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Nutritional Ergogenic Aids
Chapter 26 Nutritional Ergogenic Aids* MELVIN H. WILLIAMS AND BRIAN C. LEUTHOLTZ Introduction The optimal production, control and efficiency of human energy is the key composite determinant of all muscular power for movement in sport. In general, as noted in previous chapters, sport scientists recognize three major human muscle energy systems important for the generation of adenosine triphosphate (ATP) for muscle contraction and subsequent power production. The ATP–phosphocreatine (ATP–PCr) energy system, which uses adenosine triphosphate and creatine phosphate as its fuel sources, generates maximal anaerobic power for very short periods of time, such as 10 s for a 100-m dash. The lactic acid energy system, which utilizes carbohydrate via anaerobic glycolysis, is capable of sustaining high anaerobic power production, such as 45 s for a 400-m run. The oxidative energy system, which uses carbohydrates via aerobic glycolysis and fats via b-oxidation, can sustain aerobic power for prolonged endurance events, such as 130 min for a 42.2-km marathon. The three human muscle energy systems depend on various dietary nutrients for optimal functioning. Dietary carbohydrates and fats, two of the macronutrients, provide the main sources of energy. Protein, another macronutrient, may also serve as an energy source, but as the amino * Small segments of this chapter have been extracted from Melvin H. Williams, The Ergogenics Edge: Pushing the Limits of Sports Performance, Human Kinetics Publishers, Champaign, IL, 1998. 356 acids released by protein degradation are either reutilized or oxidized, the amount of protein oxidized per day must be replenished by dietary intake. Protein is utilized primarily to synthesize muscle tissue that serves as the structural basis for energy production, and to synthesize enzymes, hormones, and other physiological substances that, along with vitamins and minerals (micronutrients), help regulate the myriad of neural, hormonal and metabolic processes involved in the release of energy from carbohydrates and fats for use during sport-related exercise tasks. Most sport nutritionists recommend that athletes consume a balanced diet of macronutrients and micronutrients to provide adequate energy, regulate metabolic processes properly, and maintain an optimal body mass specific to their sport. In general, dietary guidelines for healthy eating developed for the average population are also applicable to athletes. However, considerable research effort has been expended to determine whether or not dietary manipulation may be able to enhance sport performance, and much of this research has focused on the identification and development of specific nutritional ergogenic aids. Nutritional ergogenic aids are purported to enhance sport performance beyond that associated with the typical balanced diet. The major categories targeted to physically active individuals include: megadoses of essential nutrients, such as 1000 mg of vitamin C; engineered metabolic byproducts of essential nutrients, such as b- nutritional ergogenic aids hydroxy-b-methylbutyrate (HMB) from leucine; nutraceuticals or phytochemicals, non-drug substances found in plants that are purported to affect metabolism, such as ginseng; non-essential nutrients, such as creatine; and drug nutrients, legal drugs found naturally in foods or beverages consumed by humans, such as alcohol and caffeine. Examples of these nutritional ergogenic aids can be categorized as follows. 1 Megadoses of essential nutrients: (a) amino acids: arginine, ornithine, lysine and tryptophan; (b) vitamins: vitamin B12, vitamin C and vitamin E; (c) minerals: boron, chromium and phosphates. 2 Engineered metabolic by-products of essential nutrients: (a) HMB (b-hydroxy-b-methylbutyrate); (b) DHAP (dihydroxyacetone plus pyruvate); (c) FDP (fructose diphosphate). 3 Non-essential nutrients: (a) carnitine; (b) choline; (c) glycerol; (d) inosine. 4 Plant extracts (phytochemicals): (a) gamma oryzanol; (b) ginseng; (c) wheat germ oil; (d) yohimbine. 5 Drug nutrients: (a) alcohol; (b) caffeine. Nutritional ergogenic aids may be used in attempts to increase sport performance in various ways, such as: increased energy supply in the muscle (e.g. creatine supplements); increased energy-releasing metabolic processes in the muscle (e.g. l-carnitine supplements); enhanced oxygen delivery to the muscle (e.g. iron supplements); increased oxygen utilization in the muscle (e.g. coenzyme Q10 supplements); decreased production or accumulation of fatigue-causing metabolites in the muscle (e.g. sodium bicarbonate supplements); and improved neural control of muscle contraction 357 (e.g. choline supplements). Because all nutrients may be involved in energy production or control in one way or another, every nutrient may be potentially ergogenic for specific sport tasks. The potential capacity of many specific essential and non-essential nutrients to enhance the three human energy systems is detailed in other chapters of this volume, including the role of creatine supplementation to enhance the ATP–PCr energy system, the ingestion of sodium bicarbonate to improve performance in sport events associated with the lactic acid energy system, and dietary carbohydrate regimens to increase aerobic endurance capacity associated with the oxygen energy system. This brief review will focus on several nutritional ergogenics commonly marketed to athletes as dietary supplements with alleged ergogenic properties to improve performance in (i) strength/power sport tasks, and (ii) aerobic endurance sport tasks. Strength/power sport tasks Arginine, ornithine and lysine theory Human growth hormone (hGH), a polypeptide, is released from the pituitary gland into the bloodstream and affects all body tissues. Supplementation with various amino acids, particularly arginine, ornithine and lysine, has been used in attempts to stimulate the release of hGH. Increased serum levels of hGH in turn may stimulate production and release of insulin-like growth factor-1 that may lead to increases in muscle mass and strength. Additionally, amino acid supplementation is theorized to stimulate the release of insulin, another anabolic hormone. efficacy In early research, Elam (1989) reported that in conjunction with a weight-training programme, supplementation with arginine (1 g · day–1) and ornithine (1 g · day–1) reduced body fat, increased 358 nutrition and exercise Fig. 26.1 Some athletes consume nutritional ergogenic aids in attempts to increase serum levels of anabolic hormones, with resultant expected benefits of increased muscle mass, strength and power. Photo © Allsport / Botterill. lean body mass, and increased strength over a 5-week period. However, this study has been criticized on the grounds of poor experimental design and statistical analysis. More recent well-controlled studies (Fogelholm et al. 1993; Lambert et al. 1993; Mitchell et al. 1993) with experienced weightlifters or bodybuilders do not support any ergogenic effect of various combinations of arginine, ornithine and lysine on hGH secretion, increased muscle mass, strength or power. Moreover, two well-controlled studies revealed that hGH supplementation itself did not increase muscle protein synthesis, muscle size or strength in untrained males undergoing a 12-week resistance-training programme (Yarasheski et al. 1992) or muscle protein synthesis or whole body protein breakdown in trained weightlifters over a 2-week period (Yarasheski et al. 1993). engineered or produced by amino acid supplementation, are unknown (Bucci 1993). safety efficacy Although moderate doses of amino acid supplements may be safe, larger doses, e.g. 170 mg ornithine · kg–1 body weight, may lead to gastrointestinal distress (osmotic diarrhoea). Moreover, the potential adverse health effects of hGH administration are substantial, and most researchers caution that the long-term health risks of hGH administration, either genetically Animal studies involving poultry, cattle and pigs have indicated that HMB supplementation may increase lean muscle mass and decrease body fat. (Nissen et al. 1994; Van Koevering et al. 1994). However, HMB research with humans is very limited and has emanated from a single laboratory. Collectively, three studies provide some evidence supportive of an anabolic, or an anti- b-Hydroxy-b-methylbutyrate theory b-Hydroxy-b-methylbutyrate is a metabolite of the essential amino acid leucine, and is currently being marketed as a dietary supplement, calcium-HMB-monohydrate. Although its metabolic role in humans is uncertain, HMB supplementation is proposed to help exercisers maximize muscle gains during resistance training by counteracting the catabolic effects of exerciseinduced stress on protein metabolism. Investigators hypothesize that HMB may be an essential component of the cell membrane that is jeopardized during exercise stress or that it may regulate enzymes important to muscle growth. nutritional ergogenic aids catabolic, effect of HMB supplementation. In one study, HMB supplementation (1.5 or 3.0 g · day–1), in a dose–response manner, induced significant improvements in lean body mass and muscle strength in untrained men over a 3-week period (Nissen et al. 1996b). In two other studies, HMB supplementation (3 g · day–1) increased strength in physically active males in the 1repetition maximal bench press (Nissen et al. 1996b) and decreased body fat and increased lean body mass and bench press strength in both trained and untrained subjects over a 4-week period of resistance training (Nissen et al. 1996a). Although these preliminary findings are impressive, replication from other laboratories is needed. Additionally, each study included several threats to internal validity, including the use of unorthodox measures of muscle strength or absence of a true placebo, and in tests of multiple dependent variables, such as multiple measures of strength, HMB benefited performance in some tests, but not all. safety Studies in humans at doses of 1.5–3.0 g · day–1 for several weeks have reported no acute adverse effects. Chronic supplementation has not evidenced adverse effects in animals, but no data appear to be available for humans. Herbal products 359 or stimulate its endogenous production, thus inducing increases in muscle size and strength. efficacy A scientific literature review revealed no research to validate the claims made by the manufacturers that g-oryzanol, smilax or yohimbine either raise serum testosterone levels or induce gains in muscle size or strength, confirming the findings of previous scientific reviews (Wheeler & Garleb 1991; Grunewald & Bailey 1993). Wheeler and Garleb (1991) speculated that g-oryzanol might actually decrease serum testosterone. Wellcontrolled research with these herbal products, and other plant-derived purported ergogenics such as dehydroepiandrosterone (DHEA), is limited, but that which is available does not substantiate advertising claims. For example, Fry and others (1997) recently reported that goryzanol supplementation (500 mg · day–1 for 9 weeks), in comparison to a placebo condition, did not increase circulating concentrations of testosterone or improve 1-repetition maximum muscular strength in the bench press or squat exercise. safety Although herbal dietary supplements may be safe, most lack appropriate safety data. Some preparations have been reported to cause various health problems, including anaphylactic reactions. theory Numerous herbal products have been marketed as potential ergogenics for physically active individuals. Three such products have been marketed as bodybuilding supplements as a means to enhance muscle size and strength: g-oryzanol, a ferulic acid ester derived from rice bran oil; yohimbine (yohimbe), a nitrogen-containing alkaloid from the bark of the yohimbe tree; and smilax, an extract of phytosterols from the dried roots of Smilax officinalis or various forms of sarsaparilla. Advertisers theorize that these herbal products contain the male hormone testosterone Aerobic endurance sport tasks Phosphorus (phosphates) theory Dietary phosphates, the source of the essential nutrient phosphorus, 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 2,3diphosphoglycerate (2,3-DPG) for red blood cell 360 nutrition and exercise 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 levels. Increased levels of 2,3-DPG could facilitate release of oxygen from haemoglobin in the red blood cell and possibly enhance aerobic endurance exercise performance. efficacy Current research is equivocal as to whether or not phosphate loading may improve physiological functions important to endurance performance. About a dozen studies have been conducted. No study has reported decreases in performance, and four well-controlled studies (Cade et al. 1984; Kreider et al. 1990, 1992; Stewart et al. 1990) have reported that phosphate supplementation may enhance exercise performance. However, the underlying mechanism has not been clarified. For example, 2,3-DPG did not increase in all studies. Increased maximal oxygen uptake and improved performance on cycle ergometer exercise tests are the most consistent findings. Although these results are impressive, a number of confounding variables in previous research have been identified and more controlled research has been recommended (Tremblay et al. 1994). in animal foods but may also be synthesized in the liver and kidney. l-Carnitine is the physiologically active form in the body and has been the form most commonly used as a dietary supplement. l-Carnitine may affect various physiological functions important to exercise; most of the effects are ergogenic in nature but some may possibly impair performance, i.e. be ergolytic (Wagenmakers 1991; Williams 1995). A primary function of l-carnitine is to facilitate transfer of free fatty acids (FFA) into the mitochondria to help promote oxidation of the FFA for energy. Theoretically, l-carnitine supplementation could enhance FFA oxidation and help to spare the use of muscle glycogen, which might be theorized to safety Phosphate supplements may cause gastrointestinal distress unless consumed with ample fluids or food. Chronic consumption, particularly with limited calcium intake, can lead to a decreased calcium to phosphate ratio, which may increase parathyroid hormone secretion and impair calcium balance. L-Carnitine theory Carnitine, a non-essential short-chain carboxylic acid, is a vitamin-like compound found naturally Fig. 26.2 Theoretically, nutritional ergogenic aids may enhance physiological or metabolic processes deemed important for aerobic energy production. Photo © Allsport / Martin. nutritional ergogenic aids improve prolonged aerobic endurance capacity. Additionally, by decreasing the ratio of acetylcoenzyme A (CoA) to CoA and hence stimulating the activity of pyruvate dehydrogenase, lcarnitine supplementation may be theorized to facilitate the oxidation of pyruvate. Such an effect could reduce lactic acid accumulation and improve anaerobic endurance exercise performance (Wagenmakers 1991). On the other hand, the increased oxidation of glucose could lead to an earlier depletion of muscle glycogen and impair performance, an ergolytic effect (Wagenmakers 1991). 361 performance in either a marathon or a 20-km run, but this dose may have been insufficient compared to chronic supplementation protocols. safety l-Carnitine appears to be safe in dosages utilized in these studies, although large doses may cause diarrhoea. Individuals should not use supplements containing d-carnitine. The d-carnitine isomer may impair the synthesis of l-carnitine in the body leading to symptoms of l-carnitine deficiency, including myopathy and muscular weakness. efficacy Although l-carnitine supplementation will increase plasma levels of carnitine, it has not been shown to consistently increase muscle carnitine levels, the site of its action relative to the use of FFA for energy production during exercise (Wagenmakers 1991; Williams 1995). The data are equivocal relative to the effects of l-carnitine supplementation on the use of FFA during exer. cise and Vo2max., with some studies providing evidence of enhanced FFA utilization and . increased Vo2max. and other studies showing no effect on energy metabolism (Kanter & Williams 1995; Williams 1995; Heinonen 1996). On the other hand, research data clearly indicate that lcarnitine supplementation does not affect lactic acid accumulation in a fashion that may be considered to be ergogenic (Kanter & Williams 1995; Williams 1995). Also, in general, in those studies that included physical performance measures, lcarnitine supplementation has not been shown to enhance either aerobic or anaerobic exercise performance (Kanter & Williams 1995; Williams 1995). However, research is needed to investigate the potential ergogenic effects of chronic lcarnitine supplementation on prolonged aerobic endurance exercise tasks, such as marathon running, to test the possibility of muscle glycogen sparing and subsequent improved performance. Colambani and others (1996) found that acute supplementation of l-carnitine (2 g · 2 h–1 before the events) had no significant effect on Coenzyme Q10 theory Coenzyme Q10 (CoQ10), a non-essential nutrient, is a lipid with characteristics common to vitamins. It is located primarily in the mitochondria of the cells, such as heart and muscle cells, and is involved in the processing of oxygen for the production of cellular energy. Increased processing of oxygen could increase sport performance in aerobic endurance events. CoQ10 is also an antioxidant. CoQ10 is also referred to as ubiquinone, or ubiquinone-10. efficacy Bucci (1993) cites six studies showing beneficial effects of CoQ10 supplementation to various subject populations, but these studies appeared in the proceedings of a conference and do not appear to have been published in peer-reviewed journals. Moreover, each study suffered one or more experimental design flaws, e.g. no control group (Williams 1999). A recent review of six well-controlled scientific studies involving CoQ10 supplementation (ª 70–150 mg · day–1 for 4–8 weeks) either administered separately or in combination with other putative ergogenic nutrients, indicated that although blood levels of CoQ10 may be increased, there was no effect on lipid peroxidation, sub- 362 nutrition and exercise strate utilization, serum lactate levels, oxygen uptake, cardiac function or anaerobic threshold during submaximal exercise or serum lactate levels and oxygen uptake during maximal exercise. Additionally, there was no effect on time to exhaustion on a cycle ergometer in two studies (Williams 1999). Bucci (1993) indicates that the long-term safety of CoQ10 has been thoroughly documented, although others indicate that it may actually serve as a pro-oxidant and generate free radicals (Demopoulous et al. 1986). In a recent study, Malm and others (1996) reported evidence of muscle tissue damage in exercising subjects who were supplemented with 120 mg CoQ10 · day–1 for 20 days. supplementation helped prevent a decrease in serum choline in triathletes and adolescent runners following long-term hard physical stress, but they did not evaluate the effects on performance. No studies of choline supplementation and physical performance were presented in a recent review (Kanter & Williams 1995). Subsequent to this review, a double-blind, placebocontrolled, crossover study with trained male cyclists, using a single dosage of 2.43 g choline bitartrate, reported that although there was a significant increase in serum choline, compared with the placebo there were no significant effects on time to exhaustion in either a high intensity . . (150% Vo2max.) or a prolonged (70% Vo2max.) cycle exercise test (Spector et al. 1995). At the present time, there are no data to support choline supplementation as an effective ergogenic, but confirming research is desirable. Choline safety safety theory Choline, a non-essential nutrient, is an amine widely distributed in foods and may also be synthesized in the body. Its primary metabolic role in humans is to serve as a precursor for the formation of phosphatidylcholine (lecithin) and other essential components of cell membranes and for the formation of acetylcholine, the neurotransmitter at the myoneural junction that initiates electrical events in muscle contraction. Conlay et al. (1992) reported significantly lower plasma choline levels following a 42.2-km marathon, suggestive as an aetiologic factor in the development of fatigue because of the possibility of decreased acetylcholine production and resultant impaired muscular contractility. Theoretically, choline supplementation will enhance acetylcholine synthesis and prevent acetylcholine depletion and subsequent fatigue in endurance events. efficacy Von Allwörden et al. (1993) noted that lecithin Choline is a natural dietary component and small supplemental doses are not considered unsafe. Inosine theory Inosine, a non-essential nutrient, is a nucleoside. Some in vitro research has led to the theory that inosine supplementation increases the amount of 2,3-DPG in the red blood cell. Theoretically, increased levels of 2,3-DPG may facilitate the release of oxygen from the red blood cells to the muscle and enhance aerobic endurance exercise. efficacy Only two well-controlled studies have evaluated the purported ergogenic effect of inosine supplementation. Two days of inosine supplementation (6000 mg · day–1) exerted no significant effect on heart rate, ventilation, oxygen consumption, or lactic acid production in highly trained runners during both submaximal and maximal exercise, nutritional ergogenic aids nor was there any effect on performance in a 4.8km treadmill run for time (Williams et al. 1990). Five days of inosine supplementation (5000 mg · day–1) did not influence peak power, end power, a fatigue index, total work, or post-test lactate in competitive male cyclists undertaking several cycle ergometer exercise tasks (Starling et al. 1996). In both studies, inosine supplementation actually impaired performance in some of the tests, including run time to exhaustion in a peak oxygen uptake test (Williams et al. 1990) and time to fatigue in a supramaximal cycling sprint (Starling et al. 1996). 363 tion, and cycling exercise performance under warm/hot environmental conditions (Lyons et al. 1990; Montner et al. 1992). However, Lamb and others (1997) reported that glycerol-induced hyperhydration exerted no significant effect on temperature regulation, physiological or metabolic responses to exercise, or prolonged cycling performance. Additional research is needed to help resolve these contradictory findings, particularly so in sports in which the extra body mass needs to be moved, such as distance running. safety safety Inosine supplementation appears to be relatively safe, but may increase production of uric acid which could lead to complications in those afflicted with gout. Glycerol theory Glycerol is an alcohol derived from triglycerides. Investigators theorize that a combination of glycerol–water supplementation may be a more effective hyperhydration technique than water hyperhydration alone. Increasing body water stores may be theorized to enhance aerobic endurance performance, either by increasing blood volume or by increasing resistance to dehydration while exercising under heat-stress environmental conditions. efficacy Glycerol-induced hyperhydration (ª 1 g glycerol · kg–1 body weight with 20–25 ml water · g–1 glycerol), when compared with water hyperhydration alone, has been shown to increase total body water, including blood volume, to a greater extent (DeLuca et al. 1993; Freund et al. 1993; Sawka et al. 1993). Several studies have shown that glycerol-induced hyperhydration improves cardiovascular responses, temperature regula- Although the dosages used in these studies appear to be safe, larger doses may lead to abnormal pressures in tissue spaces. Ginseng theory Ginseng, a plant extract, is a generic term encompassing a wide variety of compounds derived from the family Araliaceae. The ergogenic effect of ginseng is attributed to specific glycosides, also referred to as ginseng saponins or ginsenosides. The specific physiological effects of ginseng extracts depend on the plant species, the various forms including Chinese or Korean ginseng (Panax ginseng), American ginseng (P. quinquefolium), Japanese ginseng (P. japonicum) and Russian/Siberian ginseng (Eleutherococcus senticosus). Although the mechanism underlying the alleged ergogenicity of ginseng on physical performance has not been defined, theories include stimulation of the hypothalamic– pituitary–adrenal cortex axis and increased resistance to the stress of exercise, enhanced myocardial metabolism, increased haemoglobin levels, vasodilation, increased oxygen extraction by muscles, and improved mitochondrial metabolism in the muscle, all of which theoretically could enhance aerobic exercise performance (Dowling et al. 1996). 364 nutrition and exercise efficacy There are very few well-controlled studies supporting an ergogenic effect of ginseng supplementation. In their major recent review of the ergogenic properties of ginseng, Bahrke and Morgan (1994) indicated that because of methodological and statistical shortcomings, there is no compelling evidence to indicate ginseng supplementation consistently enhances human physical performance and there remains a need for well-designed research to address this issue. One recent well-designed study (Pieralisi et al. 1991) did find an ergogenic effect of Geriatric Pharmaton (a preparation including ginseng G115 and other elements, including dimethylaminoethanol) on various physiologic variables, . including Vo2max., and performance during the Bruce treadmill protocol. However, the investigators noted that the ergogenic effect is attributed to the total preparation used, i.e. Geriatric Pharmaton, and not to the standardized ginseng G115, because some research has supported a beneficial effect of dimethylaminoethanol bitartrate, possibly by affecting favourably the choline–acetylcholine complex. However, several recent studies with appropriate designs have not reported any benefits to endurance performance. For example, no significant ergogenic effects were associated with 6 weeks of Eleutherococcus senticosus Maxim L (ESML) supplementation in highly trained runners on any metabolic, psychological or performance parameters measured in both a submaximal and maximal aerobic exercise task, including heart . . . . rate, Vo2, VE, VE/Vo2, and respiratory exchange ratio during both exercise and recovery, ratings of perceived exertion during exercise, serum (lactate) following exercise, and run time to exhaustion in a maximal test (Dowling et al. 1996). Additionally, Morris and others (1996), in a double-blind, placebo-controlled study, reported no effect of a standardized ginseng extract (8 or 16 mg · kg–1 body mass for 7 days) on ratings of perceived exertion or time to exhaustion on a cycle ergometer test. Nevertheless, quality research evidence regarding the effect of ginseng supplementation on exercise performance is limited and more controlled research is needed with varying types, dosages, and physical performance parameters. safety Animal studies indicate that extracts of ginseng have a low acute or chronic toxicity and the doses normally used with humans are regarded as safe. However, Beltz and Doring (1993) noted a ginseng-abuse syndrome has been reported, with such symptoms as hypertension, nervousness, sleeplessness and oedema. Conclusion Nutritional ergogenics have been used since time immemorial, and will continue to be used as long as athletes believe they may gain a competitive advantage. However, before using such supplements for their purported ergogenic effects, one should address the following questions. Is it effective? If the supplement has not been shown to be effective, either by appropriately designed research or repeated personal experiences, there is no reason to buy it. Is it safe? Most nutrient and dietary supplements are presumed to be safe if consumed in recommended dosages. However, athletes often believe that if one is good, 10 is better, and may take amounts in excess of normal needs (Burke & Read 1993). Excess amounts of various nutrients and dietary supplements may pose health risks to some individuals. Is it legal? Most nutritional ergogenics are considered legal because they are regulated as food or dietary supplements, not drugs. However, the same dietary supplements may contain drugs, such as caffeine and ephedrine, which may lead to a positive doping test. 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