The Surgeon General's Report on NUTRITION AND HEALTH 1988 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service DHHS (PHS) Publication No. 8840210 For sale by the Superintendent of Documents, U.S. Government Printing Of&e Washington. DC 20402 GPO Stock Nuniber 017M)14O465-1 DEPARTMENT OF HEALTH & HUMAN SERVICES The Surgeon General of the Public Health Service Waehington DC 20201 MESSAGE FROM THE SURGEON GENERAL I am pleased to transmit to the Secretary of the Department of Health and Human Services this first Surgeon General's Report on Nutrition and Health. It was prepared under the auspices of the Department's Nutrition Policy Board, and its main conclusion is that overconsumption of certain dietary components is now a major concern for Americans. While many food factors are involved, chief among them is the disproportionate consumption of foods high in fats, often at the expense of foods high in complex carbohydrates and fiber--such as vegetables, fruits, and whole grain products--that may be more conducive to health. I offer this Report in the context of the obligation of the Surgeon General to inform the American public of developments in the science base that have widespread implications for human health. Perhaps the classic example of such reports is the one issued in 1964 during the tenure of one of my predecessors, Dr. Luther Terry, which summarized the epidemiologic evidence available at the time on the relationship of tobacco to health. This report called attention to the inescapable conclusion that cigarettes were a major source of illness and death for those who smoked--at that time a majority of adult men. This Surgeon General's Report on Nutrition and Health follows the tradition of the original report on smoking and health. It addresses an area of some controversy and substantial misunderstanding. And the relative magnitude of the associated health concerns is comparable, with dietary factors playing a prominent role in five of the ten leading causes of death for Americans. In addition, the depth of the science base underlying its findings is even more impressive than that for tobacco and health in 1964, with animal and clinical evidence adding to the epidemiologic studies. On the other hand there are some fundamental differences. Most obvious is the fact that food is necessary for good health. Foods contain nutrients essential for normal metabolic function, and when problems arise, they result from imbalance in nutrient intake or from harmful interaction with other factors. Moreover, we know today much more about individual variation in response to nutrients than we know about possible variations in response to tobacco. Some people are clearly more susceptible than others to problems from diets that are, for example, higher in fat or salt. Also, unlike the experience for tobacco in 1964, people are already making dietary changes, as witnessed by the shift to products lower in saturated fats. Nonetheless, the important effects of the dietary factors underlying problems like coronary heart disease, high blood pressure, stroke, some types of cancer, diabetes, obesity--problems that represent the leading health threats for Americans--indicate the potential for substantial gains to be accrued by the recommendations contained in this Report It is important to emphasize that the focus of this Report is primarily on the relationship of diet to the occurrence of chronic diseases. The Report is not intended to address the problems of hunger or undernutrition that may occur in the United States among certain subgroups uf the population. All Americans should have access to an appropriate diet, but they do not. And even though the size and numbers of problems related to inadequate access to food are proportionately much smaller than those related to dietary excesses and imbalances, the problems of access to food are of considerable concern to me, personally, wherever they may occur. The apparently sizable numbers of people resorting to the use of soup kitchens and related food facilities, as well as the possible role of poor diet as a contributor to the higher infant mortality rates associated with inadequate income, suggest the need for better monitoring of the nature and extent of the problem and for sustained efforts to correct the underlying causes of diminished health due to inadequate or inappropriate diets. This report was prepared primarily for nutritional policy makers, although the eventual beneficiaries of better nutritional policy will be the American people. I am convinced that with a concerted effort on the part of policy makers throughout the Nation, and eventually by the public, our daily diets can bring a substantial measure of better health to all Americans. I commend to them the recommendations of this Report. C. Everett Koop, M.D., Sc.D. Surgeon General U.S. Public Health Service This first Surgeon General's Report on Nutrition and Health marks a key event in the history of public health in the United States. While the Report has been developed for use by policymakers, it offers lessons that can be directly applied to the public. It responds to the increasing interest of scientists, health professionals, and the American people in the role of diet in health promotion. Within recent years, concerns about nutrition and health have expanded beyond the need to prevent deficiencies to encom- pass the effects of typical American dietary patterns on the incidence of chronic diseases that are leading causes of death and disability in this country. Although scientific research has provided substantial insight into the ways specific dietary factors influence specific diseases, there are still many uncertainties about diet-disease relationships. The Department of Health and Human Services, through the Public Health Service and the Surgeon General, welcomes the responsibility to evaluate the current state of knowledge and to advise the public accordingly. This Report reviews the scientific evidence that relates dietary excesses and imbalances to chronic diseases. On the basis of the evidence, it recommends dietary changes that can improve the health prospects of many Americans. Of highest priority among these changes is to reduce intake of foods high in fats and to increase intake of foods high in complex carbohydrates and fiber. The evidence presented here indicates the convergence of similar dietary recommendations that apply to prevention of multiple chronic diseases. The recommendation to reduce dietary fat, for example, aims to reduce the risk for coronary heart disease, diabetes, obesity, and some types of cancer. This advice is not new, But it is now substantiated by a large body of evidence derived from many different kinds of research-a research base that is now even more comprehensive than was the case for the pioneering 1964 Surgeon General's Report on Smoking and Health. The weight of this evidence and the magnitude of the problems at hand indicate that it is now time to take action. In the cause of good health for all our citizens, I urge support for this Report's recommendations by every sector of American society. Otis R. Bowen, M.D. Secretary V Preface The Public Health Service of the Department of Health and Human Ser- vices has long maintained an interest in the relationship between food and health. In the 1970's, this interest began to focus on the ways in which dietary excesses and imbalances increase the risk for chronic diseases. With the publication in 1979 of Healthy People: The Surgeon General's Report on Health Promotion and Disease Prevention, attention turned toward environmental and behavioral changes that Americans might make to reduce their risks for morbidity and mortality. Nutrition was one such priority area. The 1980 report Promoting HealthlPreventing Disease: Ob- jectives for the Nation included 17 specific, quantifiable objectives in nutrition designed to reduce risks and to prevent illness and death. Also in 1980, the Department published, jointly with the U.S. Department of Agriculture, the first edition of Dietary Guidelines for Americans. This report, revised in 1985, includes seven recommendations that, taken to- gether, address the relationship between diet and chronic diseases. Diseases such as coronary heart disease, stroke, cancer, and diabetes remain leading causes of death and disability in the United States. Substan- tial scientific research over the past few decades indicates that diet can play an important role in prevention of such conditions. The Public Health Service has now reviewed this research and has produced a comprehensive analysis of the relationship between dietary factors and chronic disease risk. This Surgeon GeneralS Report on Nutrition and Health summarizes research on the role of diet in health promotion and disease prevention. Its findings indicate the great importance of diet to health. They demonstrate that changes in present dietary practices of Americans could produce substantial gains in the health of the population. The Public Health Service is committed to improving the health of Americans through its programs in education, services, and research. One mechanism for improving the health of Americans is through the 1990 Health Objectives for the Nation. The role of nutrition in health will continue to be a focus of national health priorities as we develop new objectives for the year 2000. Federal, State, and local governments, the American public, the food industry, and scientists and health professionals can work together to encourage Americans to make healthy food choices and to achieve national health goals. vii 1 am pleased to commend to the American people this review of the scientific evidence that links diet to chronic disease, and I urge that the findings of this important Report be given your careful consideration. Robert E. Windom, M.D. Assistant Secretary for Health . . . vu1 Contents Foreword .................................................... v Preface ..................................................... vii Nutrition Policy Board ....................................... xiv Acknowledgments ............................................ xv Summary and Recommendations ................................ 1 Chapter 1: Introduction and Background ........................ 2 1 Chapter 2: Coronary Heart Disease ............................. 83 Chapter 3: High Blood Pressure ............................... 139 Chapter4:Cancer ........................................... 177 Chapter 5: Diabetes .......................................... 249 Chapter6:Obesity.. ......................................... 275 Chapter 7: Skeletal Diseases .................................. 3 11 Chapter 8: Dental Diseases ................................... 345 Chapter9:KidneyDiseases ................................... 381 Chapter 10: Gastrointestinal Diseases .......................... 403 Chapter 11: Infections and Immunity .......................... 427 Chapter 12: Anemia .......................................... 465 Chapter 13: Neurologic Disorders ............................. 491 Chapter 14: Behavior ........................................ 509 , Chapter 15: Maternal and Child Nutrition ...................... 539 Chapter16:Aging ........................................... 595 Chapter 17: Alcohol .......................................... 629 Chapter 18: Drug-Nutrient Interactions ......................... 67 1 Chapter 19: Dietary Fads and Frauds .......................... 695 Index ...................................................... 713 ix Tables 1. 2. l-l. l-2. l-3. l-4. l-5. l-6. l-7. 1-8. l-9. 2-l. 2-2. 2-3. 2-4. Recommendations..................................... 3 Estimated Total Deaths and Percent of Total Deaths for the 10 Leading Causes of Death: United States, 1987 . . . . . . . . . . . . . 4 Estimated Total Deaths and Percent of Total Deaths for the 10 + Leading Causes of Death: United States, 1987 . . . . . . . . . . . . . 22 Selected Events in the History of Nutritional Science to1950............................................... 25 Selected Federal Domestic Nutrition Policy Initiatives, 1862-1988 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 National Nutrition Surveillance Activities . . . . . . . . . . . . . . . . 38 Federal Dietary Recommendations for the General Public, 1917-1988 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 Food and Nutrition Board, National Academy of Sciences- National Research Council Recommended Daily Dietary Allowances, Revised 1980 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Estimated Safe and Adequate Daily Intakes of Selected VitaminsandMinerals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 Annual Per Capita Availability of Selected Commodities in the U.S. Food Supply, 1%5-1985 . . . . . . . . . . . . . . . . . . . . . . . . 65 Mean Daily Intake of Food Energy, Nutrients, and Food Components for Men, Women, and Young Children From the Continuing Survey of Food Intakes by Individuals (CSFII), 1985 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Death Rate for Coronary Heart Disease by Age, Race, and Sex, United States, 1985 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 Prevalence of Coronary Heart Disease by Age, Race, and Sex, United States, 1985 . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . . 86 National Cholesterol Education Program Adult Treatment Panel Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 Estimates of Serum Cholesterol Change From Given Changes in Dietary Lipids Based on Isocaloric Controlled Experiments in Humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 X 3-1. 3-2. 3-3. 3-4. 3-5. 3-6. 3-7. 4-l. 4-2. 4-3. 4-4. 4-5. 4-6. 4-7. 4-8. , 4-9. 4-10. Classification of Blood Pressure in Adults 18 Years or Older ................................................ 143 Estimated Prevalence of Cardiovascular Disease in the United States ................................................ 143 Control Mechanisms for Arterial Pressure ................ 145 Major Nutrients and Possible Mechanisms for Influencing BloodPressure.. ...................................... 147 Changes in Weight and Blood Pressure (Baseline to Followup) in Treatment (Rx) and Control Groups of Five Randomized ControlledTrials ...................................... 149 Studies of Cross-Sectional Association of Blood Pressure With Alcohol Consumption ............................. 154 Prospective Observational Studies of the Association of Blood Pressure With Alcohol Consumption ..................... 155 Proportions of Cancer Deaths Attributed to Various Factors ............................................... 180 International Changes Since 1950 in Death Certification Rates for Cancers of Stomach and Lung .................. 181 Cancer Incidence Rates in the Philippines and Among Filipinos and Caucasians in Hawaii ...................... 182 Reported Relationship Between Selected Dietary ComponentsandCancer ............................... 191 National Cancer Institute Dietary Guidelines .............. 192 Comparison of Dietary Guidelines for the American Public ...................................... 193 Summary of Epidemiologic Studies Examining Dietary Fat andBreastCancer ..................................... 196 Retrospective Human Studies Relating Body Weight and Cancer ............................................... 200 Summary of Epidemiologic Studies Examining Dietary Fiber and Colon Cancer ..................................... 205 Dietary Vitamin A and Lung Cancer Risk: A Summary of PreviousStudies ...................................... 211 xi 4-l 1. NCI-Sponsored Prevention Clinical Trials Related to VitaminA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 4-12. 5-l. 5-2. 5-3. 6-l. 6-2. 6-3. 7-l. 8-l. Summary of Epidemiologic Studies on Selenium and CancerRisk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221 History of Dietary Composition (Relative Proportion of Carbohydrate and Fat Calories) Used in Management of , Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251 Clinical Complications of Diabetes . . . . . . . . . . . . . . . . . . . . . . . 255 American Diabetes Association Dietary Recommendations for Persons With Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263 Comparison of Metropolitan Desirable Weights With Average Weights From U.S. Cohort Studies . . . . . . . . . . . . . . . . . . . . . . 282 Body Mass Index (kg/m*) Used to Define Desirable Weight and Overweight According to Three Different "Ideal" Reference Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285 Mortality Ratios for All Ages Combined in Relation to the Death Rate of Those 90 to 109 Percent of Average Weight . . . 290 Scientific Validity of Risk Factors . . . . . . . . . . . . . . . . . . . . , . . . 314 Supplemental Fluoride Dosage Scheduled (in mg F/day) According to Fluoride Concentrations of Drinking Water . . . 359 10-I. Summary of Digestive Processes . . . . . . . . . . . . . . . . . . . . . . . . 407 10-2. Gastrointestinal Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410 1 l-l. Causes of Food-Associated Illness . . . . . . . . . . . . . . . . . . . . . . . 448 12-I. Estimates for Percent Prevalence of Impaired Iron Status: Average of Estimates Using Three Methods: NHANES II, 1976-80 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 468 12-2. Total Body Iron and Storage Iron . . . . . . . . . . . . . . . . . . . . . . . . 471 14-1. Behavioral and Psychologic Hypotheses to Explain Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 515 14-2. Diagnostic Criteria for Anorexia Nervosa and Bulimia . . . . . . 520 15-1. Selected National Objectives to be Achieved by the Year 1990 Related to Maternal and Child Nutrition . . . . . . . . . . . . . . . . . . 545 xii 15-2. Content of Selected Nutrients in Human Milk, Commercial Formulas, and Other Milks Used for Feeding Normal Full- TermInfants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 565 Figures l-l. Dependence of Biologic Function or Tissue Concentration on Intake of a Nutrient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 2-l. Diagram of an Atherosclerotic Plaque . . . . . . , . . . . . . . . . . . . . 88 4-l. Range of Incidence Rates (International Comparisons) . . . . . 180 4-2. Carcinogenesis........................................ 183 4-3. Dietary Fat Intake in Relation to Breast Cancer-Related Death Rate................................................. 187 6-l. A Nomogram for Determining Body Mass Index (BMI) . . . . 284 8-l. The Distribution of Mean Decayed and Filled Coronal Surfaces (DFS) by Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348 8-2. The Distribution of Mean Decayed and Filled Root Surfaces (DFS) by Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349 8-3. Percent of Persons by Severe Loss of Periodontal Attachment (Pocket Depths Measuring 4 mm or More) andAgeGroups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351 8-4. Comparison of the Percent of Edentulous Persons in the 1985-86 NIDR Survey to That Reported From the NCHS Surveyof1960-62 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351 8-5. Schematic Cross-Section of a Typical Mandibular Molar Tooth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352 9-l. The Comparative Structures of Amino Acids, Ketoacids, and Hydroxyacids......................................... 391 . . . Xl11 Nutrition Policy Board U.S. Department of Health and Human Services J. Michael McGinnis, M.D. (Chairman), Deputy Assistant Secretary for Health (Disease Prevention and Health Promotion), Public Health Service - Faye G. Abdellah, R.N., Ed.D., Sc.D., Deputy Surgeon General, Public Health Service W. Douglas Badger, M.Div., Deputy Assistant Secretary, Office of Human Development Services Mary M. Ever& M.B.A., Director, Office of Community Services, Family Support Administration Manning Feinleib, M.D., M.P.H., Dr.P.H., Director, National Center for Health Statistics, Centers for Disease Control, Public Health Service Allan L. Forbes, M.D., Director, Office of Nutrition and Food Sciences, Center for Food Safety and Applied Nutrition, Food and Drug Administra- tion, Public Health Service William T. Friedewald, M.D., Associate Director for Disease Prevention, National Institutes of Health, Public Health Service Bernard I. Grosser, M.D., Director, Office of Science, Alcohol, Drug Abuse, and Mental Health Administration, Public Health Service John Porvaznik, M.D., F.A.C.S., Associate Director, Office of Health Programs, Indian Health Service, Public Health Service William A. Robinson, M.D., M.P.H., Chief Medical OBicer, Health Re- sources and Services Administration, Public Health Service xiv Acknowledgments The Surgeon General's Report on Nutrition and Health was prepared under the general editorship of the Department of Health and Human Services' Nutrition Policy Board, whose members are listed on the pre- vious page. Managing Editor was Marion Nestle, Ph.D., M.P.H., Office of Disease Prevention and Health Promotion. Special editorial assistance was contributed by John Bailar III, M.D., Ph.D., Science Advisor, Office of Disease Prevention and Health Promotion, and by Darla E. Danford, M.P.H., D.Sc., R.D., National Institutes of Health. Project Officer during early stages of preparation of the Report was Ann Sorenson, Ph.D., now with the National Institutes of Health. In addition to the guidance of the Nutrition Policy Board's Senior Editorial Advisors and Staff Working Group, important editorial contributions were made by Karen Donato, M.S., R.D., Nancy D. Ernst, M.S., R.D., Marilyn E. Farrand,M.S.,R.D.,andVanS. Hubbard,M.D.,Ph.D.,oftheNation- al Institutes of Health's Nutrition Education Subcommittee; and by Walter H. Glinsmann, M.D., Marilyn G. Stephenson, M.S., R.D., John E. Van- derveen, Ph.D., and Elizabeth Yetley, Ph.D., R.D., of the Food and Drug Administration's Center for Food Safety and Applied Nutrition. Senior Editorial Advisors to the Nutrition Policy Board were: C. Wayne Callaway, M.D., Director, Center for Clinical Nutrition, George Washington University Medical Center, Washington, D.C. `Johanna T. Dwyer, D.Sc., Director, Frances Stem Nutrition Center, New England Medical Center Hospitals, and Professor of Medicine, Tufts Uni- versity Medical School, Boston, Massachusetts Samuel Fomon, M.D., Professor of Pediatrics, University of Iowa, Iowa City, Iowa Richard L. Hall, Ph.D., Vice President, Science and Technology, McCor- mick & Co., Inc., Hunt Valley, Maryland Robert I. Levy, M.D., President, Sandoz Research Institute, East Hano- ver, New Jersey Walter Mertz, M.D., Director, Beltsville Human Nutrition Research Cen- ter, U.S. Department of Agriculture, Beltsville, Maryland xv Malden C. Nesheim, Ph.D., Vice President for Planning and Budget, Cornell University, Ithaca, New York Sushma Palmer, D.Sc., Executive Director, Food and Nutrition Board, National Academy of Sciences, Washington, D.C. Irwin H. Rosenberg, M.D., Director, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts Theodore Van Itallie, M.D., Professor of Medicine, Columbia University College of Physicians and Surgeons, New York, New York Nutrition Policy Board Staff Working Group members were: Elizabeth Brannon, M.S., R.D., Clinical Nutrition Specialist, Bureau of Maternal and Child Health and Resources Development, Health Resourc- es and Services Administration, Rockville, Maryland Darla E. Danford, M.P.H., D.Sc., R.D., Nutritionist, Nutrition Coordinat- ing Committee, National Institutes of Health, Bethesda, Maryland Willie M. Etheridge, M.S., Policy Analyst, Policy Planning and Legislation Division, Office of Human Development Services, Washington, D.C. James J. Heam, L.L.B., Chief, Community Food and Nutrition Program, Office of Community Services, Family Support Administration, Washing- ton, D.C. M. Yvonne Jackson, Ph.D., R.D., Chief, Nutrition and Dietetics Section, Indian Health Service, Rockville, Maryland Linda D. Meyers, Ph.D., Nutrition Advisor, Office of Disease Prevention and Health Promotion, Washington, D.C. Marion Nestle, Ph.D., M.P.H., Director, Nutrition Policy Staff, Office of Disease Prevention and Health Promotion, Washington, D.C. Lana Skirboll, Ph.D., Special Assistant to the Director, Offtce of Science, Alcohol, Drug Abuse, and Mental Health Administration, Rockville, Maryland Frederick Trowbridge, M.D., M.S., Director, Nutrition Division, Center for Health Promotion and Education, Centers for Disease Control, Atlan- ta, Georgia xvi Catherine E. Woteki, Ph.D., R.D., Deputy Director, Division of Health Examination Statistics, National Center for Health Statistics, Centers for Disease Control, Hyattsville, Maryland Individuals who contributed to the writing of draft chapters or portions of the Report were: Margaret J. Albrink, M.D., M.P.H., Professor of Medicine, West Virginia University Medical Center, Morgantown, West Virginia (Obesity) William R. Beisel, M.D., Adjunct Professor, Department of Immunology and Infectious Diseases, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland (Infections and Immunity) C. Wayne Callaway, M.D., Director, Center for Clinical Nutrition, George Washington University Medical Center, Washington, D.C. (Alcohol) Joseph E. Ciardi, Ph.D., Research Biochemist, Caries and Restoration Materials Research Branch, Extramural Program, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland (Den- tal Diseases) Phyllis A. Crapo, R.D., Department of Medicine, University of California at San Diego, LaJolla, California (Diabetes) Jeffrey A. Cutler, M.D., Chief, Prevention and Demonstration Research Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (High Blood Pressure) Peter R. Dallman, M.D., Professor, Department of Pediatrics, University of California, San Francisco, California (Anemia) Barbara H. Dennis, R.D., Ph.D., Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (Coronary Heart Disease) John Duguid, M.D., Ph.D., Neurologist, Massachusetts Institute of Tech- nology, Cambridge, Massachusetts (Neurologic Disorders) Robert Edelman, M.D., Chief, Clinical and Epidemiological Studies Branch, Deputy Director, Microbiology and Infectious Diseases Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland (Infections and Immunity) xvii Nancy D. Ernst, MS., R.D., Nutrition Coordinator, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Mary- land (High Blood Pressure) Lloyd J. Filer, Jr., M.D., Ph.D., Department of Pediatrics, University of Iowa School of Medicine, Iowa City, Iowa (Maternal and Child Nutrition) Mattie R.S. Fox, Ph.D., Chief, Nutrient Interaction Section, Experimental Nutrition Branch, Division of Nutrition, Food and Drug Administration, Washington, D.C. (Introduction and Background) Philip J. Garry, Ph.D., Professor, Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico (Aging) James Goodwin, M.D., Professor and Vice Chairman, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (Aging) Sheila Gottschalk, M.D., Associate Professor of Pediatrics, Louisiana State University School of Medicine, New Orleans, Louisiana (Maternal and Child Nutrition) , Gregory E. Gray, M.D., Ph.D., Assistant Professor, Department of Psy- chiatry and the Behavioral Sciences, Los Angeles County-University of Southern California Medical Center, Los Angeles, California (Behavior) Peter Greenwald, M.D., lX.P.H., Director, Division of Cancer Prevention and Control, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Cancer) John H. Growdon, M.D., Massachusetts Institute of Technology, Massa- chusetts General Hospital, and Harvard Medical School, Cambridge, Mas- sachusetts (Neurologic Disorders) Margaret A. Hamburg, M.D., Special Assisiant to the Director, National Institute of Allergy and Infectious Diseases-, National Institutes of Health, Bethesda, Maryland (Infections and Immunity) James P. Hat-wood, Ph.D., Executive Secretary, Scientific Review Office, National Institute on Aging,-National Institutes of Health, Bethesda, Maryland (Introduction and Background) Michael Horan, M.D., Chief, Hypertension and Kidney Diseases Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (High Blood Pressure) Richard D. Hurt, M.D., Mayo Clinic, Rochester, Minnesota (Alcohol) . . XVlll Howard Jacobson, M.D., Institute of Nutrition, University of North Car- olina, Chapel Hill, North Carolina (Maternal and Child Nutrition) Mamie Y. Jenkins, Ph.D., Research Chemist, Bioavailability Section, Experimental Nutrition Branch, Division of Nutrition, Food and Drug Administration, Washington, D.C. (Introduction and Background) Alexander Jordan, Ph.D., Supervisory Pharmacologist, Food and Drug Administration, Rockville, Maryland (Drug-Nutrient Interactions) George M. Kazzi, M.D., Chief, Department of Obstetrics and Gynecolo- gy, Harper-Grace Hospitals, and Assistant Professor, Maternal-Fetal Medicine, Wayne State University School of Medicine, Detroit, Michigan (Maternal and Child Nutrition) Joel D. Kopple, M.D., Professor of Medicine and Public Health, Univer- sity of California at Los Angeles, Chief, Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Torrance, California (Kid- ney Diseases) Markus J.P. Kruesi, M.D., Staff Psychiatrist, National Institute of Mental Health, Alcohol, Drug Abuse, and Mental Health Administration, Rock- ville, Maryland (Behavior) Elaine Lanza, Ph.D., Diet and Cancer Branch, Division of Cancer Preven- tion and Control, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Cancer) Harris R. Lieberman, Ph.D., Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts (Neu- , rologic Disorders; Behavior) Gardner C. McMillan, M.D., Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (Coronary Heart Disease) Albert I. Mendeloff, M.D., M.P.H., Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland (Gastroin- testinal Diseases) Linda D. Meyers, Ph.D., Nutrition Advisor, Office of Disease Prevention and Health Promotion, Washington, D.C. (Introduction and Background) Sanford A. Miller, Ph.D., Director, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, D.C. (Introduction and Background) xix Geraldine V. Mitchell, Ph.D., Chief, Bioavailability Section. Experimental Nutrition Branch, Division of Nutrition. Food and Drug Administration, Washington, D.C. (Introduction and Background) Eliot N. Mostow, M.D., M.P.H., Medical Staff Fellow, Division of Cancer Prevention and Control, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Cancer) Jerrold M. Olefsky, M.D., Department of Medicine, University of Califor- nia at San Diego, and San Diego Veterans Administration Medical Center, San Diego, California (Diabetes) Youngmee K. Park, Ph.D., Nutritionist, Clinical Nutrition Branch, Divi- sion of Nutrition, Food and Drug Administration, Washington, D.C. (Intro- duction and Background) Jean A.T. Pennington, Ph.D., Assistant to the Director, Division of Nutri- tion, Food and Drug Administration, Washington, D.C. (Introduction and Background) L. Ross Pierce, M.D., Group Leader, Food and Drug Administration, Rockville, Maryland (Drug-Nutrient Interactions) Peggy L. Pipes, M.P.N., R.D., Child Development Mental Retardation Center, University of Washington, Seattle, Washington (Maternal and Child Nutrition) Ernest0 Pollitt, Ph.D., Department of Applied Behavioral Sciences, Uni- versity of California, Davis, California (Maternal and Child Nutrition) Leon Prosky, Ph.D., Deputy Chief, Experimental Nutrition Branch, Divi- sion of Nutrition, Food and Drug Administration, Washington, D.C. (Intro- duction and Background) Jeanne I. Rader, Ph.D., Chief, Nutrient Toxicity Section, Experimental Nutrition Branch, Division of Nutrition, Food and Drug Administration, Washington, D.C. (Introduction and Background) Lawrence G. Raisz, M.D., Professor of Medicine and Chief, Division of Endocrinology and Metabolism, University of Connecticut School of Med- icine, Farmington, Connecticut (Skeletal Diseases) Judith L. Rapoport, M.D., Chief, Child Psychiatry Branch, National Insti- tute of Mental Health, Alcohol, Drug Abuse, and Mental Health Adminis- tration, Rockville, Maryland (Behavior) xx Merrill S. Read, Ph.D., Professor and Chairman, Human Nutrition and Food Systems, College of Human Ecology, University of Maryland, Col- lege Park, Maryland (Maternal and Child Nutrition) Basil M. Rifkind, M.D., F.R.C.P., Division of Heart and Vascular Dis- eases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (Coronary Heart Disease) Norman E. Rosenthal, M.D., Chief, Unit on Outpatient Studies, Clinical Psychology Branch, National Institute of Mental Health, Alcohol, Drug Abuse, and Mental Health Administration, Rockville, Maryland (Behav- ior) Neil L. Sass, Ph.D., Senior Scientist, ORice of Management, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Wash- ington, D.C. (Introduction and Background) Claudia Schuth, M.D., Associate Professor of Pediatrics, Louisiana State University School of Medicine, New Orleans, Louisiana (Maternal and Child Nutrition) James H. Shaw, Ph.D., Professor of Nutrition Emeritus, Harvard School of Dental Medicine, Boston, Massachusetts (Dental Diseases) Alan J. Sheppard, Ph.D., Chief, Experimental Methods Research Section, Nutrient Surveillance Branch, Division of Nutrition, Food and Drug Ad- ministration, Washington, D.C. (Introduction and Background) Solomon Sobel, M.D., Food and Drug Administration, Rockville, Mary- land (Drug-Nutrient Interactions) Robert J. Sokol, M.D., Professor and Chairman and Chief, Department of Obstetrics and Gynecology, Wayne State University, Hutzel Hospital, Detroit, Michigan (Maternal and Child Nutrition) Marilyn G. Stephenson, M.S., R.D., Assistant to the Director, OfIice of Nutrition and Food Sciences, Center for Food Safety and Applied Nutri- tion, Food and Drug Administration, Washington, DC. (Dietary Fads and Frauds) Albert Stunkard, M.D., Professor of Psychiatry, University of Pennsylva- nia School of Medicine, Philadelphia, Pennsylvania (Behavior) Robert M. Suskind, M.D., Department of Pediatrics, Louisiana State University School of Medicine, New Orleans, Louisiana (Maternal and Child Nutrition) xxi Shyy Hwa Tao, Ph.D., Research Chemist, Nutrient Interaction Section, Experimental Nutrition Branch, Division of Nutrition, Food and Drug Administration, Washington, D.C. (Imroduction and Background) Thomas Thorn, Statistician, Epidemiology and Biometry Research Pro- gram, Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Mary- land (Coronary Heart Disease) Gloria Troendle, M.D., Deputy Director, Food and Drug Administration, Rockville, Maryland (Drug-Nutrient Interactions) Momtaz Wassef, Ph.D., Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (Coronary Heart Disease) Cora E. Weeks, J.D., Ph.D., Consumer Safety Officer, Division of Reg- ulatory Guidance, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, D.C. (Introduction and Background) Robert W. Wissler, M.D., Ph.D., Donald N. Pritzker Distinguished Service Professor of Pathology Emeritus, University of Chicago, Chicago, Illinois (Coronary Heart Disease) Philip A. Wolf, M.D., Professor of Neurology and Associate Research Professor of Medicine, Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts (Neurologic Disor- ders) Bonnie S. Worthington-Roberts, Ph.D., Professor, Nutritional Sciences, University of Washington, Child Development Center, Seattle, Washington (Maternal and Child Nutrition) Catherine E. Woteki, Ph.D., R.D., Deputy Director, Division of Health Examination Statistics, National Center for Health Statistics, Centers for Disease Control, Hyattsville, Maryland (Introduction and Background) Richard J. Wurtman. M.D., Professor, Department of Brain and Cognitive Sciences, Director, Clinical Research Center, Massachusetts Institute of Technology, Cambridge, Massachusetts (Neurologic Disorders; Behavior) Elizabeth Yetley, Ph.D., R.D., Chief, Clinical Nutrition, Division of Nutri- tion, Office of Nutrition and Food Sciences, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, D.C. (In- troduction and Background) xxii During preparation of the Report, chapters were subjected to six stages of critical review, three by experts within the Public Health Service (internal reviews) and three by scientists and professionals recommended as experts by national scientific and nutrition professional organizations in the private sector (external reviews). In addition, the senior editorial advisors and staff to the Nutrition Policy Board listed above provided expert technical eval- uation throughout the review process. Individuals who reviewed chapters or potions of the Report were: Phyllis B. Acosta, Dr.P.H., R.D., Director of Metabolic Diseases, Ross Laboratories, Columbus, Ohio Lawrence Agodoa, M.D., Coordinator, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland Duane F. Alexander, M.D., Director, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Mary- land Aaron M. Altschul, Ph.D., Diet Management and Eating Disorders Pro- gram, Georgetown University, Washington, D.C. Ronald A. Arky, M.D., Professor, Department of Medicine, Harvard Medical School at Mt. Auburn Hospital, Cambridge, Massachusetts Louis Avioli, M.D., Professor of Medicine and Oral Biology, Washington University School of Medicine and Dental School, St. Louis, Missouri David Badman, Ph.D., Hematology Program Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland John Bailar III, M.D., Ph.D., Science Advisor, Office of Disease Preven- tion and Health Promotion, Washington, D.C. David H. Baker, Ph.D., Professor of Nutrition and Metabolism, Univer- sity of Illinois, Urbana, Illinois Susan Blumenthal, M.D., Medical Oflicer and Chief, Behavioral Medicine Program, National Institute of Mental Health, Alcohol, Drug Abuse, and Mental Health Administration, RockvilIe, Maryland Ronette Briefel, Dr.P.H., R.D., Nutritional Epidemiologist, Survey Plan- ning and Development Branch, National Center for Health Statistics, Centers for Disease Control, Hyattsville, Maryland . . . xx111 Benjamin Burton, Ph.D., Associate Director for Disease Prevention and Technology Transfer, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland Ritva Butrum, Ph.D., Diet and Cancer Branch, Division of Cancer Preven- tion and Control, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Charles E. Butterworth, Jr., M.D., Director, Clinical Nutrition Research Unit, University of Alabama, Birmingham, Alabama George F. Cahill, Jr., M.D., Howard Hughes Medical Institute, Boston, Massachusetts Doris H. Calloway, Ph.D., Provost Professor Schools and College, Uni- versity of California, Berkeley, California Richard Calve& M.D., Medical Research Nutritionist, Experimental Nu- trition Branch, O&e of Nutrition and Food Sciences, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washing- ton, D.C. Mona Calvo, Ph.D., R.D., Nutritionist, Clinical Nutrition, Division of Nutrition, Office of Nutrition and Food Sciences, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, D.C. James P. Carlos, D.D.S., Chief, Epidemiology Branch, Epidemiology and Oral Disease Prevention Program, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland Kenneth K. Carroll, Ph.D., Professor, Department of Biochemistry, Uni- versity of Western Ontario, London, Ontario, Canada Ranjit K. Chandra, M.D., F.R.C.P., Janeway Child Health Center, Immu- nology Department, St. John's, Newfoundland, Canada Lois Chatham, Ph.D., Director, Division of Basic Research, National Institute on Alcohol Abuse and Alcoholism, Alcohol, Drug Abuse, and Mental Health Administration, Rockville; Maryland Aram V. Chobanian, M.D., Director and Professor, Cardiovascular Insti- tute, Boston University School of Medicine, Boston, Massachusetts Joginder G. Chopra, M.D., Special Assistant, Medical Affairs, Office of Nutrition and Food Sciences, Center.for Food Safety and Applied Nutri- tion, Food and Drug Administration, Washington, D.C. Gregory Christenson, Ph.D., Special Population Studies Branch, Division of Cancer Prevention and Control, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Carolyn Clifford, Ph.D., Diet and Cancer Branch, Division of Cancer Prevention and Control, National Cancer Institute, National Institutes of Health, Bethesda, Maryland James D. Cook, M.D., Division of Hematology, University of Kansas Medical Center, Kansas City, Kansas Stephen B. Corbin, D.D.S., M.P.H., Senior Prevention Policy Advisor, Prevention Policy Staff, OfIice of Disease Prevention and Health Promo- tion, Washington, D.C. Ann Coulston, M.S., R.D., Clinical Research Center, Stanford University Hospital, Stanford, California Frances Cronin, Ph.D., R.D., Chief, Diet Appraisal Research Branch, Nutrition Education Division, Human Nutrition Information Service, U.S. Department of Agriculture, Hyattsville, Maryland Cheryl L. Damberg, M.P.H., Director of Marketing, General Health Inc., Washington, D.C. Michele DeBartolo, M.P.H., R.D., Senior Clinical Research Associate, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois Hector F. DeLuca, Ph.D., Department of Biochemistry, College of Agri- culture and Life Sciences, University of Wisconsin, Madison, Wisconsin Dominick P. DePaola, D.D.S., Ph.D., Dean, University of Medicine and Dentistry of New Jersey, New Jersey Dental School, Newark, New Jersey Vincent T. DeVita, Jr., M.D., Director, National Cancer Institute, Nation- al Institutes of Health, Bethesda, Maryland Karen Donato, M.S., R.D., Nutritionist, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Allan L. Drash, M.D., Professor of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, Penn- sylvania XXV Mary Dufour, M.D., Chief, Epidemiology Branch, Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Alcohol, Drug Abuse, and Mental Health Administration, Rockville, Maryland Harriet P. Dustan, M.D., Veterans Administration Distinguished Physi- cian and University Distinguished Professor Emeritus, Veterans Adminis- tration Medical Center, University of Alabama at Birmingham, Bir- mingham, Alabama Mary Egan, R.D., M.S., M.P.H., National Center for Education in Mater- nal and Child Health, Georgetown University, Washington, D.C. Shirley Ekvall, Ph.D., R.D., Professor and Chief of Nutrition Services, University of Cincinnati and University Affiliated Cincinnati Center for Developmental Disorders, Children's Hospital Medical Center, Cincin- nati, Ohio Lillian Emmons, Ph.D., R.D., Comprehensive Psychiatric Services, Inc., Cleveland, Ohio Arnold Engel, M.D., Commission Officer, Medical Statistics Branch, National Center for Health Statistics, Centers for Disease Control, Hyatts- ville , Maryland Frank Falkner, M.D., F.R.C.P., School of Public Health, University of California, Berkeley, California Marilyn E. Farrand, M.S., R.D., Public Health Nutrition, Prevention and Demonstration Research Branch, Division of Epidemiology and Clinical Application, National Heart, Lung, and Blood Institute, National Insti- tutes of Health, Bethesda, Maryland Owen Fennema, Ph.D., Department of Food Science, University of Wis- consin at Madison, Madison, Wisconsin John D. Femstrom, Ph.D., Professor of Psychiatry and Behavioral Neuro- science, University of Pittsburgh School of Medicine, Pittsburgh, Pennsyl- vania Willis R. Foster, M.D., Senior Staff Physician, Office of Disease Preven- tion and Technology Transfer, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland Judith Fradkin, M.D., Chief, Endocrine and Metabolic Diseases Programs Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland xxvi Victor Frattali, Ph.D., Deputy Director, Division of Nutrition, Offtce of Nutrition and Food Sciences, Center for Food Safety and Applied Nutri- tion, Food and Drug Administration, Washington, D.C. Robert A. Fried, M.D., Associate Professor and Director of Clinical Af- fairs, Department of Family Medicine, University of Colorado School of Medicine, Denver, Colorado Edward D. Frohlich, M.D., Alton Ochsner Distinguished Scientist and Vice President for Academic Affairs, Alton Ochsner Medical Foundation, Staff Member, Section on Hypertensive Diseases, Ochsner Clinic, New Orleans, Louisiana Peter Frommer, M.D., Deputy Director, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Margie Gallagher, Ph.D., R.D., School of Home Economics, Institute for Coastal and Marine Resources, East Carolina University, Greenville, North Carolina Dian Gans, M.S., Research Assistant, Department of Nutritional Sci- ences, University of Wisconsin at Madison, Madison, Wisconsin Stanley M. Gam, Ph.D., Center for Human Growth and Development, University of Michigan, Ann Arbor, Michigan Peter Gergen, M.D., Commission Officer, Medical Statistics Branch, Na- tional Center for Health Statistics, Centers for Disease Control, Hyatts- ville , Maryland Dorothy W. Gietzen, Ph.D., Assistant Research Neurophysiologist, De- partment of Physiologic Sciences, School of Veterinary Medicine, Depart- ment of Psychiatry, School of Medicine, University of California at Davis, Davis, California Susan Gilbert, M.P.A., Associate, Prospect Associates, Rockville, Mary- land Walter H. Glinsmann, M.D., Associate Director, Clinical Nutrition, Divi- sion of Nutrition, Food and Drug Administration, Washington, D.C. Vay Liang W. Go, M.D., Chairman, Nutrition Coordinating Committee, National Institutes of Health, Bethesda, Maryland Murray Goldstein, D.O., M.P.H., Director, National Institute of Neu- rological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland xxvii Dewitt S. Goodman, M.D., Professor of Medicine, Department of Medi- cine, College of Physicians and Surgeons of Columbia University, New York, New York PhiUip Gorden, M.D., Director, National Institute of Diabetes and Di- gestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland Enoch Gordis, M.D., Director, National Institute on Alcohol Abuse and Alcoholism, Alcohol, Drug Abuse and Mental Health Administration, Rockville , Maryland Stephen L. Gordon, Ph.D., Director, Musculoskeletal Diseases Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland Gilman D. Grave, M.D., Chief, Endocrinology, Nutrition, and Growth Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland Jesse F. Gregory III, Ph.D., University of Florida, Food Science and Nutrition Department, Gainesville, Florida Joan Gussow, Ed.D., Mary Swartz Rose Professor of Nutrition and Edu- cation, Department of Nutrition and Education, Teachers College, Colum- bia University, New York Wilbur Hadden, M.A., Chief, Programming Staff, National Center for Health Statistics, Centers for Disease Control, Hyattsville, Maryland Evan Hadley, M.D., Chief, Geriatrics Branch, National Institute on Aging, National Institutes of Health, Bethesda, Maryland Carole Haines, M.P.H., Data Analysis Coordinator, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Mary- land Judith G. Hallfrisch, Ph.D., Senior Staff Fellow, Metabolism Section of the Gerontology Research Center, National Institute on Aging, National Institutes of Health, Bethesda, Maryland Charles H. Halsted, M.D., Ph.D., Chief, Division of Clinical Nutrition, and Professor of Internal Medicine, School of Medicine, University of California at Davis, Davis, California Linda Harris, Ph.D., Special Assistant, Gflice of Disease Prevention and Health Promotion, Washington, D.C. . . . XXVlll Tamara Harris, M.D., Service Fellow, Office of Analysis and Epidemiolo- gy Program, National Center for Health Statistics, Centers for Disease Control, HyattsviUe, Maryland John N. Hathcock, Ph.D., Chief, Experimental Nutrition Branch, Division of Nutrition, Food and Drug Administration, Washington, D.C. Maureen Henderson, M.D., Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington Stephen P. Heyse, M.D., Director, Disease Prevention, Epidemiology and Clinical Applications, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland Jules Hirsch, M.D., Professor and Senior Physician, Rockefeller Univer- sity, New York, New York Gladys Hirshman, M.D., Director, Chronic Renal Disease Program, Na- tional Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland Peter R. Holt, M.D., Chief, Division of Gastroenterology, Professor of Medicine, College of Physicians and Surgeons, St. Luke's Hospital, New York, New York Steven S. Hotta, M.D., Ph.D., Medical Gflicer, Clinical Nutrition Branch, Division of Nutrition, Food and Drug Administration, Washington, D.C. Anastacio M. Hoyumpa, M.D., Professor of Medicine, Division of Gas- troenterology and Nutrition, University of Texas Health Science Center, San Antonio, Texas Van S. Hubbard, M.D., Ph.D., Director, Nutritional Sciences Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Nation- al Institutes of Health, Bethesda, Maryland Sandra Huckaby, R.N., M.S.N., Special Assistant, Maternal and Infant Health Branch, Bureau of Maternal and Child Health and Resources Development, Health Resources and Services Administration, RockviUe, Maryland James C. Hunt, M.D., Chancellor, University of Tennessee, Memphis, Tennessee Vince L. Hutchins, M.D., M.P.H., Deputy Director, Bureau of Maternal and Child Health and Resources Development, Health Resources and Services Administration, Rockville, Maryland xxix William T. Jan+, Ph.D., Professor of Health Education, Department of Preventive Medicine, School of Medicine, Loma Linda University, Loma Linda, California Clifford Johnson, M.S.P.H., Chief, Nutrition Statistics Branch, National Center for Health Statistics, Centers for Disease Control, Hyattsville, Maryland Norman Kaplan, M.D., Professor of Internal Medicine, University of Texas Health Science Center, Dallas, Texas Gerald T. Keusch, M.D., Professor of Medicine, Department of Medicine, New England Medical Center, Boston, Massachusetts Matthew Kinnard, Ph.D., Health Scientist Administrator, National Insti- tute of Dental Research, National Institutes of Health, Bethesda, Mary- land Samuel Korper, Ph.D., Associate Director, Offtce of Planning, Analysis, and Communications, National Institute on Aging, National Institutes of Health, Bethesda, Maryland David Kritchevsky, Ph.D., Associate Director of Anatomy and Biology, Wistar Institute, Philadelphia, Pennsylvania Robert Kuczmarksi, M.S.P.H., M.P.H., Dr.P.H., R.D., Health Statisti- cian, Nutrition Statistics Branch, National Center for Health Statistics, Centers for Disease Control, Hyattsville, Maryland William Lands, Ph.D., Department of Biochemistry, University of Illinois at Chicago, Chicago, Illinois Lynn A. Larsen, Ph.D., Associate Director, Program Development, Divi- sion of Nutrition, Office of Nutrition and Food Sciences, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, D.C. Reva C. Lawrence, M.P.H., Epidemiologist, Data Systems, Program Of- ficer, National Institute of Arthritis and Musculoskeletal and Skin Dis- eases, National Institutes of Health, Bethesda, Maryland Claude Lenfant, M.D., Director, National Heart, Lung, and Blood Insti- tute, National Institutes of Health, Bethesda, Maryland Gilbert A. Leveille, Ph.D., Staff Vice President, NABISCO Brands, Inc., East Hanover, New Jersey xxx Ephraim Y. Levin, M.D., Medical Officer, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland Christine J. Lewis, Ph.D., R.D., Chief, Experimental Clinical Research Section, Division of Nutrition, Oflice of Nutrition and Food Sciences, Center for Food Safety and Applied Nutrition, Food and Drug Administra- tion, Washington, D.C. Charles S. Lieber, M.D., Director, Alcohol Research and Treatment Cen- ter, Chief, Section of Liver Disease and Nutrition, Bronx Veterans Admin- istration Medical Center, Professor of Medicine and Pathology, Mount Sinai School of Medicine, New York, New York Jane Lin Fu, M.D., Acting Chief, Genetic Services Branch, Bureau of Maternal and Child Health and Resources Development, Health Resources and Services Administration, Rockville, Maryland Harald Lee, D.D.S., Director, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland Anne Looker, Ph.D., R.D., Health Statistician, Nutrition Statistics Branch, National Center for Health Statistics, Centers for Disease Con- trol, Hyattsville, Maryland Susan K. Maloney, M.H .S., Director, Health Communication Staff, Office of Disease Prevention and Health Promotion, Washington, D.C. Alvin Mauer, M.D., University of Tennessee, Division of Hematology/ Oncology, Memphis, Tennessee Donald B. McCormick, Ph.D., Chairman, Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia Gardner C. McMillan, M.D., Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Marilyn McMillen, Ph.D., Statistician, Surveillance and Operations Re- search Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Laura McNally, R.D., M.P.H., Nutrition Specialist, Child and Adolescent Primary Care Services Branch, Bureau of Maternal and Child Health and Resources Development, Health Resources and Services Administration, Rockville, Maryland xxxi Marsel Mesulam, M.D., Professor of Neurology, Harvard Medical School, Director, Division of Neuroscience and Behavioral Neurology, Beth Israel Hospital, Boston, Massachusetts Esteban Mezey, M.D., Professor of Medicine, Johns Hopkins Hospital, Baltimore, Maryland Angela D. Mickalide, Ph.D., Staff Coordinator, U.S. Preventive Services Task Force, Office of Disease Prevention and Health Promotion, Washing- ton, D.C. William E. Mitch, M.D., Renal Division, Emory University School of Medicine, Atlanta, Georgia Elaine R. Monsen, Ph.D., R.D., University of Washington, Seattle, Wash- ington Steven R. Moore, M.P.H., Associate Chief of Staff, Office of the Surgeon General, Rockville, Maryland Hamish N. Munro, M.D., D.Sc., Senior Scientist, USDA Human Nutri- tion Research Center on Aging, Tufts University, Boston, Massachusetts Juan M. Navia, Ph.D., Professor and Chairman, Department of Public Health Sciences, Schools of Public Health and Dentistry, University of Alabama at Birmingham, Birmingham, Alabama Buford L. Nichols, Jr., M.D., Children's Nutrition Research Laboratory, Baylor School of Medicine, Houston, Texas Phillip Nieburg, M.D., M.P.H., Medical Epidemiologist, Division of Nutri- tion, Centers for Disease Control, Atlanta, Georgia Daniel W. Nixon, M.D., Associate Director, Cancer Prevention Research Program, National Cancer Institute, National Institutes of Health, Bethes- da, Maryland Marie U. Nylen, D.D.S., Dr. Odont. h.c., Director, Extramural Program, National Institute of Dental Research, National Institutes of Health, Be- thesda, Maryland Carole A. Palmer, M.Ed., R.D., Associate Professor and Division Co- Chairman, Division of Nutrition and Prevention Dentistry, Tufts Univer- sity School of Medicine, Boston, Massachusetts xxxii Eugene Passamani, M.D., Director, Division of Heart and Vascular Dis- eases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Penelope Pollard, M.S., M.B.A., Senior Research Associate, National Health Policy Forum, Washington, D.C. Donna V. Porter, Ph.D., R.D., Specialist in Life Sciences, Science Policy Research Division, Congressional Research QIXce, Washington, D.C. Roger J. Porter, M.D., Deputy Director, National institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland Barbara Posner, D.P.H., R-D., Associate Professor and Director, Graduate Nutrition Division, Boston University, Boston, Massachusetts Ann Prendergast, R.D., M.P.H., Chief Nutritionist, Habilitative Services Branch, Bureau of Maternal and Child Health and Resources Develop- ment, Health Resources and Services Administration, Rockville, Mary- land Jeanne I. Rader, Ph.D., Chief, Nutrient Toxicity Section, Experimental Nutrition Branch, Division of Nutrition, Food and Drug Administration, Washington, D.C. Edward Roccella, Ph.D., M.P.H., Program Coordinator, National High Blood Pressure Education Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Daphne A. Roe, M.D., Professor, Division of Nutritional Sciences, Cornell University, Ithaca, New York Quinton Rogers, Ph.D., Department of Physiological Sciences, School of Veterinary Medicine, University of California at Davis, Davis, California Daniel Rudman, M.D., Associate Chief of Staff, Geriatric Medicine, North Chicago Veterans Administration Medical Center, North Chicago, Illinois Robert Russell, M.D., USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts Anna A. Sandberg, Dr.P.H., Coordinator, Clinical Trial, Kidney-Urology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland . . . xxx111 Harold H. Sandstead, M.D., Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas Howerde Sauberlich, Ph.D., Department of Nutrition Science, University of Alabama, University Station, Alabama Christopher Sempos, Ph.D., Health Statistician, Nutrition Statistics Branch, National Center for Health Statistics, Centers for Disease Con- trol, Hyattsville, Maryland Zekin Shakhashiri, M.S., M.D., M.P.H., Senior Medical Advisor, National Institute of Neurological and Communicative Disorders and Stroke, Na- tional Institutes of Health, Bethesda, Maryland Lawrence E. Shulman, M.D., Ph.D., Director, National Institute of Arthri- tis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland Robert Silverman, M.D., Ph.D., Chief, Diabetes Programs Branch, Na- tional Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland Christine Hamilton Smith, Ph.D., R.D., Home Economics Department, Food Science and Nutrition, California State University at Northridge, Northridge, California Dorothy D. Sogn, M.D., Chief, Asthma and Allergy Branch, Immunology, Allergic and Immunologic Diseases Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Mary- land David A.T. Southgate, Ph.D., AFRC Institute of Food Research, Norwich Laboratory, Norfolk, United Kingdom Reynold Spector, M.D., Executive Director, Merck Sharp & Dohme Re- search Laboratories, Rahway, New Jersey Judith S. Stem, Sc.D., University of California at Davis, Davis, California Eugene Streicher, Ph.D., Director, Division of Fundamental Neurosci- ences, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland Helene Swenerton, Ph.D., Nutritionist, Cooperative Extension, Depart- ment of Nutrition, University of California at Davis, Davis, California xxxiv Jean K. Tews, Ph.D., Department of Biochemistry, University of Wiscon- sin at Madison, Madison, Wisconsin Jeanne L. Tillotson, R.D., M.A., Crofton, Maryland Phillip P. Toskes, M.D., Professor of Medicine and Director, Division of Gastroenterology, Hepatology and Nutrition, University of Florida Col- lege of Medicine and Gainesville Veterans Administration Medical Center, Gainesville, Florida Pelagia Turyn-Einhom, M.D., Medical OfIicer, Clinical Nutrition Branch, Division of Nutrition, Office of Nutrition and Food Sciences, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Wash- ington, D.C. Emestine Vanderveen, Ph.D., Associate Director for AIDS, Division of Clinical Research, National Institute on Drug Abuse, Alcohol, Drug Abuse, and Mental Health Administration, Rockville, Maryland John E. Vanderveen, Ph.D., Director, Division of Nutrition, Food and Drug Administration, Washington, D.C. John Wallingford, Ph.D., Nutritionist, Clinical Nutrition Branch, Division of Nutrition, Office of Nutrition and Food Sciences, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, D.C. Donald M. Watkin, A.B., M.D., M.P.H., Manager, Occupational Health Division, Office of Aviation Medicine, Federal Aviation Administration, U.S. Department of Transportation, and Research Professor, Department of Medicine, School of Medicine and Health Sciences, The George Wash- ington University, Washington, D.C. Richard Weindruch, Ph.D., Health Scientist Administrator, National Insti- tute on Aging, National Institutes of Health, Bethesda, Maryland Gerald Wheeler, Commission Officer, Division of Health Examination Statistics, National Center for Health Statistics, Centers for Disease Con- trol, Hyattsville, Maryland Philip L. White, Sc.D., Wilmette, Illinois, Director, Division of Applied Medical Sciences, American Medical Association, Chicago, Illinois (Re- tired) T. Franklin Williams, M.D., Director, National Institute on Aging, Nation- al Institutes of Health, Bethesda, Maryland XXXV David E Williamson, M.S., Ph.D., Analytic Epidemiologist, Centers for Disease Control, Atlanta, Georgia Myron Winick, M.D., R.R. Williams Professor of Nutrition and Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York Deborah Winn, Ph.D., Epidemiologist, Survey Planning and Development Branch, National Center for Health Statistics, Centers for Disease Con- trol, Hyattsville, Maryland Maxwell M. Wintrobe, M.D., Ph.D., D.Sc., Distinguished Professor of Medicine, University of Utah Medical School, Salt Lake City, Utah Elisabeth I? Wirick, Food, Nutrition, and Dietetics, College of Health and Human Services, University of Northern Colorado, Greeley, Colorado Eleanor A. Young, Ph.D., R.D., L.D., Professor, Department of Medicine, Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, San Antonio, Texas William J. Zukel, M.D., Deputy Director, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland The editors gratefully acknowledge the contributions of the following staff members and others who assisted in the preparation of this Report: o Office of Disease Prevention and Health Promotion Nancy Chapman, R.D., M.P.H., President, N. Chapman Associates, Washington, D.C. Mary Jo Deering, Ph.D., Publications Manager James A. Harrell, M.A., Deputy Director Susan K. Maloney, M.H.S., Director, Health Communication Staff David G. Schardt, M.S., Ph.D., Nutrition Consultant, Nutrition Media Network, Washington, D.C. Marilyn K. Schulenberg, Staff Assistant Maureen Sullivan, M.P.H., M.I.A., Program Analyst, U.S. Food and Drug Administration, New York, New York xxxvi Herbert Szeto, Intern, Nutrition Policy Staff Sara L. White, M.S., Health Promotion Research Associate, Health Communication Staff o Technical Resources, Inc. Joanna Fringer, M.A., Program Manager Jeffrey Baughman, Graphic Artist Colleen Bolton, Graphic Artist Diane Cannon, Graphic Artist James Dofflemyer, Graphic Artist Dana Donofrio, Word Processor Robin Fagan, Graphic Artist Margaret Leahy, Editor Cathy Merritt, Word Processor Laura Pancoast, Word Processing Supervisor Cherie Phillips, Graphic Artist Theodora Radcliffe, Proofreader William Rhodes, Graphic Artist Joan Saunders, Writer/Editor Channah Springer, M . F. A., Proofreader David Tran, Information Specialist o TRITON, Inc. Clarence Johnson, Communications Manager John Borstel, Senior Graphics Editor Sharon Greenspan, Graphics Assistant xxxvii Summary and Recommendations This Report addresses the substantial impact of daily dietary patterns on the health of Americans. Good health does not always come easily. It is the product of complex interactions among environmental. behavioral, social, and genetic factors. Some of these are, for practical purposes, beyond persona1 control. But there are many ways in which each of us can influence our chances for good health through the daily choices we make. In recent years, scientific investigations have produced abundant informa- tion on the ways persona1 behavior affects health. This information can help us decide whether to smoke, when and how much to drink, how far to walk or climb stairs, whether to wear seat belts, and how or whether to engage in any other activity that might alter the risk of incurring disease or disability. For the two out of three adult Americans who do not smoke and do not drink excessively, one personal choice seems to influence long-term health prospects more than any other: what we eat. Food sustains us, it can be a source of considerable pleasure, it is a reflection of our rich social fabric and cultural heritage, it adds valued dimensions to our lives. Yet what we eat may affect our risk for several of the leading causes of death for Americans, notably, coronary heart dis- ease, stroke, atherosclerosis, diabetes, and some types of cancer. These disorders together now account for more than two-thirds of all deaths in the United States. Undernutrition remains a problem in several parts of the world, as well as for certain Americans. But for most of us the more likely problem has become one of overeating-too many calories for our activity levels and an imbalance in the nutrients consumed along with them. Although much is still uncertain about how dietary patterns protect or injure human health, enough has been learned about the overall health impact of the dietary patterns now prevalent in our society to recommend significant changes in those patterns. This first Surgeon General's Report on Nutrition and Health offers com- prehensive documentation of the scientific basis for the recommended dietary changes. Through the extensive review contained in its chapters, the Report examines in detail current knowledge about the relationships among specific dietary practices and specific disease conditions and sum- 1 O Nutrition and Health marizes the implications of this information for individual food choices, public health policy initiatives, and further research. The Report's main conclusion is that overconsumption of certain dietary components is now a major concern for Americans. While many food factors are involved, chief among them is the disproportionate consumption of foods high in fats, often at the expense of foods high in complex carbohydrates and fiber that may be more conducive to health. A list of the key recommendations based on the evidence presented in the Report is provided in Table 1. Magnitude of the Problem Diet has always had a vital influence on health. Until as recently as the 1940's, diseases such as rickets, pellagra, scurvy, beriberi, xerophthalmia, andgoiter (caused by lack of adequate dietary vitamin D, niacin, vitamin C, thiamin, vitamin A, and iodine, respectively).were prevalent in this coun- try and throughout the world. Today, thanks to an abundant food supply, fortification of some foods with critical trace nutrients, and better methods for determining and improving.the nutrient content of foods, such "deti- ciency" diseases have been virtually eliminated in developed countries. For example, the introduction of iodized salt in the 1920's contributed greatly to eliminating iodine-deficiency goiter as a public health problem in the United States. Similarly, pellagra disappeared subsequent to the dis- covery of the dietary causes of this disease. Nutrient deficiencies are reported rarely in the United States, and the few cases of protein-energy malnutrition that are listed annually as causes of death generally occur as a secondary result of severe illness or injury, child neglect, the problems of the house-bound aged, premature birth, alcoholism, or some combination of these factors. As the diseases of nutritional deficiency have diminished; they have been replaced by diseases'of dietary excess and imbalance-problems that now rank among the leading causes of illness and death in the United States, touch the lives of most Americans, and generate substantial health care costs. Table 2, for example, lists the 10 leading causes of death in the United States in 1987. In addition to the five of these causes that scientific studies have associated with diet (coronary heart disease, some-types of cancer, stroke, diabetes mellitus, and atherosclerosis), another three-cirrhosis of the liver, acci- dents, and suicides-have been associated With excessive alcohol intake. 2 Summary and Recommendations O Table 1 Recommendations Issues for Most People: o Furs and cholesterol: Reduce consumption of fat (especially saturated fat) and cholesterol. Choose foods relatively low in these substances, such as vegeta- bles, fruits, whole gram foods, fish, poultry, lean meats. and low-fat dairy products. Use food preparation methods that add little or no fat. o Energy and weight control: Achieve and maintain a desirable body weight. To do so, choose a dietary pattern in which energy (caloric) intake is consistent with energy expenditure. To reduce energy intake, limit consumption of foods relatively high in calories, fats, and sugars, and minimize alcohol consump- tion. Increase energy expenditure through regular and sustained physical ac- tivity. o Complex carbohydrates andfiber: Increase consumption of whole grain foods and cereal products, vegetables (including dried beans and peas), and fruits. o Sodium: Reduce intake of sodium by choosing foods relatively low in sodium and limiting the amount of salt added in food preparation and at the table. o Alcohol: To reduce the risk for chronic disease, take alcohol only in modera- tion (no more than two drinks a day), if at all. Avoid drinking any alcohol be- fore or while driving, operating machinery, taking medications, or engaging in any other activity requiring judgment. Avoid drinking alcohol while pregnant. Other Issues for Some People: o Fluoride: Community water systems should contain fluoride at optimal levels for prevention of tooth decay. If such water is not available, use other appro- priate sources of fluoride. o Sugars: Those who are particularly vulnerable to dental caries (cavities). espe- cially children, should limit their consumption and frequency of use of foods high in sugars. o Calcium: Adolescent girls and adult women should increase consumption of foods high in calcium, including low-fat dairy products. o Iron: Children, adolescents, and women of childbearing age should be sure to consume foods that are good sources of iron, such as lean meats, fish, certain beans, and iron-enriched cereals and whole grain products. This issue is of special concern for low-income families. 0 Nutrition and Health Table 2 Estimated Total Deaths and Percent of Total Deaths for the 10 Leading Causes of Death: United States, 1987 Percent of Total Rank Cause of Death Number Deaths la Heart diseases 759,400 35.7 (Coronary heart disease) (511,700) (24.1) (Other heart disease) (247,700) (11.6) 2a Cancers 476,700 22.4 3a Strokes 148,700 7.0 4b Unintentional injuries 92,500 (Motor vehicle) W8O'J (E, (All others) (45,700) 5 Chronic obstructive lung diseases 78,000 %' 6 Pneumonia and influenza 68,600 3:2 78 Diabetes mellitus 37,800 1.8 8b Suicide 29,600 1.4 9b Chronic liver disease and cirrhosis 26,000 1.2 10s Atherosclerosis 23,100 1.1 . . . AU causes 2,125,100 causes of death in which diet plays a part. Wauses of death in which excessive alcohol consumption plays a part. 100.0 Source: National Center for Health Statistics, Monthly Vital Statistics Report, vol. 37, no. 1 ,April25,sticsReport,vol.37, no. 1, April 25,1989. Although the precise proportion attributable to diet is uncertain, these eight conditions accounted for nearly 1.5 million of the 2.1 million total deaths in 1987. Dietary excesses or imbalances also contribute to other problems such as high blood pressure, obesity, dental diseases, os- teoporosis, and gastrointestinal diseases. Together, these diet-related con- ditions inflict a substantial burden of illness on Americans. For example: o Coronary Heart Disease. Despite the recent sharp decline in the death rate from this condition, coronary heart disease still accounts for the largest number of deaths in the United States. More than 1.25 million heart attacks occur each year (two-thirds of them in men), and more than 500,000 people die as a result. In 1985, illness and deaths from coronary heart disease cost Americans an estimated $49 billion in direct health care expenditures and lost productivity. o Stroke. Strokes occur in about 500,000 persons per year in the United States, resulting in nearly 150,000 deaths in 1987 and long-term dis- ability for many individuals. Approximately 2 million living Americans suffer from stroke-related disabilities, at an estimated annual cost of more than $11 billion. 4 Summary and Recommendations 0 o High Blood Pressure. High blood pressure (hypertension) is a major risk factor for both heart disease and stroke. Almost 58 million people in the United States have hypertension, including 39 million who are under age 65. The occurrence of hypertension increases with age and is higher for black Americans (of which 38 percent are hypertensive) than for white Americans (29 percent). o Cancer. More than 475,000 persons died of cancer in the United States in 1987, making it the second leading cause of death in this country. During the same period, more than 900,000 new cases of cancer occurred. The costs of cancer for 1985 have been estimated to be $22 billion for direct health care, $9 billion in lost productivity due to treatment or disability, and $41 billion in lost productivity due to premature mortality, for a total cost of $72 billion. o Diabetes Meflitus. Approximately 11 million Americans have diabe- tes, but almost half of them have not been diagnosed. In addition to the nearly 38,000 deaths in 1987 attributed directly to this condition, diabetes also contributes to an estimated 95,000 deaths per year from associated cardiovascular and kidney complications. In 1985, diabetes was estimated to cost $13.8 billion per year, or about 3.6 percent of total health care expenses. o Obesity. Obesity affects approximately 34 million adults ages 20 to 74 years in the United States, with the highest rates observed among the poor and minority groups. Obesity is a risk factor for coronary heart disease, high blood pressure, diabetes, and possibly some types of cancer as well as other chronic diseases. o Osteoporosis. Approximately 15 to 20 million Americans are affected by osteoporosis, which contributes to some 1.3 million bone fractures per year in persons 45 years and older. One-third of women 65 years and older have vertebral fractures. On the basis of x-ray evidence, by age 90 one-third of women and one-sixth of men will have suffered hip fractures, leading to death in 12 to 20 percent of those cases and to long-term nursing care for many who survive. The total costs of osteoporosis to the U.S. economy were estimated to be $7 to $10 billion in 1983. o Dental Diseases. Dental caries and periodontal disease continue to affect a large proportion of Americans and cause substantial pain, restriction of activity, and work loss. Although dental caries among children, as well as some forms of adult periodontal disease, appear to be declining, the overall prevalence of these conditions imposes a substantial burden on Americans. The costs of dental care were esti- mated at $21.3 billion in 1985. 5 O Nutrition and Health o Diverticular Disease. Because most persons with diverticular disease do not have symptoms, the true prevalence of this condition is un- known. Frequency increases with age, and up to 70 percent of people between the ages of 40 and 70 may be affected. In 1980, diverticulosis was accountable for some 200,000 hospitalizations. In assessing the role that diet might play in prevention of these conditions, it must be understood that they are caused by a combination (and interac- tion) of multiple environmental, behavioral, social, and genetic factors. The exact proportion that can be attributed directly to diet is uncertain. Although some experts have suggested that dietary factors overall are responsible for perhaps a third or more of all cases of cancer, and similar estimates have been made for coronary heart disease, such suggestions are based on interpretations of research studies that cannot completely dis- tinguish dietary from genetic, behavioral, or environmental causes. We know, for example, that cigarette smoking exerts a powerful influence on the occurrence of both coronary heart disease and some types of cancer. We also know that some people are genetically predisposed to coronary heart disease, stroke, and diabetes and that the interaction of genetic predisposition with dietary patterns is an important determinant of individ- ual risk. For these reasons, it is not yet possible to determine the propor- tion of chronic diseases that could be reduced by dietary changes. None- theless, it is now clear that diet contributes in substantial ways to the development of these diseases and that modification of diet can contribute to their prevention. The magnitude of the health and economic cost of diet- related disease suggests the importance of the dietary changes suggested. This Report reviews these issues in detail. Nature of the Evidence Whereas centuries of clinical observations and decades of basic and clinical research prove that dietary deficiencies of single, identifiable nu- trients can cause disease, research on the relationship of dietary excesses and imbalances to chronic disease yields results that rarely provide such direct proof of causality. Instead, investigators must piece together various kinds of information from several kinds of sources. Nevertheless, the quantity of current animal, laboratory, clinical, and epidemiologic evi- dence that associates dietary excesses and imbalances with chronic dis- ease is substantial and, when evaluated according to established princi- ples, compelling. Scientists must often draw inferences about the relationships between dietary factors and disease from laboratory animal studies or human meta- 6 Summary and Recommendations O bolic and population studies that approach the issues indirectly. Data sources for such human studies include clinical and laboratory measure- ments of physiologic indicators of nutritional status or risk factors, as well as dietary intake data estimated for populations or individuals. Epi- demiologic studies using these data compare dietary intake and disease rates in different countries or in defined groups within the same country. Interpretations of animal studies are limited by uncertainties about their applicability to people. Clinical, laboratory, and dietary intake studies can provide useful information, but each has limitations. Currently available clinical and laboratory measurements reveal only a small part of the complex physiological responses to diet, and they may reflect past rather than current nutritional status. Dietary surveys depend on accurate recall of the types and portion sizes of consumed foods as well as on the assump- tion that the food intake during any one period represents typical intake. Reported intake, however, is not always accurate, and intake reported for a given period may differ significantly from that typical of longer time periods. Dietary intake data provide useful indicators for populations, but even when an association or correlation between a dietary factor and a disease is observed, it is often ditllcult to prove that the dietary factor is an actual or sole cause of that disease. This difference between association and causation is basic to understand- ing the scientific evidence that links diet to chronic disease. Uncertainties in the ability to determine causation have sometimes made it difficult to achieve consensus on appropriate public health nutrition policies. Estab- lished principles require evaluation of the supporting evidence for a given association between a dietary factor and a disease on the basis of its consistency, strength, specificity, and biological plausibility. The evidence showing that dietary intake of saturated fat raises blood cholesterol, which in turn increases the chance of coronary heart disease, illustrates this point. The similarity in results from laboratory, clinical, and epidemiologic research, the apparent relationship between dose and effect in these stud- ies, the observations that the increase in blood cholesterol level is ~p~ifk to saturated fatty acids but not to other types, and the biological plausibility of explanations for the observations, when taken together, provide consid- erable support for concluding that the association is causal, at least for some individuals. For some of the other diseases reviewed in this Report, the available evidence is less complete and less consistent. Nevertheless, much evi- dence supports credible associations between a dietary pattern of excesses u Nutrition and Health and imbalances and several important chronic diseases. These associa- tions, in turn, suggest that the overall health of Americans could be improved by a few specific but fundamental dietary changes. Key Findings and Recommendations Even though the results of various individual studies may be inconclusive, the preponderance of the evidence presented in the Report's comprehen- sive scientific review substantiates an association between dietary factors and rates of chronic diseases. In particular, the evidence suggests strongly that a dietary pattern that contains excessive intake of foods high in calories, fat (especially saturated fat), cholesterol, and sodium, but that is low in complex carbohydrates and fiber, is one that contributes signifi- cantly to the high rates of major chronic diseases among Americans. It also suggests that reversing such dietary patterns should lead to a reduced incidence of these chronic diseases. This Surgeon General's Report on Nutrition and Health provides a com- prehensive review of the most important scientific evidence in support of current Federal nutrition policy as stated in the Dietary Guidelines for Americans. These Guidelines, issued jointly by the Department of Agri- culture and the Department of Health and Human Services, recommend: o Eat a variety of foods. o Maintain desirable weight. o Avoid too much fat, saturated fat, and cholesterol. o Eat foods with adequate starch and fiber. o Avoid too much sugar. o Avoid too much sodium. o If you drink alcoholic beverages, do so in moderation. Evidence presented in this Report expands the focus of these seven guide- lines and provides considerable insight into priorities. Clearly emerging as the primary priority for dietary change is the recommendation to reduce intake of total fats, especially saturated fat, because of their relationship to development of several important chronic disease conditions. Because excess body weight is a risk factor for several chronic diseases, mainte- nance of desirable weight is also an important public health priority. Evidence further supports the recommendation to consume a dietary pattern that contains a variety of foods, provided that these foods are generally low in calories, fat, saturated fat, cholesterol, and sodium. 8 Summary and Recommendations O Taken together, the recommendations in this Report promote a dietary pattern that emphasizes consumption of vegetables, fruits, and whole grain products-foods that are rich in complex carbohydrates and fiber and relatively low in calories-and of fish, poultry prepared without skin, lean meats, and low-fat dairy products selected to minimize consumption of total fat, saturated fat, and cholesterol. The evidence presented in this Report suggests that such overall dietary changes will lead to substantial improvements in the nutritional quality of the American diet. Consuming a higher proportion of calories from fruits, vegetables, and grains may lead to a modest reduction in protein intake for some people, but this reduction is unlikely to impair nutritional status. Average levels of protein consumption in the United States, 60 grams per day for women and 90 grams per day for men, are well above the National Research Council's recommendations of 44 and 56 grams per day, respec- tively . The evidence also suggests that most Americans generally need not con- sume nutrient supplements. An estimated 40 percent of Americans con- sume supplemental vitamins, minerals, or other dietary components at an annual cost of more than $2.7 billion. Although nutrient supplements are usually safe in amounts corresponding to the Recommended Dietary Al- lowances (and such Allowances are set to ensure that the nutrient needs of practically all the population are met), there are no known advantages to healthy people consuming excess amounts of any nutrient, and amounts greatly exceeding recommended levels can be harmful. For example, some nutrients such as selenium have a narrow range of safe level of intake. Toxicity has been reported for most minerals and trace elements, as well as some vitamins, indicating that excessive supplementation with these sub- stances can be hazardous. Finally, some recommendations for dietary change apply broadly to the general public whereas others apply only to specific population groups. These major findings and recommendations of The Surgeon General's Report on Nutrition and Health are noted below. Issues for Most People 0 Fats andcholesterol: Reduce consumption of fat (especially saturated fat) and cholesterol. Choose foods relatively low in these substances, such as vegetables, fruits, whole grain foods, bh, poultry, lean meats, and low- fat dairy products. Use food preparation methods that add little or no fat. 9 0 Nutrition and Health High intake of total dietary fat is associated with increased risk for obesity, some types of cancer, and possibly gallbladder disease. Epidemiologic, clinical, and animal studies provide strong and consistent evidence for the relationship between saturated fat intake, high blood cholesterol, and increased risk for coronary heart disease. Conversely, reducing blood cholesterol levels reduces the risk for death from coronary heart disease. Excessive saturated fat consumption is the major dietary contributor to total blood cholesterol levels. Dietary cholesterol raises blood cholesterol levels, but the effect is less pronounced than that of saturated fat. While polyunsaturated fatty acid consumption, and probably monounsaturated fatty acid consumption, lowers total blood cholesterol, the precise effects of specific fatty acids are not well defined. Dietary fat contributes more than twice as many calories as equal quanti- ties (by weight) of either protein or carbohydrate, and some studies indi- cate that diets high in total fat are associated with higher obesity rates. In addition, there is substantial, although not yet conclusive, epidemiologic and animal evidence in support of an association between dietary fat intake and increased risk for cancer, especially breast and colon cancer. Similar- ly, epidemiologic studies suggest an association between gallbladder dis- ease, excess caloric intake, high dietary fat, and obesity. More precise conclusions about the role of dietary fat await the development of im- proved methods to distinguish among the contributions of the high-calorie, high-fat, and low-fiber components of current American dietary patterns. At present, dietary fat accounts for about 37 percent of the total energy intake of Americans-well above the upper limit of 30 percent recom- mended by the American Heart Association and the American Cancer Society, and above the percent consumed by many societies, such as Mediterranean countries, Japan, and China, for example, where coronary heart disease rates are much lower than those observed in the United States. Consumption of saturated fat and cholesterol is also substantially higher among many Americans than levels recommended by several expert groups. The major dietary sources of fat in the American diet are meat, poultry, fish, dairy products, and fats and oils. Animal products tend to be higher in both total and saturated fats than most plant sources. Although some plant fats such as coconut and palm kernel oils also contain high proportions of saturated fatty acids, these make minor contributions to total intake of saturated fats in the United States. Dietary cholesterol is found only in foods of animal origin, such as eggs, meat, poultry, fish, and dairy prod- 10 Summary and Recommendations tl ucts. To help reduce consumption of total fat, especially saturated fat and cholesterol, food choices should emphasize intake of fruits, vegetables, and whole grain products and cereals. They should also emphasize con- sumption of fish, poultry prepared without skin, lean meats, and low-fat dairy products. Among vegetable fats, those that are more unsaturated are better choices. 0 Energy and weight control: Achieve and maintain a desirable body weight. To .do so, choose a dietary pattern in which energy (caloric) intake is consistent with energy expenditure. To reduce energy intake, limit consumption of foods relatively high in calories, fats, and sugars and minimize alcohol consumption. Increase energy expenditure through regular and sustained physical activity. People are considered overweight if their body mass index, or BMI (a ratio of weight to height described in the Report), exceeds the 85th percentile for young American adults (approximately 120 percent of desirable body weight); they are considered severely overweight if their BMI exceeds the 95th percentile (approximately 140 percent of desirable body weight). Overweight individuals are at increased risk for diabetes mellitus, high blood pressure and stroke, coronary heart disease, some types of cancer, and gallbladder disease. Epidemiologic and animal studies have shown consistently that overall risk for death is increased with excess weight, with risk increasing as severity of obesity increases. Type II (noninsulin-dependent) diabetes mellitus accounts for approxi- mately 90 percent of all cases of diabetes and is strongly associated with obesity. Clinical studies indicate that weight loss can improve control of Type II diabetes. Obesity increases the risk for high blood pressure, and consequently for stroke; it also increases blood cholesterol levels associated with coronary heart disease. In addition, it appears to be an independent risk factor for coronary heart disease. Weight reduction has been shown to reduce high blood pressure and high blood cholesterol. Most obese individuals who achieve a more desirable body weight improve their cholesterol profile, achieving a decrease in both total blood cholesterol and LDL (low density lipoprotein) cholesterol. Some studies have found an association between overweight and increased risk for several cancers, especially cancer of the uterus and breast. In addition, overweight increases the risk for gallbladder disease. 11 0 Nutrition and Health More than a quarter of American adults are overweight. Black women age 45 and above have the highest prevalence, about 60 percent. Although evidence suggests a genetic component to the tendency of many people to become overweight, patterns of dietary caloric intake and energy expendi- ture play a key role. Sustained and long- term efforts to reduce body weight can best be achieved as a result of improving energy balance by reducing energy consumption and raising energy expenditure through physical ac- tivity and exercise. Maintenance of desirable body weight throughout the lifespan requires a balance between energy (calorie) intake and expenditure. Weight control may be facilitated by decreasing energy intake, especially by choosing foods relatively low in calories, fats, and sugars, and by minimizing alcohol consumption. Energy expenditure can be enhanced through regular phys- ical activities such as daily walks or by jogging, bicycling, or swimming at least three times a week for at least 20 minutes. 0 Compk carbohydrates andfiber Increase consumption of whole grain foods and cereal products, vegetables (includiug dried beaus and peas), and fruits. Dietary patterns emphasizing foods high in complex carbohydrates and fiber are associated with lower rates of diverticulosis and some types of cancer. The association shown in epidemiologic and animal studies be- tween diets high in complex carbohydrates and reduced risk for coronary heart disease and diabetes mellitus is, however, difficult to interpret. The fact that such diets tend also to be lower in energy and fats, especially saturated fat and cholesterol, clearly contributes to this difficulty. Some evidence from clinical studies also suggests that water-soluble fibers from foods such as oat bran, beans, or certain fruits are associated with lower blood glucose and blood lipid levels. Consuming foods with dietary fiber is usually beneficial in the management of constipation and diverticular disease. While inconclusive, some evidence also suggests that an overall increase in intake of foods high in fiber might decrease the risk for colon cancer. Among several unresolved issues is the role of the various types of fiber, which differ in their effects on water-holding capacity, viscosity, bacterial fermentation, and intestinal transit time. Other food components associated with decreased cancer risk are com- monly found in diets high in whole grain cereal products containing com- plex carbohydrates and fiber. In addition, some epidemiologic evidence Summary and Recommendations 0 suggests that frequent consumption of vegetables and fruits, particularly dark green and deep yellow vegetables and cruciferous vegetables (such as cabbage and broccoli), may lower risk for cancers of the lung and bladder as well as some cancers of the alimentary tract. However, the specific components in these foods that may have protective effects have not yet been established. Current evidence suggests the prudence of increasing consumption of whole grain foods and cereals, vegetables (including dried beans and peas), and fruits. o Sodium: Reduce intake of sodium by choosing foods relatively low in sodium and limiting tbe amount of salt added in food preparation and at the table. Studies indicate a relationship between a high sodium intake and the occurrence of high blood pressure and stroke. Salt contains about 40 percent sodium by weight and is used widely in the preservation, process- ing, and preparation of foods. Although sodium is necessary for normal metabolic function, it is consumed in the United States at levels far beyond the 1.1 to 3.3 grams per day found to be as safe and adequate for adults by the National Research Council. Average current sodium intake for adults in the United States is in the range of 4 to 6 grams per day. Blacks and persons with a family history of high blood pressure are at greater risk for this condition. While some people maintain normal blood pressure levels over a wide range of sodium intake, others appear to be "salt sensitive" and display increased blood pressure in response to high sodium intakes. Although not all individuals are equally susceptible to the effects of so- dium, several observations suggest that it would be prudent for most Americans to reduce sodium intake. These include the lack of a practical biological marker for individual sodium sensitivity, the benefit to persons whose blood pressures do rise with sodium intake, and the lack of harm from moderate sodium restriction. Processed foods provide about a third or more of dietary sodium. Because about another third of the sodium consumed by Americans is added by the consumer, much can be done to reduce sodium consumption by using less salt at the table and substituting alternative flavoring such as herbs, spices, and lemon juice in the preparation of foods. In addition, choices can be made of foods modiied to lower sodium content and less frequent choices could be made of foods to which sodium is added in processing and preservation. 13 O Nutrition and Health o Alcohol: To reduce the risk for chronic disease, take alcohol only in moderation (no more than two drinks a day), ifat all. Avoid drinking any alcohol before or while driving, operating machinery, taking medica- tions, or engaging in any other activity requiring judgment. Avoid tkhking alcohol while pregnant. Alcohol is a drug that can produce addiction in susceptible individuals, birth defects in some children born to mothers who drink alcohol during pregnancy, impaired judgment, impaired ability to drive automobiles or operate machinery, and adverse reactions in people taking certain medica- tions. In addition, alcohol abuse has been associated with disrupted family functioning, suicides, and homicides. Excessive use of alcohol is also associated with liver disease, some types of cancer, high blood pressure, stroke, and disorders of the heart muscle. Extensive epidemiologic and clinical evidence has identified alcohol con- sumption as the principal cause of liver cirrhosis in the United States, at least in part as a result of the direct toxic effects of alcohol on the liver. Smoking and alcohol appear to act synergistically to increase the risk for cancers of the mouth, larynx, and esophagus. Less conclusive and some- what conflicting evidence suggests a role of alcohol in other types of cancers such as those of the liver, rectum, breast, and pancreas. Studies indicate a direct association between increased blood pressure and the consumption of alcohol at levels beyond about two drinks" daily. Extremely excessive alcohol consumption is associated with cardiomyop- athy. Alcohol consumption by the mother during pregnancy has also been associated with fetal malformations. Although consumption of up to two drinks per day has not been associated with disease among healthy men and nonpregnant women, surveys suggest that at least 9 percent of the total population consumes two or more drinks per day and those in this group need to reduce their alcohol consumption. A threshold level of safety for alcohol intake during pregnancy has not been established. Thus, pregnant women and women who may become preg- nant should avoid drinking alcohol. lone drink is defined as a 12 ounce beer, a 5 ounce glass of wine, or 1% fluid ounces (one jigger) of distilled spirits, each of which contains about 1 ounce of alcohol. 14 Summary and Recommendations O Other Issues for Some People 0 Fluoride: Community water systems should contain fluoride at optimal levels for prevention of tooth decay. If such water is not available, use other appropriate sources of fluoride. The most efficient means of making fluoride available to the general public to reduce dental disease is through drinking water. Numerous epidemio- logic and clinical studies have attested to the efficacy, safety and cost- effectiveness of systemic fluoride in the prevention of tooth decay. Life- time use of water containing an optimal fluoride concentration of approxi- mately 1 part per million has been shown to reduce the prevalence of dental caries by more than 50 percent. Water fluoridation is considered one of the most successful public health efforts introduced in the United States. For children living in areas with inadequate concentrations of fluoride in the water, supplementary fluoride sources should be used at dosages that depend on the fluoride content of the local water supply and the age of the child. The effectiveness of prenatal fluoride administration, however, is uncertain because clinical studies of its effects on subsequent caries inci- dence have been equivocal. Excessive fluoride should be avoided because it may cause mottling of developing teeth. 0 Sugurs: Those who are particularly vulnerable to dental caries (cavities), especially children, should limit their consumption and frequency of use of foods high in sugars. Although genetic, behavioral, and other dietary factors also influence dental health, the major role of sugars in promotion of tooth decay is well established from animal, epidemiologic, clinical, and biochemical studies. Newly erupting teeth are generally more vulnerable to decay than mature teeth. Research has shown that three conditions must exist for the formation of dental caries: the presence of fermentable carbohydrate, acid-producing bacteria, and a susceptible tooth. Caries-producing bacteria metabolize a range of sugars (glucose, fructose, maltose, lactose, and sucrose) to acids that demineralize teeth. The unique role of sucrose (common table sugar) in dental caries is related to its special ability to be converted by these bacteria into long, complex molecules that adhere firmly to teeth and form plaque. 0 Nutrition and Health The most important diet-related interventions are fluoridation of drinking water, or the use of other means of fluoride administration, and control of intake of sugars. While fluoride is the most important factor overall in dental caries prevention, reduction in the frequency of consumption and in the quantity of sugar-rich foods in the diet will also help reduce decay. Sticky sweet foods that adhere to the teeth are more cariogenic than those that wash off quickly. The longer cariogenic foods remain in the mouth, the more they are likely to increase the initiation and progression of tooth decay. 0 Calcium: Adolescent girls and adult women should increase consumption of foods high in calcium, including low-fat dairy products. Inadequate dietary calcium consumption in the first three to four decades of life may be associated with increased risk for osteoporosis in later life. Osteoporosis, a chronic disease characterized by progressive loss of bone mass with aging, occurs in both women and men, although postmenopausal women are twice as likely as men to have severe osteoporosis with conse- quent bone fractures. Evidence shows that chronically low calcium intake, especially during adolescence and early adulthood, may compromise de- velopment of peak bone mass. In postmenopausal women, the group at highest risk for osteoporosis, estrogen replacement therapy under medical supervision is the most effective means to reduce the rate of bone loss and risk for fractures. Maintenance of adequate levels of physical activity and cessation of cigarette smoking have also been associated with reduced osteoporosis risk. Although the precise relationship of dietary calcium to osteoporosis has not been elucidated, it appears that higher intakes of dietary calcium could increase peak bone mass during adolescence and delay the onset of bone fractures later in life. Thus, increased consumption of foods rich in calcium may be especially beneficial for adolescents and young women. Food sources of calcium consistent with other dietary recommendations in this Report include low-fat dairy products, some canned fish, certain vegeta- bles, and some calcium-enriched grain products. o Iron: Children, adolescents, and women of childbearing age should be sure to consume foods that are good sources of iron, such as lean meats, fish, certain beans, and iron-enriched cereals and whole grain products. This issue is of special concern for low-income families. Dietary iron deficiency is responsible for the most prevalent form of anemia in the United States. Iron deficiency hampers the body's ability to produce hemoglobin, a substance needed to carry oxygen in the blood. A 16 Summary and Recommendations O principal consequence of iron deficiency is reduced work capacity, al- though depressed immune function, changes in behavior, and impaired intellectual performance may also result. Because of the serious conse- quences of iron deficiency, continual monitoring of the iron status of individuals at high risk-particularly children from low-income families, adolescents, and women of childbearing age-is vital, as is treatment of those identified to be iron deficient. Proper infant feeding-preferably breastfeeding, otherwise use of iron- fortified formula-is the most important safeguard against iron deficiency in infants. Among adolescents and adults, iron intake can be improved by increasing consumption of iron-rich foods such as lean meats, fish, certain kinds of beans, and iron-enriched cereals and whole grain products. Also, consuming foods that contain vitamin C increases the likelihood that iron will be absorbed efficiently. Policy Implications Dietary Guidance General Public Educating the public about the dietary choices most conducive to preven- tion and control of certain chronic diseases is essential. Educational efforts should begin in primary school and continue throughout the secondary grades, and should focus on the dietary principles outlined in this Report- the potential health benefits of eating a diet that is lower in fat (especially saturated fat) and rich in complex carbohydrates and fiber. The importance of adequate physical activity should also be stressed. Efforts should con- tinue throughout each stage of life to promote the principles outlined in the Dietary Guidelines for Americans. Special Populations A disproportionate burden of diet-related disease is borne by subgroups in our population. Black Americans, for example, have higher rates of high blood pressure, strokes, diabetes, and other diseases associated with obesity (but lower rates of osteoporosis) than the general population. Some groups of Native Americans exhibit the highest rates of diabetes in the world. Pregnant and lactating women also have special nutritional needs. Particular effort should be made to identify and remove the barriers to optimal health and nutritional status in such high-risk groups, using meth- ods that take into consideration their diverse cultural backgrounds. 17 O Nutrition and Health Many older persons suffer from chronic diseases that can reduce functional independence; many take multiple medications that may adversely interact with nutrients. Sound public education directed toward this group-and professional education directed toward individuals who care for older Americans-should focus on dietary means to reduce risk factors for chronic disease, to promote functional independence, and to prevent ad- verse consequences of use of medications. Health Professionals Improved nutrition training of physicians and other health professionals is needed. Training should emphasize basic principles of nutrition, the role of diet in health promotion and disease prevention, nutrition assessment methodologies and their interpretation, therapeutic aspects of dietary in- tervention, behavioral aspects of dietary counseling, and the role of dieti- tians and nutritionists in dietary counseling of patients. Programs and Services Food Labels Food labeling offers opportunities to inform people about the nutrient content of foods so as to facilitate dietary choices most conducive to health. Food manufacturers should be encouraged to make full use of nutrition labels. Labels of processed foods should state the content of calories, protein, carbohydrate, fats, cholesterol, sodium, and vitamins and minerals. To the extent permitted by analytical methods, manufactur- ers should disclose information where appropriate on the content of satu- rated and unsaturated fatty acids and total fiber in foods that normally contain them. Descriptive terms such as "low calorie" and "sodium re- duced" in compliance with the Food and Drug Administration's regula- tions for food labeling may also be helpful, and the expanded use of these terms should be encouraged. Nutrition Services Health care programs for individuals of all ages should include nutrition services such as, when appropriate, nutrition counseling for individuals or groups, interpretation and implementation of prescribed therapeutic diets tailored to individual food preferences and lifestyle, referral to appropriate community services and food assistance programs, monitoring of prog- ress, and appropriate followup. These services should routinely incorpo- rate assessment of nutritional status and needs based on established crite- 18 Summary and Recommendations O ria to identify individuals with nutritional risk factors who would profit from preventive measures and those with nutritional disorders who need remedial care. Food Services Lack of access to an appropriate diet should not be a health problem for any American. Wherever food is served to people or provided through food assistance programs, it should reflect the principles of good nutrition stated in this Report. Whether served in hospitals, schools, military installations, soup kitchens, day care centers, or nursing homes, or whether delivered to homes, food service programs offer important opportunities for improving health and providing dietary education. Such programs should pay special attention to the nutritional needs of older people, pregnant women, and children, especially those of low income or other special dietary needs. Because a large proportion of the population takes meals in restaurants and convenience food facilities, improvements in the overall nutritional bal- ance of the meals served in such places can be expected to contribute to health benefits. Food service programs should also take particular care to ensure that special diets lower in fat, especially saturated fat, are provided to people with elevated blood cholesterol, heart disease, or diabetes; that diets low in sodium are provided to individuals with high blood pressure; and that protein-restricted diets are made available to people with end-stage kidney disease. Food Products The public would benefit from increased availability of foods and food products low in calories, total fat, saturated fat, cholesterol, sodium, and sugars, but high in a variety of natural forms of fiber and, perhaps, certain minerals and vitamins. Food manufacturers can contribute to improving the quality of the American diet by increasing the availability of palatable, easily prepared food products that will help people to follow the dietary principles outlined here. Because the public is becoming increasingly conscious of the role of nutrition in health, development of such products should also benefit the food industry. Research and Surveillance Impressive evidence already links nutrition to chronic disease. However, much more information is needed to continue to identify changes in the 19 O Nutrition and Health national diet that will lead to better health for the Nation. Gaps in our knowledge of nutrition suggest future research and surveillance needs. Examples are: o The role of specific dietary factors in the etiology and prevention of chronic diseases. o The childhood dietary pattern that will best prevent later development of chronic diseases. o The effects of maternal nutrition on the health of the developing fetus. o The nutrient and energy requirements of older adults. o How nutrient requirements translate into healthful dietary patterns. o The development of biodhemical markers of dietary intake to monitor better the effects of dietary intervention. o The identification of effective educational methods to translate dietary recommendations into appropriate food choices. o The establishment of a nutrition surveillance system that will enhance the monitoring of population-specific and State-specific trends in the occurrence of nutrition-related risk factors and conditions. 20 Chapter 1 Introduction and Background Power of nutriment reaches to bone and to all the parts of bone, to sinew, to vein, to artery, to muscle, to membrane, to flesh, fat, blood, phlegm, marrow, brain, spinal marrow, the intestines, and all their parts: it reaches also to heat, breath, and moisture. Hippocrates (-377 B.C.) Introduction It has long been understood that optimal health depends on adequate nutrition, yet knowledge of the ways in which specific dietary factors affect the risk for disease is incomplete. Dietary deficiencies can be manifested in various ways. A deficient intake of energy or nutrients can lead to protein- energy malnutrition or to classic deficiency diseases such as rickets, pel- lagra, or iron deficiency anemia. Protein-energy malnutrition and diseases due to deficiencies of various nutrients are prominent causes of premature death and disability in developing countries but, with a few exceptions, appear to have been eliminated in the United States. When nutrient deficiencies are reported in this country, they are most often observed to be associated with poverty, the additional nutrient require- ments of pregnancy or infancy (IOM 1985), the abuse or neglect of children or older persons, or some combination of these factors. They also are observed to result from the restricted food intake that sometimes accom- panies aging, alcohol or drug abuse, unusually severe and prolonged injury or illness (including prolonged hospitalization), excessive dieting, or re- strictive dietary practices. Thus, pregnant women, young infants, chil- dren, older persons, alcohol and drug abusers, and chronically ill and disabled individuals are at greatest risk for malnutrition due to dietary deficiencies, especially if their income is low. Whatever its root cause, inadequate nutrition retards normal growth, lowers resistance to infectious disease, impairs maternal and child health, and may adversely affect the ability to function at peak physical and mental capacity. These issues are discussed in detail in the relevant chapters of this Report. 21 O Nutrition and Health As problems of nutritional deficiency have diminished in the United States, they have been replaced by problems of dietary imbalance and excess. These imbalances and excesses have contributed to the increased preva- lence and severity of chronic diseases that are major causes of death and disability among Americans. Table l-1 lists the 10 leading causes of death in this country. Among them, five-coronary heart disease and generalized atherosclerosis, stroke, some types of cancer, and diabetes-have been associated with dietary excesses or imbalances, and another three-cir- rhosis of the liver, accidents, and suicides-are often the result of exces- sive alcohol intake. Together, these conditions account for as much as 70 percent of annual deaths among Americans (Collins 1986; NCHS 1986). Dietary excesses or imbalances also have been associated with high blood pressure, obesity, dental diseases, osteoporosis, and, perhaps, kidney and gastrointestinal diseases. Such conditions also contribute to much illness, disability, and death in the United States, and thus to substantial human and economic costs to society. Table l-l Estimated Total Deaths and Percent of Total Deaths for the 10 Leading Causes of Death: United States, 1987 Rank Cause of Death Number Percent of Total Deaths la 2a 3a 4b 5 6 7a 8b 9b IO= Heart diseases 759,400 (Coronary heart disease) (511,700) (Other heart disease) (247,700) Cancers 476,700 Strokes 148,700 Unintentional injuries 92,500 (Motor vehicle) W5,800) (All others) (45,700) Chronic obstructive hmg diseases 78,ooO Pneumonia and influenza w600 Diabetes mellitus 37,800 Suicide 29,600 Chronic liver disease and cirrhosis 26,000 Atherosclerosis 23,100 35.7 (24.1) (11.6) 22.4 7.0 (i::, (2.2) 3.7 3.2 1.8 1.4 1.2 1.1 . . . All causes 2,125,loo BCauses of death in which diet plays a part. Wauses of death in which excessive alcohol consumption plays a part. 100.0 Source: National Center for Health Statistics 1988. 22 Introduction and Background cl Much about the ways in which excessive intake of energy and nutrients might affect health remain to be elucidated. Yet despite uncertainties, much has been learned about diet-disease relationships. This first Surgeon General's Report on Nutrition and Health examines the current state of knowledge of associations among dietary patterns, nutrients, and certain disease conditions. Its purpose is to review the available research evidence that relates diet to health to establish a basis for policies that promote dietary means to improve health. Development and Organization of the Report This Surgeon General's Report on Nutrition and Health has been devel- oped in response to the increasing interest of the public, health profession- als, and policy leaders in the role of diet in health promotion and prevention of chronic disease. In preparing the Report, the Public Health Service (PHS) reviewed past and current research related to diet and disease as a basis for examination of the implications for public policies on nutrition education, services, and research. The Report reviews current knowledge of the influence of dietary factors on specific aspects of health. This first chapter introduces the major themes of the Report in their historical context; it also reviews and synthe- sizes basic information about essential nutrients in the human diet, the levels of intake required for human health, and American dietary patterns, and it explains the criteria used to examine the various kinds of research studies that are reviewed throughout the Report. Chapters 2 through 14 describe the scientific research that has examined associations between specific dietary factors and selected disease conditions in the United States (Coronary Heart Disease, High Blood Pressure, Cancer, Diabetes, Obesity, Skeletal Diseases, Dental Diseases, Kidney Diseases, Gastroin- testinal Diseases, Infections and Immunity, Anemia, Neurologic Disor- ders, and Behavior). Chapters 15 (Maternal and Child Nutrition) and 16 (Aging) review the special nutritional challenges at especially vulnerable stages of the human life cycle. The interactions between nutrients and alcohol and between nutrients and drugs, and the effects of these sub- stances on human nutritional status, are reviewed in chapters 17 and 18, respectively. The Report closes with a final chapter on dietary fads and frauds. Most of the chapters follow a common format. Each begins with a brief introduction and a section entitled Historical Perspective that is designed to establish a historical context for the area under review. A section on 23 O Nutrition and Health Significancefor Public Health contains information currently available on the incidence, prevalence, and cost to the Nation of each of the conditions under review. Many of the chapters contain a further introductory Scien- tific Background section that summarizes technical information needed to understand the research issues reviewed in the Report. The major part of the chapters is devoted to a review of Key Scientific Issues that summarizes current knowledge about possible associations between dietary factors and disease that are most relevant to public policy. Each chapter closes with a section entitled Implications for Public Health Policy that summarizes the signiftcance of the research evidence for di- etary guidance and education, nutrition programs and services, and nutri- tion research and surveillance. Finally, Literature Cited provides an exten- sive list of references to support the scientific findings in each chapter. Historical Perspective Throughout history, human societies have observed relationships between the consumption of certain foods and the preservation of good health or the prevention or treatment of diseases. Although the word "diet" occurs frequently in writings attributed to Hippocrates and to Galen, the term "nutrition" did not appear as an English word until the mid-1400's and was used infrequently until the second half of the 19th century (Todhunter 1973). The modem concept of nutrition-that human life depends on a steady intake of a variety of specific dietary substances in defined amounts-is less than 200 years old. Development of Nutritional Science Conditions related to nutritional deficiency, such as beriberi, rickets, or scurvy, were described in very early writings, but the identification of the specific dietary factors required to prevent or treat these conditions began to occur only in the late 18th century and did not approach completion for another 150 years. Some of the major events in this gradual development of nutrition as a science from the earliest records to 1950 are listed in Table l-2. The chapters of this Report review the great expansion of nutrition research and knowledge that has occurred since then. The earliest efforts to establish the scientific basis of nutrition are usually attributed to the French chemist Lavoisier, who demonstrated in 1789 that the oxygen breathed in air was consumed in the body to produce carbon dioxide and water, and that this central metabolic process was measurable, variable, and related to both the level of physical activity and the amount of 24 Introduction and Background 0 Table 1-2 Selected Events in the History of Nutritional Science to 1950 c. 1500 B.C. c. 400 B.C. c. 300 B.C. c. 200 A.D. 1250 1614 1650 1730 1747 1752 1780 1789 17% 1807 1810-23 1810 1816 1827 1833 1838 1839 1840 Papyrus Ebers contains prescription believed to refer to diabetes. Hippocrates wrote of relationship of diet to health. Beriberi described in ancient Chinese texts. Arataeus gave the name diabetes to the condition of "too much passing of urine." Joinville described scurvy among troops of Louis IX at the siege of Cairo. Sanctorius published studies relating body weight to food intake. Glisson described rickets in De Rachitide. Casal described pellagra, calling it "ma1 de la rosa." Lind proved that citrus fruits cure scurvy in first controlled human dietary experiment. Menghini established presence of iron in blood. Reaumur published experiments on digestion in birds. Spallanzani produced evidence that digestion was the chemical action of gastric juices. Lavoisier and Seguin make first measurements relating oxygen consumption to human energy metabolism. Cod liver oil used as treatment for rickets. Lemon juice offtcially introduced in British Navy to prevent SCUNY. Davy isolated sodium, potassium, calcium, magnesium, sulphur, and boron. Chevreul studied chemistry of animal fats. WolIaston isolated cystic oxide (later named cystine) from urine--first amino acid discovered. Magendie identified dietary nitrogen requirements in dogs. Prout classified food constituents as saccharine, oily, and albuminous (sugar, fat, and protein). Beaumont reported observations and experiments on digestion in his patient St. Martin. Mulder introduced the term "protein." Boussingault conducts first nitrogen balance studies in animals. Liebig published Animal Chemistry, stating basic principles of metabolism. 25 O Nutrition and Health Table l-2 (continued) 1843 1848 1849-57 1850 1850-52 186641 1867 1877 1885 18% 1897 1902 1909-28 1912 1914 1916 1918 1919-22 1921-24 1922 1928 1929 1931-37 1932 1933 Chossat studied the effect of starvation on the body using pigeons. Addison described pernicious anemia. Bernard elucidated digestive action of pancreatic juices and glycogenic function of liver. Livingstone described xerophthalmia (due to vitamin A deficiency) in Africa. Chatin in France used iodine to prevent goiter. Voit and Pettenkofer explained protein metabolism. Boussingault recognized iron as essential nutrient. Pavlov began classic studies on digestion in dogs. Takaki demonstrated in controlled dietary experiments with Japanese Navy sailors that beriberi could be prevented. Atwater and Bryant introduced their basic reference, Chemical Composition of American Food Materials. Eijkman published his work on causes of beriberi. Rubner showed that food components increased metabolism by different amounts. Osborne and Mendel studied the nutritive value of protein. Funk coined the term "vitamine." Goldberger established dietary cause of pellagra. McCollum and Davis and Osborne and Mendel discovered accessory dietary factors "fat-soluble A" and "water-soluble B." Mellanby showed that experimental rickets in dogs is due to lack of fat-soluble vitamin. Water-soluble B factor shown to be more than one factor. Blindness in children shown to be result of lack of vitamin A. McCollum identified vitamin D in cod liver oil. Goldberger identified pellagra-preventing factor in yeast. Role of intrinsic and extrinsic factors in pernicious anemia discovered. Fluoride content of drinking water identified as cause of mottled enamel of teeth and prevention of tooth decay. Vitamin C isolated from lemon juice. Warburg and Christian identified riboflavin and defined its molecular function. Williams identified kwashiorkor as a nutritional disease. 26 Introduction and Background O Table l-2 (continued) 1938 1941 Rose classified amino acids as essential and nonessential. Evidence provided for the influence of prenatal diet on the health of the newborn infant. ! 944-46 Keys and coworkers studied effects on young men of experimentally induced semistarvation and methods of dietary rehabilitation. I945 1948-49 Grand Rapids. Michigan. becomes the first city in the world to fluoridate its drinking water to prevent tooth decay. Crystalline vitamin B,, isolated from liver extract and shown to contain cobalt. 1949 Framingham Study of coronary heart disease risk factors begins. Sources: Darby 1985; McCollum 1957; Murlin 1948; Olson 1978; Todhunter 1962, 1973, 1976. food ingested (Lusk 1933). In the 19th century, European and American scientists isolated and began to identify the major groups of nutrients in the diet, to develop the first estimates of nutrient requirements, and to explore the basics of energy metabolism. For example, in 1816, Magendie of France established that nitrogen-containing compounds were essential in the diet of dogs; in 1838, these compounds were given the name protein (from the French word for "primary substance"). In 1814, the French chemist Chevreul discovered that fats consisted of fatty acids attached to a glycerol molecule. By 1834, the London physician Prout was able to introduce the idea that food consists of substances called saccharine, oily, and albuminous-today called carbohydrates, fats, and proteins (Todhunter 1959). Later in the century, Rubner ofGermany and Atwater of the United States established the energy values of these substances as approximately 4, 9, and 4 kcal/g, respectively (McCollum 1957). Thus, from the time of Lavoisier to the end of the 19th century, knowledge of nutritional science grew to encompass the metabolic basis of energy production from food, the classification of nutrients and sources of energy, the dependence of energy requirements on physical activity, the influence of diet on body weight and of fevers on metabolism of food substances, the principles of metabolic homeostasis, and the roles of specific essential nutrients in human physiology (Murlin 1948). During this period, lemon juice was found to prevent scurvy, iodine to prevent goiter, and in- completely milled rice to prevent beriberi. Despite these advances, the most fundamental concepts about nutrition were still poorly developed at the beginning of the 20th century. It was not until the first half of this 27 O Nutrition and Health century that scientists identified human nutritional requirements, charac- terized the nutritional value of proteins, and identified the amino acids, vitamins, fatty acids, and minerals essential in the human diet (Todhunter 1976). For example, Osborne and Mendel of Yale University elucidated the differences between complete and incomplete proteins during the first decades of this century. Later, Rose of the University of Illinois estab- lished which of the amino acids were essential and estimated how much of each was required each day. The diseases of scurvy, beriberi, rickets, and pellagra had been described in very early writings, but their specific causes were not identified until after 1900. In 1906, Hopkins of Cambridge University suggested that food contained certain accessory factors necessary for prevention of these conditions. In 1912, Funk named these factors "vitamines," later called vitamins as more was learned about their chemical structure (Rosen 1958). Early in the century, the dietary cause of pellagra was established by Goldberger, a PHS physician, and fat- and water-soluble vitamins were isolated and characterized (McCollum 1957). Also during this period, kwashiorkor was identified as a nutritional disease and the importance of prenatal diet on the health of newborn infants began to be appreciated (Darby 1985). Over the next three decades, all of the vitamins were identified, starting with the isolation of a fat-soluble substance in egg yolk by McCollum at the University of Wisconsin, now known as vitamin A, and continuing with the discoveries of folic acid, vitamin Br2, and other B vitamins in the 1930's and 1940's (McCollum 1957). The essential nature of trace elements such as selenium and zinc were finally recognized in the 1950's and 1960's (Darby 1985). After World War II, the major focus of attention in nutrition began to shift away from acute nutrient deficiency diseases. The advent of improved transportation systems and home refrigeration and frozen foods expanded the year-round availability of fresh and wholesome foods, and food for- tification helped to increase the availability of previously scarce nutrients. At the same time, vaccines, antibiotics, and other advances in medicine and health prevented and controlled many of the infectious diseases that had previously shortened the human lifespan. Thus, chronic degenerative diseases became more important as causes of illness and death. Nutrition scientists began to examine the relationship of modem dietary patterns and practices to these chronic diseases-cardiovascular disease, cancer, and diabetes, for example-that were becoming increasingly prevalent among 28 Introduction and Background cl Americans in middle and late life, and attention shifted to the effects of specific nutrients and dietary factors on the long. slow development of these conditions. Evolution of .Federal Nutrition Policy As knowledge developed in the nutrition sciences and on the health effects of food, and as food availability and consumption patterns became more apparent, nutrition assumed an increasingly visible role in pubtic policy. By 1979, the Federal Government was involved in efforts to ensure an adequate, safe, and nutritious food supply for Americans through spon- sorship of more than 350 programs in key areas of nutrition policy: agricul- tural support, food safety and regulation, food fortification, food assis- tance, nutrition services and training, food intake and nutritional status monitoring, food and nutrition research, and food and nutrition education (Comptroller General 1979). Some of these programs had rdots that reached back to the turn of the century. but since World War I1 the Government's efforts have increasingly focused on meeting the needs of high-risk groups and on the role of-diet in health promotion and disease prevention. Table l-3 presents a chronological listing of selected events in the development of Federal domestic nutrition policies; the history of Federal initiatives in the major areas of nutrition policy is reviewed below. Table 1-3 Selected Federal Domestic Nutdtion Policy Initiatives, 1862-1988 1862 1867 1887 1889 U.S. Department of Agriculture (USDA) created. Morrill Act establishes land grant colleges. O&e of Education established-wi;h responsibilities for nutrition education within public schools. Hatch Act establishes agricultural experiment stations. Federal research laboratory established at Staten Island. Name is changed to the National Institute of Health in 1930. U.S. Public Health Service Commissioned Corps authorized for duty on communicable, nutritional, and other diseases. 1893 1906 1914 1916 USDA authorized by Congress to conduct research on agriculture and human nutrition. The Pure Food and Drug (Wiley) Act prohibits interstate commerce and misbranded and adulterated foods, drinks, and drugs. Federal Meat Inspection Act passed. Cooperative Extension Service created as part of USDA. USDA publishes Food for Young Children, first dietary guidance pamphlet. 29 u Nutrition and Health Table l-3 (continued) 1917 1921-29 1924 1927 1930 1933 1935 1936-37 1938 1939 1940 1941 1946 1947 1954 U.S. Food Administration established to supervise World Wa, I food supply. First dietary recommendations issued by USDA-Five Food Groups. Maternity and Infancy Act enabled State health departments to employ nutritionists. Addition of iodine to salt to prevent goiter is first U.S. food fortification program. Food, Drug, and Insecticide Administration established. Name is changed to Food and Drug Administration (FDA) in 1932. USDA and Federal Emergency Relief Administration buy and distribute surplus agricultural commodities as food relief. Public Health Service Hygienic Laboratory designated as National Institute of Health (later changes to National Institutes of Health). Agricultural Act amendments permit purchase of surplus commodities for donation to child nutrition and school lunch programs. Food Distribution Program established. Social Security Act authorizes grants to States for nutrition services to mothers and children . USDA conducts first Nationwide Food Consumption Survey (NFCS). The Food, Drug and Cosmetic (FD&C) Act includes provisions for food standards. FDA nutrition research program established. Social Security Act provides support for role of nutrition in health. Federal Surplus Commodities Corporation initiates experimental Food Stamp Program. National Defense Advisory Commission draws attention to malnutrition in the United States. President Roosevelt calls National Nutrition Conference, with announcement of the first Recommended Dietary Allowances by the Food and Nutrition Board. FDA promulgates standards for enrichment of flour and bread with B-complex vitamins and iron. National School Lunch Program established. Laboratories of Nutrition, Chemistry, and Pathology of the National Institutes of Health incorporated into Experimental Biology and Medicine Institute. Special Milk Program established. 30 Introduction and Background 0 Table 1-3 (continued) 1955 1956 1958 1961 1%3 and 1965 1%5 1966 1966-70 1968 1968-70 I%9 1971-74 Interdepartmental Committee on Nutrition for National Defense established (discontinued 1%7). Title VII of the Public Health Service Act authorizes funds to support graduate training in public health nutrition. Food Additives Amendment to FD&C Act prohibits use of a food additive until safety established by manufacturer. Delaney Clause prohibits carcinogenic additives. GRAS (Generally Recognized As Safe) list established. President Kennedy expands the use of surplus food for needy people at home and abroad and announces a new pilot Food stamp Program. Maternal and Child Health and Mental Retardation Planning Amendments to the Social Security Act allow for an expanded number of nutritionists in health care programs. Food Stamp Act passed by Congress. Nationwide Food Consumption Survey collects first data on dietary intake of individuals. Child Nutrition Act passed. School Breakfast Program established. President Johnson outlines Food for Freedom Program, the "war on hunger." Allied Health Professions Personnel Training Act includes support for training of dietitians. The Department of Health, Education, and Welfare (DHEW), which later becomes the Department of Health and Human Services (DHHS), sponsors a National Academy of Sciences study, Maternal Nutrition and the Course of Pregnancy, which makes major recommendations related to the role of nutrition in human reproduction. U.S. Senate Select Committee on Nutrition and Human Needs established. DHEW sponsors Preschool and Ten-State Nutrition Surveys that report evidence of hunger and malnutrition in poverty groups in the United States. President Nixon calls White House Conference on Food, Nutrition, and Health. Secretary of Agriculture establishes the Food and Nutrition Service to administer Federal food assistance programs. The National Center for Health Statistics conducts the first National Health and Nutrition Examination Survey (NHANES) to measure the nutritional status of the U.S. population. This is followed by NHANES II in 1976-80, Hispanic HANES in 1982-84, and NHANES III in 1988. 31 0 Nutrition and Health 1974 1975 1977 1978 1979 1980 1981 1984 1985 Table l-3 (continued) 1972 USDA establishes Special Supplementary Food Program for Women, Infants, and Children (WIC). Agriculture and Consumer Protection Act provides price supports to farmers. Amendments to the Older Americans Act of 1%5 establish a congregate and home-delivered meals program for older Americans. U.S. Senate Select Committee on Nutrition and Human Needs issues Guidelines for a National Nutrition Policy, prepared by the National Nutrition Consortium. Safe Drinking Water Act passed. National Institutes of Health establishes Nutrition Coordinating Committee. U.S. Senate Select Committee on Nutrition and Human Needs issues two editions of Dietary Goals for the United States. Food and Agricultural Act and Child Nutrition and National School Lunch Amendments passed. Joint Subcommittee on Human Nutrition Research established in Office of Science and Technology Policy (in 1983 becomes Interagency Committee on Human Nutrition Research under joint direction of USDA and DHHS). DHEW and USDA submit proposal to Congress for National Nutrition Monitoring System. DHEW establishes Department-wide Nutrition Policy Board and issues Healthy People: The Surgeon General's Report on Health Promotion and Disease Prevention. USDA and DHHS jointly issue Nutrition and Your Health: Dietary Guidelines fcr Americans. A second edition follows in 1985. DHHS issues Promoting Health/Preventing Disease: Objectives for the Nation, which contains 17 nutrition objectives to be achieved by the year 1990. The Surgeon General's Workshop on Maternal and Infant Health makes recommendations about improving nutrition for these vulnerable groups. DHHS and USDA issue Joint Implementation PIan for a Comprehensive National Nutrition Monitoring System, revised in 1987 as the Operational Plan for the National Nutrition Monitoring System. The Select Panel for the Promotion of Child Health, created by Public Law 95-626, submits to Congress and the Secretary of DHHS its report, which includes recommendations on nutrition. The Surgeon General's Workshop on Breastfeeding and Human Lactation develops strategies for promoting breastfeeding. USDA initiates Continuing Survey of Food Intakes by Individuals. repeated in 1986. 32 Introduction and Background O Table l-3 (continued) 1986 DHHS and USDA issue Nutrition Monitoring in the United States, the report of the Joint Nutrition Monitoring Evaluation Committee. 1988 DHHS publishes The Surgeon General's Report on Nutrition and Health. Agricultural Support. The earliest Federal nutrition policies in this area were designed to strengthen the agricultural production system and to ensure a consistent and adequate food supply. In 1862. the U.S. Depart- ment of Agriculture (USDA) was created, and the Morrill Act established land grant universities as sites for agricultural training and research. The Hatch Act of 1887 authorized the creation of agricultural experiment stations. As a result of these and other policies. food production increased and farmers began to produce more food than could be consumed. Even- tually, a system of commodity price and income supports was developed to stabilize the economic condition of the farm sector. The Agricultural and Consumer Protection Act of 1973 and the Food and Agriculture Act of 1977 established the basis for current agricultural support policies (Stucker and Boehm 1978; Boehm 1979). Food Safety and Regulation. The pure food movement of the late 1800's, led by Dr. Harvey Wiley, chief of the Government's Bureau of Chemistry, and popularized by the publication of Upton Sinclair's novel of 1906, The Jungle, led Congress to pass the Pure Food and Drug Act of 1906-then known as the Wiley Act-which prohibited interstate transport and sale of misbranded or adulterated foods (Ziporyn 1985). This Act and the Federal Meat Inspection Act, also passed that year, extended Federal responsibil- ity into the arena of food safety. Significant revisions to the legislation occurred in 1938 when the Food, Drug, and Cosmetic Act established standards of identity and quality for certain foods, required ingredient listings on food labels, and prohibited sales of foods that were determined to be harmful to health. In 1958, the Food Additives Amendment to the 1938 Act shifted the burden of proof of safety to the manufacturer, required that additives known to cause cancer in either humans or animals be deemed unsafe (the Delaney Clause), and established the list of ingredients in common use that were "Generally Recognized As Safe" (GRAS) for human consumption. A 1960 Color Additives Amendment applied the Delaney Clause to all chemical food coloring agents. Since 1969, a major review has been under way of the safety of substances on the GRAS list (Smith and Rulis 1981). Regulation of food safety is a shared responsibility 33 u Nutrition and Health of several Federal agencies, primarily the USDA for plant, animal, poultry production; the Food and Drug Administration (FDA) for all c foods and additives; and the Environmental Protection Agency pesticide contaminants. The food labeling provisions of the 1906 and 1938 Acts were designe protect consumers against fraudulent misbranding of foods, and this pc was extended by the Fair Packaging and Labeling Act of 1%6, which cz for accurate ingredient labeling on foods in interstate commerce (PC 1987). More recently, interest has grown in the use of food labels to edu consumers about the nutritional quality of food and the role of nutritic health. Regulations published in 1973 authorized voluntary nutrition la ing and required nutrition labeling for fortified foods and those for WI nutritional claims were made (Hutt 1981). In 1987, the FDA proposed a policy for public health messages on food labels to permit health claim package labels when the information is true and certain criteria are (FDA 1987). Responsibility for regulating labeling and marketing prc dures related to foods is shared by the USDA (meat, poultry, eggs), F (all other foods) and, for advertising, the Federal Trade Commission (. ter 1987). Food Fortrjication. The onset of World War I brought new nutritic concerns and focused attention on the need for an overall improvemer, the availability of nutrients to the general population. The first food tification program, instituted in 1924, was the addition of iodine to sal prevent goiter. During the Second World War, this program was extendel include enrichment of wheat flour with iron and the vitamins thian niacin, and riboflavin. Also during the 1940's, milk was fortified v vitamin D and margarine with vitamin A. Food Assisrunce. As early as 1918, the idea of targeting food assistance vulnerable population groups was proposed in the Children's Bureau p lication Milk-The Indispensable Food for Children. Milk supplies 1 decreased and prices increased due to the effects of World War I, and Children's Bureau advocated that children be given priority in allocat milk supplies. Charitable organizations established milk stations and cc munity kitchens to provide food supplements to the poor and to help peo with limited income choose and prepare an adequate diet (Egan 1980 Widespread unemployment anda overty during the 1930's stimulated I development of new Federal programs to provide food assistance to i poor. At first, these programs focused exclusively on distribution of surp agricultural commodities. In 1930, for example, the USDA and the Fede 34 Introduction and Background 0 Emergency Relief Administration began a distribution program as food relief. The donation of surplus foods to child nutrition and school lunch programs was authorized by amendments to the Agricultural Act in 1933. The more formally organized Food Distribution Program was established in 1935. An experimental Food Stamp Program was initiated by the Surplus Commodities Corporation in 1939. The National School Lunch Program was established in 1946, and the Special Milk Program was added in 1954 (U.S. Senate 1976). In the early 1960's, as a result of surveys and assessments indicating special needs among low-income populations (Citizens' Board 1968), the Federal Government expanded its involvement in income support and direct deliv- ery of food services. A pilot study in 1961 led to the Food Stamp Act of 1965, which authorized a small-scale program to meet limited needs for food assistance. The Child Nutrition Act of 1966 established the School Breakfast Program. Following the 1969 White House Conference on Food, Nutrition, and Health (White House Conference 1970), eligibility and benefits were enlarged for the Food Stamp, School Lunch, School Break- fast, Special Milk, and Summer Food Programs; the Special Supplemental Food Program for Women, Infants, and Children (WIG) was created; general assistance reimbursements were increased (for the School Break- fast and School Lunch Programs); and the Nutrition Program for the Elderly was established through an amendment to the Older Americans Act. From I%9 to 1977, Federal expenditures for these programs increased from about $1.2 to $8.3 billion (U.S. Senate 1977a). By 1986, as many as 50 million Americans (the exact number is uncertain due to overlapping benefits) were served by food assistance programs administered by the USDA. The cost of these programs exceeded $18.8 billion in 1986 and $20 billion in 1987 (Matsumoto 1987). Nutrition Services and Training. In the 1920's under the Federal Maternity and Infancy Act, nutrition services were launched in nine State depart- ments of public health. Enactment of the Social Security Act in 1935, authorizing grants-in-aid to the States for health services for mothers and children, was a major impetus for the further development of nutrition services in State health agencies. By 1945, all but three States had one or more nutrition consultant positions included in their budgets. Nutrition services began to extend beyond maternal and child health during the late 1950's and early 1960's in response to new mental retardation, chronic disease control, home health service, and nursing home and other ex- tended care programs. Initiatives in primary health care, family planning, and comprehensive health planning during the 1970's further expanded the availability of nutrition services (Nutrition Services Project Committee 35 cl Nutrition and Health 1983), as did establishment of the Community Food and Nutrition Program (CFN) in the 1980's to provide nutrition services to low-income popula- tions (Office of Community Services 1987). To ensure an adequate supply of health professionals to serve the popula- tion, the Federal Government also supports health professions education in primary care as well as public health practice. Since the 1940's, funds have been available from Title V of the Social Security Act for nutrition training of health professionals, and since 1957, various authorities under Title VII of the Public Health Service Act have supported health profes- sions students and curriculum development in applied nutrition, including capitation grants to schools of public health that support traineeships for public health nutrition students. Food Intake and Nutrition Status Monitoring. The involvement of the Federal Government in monitoring of food intake dates back to 1893 when the USDA received an appropriation for this purpose (Porter 1986). The USDA first began to collect data on the wholesale availability or "disap- pearance" of food commodities in 1909. The subsequent annual collection of such data has provided an important source of information on trends in the availability of food, an indirect indicator of food use by the population (Bunch 1987). Attempts to estimate actual food intake by the population began in the 1930's. For example, household food purchases were exam- ined by the USDA in 1936-37 through the first Nationwide Food Consump- tion Survey (NFCS); such surveys have been conducted about every 10 years since, most recently in 1987-88 (USDA 1986,1987a, 1987b). Estima- tions of the per capita nutrient content of the food supply began in the 1940's and are now reported annually (Marston and Raper 1986). The first collections of data on the food consumption habits of individuals in sampled households were performed by the USDA in 1%5 (NRC 1984). Examples of food intake and availability data are given later in this chapter in the section on dietary patterns. Assessment of nutritional status emerged as a concern as early as 1918 when infants and children were weighed and measured during the opening event of the Children's Year Campaign (initiated to "protect children from the effects of war"). The impetus for this activity was the high percentage of Selective Service rejections in World War I caused by conditions that might have been prevented or corrected by adequate nutrition in early childhood. The first studies of nutrition and child health were conducted by the Children's Bureau in a mountainous section of Kentucky in 1920 and in the industrial area of Gary, Indiana, in 1922 (Egan 1980). 36 Introduction and Background O Much of the recent expertise in measuring human nutritional status was developed through the work of the Interdepartmental Committee on Nutri- tion for National Defense, which conducted nutrition surveys in more than 30 countries during the 1950's and 1960's. Attempts to evaluate the nutri- tional status of the U.S. population began in 1956 when Congress autho- rized the Department of Health, Education, and Welfare (DHEW) to conduct periodic national health examination surveys; with the addition in 1971 of additional status measures, including a dietary intake component, these surveys evolved into the National Health and Nutrition Examination Surveys (NHANES). The first NHANES was conducted from 1971-74, the second from 1976-80, and the Hispanic HANES from 1982-84 (DHHS/ USDA 1986). The third NHANES started in 1988. In l%8-70, in response to increasing concern about the nutritional status of low-income popula- tions, DHEW sponsored the Preschool (Owen et al. 1974) and Ten-State (DHEW 1972) Nutrition Surveys and identified evidence of malnutrition in these populations. The dietary intake, health, and nutritional status surveys and surveillance systems listed in Table l-4 and described above are components of the National Nutrition Monitoring System-a complex assortment of inter- connected activities that provide regular information about dietary intake and nutritional status to the health of the American people and about factors that affect diet and nutritional status (DHHS/USDA 1987). The present system was proposed in 1978 in response to a congressional re- quest in the 1977 Food and Agriculture Act that the Secretaries of Agri- culture and of Health, Education, and Welfare, now Health and Human Services (DHHS), develop a joint proposal for a comprehensive system that would monitor the nutritional status of the American people. In 1981, a Joint implementation Pfun (revised in 1987) committed the two Depart- ments to close coordination of survey methods and to submission of reports to Congress every 3 years on information gained from monitoring activities. The National Nutrition Monitoring System includes efforts by several Federal agencies to provide information about health and nutri- tional status, food consumption, food composition, dietary knowledge and attitudes, and food safety and quality. Food and Nutrition Research. The Federal role in nutrition research began in 1887 with the development of the forerunner of the National Institutes of Health (NIH) as a one-room laboratory on Staten Island. In 1893, the USDA was authorized to perform agricultural and human research. The PHS Hygienic Laboratory developed into the first National Institute of Health in 1930; subsequently, it was joined by other laboratories to create 37 Table 14 National Nutrition Surveillance Activities 0 2 1. Category Activity Departmenta Agencya Population Timing g. J Health and Nutritional Status Measurements National Health and Nutrition Examination Surveys NHANES 1 NHANES I1 Hispanic HANES NHANES III DHHS CDC/NCHS National Health DHHS Interview Survey NHIS Special Topics DHHS NHANES I Epidemiologic DHHS Followup National Survey of Family DHHS Growth National Maternal and DHHS Infant Health Survey National Mortality Survey DHHS CDC/NCHS CDCR'XHS CDC/NCHS CDC/NCHS CDC/NCHS Planned 1988 CDCMCHS Vital Statistics DHHS CDC/NCHS U.S. population, special groups l-74 yrs 1971-74 6 mo-74 yrs 1976-80 6 mo-74 yrs 1982-84 2 mo+ 1988-94 U.S. Annual U.S. Selected topics NHANES I older 1982-84, 1986, persons 1987 Women 15-44 yrs 1976, 1983, 1987 Annual l%l-68, 1986 U.S. States, counties, local areas Annual Health and Nutritional Status Measurements (continued) Coordinated State Surveillance System Behavioral Risk Factor Surveillance System Nutrition Research in Support of Nutrition Monitoringb Food Consumption Measurements Nationwide Food Consumption Survey (NFCS) Continuing Survey of Food Intakes by Individuals (CSFII) 1985 and 1986 1989 and beyond NHANES DHHS CDCKHPE Pregnant women, Continuous children CDCKHPE Adults Continuous DHHS USDA NIH Varies Ongoing ARS CDCKHPE FDA USDA HNIS U.S., low-income Every 10 years, sample current 1987-88 USDA HNIS DHHS CDCINCHS Women 19-50, Annual their children, men, low-income sample zi U.S. population, Annual (planned) E low-income a sample, other !? U.S. population 1971-74, 1976-80, 1982-84, 1988-94 g s ii Table 14 (continued) Food Consumption Total Diet Study Measurements (continued) Vitamin/Mineral Supplement Adverse Reactions Food Composition Measurements Nutrient Data Bank Nutrient Composition Laboratory Food Labeling and Package Survey Total Diet Study Fiber, Carotenoid, and Vitamin A Comp. Studies; Taurine and Biotin Comp. Studies Dietary Knowledge Health and Diet Survey and Attitude Assessment Survey of Infant Feeding Practices Survey of Weight-Loss Practices Cholesterol Awareness Survey DHHS FDA DHHS FDA USDA USDA DHHS DHHS DHHS DHHS DHHS DHHS DHHS HNIS ARS FDA FDA NIH/NCI NIHI NIDDK FDA FDA FDA NIHI NHLBI NIHI NHLBI + FDA Specific age-sex Annual groups U.S. Continuous Continuous Continuous Annual and biennial parts Annual Ongoing Ongoing U.S. adults .18-22 mo intervals Pregnant women 1988 or 1989 U.S. adults 1987 or 1988 Physicians 1986 Adults e Dietary Knowledge and Attitude Assessment (continued) Nursing and Dietitian Survey NHIS Special Topics Health Promotion/ Disease Prevention . VitMn Supplement Cancer Control Food Supp!y - CSFII Followup (Consumer Perceptions Survey) Physician Knowledge Survey on Hypertension Cancer Prevention Awareness Program Demand Studies DHHS NIH/ NHLBI DHHS CDC/NCHS U.S. adults + NIH/NCI USDA/DHHS HNIS FSIS FDA DHHS NIH/NHLBI DHHS NIH/NCI USDA ERS Nurses, dietitians 1986, 1987 1985 1986 1987 U 3. population Planned 1989-% Physicians 1978-88 U.S. adults 1984 + ongoing U.S. population Continuous Determinations aARS = Agricuftural Research Service, CDC = Centers for Disease Control, CHPE = Center for Health Promotion and Education, DHHS = Department of Health and Human Services, ERS = Economic Research Service, FDA = Food and Drug Administration, FSIS = Food Safety and Inspection Service, HNIS = Human Nutrition information Service, NCHS = National Center for Health Statistics, NCI = National Cancer Institute, NHIS = National Health Interview Survey, NHLBI = National Heart, Lung, and Blood Institute, NIDDK = National Institute of Diabetes and Digestive and Kidney Diseases, NIH = National Institutes of Health, USDA = U.S. Department of Agriculture. blncludes research on nutritional status assessment and requirements throughout the life cycle. The nutritional status research focuses on (1) indices of nutritional status, (2) micromethods to measure nutrient concentrations in various tissues and plasma, and (3) methods that improve accuracy of dietary intake data. Source: U.S. Department of Health and Human Services and U.S. Department of Agriculture 1987. n u Nutrition and Health the present research enterprise of NIH (Simopoulos 1986). In 1975, the NIH Nutrition Coordinating Committee was established to address NIH nutrition issues that span the goals and purposes of 12 Institutes, 2 Divi- sions, and 2 Centers within the agency. The FDA began conducting nutri- tion research in 1938. By 1976, Federal expenditures for nutrition research and research training exceeded $73 million (U.S. Senate 1976). The amount was reported as nearly $200 million by 1979 (JSHNR 1980) and $270 million in 1984, of which nearly $200 million represented research supported by NIH (ICHNR 1986; NIH 1987). In 1987, NIH expended a total of $261 million, reinforcing its longstanding position as the major Federal agency in biomedical and behavioral nutrition research and training support. This nutrition research encompasses a broad range of topics, including health maintenance, human development throughout the life cycle, disease pre- vention, and disease treatment. The Interagency Committee on Human Nutrition Research (ICHNR) was established by the Secretaries of DHHS and USDA to succeed the Joint Subcommittee on Human Nutrition Research that operated out of the White House Office of Science and Technology Policy to coordinate all Federal nutrition research activities. The ICHNR produced a 5-year plan for human nutrition research that reviewed the research activities of eight Federal agencies, listed research priorities, and identified six areas for expanded research investigation: nutritional requirements at various stages of the life cycle, nutrition interactions and bioavailability, nutrition and chronic diseases, energy regulation and eating disorders, nutrition monitoring, and nutrition education methodology (ICHNR 1986). Dietary Guidance and Nutrition Education. The Federal Government has supported efforts to teach the public about nutrition since 1867 when the Office of Education was established with responsibility for nutrition educa- tion within the public schools. The Children's Bureau of the Department of Labor published Prenatal Care in 1913 and Znfant Care in 1914 to provide dietary guidance to mothers. These books have been in publication ever since and are all-time best sellers of the U.S. Government Printing Offtce. The USDA also had an early role and published its first food selection guide, designed to help parents meet the nutritional needs of young chil- dren, in 1916 (Hunt 1916). Since that time, federally supported dietary guidance materials have been issued and revised regularly to meet the needs of specific target audiences and to reflect emerging knowledge of nutritional science. A list of Federal dietary guidance publications for the general public since 1917 is presented in Table l-5. 42 e Table l-5 Federal Dietary Recommendations for the General Public, 1917-1988 Recommendationa Year Agencyb Publication Maintain Include Ideal Starch Limit Body and Limit Limit Choles- Limit Limit Variety Weight Fiber Sugar Fat terol Salt Alcohol 1917 USDA 1942 USDA 1943 USDA 1946 USDA 1946 USDA 1958 USDA 1977 U.S. Senate 1979 USDA 1979 DHEW 1979 DHEWINCI What the Body Needs- Five Food Groups Food for Freedom- Daily Eight National Wartime Nutrition Guide-Basic Seven National Food Guide- Basic Seven Food for Growth- Four Food Groups Food for Fitness- Four Food Groups Dietary Goats for the U.S. Building a Better Diet- Five Food Groups Healthy People: The Surgeon General's Report on Health Promotion and Disease Prevention Statement on Diet, Nutrition, and Cancer--Prudent Interim Principles + + + + * * + * + * + * + + + + + + + + + + + + + + + + + + + + + t -I- t + + Year Agencyb Publication 0 z 5 Table l-5 (continued) g Ei Recommendationa 5 Maintain Include Ideal Starch Limit i Body and Limit Limit Choles- Limit 2 Variety Weight Fiber Sugar Fat terol salt Limit 5 Alcohol 1980 USDA/DHHS Dietary Guidelines for Americans + + + + + + + + 1980 DHHS National 1990 Nutrition Objectives + + + + + + + + I984 DHHS/NHLBI Recommendations for Control + + + + % 1985 USDA/DHHS of High Blood Pressure Dietary Guidelines for Americans, + + + + + + + + 2nd edition I986 DHHS/NCI Cancer Control Nutrition Objectives + + + + for the Nation: 1985-2000 1987 DHHS/NHLBI National Cholesterol Education + + + + + + Program Guidelines 1988 DHHS/NCI Dietary Guidelines for Cancer + + + + + + Prevention `!7ecommended for inclusion in the daily diet, as opposed to subsequent recommendations to limit intake. aOther recommendations include: increased consumption of foods containing vitamins and minerals (USDA 1917-l 958; NCI 1988) increased physical activity (USDA/DHHS 18881985; DHHS 1980). and reduced intake of salt-cured or smoked foods (NC1 1988). bUSDA = U.S. Department of Agriculture, U.S. Senate = U.S. Senate Select Committee on Nutrition and Human Needs, DHEW = Department of Health, Education, and Welfare, DHHS = Department of Health and Human Services, NCI = National Cancer Instiiute. NHLBI = National Heart, Lung, and Blood Institute. Introduction and Background O The earliest federally sponsored guidelines advised the public to consume portions from a variety of food groups every day to obtain sufficient energy and to avoid nutritional deficiencies. As more was learned about nutrients essential in the diet, recommendations began to emphasize consumption of foods containing vitamins, minerals, and other "protective" dietary com- ponents (Hertzler and Anderson 1974). In response to the economic crisis of the 1930's, the USDA began to develop meal plans for consumers at different levels of income to address issues of cost (Haughton, Gussow, and Dodds 1987). The first Recommended Dietary Allowances (RDA's) for intake of energy and eight nutrients were developed by the National Research Council and adopted at the wartime National Nutrition Conference in 1941 (Roberts 1958). RDA's have been published periodically since; the most recent (ninth) edition appeared in 1980 (NRC 1980). Its recommendations are reviewed later in this chapter. Also in 1941, the USDA, in cooperation with the Offtce of Education and the PHS, published the first Federal guide to incorporate information on specific vitamins and minerals and the first to use the term "enriched." Meal plans and dietary guidelines published since the 1940's have been designed increasingly to translate the RDA's into terms usable by consumers (Hertzler and Anderson 1974). The USDA's 1958 Food for Fitness-A Daily Food Guide, written in terms of four food groups, was the first to promote intake of specific nutrients-alcium, vitamin A, and vitamin C-that were commonly consumed in amounts substantially below RDA levels (Haughton, Gussow. and Dodds 1987). Typically, an adequate diet has been defined as providing the basic food groups that would contain amounts of essential nutrients-protein, vi- tamins, and minerals-sufficient to prevent deficiency diseases. In the mid-1970's, however, the focus of national policy objectives expanded to encompass the role of overconsumption of fat, cholesterol, salt, sugar, and alcohol as dietary factors associated with chronic disease. The increasing scientific interest in these relationships led the U.S. Senate to hold hear- ings on diet and health from 1973 through 1977 (U.S. Senate 1977a). Expanding knowledge of the role of diet in health maintenance also led to the development in 1975 of a DHEW Policy Statement on Health Aspects of Nutrition (U.S. Senate 1976). Thus, dietary adequacy began to include consideration of the most reasonable proportions of dietary factors for prevention of chronic-rather than deficiency--diseases. This new perspective was reflected in the two editions of the 1977 report Dietary Goals for the United States, produced by the Senate Select Com- mittee on Nutrition and Human Needs (U.S. Senate 1977b. 1977~). These u Nutrition and Health reports recommended significant changes in average dietary intake pat- terns to improve protection against the principal chronic diseases. To accomplish this goal, they established quantitative targets for consumption of complex carbohydrates and naturally occurring sugars (greater than 48 percent of energy), refined and processed sugars (10 percent of energy), total fats (less than 30 percent of energy), saturated fat (less than 10 percent of energy), cholesterol (less than 300 mglday), and salt (less than 5 g/day) (U.S. Senate 1977~). These principles, although not the quantitative targets, were supported and expanded in the 1979 report Healthy People: The Surgeon General's Report on Health Promotion and Disease Prevention (DHEW 1979) and by the 1980 publication Nutrition and Your Health: Dietary Guidelines for Americans, jointly issued and revised in 1985 by the Departments of Agriculture and of Health and Human Services (USDAIDHHS 1985). The Guidelines recommend: o Eat a variety of foods. o Maintain desirable weight. o Avoid too much fat, saturated fat, and cholesterol. o Eat foods with adequate starch and fiber. o Avoid too much sugar. o Avoid too much sodium. o If you drink alcoholic beverages, do so in moderation. This approach reflects the increase in interest in the relation between nutrition and prevention of chronic diseases, a development that has shaped and mandated Federal nutrition education activities of the past decade (see Table l-4) and is the principal focus of the discussion, conclu- sions, and recommendations of this Report. Scientific Background Human Nutritional Requirements Essential nutrients must be obtained from the diet in the proper amounts and proportions to maintain good health and to prevent deficiency dis- eases. A deficiency of an essential nutrient causes signs and symptoms that can be prevented or cured by an increased intake of the nutrient. Such deficiencies may be due to inadequate dietary intake, or they may be 46 Introduction and Background 0 induced by either inherited or acquired inabilities to absorb, transport, store, or metabolize nutrients or by excessive losses of nutrients from the body (for example, from vomiting, bleeding, or diarrhea). Just as a deficiency of a nutrient can cause disease, too much of a nutrient can also lead to disease. For example, as discussed throughout this Report, the excessive consumption of energy, fat (especially saturated fat), and alcohol have been associated with the development of specific chronic disease conditions in some individuals. Excessive intake of some vitamins and most of the minerals also has been shown to result in either acute or long-term disorders. For most nutrients, there appears to be a safe and adequate range of dietary intake that satisfies nutritional requirements but does not cause untoward symptoms. This concept is illustrated in Figure l-1. Ideally, the diet should contain energy and all of the essential nutrients in amounts that fall within these ranges of intake. I ( )I Y'o .:.:.:.:.:.:.:.:.:.:.:.~..:.~.~:.:.~:.~.~: .: ......................................... . . ........ . . ......................... , . . . . ..:.1:.:.~:.:.:.:.:.:.:.:.: .:. . . . . . . ...... . . . . . . ... . ...... . . . . . . ... . ............................ ..................................... ...................................... .......................................................................... C :.:2..~:.:.~:.~:.:.:.:.:.:.:.~..~:.:.:.~:.:.:.:.:.:.:.:.:.:.: . ...................................... .z .............................................................................. . ..... . . . . . . . . . . . ...... . ... . . . . . . . .... . . . . . . . . . . . . ...... . . . . . . . . . . ...... ...................................... . . ..................................... 5 .................................... ..................................... .................................... . . C :.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.~:.:.:.:.:.~:.:.~.~.:.~~ ... ..................................... 3 .:::::::~::::::::~~::::::::::::::::::::::::::~::::~.::::~::: L . ........................................ . . . .... . . . . . . ... . . ..... ................................................. ..................................... . ..................................... .................................... .................................... . . ..................................... ..................................... ..................................... . ....................................... . . . . . . . . .... . . . . . . . ...................................................... ..................................... ................................................. . . . . . . . . . . . ....................................................... ... . . ... ...... ...... . ... . . . . ............................................................ . . . . . . -. . . . . . . . . . .... ... ..... . . . ........ . . . . . . . . .................................................. . . . . ...... . . . . . . .... ...... . . . ... .... . . ........ . ......... ............................................................ ..................................... . .................................... .:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.: . . ............................. ............... ~:.:.~:.:.~..:.:.:.:.:.:.:.:.:.:.:.~:.:.~:.:.:.~:.:.~..:.:.:.: .: * Concrnkltion or intake of nutrient - Figure l-l. Dependence of biologic function or tissue concentration on in- take ol a nutrient. For nutrients and energy sources, there is a range of intake that confers optiil physiologic function. Below thII range, deficiincies can cause dii or death. Excecrsive intake also can lead to increasiing symptoms of toxkity. The op- timal range varies for each nutrient and is affected by many indiiidual and environmental factors. Source: Merlz, W. 1981. The essential trace elements. Science 213:1332-38. Copy- right 1981 by the American Association for the Advancement of Science, re- printed with permission. 47 u Nutrition and Health Recommended Dietary Allowances The need to establish goals for good nutrition in the United States was recognized in the 1930's and led to the establishment in 1940 of the Committee on Food and Nutrition, now called the Food and Nutrition Board, of the National Research Council, National Academy of Sciences. The Committee's initial purpose was to make sure that the population was adequately nourished during World War II, and one of its early functions was to recommend quantities of nutrients that should be provided to the Armed Forces and the general population. These recommendations led to the development of goals for intake of nine specific nutrients that would meet the known nutritional requirements of men, women, and children of varying ages. These first RDA's were adopted in 1941 (Roberts 1958), and they have been published at 5- to lo-year intervals since 1943. Although the original purpose of the RDA's was to promote nutritional health during wartime, their purpose has expanded over the years to include use for development of standards for food assistance programs, food labels, and evaluation of dietary adequacies. Because research on human nutritional requirements is often incomplete or inconsistent, and because of variability in individual nutrient require- ments, the RDA's represent an estimated, rather than an absolute, stan- dard of dietary adequacy, and they are revised periodically to reflect current scientific evaluation of the available nutrition research. The most recent revision was published in 1980 and is presented in Table l-6 (NRC 1980). The RDA's are defined as ". . . the levels of intake of essential nutrients considered, in the judgment of the Committee on Dietary Allow- ances of the Food and Nutrition Board on the basis of available scientific knowledge, to be adequate to meet the known nutritional needs of prac- tically all healthy persons." Thus, each RDA is deliberately set higher than the.actual requirement for that nutrient in most individuals. Specific RDA's have been established for protein, 10 vitamins, and 6 minerals; they are presented in categories that vary according to body size. gender, and energy consumption (NRC 1980). RDA's are usually higher for males than for females, except for women who are pregnant or lactating. For 12 additional nutrients, research has been too limited to establish specific RDA's and the Food and Nutrition Board has proposed ranges of daily intake that are considered "safe and adequate." These are presented in Table l-7. The RDA's are designed to exceed the nutrient requirements of most individuals, but the allowances for energy are designed to reflect average needs for people of different heights and weights, ages, and activi- ty levels. 48 Table l-6 Food and Nutrition Board, National Academy of Sciences- National Research Council Recommended Daily Dietary Allowances,a Revised 1960 Designed for the maintenance of good nutrition of practically all healthy people in the U.S.A. Fat-Soluble Vitamins Age Weight Height Protein Vitamin A Vitamin D Vitamin E (years) (kg) (lb) (cm) (in) w ha REJb (CLkT)C (mg a-TE)d Infants 0.0-0.5 60 24 kgx2.2 420 IO 3 0.5-I .o x s 71 28 kgx2.0 400 IO 4 Children 1-3 13 29 90 35 23 400 IO 5 20 44 112 44 30 500 IO 6 7% 28 62 132 52 34 700 IO 7 Males 11-14 45 99 157 62 45 loo0 IO 8 % 15-18 66 145 176 69 56 looo IO IO B-22 154 177 70 loo0 7.5 10 23-50 z 154 178 i: loo0 5 IO 51+ 70 154 178 :: 56 loo0 5 IO $ Females 11-14 46 101 157 62 46 800 IO 8 1 15-18 55 120 163 64 46 800 IO 19-22 55 120 163 64 44 800 7.5 t 0 g. 23-50 55 120 163 44 800 5 8 1 51+ 55 120 163 iii 44 800 5 8 B Pregnant +30 +200 +5 +2 e Lactating +20 +400 +5 +3 m R aThe allowances are intended to provide for individual variations among most normal persons as they live in the United States under usual en- 9 vironmental stresses. Diets should be based on a variety of common foods to provide other nutrients for which human requirements have been less well defined. s Wetinol equivalents; 1 RE = 1 kg retinol or 6 pg $ carotene. CAs cholecalciferol; 10 pg cholecalciferol = 4000 IU of vitamin D. da-tocopherol equivalents: 1 mg d-a tocopherol = 1 a-TE. Table l-6 (continued) 0 2 Water-Soluble Vitamins Age Weir& s: Height Vitamin C Thiamin Riboflavin Niacin Vitamin B, Folacinr Vitamin B,, (years) (kg) (lb) (cm) (in) b-fg) (mg) (mg) (mg NEP (mg) h3) (Ia) iz E infants 0.0-0.5 6 13 0. 60 24 35 0.3 0.4 6 0.3 30 0.5g X 0.5-1.0 9 20 71 28 35 0.5 0.6 8 0.6 45 1.5 i! Children l-3 29 90 35 45 0.7 0.8 9 0.9 loo 2.0 g :i 44 II2 44 45 0.9 1.0 II 1.3 200 2.5 7% 28 62 132 52 45 1.2 1.4 I6 1.6 300 3.0 Males II-14 45 99 I57 62 50 I.4 1.6 18 400 3.0 15-18 66 I45 176 69 60 I.4 1.7 I8 :*: 400 3.0 19-22 70 154 177 70 60 1.5 1.7 19 212 400 3.0 3 23-50 70 154 178 70 60 I.4 1.6 18 2.2 51+ 70 154 I78 70 60 1.2 I.4 16 2.2 z :-I Females II-14 46 IO1 157 62 50 I.1 1.3 I5 1.8 400 3:o 15-18 55 120 163 64 60 I.1 1.3 14 2.0 400 3.0 19-22 55 120 163 64 I.1 1.3 14 2.0 3.0 23-50 55 I20 163 64 2 1.0 1.2 I3 iti 3.0 51+ 55 120 163 64 60 1.0 1.2 I3 El 400 3.0 Pregnant +20 +0.4 + 0.3 +2 + 0.6 +400 +1.0 Lactating +40 +0.5 +0.5 +5 +0.5 +100 +1.0 eNiacin equivalent; 1 NE = 1 mg of niacin or 60 mg of dietary tryptophan. f The folacin allowances refer to dietary sources as determined by Lactobacillus casei assay after treatment with enzymes (conjugates) to make polyglutamyl forms of the vitamin available to the test organism. @Ihe recommended dietary allowance for vitamin B12 in infants is based on average concentration of the vitamin in human milk. The allowances after weaning are based on energy intake (as recommended by the American Academy of Pediatrics) and consideration of other factors, such as intestinal absorption. Table l-6 (continued) Age (years) Minerals Weight Height Calcium Phosphorus Magnesium Iron Zinc Iodine (kg) (lb) (cm) (in) bud (mid @x3) kg) bf3) (I%) Infants 0.045 6 13 60 24 360 240 50 10 : 40 0.5-1.0 9 20 28 540 360 70 15 50 Children l-3 13 29 iz 35 800 800 150 15 10 70 7% 20 28 44 62 112 132 44 52 800 800 800 800 200 250 IO 10 IO IO 120 90 Males 11-14 45 1: 157 62 1200 1200 350 18 I5 150 15-18 66 176 69 1200 1200 400 18 15 150 Y 19-22 70 154 177 70 800 800 350 10 15 150 23-50 70 154 178 70 800 800 350 IO 15 150 51+ 70 154 178 70 800 800 350 10 15 I50 Females II-14 46 101 157 62 1200 1200 300 I8 I5 150 15-18 55 120 163 64 1200 1200 300 I8 I5 150 z 19-22 55 120 163 64 800 800 300 18 I5 I50 8 23-50 55 120 163 64 800 800 300 I8 I5 I50 E 51+ 55 120 163 64 800 800 300 IO I5 I50 g Pregnant +400 +400 + I50 h +5 + 25 3 Lactating +400 +400 + I50 h + 10 +50 B a hThe increased requirement during pregnancy cannot be met by the iron content of habitual American diets nor by the existing iron stores of m many women; therefore, the use of 3040 mg of supplemental iron is recommended. Iron needs during lactation are not substantially different Pi from those of nonpregnant women, but continued supplementation of the mother for 2-3 months after parturition is advisable to replenish stores depleted by pregnancy. f Source: National Research Council 1980. bi 0 O Nutrition and Health Table 1-7 Estimated Safe and Adequate Daily Intakes of Selected Vitamins and Mineralsa Age (years) Vitamins Vitamin K (PIit) Biotin (Ia) Panto- thenic Acid (mg) Infants O-O.5 12 35 2 0.5-l lo-20 50 3 Children and l-3 15-30 65 3 Adolescents 30 20-40 85 3-4 30-60 120 4-5 11+ 50-100 100-200 47 Adults 70-140 100-200 &7 Trace Element+ Man- Molyb- Age Copper ganese Fluoride Chromium Selenium denum Wars) (mg) (mg) (mg) (mg) (mg) Ow) Infants O-O.5 0.5-0.7 0.5-0.7 0.14.5 0.014.04 0.01-0.04 0.03-0.06 0.5-l 0.7-1.0 0.7-1.0 0.2-1.0 0.02-0.06 0.02-0.06 0.0.08 Children and l-3 1.0-1.5 1.0-1.5 0.5-1.5 0.02-0.08 0.02-0.08 0.05-0.1 Adolescents 4-6 1.5-2.0 1.5-2.0 l&2.5 0.03-0.12 0.03-0.12 0.06-0.15 7-10 2.0-2.5 2.0-3.0 1.5-2.5 0.05-0.2 0.05-0.2 0.10-0.3 II+ 2.0-3.0 2.5-5.0 1.5-2.5 0.05-0.2 0.05-0.2 0.15-0.5 Adults 2.0-3.0 2.5-5.0 1.54.0 0.05-0.2 0.05-0.2 0.15-0.5 - Electrolytes Age Sodium Potassium Chloride (years) (mg) (mg) (mg) Infants O-O.5 I 15-350 350-925 275-700 0.5-l 25fL750 425-1275 400-1200 Children and l-3 325-975 550-1650 500-1500 Adolescents EO 450-1350 775-2325 700-2100 600-1800 100&3000 925-2775 11+ 900-2700 1525-4575 14Ot+t200 Adults 1100-3300 1875-5625 1700-5100 aBecause there is less information on which to base allowances, these figures are not given in the main table of RDA and are provided here in the form of ranges of recom- mended intakes. Wecause the toxic levels for many trace elements may be only several times usual in- takes, the upper levels for the trace elements given in this table should not be habitually exceedad. Source: National Research Council 1980. 52 Introduction and Background 0 The fact that most RDA's are intentionally established to exceed the nutrient requirements of most people means that a dietary intake below the RDA is not necessarily inadequate for an individual whose requirement for a nutrient is average or even above average (NRC 1980). It also means that the small percent of persons who- have unusually high nutrient require- ments may not meet nutritional needs even when they consume nutrients at RDA levels. The RDA's are estimates of the nutrient requirements for populations rather than for individuals. In addition, RDA's may need to be modified for people who are ill or injured. Translating the RDA's into a single, universally applicable, ideal pattern of food choices that best supports health and longevity is, for many reasons, difficult. As noted above, individual nutrient requirements depend upon complex interactions between genetic and environmental factors and the stage of physiologic development. The nutritional needs of infants. young adults, and older persons vary, and dietary habits and preferences differ markedly from culture to culture and from individual to individual. A definition of the food choices that best fu!fill nutrient requirements has been a goal of the many Federal agencies and private health organizations that have developed sets of dietary recommendations during the past decade (Dwyer 1983; McNutt 1980). Some of these recommendations are noted in Table 1-5; the evidence on which they are based is presented throughout this Report. Most current recommendations emphasize that it is the overall dietary pattern that determines whether or not nutrient intakes are likely to fall within desirable ranges. Public health concerns about specific nutrients, therefore, usually are directed to the kinds and amounts of foods consumed and to the genetic, behavioral, and environ- mental factors that affect food choices. The diet must contain adequate energy, all essential nutrients, and certain other dietary factors to sustain normal growth, development, and health. The nutrients and dietary factors discussed in this Report include carbohy- drates, fats, and proteins-the macronutrients-which are sources of ener- gy as well as of essential fatty acids and amino acids that either cannot be synthesized or are synthesized in amounts inadequate to meet body needs; micronutrients-vitamins and mineral elements-which are necessary in small amounts; and substances such as fiber, which does not fall into either category but is nonetheless beneficial for good health. This section defines these nutrients as background for this Report. Basic information on essen- tial nutrients has been reviewed extensively (see, for example, Nutrition Reviews 1984; Passmore and Eastwood 1986; Schneider, Anderson, and Coursin 1983; Shils and Young 1988). 53 LJ Nutrition and Health Energy The diet must supply sufficient energy to support growth and development, maintain basic physiologic functions, meet the demands of muscle activity, and repair damage caused by illness or injury. In the United States, energy intake and expenditure are measured in kilocalories, abbreviated as kcal, and referred to as Calories or, commonly, calories. In international usage, the term is kilojoules, abbreviated kJ (1 kcal=4.184 kJ). In this Report, the terms energy and calories are used interchangeably to refer to the general concept of energy; specific measures of energy intake or expenditure or the energy value of food are given in kilocalories. The body obtains chemical energy from food from the oxidation (chemical burning) of protein, fat, carbohydrate, and, when it is consumed, alcohol. The oxidation within the body of 1 g each of these substances in pure form yields about 4,9, 4, and 7 kcal, respectively. Thus, fat contains more than twice the caloric value of either protein or carbohydrate. The health signiti- cance of the relatively high energy value of alcohol is discussed in the chapter devoted to this topic. Body weight depends on complex physiologic controls of the balance between energy intake and energy expenditure. Both intake and expendi- ture are equally important in regulation of body weight. Weight increases when more energy is consumed than expended. Over time, such an imbal- ance can lead to obesity. The physiologic controls of that balance and the ways in which diet and exercise affect body weight are reviewed in the chapter on obesity. Carbohydrates Carbohydrates are sources of energy for vital metabolic processes and also are constituents of cellular substances such as nucleic acids, glycoproteins, and enzyme cofactors and structural components of cell walls and cell membranes. Carbohydrates are classified as monosaccharides, disac- charides, and polysaccharides. Monosaccharide and disaccharide sugars are referred to as simple carbohydrates and the polysaccharides (starches and fibers) as complex carbohydrates. Monosaccharides. Monosaccharides are simple sugars that do not need to be further digested to be absorbed. The most important dietary monosac- charides are glucose, fructose, and galactose. Glucose and fructose are found in fruits, vegetables, and honey. They are also products of the digestion of sucrose (table sugar) and, in the case of glucose, other disac- charides. The glucose obtained from corn starch can be converted by 54 Introduction and Background O enzymatic processes to fructose to produce high fructose corn sweeteners. As discussed below, galactose is a subunit of the disaccharide lactose. Disaccharides. Sugars formed from two monosaccharides are called disac- charides. Sucrose, common table sugar, is composed of glucose and fruc- tose. It is found in many fruits and vegetables but occurs in especially high concentrations in sugar beets and sugar cane. Maltose is a disaccharide of two glucose molecules and is found in beer, glucose syrups, and cereals. Lactose, the sugar of milk, is composed of one molecule of glucose and one of galactose. Polysaccharides. Starch, glycogen, and most types of fiber are large. high- molecular weight polysaccharides. Starch and glycogen are composed of glucose molecules. Fiber includes a variety of carbohydrates and other components. These molecules differ from each other in the ways their monosaccharide units are linked to each other and, therefore, in their ability to be digested to sugars that can be absorbed into the body. The chemical linkages in starch and glycogen can be split by human intestinal enzymes, but those of polysaccharides found in fiber are, by definition, indigestible although some fiber components can be broken down by enzymes released by bacteria in the digestive tract to short-chain fatty acids that can be reabsorbed and furnish small amounts of energy. Fiber. Dietary fiber is a term used to describe a heterogeneous group of plant food components that are resistant to human digestive enzymes (LSRO 1987). Not all are fibrous in the usual sense of the word, and some are even soluble. Dietary fiber includes some of the structural components of plant cell walls (e.g., cellulose and noncellulosic polysaccharides such as hemicellulose) and certain nonstructural components of cells such as pec- tins, gums, brans, mucilages, algal polysaccharides, and modified cel- lulose. Specific types of dietary fiber are often classified as soluble or insoluble on the basis of their response to extraction methods. In general, the soluble fibers include gums, mucilages, and some pectins and hemicelluloses, while insoluble fibers include cellulose, lignin, and other pectins and hemicelluloses. Although all fruits, vegetables, and grains contain these fiber components, some are especially good sources of one or another type. Oat bran and beans, for example, contain relatively large proportions of soluble fibers whereas wheat bran is a good source of insoluble fiber. In general, diets that contain large amounts of fiber add bulk and may confer greater feelings of satiety. 55 The effect\ of the WI'WU~ fiber types on intestinal function differ, however. Insoluble fibers that adsorb water increase stool weights. Some soluble fibers have been found in short-term studies to reduce blood cholesterol, enhance glucose tolerance, and increase insulin sensitivity (LSRO 1987). These issues are reviewed in appropriate chapters of this Report. Lipids Dietary fats or lipids include a variety of substances soluble in organic solvents, such as chloroform or benzene, but insoluble in water. Food lipids include triglycerides (composed of fatty acids and glycerol), phospholipids, and cholesterol. Any excess of energy in the body, whether derived from carbohydrate, fat, protein, or alcohol, can be converted to fatty acids and stored in adipose tissue triglyceride, but dietary fat is essential because it supplies linoleic acid (an essential fatty acid) and it is a vehicle for absorp- tion of fat-soluble substances such as the vitamins A, D, E, and K (NRC 1980). Lipids are concentrated sources of energy as well as structural components of cell membranes and are molecular precursors for the synthesis of hor- mones and other substances. In adults, these functions usually can be met by a daily intake of 15 to 25 g of fat (NRC 1980), a level well below that typical of current American diets. In addition, fats impart characteristic mouth-feel and flavors to foods and increase the feeling of satiety after meals by delaying the passage of food from the stomach to the small intestine. The reservoirs of fat stored in the body protect the body's organs, provide insulation from heat loss, and maintain energy production during long periods of reduced food consumption, such as in starvation, dieting, or serious illness or injury. Furt.v Acids. Fatty acids are molecules containing carbon. hydrogen, and oxygen with chain lengths ranging from 4 to about 25 carbon atoms. A small amount of food fat occurs as phospholipid. Most fat in food, however, occurs as triglycerides, three fatty acid chains attached to a glycerol molecule. Triglycerides are called fats or oils depending on whether they are solid or liquid at room temperature. Both provide concentrated sources of metabolizable energy, about 9 kcal/g, more than twice the level of either proteins or carbohydrates. Recent studies suggest that the caloric value of fat may appear even higher in growing rats, reflecting greater efficiency of utilization under certain circumstances (Donato and Hegsted 1985; Donato 1987). 56 Introduction and Background 0 The fatty acids commonly found in food are usually composed of an even number of carbon atoms, usually 12 to 22, and contain from 0 to 6 double bonds-sites where additional hydrogen atoms can be attached. The number of double bonds determines the degree of saturation of fats. Fatty acids with no double bonds are saturated, those with one double bond are monounsaturated, and those with two or more double bonds are polyun- saturated. Although all dietary fats consist of a mixture of saturated, monounsatu- rated, and polyunsaturated fatty acids, fatty acids in foods of animal origin are more often saturated, while those in plants are more likely to be monounsaturated and polyunsaturated. There are some important excep- tions to this generalization. Coconut oil and palm kernel oil contain a high proportion of saturated fatty acids even though they are derived from plants, and as discussed below, certain fish are good sources of polyunsatu- rated fatty acids. The location of double bonds along the carbon chain is also of physiologic importance. The site of the double bonds is used to categorize unsaturated fatty acids into three groups-the omega-3, omega-6, and omega-9 fatty acids. In the metabolism of fatty acids, the end of the carbon chain containing the methyl group (whose carbon atom is known as the omega carbon) tends to remain unchanged, whereas enzymes can add or subtract carbon atoms or double bonds starting from the end of the molecule that contains the carboxyl group. For convenience, the chemical features of fatty acids are usually described in terms of the structure at the methyl end of the chain. Oleic acid has nine carbon atoms between its methyl omega carbon atom and its closest double bond, so it belongs to the omega-9 family of fatty acids. Linoleic acid and the compounds to which it is connected in the body have six carbons between their omega carbons and closest double bonds, and they are omega-6 fatty acids. Linolenic acid and its derivatives have three carbons between the omega carbon and the closest double bond and are omega-3 fatty acids. Monounsaturated omega-9 fatty acids such as oleic and palmitoleic acids are not essential in the human diet because they can be synthesized biochemically within the body. Linoleic acid, an omega-6 fatty acid, can- not be synthesized by the human body and must be consumed in the diet. It is a component of cell membranes and is required for the synthesis of arachidonic acid, the major precursor of prostaglandins, prostacyclins, thromboxanes, and leukotrienes that influence many physiologic pro- 51 0 Nutrition and Health cesses, including blood vessel dilation, platelet aggregation, smooth mus- cle contraction, inflammation, and reproduction. Linoleic acid is widely distributed in the fatty portion of both plant and animal foods. Vegetable seed oils are especially rich sources. Symptoms of its deficiency have been reported among infants restricted to skim milk and among children and adults fed intravenous solutions lacking fat (Rivers and Frankel 1981). Linoleic acid deficiency can be prevented by consuming about 3 to 5 g of linoleic acid a day, an amount considerably less than that consumed by the average adult in the United States. Thus, essential fatty acid deficiencies are reported rarely in the United States (NRC 1980). The role of omega-3 fatty acids, particularly eicosapentaenoic acid and docosahexaenoic acid, in human nutrition and health is under active inves- tigation. Omega-3 fatty acids are present in the human brain, retinal lipids, and phosphoglycerides of synaptic membranes. Of current interest are the potential health effects of these highly polyunsaturated fatty acids derived from linolenic acid (omega-3). Recent epidemiologic, clinical, and experimental data suggest that omega-3 fatty acids may have important physiologic effects that cannot be met by omega-6 or omega-9 fatty acids. Some of these effects are reviewed in the chapter on coronary heart disease. Cholesterol. Cholesterol is a fatty substance required for synthesis of sex hormones, bile acids, and vitamin D, and it is an important constituent of all cell membranes. It is both synthesized in the body (endogenous) and obtained from the diet (exogenous) and is not, therefore, an essential nutrient. In normal individuals, endogenous synthesis of cholesterol is reduced when blood cholesterol levels are high. When the physiologic mechanisms that regulate this feedback mechanism are insufficient, blood cholesterol levels can rise and increase the risk for coronary heart disease (see that chapter). Dietary cholesterol is found only in foods derived from animals (meat, poultry, fish, eggs, and dairy products); it is not present in plants. Protein Body proteins serve many functions; they include structural components of cells and tissues, enzyme catalysts of biochemical reactions, peptides and hormone messengers, and components of the immune system. The amino acids in proteins can also serve as sources of energy, and most can be used to synthesize glucose when dietary carbohydrate is inadequate. Some amino acids are needed for the synthesis of special compounds; 58 Introduction and Background 0 tryptophan, for example, is required for synthesis of serotonin (a neu- rotransmitter) and niacin (a vitamin). Proteins are formed from various combinations of amino acids that are linked together in chains ranging from several to hundreds in length. Each plant and animal species has its own characteristic proteins that are distin- guished by the sequence of amino acids. Plants can synthesize all of their amino acids from the elements carbon, oxygen. hydrogen, nitrogen, and sulfur, but humans lack the ability to synthesize at least eight amino acids and must obtain them from the diet. The rest are called nonessential amino acids because, although needed for protein synthesis, they are not required in the diet. Essential amino acids include isoleucine, leucine, lysine, methi- onine, phenylalanine, threonine, tryptophan, and valine. The amino acid cystine can replace part of the requirement for methionine, and tyrosine can replace part of the requirement for phenylalanine. Histidine is an essential amino acid for infants, but its essentiality for adults has not been conclusively demonstrated (NRC 1980). The proteins in different foods vary in their biologic value due to their content and balance of amino acids. When the concentration of one essen- tial ammo acid is low relative to the others, that amino acid is considered limiting and the protein is said to be incomplete. The presence of limiting amino acids in incomplete proteins can be compensated for at least par- tially by dietary intake of complementary proteins, those with different limiting amino acids. When consumed together or within a short time (the exact length of time has not been defined), such proteins can meet require- ments for essential amino acids. This explains, in part, why strict vege- tarians can maintain good health without eating foods derived from ani- mals. The addition of even a small amount of protein from animal foods can improve amino acid intake. The RDA's for protein intake of men, women, and children of different ages are given in Table l-6. Vitamins Vitamins are organic (carbon-containing) compounds that are essential in very small amounts for health, growth, and reproduction. They must be obtained from the diet either because they cannot be synthesized at all by the body or because the amounts made are insufficient to meet require- ments. Vitamins are classified according to their solubility in fat or water, and this property affects their occurrence in foods as well as their absorp- tion, transport, storage, and metabolism. 59 t.~,r-.~,,/rr/~/e C'itclmins. The fat-soluble vitamins are vitamins A, D, E, and k. These vitamins are generally found in high concentrations in the fatty portions of food and are absorbed, transported, metabolized, and stored along with fat. Their absorption requires bile and dietary fat. They are transported in the body by the same mechanisms by which fat is trans- ported, are bound to lipoproteins or specific transport proteins, and are stored in liver and fat tissue. Fat-soluble vitamins are excreted into the intestine in bile and are either reabsorbed or are eliminated in feces. They are not excreted to any appreciable extent in urine. Because excretion of fat-soluble vitamins is minimal, excess intake is more likely to cause toxicity symptoms. For the same reason, deficiencies are reported rarely among healthy adults, although they are observed among children who are growing rapidly and who lack adequate fat stores and among children or adults who have disease conditions that interfere with fat metabolism, such as malabsorption, biliary obstruction, or renal or liver disease. The RDA's for vitamins A, D, and E are given in Table 1-6; the estimated safe and adequate intake of vitamin K is shown in Table l-7. Vitamin A is present in the diet both as the vitamin and its precursor. Retinol, or preformed vitamin A, is found in foods derived from animals (milk, butter, egg yolks, liver) and, when bound to a fatty acid, is used to fortify many foods. Retinol occurs in foods primarily in the ester form. Certain carotenoids (pigments found in many dark green, yellow, and orange vegetables, fruits, and egg yolks) can be converted by the body into retinol. The conversion of beta-carotene into retinol occurs mainly in the intestinal mucosa. Retinol circulates in the plasma bound to a specific transport protein called retinol-binding protein. Excess amounts are stored in the liver. Bxcessive intake of retinol has caused toxic symptoms (head- ache, skin and bone disorders, and renal failure) among people consuming abnormally large amounts of vitamin supplements, or-less commonly- liver from animals with high vitamin A levels (Selhorst et al. 1984; Ma- honey et al. 1980). High intakes of retinol supplements have also been associated with birth defects (Rosa 1986); synthetic retinoid analogs, used to treat a variety of skin disorders (Bollag 1983), can cause fetal malforma- tions. They are hazardous to pregnant women or women planning to become pregnant (Lammer et al. 1985) and should be used only under medical supervision. Excess amounts of beta-carotene are stored in body fat deposits. Excessive intake of foods rich in beta-carotene, such as carrots, is not known to cause toxic effects. It raises levels of carotene in the blood and can cause the skin to take on an orange color that disappears when the carotene consumption declines. Vitamin A is essential for visual processes, for the normal differentiation of epithelial tissue, for the regula- tion of cell membrane structure and function, and for the maintenance of 60 Introduction and Background O immunocompetence. Vitamin A deficiency, through adverse effects on eye epithelial tissues, is a major cause of blindness among children in many developing countries, and it is also responsible for substantial additional illness. Recent studies of children consuming inadequate levels of retinol or carotenes suggest that retinol supplementation may improve their sur- vival (Sommer et al. 1986; Tarwotjo et al. 1987). Vitamin D, (cholecalciferol or calciol) is synthesized from a precursor (7- dehydrocholesterol) in skin that becomes activated by exposure to ultra- violet light from the sun. It is essential in the diet only when exposure to sun is inadequate. The vitamin is converted by the liver to 25-dihydrox- yvitamin D (calcidiol) and then further converted by the kidney to 1,25- dihydroxyvitamin D (calcitriol), the metabolically active form. Excess vitamin D can be toxic, especially to children and adults who have kidney disease or certain metabolic disorders. The metabolism and functions of vitamin D are reviewed in detail in the skeletal diseases chapter. Vitamin E functions as an antioxidant. Its principal dietary sources are vegetable seed oils. Its deficiency has been associated with a hemolytic anemia in premature infants and with neurologic symptoms in adults. Vitamin K functions as an activator of blood clotting proteins, proteins in bone and kidney, and the formation of other proteins that contain gamma- carboxyglutamic acid (GLA). It is synthesized by intestinal bacteria. Thus, deficiencies generally occur only in infants whose intestinal flora has not yet been established, in children and adults receiving antibiotic or anti- coagulant therapy (see chapter on drug-nutrient interactions), and in indi- viduals with disease conditions that interfere with intestinal absorption. Vitamins E and K are less toxic than vitamins A or D. Water-Soluble Vitamins. The water-soluble vitamins include vitamin C (ascorbic acid) and those of the B-complex group: biotin, folate, niacin, pantothenic acid, riboflavin, thiamin, vitamin B,, and vitamin B,,. The RDA's for vitamin C, thiamin, riboflavin, niacin, vitamin B,, folacin, and vitamin B,, are presented in Table 1-6; the safe and adequate ranges of intake of biotin and pantothenic acid are given in Table l-7. These vitamins are generally found in whole grain cereals, legumes, leafy vegetables, and meat and dairy foods. The two exceptions are vitamin C, which can be obtained in adequate amounts only from fruits and vegetables, and vitamin B,,, which is made by bacteria and found only in foods of animal origin. Water-soluble vitamins are absorbed from the intestine, and most are stored in a form that is bound to enzymes or transport proteins and excreted in urine. Thus, they should be supplied in adequate amounts in the daily diet even though tissue depletion may take as long as weeks or months. 61 0 Nutrition and Health Water-soluble vitamins are essential components of enzymes and enzyme systems that catalyze a wide variety of biochemical reactions in cellular energy production and biosynthesis. Thus, deficiencies of these vitamins particularly affect tissues that grow or metabolize rapidly, such as skin, blood, and the cells of the digestive tract and nervous system. Common deficiency symptoms are skin disorders, anemia, malabsorption and diar- rhea, neurologic disorders, and defects in tissues of the mouth. Specific vitamin deficiencies infrequently occur in the United States. When defi- ciencies occur, they usually are found along with other deficiencies and are due to diseases or to consumption of highly restricted diets or excessive amounts of alcohol or drugs that interfere with vitamin metabolism. The risk for deficiencies is greater in growing infants (see maternal and child nutrition chapter) and, perhaps, in older persons (see chapter on aging). Substantial intake of these vitamins causes toxicity infrequently, although severe toxic reactions have been reported from very excessive intakes of niacin and vitamin B,. Minerals Minerals perform a number of roles in the body. They function as inorganic components of enzyme systems that catalyze the metabolism of protein, carbohydrate, and lipids. Some act to regulate fluid and electrolyte bal- ance, to provide rigidity to the skeleton, and to regulate the function of muscles and nerves. Minerals also work together with vitamins, hormones, peptides, and other substances to regulate the body's metabolism. Essential minerals are often classified as macrominerals, required in amounts from several hundred milligrams to 1 or more grams a day (cal- cium, phosphorus, magnesium, sodium, potassium, and chloride), or as trace elements-iron, zinc, iodine, copper, manganese, fluoride, chro- mium, selenium, molybdenum, and cobalt (as a component of vitamin B&-which are required in small amounts (Underwood 1977). Other minerals such as nickel, vanadium, silicon, or boron have been shown to be essential under rigorous conditions for experimental animals but do not have well-established functions in humans. Still others, such as lead or mercury, are potentially toxic. RDA's for six minerals are given in Table 1-6. Ranges of dietary intake considered safe and adequate are given for nine others in Table l-7. Minerals are distributed in a variety of foods, but they usually are present in limited amounts. Thus, diets must contain enough of a variety of foods to meet daily requirements. People consuming diets low in energy for pro- 62 Introduction and Background 0 longed intervals are at risk of developing mineral deficiencies. Deficiencies can also result from therapy with medications that interfere with mineral absorption and metabolism; alcoholism, renal disease, or gastrointestinal diseases (see relevant chapters); and causes of mineral loss such as bleed- ing or diarrhea. Toxic symptoms can result from consumption of excessive amounts of almost any mineral or as a result of defective regulation of absorption or inadequate excretion. Dietary Patterns There are two types of data for monitoring dietary patterns: food availabili- ty and dietary intake. Food availability data are derived from annual estimates of per capita availability of selected commodities in the food supply. These data are useful in examining changes over time in the availability of agricultural commodities. Estimates of dietary intake come from periodic national food consumption surveys of individuals. Time Trends in the Availability of Foods Food availability data are produced by the USDA and are derived from annual production and marketing estimates of food products that are then usually adjusted for imports, exports, and stock changes. Such data have been collected since 1909 and have been published as a historical series from 1909 to the mid-MO's (USDA 1968). Data for the most recent 20 years are published annually (Bunch 1987). Per capita estimates of food availability are derived by dividing the total amount of food available by the total U.S. population. These data represent economic rather than phys- iologic consumption because they estimate the amount of food available at wholesale and retail levels rather than actual intake by individuals. Certain limitations restrict use of such data as proxies for consumption--for exam- ple, the difficulty in correcting for wastes and losses that occur before consumption by individuals, for inedible food components and food for human consumption fed to pets, or for variabilities in intakes of population subgroups. Nonetheless, food availability data provide useful information when used within their appropriate limits of interpretation. Time trend changes in availability of foods are best estimated from these data because the data have been available on an annual basis for many years. At the current time, these data are also the best source of information for tracking changes in the use of commodities or products that can be substituted for one another (e.g., partial substitution of high-fructose corn syrup for refined sugar). 63 O Nutrition and Health A summary of the recent trends is noted below, taken mainly from the data of the last two decades as presented in Table 1-8 (Bunch 1987), but in part from the early data series as well (USDA 1968). Overall, total per capita availability of meat, poultry, andfish increased by about 10 percent since 1965-67, primarily due to increases in poultry and fish and shellfish. Availability of red meat increased substantially after World War II (USDA 1968) but, after peaking in about 1970, has since declined to approximately 1965-67 levels. Egg availability reached its peak about 1950. During the past 20 years, it has declined by about 18 percent; this is approximately equivalent to a decrease of one egg per week per person (from about six to five eggs per week). The availability of fluid whole milk declined by 48 prp"nt from 1965-67, while available levels of low-fat milk and milk products (including yogurt) more than doubled from 1%547 to 1983-85. Cheese availability also more than doubled during this period. Availability off&s and oils increased by approximately 23 percent since 1965-67, primarily due to a 77 percent increase in salad and cooking oil and a 36 percent increase in shortening. Butter availability was about 18 lb per capita per year in 1909 (USDA 1968) and has declined to about 5 lb, including about a 20 percent decline since 1965-67 (Bunch 1987). Availabil- ity of total animal fat also declined by 1983-85, to levels approximately 80 percent of those in 1%5-67, but with a slight recent increase. Over the two decades, vegetable sources increased from 67 percent to 79 percent of all fats and oils-in marked contrast to the first half of the century when animal sources provided most of the fats and oils (USDA 1968). As noted earlier, these data represent availability of commodities and thus do not necessarily reflect changes in actual intakes of fats and oils by the U.S. population. For example, there is no correction for losses of fats and oils used for deep fat frying, which are discarded after use rather than consumed. Second, the bulk data represent only fats and oils that are added to foods or used in table spreads; they do not include "hidden" fats in foods such as marbled fat in meats or the fats in nuts. Vegetable undfruit availability increased from 1%567 by 19 percent and 7 percent, respectively, primarily due to increases in availability of fresh produce. There was, however, no consistent change in availability of legumes (beans, peas, and nuts) or starchy vegetables (potatoes and sweet notatoes). 64 Table 1-8 Annual Per Capita Availability of Selected Commodities in the U.S. Food Supply, 198!%1989 (pouts) Meat, Poultry, and Fishb Dairy Productsd Low-fat Milke Fluid and Milk Fish and Whole Products Year Meat Poultry Shellfish Total Ew Milk (fluid) Cheese' Totab 1965-67 123.6 30.6 10.8 165.0 40.0 240.3 41.7 9.8 343.9 z 1968-70 130.8 33.0 11.3 175.1 39.5 219.5 54.6 11.0 334.6 1971-73 129.5 35.1 12.3 176.9 38.2 199.2 69.3 12.9 327.7 1974-76 128.7 35.5 12.4 176.6 35.1 176.0 82.9 14.9 317.1 1977-79 126.2 40.1 13.0 179.3 34.6 155.9 95.3 16.8 310.2 g 1980-82 120.9 44.2 12.7 177.8 33.9 138.1 101.7 18.7 299.7 1983-85 120.9 47.6 13.8 182.3 32.8 125.3 111.4 21.5 301.7 & C aTotals may include more categories than the selected commodities. a. bMeat (beef, veal, pork, lamb), poultry, and fish, edible weight. Fish excludes game fish (Bunch 1987, Table 9, p. 15). B cEggs, retail weight. Weight of a dozen eggs is assumed to be 1.57 lb (Bunch 1987, Table 8, p. 14). d Dairy products are for civilian population, except fluid milk and cream data, which use U.S. resident population (Bunch 1987, Table 10. p. 16). f2 BLOW-fat and other milk products include low-fat, skim, buttermilk, flavored drinks, and yogurt. 2 `Cheese is whole and part-whole milk cheese, excluding pot, baker's, and cottage cheese. 6 gTotal dairy products calculated as total retail product weight minus butter (Bunch 1987, Table 10, p. 16). Includes frozen dairy products, cot- g tage cheese, and other products not indicated in table. The amount of calcium contributed by this food group has actually increased slightly during the 20-year period shown, as a result of increases in products such as dry milk powder. g 0 Table l-8 (continued) Year 1965-67 I 968-70 g: 1971-73 1974-76 1977-79 1980-82 1983-85 Fats and Oil@ Animal Vegetable Salad and Total Cooking Total Butter Lard Animal Margarine Shortening Oil Vegetable Total 5.9 5.7 16.9 10.3 15.4 12.6 35.2 52. I 5.5 5.0 16.0 10.7 16.9 14.4 38.8 54.9 4.9 3.7 14.1 11.0 17.2 16.7 41.9 56.0 4.5 2.9 II.6 Il.4 17.2 18.5 44.8 56.4 4.4 2.3 II.6 Il.3 17.9 20.0 46.3 57.9 4.4 2.5 12.8 II.2 18.4 21.6 48.1 60.9 4.9 2.0 13.5 10.5 20.9 22.3 50.6 64.1 Fruit@ 2. Fresh Processed Total 79.0 35.3 114.3 77.1 37.6 114.7 75.5 39.4 114.9 79.9 80.4 2: 120.5 120.2 84.8 37:1 121.9 87.9 34.8 122.7 hFood fats and oils calculated on a total population basis except butter, which is based on civilian population (Bunch 1987; animal and vegeta- ble fats are from Table 2, p. 7; butter, lard, margarine, shortening, and salad and cooking oil are from Table 12, p. 18). The animal and vegeta- ble categories are not strictly distinct because some margarines and shortenings include animal fats. I Selected fruits, retail weights. Include fruits for which data are available for the entire series: oranges, tangerines, tangelos, lemons and limes, grapefruit, apples, avocados, bananas, cherries, grapes, nectarines, peaches, pears, pineapples, plums and prunes, strawberries, minor fruits, and a variety of canned, frozen, and chilled fruit and juices (Bunch 1987, Table 2, p. 7). Table l-8 (continued) Vegetablesi Sugar and Sweeteners' Potatoesk Beans, and Flour and Refined Total Peas, and sweet Cereal Cane Corn Caloric Coffee, Tea Year Fresh Processed Total Nuts Potatoes Pruducts and Beet Sweeteners Sweeteners and Cocoa 1%5-67 62.6 41.4 104.0 14.8 84.5 143.8 97.6 15.5 114.8 15.1 % 1968-70 65.2 45.4 110.6 14.8 85.1 141.9 100.6 18.2 120.4 14.5 1971-73 66.1 45.9 112.0 14.2 80.6 138.5 101.7 21.8 125.0 14.2 1974-76 68.9 46.1 115.0 15.1 81.5 143.6 92.7 27.3 121.4 13.1 1977-79 71.7 46. I 117.7 14.3 81.5 145.8 91.7 33.8 126.X II.1 1980-82 74.3 44.2 118.6 * 14.0 76.3 150.2 78.9 44.4 124.6 II.3 $ 1983-85 79.7 44.7 123.3 14.6 79.5 150.5 67.4 58.3 127.1 II.6 0 I Selected vegetables: fresh vegetables for which data are available for entire series include broccoli, carrots, cauliflower, celery, corn, lettuce, g onions and shallots, and tomatoes; 1985 data for processed vegetables are unavailable (Bunch 1987, Table 2, p. 7). g. kPotatoes and sweet potatoes: data not comparable to pre-1980 figures. Data revised to reflect conversion from processed weight to fresh- 1 weight equivalent to dehydrated potatoes, frozen potatoes, chips, and shoestrings (Bunch 1987, Table 2, p. 8). E a 1 Sugars and sweeteners, dry weight basis (Bunch 1987, Table 27, p. 33). r m Nutrition and Health Availability of jlour and cereal products showed both decreasing and increasing fluctuations during the 20-year period; 1983-85 levels were approximately 5 percent higher than 1%5-67 levels. Availability of grains was at its lowest point this century in 1971-73, but has since increased by about 9 percent. Availability of sugars and sweeteners increased by about 11 percent since 1965-67. It should be noted that the availability data for sugars and sweet- eners are for bulk commodity forms only; they do not include estimates of sugars that are consumed as a natural constituent of food products, for example, lactose in milk or sugars naturally present in fruits. Availability of coffee, tea, and cocoa decreased approximately 25 percent since 1%5-67. Current Dietary Intakes Food consumption surveys can be used to estimate food and nutrient intakes of populations and population subgroups. The most recent nation- ally representative survey is the first Continuing Survey of Food Intakes by Individuals (CSFII), conducted by the USDA in 1985. Data are limited to three subgroups: children 1 through 5 years and adult men and women 19 through 50 years of age. Results are presented based on 1 day of intake (Table l-9). When applicable, estimated mean intakes are compared with recommendations in the latest report on RDA's (NRC 1980). In interpret- ing results, it should be noted that the RDA's (except for energy) have a margin of safety above average requirements. Thus, diets that do not meet the RDA's do not by themselves provide conclusive evidence of nutritional deficiencies. Corroborating health data are needed. Food Energy. Men and children had estimated mean intakes of more than 90 percent of the Recommended Energy Intakes (REI); for women, the estimated mean intake was 82 percent of the REI. Total Fat, Fatty Acids, and Cholesterol. Fat contributed 34 percent of total energy intake for children and 36 to 37 percent for men and women. The relative fatty acid contributions were approximately 40 percent saturated, 40 percent monounsaturated, and 20 percent polyunsaturated. Cholesterol intakes ranged from a mean of 254 mglday for children to 304 and 435 mg for women and men, respectively. Protein. For men, women, and children, estimated mean intakes were 140 percent or more of the RDA. Protein contributed approximately 16 percent of total energy intakes. 68 Introduction and Background cl Table l-9 Mean Daily Intake of Food Energy, Nutrients, and Food Components for Men, Women, and Young Children From the Continuing Sutvey of Food Intakes by Individuals (CSFII), 198!jb Men Women Children Total Food Energy (% REW (94) (82) (loo) Fat [% total energy] Total fat Saturated fatty acids Monounsaturated fatty acids polyunsaturated fatty acids Cholesterol mg Protein [(9$ tgflrgyl Carbohydrates I% total energy] Dietary Fiber g Vitamins (% RDA) Vitamin A Vitamin E Vitamin C Thiamin Riboflavin Niacin Vitamin B, Vitamin B,* Folacin Minerals (% RDA) Calcium Phosphorus Iron Zinc Magnesium Minerals (ESADDI)' Sodium Potassium 1361 t131 (141 171 435 1163 (175) [451 18 (122) (98) (182) (124 (129) (146) (85) (245) (76) (115) (78) (192) (126) (159) (61) (94) (60) (94) (72) (exceeds) (within) (within) (within) (371 [I31 If41 t71 304 [161 (144) 1461 12 (127) (97) (133) (110) (115) (130) (61) (156) (51) [341 [I41 1121 161 254 [161 (222) 1521 10 (215) (108) (186) (153) (197) (151) (127) (192) (157) (105) (132) (88) (84) (121) (exceeds) (l-3 years exceeds) (4-5 years within) (below) (below) Copper (below) +&mated mean daily intake is expressed in several ways: amount of intake, percent of total energy intake, percent of Recommended Dietary Allowance, or comparison wrth Es- timated Safe and Adequate Daily Dietery Intake. bData based on 1 -day dietary recalls obtained by personal interview for !58 men 19 to 50 years of age for 1 459 women 19 to 50 yeers of age, and for 489 of !herr chrldren.1 to 5 years of age'in 19& (unweighted numbers). Nutrient Intakes do not Include vrtamln and mineral supplements or sodium from salt added at the table. ~Recommended Energy Intake (NRC 1980); Source of percentages: NFCS, CSFII Report Nos. 85-l and 85-3 (USDA 1985,1986). dRecommended Dietery Allowance (NRC 1980); Source of percentages: NFCS, CSFII Re- port Nos. 65-1 and 85-3 (USDA 19851989). *Estimated Safe and Adequate Daily Dietary Intake (NRC 1980). 69 O Nutrition and Health Diel240 - Source: National Cholesterol Education Program 1988a. LDL Cholesterol mg/dl Cl30 130-159 >160 - 94 Coronary Heart Disease 0 obesity-and most of the reports also recommend a reduction in dietary cholesterol and partial replacement of saturated with polyunsaturated fat (Truswell 1983). In response to a congressional directive, DHHS and USDA jointly spon- sored an assessment of the existing evidence relating dietary cholesterol to blood cholesterol and human health, as well as recommendations for further research. Their report to Congress, The Relationship Between Dietary Cholesterol and Blood Cholesterol and Human Health and Nutri- tion (1986). concluded that high blood cholesterol is one of the major risk factors for CHD and that cholesterol in the diet, but even more the amount and types of fat in the diet, affect blood cholesterol; dietary cholesterol raises blood cholesterol in most people; in some there is a small response and in others the increase is more pronounced. The prevalence of different degrees of response in the population is not known. A broad program of research was recommended. The National Research Council of the National Academy of Sciences recently conducted a 3-year review of the role of animal products in the American diet (NRC 1988). Its report, Designing Foods. Animal Product Options in the Marketplace, concluded that nutrition-related health prob- lems affect nearly every American family and recommended measures to reduce the quantity of animal fat in the diet and to increase consumers' access to fat and cholesterol information. Key Scientific Issues o Role of Dietary Fat and Cholesterol in CHD o Role of Other Dietary Factors in CHD o Efficacy of Dietary Interventions in CHD Role of Dietary Fat and Cholesterol in CHD Of the many dietary factors that have been studied, the strongest and most consistent evidence relates to dietary fat. Systematic examination of the diet-blood cholesterol-CHD link through clinical, epidemiologic, and ani- mal research implicates both the amount and nature of dietary fats as important determinants of plasma cholesterol levels. Clinical Studies Clinical studies have addressed the role of dietary fat and cholesterol upon CHD through their effects upon blood cholesterol and by their effects upon 95 13 Nutrition and Health development and severity of heart disease. The latter type of clinical studies is summarized in the section on Efficacy of Dietary Interventions in CHD, while studies on blood cholesterol are summarized below. A variety of clinical studies carried out over the past several decades have shown that the type of fat and amount of cholesterol in the diet affect blood cholesterol levels. In these studies, the composition of the diet is controlled so that the effects of single constituents can be tested. Fatty acid sources examined include butter fat, olive oil, cottonseed oil, sunflower oil, hy- drogenated coconut oil, sardine oil, safflower oils, margarines, and cocoa 1 butter(Keys, Grande, and Anderson 1974). Typically, saturated fatty acids were shown to raise and polyunsaturated fatty acids to lower plasma cholesterol levels in comparison with monounsaturated fatty acids, which were considered to be neutral. The degree of response to saturated fatty acids depends on the individual fatty acid content. Myristic (14 carbon atoms, C:14) and lauric acids (C:12) have a more powerful effect than palmitic acid (C: 16), but palmitic acid is more abundant in the food supply. Saturated fatty acids with more than 18 or fewer than 10 carbon atoms appear to have little or no effect on plasma cholesterol levels (Keys 1967). Likewise, stearic acid (C: 18) has been reported not to raise blood choles- terol levels or, when substituted for palmitic acid, to lower blood cholester- ol levels (Bonanome and Grundy 1988). Trans fatty-acids are isomers of naturally occurring cis unsaturated fatty acids. They are produced in fats as a result of commercial hydrogenation of cooking oils and also occur in ruminant fats, including milk fat, beef fat, and lamb fat. Trans fatty acids as consumed in hydrogenated vegetable oil appear to be the equivalent of oleic acid in their cholesterolemic properties in humans. In this respect, they are similar to stearic acid, but dissimilar to palmitic, myristic, and lauric acids (LSRO 1985). Equations to estimate the change in serum cholesterol from changes in dietary fats and cholesterol (Keys, Anderson, and Grande 1965; Hegsted et al. 1965) derived from such clinical experiments are presented in Table 2-4. They show that saturated fatty acids are about twice as powerful in raising plasma cholesterol levels as polyunsaturated fatty acids are in lowering them, while dietary cholesterol has a smaller effect (Blackbum 1979). It has been estimated that increasing the dietary cholesterol intake by 100 mg/1,000 kcal increases the plasma total cholesterol by about 10 mg/dl (Grundy et al. 1988). Thus, if a person consuming 2,000 calories per day increases his or her dietary cholesterol from 300 to 500 mg/day, plasma cholesterol will rise about 10 mg/dl. 96 Coronary Heart Disease O Table 2-4 Estimates of Serum Cholesterol Change From Given Changes in Dietary Lipids Based on kocaMc Controlled Experknents in Humans Keys (Minnesota) equation: ACHOL = 1.35(2AS - AP) + 1.52AZ Hegsted (Harvard) equation: ACHOL = 2.16AS - 1.65AP + 0.0677AC - 0.53 Where A CHOL = estimated change in serum cholesterol in mg/dl; A S = change in percent daily calories from saturated fat; A P = change in percent daily calories from polyunsaturated fat; A 2 = change in the square root of daily dietary cholesterol in mg/l,OOO calories; and A C = dietary cholesterol in mg/ day. Source: Blackbum, Ii. 1979. Diet and mass hyperlipidemia: public health considerations- a point of view. In Nutrition, lipids, and coronary heat7 disease, ed. Ft. Levy, 8. Riind, 8. Dennis, and N. Ernst, pp. X9-47. New York: Raven. Reprinted with permission from Raven Press, New York. Numerous studies have predicted group mean plasma cholesterol levels on the basis of the dietary content of saturated and polyunsaturated fatty acids and cholesterol alone (Keys, Grande, and Anderson 1974). Other clinical studies have shown that although saturated fat raises and polyunsaturated fat lowers plasma cholesterol levels, the magnitude of the change differs from that predicted by the equations. Results of six European experiments were compared with those predicted by equations such as those shown in Table 2-4 (Grande 1983). The predicted changes in serum cholesterol were generally in agreement with the observed changes, with some variability. For example, in the Finnish Mental Health Study, a dietary change that was predicted to raise cholesterol 33 mg/dl produced an average elevation of 49 mg/dl. In another experiment, the cholesterol-lowering effect of corn oil and olive oil were compared with a control diet. Mean serum cholesterol reductions were 50 mg/dl and 38 mg/dl, respectively, whereas the equa- tions predicted the same decrease for both diets, 43 mg/dl. In another experiment, the effect of dietary cholesterol added to a diet rich in polyun- saturated fat was in agreement with the predicted value but was underesti- mated when cholesterol was added to a diet high in saturated fat. More recently, the effects of high-oleic safflower oil (monounsaturated), high-linoleic safflower oil (polyunsaturated), and palm oil (saturated) on 97 cl Nutrition and Health blood cholesterol levels were compared in normal and hypertriglyceridem- ic patients. Both the high monounsaturated and high polyunsaturated fatty acid oils achieved similar lowering of total cholesterol (35 mg/dl), compared with 78 mg/dl predicted for the high polyunsaturated and 45 mg/dl predicted for the high monounsaturated fat diets (Mattson and Grundy 1985). In another study, beef fat, coconut oil, and safflower oil were isocalorically exchanged in the diets of healthy normal volunteers (Reiser et al. 1985). Mean plasma total cholesterol was 21 mg/dl lower on the safflower oil diet compared with the habitual diet. Mean plasma total cholesterol on the beef fat diet was 14 mg/dl higher than on the diet containing safflower oil and 13 mg/dl lower than on the diet containing coconut oil. The authors suggested that the relatively higher proportion of stearic acid in the beef fat might contribute to these differences. Despite some inconsistencies in the degree of plasma cholesterol re- sponses, clinical studies have generally shown a fall in response to polyun- saturated fat and a rise in response to saturated fat. However, the above two experiments suggest that the interaction of dietary factors in regulating blood cholesterol levels may be more complex than can be accounted for solely by the amount of saturated and polyunsaturated fats and dietary cholesterol. Other factors that might contribute to inconsistencies across studies include differences in baseline plasma cholesterol levels, composi- tion and form (food vs. liquid formula) of the diet, age, metabolic status of the participants, and duration of the experiment (Mattson and Grundy 1985). Most clinical studies have noted a high degree of individual variability in response to dietary cholesterol, a characteristic also noted among some animal species (Jokinen, Clarkson. and Prichard 1985). Humans are gener- ally less sensitive to dietary cholesterol than most animal species, and the high degree of individual variability in plasma cholesterol responses to dietary cholesterol suggests that some people may be overly sensitive to dietary cholesterol while others are relatively resistant. The proportion of the population that might be cholesterol-sensitive and the factors that contribute to that sensitivity are not well understood. The response to dietary cholesterol may be affected by such factors as previous diet, age, or genetic makeup (McGill 1979) and the relative proportions of other nu- trients in the diet. For example, one controlled clinical study compared the effects of adding three or six eggs to basal diets containing 40 percent fat and 300 mg of cholesterol and differing ratios of polyunsaturated to saturat- ed fat (P/S). At P/S ratios of 0.25 and 0.4, the addition of three and six eggs raised LDL cholesterol by 16 mg/dl and 25 mg/dl, respectively. At P/S 98 Coronary Heart Disease- 0 ratios of 0.8 and 2.5, the addition of three eggs had little effect, but the addition of six eggs at the P/S ratio 0.8 raised LDL cholesterol 17 mgidl. On the diet with a P/S of 2.5, neither three nor six eggs produced significant changes. Thus, both the cholesterol content and the P/S ratios were impor- tant in determining LDL level (Schonfeld et al. 1982). Another example suggests that type of protein may influence response to dietary cholesterol. In a controlled dietary study in Type II hypercholesterolemia patients. substitution of soybean for animal protein caused a reduction in serum cholesterol concentrations, and the decrease was about the same with or without the addition of 500 mg of cholesterol to the diet (Sir-tori, Gatti. and Mantero 1979). A total of 75 studies were carried out in 50 male outpatient volunteers fed high cholesterol (approximately 800 mg/dl) versus low cholesterol (approx- imately 250 mg/dl) in a diet containing 35 percent of calories as either polyunsaturated or saturated fat. In 69 percent of the studies. participants compensated for the increased dietary cholesterol by decreasing cholester- ol absorption or endogenous synthesis. The type of dietary fat had a larger and more consistent effect on plasma cholesterol (McNamara et al. 1987). The main effect of dietary cholesterol on lipoproteins is to raise LDL levels, but it also affects other lipoprotein fractions. For example, human volunteers who ate three to six eggs per day showed increased binding activity of an HDL subfraction that might be associated with increased risk for the development of atherosclerosis (Mahley et al. 1978). It is hypothe- sized that dietary cholesterol might increase the cholesterol content of chylomicron and VLDL remnants, making them more atherogenic; these changes would not be detected in fasting blood samples. indicating the need for information on postprandial lipoproteins (Grundy et al. 1988). Epidemiologic Studies Extensive evidence relating diet to high blood cholesterol has been amassed in a variety of observational-epidemiologic studies. These investi- gations involve comparisons of different populations, comparisons of mi- grant with native populations, and comparisons of groups within popula- tions. Between-Population Studies (International Comparisons). In one type of international analysis, nutrient and food commodity data from Food and Agriculture Organization food balance sheets have been compared with World Health Organization CHD mortality data for sets of countries (Stamler 1983). Univariate analyses consistently showed statistically sig- 99 O Nutrition and Health nificant positive associations of CHD mortality with calories, total fat, animal fat, saturated fat, dietary cholesterol, total protein, animal protein, animal products (dairy products, meat, poultry, and eggs), and refined sugars. Similar analyses have also shown an inverse association between vegetable products and CHD mortality. Since many of these variables occur together, the independent effect of a single nutrient cannot be determined in such analyses. When the data were reanalyzed, combining the saturated and polyunsaturated fatty acids and dietary cholesterol into a single score based on defined equations (see Table 2-4) and using analysis of variance to control separately for the influence of sugar, vegetable products, and fat, the significant effects of dietary fats persisted while sugar and vegetable products no longer related to CHD mortality (Liu et al. 1982). In a second type of international comparison, autopsy records were used to compare the degree of atherosclerosis with dietary data. The most system- atic study was the International Atherosclerosis Project (McGill 1%8), in which severity of atherosclerosis was quantified in autopsies of 23,000 people in 12 countries. The percent of calories consumed as fat ranged from 10 to I5 percent in Costa Rica and Guatemala to nearly 50 percent in the United States. Dietary composition was estimated from available survey data and subjective judgment. The countries were ranked on the basis of severity of disease, dietary indices, and serum cholesterol. The results showed that the percentage of calories from dietary fat was related to the severity of the atherosclerosis (r = 0.67) and to population levels of blood cholesterol (r = 0.74). A third type of international comparison involves the direct measurement of cardiovascular risk factors and dietary assessment. These epidemiologic surveys provide further descriptive data on dietary factors associated with the prevalence of heart disease in the populations studied. For example, the Seven Countries Study (Keys 1970) has involved 12,000 men from I8 populations sampled in Finland, Greece, Italy, Japan, the Netherlands, the United States, and Yugoslavia. Fourfold differences in prevalence and incidence of CHD were shown among these populations. The highest incidence rates were recorded for Finland and the United States and the lowest for Japan and three populations in Greece (Co&, Crete, and Dalmatia). Seven-day food records supplemented by chemical analyses of the diets consumed by study participants showed wide variability across population samples in both amount and type offat. Saturated fat intake was highest in Finland, the United States, and the Netherlands (I7 to 22 percent of calories, compared with 5 to 9 percent of calories in the other countries). Saturated fat intakes and 5-year CHD incidence rates for these populations were highly and significantly correlated (r = 0.84), as were saturated fat and 100 Coronary Heart Disease LJ serum cholesterol levels (r = 0.89) and serum cholesterol levels and CHD incidence rates (r=O.81) (Keys 1972). Followup after 10 years still support- ed these findings (Stamler 1979). International migration studies are yet another type of cross-country com- parison. The movement of population groups from less affluent to more affluent societies provides a special opportunity to evaluate changes in risk factors among persons sharing the same genetic and cultural background. Such observations have helped to dispel the view that atherosclerosis and CHD essentially represent an immutable aging process, with most of the variations representing the inherited population pattern, or that the choles- terol levels encountered in most people in the United States can be re- garded as normal. They indicate that as populations move and show a rise in dietary fat and saturated fat intake, they move from areas with low incidence of CHD to high incidence. They also display concurrent eleva- tions in serum cholesterol. For example, the Ni-Hon-San Study, initiated in 1%5 with middle-aged men of Japanese ancestry residing in Japan, Honolulu, and the San Francisco Bay area, showed intakes of saturated fat to be about 7 percent, 12 percent, and 14 percent, respectively. Average dietary cholesterol intakes were 464,545, and 533 mg/day, and mean body weights were 55, 63, and 66 kg for the respective populations. Compared with Japan, serum cholesterol was 12 percent higher in Hawaii and 21 percent higher in San Francisco, and CHD mortality was 1.7 times higher in Hawaii and 2.8 times higher in San Francisco (Kato et al. 1973; Marmot et al. 1975; Robertson, Kato, Gordon, et al. 1977; Robertson, Kato, Rho- ads, et al. 1977; Worth et al. 1975). Within-Population Studies. The existence of groups within populations who consume diets different from the rest of the population provides another opportunity to examine the relationship between diet, serum cho- lesterol, and CHD. For example, studies in the United States comparing serum cholesterol levels in communities of omnivores (consuming animal and vegetable products), vegans (consuming only vegetable products), and lacto-ovo vegetarians (consuming milk, egg, and vegetable products) showed that vegans, who habitually consume a low saturated fat and cholesterol-free diet, had mean serum cholesterol levels 29 percent lower than omnivores, and those of lacto-ovo vegetarians were 16 percent lower (Hardinge and Stare 1954). Seventh-day Adventists who consume lacto- ovo vegetarian diets have lower mean serum cholesterol levels than the general American population. A dyear prospective study of 20.044 Sev- enth-day Adventists in California showed that CHD mortality rates among those 35 to 64 years of age and over age 65 were 72 percent lower and 50 percent lower, respectively, than rates found in the general population. 101 O Nutrition and Health Among Seventh-day Adventists, risk for CHD in nonvegetarian males 35 to 64 years of age was threefold greater than in vegetarian males (Phillips, Lemon, and Kuzma 1978). All these types of epidemiologic studies involve analysis of data for groups. Despite the strength and consistency of results of group comparisons across and within populations, it has been difficult in studies of individuals within a given population to demonstrate similar relationships of dietary fat with either the plasma cholesterol level or CHD. While studies of individu- als have revealed strong relationships between plasma cholesterol and CHD, only weak associations of dietary factors with plasma cholesterol levels or CHD have been shown. In the Puerto Rico Heart Study, for example, baseline serum cholesterol levels in the urban sample were positively related to percent of calories from protein, fat, and saturated fat, and serum cholesterol was negatively related to percent of calories from total carbohydrate and complex carbo- hydrate (Garcia-Palmieri et al. 1977). In the Honolulu Heart Study, baseline serum cholesterol was positively related to dietary cholesterol, animal protein, and saturated fat and to percent of calories from total protein, total fat, animal protein, and saturated fat; it was negatively associated with percent of calories from complex carbohydrate and total carbohydrate (Kato et al. 1973). Multivariate analysis controlling for age, relative weight, systolic blood pressure, serum cholesterol, and cigarette smoking showed CHD incidence after 6 years to be inversely related to alcohol, starch, and caloric intake per kilogram of body weight (Gordon et al. 198 1). Followup of the Honolulu cohort after 10 years showed that percentage of calories from fat, saturated fat, and dietary cholesterol was related directly to CHD mortality, although percentage of calories from fat was inversely related to total mortality, cancer mortality, and stroke mortality (McGee et al. 1985). The Western Electric Study examined diet, serum cholesterol, and other variables in 1,900 middle-aged men, who were examined at entry, 1 year later, and 20 years later. Changes in the intake of saturated fat and dietary cholesterol between entry and l-year visits were positively related to change in the level of serum cholesterol. The dietary data collected at the first two visits were averaged to provide baseline estimates of intake for the followup study analysis. Results showed that the 19-year risk for death from CHD was inversely related to polyunsaturated fat intake and positively related to dietary cholesterol intake. These correlations per- sisted after adjustment for baseline serum cholesterol, body mass index, systolic pressure, cigarette smoking, monthly alcohol intake, and age (Shekelle et al. 1981). After 25 years of followup, dietary cholesterol was 102 Coronary Heart Disease O still positively and independently related to risk for death from CHD (Shekelle and Stamler 1988). The Ireland-Boston Heart Study reported within-population analyses showing that individuals who died of CHD had a higher intake of saturated fatty acids and cholesterol and a lower intake of polyunsaturated fatty acids. Mean total fat intake was higher(39.4 percent vs. 38.5 percent) in the group who died of CHD, but the difference was not statistically significant. Fiber intake was significantly lower among those who died of CHD (Kushi et al. 1985). Although these epidemiologic studies have shown that diet. particularly the amount and type of fat in the diet, influences the level of plasma cholester- ol, other studies of individuals within populations. such as Framingham, Tecumseh, and Evans County, have failed to find any association of diet with plasma cholesterol or CHD (Kannel and Gordon 1970; Nichols et al. 1976; Cassel 1971; Gordon et al. 1981). Difficulties in establishing a consistent correlation between diet and plasma cholesterol in individuals within a given population (short of such extremes as comparing vegetarians with the general public) have been attributed to several factors. First, most methods used for measuring habitual dietary patterns in free-living populations have a high degree of technical error (Bingham 1982). Daily variability in dietary intakes of individuals is greater than the variability among individuals. Hence, methods that measure dietary intake only over 1 day, as was done in Puerto Rico (Garcia-Palmieri et al. 1980), Honolulu (Katoet al. 1973), andTecumseh (Nichols et al. 1976), can result in considerable misclassification of individuals on the basis of long-term dietary patterns (Liu et al. 1978). Intake of fat, especially saturated fat, and cholesterol tends to be uniformly high in Western industrialized countries. Under such circumstances, possi- ble fallacies may arise (Rose 1985). If nearly everyone in a population is exposed to a causal agent such as smoking or high saturated fat intake, then the presence of disease in an individual will appear to be attributable to individual genetic and personal characteristics, and traditional case-con- trol and cohort methods will fail to identify the causal agents. Under these circumstances, causal agents are better revealed by differences between populations or by contrasting changes within populations over time (Rose 1985). Other problems arise from the variability and error in measurement of factors such as plastia cholesterol. These dificulties weaken considerably 103 O Nutrition and Health any attempt to correlate diet with other CHD indices (Liu et al. 1978). Conversely, epidemiologic correlations based on group averages of popula- tions, such as the international comparisons cited earlier, tend to overesti- mate the true effect (McGill, McMahn, and Wene 1981). Thus, the true contribution of diet to plasma cholesterol levels probably lies somewhere between the estimates obtained in comparisons between groups and be- tween individuals within a group. Animal Studies Animal models extend the observations made in humans by providing opportunities to explore directly mechanisms by which dietary factors mediate the development, progression, and regression of atherosclerotic lesions. Such studies often cannot be done in humans because the disease develops slowly over a long period of time, and techniques to measure the severity of the disease carry risk and have technical limitations. The advantages and disadvantages of the use of various animal models in atherosclerosis research have been reviewed (Jokinen. Clarkson, and Prichard 1985). Because no single animal model can duplicate the range of human arterial lesions that develop over long periods of time, several animal species have been used, depending on the mechanism to be investi- gated. These species vary in the natural occurrence and sensitivity to induction of experimental atherosclerosis. Hyperlipidemia, which leads to the development of atherosclerosis, is readily produced in rabbits, pigeons, chickens, turkeys, Japanese quail, pigs, and some nonhuman primates by feeding diets high in cholesterol and saturated fats. Dogs and rats have generally been considered to be resistant to both naturally occurring and experimentally induced atherosclerosis, although, even in these species, advanced atherosclerotic lesions have been produced by adding to the diet cholesterol and coconut oil (dogs) and cholesterol and cholic acid (rats). Of all the animal models, many breeds of pigs and several species of nonhuman primates tend to resemble humans most closely in lipoprotein patterns and the pathologic components of the lesion (Jokinen, Clarkson, and Prichard 1985). For example, studies in miniature pigs fed hog chow supplemented with cholesterol and either lard or beef fat showed elevations in plasma choles- terol. Myocardial infarctions were observed, and the diet-induced athero- sclerosis was very similar to the proliferative lesions of human atheroscle- rosis. As in humans, individual variability in response to diet was observed (Mahley 1979). 104 Coronary Heart Disease 0 Nonhuman primates have several characteristics that make them valuable as animal models: They are phylogenetically close to human beings; they develop arterial lesions similar to those seen in humans; and dietary manipulation can produce hyperlipidemia that, in some species. resembles that of humans. Some nonhuman primates develop atherosclerosis in their natural habitat, but their lesions are minimal compared with monkeys that consume diets like humans consume in Western societies. Both human and nonhuman primates are variable in their response to dietary cholesterol and subsequent amount of atherosclerosis that develops. Atherogenic diets--high in saturated fatty acids and dietary cholesterol-have reported- ly been associated with myocardial infarction in rhesus monkeys and cynomolgus monkeys (Jokinen, Clarkson, and Prichard 1985). Baboons are apparently relatively resistant to diet-induced hyperlipidemia in compari- son with other nonhuman primates and rabbits (McGill, McMahn. Kruski, Kelley, et al. 1981) but they develop experimental atherosclerosis, which is positively associated with LDL cholesterol concentrations and inversely associated with HDL cholesterol concentrations (McGill, McMahn, Kruski, and Mott 1981). Although much of the diet-induced atherosclerosis in animals has been achieved with extreme diets and is thus not directly applicable to humans, some studies illustrate the effects of more moderate diets. Rhesus monkeys fed diets resembling the typical American diet compared with those fed a "prudent" ration reduced in calories, cholesterol, fat, and saturated fat had much higher cholesterol levels and more frequent and more severe athero- sclerotic lesions. The lesions seen in the animals fed the average American regimen resembled those seen in autopsy examination of the coronary arteries and aorta of young adult Americans (Wissler et al, 1983). Cholester- ol feeding of rhesus monkeys-at levels that do not elevate plasma choles- terol above those achieved on a cholesterol-free diet-may also stimulate atherosclerosis (Armstrong, Megan, and Warner 1974). Regression of diet-induced atherosclerosis by the reduction of serum cho- lesterol to normal levels has been demonstrated in pigs, dogs, fowl, and nonhuman primates (Vesselinovitch and Wissler 1978). Extensive investi- gation of lesion regression has been conducted in rhesus monkeys. Over a dozen studies in at least five centers found that lesions undergo substantial regression on cholesterol lowering regimens (Wissler and Vesselinovitch 1984; Malinow et al. 1983). Rhesus monkeys fed rations containing 25 percent peanut oil and 2 percent cholesterol or 25 percent coconut oil- butter fat and 2 percent cholesterol for 12 to 14 months developed severe 105 O Nutrition and Health hyperlipidemia and aortic and coronary artery atherosclerosis typical of advanced atherosclerosis in humans (Vesselinovitch and Wissler 1978). A subsequent change to a l2- to ICmonth diet in which calories, cholesterol, and fat were reduced to resemble levels recommended by the American Heart Association resulted in a prompt and sustained low serum cholester- ol level and a substantial arrest and reversal of advanced aortic and coro- nary atherosclerosis. Similar evidence of regression was seen when choles- tyramine was added either to the low-fat, low-cholesterol diet or to the atherogenic diet. Regression of atherosclerosis has also been demonstrated in swine. Ad- vanced atherosclerosis was produced by a combination of mechanical injury and a 4-month high-cholesterol, high-fat diet. Fourteen months after the animals were returned to their normal mash diet, significant regression had occurred (Fritz et al. 1976). A new animal model for endogenous hypercholesterolemia has become available through the discovery of a strain of rabbits designated Watanabe heritable hyperlipidemic (WHHL). In these animals,. severe hyper- cholesterolemia results from a single genetic defect, and fulminant athero- sclerosis occurs despite the ingestion of a cholesterol-free diet. The WHHL-rabbit has the same defect in the LDL receptor gene that occurs in persons with familial hypercholesterolemia (Goldstein, Kita, and Brown 1983). Effects of Fatty Acids on Thrombosis Because atherosclerosis is a multifactorial disease, diet may have effects on CHD that are not mediated through plasma cholesterol and lipoprotein levels. Arterial thrombosis is induced by vascular injury and the response of blood platelets. Dietary studies have shown that platelet reactivity is associated with the fatty acid composition of the diet. Epidemiologic studies in France and Great Britain (Renaud 1987) have shown that clotting activity of platelets and their response to thrombin- induced aggregation were more closely related to the intake of saturated fatty acids than to serum cholesterol levels. Intervention studies also show that replacement of dietary saturated fat with polyunsaturated vegetable oils is associated with decreased platelet aggregation and clotting activity (Hornstra 1980; Renaud 1987). In animal studies, most saturated fatty acids were found to induce platelet aggregation and arterial thrombosis and to increase plasma cholesterol levels, whereas unsaturated fatty acids tended -to reduce platelet-aggregation and also tended to lower plasma cholesterol levels. (Goodnight et al. 1982). 104 Coronary Heart Disease O While long-chain saturated fatty acids tend to induce thrombosis in animal studies, long-chain unsaturated dietary fats are either neutral or antithrom- botic. In rats, the most thrombogenic fatty acid is stearic acid (Renaud 1969) despite its apparent neutral effect on serum cholesterol (Keys 1967: Bonanome and Grundy 1988). One study in rats showed that palm oil (containing about 50 percent saturated fat) was similar to polyunsaturated vegetable oils in thrombotic tendency. The reasons for this anomaly are not clear but might be related to some other constituents in palm oil that counteract the thrombogenic properties of the saturated fatty acids (Hornstra and Lussenberg 1975). Oleic acid, the major dietary monoun- saturated fatty acid, seems to have little or no effect on thrombosis (Good- night et al. 1982). The mechanisms by which dietary fatty acids may affect thrombosis are poorly understood but may be related to prostaglandin metabolism (Goodnight et al. 1982). Linoleic acid, the most common dietary polyunsaturated fatty acid, is the precursor of arachidonic acid and prostaglandins that regulate platelet aggregation and, accordingly, thrombogenesis. Prostacyclin (PGI,). for example, has been shown to be the most potent in rli\vo vasodilator and antiaggregatory agent in animals and in humans, and to inhibit white cell adherence to vessel walls, nylon fibers, and endotheliel monolayers in l&-o (Moncada 1982). Its effects are counterbalanced by another prostaglandin, thromboxane A,, a powerful vasoconstrictor and platelet aggregator. It is theorized that arterial thrombosis may depend partly on the ratio between these two prostaglandins. Linoleic acid is also incorporated directly into membrane phospholipids, thereby altering the structure and the function of the platelet membrane. This process affects the fluidity and, therefore, the permeability of the cells and influences processes including thrombus formation. Contrary to ex- pectation, increasing the dietary intake of linoleic acid does not increase the synthesis of arachidonic acid in platelet membranes, perhaps because of competitive inhibition of certain enzymes. Increased dietary intake of linoleic acid, however, has been associated in humans with significant reduction in platelet aggregability (Hornstra et al. 1973: Jakubowski and Ardlie 1978). Fish Oils. The consumption of fish and other marine animals may confer special benefits in reducing CHD mortality (Kromhout, Bosschieter. and Coulander 1985). The fatty acids in these species are rich in long-chain polyunsaturated fatty acids of the omega-3 series. particularly eicosapen- taenoic acid and docosahexaenoic acid. Most polyunsaturated fatty acids commonly found in vegetables belong to the omega-6 series. The differ- 107 O Nutrition and Health ences in chemical structure between omega-3 and omega-6 fatty acids affect several metabolic processes related to blood platelet function, thrombosis, and lipid metabolism that may relate to CHD. Early observations in Greenland suggested that Eskimos who habitually consumed large quantities of fish and other marine animals had a low incidence of CHD despite a high fat and cholesterol intake (Kromann and Green 1980; Dyerberg and Jorgensen 1982). Similar observations have been made in other maritime communities (Kagawa et al. 1982; Yotakis 1981). Subsequent examinations of Greenland Eskimos showed that they have lower serum triglycerides and cholesterol levels and higher HDL levels than Danes consuming a Western-type diet. The blood of Eskimos also takes longer to clot. It has been hypothesized that the low incidence of atherosclerosis and thrombosis in Greenland Eskimos is partly attributable to the high proportion of omega-3 fatty acids in traditional Eskimo diets (Dyerberg and Jorgensen 1982). A recent prospective study of Dutch men showed that 20-year mortality from CHD was reduced by 50 percent in men who consumed at least 1 oz of fish per day (Kromhout, Bosschieter, and Coulander 1985). Whether the benefit shown in this study can be attributed to omega-3 fatty acid intake or to some other factor associated with fish consumption is uncertain. Men who consumed low-fat fish derived the same benefit as those consuming higher fat varieties. The effect of fish consumption on CHD mortality has been examined in other large prospective studies. One found no relation- ship (Vollset, Heuch, and Bjelke 1985). In another, fish consumption at entry into the study was inversely associated with 25year risk of CHD (Shekelle et al. 1985), and in the third study, CHD death rate was higher in the group that consumed no fish compared with the group that consumed fish (Curb and Reed 1985). Early clinical experiments in which different sources of fat were given showed that fish oils were at least as effective as polyunsaturated vegetable oils in reducing serum cholesterol levels. More recently, fish oils have been studied in relation to their effects on lipoprotein metabolism and other CHD parameters. Clinical studies in normal volunteers and patients with hypertriglycetidemia who were fed diets enriched in omega-3 fatty acids generally showed variable reductions in total cholesterol and LDL choles- terol. In some cases, LDL increased; HDL levels were either unchanged or increased (Phillipson et al. 1985; von Lossonczy et al. 1978). The most consistent and striking effect of fish oil on lipoprotein metabolism has been a reduction in triglyceride and VLDL levels, an effect not observed with vegetable oils (von Lossonczy et al. 1978; Saynor, Verol, and Gillott 1984; Harris and Connor 1980; Nestel et al. 1984). 108 Coronary Heart Disease O Most experimental studies have used rather large amounts of fish (200 to 300 g/day) or fish oil (more than 20 g/day). One study sought to determine the effects of more moderate fatty fish consumption. One hundred male volunteers each consumed 3 oz or more of fatty fish at least twice a week for 3 months and little or no fatty fish for another 3 months. Mean plasma triglyceride concentration decreased significantly, by nearly 7 percent, on the fish diet. There were no significant changes in plasma total cholesterol, HDL, or LDL (Fehily et al. 1983). Another line of investigation involves studies on the effects of fish oils on the vessel wall. A (i-week study in seven healthy men indicated that diets supplemented with 18 g of fish oil per day may have anti-inflammatory properties that could diminish infiltration of lipids in the vessel wall in response to tissue injury (Lee et al. 1985). In another study, the effect of cod liver oil on the development and progres- sion of atherosclerosis in a hyperlipidemic swine model was assessed. All animals were fed an atherogenic diet, 7 were given a cod liver oil supple- ment, and 11 controls did not receive the supplement. Significantly less disease was seen in coronary arteries from the animals fed cod liver oil despite severe hyperlipidemia. Differences in the extent of coronary ath- erosclerosis were not related to differences in plasma lipid levels. Pros- taglandin synthesis from arachidonic acid was markedly reduced in the oil- fed group (Weiner et al. 1986). Role of Other Dietary Factors in CHD Obesity Obesity is associated with many important CHD risk factors such as hypertension, low levels of HDL, elevated plasma glucose levels, high blood cholesterol, and hypertriglyceridemia (see chapter on obesity) and hence increases the risk for CHD. Data from the Framingham Heart Study, in which 5,209 men and women were observed for 26 years for the develop- ment of CHD, showed that relative weight was a significant independent long-term predictor of CHD incidence, especially in women (Hubert et al. 1983). The association of weight with CHD incidence was most pronounced in those under age 50. Weight gain in adulthood conveyed an added risk. Total calorie consumption has been associated with CHD prevalence in international comparisons. However, studies within populations have shown that a greater caloric intake is associated with a reduced risk for CHD, but increased body weight is associated with increased CHD risk. This suggests that increased energy expenditure, which would tend to increase caloric requirements, may be related to reduced risk for CHD 109 O Nutrition and Health (Gordon et al. 1981). Current evidence suggests that leanness and avoid- ance of weight gain before middle age are advisable goals in the prevention of CHD for most men and women (Hubert et al. 1983; Bray 1983). In addition, weight loss often improves the status of other risk factors such as diabetes and high blood pressure (see respective chapters). Alcohol The relationship between alcohol consumption and CHD is complex (Hulley and Dzvonik 1984). High alcohol intake has been associated with CHD deaths, as well as deaths from other causes (see chapter on alcohol), but some epidemiologic studies have shown an association between light to moderate alcohol intake and a decreased incidence of CHD (LaPorte, Cresanta, and Kuller 1980). In these studies, light intake is generally considered to be more than one drink per month but fewer than one per day and moderate intake is 1 to 3 oz per day. Numerous cross-sectional studies have shown positive correlations of alcohol intake with HDL cholesterol levels (Castelli et al. 1977), with the response related to doses of alcohol ranging from 0 to 3 oz per day (Ernst et al. 1980; Haskell, Camargo, and Williams 1984). Thus, it has been postulated that the decreased incidence of CHD in those who consume moderate amounts of alcohol might be attrib- utable to an ethanol-induced increase in HDL cholesterol levels. Recent reports suggest, however, that moderate alcohol consumption induces compositional changes in HDL that are inconsistent with current under- standing of the anti-atherogenic properties of HDL subfractions, because it increases HDL-3 levels but not those of the antiatherogenic HDL-2 sub- fractions (Haskell, Camargo, and Williams 1984). The significance of alco- hol-induced changes in apoprotein fractions (Camargo et al. 1985) is also uncertain. Since heavy drinking has numerous adverse effects, including several on the cardiovascular system (Burch and Giles 1971), the use of alcohol, even in moderate quantities, for its possible beneficial effects on CHD is not recommended. Carbohydrate Major dietary carbohydrates include starch, fiber, and sugars. Customary diets containing 60 to 70 percent of calories from starch, such as those consumed in Asian countries, are associated with low plasma cholesterol levels and a low risk for CHD (Keys 1970). Such diets tend to be relatively high in fiber and very low in fat and thus have been widely advocated for the treatment of hypercholisterolemia. Epidemiologic studies cited previously have shown that intake of starch (Gordon et al. 1981) and intake of fiber (Kushi et al. 1985) were negatively related to CHD. Furthermore, the effect of starch did not appear to be an indirect effect of lowered fat intake. On the 110 Coronary Heart Disease O other hand, total carbohydrate was inversely associated with HDL choles- terol-and positively associated with LDL cholesterol-in cross-sectional studies, but these correlations were very weak (U.S.-U.S.S.R. Steering Committee 1984). Some experimental studies have shown that hyper- triglyceridemia can be induced with high-starch (70 percent of calories) diets, but the effect is temporary and appears to occur mainly after chang- ing from a high-fat to a high-carbohydrate diet (Little, McGuire. and Derksen 1979; Ahrens 1986). The water-soluble fiber fractions, as found in oat bran. guar gum, psyllium seeds, certain beans, and pectin, for example, have been shown to have hypocholesterolemic effects in humans (Jenkins et al. 1975: Kirby et al. 1981; Anderson et al. 1984). Addition of fiber to high-carbohydrate diets has been reported to prevent triglyceride elevation on high-carbohydrate diets (Anderson, Chen, and Sieling 1980). A high fiber intake is often associated with low-fat diets, and the net effect may provide additional benefits in cholesterol reduction. The role of sugars in CHD is unclear. A high sucrose intake has been claimed to play a causal role in CHD (Yudkin and Roddy 1964). but there is little evidence to sustain this view. Although some animal studies have suggested that substitution of sucrose for other sources of calories in- creases atherogenesis, the major epidemiologic studies of diet and CHD risk have failed to identify an association with sucrose intake (Glinsmann, Irausquin, and park 1986). Sucrose and fructose have been shown experi- mentally to promote hypertriglyceridemia in susceptible (carbohydrate- sensitive) individuals. Men appear to be more susceptible than pre- menopausal women, older persons more than younger persons, and hyper- triglyceridemic persons more than normal triglyceridemic persons (Reiser et al. 1981; Coulston et al. 1987). Recommended treatment for patients with elevated plasma triglyceride and VLDL levels includes weight control, alcohol restriction, increased physical activity, and restriction of saturated fat and cholesterol. Substitution of carbohydrate for fat is favored; al- though increasing dietary carbohydrate may raise triglycerides, the re- sponse is usually transient and triglyceride levels (and VLDL) later decline (NIH 1983). Protein In animals, high protein levels accelerate the formation of atheromatous lesions. Casein appears to be more atherogenic than soy protein (Kritchev- sky 1979). Recent studies on rabbits showed that LDL receptors were suppressed after feeding a cholesterol-free diet composed of carbohydrate and casein (Goldstein, Kita, and Brown 1983). The low levels of plasma 111 O Nutrition and Health cholesterol observed among strictly vegetarian populations (West and Hayes 1%8) may be attributable to the quantity and quality of protein. However, their diets also tend to be lower in saturated fat and cholesterol and higher in complex carbohydrate and fiber than diets of lacto-ovo vegetarian or nonvegetarian groups (Sacks et al. 1985; Sacks et al. 1975; Burslem et al. 1978). Studies involving the substitution of soy protein and other vegetable proteins for animal protein in the diets of hyperlipidemic patients have shown a marked reduction in serum cholesterol levels (Des- covich et al. 1980; Sirtori, Gatti, and Mantero 1979) but only a small change in persons with normal plasma cholesterol levels (Forsythe, Green, and Anderson 1986). The mechanism for these effects has not been established. coffee Evidence relating coffee consumption to increases in serum total and LDL cholesterol levels or to CHD has been inconsistent. Recent reports from cross-sectional epidemiologic studies in Norway, Israel, and the United States have shown an independent, positive, linear association with serum cholesterol, nearly all of which can be accounted for by LDL cholesterol (Thelle, Amesen, and Forde 1983; Kark et al. 1985; Williams et al. 1985). One study associates coffee drinking (five or more cups per day) with increased risk for CHD (LaCroix et al. 1986). The effect of coffee drinking on serum cholesterol has also been examined in controlled experiments. Coffee taken in amounts of six cups or more per day has been reported to increase serum cholesterol levels (Arnesen, Forde, and Thelle 1984). De- caffeinated coffee has also been reported to be associated with such eleva- tions in some studies (Naismith et al. 1970), although not all (Mathias et al. 1985); in most studies, tea did not affect blood cholesterol levels (Frineas et al. 1980; Little et al. 1%6; Kark et al. 1985). Such findings would appear to rule out caffeine as a causal factor (Klatsky et al. 1985). Other studies have found no association between coffee and cholesterol (Kovar, Fulwood, and Feinleib 1983) or different effects in men and women (Shirlow and Mathers 1983). Inconsistencies in the results of different studies have been attribut- ed to confounding effects of cigarette smoking and diet as well as to variations in method of preparation. At present, the information regarding the relationship between coffee intake and blood cholesterol levels is insufflcient to allow conclusions to be drawn. Vitamins and Minerals The relationship of micronutrients (vitamins and minerals) to cardiovascu- lar disease risk has been studied to a much lesser extent than the macronu- trients. except in the case of sodium and hypertension (see chapter on high blood pressure). Although dietary patterns that promote high plasma cho- 112 Coronary Heart Disease 0 lesterol levels would be expected to be different in micronutrient content from dietary patterns associated with low plasma cholesterol levels, there is at present no strong evidence linking vitamin and mineral intake to high plasma cholesterol levels or to CHD. Virumin E. Vitamin E was once widely advocated for prevention and treatment of CHD (Shute and Taub 1972). Early studies supporting these claims were marred by lack of controls and doubtful diagnosis of CHD, and subsequent studies have failed to confirm them (Hodges 1979). Vitumin C. Vitamin C (ascorbic acid) deficiency results in scurvy, which is sometimes associated with cardiac abnormalities. Observations that high doses of ascorbic acid reduce serum cholesterol in cholesterol-fed rabbits and guinea pigs have led to the idea that high doses of vitamin C might reduce blood cholesterol levels in patients with elevated levels. To date, uncontrolled clinical trials have yielded conflicting results. and there is no convincing evidence that vitamin C is related to CHD (Hodges 1979; Anonymous 1984). Thiumin. Thiamin deficiency leads to beriberi, and congestive heart failure is associated with the "wet" form of this disease. Cardiac impairment is generally completely reversible with appropriate administration of thiamin. Thiamin deficiency is uncommon in the United States today, largely be- cause of effective food enrichment programs. Nevertheless, inadequate intakes are sometimes observed among persons with faulty dietary pat- terns or among hospitalized patients who have been ill for prolonged periods (Hodges 1979). Niacin. Niacin (nicotinic acid) in pharmacologic (large) doses far in excess of its requirements for vitamin function exerts HDL-raising and lipid- lowering effects, principally in the VLDL fraction (Fredrickson and Levy 1972). The long-term followup of patients treated with niacin in the Coro- nary Drug Project (as mentioned in the section on Effkacy of Dietary Interventions in CHD) showed significant reduction in coronary and total mortality. In a recent study, nicotinic acid in combination with colestipol and a cholesterol-lowering diet slowed progression of coronary artery lesions in men who had undergone coronary bypass surgery (Blankenhom et al. 1987). There is no evidence, however, that niacin ingested at phys- iologic levels exerts any protective effect against factors that elevate blood lipid levels. Calcium. High serum cholesterol levels have been observed in calcium- deficient rats. and calcium-deficient rabbits and rats fed an atherogenic diet 113 0 Nutrition and Health significantly increased their serum cholesterol and triglyceride levels over control animals fed a stock ration. Supplementation of experimental diets with calcium reduced the plasma lipid levels to near or below the levels of the control group but also was associated with increased incidence of kidney and heart lesions (Mertz 1979). In humans, an uncontrolled study of 10 hyperlipidemic subjects showed that the addition of 800 mg of calcium (as calcium carbonate) daily over 1 year reduced blood cholesterol levels by 25 percent, and another uncontrolled study in older women showed that 750 mg of daily calcium supplementation reduced cholesterol levels 36 mg/ dl from a mean 266 mg/dl (Mertz 1979). Such observations remain to be confirmed by controlled clinical trials. The possible role of calcium con- tinues to be a subject of investigation (Renaud 1987). Magnesium. Magnesium therapy may correct some cardiac arrhythmias, although it is uncertain whether magnesium deficiency causes them (Laban and Chorbon 1986). Magnesium and calcium may interact with dietary fat in the promotion of atherosclerotic lesions. In animals, the increased incidence of kidney and heart lesions associated with very high intake of calcium is reduced or eliminated by high levels of dietary magnesium. This protective effect, however, was evident only at very high dietary calcium levels (0.6 percent by weight) and only in the presence of elevated serum cholesterol (Mertz 1979). Copper. Copper deficiency has been associated with cardiovascular dam- age and abnormalities in cholesterol metabolism in animals. In one human study, copper deficiency was shown to produce a rise in plasma cholesterol concentrations, perhaps because copper is a cofactor for enzymes involved in cholesterol synthesis and lipoprotein degradation (Klevay et al. 1984). Zinc. Because dietary zinc increases the copper requirement (Sandstead et al. 1982) it has been postulated that a high ratio of zinc to copper in the modem American diet could be a risk factor for CHD (Klevay 1975). Long- term zinc supplementation in children, however, has not been associated with any detectable rise in plasma cholesterol levels (Mertz 1979). Al- though administration of high-dose zinc supplements has been reported to reduce blood levels of HDL cholesterol in human subjects (Hooper et al. 1980) more physiologic doses had no effect on blood lipid values (Crouse et al. 1984). Selenium. In China, very low levels of dietary selenium have been associ- ated with juvenile cardiomyopathy (Chen et al. 1980). Although a causal role has not been firmly established, epidemiologic studies have also suggested a role for selenium deficiency in CHD. Cardiovascular disease 114 Coronary Heart Disease cl mortality rates are significantly lower in areas of the United States with high selenium soils. In Sweden, the lowest death rate from cardiovascular diseases was reported in the city of Malmo, which has a higher selenium content of tap water than Stockholm or Gothenburg. Other studies. how- ever, have failed to demonstrate any differences in selenium concentrations in serum and urine of patients with hypertension or in the coronary arteries of persons who died from myocardial infarction and atherosclerosis as compared with control groups (Thomson and Robinson 1980). Human platelets contain more selenium than other human tissues. suggest- ing that selenium deficiency may affect thrombosis. Experimental se- lenium deficiency reduces platelet antioxidant activity, and this activity is restored by selenium supplementation (Levander 1982). A low serum selenium concentration has been associated with increased clinical manifestations of CHD in a prospective study in Finland (Salonen et al. 1982), yet a subsequent longitudinal case control study in another Finnish population showed that levels of selenium in blood were highly correlated to blood levels of eicosapentaenoic acid. Because fish is a major source of selenium in the Finnish diet, it is difficult to distinguish the antiatherogenic effects of selenium from those of polyunsaturated fatty acids in these studies (Miettinen et al. 1983). Efficacy of Dietary Intervention in CHD Clinical studies in free-living populations over long periods of time have been conducted to determine the potential of dietary change,to influence blood cholesterol and CHD. In general, large-scale diet studies have achieved 10 to 15 percent blood cholesterol reductions (Rifkind et al. 1983), compared with about 25 percent in controlled metabolic ward studies, probably because of less rigorous adherence to the diet. For example, the National Diet-Heart Study, in which the experimental diets contained either 30 percent fat with 15 percent polyunsaturated fatty acids or 40 percent fat with 18 to 20 percent polyunsaturated fatty acids, showed that reductions in serum cholesterol were proportional to the degree of ad- herence to the diets and that excellent adherence produced an average serum cholesterol reduction of about 13 percent in free-living adults (Na- tional Diet-Heart Research Group 1968). The Oslo Study achieved 13 to 15 percent reductions (Hjermann et al. 1981). The Multiple Risk Factor Intervention Trial (MRFIT) was a randomized primary prevention trial to test the effect of a multifactor intervention program on CHD mortality in 12.866 men in the upper 10 percent of risk on 115 O Nutrition and Health account of their levels of cigarette smoking, blood cholesterol, and blood pressure. It resulted in a 5 percent reduction in blood cholesterol in the special care (diet and other intervention) group and 3 percent in the usual care group, suggesting that many people were making changes in their diets even in the absence of direct intervention (MRFIT Research Group 1982). The results of this study were further complicated because of the cholester- ol raising effect of diuretics in the hypertensive group and because the men who stopped smoking were less successful in weight control than the men who continued to smoke. Greater reductions in cholesterol were achieved among MRFIT men with elevated cholesterol who were nonhypertensive and nonsmokers over the 6-year intervention trial (Dolecek et al. 1986). The impact of dietary-induced cholesterol lowering on CHD incidence has also been assessed in several other clinical trials. They have generally reported some reduction in CHD incidence and, taken together, have shown a consistent relationship between degree of cholesterol lowering and CHD risk reduction (Mann and Marr 1981). However, the ability to draw definite conclusions from such trials is made difftcult by problems such as small sample size, failure to randomize subjects into treatment and control groups, failure to mask treatment assignment (a pervasive and essentially insoluble problem in all large-scale diet studies), and inadequate followup (Cornfield and Mitchell 1%9), as well as the type of problems cited above in the MRFIT. The Finnish Mental Hospital Study was a trial conducted in two hospitals, one of which replaced whole milk and butter with a skim milk emulsion containing soy oil and a high polyunsaturated margarine while the other retained the usual diet. After 6 years, the diets were reversed, and the study continued an additional 6 years. The study involved the total hospital population in each site and encompassed 29,217 person-years of experi- ence. Results showed that mean serum cholesterol values were reduced 12 to 18 percent and that death rates from all cardiovascular diseases for men and women were 39 percent and 14 percent lower, respectively, on the experimental diet. All-cause mortality for men was 12 percent lower on the experimental diet, but for women it was similar on both diets (Miettinen et al. 1972). The authors attribute the findings in women to an exceptionally low death rate experienced in one hospital during the control period follow- ing transfer of chronic cases to another hospital. The dietary trial conducted in a Veterans Administration domiciliary facility in Los Angeles used a double-blind experimental design in which 846 middle-aged and older male participants were randomly assigned to either a control or a cholesterol-lowering diet group. Although the results 116 Coronary Heart Disease 0 suggested that a diet low in saturated fats and cholesterol and high in polyunsaturated fats reduced coronary events, the experimental and con- trol groups did not differ in overall mortality (Dayton et al. 1969). The excessive mortality rate from cancer observed at first in the intervention group has been reinterpreted, and subsequent analysis of the data and those of four similar trials has found no association of cholesterol-lowering diets with any increase in either cancer incidence or mortality rate (Ederer et al. 1971). The Oslo Study was a primary prevention trial designed to test whether lowering serum lipids by dietary measures and smoking reduction would reduce incidence of new CHD in 1,232 high-risk participants studied over 5 years. The dietary intervention consisted of advice to substitute polyun- saturated fats for saturated fat, to increase intake of whole grain cereals, and to reduce energy intake (in cases of elevated triglyceride levels). At the completion of the trial, mean serum cholesterol levels were reduced 13 percent in the intervention group, and the combined incidence of myocar- dial infarction and sudden death was significantly reduced in the treated group by 47 percent compared with controls. Statistical analysis identified the predominant effect as the decrease in plasma total cholesterol by diet (Hjermann et al. 1981). It is widely accepted that diet is a major cause of high blood cholesterol and high LDL levels and that these play a causal role in atherosclerosis. Evidence from animal-experimental studies has shown that reducing diet- induced hypercholesterolemia, whether by diet or other means, reverses the atherosclerotic process. The consistency of these studies supports the conclusion that blood cholesterol lowering per se rather than a specific action of the cholesterol-lowering agent produces the benefit. Hence, consideration of evidence from the clinical trials using drugs to lower cholesterol is relevant to assessment of the efficacy of dietary intervention to lower CHD risk. The Coronary Drug Project assessed the long-term efficacy of live lipid- influencing drugs in 8,341 middle-aged men. Treatment with niacin signifi- cantly decreased nonfatal recurrent myocardial infarction but not coronary mortality during the treatment phase of the study (Canner et al. 1986). However, followup at 9 years beyond the study demonstrated that total mortality was reduced in the niacin-treated group. The Lipid Research Clinics Coronary Primary Prevention Trial (LRC- CPPT) was a double-blind placebo-controlled clinical trial in high-risk middle-aged men to test the efficacy of lowering cholesterol levels for the 117 O Nutrition and Health primary prevention of CHD. The LRC recruited 3,806 men with primary hypercholesterolemia, free of symptomatic CHD at entry, but at high risk for CHD due to elevated LDL cholesterol levels. The study participants were randomly assigned to two groups that were similar in baseline charac- teristics. The treatment group received the bile acid sequestrant cholesty- ramine, and the control group received a matched placebo. Although the LRC-CPPT was not designed as a dietary intervention trial, both groups followed a diet plan calculated to achieve a 3 to 5 percent reduction in plasma cholesterol. A net reduction in plasma cholesterol of 9 percent in the treatment group resulted in a 19 percent reduction in fatal and nonfatal myocardial infarctions. Corresponding reductions in angina pectoris, elec- trocardiographic abnormalities, and bypass surgery were also found in the treatment group (Lipid Research Clinics Program 1984a, 1984b). The Helsinki Heart Study reported substantial benefit in reducing the incidence of CHD by drugs (Frick et al. 1987). The study was a randomized double-blind placebo-controlled primary prevention trial involving 4,081 middle-aged men in a j-year followup. To qualify, participants had to have LDL plus VLDL cholesterol concentrations equal to or greater than 200 mg/dl. Treatment with gemfibrozil resulted in several changes in plasma lipids: modest (8 percent) reductions in total and LDL cholesterol, a more pronounced (34 percent) decrease in triglycerides, and a moderate (greater than 10 percent) increase in HDL cholesterol. At the end of 5 years, nonfatal myocardial infarction alone was reduced by 37 percent and CHD mortality alone by 26 percent. These results were obtained despite an incidence of CHD in the placebo group that was considerably lower than expected. Total mortality, however, was not significantly affected. Another approach to assessing benefit of cholesterol lowering is to measure changes in atherosclerotic lesions. Early studies in nonhuman primates demonstrated regression of atherosclerotic lesions with cholesterol-lower- ing diets or with drugs (Armstrong, Warner, and Connor 1970; Wissler and Vesselinovitch 1984). The effect of cholesterol lowering on coronary ar- teries can now be assessed with serial angiograms in humans. In the Leiden Study, 39 men with stable angina pectoris and advanced arteriosclerosis, as assessed by coronary angiography, were prescribed a vegetarian diet containing a polyunsaturated-to-saturated-fatty-acid ratio of 2, and dietary cholesterol of less than 100 mg/day. Mean serum cholester- ol decreased IO percent from a baseline value of 267 mg/dl. Since there was no control group, the effect of dietary intervention could not be assessed directly. However, angiographic examination performed after 24 months showed no progression of disease in the group that had maintained lower 118 Coronary Heart Disease 0 values for the ratio of total cholesterol to HDL cholesterol throughout the trial or who significantly lowered their ratio of total cholesterol to HDL cholesterol (Amtzenius et al. 1985). Another double-blind placebo-controlled trial, the NHLBI Type II Coro- nary Zntervention Study, evaluated the efficacy of reduction in cholesterol levels induced by cholestyramine on progression of coronary artery dis- ease. The rate of progression, defined angiographically, was compared in patients treated with cholestyramine plus diet with that of patients treated with placebo plus diet. When the relationship between coronary artery disease progression and lipid changes was examined independent of a specific treatment group, a significant inverse relationship was found be- tween progression at 5 years and the combination of an increase in HDL and a decrease in LDL. These trends were observed in both the placebo- treated and the cholestyramine-treated group (Levy et al. 1984). The Cholesterol-Lowering Atherosclerosis Study (CLAS) was a random- ized placebo-controlled angiographic investigation of the ability of drugs (colestipol and niacin) and diet to reduce blood cholesterol levels and to cause regression of atherosclerosis in the coronary arteries. Participants were 162 men who had undergone coronary bypass surgery. The study reported 26 and 43 percent reductions in total blood cholesterol and LDL, respectively, in the treatment plus diet group compared with 4 and 5 percent reductions, respectively, in the placebo plus diet group. There was also a considerable increase in HDL and considerable decrease in triglycer- ides in the drug plus diet group. These changes were associated with significantly less progression of overall coronary disease in both the grafts and the native coronary arteries with some suggestive evidence of regres- sion (Blankenhom et al. 1987). Despite some deficiencies in definition of lesions, control groups, and small numbers of patients, these coronary angiographic studies support the benefit of intervening with blood cholesterol reduction in the presence of established disease. Aggregate Analysis of Clinical Trials of Blood Cholesterol Lowering Many of the clinical trials of blood cholesterol lowering to prevent CHD have been hampered by small numbers and modest cholesterol lowering (Mann and Marr 1981; Oliver 1985). However, additional information has been obtained by evaluating them in aggregate. Joint analysis of dietary trials has shown a linear relationship of cholesterol lowering to risk reduction, with a 1 to 1.5 percent reduction in relative risk 119 13 Nutrition and Health found for each 1 percent reduction in blood cholesterol (Hulley et al. 1981: Mann and Marr 1981). When the various drug studies are analyzed, the results are almost comparable, with a 2 percent reduction in risk resulting from a I percent reduction in cholesterol (Lipid Research Clinics Program 1984b). This relationship is close to that predicted from the results of prospective epidemiologic studies such as the Framingham study. In the Helsinki Heart Study, a greater effect was observed: An 8 percent reduction in total cholesterol resulted in a 34 percent reduction in CHD incidence. This suggests that the moderate increase in HDL cholesterol and marked fall in triglycerides might also have contributed to the benefit (Frick et al. 1987). Taken together, these clinical trials provide compelling evidence that lower- ing plasma cholesterol reduces CHD morbidity and mortality. However, the total mortality has generally not been reduced in these studies. A small increase in noncardiovascular deaths was observed in the Los Angeles Veterans Administration Trial, the Helsinki Mental Hospital Study, the WHO Clotibrate Trial, the LRC-CPPT (Oliver 1981; Lipid Research Clinics Program 1984a), and the Helsinki Heart Study (Frick et al. 1987). There is a lack of consistency in the various noncardiovascular causes of death in these studies; in some studies, more cancers have occurred, while in others, more accidental or violent deaths. In the drug trials, some of the observed mortality from various noncoronary causes may have been spe- cific to the drug itself. One study has reported a significant reduction in total mortality. In the Coronary Drug Project, total mortality in the niacin- treated group was 11 percent lower than in the placebo group, a benefit that became evident during a 9-year followup after termination of the trial (Canner et al. 1986). This raises the possibility that the effect of cholesterol lowering on mortality takes longer to emerge than its impact on nonfatal heart attacks. The difficulties in showing an effect on total mortality may reflect the problem that no clinical trial to date has had a sample size sufficiently large to address this issue with adequate statistical power. Implications for Public Health Policy Dietary Guidance General Public High blood cholesterol is one of the three major modifiable risk factors for CHD. The principal nutritional factors identified with high blood cholester- ol and the development of CHD are dietary fat, particularly saturated fatty 120 Coronary Heart Disease O acids and cholesterol, and energy imbalance leading to obesity. Other dietary constituents, such as fiber or alcohol, may interact with these factors in ways that are not clearly understood. The relationship of dietary fat and cholesterol to CHD is supported by extensive and consistent clinical, epidemiologic, metabolic, and animal evidence. These studies strongly indicate that the formation of atheroscle- rotic lesions in coronary arteries-contributing to the risk for CHD-is increased in proportion to levels of total and LDL cholesterol in blood, which, in turn, are increased by diets high in total and saturated fat but decreased by diets containing polyunsaturated and/or monounsaturated fat. International epidemiologic comparisons and migration studies have revealed strong associations of fat, especially saturated fat, intake to development of elevated blood cholesterol levels, atherosclerosis, and CHD. Evidence from studies within a given population has been less consistent but points in a similar direction. Dietary intervention trials in men with elevated blood cholesterol levels have demonstrated small but significant proportionate improvements such that each 1 percent reduction in total blood cholesterol is accompanied by about a 1.5 percent reduction in heart disease risk. Intervention to lower elevated blood cholesterol levels has been shown in both human and animal studies to reduce CHD risk and to slow lesion progression. Animal studies have shown lesion regression, and there is suggestive evidence from some clinical studies that this also occurs in humans. Taken together, these studies provide strong support for recommendations for an overall considerable decrease in dietary fat intake by the general public from the present level of 37 percent of total caloric intake and decrease in saturated fat from the present level of about 13 percent of total caloric intake. Although the effect of dietary cholesterol on blood cholesterol is somewhat weaker and more variable among individuals than that for dietary saturated fatty acids, a reduction in the amount of cholesterol consumed by the general public from present average levels of approximately 305 mg/day for women and 440 mg/day for men seems appropriate. Obesity is associated with such CHD risk factors as elevated LDL and total blood cholesterol, lower HDL cholesterol, high blood pressure, and di- abetes melhtus. It is also a significant independent predictor of CHD, especially in women and in persons under age 50. Thus, current evidence suggests that an overall decrease in the prevalence and severity of over- weight in the population, through both a decrease in caloric intake and an Ll Nutrition and Health increase in caloric expenditure, is advisable on the basis of the relationship of obesity to heart disease risk. Studies of animal protein, coffee, and sugar have shown variable associa- tions with increased blood lipid levels, but present evidence of their rela- tionship to CHD, if any, is too weak and insufficient to draw implications for changes in the consumption of these substances. Likewise, evidence from some studies that certain components of dietary fiber and omega-3 fatty acids from fish oils reduce blood cholesterol levels and heart disease risk is too preliminary to recommend changes in average intake of these substances. In addition, advice concerning vitamin and mineral supple- ments on the basis of their relationship to CHD is unwarranted. Special Populations There is a need to identify those individuals with high cholesterol levels, who are therefore at greatest risk. For individuals whose high total and LDL cholesterol levels warrant treatment, the first line of intervention is diet therapy. The recently released National Cholesterol Education Pro- gram guidelines on the treatment of high blood cholesterol in adults recom- mend that intensive dietary treatment should generally be carried out for at least 6 months. As indicated in this Report, only after that period of time, and if the cholesterol level remains significantly high, should the addition of drugs to the dietary regimen be considered. Even then, continuation of diet therapy can reduce the need for drugs and thus their risk of side effects and cost. Furthermore, studies in persons with CHD suggest that diets low in fat, saturated fat, and cholesterol can retard the progression of the disease, including recurrent heart attacks, and perhaps induce regression of atherosclerotic lesions. Persons with such high blood cholesterol levels should receive dietary guidance by qualified health professionals. Adults with total cholesterol levels of 240 mg/dl or above (whose LDL cholesterol levels are also significantly elevated), and those with total cholesterol levels of 200 to 239 mg/dl with CHD or two or more CHD risk factors should begin a program of supervised dietary treatment. The NCEP guidelines recommend starting dietary therapy with a step-one diet, in which the intake of total fat is less than 30 percent of calories, saturated fat is less than 10 percent of calories, and cholesterol is less than 300 mg/day. If after 3 months on this diet cholesterol lowering is insufficient, the person should progress to a step-two diet, in which saturated fat is further reduced to less than 7 percent of total calories and cholesterol intake is further reduced to less than 200 mg/day. 122 Coronary Heart Disease 0 Although in epidemiologic studies light to moderate alcohol consumption is associated with reduced heart disease risk, a cause-and-effect relationship has not been proved. Since heavy drinking has numerous adverse health consequences (see chapters on maternal and child nutrition and on alco- hol), including several on the cardiovascular system, the use. even in moderate quantities, of alcohol for its possible beneficial effects on CHD is not recommended. Nutrition Programs and Services Food I .abels Evidence related to the role of dietary factors in CHD supports the need for manufacturers to increase the number of food labels with their total fat, fatty acids, and cholesterol content. Food Services Evidence related to the role of dietary factors in CHD suggests that the public would benefit from increased availability of foods low in fat, saturat- ed fat, and cholesterol in food service programs. The need is critical for the one in four persons with cholesterol levels that put them at appreciably high risk for CHD. Food Products Evidence related to the role of dietary factors in CHD suggests that food manufacturers should increase availability of foods and food products that are low in fat, saturated fat, and cholesterol. Special Populations Persons with high blood cholesterol and their food preparers should be given access to counseling by qualified health professionals and assistance in the development of diets low in fat, saturated fat, and cholesterol as well as in the appropriate balance of caloric intake and expenditure. Education and training opportunities for health professionals should be expanded to meet this need. Research and Suweillance Research and surveillance issues of special priority related to the role of diet in CHD should include investigations into: 123 0 Nutrition and Health o The identification and management of individuals with high blood cholesterol in the general population. o The most effective educational and dietary intervention strategies to reduce blood lipid levels and heart disease risk. o Improved methods for assessing American dietary patterns in relation to CHD risk. o Refinement of current dietary recommendations, including evaluation of other potentially efficacious dietary regimens, evaluation of dietary fiber, and optimal intakes of omega-3 and omega-6 fatty acids to prevent CHD. o The mechanisms by which alterations in dietary fatty acids affect atherogenesis and the risk for CHD, including degree of saturation, chain length, and fatty acid series. o Clarification of the role of dietary cholesterol in atherogenesis, includ- ing variability in response, effects on cholesterol metabolism in both fasting and postprandial states, and interactions of postprandial lipoproteins and lipoprotein remnants with cells of the arterial wall. 124 Coronary Heart Disease 0 Literature Cited AAP See American Academy of Pediatrics. .AHA. 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Mortality. American Journal dEpidemio/ogy 102:481-90. Yotakis, L.D.O. 1981. The preventive effect of the polyunsaturated fats on thrombosis [abstract]. Thrombosis and Haemostasis 46~65. Yudkin, J., and Roddy, J. 1964. Levels of dietary sucrose in patients with coronary atheroscle- rotic disease. L.ancet ii6-8. 137 Chapter 3 High Blood Pressure Hence if too much salt is used in food. the pulse hardens. Huang Ti (the Yellow Emperor, 2697-2597 B.C.) The Yellow Emperor's Classic of Internal Medicine Introduction Hypertension, the medical name for high blood pressure, is a common chronid medical problem in the United States responsible for a major portion of cardiovascular disease. In recent years. public health efforts have increased public awareness and knowledge of the risks and appropri- ate treatment of this condition. As a result, almost the entire adult U.S. population has had at least one blood pressure measurement and 73 percent of Americans have had their blood pressure checked within the previous 6 months. By 1985,77 percent of the public identified high blood pressure as the factor that most increases a person's chances of having a stroke, and 91 percent indicated that high blood pressure increases a persons chances of getting heart disease (Lenfant 1987). The proportion of hypertensive per- sons who have their high blood pressure under control more than doubled from the early 1970's to 1980 (Subcommittee 1985). The significant de- crease in cardiovascular disease deaths and disability that has occurred since the 1970's is believed by many experts to be due to the increased detection and treatment of high blood pressure. This success in the control of hypertension is generally credited to a combination of improved detection and the use of antihypertensive medi- cation. However, the implications of long-term drug therapy for millions of Americans are unknown. There are documented side effects of the anti- hypertensive drugs. Thiazide diuretics, for example, can induce short-term increases in serum cholesterol, low density lipoproteins (LDL), and tri- glyceride levels in some persons. Some studies suggest that these effects 139 O Nutrition and Health decrease or disappear with long-term therapy, although some clinical trials have shown persistence of the adverse effects (JNC IV 1988). Beta-block- ers tend to lower high density lipoprotein (HDL) levels. These and other risks of drug therapy call attention to the potential benefits of nonphar- maceutical treatment of high blood pressure (Kaplan 1985). Currently, three nondrug methods-weight control, alcohol restriction, and sodium restriction-are recommended as part of the treatment for established hypertension (JNC IV 1988). These measures have also gained support as likely to aid in the prevention of high blood pressure, particu- larly for those at high risk. Historical Perspective The first successful dietary treatment of human hypertension has been attributed to Kempner's rice-fruit diet that provided 20 g of protein, less than 5 g of fat, 150 mg of sodium, 200 mg of chloride, and 3,000 mg of potassium per day (Kempner 1944). Other studies confirmed that a very low sodium intake, for example, 200 mg/day, was effective in lowering blood pressure, although the effect on blood pressure of a moderate sodium intake, for example, 2,000 mg/day, was inconsistent (Watkin et al. 1950). Such studies laid the groundwork for subsequent investigations into the role of sodium in the development of hypertension. The positive association between body weight and blood pressure was documented more than 60 years ago (Faber 1924). Clinical treatment of hypertension with weight reduction was reported over 60 years ago by Rose, who documented lower blood pressure and relief of edema in obese patients who lost weight (Rose 1922). The historical evidence for dietary associations with high blood pressure has been reviewed extensively (McCarron and Kotchen 1983; McCarron, Filer, and Van Itallie 1982; Horan et al. 1985). A review of the development of U.S. public health policy on nutrition and hypertension indicates that in a rather brief time period, the focus shifted from acceptance of the association between sodium intake and blood pressure-an emphasis of the 1969 White House Conference on Food, Nutrition, and Health-to congressional attention on the topic of sodium labeling and FDA action to promote sodium labeling to the 1980 issuance of the DHHS/USDA recommendation in the Dietary Guidelines for Ameri- 140 High Blood Pressure tl ~XVLV to avoid excessive sodium intake. The relatively fast pace of this nutrition policy development can be appreciated by contrasting it with the history of recommendations for dietary change for high blood cholesterol levels (see chapter on coronary heart disease). A few milestones in the development of nutrition-hypertension policy are noted here. The role of dietary salt in hypertension was a major issue at the White House Conference on Food, Nutrition, and Health and at the Senate Select Committee hearings in I%9 (Mayer 1969). Subsequently, a committee of the National Academy of Sciences recommended that no more than 0.25 percent salt be added to the commercial preparation of infant food (Sub- committee 1970). In 1970, the infant food industry initiated restriction of added salt. In 1974, the American Academy of Pediatrics Committee on Nutrition recommended dietary modification of sodium intake for the pediatric population at risk for hypertension. The committee also favored the devel- opment of guidelines for reducing the use of salt by food processors and recommended that information about the amount of salt added to pro- cessed food be made available to consumers (AAP Committee on Nutrition 1974). The Food and Drug Administration (FDA) sponsored a review of the health implications of added salt as part of an evaluation of substances designated "Generally Recognized As Safe" for use in foods. This evaluation, com- pleted in 1979 by a committee of the Federation of American Societies for Experimental Biology, concluded that consumption of sodium chloride in the United States should be reduced, guidelines should be developed for restricting salt in processed foods, and the sodium content of processed foods should be labeled (Select Committee on GRAS Substances 1979). Subsequently, the FDA proposed that more information on the sodium content of foods be provided as part of nutrition labeling (U.S. Congress 1981; FDA 1982). Sodium labeling is part of the FDA's five-point sodium program that involves collaboration between the food industry and Government. The effort intends to achieve changes in food labeling and to encourage the food industry to reduce the amount of sodium added to processed foods and to market a greater variety of foods with lowered sodium. The FDA will encourage consumer education about the relationship between sodium and 141 O Nutrition and Health hypertension. It is intended to monitor changes in the marketplace to see whether efforts to reduce sodium in the food supply and to increase sodium labeling are successful. Legislation to mandate sodium labeling might be considered if voluntary efforts fail (Forbes and Stephenson 1985). Appropriate caloric intake to maintain desirable weight and avoidance of excessive sodium intake are goals included in the Surgeon General's Report on Health Promotion and Disease Prevention (DHEW 1979) and the nutrition component of the 1990 Objectives for the Nation (DHHS 1980). These goals are also recommended by the Food and Nutrition Board of the National Academy of Sciences (NRC 1980) and are consistent with the Dietary Guidelines for Americans, published by the Departments of Agriculture and Health and Human Services (USDA/DHHS 1980, 1985). In recognition of the clear social need to reduce illness, disability, and death from uncontrolled hypertension, the National High Blood Pressure Education Program (NHBPEP) was initiated in 1972, led and coordinated by the National Heart, Lung, and Blood Institute. This program includes an extensive network of Federal agencies and major national health organi- zations. During the time the NHBPEP has been in operation, age-adjusted death rates for stroke and coronary heart disease have substantially de- clined. The activities of the NHBPEP on improving hypertension control are believed to have contributed to this decline (Lenfant and Roccella 1984). Significance for Public Health In the United States, hypertension is a public health problem of enormous magnitude. Estimates of the prevalence of hypertension vary, however, depending upon differences in interpretation and extrapolation of the data. Current definitions of hypertension are listed in Table 3-l. A change in the blood pressure threshold from 160/95 mm Hg (systolic/diastolic measure- ments in millimeters of mercury) to 140/90 mm Hg was recommended in 1984 (JNC III 1984) and is maintained in the most recent report (JNC IV 1988). According to this definition, almost 58 million individuals have been found to have elevated blood pressure or have reported taking antihyper- tensive drugs prescribed by a physician (Table 3-2). About 39 million of these people are under the age of 65; less than 3 percent are children. Prevalence of hypertension increases with age in the U.S. population and is higher for black Americans (38 percent) than for white Americans (29 percent) (Subcommittee 1985). 142 High Blood Pressure O Table 3-l Classification of Blood Pressure' in Adults 18 Years or Older Range, mm Hg Diastolic -=c 85 85-89 90-104 105-l 14 > 115 Systolic, when diastolic blood pressure is < 90 < 140 14&159 > 160 Categoryb Normal blood pressure High normal blood pressure Mild hypertension Moderate hypertension Severe hypertension Normal blood pressure Borderline isolated systolic hypertension Isolated systolic hypertension aBased on the average of two or more readings on two or more occasions. bA classification of borderline isolated systolic hypertension (SBP 140 to 159 mm Hg) or isolated systolic hypertension (SBP > 180 mm Hg) takes precedence over high normal blood pressure (diistolii blood pressure 85 to 89 mm Hg) when both occur in the same person. High normal blood pressure (DBP 85 to 89 mm Hg) takes precedence over a classification of normal blood pressure (SBP < 140 mm Hg) when both occur in the same person. Source: 1988 Joint National Committee. Table 3-2 Estimated Prevalence of Cardiovascular Disease in the United States Hypertension (> 140/90 or on Rx) 57,700,ooo Rheumatic fever with or without heart disease 1,500,ooo Coronary heart disease 6,700,OW Cardiac arrhythmias 1.4WooO Cerebrovascular disease 2,700,OOO Sources: Subcommittee on Definition and Prevalence of the 1984 Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure 1985; National Center for Health Statistics 1988. Hypertension is a major risk factor both for heart disease, which is the leading category of causes of death in the United States, and for stroke, 143 0 Nutrition and Health which is the third most frequent cause of death. All of the cardiovascular diseases are highly prevalent in this country (Table 3-2). A high proportion of end-stage renal failure is due to hypertension. The magnitude of the high blood pressure problem is demonstrated by the fact that in 1980 and 1981, the estimated annual number of visits to physicians' o&es by patients with cardiovascular disease was over 56 million. The largest subgroup was for hypertension, a total of 29 million visits (Ezzati and McLemore 1980; NCHS 1984). Scientific Background Regulation of Blood Pressure Blood pressure is regulated by a complex process involving the interac- tions of multiple factors that are not completely understood. Ultimately, the regulation of blood pressure reflects the interaction of cardiac output (the amount of blood the heart pumps per unit of time) and total peripheral resistance (the resistance to flow that blood encounters in the arteries and arterioles). Therefore, hypertension is an imbalance of the mechanisms that affect either output or resistance, or both. Some of the many mecha- nisms that affect these functions and, therefore, blood pressure are listed in Table 3-3. These include alterations in hemodynamic factors (plasma vol- ume, cardiac output, and arterial pressure); central nervous system mecha- nisms that influence the hemodynamic mechanisms; interactions of the renin-angiotensin and adrenergic system that elevate arterial pressure; adrenal hormone secretion and maintenance of water, sodium, and other electrolyte balance; and various other hormonal influences. In over 95 percent of individuals with high blood pressure, the specific cause cannot be determined, and the condition is referred to as primary or essential hypertension. Primary hypertension may sometimes represent nonspecific disturbances in blood pressure regulation, and the specific mechanism is not always identifiable. Methodological Issues Each approach to investigating the effects of diet on blood pressure has limitations. Animal experimentation provides optimal control over intake of specific nutrients, and hypotheses generated from animal models have been useful in the study of human primary hypertension. Different mecha- nisms, however, may be important in humans. Epidemiologic studies that compare customary diets and average blood pressure levels among popula- tions or among smaller groups within populations can lead to inferences about the relative importance of various nutritional factors, particularly if 144 High Blood Pressure O Table 3-3 Control Mechanisms for Arterial Pressure Mechanical (posture, etc.) Hemodynamic Autonomic nervous system Central nervous system Gastrointestinal system (absorption of fluids and electrolytes) Renal parenchymal function Maintenance of sodium and fluid balance Regulation of excretion of other electrolytes Renin-angiotensin-aldosterone system Other hormonal factors Adrenal cortical hormones Vasopressin Growth hormone Parathormone Thyroid hormone Kallikrein-kinin system Prostaglandin system Histaminergic mechanisms !%urcx: Adapted from Frohlii 1963. data are collected longitudinally. Cross-sectional studies have two key drawbacks: (1) only a few observations may be used to characterize factors that often have large individual fluctuations (e.g., diet, blood pressure), and (2) they do not consider whether the observed dietary intake is typical of long-term habits, reflects an aberration in usual intake, or reflects a dietary pattern that has been recently modified in response to health concerns. Observational studies cannot distinguish between the effects of highly correlated dietary constituents. For example, in an observational study, both a low intake of potassium and a high intake of sodium may be associated with high blood pressure. A well-designed human intervention study can yield information on the independence or interaction of the nutrients. Such studies require reliable dietary assessment and use of objective measures whenever feasible as well as standardized blinded blood pressure measurements, adequate length of followup. and control of potentially confounding variables such as other nutrients or weight change. 145 O Nutrition and Health Nutritional Correlates Research on diet and hypertension is complicated by the need to assess the relative importance of about 50 essential nutrients, dietary fiber, and nutrition-related factors such as obesity in the face of serious meth- odological problems inherent in studies of the role of diet in chronic disease (Reed et al. 1985). Although certain individual nutrients are implicated in hypertension, future nutrition research may need to focus more on the interrelationships among dietary factors than to consider each separately (Hegsted 1985). Several symposia have reviewed the role of nutrition in blood pressure regulation as well as the mechanisms by which dietary factors are known or thought to influence blood pressure regulation (McCarron, Filer, and Van Itallie 1982; Horan et al. 1985). The major dietary factors thought to influence blood pressure and the mechanisms by which they may do so are summarized in Table 3-4. The complexity of these interactions explains why ". . . even where there is general agreement about the importance of a specific nutrient's effect on blood pressure, there is not necessarily con- sensus on the mechanisms involved" (McCarron, Filer, and Van Itallie 1982). Key Scientific Issues o Role of Obesity in Hypertension o Role of Sodium in Hypertension o Role of Alcohol in Hypertension o Role of Other Minerals in Hypertension o Role of Macronutrients in Hypertension o Role of Caffeine in Hypertension Of the many dietary factors listed in Table 3-4 that affect blood pressure. three-obesity, sodium, and alcohol-have a role that is well supported by scientific evidence (JNC IV 1988). At present, research on the effects of other dietary factors is suggestive but not conclusive. Role of Obesity in Hypertension As was noted in a special supplement on nutrition and blood pressure control (Dustan 1983; Havlik et al. 1983), early studies on the association between body weight and blood pressure have been confirmed in epi- demiologic studies of primitive as well as developed populations. In many 146 High Blood Pressure 0 Table 3-4 Major Nutrients and Possible Mechanisms for Influencing Blood Pressure Calories and Macronutrients rotal calories Possible Mechanisms Obesity Energy generation carbohydrates (and alcohol) Energy metabolism Membrane synthesis insulin regulation-sodium excretion Catecholamine regulation-vascular tone Proteins Lipids Electrolytes and Minerals ProteinIpeptide synthesis Control of cellular function Membrane transport systems Energy source Cell membrane components Prostaglandin synthesis Sodium Potassium Intravascular volume Hormone regulation Membrane potential Vascular tone Hormone regulation Cation transport Calcium Receptor-ligand binding Hormone synthesis/release Vascular tone Contractile protein interactions Magnesium Regulation of calcium channels ATP production Contractile protein interaction Phosphorus Membrane structure ATP-energy metabolism CAMP component Trace elements Copper-vascular integrity Manganese-energy metabolism Chromium-lipid metabolism Vanadium-sodium/potassium ATPase Source: Adepted from McCerron. Henry, and Morris 1982. 147 0 Nutrition and Health populations where body weight does not increase with age, neither does blood pressure. Further connection between hypertension and obesity has been demonstrated in the Hypertension Detection and Follow-Up Pro- gram, which reported that 60 percent of the participants with hypertension were more than 20 percent overweight (Hypertension Detection and Fol- low-Up Program Cooperative Group 1977). Evidence for the effect of weight reduction on blood pressure began to accumulate in the early part of this century. This association has now been investigated in many epidemiologic studies and several clinical trials (as reviewed by MacMahon et al. 1987). Although a few studies have reported that treatment of hypertension with weight loss did not result in lower blood pressure, many investigators have reported significant reduction of elevated blood pressure by weight loss (Table 3-5). Complicating the relationship of obesity to blood pressure is the role of sodium. An early hypothesis was that obese individuals with hypertension are sensitive to the blood pressure-raising effects of a high sodium intake associated with long-term calorie excess (Dahl, Silver, and Christie 1958). However, other investigators have dissociated the two factors and demon- strated that weight loss is effective in lowering blood pressure even in the absence of sodium restriction (Reisen et al. 1981; Maxwell et al. 1984). In conclusion, increased body weight is related to increased blood pres- sure. Furthermore, a fall in blood pressure can be expected with weight reduction. Further studies may help to define other factors such as the distribution of body fat (Kalkhoff et al. 1983; Krotkiewski et al. 1983; Berchtold 1985) or specific mechanisms by which obesity might be in- volved in the development of hypertension, Weight loss is recommended for all overweight persons, particularly for those with hypertension. It has been suggested that control of obesit) would eliminate hypertension in 48 percent of whites and 28 percent of blacks (Tyroler, Heyden, and Hames 1975). Even when weight loss does not reduce blood pressure to normal, health risks may be reduced, and smaller doses of antihypertensive medication may be needed as a result. Role of Sodium in Hypertension Definitions In most human studies, sodium intake is estimated from reported dietary intake of salt (sodium chloride) among the study participants. A more 148 Table 3-5 Changes in Weight and Blood Pressure (Baseline to Followup) in Treatment (Rx) and Control Groups of Five Randomized Controlled Trials N Followup Weight Change (kg) Systolic BP Change Diastolic BP Change Rx Control (months) Rx Control Rx Control Rx Control Diet trials Reisin et al. 57 26 4 - 14.9 - 1.2 - 37.4 -6.9 -23.3 -2.5 Heyden et al. 63 64 12 -8.1 -1.9 - 18.0 - 12.0 - 13.0 -8.0 Ramsay et al. 15 34 12 -5.1 -2.4 -11.9 -8.9 -6.9 -4.4 Haynes et al. 30 30 6 -4.1 -0.8 +4.8 -0.2 + 1.4 -0.1 MacMahon et al. 20 18 5 -7.4 +0.5 - 13.3 -7.4 -9.8 -3.1 Pooled estimatesa i D (Rx vs. control) Diet trials 185 172 -9.2 -6.3 -3.1 (95% confidence limits) (-8.2, - 10.2) (-3.3, -9.4) (- 1.5, -4.7) Pooled estimatesa (Rx vs. control) All trials 336 254 -8.7 -5.3 -3.3 (95% confidence limits) (-7.9, -9.5) (-3.4, -7.31, (- 1.8, -4.7) s Gee MacMahon et al. 1987 for methods. B Source: Adapted from MacMahon et al. 1987. B `Z 3 E 5 O Nutrition and Health precise measure of sodium intake is 24-hour urinary sodium output, con- sidered to be an accurate reflection of recent dietary sodium intake in persons with normal kidney function. An average urinary sodium output can be estimated to be about 150 mEq/24 hours. Dietary sodium intakes are commonly reported in mEq, mM, or g. One mEq or one mM of sodium equals 23 mg, and 1 g of sodium equals 44 mEq or mM and is equivalent to 2.5 g of sodium chloride (table salt). The average daily sodium intake of adults is about 4 to 6 g (175 to 265 mEq). Research Evidence Epidemiology. A relationship of sodium to hypertension is supported by several lines of evidence. In non-western populations with low salt con- sumption, blood pressure does not rise with age. Populations with low blood pressure generally do not consume much salt. These associations have been reported among numerous populations such as the Bushmen of Kalahari, Indian tribes in Brazil, and other groups in New Guinea, Malay- sia, the Polynesian Islands, and Solomon Islands. Salt intake is positively correlated with average systolic and diastolic blood pressures in samples of men and women from 25 diverse populations, regardless of methods of measurement (Gleibermann 1973; McCarron, Henry, and Morris 1982); significant positive associations have not been observed in other populations (see review, Subcommittee 1986). Associa- tions among individuals within a population have been less consistent, perhaps for methodological reasons (Liu et al. 1979). Cfinical Studies. Many studies have examined the effect of moderate restriction of sodium consumption on blood pressure in adults. One non- randomized crossover study, for example, found that a diet considered to be moderate in sodium restriction-that is, "avoiding all foods which had sodium added during preparation"- reduced sodium excretion from 191 to 93 mEq and was accompanied by reductions in systolic and diastolic blood pressure that averaged 7.7 and 4.4 mm Hg, respectively (Parijs et al. 1973). A randomized study of 37 hypertensive patients with initial diastolic blood pressures of 90 to 110 mm Hg reported that dietary restriction to 50 mEq of sodium/day for 15 to 21 months produced reductions in systolic and di- astolic blood pressure that were similar to those achieved by drug treat- ment (Magnani et al. 1976). Long-term studies have shown that 39 percent of hypertensive patients could control blood pressure with sodium intakes below 50 mEq/day and close supervision by a dietitian and physician, and about one-third of patients with mild hypertension could control blood pressure with a sodium intake of 75 mEq/day or less (Hunt 1977). 150 High Blood Pressure 0 .4dditional studies suggest that even smaller reductions in sodium intake over an extended period may reduce blood pressure, as discussed below. In a 2-year controlled trial, 31 hypertensive patients were instructed to reduce sodium intake by about 70 to 100 mEq. Although sodium excretion declined only from 191 to 157 mEq, indicating a much smaller reduction in intake, the average diastolic blood pressure fell by 7.3 mm Hg, a result similar to that obtained by drug treatment (Morgan et al. 1978). Similar results have been obtained in even shorter time periods. In a 12- Lveek randomized trial, one-half of 90 drug-treated hypertensive patients :vere placed on a no-added-sodium diet (estimated to be equivalent to a maximum intake of about 100 to 150 mEq, or 2,300 to 3,450 mg of sodium). Among the salt-restricted patients, sodium excretion decreased from 150 .o 37 mEq and diastolic blood pressure decreased by 6.3 mm Hg (compared with a fall of 2.9 mm Hg in the drug-treated control group), and four of five patients were able to discontinue or reduce medication (Beard et al. 1982). In a randomized 8-week crossover study of 19 hypertensive patients, dietary restriction was associated with a reduction in sodium excretion `ram 191 to 83 mEq and a fall in mean blood pressure of 7.6 mm Hg MacGregor, Markandu, et al. 1982). During a later double-blind phase of .he trial, a level of sodium excretion of 76 mEq was associated with a mean 31ood pressure of 7.1 mm Hg lower than that of the control group (Mac- Sregor, Smith, et al. 1982). Results of a nearly identical trial, however, showed no difference in patients' blood pressures (Watt et al. 1983). The .lifferences between these results may be related to a somewhat lower llood pressure at entry, to a slight difference in average sodium excretion, 3r to chance variation. 4 recent review of 13 randomized clinical trials concluded that moderate 37 to 153 mEq/day) sodium restriction does reduce blood pressure, at least :o some small extent, and that this practice is most effective for systolic pressures, for older hypertensive patients, and for patients with higher nitial blood pressures (Grobbee and Hofman 1986a). 3evention The important question of whether reduction in sodium intake might ?revent the rise in blood pressure with age has been addressed in a few short-term studies of adults, children, and infants with normal blood pres- cures (normotensives). Blood pressure response to moderate sodium re- itriction (to 60 mEq) for 3 months in 16 healthy normotensive husbands and wives was associated with a decrease in sodium excretion from 152.7 to 59.5 mEq/day and significant decreases in systolic and diastolic blood 151 u Nutrition and Health pressure of 4 and 3 mm Hg, respectively (Miller et al. 1983). In a ran- domized double-blind trial, 23 1 infants fed a diet reduced in sodium content by two-thirds during the first 6 months of life had a mean systolic blood pressure that was significantly lower (2.1 mm Hg) than that of 245 infants fed a customary diet (Hofman, Hazebrock, and Valkenburg 1985). These two studies indicate that apparently normal blood pressures can be re- duced by dietary sodium restriction, and they suggest that this practice might prevent age-related increases in blood pressure. To date, however, no reported studies have tested this hypothesis directly. Variability in Response The disparate blood pressure responses to sodium intake in animals at- tributed to genetic influence (Dahl, Heine, and Tassinari 1%2) have led to the proposal that dietary sodium and blood pressure relationships are controlled by similargenetic factors in humans (DahIl972). Support for the concept of individual variability in human blood pressure response has been provided by a study of 20 hypertensive patients in hospital metabolic units who were fed daily sodium intakes of 9 mEq, 109 mEq, and 249 mEq. Investigators were able to distinguish a salt-sensitive group, whose blood pressures fell in response to sodium restriction, and a salt-resistant group, whose blood pressures tended not to be influenced by changes in salt intake (Kawasaki et al. 1978). It has not yet been possible, however, to identify a way to consistently distinguish salt-sensitive from salt-resistant persons other than by measuring the blood pressure response itself. While acknowledging that there are some hype,tiensive individuals whose blood pressures do not respond to sodium restriction, some investigators believe that patients who continue to consume low-salt diets have a more benign course than those who revert to a high salt intake (Dahl 1977). Two dietary intervention studies suggest that weight loss or sodium restric- tion or both can retard the return of high blood pressure in patients who have achieved normal blood pressure levels through drug treatment. The Dietary Intervention Study in Hypertension assessed whether hyperten- sive patients whose hypertension was controlled with drugs could discon- tinue these medications with or without dietary therapy. The 415 patients who discontinued medications were randomized, stratified by body weight, either to control, weight loss (mean loss of 10 lb), or sodium restriction (mean decrease of 40 mEq/day). The patients in the dietary intervention groups were more than twice as successful as those in the control group in maintaining normal blood pressure. At the end of 56 weeks, 50 percent of these patients remained normotensive without medi- cation. This success rate was higher for patients with pretreatment mild 152 High Blood Pressure 0 hypertension than for those with pretreatment severe hypertension. In the former group, 71.5 percent in the weight loss group and 78 percent in the nonobese sodium restriction group remained normotensive (Langford et al. 1985). Similar results were noted in a 4-year trial, the Hypertension Control Program. Among patients with pretreatment mild hypertension who dis- continued antihypertensive medications but who restricted calories and sodium and alcohol intake, 39 percent maintained normal blood pressure after 4 years. In contrast, only 4 percent of those patients who did not receive nutritional intervention remained normotensive (Stamler et al. 1987). It should be noted that in the two studies previously described, the patients had relatively mild hypertension that had been controlled successfully with drugs for the preceding 5 years. Although the long-term effectiveness of dietary intervention in persons with more severe elevations in blood pres- sure remains to be established, these studies have important implications for the millions of Americans who are being treated for high blood pressure or who have elevated diastolic blood pressure. Many persons who adhere to a dietary regimen to control blood pressure can reduce or stop drug therapy, with potential economic and health advantages. Role of Alcohol in Hypertension Epidemiologic studies have shown that individuals who regularly consume large amounts of alcohol have higher blood pressure than people who abstain from alcohol or who drink only moderate amounts. The epi- demiologic literature for the existence and nature of an association be- tween blood pressure and alcohol consumption has been reviewed (Mac- Mahon 1987). In the 12 cross-sectional North American studies reviewed (Table 3-6), with the exception of the Canada Health Study, all reports showed a significant positive association that was independent of age, relative body weight, exercise, and smoking status. In most U.S. studies, a J-shaped or U-shaped association is observed between blood pressure and alcohol consumption, with blood pressure greater in nondrinkers than in those consuming one to two drinks per day. It is not clear whether this might be partially explained by other factors, such as obesity. A more consistent finding was elevation of blood pressure at levels of three drinks or more per day. The prospective, observational studies of the association of blood pressure with alcohol consumption (Table 3-7) have also been reviewed (MacMahon 1987). In this group of investigators, only the Hono- lulu Heart Study failed to show a positive association with either systolic or 153 O Nutrition and Health Table 3-6 Studies of the Cross-Sectional Association of Blood Pressure With Alcohol Consumption Year Studya No. of Male Age Subjects Subjects (o/o) (years) 1967 Los Angeles Heart 865 100 1977 Chicago W. Electric 1,899 100 1977 Kaiser-Permanente I 83,947 45 1980 Tecumseh 3,390 47 1981 Lipid Research Clinics 4,783 52 1981 Honolulu Heart 8,006 100 1983 Stanford Five City 1,842 48 1983 Framingham 5,209 42 1985 Canada Health 1,418 51 1985 NHANES 9,553 45 1986 Kaiser-Permanente II 66,510 44 1986 Albany 1,910 100 21+ 40-55 15-79 18+ 20+ 46-68 20-74 29-62 20+ 18-74 - 38-55 1974 1980 1982 1983 1984 1985 1985 European Copenhagen 5,249 Yugoslavia 11,121 Lyon 1,134 North KarelialKuopio 8,479 Munich Blood Pressure 3,198 Wurttemberg 3,351 Zutphen 794 Australian and New Zealand 100 40-59 100 35-62 100 20-59 50 30-64 33 30-69 88 20-65 100 a59 1980 1981 1982 1982 1984 1984 1985 1985 Tasmania CSIRO Sydney Hospital Perth Medicheck Australian RFPS Milton Auckland Japanese 85 350 20,920 491 11,000 5,550 901 1.429 loo 100 65 100 75 :: 66 36" 23b 18-70 2Od5 43b 19+ 19+ 35-64 1984 OsakalAkita 887 100 40-69 1984 Minamikawachi 3,083 37 53b North American aCSlR0 = Commonwealth Scientific and Industrial Research Organization; NHANES = National Health and Nutrition Examination Survey; RFPS = Risk Factor Prevalence Study. Wean age. Source: Adapted from Macblahon 1987. 154 High Blood Pressure O Table 3-7 Prospective Observational Studies of the Association of Blood Pressure Wii Alcohol Consumption Year Studv No. of Subiects 1977 Chicago People's Gas 1,340 100 1981 Chicago W. Electric 871 100 1982 Honolulu Heart 6,858 loo 1983 Framingham 5,209 42 1985 Zutphen 794 100 1986 Albanv I .910 loo Subjects (%) Age Followup (years) (years) 40-59 40-55 t 46-68 6 29-62 4 40-59 10 38-55 18 Source: Adapted from MacMahon 1987. diastolic blood pressure at followup with alcohol intake either at baseline or followup. This evidence, in summary, indicates the potential impor- tance of alcohol restriction in blood pressure control. Role of Other Minerals in Hypertension Potassium One of the earliest observations of the association of dietary potassium with reduced blood pressure concluded that "potassium salt regularly produced a decline in blood pressure, while sodium salt just as regularly produced a rise" (Addison 1928). It was later observed that potassium lowered blood pressure in individuals with hypertension even when dietary salt intake remained high (McQuarrie, Thompson, and Anderson 1936). This protective effect has also been observed in rats (Meneely, Ball, and Youmans 1957). These inverse associations have been reviewed exten- sively (Meneely and Battarbee 1976; Tannen 1983; Prineas and Blackbum 1985). Population studies have shown both a positive relationship between so- dium intake and blood pressure and an inverse relationship between po- tassium intake and blood pressure (Maddocks 1967; Sinnett and Whyte 1973; Bulpitt et al. 1986). Although the Framingham study showed no relationship between urinary potassium levels and blood pressure (Dawber et al. 1%7), potassium intake was more strongly correlated than any other dietary factor to blood pressure in a Hawaii study (Reed et al. 1985). In disease prevalence studies in Evans County, Georgia, hypertension was more strongly associated with lower potassium intake in black adults than in white adults with similar sodium intakes (Grim et al. 1980). In a Southern California cohort of 859 men and women ages 50 to 79 years, an inverse relationship was observed between dietary potassium, estimated by 24- 155 u Nutrition and Health hour dietary recall at the baseline examination, and death from stroke, identified by examination of death certificates, in the 1Zyear followup (Khaw and Barrett-Connor 1987). Intervention trials have attempted to lower blood pressure in hypertensive patients with the use of potassium supplements. The effect of 60 mEq of potassium supplementation was compared with that of placebo and was documented in a double-blind 4-week crossover trial in 23 patients with hypertension. A small but significant lowering of both systolic and diastolic blood pressure occurred in the supplementation period compared with the placebo period (MacGregor, Smith, et al. 1982). In another double-blind crossover trial, 20 normotensive subjects taking a 64 mEq of potassium supplement reduced diastolic blood pressure significantly (by 2.4 mm Hg) in 2 weeks compared with subjects taking a placebo (Khaw and Thorn 1982). A double-blind clinical trial that enrolled 116 adults with mild hypertension for 8 weeks found a 3.4 mm Hg greater decrease in systolic blood pressure and a 1.8 mm Hg greater decrease in diastolic blood pressure in the group taking potassium supplements of 120 mEq/day than in the group taking placebo. A much greater decrease was observed in the five black patients taking potassium compared with placebo (Svetkey et al. 1987). In a 15-week clinical trial that randomized 37 mildly hypertensive patients, there was a mean difference (lower) of 14 mm Hg in systolic blood pressure and 10.5 mm Hg in diastolic blood pressure in the patients taking 48 mEq/day of potassium compared with placebo (Siani et al. 1987). These beneficial effects of potassium on blood pressure in hypertensive patients have been confirmed in another randomized blinded crossover study of 19 hypertensive patients with diuretic-induced potassium depletion. Po- tassium supplements of 60 mEq/day reduced mean blood pressures by 5.5 mm Hg (Kaplan, Carnegie, and Raskin 1985). In contrast to these findings, an unblinded crossover study of 12 mildly hypertensive subjects showed no influence of potassium supplementation on blood pressure (Richards et al. 1984). One extensive review of the literature concluded that a high potassium intake has no effect on blood pressure in normotensive animals or humans, although a potassium intake of 120 to 175 mEq/day appears to reduce blood pressure in hypertensive patients by 3 to 10 percent (Tannen 1983). If potassium does have an effect, it is likely influenced by sodium. In a randomized 12-week crossover study of increased sodium intake and added potassium in hypertensive and normotensive adults, blood pressure rose in both hypertensive and normotensive subjects who consumed in- creased sodium, but among hypertensives who consumed supplemental potassium, blood pressure fell (Parfrey et al. 1981). I56 High Blood Pressure Ll The relationship between sodium, potassium, and blood pressure in nor- motensive adults has been found to be dependent on family history of hypertension (Pietinen, Wong, and Altschull979). The response to dietary potassium and sodium has been assessed in male medical students with and without a family history of hypertension. In just the group with a positive family history, diastolic blood pressure was reduced by about 11 mm Hg when sodium intake was lowered in the presence of high potassium intake compared with 7 mm Hg with reduced sodium intake alone (Parfrey et al. 1981). A reanalysis of these data confirmed this effect of potassium (Holly et al. 1981). Also consistent with these data that show a lack of potassium influence in those with a negative family history of hypertension are two trials that failed to find a blood pressure-lowering effect of potassium in those persons who achieved substantial reduction of sodium intake (Mor- gan et al. 1983; Smith et al. 1985). Because the duration of the majority of these studies has been only weeks or months, longer term intervention studies have been recommended to evaluate the effects on blood pressure of both increased potassium and reduced sodium (Prineas and Blackbum 1985). Calcium A possible role for dietary calcium in the regulation of blood pressure is suggested by experimental studies in animals, epidemiologic studies, and clinical studies, including clinical trials (Kaplan and Meese 1986). Experimental studies in spontaneously hypertensive rats have suggested that supplemental dietary calcium may prevent the development of hyper- tension (Ayachi 1979; McCarron, Henry, and Morris 1982; Schleiffer et al. 1984). One study, however, reported no such effect (Stem et al. 1984). An association between calcium and blood pressure was suggested by reports that "hard" drinking water (containing calcium) was associated with reduced prevalence of cardiovascular disease (Schroeder 1960). This association between calcium and blood pressure is supported by observa- tions from the Puerto Rico Heart Health Program that individuals who drank no milk (which is high in calcium) had twice the prevalence of hypertension as those who consumed a quart of milk or more per day (Garcia-Pahnieri et al. 1984). An analysis of data for 5,050 adults in South- em California surveyed for heart disease risk factors as part of a Lipid Research Clinics population study indicated that hypertensive men, but not hypertensive women, had a significantly lower intake of calcium from milk than normotensive individuals; in men, diastolic blood pressure de- creased significantly with reported increasing milk consumption (Ackley, Barrett-Connor, and Juarez 1983). In a case-control study, dietary calcium 157 0 Nutrition and Health intake assessed by 24-hour dietary recall in 46 hypertensive patients and normotensive controls showed that calcium intake was 22 percent less in the hypertensive group (McCarron, Morris, and Cole 1982). An analysis of the National Health and Nutrition Examination Survey I (NHANES I) data found an inverse, although inconsistent, association between dietary calcium and blood pressure; the lower blood pressures were correlated with higher levels of serum calcium (Harlan et al. 1984). Although a subsequent examination of a subset of NHANES I data also suggested an inverse relationship between dietary calcium intake and blood pressure (McCarron et al. 1984), the analysis was hindered by methodological shortcomings: the salt added in food preparation and at the table were excluded from dietary intake data; the results were examined using only systolic blood pressure measures; and the analyses did not control consistently for age, race, sex, and body mass index (Feinleib, Lenfant, and Miller 1984). Subsequent analyses of both NHANES I and II data have failed to identify a relationship between dietary calcium and blood pressure except among black males in NHANES I (Sempos et al. 1986). In a randomized placebo-controlled clinical trial, normotensive adults taking 1,000 mg of calcium per day for 8 weeks had blood pressures that were 6 to 9 percent lower than those receiving placebos (Belizan et al. 1983). In an uncontrolled clinical study, 2,000 mg of oral calcium carbonate taken for 5 days lowered blood pressure in people with low plasma renin activity (Resnick, Nicholson, and Laragh 1984). A blood pressure-lower- ing effect of calcium has been noted after 5 months in an uncontrolled study of individuals with mild-to-moderate hypertension (Resnick, Nicholson, and Laragh 1984). Another randomized placebo-controlled crossover trial provided 1,000 mg/ day of oral calcium for 8 weeks to 48 hypertensive and 32 normotensive individuals. In the hypertensive group, standing systolic and diastolic pressures were significantly reduced (by 6 and 2 mm Hg, respectively), as was supine systolic (by 3 mm Hg)-but not diastolic-pressure. Among normotensive persons, only supine diastolic blood pressure was signifi- cantly lowered with calcium (McCarron and Morris 1985). Supplements of 1,500 mg of calcium per day produced modest (2 to 3 mm Hg) reductions of systolic and diastolic pressures in both white and black normotensive men in a recent study (Lyle et al. 1987). An oral calcium supplement of 10 or 20 mM/day was given for 2 months in a double-blind randomized crossover study involving 5 1 hypertensive and 5 1 normotensive patients. There was an apparent trend for lower systolic blood pressure. The diastolic blood High Blood Pressure 0 pressure did not change significantly. In the normotensive group, there were no significant changes in blood pressure (Nowson and Morgan 1986). The effect of 1 g of calcium lactate gluconate or calcium carbonate in 23 patients with mild-to-moderate hypertension was observed for 8 weeks in another double-blind crossover study. These investigators reported no evidence that oral calcium supplements lowered blood pressure in these patients (Zoccali et al. 1986). Analyzed collectively, the preceding evidence suggests that a disturbance in cellular calcium metabolism may contribute to the development of hypertension, although the physiologic mechanism for this effect is as yet unknown (Pak 1985). The possibility that calcium supplements may lower blood pressure only in patients with mildly elevated levels of parathyroid hormone that have occurred as a result of abnormally high kidney excre- tion of calcium (and consequent lowering of blood calcium levels) has been proposed on the basis of a study of 90 hypertensive patients (Grobbee and Hofman 1986b). At present, the role of calcium in blood pressure regula- tion must be considered uncertain and the clinical evidence considered inconclusive (Kaplan and Meese 1986). Chloride In early studies, the blood pressure-raising effect of sodium chloride was attributed to its chloride portion. Since the mid-1950's, however, the sodium component of sodium chloride typically has been considered more important (Dahl and Love 1954). The effect of dietary chloride on the pathogenesis of sodium-dependent hypertension has been examined in experimental animals. Steroid-treated rats with one kidney removed developed hypertension when fed sodium chloride but not when they were fed sodium bicarbonate. These different responses could not be explained by differences in caloric intake, weight gain, or the balance of sodium, water, or potassium (Kurtz and Morris 1983). The observation that salt-sensitive hypertension depends on the presence of both chloride and sodium has induced some investigators to suggest that chloride-rather than sodium-induces hypertension. In one study of salt- sensitive rats, for example, blood pressures were shown to be significantly higher after 5 weeks of loading with sodium chloride, but they remained normal when sodium bicarbonate was substituted for sodium chloride in the diet (Kotchen, Luke, and Ott 1983). The effect of a nonchloride sodium salt on blood pressure was recently tested in five hypertensive men. At 10 mEq/day of sodium chloride, blood pressure was normal. A 230 mEq of 159 0 Nutrition and Health sodium chloride supplement induced a significant increase in blood pres- sure, which was reversed with a supplement of an equimolar amount of sodium as sodium citrate (Klutz, Al-Bander, and Morris 1987). This study again raises the possibility that the chloride ion may independently contrib- ute to the sodium chloride-induced increases in blood pressure. The need for further investigation is reinforced by the report that chloride concentra- tions and activity are decreased in erythrocytes of humans with essential hypertension (Kurtz and Morris 1985). Magnesium An early study showed that clinical administration of magnesium salts lowered blood pressure (Blackfan and Hamilton 1925), and recent epi- demiologic data have rekindled an interest in this effect (Joffres, Reed, and Yano 1987). Because magnesium, along with calcium, is present in "hard" drinking water, an association between dietary magnesium and blood pressure is also suggested by the finding of lower rates of cardiovascular disease in hard-water areas. The possible association between magnesium and blood pressure is supported to some extent by an observation that magnesium-deficient rats had both higher blood pressure levels and re- duced diameter of tiny blood vessels than control animals (Altura et al. 1984). Among elderly people in Denmark, low serum magnesium concentration has been associated with increased blood pressure (Petersen et al: 1977), and magnesium intakes have been found to be reduced among hyperten- sive patients (McCarron 1982). One randomized study of 18 patients taking diuretic medications for hypertension or congestive heart failure showed that magnesium supplementation was followed by a significant fall in both systolic (by 12 mm Hg) and diastolic (by 8 mm Hg) blood pressure (Dyck- ner and Webster 1983). As stated in the chapter on drug-nutrient interac- tions, thiazide diuretics have been associated with magnesium depletion, and this may be a factor in the blood pressure changes seen during magne- sium supplementation. However, in another study in which patients with mild to moderate hypertension not on diuretics were given either magne- sium supplements or a placebo, blood pressures did not fall in either group, despite a significant increase in plasma magnesium concentration and in urinary magnesium in the group taking the supplement (Cappuccio, Mark- andu, and Beynor 1985). The inconsistency of data regarding magnesium and blood pressure levels indicates that there are many unanswered ques- tions regarding the role of magnesium in hypertension. 160 High Blood Pressure 0 Trace Elements Little is known about the role of trace elements in the regulation of blood pressure. Because trace elements such as zinc, copper, and iron participate in enzyme reactions related to blood pressure regulation, they could be factors in the development of hypertension, although they are unlikely to be its primary cause (Saltman 1983). In a comprehensive review of this topic, cadmium was the only trace element that appeared to be related to blood pressure (Mertz 1985), and experimental data from animals and the results of some human studies are consistent with a potential causative role for this element. This role, however, lacks confirmation and is complicated by the many interactions of cadmium with selenium, copper, zinc, and lead. Epidemiologic and animal data also suggest a direct relationship between lead levels and blood pressure (Pirkle et al. 1985), but existing data do not support a major role for this or any other trace element in the pathogenesis of hypertension. Role of Macronutrients in Hypertension Carbohydrates There is some evidence that carbohydrates may play a role in blood pressure regulation. Studies in rats have indicated that dietary sucrose increases blood pressure, whereas starch decreases it (Ahrens et al. 1980). Normotensive humans who supplemented their diets with 200 g/day of sucrose had diastolic blood pressures 5 mm Hg higher than those who consumed no added sucrose (Ahrens 1974). Both a high sucrose and a high glucose solution-but not galactose or lactose-consumed after an over- night fast produce transient increases in blood pressure in normotensive men. These observations suggest that carbohydrates might influence blood pressure-regulating hormones in rats, but investigations conducted to date have failed to find a similar effect in humans (Hodges and Rebello 1985). Fiber There is some indication that plant fiber may reduce blood pressure levels (Anderson 1983; Anderson and Tietyen-Clark 19861, but it is uncertain whether dietary fiber plays a role in blood pressure regulation that is independent of other concomitant dietary changes, such as replacement of fat or facilitation of lower sodium intake (Mendeloff 1985). 161 O Nutrition and Health Fat The effect of dietary fats on blood pressure has been recently reviewed (Sacks et al. 1987). Neither the effect of total fat content nor responses to major changes in fatty acid intake have been sufficiently studied with desirable methodology, controlling potentially confounding variables for an adequate time period. Polyunsaturated Fatty Acids. Considerable interest has focused on obser- vational studies indicating that an increased intake of polyunsaturated fatty acids is associated with lower blood pressure (Iacono, Puska, and Dough- erty 1983; Puska et al. 1985). Although it is uncertain whether the lower blood pressures were attributable to the change in the type of dietary fat, an action of the fatty acids on blood pressure might be mediated through changes in prostaglandin metabolism caused by increased intake of the polyunsaturated fatty acid, linoleic acid. Some prostaglandin metabolites influence salt and water excretion and can cause contraction or dilation of small blood vessels, thereby affecting blood pressure (Iacono et al. 1981). A single-blind randomized control experiment among hypertensive and normotensive men and women in North Karelia, Finland, found that a low- fat diet with a P/S ratio of 1 .O was associated with reductions in systolic and diastolic blood pressure of 8.9 and 7.6 mm Hg, respectively, reductions greater than those observed in parallel control groups receiving sodium restriction or no dietary change (Puska et al. 1983). Another team of investigators has shown that compared with the baseline diet, decreasing saturated fats and increasing polyunsaturated fats are associated with lower blood pressure (Iacono et al. 1975; Iacono et al. 1981; Iacono, Dougherty, and Puska 1982). No significant change in blood pressure was observed after feeding either a low-fat diet (22 percent of calories from fat) or a diet high in polyunsatu- rated fatty acids (19 percent of calories from polyunsaturated fatty acids- compared with the U.S. average of about 7 percent) to 15 to 18 normoten- sive young adults (Brussaard et al. 1981). A double-blind randomized control trial of 6 weeks studying 21 mildly hypertensive patients found that increasing the polyunsaturated fatty acid linoleate from 4.6 to 13 percent of calories and reducing saturated fatty acids from 16 to 10 percent failed to produce any significant changes in blood pressure (Sacks et al. 1987). Monounsaturated Fatty Acids. An association between increased con- sumption of the monounsaturate oleic acid and reductions in both systolic and diastolic blood pressures has been observed recently in a cross- sectional survey that examined 3-day food records and resting blood 162 High Blood Pressure O pressure in 76 normotensive men. Although no physiologic explanation for this association is evident, it is consistent with the lower prevalence of hypertension among Mediterranean populations who consume diets rich in oleic acid-containing olive oil; Mediterranean populations also have a high carbohydrate intake and low saturated fatty acid intake compared with the U.S. population (Williams et al. 1987). Omega-3 Fatty Acids. The role of omega-3 fatty acids in blood pressure lowering has also received attention. Investigators have reported that the ingestion of enough fish to provide 5 g of omega-3 fatty acids per day for 2 weeks caused a significant fall in blood pressure, and the lower blood pressure could be maintained subsequently by the weekly consumption of 20 oz of fish that provided 1.2 g/day of omega-3 fatty acids (Singer et al. 1986). In summary, these results indicating that the type of fat intake may influ- ence blood pressure level require further investigation to resolve inconsis- tencies, confirm the observations, and establish their clinical significance (Iacono, Dougherty, and Puska 1982). Protein The possibility of an effect of protein level on blood pressure regulation and whether specific amino acids might have an antihypertensive role has received little scientific study. In a study of spontaneously hypertensive rats, those rats fed American rat chow containing 25.3 percent protein, compared with rats fed Japanese rat chow containing 19.7 percent protein, developed a lower incidence of stroke (30 percent versus 80 percent). When the rats previously fed American rat chow were fed the Japanese diet, an accelerated rate of cerebral lesions and stroke occurred. This observation led to a search for specific amino acids in proteins that might affect blood pressure; tryptophan and tyrosine, as well as total protein intake, were cited as leading possibilities. Taurine has been demonstrated as having an antihypertensive effect in patients with hypertension (Kohashi et al. 1983) as well as in rats (Abe et al. 1987). One hypothesis is that amino acids or protein may affect blood pressure either at the vascular level or through changes in neuronal control of the cardiovascular system (Yamori et al. 1984), but this idea has yet to be confirmed. Role of Caffeine in Hypertension The consumption of 150 mgof caffeine (two to three cups of brewed coffee) may promote an increase in blood pressure by 5 to 15 mm Hg within 15 163 0 Nutrition and Health minutes that is maintained for as long as 2 hours. These short-term effects are primarily mediated by an increase in cardiac output, with systolic pressure usually rising more than diastolic; they are demonstrable both in individuals who do not habitually consume caffeine and in those who do habitually ingest caffeine if they abstain for 12 hours or more. The cause of these effects is uncertain; short-term effects are not directly attributable to rises in plasma catecholamines, vassopressin, or renin activity (Izzo et al. 1983). Chronic caffeine consumption, however, neither maintains high blood pressure nor is it associated with increased rates of hypertension (Robertson et al. 1984). Prolonged administration of caffeine-as much as 504 mg/day for 4 weeks-has not been associated with significant rises in blood pressure either in normotensive (Ammon et al. 1983) or hypertensive individuals (Robertson et al. 1984). Thus, there appears to be adaptation or tolerance to the hemodynamic effects of caffeine. Implications for Public Health Policy Dietary Guidance General Public Dietary factors that clearly contribute to high blood pressure include obesity and excessive intake of sodium and alcohol. The average daily sodium consumption of 4 to 6 g by adult Americans is substantially above the National Research Council's recommended range of 1.1 to 3.3 g for safe and adequate intake and is 5 to 10 times higher than the amount required. Many individuals are able to maintain normal blood pressure levels over a large range of sodium intake; the lack of known harm from moderate sodium restriction, however, and the potential benefit to people whose blood pressures rise with increased sodium intake suggest that those who ingest excess sodium-most Americans-should consider reducing their dietary sodium intake. The strong association between obesity and hypertension and the demon- strated reduction in blood pressure that occurs with weight loss suggest that maintenance of desirable body weight should be a goal for the popula- tion. Similarly, there is a direct association between blood pressure and alcohol consumption beyond about two standard-sized drinks daily. (One stan- dard-sized drink is defined as 12 oz of regular beer, 5 oz of wine, or 1 `/z oz of distilled spirits.) 164 High Blood Pressure O Some evidence indicates that a reduction in blood pressure is associated with increased dietary intake of potassium, calcium, magnesium, and fiber. This evidence is, as yet, too preliminary to recommend increased intake of these factors for the general population for the purpose of hypertension control. Likewise, although increased intake of certain lipids (e.g., omega-6 or omega-3 polyunsaturated fatty acids) may decrease blood pressure, additional research is needed before any recommendations can be made. Special Populations Achieving and maintaining desirable body weight and moderating sodium and alcohol intake can lower blood pressure in patients with mild and moderate hypertension and reduce the need for antihypertensive medica- tions. Such patients should be informed of the likely benefit ofthese dietary practices, along with the importance of adequate caloric expenditure through exercise, and the moderation of fat intake, especially saturated fatty acids, to reduce high blood cholesterol levels and the risk for heart attack. Nutrition Programs and Services Food Labels Evidence related to the role of dietary factors in hypertension supports the need for nutrition labeling on a wide selection of foods so that the consumer has the option of choosing foods with known amounts of calories and sodium. Food Services Evidence related to the role of dietary factors in hypertension suggests that food service programs should provide adequate choices of foods that provide essential nutrients and energy to maintain desirable body weight and should include foods that are low in sodium. Food Products Evidence related to the role of dietary factors in hypertension suggests that food manufacturers should continue to reduce sodium in products and continue the research and development of products low in calories and sodium. Special Populations Counseling and assistance in the selection and preparation of foods low in sodium and calories and assistance with the development of dietary pat- 165 O Nutrition and Health terns that control energy, sodium, and alcohol should be available to individuals whose blood pressure places them in the mild-to-moderate as well as high range of hypertension. Research and Surveillance Special priority is attached to the following research and surveillance tasks related to the role of diet in hypertension: o Development of practical methods for the rapid and reliable identifica- tion of individuals at high risk for hypertension because they are salt sensitive. o Investigation of the interactions of sodium with other nutrients-such as potassium, calcium, chloride, magnesium, fatty acids, and fiber-in influencing blood pressure. 0 Investigation of the role of specific dietary factors, including po- tassium, calcium, fatty acids, fiber, amino acids, trace elements, and alcohol, in the cause and potential prevention of hypertension and the mechanisms for these effects. o Investigation of the mechanism of obesity-associated hypertension and determination of the ratio of fat to lean body mass that might prevent development of hypertension. 166 High Blood Pressure O Literature Cited AAP. See American Academy of Pediatrics. 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Anna/s of Internal Medicine 98(5, suppl., pt. 2):709-14. Garcia-Palmieri, M.R.; Costas, R.; Cruz-Vidal. M.; Sorlie, P.; Tillotson, J.; and Havlik, R.J. 1984. Milk consumption, calcium intake and decreased hypertension in Puerto Rico: Puerto Rico Heart Health Program Study. Hypertension 6:322-28. Gleibermann, L. 1973. Blood pressure and dietary salt in human populations. Ecology ofFood and Nutrition 2: 143-56. 168 High Blood Pressure 0 Grim,C.E.;L~,F.C.;Miller,J.Z.;Meneely,G.R.;Batterbee,H.D.;andDahl,L.K.l980. Racial differences in blood pressure in Evans County, Georgia: relationship to sodium and potassium intake and plasma renin activity. Journal of Chronir Diseases 33:87-94. Grobbee, D.E., and Hofman, A. 1986a. Does sodium restriction lower blood pressure? British Medical Journal 293~27-29. -. 19t36b. Effect of calcium supplementation on diastolic blood pressure in young people with mild hypertension. Loncet ii:703-7. 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Journal of Hypertension 4(suppl. 6):S676-78. 175 Chapter 4 Cancer One should eat and drink in moderation (not in excess, not at a rapid rate, foods not too hot and not overly hard), maintain an even temperament, eat a good diet and Ye Ge (esophageal cancer) will not develop. Ancient Chinese aphorism of Yan, quoted in O'Connor and Campbell ( 1986) Introduction Cancer, the second leading cause of death in the United States, is a group of conditions of uncontrolled growth of cells originating from almost any tissue of the body. The fundamental basis of cancer has been explained as follows: "Every minute 10 million cells divide in the human body. Usually, they divide in the right way and at the right time, governed by a complex set of controls that have yet to be fully elucidated. When those controls fail, cancer may arise. The carefully ordered pattern of cell growth, division, and differentiation is lost" (Bishop 1984). This chapter reviews the scien- tific evidence for the role of dietary factors in these processes. Histwical Perspective Although diet has been suspected as a cause of cancer since the disease was recognized in the 1st century (Armstrong and Mann 1985). empirical evi- dence was not reported until the early 20th century (Van Alstyne and Beebe 1913). The current era of research grows out of studies that were reported more than 50 years ago. In one of the earliest investigations, dietary information obtained from 462 cancer patients suggested protective effects of whole meal bread, cruciferous vegetables, and fresh milk (Stocks and Kay 1933). Records from insurance companies suggested that overweight people were at higher risk for cancer than normal or underweight people (Tannenbaum 194Ob). This finding stimulated a series of animal experiments that demonstrated a lower incidence of skin tumors, mammary tumors, sarcomas, hepatomas, lung adenomas, and pituitary adenomas in severely underfed animals 177 0 Nutrition and Health (Tannenbaum 1940a; Tannenbaum and Silverstone 1957). Early rodent studies showed that high-fat diets favored development of mammary tu- mors (Silverstone and Tannenbaum 1950) and that vitamin A deficiency was associated with gastric papillomas (Fujimaki 1926). These and other early studies of diet and cancer causation have been reviewed (Armstrong and Mann 1985; Carroll and Khor 1975). Although research on the effects of dietary modification on induction of cancer in rodents continued, there was little attempt to relate the results of this research to humans. Interest in the role of nutrition in human carcino- genesis renewed in the 19605 when a report from the World Health Organi- zation examined lifestyle and environmental factors associated with cancer risk and concluded "that the majority of human cancer is potentially preventable" (WHO 1964). Since then, epidemiologic and experimental research on the relationship between diet, nutrition, and cancer has ex- panded rapidly. In 1980, the National Cancer Institute commissioned the National Academy of Sciences (NAS) to review available information, develop dietary recommendations for public distribution, and develop recommendations for further research on diet, nutrition, and cancer (NRC 1982). This chapter reviews the evidence available at the time the recom- mendations of the NAS report were developed as well as findings since that time. Significance for Public Health Cancer accounted for 22 percent of all deaths in the United States in 1984. It has been estimated that 965,000 new cases of cancer were diagnosed and 483,000 people died of cancer in the United States in 1987 (Silverberg and Lubera 1987). An American born in- i98S has an approximately 30 percent chance of eventually dying of cancer (Seidman et al. 1985). Although the annual number of cancer cases has been steadily increasing as the popula- tion grows, the age-adjusted total cancer incidence and mortality rates for sites other than respiratory tract (cancers that are primarily due to cigarette smoking) have as a whole remained stable during the past 30 to 40 years (NRC 1982). Incidence and mortality rates for cancer are significantly higher in black than in white Americans or members of other minority groups. This differ- ence is especially pronounced in males. Blacks also have the lowest surviv- al rates for cancers at most sites. These differences in cancer experience are more readily explained by social and environmental factors than by biologic differences. Although their cancer rates vary greatly according to 178 Cancer 13 disease site and specific tribal grou