Fluge, Øystein, Mella, Olav, Bruland, Ove et al. · JCI insight · 2016 · DOI
This study found that people with ME/CFS have abnormal patterns of amino acids (building blocks of protein) in their blood, suggesting their bodies struggle to produce energy efficiently through normal metabolic pathways. The research identified a specific problem with an enzyme called pyruvate dehydrogenase that helps convert fuel into cellular energy, and showed that cells from ME/CFS patients produce excess lactate (a byproduct of incomplete energy metabolism) when stressed. These findings help explain why ME/CFS patients experience exhaustion after exertion and poor recovery.
This study provides evidence for a specific, measurable metabolic mechanism underlying ME/CFS symptoms—particularly postexertional malaise and fatigue—rather than attributing symptoms to deconditioning or psychological factors. Identifying pyruvate dehydrogenase dysfunction as a potential therapeutic target offers a biological framework for developing treatments. These findings validate patient reports of energy metabolism problems and could guide development of metabolic interventions.
This study demonstrates associations between metabolic markers and ME/CFS diagnosis but does not prove that pyruvate dehydrogenase dysfunction is the primary cause of the disease or sufficient to cause all symptoms. The findings are observational and correlational; it remains unclear whether the metabolic changes drive disease pathogenesis or represent secondary adaptations to an underlying process. The study does not establish whether these metabolic abnormalities are present in all ME/CFS patients or are disease-specific rather than found in other conditions.
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
Fluge, Øystein, Mella, Olav, Bruland, Ove, Risa, Kristin, Dyrstad, Sissel E, Alme, Kine, et al. (2016). Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome.. JCI insight. https://doi.org/10.1172/jci.insight.89376
BibTeX
@article{mecfsatlas-fluge-2016-metabolic-profiling,
author = {Fluge, Øystein and Mella, Olav and Bruland, Ove and Risa, Kristin and Dyrstad, Sissel E and Alme, Kine and Rekeland, Ingrid G and Sapkota, Dipak and Røsland, Gro V and Fosså, Alexander and Ktoridou-Valen, Irini and Lunde, Sigrid and Sørland, Kari and Lien, Katarina and Herder, Ingrid and Thürmer, Hanne and Gotaas, Merete E and Baranowska, Katarzyna A and Bohnen, Louis Mlj and Schäfer, Christoph and McCann, Adrian and Sommerfelt, Kristian and Helgeland, Lars and Ueland, Per M and Dahl, Olav and Tronstad, Karl J},
title = {Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome.},
journal = {JCI insight},
year = {2016},
doi = {10.1172/jci.insight.89376},
note = {PubMed: 28018972},
url = {https://www.mecfsatlas.com/evidence/fluge-2016-metabolic-profiling},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/fluge-2016-metabolic-profiling
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