Creatine for Neuroprotection

Research suggests that creatine supplementation shows meaningful neuroprotective potential across a range of conditions, supported by mechanistic studies, preclinical animal research, and a smaller body of human clinical and observational data. Studies indicate that creatine and phosphocreatine may protect neurons by bolstering cellular energy reserves, reducing oxidative stress, modulating neurotransmitter receptor activity, and in stroke models, improving cerebral blood flow — though the relative contribution of each mechanism remains under investigation. The evidence base includes several systematic reviews and narrative reviews drawing on randomized controlled trials, animal studies, and in vitro work, with findings generally supportive for conditions such as traumatic brain injury, hypoxic-ischemic encephalopathy, and cognitive function under stress, while results for broader cognitive outcomes in healthy young adults remain mixed and inconclusive. Limitations across the literature include small sample sizes, short study durations, heavy reliance on preclinical models, a notable lack of large adult clinical trials, and considerable variability in study design and dosing protocols, meaning that while the overall direction of the evidence is encouraging, firm conclusions about creatine's neuroprotective efficacy in humans await more rigorous and targeted investigation.