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.
Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome,by Øystein Fluge, Olav Mella, Ove Bruland, Kristin Risa, Sissel E. Dyrstad, Kine Alme, Ingrid G. Rekeland, Dipak Sapkota, Gro V. Røsland, Alexander Fosså, Irini Ktoridou-Valen, Sigrid Lunde, Kari Sørland, Katarina Lien, Ingrid Herder, Hanne Thürmer, Merete E. Gotaas, Katarzyna A. Baranowska, Louis M.L.J. Bohnen, Christoph Schäfer, Adrian McCann, Kristian Sommerfelt, Lars Helgeland, Per M. Ueland, Olav Dahl, and Karl J. Tronstad in JCI Insight. 2016;1(21) [Published December 22, 2016]
Kavlifondet blog post, 22 Dec 2016: New study on pathological mechanisms in ME from Bergen research group
A new study, partly funded by the Kavli Trust, suggests that the PDH enzyme is inhibited in ME/CFS patients, which may explain both energy shortage and increased lactate production in these patients. These findings have now been published in the Journal of Clinical Investigation Insight. By Øystein Fluge, Karl Johan Tronstad and Olav Mella