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Hyperbaric Oxygen Therapy Research: What the Science Shows

A closer look at cell signaling, gene expression and the neurological research behind HBOT, including where the evidence is still limited.

HBOT is often described simply as oxygen delivered under pressure. That is part of the story, but likely not all of it. Repeated rises in oxygen, followed by a return toward normal levels, appear to act as a biological signal. Researchers are studying how that signal affects transcription factors, blood-vessel growth, inflammation, antioxidant defenses, mitochondrial function and neuroplasticity.

Beyond Oxygen: The Hyperoxic-Hypoxic Paradox

During a course of HBOT, oxygen levels rise sharply during each session and fall back afterward. Cells seem to respond not only to how much oxygen is present, but also to the repeated change.

The hyperoxic-hypoxic paradox is a proposed framework for this effect. It suggests that intermittent high oxygen can switch on some of the same oxygen-sensing pathways normally triggered by low oxygen, without ever making the patient hypoxic.

How HBOT Affects Gene Expression

In a prospective study, 35 healthy adults aged 64 and older completed 60 HBOT sessions. Blood samples taken afterward showed significant changes in gene activity compared with baseline: 1,342 genes were more active and 570 were less active, using the study’s statistical threshold. This does not change a person’s DNA. It means cells changed how certain genes were being expressed after the treatment course.

Source: doi.org/10.18632/aging.203709

Key Cellular Pathways

HIF-1α and VEGF

Repair and Blood-Vessel Growth

Intermittent oxygen exposure may influence hypoxia-inducible factor (HIF-1α) signaling and downstream pathways such as VEGF, which are linked to new blood-vessel growth (angiogenesis), cellular adaptation and tissue repair.¹

Source: doi.org/10.3390/biom10060958

Nrf2

Antioxidant Defenses

High-oxygen exposure produces reactive oxygen species that act as signals. With repeated exposure, the body may strengthen its own antioxidant response.

SIRT1

Mitochondrial and Metabolic Response

SIRT1 helps regulate metabolic sensing, oxidative-stress responses and mitochondrial function.¹

Source: doi.org/10.3390/biom10060958

Hyperbaric Oxygen Therapy Research by Condition

HBOT for Healthy Cognitive Aging

A randomized controlled trial of 63 healthy adults over 64 found improved overall cognition after 60 HBOT sessions. The biggest gains were in attention and information-processing speed. Perfusion MRI also showed increased blood flow in specific brain regions.³

Source: doi.org/10.18632/aging.103571

HBOT for Chronic Stroke Recovery

A prospective randomized crossover trial studied patients 6 to 36 months after a stroke. After 40 sessions at 2.0 ATA, participants showed improvements in neurological function and quality of life, along with changes on SPECT brain imaging.⁴ The crossover design is informative, but it is not the same as a blinded, sham-controlled trial.

Source: doi.org/10.1371/journal.pone.0053716

HBOT for Post-Concussion Syndrome and TBI

A randomized prospective crossover study in people with lasting symptoms after mild traumatic brain injury reported better cognitive scores, quality of life and SPECT findings after 40 sessions at 1.5 ATA.⁵ As with the stroke trial, the comparison group received no treatment rather than a blinded sham.

Source: doi.org/10.1371/journal.pone.0079995

HBOT for Parkinson’s Disease

A systematic review and meta-analysis (online 2024, print 2025) pooled 13 studies with 958 participants. Adding HBOT to standard therapy was associated with improvements in selected motor, cognitive and sleep outcomes.⁷ All included trials were conducted in China, and study quality and risk of bias limit how confident we can be. HBOT remains investigational for Parkinson’s disease.

Source: doi.org/10.1159/000542619

Additional Health Benefits
HBOT for Alzheimer’s Disease and Mild Cognitive Impairment
  • A 2018 case report described symptom improvement and increased brain metabolism on FDG-PET after HBOT in one patient with Alzheimer’s dementia.⁶
  • A 2020 clinical study in patients with Alzheimer’s disease and amnestic mild cognitive impairment reported short-term gains in cognitive scores and, in a subset, improved brain glucose metabolism.⁹
  • A 2024 meta-analysis of 11 randomized trials found favorable pooled results for cognition and daily function, though study quality and methods varied widely.⁸
  • A 2025 double-blind, sham-controlled trial in older adults with type 2 diabetes and mild cognitive impairment did not find sustained benefits for HBOT over sham.¹⁰

Sources:

doi.org/10.4103/2045-9912.248271

doi.org/10.1002/trc2.12030

doi.org/10.3389/fnagi.2024.1360148

doi.org/10.1002/alz70861_108814

Limitations of the Current Research

The research is promising in selected areas, and it is also uneven. Studies differ in pressure, oxygen exposure, number of sessions, patient selection and outcomes measured. Several influential neurological studies are small, come from a single center, or use crossover or no-treatment controls instead of sham controls. Encouraging findings at the cellular level do not automatically prove a clinical benefit.

How WellMax Uses This Evidence

For chronic neurological and cognitive conditions, WellMax considers HBOT on an individual, physician-supervised basis. We describe these uses as investigational or off-label, and we review the potential benefits, uncertainties, time commitment and risks with every patient.

References

  • 1
    Hadanny A, Efrati S. The Hyperoxic-Hypoxic Paradox. Biomolecules. 2020;10(6):958. doi.org/10.3390/biom10060958
  • 2
    Hadanny A, Forer R, Volodarsky D, et al. Hyperbaric oxygen therapy induces transcriptome changes in elderly: a prospective trial. Aging (Albany NY). 2021;13(22):24511–24523. doi.org/10.18632/aging.203709
  • 3
    Hadanny A, Daniel-Kotovsky M, Suzin G, et al. Cognitive enhancement of healthy older adults using hyperbaric oxygen: a randomized controlled trial. Aging (Albany NY). 2020;12(13):13740–13761. doi.org/10.18632/aging.103571
  • 4
    Efrati S, Fishlev G, Bechor Y, et al. Hyperbaric oxygen induces late neuroplasticity in post stroke patients — randomized, prospective trial. PLoS One. 2013;8(1):e53716. doi.org/10.1371/journal.pone.0053716
  • 5
    Boussi-Gross R, Golan H, Fishlev G, et al. Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury — randomized prospective trial. PLoS One. 2013;8(11):e79995. doi.org/10.1371/journal.pone.0079995
  • 6
    Harch PG, Fogarty EF. Hyperbaric oxygen therapy for Alzheimer’s dementia with positron emission tomography imaging: a case report. Med Gas Res. 2018;8(4):181–184. doi.org/10.4103/2045-9912.248271
  • 7
    Bu S, Liu W, Sheng X, Jin L, Zhao Q. Hyperbaric oxygen therapy improves motor symptoms, sleep, and cognitive dysfunctions in Parkinson’s disease. Dement Geriatr Cogn Disord. 2025;54(3):187–200. doi.org/10.1159/000542619
  • 8
    Lin G, Zhao L, Lin J, Li X, Xu L. Clinical evidence of hyperbaric oxygen therapy for Alzheimer’s disease: a systematic review and meta-analysis of randomized controlled trials. Front Aging Neurosci. 2024;16:1360148. doi.org/10.3389/fnagi.2024.1360148
  • 9
    Chen J, Zhang F, Zhao L, et al. Hyperbaric oxygen ameliorates cognitive impairment in patients with Alzheimer’s disease and amnestic mild cognitive impairment. Alzheimers Dement (N Y). 2020;6(1):e12030. doi.org/10.1002/trc2.12030
  • 10
    Benari O, et al. Results of a double-blind sham-controlled trial examining the effects of hyperbaric oxygen therapy on cognition and brain biomarkers. Alzheimer’s & Dementia. 2025 (conference abstract). doi.org/10.1002/alz70861_108814

Scientific material is presented for education and discussion with a physician. Off-label and investigational uses should not be read as established treatment indications. © 2026 WellMax.