Creatine Supplementation and the Brain: Have We Put the Cart Before the Horse?

Document Type

Article

Publication Title

Journal of Dietary Supplements

Abstract

Creatine is an important regulator of brain bioenergetics, yet the efficacy of creatine supplementation (CrS) in the brain remains largely unknown. Measurement of brain creatine using proton (1H) and phosphorus (³1P) magnetic resonance spectroscopy is highly sensitive to voxel placement, signal quality, analysis pipelines, and reporting conventions which can obscure the detection of biological responses to CrS. There is evidence that CrS increases brain creatine, but this response may be dose and/or duration dependent. CrS provides some benefits during acute periods of metabolic stress such as sleep deprivation, mental fatigue, and hypoxia. Emerging clinical data also suggest potential therapeutic effects from CrS for Alzheimer’s disease, major depressive disorder, and mild traumatic brain injury (mTBI), although findings across conditions remain preliminary and inconsistent. Further, CrS shows some promise for improving aspects of sleep quality. The purpose of this narrative review is to: (1) outline methodological considerations in the quantification of brain creatine, (2) discuss the divergent effects of CrS on brain creatine levels and measures of brain function, (3) examine the purported mechanistic actions of CrS for improving brain health and function, (4) highlight critical gaps and limitations which should be considered moving forward, and (5) identify future research directions involving CrS and the brain.

Research Highlights

  • The Problem: The efficacy of creatine supplementation (CrS) in the brain remains largely unknown due to measurement sensitivities in proton (1H) and phosphorus (31P) magnetic resonance spectroscopy that obscure biological responses.

  • The Method: This narrative review outlines methodological considerations, divergent effects on brain function, mechanistic actions, and critical research gaps regarding CrS.

  • Qualitative Finding: CrS provides benefits during acute metabolic stress including sleep deprivation, mental fatigue, and hypoxia; emerging data suggests potential therapeutic effects for Alzheimer’s disease, major depressive disorder, and mild traumatic brain injury.

DOI

https://doi.org/10.1080/19390211.2026.2616440

Publication Date

1-2026

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