= National Institutes of Health Office of Dietary Supplements Dietary Supplements for Exercise and Athletic Performance Fact Sheet for Health Professionals Introduction This fact sheet provides an overview of selected ingredients in dietary supplements Health Professional designed or claimed to enhance exercise and athletic performance. Manufacturers and sellers promote these products, sometimes referred to as “ergogenic aids” by claiming that they improve strength or endurance, increase exercise efficiency, achieve a performance goal more quickly, and increase tolerance for more intense training. These effects are the main focus of this fact sheet Some people also use ergogenic aids to prepare the body for exercise, reduce the chance of injury during training, and enhance recovery from exercise [1,2] Dietary supplements to enhance exercise and athletic performance come in a variety of forms, including tablets, capsules, liquids, powders, and bars. Many of these products contain numerous ingredients in varied combinations and amounts. Among the more common ingredients are amino acids, protein, creatine, and caffeine. According to one estimate, retail sales of the category of “sports nutrition supplements” totaled $5.67 billion in 2016, or 13.8% of $41.16 billion total sales for dietary supplements and related nutrition products for that year [3] Several surveys have indicated the extent of dietary supplement use for bodybuilding and to enhance exercise and athletic performance: + International surveys found that two-thirds of 3,887 adult and adolescent elite track and field athletes participating in world-championship competitions took one or more dietary supplements containing such ingredients as vitamins, minerals, creatine, caffeine, and amino acids [4] ‘Supplement use increased with age and was significantly more common among women than men. + Asurvey of 1,248 students aged 16 years or older in five U.S. colleges and universities in 2009- 2010 found that 66% reported use of any dietary supplement. The reasons for use included enhanced muscle strength (20% of users), performance enhancement (19% of users), and increased endurance (7% of users) [5]. Products taken for these purposes included protein, amino acids, herbal supplements, caffeine, creatine, and combination products. + Inanational survey of about 21,000 U.S. college athletes, respondents reported taking protein products (41.7%), energy drinks and shots (28.6%), creatine (14.0%), amino acids (12.1%),multivitamins with caffeine (5.7%), beta-hydroxy-beta-methylbutyrate (HMB; 0.2%), dehydroepiandrosterone (DHEA; 0.1%), and an unspecified mix of “testosterone boosters” (1.6%) [6]. Men were much more likely to take performance-enhancing products than women, except for energy drinks and shots. Among the sports with the highest percentage of users of performance- enhancing products were ice hockey, wrestling, and baseball among the men and volleyball, swimming, and ice hockey among the women + Ina review of studies on adolescent use of performance-enhancing substances, the American Academy of Pediatrics concluded that protein, creatine, and caffeine were the most commonly used ingredients and that use increased with age [7]. Although athletes used these ingredients more than nonathletes, teenagers not involved in organized athletic activities often took them to enhance their appearance. + Asurvey of 106,698 U.S. military personnel in 2007-2008 found that 22.8% of the men and 5.3% of the women reported using bodybuilding supplements, such as creatine and amino acids, and 40.5% of the men and 35.5% of the women reported using energy supplements that might contain caffeine and/or energy-enhancing herbs [8]. Use of these products was positively associated with deployment to combat situations, being younger than 29 years, being physically active, and reporting 5 or fewer hours of sleep a night. Itis difficult to make generalizations about the extent of dietary supplement use by athletes because the studies on this topic are heterogeneous. But the data suggest that [9]: + Alarger proportion of athletes than the general U.S. population takes dietary supplements. + Elite athletes (e.g,, professional athletes and those who compete on a national or international level) use dietary supplements more often than their non-elite counterparts. + The supplements used by male and female athletes are similar, except that a larger proportion of women use iron and a larger proportion of men take vitamin E, protein, and creatine. For any individual to physically perform at his or her best, a nutritionally adequate diet and sufficient hydration are critical. The Dietary Guidelines for Americans [10] and MyPlate [11] recommend such an eating plan for everyone. Athletes require adequate daily amounts of calories, fluids, carbohydrates (to maintain blood glucose levels and replace muscle glycogen; typically 1.4 to 4.5 g/lb body weight [3 to 10 g/kg body weight]), protein (0.55 to 0.9 g/lb body weight [1.2 to 2.0 g/kg body weight), fat (20% to 35% of total calories), and vitamins and minerals [12] A few dietary supplements might enhance performance only when they add to, but do not substitute for, this dietary foundation. Athletes engaging in endurance activities lasting more than an hour or performed in extreme environments (e.g., hot temperatures or high altitudes) might need to replace lost fluids and electrolytes and consume additional carbohydrates for energy. Even with proper nutritional preparation, the results of taking any dietary supplement(s) for exercise and athletic performance vary by level of training; the nature, intensity, and duration of the activity; and the environmental conditions fis]Sellers claim that dozens of ingredients in dietary supplements can enhance exercise and athletic performance. Welltrained elite and recreational athletes might use products containing one or more of these ingredients to train harder, improve performance, and achieve a competitive edge. However, the National Athletic Trainers’ Association acknowledges in a position statement that because the outcomes of studies of various performance-enhancing substances are often equivocal, using these substances can be “controversial and confusing” [14]. Most studies to assess the potential value and safety of supplements to enhance exercise and athletic performance include only conditioned athletes. Therefore, it is often not clear whether the supplements discussed in this fact sheet may be of value to recreational exercisers or individuals who engage in athletic activity only occasionally. in addition, much of the research on these supplements involves young adults (more often male than female), and not adolescents who may also use them against the advice of pediatric and high-school professional associations [7,15]. The quality of many studies is limited by their small samples and short durations, use of performance tests that do not simulate real world conditions or are unreliable or irrelevant, and poor control of confounding variables (12] Furthermore, the benefits and risks shown for the supplements might not apply to the supplement's use to enhance types of physical performance not assessed in the studies. In most cases, additional research is needed to fully understand the efficacy and safety of particular ingredients. Selected Ingredients in Dietary Supplements for Exercise and Athletic Performance Many exercise and athletic-performance dietary supplements in the marketplace contain multiple ingredients (especially those marketed for muscle growth and strength). However, much of the research has focused only on single ingredients. One therefore cannot know or predict the effects and safety of combinations in these multi-ingredient products unless clinical trials have investigated that particular combination, Furthermore, the amounts of these ingredients vary widely among products. In some cases, the products contain proprietary blends of ingredients listed in order by weight, but labels do not provide the amount of each ingredient in the blend. Manufacturers and sellers of dietary supplements for exercise and athletic performance rarely fund or conduct scientific research on their proprietary products of a caliber that reputable biomedical journals require for publication. Table 1 briefly summarizes the findings discussed in more detail in this fact sheet on the safety and efficacy of selected ingredients in dietary supplements to enhance exercise and athletic performance. Some research-derived data is available on these ingredients on which to base a judgment about their potential value to aid exercise and athletic performance. These dietary supplement ingredients are listed and discussed in the table, and in the text that follows the table, in alphabetical order. Table 1: Selected Ingredients in Dietary Supplements for Exercise and Athletic Performance* Proposed Mechanism of Evidence of Ingredient Action Efficacy** Evidence of Safety**Ingredient Antioxidants (vitamin C, vitamin E, and coenzyme Qi9) Arginine Proposed Mechanism of Action Minimize free- radical damage to skeletal muscle, thereby reducing muscle fatigue, inflammation, and soreness Increases blood flow and delivery of oxygen and nutrients to skeletal muscle; serves as a substrate for creatine production; increases secretion of human growth hormone to stimulate muscle growth Evidence of Efficacy** Several small clinical trials Research findings: Do not directly improve performance; appear to hinder some physiological and physical exercise-induced adaptations Limited clinical trials with conflicting results Research findings: Little to no effect on vasodilation, blood flow, or exercise metabolites; little evidence of increases in muscle creatine content Evidence of Safety** Safe at recommended intakes; some safety concerns reported with high doses Reported adverse effects: Potential for diarrhea, nausea, abdominal cramps, and other gastrointestinal disturbances with vitamin C intakes of more than 2,000 mg/day in adults; increased risk of hemorrhagic effects with vitamin E intakes of more than 1,800 IU/day (natural form) or 1,100 IU/day (synthetic form) in adults; nausea, heartburn, and other side effects with coenzyme Qo No safety concerns reported for use of up to 9 g/day for weeks; adverse effects possible with larger doses Reported adverse effects: Gastrointestinal effects, such as diarrhea and nauseaIngredient Beetroot or beet juice Proposed Mechanism of Action Dilates blood vessels in exercising muscle, reduces oxygen use, and improves energy production Increases synthesis of camosine, a dipeptide that buffers changes in muscle pH, thereby reducing muscle fatigue and loss of force production; considerable individual variation in associated muscle carnosine synthesis Evidence of Efficacy** Limited clinical trials with conflicting results Research findings: Might improve performance and endurance to some degree in time trials and time-to- exhaustion tests among runners, swimmers, rowers, and cyclists; appears to be most effective in recreationally active non-athletes Numerous clinical trials with conflicting results Research findings: Inconsistent effects on performance in competitive events requiring high- intensity effort over a short period, such as team sports; little or no performance benefit in activities lasting more than 10 minutes Evidence of Safety** No safety concems reported for short-term use at commonly recommended amounts (approximately 2 cups) Reported adverse effects: None known No safety concerns reported for use of 1.6-6.4 g/day for up to 8 weeks Reported adverse effects: Paresthesia (tingling) in face, neck, back of hands, and upper trunk with at least 800 mg or over 10 mg/kg body mass; pruritus (itchy skin)Ingredient Beta-hydroxy-beta- methylbutyrate (HMB), Betaine Branched-chain amino acids (leucine, isoleuci and v: 1e) Proposed Mechanism of Action Helps stressed and damaged skeletal muscle cells restore their structure and function Might increase creatine production, blood nitric-acid levels, or water retention incells Can be metabolized by mitochondria in skeletal muscle to provide energy during exercise Evidence of Efficacy** Numerous clinical trials with conflicting results Research findings: Might help speed up recovery from exercise of sufficient amount and intensity to induce skeletal muscle damage Limited clinical trials in men with conflicting results Research findings: Potential but modest strength and power-based performance improvements in bodybuilders and cyclists Limited number of short-term clinical trials Research findings: Little evidence of improved performance in endurance-related aerobic events; possibility of greater gains in muscle mass and strength during training Evidence of Safety** No safety concerns reported for typical dose of 3 g/day for up to 2 months Reported adverse effects: None known No safety concerns reported for 2-5 g/day for up to 15 days Reported adverse effects: None known No safety concerns reported for 20 g/day or less for up to 6 weeks Reported adverse effects: None knownIngredient Caffeine Proposed Mechanism of Action Blocks activity of the neuromodulator adenosine; reduces perceived pain and exertion Dilates blood vessels to increase delivery of oxygen and nutrients to skeletal muscle Evidence of Efficacy** Numerous clinical trials with mostly consistent results Research findings: Might enhance performance in endurance-type activities (e.g., running) and intermittent, long- duration activities (e.g., soccer) when taken before activity Few clinical trials with conflicting results Research findings: Little research support for use to enhance performance Evidence of Safety** Reasonably safe at up to 400- 500 mg/day for adults Reported adverse effects: Insomnia, restlessness, nausea, vomiting, tachycardia, and arrhythmia; risk of death with acute oral dose of approximately 10-14 g pure caffeine (150-200 mg/kg) Few safety concerns reported for up to 9 g for 1 day or 6 g/day for up to 16 days Reported adverse effects: Gastrointestinal discomfortIngredient Creatine Deer antler velvet Proposed Mechanism of Action Helps supply muscles with energy for short- term, predominantly anaerobic activity Contains growth factors (such as insulin-like growth factor-1 [IGF-1]) that could promote muscle tissue growth Evidence of Efficacy** Numerous clinical trials generally showing a benefit for high-intensity, intermittent activity; potential variation in individual responses Research findings: May increase strength, power, and work from maximal effort muscle contractions; over time helps body adapt to athlete- training regimens; of little value for endurance sports Few short-term clinical trials that show no benefit for physical performance Research findings: No evidence for improving aerobic or anaerobic performance, muscular strength, or endurance Evidence of Safety** Few safety concerns reported at typical dose (e.g, loading dose of 20 g/day for up to 7 days and 3-5 g/day for up to 12 weeks) Reported adverse effects: Weight gain due to water retention; anecdotal reports of nausea, diarrhea, muscle cramps, muscle stiffness, heat intolerance Safety not well studied Reported adverse effects: Hypoglycemia, headache, edema, and joint pain (from prescription \GF-1); banned in professional athletic competitionIngredient Dehydroepiandrosterone (DHEA) Ginseng Proposed Mechanism of Action Steroid hormone that can be converted into testosterone and estradiol Unknown mechanism of action; Panax ginseng used in traditional Chinese medicine as a tonic for stamina and vitality; Siberian ginseng used to reduce fatigue Evidence of Efficacy** Small number of clinical trials that show no benefit for physical performance Research findings: No evidence of increases in strength, aerobic capacity, lean body mass, or testosterone levels inmen Numerous small clinical trials, most showing no benefit for physical performance Research findings: In various doses and types of preparations, no effects on peak power output, time ‘to exhaustion, perceived exertion, recovery from intense activity, oxygen consumption, or heart rate Evidence of Safety** Safety not well studied; no safety concerns reported for up to 150 mg/day for 6-12 weeks Reported adverse effects: Over several months, raises testosterone levels in women, which can cause acne and growth of facial hair Few safety concerns reported with short-term use Reported adverse effects: For Panax ginseng: headache, sleep disturbances, and gastrointestinal disorders; for Siberian ginseng: none knownProposed Mechanism of Evidence of Ingredient Action Efficacy** Evidence of Safety** Glutamine Involved in Few studies of use No safety concerns reported with metabolism and to enhance about 45 g/day for 6 weeks; safe energy production; performance use of up to 0.42 g/kg body contributes directly weight (e.g., 30 g/day in a person nitrogen for many weighing 154 Ib) by many patients critical Research findings: _ with serious conditions (e.g., biochemical In adult weight infections, intestinal diseases, reactions lifters, no effect on and burns) muscle performance, body Reported adverse effects: None composition, or known muscle-protein degradation; may help with recovery of muscle strength and reduce muscle soreness after exercise ron Increases oxygen Numerous clinical No safety concerns reported for uptake,reduces trials with use at recommended intakes (8 heart rate, and conflicting results mg/day for healthy men and decreases lactate postmenopausal women and 18 concentrations Research findings: _ mg/day for healthy during exercise Improved work premenopausal women) capacity with correction of iron Reported adverse effects: Gastric deficiency anemia; upset, constipation, nausea, conflicting evidence abdominal pain, vomiting, and on whether milder fainting at intakes above 45 iron deficiency mg/day without anemia impairs exercise performanceIngredient Protein Quercetin Ribose Sodium bicarbonate Proposed Mechanism of Action Builds, maintains, and repairs muscle Increases mitochondria in muscle, reduces oxidative stress, decreases inflammation, and improves blood flow Involved in production of adenosine triphosphate (ATP) Enhances disposal of hydrogen ions generated from intense muscle activity, thereby reducing metabolic acidosis and resulting fatigue Evidence of Efficacy** Evidence of Safety** Numerous clinical No safety concerns reported at trials daily recommended intakes for athletes of up to about 2.0 g/kg Research findings: body weight (e.g,, 136 g fora Optimizes muscle _ person weighing 150 Ib) training response during exercise and Reported adverse effects: None subsequent known recovery period Numerous small, No safety concerns reported for shortterm clinical 1,000 mg/day or less for up to 8 trials weeks Research findings: Reported adverse effects: None Little to no effect on known endurance performance or maximal oxygen consumption A few small, short- Safety as a dietary supplement term, clinical trials not well studied; no safety concerns reported for up to 10 Research findings: g/day for 8 weeks Little to no effect on exercise capacity in Reported adverse effects: None both trained and known untrained adults Many small, short- No safety concerns reported for term clinical trials short-term use of up to 300 mg/kg body weight Research findings: Might provide minor Reported adverse effects: to moderate Nausea, stomach pain, diarrhea, performance benefit and vomiting for short-term and intermittent high- intensity activity, especially in trained athletesProposed Mechanism of Evidence of Ingredient Action Efficacy** Evidence of Safety** Tart or sour cherry Phytochemicals in A few clinical trials No safety concerns reported for tart cherries may with conflicting about 1/2 quart of juice or 480, facilitate exercise results mg freeze-dried Montmorency recovery by tart-cherry-skin powder per day reducing pain and Research findings: for up to 2 weeks inflammation Variable results for aiding muscle Reported adverse effects: None strength recovery, known reducing soreness, or reducing inflammatory effects on lungs after exercise; insufficient research on ability to improve aerobic performance Tribulus terrestris Increases serum Afewsmall, short- Safety not well studied; no safety testosterone and termclinical trials concerns reported at up to 3.21 luteinizing mg/kg/day for 8 weeks hormone Research findings: concentrations, No effect on Reported adverse effects: One thereby promoting strength, lean body _ case report of harm from product skeletal muscle mass, or sex labeled but not confirmed to hypertrophy hormone levels contain Tribulus terrestris * References to support statements in Table 1 are provided in subsequent text, ** The evidence of efficacy and safety is for the individual ingredients. The efficacy and safety of these ingredients might be different when they are combined with other ingredients in a product or training plan. In the text below, each ingredient’s section begins with an introduction, followed by a summary of the scientific evidence of that ingredient's efficacy and safety. Each section concludes with information and advice from expert sources, when available, on use of the ingredient as an ergogenic aid. Antioxidants (vitamin C, vitamin E, and coenzyme Qo) Exercise increases the body's consumption of oxygen and induces oxidative stress, leading to the production of reactive oxygen and nitrogen species (i.., free radicals) and the creation of more oxidized molecules in various tissues, including muscle. In theory, free radicals could impair exerciseperformance by impeding muscles’ ability to produce force, thereby accelerating muscle damage and fatigue and producing inflammation and soreness [16-18]. Some researchers have suggested that supplements containing antioxidants, such as vitamins C and E and coenzyme Qig (CoQi), could reduce this free-radical formation, thereby minimizing skeletal muscle damage and fatigue and promoting recovery [19] Efficacy: Studies suggest that the use of large doses of antioxidant supplements, especially vitamins C and E, may actually reduce rather than promote some of the beneficial effects of exercise. One study, for example, randomly assigned 54 healthy Norwegian men and women aged 20-30 years, most of whom were recreational exercisers, to receive 1,000 mg vitamin C and 235 mg (about 520 IU) vitamin E as DL-alpha-tocopherol or a placebo daily for 11 weeks while engaging in an endurance training program consisting mostly of running. Compared with placebo, the supplements had no effect on maximal oxygen consumption (VOzmax, a measure of aerobic fitness and endurance capacity) or running performance. However, they significantly lowered levels of biochemical markers related to mitochondrial creation and exercise-induced cell signaling, thereby diminishing the desirable training- induced adaptations within skeletal muscle [20]. The same research group conducted another trial using the same doses of vitamins C and E in 32 young men and women who followed a strength- training program for 10 weeks. Compared with placebo, the supplements did not affect muscle growth, but they significantly reduced the gain in arm strength as measured by biceps curls and blunted cellular signaling pathways linked to muscle hypertrophy [21]. Another study randomly assigned 18 young men aged 20 to 34 years to receive 120 mg/day Coo for 22 days or a placebo [22]. After 7 days of high- intensity cycling sprints, the CoQ;9 group had, on average, a significantly smaller improvement in mean power output than the placebo group, suggesting a poorer adaptation to training. The preponderance of research to date suggests that exercise-induced reactive oxygen species and nitric oxide are beneficial. These free radicals induce adaptive changes in muscle that lead to greater production of mitochondria and hypertrophy of myofibers [17,21,23,24]. Exposure of cells to high concentrations of various antioxidant supplements (of which vitamins C and/or E have the most evidence) appears to blunt or block cell signaling and thereby inhibit some favorable physiological and physical adaptations to exercise. However, these adaptations might not prevent improvements in \VO2max or endurance performance [25]. Safety: Studies on the safety of vitamins C, E, and other antioxidant supplements taken during exercise show no evidence of adverse effects, aside from potentially reducing some of the benefits of exercise, but such studies have only lasted a few weeks or months, The Tolerable Upper Intake Level (UL) of vitamin C that the Food and Nutrition Board established as the maximum amount associated with little or no risk of adverse health effects is 1,800 mg/day for adolescents and 2,000 mg/day for adults [26] These amounts are substantially higher than the doses that studies have typically used for exercise and athletic performance. The UL of vitamin E, at 800 mg/day for adolescents and 1,000 mg/day (1,100-1,500 IU) for adults, is likewise higher than the dose that these studies typically used [26] Among the potential adverse effects of excess vitamin C are diarrhea, nausea, abdominal cramps, and other gastrointestinal disturbances. The intake of excessive amounts of vitamin E increases the risksof hemorrhagic effects. Moreover, results from a large clinical trial show that vitamin E supplements, even at doses below the UL (400 IU/day taken for several years), might increase men's risk of prostate cancer [27]. The side effects of CoQ19 are mild and can include fatigue, insomnia, rashes, nausea, upper abdominal pain, heartburn, sensitivity to light, irritability, dizziness, and headaches [28] Implications for use: Little research supports the use as ergogenic aids of antioxidant supplements containing greater amounts than those available from a nutritionally adequate diet [19,25]. In fact, they can adversely affect some measures of exercise and athletic performance. The Australian Institute of Sport, part of the government of Australia, does not recommend supplementation with vitamins C and E by athletes, except when they use these products as part of a research protocol or with proper monitoring [29]. More information on vitamin C and vitamin E is available in the Office of Dietary Supplements (ODS) health professional fact sheets on these nutrients. Arginine Larginine is an amino acid found in many protein-containing foods, especially animal products and nuts. The typical dietary intake is 4-5 grams/day [20]. The body also synthesizes arginine (from citrulline), mainly in the kidneys, Some experts suggest that taking arginine in supplement form enhances exercise and athletic performance in several ways [30-32]. First, some arginine is converted to nitric oxide, a potent vasodilator that can increase blood flow and the delivery of oxygen and nutrients to skeletal muscle. Second, increased vasodilation can speed up the removal of metabolic waste products related to. muscle fatigue, such as lactate and ammonia, that the body produces during exercise. Third, arginine serves as a precursor for the synthesis of creatine, which helps supply muscle with energy for short- term, intense activity. Fourth, arginine may increase the secretion of human growth hormone (HGH), which in turn increases insulin-like growth factor-1 (IGF-1) levels, both of which stimulate muscle growth, Efficacy: The research to support supplemental arginine as a performance enhancer is limited and conflicting. Overall, it suggests that doses of 2-20 g/day arginine have little to no effect on performance in either anaerobic or aerobic exercise [30,31]. Furthermore, arginine typically had no effect on nitric oxide concentration, blood flow, or exercise metabolites (e.g,, lactate and ammonia), especially when well-trained athletes—including cyclists, tennis players, and judo practitionerstook the supplement for 1-28 days [30]. A recent review assessed 54 clinical studies examining the effects of arginine supplementation on strength performance, endurance, muscle blood volume and flow, cardiorespiratory measures, and nitric oxide production in healthy, active adults. The authors concluded that supplemental arginine (either alone or, more commonly, in combination with other ingredients, such as branched-chain amino acids [BCAAs] and lysine) provided little or no enhancement of athletic performance and did not improve recovery from exhaustion [33]. Most of the studies included few participants, primarily young men aged 18-25 years (only four studies included women), and lasted only 4-8 weeks (with none lasting 3 months or longer). In the 18 studies that compared arginine alonewith a placebo, the most common doses were 2-10 g/day as a single dose and up to 20 g/day divided into three doses. Research on the ability of supplemental arginine to raise HGH and IGF-1 serum concentrations also has had conflicting findings. Depending on the study (and therefore participants’ age, fitness level, and use of other supplements as well as the nature and duration of the exercise), extra arginine might either reduce HGH secretion [34] or raise HGH and IGF-1 secretion [35]. Even raised HGH secretion, however, might not translate into more blood flow into muscle or greater protein synthesis [31]. Little evidence shows supplemental arginine by itself increases muscle creatine concentrations or is superior or complementary to direct consumption of creatine [30] Safety: Most study results suggest that up to 9 g/day arginine for several days or weeks is safe and well tolerated. At doses of 9-30 g/day, the most commonly reported adverse reactions are gastrointestinal discomfort, such as diarrhea and nausea, and slightly reduced blood pressure [33,36,37]. The safety of taking high-dose arginine supplements for more than 3 months is not known (33) Implications for use: Arginine supplementation's ability to enhance strength, improve exercise or athletic performance, or promote muscular recovery after exercise has little scientific support [30- 33,38,39) Beetroot or beet juice Beets are one of the richest food sources of inorganic nitrate. Ingested nitrate might enhance exercise and athletic performance in several ways, primarily through its conversion into nitric oxide in the body. Nitric acid is a potent vasodilator that can increase blood flow and the delivery of oxygen and nutrients to skeletal muscle. Ingested nitrate might also enhance performance by dilating blood vessels in exercising muscle when oxygen levels decline, thereby increasing oxygen and nutrient delivery, reducing the oxygen cost of submaximal exercise, attenuating the adenosine triphosphate (ATP)- creatine phosphate energy system's cost associated with skeletal muscle force production, and improving oxidative phosphorylation in mitochondria [40,41]. Beetroot is available as a juice or juice concentrate and in powdered form; the amount of nitrate can vary considerably among products. Efficacy: A growing number of clinical trials investigating beetroot juice or concentrate as an ergogenic aid have been published since 2007. Beetroot has generally improved performance and endurance to different extents compared with placebo among runners, swimmers, rowers, and cyclists in time trials and time+to-exhaustion tests, but not in all studies [40,41-45]. Performance benefits are more likely in recreationally active non-athletes than elite athletes [42,46]. One study in 10 recreationally active, young male cyclists suggested a dose-response relationship [47]. Although consuming beetroot juice concentrate on each of 4 days to supply 4.2 mmol nitrate (70 mi) provided no performance benefits compared with placebo, larger amounts of juice supplying 8.4 mmol nitrate (140 mi) did. However, consumption of even more beetroot juice supplying 16.8 mmol nitrate (280 ml) produced no further performance benefits. There has been little study of the effects of beetroot on anaerobic performance, such as high-volume resistance exercise with many repetitions [40].More research is needed to clarify the potential benefits of nitrate supplementation from beetroot juice on exercise and athletic performance and to determine the best doses and dosing protocols [48]. No research has assessed longer-term supplementation with beetroot-derived nitrate beyond several weeks as an ergogenic aid. Safety: Studies have not identified any safety concerns with the consumption of beetroot juice in moderate amounts (about 2 cups/day) for several weeks. The amount of nitrate that this amount of juice provides is less than half the total nitrate consumption from a diet rich in vegetables and fruits [49]. Although not a safety concern, beetroot consumption can color the urine pink or red due to the excretion of red pigments in the beets [50]. Implications for use: In a position statement, the Academy of Nutrition and Dietetics (AND), the Dietitians of Canada (D0C), and the American College of Sports Medicine (ACSM) state that nitrate sources, such as beetroot juice, enhance exercise tolerance and economy and they improve endurance exercise performance in recreational athletes [12]. The Australian Institute of Sport supports the use of beetroot juice for improving sports performance in suitable athletic competitions under the direction of an expert in sports medicine, but it notes that more research might be required to understand how the supplement should be used for best results [29]. Most studies have used 500 mi/day (about 2 cups) of beetroot juice taken once (about 2.5 to 3 hours before exercise) or daily for up to 15 days [40]. This amount of juice provides about 5-11 mmol (or 310-682 mg) nitrate, depending on the product [41]. Potential benefits persist for up to 24 hours after ingestion [40]. The labels on beetroot juice and concentrate usually indicate that these products are foods and not dietary supplements. Some dietary supplements contain beetroot powder in varying amounts, but studies have not assessed whether these are viable alternatives to beetroot juice or beetroot juice concentrate. Beta-alanine Beta-alanine, a type of amino acid that the body does not incorporate into proteins, is the rate-limiting precursor to the synthesis of carnosine—a dipeptide of histidine and beta-alanine—in skeletal muscle, Carnosine helps buffer changes in muscle pH from the anaerobic glycolysis that provides energy during high-intensity exercise but results in the buildup of hydrogen ions as lactic acid accumulates and dissociates to form lactate, leading to reduced force and to fatigue [51]. More carnosine in muscle leads to greater potential attenuation of exercise- induced reductions in pH, which could enhance performance of intense activities of short to moderate duration, such as rowing and swimming [52] Beta-alanine is produced in the liver, and relatively small amounts are present in animal-based foods such as meat, poultry, and fish. Estimated dietary intakes range from none in vegans to about 1 g/day in heavy meat eaters [52]. Carnosine is present in animal-based foods, such as beef and pork. However, oral consumption of carnosine is an inefficient method of increasing muscle carnosine concentrations because the dipeptide is digested into its constituent amino acids. Consumption of beta-alanine, in contrast, reliably increases the amount of carnosine in the body. Four to six grams of beta-alanine for 10 weeks, for example, can increase muscle carnosine levels by up to 80%, especially in trainedathletes, although the magnitude of response differs widely [53,54]. For example, in one study of young, physically active but untrained adult men who took 4.8 g/day beta-alanine for 5-6 weeks, the percent increase in muscle carnosine content after 9 weeks of follow-up ranged from 2% to 69% [55]. Among the “low responders,” the duration of the washout period when beta alanine concentrations returned to baseline values was less than half that for the "high responders” (6 weeks vs. 15 weeks). Efficacy: Studies have evaluated beta-alanine as a potential ergogenic aid with a variety of participants, exercise and activity protocols, and dosing regimens. Some studies suggest that beta-alanine consumption could provide small performance benefits in competitive events requiring high-intensity effort over a short period, such as rowing, swimming, and team sports (e.g., hockey and football) that involve repeated sprints and intermittent activity [52]. Other studies have found no such benefits [53]. Evidence is conflicting on whether beta-alanine consumption improves performance in endurance activities, such as cycling [53,56]. Experts have not reached consensus on whether beta-alanine consumption primarily benefits trained athletes or recreationally active individuals [53,57]. Studies provide little consistent evidence of a relationship between the dose of beta-alanine and performance effect [51,58] The authors of a Department of Defense-sponsored review concluded that the limited evidence from 20 human trials did not support consumption of beta-alanine (alone or in combination products) by active adults to enhance athletic performance or improve recovery from exercise-related exhaustion [59]. Most of the studies in this review included young men aged 18-25 years who took 1.6-6.4 g/day beta- alanine supplements (in two to four separate servings) over 4-8 weeks. In contrast, the International Society of Sports Nutrition (ISSN) concluded from its literature review that beta- alanine supplements (4-6 g/day consumed for at least 2-4 weeks) can improve high-intensity exercise performance that lasts over 60 seconds, especially in time-to-exhaustion tasks [54]. However, performance benefits are more modest in exercise tests lasting more than 4 minutes because aerobic metabolic pathways increasingly meet energy demands. The ISSN called for more research to determine whether beta- alanine increases the strength and muscle mass that regular resistance exercise, such as weightlifting, can produce. The authors of the most recent review of studies on beta-alanine's effects on exercise concluded that supplementation has a statistically significant and positive effect on performance (including in both isolated-limb and whole-body exercises), especially in protocols lasting 30 seconds to 10 minutes [58] However, this review also highlighted the fact that small studies of short duration using varied exercise and supplement protocols dominate this scientific literature. The 40 placebo-controlled studies reviewed, for example, employed 65 exercise protocols and 70 exercise measures in a total of 1,461 participants. Furthermore, the total dose of beta-alanine that participants consumed ranged from 84 to. 414 qin studies lasting 28-90 days. Safety: Beta-alanine supplementation appears to be safe at 1.6~6.4 g/day for up to 8 weeks [54]. Some evidence does show, however, that consuming a conventional dose of beta-alanine of at least 800 mg or exceeding 10 mg/kg body mass can provoke moderate to severe paresthesia [54,59]. This tingling, prickling, or burning sensation is common in the face, neck, back of the hands, and upper trunk andtypically lasts 60-90 minutes but is not a painful, serious, or harmful reaction. Use of divided doses or a sustained-release form of the supplement can attenuate paresthesia resulting from beta-alanine consumption [52,54]. Some research has also found that beta-alanine supplements can produce pruritus (itchy skin), but the authors do not indicate the severity of this effect [59]. There are no safety data on use of the supplement for more than 1 year [54,60] Implications for use: There is insufficient expert consensus on the value of taking beta-alanine to. enhance performance in intense, short-term activities or its safety, particularly when users take it regularly for at least several months. In a position statement, AND, DoC, and ACSM advise that beta- alanine supplementation might improve training capacity and does enhance performance, especially of high-intensity exercise lasting 60-240 seconds, that acid-base disturbances resulting from increased anaerobic glycolysis would otherwise impair [12]. In its position statement, ISSN concludes that beta- alanine supplementation improves exercise performance and attenuates neuromuscular fatigue [54]. The Australian Institute of Sport supports the use of beta- alanine for improving sports performance in suitable athletic competitions under the direction of an expert in sports medicine, but it notes that more research might be required to understand how the supplement should be used for best results (291 For healthy individuals willing to use beta-alanine supplements, ISSN recommends a daily loading dose of 4 to 6 g/day in divided doses of 2 g or less for at least 2 weeks. The society states that bepnefits increase after 4 weeks, when muscle carnosine concentrations rise by 40-60% [54]. It advises users to take beta-alanine supplements with meals to augment muscle carnosine levels and to use divided lower doses or take a sustained-release form if paresthesia occurs. Beta-hydroxy-beta-methylbutyrate Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the branched-chain amino acid leucine. About 5% of the body's leucine is converted into HMB, which is then converted in the liver to a precursor (known as beta-hydroxy-beta-methylglutaryl coenzyme A) needed for cholesterol biosynthesis [61]. Some experts hypothesize that skeletal muscle cells that become stressed and damaged from exercise require an exogenous source of the coenzyme for synthesis of cholesterol in their cellular membranes to restore structure and function [62,63]. Experts also believe that the conversion of leucine to HMB activates muscle protein synthesis and reduces protein breakdown [63] Supplementation is the only practical way to obtain 3 g/day HMB because one would otherwise need to consume over 600 g/day of high-quality protein (from 5 Ib of beef tenderloin, for example) to obtain enough leucine (60 g) for conversion into HMB [63] Efficacy: Although studies have investigated HMB for two decades, they have used substantially different periods of supplementation (1 day to 6 weeks) and daily doses (1.5 to 6 g; most commonly 3 g based on evidence that this dose provides equivalent results to 6 g and better results than 1.5 9) [61,63,64]. Studies also used participants of different ages (19 to 50 years), training status (e.g., untrained or trained athletes), training protocols (e.g., with machines or free weights), training duration (10 days to 12 weeks), consumption of other supplements (such as creatine), and other factors. itis,therefore difficult to predict what, if any, benefits an exercising individual might experience from consuming HMB. There is general agreement that HMB helps speed up recovery from exercise of sufficient amount and intensity to induce skeletal muscle damage [63,65]. Therefore, trained athletes must exert themselves more than untrained individuals to potentially benefit from using the supplement. Some studies suggest that HMB use has additional benefits, including an ability to enhance strength, power, skeletal muscle hypertrophy, and aerobic performance in both trained and untrained people [63] Safety: A review of safety data from nine studies found that users tolerate HMB well, and it is safe at daily intakes of 3 g for 3 to 8 weeks in younger (ages 18-47 years) and older (ages 62-81) adults of both sexes who do or do not exercise [66]. Assessments of blood chemistry, hematology, and emotional affect found no adverse effects. Another study randomized 37 untrained males aged 18-29 years participating in a resistance training program to take either no HMB or about 3-6 g/day HMB [62]. Use of HMB did not alter or adversely affect any measured hematologic, hepatic, or renal-function parameters in these young men. Although 3 g/day HMB appears to be safe for short-term use in adults, its safety profile (and efficacy) has not been studied in adolescents [63] Implications for use: There is no expert consensus on the value of taking HMB for several months or longer or its safety. HMB is not on alist of evidence-based ergogenic aids issued by the AND, DoC, and the ACSM [12]. The Australian Institute of Sport does not recommend HMB supplementation by athletes, except as part of a research protocol or with proper monitoring [29]. However, ISSN notes that HMB can enhance recovery by reducing exercise-induced skeletal muscle damage in both trained and untrained individuals [63] HMB is available in two forms: as a mono-hydrated calcium salt (HMB-Ca) and a calcium-free form (HMB-free acid [HMB-FA]). HMB-Ca is approximately 13% calcium by weight, and a daily dose of 3 g/day adds about 400 mg calcium to the diet [66]. Those who wish to limit their calcium intake can use HMB-FA [63]. Although the latter form appears to have a faster and greater effect based on its ability to raise HMB plasma levels, more studies are needed to compare the effects of HMB-Ca with those of HMB-FA [63] The ISSN recommends that healthy adults interested in using HMB supplements take 1-2 g HMB-Ca 60 to 120 minutes before exercise or 1-2 g HMB-FA 30 to 60 minutes before exercise [63]. It also suggests that supplement users ideally consume 3 g/day HMB (in three equal servings of 1 g) for at least 2 weeks before high-intensity exercise to optimize HMB's protective effects on muscle. Betaine Betaine, also known as trimethylglycine, is found in foods such as beets, spinach, and whole-grain breads. Average daily intakes of betaine range from 100 to 300 mg/day [67]. The mechanisms by which betaine might enhance exercise and athletic performance are not known, but many are hypothesized For example, betaine might increase the biosynthesis of creatine, levels of blood nitric acid, and/or the water retention of cells [68].Efficacy: A limited number of small studies in men have assessed betaine in supplemental form as a potential ergogenic aid. These studies, which typically examined strength- and power- based performance in bodybuilders and, occasionally, cyclists, provided conflicting results, and performance improvements tended to be modest [68-71]. The typical dose of betaine that studies used ranged from 2.to 5 g/day [21] for up to 15 days. Safety: The several small studies of athletes described in the previous paragraph who took betaine supplements for up to several weeks found no side effects or safety concerns, However, research has not adequately evaluated the safety of betaine. Implications for use: More research on betaine supplementation to enhance various types of performance, training protocols, and exercise during specific sports is needed before any recommendations for its use can be made [Z1] Branched-chain amino acids Three essential amino acids—leucine, isoleucine, and valine—are the branched-chain amino acids (BCAAs), whose name reflects their chemical structure. BCAAs make up approximately 25% of the amino acids in foods containing complete proteins (including all essential amino acids) [72]; most of these foods are animal products, such as meat, poultry, fish, eggs, and milk (see section on protein). BCAAs comprise about 14%-18% of the amino acids in human skeletal muscle proteins [Z3]. Unlike other essential amino acids, the BCAAs can be metabolized by mitochondria in skeletal muscle to provide energy during exercise [74,75]. The BCAAs, especially leucine, might also stimulate protein synthesis in exercised muscle [72,76]. Efficacy: The limited research on the potential ergogenic effects of the BCAAs has found little evidence to date that supplements of these amino acids improve performance in endurance-related aerobic events [75]. The BCAAs might delay feelings of fatigue or help maintain mental focus by competing with the amino acid tryptophan (a precursor of the neurotransmitter serotonin that regulates mood and sleep) for entry into the brain, but this effect has not been well studied [72.74.75]. The results of several short-term studies lasting about 3 to 6 weeks suggest that about 10-14 g/day supplemental BCAAs might enhance gains in muscle mass and strength during training [1]. Overall, however, studies to date provide inconsistent evidence of the ability of BCAAs to stimulate muscle protein synthesis beyond the capacity of sufficient dietary amounts of any high-quality protein to perform this function [76] Furthermore, it is not clear from existing research whether consumption of protein and BCAAs before versus after a workout affects their ability to maximize muscle protein synthesis and reduce protein catabolism [12,77-79]. Safety: Up to 20 g/day BCAA supplements in divided doses appear to be safe [75]. For leucine alone, studies suggest an upper safe limit of intake of 500 mg/kg per day in healthy young and elderly men, or about 38 g/day for a man weighing 75 kg (165 Ib) [80-82 Implications for use: Studies have not consistently shown that taking supplements of BCAAs or any of their three constituent amino acids singly enhances exercise and athletic performance, builds musclemass, or aids in recovery from exercise. Consuming animal foods containing complete proteins—or a combination of plant-based foods with complementary proteins that together provide all essential amino acids—automatically increases consumption of BCAAs (see section on protein). This is also true of consuming protein powders made from complete proteins, especially whey, which has more leucine than either casein or soy [78]. Caffeine Caffeine is a methylated xanthine naturally found in variable amounts in coffee; tea; cacao pods (the source of chocolate); and other herbal/botanical sources, such as guarana, kola (or cola) nut, and yerba mate. Caffeine stimulates the central nervous system, muscles, and other organs, such as the heart, by binding to adenosine receptors on cells, thereby blocking the activity of adenosine, a neuromodulator with sedative-like properties [83,84]. in this way, caffeine enhances arousal, increases vigor, and reduces fatigue [13,85,86]. Caffeine also appears to reduce perceived pain and exertion [13,85]. During the early stages of endurance exercise, caffeine might mobilize free fatty acids as a source of energy and spare muscle glycogen [38] Caffeine is commonly used in energy drinks and “shots” touted for their performance-enhancement effects [87,88]. It is also found in energy gels containing carbohydrates and electrolytes as well as in anhydrous caffeine-only pills. Efficacy: Many studies have shown that caffeine might enhance performance in athletes when they ingest about 2-6 mg/kg body weight before exercise by improving endurance, strength, and power in high-intensity team sports activities [13,85,89,90]. For an individual weighing 154 pounds (70 kg), this dose is equivalent to 210-420 mg caffeine. Taking more, however, is unlikely to improve performance further and increases the risk of side effects A review of the literature found that caffeine intake affected sport-specific performance (e.g., running, cycling, swimming, and rowing), as measured in time trials. Although 30 of the 33 trials showed positive improvements in performance, the improvements were not statistically significant in half of them [85]. In these studies, performance improvement ranged from a decrease of 0.7% to an increase of 17.3%, suggesting that the caffeine was very helpful to some participants but slightly impaired performance in others. Factors such as the timing of ingestion, caffeine intake mode or form, and habituation to caffeine could also have accounted for the varied effects on performance. Caffeine supplementation is more likely to help with endurance-type activities (such as running) and activities of long duration with intermittent activity (such as soccer) than more anaerobic, short-term bouts of intense exercise (such as sprinting or lifting weights) [91]. Some evidence suggests that caffeine is more likely to improve performance in people who are not habituated to it [85]. Limiting caffeine intake to 50 mg/day or abstaining from caffeine for 2-7 days before taking it for an athletic event might maximize any ergogenic effect. However, other evidence shows no habituation effect of caffeine consumption on performance [92].Safety: Heavy caffeine use (500 mg/day or more) might diminish rather than enhance physical performance and could also disturb sleep and cause irritability and anxiety [93]. Other adverse effects of caffeine include insomnia, restlessness, nausea, vomiting, tachycardia, and arrhythmia [94-97] Caffeine does not induce diuresis or increase sweat loss during exercise and therefore does not reduce fluid balance in the body that would adversely affect performance [13.90.98] For healthy adults, the U.S. Food and Drug Administration (FDA) states that 400 mg/day caffeine does not usually have dangerous adverse effects [99]. The American Medical Association recommends that adults limit their intake of caffeine to 500 mg/day and that adolescents consume no more than 100 mg/day [100]. The American Academy of Pediatrics warns that caffeine-containing energy drinks in particular “have no place in the diets of children or adolescents” and are not suitable for use during routine physical activity [101] Pure powdered caffeine is available as a dietary supplement and is very potent. A single tablespoon contains 10 g caffeine, and an acute oral dose of 10 to 14 g caffeine (approximately 150-200 mg/kg) can be fatal [91]. Furthermore, combining caffeine with other stimulants could increase the potential for adverse effects [94]. At least two young men have died as a result of taking an unknown amount of pure powdered caffeine [102]. Implications for use: Caffeine is easily and rapidly absorbed, even from the buccal membranes in the mouth, and is distributed throughout the body and brain. It reaches peak concentrations in the blood within 45 minutes of consumption and has a half-life of about 4-5 hours [83]. For a potential benefit to athletic performance, users should consume caffeine 15 to 60 minutes before exercise [13,85]. Consumption of caffeine with fluid during exercise of long duration might extend any performance improvements [85]. Ina position statement, AND, DoC, and ACSM state that caffeine supplementation reduces perceived fatigue and enables users to sustain exercise at the desired intensity longer [12]. The U.S. Department of Defense states that caffeine supplementation at 2-6 mg/kg body weight is linked to enhanced physical performance and the effects of smaller doses usually last longer and are greater in people who do not usually consume caffeine [89]. It adds that caffeine could reduce perceived exertion when exercise lasts longer. In a position statement, ISSN describes caffeine as effective in trained athletes for improving sports performance and notes that supplementation with about 3-6 mg/kg has an ergogenic effect on “sustained maximal endurance exercise” but not necessarily on “strength-power performance” [13]. The Australian Institute of Sport supports the use of caffeine for improving sports performance in suitable athletic competitions under the direction of an expert in sports medicine, but it notes that more research might be required to understand how caffeine should be used for best results [29]. The International Olympic Committee considers caffeine to be a “controlled or restricted substance,” Olympic athletes may consume it until urinary concentrations exceed 12 meg/mi [103]. The National Collegiate Athletic Association prohibits use of caffeine from any source in amounts that would lead to urine concentrations exceeding 15 mcg/ml [104,105]. (Consuming about 500 mg caffeine produces aurinary caffeine concentration of 15 meg/ml within 2-3 hours [106].) The World Anti-Doping Agency does not prohibit or limit caffeine use [107 Citrulline Lcitrulline is a nonessential amino acid produced in the body, mainly from glutamine, and obtained from the diet. Watermelon is the best-known source; 1 cup diced seedless watermelon has about 365 mg citrulline [108]. About 80% of the body's citrulline is converted in the kidneys into arginine, another amino acid (see section on arginine) [30]. The subsequent conversion of arginine to nitric oxide, a potent dilator of blood vessels, might be the mechanism by which citrulline could serve as an ergogenic aid. In fact, consumption of citrulline might be a more efficient way to raise blood arginine levels than consumption of arginine because more citrulline is absorbed from the gut than arginine. Most studies have used citrulline malate, a combination of citrulline with malic acid (a constituent in many fruits that is also produced endogenously), because malate, an intermediate in the Krebs cycle, might enhance energy production [30] Efficacy: The research to support supplemental citrulline as an ergogenic aid is limited and conflicting at best. The few published studies have had heterogeneous designs and ranged in duration from 1 to 16 days. As an example, in one randomized controlled study with a crossover design, 41 healthy male weight lifters aged 22-37 years consumed 8 g citrulline malate or a placebo 1 hour before completing barbell bench presses to exhaustion [109]. Overall, participants could complete significantly more repetitions when taking the supplement and reported significantly less muscle soreness 1 and 2 days after the test. Another study that randomized 17 young healthy men and women to take citrulline without malate (either 3 g before testing or 9 g over 24 hours) or a placebo found that participants using the citrulline did not perform as well as those taking the placebo on an incremental treadmill test to exhaustion [110]. Although citrulline supplementation might increase plasma levels of nitric oxide metabolites, such a response has not been directly related to any improvement in athletic performance {30} Safety: Studies have not adequately assessed the safety of citrulline, particularly when users take it in supplemental form for months at a time. In the study of weight lifters described above, 6 of the 41 participants reported “stomach discomfort” after taking the supplement [109]. Additional short-term studies in which supplemental citrulline was provided to non-athletes at up to 6 g/day for 4 weeks and 1.35 g/day for 6 weeks found no adverse effects [111] Implications for use: The research to date does not provide strong support for taking citrulline or citrulline malate to enhance exercise or athletic performance [30]. Whether athletes in specific sports or activities might benefit from taking supplemental citrulline remains to be determined [109 Dietary supplements that contain citrulline provide either citrulline or citrulline malate. Citrulline malate is 56.64% citrulline by weight so, for example, 1 g citrulline malate provides 566 mg of citrulline. Sellers of some citrulline malate dietary supplements claim that they provide a higher percentage of citrulline (with labels listing, for example, citrulline malate 2:1 or tri- citrulline malate), but studies have not