CREATINE AND BRAIN HEALTH: A COMPREHENSIVE REVIEW OF UPTAKE, BIOENERGETICS, COGNITIVE EFFECTS, AND THERAPEUTIC POTENTIAL
CREATINE AND BRAIN HEALTH: A COMPREHENSIVE REVIEW OF UPTAKE, BIOENERGETICS, COGNITIVE EFFECTS, AND THERAPEUTIC POTENTIAL

Summary/Abstract: Background: Creatine plays a key role in cellular energy metabolism via the phosphocreatine–creine kinase system, enabling rapid ATP regeneration to support brain function. Evidence suggests that creatine supplementation may enhance cognition, improve brain bioenergetics, and provide neuroprotection in conditions associated with energy deficits, including sleep deprivation, hypoxia, depression, neurodegenerative diseases, and traumatic brain injury. However, findings remain inconsistent, and the optimal strategies for increasing brain creatine levels are still unclear.Aim of the study: To summarize the current evidence on the effects of creatine supplementation on brain creatine levels, cognitive function, and neuroprotection, particularly in stress-related and neurological conditions. Materials and methods: A narrative review of human and animal studies was conducted, including NMR spectroscopy research on brain creatine, randomized trials investigating cognition, and studies on depression, neurodegeneration, and brain injury. Research on guanidinoacetic acid (GAA) supplementation was also included. Results: Creatine supplementation increased brain creatine levels by 3–10% in most studies, with effects varying according to dose, duration, and brain region. GAA demonstrated greater efficacy, increasing brain creatine levels by up to 16%. Cognitive outcomes were mixed but generally showed improvement under conditions of high energy demand (e.g., sleep deprivation and hypoxia). Benefits were observed in memory performance among older adults and individuals with low baseline creatine levels. Preliminary evidence also suggests potential benefits in depression (especially in combination with SSRIs), neuroprotection following traumatic brain injury, and possible therapeutic effects in Alzheimer’s disease, although human data remain limited. Conclusions: Creatine is a safe and accessible supplement with the potential to support brain metabolism, enhance cognition under stress, and provide neuroprotection. GAA may be more effective than creatine in increasing brain creatine levels. Further clinical trials are needed to confirm its efficacy and optimize supplementation strategies.

• Details
• Contents