Bio-oxidative Therapy and Redox Medicine

At a glance:

1. Redox reactions refer to chemical reactions where there are transfers of electrons from one molecule to another. They’re central to key processes in the cell, such as energy production, immune response, and cell growth.
2. Balance is key when it comes to redox in the human body. Too many oxidants or antioxidants can cause disease or throw things off balance.
3. Modern lifestyle factors like the standard American diet, a sedentary lifestyle, and stress tend to produce excess oxidative stress.
4. Bio-oxidative therapy includes ozone therapy, oxygen therapy, hyperbaric oxygen therapy, and hydrogen peroxide therapy. They work by providing oxygen and a small amount of oxidative stress that jumpstarts Nrf2, the body’s antioxidant cell manager. They also tend to increase nitric oxide and plasma oxygenation, in addition to hemoglobin oxygenation.
5. Redox medicine includes bio-oxidative therapy, medications, and treatments that manipulate redoxes in the body for health and disease treatments.
6. Bio-oxidative therapies all have similar and overlapping benefits.
7. Oxygen therapy can help replenish oxygen in patients who lack oxygen or cannot oxygenate their blood effectively.
8. HBOT is particularly beneficial for sepsis, altitude sickness, decompression sickness, and non healing wounds. Some evidence suggests it can also help with long-haul syndrome, pain, and brain and psychiatric issues, along with anti-aging.
9. Ozone therapy is best for infections, circulation, and pain.
10. Hydrogen peroxide has the least evidence, although it’s commonly used to treat infections.

What Is Bio-oxidative Therapy?

Bio-oxidative therapy and redox medicine are emerging fields in medical science that focus on using oxidative agents to promote health and treat various medical conditions. These therapies harness the power of oxygen and other oxidative molecules to modulate biological processes, aiming to restore balance in the body's oxidative and antioxidative systems. 

Bio-oxidative therapy involves introducing reactive oxygen species (ROS) into the body in controlled amounts. ROS are oxidative molecules that contain oxygen. Too many ROS can cause cellular damage. However, in regulated amounts these molecules and redox reactions play a crucial role in cell signaling and homeostasis throughout the human body.

Aside from ozone therapy, bio-oxidative therapies include pure oxygen therapy, hyperbaric oxygen therapy, and hydrogen peroxide therapy (IV or injections).

Each utilizes different mechanisms to deliver oxygen or induce small amounts of oxidative stress to elicit health effects. In this article, we’re NOT referring to the direct exposure of these substances on pathogens outside the human body.

The primary mechanisms of action in bio-oxidative therapies involve the induction of controlled oxidative stress. This mild oxidative stress can:

• Jumpstart the body’s antioxidant defense
• Improve oxygen utilization
• Enhance immune function
• Modulate cell signaling, improving tissue repair and regeneration

Applications and Benefits: Bio-oxidative therapies are used to treat a wide range of conditions, including:

• Infections
• Chronic inflammatory diseases
• Cardiovascular disorders
• Neurodegenerative diseases
• Potential in cancer therapy
• Wound healing, especially in conditions that heal poorly due to low blood flow or oxygenation such as diabetes
• As adjuncts to conventional treatmentsc

Through controlled induction of oxidative stress and modulation of redox processes, these therapies offer promising avenues for treating various medical conditions and enhancing overall health.

‍

What Is Redox Medicine?

Redox medicine focuses on the role of oxidative stress and redox signaling in health and disease. It aims to restore the balance between oxidants and antioxidants, often disrupted in diseases. In some cases, redox medicine also involves harnessing differences in redox tolerances to kill cancer cells or pathogens. By modulating redox processes, these therapies can enhance cellular function, reduce inflammation, and promote healing.

Aside from bio-oxidative therapies, redox medicine can also use drugs or substances that modify the redox status in the body [1]. These substances can be:

• Indirect antioxidants that activate your own antioxidant systems
• Inhibitors of ROS formation
• Inhibitors of downstream toxic effects of ROS
• Stimulators of repair from ROS dama

What Is Redox and Why Is It Important for Health?

Redox, short for reduction-oxidation, refers to a set of chemical reactions involving the transfer of electrons between two molecules.

One substance loses electrons (oxidation) while another receives electrons (reduction) during a redox reaction.

These reactions are coupled, meaning that oxidation and reduction typically occur simultaneously. In some cases, redox reactions create unstable molecules that have an extra high-energy electron like peroxides and free radicals. The peroxides and free radicals can be very reactive and may react with cell components or tissues, creating damage. At the same time, the presence of peroxides and free radicals can increase readouts from antioxidant genes like Nrf2.

Inside your body, redox reactions and their balance are crucial for numerous processes, including [2, 3]:

• Cellular metabolism
• Energy production
• Immune response
• Blood sugar control
• Wound healing
• Cell growth, division, and specialization (differentiation)
• Communications within and between cells (redox signaling) which helps to maintain cellular homeostasis and respond to appropriately to stimuli [4]

For example, in cellular respiration, glucose is oxidized to produce carbon dioxide, while oxygen is reduced to form water. This process releases energy, which is then used to produce adenosine triphosphate (ATP), the primary energy currency of cells [5].

Health Implications: Proper redox balance is essential for health. Modern day lifestyle factors such as excess caloric intake, sedentary lifestyle, and chemical exposures tend to tip the balance towards excessive oxidative stress. These contribute to accelerated aging and chronic diseases.

Conversely, enhancing the body's redox capacity, such as with redox medicine and improved lifestyle choices, can improve health outcomes. Strategies to support redox balance include a diet rich in antioxidants, regular physical activity, and potentially interventions like bio-oxidative therapies.

Bio-Oxidative Therapy: Ozone Therapy vs HBOT vs Hydrogen Peroxide Therapy Comparisons

Bio-oxidative therapies such as ozone therapy, hyperbaric oxygen therapy (HBOT), and hydrogen peroxide therapy all involve the use of oxidants to stimulate a redox re-balance. Each therapy generates different types and strengths of oxidative species, that influence their mechanisms of action and therapeutic effects.

Ozone Therapy

Ozone therapy refers to  exposing  the body to 95-99.5% medical-grade oxygen and 0.05 - 5% of ozone gas for therapeutic purposes. It includes the exposure of any body part except the lungs to the ozone gas, or ozonated oil or water. Ozone (O₃) is a highly reactive gas with each molecule being composed of three oxygen atoms.

When introduced into the body, ozone rapidly breaks down into ROS, including oxygen radicals, superoxide, and hydrogen peroxide. The overall strength of oxidants generated by ozone therapy is considerable due to ozone's high reactivity. Ozone therapy induces controlled oxidative stress, stimulates antioxidant defenses, and modulates immune responses. At the same time, the oxygen gas oxygenates blood and tissues (where applied), stimulating metabolic capacity and resolving hypoxia.

 Blood ozone exposures and rectal ozone insufflation provide the most systemic bio-oxidative effects, perhaps the most similar to HBOT and hydrogen peroxide therapy.

Hyperbaric Oxygen Therapy (HBOT)

HBOT involves breathing pure oxygen in a pressurized chamber, which significantly increases the amount of oxygen dissolved in the blood. This elevated oxygen level enhances tissue oxygenation and metabolism, promoting the production of ROS in the body. The ROS stimulate crucial immune functions and cellular repair responses.

Hydrogen Peroxide Therapy

Hydrogen peroxide therapy refers to the intravenous administration of hydrogen peroxide. Hydrogen peroxide (H₂O₂) is a mild oxidative antiseptic used in medical settings. Inside the human body, several more reactive molecules are disarmed to create H₂O₂, so H₂O₂ provides some important cellular signals. It also decomposes to form water and oxygen, oxygenating tissues and releasing ROS. The oxidative species produced by hydrogen peroxide therapy are primarily hydrogen peroxide itself and its breakdown products. These species are less reactive compared to those produced by ozone therapy but can still induce oxidative stress and biological responses. Because hydrogen peroxide releases oxygen, it’s crucial to administer it very slowly in IV therapy to prevent gas embolism.

Currently, HBOT is a mainstream treatment for sepsis, diabetic ulcers, ischemia, carbon monoxide poisoning, and several other infectious conditions. In the US, ~2000 hospitals have hyperbaric chambers and there are up to 700 outpatient hyperbaric clinics.

Each bio-oxidative therapy has unique strengths and applications based on the type and strength of oxidative species they produce. Of these, however, hydrogen peroxide IV has the least evidence, so some of [1] 

Conditions that All Three Bio-oxidative Therapies May Help

Infections

Bio-oxidative molecules are broad-spectrum antimicrobials that spare good bacteria, making them a great option to have for emerging or hard-to-treat infections. These therapies help with infections, especially deep and chronic ones, by [6, 7]:

• Oxidative species, such as lipid oxidation byproducts, oxygen, and hydrogen peroxide having antimicrobial effects inside the human body 
• Activation of the immune system and the right cytokines
• Enhancement of antioxidant defenses to protect tissues from oxidative damage
• Improving mitochondrial function
• Improving blood flow and tissue oxygenation, which can help with infections that are hard to treat due to lack of blood flow. Better tissue oxygenation can also inhibit pathogen growth
• Breaking biofilms and working as adjuvants with the drugs

For a full coverage of ozone therapy for infections, check out our ozone therapy for infections article.

A clinical trial investigated the effects of hyperbaric oxygen therapy (HBOT) on the prevention and treatment of burn infections by analyzing its impact on serum levels of soluble interleukin 2 receptor (sIL-2R) and fibronectin (Fn) in 42 severe burn patients. sIL-2R increases and Fn level decreases in burn patients are closely associated with the development of burn-related sepsis.

Patients were randomly divided into two groups: an HBOT group (25 patients) and a non-HBOT group (17 patients) and tracked for 35 days post-burn.

In the non-HBOT group, sIL-2R levels were significantly elevated, while Fn levels were markedly decreased at all measured time points compared to healthy controls. In contrast, the HBOT group exhibited much lower increases in sIL-2R and maintained higher levels of Fn, with significant differences observed across all 35 days. The incidence of sepsis was significantly reduced in the HBOT group.

The study results indicated that HBOT may play a beneficial role in the prevention and treatment of burn infections [8].

Hydrogen peroxide IV therapy is a common option to treat minor infections in some naturopathic clinics. The only published studies refer to influenza and chikungunya virus.

Early 20th century cases of severe influenzal pneumonia were treated with injections of hydrogen peroxide. Although significant improvements in mortality did not occur, breathing (depth and rate of breathing) profiles changed for the better [9].

Fifty-six patients with moderate to severe pain from the chikungunya virus received a single infusion of ascorbic acid (25-50 grams) and hydrogen peroxide (3 cc of a 3% solution). Pain levels were assessed using the Verbal Numerical Rating Scale-11 before and after treatment [10]. The results of the treatment showed:

• A significant reduction in pain, with the average pain score dropping from 8 to 2 (a 60% decrease, p < 0.001)
• 9% of patients reported a complete absence of pain

Sepsis

Sepsis is a condition with a 30 - 50% mortality rate. It’s especially hard to treat as it could come from common infections that spiral out of control, partly due to the immune system’s failure. There is no specific treatment for sepsis [2] [3] beyond managing the symptoms. When the blood pressure drops, damage to internal organs and deaths is imminent. Bio-oxidative therapy provides a powerful option that may prevent or resolve sepsis, perhaps saving limbs or lives [11].

A 65-year-old man with multidrug-resistant Klebsiella pneumoniae osteomyelitis and a history of type 2 diabetes had also developed a necrotic wound. He was treated with 30 hyperbaric oxygen therapy (HBOT) sessions instead of antimicrobials due to the resistance of the infection.

Treatment led to the healing of the wound, resolution of pain, and normalization of inflammatory markers without the use of any antibiotics. MRI imaging confirmed improvement in the condition, and no recurrence of infection was reported after one year.

The case underscores the potential of HBOT as an alternative treatment for severe infections where antimicrobial options are limited [12].

53 patients who suffered burns from the 2015 Formosa Fun Coast dust explosion disaster were treated with either standard burn therapy or standard burn therapy combined with adjunctive hyperbaric oxygen therapy (HBOT).

The HBOT group showed:

• Significantly faster normalization of procalcitonin (PCT) levels (a biomarker for sepsis) compared to the control group (p = 0.007)
• Fewer rates of reoperation or additional interventions
• Lower rates of complications, such as tracheostomy and hemodialysis

There was no significant difference between the groups in terms of hospital stay, number of skin grafts, or regraft area.

Adjunctive HBOT improved sepsis control and reduced the need for additional surgeries in severe burn patients, making it a promising complementary therapy [13].

An in vitro study explored the potential of using ozone (O3) as a treatment for sepsis, particularly focusing on its bactericidal properties against Escherichia coli (E. coli).

Results showed that a single pass of ozone treatment reduced E. coli levels by 27% in infected human blood. In vivo studies using a swine model of E. coli-induced sepsis showed that ozone treatment was technically feasible and physiologically tolerable, with no significant impact on circulatory, respiratory, or metabolic parameters in the animals. Further research is recommended to explore the clinical applications of ozone therapy in treating sepsis [14].

Some experts believe that HBOT (and perhaps all oxidative therapy) can be too much for septic patients, because it increases oxygen levels significantly, which may lead to hyperoxia (too much oxygen).

Hyperoxia can disrupt the delicate balance of reactive oxygen species (ROS) and antioxidants, potentially worsening oxidative stress and cellular damage in septic patients. Sepsis already induces oxidative stress, and excessive oxygen can amplify inflammation and tissue injury, exacerbating organ dysfunction. Therefore, while oxygen therapy is crucial for treating hypoxia in sepsis, it must be carefully controlled to avoid detrimental effects from over-oxygenation [15].

Diabetic foot ulcers and skin ulcers

Bio oxidative therapies—ozone, hydrogen peroxide, and hyperbaric oxygen—are highly effective for skin, wound, and pain conditions because of the superficial nature of the damage. All of them seem to support collagen production, circulation, disinfection, tissue regeneration, and pain relief. Together, these therapies boost recovery and target the root causes of pain and tissue damage.

[4] [5] A clinical trial explored the effectiveness of combining standard wound care with ozone therapy in the treatment of diabetic foot ulcers (DFUs), The control group (12 patients) received standard wound care with antimicrobial dressings every 3 days for 21 days, while the intervention group (15 patients) received the same care plus ozone bagging therapy at a concentration of 70 μg/mL for 10 minutes every 3 days over the same period.

Combining standard wound care with ozone therapy significantly reduced the number of bacterial colonies in the DFUs (p = 0.001). However, there was no significant difference in the overall DFU assessment scores between the intervention and control groups (p > 0.05).

While ozone therapy can reduce bacterial load in DFUs, its effect on wound healing may depend on the dose and duration of therapy. Future research should focus on optimizing the concentration and exposure time of ozone therapy to achieve better healing outcomes [16].

A RCT evaluated the impact of HBOT as an adjunct to standard wound care in the treatment of diabetic foot ulcers (DFUs) in 58 diabetic patients with a Grade 2 ulcer or higher on the Wagner scale. The progress of wound healing was measured at days 0, 10, 20, and 30.

Results showed that patients in the HBOT group experienced significantly greater reductions in wound size over time compared to those in the control group (p<0.001). HBOT treatment was significantly more likely to achieve at least a 30% reduction in wound size within the study period (p<0.001).

The study demonstrated that HBOT significantly enhances the rate of wound healing in diabetic foot ulcers when used as an adjunct to conventional wound care [17].

Aside from topical use, there is no direct clinical evidence supporting the use of hydrogen peroxide therapy in diabetic foot ulcers. However, by speculation, it should somewhat help based on similar mechanisms.

Wound healing

Various clinical studies have demonstrated the effectiveness of ozone therapy and HBOT on difficult wound cases. Most of these studies are small, but the results are promising.

A RCT aimed to compare the effects of laser photobiomodulation (PBM) and topical ozone therapy on the reepithelialization of palatal donor site wounds on 36 patients following free gingival graft (FGG) surgeries.

By day 14, the ozone group had significantly smaller wounds according to digital image analysis compared to the control group (p = 0.034). Additionally, the control group reported significantly higher postoperative discomfort compared to both the laser group (p = 0.002) and ozone group (p < 0.001) at day 7.

Adjunctive ozone therapy may significantly accelerate palatal wound healing following FGG procedure [18].

A prospective, randomized, open-label, controlled study of 38 patients with non healing DFUs, were recruited to compare the effects of standard wound care combined with adjunctive hyperbaric oxygen therapy (HBOT) versus standard wound care alone. The outcomes evaluated included wound healing, markers of inflammation, glycemic control, amputation rate, survival rate of tissue, and health-related quality of life.

Complete closure of DFUs was achieved in 25% of patients in the HBOT group compared to 5.5% in the routine care group (p = 0.001). The amputation rate was lower in the HBOT group (5%) compared to the routine care group (11%) (p = .001). The HBOT group also showed significant improvements in inflammation markers, blood flow, and health-related quality of life from pretreatment to two weeks post-treatment (p < 0.05).

Adjunctive HBOT significantly improved wound healing in patients with DFUs, reduced the risk of limb amputation, and enhanced overall health-related quality of life. The study suggests that a minimum of 20 HBOT sessions is necessary to achieve these beneficial outcomes [19].[6] [7]  

A comparative cohort study evaluated HBOT as an adjunctive treatment for brain abscesses in 40 patients. Twenty patients received standard treatment (surgery and antibiotics), while the other 20 patients received the same treatment with the addition of HBOT.

Results showed:

• Significantly fewer reoperations in the HBOT group (10% vs 45%, p = 0.03)
• Significantly lower recurrence rates in the HBOT group, (14% vs 58%, p < 0.01) 
• 80% of patients in the HBOT group achieved a good outcome (Glasgow Outcome Score of 5), compared to 45% in the non-HBOT group (p = 0.04)

HBOT is associated with fewer treatment failures, reduced need for reoperations, and improved long-term outcomes in patients with brain abscesses. HBOT was also well-tolerated and safe, warranting further prospective studies to confirm its role in brain abscess treatment [20].

A triple-blinded, parallel, randomized controlled clinical trial involved 114 patients who underwent the extraction of impacted, partially erupted, or completely erupted third molars. This study aimed to evaluate the effectiveness of a combination of hydrogen peroxide (H2O2) and hyaluronic acid (HA) in promoting socket healing after third molar surgery.

Results showed significant reductions (p<0.001) in pain levels and other outcome measures in the H2O2 and HA group compared to the placebo group, indicating a positive effect of the combination on socket healing after third molar surgery [21].

Pain

Biooxidation therapies, such as ozone and hydrogen peroxide (H2O2) injections, offer a unique approach to pain management by leveraging oxidative stress to promote healing and reduce inflammation.

When injected into joints or affected areas, these agents stimulate the body's natural healing processes by increasing oxygenation and inducing mild oxidative stress. This activates the release of growth factors and anti-inflammatory cytokines, supporting tissue regeneration. 

Ozone therapy, for instance, enhances tissue oxygenation, while H2O2 injections work by breaking down into water and oxygen, delivering oxygen directly to the tissues and promoting cellular repair ithout the side effects commonly associated with traditional pain medications. This makes them promising alternatives for joint pain and inflammatory conditions.

A systematic review of 25 small clinical and animal studies suggests that HBOT is also very effective for pain disorders, especially chronic pain. These include migraine, fibromyalgia, and complex regional pain syndrome. Researchers are still trying to understand how HBOT helps with pain. In mice, HBOT stimulates opioid receptors, suggesting that it does the same thing in humans, in addition to increasing circulation and stimulating the mitochondria [22].

A RCT evaluated the impact of photobiomodulation therapy (PBM) and ozone therapy on 36 patients' quality of life following gingivectomy and gingivoplasty procedures.

Pain levels were assessed using a visual analogue scale (VAS) on the 3rd, 7th, 14th, and 28th days after surgery. Additionally, the Oral Health Impact Profile (OHIP-14) was used to measure quality of life before surgery and on the 7th and 14th days post-surgery.

The control group experienced significantly higher pain levels than both the PBM and ozone groups (p < 0.05) on the 7th day. The total OHIP-14 score for the control group on the 7th day was also higher than that of the PBM group (p < 0.05), indicating a lower quality of life [23].

Intravenous hydrogen peroxide (IVHP) has been shown to bring significant improvement in patients with chronic pain. IVHP generates ROS that help reduce inflammation and eliminate infections that may contribute to pain. The study reported that 66% of patients experienced significant pain relief, and 85% used less medication or found their current analgesics more effective. By addressing underlying infections and inflammation, hydrogen peroxide therapy provides a comprehensive approach to pain management, improving overall patient outcomes [24].

Blood sugar regulation

Hydrogen peroxide mimics some of insulin’s actions, playing a role in blood sugar regulation. This is why hyperbaric technicians know that diabetic patients tend to have a blood sugar drop inside a hyperbaric chamber. Similarly, ozone therapy can improve blood sugar control in diabetics. All types of bio-oxidative therapy generate hydrogen peroxide in the blood.

In the context of blood sugar regulation, H2O2 appears to enhance the insulin signaling pathway, promoting the uptake of glucose into cells.

When insulin binds to its receptor on the cell surface, it activates a signaling cascade which relocates the glucose transporter type 4 (GLUT4) to the cell membrane. GLUT4 is responsible for the uptake of glucose from the bloodstream into the cell, where it can be used for energy production.

Hydrogen peroxide enhances this process by acting as a secondary messenger in the insulin signaling pathway. H2O2 allows for sustained phosphorylation of IRS, enhancing insulin signaling. This results in increased GLUT4 translocation to the cell membrane, promoting glucose uptake into cells and lowering blood sugar levels [25].

Long-haul syndrome/chronic fatigue

A follow-up study assessed the long-term effects of HBOT on 31 longhaulers one year after completing the therapy. Thirty-one patients with long-haul cognitive symptoms underwent 40 daily HBOT sessions and were evaluated more than a year later.

The study found that the improvements in quality of life, sleep, neuropsychiatric symptoms, and pain observed shortly after HBOT persisted over the long term. Specifically, quality of life, sleep quality, and neuropsychiatric symptoms maintained their improvement with a large effect size. Pain severity and interference also showed significant, lasting reductions [26].

Conditions Helped by HBOT but Not Other Oxidative Therapies

Decompression sickness

Decompression sickness, commonly known as "the bends," is a condition that occurs when a person experiences a rapid decrease in pressure, such as when a diver ascends too quickly from deep water. This rapid pressure change causes nitrogen, which has dissolved in the body's tissues and blood under high pressure, to form bubbles as the pressure decreases. These nitrogen bubbles can obstruct blood vessels, causing:

• Joint pain
• Dizziness
• Paralysis 
• Or even death

Decompression sickness can affect any part of the body, including:

• Central nervous system
• Lungs
• Muscles
• Joints

Hyperbaric oxygen therapy (HBOT) is the primary treatment for decompression sickness. Ozone or hydrogen peroxide therapy cannot help with decompression sickness

HBOT works by providing 100% oxygen at high pressures, typically in a hyperbaric chamber. This high-pressure environment increases the amount of oxygen dissolved in the blood, which has several crucial effects in treating decompression sickness [27]:

1. Reduction of Nitrogen Bubbles: As the oxygen pressure increases, the gas bubbles decrease in size, which helps alleviate the blockage in blood vessels and the associated symptoms.
2. Enhanced Oxygen Delivery: This enhanced oxygenation helps maintain tissue viability and reduces the risk of permanent damage due to hypoxia (lack of oxygen).
3. Reduction of Inflammation and Edema: The anti-inflammatory effects of HBOT help reduce the swelling and inflammation caused by nitrogen bubbles. By reducing edema, HBOT can help restore normal blood flow and reduce the pressure on nerves and other structures affected by the bubbles.
4. Promotion of Healing: The high oxygen levels stimulate the production of growth factors and the formation of new blood vessels (angiogenesis), which are essential for repairing damaged tissues and restoring normal function.

Altitude sickness

Altitude sickness, also known as acute mountain sickness (AMS), occurs when individuals ascend to high altitudes too quickly, exposing their bodies to reduced atmospheric pressure and lower oxygen levels.

This condition is common among climbers, hikers, and travelers who rapidly reach elevations above 8,000 feet (2,400 meters). The symptoms of altitude sickness can range from mild to severe and include:

• Headache
• Dizziness
• Fatigue
• Nausea
• Shortness of breath
• High-altitude pulmonary edema (HAPE) 
• High-altitude cerebral edema (HACE)

The last two conditions result from the body's inability to adapt quickly enough to the lower oxygen levels at high altitudes, leading to a dangerous buildup of fluid in the lungs or brain.

Hyperbaric oxygen therapy (HBOT) is an effective treatment for altitude sickness, particularly in severe cases where rapid intervention is necessary to prevent life-threatening complications. HBOT helps alleviate the symptoms of altitude sickness through the following mechanisms [28]:

1. Immediate Oxygenation: The patient breathes 100% oxygen in a pressurized environment, which significantly increases the amount of oxygen delivered to the body's tissues, alleviating symptoms such as headache, fatigue, and shortness of breath, and providing immediate relief from hypoxia.
2. Reduction of Lung and Brain Swelling: By increasing oxygen availability, HBOT decreases blood vessel constriction that contributes to fluid leakage into these areas. The pressurized environment also helps drive oxygen into tissues that are poorly oxygenated due to swelling, further aiding in the reduction of edema and the prevention of further complications.
3. Stabilization of Patients: HBOT can effectively "simulate" a lower altitude environment, buying critical time and reducing the risk of permanent damage or death. This is especially important in remote locations where immediate descent may not be feasible.
4. Support for Recovery: The high oxygen levels in HBOT stimulate the production of antioxidants and reduce inflammation, aiding in the overall recovery process and preventing long-term effects of altitude exposure.

Concussions

A concussion is a type of traumatic brain injury (TBI) that occurs when a blow to the head or a sudden jolt causes the brain to move rapidly within the skull. This movement can lead to brain tissue being bruised, nerves being stretched, and blood vessels being damaged, resulting in a temporary disruption of normal brain function.

Symptoms of a concussion can vary widely and may include:

• Headache
• Dizziness
• Confusion
• Memory problems
• Nausea
• Balance issues
• Sensitivity to light and noise

While many concussions resolve with rest and proper care, some can lead to prolonged symptoms or complications, a condition known as post-concussion syndrome.

HBOT has emerged as a promising treatment for concussions, particularly for those with persistent symptoms that do not resolve with standard care. HBOT helps in the treatment of concussions through the following mechanisms [29]:

1. Enhanced Oxygen Delivery to the Brain: One of the primary challenges following a concussion is the disruption of blood flow and oxygen delivery to the brain, which can exacerbate symptoms and delay recovery. HBOT significantly enhances the amount of oxygen dissolved in the blood plasma. Enhanced oxygenation supports the brain's natural healing processes, helping to reduce symptoms and accelerate recovery.
2. Reduction of Inflammation and Edema: Inflammation and swelling in the brain are common responses to concussion and can contribute to ongoing symptoms. HBOT has potent anti-inflammatory effects, which is crucial for reducing pressure within the skull and minimizing further damage to brain tissue.
3. Neuroprotection and Tissue Repair: High levels of oxygen in HBOT enhance the production of growth factors and stem cells, which are essential for neurogenesis (the formation of new neurons) and synaptogenesis (the formation of new connections between neurons). This promotes the healing of injured neurons and the restoration of neural networks, reducing long-term deficits associated with concussions.
4. Reduction of Oxidative Stress: Antioxidants produced by HBOT neutralize free radicals, reducing cellular damage and supporting overall brain health.

Psychiatric conditions

A randomized controlled trial aimed to evaluate the impact of ozone therapy on anxiety and depression in patients with refractory symptoms from cancer treatment.

The study assessed patients before and after ozone therapy using the Hospital Anxiety and Depression Scale (HADS) and the EQ-5D-5L questionnaire, which includes measures for anxiety, depression, and self-perceived general health via a visual analog scale (VAS). Before treatment, 56% of patients were on anxiolytic and/or antidepressant medications.

Following ozone therapy, there was a significant improvement in both anxiety and depression, as evidenced by better scores on the HADS subscales and the EQ-5D-5L questionnaire. The findings suggest a potential role for ozone therapy in improving mental health in these patients, although further studies are needed to explore and confirm these results [30].

A prospective crossover study evaluated the effects of HBOT on 30 women with fibromyalgia syndrome (FMS) related to childhood sexual abuse (CSA). Participants were randomly divided into a treatment group, receiving 60 sessions of HBOT, and a control group, which received psychotherapy. After the control period, the control group crossed over to receive HBOT as well.

Clinical outcomes were assessed using fibromyalgia, post-traumatic stress disorder (PTSD), and quality of life questionnaires. Brain imaging was also used to assess objective changes in brain function and structure.

The HBOT group showed significant improvements in

• Fibromyalgia symptoms, including pain
• Quality of life
• PTSD symptoms

Brain SPECT imaging revealed increased activity in the prefrontal cortex, orbital frontal cortex, and subgenual area, while MRI-DTI showed improvements in brain microstructure in the anterior thalamic radiation, left insula, and right thalamus [31]. Overall HBOT might be a good supportive therapy for PTSD and psychiatric conditions.

Benefits Shared by Both HBOT and Ozone IV

Improved tissue oxygenation

One of the most significant benefits shared by both hyperbaric oxygen therapy (HBOT) and intravenous ozone therapy (Ozone IV) is their ability to enhance tissue oxygenation. Adequate oxygen delivery to tissues is crucial for:

• Maintaining cellular function
• Promoting healing
• Supporting the body’s ability to fight infections and manage inflammation

Under normal conditions, oxygen is primarily carried by hemoglobin in red blood cells; however, the enhanced pressure in HBOT increases the solubility of oxygen in the water portion of the blood, allowing it to diffuse more readily into tissues, even those with compromised blood flow or areas affected by inflammation [32].

When introduced into the bloodstream, ozone breaks down into oxygen (O2) and reactive oxygen species (ROS). This process increases the overall oxygen content in the blood and improves the ability of red blood cells to deliver oxygen to tissues.

Additionally, ozone therapy makes red blood cells more flexible, making it easier for them to navigate through small capillaries and deliver oxygen more effectively to tissues.

Improved NO

Nitric oxide is a crucial signaling molecule in the body, playing a vital role in various physiological processes, including:

• Vascular dilation
• Immune response
• Cellular communication

Enhanced NO production in the blood vessel wall can lead to better blood flow and less inflammation.

HBOT increases the availability of oxygen, which stimulates the production of nitric oxide synthase (NOS), the enzyme responsible for producing nitric oxide from the amino acid L-arginine [33].

Ozone IV therapy also promotes increased NO production through its oxidative effects. ROS molecules trigger the activation of endothelial cells that line blood vessels. Endothelial cells produce nitric oxide as a response to the mild oxidative stress induced by ozone, leading to improved blood flow [34].

Improved mental clarity and wellbeing

Both HBOT and  Ozone IV enhance mental clarity and overall well being, offering significant benefits for cognitive function and emotional health. The brain is highly sensitive to oxygen levels, and even slight improvements in oxygenation can have profound effects on cognitive function.

By delivering pure oxygen at high pressure, HBOT ensures that oxygen reaches even the most compromised areas of the brain, improving neuronal function and promoting neurogenesis (the growth of new neurons). This enhanced oxygenation can alleviate symptoms of brain fog, improve focus, and support better memory and cognitive processing [35].

Ozone IV therapy contributes to improved mental clarity and wellbeing through its unique oxidative effects. ROS can activate the release of neurotrophic factors, which are proteins that support the growth and survival of neurons, and the activation of antioxidant defenses that protect the brain from oxidative damage [30].

Improved sleep

Adequate sleep is essential for physical health, cognitive function, and emotional wellbeing.

By increasing the amount of oxygen dissolved in the blood plasma, HBOT enhances oxygen delivery to these areas, supporting their proper function. Moreover, HBOT reduces inflammation and oxidative stress, both of which can interfere with sleep [30]. Therefore, some people sleep better after HBOT therapy.

Systemic ozone therapy helps optimize mitochondrial function, which is essential for energy production and metabolic regulation, including processes that govern sleep. Ozone therapy has also been shown to modulate the autonomic nervous system, particularly by reducing sympathetic nervous system activity (the "fight or flight" response) and enhancing parasympathetic activity (the "rest and digest" response) [30].

Temporary boost in immune functions

HBOT contributes to a temporary boost in immune functions primarily by increasing oxygen levels in the blood, which enhances the activity of immune cells. Oxygen is vital for the production and function of white blood cells, particularly neutrophils and macrophages, which are crucial for fighting infections and clearing debris from tissues.

Ozone IV therapy provides some oxygen to the blood. Also, the ozone enhances immune function by reacting with blood components to produce ROS and other bioactive molecules. These ROS stimulate the immune system by activating various immune cells, including lymphocytes, neutrophils, and macrophages.

Contraindications for HBOT that Ozone and Other Therapies Can Help

Very high and poorly controlled blood pressure

One of the primary contraindications for HBOT is very high and poorly controlled blood pressure (hypertension). HBOT involves exposure to high atmospheric pressures, which can exacerbate existing hypertension by further increasing blood pressure levels [36].

This heightened pressure can strain the cardiovascular system, increasing the risk of complications such as:

• Stroke
• Heart attack

Intravenous ozone or topical ozone treatments offer a safer alternative. Ozone therapy does not involve exposure to high atmospheric pressures, making it a gentler option for those with cardiovascular or ear concerns.

Ozone IV therapy, in particular, improves blood circulation and oxygen utilization, supporting overall cardiovascular health without the risks associated with pressure changes.

Poorly-controlled diabetes

Another important contraindication for HBOT is poorly-controlled diabetes. In a pressurized chamber during HBOT, the rapid drop in blood sugar can be difficult to manage because the patient is confined and cannot easily consume food or glucose to counteract the hypoglycemia.

Since Ozone IV is administered while the patient remains outside of a pressurized chamber, they can more easily monitor their blood sugar levels and respond quickly if their glucose drops [36].

Additionally, the controlled oxidative stress induced by ozone therapy can help improve insulin sensitivity and glucose metabolism over time, potentially offering long-term benefits for managing diabetes.

Less than 24 hours before flights

Ironically, receiving HBOT hours before a flight increases the risk of decompression sickness. HBOT exposes the patient to elevated atmospheric pressures, which can increase the amount of dissolved gasses (such as nitrogen) in the bloodstream. If a patient flies shortly after HBOT, the rapid decrease in pressure during ascent can cause these gasses to come out of solution too quickly, forming bubbles in the blood or tissues.

This can lead to serious and potentially life-threatening complications, including joint pain, dizziness, and neurological symptoms.

Ozone IV therapy delivers many of the same benefits as HBOT, including improved oxygenation, enhanced immune response, and reduced inflammation, without the associated risks of pressure-related complications.

An inability to equalize with the elevated pressure

HBOT requires patients to equalize their pressures in the ears and sinus cavities [36]. The following ear and nose conditions can make it difficult for a patient to equalize to higher pressure.

• Severe sinusitis
• Ear infections
• Eustachian tube dysfunction

HBOT with these contraindications can cause:

• Discomfort
• Pain
• Injury to the ear or sinus structures

Additionally, certain respiratory conditions, such as severe asthma or chronic obstructive pulmonary disease (COPD), may be exacerbated by the increased pressure, making HBOT risky or intolerable for these patients.

Since ozone IV therapy does not involve changes in atmospheric pressure, patients are not required to equalize pressure, making it a much more comfortable and safer option for those with ear or sinus issues.

Conclusion

In the evolving landscape of integrative and complementary medicine, hyperbaric oxygen therapy (HBOT), intravenous ozone therapy, and hydrogen peroxide therapy each stand out for their unique therapeutic potentials. These modalities share common benefits, such as

• Improved tissue oxygenation
• Enhanced immune function
• Better mental clarity
• Sleep
• Overall wellbeing

These benefits make them valuable tools in treating a wide range of conditions. However, each therapy also comes with specific contraindications and considerations that require careful patient selection.

Together, these therapies offer a versatile and powerful approach to improving health outcomes, particularly when traditional treatments fall short. By understanding the strengths and limitations of each modality, healthcare providers can better tailor treatments to individual patient needs, optimizing outcomes and expanding the possibilities for healing and recovery.