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This supplement includes the scientific papers presented at the National Institutes of Health (NIH) Workshop on The Role of Dietary Supplements for Physically Active People. This workshop was organized by the Office of Dietary Supplements (ODS) at the NIH and was held in conjunction with The American Society for Clinical Nutrition and the American Society for Nutritional Sciences. The workshop was cosponsored by 11 institutes, centers, and offices of the NIH: the National Institute on Aging; the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Child Health and Human Development; the National Institute on Deafness and Other Communication Disorders; the National Institute of Dental and Craniofacial Research; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Heart, Lung, and Blood Institute; the National Institute of Mental Health; the National Center for Complementary and Alternative Medicine; the Office of Research on Women's Health; and the NIH Division of Nutrition Research Coordination. The workshop included > 850 participants and was held at the Natcher Conference Center at the NIH, Bethesda, MD, June 3–4, 1996.
The purpose of the workshop was to critically evaluate the scientific relation between physical activity, metabolism, and diet, specifically the role of selected dietary supplements for people who actively engage in regular physical activity or routine exercise. The meeting focus was not on elite athletes, but rather, on healthy Americans attempting to become or remain physically fit by engaging in regular physical activity. In the articles that follow, as in the presentations at the workshop, the authors were asked to critically review the current literature in their specific topic area, outline barriers to research, and conclude with suggestions for future research directions. The meeting was developed as a discourse among scientists from a wide array of disciplines to focus research needs at the interface of nutrition, supplementation, and physical activity. The speakers and discussants included scientific specialists in the fields of aging, anatomy, child development, clinical nutrition, cognitive sciences, dietary supplements, dietetics, endocrinology, exercise physiology, exercise science, growth and development, kinesiology, medicine, nutrition, nutritional biochemistry, pediatrics, physiology, sports medicine, and women's health issues. Since the time the workshop was held in June 1996, each contributing author has updated his or her paper to reflect the current state of the science in his or her respective area.
The ODS was authorized by Congress as part of the Dietary Supplement Health and Education Act (DSHEA) of 1994 (1) to promote the scientific study of dietary supplements in "maintaining health and preventing chronic disease and other health-related conditions." The DSHEA placed the ODS at the NIH and mandated specific research and advisory duties for the office. This workshop was the first major activity of the ODS in its role of identifying and promoting key areas for research on dietary supplements. In 1996 several significant events prompted the ODS to select this topic. As mentioned in the "Opening Remarks" by Koop, the 1996 Olympics were held in Atlanta shortly after the workshop. The Olympics focused the eyes of the nation on the performance and the training regimens of the nation's foremost athletes. In addition, earlier that year, the Surgeon General's Office released the report Physical Activity and Health (2). Individually and concurrently, these activities resulted in a focus on physical activity. The workshop planning committee, which included Peggy R Borum, Gail E Butterfield, Edward F Coyle, William H Hall, Mitchell Kanter, Henry C Lukaski, Melinda M Manore, Robert J Moore, Marilyn Schorin, William C Wenger, and Steven H Zeisel, in addition to a host of advisors, believed it was time to summarize the scientific evidence on the potential role that supplements might play in athletic performance. The committee also wanted to establish that scientific data are relevant to normal Americans engaged in regular exercise.
Scientific research linking dietary supplements to life span health can be viewed as a relatively new area of research. In the early part of this century, nutrition science and dietary recommendations focused on the identification and treatment of nutritional deficiency diseases. Although Americans have been consuming vitamin and mineral supplements for decades, the direct relation between supplementation and diet and health and the potential role of nutrients beyond the minimum dose required to avoid deficiency has become apparent only within the past 15 y. The possible roles of other food components and natural product derivatives in promoting health and preventing disease are also now being recognized. The publication of the Surgeon General's Report on Nutrition and Health (3) and Diet and Health (4) from the National Academy of Sciences further highlighted the breadth of understanding of the diet-health relation. Scientific research on the characterization of the potential roles of individual nutrients and compounds as dietary supplements has grown dramatically throughout the 1990s.
Dietary supplements in the United States usually are defined as plant extracts, enzymes, vitamins, minerals, and hormonal products that are available without prescription and that may be consumed in addition to the regular diet. Considerable research on the effects of dietary supplements has been conducted in Asia and Europe, where plant products have long been used. However, the overwhelming majority of supplements have not been studied scientifically; therefore it is important to conduct research to determine the benefits and risks of dietary supplements and to interpret available scientific information for the public.
One strong and continuing public health message to Americans on the basis of such scientific information is that moderate exercise should become a part of daily life. Physical activity has been shown to reduce the risk of cardiovascular disease through its effect on high blood pressure, high blood cholesterol, diabetes mellitus and insulin resistance, and obesity. Americans must heed the advice of health professionals and adopt a more physically active lifestyle that includes planned exercise.
The articles presented in this supplement represent the confluence of 2 major scientific disciplines: exercise physiology and nutrition. In particular, these articles address the use of dietary supplements throughout life as they might intersect with activity and health. The supplement is divided into 5 sections: Determining the metabolic basis of supplementation, Macronutrients and amino acids, Minerals, Other supplements of potential interest for the physically active, and Antioxidants.
In the first section, Determining the metabolic basis of supplementation, Zeisel addresses the question of metabolism and supplementation from a broad perspective. He discusses both the concept of supplementation at the cellular and organism levels and the research dealing with bioavailability and efficacy of supplements. He also describes the metabolic perspective of supplement use that forms the basis of this workshop. From the perspective of exercise physiology, Coyle provides the operating definitions of dietary supplements and physical activity used in subsequent articles. He discusses how physical activity increases metabolism and how the stress of physical activity is categorized, measured, and related to substrate use and protein synthesis. From the developmental perspective, Rogol et al review the interplay of nutrition, physical activity, and hormone processes on the genetically determined template for growth in children, from infancy through adolescence. Russell next looks at the aging process as a modifier of metabolism. In particular, Russell provides an overview of the specific nutrients whose requirements change with age because of metabolism modification. Pi-Sunyer addresses other common modifiers of metabolism: overnutrition, undernutrition, and disease. He focuses on energy metabolism and the intersection of these factors with physical activity. Borum and Haskell and Kierman conclude this section with descriptions of the complexities of research design and measurement. After setting the tone of supplementation and activity in the context of metabolism, the following sections review the state of science on the use of specific categories of supplements and physical activity.
In the second section, Macronutrients and amino acids, Wolfe, Horowitz and Klein, Sawka and Montain, and Davis et al critically review the current basic physiology and data on protein, lipid metabolism, fluid and electrolytes, and neurotransmitters as supplements with regard to exercise and fatigue. Wolfe stresses the importance of assessing the goals of the individual in addressing protein needs. Does the individual want to maintain or increase his or her muscle mass? To maintain muscle mass with endurance exercise, Wolfe recommends 0.94 g protein • kg-1 • d-1. This recommendation is well within the normal dietary intake of most Americans. How an individual increases muscle mass is not well understood. Horowitz and Klein address the issue of dietary fat and fat utilization during exercise. They illustrate how the rate of fatty acid utilization during exercise depends on the mobilization of fatty acids, blood flow, oxidative capacity of the muscle, and total number of mitochondria. They suggest that research on medium-chain fatty acid supplementation may prove to be promising. Sawka and Montain discuss the importance of euhydration during physical activity and review data on hyperhydration and performance. They stress that the thermoregulatory function in an individual could be compromised with even a 1% decrease in body weight as a result of fluid loss. Sawka and Montain contend that for the physically active, the best time to maintain adequate fluid intake is during regular meals.
The third section focuses on minerals and begins with Weaver's overview of calcium requirements for the physically active. Weaver reviews the calcium requirements at various ages for both sexes and stresses the problem of low calcium intake in American females and the resulting impact on bone health. She also reviews the data on effects of weight-bearing exercise and the interaction of dietary calcium and exercise. Weaver requests more research on lifestyle factors that may impinge on both calcium and exercise requirements for healthy bones. Lukaski next reviews the scientific evidence of benefits of 3 popular mineral supplements related to physical performance: magnesium, zinc, and chromium. Lukaski contends that the indiscriminate use of high doses of mineral supplements can be hazardous and provides specific examples. Beard and Tobain review the consequences of poor iron status and describe the current understanding of the interaction between iron and exercise performance. They indicate that female athletes, distance runners, and vegetarian athletes particularly may be at risk of iron deficiency.
In the fourth section, articles under the category Other supplements of potential interest for the physically active are reviewed. Manore addresses whether exercise increases the need for B vitamins and whether B vitamin supplementation improves exercise performance. Manore reviews the dietary sources and functions of these vitamins and evaluates the relation of increased physical activity to requirements and supplementation. Casey and Greenhaff review the role of creatine in muscle energy metabolism and discusses the available literature, which shows that creatine supplementation increases exercise performance in repeated bouts of short-term, high-intensity exercise. Casey and Greenhaff stress that the extent of muscle creatine accumulation during supplementation is highly individual and suggest specific doses and areas for productive research on this intensely debated topic. In contrast, although many studies have been conducted, Brass contends that there is insufficient carefully controlled research to show that carnitine supplementation actually enhances exercise performance. Brass reviews carnitine metabolism, the rationale for use of carnitine, and the latest clinical studies on the effects of carnitine supplementation on exercise performance. Bucci reviews the broad area of herbal supplements and physical activity. Although considerable research on herbal supplements and health outcomes has been conducted, Bucci concludes that the area of herbal supplements and performance remains largely unstudied.
The last section reviews the role of antioxidants in physical activity. Clarkson and Thompson present an overview of the human body's natural antioxidant defense system, exercise, and oxidative stress, and the data on antioxidant supplementation in athletes. They include in their discussion the potential benefit of antioxidant supplementation for "weekend athletes." Evans focuses his review on vitamins E and C and exercise. He examines and contrasts the effects of these vitamins as supplements on muscle damage and repair in individuals of various ages. Sen and Packer discuss exercise, oxidative stress, and antioxidant recycling. They review the roles of glutathione, N-acetylcysteine, and protein and nonprotein thiols in the context of exercise. The last article by Jenkins presents the methodologic problems of antioxidant research. Jenkins reviews current approaches and recommends reliable techniques and assays.
A major purpose of the workshop was not only to review the existing literature but also to recommend future areas for research. Each paper thus concludes with the authors' recommendations for research that will significantly move the field forward. At the end of the workshop, the moderators of each session presented an overview of the research recommendations from the papers presented in their respective sessions, and a panel of 4 discussants commented on the papers presented at the workshop as a whole and identified areas for future research.
The following key points and recommendations were made in the summary sessions. The first session identified that the metabolic basis for the use of supplements is grounded in the wide variation in individual requirements for nutrients because of genetics, the effects of activity and exercise, life cycle differences (ie, age, pregnancy, and growth), and lifestyle behavior (eg, diet and smoking). It was addressed that compound purity, form, matrix, dose, and route of administration; subject status; and the duration of the study must be presented in every scientific report that deals with dietary supplements for data to be comparable and for general policy conclusions to be reachable. In his summary remarks, Zeisel posed an important question. He asked, "If we can assume that nutrients and food constituents can be divided into 3 major groups, those that reduce our risk of disease, optimize a specific function, or serve as a pharmaceutical, what is our priority for research among these 3 outcomes?" He urged the research community to make this decision to help focus research efforts. A final point that emerged from the first session was the continued need to identify surrogate endpoints for performance.
From the second through the last sessions, both the session moderators and the discussants echoed the point made by Butterfield in her summary of session 2. She stated that "first and foremost" there is very little information available for women, the elderly, specific ethnic groups, and persons with disabilities. In particular, Sawka identified the need for research on fluid regulation in individuals whose ability to thermoregulate may be compromised (eg, the elderly and persons with spinal cord injuries). Slavin similarly indicated that there is a need for research on mineral status in ethnic groups and on minerals, physical activity, and bone loss in persons with disabilities. It was speculated that women, who have less muscle mass than men, who consume energy-restricted diets, may have suboptimal antioxidant intake and may be more susceptible to exercise-induced free radical damage. However, there are few data on women, particularly on women from different ethnic groups, that can address this issue. A similar question needs to be addressed more fully for the elderly.
Nutrient and food constituent interactions and bioavailability of different forms of minerals remain key areas for future research in regard to mineral supplements in general and in regard to exercise and performance and bone health in particular. Mineral status continues to be difficult to measure, often presents a barrier to quality research, and, therefore, needs focused study. An important question posed by the audience was whether taking supplemental antioxidants in excess of need would interfere with the natural defense system. This concept could be extended to include nutrients and their interactions that could lead to toxicity.
It was generally acknowledged that there is a paucity of data on the target population—the average, fit, healthy, not chronically diseased person. Wenger addressed the importance of not only stressing supplementation for the "weekend warrior" during exercise, but also studying the effects on nutrient requirements and supplementation of initiating an exercise program or of exercising on and off. It was suggested that within this target population, some research be focused on those groups who are more at risk with regard to making mistakes in their use of supplements (eg, children, the elderly, and the obese). For these subpopulations, a key issue would be clear proof of safety for supplement use that is based on careful research, not an absence of data showing no adverse consequences.
Shorin commented that she noticed a change in approach during this workshop. She found that the scientists appeared to be taking a more toxicologic approach to nutrients and food constituents when discussing them as supplements with regard to physical activity. She further explained that nutritionists traditionally take a threshold viewpoint and focus on identifying the minimum amount of a nutrient needed to prevent a deficiency. In this workshop, the discussion was targeted toward the safe range for a nutrient or herbal supplement and the conditions of use for safety. She further suggested that the scientific communities represented by the workshop consider taking a risk-benefit perspective with subpopulations and dietary supplements. If, for example, physically active adolescents with poor diets are at great risk of osteoporosis later in life, then research might best be focused on the physiologic, biochemical, genetic, and behavioral issues around mineral supplementation to enhance peak bone mineral accretion in this age group. Such an approach will have the greatest benefit for society by helping future generations live long and healthy lives. In concluding, Friedl and Moore agreed with Wenger's point that there is a great need for a source of science-based information on demographic-specific supplement use. All agreed that the data are only as good as the methods used for science to bring meaningful results to the role of dietary supplements for physically active people. The discussants encouraged all researchers to heed the recommendations of Borum, Haskell, Kierman, and Jenkins on research design. The research needs identified in this supplement, we trust, will be the impetus for heightened, high-quality, interdisciplinary research and research support in this very topical area.
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