Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?

Athletes, body builders, and military personnel use dietary creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Lesser known is the essential role creatine, a natural regulator of energy homeostasis, plays in brain function and development. Creatine supplementation has shown promise as a safe, effective, and tolerable adjunct to medication for the treatment of brain-related disorders linked with dysfunctional energy metabolism, such as Huntington's Disease and Parkinson's Disease. Impairments in creatine metabolism have also been implicated in the pathogenesis of psychiatric disorders, leaving clinicians, researchers and patients alike wondering if dietary creatine has therapeutic value for treating mental illness. The present review summarizes the neurobiology of the creatine–phosphocreatine circuit and its relation to psychological stress, schizophrenia, mood and anxiety disorders. While present knowledge of the role of creatine in cognitive and emotional processing is in its infancy, further research on this endogenous metabolite has the potential to advance our understanding of the biological bases of psychopathology and improve current therapeutic strategies.

► Creatine is an antioxidant, neuromodulator, and key regulator of energy metabolism.
► Alterations in the brain creatine pathway are linked with psychiatric disorders.
► Creatine supplements, commonly consumed by athletes, are bioavailable to the brain.
► Intervention studies report benefit of creatine treatment for depression and PTSD.
► Possible therapeutic mechanisms and methodological challenges are considered.