Both creatine, a natural amino acid derivative, and androstenedione, a testosterone precursor, are marketed and sold as “dietary supplements.” Widely believed to enhance athletic performance, these products received national attention following the record-breaking home-run performance of baseball player Mark McGwire, who reportedly takes both. Neither supplement is labeled by the U.S. Food and Drug Administration for any indication. Consultants from The Medical Letter reviewed the available data.

Creatine is naturally present in food sources such as meat and fish. Cells with high energy requirements use creatine in the form of phos-phocreatine, which serves as a phosphate donor to generate adenosine triphosphate (ATP) from adenosine diphosphate. There is enough phosphocreatine and ATP in skeletal muscle cells for about 10 seconds of high-intensity activity. In one short-term study, the use of creatine supplements increased body mass primarily because of increased water retention. A 28-day placebo-controlled trial that studied eight weightlifters found that taking 20 g per day of creatine produced a significant increase in strength, body weight and fat-free mass. A summary of 31 studies of short, high-intensity tasks suggested that oral creatine supplements modestly improved performance. However, most of these studies were performed in the laboratory. In actual field trials, no benefit was demonstrated. Other studies failed to show a consistent advantage to creatine use during aerobic activity.

Oral creatine appears to be well tolerated with no adverse effects reported in healthy men who used recommended dosages. Creatine supplements are not banned by athletic organizations such as the International Olympic Committee (IOC) and the National Collegiate Athletic Association (NCAA).

Androstenedione is available in the United States in tablet form, often in combination with other steroids. By itself, androstenedione has little intrinsic activity, although it is a direct precursor of estrone and testosterone. Taking supraphysiologic dosages of testosterone has been shown to increase nitrogen retention and muscle strength and mass. Whether these same effects are achieved with the use of androstenedione is unknown. There are few published studies on the effects of androstenedione use. One study demonstrated a four- to sixfold increase in the levels of blood testosterone within one hour of ingesting 100 mg of androstenedione.

Long-term data on the safety of andro-stenedione are not available. Adverse effects from the use of exogenous testosterone in men are well known and include acne, testicular atrophy and behavioral changes. In women, adverse effects include hirsutism, malepattern baldness, amenorrhea and clitoral hypertrophy. Adolescents who take exogenous testosterone may experience early closure of the bone growth plates and decreased adult height. Many athletic organizations, including the IOC, NCAA and National Football League, ban the use of androstenedione.

The Medical Letter consultants concluded that although creatine supplements may modestly improve athletic performance in some brief, high-intensity activities in laboratory settings, the benefits have not been documented in actual on-field activities. Although androstenedione can increase the levels of blood testosterone, the effect it has on muscle mass remains to be established. Currently, it is assumed that androstenedione produces the same adverse effects as exogenous testosterone. The potency and purity of both creatine and androstenedione supplements in the U.S. market are currently unknown.