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Objective: Strenuous exercise can induce apoptosis in a variety of tissues. We investigated the effects of creatine loading on apoptosis markers after downhill running. Design: Twenty-two middle-aged men were randomly assigned to either a creatine or a placebo group. Crossover design, double-blind controlled supplementation was performed using 20 g/d-1 of creatine ormaltodextrin for 7 days. Downhill running (12% incline) at 70% of heart ratemaximum for 40 mins was performed on the eighth day. Blood samples were taken on the day before supplementation, after supplementation and after running. Results: There were no significant changes in the caspase-3, caspase-9, p53, Bax, and IGF-1 concentrations from presupplementation to postsupplementation in both groups of creatine and placebo (P > 0.05). There were significant increases (P < 0.05) in serum caspase-3, caspase- 9, p53, andBax after running in the placebo group. Thesemarkerswere not noticeably changed in the creatine group (P > 0.05). Bcl-2was unchanged in the placebo group but substantially increased (P < 0.05) in the creatine group. No significant changes were observed in IGF-1 concentration after running comparing to prerunning in both groups (P > 0.05). Lactate levels increased similarly in both groups (P < 0.05). Conclusions: The findings indicate that creatine supplementation could prevent exercise-induced apoptotic markers. [ABSTRACT FROM AUTHOR]