Creatine Supplementation and the Brain: Have We Put the Cart Before the Horse?
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing existing literature without systematic review methodology
PubMed 41556609 · doi:10.1080/19390211.2026.2616440
What was done
This narrative review examined the literature on creatine supplementation and brain bioenergetics. It evaluated methodological challenges in quantifying brain creatine via proton (1H) and phosphorus (31P) magnetic resonance spectroscopy, synthesized evidence on brain uptake and functional outcomes across acute metabolic stressors and clinical conditions (Alzheimer's disease, major depressive disorder, mild traumatic brain injury, and sleep quality), and identified critical research gaps.
What was found
The abstract reports no quantitative data or effect sizes. It notes that creatine supplementation increases brain creatine in a dose- and/or duration-dependent manner and confers benefits during acute metabolic stressors such as sleep deprivation, mental fatigue, and hypoxia. It also notes preliminary, inconsistent therapeutic signals across Alzheimer's disease, major depressive disorder, mild traumatic brain injury, and sleep quality.
Why it matters
While creatine is widely investigated for cognitive and neurological benefits, significant heterogeneity in magnetic resonance spectroscopy acquisition and reporting complicates interpretations of brain bioenergetic responses.
Limits
As a narrative review, it lacks a systematic search protocol and risk-of-bias grading. The abstract provides no sample sizes, study counts, or quantitative metrics, and highlights that primary clinical findings in neurological conditions remain preliminary and inconsistent.