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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 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, 2101 Constitution Avenue, N.W., Lock 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.nas.edu/iom. Copyright 1998 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.

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline “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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline     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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline     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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline     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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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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 DRI DIETARY REFERENCE INTAKES FOR Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline

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