Athletic ergogenic aids.
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 (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 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 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) 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 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)
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 1994. (22) 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.
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. (24-26) Ephedra and related ephedrine alkaloids are sympathomimetic agents that 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 ephedra-containing 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 life-threatening side effects. (2,34)
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) [left arrow][right arrow] Creatine + ATP.(metzl)
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 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)
Recombinant EPO (r-EPO) was approved by the FDA for manufacture in 1989 after the EPO gene was cloned in 1985. (14) 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)
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 (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 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 [micro]g/ml (IOC standards) and 15 [micro]g/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 legal limit. (3)
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.
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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 10003.
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 Table 2 Ergogenic Aids in Athletes Prohibited How Substance has been Classes Employed by Athletes Mechanism of Action and of Substances (Sport Example) Effects Stimulants Amphetamines Central nervous system Release: various neuro- stimulant transmitters Reduce fatigue Inhibition: uptake of Improve reaction times neurotransmitter Increase alertness and Direct impact: neuro- aggression (Endurance transmitter receptors sports) aggression Inhibition: monamine oxidate activity Sympathomime- Create vasoconstrition Activation of alpha-1 tics (OTC and higher blood pressure adrenoreceptors in decongestants) (Milder) centeral nervous vascular smooth muscle, system effects (see decrease in mucus above) secretion (Aid in fat loss, e.g., Effects on central ephedrine use by female nervous system, similar body builders, also to amphetamines, but endurance sports) weaker (see above) Caffeine Delay of fatigue by (Milder) centeral enhancing muscle nervous system effects contractility Antagonist of adosine Enhance performance on receptors short, intense periods Inhibits phosphodieste- of exercise rase type enzymes, Sparing of muscle glyco- resulting in activation gen levels of cyclic AMP, link (Various sport activi- between receptor acti- ties, endurance sports) vity and cell response Cocaine Possible distortion of Includes inhibition of perception of enhanced various neurotransmi- performance and reduce tters, such as dopamine strength (Ergogenic effects in sport are inconclusive; accumulation more likely from recreational use by athletes) Agonists Improves activities Bronchodilation (also (Beta2) dependent on aerobic used for asthma) by (GREEK BETA) function stimulation of Beta2 Promotes muscle growth adrenoreceptors in Reduction in body fat respiratory tract Used as alternative to (smooth muscle) anabolic steroids (see Also anabolic effect below) (see below) (Endurance sports, sports Higher doses: stimulate with an "appearance" Beta1 adrenoreceptors aspect, like weight (with side effects) lifting) Narcotics Pain reliever Interaction with brain (Variable use across receptors sensitive to athletic activities) endorphin transmitters (also affecting emotions) Anabolic Improve lean body mass/ Act on endogenous androgenic strength androgen receptors steroids Reduction of body fat Increase protein syn- Relative to training, thesis enhances recover time, Antagonist to glucocor- promotes energy and ticoid hormones/anti- aggressive performance catabolic effects Concomitant drugs (hGH, Tissue building/anabo- hCG) * have been taken to lic effect enhance anabolic effects Virilizing/androgenic or to minimize adverse effect effects (diuretics, opiates, among others) or to maximize intensity of training (added stimulant). No solid evidence to support above practices. (2,4,5) (Strength-dependent/ Endurance sports) Diuretics No sport enhancing Effect on kidney resul- effects ting in excessive loss Reduce weight of fluid Manage fluid retention Increase urine to dilute other doping agents Human Growth Increase muscle mass Polypeptide hormone of Hormone Spares muscle glycogen pituitary gland. More intense training may Activates growth hormo- be possible ne receptors to allow Quicker recovery follo- the producton of wing training insulin-like growth (No support for enhanced factor-1 (IGF-1) with performance (3,52,53) anabolic effects Erythropoietin Increases oxygen capacity A glycoprotein hormone. of red blood cells Manufactured mostly in An alternative to blood kidney. Endogenous doping production influenced (Endurance sports) by a decrease in oxygen to the kidney. Result: increased number of RBCs produced from bone marrow and increased rate of RBCs into blood circulation Peptide hor- Acquire substances which hCG and LH provoke mones, mime- provoke other agents that testosterone release tics and have ergogenic attribu- Insulin may ease glu- analogues tes, such as testosterone cose entry into cells with its effects or those and promote bulking of that increase muscle muscle tissue tissue (Variety of activities) Prohibited Classes of Substances Adverse Affects * Stimulants Amphetamines Milder doses: insomnia, irritablity, tremor, increase in aggressive behavior, restlessness Higher doses: tachycardia, sweating, arrhythmias higher blood pressure; can impede ability to to reduce body temperature Chronic use: danger of amphetamine psychosis Abuse in endurance sports: contribute to heats- troke Sympathomime- Headache, dizziness, hypertension, irritability, tics (OTC some anxiety tachycardia decongestants) Higher doses: mania or psychosis; possible cerebral hemorrhage/stroke Caffeine Mild: insomnia, irritablitiy, GI disturbances More severe: peptic ulcer, seizure, coma, arrhythmias, hallucinations, death Cocaine Note: complex pharmacology Abuse can effect: hypertension, seizures, psycho- sis, negative impact on glycogenolysis, myocardial toxicity/intense exercise (possible ischemia, arrhythmias, sudden death) Agonists Beta2 adrenoreceptors: higher doses allow Beta1 (Beta2) adrenoreceptor stimulation (GREEK BETA) At higher doses: Beta1 adrenoreceptor stimulation: hand tremor, tachycardia, arrhythmias, insomnia, headache, nausea Anabolic effects (related to high dose): example of clenbuterol-myalgia, dizziness, nausea, periorbital pain, and/or asthenia (also see below) Narcotics Absence of pain could exacerbate underlying or mask new condition High doses: coma and stupor, possible lethal from respiratory depression Withdrawal symptoms following dependence: sweating, nausea, insomnia, anxiety, aching muscles, and others More severe--cardiovascular collapse Anabolic Adverse effects historically overstated. (4,12) androgenic Majority are minor and reversible following steroids stoppage. (4) Incidence of serious effects are catastrophic, but low. (13) Long term effects generally unknown. (3,11) Broad classes--cosmetic: masculinization and gynecomastia; liver abnormalities: dysfunction, tumor; infection/injection techniques: hepatitis mycobacterial, HIV/AIDS; cardiovascular: may increase risk of atherosclerosis; reproductive: atrophy of testicles, decreased sperm producation; psychiatric/psychological: mood swings, depression and mania/hypomania Diuretics Diuretic use during exercise produces harmful effects Hypohydration: electrolyte disturbances can compromise the muscles and heart Side effects can worsen if accompanied by fatigue and/or glycogen production Human Growth Adverse effects in sport are not well evidenced Hormone due to short-term substance usage, where effects and features of acromegaly do not occur Erythropoietin Little published research on EPO and athletes. In patient use headaches, flu-like symptoms, joint pain may occur (all of which appear to resolve). Abuse risk involves too high a hematocrit. An increase in hematocrit occurs which increases blood 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 hor- Little published research in sports. Information mones, mime- becomes constrained to studies of individual agent tics and effects, e.g., hCG may produce symptoms of analogues fatigue, headache, and mood swings, among others. There are no published reports of adverse effects of insulin use in sports.
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|Author:||Bernstein, Adam; Safirstein, Jordan; Rosen, Jeffrey E.|
|Publication:||Bulletin of the NYU Hospital for Joint Diseases|
|Date:||Dec 22, 2003|
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