GUIDING PRINCIPLES FOR

Developing Dietary Reference Intakes
Based on Chronic Disease

Committee on the Development of Guiding Principles for the Inclusion
of Chronic Disease Endpoints in Future Dietary Reference Intakes

Shiriki Kumanyika and Maria P. Oria, Editors

Food and Nutrition Board

Health and Medicine Division

A Consensus Study Report of

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This activity was supported by the Agricultural Research Service of the U.S. Department of Agriculture (Grant # 59-0204-5-001); Health Canada (Contract No. 4500358459); the National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Dietary Supplements of the National Institutes of Health; the Office of Disease Prevention and Health Promotion of the U.S. Department of Health and Human Services; the U.S. Centers for Disease Control and Prevention (Contract No. HHSN263201200074I); and the U.S. Food and Drug Administration. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-46256-3
International Standard Book Number-10: 0-309-46256-8
Digital Object Identifier: https://doi.org/10.17226/24828

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2017. Guiding principles for developing Dietary Reference Intakes based on chronic disease. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/24828.

COMMITTEE ON THE DEVELOPMENT OF GUIDING PRINCIPLES FOR THE INCLUSION OF CHRONIC DISEASE ENDPOINTS IN FUTURE DIETARY REFERENCE INTAKES

SHIRIKI KUMANYIKA (Chair), Emeritus Professor of Epidemiology, University of Pennsylvania Perelman School of Medicine, Research Professor, and Chair, African American Collaborative Obesity Research Network, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania

CHERYL ANDERSON, Associate Professor, Department of Family and Preventive Medicine, University of California, San Diego

SUSAN I. BARR, Professor Emeritus of Food Nutrition and Health, University of British Columbia, Vancouver

KATHRYN G. DEWEY, Distinguished Professor, Department of Nutrition, University of California, Davis

GORDON GUYATT, Distinguished Professor, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario

JANET C. KING, Professor Emeritus, University of California, Berkeley and Davis, Senior Scientist, Children’s Hospital Oakland Research Institute, Oakland, California

MARIAN L. NEUHOUSER, Full Member, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington

ROSS L. PRENTICE, Member, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington

JOSEPH RODRICKS, Founding Principal, Ramboll Environ, Arlington, Virginia

PATRICK J. STOVER, Professor and Director, Division of Nutritional Sciences, Cornell University, Ithaca, New York

KATHERINE L. TUCKER, Professor of Nutritional Epidemiology, University of Massachusetts Lowell

ROBERT B. WALLACE, Irene Ensminger Stecher Professor of Epidemiology and Internal Medicine, The University of Iowa

Study Staff

MARIA P. ORIA, Study Director

ALICE VOROSMARTI, Research Associate

RENEÉ GETHERS, Senior Program Assistant

FAYE HILLMAN, Financial Officer

ANN L. YAKTINE, Director, Food and Nutrition Board

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NOTE: See Appendix F, Disclosure of Conflict of Interest.

Consultants

WEIHSUEH A. CHIU, Professor, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University

ANNE RODGERS, Science Writer

Reviewers

This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, 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 thank the following individuals for their review of this report:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by Diane F. Birt, Iowa State University, and David B. Allison, University of Alabama at Birmingham. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.

Preface

Identifying minimum recommended intakes of food substances known to be essential for preventing life-threatening nutritional deficiency diseases has been a prominent and longstanding stream in nutrition research, with a complementary focus on identifying high intakes likely to result in adverse health effects. Adequate and safe (non-toxic) intakes are expressed as quantitative thresholds around the lower and upper ends, respectively, of a distribution of possible intakes of the nutrient or food substance in question. Having such thresholds—termed Dietary Reference Intakes (DRIs)—is critical for a variety of food and nutrition policy uses. DRIs are intended for application to the apparently healthy population rather than those with medical conditions requiring specialized diets. However, within healthy populations, DRIs also must account for potential differences in nutritional needs and vulnerabilities by age, developmental stage, gender, reproductive status, and other population characteristics that may influence the adequacy and safety of a given nutrient intake.

The process of developing DRIs involves deliberations of expert panels convened under the rubric of the Food and Nutrition Board (FNB) of the Health and Medicine Division of the National Academies of Sciences, Engineering, and Medicine (the National Academies) and involves collaboration between the United States and Canada. This is both a policy-driven and science-driven process. The policy relevant questions about nutrition and health issues are developed by federal agencies. Scientists on DRI committees consider relevant evidence and draw conclusions about intake levels appropriate as DRI values, which are then translated by the

agencies for policy purposes. This consensus study reflects a new set of challenges that has entered into the realm of DRI development for which the study sponsors identified a need for clearer guidance to DRI committees. The challenges relate to how to formally incorporate chronic disease considerations.

Chronic disease considerations have already been included in some DRI committee deliberations to enhance the evidence picture for making judgments about adequacy and safety or because of the DRI committee’s awareness of extant chronic disease issues in their particular sphere of interest. The statement of task for this consensus study asks the committee to develop guidance for making judgments about reference intakes for reducing chronic disease risk per se. As explained in detail in the committee’s Consensus Study Report, nutrient-chronic disease risk questions, concepts, and methods are qualitatively different from those for adequacy and safety issues. Nutrient-related chronic disease questions address risk within the range already determined to be safe and adequate and address probable, long-term effects on multifactorial pathways instead of the rapid-onset effects of specific nutrients that are associated with traditional DRI questions. The multiple U.S. federal agencies collaborating to sponsor this study indicate the breadth of policy interests and considerations for which chronic disease DRIs may be relevant: the Agricultural Research Service of the U.S. Department of Agriculture; the National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Dietary Supplements at the National Institutes of Health; the Office of Disease Prevention and Health Promotion of the U.S. Department of Health and Human Services; the U.S. Centers for Disease Control and Prevention; and the U.S. Food and Drug Administration. Health Canada is also a sponsor of this study, reflecting a longstanding tradition of U.S.–Canadian collaboration on DRIs.

The statement of task was based on results of prior, substantive deliberations over a 2-year period on the question of how to develop chronic disease DRIs. These deliberations resulted in the publication Options for Basing Dietary Reference Intakes (DRIs) on Chronic Disease Endpoints: Report from a Joint US-/Canadian-sponsored Working Group¹ (i.e., the Options Report), which articulated the scientific and policy context for such an undertaking. It identified a series of issues to be resolved and set

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¹ Yetley, E. A., A. J. MacFarlane, L. S. Greene-Finestone, C. Garza, J. D. Ard, S. A. Atkinson, D. M. Bier, A. L. Carriquiry, W. R. Harlan, D. Hattis, J. C. King, D. Krewski, D. L. O’Connor, R. L. Prentice, J. V. Rodricks, and G. A. Wells. 2017. Options for basing Dietary Reference Intakes (DRIs) on chronic disease endpoints: Report from a joint US-/Canadian-sponsored working group. Am J Clin Nutr 105(1):249S-285S.

out specific options for resolving them, including addressing the question of how a chronic disease DRI process would relate to the existing process. The study committee was asked to consider these options and develop guiding principles that would serve future DRI committees. The 12 members and 1 consultant named to the committee included scholars whose combined expertise covers a spectrum of relevant areas: nutrient requirements and metabolism, maternal and child nutrition, methods in nutrition epidemiology and chronic disease epidemiology, preventive medicine, biostatistics, methods of systematic literature review and use of evidence in guideline development, toxicology and risk analysis, the DRI process, and other areas of dietary guidance and nutrition policy. At a day-long workshop early in its deliberations, the committee also obtained vital input from top experts on the topics it was to address, particularly about emerging methodological advances that could improve the ability of future DRI committees to make judgments about nutrient-chronic disease relationships and intake-response relationships.

The committee members and consultant, three of whom had participated in developing the above-mentioned Options Report, exhibited an outstanding depth of knowledge, collegiality, and commitment to achieving the assigned tasks. Over the course of three in-person meetings and several teleconferences, it became clear that they understood that this next phase of DRI development would require bridging across disciplinary perspectives and blending various areas of knowledge and experience, and that doing so would be necessary for nutrition guidance to evolve along with changing public health contexts.

This report would not have been possible without the energy, patience, dedication, and expertise of the FNB staff. Maria Oria, the study director, together with Ann Yaktine, Alice Vorosmarti, and Reneé Gethers, have worked tirelessly and creatively to help us with our task within the relatively short, 10-month, period available to complete this fast-track study. On behalf of the committee, I express my utmost appreciation for their efforts.

Finally, I remind readers that this guiding principles report points to pathways for finding answers rather than providing answers themselves. Its value will be found only as it helps future DRI committees draw conclusions that do justice to the unique aspects of nutrition—as a universal and fundamental exposure affecting the health of all people—while also using the most rigorous methodologies available when making judgments about how a nutrient or other food substance contributes to health risks and benefits. Some level of uncertainty will be inherent in any judgments about nutrient-chronic disease associations, especially when substantial

gaps in the relevant evidence exist. The committee sought to minimize this uncertainty wherever possible by facilitating use of a comprehensive and rigorous process for evaluating the evidence that is available. We hope the report will have a positive influence on standards for evidence generation in this critical area of public health.

Shiriki Kumanyika, Chair
Committee on the Development of Guiding Principles for the Inclusion of Chronic Disease Endpoints in Future Dietary Reference Intakes

Contents

Summary

1 Introduction

2 The Current Process to Establish Dietary Reference Intakes

3 Conceptual and Methodological Challenges in Establishing Chronic Disease Dietary Reference Intakes

4 Methodological Considerations Related to Assessing Intake of Nutrients or Other Food Substances

5 Measuring Chronic Disease Outcomes

6 Evidence Review: Judging the Evidence for Causal Relationships

7 Intake-Response Relationships and Dietary Reference Intakes for Chronic Disease

8 The Process for Establishing Chronic Disease Dietary Reference Intakes

APPENDIXES

A Open Session Agendas

B Options Report

C Acronyms and Abbreviations

D Definitions

E Biographical Sketches of Committee Members

F Disclosure of Conflict of Interest