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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Dietary Reference Intakes for Sodium and Potassium. Washington, DC: The National Academies Press. doi: 10.17226/25353.
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Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Dietary Reference Intakes for Sodium and Potassium Committee to Review the Dietary Reference Intakes for Sodium and Potassium Virginia A. Stallings, Meghan Harrison, and Maria Oria, editors Food and Nutrition Board Health and Medicine Division A Consensus Study Report of PREPUBLICATION COPY: UNCORRECTED PROOFS

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 This activity was supported by contracts between the National Academy of Sciences and the Centers for Disease Control, Food and Drug Administration, Health Canada, National Institutes of Health, Public Health Agency of Canada, and the U.S. Department of Agriculture. This activity was also supported in part, by the National Academy of Sciences W. K. Kellogg Foundation Fund and the National Academy of Medicine. 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-XXXXX-X International Standard Book Number-10: 0-309-XXXXX-X Digital Object Identifier: https://doi.org/10.17226/25353 Library of Congress Control Number OR Cataloging-in-Publication: Additional copies of this publication are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu. Copyright 2019 by the National Academy of Sciences. All rights reserved. Printed in the United States of America Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2019. Dietary Reference Intakes for sodium and potassium. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/25353 PREPUBLICATION COPY: UNCORRECTED PROOFS

The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president. The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. C. D. Mote, Jr., is president. The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president. The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine. Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org. PREPUBLICATION COPY: UNCORRECTED PROOFS

Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task. Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies. For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo. PREPUBLICATION COPY: UNCORRECTED PROOFS

COMMITTEE TO REVIEW THE DIETARY REFERENCE INTAKES FOR SODIUM AND POTASSIUM VIRGINIA A. STALLINGS (Chair), Professor of Pediatrics, University of Pennsylvania Perelman School of Medicine, Director, Nutrition Center, Jean A. Cortner Endowed Chair in Gastroenterology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA CHERYL A. M. ANDERSON, Associate Professor, Department of Family and Preventive Medicine, University of California, San Diego, San Diego, CA (until September 2018) PATSY M. BRANNON, Visiting Professor, Division of Nutritional Sciences, Cornell University, Ithaca, NY ALICIA CARRIQUIRY, Distinguished Professor, Liberal Arts and Sciences, Professor of Statistics, Iowa State University, Ames, IA WEIHSUEH CHIU, Professor, Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX NANCY R. COOK, Professor, Division of Preventative Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA ERIC A. DECKER, Professor, Department Head, Department of Food Science, University of Massachusetts Amherst, Amherst, MA JIANG HE, Joseph S. Copes Chair and Professor, Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA JOACHIM H. IX, Professor and Chief, Division of Nephrology-Hypertension, University of California San Diego School of Medicine, San Diego, CA ALICE H. LICHTENSTEIN, Gershoff Professor of Nutrition Science and Policy, Director and Senior Scientist, Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA JOSEPH V. RODRICKS, Principal, Ramboll Environ, Arlington, VA JANET A. TOOZE, Professor, Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC GEORGE A. WELLS, Professor, Department of Epidemiology and Community Medicine, Director, Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Ontario, CA ELIZABETH A. YETLEY, Senior Nutrition Research Scientist (retired), National Institutes of Health, Office of Dietary Supplements, Bethesda, MD Study Staff MEGHAN HARRISON, Study Director MARIA ORIA, Senior Program Officer ANNA BURY, Research Associate (until August 2018) ALICE VOROSMARTI, Research Associate (from August 2018) MEREDITH YOUNG, Senior Program Assistant ANN L. YAKTINE, Director, Food and Nutrition Board PREPUBLICATION COPY: UNCORRECTED PROOFS v

Consultants EMILY A. CALLAHAN, Science Writer MEI CHUNG, Associate Professor, Public Health and Community Medicine, Tufts University, Boston, MA PAUL WHELTON, Clinical Professor, Show Chwan Health System Endowed Chair in Global Public Health, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA PREPUBLICATION COPY: UNCORRECTED PROOFS vi

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: Lawrence J. Appel, Johns Hopkins Medical Institutions Stephen R. Daniels, University of Colorado School of Medicine Paul Elliott, Imperial College London Mark Espeland, Wake Forest School of Medicine Joseph Lau, Brown University School of Public Health Laura Martino, European Food Safety Authority Andrew Mente, McMaster University Suzanne Murphy, University of Hawaii Cancer Center Martin O’Donnell, National University of Ireland Suzanne Oparil, University of Alabama at Birmingham Hildegard Przyrembel, Federal Institute for Risk Assessment Kristin Reimers, Conagra Brands A. Catharine Ross, The Pennsylvania State University Frank Sacks, Harvard T.H. Chan School of Public Health Barbara Schneeman, University of California, Davis Stephen L. Taylor, University of Nebraska-Lincoln Paula Trumbo, Food and Drug Administration (retired) Connie Weaver, Purdue University Walt Willett, Harvard T.H. Chan School of Public Health 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 Eileen T. Kennedy, Tufts University, and Catherine E. Woteki, Iowa State University. 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. PREPUBLICATION COPY: UNCORRECTED PROOFS vii

Preface As essential nutrients, sodium and potassium contribute to the fundamental physiology of human health. In the clinical setting, these are frequently measured blood electrolytes. Yet, blood electrolyte concentrations are rarely influenced by typical dietary intake in healthy individuals, as the kidney and hormone systems carefully regulate blood values. However, the sodium and potassium intake story is more dynamic in the public health setting. Evidence suggests that sodium and potassium intakes influence current and longer-term population health in children and adults mostly through complex and not fully understood mechanisms between dietary intake and blood pressure and cardiovascular health status. Based on a 2017 report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, 50 percent of men and 44 percent of women ages 45–54 years have clinically significant hypertension, and the prevalence increases with age. This information—such high prevalence of hypertension beginning early in adult life, was a surprise to me. Cardiovascular disease, including diagnoses of cardiovascular disease risk factors such as prehypertension, hypertension, and abnormal blood lipids, is common, and a majority of adults in the United States has more than one cardiovascular disease risk factor. The public health importance of the relationships of sodium and potassium intakes and health is clear. Congress asked the Centers for Disease Control and Prevention (CDC) to undertake a review of the Dietary Reference Intakes (DRIs) for sodium. Given the interrelationship between sodium and potassium, it was determined that assessing both together would be prudent. The CDC, together with the Food and Drug Administration, Health Canada, National Institutes of Health, Public Health Agency of Canada, and the U.S. Department of Agriculture, sponsored this study. The National Academy of Sciences W. K. Kellogg Foundation Fund and the National Academy of Medicine provided additional financial support. The committee was charged to review the available evidence and to update the current DRIs for sodium and potassium. In 2005, the evidence supported an Adequate Intake (AI) for both nutrients, and a Tolerable Upper Intake Level (UL) only for sodium. In addition, we were asked to consider adding, if relevant, sodium and potassium intake values to reduce the risk of chronic disease endpoints. Committee deliberations were guided by three sources: Effects of Dietary Sodium and Potassium Intake on Chronic Disease Outcomes and Related Risk Factors, an Agency for Healthcare Research and Quality (AHRQ) systematic review of the evidence commissioned to be used by this committee; Guiding Principles for Developing Dietary Reference Intakes Based on Chronic Disease; and, the DRI organizing framework. The 2011 DRIs for Calcium and Vitamin D also served as a resource, as it was the most recent DRI report that considered the evidence of dietary intake and chronic disease indicators to make recommendations. PREPUBLICATION COPY: UNCORRECTED PROOFS ix

In addition to these reports, the committee gained insight from expert testimony, additional comprehensive literature searches as needed to ascertain the state of the science on specific questions, and committee expertise and deliberation. Our committee members represented key disciplines and skill sets needed for this work; they dedicated not only significant time and effort, but also created a collaborative environment of learning, lively debate, and commitment to a thorough review prior to making decisions. Implementing the new DRI concept of dietary intake recommendations of reduce the risk of chronic disease was a responsibility the committee embraced. This report provides the first DRI based on chronic disease recommendations and documents both the evidence and the deliberative process to inform future DRI committees considering chronic disease recommendations. Research into cardiovascular disease, hypertension, and diet has been among the priority areas for decades, yet numerous knowledge gaps persist. Additional research is essential to inform the next review of how sodium and potassium dietary intakes affect health across the DRI life stages. High-quality evidence exists to guide dietary recommendations to support the health of the youngest children, oldest adults, and pregnant and lactating women in the United States and Canada is also sparse. Understanding the food and beverage sources of dietary sodium and potassium was not examined in detail, nor were the complex interactions of nonprocessed and processed food availability, cultural and personal taste preference and behavioral components of food choice. However, some common misconceptions came to light. Most of the salt in our modern diet pattern comes from commercially prepared food and beverage components and products, not from salt added by consumers cooking at home or from salt added by the consumer at the time of consumption. When considering sodium sources for the population over 2 years of age, most common sodium sources are breads, pizza, and cured meats and poultry. For children specifically, cheese is the top food category source of sodium, followed by cured meats and poultry, and then mixed dishes including pizza. For the desired public health benefit of reduced sodium intake to be achieved, more attention must be paid by industry to reducing sodium in the food supply and by consumers who have the needed sodium content information and an understanding of how to make health-inspired food choices. Dietary potassium intake is related to specific vegetable or fruit intakes—and then remember that as a population, our vegetable and fruit intake rarely meets the recommended servings per day. When you consider all ages, higher dietary sources of potassium are from milk, white potatoes, and fruit. Coffee is the top source of potassium in people in the 51 years of age and older group in the United States. The committee thoroughly considered the totality of evidence available and used processes now established for DRI review and revisions. Our DRI report provides a sodium intake level as an AI, and with sodium, the report establishes the first Chronic Disease Risk Reduction Intake (CDRR) level. Our report provides a potassium intake level as an AI, and the committee determined there was insufficient evidence to establish a CDRR for potassium. In addition, using the evolving toxicological risk assessment approach, the committee found there was insufficient evidence of risk of excess sodium or potassium intake within the healthy populations to establish a UL for either nutrient. Many other people contributed to this report. Two consultants, Paul Whelton and Mei Chung, provided their advice and guidance to the committee. Emily Callahan provided editorial assistance with the report. The National Academies Research Center, particularly Jorge Mendoza-Torres, provided support and assistance with the design and execution of the committee’s scoping literature searches. The committee was also assisted by Jennifer Garner, PREPUBLICATION COPY: UNCORRECTED PROOFS x

who was an intern on the Food and Nutrition Board in the spring of 2018. The committee would also like to thank both the CDC and Health Canada for providing intake distribution tables and other information requested by the committee. Lastly, as chair, I express my sincere appreciation to each committee member and to each member of our National Academies staff, including Meghan Harrison and Maria Oria, for your extraordinary commitment to the project and to our shared goal to complete this complex task in a way that serves the public’s health and health care in general. We worked well together to prepare a report that will contribute to actively improving the health of children and adults. Virginia A. Stallings, Chair Committee on Dietary Reference Intakes for Sodium and Potassium PREPUBLICATION COPY: UNCORRECTED PROOFS xi

CONTENTS SUMMARY S-1 PART I 1 INTRODUCTION 1-1 Study Overview and Statement of Task, 1-2 Design and Approach to the Study, 1-11 Organization of This Report, 1-12 References, 1-13 2 APPLYING THE GUIDING PRINCIPLES REPORT 2-1 Background, 2-1 The Committee’s Interpretation of the Guiding Principles Report, 2-2 The Chronic Disease Risk Reduction Intake in Context of the Other DRI Categories, 2-17 Summary, 2-19 References, 2-19 3 METHODOLOGICAL CONSIDERATIONS 3-1 Relevant Biological Roles of Potassium and Sodium, 3-1 Methods for Estimating Potassium and Sodium Intake, 3-4 Interactions of Potassium and Sodium, 3-14 Evidence on Subpopulations, 3-19 Summary, 3-20 References, 3-21 PART II 4 POTASSIUM: DIETARY REFERENCE INTAKES FOR ADEQUACY 4-1 Potassium Adequate Intake Levels Established in the 2005 DRI Report, 4-2 Review of Potential Indicators of Potassium Adequacy, 4-2 Dietary Reference Intakes of Potassium Adequacy, 4-9 Summary of Updated Potassium Adequate Intake Values, 4-19 References, 4-20 5 POTASSIUM: DIETARY REFERENCE INTAKES FOR TOXICITY 5-1 Potassium Tolerable Upper Intake Levels in the 2005 DRI Report, 5-1 Review of Potential Indicators of Toxicological Adverse Effects of Excessive Potassium Intake, 5-2 The Committee’s Conclusion Regarding the Tolerable Upper Intake Level for Potassium, 5-12 References, 5-13 PREPUBLICATION COPY: UNCORRECTED PROOFS xiii

6 POTASSIUM: DIETARY REFERENCE INTAKES BASED ON CHRONIC DISEASE 6-1 Review of Chronic Disease Indicators, 6-1 The Committee’s Conclusion Regarding Chronic Disease Risk Reduction Intakes for Potassium, 6-27 References, 6-29 7 POTASSIUM DIETARY REFERENCE INTAKES: RISK CHARACTERIZATION AND SPECIAL CONSIDERATIONS FOR PUBLIC HEALTH 7-1 Risk Characterization Based on Potassium Intake Levels in the U.S. and Canadian Populations, 7-1 Sources of Potassium in the Diet, 7-11 Public Health Implications and Special Considerations, 7-16 References, 7-19 PART III 8 SODIUM: DIETARY REFERENCE INTAKES FOR ADEQUACY 8-1 Sodium Adequate Intake Levels Established in the 2005 DRI Report, 8-2 Review of Potential Indicators of Sodium Adequacy, 8-2 Additional Evidence Considered: Potential Harmful Health Effects of Low Sodium Intakes, 8-9 Dietary Reference Intakes of Sodium Adequacy, 8-18 Summary of Updated Sodium Adequate Intake Values, 8-24 References, 8-26 9 SODIUM: DIETARY REFERENCE INTAKES FOR TOXICITY 9-1 Sodium Tolerable Upper Intake Levels Established in the 2005 DRI Report, 9-1 Review of Potential Indicators of Adverse Effects of Excessive Sodium Intake, 9-2 The Committee’s Conclusion Regarding Tolerable Upper Intake Levels for Sodium, 9-13 References, 9-14 10 SODIUM: DIETARY REFERENCE INTAKES BASED ON CHRONIC DISEASE 10-1 Review and Selection of Chronic Disease Indicators, 10-1 Assessment of Intake–Response for Chronic Disease Indicators, 10-36 The Chronic Disease Risk Reduction Intakes for Sodium, 10-66 Summary, 10-72 References, 10-73 Annex 10-1, 10-82 Annex 10-2, 10-91 PREPUBLICATION COPY: UNCORRECTED PROOFS xiv

11 SODIUM DIETARY REFERENCE INTAKES: RISK CHARACTERIZATION AND SPECIAL CONSIDERATIONS FOR PUBLIC HEALTH 11-1 Risk Characterization Based on Sodium Intake Levels in the U.S. and Canadian Populations, 11-1 The Role of Sodium in the Food Supply and Sources of Sodium in the Diet, 11-15 Public Health Implications and Special Considerations, 11-21 References, 11-25 PART IV 12 KNOWLEDGE GAPS AND FUTURE DIRECTIONS 12-1 Knowledge Gaps and Research Needs, 12-1 Opportunities to Enhance the DRI Process, 12-19 Concluding Remarks, 12-13 References, 12-14 APPENDIXES A ABBREVIATIONS AND ACRONYMS A-1 B OPEN SESSION AGENDAS B-1 C COMMITTEE’S ASSESSMENT OF THE AGENCY FOR HEALTHCARE RESEARCH AND QUALITY SYSTEMATIC REVIEW C-1 D INDICATORS NOT RELEVANT FOR ESTABLISHING DIETARY REFERENCE INTAKE VALUES D-1 E SUPPLEMENTAL LITERATURE SEARCHES E-1 F ESTIMATES OF POTASSIUM AND SODIUM INTAKES FROM BREAST MILK AND COMPLEMENTARY FOODS F-1 G SOURCES OF EVIDENCE FOR POTASSIUM AND SODIUM INTAKE DISTRIBUTIONS G-1 H SUPPLEMENTAL RISK CHARACTERIZATION FIGURES H-1 I COMMITTEE MEMBER BIOGRAPHICAL SKETCHES I-1 J DIETARY REFERENCE INTAKE SUMMARY TABLES J-1 PREPUBLICATION COPY: UNCORRECTED PROOFS xv

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As essential nutrients, sodium and potassium contribute to the fundamentals of physiology and pathology of human health and disease. In clinical settings, these are two important blood electrolytes, are frequently measured and influence care decisions. Yet, blood electrolyte concentrations are usually not influenced by dietary intake, as kidney and hormone systems carefully regulate blood values.

Over the years, increasing evidence suggests that sodium and potassium intake patterns of children and adults influence long-term population health mostly through complex relationships among dietary intake, blood pressure and cardiovascular health. The public health importance of understanding these relationships, based upon the best available evidence and establishing recommendations to support the development of population clinical practice guidelines and medical care of patients is clear.

This report reviews evidence on the relationship between sodium and potassium intakes and indicators of adequacy, toxicity, and chronic disease. It updates the Dietary Reference Intakes (DRIs) using an expanded DRI model that includes consideration of chronic disease endpoints, and outlines research gaps to address the uncertainties identified in the process of deriving the reference values and evaluating public health implications.

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