Dietary Supplementation for Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systematic Review.
Dorczok, Marie Celine, Mittmann, Gloria, Mossaheb, Nilufar et al. · Nutrients · 2025 · DOI
Quick Summary
This review looked at 14 studies examining whether dietary supplements can help reduce fatigue in ME/CFS patients. Some supplements like L-carnitine, CoQ10 combined with selenium, and NADH showed promise in reducing fatigue symptoms. However, the studies had significant quality issues, making it difficult to draw firm conclusions about which supplements truly work.
Why It Matters
This review is important because many ME/CFS patients use dietary supplements for fatigue management despite limited evidence. By synthesizing available research and identifying which supplements show the most promise, it helps patients and clinicians make more informed decisions about supplement use while highlighting the urgent need for higher-quality research in this population.
Observed Findings
Some supplements showed significant fatigue reduction: L-carnitine, guanidinoacetic acid, oxaloacetate, CoQ10-selenium combination, NADH, and NADH-CoQ10 combination.
Mixed results were reported for secondary outcomes including cognitive function and inflammatory markers.
Six studies documented adverse effects, including nausea and insomnia.
All 14 studies showed high risk of bias, primarily due to missing data and selection bias.
Heterogeneity in study designs and supplement formulations limited ability to perform meta-analyses.
Inferred Conclusions
Several dietary supplements demonstrate potential for reducing fatigue in ME/CFS, but methodological limitations prevent firm conclusions about efficacy.
Current evidence quality is insufficient to recommend specific supplements as evidence-based ME/CFS treatments.
Future research must employ rigorous designs with larger sample sizes, complete data reporting, and standardized ME/CFS diagnostic criteria.
Remaining Questions
Which supplements, if any, are truly effective versus placebo when tested in well-designed randomized controlled trials?
What are the mechanisms by which these supplements may improve fatigue—are they addressing underlying biological dysfunction or providing symptomatic relief?
What This Study Does Not Prove
This review does not definitively prove that any supplement effectively treats ME/CFS fatigue due to methodological limitations including small sample sizes, missing data, and selection bias in included studies. The findings suggest potential rather than established efficacy, and individual supplement effects cannot be reliably distinguished from placebo effects without better-designed trials. Adverse effects were reported in some studies but remain incompletely characterized.
Tags
Symptom:Cognitive DysfunctionFatigue
Biomarker:Metabolomics
Method Flag:Weak Case DefinitionSmall SampleMixed Cohort
How do adverse effects compare across supplements, and which populations are most at risk for tolerability issues?
Why do results vary so dramatically across studies—is this due to methodological differences, population heterogeneity, or genuine variability in supplement effectiveness?