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    Scientific Review of Hyperbaric Oxygen Therapy (HBOT & mHBOT): Benefits, Mechanisms, Myths, and Evidence

    Scientific Review of Hyperbaric Oxygen Therapy (HBOT & mHBOT): Benefits, Mechanisms, Myths, and Evidence

    Author:
    Dr. Olli Sovijärvi, MD & Science Author, Medical Director of Hololife Center

    Preface

    This article aims to explain how hyperbaric oxygen therapy affects the human body and how it may support wellbeing. The article reviews the core mechanisms of the treatment, the most common myths and their corrections, and provides a broad yet accessible overview of the treatment's scientific background.

    Hyperbaric oxygen therapy is a relatively new topic for many people, and the concepts surrounding it are often misunderstood. In particular, medical hyperbaric oxygen therapy and the milder, wellbeing-oriented form known as mHBOT are frequently viewed as identical, even though their pressure levels, goals, and usage differ clearly. This article clarifies these differences and provides a basis for understanding the therapy's actual physiological foundations.

    Introduction

    Hyperbaric oxygen therapy uses a combination of pressure and oxygen to enhance the body’s repair processes. During treatment, the individual breathes oxygen in a pressurized environment. This increases tissue oxygen levels beyond those achievable at normal atmospheric pressure. The added oxygen and pressure strengthen cellular energy production and support tissue recovery. Hyperbaric oxygen therapy is commonly used in regenerative medicine.(1)

    Cells respond sensitively to changes in oxygen levels. Repeated exposure to higher oxygen levels activates cellular processes similar to those induced by hypoxia. This increases HIF, VEGF, and SIRT levels. These factors influence tissue regeneration and stem cell activity. This phenomenon is known as the hyperoxic-hypoxic paradox (HHP). It means that cells interpret fluctuating oxygen levels as a signal that activates repair mechanisms, even though no actual oxygen deprivation occurs.(2)

    Hyperbaric oxygen therapy increases the dissolution of oxygen into plasma. This enhances ATP production, the primary energy source of cells. Increased energy production supports tissue repair processes, immune function, and metabolism. The therapy also affects gene expression. It activates antioxidant systems and reduces inflammation. This may lower long-term inflammatory burden and support recovery during physiological stress.(3)

    Both HBOT and mHBOT are based on the same exact physiological mechanisms. Differences arise from pressure and oxygen concentration. Higher pressure produces a stronger response. Lower pressure is sufficient for many physiological benefits without the risk factors associated with higher-pressure chambers.(4–5)

    HBOT vs. mHBOT: Key Differences

    Treatment type

    Pressure

    Oxygen concentration in the chamber

    Supplemental oxygen (nasal cannula, mask)

    mHBOT

    1.2–1.5 ATA

    24–25% O₂ (ambient air circulation reduces oxygen concentration)

    max 90–95% O₂; actual 30–70% O₂ (due to chamber ventilation and leakage)



    Medical HBOT (monoplace)

    ≥ 1.5 ATA (typically 1.5–3.0 ATA)

    100% O₂

    100% O₂

     

    mHBOT is a lower-pressure form of treatment. It increases oxygen dissolution and activates the same cellular responses as HBOT, but to a milder degree. HBOT uses higher pressure and pure oxygen. This produces strong hyperoxia and is used in medical treatment settings.(6)

    Cellular Effects of Hyperbaric Oxygen Therapy

    Hyperbaric oxygen produces its effects through two primary physiological mechanisms: increased oxygen dissolution into plasma and activation of cellular signaling pathways. These mechanisms act concurrently and reinforce each other. HBOT produces these effects more strongly; mHBOT produces the same effects more mildly, but without the risks associated with higher pressure.

    1. Increased Oxygen Dissolution Into Plasma

    Pressure increases the amount of dissolved oxygen in plasma. This is a physical process described by Henry’s law (C = kₕ · P). Plasma oxygen content may increase several-fold compared to normal conditions.(7)

    • C = dissolved gas concentration in the liquid
    • kₕ = Henry’s constant (specific to gas and temperature)
    • P = partial pressure of the gas above the liquid

    Cells receive more oxygen because oxygen delivery is no longer limited solely by hemoglobin. Oxygen diffuses more effectively into tissues with reduced circulation. ATP production improves because mitochondria use oxygen to generate energy. When more oxygen is available, mitochondria produce more ATP. This strengthens tissue repair, immune function, and cellular metabolism.(5,8)

    The oxygen gradient in tissues changes, enhancing oxygen diffusion into cells and affecting cellular energy balance. Cellular viability improves. Tissues with limited blood flow benefit from increased oxygen diffusion, which appears as improved metabolism and faster repair processes.(6,9)

    2. Activation of Cellular Signaling Mechanisms

    Fluctuating oxygen levels simulate hypoxia without its harmful effects. Cells interpret these fluctuations as a signal, even though no actual oxygen deprivation occurs. This phenomenon, the hyperoxic-hypoxic paradox, activates HIF, VEGF, and SIRT:(2,10)

    • HIF (hypoxia-inducible factor) regulates cellular repair processes and promotes angiogenesis.
    • VEGF (vascular endothelial growth factor) stimulates the formation of new blood vessels.
    • SIRT (sirtuins) regulate metabolism and cellular stress tolerance.

    Stem cell mobilization and proliferation increase, improving tissue regeneration. The effect is notable in skin, muscle, and vasculature. Tissue repair and angiogenesis are strengthened due to activation of fibroblasts, improved mitochondrial ATP production, and enhanced cellular signaling.(11–13)

    Antioxidant systems activate, increasing the production of endogenous protective enzymes. This balances transient oxidative load. Inflammatory signaling decreases, lowering chronic inflammatory burden and supporting recovery.(10,14)

    Applications of Hyperbaric Oxygen Therapy

    HBOT

    Medical HBOT is suitable for conditions where tissue oxygen demand is high and strong hyperoxia provides a clear therapeutic benefit. These include:

    • Non-healing wounds
    • Infections where added oxygen supports immune function and inhibits bacterial growth
    • Radiation injury, where tissue vascularization is reduced
    • Severe tissue damage, such as ischemia, trauma, and major burns

    Higher pressure in HBOT is beneficial when a rapid and strong physiological response is required.

    HBOT requires medical supervision and careful evaluation of contraindications. The complete list of medical HBOT indications is provided in reference 9 (Sen, S. et al., 2021).

    mHBOT

    mHBOT is suited for milder and long-term applications, where the goal is to improve energy production, reduce inflammation, and enhance microcirculation at low pressure. These include:(4)

    • Recovery from physical exertion, especially in athletes and physically stressed individuals
    • Regulation of stress responses in states of autonomic load
    • Optimization of microcirculation to support tissue oxygenation and metabolism
    • Skin and tissue rehabilitation, including scar tissue remodeling, elasticity, and collagen production
    • Management of low-grade inflammation
    • Improvement of aerobic performance(15)

    mHBOT is a practical option for achieving long-term physiological adaptations without the demands of high-pressure environments. It is effective as a series of treatments when gradual and cumulative effects are desired.(16,4)

    mHBOT Treatment Protocols

    mHBOT relies on low pressure and repeated hyperoxia. Treatment parameters include pressure, session duration, frequency, and supplemental oxygen. The goal is to increase tissue oxygen availability safely and activate cellular repair processes.(4,18)

    Pressure:

    • 1.2–1.5 ATA
    • 1.2–1.3 ATA is suited for recovery and autonomic balance(17,19)
    • 1.3–1.5 ATA enhances oxygen diffusion and tissue repair

    Duration:

    • Single sessions last 60–90 minutes
    • Longer sessions may intensify tissue response, but the cumulative effect arises mainly from repeated treatments

    Treatment frequency:

    • Best results occur with series protocols

    • Initial phase: 3–5 sessions/week, total 20–40 sessions

    • Maintenance: 1–2 sessions/week or periodic intensive blocks

    Supplemental oxygen: Options during treatment

    • Room air (21% O₂)
    • Nasal cannula (24–40% O₂)
    • Mask (higher O₂ levels, typically 40–70%)

    Supplemental oxygen strengthens hyperoxia and enhances outcomes without significant added risk at low pressure.

    Individual optimization:
    The protocol may be adjusted based on recovery status, inflammatory load, tissue needs, and autonomic balance. Treatment responses are monitored and adjustments made as needed.

    Misconceptions About Hyperbaric Oxygen Therapy and What Research Shows

    Readers should now have a clear understanding of the differences between HBOT and mHBOT. However, several myths, misunderstandings, and prejudices persist, particularly regarding mild wellbeing-oriented hyperbaric oxygen therapy (mHBOT). This section addresses ten common myths and provides scientific rebuttals.

    1. Myth: “Supplemental oxygen causes oxygen toxicity.”

    Rebuttal:(20,21)

    • mHBOT uses low pressure (1.2–1.5 ATA) and moderate oxygen levels.
    • Oxygen toxicity occurs primarily at high pressures (2.0–3.0 ATA) and long exposures (hours).
    • Studies show that low-pressure therapy does not cause oxygen-toxic effects.

    2. Myth: “Supplemental oxygen causes dangerous oxidative stress.”

    Rebuttal:(22,23)

    • Oxygen produces a short-term oxidative load, which the body effectively regulates.
    • Studies show no harmful rise in oxidative markers during mHBOT.
    • The load is comparable to that produced by exercise.

    3. Myth: “The treatment can damage the lungs.”

    Rebuttal:(20)

    • Lung injury is associated with high-pressure medical hyperbaric exposure (>2.0 ATA).
    • mHBOT does not use pressures or ventilation forces that strain the lungs.
    • The risk for healthy individuals is very low.

    4. Myth: “mHBOT weakens respiratory regulation.”

    Rebuttal:(4,24)

    • Respiratory regulation remains normal because pressure and oxygen levels stay within physiological ranges.
    • Studies show no impairment in respiratory control after mHBOT.
    • Even in high-pressure HBOT, such effects are extremely rare.

    5. Myth: “Cannulas or masks make the treatment dangerous.”

    Rebuttal:(6,20)

    • Supplemental oxygen increases tissue oxygen mildly at low pressure.
    • Studies report no significant risks associated with supplemental oxygen at 1.2–1.5 ATA.
    • Even 100% O₂ at 2.0–2.5 ATA is usually safe; serious effects are rare.

    6. Myth: “The treatment poses serious risks to the ears.”

    Rebuttal:(16,25)

    • The most common issue is a sense of ear pressure, not barotrauma.
    • This is a normal adaptation to pressure change and not a serious injury.
    • Proper pressure equalization resolves the issue in nearly all cases.

    7. Myth: “Too much oxygen makes the body dependent.”

    Rebuttal:(26)

    • No evidence suggests physiological dependency.
    • HBOT/mHBOT produces a hormetic, not suppressive, response: mild oxidative stimulus → anti-inflammatory state, angiogenesis, stem cell mobilization.
    • Oxygen exposure does not impair hemoglobin function or regular oxygen transport.

    8. Myth: “Low pressure prevents therapeutic benefits.”

    Rebuttal:(4,23,27,28)


     Studies using 1.25–1.3 ATA and FiO₂ 24–40% show measurable effects:

    • Improved microcirculation
    • Improved autonomic balance
    • Better tissue oxygenation
    • Enhanced recovery
    • Reduced inflammation

    Lower pressure does not eliminate physiological benefits.

    9. Myth: “Benefits are placebo only.”

    Rebuttal:(4,19,23,27,28) Objective findings include:

    • Increased capillary blood flow
    • Increased stem cell counts
    • Changes in blood oxygen saturation
    • Changes in heart rate variability
    • Improved tissue healing

    The placebo effect cannot explain these objective physiological changes.

    10. Myth: “Supplemental oxygen accelerates free radicals and aging.”

    Rebuttal:(23,26,29)

    • Short exposure does not cause a lasting oxidative burden.
    • Adaptive response enhances antioxidant systems and may slow cellular aging.
    • No long-term harm observed in research.

    11. Myth: “mHBOT devices are dangerous and explosive.”

    Rebuttal:(20,31,33,34)

    • mHBOT uses room air and low pressure → no flammable oxygen-rich environment.
    • Devices meet pressure-vessel safety standards.
    • No explosion or fire risk is reported in safety reviews of mHBOT devices.
    • Explosion risks apply to 100% O₂ high-pressure chambers, not to mHBOT.
    • There are no reported explosions or fires of mHBOT chambers in the literature.

    Safety of Hyperbaric Oxygen Therapy

    Both mHBOT and HBOT are safe when pressure, oxygen level, and session duration are appropriate. Studies show high tolerance and low incidence of serious adverse events. Differences in safety arise from pressure: mHBOT uses lower pressure, which further reduces risk.

    Common Mild Adverse Effects

    Common transient effects include:(20,21)

    • Ear pressure sensation
    • Mild sinus symptoms, especially with mucosal swelling
    • Mild fatigue or relaxation after treatment due to autonomic changes

    These are temporary and related to pressure equalization.

    Rare Risks

    Less common but possible adverse effects include:(20,31)

    • Ear barotrauma if pressure equalization fails
    • Sinus pressure issues during congestion
    • Very rare oxygen-related toxicity at higher pressures (HBOT 2.0–3.0 ATA)
    • Temporary vision changes related to refractive shifts during long treatment periods
    • Claustrophobia in enclosed spaces

    Absolute Contraindications

    Hyperbaric oxygen therapy must not be performed under any pressure in these cases:(32)

    • Untreated pneumothorax
    • Trapped gas situations with risk of lung rupture
    • Untreated severe emphysema with air trapping
    • Active, untreated airway obstruction

    Relative Contraindications

    These require caution, medical evaluation, or adjustment of treatment parameters:(32)

    Medications previously considered absolute contraindications:

    • Doxorubicin
    • Bleomycin
    • Disulfiram
    • Cisplatin
    • Mafenide

    Respiratory conditions:

    • COPD, asthma, bullae, air-trapping structures
    • Previous spontaneous pneumothorax
    • Previous thoracic surgery
    • Unclear pulmonary findings

    Infections and acute conditions:

    • Upper respiratory infections
    • Sinus infections
    • High fever (>39°C)
    • Tuberculosis reactivation risk

    Ears and sinuses:

    • Pressure equalization difficulties
    • Eustachian tube dysfunction
    • Perilymphatic fistula

    Neurological factors:

    • Epilepsy
    • Lowered seizure threshold

    Implants:

    • Implanted devices
    • Epidural pain pumps

    Eyes:

    • Previous eye surgery
    • Intraocular gas
    • Optic neuritis
    • AMD, keratoconus, glaucoma

    Metabolic and hematologic factors:

    • Insulin-dependent diabetes
    • Congenital spherocytosis

    Psychological factors:

    • Claustrophobia

    Vasoconstrictors:

    • Nicotine, caffeine, and similar compounds

    Pregnancy is a relative contraindication for both HBOT and mHBOT unless medically justified.

    Safety Profile of mHBOT

    mHBOT is very safe for the vast majority of users, as low pressure prevents plasma oxygen levels from rising into ranges associated with toxicity. Adverse effects are usually mild and manageable, and serious adverse effects are extremely rare. mHBOT is well-suited for long-term, cumulative treatment without the risks associated with high-pressure therapy.(20)

    Summary

    Medical hyperbaric oxygen therapy (HBOT) and its milder form, mHBOT, affect cells by increasing tissue oxygen availability and activating cellular repair mechanisms. The treatment enhances energy production, improves microcirculation, and initiates processes that support tissue regeneration and reduce inflammation. These effects arise from increased plasma oxygen dissolution and activation of intracellular signaling. The mechanisms are physiologically well-grounded and supported by growing research.

    mHBOT produces these effects at lower pressure, making it suitable for supporting recovery, autonomic regulation, tissue metabolism, and management of low-grade inflammation. HBOT, due to higher pressure, provides stronger responses and is suited for medical conditions such as non-healing wounds, ischemia, and radiation injury.

    The safety profile of mHBOT is excellent due to moderate pressure and controlled oxygen exposure. Risks are low and mostly mild, while serious adverse effects are rare. Many claims about the dangers of mHBOT are based on misunderstandings rather than on physiology or evidence. When pressure, oxygen levels, and settings are appropriate, the mechanisms are clear, predictable, and measurable. Findings are consistent across research and clinical practice.

    Overall, hyperbaric oxygen therapy forms a coherent and evidence-supported treatment model in which mechanisms, benefits, and safety are clearly defined and physiologically understandable. This strengthens its position as a method that supports recovery and functional tissue capacity in both medical and well-being contexts.

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