Review Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with [ME/CFS], 2025, Campenhout et al

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Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Jente Van Campenhout, Yanthe Buntinx, Huan-Yu Xiong, Arne Wyns, Andrea Polli, Jo Nijs, Joeri L. Aerts, Thessa Laeremans, Jolien Hendrix

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Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease, characterized by a diverse array of symptoms including post-exertional malaise (PEM), severe fatigue, and cognitive impairments, all of which drastically diminish the patients’ quality of life. Despite its impact, no curative treatments exist, largely due to the limited understanding of the disease’s underlying pathophysiology.

Mitochondrial dysfunction, leading to impaired energy production and utilization, is believed to play a key role in the onset of fatigue and PEM, positioning it as a potential key pathophysiological mechanism underlying ME/CFS. Additionally, the disorder shows similarities to chronic viral infections, with frequent reports of immune system alterations, suggesting a critical role for immune (dys)functioning. In particular, the roles of immune senescence and immune exhaustion—two fundamental immune states—remain poorly understood in ME/CFS.

This state-of-the-art review explores how metabolic dysfunction and immune dysfunction may be interconnected in ME/CFS, proposing that energy deficits may directly impair immune function. By examining this metabolic–immune interplay, this review highlights potential pathways for developing innovative therapeutic strategies that target both energy metabolism and immune regulation, offering hope for improving patient outcomes.

Link | PDF (Biomolecules) [Open Access]
 
ME Research UK:

Jente Van Campenhout and colleagues at Vrije Universiteit Brussel have recently published a review in the journal, Biomolecules, summarising the evidence connecting energy metabolism (the process of energy production and utilisation in the body) and dysfunction of the immune system in people with ME/CFS.

ME Research UK is currently funding Jente’s PhD-level research project looking at links between mitochondrial function and the autonomic nervous system in ME/CFS, and the review provides useful background to this area.

Read more: bit.ly/41w6HyJ
 
I find this unconvincing. Pretty much every paragraph start by assuming what it is going to argue.
I don't see it as likely that 'mitochondrial dysfunction' in the sense of impaired ability cogenerate ATP is awn important aspect of ME/CFS. I think it much more likely that the inability to perform activities is due to inhibitory signalling, maybe telling mitochondria togo slow but much more likely telling other rate limiting paths to go slow.

It isn't terribly encouraging when one of the first references is to Myhill.

I agree with @DMissa that there is need to nail down the direction of effects here. Cytokine and or neural signalling from an abnormal immune response may well altering usage of pathways.

But I intend to put my version of events out fairly soon and people can pick that to pieces too.
 
Studies have reported significantly lower plasma CoQ10 levels in patients with ME/CFS compared to HCs, suggesting that CoQ10 deficiency is a significant contributor to the pathophysiology of ME/CFS
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I did not think that was the case?

These are the 4 citations provided to back this claim.
  1. Maes, M.; Mihaylova, I.; Kubera, M.; Uytterhoeven, M.; Vrydags, N.; Bosmans, E. Coenzyme Q10 Deficiency in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Is Related to Fatigue, Autonomic and Neurocognitive Symptoms and Is Another Risk Factor Explaining the Early Mortality in ME/CFS Due to Cardiovascular Disorder. Neuro Endocrinol. Lett. 2009, 30, 470–476. [Google Scholar]
  2. Castro-Marrero, J.; Domingo, J.C.; Cordobilla, B.; Ferrer, R.; Giralt, M.; Sanmartín-Sentañes, R.; Alegre-Martín, J. Does Coenzyme Q10 Plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Antioxid. Redox Signal 2022, 36, 729–739. [Google Scholar] [CrossRef]
  3. Castro-Marrero, J.; Segundo, M.J.; Lacasa, M.; Martinez-Martinez, A.; Sentañes, R.S.; Alegre-Martin, J. Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients 2021, 13, 2658. [Google Scholar] [CrossRef]
  4. Morris, G.; Anderson, G.; Berk, M.; Maes, M. Coenzyme Q10 Depletion in Medical and Neuropsychiatric Disorders: Potential Repercussions and Therapeutic Implications. Mol. Neurobiol. 2013, 48, 883–903. [Google Scholar] [CrossRef] [PubMed]
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Might be interesting to have a S4ME thread for (1)
S4ME Link for 2
 
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