Fatigue, ME/CFS & mitochondrial function: what research on cellular energy shows
N. Thornton, MSc. · Molecular Biologist · 8 min · RARE Labs
Editorially updated:
Why mitochondria are discussed in ME/CFS and long COVID research, what cell measurements show — and how robust the existing studies on coenzyme Q10 and NADH are.
Mitochondria produce most cellular ATP through oxidative phosphorylation. Coenzyme Q10 shuttles electrons within the respiratory chain, while NADH supplies them as an electron donor. Because both molecules are so central, they attract attention whenever researchers study exhaustion at the cellular level.
ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) is a severe multisystem disease marked by pronounced exertion intolerance. Booth et al. (2012) described abnormalities in an ATP profile test in blood cells of patients and discussed mitochondrial involvement. The method, however, is not standardised and has not been independently validated.
Tomas et al. (2017) measured cellular bioenergetics using extracellular flux analysis: peripheral mononuclear cells from ME/CFS patients showed, on average, reduced glycolysis and mitochondrial reserve capacity compared with controls. This points to altered energy provision — whether as cause or consequence remains open.
For long COVID, Davis et al. (2023) summarise that a relevant share of patients meet ME/CFS criteria. Among the mechanisms discussed, the authors list viral persistence, immune dysregulation, microclots and mitochondrial dysfunction. None of these mechanisms has yet been established on its own.
Controlled studies on supplementation are few. Castro-Marrero et al. (2015) tested a combination of coenzyme Q10 and NADH in a randomised, placebo-controlled trial with 73 ME/CFS patients over eight weeks, reporting changes in fatigue scales and biochemical parameters. The trial is small, single-centre and has not been replicated in larger cohorts.
No health claims are authorised in the EU for coenzyme Q10 or NADH. Claims are authorised for certain nutrients instead: magnesium, iron and several B vitamins, for example, contribute to normal energy-yielding metabolism and to the reduction of tiredness and fatigue. These claims refer to healthy people, not to the treatment of ME/CFS or long COVID.
Study design at a glance
- Type
- Evidence overview (cell studies, reviews, one RCT)
- Participants
- ME/CFS and long COVID cohorts
- Duration
- 2012–2023
What this means — and what it does not
- Mitochondrial changes are intensively studied in ME/CFS and long COVID, but are not established as the sole cause.
- Cell measurements show differences in energy provision; cause and effect remain unclear.
- Evidence on coenzyme Q10 and NADH rests on few, small studies.
- ME/CFS and long COVID require medical diagnosis and care.
Limitations
- The cited cell studies are small and methodologically heterogeneous.
- Large, independently replicated intervention trials on coenzyme Q10 and NADH are lacking.
- This article provides scientific information and makes no claim about the effect of any RARE product.
Sources
- Castro-Marrero J et al., Antioxid Redox Signal 2015 — Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome?Castro-Marrero J, Cordero MD, Segundo MJ et al. · Antioxid Redox Signal · 2015 · PMID: 25386668
- Tomas C et al., PLoS One 2017 — Cellular bioenergetics is impaired in patients with chronic fatigue syndromeTomas C, Brown A, Strassheim V et al. · PLoS One · 2017 · PMID: 29065167
- Booth NE et al., Int J Clin Exp Med 2012 — Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)Booth NE, Myhill S, McLaren-Howard J · Int J Clin Exp Med · 2012 · PMID: 22837795
- Davis HE et al., Nat Rev Microbiol 2023 — Long COVID: major findings, mechanisms and recommendationsDavis HE, McCorkell L, Vogel JM et al. · Nat Rev Microbiol · 2023 · PMID: 36639608
Editorial note: these articles are contextual knowledge pieces and do not replace medical advice.
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