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From the * US Air Force Academy, Colorado Springs, Colorado, Harvard Medical School and Harvard School of Public Health, Boston, Massachusetts, and Steadman Hawkins Sports Medicine Foundation, Vail, Colorado
Address correspondence to Richard J. Hawkins, MD, FRCS, Steadman Hawkins Sports Medicine Foundation, Attn Clinical Research, 181 West Meadow Drive, Suite 1000, Vail, CO 81657.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONANABOLIC STEROIDSHUMAN GROWTH HORMONEAMPHETAMINES AND OTHER...ERYTHROPOIETIN AND BLOOD DOPINGCREATINEBETA-HYDROXY-BETA-METHYLBUTYRATEANDROSTENEDIONESUMMARYCONCLUSIONREFERENCES |
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Key Words: performance-enhancing drugs • anabolic agents • steroids • stimulants
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INTRODUCTION |
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The poll results6 lend insight into why performance-enhancing substances remain a core discussion in competitive sports. As athletics becomes more competitive and lucrative, many athletes turn to chemical performance enhancement. In an anonymous survey of 26 USA Powerlifting Team members who competed internationally since 1988, 15 returned questionnaires. The survey solicited yes-no responses about current and previous use of anabolic steroids in power lifting. Analysis indicated that 10 of the 15 team members admitted to use of these drugs, and 5 of those admitted to beating the International Olympic Committee’s (IOC’s) doping control procedures.25
More recent reports reveal that this phenomenon is not limited to the Olympic athlete. In a survey of high school football players in Indiana, Stilger and Yesalis92 noted a use rate of more than 6%, with a mean age for initiation of use at 14 years. Fifteen percent of users in that study92 began use before the age of 10. In addition, a survey of more than 1600 Canadian students, sixth grade and above, self-reported a usage rate of 2.8%. Of those who admitted using steroids, 29% reported injecting them, and 29% of those reported sharing needles for injection.64 Fifty-four percent of all users thought steroids were bad for them.64
Although anabolic steroids have received the most attention as ergogenic aids, a number of other substances have come under scrutiny in more recent years. Human growth hormone (hGH) is rumored as a widely used anabolic agent, in spite of no scientific evidence that it improves strength, power, or athletic performance. Amphetamines are rumored to be the most commonly abused drug in professional baseball. Professional cyclers and others in endurance sports use erythropoietin (EPO). The supplement industry, led by makers of creatine and androstenedione (andro), has become a multimillion-dollar-per-year industry.
Regulation of these various ergogenic aids is an extremely difficult task. Testing for banned substances requires expensive and ever-improving techniques to keep up with so-called designer drugs that have been chemically altered to avoid detection. In addition, several ergogenic aids are so similar to naturally occurring body substances that testing is all but impossible. Even with detection, governing bodies are often not equipped with the resources to defend test results against the inevitable legal battles that come with suspension of an athlete.
The purpose of this article is to review the impact, basic science, performance benefits, and potential health risks of the most commonly used performance-enhancing substances, as well as the policies for dealing with these substances.
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ANABOLIC STEROIDS |
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Recently, there has been increasing concern over so-called designer steroids. These are simple chemical modifications of known banned anabolic steroids that will not be detected in existing testing protocols. The most popular of these is tetrahydrogestrinone (THG), and it is currently under intense scrutiny after being detected in several athletes. The drug, which has been linked to the Bay Area Laboratory Co-operative, was originally detected at a University of California Los Angeles laboratory after a coach sent an anonymous tip and a sample to the laboratory. Since then, several professional and Olympic-caliber athletes have tested positive for the steroid, and the investigation is currently ongoing. Although there are no published data on THG and its role in human performance, one could reasonably conclude that its chemical similarity to other anabolic steroids would make it likely to have similar results and side effects to others in that class.
Basic Science
Anabolic-androgenic steroids (AAS) are chemically modified analogs of testosterone, the endogenous hormone primarily responsible for male sexual characteristics and muscle anabolism. First isolated in 1935,86 AAS have been modified many times to maximize the anabolic effects of the drug and to minimize the androgenic effects by alkylation of the 17-alpha position or carboxylation of the 17-beta hydroxyl group on the sterol D ring. These analogs are degraded much more slowly than endogenous testosterone is, resulting in a higher prolonged concentration of the analog.
The physiologic action of AAS is thought to be similar to native testosterone. The molecule diffuses across the cell membrane after binding to a receptor. This complex then binds to the nucleus of a cell, stimulating messenger RNA synthesis, which leads to an increase in structural and contractile protein.18 In addition, AAS are thought to combat the catabolic effects of cortisol through competitive inhibition of the glucocorticoid receptor and are thought to have a direct neural action through androgen receptors on alpha motor neurons.101
Performance Studies
Results of clinical trials evaluating anabolic steroids are difficult to evaluate because of methodological and dosing differences. Some studies have shown minimal effects on body composition and strength,24,35 whereas others have shown that supraphysiologic doses of testosterone or its derivatives can lead to an increase in fat-free mass and muscle size and strength in humans.10,34,40 In studies using higher dosing over longer periods, the effects seem to be more pronounced. In a prospective, placebo-controlled study of testosterone enanthate (TE) with and without exercise over a 10-week period, Bhasin et al10 showed that supraphysiologic weekly doses of TE increased triceps (505 mm2 difference) and leg area (738 mm2 difference) as well as strength in the bench press (10 kg difference) and squat (17 kg difference) in subjects not engaged in strength training. In addition, those subjects assigned to TE administration and exercise had greater increases in fat-free mass (6 kg) and muscle size as well as strength (22 kg increase in bench press, 38 kg increase in squat) than did those assigned to either no-exercise group. The authors concluded that supraphysiologic doses of TE, especially when combined with strength training, lead to an increase in fat-free mass, muscle size, and strength in normal men.
In another study of the effects of anabolic steroids on body composition and strength,40 21 weight-training men were randomly assigned in a double-blind fashion to either TE or placebo for 12 weeks, with a 12-week follow-up period. The TE group had significant increases in body weight, fat-free mass, arm girth, rectus femoris circumference, and libido compared with that of the placebo group. The TE group also experienced an increase in systolic blood pressure, frontal alopecia, mild acne, and subjective changes to personality including increased aggression and irritability. The authors concluded that moderate doses of TE combined with weight training can result in short-term changes in upper body strength and composition, with changes to baseline health in some individuals.
Forbes et al34 also studied the effects of testosterone on healthy subjects, and in addition, they studied the effects on these subjects after the drug was stopped. These authors found that TE administration led to a progressive increase in lean body mass and a decrease in body fat. They also found that body composition reverted slowly toward normal when the injections were stopped but that the effects of the drug lingered for some time. They concluded that testosterone is a powerful anabolic agent that can have profound and lasting effects on body composition.
These types of results have led to the use of anabolic steroids (1) in the treatment of conditions such as HIV,83 (2) for the constitutional delay of growth,73 and (3) in the normal aging process.91
Side Effects
Studying the side effects and health risks of anabolic steroid use in athletes is difficult. Because the drugs are illegal, there is a paucity of well-controlled studies available for review. Inconsistencies in type, dosing, and training habits often make it difficult to draw statistically valid conclusions. Thus, we find conflicting results in the literature. Nevertheless, a number of studies|| have investigated the health consequences associated with these drugs and have provided strong evidence of their risks, including hepatic cellular damage, testicular atrophy, cardiovascular disease, and psychological disturbance.
With regard to cardiovascular effects, there appears to be an association between an atherogenic blood lipid profile and endothelial dysfunction with steroid use. Ebenbichler et al28 studied blood lipid profiles and flow-mediated dilatation (FMD) as an indicator for endothelial function in 20 nonsmoking male bodybuilders and compared their results with those of nonsmoking controls. The authors found that during a steroid cycle, bodybuilders decreased high-density lipoprotein (HDL) and FMD and that they suppressed luteinizing hormone and follicle-stimulating hormone levels compared with controls. In addition, FMD was decreased both during and after completion of a steroid cycle. The authors concluded that intake of anabolic steroids is associated with both an atherogenic blood lipid profile and endothelial dysfunction and, thus, may pose an increased risk of atherosclerosis.28
In another study, Kuipers et al57 found that anabolic steroids induced a 25% to 27% decrease in HDL cholesterol and an increase in diastolic blood pressure after 8 weeks of use. The authors found no significant changes in liver enzyme levels, and the blood pressures and HDL abnormalities had returned to normal by 6 weeks after cessation of drug use. In a follow-up study by the same group,49 steroid users were examined for a number of cardiovascular risk factors after 3 months of cessation of use of the drug. The authors found no differences in blood pressure, lipoprotein profiles, or liver enzyme levels compared with those of controls. These findings suggest that the negative cardiovascular effects induced by anabolic steroids may be reversible. It should be noted that the dosing recorded in these studies may be far less than those used out of a controlled environment. Other studies33,94 have cited anabolic steroid use associated with hypertension, myocardial ischemia, and sudden cardiac death.
Another area of concern with anabolic steroids is the potential psychological effects associated with their use. Cooper et al23 found that anabolic steroid use directly caused significant disturbances in personality profile as assessed by the Diagnostic and Statistical Manual of Mental Disorders (3rd ed, rev). In addition, a study by Midgley et al66 showed anabolic steroid users reported being significantly less in control of their aggression than did controls.
Other authors have taken a more bottom-line approach to the study of side effects associated with anabolic steroid use. Parssinen et al74 compared mortality rates among elite power lifters suspected of steroid abuse with those of population controls. The authors found that the mortality rate during the 12-year follow-up was 12.9% in the bodybuilders compared with 3.1% in the control population. The causes of death among the power lifters included suicide, acute myocardial infarction, hepatic coma, and non-Hodgkin’s lymphoma. Although the power lifters were "strongly suspected" of steroid use, no actual documentation of rate, dosing, or chronicity was established in the study. In another study on cause of death among steroid abusers, Thiblin et al96 investigated the demise of 34 known users of these drugs. Nine users were victims of homicide, 11 had committed suicide, 12 deaths were judged accidental, and 2 causes of death were not determined. Chronic cardiac changes were observed in 12 cases. The authors concluded that anabolic steroid use was associated with an increased risk of violent death from impulsive, aggressive behavior or depressive symptoms.
An additional and perhaps underappreciated health risk associated with the use of anabolic steroids is that of infection associated with needle sharing. Rich et al79 reported a 25% rate of needle sharing among adolescent anabolic steroid users. Human immunodeficiency virus, hepatitis B and C, and abscesses have been documented among anabolic steroid injectors who share needles.80
Testing and Policy
Overall, AAS are generally available only with a physician’s prescription. This class of drugs is banned and tested for by the IOC and most American sporting organizations, including the National Collegiate Athletic Association (NCAA), the National Football League (NFL), and the National Basketball Association. Major League Baseball does not test for these agents, although recent claims by former players have led to congressional hearings on the topic. Testing for anabolic steroids is fraught with complications, as there is considerable variation among normal results, testing is expensive, a positive result often results in costly legal ramifications, and newer versions of drugs that go undetected are being developed rapidly. One example of how far the legal battles have pushed the testing issues is shown in what is considered a negative test result for testosterone. According to the Olympic Movement Anti-doping Code, a test for illegal testosterone supplementation is considered to have a positive result if the ratio of testosterone to epitestosterone is 6 or greater. A normal man’s ratio rarely goes above 1.3. In fact, only 1 in 1000 men has a ratio of 4. The allowable ratio is 6:1; this is also the standard for women.
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HUMAN GROWTH HORMONE |
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Basic Science
Much of the basic science of hGH remains unknown. The hormone is a 191-residue, 22kDa peptide that is released from the anterior pituitary gland. Secretion of hGH is regulated by a number of factors, including growth hormone–releasing hormone, sleep, exercise, L-dopa, and arginine.101 The half-life of hGH is short but does stimulate the release of somatomedins like the insulin-like growth factors. In addition, hGH stimulates renal and hepatic gluconeogenesis as well as lipolysis.101
Animal studies have shown that administration of recombinant hGH leads to muscle hypertrophy, but this is not accompanied by increases in strength.62 In acromegaly, increased hGH levels lead to larger but functionally weaker muscles.62
Performance Studies
Little research has been done with hGH supplementation. That which has been done is generally in populations with endocrine dysfunction. One study in critically ill patients showed that patients treated with hGH experienced higher rates of morbidity and mortality than did their nontreated counterparts.19 Another study of hGH supplementation in elderly men with low endogenous hGH levels showed that hGH had no effect on muscle strength at any time in the study.95 Yarasheski,102 in his review, reported that daily growth hormone treatment modestly increases nitrogen retention in most normal adults but only for a few weeks. Resistance seems to occur with longer use. The author stated that it is doubtful that nitrogen retention results in an increase of contractile protein and improved muscle function, strength, or athletic performance. Supplementation with hGH did lead to increases in lean body mass, but with further investigation, these increases were noted to be nonmuscular. In a further review by Frisch,36 the author reported that although hGH may lead to an increase in size of a muscle, it is not associated with an increase in strength or performance. He also stated that in weight lifters, the incorporation of amino acids into skeletal muscle protein was not increased with hGH supplementation. These authors36,95,102 concluded that there is no evidence that growth hormone supplementation will lead to an increase in performance.
Side Effects
From the experience with acromegalics, it is known that high levels of hGH over long periods of time can lead to muscles that are myopathic.62 Side effects also include water retention, carpal tunnel syndrome, and insulin resistance.102
Testing and Policy
Only through a physician’s prescription is hGH available. It is banned by the IOC, although Olympic participants are not officially tested for hGH. Testing in professional sports in the Unites States awaits an accurate method.
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AMPHETAMINES AND OTHER STIMULANTS |
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Basic Science
Amphetamines are chemically related to the catecholamines, with the exception of the hydroxyl groups at the meta and para positions of the benzene ring that they share in common. They have an indirect action on catecholamine metabolism. In this way, they stimulate the release of norepinephrine from sympathetic nerves, resulting in vasoconstriction and increased blood pressure. In addition, mood elevation and resistance to fatigue have also been reported through a dopaminergic pathway.22 Ephedrine has a similar mechanism of action.
Performance Studies
Although not normally studied for their ergogenic potential, several studies have evaluated the effect of amphetamine on performance. One such study noted improvements in quadriceps strength and anaerobic capacity with Dexedrine administration. The study showed no increase in VO2 max, but it did show increases in time to exhaustion, suggesting resistance to fatigue.21 Other authors39 have noted that pseudoephedrine given before testing induced significant improvements in maximum torque, peak power during cycling, and lung function. Still other studies7,8 have shown that the drugs were effective in decreasing medium-distance run times.
Side Effects
The use of amphetamines has been associated with a number of negative side effects, including anxiety, ventricular dysrhythmias, hypertension, and hallucinations. In addition, use among weight lifters has been associated with dependence and addiction.45
Testing and Policy
Several amphetamines and stimulants are available over the counter. Most classes are banned by the IOC, and several forms are prohibited in American professional sports. As mentioned above, the NFL has recently banned ephedrine.
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ERYTHROPOIETIN AND BLOOD DOPING |
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Basic Science
Erythropoietin is a hormone naturally produced in the kidney. Once released, it serves to stimulate an increase in hemoglobin. In this way, it increases the oxygen-carrying capacity of the blood. Williams and Branch101 reported that an increase of 1 g/dL of hemoglobin in an athlete with an exercise cardiac output of 25 L/min would increase oxygen transport by 335 mL, which extrapolates to an 8% increase given a normal VO2max of 4000 mL O2/min. Lavoie et al59 investigated the effects of recombinant EPO (rEPO) on metabolism in rats. The authors found that 15 days of rEPO administration resulted in a significant increase in hematocrit. In addition, they found that exercised rats in the rEPO group had higher muscle glycogen and free fatty acids and lower lactate levels compared with those of controls. The results suggest that energy substrate use during exercise is affected by enhanced oxygen availability. They concluded that supplementation with rEPO resulted in a lower contribution of anaerobic metabolism to energy production.59
Performance Studies
Although popular since the 1960s, blood doping was not extensively studied until later decades. Williams and Branch101 summarized studies on the various effects of blood doping with ample volumes and time for recovery in trained athletes. With blood doping, approximate findings included a 7% increase in hemoglobin, a 5% increase in VO2 max, a 34% increase in time to exhaustion at 95% VO2 max, and a 44-second improvement in 5-mile treadmill run time performance.
Although few studies on the ergogenic potential of rEPO have been done, a few recent studies12,30 have come to similar conclusions to those achieved in studies of blood doping. Birkeland et al12 performed a double-blind, placebo-controlled study of 4 weeks of rEPO supplementation using a cycle ergometer to measure effects. The authors reported that in rEPO subjects, hematocrit increased from 42.7% to 50.8%. In addition, VO2 max increased from 63.6 to 68.1 mL · kg–1 · min–1, a 7% increase. Neither outcome measure showed a significant increase in the placebo group. Similar findings were noted by Ekblom and Berglund.30 They reported a 6% to 11% increase in hematocrit and increases in VO2 max in time to exhaustion after 7 weeks of rEPO administration.
Side Effects
Artificially raising hemoglobin levels can have dangerous consequences. In 1987, the first year of EPO release in Europe, 5 Dutch cyclists died of unexplained reasons. Between 1997 and 2000, 18 cyclists died from stroke, myocardial infarction, or pulmonary embolism. These events have brought the drug into the forefront of discussion in endurance sport. Ramifications like these prompted the American College of Sports Medicine to take a position stand against the use of any ergogenic aid designed to artificially raise hemoglobin mass, calling them unethical and unfair, and they stated that this practice exposes the athlete to unwarranted and potentially serious health risks.84
Blood transfusions, when conducted under standard hospital procedures, are a safe and effective method to increase red blood cell mass. Even in these conditions, however, risks of infection with such pathogens as HIV and hepatitis, as well as transfusion reactions, require a detailed informed consent discussion. The unsupervised practice of transfusing blood products would assuredly increase those risks. In addition, raising one’s hematocrit beyond physiologically normal levels leads to an increase in blood viscosity, thrombogenic potential, and myocardial infarction risk. These outcomes have been reported in cyclists who have supplemented with rEPO.76
Testing and Policy
The drug EPO is available only by a physician’s prescription. It is not legal in any sport. Since the 1996 Atlanta Olympics, gas chromatography–mass spectrometry evaluations have been used for screening of exogenous EPO in the urine. Recently, high-performance liquid chromatography has also been used to detect subtle peptides in the urine.13 Despite these recent advances, exogenous EPO remains a particularly difficult substance to detect through tests. Organizations that ban its use, such as the IOC, the United States Olympic Committee, and the International Cycling Union, face a considerable challenge in detecting and eliminating this drug from competitive athletics. One governing body has used an upper limit of hemoglobin as a rule for competition. This rule resulted in dramatic decreases in the hemoglobin values in world-class skiers.98
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CREATINE |
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Although discovered by Chevreul in 1832, according to Todhunter,97 the first reported use of creatine by elite athletes occurred during the 1992 Barcelona Olympics.29 The evidence was reported in British track and field athletes. Creatine use has become popular in anaerobic sporting events. Several prevalence studies of its use among college athletes quote a usage rate of 41% to 48% among men.43,58 In a recent survey of NFL trainers and team physicians, all teams had players actively taking the supplement, with estimates of use averaging 33% and reports as high as 90% (Tokish, unpublished data, 2002).
Basic Science
Creatine is a naturally occurring compound made from the amino acids glycine, arginine, and methionine. Primarily synthesized in the liver, pancreas, and kidney, 95% of the creatine is stored in skeletal muscle. These stores are broken down at a relatively constant rate of 2 g/dL into creatinine, which is excreted by the kidney. Exogenous sources of creatine include fresh fish and meat—but in small amounts that do not equal the estimated 2 g daily turnover.5 Creatine concentrations in skeletal muscle average around 125 mmol/kg of dry muscle,42 with a higher capacity for storage in type II muscle fibers.20 In its phosphorylated form, creatine contributes to the rapid resynthesis of adenosine triphosphate during short-duration maximal bouts of anaerobic exercise. This mechanism forms the basis for creatine supplementation.
In 1992, Harris et al47 showed that oral creatine supplementation resulted in a significant increase in the total creatine content of the quadriceps femoris muscle, in some subjects reaching as high as 50%. Further studies by Balsom et al4 have shown that creatine supplementation may put off or decrease anaerobic glycolysis during brief maximal exercise. These mechanisms may enhance anaerobic training, leading to strength and performance gains in these athletes.
Performance Studies
Human performance with creatine supplementation has been studied extensively. Typical designs of these studies have been longitudinal, prospective, randomized, and placebo controlled. Each study population was a relatively small group of athletes. Athletes were evaluated with a sport-specific test before and then after a period of creatine supplementation, usually for a duration of several weeks.
In weight lifters, the number of repetitions at a specified percentage of single-repetition maximum goes up approximately 20% to 30% after a short-term creatine supplementation period.27,56,93
In cyclists, most studies have shown that creatine supplementation is effective in maintaining muscular force and power output.4,11,26,82 In swimming, performance hasbeen measured with repeated short sprints of maximal intensity. Results have been mixed, with some studies showing a significant reduction in sprint times,44,61 whereas others have found the opposite and concluded that creatine supplementation is not effective in swimmers.17,67 Differences in these studies may be attributed to different outcome measures, the complex mechanics of the swimming stroke, or different supplementation regimens.
In track and field sprinters, several studies have shown an improvement in mean sprint times in the range of 1% to 2%,1,48,68,85 whereas authors50,78 of 2 other studies concluded that creatine had no effect on single sprint times.
In terms of body composition changes, creatine supplementation appears to increase weight and lean body mass4,5,42,56 by around 1 to 2 kg over a short-term supplementation cycle.
There have also been studies in which creatine has been shown to be ineffective. These areas include supplementation in the older athlete (60–87 years of age)90 and most aerobic endeavors,31,32 although the latter study did find an approximate 18% benefit in the final "kick" phase of an aerobic event.
A summary statement on these studies would be that creatine can be an effective ergogenic supplement maximized when used for simple, short-duration, maximal-effort anaerobic events.
Side Effects
Since the introduction of creatine in the early 1990s, there have been a number of isolated case reports of possible renal side effects associated with its use.41,54,75 Although creatine is commonly thought to lead to dehydration, to date, there has been no study that has demonstrated a negative side effect with the use of creatine in athletes. It should be cautioned, however, that the studies that have been done are mostly short term and pertained to healthy individuals. We do not know the long-term effects of this supplement, nor do we have sufficient data on its possible effects on other creatine-containing tissues such as the brain, cardiac muscle, or testes.51 In addition, several authors9,46,84,87 caution that long-term administration of creatine will likely lead to the down-regulation of the creatine transporter protein and, thus, an increased resistance to the compound. This effect has been authenticated in a rat model.46
Thus, it appears that short-term supplementation with creatine is safe, although much more research needs to be done to investigate long-term effects, possible harm to other tissues, and the consequences of down-regulation.
One additional drawback to creatine deserves further mention. Because it is not classified as a drug, creatine is not under direct regulation by the Food and Drug Administration. This is a problem receiving much attention throughout the supplement industry, and although there is effort to control nutritional supplements in the United States, the quality of individual brands of creatine and other nutritional supplementation remains far from uniform. This lack of uniformity makes creatine difficult to study and harder to control.
Testing and Policy
Creatine is available over the counter in several nutritional supplements. It is not tested for or banned by any major athletic organization. The NCAA does have a policy that none of its member teams will provide creatine to their players. In a recent survey of NFL trainers and team physicians, 40% of NFL teams provided creatine for their players, although in no case was the medical staff involved in this distribution (Tokish, unpublished data, 2002).
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Basic Science
The mechanism by which HMB may function is not known. Some have postulated that it may act through increasing the testosterone-epitestosterone ratio, similar to anabolic steroids. Slater et al,89 however, showed that supplementation with HMB over 2 weeks resulted in no significant increase in the urinary testosterone-epitestosterone ratio, and they concluded that this supplement does not work through a testosterone-mediated pathway.
Other researchers have postulated that HMB supplementation may delay the onset of markers of anaerobic metabolism. Vukovich and Dreifort99 examined VO2 peak and lactate accumulation in cyclists in a prospective, randomized double-blind trial of HMB versus placebo over three 2-week supplementations. The authors noted that although VO2 peak was unaffected by HMB supplementation, the onset of blood lactate accumulation, a marker of anaerobic metabolism, was significantly increased in the HMB group compared with controls.
If HMB is to work as a protein breakdown suppressor, then it would follow that supplementation with HMB should decrease the concentration of markers of muscle damage. This hypothesis has been tested by Knitter et al,53 who examined the effect of HMB supplementation on creatine phosphokinase and lactate dehydrogenase activities before and after a long run in a prospective, randomized, placebo-controlled 6-week trial. The authors found that the HMB group exhibited significantly lower creatine phosphokinase and lactate dehydrogenase levels than did controls and concluded that HMB supplementation may prevent exercise-induced muscle damage. Several other authors70–72 have noted similar findings.
Performance Studies
A number of studies have evaluated the effects of HMB supplementation on various markers of human performance. It has been shown that although upper body strength72 and peak torque generation37 may show modest improvements after HMB supplementation in untrained individuals, measures such as bench press and leg press one-repetition maximum in trained individuals are not affected by HMB.37,56,89 When performance with this supplement is examined based on body composition changes, the results are modest at best. Some studies37,70–72 have shown significant increases in fat-free mass and decreases in body fat percentage of around 1% over that of controls, whereas other studies56,89 have shown no significant changes in body composition after HMB supplementation.
Thus, although there is some evidence that HMB may act to suppress protein breakdown, there is little evidence in the literature to support that this translates into an ergogenic advantage.
Side Effects
There have been only a few studies on the side effects of HMB supplementation. Gallagher et al38 evaluated these effects on hematologic, hepatic, and renal function. Although an increase in basophils was noted in the HMB group, no effect was noted on glucose, blood urea nitrogen, hemoglobin, hepatic enzymes, lipid profile, or total leukocytes. In addition, no change in urinalysis was noted. The authors concluded that HMB supplementation is safe for these systems in healthy individuals over an 8-week period. In a comprehensive review, Nissen et al71 evaluated 9 previous studies done on the safety of HMB supplementation. They found that HMB had no negative effects on blood chemistry. In addition, in review of all the studies, HMB supplementation lowered total cholesterol, low-density lipoprotein cholesterol, and systolic blood pressure. These findings suggest that HMB supplementation appears to be a safe practice and may be cardioprotective.
Testing and Policy
Finally, HMB is available in many over-the-counter nutritional supplements. It has not been banned by any sporting organization to date.
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ANDROSTENEDIONE |
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Basic Science
The concept of how andro works is based on the knowledge of the effectiveness of testosterone as an ergogenic aid. It is a natural precursor to testosterone. It has been postulated that if the concentration of andro is increased, it will allow for conversion to testosterone and, thus, a more anabolic profile. This claim has been evaluated by a number of studies.3,14–16,52,77,100 Whether testosterone is increased with andro supplementation is still being debated. The majority of well-designed studies3,14,52,77,100 showed no increase in testosterone concentrations with supplementation. Investigators of 2 studies15,60 have found an increase in testosterone with supplementation. What has been shown in the science but that is absent from the marketing is that all major studies on andro supplementation have shown a significant increase in estrogen concentration, a most unergogenic effect.
Performance Studies
Androstenedione supplementation has been studied for ergogenic properties such as lean body mass changes and strength increases.14,52,100 No study has shown a significant ergogenic effect of any kind with andro supplementation.
Side Effects
A number of studies have evaluated the effects of andro supplementation on blood lipid profiles.14,16,52 In each of these studies, supplementation has been shown to lower HDL profiles and, thus, may pose a cardiovascular risk. In addition to this, Broeder et al14 have shown that supplementation with andro may lead to the down-regulation of endogenous testosterone synthesis.
Testing and Policy
Androstenedione is available in many over-the-counter nutritional supplements. It is banned by the IOC, N CAA, and NFL, but it is not banned by Major League Baseball.
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SUMMARY |
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). The "just say no" approach to advising the athlete about these supplements will continue to fail because there is such a potent marketing influence to take these supplements and such a powerful drive in athletes to find a competitive advantage. An understanding of the science, or lack thereof, behind ergogenic aids is essential for those who care for athletes. Team physicians, trainers, and coaches must give meaningful and safe advice to these athletes.
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CONCLUSION |
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TOPABSTRACTINTRODUCTIONANABOLIC STEROIDSHUMAN GROWTH HORMONEAMPHETAMINES AND OTHER...ERYTHROPOIETIN AND BLOOD DOPINGCREATINEBETA-HYDROXY-BETA-METHYLBUTYRATEANDROSTENEDIONESUMMARYCONCLUSIONREFERENCES |
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FOOTNOTES |
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|| References 23, 28, 33, 49, 57, 66, 74, 79, 80, 94, 96. 
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REFERENCES |
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TOPABSTRACTINTRODUCTIONANABOLIC STEROIDSHUMAN GROWTH HORMONEAMPHETAMINES AND OTHER...ERYTHROPOIETIN AND BLOOD DOPINGCREATINEBETA-HYDROXY-BETA-METHYLBUTYRATEANDROSTENEDIONESUMMARYCONCLUSIONREFERENCES |
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