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

Abstract

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.

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Abbreviations

ME/CFS:

Myalgic encephalomyelitis/chronic fatigue syndrome

PCA:

Principal components analysis

BCAAs:

Branched chain amino acids

AST:

Aspartate transaminase

ROS:

Reactive oxygen species

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Acknowledgments

The authors of this work would like to thank the nursing and administrative staff at the CFS Discovery clinic for their important help throughout this study. This work was supported by grants from the Judith Jane Mason & Harold Stannett Williams Memorial Foundation (The Mason Foundation) and equipment grants from the Rowden White foundation and State of Victoria.

Conflict of interest

There were no conflict of interest.

Compliance with ethical requirements

This study was approved by the University of Melbourne human research ethics committee (HREC# 0723086).

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Correspondence to Paul R. Gooley.

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Data Deposition

The data for this study has been deposited at MetaboLights (http://www.ebi.ac.uk/metabolights) with accession number MTBLS161.

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Armstrong, C.W., McGregor, N.R., Lewis, D.P. et al. Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients. Metabolomics 11, 1626–1639 (2015). https://doi.org/10.1007/s11306-015-0816-5

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Keywords

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