, Volume 11, Issue 6, pp 1626–1639

Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients

  • Christopher W. Armstrong
  • Neil R. McGregor
  • Donald P. Lewis
  • Henry L. Butt
  • Paul R. Gooley
Original Article

DOI: 10.1007/s11306-015-0816-5

Cite this article as:
Armstrong, C.W., McGregor, N.R., Lewis, D.P. et al. Metabolomics (2015) 11: 1626. doi:10.1007/s11306-015-0816-5


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating long-term multisystem disorder with a central and inexplicably persistent fatigue symptom that is unable to be relieved by rest. Energy metabolism and oxidative stress have been recent focal points of ME/CFS research and in this study we were able to elucidate metabolic pathways that were indicative of their dysfunction. Blood and urine samples were collected from 34 females with ME/CFS (34.9 ± 1.8 SE years old) and 25 non-ME/CFS female participants (33.0 ± 1.6 SE years old). All samples underwent metabolic profiling via 1D 1H Nuclear magnetic resonance spectroscopy and quantitated metabolites were assessed for significance. Blood glucose was elevated while blood lactate, urine pyruvate, and urine alanine were reduced indicating an inhibition of glycolysis that may potentially reduce the provision of adequate acetyl-CoA for the citric acid cycle. We propose that amino acids are being increasingly used to provide an adequate carbohydrate source for the citric acid cycle. We suggest that this is via glutamate forming 2-oxoglutarate through an enzyme that deaminates it and subsequently elevates blood aspartate. Dysfunctional energy metabolism appears to have impacted creatinine and its elevation in urine suggests that it may be used as an alternative for anaerobic ATP production within muscle. A decrease in blood hypoxanthine and an increase in urine allantoin further suggest the elevation of reactive oxygen species in ME/CFS patients. These findings bring new information to the research of energy metabolism, chronic immune activation and oxidative stress issues within ME/CFS.


Chronic fatigue syndrome Metabolic Blood Urine Oxidative Stress Energy metabolism Amino Acids 



Myalgic encephalomyelitis/chronic fatigue syndrome


Principal components analysis


Branched chain amino acids


Aspartate transaminase


Reactive oxygen species

Funding information

Funder NameGrant NumberFunding Note
Judith Jane Mason & Harold Stannett Williams Memorial Foundation

    Copyright information

    © Springer Science+Business Media New York 2015

    Authors and Affiliations

    • Christopher W. Armstrong
      • 1
    • Neil R. McGregor
      • 2
    • Donald P. Lewis
      • 3
    • Henry L. Butt
      • 4
    • Paul R. Gooley
      • 1
    1. 1.Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology InstituteUniversity of MelbourneParkvilleAustralia
    2. 2.Faculty of Medicine, Dentistry & Health SciencesUniversity of MelbourneParkvilleAustralia
    3. 3.CFS Discovery, Donvale Medical CentreDonvaleAustralia
    4. 4.Bioscreen (Aust) Pty LtdYarravilleAustralia

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