CONTEXT: Allegations about side effects of creatine supplementation by athletes have been published in the popular media and scientific publications. PURPOSE: To examine the experimental evidence relating to the physiological effects of creatine supplementation. RESULTS: One of the purported effects of oral creatine supplementation is increased muscle mass. A review of the literature reveals a 1.0% to 2.3% increase in body mass, which is attributed to fat-free mass and, more specifically, to skeletal-muscle mass. Although it is unlikely that water retention can completely explain these changes, increase in muscle-protein synthesis has never been observed after creatine supplementation. Indirect evidence based on mRNA analyses suggests that transcription of certain genes is enhanced. Although the effect of creatine on muscle-protein synthesis seems irrefutable according to advertising, this allegation remains under debate in the scientific literature. The kidneys appear to maintain their functionality in healthy subjects who supplement with creatine, even over several months. CONCLUSION: The authors, however, think that creatine supplementation should not be used by an individual with preexisting renal disease and that risk should be evaluated before and during any supplementation period. Even if there is a slight increase in mutagenic agents (methylamine and formaldehyde) in urine after a heavy load of creatine (20 g/day), their excretion remains within a normal range. No data are currently available regarding the potential production of heterocyclic amines with creatine supplementation. In summary, the major risk for health is probably associated with the purity of commercially available creatine.
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