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DRI Dietary Reference Intakes Calcium Vitamin D DRI DIETARY REFERENCE INTAKES Calcium Vitamin D Committee to Review Dietary Reference Intakes for Vitamin D and Calcium Food and Nutrition Board A. Catharine Ross, Christine L. Taylor, Ann L. Yaktine, and Heather B. Del Valle, Editors INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu
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DRI Dietary Reference Intakes Calcium Vitamin D THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 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 study was supported by Contract No. 4500196976 between the National Academy of Sciences and Health Canada; Contract No. 59-0204-8-155 between the National Academy of Sciences and the U.S. Department of Agriculture, Agriculture Research Service; Contract No. CNPP-08-0001 between the National Academy of Sciences and the U.S. Department of Agriculture (Center for Nutrition Policy and Promotion); Contract No. W81XWH-09-1-0288 between the National Academy of Sciences and the U.S. Department of the Army; Contract No. HHSF223200811157P between the National Academy of Sciences and the U.S. Department of Health and Human Services, Food and Drug Administration; Contract No. N01-OD-4-2139 between the National Academy of Sciences and the U.S. Department of Health and Human Services (National Institutes of Health); Contract No. HHSP223200800002T between the National Academy of Sciences and the U.S. Department of Health and Human Services (Office of Disease Prevention and Health Promotion). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project. Library of Congress Cataloging-in-Publication Data Dietary reference intakes for calcium and vitamin D / Committee to Review Dietary Reference Intakes for Vitamin D and Calcium, Food and Nutrition Board ; A. Catharine Ross … [et al.], editors. p. ; cm. Includes bibliographical references and index. ISBN 978-0-309-16394-1 (hardcover : alk. paper) — ISBN 978-0-309-16395-8 (pdf) 1. Calcium in the body. 2. Vitamin D in the body. 3. Calcium in human nutrition. 4. Vitamin D in human nutrition. 5. Dietary supplements. I. Ross, A. Catharine. II. Institute of Medicine (U.S.). Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. [DNLM: 1. Calcium, Dietary. 2. Vitamin D. 3. Nutrition Policy. 4. Nutritional Requirements. QU 130] QP535.C2D54 2011 612.3’99—dc22 2011004590 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu. Copyright 2011 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 serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin. Suggested citation: IOM (Institute of Medicine). 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press.
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DRI Dietary Reference Intakes Calcium Vitamin D “Knowing is not enough; we must apply. Willing is not enough; we must do.” —Goethe INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES Advising the Nation. Improving Health.
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DRI Dietary Reference Intakes Calcium Vitamin D THE NATIONAL ACADEMIES Advisers to the Nation on Science, Engineering, and Medicine 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. Ralph J. Cicerone 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. Charles M. Vest 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. Harvey V. Fineberg 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. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council. www.national-academies.org
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DRI Dietary Reference Intakes Calcium Vitamin D COMMITTEE TO REVIEW DIETARY REFERENCE INTAKES FOR VITAMIN D AND CALCIUM A. CATHARINE ROSS (Chair), Professor of Nutrition and Occupant of Dorothy Foehr Huck Chair in Nutrition, The Pennsylvania State University STEVEN A. ABRAMS, Professor of Pediatrics, Baylor College of Medicine JOHN F. ALOIA, Professor, SUNY at Stony Brook, Chief Academic Officer, Winthrop-University Hospital PATSY M. BRANNON, Professor, Division of Nutritional Sciences, Cornell University STEVEN K. CLINTON, Professor, Division of Medical Oncology, The Ohio State University RAMON A. DURAZO-ARVIZU, Associate Professor, Stritch School of Medicine, Loyola University Chicago J. CHRISTOPHER GALLAGHER, Professor of Medicine, Creighton University Medical Center RICHARD L. GALLO, Professor of Medicine and Pediatrics, University of California–San Diego GLENVILLE JONES, Head, Department of Biochemistry and Professor of Biochemistry & Medicine, Queens University, Ontario CHRISTOPHER S. KOVACS, Professor of Medicine (Endocrinology), Memorial University of Newfoundland JOANN E. MANSON, Professor of Medicine and the Elizabeth Brigham Professor of Women’s Health, Harvard Medical School SUSAN T. MAYNE, Professor of Epidemiology and Public Health, Yale School of Public Health CLIFFORD J. ROSEN, Senior Scientist, Maine Medical Center Research Institute SUE A. SHAPSES, Professor, Department of Nutritional Sciences, Rutgers University Consultant HECTOR F. DELUCA, University of Wisconsin–Madison Study Staff CHRISTINE L. TAYLOR, Study Director ANN L. YAKTINE, Senior Program Officer HEATHER B. DEL VALLE, Associate Program Officer HEATHER BREINER, Program Associate
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DRI Dietary Reference Intakes Calcium Vitamin D ANTON BANDY, Financial Officer GERALDINE KENNEDO, Administrative Assistant, Food and Nutrition Board LINDA D. MEYERS, Director, Food and Nutrition Board MARLA SHEFFER, Consultant Technical Editor, Orleans, Ontario
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DRI Dietary Reference Intakes Calcium Vitamin D 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 National Research Council’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: Stephanie A. Atkinson, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada Dennis M. Black, Division of Clinical Trials and Multicenter Studies, University of California, San Francisco Edward M. Brown, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA Lenore M. Buckley, School of Medicine, Virginia Commonwealth University Bess Dawson-Hughes, Bone Metabolism Laboratory, Jean Mayer Human Nutrition Research Center, Tufts University, Boston, MA James C. Fleet, Department of Foods and Nutrition, Purdue University, West Lafayette, IN Richard David Granstein, Department of Dermatology, Weill Cornell Medical College, Ithaca, NY
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DRI Dietary Reference Intakes Calcium Vitamin D Susan Harris, Bone Metabolism Laboratory, Jean Mayer Human Nutrition Research Center, Tufts University, Boston, MA Robert P. Heaney, Creighton University Medical Center, Omaha, NE Janet C. King, University of California at Berkeley and Davis, Children’s Hospital Oakland Research Institute, Oakland Michal Leora Melamed, Department of Medicine and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY Robert L. Modlin, University of California, Los Angeles Ann Prentice, MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom Connie M. Weaver, Department of Foods and Nutrition, Purdue University, West Lafayette, IN Walter C. Willett, Department of Nutrition, Harvard School of Public Health, Boston, MA Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Irwin H. Rosenberg, Friedman School of Nutrition Science and Policy, Tufts University, and Enriqueta C. Bond, Burroughs Wellcome Fund (retired). 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 committee and the institution.
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DRI Dietary Reference Intakes Calcium Vitamin D Preface It has been an honor to chair this committee tasked with reviewing Dietary Reference Intake (DRI) values for calcium and vitamin D. In this preface, I would like, first and foremost, to thank those persons without whose help this report would not have been possible. I also would like to comment briefly on the nature of the task we had at hand, and how our committee proceeded, from its first meeting in 2009 to the final stage of its report. The work of our committee was preceded by three important papers and reports. At a time when interest in vitamin D had reached new heights, and many various claims for benefits were reported, health professionals in the governments of the United States and Canada worked together to address the question: Since the 1997 IOM report on DRIs, including vitamin D, is there sufficient new evidence on this micronutrient to warrant a new DRI study? The publication from this group, “Dietary reference intakes for vitamin D: justification for a review of the 1997 values”1 concluded that there were sufficient new data to warrant a reevaluation. In funding the DRI review for vitamin D, the sponsors also judged that calcium should be reviewed as well, given its interrelationship with vitamin D. I thank the many individuals from the U.S. and Canadian governments who put into motion the processes that led to this report. Moreover, understanding that 1 Yetley, E. A., D. Brule, M. C. Cheney, C. D. Davis, K. A. Esslinger, P. W. Fischer, K. E. Friedl, L. S. Greene-Finestone, P. M. Guenther, D. M. Klurfeld, M. R. L’Abbe, K. Y. McMurry, P. E. Starke-Reed and P. R. Trumbo. 2009. Dietary reference intakes for vitamin D: justification for a review of the 1997 values. American Journal of Clinical Nutrition 89(3): 719-27.
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DRI Dietary Reference Intakes Calcium Vitamin D a review of the literature would be a tremendous undertaking by itself, this group also commissioned an independent systematic review of the literature on vitamin D and health outcomes for the use of this DRI committee, and intended to update an earlier systematic review on vitamin D and bone health. The systematic review carried out by Dr. Joseph Lau and his colleagues at the Tufts Evidence-based Practice Center, and a preceding systematic review led by Dr. Ann Cranney of the University of Ottawa, both greatly aided the work of the current committee. In the Statement of Task, the sponsors requested that our report be developed using a risk assessment framework. Such a framework is not one that committee members would naturally have been familiar with at the outset, and some readers of this report may also wonder, “What is that?” The process is discussed and diagrammed in the report in Chapter 1 and referred to throughout. We were greatly helped in adhering to the risk assessment approach by Christine Taylor, Ph.D., Study Director for this DRI study, whose previous background paper, “Framework for DRI Development,”2 provided us with a much-needed understanding of the uses of risk assessment and the steps in conducting it that we would follow. Chris’ insights, as well as her discipline, good humor, and willingness to engage over and over in discussions to obtain a broad understanding and consensus were very much at the heart of the committee’s process. I thank her for being the amazing study director she has been. Our committee’s work also benefited from the excellent research and support of Ann Yaktine, Ph.D., Heather Del Valle, and Heather Breiner. Linda Meyers, Ph.D., Director, Food and Nutrition Board, kept a watchful eye on our progress and willingly provided guidance as needed. The committee never lacked for exceptionally well-qualified, rigorous, hardworking, professional, and friendly support from the FNB staff, and I sincerely thank each one of them. It may be of interest to briefly comment on the committee’s approach, and how work evolved during its deliberations. The development of IOM reports is a consensus process. Thus, throughout we worked together, dividing specific tasks according to expertise but making sure that discussions proceeded and decisions were always made as a group. During this time, research did not stand still; not a week passed without new publications on these nutrients. We spent a good deal of effort, and staff performed invaluable service for us, in arraying new data, comparing aspects of study design, etc. The committee worked not only at the scheduled committee meetings, but also in a myriad of working groups by conference calls and emails. It was important to keep firmly in mind that DRIs are values meant for im- 2 Taylor, C. L. 2008. Framework for DRI Development: Components “Known” and Components “To Be Explored.” Washington, DC.
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DRI Dietary Reference Intakes Calcium Vitamin D proving public health—the health of the general population of the United States and Canada. They provide recommendations for adequate and safe daily intakes of nutrients consumed over many years, possibly a lifetime, not just for days, weeks, months, or a year. Thus, the need for sound, causal evidence to make the evidence-based recommendations in this report was always at the forefront of our thinking and deliberations. The terms causality, dose–response, evidence-based, totality of evidence, uncertainty, caveats were often on the committee minds and prominent in our discussions. On some points, we consulted with experts, whom we thank for generously providing their input in response to our needs, sometimes on quite short notice. New data on the intakes of vitamin D and calcium in the United States and Canada arrived from the Centers for Disease Control and Prevention and Health Canada just as we needed them, and here I would like to thank the persons in these organizations who worked diligently to make these new intake data available for the committee’s use. As DRI values evolved, we thought carefully about the implications of these recommendations for practitioners and decision makers in public health and policy who will use this report in their work, and for special populations in both the United States and Canada. Lastly, we considered research recommendations, linking our recommendations to knowledge gaps identified while using the risk assessment framework. This, of course, was a future-directed activity, and we hope that our recommendations will clarify the types of research and resulting new information that will make determining DRIs for calcium and vitamin D easier and more accurate in the future. Throughout, the committee members worked together with common purpose and always amicably, even when viewpoints differed, and this made working on this study a remarkable experience for all of us. I sincerely thank all the members of the committee for sharing their expertise and greatly enriching the development of this report. Finally, it is important to acknowledge the many people who assisted the committee with its work and who provided technical input and invaluable perspectives through a variety of venues ranging from white papers to participation in workshops and public information gathering meetings. Foremost, the committee is grateful to Dr. Hector DeLuca, who served as a tireless consultant and generously offered his wisdom and considerable experience to the committee. Many discussions were enriched by his input. Others who provided scientific evaluations and background information for the committee include: Dr. David Bushinsky, Dr. Thomas Carpenter, Dr. Gary Curhan, Dr. Gordon Guyatt, Dr. Craig Langman, Dr. Dwight Towler, and Dr. Susan Whiting. The committee is deeply appreciative of the heroic efforts of those who worked long hours to provide the committee timely national data on calcium and vitamin D intake as well as measures of serum 25-hydroxyvitamin D concentrations, specifically the
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DRI Dietary Reference Intakes Calcium Vitamin D National Center for Health Statistics (Mr. Clifford Johnson, Dr. Lester R. Curtin, and Dr. Te-Ching Chen), the U.S. Department of Agriculture (Ms. Alanna Moshfegh and Ms. Joanne Holden), the National Cancer Institute (Dr. Kevin Dodd), and Statistics Canada (Mrs. Jeanine Bustros, Mr. Didier Garriguet, Mr. Christopher Oster, and Miss Dawn Warner). Also, invaluable and illuminating analytical assistance was provided by statisticians at Cornell University, Dr. Francoise Vermeylen and Dr. Shamil Sadigov. Finally, the committee wishes to thank the sponsors of this report for their support and without whom there would not have been the opportunity to carry out this important study. A. Catharine Ross, Chair Committee to Review Dietary Reference Intakes for Vitamin D and Calcium
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DRI Dietary Reference Intakes Calcium Vitamin D Contents SUMMARY 1 The Committee and Its Charge, 2 DRI Context for Committee’s Work, 2 The Committee’s Approach and Examination of Data, 3 Key Challenges, 6 The Committee’s Outcomes, 7 Dietary Intake Assessment, 10 Implications and Special Concerns, 11 Conclusions About Vitamin D Deficiency in the United States and Canada, 13 1 INTRODUCTION 15 The Task, 16 The Dietary Reference Intake Framework, 17 The Approach, 29 2 OVERVIEW OF CALCIUM 35 Introduction, 35 Sources of Calcium, 36 Metabolism of Calcium, 38 Functions and Physiological Actions of Calcium, 42 Calcium Across the Life Cycle, 52 Bone Mass Measures Associated with Calcium, 57 Other Factors Related to Calcium Nutriture, 62
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DRI Dietary Reference Intakes Calcium Vitamin D 3 OVERVIEW OF VITAMIN D 75 Introduction, 75 Sources of Vitamin D, 79 Metabolism of Vitamin D, 83 Functions and Physiological Actions of Vitamin D, 89 Vitamin D Across the Life Cycle, 94 Measures Associated with Vitamin D: Serum 25OHD, 96 Measures Associated with Vitamin D: Parathyroid Hormone, 111 4 REVIEW OF POTENTIAL INDICATORS OF ADEQUACY AND SELECTION OF INDICATORS: CALCIUM AND VITAMIN D 125 Approach, 125 Review of Potential Indicators, 134 Considerations Related to African American Ancestry, 294 Selection of Indicators, 298 5 DIETARY REFERENCE INTAKES FOR ADEQUACY: CALCIUM AND VITAMIN D 345 Overview, 345 Calcium: Dietary Reference Intakes for Adequacy, 348 Vitamin D: Dietary Reference Intakes for Adequacy, 362 6 TOLERABLE UPPER INTAKE LEVELS: CALCIUM AND VITAMIN D 403 Calcium Upper Levels: Review of Potential Indicators and Selection of Indicators, 405 Calcium Upper Levels: Intake-Response Assessment and Specification of Upper Levels, 418 Vitamin D Upper Levels: Review of Potential Indicators and Selection of Indicators, 424 Vitamin D Upper Levels: Intake-Response Assessment and Specification of Upper Levels, 440 7 DIETARY INTAKE ASSESSMENT 457 The National Surveys and Approach Used, 457 Calcium Intake, 463 Vitamin D Intake and Serum 25OHD Concentrations, 468 Differences Between the United States and Canada: National Survey Data for Calcium and Vitamin D, 474 Summary, 477 8 IMPLICATIONS AND SPECIAL CONCERNS 479 Summary of Assessment, 479 Implications, 481 Population Segments and Conditions of Interest, 490
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DRI Dietary Reference Intakes Calcium Vitamin D 9 INFORMATION GAPS AND RESEARCH NEEDS 513 Step 1: “Hazard Identification” or Indicator Review and Selection, 516 Step 2: “Hazard Characterization” or Intake-Response Assessment and Specification of Dietary Reference Intakes, 519 Step 3: Intake Assessment, 520 Related Research Need, 521 Concluding Remarks, 522 APPENDIXES* A Acronyms, Abbreviations, and Glossary 523 B Issues and Interests Identified by Study Sponsors 537 C Methods and Results from the AHRQ-Ottawa Evidence-Based Report on Effectiveness and Safety of Vitamin D in Relation to Bone Health 539 D Methods and Results from the AHRQ-Tufts Evidence-Based Report on Vitamin D and Calcium 725 E Literature Search Strategy 1013 F Evidence Maps 1019 G Case Studies of Vitamin D Toxicity 1025 H Estimated Intakes of Calcium and Vitamin D from National Surveys 1035 I Proportion of the Population Above and Below 40 nmol/L Serum 25-Hydroxyvitamin D Concentrations and Cumulative Distribution of Serum 25-Hydroxyvitamin D Concentrations: United States and Canada 1045 J Workshop Agenda and Open Session Agendas 1059 K Biographical Sketches of Committee Members 1065 INDEX 1075 SUMMARY TABLES Estimated Average Requirements, 1104 Recommended Dietary Allowances and Adequate Intakes, Vitamins, 1106 Recommended Dietary Allowances and Adequate Intakes, Elements, 1108 Recommended Dietary Allowances and Adequate Intakes, Total Water and Macronutrients, 1110 Acceptable Macronutrient Distribution Ranges, 1111 Additional Macronutrient Recommendations, 1111 Tolerable Upper Intake Levels, Vitamins, 1112 Tolerable Upper Intake Levels, Elements, 1114 * Appendixes B through K are not printed in this book, but can be found on the CD at the back of the book or online at http://www.nap.edu.
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