Abstract
Introduction
Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a complex and severe condition with unknown aetiology which affects over 20,000 people in New Zealand. Only in the last 20 years has it been considered to have a biological basis as opposed to being a psychiatric condition, and this has been strongly confirmed in the last 5 years. However, no specific aetiology or treatments have been found. There are reports the essential component of the electron transport chain, Coenzyme Q10 (CoQ10), is decreased in plasma and in peripheral blood mononuclear cells (PBMCs) of patients with ME/CFS, and that there may be contributing or exacerbating dysfunctions in mitochondrial and metabolic pathways. CoQ10, and the modified analogue that targets the molecule to mitochondria, MitoQ, have been investigated as potential therapies in ME/CFS. The aim of this research is to investigate the relationship between CoQ10 levels and mitochondrial function in ME/CFS and investigate the impact of CoQ10 and MitoQ on mitochondrial function.
Methods
Two ME/CFS cohorts totalling 23 participants were investigated in this research study, and there were 22 age/sex matched healthy controls. Plasma and purified PBMCs from the participants were analysed using an ELISA kit that could detect CoQ10.The mitochondrial functions of the participants were measured with a mitochondrial ‘stress test’ on the Seahorse Analyzer, before and after incubation with CoQ10 and MitoQ.
Results
Surprisingly, there was no significant difference in plasma or PBMC CoQ10 levels between the ME/CFS patients and the controls as previously reported, although the well-established decrease with age was seen in ME/CFS and control cohorts. PBMC CoQ10 levels however, of both patients and controls showed an association with their mitochondrial function. Incubation of CoQ10 in PBMCs enhanced the mitochondrial functions in ME/CFS in patients, however, the analogue MitoQ incubation, at the concentration used, caused major uncoupling of electron transfer from oxidative phosphorylation. An exploratory longitudinal supplementation study with the nutraceutical MitoQ in one patient showed an improvement in mitochondrial function by two months that was sustained through to month four, but then returned to pre -supplementation levels, possibly as a result of the stress of surgery.
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Discussion
Our results demonstrate that plasma or PBMC CoQ10 concentration is not a distinct biomarker for ME/CFS, despite the low levels reported in other studies. The results from the incubation of PBMCs suggest CoQ10 can act to restore mitochondrial respiration in ME/CFS, which may result in positive clinical benefits, especially in individuals with low CoQ10. Given that the levels of CoQ10 can be influenced indirectly by lifestyle factors, and ME/CFS is a severely fatiguing illness that affects lifestyle practices, the study needs to be repeated with closer consideration given to confounding variables such as exercise and diet, and with larger cohorts. MitoQ needs to be tested in vitro at a much lower concentration range than that chosen for this study to avoid this undesirable uncoupling that masks any possible positive effects on functions involved in energy production. Further, a larger longitudinal supplementary study of MitoQ would be of benefit to investigate its potential in ME/CFS.
Conclusion
ME/CFS patients of a New Zealand cohort do not have lower plasma or immune cell concentrations of CoQ compared with an age/gender matched healthy controls as previously reported for another cohort. Differences in the bioenergetic capacity of mitochondria for the New Zealand ME/CFS patient group compared with the healthy controls were: increased rate of basal but decreased rate of maximum oxygen consumption, decreased ATP production, decreased spare respiratory capacity that would impact on the ability to respond to stress, and an increase in proton leak. These changes suggest there is a dysfunction in mitochondrial energy production in ME/CFS.