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Energy & sleep

ME/CFS and chronic fatigue

The research here is small but consistent in direction. A 2013 open trial of 16 people with chronic fatigue syndrome reported lower fatigue scores and better quality of life after 15 sessions, and a 2026 cohort of 30 people with ME/CFS reported improvements in fatigue, pain, exercise capacity and processing speed after 40 sessions, with brain imaging changes alongside. Neither was a randomised trial, and the authors of both call for one.

Evidence so far
Early
Reading timeAbout 12 minutes

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Why this is being studied

Myalgic encephalomyelitis, or chronic fatigue syndrome, is a long-term illness marked by exhaustion that rest does not fix, a characteristic worsening after exertion, unrefreshing sleep, cognitive difficulty and often problems with standing upright. Research points to impaired energy production in cells, reduced blood flow and altered brain metabolism rather than any single damaged organ, which is why treatments that change how tissues use oxygen are being explored. The evidence for hyperbaric oxygen in ME/CFS is at a very early stage: small uncontrolled studies and a single case report, with no sham-controlled trial yet published.

Where the evidence stands

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The mechanism

What is going on, and why this might help

What is going on in the body

Myalgic encephalomyelitis / chronic fatigue syndrome is defined by profound fatigue with post-exertional malaise, unrefreshing sleep and cognitive difficulty. Research points to several interacting problems rather than one lesion: reduced mitochondrial energy production and an impaired ability to switch metabolic pathways under load; low-grade immune activation with altered cytokine profiles; autonomic dysfunction affecting blood pressure and heart-rate regulation; reduced cerebral blood flow, particularly on standing; and, in some studies, endothelial dysfunction and reduced oxygen extraction by muscle during exercise. The tissue-level picture is one of cells that cannot meet energy demand, with a nervous and immune system stuck in a defensive state.

Where oxygen comes in

Hyperbaric oxygen raises dissolved oxygen in plasma, which may matter where muscle or brain extract oxygen poorly or where flow is reduced. In laboratory and animal work it improves mitochondrial respiration and stimulates mitochondrial biogenesis, and the hyperoxic-hypoxic paradox (Hadanny and Efrati 2020) proposes that intermittent hyperoxia activates HIF-1α-dependent regenerative programmes without the harm of true hypoxia. Down-regulation of pro-inflammatory cytokines such as TNF-α and IL-6 is relevant to immune activation, and effects on cerebral perfusion seen in brain injury studies are relevant to cognitive symptoms and orthostatic intolerance. These are extrapolations: none of these mechanisms has been directly demonstrated in ME/CFS tissue.

How solid is this

This is largely theoretical, supported by mechanistic work in other conditions and by very small uncontrolled human series (for example Akarsu et al. 2013, 16 participants) reporting reduced fatigue scores. There is no sham-controlled trial in ME/CFS, and post-exertional malaise means any intervention needs cautious pacing. The strongest indirect support comes from long Covid, which shares much of this physiology, where one randomised trial exists. Key references: Hadanny and Efrati 2020; Akarsu et al. 2013.

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The studies

Every study is laid out the same way: what the researchers wanted to find out, who took part, what they actually did, what they found, why it might work and where the limits are. No jargon, and a link to the original if you want to read it yourself.

Each study is laid out the same way: what the researchers asked, who took part, what they did, what they found, why it might work, and where the limits are. The clinician layer at the end of each one carries the numbers.

Paper 1

The efficacy of hyperbaric oxygen therapy in the management of chronic fatigue syndrome

Akarsu et al. · Undersea and Hyperbaric Medicine · 2013 · prospective open-label trial, n=16

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What they asked

Chronic fatigue syndrome (ME/CFS) is defined by profound fatigue that rest does not relieve, made worse by exertion, with no single test to confirm it. This small Turkish study from a military medical academy asked a basic question: do people with the condition report less fatigue and better quality of life after a short course of hyperbaric oxygen?

Who took part

Sixteen people diagnosed with chronic fatigue syndrome according to the 1994 Fukuda criteria, which are the most widely used research definition. We could only access the abstract, which does not give age or sex breakdown. There was no control group.

What they did

Participants received 15 hyperbaric oxygen sessions over three consecutive weeks, five days a week. The abstract we could obtain does not state the pressure or session length; secondary sources describe the academy's standard protocol as 100 per cent oxygen at around 2.4 ATA for 90 minutes, but we cannot confirm this from the paper itself. Fatigue was measured before and after the course with three questionnaires: a visual analogue fatigue scale, the Fatigue Severity Scale, and a fatigue-specific quality-of-life score.

What they found

All three scores improved after treatment, and the changes were statistically significant (p below 0.005 for each). The abstract does not report the size of the change or individual results, so we cannot say how large the improvement was in practical terms or how many people responded.

Why it might work

The rationale offered is that ME/CFS may involve impaired oxygen delivery or use in muscle and brain, mitochondrial dysfunction and low-grade inflammation, and that high-dose oxygen might improve cellular energy production and dampen inflammation. This remains a hypothesis; the study measured no biological markers.

Limits

Sixteen people, no control group, no blinding, and only immediate post-treatment measurement, all of which leave a large opening for expectation effects and normal fluctuation in a condition that varies week to week. The authors themselves call for larger controlled studies. Details of pressure, session length, funding and conflicts could not be verified because only the abstract was accessible. This paper is best read as an early signal, not evidence of efficacy.

Paper 2

Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study

Kim, Scheibenbogen et al. · Journal of Translational Medicine · 2026 · prospective cohort, n=30 plus 30 controls

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What they asked

This German study asked whether a full course of hyperbaric oxygen improves physical functioning, fatigue, pain, exercise capacity and thinking speed in people with ME/CFS, and whether any improvement is reflected in changes in brain network connectivity on MRI. It is the largest prospective ME/CFS study of hyperbaric oxygen published to date.

Who took part

Thirty-seven adults meeting both the Canadian Consensus Criteria and the Institute of Medicine criteria for ME/CFS enrolled, and 30 completed treatment (23 women, 7 men, average age 42). Ninety per cent had developed ME/CFS after COVID-19, with an average illness duration of just over two years and moderate to severe disability. Around 43 per cent also had postural tachycardia syndrome. Thirty healthy people matched for age and sex had MRI scans for comparison only; they were not treated. House-bound and very severely affected people were not included.

What they did

Participants received 40 sessions of 100 per cent oxygen at 2 ATA for 90 minutes with five-minute air breaks every 20 minutes, up to five times a week, spread flexibly over 8 to 16 weeks to accommodate post-exertional malaise. There was no sham or untreated ME/CFS control group. The primary outcome was the physical functioning scale of the SF-36, measured at the end of treatment and four weeks later. Secondary outcomes included the Chalder Fatigue Scale, pain, a one-minute sit-to-stand test, handgrip strength, a processing-speed test, a standing test for orthostatic tolerance, and MRI of brain volume and resting connectivity.

What they found

Physical functioning improved by about 6 points on the 0 to 100 scale at the end of treatment and about 4.5 points four weeks later; 11 of 30 people (37 per cent) reached the 10-point threshold considered clinically meaningful. Fatigue scores fell, pain improved, sit-to-stand repetitions rose from 14 to 17.5, grip strength and processing speed improved modestly. On MRI, the ME/CFS group started with excessive connectivity between the thalamus and sensorimotor regions compared with healthy people; after treatment this moved back towards the healthy pattern, and more so in responders. Brain volume did not change. Seven people stopped early, mostly for ear or sinus pain or anxiety; nobody dropped out because of post-exertional malaise. Reversible short-sightedness was common (57 per cent).

Why it might work

The authors propose that ME/CFS involves functional dysregulation of thalamocortical circuits, the relay through which the brain filters sensory and bodily signals, rather than structural damage. They suggest hyperbaric oxygen acts through the hyperoxic-hypoxic paradox, stabilising HIF-1 alpha, improving oxygen delivery and lowering inflammatory cytokines, which might allow these circuits to settle. The correlation between reduced thalamic hyperconnectivity and physical improvement is consistent with this but does not prove it.

Limits

No sham or untreated control, so placebo response, regression to the mean and natural fluctuation cannot be excluded; the authors say plainly that efficacy cannot be concluded. Thirty people, mostly post-COVID onset, so findings may not transfer to ME/CFS of other origin. Severely affected people were excluded. Only four weeks of follow-up. Average improvements were modest, with a minority responding clearly. Publicly funded with declared academic conflicts and no industry involvement.

Paper 3

Reversible widespread brain FDG-PET hypometabolism in chronic fatigue syndrome treated by hyperbaric oxygen therapy

Mairal et al. · European Journal of Nuclear Medicine and Molecular Imaging · 2021 · case report

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What they asked

This is a single-patient report published as an Image of the Month in a nuclear medicine journal. The question it raises rather than answers is whether the brain's energy metabolism, which is often reduced in ME/CFS on FDG-PET scanning, can change after hyperbaric oxygen, and whether that change goes along with clinical improvement.

Who took part

One 31-year-old patient with chronic fatigue syndrome. The report itself is behind a paywall, so we are working from the abstract and from the description given in a 2025 review of metabolic neuroimaging in ME/CFS; we could not verify sex, illness duration or other clinical details from the original.

What they did

The patient had an FDG-PET brain scan (which maps glucose use as a proxy for neuronal activity) before and after a course of hyperbaric oxygen, and the scans were compared with a database of age-matched healthy controls. We were unable to confirm the pressure, session length or number of sessions from the accessible sources, and we would not want to guess.

What they found

Before treatment the scan showed widespread reduced metabolism, including in the amygdala, hippocampus, thalamus and cerebellum, regions repeatedly implicated in ME/CFS imaging studies. After treatment, metabolism in these regions had moved back towards normal, and this coincided with reported clinical improvement. The title of the report describes the hypometabolism as reversible.

Why it might work

FDG-PET hypometabolism suggests neurons that are alive but underactive, which is exactly the situation in which improved oxygen delivery, reduced inflammation and restored mitochondrial function might be expected to help. A before-and-after scan in one person is consistent with this idea but cannot distinguish a treatment effect from natural fluctuation, scanner variability or the passage of time.

Limits

One patient, no control, no blinding, and the imaging change could reflect many things. Case reports exist to generate hypotheses and illustrate imaging findings; they carry no weight as evidence of efficacy. We had access only to the abstract and secondary descriptions, so protocol, funding and conflict details are unverified. Its value is in pointing to FDG-PET as a possible objective marker for future controlled trials.