Objective: To critically review the current data concerning potential safety concerns of oral creatine supplementation.
Data sources and study selection: Medline was searched using keywords to locate published works relating to creatine supplementation and adverse effects. Abstracts that specifically studied potential adverse effects of creatine were also utilized, as were human and animal studies of creatine metabolism in various organ systems.
Data extraction and synthesis: Specific data from studies that investigated creatine's side effects and metabolism were grouped by organ system to better describe potential safety issues.
Conclusions: Creatine supplementation results in weight gain due to water retention, which may impede performance in mass-dependent activities such as running and swimming. Although short-term use (fewer than 28 days) at recommended does has not been shown to cause significant adverse effects, the studies on which this is based involved small numbers of subjects, and none of the studies provided a sample size calculation. Furthermore, despite the fact that creatine is normally found in cardiac muscle, brain, and testes, these areas remain essentially unstudied with respect to oral creatine supplementation. Future studies should include large randomized controlled trials evaluating the short and long term effects of oral creatine supplementation on the renal and hepatic systems, as well as the many other organ systems in which creatine plays a metabolic role.