2016
DOI: 10.1038/srep34990
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Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles

Abstract: Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, lasting at least 6 consecutive months. Its pathogenesis remains incompletely understood. Here, we performed comprehensive metabolomic analyses of 133 plasma samples obtained from CFS patients and healthy controls to establish an objective diagnosis of CFS. CFS patients exhibited significant differences in intermedi… Show more

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Cited by 107 publications
(126 citation statements)
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“…Interestingly, a study of ME/CFS patients found changes in urine amino acid concentrations consistent with the specific amino acid pattern we found in serum, and a reduced urinary excretion of the TCA cycle intermediates succinic acid and citric acid was also reported (15). A recent metabolomics study reported reduced concentrations of TCA cycle intermediates, accompanied by an increased pyruvate/isocitrate ratio, in ME/CFS plasma (30). This further supports the hypothesis that fueling of the TCA cycle by pyruvate is obstructed in ME/CFS patients, which is in line with the suggested PDH inhibition.…”
Section: Discussionmentioning
confidence: 71%
“…Interestingly, a study of ME/CFS patients found changes in urine amino acid concentrations consistent with the specific amino acid pattern we found in serum, and a reduced urinary excretion of the TCA cycle intermediates succinic acid and citric acid was also reported (15). A recent metabolomics study reported reduced concentrations of TCA cycle intermediates, accompanied by an increased pyruvate/isocitrate ratio, in ME/CFS plasma (30). This further supports the hypothesis that fueling of the TCA cycle by pyruvate is obstructed in ME/CFS patients, which is in line with the suggested PDH inhibition.…”
Section: Discussionmentioning
confidence: 71%
“…A summarized comparison with their female cohort is presented in Table 6. An additional study 33 with stronger statistical power, thanks to a larger cohort along with a validation dataset, also points to deficiencies we noticed, namely the urea cycle which takes place in the liver, and the TCA cycle which in part generates energy from lipids and sugars to make ATP, all compounds/pathways we found to be affected in our CFS cohort when compared to healthy controls. An even larger study with the latest methods for discovery metabolomics might reveal a larger set of metabolites that can distinguish cases from controls with greater accuracy, as well as allowing us to generate additional hypotheses regarding metabolic dysregulation in ME/CFS.…”
Section: Discussionmentioning
confidence: 75%
“…Recent metabolomics studies have found deficits in the pathways that generate energy from simple sugars, fatty acids, and amino acids (6)(7)(8)(9). Indeed, one study of over 600 metabolites, published in PNAS, found that the levels of most were unusually low, as occurs in states of hibernation (6).…”
Section: Studies Of Energy Metabolism Oxidative and Nitrosative Stressmentioning
confidence: 99%