THE POWERS OF O2 AND HYPERBARIC OXYGEN THERAPY: BENEFITS, SAFETY, AND MORE

Over the past two centuries, studies into the characteristics of oxygen have revealed that it has two distinct roles: one as a catalyst for combustion and the other as the chief regulator of metabolism. Without it, life on the planet would not have evolved into what it is today. 

Hyperbaric oxygen therapy increases oxygen levels in all tissues, which has been documented to improve many aspects of health and well-being in both humans and animals. On the flip side, oxygen administration has been associated with severe forms of toxicity, even leading to fatal outcomes in uncontrolled settings.

This article covers the advantages and potential negative consequences of hyperbaric oxygen therapy on health. The discussion also explores oxygen deficits and overload, approved uses and contraindications, as well as tips for improving body oxygenation.

The Biological Importance of Oxygen

Oxygen is vital to all life on the planet. Despite this fact, its role is widely underestimated by doctors and nutritionists.[1] [2] The importance of oxygen is highlighted when looking at its essential functions in the body.

Oxygenation. Every time we inhale, a mixture of gases perfuse our lungs, including hydrogen, nitrogen and oxygen. Oxygen makes up approximately 21% of the air we breathe. As it enters the alveoli of the lungs, it diffuses across membranes into the bloodstream following a natural pressure gradient. The alveoli are required to be permanently moist in order to facilitate this process. Once oxygen enters the bloodstream, it rapidly binds to hemoglobin in blood cells, after which it is transported to every tissue in the body. Some oxygen remains dissolved in the bloodstream (unbound to hemoglobin), helping to promote better saturation of tissues. ^[1]

Oxygen’s Role in Respiration and Metabolism. As an electron acceptor, it plays a key role in energy production by guiding the electron supply chain inside the folded membranes of the mitochondria. Oxygen achieves this by enabling the production of ATP from both glucose and fats, allowing for the movement of electrons, aiding the chemical reduction of several important substrates, and facilitating both Krebb’s cycle and urea production.

Hypoxia, Inflammation, and Disease. Faulty oxygenation can promote a series of metabolic deficits pertaining to low oxygen status, referred to as hypoxia. It has been observed that hypoxia results in cellular stress that typically increases glucose and/or fat utilization in order to meet energy requirements. This naturally results in heightened inflammation levels, which, if left unchecked, can be detrimental to health.

What Constitutes Hypoxia? All tissues in the body have unique mitochondria as well as oxygen and energy requirements. In general, the optimal oxygenation of tissues occurs roughly at the same concentrations as that of air (21%). Studies also highlight that intermittent low oxygen (hypoxic) exposures of between 9-16% show potential health benefits, while those lower than 9% typically promote pathology.^[2]

How HBOT Works

Hyperbaric Oxygen Therapy (HBOT) is used to improve cellular respiration and combat hypoxia by increasing overall oxygen levels. While it typically saturates red blood cells with oxygen, HBOT was shown to work independently of blood hemoglobin. Instead, it diffuses evenly throughout the body, reaching deeper body compartments.

The therapy consists of a pressurized oxygen chamber in which the patient usually lies inside. Once sealed, the chamber fills with filtered air, filling up with a higher concentration of oxygen than other gases. HBOT chambers typically administer very high oxygen concentrations at a pressure of between 2-3 atms for 1 to 2 hours at a time. Some guidelines suggest taking air breaks every 20-30 mins to reduce the risk of complications. Most studies quote a concentration of up to 100%, however, some HBOT providers offer lesser amounts at higher pressure values.

After the pressure builds in the chamber and the patient has equalized, the remainder of the treatment does not feel any different from being outside the tank. The patient is often free to entertain themselves in the chamber until the time is up.

There are three main principles that underscore the efficacy of HBOT:

1. Henry’s Law. HBOT works in accordance with Henry’s Law, which states that the concentration of dissolved gases in a given liquid is proportional to its pressure. Thus, the increased pressure inside the chamber increases the amount of dissolved oxygen in the blood, allowing for complete saturation.
2. An Enhanced Diffusion Gradient. Once the bloodstream is saturated with oxygen, it creates a large positive gradient, whereby oxygen is easily able to move into tissues with lower oxygen concentrations.
3. Reduced O2 Particle Size. HBOT also reduces the size of oxygen particles in the blood, further enhancing the oxygenation of all body tissues.

Hyperoxia-Hypoxia Paradox. Both hyperoxemia[3] and hypoxia appear to trigger the same cellular systems, giving rise to similar acute effects (e.g., free radical formation) yet different long-term effects, which ultimately pertain to overall oxygen status. As hyperoxia gives rise to inflammation, exposures need to be as short as possible to achieve the desired effects.

10 Health Benefits of HBOT

HBOT induces a transient state of beneficial hyperoxemia (oxygen overload). Proven benefits and promising effects are discussed below.

1. Lowers Stress Response. HBOT slows down the heart rate^[3] and is thought to activate the autonomic nervous system by stimulating the brain stem and vagus nerve.^[4] Studies examining animal models of PTSD revealed that HBOT is capable of reversing stress-related behavioral and cognitive symptoms induced by fear conditioning. The animals displayed lower levels of stress chemicals in response to the therapy^[5]. Similar stress chemical reductions were seen in a small group of healthy professional divers that underwent HBOT.^[6]
2. Increases Body-Derived Antioxidants. HBOT oxygen saturation in tissues transiently increases cellular free radical production, specifically radical oxygen species or ROS. This combats hypoxia by degrading cellular signals and correcting any potential oxygen deficits in the cell. In response to increased ROS, cell-derived antioxidants are also produced including, glutathione peroxidase and superoxide dismutase. These scavenge free radicals lower inflammation. Cellular antioxidant levels have a longer half-life than ROS, and their production remains enhanced after ROS levels drop after therapy. Evidence suggests that it takes several sessions for antioxidant concentrations to increase above the level of ROS that the therapy induces, which is when the true benefits begin to take effect.^[7]
3. Enhances Regeneration and Recovery. In animal studies, HBOT has been shown to improve regeneration of wounded tissues. Wounds commonly exhibit hypoxic conditions, which contribute to signals that initiate stem cell activity and wound repair. HBOT can increase these signals by promoting ROS, which serves to promote stem cell growth, migration to the wound site and differentiation. These effects have been observed in the brain, liver, and intestine-related injuries of rats. Furthermore, HBOT is associated with elevations in Vascular Endothelial Growth Factor (VEGF), the growth of new blood vessels, and reduced swelling of ischemic wounds^[8]. In human studies, HBOT has been effective for treating diabetic foot, traumatic brain injuries^[9] and other ischemic wounds, owing to similar results.
4. Antimicrobial Effects. HBOT may be able to improve upon the efficacy of antibiotics that work through increased ROS production in cells. At high doses, HBOT was shown to have similar properties, able to inhibit, kill off and neutralize the toxins of various pathogenic bacteria. Oxygen administration post-surgery has been shown to improve outcomes by reducing the risk of infection and sepsis.^[10] Animal studies have shown that HBOT can increase the sepsis survival rate to over 50%, as well as lower resultant inflammation.
5. Tones Down Immune Response. High oxygen environments appear to promote a more balanced immune system profile. Immunological changes include a reduced number of CD4+ T lymphocytes (associated with various autoimmune diseases and allergies), lower lymphocyte proliferation (indicative of less inflammation) and activation of neutrophils that migrate to tissues high in oxygen.^[11] Further evidence has verified these findings by linking HBOT to a decreased response towards antigens (pathogenic/allergenic proteins) and a reduced tendency for autoimmunity. In arthritic rats, HBOT administration proved to increase the number of T reg cells and encourage an anti-inflammatory, immune response.^[12]
6. May Discourage Tumor Formation. Tumors seem to appear in low oxygen conditions when growth mechanisms fail and the immune system is unable to detect them. HBOT facilitates the removal of tumors from the body by increasing oxygen, which leads to the generation of ROS and ultimately promotes the destruction of faulty (malignant) cells. The immune effects of HBOT help to regulate the immune response and may also enhance the detection of tumors. Some studies reveal that HBOT may increase the risk for some types of cancer and may be better used in conjunction with other cancer therapies. More research is required before HBOT can be confirmed as an effective complementary cancer treatment.
7. Improves Cardiorespiratory Fitness. In a small study on 49 participants, HBOT helped to improve factors associated with cardiorespiratory fitness when coupled with sprint training compared to exercise alone. The findings revealed that the results were unrelated to an increase in oxygen consumption in the HBOT group.^[13]
8. Pain Relief. In several small clinical trials, HBOT has shown promise as a treatment option for disorders of chronic pain. Patients with fibromyalgia, myofascial pain syndrome, postherpetic neuralgia, trigeminal neuralgia, and other painful neuropathies experienced an increase in pain tolerance in response to hyperbaric oxygen therapy, as well as a vast improvement in symptoms and quality of life.^[14] These effects were linked to stimulating the pain relief mechanisms of the body, including endogenous opioid production.^[15]
9. Insulin Signaling. HBOT has been shown to lower blood sugar levels in human subjects, as well as improve insulin sensitivity and reduce hyperglycemia in both diabetic and non-diabetic men^[16]. In a study on obese diabetic rats with fatty liver disease, HBOT reduced weight and lowered markers associated with such diseases as insulin resistance, dyslipidemia, and faulty liver metabolism.^[17]
10. Pro Longevity. In vitro studies reveal that HBOT is capable of protecting against telomere shortening as well as promoting the destruction of aged or senescent immune cells. In studies conducted on aged rats, HBOT enhanced blood flow to the brain, improved cognition^[18], and helped to preserve bone integrity^[19].

HBOT as a Complementary Treatment Option

Hyperbaric oxygen therapy was initially used to treat decompression sickness or “the Bends”. It is now recognized that hypoxia is a component of numerous states of disease which can be effectively treated with HBOT. Currently, it is approved for treating roughly 15 medical conditions and has been proven to be a successful therapy option for many more health conditions, including diabetic foot and carbon monoxide poisoning.

The following medical applications for HBOT have been acknowledged by the Undersea and Hyperbaric Medical Society^[20]:

• Acute arterial gas emboli*
• Acute blood loss anemia and other severe types of anemia
• Acute sensory hearing loss
• Acute thermal injury (i.e. burns)
• Arterial insufficiency*
• Carbon monoxide poisoning*
• Chronic radiation injury
• Compartment syndromes*
• Compression injury
• Cranial abscess
• Decompression sickness
• Failed skin grafts
• Gas gangrene
• Necrotizing fasciitis
• Refractory osteomyelitis

*In the absence of contraindications (see safety below).

Preliminary research indicates that HBOT may be useful in the treatment of several other health conditions and diseases, including stroke, traumatic brain injury, severe fungal infections, autoimmune disorders including psoriasis, and arthritis, fibromyalgia and other conditions symptomatic of widespread chronic pain, various forms of cancer, and COVID-19.^[21]

Despite showing promising results, more testing needs to be done to ensure safety.

Safety

HBOT is generally regarded as safe at the pressures utilized for treatment. Most HBOT protocols saturate body tissues with up to 40% oxygen, using 100% oxygen or highly oxygenated air at a pressure of between 2-3 atms. Tissue oxygen saturation should not exceed 42% to avoid toxicity.

The higher the pressure inside the HBOT tank, the more saturated body tissues will become with oxygen. Hence, pressure over 3 atms is associated with oxygen toxicity. HBOT at pressures of up to 6 atms is occasionally used as an emergency protocol to treat gas embolisms.

Side Effects

HBOT does not usually cause any side effects. Common side effects include feeling sleepy, light-headed, or breaking out in a sweat. In some cases, patients may experience symptoms during treatment that are specific to their condition.

Rare complications include seizures and arrhythmias, however, these usually occur in patients with conditions that are contraindicated.

Contraindications

HBOT is contraindicated in the following cases:

• Claustrophobia. Due to the size of most HBOT chambers, anyone with claustrophobia should not opt for the therapy.
• Blocked Ears or Sinuses. If the patient is unable to equalize, they should not opt for HBOT as it may result in ear injury upon pressurization.
• Barotrauma Complications. In cases where there is damage to an internal body compartment that results in an air-filled space, HBOT is not advisable. The change in pressure can cause the space to expand and intensify the damage.
• Pneumothorax or Lunge Collapse. Despite seeming like a compatible treatment option, HBOT is potentially fatal to those with a collapsed lung.
• Premature Infantile Respiratory Issues. Oxygen is commonly administered to premature infants to treat breathing problems and improve overall health outcomes. However, it may increase the risk for preterm eye problems^[22] (retinopathy of prematurity) if the infant is exposed to 100% oxygen^[23]. It is advisable to opt for lesser forms of HBOT therapy that administer oxygen at concentrations of 85% or less for short periods of time.
• Pregnancy. Pregnant mothers should not opt for HBOT as it may increase the risk of eye problems if the baby is born prematurely.
• Heart Frailty. Pulmonary edema has been shown to be a rare complication of HBOT in those with heart conditions indicative of frailty, including stable systolic heart failure^[24] and heart conditions indicative of reduced ejection fractions in the left ventricle^[25]. The left ventricle is placed under more pressure than other chambers of the heart, being surrounded by a thicker wall of muscle that drives the circulation of oxygenated blood.^[26] Individuals with these types of heart problems appear to be at an increased risk for pulmonary edema in response to HBOT, possibly due to the increase in atmospheric pressure coupled with a slowing heart rate.
• Cataracts, Macular Degeneration and other Eye Problems. As HBOT increases the generation of free radicals in exposed tissues, those with pre-existing inflammatory eye conditions should avoid it. While it may improve vision and eye function in some individuals, those with cataracts or macular degeneration should be especially wary, being highly sensitive to ocular inflammation.^[27] Eye problems as a result of HBOT are rare and have not been documented in those without an eye condition.
• Stroke, Brain Injury or Epilepsy. Seizures have been rarely documented in an extremely small number of patients opting for HBOT. They are estimated to occur in less than 0.3% of individuals, at a rate of approximately 0.011%. The risk is thought to be higher for those undergoing treatment for strokes or traumatic brain injury, in which the generation of oxygen radicals may induce excessive brain activity.
• Carbon Monoxide Poisoning. While some studies have shown that HBOT is a potential option for treating carbon monoxide poisoning, oxygen administration at normal pressures appears to be more effective and subject to fewer complications. In a rare case, a patient suffered from pulmonary edema and a convulsive seizure in response to HBOT as a result of carbon monoxide poisoning.^[28]
• Other. HBOT has been contraindicated for use with patients who have medical implants (especially pacemakers), various medications, hereditary spherocytosis, current infections with fever, and diabetics with low blood sugar levels.

5 Supporting Factors Known to Improve Oxygenation

Enhancing body oxygenation supports overall health and may contribute to reducing the risk of contracting hypoxia-related diseases.

1. Antioxidants

Antioxidants facilitate optimal oxygenation by enhancing mitochondrial utilization of oxygen and helping to regulate the production of ROS, which can lead to excess inflammation if left unchecked. Moreover, antioxidants have been shown to protect against hypoxia, as discussed below.

Body-Derived Antioxidants. Under severely hypoxic conditions, experimental evidence reveals that endogenous (body-derived) antioxidants are capable of binding to hemoglobin and being transported directly to tissues that are in dire need of oxygen. In this way, it was shown that hemoglobin Superoxide Dismutase protected pancreatic beta cells subject to extremely low levels of oxygen (6, 3, and 1%) after transplantation.^[29]

Levels of endogenous antioxidants can be increased through several means:

• Reducing bodily inflammation through lowering exposure to pollutants, allergens,radiation, etc.
• Increasing antioxidant intake which serves to recycle and preserve the levels of endogenous antioxidants in tissues.
• Consuming a nutritionally balanced diet that promotes overall metabolism, antioxidant production as well as the health of organs that produce large amounts of antioxidants, such as the liver.

Diet-Derived Antioxidants. Preliminary evidence reveals that various plant-based antioxidants are able to increase levels of cellular antioxidants in hypoxic cells, thereby reducing inflammation and improving their chances of survival. This specifically applied to any antioxidant capable of activating the NRF2 pathway in the cell, including sulforaphane.

2. Heart Rate and Cardiorespiratory Fitness

Aerobic exercise that increases the heart rate and improves cardiorespiratory fitness is an effective way to boost blood oxygen levels and the oxygenation of tissues. This applies both in the short and long term, with the most benefit being gained through consistent effort over time. 

Improved Oxygen Uptake and Delivery. As the heart rate increases, we breathe more deeply and take in more oxygen, forcing the blood to become more saturated than at rest. Simultaneously, it increases the rate at which our blood flows, allowing more blood to circulate through the lungs and collect oxygen. Regular exercise promotes red blood cell production and turnover, as well as the renewal of faulty blood cells. This helps to increase and maintain optimal tissue oxygenation in the long run.

Moderation is Key. Acute exercise shows a cutoff point for optimal oxygen uptake, with prolonged activity often showing diminished uptake. This is possibly related to a sharp rise in body temperature and/or the generation of excess inflammation in response to overly intensive exercise. Both of these factors can lead to reduced oxygenation. It is important not to overexert oneself and to rehydrate after intensive exercise.

3. Breathing Exercises

Practicing how to breathe through the use of deep breathing techniques can enhance oxygen uptake and promote better overall respiratory function.

Respiratory Muscle Control. These exercises typically emphasize taking in large breaths, holding them, and breathing out in a slow controlled manner. This works the diaphragm and supports all the muscles required for breathing.

Breath Suspension. In between increasing oxygen levels, some breathing techniques also induce short states of low oxygen intake (breath suspension) that may benefit overall health by promoting states of mild hypoxia.

There are various types of breathing exercises that can increase body oxygen levels, including pranayama yoga and CPAP breathing.

4. Maintaining Healthy Blood pH

If blood pH decreases and becomes more acidic, it can promote less binding of oxygen.^[30] Reduced blood oxygen as a result of increased bodily acidity typically only reaches a critical point during the end stage of severe chronic diseases such as seen in lung or kidney failure. Chronic acidosis may result in or be a symptom of various health conditions, including osteoporosis, kidney stones, diabetes, and other metabolic diseases. Smokers, those on various pharmaceuticals, and highly allergic individuals are also at an increased risk for bodily acidosis.

Lung and Kidney Support. The lungs and kidneys are two of the greatest regulators of bodily acidity. The lungs dispose of carbon dioxide (which increases blood acidity) and the kidneys regulate levels of alkalizing electrolytes such as bicarbonate while eliminating other acidic substances. ^[31] Therefore, protecting the lungs and kidneys can contribute toward maintaining optimal tissue oxygenation.

Factors that increase bodily acidity through affecting kidney function include:

• Electrolyte imbalance (particularly bicarbonate deficiency and sodium or calcium overload)
• High sugar and sweetened beverage intake, including fruit juices with high phosphorus content
• Diets rich in animal products and alcohol, with less fresh fruit and vegetables
• Excessive consumption of cereal grains
• Smoking

5. Keeping a Constant Temperature

Both high and low temperatures can reduce tissue oxygenation in the following ways:

High Temperatures from chronic infections and fevers have been associated with the onset of cellular hypoxia and the progression of metabolic diseases. In children running high fevers, reducing the fever proved to increase blood oxygen saturation between 1.45-1.57% on average.^[32]

Cold exposure typically induces vasoconstriction, which detracts from blood flow and oxygen diffusion into cells.^[33]

Temperature Regulation Enhances O2 Utilization. Taking a shower in cold water after exercise has been shown to improve tissue oxygenation^[34] as well as mitochondrial production and regeneration (known as biogenesis)^[35]. It may additionally enhance mitochondrial oxygen utilization through two oxygen-related pathways.^[36]

In light of all the above points, keeping one’s temperature constant and within a healthy range helps to preserve optimal tissue oxygenation.

Conclusion

Oxygen is critical to cellular energy production, mitochondrial function and many other cellular processes revolving around tissue growth, and regeneration. Hyperbaric oxygen therapy saturates body tissues with oxygen through increasing environmental pressure, and its propensity to dissolve in body fluids. Benefits associated with its use include stress reduction, enhanced wound repair, pain relief and the regulation of immune processes. Most of its approved applications revolve around treating wounds or poisoning, however,research indicates that it may be pertinent as a complementary therapy in the context of pain-related disorders, diabetes, and autoimmune diseases. Therapy may be enhanced by improving one’s overall oxygen status.

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