Yamano, Emi, Sugimoto, Masahiro, Hirayama, Akiyoshi et al. · Scientific reports · 2016 · DOI
Researchers analyzed blood samples from ME/CFS patients and healthy people to look for chemical markers that could help diagnose the disease. They found that certain metabolites—molecules involved in energy production and waste removal—were abnormal in ME/CFS patients. Two specific chemical ratios in the blood showed promise as potential diagnostic tools, correctly identifying CFS patients about 75-80% of the time.
ME/CFS currently lacks objective diagnostic tests, making diagnosis challenging and delaying treatment. This study provides evidence that specific blood metabolite abnormalities could form the basis for an objective diagnostic tool, potentially improving diagnostic accuracy and helping establish CFS as a biological disease rather than a psychiatric condition.
This study does not prove that these metabolite abnormalities cause ME/CFS—only that they are associated with the disease. It does not establish whether these changes are primary features of CFS or secondary consequences of illness, activity limitation, or other factors. The modest validation performance (AUC 0.750) means this biomarker combination is not yet ready for clinical use without further refinement.
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
Yamano, Emi, Sugimoto, Masahiro, Hirayama, Akiyoshi, Kume, Satoshi, Yamato, Masanori, Jin, Guanghua, et al. (2016). Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles.. Scientific reports. https://doi.org/10.1038/srep34990
BibTeX
@article{mecfsatlas-yamano-2016-index-markers,
author = {Yamano, Emi and Sugimoto, Masahiro and Hirayama, Akiyoshi and Kume, Satoshi and Yamato, Masanori and Jin, Guanghua and Tajima, Seiki and Goda, Nobuhito and Iwai, Kazuhiro and Fukuda, Sanae and Yamaguti, Kouzi and Kuratsune, Hirohiko and Soga, Tomoyoshi and Watanabe, Yasuyoshi and Kataoka, Yosky},
title = {Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles.},
journal = {Scientific reports},
year = {2016},
doi = {10.1038/srep34990},
note = {PubMed: 27725700},
url = {https://www.mecfsatlas.com/evidence/yamano-2016-index-markers},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/yamano-2016-index-markers
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