Creatine has become one of the most extensively studied and scientifically validated nutritional ergogenic aids for athletes. Additionally, creatine has been evaluated as a potential therapeutic agent in a variety of medical conditions. In terms of exercise, the energy supplied to rephosphorylate adenosine diphosphate (ADP) to adenosine triphosphate (ATP) during and following intense exercise is dependent to a large degree on the amount of phosphocreatine (PCr) stored in the muscle.1,2 As PCr stores become depleted during intense exercise, energy availability deteriorates due to the inability to resynthesize ATP at the rate required.1,2 Consequently, the ability to maintain maximal-effort exercise declines. Since the availability of PCr in the muscle may significantly influence the amount of energy generated during brief periods of high-intensity exercise, it has been hypothesized that increasing muscle creatine content via creatine supplementation may increase the availability of PCr and allow for an accelerated rate of resynthesis of ATP during and following high-intensity, short-duration exercises.1-7 Theoretically, creatine supplementation during training may lead to greater training adaptations due to an enhanced quality and volume of work performed. In terms of potential medical applications, creatine is intimately involved in a number of metabolic pathways. Creatine deficiencies or lack of creatine availability has also been identified as a limiting factor in the pathology of a number of neurological and chronic diseases. For this reason, medical researchers have been investigating the potential therapeutic role of creatine supplementation in a variety of patient populations. The purpose of this chapter is to provide an overview of the available literature regarding the effects of creatine supplementation on muscle bioenergetics and training adaptations, potential medical uses of creatine, and medical safety of creatine.

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