The term ergogenic stems from the Greek roots

Transcription

1 164 Bulletin Hospital for Joint Diseases Volume 61, Numbers 3 & Athletic Ergogenic Aids Adam Bernstein, M.D., Jordan Safirstein, M.D., and Jeffrey E. Rosen, M.D. The term ergogenic stems from the Greek roots Ergon and genes, meaning work and born, respectively. Any means of enhancing energy production or utilization may be described as an ergogenic aid. 1 Ergogenic aids have classically been classified into five categories: mechanical, psychological, physiologic, pharmacologic, and nutritional. 2 The present use of the term ergogenic aid usually revolves around the physiologic, pharmacologic, and nutritional categories. While ergogenic aids have been linked to athletic doping, the terms are not synonymous. Doping is a term used by the International Olympic Committee (IOC) to describe the administration or use of a substance by a competing athlete with the sole intention of increasing in an artificial and unfair manner his or her performance in competition. 3 Not all ergogenic aids are banned by the IOC. A partial listing of substances banned by the United States Olympic Committee is found in Table 1. 2,3 Table 2 provides a list of commonly used athletic ergogenic aids. Anabolic-Androgenic Steroids Anabolic-androgenic steroids (AAS) are testosterone derivatives that exert anabolic (tissue building) and androgenic (masculinizing) influences on the body. 3 Since the discovery of the chemical structure of testosterone in 1935, attempts to separate the anabolic and androgenic effects of AAS Adam Bernstein, M.D., is a Senior Resident, NYU-Hospital for Joint Diseases Department of Orthopaedic Surgery, New York, New York. Jordan Safirstein, M.D., is a Resident, Department of Internal Medicine, Albert Einstein College of Medicine, New York, New York. Jeffrey E. Rosen, M.D., is in the NYU-Hospital for Joint Diseases Department of Orthopaedic Surgery, New York, New York. Reprint requests: Jeffrey E. Rosen, M.D., NYU-Hospital for Joint Diseases Department of Orthopaedic Surgery, 303 Second Avenue, Suite 2, New York, New York have been unsuccessful. 3 Athletes have been using AAS since the 1940s in efforts to improve their performance. 2 Concerned with widespread abuse of AAS among athletes, the IOC banned AAS use in the early 1960s. 2 The Anabolic Steroids Control Act was legalized in 1990, making it a felony to possess or distribute AAS for non-medical purposes in the United States. 3,4 Oral, parenteral, transdermal, and intra-nasal forms of AAS are available. The vast majority of AAS used by athletes is thought to be obtained on the black market, as only an estimated 10% to 15% of AAS used by athletes for performance enhancement are obtained by prescription. 3 AAS are believed to exert their main effect by increasing anabolic processes and inhibiting catabolic processes via specific receptor mediated responses within the target cells. 5 Effects of AAS include: the anabolic build-up of muscle mass, the androgenic development of secondary male sexual characteristics, an anti-catabolic reversal of cortisol s action, and a direct psychological effect thought to allow a more intense and sustained workout. 2,5-8 Early studies of AAS and athletes produced mixed results. 5,6 More recent reviews support the notions that AAS can provide significant increases in muscle mass and strength in athletes. 2,5,6 In order to maximize the effects of AAS on strength and power athletes, an adequate diet and exercise regimen is needed. 5 There seems to be little advantage gained while using AAS in the untrained individual. 5,9 Benefits obtained from AAS are more established in strength-dependent sports. Data supporting increased aerobic capacity and improved endurance with AAS use is limited and inconclusive. 4 AAS effect on endurance sports is currently an area of great interest given the large number of endurance athletes who still use AAS. 4,10 An intricate terminology describing the dosing practices of athletes has evolved. Athletes will commonly use AAS over 6 to 12 week cycles. 4 Pyramiding describes a

2 Bulletin Hospital for Joint Diseases Volume 61, Numbers 3 & Table 1 Partial List of Substances Banned by the United States Olympic Committee Prohibited Classes of Substances Stimulants Narcotics Anabolic agents Diuretics Peptide hormones, mimetics and analogues This is not an exhaustive list of prohibited substances many substances not appearing on this list are considered prohibited under the term and related substances. Prohibited Methods Blood doping Pharmacological, chemical and physical manipulation Use of substances and methods that alter the integrity and validity of urine samples during drug testing Classes Subject to Certain Restrictions Alcohol Cannabinoids Local anesthetics Glucocorticosteroids Beta-Blockers Caffeine gradual escalation in the dose of AAS taken over a cycle. 2,11 Stacking involves the use of more than one AAS, usually with staggered cycles of the individual drugs. 2-4 An array describes the practice of using other drugs to counteract side effects or enhance the effects of AAS. 3 The practices of cycling, pyramiding, and stacking are used by athletes in an attempt to minimize the negative effects of AAS while maximizing the desired enhancements. 2,4 At the current time, no solid scientific support exists for these practices. 2,4,5 The adverse effects attributed to AAS abuse have been historically overstated. 4,12 The majority of AAS side effects are considered minor and reversible following the cessation of use. 4 While the incidence of serious side effects from AAS use has been low, devastating consequences have been reported. 13 Documented fatalities from myocardial infarction, stroke, and hepatocarcinoma have been attributed to AAS use. 2,3 The long-term effects of AAS use are generally unknown. 3,11 Dehydroepiandrosterone (DHEA) Dehydroepiandrosterone (DHEA) is a precursor to testosterone produced primarily in the adrenal glands. 4,14 Natural sources of DHEA include wild yams. The FDA banned sale of DHEA in 1996 due to insufficient evidence of safety and value; however, DHEA remains a legal and popular item sold as a nutritional supplement. 14,15 The mechanism of action of DHEA is poorly understood but most likely revolves around the conversion of DHEA to testosterone in peripheral tissues. 4,14 Preliminary studies suggest that DHEA may have a broad range of clinical uses including anti-alzheimer and anti-parkinson capabilities, however randomized, double-blinded clinical studies are lacking. 5 DHEA is a pre-cursor to testosterone and theoretically may enhance athletic performance in a manner similar to AAS. Investigations of DHEA use and athletic performance are scarce. 14 Existing studies do not support a significant increase in lean body mass, strength, or testosterone levels with the use of DHEA in athletes. 14,16-18 Long-term side effects of DHEA use are currently unknown but are probably similar to those associated with AAS use. 6,14 Androstenedione Androstenedione is a testosterone pre-cursor produced in the adrenal glands and gonads. Several professional athletes have used this substance, bringing it to national attention. 2 Androstenedione is found naturally in the pollen of Scottish pine trees. 19 Similar to DHEA, the mechanism of action and side effects attributed to androstenedione are poorly understood and thought to be related to the conversion of androstenedione to testosterone in the peripheral tissues. 5 Despite manufacturers claims to the contrary, there is little scientific evidence of the purported ergogenic effects of androstenedione. 2,5,16,20 Recently concerns have grown over the unfavorable alterations in blood lipid and coronary heart disease profiles seen in men using androstenedione as an ergogenic aid. 2,20,21 Dietary Supplements The increased visibility of ergogenic aids in the last decade has occurred primarily because of the passage of the United States Dietary Supplement Health and Education Act (DSHEA) of Certain vitamins, minerals, amino acids, herbs, and other botanical preparations can be classified as a dietary supplement under the DSHEA guidelines. Dietary supplements, as a result of DSHEA, are no longer under the direct regulatory control of the FDA. In fact, substances sold as a dietary supplement do not require FDA evaluation for safety or efficacy, and do not have to meet quality control standards expected of approved drugs. 5 The content and purity of dietary supplements are not regulated and can vary widely. 5,23 Since androstenedione and DHEA have been found to occur naturally in plant sources, these testosterone precursors can be labeled as dietary supplements and sold legally over-the-counter. Ephedra Dietary supplements containing Chinese ephedra, also known as Mahaung, are marketed as performance enhancers and weight-loss aids. 24 Ephedra species of herb have been used for over 5,000 years for respiratory ailments. 25 Currently, ephedrine alkaloids are found in hundreds of prescriptions and over-the-counter products, such as antihistamines, decongestants, and appetite suppressants Ephedra and related ephedrine alkaloids are sympathomimetic agents that

3 166 Bulletin Hospital for Joint Diseases Volume 61, Numbers 3 & mimic epinephrine effects. Multiple studies of isolated ephedrine alkaloids have shown no significant enhancement of power or endurance at dosages considered to be safe. 24,27-31 In contrast, the combination of caffeine with ephedrine has been associated with improvements in performance and may promote metabolic effects that are conducive to body fat loss. 26,32 The actual content of ephedra alkaloids in 20 ephedracontaining dietary supplements was studied using highperformance liquid chromatography. 33 Ten of the twenty supplements exhibited marked discrepancies between the label claim for ephedra content and the actual alkaloid content. Between 1995 and 1997, 926 cases of possible Mahuang toxicity were reported to the Food and Drug Administration. 34 A temporal relationship between Mahuang use and severe complications including stroke, myocardial infarction, and sudden death was established in 37 of the 926 cases. In 36 of these 37 cases, the Mahuang use was reported to be within the manufacturers dosing guidelines. Ephedra and related ephedrine alkaloids are currently banned by the U.S.O.C. and cannot be recommended for general use given their association with potentially lifethreatening side effects. 2,34 Creatine Creatine use in athletes has grown as a result of a 1992 study that showed that creatine supplementation produced a 20% increase in skeletal muscle creatine concentration. 2,35 In the phosphorylated form, creatine serves as an energy substrate that contributes to adenosine triphosphate (ATP) re-synthesis during high-intensity exercise. 36 Creatine remains popular with power and resistance athletes as it is thought to produce increases in strength, muscle mass, and to delay fatigue. 2,14,36 Creatine is synthesized from amino acids primarily in the liver, pancreas, and kidney and is excreted by the kidneys. Creatine is found in skeletal muscle, cardiac muscle, brain, retinal, and testicular tissues. 2,37 The interest in creatine as an ergogenic aid revolves around its ability to participate as an energy substrate for muscle contraction. 14 Creatine, which easily binds phosphorus, can act as a substrate to donate phosphorus for the formation of ATP. Furthermore, creatine-phosphate (PCr) can help buffer lactic acid because hydrogen ions are used when ATP is regenerated. 14,36,38 This role of creatine in exercise is governed by the following reaction: PCr + ADP (adenosine diphosphate) Creatine + ATP.(metzl) Creatine kinase Normally PCr stores deplete within 10 seconds of short, high-intensity exercise. 14,39 Increasing the level of PCr in skeletal muscle, in theory, should result in the ability to sustain high-power output longer and lead to a greater resynthesis of PCr after exercise. 14 The beneficial effects of creatine in response to resistance training are most likely mediated by the following sequence: increased muscle creatine concentration, increased training intensity, which lead to an enhanced physiologic adaptation to training with increased muscle mass and strength. 36 Studies evaluating the effectiveness of creatine as an ergogenic aid are mixed. 2,36,40 Multiple reports do conclude that short-term creatine supplementation significantly enhances the ability to maintain muscular force and power output during high-intensity exercise. 2,36,41,42 Data on results of creatine supplementation with highly trained athletes is inconclusive. While some papers report improvements with creatine use in highly trained individuals with regards to high-intensity exercise, many show no improvements. 2,36,43 Most investigators agree that creatine supplementation does not seem to enhance aerobic-oriented activities. 2,36,44 Human muscle is thought to have a maximum concentration of creatine that it can hold. 14,45 There appears to be no additional benefits of increasing creatine supplementation above this storage capacity of muscle as the excess is simply excreted by the kidneys. 2,46 Humans have differing baseline levels of muscle creatine. 14 Accordingly, athletes with lower baseline levels of creatine may be more sensitive to creatine supplementation than those with a relatively higher baseline creatine level. 14,36 The terms responder and nonresponder have been used to describe two groups of athletes: those with relatively low baseline creatine levels that may show significant performance enhancement with creatine supplementation, and those with high baseline creatine levels that do not show marked improvements with creatine supplementation. 14,36,47 These differences in creatine concentrations are thought to play a significant role in the varied results on performance found in the literature examining creatine supplementation. 14 Reported side effects from creatine use have been scarce. 2,14 The major reported side effect associated with creatine use is weight gain, which is thought to be primarily a result of water retention. 2,14,48 Some reported longer-term side effects include dehydration, muscle cramping, nausea, and seizures. 2,49 Given the relative lack of studies, caution still remains about the long-term effects of creatine usage. 14 As creatine use among younger athletes continues to increase, concern is growing over the lack of studies that examine the possible side effects specific to this age group. 14,38 Human Growth Hormone Human growth hormone (hgh) is a polypeptide produced in the anterior pituitary gland. After its release from the pituitary, hgh can exert its effect in all cells of the body via tissue specific receptors. Human growth hormone is shown to promote protein anabolism, carbohydrate tolerance, lipolysis, natriuresis, and bone and connective tissue turnover. 4,50 Potential benefits of hgh abuse in athletes revolve around

4 Bulletin Hospital for Joint Diseases Volume 61, Numbers 3 & Table 2 Ergogenic Aids in Athletes Prohibited Classes How Substance has been Employed of Substances by Athletes (Sport Example) Mechanism of Action and Effects Adverse Affects* Stimulants Amphetamines Central nervous system stimulant Release: various neurotransmitters Milder doses: insomnia, irritablity, tremor, Reduce fatigue Inhibition: uptake of neurotransmitter increase in aggressive behavior, restlessness Improve reaction times Direct impact: neurotransmitter receptors Higher doses: tachycardia, sweating, arrhythmias Increase alertness and aggression Inhibition: monamine oxidate activity higher blood pressure; can impede ability to (Endurance sports) to reduce body temperature Chronic use: danger of amphetamine psychosis Abuse in endurance sports: contribute to heatstroke Sympathomimetics Create vasoconstrition and higher blood Activation of alpha-1 adrenoreceptors in Headache, dizziness, hypertension, irritability, (OTC decongestants) pressure vascular smooth muscle, decrease in mucus some anxiety tachycardia (Milder) centeral nervous system effects (see secretion Higher doses: mania or psychosis; possible above) Effects on central nervous system, similar cerebral hemorrhage/stroke (Aid in fat loss, e.g., ephedrine use by to amphetamines, but weaker (see above) female body builders, also endurance sports) Caffeine Delay of fatigue by enhancing muscle (Milder) centeral nervous system effects Mild: insomnia, irritablitiy, GI disturbances contractility Antagonist of adosine receptors More severe: peptic ulcer, seizure, coma, Enhance performance on short, intense Inhibits phosphodiesterase type enzymes, arrhythmias, hallucinations, death periods of exercise resulting in activation of cyclic AMP, link Sparing of muscle glycogen levels between receptor activity and cell response (Various sport activities, endurance sports) Cocaine Possible distortion of perception of enhanced Includes inhibition of various Note: complex pharmacology performance and reduce strength neurotransmitters, such as dopamine Abuse can effect: hypertension, seizures, psychosis, (Ergogenic effects in sport are inconclusive; negative impact on glycogenolysis, myocardial accumulation more likely from recreational toxicity/intense exercise (possible ischemia, use by athletes) arrhythmias, sudden death) Agonists (Beta2) Improves activities dependent on aerobic Bronchodilation (also used for asthma) by Beta2 adrenoreceptors: higher doses allow Beta1 (GREEK BETA) function stimulation of Beta2 adrenoreceptors in adrenoreceptor stimulation Promotes muscle growth respiratory tract (smooth muscle) At higher doses: Beta1 adrenoreceptor stimulation: Reduction in body fat Also anabolic effect (see below) hand tremor, tachycardia, arrhythmias, insomnia, Used as alternative to anabolic steroids Higher doses: stimulate Beta1 adrenoreceptors headache, nausea (see below) (with side effects) Anabolic effects (related to high dose): example of (Endurance sports, sports with an appearance clenbuterol-myalgia, dizziness, nausea, periorbital aspect, like weight lifting) pain, and/or asthenia (also see below) Narcotics Pain reliever Interaction with brain receptors sensitive to Absence of pain could exacerbate underlying or (Variable use across athletic activities) endorphin transmitters (also affecting mask new condition emotions) High doses: coma and stupor, possible lethal from respiratory depression Withdrawal symptoms following dependence: sweeting, nausea, insomnia, anxiety, aching muscles, and others More severe - cardiovascular collapse (continued on next page)

5 168 Bulletin Hospital for Joint Diseases Volume 61, Numbers 3 & Table 2 Ergogenic Aids in Athletes (continued) Prohibited Classes How Substance has been Employed of Substances by Athletes (Sport Example) Mechanism of Action and Effects Adverse Affects* Anabolic androgenic Improve lean body mass/strength Act on endogenous androgen receptors Adverse effects historically overstated. 4,12 steroids Reduction of body fat Increase protein synthesis Majority are minor and reversible following Relative to training, enhances recover time, Antagonist to glucocorticoid hormones/ stoppage. 4 Incidence of serious effects are promotes energy and aggressive performance anti-catabolic effects catastrophic, but low. 13 Long term effects generally Concomitant drugs (hgh, hcg)* have been Tissue building/anabolic effect unknown. 3,11 taken to enhance anabolic effects or to Virilizing/androgenic effect Broad classes cosmetic: masculinization and minimize adverse effects (diuretics, opiates, gynecomastia; liver abnormalities: dysfunction, among others) or to maximize intensity of tumor; infection/injection techniques: hepatitis training (added stimulant). No solid evidence mycobacterial, HIV/AIDS; cardiovascular: may to support above practices. 2,4,5 increase risk of atherosclerosis; reproductive: (Strength-dependent/Endurance sports) atrophy of testicles, decreased sperm producation; psychiatric/psychological: mood swings, depression and mania/hypomania Diuretics No sport enhancing effects Effect on kidney resulting in excessive loss Diuretic use during exercise produces harmful Reduce weight of fluid effects Manage fluid retention Hypohydration: electrolyte disturbances can Increase urine to dilute other doping agents compromise the muscles and heart Side effects can worsen if accompanied by fatigue and/or glycogen production Human Growth Hormone Increase muscle mass Polypeptide hormone of pituitary gland. Adverse effects in sport are not well evidenced due Spares muscle glycogen Activates growth hormone receptors to allow to short-term substance usage, where effects and More intense training may be possible the producton of insulin-like growth factor-1 features of acromegaly do not occur Quicker recovery following training (IGF-1) with anabolic effects (No support for enhanced performance 3,52,53 ) Erythropoietin Increases oxygen capacity of red blood cells A glycoprotein hormone. Manufactured mostly Little published research on EPO and athletes. In An alternative to blood doping in kidney. Endogenous production influenced patient use headaches, flu-like symptoms, joint (Endurance sports) by a decrease in oxygen to the kidney. Result: pain may occur (all of which appear to resolve). increased number of RBCs produced from Abuse risk involves too high a hematocrit. An bone marrow and increased rate of RBCs into increase in hematocrit occurs which increases blood blood circulation viscosity, a state that can be exacerbated by dehydration, possibly viscosity syndrome (hypertension, decreased output, possible heart failure). At a certain level of increased hematocrit, a risk of cerebral or coronary occlusion. Peptide hormones, Acquire substances which provoke other hcg and LH provoke testosterone release Little published research in sports. Information mimetics and analogues agents that have ergogenic attributes, such as Insulin may ease glucose entry into cells and becomes constrained to studies of individual agent testosterone with its effects or those that promote bulking of muscle tissue effects, e.g., hcg may produce symptoms of increase muscle tissue fatigue, headache, and mood swings, among others. (Variety of activities) There are no published reports of adverse effects of insulin use in sports.

6 Bulletin Hospital for Joint Diseases Volume 61, Numbers 3 & its anabolic effect on the body. 4 Human growth hormone is thought to increase muscle mass, and spare muscle glycogen by stimulating lipolysis during exercise. 2,3 The popularity of hgh among athletes is furthered by the fact that hgh remains extremely difficult to detect by current drug screening processes. 3,51 Human growth hormone may be particularly attractive to female athletes as the virilization side effects associated with AAS use are not thought to occur with hgh. 4 There are no studies that demonstrate significant increases in athletic performance with the use of hgh. 3,52,53 Neither human or animal studies show any significant strength gains with supplemental hgh use in non-deficient individuals. 4 The abuse of hgh is thought to be increasing despite the lack of scientific evidence linking hgh to improved athlete performance. 3,52 A survey of high school males revealed that as many as 5% reported past or present use of hgh. 54 The purity of hgh abused by athletes may be poor as Drug Enforcement Agency estimates project that up to 30% to 50% of the hgh products sold are phony. 4,55 Adverse effects of exogenous hgh use are extrapolated from the findings seen in patients with endogenous oversecretion of hgh. 2 Adults with high levels of hgh are at risk for the clinical syndrome of acromegaly. Medical complications associated with acromegaly include: diabetes, hypertension, coronary heart disease, cardiomyopathy, menstrual irregularities, and osteoporosis. 2,4 High levels of hgh in individuals with open physis may lead to gigantism. 2 Erythropoietin (EPO) Recombinant EPO (r-epo) was approved by the FDA for manufacture in 1989 after the EPO gene was cloned in Since its approval, r-epo has been abused for athletic personal gain as an alternative to blood doping. 3,14 Recombinant EPO has largely replaced the practice of blood doping, as r-epo produces a dose-dependent increase in hematocrit. 2 In theory, r-epo should provide all of the benefits of blood doping without the risks involved in blood transfusion. 3 There are few studies evaluating the use of r-epo in healthy athletes; however, numerous studies have shown a significant increase in work capacity due to r-epo use in patients with renal disease. 14 Berglund and Ekblom reported an increased maximal oxygen consumption and increased time to exhaustion in male athletes after a 6 week trial of r-epo. 56 The risks associated with r-epo abuse involve the potential for dangerously high hematocrit levels. 14 A resulting hyperviscosity syndrome may lead to a decreased cardiac output, hypertension, and potential heart failure. 3 Furthermore, thrombosis could be manifest as myocardial infarction, pulmonary embolism, or cerebrovascular accidents. 2,3 Although the use of r-epo has been banned by the IOC since 1990, its use is extremely difficult to detect with current drug screening measures. 2,14 Antioxidants The antioxidant capabilities of certain vitamins are believed by many to counter-act the production of free-radials that occurs during exercise. 14 Most of the research to date involves vitamin E, vitamin C, and beta carotene. 2 The existing literature does not support the notion that antioxidants have significant ergogenic capabilities. 2,14,57 There are currently no recommendations for antioxidant use in athletes that exceeds the normal adult recommended daily allowance (RDA). Beta-hydroxy-beta-methylbutyrate Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the branched-chain amino acid leucine. HMB is theorized to inhibit muscle breakdown during strenuous exercise but its exact mechanism of action remains unknown. 14,58 Studies show that HMB supplementation may significantly lower serum lactate dehydrogenase (LDH), lower serum creatine phosphokinase (CPK) levels and delay blood lactate accumulation after endurance training compared to placebo. 59,60 Furthermore, short-term HMB use has been shown to significantly increase strength gains with resistance-exercised training over placebo in one double-blinded study. 61 HMB is a relatively new ergogenic aid and published results are considered preliminary. 14,58 Although there is evidence for a potential ergogenic advantage with HMB use in resistance and endurance training, its use can not be recommended until more studies are performed and potential side effects are elicited. Caffeine Caffeine is a methylxanthine occurring naturally in many species of plants. Caffeine is thought to work through a variety of mechanisms. The central nervous system effect of caffeine is probably the result of adrenergic receptor antagonism. 3 Its use by athletes stems from the theory that caffeine may delay fatigue by enhancing skeletal muscle contractility and spare muscle glycogen levels by enhancing fat metabolism. 6 Multiple studies have reported an improved endurance time with caffeine use. 6,62,63 There is evidence that caffeine use may enhance performance with more intense short-duration exercise as well. 2 The caffeine dosages most associated with an ergogenic effect range in the literature from 3 to 9 mg per kilogram of body weight. 2,6 Side effects associated with caffeine use include anxiety, diuresis, insomnia, irritability and gastrointestinal discomfort. 2,6 Higher doses of caffeine ingestion can lead to more serious consequences such as cardiac arrhythmia, hallucinations, and even death. 2,3 The legal urine level of caffeine for athletes is 12 µg/ml (IOC standards) and 15 µg/ml (National Collegiate Athletics Association standards). 6 An athlete would need to drink six to eight cups of coffee in one sitting and be tested within 2 to 3 hours to reach urine levels over the IOC legal limit. 3 The amount of caffeine needed to produce ergogenic benefits is potentially far less than that required to exceed the athletic

7 170 Bulletin Hospital for Joint Diseases Volume 61, Numbers 3 & legal limit. 3 Summary Claims championing exotic substances that produce healing or ergogenic powers have been around for centuries. The competitive, peer-pressured environment enveloping today s athletes and adolescences makes these groups particularly susceptible to the uproar surrounding the current ergogenic aid market. Presently, it seems that rumor and anecdotal information overwhelms the available scientific data. While there is evidence that some touted ergogenic aids do indeed enhance performance, there are many unanswered questions about product safety, efficacy, and long-term consequences. A working knowledge of specific ergogenic aids is essential for the treating physician in order to best advise patients and athletes as to the possible benefits and risks of any substance they may be using. References 1. Williams MH: Ergogenic and ergolytic substances. Med Sci Sports Exerc 24(9 Suppl):S344-S348, Silver MD: Use of ergogenic aids by athletes. J Am Acad Orthop Surg 9(1):61-70, Knopp WD, Wang TW, Bach Jr BR: Ergogenic drugs in sports. Clin Sports Med 16(3): , Sturmi JE, Diorio DJ: Anabolic agents. Clin Sports Med 17(2): , Blue JG, Lombardo JA: Steroids and steroid-like compounds. Clin Sports Med 18(3): , Ahrendt DM: Ergogenic aids: counseling the athlete. Am Fam Physician 63(5): , Adolescents and anabolic steroids: A subject review. American Academy of Pediatrics. Committee on Sports Medicine and Fitness. Pediatrics 99(6): , Haupt HA: Anabolic steroids and growth hormone. Am J Sports Med 21(3): , Kuipers H, et al: Influence of anabolic steroids on body composition, blood pressure, lipid profile and liver functions in body builders. Int J Sports Med 12(4): , Lombardo JA: Medical and performance-enhancing effects of anabolic steroids. Psychiatr Ann 22:19-23, Yesalis CE, Bahrke MS: Anabolic-androgenic steroids: current issues. Sports Med 19(5): , Friedl KE: Effects of anabolic steroids on physical health. In: Yesalis CE (ed): Anabolic Steroids in Sports and Exercise (2nd ed). Champaign, IL: Human Kinetics Publishers, Inc., 2000, pp Bahrke MS, Yesalis CE, Brower KJ: Anabolic-androgenic steroid abuse and performance-enhancing drugs among adolescents. Child Adolesc Psychiatr Clin N Am 7(4): , Stricker PR: Other ergogenic agents. Clin Sports Med 17(2): , Dehydroepiandrosterone (DHEA). Med Lett Drugs Ther 38(985):91-92, Wallace MB, et al: Effects of dehydroepiandrosterone vs androstenedione supplementation in men. Med Sci Sports Exerc 31(12): , Nestler JE, et al: Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J Clin Endocrinol Metab 66(1):57-61, Welle S, Jozefowicz R, Statt M: Failure of dehydroepiandrosterone to influence energy and protein metabolism in humans. 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Lawrence Rev Nat Prod, DiPasquale M: Stimulants and adaptogens: Part I. Drug Sports 1:2-6, Sidney KH, Lefcoe NM: The effects of ephedrine on the physiological and psychological responses to submaximal and maximal exercise in man. Med Sci Sports 9(2):95-99, Bright TP, Sandage Jr BW, Fletcher HP: Selected cardiac and metabolic responses to pseudoephedrine with exercise. J Clin Pharmacol 21(11-12): , DeMeersman R, Getty D, Schaefer DC: Sympathomimetics and exercise enhancement: all in the mind? Pharmacol Biochem Behav 28(3): , Swain RA, et al: Do pseudoephedrine or phenylpropanolamine improve maximum oxygen uptake and time to exhaustion? Clin J Sport Med 7(3): , Gillies H, et al: Pseudoephedrine is without ergogenic effects during prolonged exercise. J Appl Physiol 81(6): , Bell DG, Jacobs I, Zamecnik J: Effects of caffeine, ephedrine and their combination on time to exhaustion during high-intensity exercise. Eur J Appl Physiol Occup Physiol 77(5): , Gurley BJ, Gardner SF, Hubbard MA: Content versus label claims in ephedra-containing dietary supplements. Am J Health Syst Pharm 57(10): , Samenuk D, et al: Adverse cardiovascular events temporally associated with ma huang, an herbal source of ephedrine. Mayo Clin Proc 77(1):12-16, Juhn MS: Orla creatine supplementation: Separating fact from hype. Phys Sportsmed 27:47-56, Kraemer WJ, Volek JS: Creatine supplementation: Its role in human performance. Clin Sports Med 18(3): , Williams MH: The use of nutritional ergogenic aids in sports: is it an ethical issue? Int J Sport Nutr 4(2): , 1994.

8 Bulletin Hospital for Joint Diseases Volume 61, Numbers 3 & Metzl JD, et al: Creatine use among young athletes. Pediatrics 108(2): , Spriet LL: Ergogenic aids: recent advances and retreats. In: Lamb DR, Murray R (eds): Perspectives in Exercise Science and Sports Medicine. Indianapolis, IN: Benchmark Press, 1998, pp Johnson WA, Landry GL: Nutritional supplements: fact vs. fiction. Adolesc Med 9(3): , Williams MH, Branch JD: Creatine supplementation and exercise performance: an update. J Am Coll Nutr 17(3): , Mujika I, Padilla S: Creatine supplementation as an ergogenic aid for sports performance in highly trained athletes: a critical review. Int J Sports Med 18(7): , Kreider RB, et al: Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc 30(1):73-82, Balsom PD, et al: Creatine supplementation per se does not enhance endurance exercise performance. Acta Physiol Scand 149(4): , Harris RC, Soderlund K, Hultman E: Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond) 83(3): , Clark JF: Creatine: A review of its nutritional applications in sport. Nutrition 14(3): , Casey A, et al: Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol 271(1):E31-E37, Volek JS: Creatine supplementation: its effect on human muscular performance and body composition. J Strength Cond Res 10: , Feldman EB: Creatine: a dietary supplement and ergogenic aid. Nutr Rev 57(2):45-50, Yarasheski KE: Growth hormone effects on metabolism, body composition, muscle mass, and strength. Exerc Sport Sci Rev 22: Risser WL: Sports medicine. Pediatr Rev 14(11): , Bidlingmaier M, Wu Z, Strasburger CJ: Doping with growth hormone. J Pediatr Endocrinol Metab 14(8): , Jenkins PJ: Growth hormone and exercise: physiology, use and abuse. Growth Horm IGF Res 11(Suppl A):S71-S77, Rickert VI, et al: Human growth hormone: a new substance of abuse among adolescents? Clin Pediatr (Phila) 31(12): , Council Report: Drug abuse in athletes, anabolic steroids and human growth hormone. J Am Med Assoc 259: , Berglund B, Ekblom B: Effect of recombinant human erythropoietin treatment on blood pressure and some haematological parameters in healthy men. J Intern Med 229(2): , Williams MH: Nutritional supplements for strength trained athletes. Sports Sci Exchange 6:1-6, Williams MH: Facts and fallacies of purported ergogenic amino acid supplements. Clin Sports Med 18(3): , Vukovich MD, Dreifort GD: Effect of beta-hydroxy betamethylbutyrate on the onset of blood lactate accumulation and VO2 peak in endurance-trained cyclists. J Strength Cond Res 15(4): , Knitter AE, et al: Effects of beta-hydroxy-beta-methylbutyrate on muscle damage after a prolonged run. J Appl Physiol 89(4): , Jowko E, et al: Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program. Nutrition 17(7-8): , Graham TE, Spriet LL: Performance and metabolic responses to a high caffeine dose during prolonged exercise. J Appl Physiol 71(6): , Kalmar JM, Cafarelli E: Effects of caffeine on neuromuscular function. J Appl Physiol 87(2): , 1999.