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Am Fam Physician. 2001;63(5):913-923

See editorial on page 842.

Numerous ergogenic aids that claim to enhance sports performance are used by amateur and professional athletes. Approximately 50 percent of the general population have reported taking some form of dietary supplements, while 76 to 100 percent of athletes in some sports are reported to use them. Physicians can evaluate these products by examining four factors (method of action, available research, adverse effects, legality) that will help them counsel patients. Common ergogenic aids include anabolic steroids, which increase muscle mass. These illegal supplements are associated with a number of serious adverse effects, some irreversible. Creatine modestly improves athletic performance and appears to be relatively safe. Dehydroepiandrosterone and androstenedione do not improve athletic performance but apparently have similar adverse effects as testosterone and are also banned by some sports organizations. Caffeine has mild benefits and side effects and is banned above certain levels. Products that combine caffeine with other stimulants (e.g., ephedrine) have been linked to fatal events. Protein and carbohydrate supplementation provides modest benefits with no major adverse effects.

Ergogenic aids are substances or devices that enhance energy production, use or recovery and provide athletes with a competitive advantage.

Numerous products claim to bolster strength or endurance in sports. In 1996, approximately 50 percent of the general population reported some supplement use.1 Other surveys have shown that 76 percent of college athletes, and 100 percent of body builders take supplements.2 Americans spent $11.8 billion on supplements in 1997, with a predicted growth rate of 10 to 14 percent in 2000 (Table 1).3

ProductCost*
Creatine powder$ 26
Creatine mixture†60
DHEA14
Androstenediol30
Androstenedione30
HMB100
Protein powder (50 g daily)85
Antioxidant formulations30
Energizing/diet capsules35
Multivitamins5 to 20

New products with ergogenic claims appear on the market almost daily. Most are classified as supplements, which means the contents of the product and the claims on the label have not been evaluated by the U.S. Food and Drug Administration and may not have any scientific basis. The following questions will help the physician and patient determine whether a product is worth taking:

1. What is the physiologic basis or theory for this product's action?

2. Are there any scientific studies published in peer-reviewed journals that support or refute the claims that the product makes?

3. Are there any side effects, especially any potentially serious adverse effects?

4. Is the product legal?4

This article reviews some of the more popular supplements and provides some basic information on others.

Anabolic Steroids

Action

Anabolic steroids are testosterone derivatives with three mechanisms of action. First, anticatabolic effects reverse the actions of glucocorticoids and help metabolize ingested proteins, converting a negative nitrogen balance into a positive one. Second, anabolic effects directly induce skeletal muscle synthesis. Third, there is a “steroid rush”—a state of euphoria and decreased fatigue that allows the athlete to train harder and longer.5

Research

Many early studies used physiologic doses, or doses only two to three times these amounts, and provided mixed results. More recent reviews,5 controlling for various measurement methods, have concluded that anabolic steroids do indeed cause increased strength and muscle mass. A randomized, double-blind, 10-week study6 of 40 men examined the effect of supraphysiologic testosterone doses. The participants were divided into four groups: those given a placebo with or without weight training, and those given 600-mg testosterone enanthate with or without weight training. Diet and training times were controlled. Fat-free mass, muscle size and strength increased more than placebo in both groups taking testosterone than in the groups taking placebo. The subjects in the exercise plus testosterone group had a 9 percent increase in mass and 23 percent increase in bench-press strength, compared with 3 percent and 9 percent, respectively, in the subjects in the exercise plus placebo group.6 These doses were comparable with the doses that many athletes who use steroids take.

Adverse Effects

Anabolic steroids have many adverse effects, most related to the unwanted androgenic effects. Some of the adverse effects are potentially serious and irreversible (Table 2).

Reversible side effects
Sexual effects
Increased or decreased libido
Decreased sperm production
Scrotal pain
Gynecomastia
Cutaneous effects
Acne
Hirsutism
Edema
Psychiatric effects
Euphoria
Nervousness
Aggression
Personality disorders
Other
Increased tramsaminases
Nausea
Increased urination
Serious and irreversible side effects
Hypertension from mineralocorticoid effects
Dysplastic changes in collagen fibrils, resulting in severe tendon ruptures
Liver tumors (hepatocellular carcinoma, hepatic adenoma, hepatic cholangiocarcinoma)
Psychosis (i.e., “steroid rage”)
Irreversible hirsutism, clitoral hypertrophy and deepening of voice in women
Premature closure of growth plates, causing shorter stature in adolescents

Legality

Anabolic steroids such as testosterone and its derivatives are prescription medications with clearly defined indications. Procuring and using them without a prescription is illegal. Most sports organizations have rules that ban the use of anabolic steroids for any reason.

Creatine

Action

During brief, high intensity exercise, adenosine diphosphate is rephosphorylated to adenosine triphosphate (ATP) by muscle phosphocreatine stores. As muscle phosphocreatine stores become depleted, performance decreases. Oral creatine supplementation can increase muscle phosphocreatine stores by 6 to 8 percent. Increasing the available muscle stores of phosphocreatine causes faster regeneration of ATP, allowing decreased rest time between activities and increased energy for repeated bouts of exercise. Increased muscle creatine also buffers the lactic acid produced during exercise, delaying muscle fatigue and soreness. As with any ergogenic aid, increased motivation can spring from expected or perceived benefits, causing increased effort (placebo effect).

Research

Creatine research shows generally positive results. A short-term, double-blind, placebo-controlled study7 examined the effects of 28 days of creatine supplementation on 25 football players. Diet and exercise were tightly controlled, and strength and body composition were measured. Body weight, dual-energy radiograph absorptiometry-scanned body mass, fat-free and bone-free mass, and bench-press strength all increased in the athletes taking creatine. Overall lifting volume (sum of all lifts) was increased by 41 percent in this group. A five-week study8 of 42 football players also showed gains in strength and mass. Another report9 of 19 women who took supplements for 10 weeks also described increases in strength and mass. Some researchers10,11 have seen strength gains with as little as five to seven days of supplementation.10,11 Studies12 examining the effects of creatine in older individuals (60 to 82 years of age) have found no effect on body composition or strength. Investigations7,13 of the benefits on short-term sprint performance have shown increases in endurance time. A summary of 31 studies14 on sprint performance showed that supplemental creatine is associated with some improvement in athletic performance in laboratory settings, but most findings indicated no benefit on the field.

A typical regimen for creatine supplementation uses a loading dosage of 20 g daily, divided in four doses, for five to seven days, followed by a maintenance dosage of 5 g daily. Creatine monohydrate is not dehydrating, and may be safer.

Adverse Effects

Weight gain is the most consistent adverse effect reported. In studies that investigated side effects, no other adverse effects were found, including no changes in electrolyte concentrations, muscle cramps or strains.7 Researchers15 examined the renal function of patients who had been using creatine for as long as five years and found no detrimental effects.15 Some studies have shown improved cholesterol profiles in persons taking creatine.7 It must be noted, however, that most research to date has examined creatine use of three months or less, leaving questions about long-term use unanswered.

Legality

Creatine is legal for use in amateur and professional sports.

Dehydroepiandrosterone and Androstenedione

Action

Both of these supplements are precursors in the gonadal steroid pathway (Figure 1). Increasing supplies of precursors theoretically cause a physiologic increase in testosterone synthesis.

Research

Dehydroepiandrosterone (DHEA) has been studied for its replacement role in older men and women. These studies16,17 found testosterone levels increased in women, but were unchanged in men, with no changes in body composition noted. No published studies of its ergogenic benefit in younger athletes exist. One eight-week study18 evaluated androstenedione supplementation in 30 men, aged 19 to 29 years, during resistance training. No differences in muscle size, strength or overall body composition were noted. One study19 has shown transient increases in serum testosterone levels but no ergogenic benefit has been demonstrated.

Adverse Effects

No long-term studies of adverse effects are available. If these precursors could successfully increase testosterone production, they would likely cause the many adverse effects associated with anabolic steroids.

Legality

DHEA is banned by the International Olympic Committee (IOC). Androstenedione is banned by the IOC, the National Collegiate Athletic Association (NCAA) and the National Football League.

Caffeine

Action

Caffeine enhances the contractility of skeletal and cardiac muscle, and helps metabolize fat, thereby sparing muscle glycogen stores. It is also a central nervous system stimulant, which can aid in activities that require concentration.

Research

Many small studies20,21 using randomized, double-blind design have associated caffeine use with increased endurance times. The smallest dose linked to positive results was 250 mg (approximately 3.0 to 3.5 mg per kg).22 Other studies have used doses of 6 to 9 mg per kg.

Adverse Effects

Ergogenic doses of caffeine may cause restlessness, nervousness, insomnia, tremors, hyperesthesia and diuresis. Caffeine use has no adverse effects on body temperature or sweating.23

Legality

Caffeine is part of a regular diet for most people and is legal to a certain level. The legal urine level for athletes is 12 μg per mL (IOC standards) or 15 μg per mL (NCAA standards). The ergogenic dose is approximately one half of this—250 to 500 mg (three cups of coffee or six to eight sodas). Many athletes take caffeine in pill form.

Caffeine and Ephedrine Combination

Action

Sympathomimetics such as ephedrine, pseudoephedrine, phenylpropanolamine and herbal ephedrine (ma huang) are used for their stimulant properties. This combination is found in many “energizing” and diet supplements and is used to increase subjective energy, decrease appetite and increase metabolism without exercise.24

Research

A double-blind study24 of eight patients showed prolonged time to exhaustion and decreased perception of exertion with a caffeine and ephedrine combination. Studies24,25 of sympathomimetics alone have not shown benefit.

Adverse Effects

The combined adverse effects of these stimulants include restlessness, nervousness, tachycardia, arrhythmias and hypertension. As of August 1998, at least 17 deaths have been linked to use of these products in combination.26

Legality

Use of ephedrine products and elevated levels of urinary caffeine, as noted above, are banned by the IOC.

Protein

Action

Protein and its constituent, amino acids, are the building blocks of muscle. Protein supplements are used by some athletes to enhance muscle repair and growth. Inadequate protein intake does cause a negative nitrogen balance, which slows muscle growth and causes fatigue.

Research

Athletes in training have increased protein needs. A study27 examining the protein requirements of experienced resistance-training athletes found that those consuming the recommended daily allowance for protein (0.8 g per kg daily) had a negative nitrogen balance. The protein intake required for a zero balance was 1.4 g per kg daily, with a recommended intake of 1.8 g per kg daily. Another study28 using novice resistance-training athletes found their requirements to be 1.6 to 1.7 g per kg daily. Both studies found that protein intakes in excess of these recommendations did not provide additional gains in strength or mass.

Adverse Effects

In an athlete with normal renal function, there are no notable adverse effects to increased protein consumption. It may be more healthy, however, to avoid acquiring protein from foods that also contain increased amounts of fat and cholesterol.

Legality

Protein supplements are legal.

Carbohydrates

Action

While fat stores constitute the largest reservoir of stored energy, carbohydrates are the body's main source of rapidly available energy. It has been suggested that taking proper quantities of carbohydrates at the right time could improve athletic performance by ensuring adequate energy stores are available when necessary.

Research

Loading, or increasing the carbohydrate content of the diet for several days before an event, has been promoted as a means to prolong exercise endurance. One study29 evaluated its impact on continuous, short-term events of less than one hour and found no benefit, because muscle glycogen content was not depleted at the end of the exercise.

A meal prior to exercise will ensure that muscle and liver glycogen stores are maximized. Studies30,31 investigating a meal two to four hours prior to exercise have shown positive effect, regardless of the “glycemic index” of the foods ingested. Evaluation of six endurance athletes ingesting carbohydrates only 45 minutes prior to a two-hour exercise test revealed no benefit.32

Replenishment with carbohydrate-containing fluids during an endurance event may help to delay fatigue. Thirty marathon runners in a double-blind study33 described decreased subjective exertion when ingesting 60 g per hour of a liquid carbohydrate solution during a two and one-half hour run. Another study34 found that ingesting a carbohydrate-electrolyte drink during one hour of high-intensity exercise improved performance in 19 bicyclists. Many studies have demonstrated similar results. One study35 that evaluated solid versus liquid carbohydrate replenishment showed no difference, as long as adequate water intake was maintained. Eating a mixture of carbohydrates and protein within two hours after an activity has also been associated with benefits, including replenishment of depleted muscle and liver glycogen stores and decreased muscle catabolism. A study36 of nine weight lifters showed increased levels of plasma growth hormone and insulin when athletes ingested protein and carbohydrate immediately and two hours after exercise, which would theoretically provide a physiologic environment favorable for muscle growth. Another placebo-controlled study37 of endurance athletes ingesting a carbohydrate-containing solution after exercise reported increased glycogen resynthesis.

Adverse Effects

Theoretic disadvantages have been reported with carbohydrate supplementation. Increased insulin levels after carbohydrate consumption were shown to significantly decrease blood glucose levels in some athletes, though not all athletes seem to be subjectively sensitive to these decreased levels.38 Fructose-containing solutions have been associated with adverse gastrointestinal effects in some studies.39

Legality

Carbohydrate supplements are legal.

Many other dietary supplements have been advertised for their purported ergogenic properties, and the list grows each year. Table 3 provides a brief summary of the most common agents that physicians may hear about from their patients who are athletes. When counseling patients about ergogenic aids, it is important that the physician be knowledgeable about the topic. The intervention that carries the most impact is ensuring optimal dietary habits. Supplying adequate energy intake, carbohydrates and protein in the diet, and timing these to be efficiently used by the body, will provide the most effective and safe results.36,40

Ergogenic aidActionResearch on ergogenic effectsSide effectsLegality
AlcoholDecreases anxietyNo benefitsSignificantBanned for shooting events
AmphetaminesImprove concentration, decrease fatigue and appetiteMixed, some positiveSignificant, dangerousIllegal
Anabolic steroidsIncrease strength, lean muscle mass and motivationPositiveSignificant, dangerousIllegal
AndrostenediolSame as steroidsLimited, refutesUnknownBanned by IOC
AndrostenedioneSame as steroidsRefutes, no benefitsSignificantBanned by IOC, NCAA
AntioxidantsDecrease muscle breakdownMixed, no clear benefitsMild at high dosesLegal
Arginine, ornithine, lysineStimulate growth hormone releaseNo benefitNone at doses usedLegal
AspartatesIncrease free fatty acid use, sparing muscle glycogenMixed, some positive benefitsMild at high dosesLegal
AspirinDecreases pain with muscle fatigue and muscle breakdownNo benefitMildLegal
Avena sativaIncreases steroid productionLimited, refutesNoneLegal
Bee pollenIncreases strength and enduranceRefutes, no benefitsAllergic reactionLegal
Beta blockersDecrease anxietyPositive effect on fine motor control, negative effect on aerobic capacitySignificantBanned by IOC
Beta2 agonistsIncrease lean muscle massMixed, no benefit from inhaled formulationsMildBanned by IOC, legal when prescribed
Blood dopingIncreases aerobic capacitySupportsSignificant, dangerousIllegal
BoronIncreases endogenous steroid productionRefutes, no benefitMild at high dosesLegal
Branched chain amino acidsDecrease mental fatigueMixed, negativeMild at high dosesLegal
CaffeineIncreases muscle contractility and aerobic endurance, enhances fat metabolismSupportsMildLegal to urine level of 12 to 15 μg per mL
CalciumIncreases muscle contractility, enhances glycogen metabolismRefutes, no benefitMild at high dosesLegal
CarbohydratesIncrease endurance, decrease fatigueSupportsMild at high dosesLegal
CarnitineIncreases fat metabolismRefutesNoneLegal
CholineIncreases enduranceMixed, inconclusiveNoneLegal
ChromiumIncreases lean massRefutes, no benefit unless prior deficiencySafe to 400 μg daily, potentially dangerous above this levelLegal
ChrysinInhibits aromatase, increases endogenous steroidsLimited, refutesNoneLegal
CocaineStimulates CNS, delays fatigueMixedSignificant, dangerousIllegal
Coenzyme Q10 (ubiquinone)Delays fatigue, acts as antioxidantRefutes, no benefitNoneLegal
Coenzyme Q12Increases aerobic capacity, speeds muscle repairRefutes, no benefitNoneLegal
CreatineIncreases muscle energy, endurance, strength and lean muscle massSupports, insufficient data on long-term useMildLegal
DHEAIncreases endogenous steroid productionNo benefit in healthy athletesPotentially dangerousBanned by IOC, some other organizations
DiureticsDecrease body massLimited benefitPotentially dangerousBanned by IOC
Ephedrine, other sympathomimeticsStimulate CNS, increase energy, delay fatigue, stimulate weight lossNo benefitPotentially dangerousBanned by IOC, some other organizations
Ephedrine plus caffeineIncreases energy, stimulates weight lossSupportsPotentially dangerous, fatal at high dosesBanned by IOC, some other organizations
ErythropoietinIncreases aerobic capacitySupportsSignificant, dangerousIllegal
Fat supplementsIncrease enduranceRefutesMildLegal
FluidsIncrease enduranceSupportsMildLegal
Folic acidIncreases aerobic capacityRefutesNoneLegal
GHBStimulates growth hormone release and muscle growthLimited, refutesSignificant, dose-related; abuse potentialIllegal
GinsengIncreases endurance, enhances muscle recoveryLimited, refutes, no benefitMild, abuse syndrome reportedLegal
GlucosamineServes as NSAID alternative, enhances recoveryLimited, may have limited NSAID abilitiesNoneLegal
GlutamineBoosts immunity and growth hormone levelsMay boost immunity, no other benefitsNoneLegal
GlycerolImproves hydration and enduranceLimited, supportsMildLegal (oral)
Guarana (herbal caffeine)Same as caffeine
HMBDecreases muscle breakdown, enhances recoveryLimited, some strength benefitsNoneLegal
Human growth hormoneAnabolic effect on muscle growth, increases fat metabolismRefutes, limited ergogenic benefitsSignificant, dangerousIllegal
InosineEnhances energy production, improves aerobic capacityRefutes, no benefitMildLegal
IronIncreases aerobic capacityNo benefit unless preexisting deficiencyMild, toxic at high dosesLegal
LeucineDecreases muscle breakdown and spare muscle glycogen storesLimited, no ergogenic effectNoneLegal
Ma huang (herbal ephedrine)Same as ephedrine
MagnesiumEnhances muscle growthNo benefit unless preexisting deficiencyMild at high dosesLegal
MarijuanaDecreases anxietyRefutes, negative effectSignificant, dangerousIllegal
MultivitaminsIncreases energy, endurance and aerobic capacity, enhances recoveryNo benefit unless preexisting deficiencyNone at RDA, some toxicities at high dosesLegal
NarcoticsIncrease endurance by suppressing pain, decrease anxietyMixed, negativeSignificant, dangerousIllegal
NiacinIncreases energy and enduranceNo benefit unless a preexisting deficiencyMild at high dosesLegal
OxygenIncreases aerobic capacity, enhances recoveryNo benefit if given before or after activityMildLegal
PhosphatesIncrease ATP production, energy and muscle enduranceMixed, negativeMild at high dosesLegal
PhytosterolsStimulates release of endogenous steroids and growth hormoneRefutes, no benefitLittle data, allergic reaction possibleLegal
ProteinOptimizes muscular growth and repairSupports, increased need for protein with activityNone unless underlying medical conditionLegal
PycnogenolBoosts antioxidant levels, enhances recoverySupports, dietary sources offer same benefitNoneLegal
PyruvateIncreases lean body massLimited research, benefit only in specific casesNoneLegal
D-RiboseIncreases cellular ATP and muscle powerNo human researchNone knownLegal
SeleniumEnhances antioxidant functionsLimited, no benefitMild at high dosesLegal
Sodium bicarbonateBuffers lactic acid production, delays fatigueSupportsMild, dangerous at high dosesLegal
StrychnineUnknownNo research on ergogenic benefitsSignificant, dangerousLegal
Tribulus terrestrisIncreases endogenous steroid productionRefutesPotentially dangerous at high dosesLegal
TryptophanDecreases pain perception, increases enduranceMixed, no benefit in trained athletesMild, potentially dangerousLegal
Vanadyl sulfateIncreases glycogen synthesis, enhances muscle recoveryRefutes, no benefit in healthy individualsMildLegal
Vitamin B1 (thiamin)Enhances energy production, increases aerobic capacity, improves concentrationNo benefit unless preexisting deficiencyNoneLegal
Vitamin B2 (riboflavin)Increases aerobic enduranceNo benefit unless preexisting deficiencyNoneLegal
Vitamin B6 (pyridoxine)Enhances muscle growth, decreases anxietyNo benefit unless preexisting deficiencyMild at high dosesLegal
Vitamin B12 (cyanocobalamin)Enhances muscle growthNo benefit unless preexisting deficiencyNoneLegal
Vitamin B15 (dimethylglycine)Increases muscle energy productionMixed, negativeNone proven, but concerns raisedLegal
Vitamin CActs as antioxidant, increases aerobic capacity and energy productionNo benefit unless preexisting deficiencyMild at high dosesLegal
Vitamin EActs as antioxidant, improves aerobic capacityMixed, some positiveMildLegal
YohimbineIncreases endogenous steroid productionRefutes, no benefitMildLegal
ZincEnhances muscle growth, increases aerobic capacityLimited, negativeMildLegal

If a patient asks about a specific ergogenic aid, he or she should be told what is known and unknown about the product based on current research, including the side effect profile. The danger is that once athletes start using a commercial supplement, they will continue to use more, eventually trying something that may not be safe. Many athletes feel pressured to use supplements to maintain a competitive advantage over their supplement-using peers. If physicians can guide athletes away from disproven and dangerous supplements, while maintaining open and honest lines of communication, then more serious health risks may be prevented.

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