canada,
36
Summary,
38
References,
38
3
A MODEL FOR THE DEVELOPMENT OF TOLERABLE UPPER INTAKE LEVELS
41
Background,
41
A Model for the Derivation of Tolerable Upper Intake Levels,
42
Risk Assessment and Food Safety,
42
Application of the Risk Assessment Model to Nutrients,
47
Steps in the Development of the Tolerable Upper Intake Level,
50
References,
56
4
THIAMIN
58
Summary,
58
Background Information,
58
Selection of Indicators for Estimating the Requirement for Thiamin,
60
Factors Affecting the Thiamin Requirement,
62
Findings by Life Stage and Gender Group,
65
Intake of Thiamin,
79
Tolerable Upper Intake Levels,
81
Research Recommendations for Thiamin,
82
References,
83
5
RIBOFLAVIN
87
Summary,
87
Background Information,
87
Selection of Indicators for Estimating the Requirement for Riboflavin,
90
Factors Affecting the Riboflavin Requirement,
95
Approaches for Deriving the Estimated Average Requirement,
97
Findings by Life Stage and Gender Group,
103
Intake of Riboflavin,
113
Tolerable Upper Intake Levels,
115
Research Recommendations for Riboflavin,
117
References,
117
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6
NIACIN
123
Summary,
123
Background Information,
123
Selection of Indicators for Estimating the Requirement for Niacin,
126
Factors Affecting the Niacin Requirement,
128
Findings by Life Stage and Gender Group,
130
Intake of Niacin,
137
Tolerable Upper Intake Levels,
138
Research Recommendations for Niacin,
145
References,
145
7
VITAMIN B6
150
Summary,
150
Background Information,
150
Selection of Indicators for Estimating the Requirement for Vitamin B6,
154
Factors Affecting the Vitamin B6 Requirement,
160
Findings by Life Stage and Gender Group,
164
Intake of Vitamin B6,
179
Tolerable Upper Intake Levels,
182
Research Recommendations for Vitamin B6,
188
References,
188
8
FOLATE
196
Summary,
196
Background Information,
197
Selection of Indicators for Estimating the Requirement for Folate,
200
Methodological Issues,
205
Factors Affecting the Folate Requirement,
207
Findings by Life Stage and Gender Group,
214
Reducing Risk of Developmental Disorders and Chronic Degenerative Disease,
240
Intake of Folate,
269
Tolerable Upper Intake Levels,
273
Research Recommendations for Folate,
283
References,
284
9
VITAMIN B12
306
Summary,
306
Background Information,
307
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Selection of Indicators for Estimating the Requirement for Vitamin B12,
312
Methodological Issues,
315
Diagnosis,
316
Factors Affecting the Vitamin B12 Requirement,
318
Findings by Life Stage and Gender Group,
322
Intake of Vitamin B12,
342
Tolerable Upper Intake Levels,
346
Research Recommendations for Vitamin B12,
348
References,
348
10
PANTOTHENIC ACID
357
Summary,
357
Background Information,
357
Selection of Indicators for Estimating the Requirement for Pantothenic Acid,
359
Factors Affecting the Pantothenic Acid Requirement,
361
Findings by Life Stage and Gender Group,
362
Intake of Pantothenic Acid,
368
Tolerable Upper Intake Levels,
370
Research Recommendations for Pantothenic Acid,
371
References,
371
11
BIOTIN
374
Summary,
374
Background Information,
374
Selection of Indicators for Estimating the Requirement for Biotin,
378
Factors Affecting the Biotin Requirement,
380
Findings by Life Stage and Gender Group,
380
Intake of Biotin,
384
Tolerable Upper Intake Levels,
384
Research Recommendations for Biotin,
385
References,
386
12
CHOLINE
390
Summary,
390
Background Information,
390
Selection of Indicators for Estimating the Requirement for Choline,
396
Factors Affecting the Choline Requirement,
398
Findings by Life Stage and Gender Group,
400
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Intake of Choline,
406
Tolerable Upper Intake Levels,
408
Research Recommendations for Choline,
413
References,
414
13
USES OF DIETARY REFERENCE INTAKES
423
Overview,
423
Using Recommended Dietary Allowances,
424
Using Adequate Intakes,
425
Using Tolerable Upper Intake Levels,
426
Using Estimated Average Requirements,
427
Other Uses of Dietary Reference Intakes,
432
Specific Applications,
432
Summary,
435
References,
436
14
A RESEARCH AGENDA
437
Approach,
437
Important Features of Studies to Estimate Requirements,
438
Major Knowledge Gaps,
439
The Research Agenda,
442
APPENDIXES:
A
Origin and Framework of the Development of Dietary Reference Intakes,
443
B
Acknowledgments,
448
C
Système International d’Unités,
451
D
Search Strategies,
453
E
Methodological Problems Associated with Laboratory Values and Food Composition Data for B Vitamins,
456
F
Dietary Intake Data from the Boston Nutritional Status Survey, 1981–1984,
460
G
Dietary Intake Data from the Continuing Survey of Food Intakes by Individuals (CSFII), 1994–1995,
466
H
Dietary Intake Data from the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994,
478
I
Daily Intakes of B Vitamins by Canadian Men and Women, 1990, 1993,
502
J
Options for Dealing with Uncertainties in Developing Tolerable Upper Intake Levels,
507
K
Blood Concentrations of Folate and Vitamin B12 from the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994,
512
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L
Methylenetetrahydrofolate Reductase,
520
M
Evidence from Animal Studies on the Etiology of Neural Tube Defects,
523
N
Estimation of the Period Covered by Vitamin B12 Stores,
527
O
Biographical Sketches,
531
P
Glossary and Abbreviations,
537
INDEX
541
SUMMARY TABLE, Dietary Reference Intakes: Recommended Intakes for Individuals,
566
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DRI DIETARY REFERENCE INTAKES
FOR Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline
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