Hyperbaric Oxygen Therapy (HBOT) Research

This 2025 systematic review and meta-analysis evaluated the effectiveness of HBOT for treating neurocognitive deficits following traumatic brain injury.

The analysis found significant improvements in cognitive function across multiple domains. However, the authors note that larger trials with standardized protocols are needed to establish optimal therapeutic use.

Current evidence suggests HBOT may be recommended for chronic TBI patients with prolonged post-concussion syndrome who show evidence of metabolic dysfunction on neuroimaging.

This 2025 double-blind randomized trial compared 40 hyperbaric oxygen sessions to 40 sham sessions over 12 weeks in adults with persistent symptoms following non-stroke brain injury.

The study used 1.5 ATA, which has been studied extensively for brain injury sequelae. Prior trials of HBO2 show encouraging results for improvement of symptoms months to years after traumatic brain injury, stroke, and long COVID.

This 2024 review article comprehensively examines the mechanisms by which HBOT may promote regeneration and combat aging.

Key mechanisms reviewed:

• Hyperoxia-hypoxia paradox and HIF-1α activation
• Telomere lengthening effects
• Senescent cell clearance
• Stem cell mobilization
• Angiogenesis and neurogenesis
• Mitochondrial biogenesis

The authors conclude HBOT has enormous potential in regenerative and anti-aging therapy.

This systematic review and meta-analysis assessed the safety profile of hyperbaric oxygen therapy by examining adverse effects reported across randomized controlled trials. The authors searched multiple databases and included studies that compared HBOT to sham or conventional treatments across various clinical conditions.

The pooled analysis found that HBOT was associated with a statistically significant increase in overall adverse events compared to control groups. Ear barotrauma (middle ear pain and pressure injuries) was the most frequently reported side effect, consistent with the known mechanical effects of pressure changes on the ear. Other adverse effects included transient myopia, claustrophobia, and fatigue, though serious complications such as seizures or pulmonary oxygen toxicity were rare.

Subgroup analyses examined whether adverse event rates varied by number of sessions, chamber pressure, and clinical indication. Higher pressures (>=2.0 ATA) and greater session counts tended to be associated with more adverse events, though heterogeneity across studies was notable. The findings support HBOT as a generally safe intervention when administered under proper clinical supervision, while reinforcing the importance of patient screening and monitoring.

This narrative review examined the evidence and mechanistic rationale for using hyperbaric oxygen therapy in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis (ALS). The authors synthesized preclinical and clinical findings to evaluate HBOT's potential as a neuroprotective intervention.

The review highlighted several key mechanisms by which HBOT may combat neurodegeneration. Increased oxygen delivery enhances mitochondrial function and ATP production in oxygen-deprived neural tissue. HBOT also modulates neuroinflammatory pathways, reducing pro-inflammatory cytokines and microglial activation that contribute to disease progression. Additionally, the hyperoxia-hypoxia paradox triggers upregulation of antioxidant defenses and growth factors including BDNF and VEGF, which support neuronal survival and angiogenesis.

Preclinical studies in animal models of Alzheimer's showed reduced amyloid-beta plaque burden and improved spatial memory following HBOT. Parkinson's models demonstrated preservation of dopaminergic neurons and motor function. Clinical evidence, while limited, included small trials showing cognitive improvements in Alzheimer's patients and symptom stabilization in Parkinson's patients. The authors concluded that HBOT holds meaningful promise as an adjunct therapy for neurodegeneration but emphasized the need for large-scale randomized controlled trials to establish efficacy, optimal dosing, and long-term safety.

This systematic review evaluated the evidence for hyperbaric oxygen therapy's effects on cognitive function across a range of neurological and non-neurological conditions. The authors systematically searched the literature for clinical studies that used validated neuropsychological assessments to measure cognitive outcomes before and after HBOT courses.

The review found that HBOT was associated with improvements across multiple cognitive domains, including attention, memory, executive function, and information processing speed. The most robust evidence came from studies in traumatic brain injury (TBI) and post-stroke populations, where patients showed measurable gains on standardized cognitive tests following HBOT protocols. Studies in aging populations and those with mild cognitive impairment also reported positive trends, though with smaller sample sizes.

The authors noted considerable variability in study protocols, including differences in pressure levels, session counts, and timing of assessments. While the overall direction of evidence was positive, the heterogeneity and lack of large-scale RCTs limited the strength of conclusions. The review highlighted that HBOT's cognitive benefits likely stem from enhanced cerebral oxygenation, neuroplasticity, and reduced neuroinflammation, and called for standardized protocols in future research.

This landmark prospective trial from Tel Aviv University examined the effects of 60 daily hyperbaric oxygen sessions (2.0 ATA, 90 min) on telomere length and cellular senescence in 35 healthy adults aged 64+.

Key findings:

• T helper cell telomeres: +20%
• T cytotoxic cell telomeres: +25%
• Natural killer cell telomeres: +38%
• B cell telomeres: +29%
• Senescent T helper cells: -37%
• Senescent T cytotoxic cells: -11%

The study demonstrated that HBOT can reverse two hallmarks of aging, telomere shortening and cellular senescence, through the hyperoxia-hypoxia paradox.

This randomized controlled trial examined the effects of hyperbaric oxygen therapy on cognitive function in healthy aging adults.

Key findings:

• 63 healthy adults aged 64+ completed the study
• 60 HBOT sessions over 3 months
• Significant improvements in attention, information processing, and executive function
• Increased cerebral blood flow on imaging

Results:

• Memory improvement: Significant gains in multiple domains
• Processing speed: Enhanced information processing
• Brain imaging: Increased blood flow to cognitive regions

Protocol:

• 60 sessions, 5 days/week for 12 weeks
• 100% oxygen at 2 ATA
• 90 minutes per session

Clinical significance:

While this is HBOT (hyperbaric), it supports the concept that enhanced oxygen delivery benefits brain function, providing mechanistic support for EWOT approaches.

This prospective study evaluated hyperbaric oxygen therapy for cognitive rehabilitation in chronic stroke patients.

Patients received 60 daily HBOT sessions at 2 ATA for 90 minutes. Results showed significant improvements in memory, attention, and executive function that correlated with increased brain metabolism on imaging.

This Cochrane systematic review analyzed randomized trials of hyperbaric oxygen therapy for diabetic foot ulcers.

Analysis showed HBOT significantly improved the likelihood of ulcer healing and reduced the risk of major amputation compared to standard care alone.