CREATINE IN HUMAN HEALTH: EXERCISE PERFORMANCE AND SELECTED CLINICAL APPLICATIONS

Creatine is a naturally occurring compound synthesized from arginine, glycine, and methionine through a two-step pathway involving arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT). It is transported into cells primarily by the sodium- and chloride-dependent creatine transporter (SLC6A8) and participates in cellular energy buffering through the creatine-phosphocreatine system. Creatine is degraded spontaneously to creatinine, which is eliminated primarily by the kidneys. Creatine monohydrate is well established as an aid to high-intensity exercise and resistance-training adaptations. Research is also examining potential applications in aging and disease, but the strength of evidence varies. A small, single-arm pilot study in people with Alzheimer’s disease reported increased brain total creatine and improvement on some cognitive measures; without a control group, it cannot establish that creatine caused those changes. A large clinical trial did not find that creatine slowed clinical progression in Parkinson’s disease. Evidence for cognitive, cardiac, and metabolic benefits remains preliminary or mixed. Creatine has not been shown to prevent cancer or age-related chronic diseases in humans. This review summarizes creatine metabolism and transport, evidence related to exercise and selected clinical conditions, and possible interactions with carbohydrate, fenugreek, ashwagandha, and antioxidants. These combinations should not be described as established ways to increase creatine’s effectiveness.