Creatine in ME/CFS: brain levels, fatigue and strength
What it found
In 11 people with ME/CFS, six weeks of high-dose creatine raised creatine levels in two brain regions and was followed by less fatigue, faster reaction times and stronger hand grip.
The study had no placebo group, so the authors say these results need caution.
What they found
Studies in people
Brain creatine rose
After six weeks, total creatine rose by 8.3% in the pregenual anterior cingulate cortex and by 2.9% in the dorsolateral prefrontal cortex. Levels of another brain metabolite, NAA, did not change.
Fatigue improved
Scores on two fatigue questionnaires fell over the treatment period. Depression, pain and sleep scores also went down but the changes were not statistically significant.
Cognition mixed
Reaction times got faster on both congruent and incongruent trials of the Stroop test, and on 1-back trials of the N-back test. There was no significant change in inhibitory control, Stroop accuracy, or any memory test measure.
Grip strength up
Hand-grip strength increased significantly from a mean of 48.9 to 61.9. Muscle creatine was not measured, so the rise could not be directly linked to muscle creatine changes.
Brain changes and tests
The rise in pregenual anterior cingulate creatine correlated with faster reaction times on both Stroop trial types. The rise in dorsolateral prefrontal cortex creatine correlated with accuracy on 3-back N-back trials. No other significant correlations were found.
Tolerability
Creatine was generally well tolerated and no participant stopped treatment. One person gained 5.2 kg, one reported nausea and vomiting, and one had trouble sleeping if creatine was taken at night.
What the authors conclude
“Creatine supplementation over six weeks in ME/CFS patients increased brain creatine and improved fatigue and some aspects of cognition.”
Also in their conclusions
- They say creatine supplementation over six weeks in ME/CFS patients increased brain creatine and improved fatigue and some aspects of cognition.
- They state that despite its methodological limitations, this study encourages placebo-controlled investigations of creatine treatment in ME/CFS.
- They advise further investigations ideally using different doses and treatment durations with a placebo as a control.
How it was done
ME/CFS has no specific licensed drug treatment, and creatine is needed for energy in cells including the brain. A previous scan study found lower creatine in one brain region of people with ME/CFS.
Fourteen people with ME/CFS took 16 g of creatine monohydrate daily for six weeks. Eleven completed the study. Before and after treatment they had brain scans, symptom questionnaires, cognitive tests and hand-grip strength measurements.
What it can’t tell you
- There was no placebo group, so the improvements in fatigue and cognition could be due to taking part in the study rather than creatine itself.
- The study was small and made no correction for multiple comparisons, so some findings may be false positives.
- Only two brain regions were scanned, so it is not known whether creatine rises in other parts of the brain.
Who paid
- Funding
- Funded by Wellcome Trust; MRC (from the PubMed record).
- Conflicts
- B.R.G. received consultancy fees from Tiefenbacher Pharmaceuticals. Other authors have no conflicts of interest to declare. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
- Authors work at
- University of Oxford, UK; Oxford Health NHS Foundation Trust, UK; Maastricht University, The Netherlands
The paper
- Title
- Six-Week Supplementation with Creatine in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Magnetic Resonance Spectroscopy Feasibility Study at 3 Tesla
- Type
- Study
- Evidence
- Studies in people
- Summarised from
- Full text
- Licence
- CC BY. Words in quotation marks are the authors’; the rest is our summary.
- Cite
- Godlewska BR, Sylvester AL, Emir UE, et al (2024). Six-Week Supplementation with Creatine in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Magnetic Resonance Spectroscopy Feasibility Study at 3 Tesla. Nutrients. doi:10.3390/nu16193308Free full textPubMed 39408275DOI
Summary written 29 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error