Ostojic, Sergej M, Stojanovic, Marko, Drid, Patrik et al. · Nutrients · 2016 · DOI
Researchers tested whether a supplement called guanidinoacetic acid (GAA) could help women with ME/CFS. Twenty-one women took either GAA or a placebo for three months. While GAA increased muscle creatine levels and improved some measures of strength and aerobic power, it did not reduce fatigue or muscle pain—the main symptoms patients care about most.
This study directly addresses the need for evidence-based interventions in ME/CFS, a condition with no approved treatments. It illustrates an important disconnect: a supplement can produce measurable metabolic changes (increased creatine) without improving the core symptoms that disable ME/CFS patients (fatigue and pain).
This study does not prove that GAA is ineffective for ME/CFS—it only shows no effect on the primary clinical outcomes measured in this small sample. It does not establish that creatine metabolism abnormalities are not important in ME/CFS, only that increasing creatine alone does not resolve fatigue or pain. The small sample size and short intervention period limit generalizability.
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 →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Ostojic, Sergej M, Stojanovic, Marko, Drid, Patrik, Hoffman, Jay R, Sekulic, Damir, & Zenic, Natasa (2016). Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome.. Nutrients. https://doi.org/10.3390/nu8020072
BibTeX
@article{mecfsatlas-ostojic-2016-supplementation-guanidinoacetic,
author = {Ostojic, Sergej M and Stojanovic, Marko and Drid, Patrik and Hoffman, Jay R and Sekulic, Damir and Zenic, Natasa},
title = {Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome.},
journal = {Nutrients},
year = {2016},
doi = {10.3390/nu8020072},
note = {PubMed: 26840330},
url = {https://www.mecfsatlas.com/evidence/ostojic-2016-supplementation-guanidinoacetic},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-25. https://www.mecfsatlas.com/evidence/ostojic-2016-supplementation-guanidinoacetic
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