The science of hyperbaric oxygen.

Hadanny and colleagues (2020, Aging 12(13): 13740-13761) ran a parallel cognitive arm on the same cohort. Healthy adults aged 64+ with no neurological diagnosis completed standardised neuropsychological testing before and after 60 HBOT sessions.

Eight of nine cognitive domains showed statistically significant improvement: attention, information processing speed, executive function, and global cognitive score were the largest movers. This is in healthy people — the effect was not contingent on a baseline deficit.

Mechanistically the authors point to two converging pathways. The first is increased cerebral blood flow: post-HBOT MRI showed increased perfusion in the frontal, temporal and parietal cortex. The second is the hyperoxic-hypoxic paradox (see below), which appears to trigger the same regenerative signalling as exercise and intermittent fasting, without the metabolic load.

Robbins et al. (2021, Practical Neurology) ran a small case series on long-COVID patients receiving HBOT and reported significant improvements in fatigue, cognition and the FACIT-Fatigue questionnaire after 10 sessions. Zilberman-Itskovich et al. (2022, Scientific Reports 12: 11252) followed up with a larger randomised sham-controlled trial — 73 patients with long-COVID symptoms more than three months post-infection received either 40 sessions of HBOT or sham. The HBOT group showed significant improvements in cognitive function, energy, sleep, psychiatric symptoms and pain.

Critically, the trial used sham pressurisation (a small pressure increase with normal air rather than 100% oxygen at high pressure), making it the strongest blinding HBOT research has produced to date. The treatment effect held.

The mechanism overlaps with the broader HBOT story: improved cerebral perfusion, reduced neuro-inflammation, and angiogenesis. Long COVID appears to involve sustained micro-vascular and inflammatory changes that HBOT directly targets.

Hyperbaric oxygen is approved by the Undersea & Hyperbaric Medical Society (UHMS) for 14 medical indications, with diabetic foot ulcer treatment among the most-cited. A 2015 Cochrane review (Kranke et al.) concluded that HBOT significantly improves ulcer healing rates in diabetic patients with non-healing wounds.

The mechanism is direct: oxygen drives fibroblast proliferation, collagen synthesis, and angiogenesis — the three pillars of wound healing. In tissue that is functionally hypoxic (as diabetic foot tissue often is), restoring oxygen delivery via dissolved plasma oxygen (rather than haemoglobin-bound, which is already saturated) accelerates every downstream repair pathway.

The wellness-side relevance: the same fibroblast, collagen, and angiogenic responses operate on healthy tissue. The skin and recovery benefits cited in the popular HBOT literature trace back to these same mechanisms.

Modern HBOT protocols (the Shamir / Efrati / Hadanny school) use intermittent air breaks during the session: typically 20 minutes of 100% oxygen, then 5 minutes of normal air, repeated three or four times. This isn't just a safety measure against oxygen toxicity — it's the active ingredient.

When tissue suddenly drops from very high oxygen pressure back to room air, it experiences a relative hypoxia. The cell detects the drop and turns on the same hypoxia-inducible factor (HIF-1α) signalling that exercise, fasting and altitude trigger. HIF-1α drives mitochondrial biogenesis, angiogenesis, and stem cell mobilisation.

This is why HBOT outcomes resemble exercise outcomes at the cellular level. The hyperoxic-hypoxic paradox is, in effect, exercise-mimetic signalling triggered by oxygen rather than metabolism. Efrati and colleagues have argued (Restorative Neurology and Neuroscience, 2017) that this paradox is the main mechanism underlying the regenerative effects observed in the cognitive, telomere, and brain-injury studies.