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Supplements and Performance Enhancers Family Medicine Review, Austin, Texas (2012) R. Marc Via, MD Educational Objectives: 1. Counsel athletes about adequate intake of carbohydrates, proteins, and fat before and after physical activity. 2. Address vitamin D, iron, and sodium deficiency in athletes. 3. Explain efficacy and safety of supplements used to improve muscle strength and power, such as creatine. 4. Review side effects of anabolic steroids. 5. Discuss off-label use of growth hormone and banned performance enhancers. Faculty Disclosures: I have no personal or financial relationships with any of the products/topics discussed or mentioned in this lecture. Sport/General Nutrition 101: Optimum nutrition may help maximize athletic performance by: Maximizing energy stores Achieving ideal weight for performance Ensuring sufficient intake of vitamins and minerals Maintaining adequate hydration Optimizing pre-competition and competition food intake Aiding recovery from intense training Energy Production: The source of energy in humans is ATP. Production of ATP is accomplished by breaking down nutrients such as sugar, amino acids, and fatty acids. Energy needed to perform short lasting, high intensity bursts of activity is derived from anaerobic sources within the cytosol of muscle cells, as opposed to aerobic respiration which utilizes oxygen, is sustainable, and occurs in the mitochondria. Anaerobic metabolism provides quick energy sources and consists of phosphocreatine system (supplies creatine phosphate stores), fast glycolysis, and adenylate kinase. All of these systems re-synthesize ATP. ATP within muscle cells depleted within 5-10 seconds of high intensity activity. Most rapid source is phosphorcreatine system utilizing the enzyme creatine kinase. Depleted in about 10-15 seconds of high intensity activity. Gylcolysis breaks down glucose (obtained from muscle glycogen via glycogen phosphorylase) into pyruvate, which can then be either be reduced to lactic acid 1 (providing ATP in the process) or funneled through the Kreb’s cycle. Fast glycolysis refers to the “fate” of pyruvate. which yields ATP and lactic acid. This process promotes acidosis and therefore cannot be sustained for long periods of time.7 Fast glycolysis can function for approximately 2 minutes prior to fatigue (lactate inhibits function ultimately).3,4 Adenylate cyclase catalyzes a reaction by which 2 ADP are combined to form ATP and AMP. This reaction takes place under extreme exercise and hypoxic circumstances, but is not a significant source of energy. Aerobic metabolism requires oxygen in order to generate energy (ATP). Under these circumstances, pyruvate is converted into acetyl coenzyme A instead of lactic acid and is funneled to the mitochondria and the Kreb’s cycle. Kreb’s cycle produces ATP, CO2, and H+. The H+ combines with two enzymes, NAD and FAD, and is transported to the electron transport chain. The electron transport chain requires oxygen (oxidative phosphorylation) and, through a series of chemical reactions, produces 34 ATP and H2O. Total yield under ideal circumstances from one glucose molecule is 36-38 ATP. Beta Oxidation Unlike glycolysis, the Krebs cycle and electron transport chain can metabolise fat as well as carbohydrate to produce ATP. Lipolysis is the term used to describe the breakdown of fat (triglycerides) into the more basic units of glycerol and free fatty acids. Before these free fatty acids can enter the Krebs cycle they must undergo a process of beta oxidation... a series of reactions to further reduce free fatty acids to acetyl coenzyme A and hydrogen. Acetyl coenzyme A can now enter the Krebs cycle and from this point on, fat metabolism follows the same path as carbohydrate metabolism. The key difference between production of ATP from fat versus carbohydrate is that complete combustion of a fatty acid molecule produces significantly more acetyl coenzyme A and hydrogen (and hence ATP) compared to a glucose molecule. However, because fatty acids consist of more carbon atoms than glucose, they require more oxygen for their combustion. So if your body is to use fat for fuel it must have sufficient oxygen supply to meet the demands of exercise. If exercise is intense and the cardiovascular system is unable to supply cells with oxygen quickly enough, carbohydrate must be used to produce ATP. Put another way, if you run out of carbohydrate stores (as in long duration events), exercise intensity must reduce as the body switches to fat as its primary source of fuel. Protein Metabolism Protein is thought to make only a small contribution (usually no more 5%) to energy production and is often overlooked. However, amino acids, the building blocks of protein, can be either converted into glucose or into other intermediates used by the Krebs cycle such as acetyl coenzyme A. Protein may make a more significant contribution during very prolonged activity, perhaps as much as 18% of total energy requirements. 2 The oxidative system as a whole is used primarily during rest and low-intensity exercise. At the start of exercise it takes about 90 seconds for the oxidative system to produce its maximal power output and training can help to make this transition earlier. Beyond this point the Krebs cycle supplies the majority of energy requirements but slow glycolysis still makes a significant contribution. In fact, slow glycolysis is an important metabolic pathway even during events lasting several hours or more. Energy Stores: Carbohydrate and fat are the two main energy sources used in athletic activity.1 Protein makes relatively small contribution apparent with depletion of carbohydrate stores and inadequate energy intake. Carbohydrates: Simple – monosaccharides (e.g., glucose, galactose, fructose). Disaccharides (e.g., glucose + fructose = sucrose and glucose + galactose = lactose). Rapidly utilized for energy production directly or indirectly via glycogen production. Complex – oligosaccharides (e.g., saccharide polymer containing 2-10 monosaccharides) and polysaccharides (long carbohydrate molecules of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched). Sources include: foods such as whole grains, fruits, vegetables, legumes and body storage forms such as muscle and liver glycogen. Average amount of energy available from stored carbohydrate (i.e., glycogen) is about 2000 kcal, which would provide fuel for a run of approximately 25 miles. Untrained individuals have muscle glycogen stores of 80-90 mmol/kg, whereas trained individuals may have muscle stores as high as 130-135 mmol/kg. 1.0 gram of carbohydrates provides 4.2 kcal (extra intake leads to glycogen storage or conversion to fat or protein). Athletes need 5-10 g/kg per day and diet composed of 60%-70% carbohydrates. Fats: Provides the body’s largest store of potential energy. 1.0 gm fat supplies 9.0 kcal. Body fat varies; however, even the leanest athlete has about 7 kg fat (enough energy to run 750 miles). Vitamins A, D, E, and K are fat soluble. Proteins: Major role for athletes to repair and build muscle tissue. Can be used as fuel; however, contribution relatively small: 5-10% of total energy needs. 3 Amino acids can be converted to glucose. Branched-chain amino acids (valine, leucine, isoleucine) directly converted to acetyl coenzyme A to be oxidized. 1.0 gm protein supplies 4.1 kcal. 0.6-0.8 g/kg per day needed. Strength and power athletes need 2.0 g/kg per day. Aerobic athletes need 1.5 kg/kg per day. Contribution of protein to total energy increases with duration of exercise and depletion of carbohydrate stores.2 Energy Systems and Training: Each of the three energy systems can generate power to different capacities and varies within individuals. Best estimates suggest that the ATP-PCR systme can generate energy at a rate of roughly 36 kcal per minute. Glycolysis can generate energy only half as quickly at about 16 kcal per minute. The oxidative system has the lowest rate of power output at about 10 kcal per minute.6 The capacity to generate power of each the three energy systems can vary with training. The ATP-PCr and glycolytic pathways may change by only 10-20% with training. The oxidative system seems to be far more trainable although genetics play a limiting role here too. VO2max, or aerobic power can be increased by as much as 50% but this is usually in untrained, sedentary individuals.6 The three energy systems do not work independently of one another. From very short, very intense exercise, to very light, prolonged activity, all three energy systems make a contribution however, one or two will usually predominate.7 Two factors of any activity carried out affect energy systems more than any other variable they are the intensity and duration of exercise. Here is a list of sports and approximately how the each of the energy systems contributes to meet the physical demands: 4 Water: Water comprises about 60-70% of a person's body weight. Because muscle tissue is 7075% water, the body weights of lean, muscular athletes may exceed 70% water. Inadequate fluid intake will have powerful negative effects on blood, brain, and muscle. Essential functions of water for athletes include maintaining normal body temperature and normal blood volume. Because these functions are critical to survival as well as to athletic training and performance, athletes need to drink enough fluid throughout the day to replace water lost in sweat, respiration, urine, and feces. Research has shown that depending on the temperature, humidity and overall conditioning, athletes engaged in vigorous exercise can lose 1500-3500 ml of sweat and 1300-5000 mg of sodium per hour. Several studies have also demonstrated that on average, women lose much less fluid through sweat than men, an average of 450-570 ml per hour compared to 780-1120 ml per hour for men. Fluid needs are linked to energy expenditure. Heat is a byproduct of energy production, and excess heat must be transferred from the body to the environment to maintain normal body temperature. Evaporation of sweat from the athlete's body is the primary way of dissipating excess heat. To maintain adequate hydration, sweat loss must be replaced. Consuming 1.0 to 1.5 ml of fluid for each kilocalorie that is expended is optimal. Thus, an athlete who expends 5,000 calories a day needs 5,000 to 7,500 ml (5.07.5 L) of fluid intake a day to maintain fluid balance. Fluid consumption includes all liquids plus water in foods.8,9 Supplement with 3-6 ounces every 15 minutes. 16-fl oz required after exercise if 1 lb of body weight loss. Minerals: Minerals are essential for a wide variety of metabolic and physiologic processes in the human body. Some of the physiologic roles of minerals important to athletes are their involvement in: muscle contraction, normal hearth rhythm, nerve impulse conduction, oxygen transport, oxidative phosphorylation, enzyme activation, immune functions, antioxidant activity, bone health, and acid-base balance of the blood. The two major classes of minerals are the macrominerals and the trace elements. Although all minerals may play a role in a variety of metabolic and physiologic processes, this presentation will focus on those minerals that have received research attention or consideration relative to effects on physical performance or health of the athlete. These include: sodium, potassium, calcium, iron, phosphates, magnesium, zinc, chromium, boron, and vanadium. Mineral Deficiencies: Iron o Iron is important in hemoglobin synthesis, but also for myoglobin in muscle, many enzymatic reactions including the cytochrome oxidase system (responsible for generating ATP). o Normal ferritin level is 8-10 ng/mL. o In athletes 40 ng/mL is recommended by many experts (there is not consensus on this value), especially in the context of low-normal hemoglobin.11, 12 5 o Deficiency may be due to poor dietary intake, especially in female athletes who do not eat meat. o Much is lost during exercise; e.g., 90% of distance runners test positive for occult blood in their stool. o Reasonable diets include 5 to 7 mg iron per 1,000 kcal. o Consider checking ferritin and hemoglobin in at risk individuals (runners, endurance athletes, females, eating disorders, and medical risks such as sickle trait/disease, thalessemia, etc.) or those who have had a significant drop in their performance (expert opinion). o A low hemoglobin requires a thorough workup, regardless. Calcium o Calcium is important for bone health, muscle contraction; however, it is not considered an ergogenic aid as muscle tissue can draw on the vast bone stores available. o Athletes at risk for low calcium (hence risk for stress fractures, later osteoporosis, etc.) are young women involved in weight-control sports such as figure skating and distance running.13 o High intensity training in endurance athletes has been shown to significantly increase urinary calcium excretion.14 o Long distance runners with oligomenorrhea have greater decreases in bone mineral density in the spine compared with eumenorrheic runners with similar energy, calcium, and protein intakes.15 o Consider calcium supplementation with vitamin D in the female athlete triad (disordered eating, amenorrhea, osteoporosis.15, 16 o Adequate calcium intake especially important for girls 6 months before menarche.16 Sodium o Extremely important for the athlete for optimized performance, avoidance of dehydration, avoidance of hyponatremia, and recovery after training/competition. o Most is lost through sweat and is associated with muscle cramping in athletes. o Sodium loss via sweat can be calculated by multiplying sweat concentration (e.g., 50 mmol/L x 0.0263) by volume of sweat loss (i.e., weight loss during exercise). For example, an athlete loses 10 lb during competition and has average sweat concentration of 50 mmol/L, then the athlete loses 13 grams of sodium. Concentration of sodium in sweat can vary typically between 30-65 mmol/L.17 Concentrations in athletes can reach >90 mmol/L. o If athlete routinely loses >5 pound, then consider supplementing with 1gm salt tablets and 16 fl ounces of water for every pound lost over 5 pounds (use as a guideline). 20-fl oz bottle of sports drink contains 0.7 grams sodium. 6 Magnesium o Magnesium is a component of over 300 enzymes, some involved in the regulation of muscle contraction, oxygen delivery, and protein synthesis. o Several studies have investigated the effect of magnesium supplementation on performance. Lukaski noted that some earlier studies have shown that magnesium supplementation improved strength and cardiorespiratory function in healthy persons and athletes, but also noted it is unclear as to whether these observations related to improvement of an impaired nutritional status or a pharmacologic effect.18, 19 o Recent research has demonstrated a popular supplement called Sport Legs (contains calcium lactate monohydrate, magnesium lactate monohydrate, and calcium lactate monohydrate) does not improve performance in 20 km time trial in cyclists.20 Phosphates o Phosphates are incorporated into many compounds in the body that are involved in energy metabolism, such as ATP as an energy substrate, thiamin pyrophosphate as a vitamin cofactor, sodium phosphate as a buffer, and 2,3- diphosphoglycerate (2,3-DPG) for RBC function. All of these roles could provide ergogenic potential, but the most researched theory involves the effect of phosphate salt supplementation on 2,3-DPG. o Several studies have demonstrated impressive increases in performance at VO2 max effort (such as 40 km time trials)21-24; however, there has been criticism citing potential confounders and other trials have not demonstrated the same effects on performance. o No trials have demonstrated a decrease in performance. o Studies have consistently demonstrated improvement in performance during the first two days at altitude when supplementing 1 gram 4 times daily starting several days prior to travel and throughout stay at altitude. This effect begins to diminish after 2-3 days at altitude.25, 26 Vitamins: A vitamin is an organic compound required as a vital nutrient in tiny amounts by an organism.10 In other words, an organic chemical compound (or related set of compounds) is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. This presentation will consider the role of vitamin D and B12 in the athlete. Vitamin B12 o Also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins. It is normally involved in the metabolism of every cell of the human body, especially affecting DNA synthesis and regulation, but also fatty acid synthesis and energy production. It is the largest and most structurally complicated vitamin and 7 can be produced industrially only through bacterial fermentationsynthesis. o B12 (along with B1, B6) believed to affect the formation of seratonin, which is involved, among other things, with relaxation. Some research with large doses (60-200 times the RDA) of these vitamins has shown increases in fine motor control and performance in pistol shooting. Others have suggested that the beneficial effect was related to the role of these vitamins in promoting the development of neurotransmitters that induce relaxation.27 o Consider supplementing in vegetarians (expert opinion). Vitamin D o Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it (as vitamin D3) when sun exposure is adequate. o Although there is no consensus on optimal levels of 25-hydroxyvitamin D as measured in serum, vitamin D deficiency is defined by most experts as a 25-hydroxyvitamin D level of less than 20 ng per milliliter (50 nmol per liter).28-31 o Vitamin D deficiency causes muscle weakness.32-35 o Skeletal muscles have a vitamin D receptor and may require vitamin D for maximum function.32, 34 o Performance speed and proximal muscle strength were markedly improved when 25-hydroxyvitamin D levels increased from 4 to 16 ng/mL and continued to improve as the levels increased to more than 40 ng/mL.34 o Given data from several studies36-39, a level of 25-hydroxyvitamin D of 21 to 29 ng/mL can be considered to indicate a relative insufficiency of vitamin D, and a level of 30 ng/mL or greater can be considered to indicate sufficient vitamin D.40 Vitamin D intoxication is observed when serum levels of 25-hydroxyvitamin D are greater than 150 ng/mL. o Vitamin D may improve athletic performance in vitamin D-deficient athletes. Peak athletic performance may occur when 25-hydroxyvitamin D levels approach those obtained by natural, full-body, summer sun exposure, which is at least 50 ng/mL. Such 25-hydroxyvitamin D levels may also protect the athlete from several acute and chronic medical conditions. o Consider supplementation with vitamin D3 (more bioavailability). o Encourage appropriate sun exposure (best source). “Game Day” Nutrition: Consider “tapering” physical activity (typically involves decreasing overall volume while keeping intensity high) the week prior to competition depending on event and point in training cycle. If tapering physical activity be mindful of decreased caloric needs. Consider additional carbohydrate during the 48 hours prior to event. 8 24 hours prior to competition, consider very brief workout with 4-5 intervals of high intensity efforts lasting no more than one minute with full recovery between. Concept is super-saturation of muscle glycogen. NOTE: the taper will need to be tailored to sport, demands, and duration of competition. NEVER try new foods, drinks, protocols before competition. Always experiment with nutrition changes during training. Adequate salt (depends on event) and fluid intake (want urine to be clear). Solid foods 2-3 hours prior to competition. Avoid glucose in the hour before event (insulin drives down blood glucose and may affect mental performance). Avoid fructose in the hours prior to event (some athletes get GI upset secondary to delayed gastric emptying caused by fructose). Consider glucose 10-15 minutes prior to event especially if endurance (e.g., GU, Cliff Shots, etc.). During event: prevent dehydration (fluid intake), cramps (sodium containing fluid), hyponatremia (avoid hypotonic fluids). After event: depends on next competition, training schedule, etc. However, quickly replace carbohydrates within 30 minutes after event (and training) to replenish glycogen stores. System is geared to absorb and assimilate carbohydrates after exercise. Most efficient if carbohydrates are combined with protein in 3:1 (carb:protein) ratio (e.g., Accelerade). Replace fluid (16 ounces for each pound lost) and sodium (calculate/estimate from above stated guideline). Ergogenic Aids: Ergogenic aids are any external influences that can be determined to enhance performance. These include mechanical aids (such as ergogenic fabrics), pharmacological aids, physiological aids, nutritional aids (sports supplements), and psychological aids. Branched-chain amino acids o Valine, leucine, isoleucine are oxidized for energy. o Not found to improve performance; may affect muscle recovery and immune response to exercise but the evidence is weak.42 o Still regularly used by athletes. L-Glutamine o Glutamine is a naturally occurring non-essential amino acid that is commonly stored in muscles and released into the blood stream during times of stress. It is used by the immune system during times of stress such as physical trauma, burns, starvation, and even during prolonged and intense exercise such as training for marathons. When there is a deficiency of glutamine or when the amount of glutamine is drastically reduced during increased stress, the body experiences a suppression of the immune system until glutamine levels are restored through either diet or supplements. o Acts as a nitrogen donor and promotes protein synthesis. o Studies have demonstrate mixed results: some demonstrating decreased illness following intense training/competition and possible improved 9 muscle recovery, while others have not. No studies to date have demonstrated harm or decreased performance.43-48 Hydroxymethylbutyrate (HMB) o HMB is a chemical that occurs naturally in the body when the amino acid leucine breaks down. o Leucine is found in particularly high concentrations in muscles. During athletic training, damage to the muscles leads to the breakdown of leucine as well as increased HMB levels. Evidence suggests that taking HMB supplements might signal the body to slow down the destruction of muscle tissue. However, while promising, the research record at present is contradictory and marked by an absence of large studies. o The evidence supports its use in novices or strength training individuals during the first 3-6 weeks of initiating exercise/training. o Overall, efficacy is not supported by research.49-74 Creatine o Creatine monohydrate (Cr) is perhaps one of the most widely used supplements taken in an attempt to improve athletic performance. o It is hypothesized that Cr can act though a number of possible mechanisms as a potential ergogenic aid but it appears to be most effective for activities that involve repeated short bouts of high-intensity physical activity. Additionally, investigators have studied a number of different Cr loading programs; the most common program involves an initial loading phase of 20 g/day for 5–7 days, followed by a maintenance phase of 3–5 g/day for differing periods of time (1 week to 6 months).75 o Average creatine phosphate levels 90-160 grams. If genetically, athlete is on high end, probably not helpful (no way to know this clinically). o Evidence supports improved performance in power sports: e.g., sprintin, power-lifting, jumping. o Improves muscle strength and power. o One study noted improvement in testosterone profile, suggesting anabolic properties (not been repeated and correlation does not prove causality). o Increases body weight (water retention). o Does not cause kidney failure. o May cause muscle cramping. o References.76-82 Bicarbonate Loading o During high-intensity exercise, energy needs are mainly provided by anaerobic glycolysis. This is associated with a high level of lactic acid production, its dissociation into hydrogen ions and lactate ions, within physiologic pH ranges, and a concomitant fall in blood and muscle pH. Decreases in pH produce fatigue, defined as a decrease in force production in the presence of increased perception of effort. o Bicarbonate binds with lactic acid to decrease acidosis. 10 o 300-500 mg/kg 1 hour before exercise improves performance limited by lactic acid (high-intensity exercises that last >15 seconds; e.g., 400- and 800-meter races. o Not banned. o Can cause GI upset. o References.83-90 Anabolic Steroids o Anabolic steroids are drugs that mimic the effects of testosterone and dihydrotestosterone in the body. They increase protein synthesis within cells, which results in the buildup of cellular tissue (anabolism), especially in muscles. o Oral and injecable agents. o Approximately 10% high school boys and 3%-5% of girls have used anabolic steroids. o Effects: increased muscle mass, spermatogenesis, and protein synthesis, increased hematopoiesis, increased aggression, increased libido in men and women, increased muscle strength and power, and improved recovery after exercise. o Side effects: long-term cardiovascular (cardiomyopathy with decades-long use), psychogenic effects, parkinsonism. Approximately 30% of anabolic steroid users have problems with dependence or manic depression during or after use. o Anabolic steroids have been demonstrated to improve athletic performance in both power and endurance sports.91 o Banned substance. Human Chorionic Gonadatropin o Taken for approximately 4 weeks when tapering off anabolic steroids to allow endogenous testosterone to rebound. o Side effects: morning sickness. Growth Hormone o Major effects through stimulation of insulin-like growth factor 1 production in liver (associated with anabolic effects). o Increases amino acid uptake of muscle. o Increases protein synthesis o Decreases glucose utilization. o Increases collagen synthesis, axial growth, muscle hypertrophy, endurance, and growth. o Decreases body fat, enhances healing. o Often used in combination with anabolic steroids. o Banned substance. Blood Doping o Blood transfusion: increases oxygen-carrying capacity o Leads to longer duration of aerobic exercise. 11 o Blood taken months before competition and stored. o Transfusion of 2 units PRBCs during competition improves performance significantly. o Erythropoietin: improves red cell mass and oxygen-carrying capacity. o Can cause clotting problems and death. o Banned. Stimulants o Effective. o Studied in military personnel. o Improves performance, concentration, and wakefulness. o Sympathomimmetics (i.e., amphetamines). o Β-agonists: albuterol (banned). Improves performance in certain athletes. Clenbuterol (not available in US) has anabolic properties, builds tissue, antilipolytic; improves fat metabolism, preserves glycogen stores. Β-Blockers o Used by competitors who need slowed heart rate and decreased anxiety for performance; e.g., shooting, archery, golfers, etc. o Banned. Diuretics o Used for weight loss and masking doping agents in urine. o Banned. 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