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JCI Insight. 2016 Dec 22;1(21):e89376. doi: 10.1172/jci.insight.89376.

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome.

Author information

Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
Department of Biomedicine, University of Bergen, Bergen, Norway.
Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
CFS/ME Center, Division of Medicine, Oslo University Hospital, Oslo, Norway.
Telemark Hospital, Department of Medicine, Notodden, Norway.
Department of Pain and Complex Disorders, St. Olav's Hospital, Trondheim, Norway.
Division of Rehabilitation Services, University Hospital of Northern Norway, Tromsø, Norway.
Bevital AS, Bergen, Norway.
Department of Pediatrics and.
Department of Pathology, Haukeland University Hospital, Bergen, Norway.


Myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is a debilitating disease of unknown etiology, with hallmark symptoms including postexertional malaise and poor recovery. Metabolic dysfunction is a plausible contributing factor. We hypothesized that changes in serum amino acids may disclose specific defects in energy metabolism in ME/CFS. Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients. The amino acid pattern suggested functional impairment of pyruvate dehydrogenase (PDH), supported by increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPARδ in peripheral blood mononuclear cells from both sexes. Myoblasts grown in presence of serum from patients with severe ME/CFS showed metabolic adaptations, including increased mitochondrial respiration and excessive lactate secretion. The amino acid changes could not be explained by symptom severity, disease duration, age, BMI, or physical activity level among patients. These findings are in agreement with the clinical disease presentation of ME/CFS, with inadequate ATP generation by oxidative phosphorylation and excessive lactate generation upon exertion.

Conflict of interest statement

Conflict of interest: Haukeland University Hospital has patents and pending patent applications on the issue of B cell depletion therapy for myalgic encephalopathy/chronic fatigue syndrome, a treatment principle mentioned in the discussion of the article. Family members of WO2009083602 A1 are pending and some of them are granted, including US 7.914.785. Øystein Fluge and Olav Mella are named as inventors.

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