Review Chronic fatigue syndrome and epigenetics: The case for hyperbaric oxygen therapy in biomarker identification 2021 Shah

[Andy]

Chronic fatigue syndrome (CFS) is a poorly-understood respiratory condition that affects millions of individuals. Hyperbaric oxygen therapy (HBOT) is a treatment option being considered to address CFS as it is suggested to combat fatigue and increase oxygenation. HBOT provides two opportunities in advancing research of CFS: it may provide data on symptom amelioration and be utilized in the search for a biomarker. By either identifying biomarkers before using HBOT to compare epigenomes of patients before and after treatment or using HBOT to find epigenetic discrepancies between patients with and without treatment, matching epigenetic regulation with symptom amelioration may significantly advance the understanding of the etiology and treatment mechanism for CFS. EPAS1/HIF-2α is a leading candidate for an epigenetic biomarker as it responds differentially to hypoxic and normoxic conditions, which degrades more slowly in hypoxic conditions. Epigenetic regulation of EPAS1/HIF-2α in such differential conditions may be explored in HBOT experiments. In addition to HBOT as a promising treatment option for CFS symptoms, it may aid the identification of biomarkers in CFS. Further research into both outcomes is strongly encouraged.

Open access, https://www.pulmonolrespirjournal.com/articles/jprr-aid1020.php

 

[Jonathan Edwards]

Except that chronic fatigue syndrome isn't a respiratory condition.

 

[Creekside]

Might "the case for HBOT treatments" involve profit for those selling the treatments or equipment?

 

[SNT Gatchaman]

I doubt that HBOT will end up being helpful. Obviously not a trial, but a few local LC people have tried it, some having no effect, some temporary improvement but some also describing symptom deterioration. I'm sure there's a wide range of what is being described as "HBOT" though.

Whether HBOT can theoretically help, I don't know, but it may also do the opposite. There are observations that a period of hyperoxia can have the paradoxical effect that on return to normoxia there is a hypoxic response — which might have detrimental or beneficial effects, depending on the scenario.

Eg in Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the “Normobaric Oxygen Paradox” (2024, International Journal of Molecular Sciences) —

The “normobaric oxygen paradox” (NOP) describes the response to the return to normoxia after a hyperoxic event, sensed by tissues as an oxygen shortage, up-regulating redox-sensitive transcription factors.

We have previously characterized the time trend of oxygen-sensitive transcription factors in human PBMCs, in which the return to normoxia after 30% oxygen is sensed as a hypoxic trigger, characterized by hypoxia-induced factor (HIF-1) activation. On the contrary, 100% and 140% oxygen induce a shift toward an oxidative stress response, characterized by NRF2 and NF-kB activation in the first 24 h post exposure.

Previously The Normobaric Oxygen Paradox—Hyperoxic Hypoxic Paradox: A Novel Expedient Strategy in Hematopoiesis Clinical Issues (2022, International Journal of Molecular Sciences)

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ME may well turn out to be a mitochondrial respiratory condition at its core, ie histotoxic hypoxia (like cyanide poisoning of complex IV/cytochrome oxidase) [1, 2].

[1] WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome (2023, PNAS)
[2] An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients (2020, International Journal of Molecular Sciences)

 

[Mithriel]

I found some of the reports of HBOT use in LC strange. With MS HBOT is used as a regular treatment not a one off bout so any good effect continuing after sessions stop did not seem likely.

Healing after a broken bone or a wound does work very well with HBOT though so I wonder if the initial idea was that it would help heal the lingering effects from the initial infection before it was realised that LC can be an ongoing disease.