Differential effect of creatine on oxidatively-injured mitochondrial and nuclear DNA

Creatine is a naturally occurring compound obtained in humans from endogenous production and consumption through the diet. It is used as an ergogenic aid to improve exercise performance and increase fat-free mass. Lately, creatine’s positive therapeutic benefits in various oxidative stress-associated diseases have been reported in literature and, more recently, creatine has also been shown to exert direct antioxidant effects. Oxidatively-challenged DNA was analysed to show possible protective effects of creatine. Acellular and cellular studies were carried out. Acellular assays, performed using molecular approaches, showed that creatine protects circular and linear DNA from oxidative attacks.Nuclear and mitochondrial DNAs from oxidatively-injured human umbilical vein endothelial cells were analyzed. Creatine supplementation showed significant genoprotective activity on mitochondrial DNA. This evidence suggests that creatine may play an important role in mitochondrial genome stability in that it could normalize mitochondrial mutagenesis and its functional consequences. Thus, creatine supplementation could be used to prevent or ameliorate diseases related to mitochondrial DNA mutations, and possibly to delay aging.