E3 PreliminaryPreliminaryPEM unclearMechanisticPeer-reviewedReviewed
Six-Week Supplementation with Creatine in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Magnetic Resonance Spectroscopy Feasibility Study at 3 Tesla.
Godlewska, Beata R, Sylvester, Amy L, Emir, Uzay E et al. · Nutrients · 2024 · DOI
Quick Summary
Researchers gave 11 people with ME/CFS a creatine supplement (a natural substance that helps cells produce energy) for 6 weeks. Brain scans showed the supplement increased creatine levels in key brain regions, and participants reported feeling less fatigued, had faster reaction times on thinking tests, and showed stronger hand grip strength. The supplement was well tolerated with no side effects reported.
Why It Matters
ME/CFS lacks specific approved treatments, making investigation of bioenergetic interventions particularly important. This study provides mechanistic evidence that creatine reaches the brain and correlates with measurable improvements in fatigue and cognition—two core ME/CFS symptoms—supporting the rationale for larger controlled trials.
Observed Findings
- Creatine supplementation increased creatine concentration in the pregenual anterior cingulate cortex (pgACC) and dorsolateral prefrontal cortex (DLPFC)
- Fatigue scores decreased after 6 weeks of supplementation
- Reaction time improved on both congruent and incongruent Stroop test trials
- Hand-grip strength significantly increased
- Creatine was well tolerated with 100% treatment completion (11/11 participants)
Inferred Conclusions
- Creatine supplementation successfully increases brain creatine levels in ME/CFS patients
- Increased brain creatine correlates with improvements in processing speed and fatigue
- Creatine may support cellular energy production in brain regions involved in cognition and fatigue regulation
- Creatine supplementation warrants further investigation via placebo-controlled randomized trials
Remaining Questions
- Does the cognitive and fatigue improvement persist beyond 6 weeks, and is there an optimal dosing duration?
- How does creatine's effect in ME/CFS compare to placebo, and what is the true effect size?
What This Study Does Not Prove
This study does not prove creatine is an effective ME/CFS treatment because it lacked a placebo control group; improvements could partially reflect placebo effect or natural variation. The small sample size and short duration limit conclusions about long-term efficacy and population generalizability. Correlation between brain creatine and reaction time does not establish causation.
Tags
Method Flag:EXPLORATORYPEM_UNCLEARPEM Not DefinedNo ControlsSmall SampleExploratory Only
Symptom:Cognitive DysfunctionFatigue
Biomarker:MetabolomicsNeuroimaging
Metadata
- DOI
- 10.3390/nu16193308
- PMID
- 39408275
- Review status
- Editor reviewed
- Evidence level
- Early hypothesis, preprint, editorial, or weak support
- Last updated
- 7 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
Contribute
Private, reviewed by a human. Not a public comment thread.