Mild Hyperbaric Oxygen Therapy (M-HBOT): mechanisms and effects

A mild hyperbaric environment will allow the necessary amount of oxygen to penetrate fully into the body’s tissues and work their magic without the risk of oxidative damage.

Oxygen is essential for energy production in most cells and is carried by red blood cells that flow in blood vessels. The oxygen bound to hemoglobin in red blood cells is referred to as the ‘oxygen bound to hemoglobin’. When dissolved in blood plasma, oxygen is then referred to as ‘dissolved oxygen’. Although the quantity of dissolved oxygen is less than that of oxygen bound to hemoglobin, it can flow to peripheral cells, especially those in the brain, heart and eyes, even if capillaries are very narrow since it is dissolved directly in blood plasma (Fig. 1a).

What are the benefits of mild hyperbaric oxygen therapy?

A clean supply of oxygen-enriched air under pressures of 1.3 or 1.4 ATA causes an increase in oxygen delivery to injured or hypoxic tissues at a 400% deeper level than our normal blood supply can penetrate. Breathing oxygen inside the pressure chamber increases the total amount of oxygen delivered to the cells by the bloodstream (Henry’s law).

An increase in ambient pressure (and thus partial pressure) results in more gas dissolving into the liquid portion of blood and tissues. This causes oxygen to dissolve into fluids such as plasma, cerebrospinal fluid and synovial fluid, resulting in a systemic saturation of the brain, neurological system, muscles, joints and organs, reaching difficult-to-reach areas in an attempt to promote healing.

Mild hyperbaric oxygen therapy provides a number of benefits, including:

• Decreases inflammation and swelling
• Increases concentration and alertness during mental activity
• Forces oxygen 400% deeper into bodily tissues
• Saturates plasma with oxygen and promotes healing of all tissues within the body
• Increases white blood cell formation
• Strengthen the immune system
• Promotes new blood vessels growth
• Increases the synthesis of stem cells as well as their translocation to the central nervous system
• Direct production of stem cells in the brain
• Antimicrobial effect
• Has a favorable effect on sleep
• Smoothing of wrinkles and fine lines
• Increases blood flow
• Antioxidant enzymes are upregulated, and oxidative stress is reduced
• Reduces the bacterial/yeast burden in the intestines and in the gut
• Improves athletic performance and recovery, as well as faster injury recovery
• Increases readiness score for athletes
• Reduces viral load present throughout the body
• Serotonin production is increased
• Detoxification involves removal of mercury and other heavy metals from the body

Adequate oxygen supply by exposure to mild hyperbaric oxygen at appropriately high atmospheric pressure 1266–1317 hPa (1,266 – 1,317 bar) and increased oxygen concentration (35–40% oxygen) has a possibility of improving the oxidative metabolism in cells and tissues without barotrauma and excessive production of reactive oxygen species. Therefore, metabolic syndrome and lifestyle-related diseases, including type 2 diabetes and hypertension, were inhibited and improved by exposure to mild hyperbaric oxygen. It accelerated the growth-induced increase in oxidative capacity of the skeletal muscle in rats and inhibited the age-related decrease in oxidative capacity of the skeletal muscle in mice. A decrease in dopaminergic neurons in the substantia nigra of mice with Parkinson’s disease was inhibited by exposure to mild hyperbaric oxygen. This review describes the beneficial effects of exposure to mild hyperbaric oxygen therapy on some metabolic diseases and their perspectives.

REVIEW – Mild hyperbaric oxygen: mechanisms and effects

In normal circumstances, O2 is transported in the blood only with haemoglobin in red blood cells, which constitutes 98% of blood saturated with O2. In the conditions of normal atmospheric pressure (1 ATA), red blood cells make up only 45% of the blood whereas the plasma transports very small quantities of O2. What is crucial in the case of HBOT, when the pressure rises to 3 ATA, the amount of O2 delivered with the blood increases from 10 to 15 times above the normal, which gives us a quantity sufficient for life support, even in the case of absence of haemoglobin.

Even a slight increase in the partial pressure, such as 1.05 ATM at the depth of 402 below sea level, may induce observable physiological changes.

It is possible to distinguish several factors that play a major role in treatments based on HBOT. These include: neutrophils, metaloproteinases, caspases and hypoxia-induced factor (HiF-1). Since 1cm3 of a regular nervous tissue contains approximately one kilometer of blood vessels, a sufficient oxygen supply is absolutely necessary to repair damaged regions.

Is high pressure hyperbaric oxygen therapy safe for non-medical setups (wellness or personal use)?

Side effects associated with enhanced atmospheric pressure and/or increased oxygen concentration, including barotrauma and excessive production of reactive oxygen species in tissues and organs, are thought to occur. Hyperbaric oxygen therapy at 2026–3039 hPa (2.0 – 3.0 ATA) with 100% oxygen for medical treatment is associated with the risk of inducing myopia and cataracts. A previous study reported that exposure to hyperbaric oxygen at 2534 hPa (2.5 ATA) with 100% oxygen for 2–2.5 hours, twice a week, up to 100 sessions, induces cataracts in guinea pigs. Similarly, myopia and cataracts developed in human lenses after exposure to prolonged hyperbaric conditions of 2026–2534 hPa (2.0 – 3.0 ATA) with 100% oxygen for 90 minutes, once a day, from 150 to 850 sessions; however, it was rarely seen to occur after only 48 sessions of hyperbaric oxygen conditions at 2534 hPa (2.5 ATA) for 90 min. Hyperbaric oxygen therapy increases the number of invasive inflammatory cells in mice and causes excessive production of reactive oxygen species in rats, rabbits, and humans.

Mild hyperbaric oxygen: mechanisms and effects

Excessive production of reactive oxygen species plays a key role in the pathogenesis of many diseases and their complications; generation of free radicals and increased levels of oxidative stress are associated with atherosclerosis, cataracts, retinopathy, myocardial infarction, hypertension, diabetes, renal failure, and uremia. In addition, regardless of pressure, oxygen treatments involving > 40% oxygen have shown adverse effects, e.g., damage of erythrocytes due to reactive oxygen species and reduced quantity of oxygen bound to hemoglobins in rats.

The Journal of Physiological Sciences (2019) 69:573–580

Is low pressure Hyperbaric Therapy (M-HBOT) safe and effective for metabolic diseases?

Growing life expectancy will add to the ongoing trend of a world population that is becoming increasingly elderly. This demographic transition is linked to an increase in the frequency of age-related diseases. Among all age-related pathologies, it is critical to comprehend age-related cognitive alterations, which continue to be a key risk factor for the development of vascular cognitive impairment and dementia (VCID). Furthermore, age-related Alzheimer’s disease and other neurodegenerative disorders with a vascular etiology are the most common causes of cognitive decline in older people.

Increased oxygen tension (PO2), increased oxygen tissue levels, decreased intracranial pressure, and relieved cerebral edema are all physiological consequences of mild hyperbaric oxygen therapy (mHBOT). Many of mild HBOT’s positive effects occur at the microcirculation level, where they safeguard the body. Furthermore, because of its exquisite widespread presence throughout the body, microcirculation is uniquely able to influence the local environment of most tissues and organs, including the brain. As a result, interventions aiming at reversing aging-induced functional and structural changes in the cerebral microcirculation may help to alleviate a variety of age-related diseases such as vascular cognitive impairment, Alzheimer’s disease and vascular dementias.

Exposure to mild hyperbaric oxygen at a low oxygen concentration (35–40% oxygen) does not result in enhanced levels of oxidative stress in rats and humans. Based on previous findings from experimental animal and human clinical studies, the effects of exposure to mild hyperbaric oxygen at 1266–1317 hPa (1,2 – 1,3 ATA) with 35–40% oxygen are sumbcwmarized in Table 1. It is noteworthy that these findings were obtained in the first step of exposure to mild hyperbaric oxygen. Therefore, it is expected to define a suitable recommendation regarding a generally applicable protocol for exposure to mild hyperbaric oxygen in the subsequent step. This review describes the beneficial effects of exposure to mild hyperbaric oxygen on some metabolic diseases and related perspectives.

Mild hyperbaric oxygen therapy is generally considered to be quite safe. Due to problems equalizing the ear pressure, otic barotrauma (ear discomfort) is a risk. Nevertheless, in mild hyperbaric conditions it is usually only temporary and easy to manage. It can be relieved by yawning or swallowing, much like when taking off and landing while on an airplane.

Mild hyperbaric oxygen therapy (M-HBOT) and Cerebral Palsy

Cerebral palsy (CP) is caused by a child’s inability to control his or her muscles due to aberrant brain development or harm to the growing brain. This anomaly in the brain could be caused by a number of factors. The brain injury that causes CP can occur at any moment during a child’s development, from before birth to the earliest years of life. Brain injury can also occur during a protracted, painful or prolonged birth in which the baby is depleted of oxygen.

Muscle stiffness or floppiness, unpredictable movement (dyskinesia), and impaired balance and coordination are all symptoms of CP damage (ataxia). 

For many years, medical schools have taught that perinatal brain injury is ‘fixed’, yet if we truly want to be honest, we must acknowledge our knowledge gaps. There is mounting evidence that this claim is no longer true.

We are discovering novel facts about human neurophysiopathology and cerebral plasticity, as well as novel treatments for what appeared to be permanent brain injury. We now have a better understanding of stem cells and their potential for regeneration, and studies suggest that Mild Hyperbaric Oxygen Therapy has highly promising results in improving brain function in a variety of neurological diseases.

The study of 2001 was conducted on 111 cerebral palsy patients aged between 3 and 12 years. The participants were randomly assigned to a group staying in a hyperbaric chamber for 60 minutes, at a pressure of 1.75 ATA, with 100% oxygen concentration, or to a sham treatment group with the use of 1.3 ATA (the smallest pressure change sensed by humans).

Both groups were subjected to 40 sessions lasting one hour. The neuropsychological tests performed on 75 patients included: a computer version of Corsi blocks, Word span and a Test of Variables of Attention (TOVA). Research results showed an improvement in time in both groups in general results of working memory and attention tests, however no such improvement was noted with regard to response time in attention measurement tests.

The authors, as well as others determined that the use of HBOT with the applied pressure of 1.3 ATA may induce significant physiological changes in patients, hence the use of such an intervention in the sham treatment group serves no purpose. On the one hand, a pressure increase to 1.3 ATA is the smallest increase that the patients are capable of sensing, thus it would be an ideal type of intervention for studies with the use of HBOT if such a pressure rise did not possibly induce an over 50% oxygenation increase in tissues, a situation which could suggest that therapies using the pressures of 1.75 ATA and 1.3 ATA can be equally effective.

An additional source of conclusions from the above studies [46] is found in the correspondence of other researchers with the authors published in The Lancet; these suggested that each study measuring the effects of therapy among patients with brain damage should be enriched with SPECT in order to ensure maximum objectivity.

Furthermore, the authors emphasized that despite the convincing evidence from scientific research on HBOT effectiveness in children with cerebral palsy it was not possible to find a link between the applied therapy, the results of neuroimaging tests and a clinical improvement in patients.

THE EFFECT OF HYPERBARIC OXYGEN THERAPY ON THE NERVOUS SYSTEM. SYSTEMATIC REVIEW – Polish Hyperbaric Medicine and Technology Society

Mild hyperbaric oxygen therapy and Autism Spectrum

Autism is a neurological condition that affects around 1 in every 166 children in the United States. It is characterised by impairments in social interaction, difficulty with communication, and restrictive and repetitive behaviours. It affects children from all socioeconomic and ethnic backgrounds.

Autism was considered a rare condition before the 1990’s with a prevalence of approximately 1 in 2500 children. However, according to the US Department of Developmental Services, the prevalence of autism spectrum disorders increased by 556% from 1991 to 1997. It is now more common than childhood cancer, cerebral palsy, Down’s syndrome, spina bifida or cystic fibrosis. In addition, autism is found throughout the globe and the prevalence worldwide is increasing by 3.8% per year. Autism is a completely misunderstood disorder, but new clinical research is beginning to unravel some of its mysteries.

Cerebral palsy, fetal alcohol syndrome, closed head injury and stroke have all been treated with hyperbaric oxygen therapy. HBOT can compensate for decreased blood flow by increasing the oxygen content of plasma and body tissues and can even normalize oxygen levels in ischemic tissue. In addition, others studies have shown that HBOT has potent anti-inflammatory effects and reduces oxidative stress. Furthermore, recent evidence demonstrates that HBOT mobilizes stem cells from human bone marrow, which may aid recovery in neurodegenerative diseases.

There is a strong possibility that HBOT could play an integral role in improving brain disorders associated with hypoxia, hypo-perfusion, inflammation, fusion disorders, it was hypothesized that low pressure HBOT would also help autism, a disease in which cerebral hypo-perfusion is an integral component. Recently, evidence has accumulated that low pressure hyperbaric therapy at 1.3 ATA and less than 100% delivered oxygen may improve symptoms in some diseases associated with cerebral hypoperfusion. For instance, one study using hyperbaric therapy at 1.3 ATA and room air demonstrated clinical improvements in some children with CP, a disease shown to have evidence of diminished cerebral blood flow. Furthermore, one case report indicated ‘‘striking improvement’’ in a 4 year old child with autism after using hyperbaric therapy for 10 sessions at 1.3 ATA and room air. The child also had improvement of cerebral hypo-perfusion as measured by pre-HBOT and post-HBOT SPECT scans. Based upon these findings and many others published over the years, we know that low pressure HBOT can improve symptoms of autism.

Hyperbaric oxygen therapy may improve symptoms in autistic children – Daniel A. Rossignol a,b,*, Lanier W. Rossignol
a Blue Ridge Medical Center, 4038 Thomas Nelson Highway, Arrington, VA 22922, USA 
b University of Virginia, P.O. Box 800729, Charlottesville, VA, USA

Is low-pressure hyperbaric oxygen therapy effective for Metabolic Syndrome?

Metabolic syndrome, linked to chronic physical inactivity and consumption of a high-fat and high-calorie diet, is characterised by obesity, high blood pressure and increased blood glucose, low density lipoprotein-cholesterol and triglyceride levels.

Experimental animals with metabolic syndrome have a nonsense mutation in the leptin receptor. Rats with metabolic syndrome have a low oxidative capacity in the skeletal muscle compared to normal rats. Reduced oxidative capacity in the skeletal muscle is suggested to impair glucose metabolism and increase the risk of development of metabolic syndrome. Rats with metabolic syndrome exposed to mild hyperbaric oxygen had lower blood pressure, blood glucose, total cholesterol, triglyceride, and insulin levels, but higher adiponectin levels than those not exposed to mild hyperbaric Oxygen. In addition, rats with metabolic syndrome exposed to mild hyperbaric oxygen had high oxidative capacity and increased levels of peroxisome proliferator activated receptor γ coactivator-1α mRNA, which plays an important role in oxidative metabolism by regulating mitochondrial biogenesis in the skeletal muscle

Mild hyperbaric oxygen: mechanisms and effects
Akihiko Ishihara1

Exposure to mild hyperbaric oxygen is thus considered to inhibit the growth-related increase in blood glucose levels and decrease the muscle oxidative capacity of rats with metabolic syndrome owing to the improved oxidative metabolism.

Mild pressure hyperbaric therapy and type 2 Diabetes

Type 2 diabetes is a condition in which the body’s ability to control and utilise sugar (glucose) as a fuel is impaired. Too much sugar circulates in the bloodstream as a result of this long-term chronic disease. High blood sugar levels can eventually cause problems with the circulatory, neurological and immunological systems.

The growth-related increase in blood glucose levels in rats with type 2 diabetes was inhibited by exposure to mild hyperbaric oxygen. The decreased blood glucose levels induced by exposure to mild hyperbaric oxygen in rats with type 2 diabetes were maintained even after these rats were subsequently returned to breeding under normobaric conditions. The increased blood glucose levels of adult rats with type 2 diabetes not exposed to mild hyperbaric oxygen were lowered even if they were exposed to mild hyperbaric oxygen afterward. These results indicate that low blood glucose levels in rats with type 2 diabetes can be maintained by exposure to mild hyperbaric oxygen compared to those not exposed to it, both when blood glucose levels are increasing during growth and after blood glucose levels are high in adulthood.

Exposure to mild hyperbaric oxygen, therefore, seems to prevent the decrease in oxidative capacity of the skeletal muscle of rats with type 2 diabetes, irrespective of their age. In addition, exposure to mild hyperbaric oxygen is effective for the inhibition as well as improvement of hyperglycaemia in rats with type 2 diabetes.

The morphological and histochemical properties of fibres in the skeletal muscle correspond well with those of spinal motoneurons that innervate muscle fibres. A previous study had shown decreased oxidative capacity of spinal motoneurons in rats with type 2 diabetes. In addition, this study had examined the effects of exposure to mild hyperbaric oxygen on oxidative capacity of spinal motoneurons. The inhibition of growth-related decrease in oxidative capacity of spinal motoneurons by exposure to mild hyperbaric oxygen corresponds well with that observed in muscle fibres innervated by spinal motoneurons, thereby implying that the properties and responses of spinal motoneurons and their innervating muscle fibres are closely related under diabetic, as well as normal conditions.

Nagatomo F, Takemura A, Roy RR, Fujino H, Kondo H, Ishi- hara A (2018) Mild hyperbaric oxygen inhibits the growth-related decline in skeletal muscle oxidative capacity and prevents hyper- glycemia in rats with type 2 diabetes. J Diabetes 10:753–763

Mild HBOT (Hyperbaric oxygen therapy) and Arthritis

Rheumatoid arthritis (RA) is a painful autoimmune disease that affects the joints. Swelling, joint stiffness, weariness, weight loss and redness are all common symptoms. Bone degradation can occur as a result of rheumatoid arthritis, which has no cure.

International studies are finding that hyperbaric oxygen therapy is markedly superior to the routine treatment of RA. In 1995, the Proceedings of the Eleventh International Congress on Hyperbaric Medicine published the results of one particular study. These results indicated the following effects of hyperbaric oxygen on the disease:

• Remission: 23.4%
• Obvious effect: 51.4%
• Improvement: 16.2%
• No effect: 8.1%

The total summarized effective rate of hyperbaric oxygen in treating RA was 91.9%. The authors of the study concluded: “In the treatment we find that hyperbaric oxygen is markedly superior to the routine treatment of rheumatoid arthritis.” Hyperbaric oxygen therapy has become a standard of practice for RA in many countries.

Exposure to mild hyperbaric oxygen is effective in decreasing levels of reactive oxygen species overproduced in arthritis. Oxidative stress and creative protein levels are high in rats with arthritis, whereas the levels shifted to those in normal rats by exposure to mild hyperbaric oxygen. Arthritic joints are characterised by hypoxia caused by an increased oxygen demand and decreased blood flow triggered by the increased intra articular pressure. Therefore, exposure to mild hyperbaric oxygen is effective in reducing reactive oxygen species levels overproduced during arthritis.

Nagatomo F, Gu N, Fujino H, Okiura T, Morimatsu F, Takeda I, Ishihara A (2010) Effects of exposure to hyperbaric oxygen on oxidative stress in rats with type II collagen-induced arthritis. Clin Exp Med 10:7–13

Mild hyperbaric oxygen therapy and anti-aging effects

Pigmentation and proliferation

Tissue dryness and transepidermal water loss are examples of age-related degenerative alterations in the skin. With age, epidermal basal cell proliferation slows down. The proliferative activity of epidermal basal cells in aged mouse skin has been shown to be accelerated by exposure to mild hyperbaric oxygen. An adequate oxygen supply from exposure to mild hyperbaric oxygen may accelerate the turnover rate of aged skin by enhancing the proliferative activity of epidermal basal cells. Therefore, the dissolved oxygen, which is increased by exposure to mild hyperbaric oxygen, is considered to diffuse from the dermis to the epidermis through blood microcirculation, thus accelerating proliferation of epidermal basal cells and inhibiting epidermal aging.

Suppression of ultraviolet B irradiation-induced pigmentation is due, at least in part, to the reduction in prostaglandin synthesis via the inhibition of cyclooxygenase by indomethacin and to the induction of annex-in or lipoprotein by corticosteroids. Exposure to mild hyperbaric oxygen was found to accelerate the fading of ultraviolet B irradiation-induced melanin pigmentation of the skin. Furthermore, senile spot sizes on faces became smaller after exposure to mild hyperbaric oxygen. Keratinocyte proliferation and epidermal cell regeneration are considered to be activated by enhanced oxidative metabolism induced by exposure to mild hyperbaric oxygen, which may be effective for damage repair in the epidermis.

Nishizaka T, Nomura T, Higuchi K, Takemura A, Ishihara A (2018) Mild hyperbaric oxygen activates the proliferation of epi- dermal basal cells in aged mice. J Dermatol 45:1141–1144

Mild hyperbaric oxygen therapy and Parkinson’s disease

Parkinson’s disease is a progressive neurodegenerative disorder in the elderly that is characterized by typical motor symptoms such as resting tremors, rigidity, bradykinesia and gait disturbances. Parkinson’s disease results from the progressive decrease in dopaminergic neurones in the substantia nigra.

Exposure to mild hyperbaric oxygen was shown to inhibit the decrease in dopaminergic neurons in the substantia nigra of a neurotoxic experimental animal with Parkinson’s disease. The number of times the feet of the mouse slid off the stick in a balance beam test was fewer in mice with Parkinson’s disease exposed to mild hyperbaric oxygen than in those not exposed to mild hyperbaric oxygen. PGC-1α, a transcriptional co-activator, may be one of the factors that contribute to the improvement in oxidative metabolism of dopaminergic neurons in Parkinson’s disease, since oxidative metabolism, mitochondrial biogenesis, oxidative stress, and gene expression are regulated by PGC-1α.

It is concluded that exposure to mild hyperbaric oxygen activates oxidative metabolism in the dopaminergic neurones in the substantia nigra and inhibits the reduction in dopaminergic neurones, thereby resulting in the inhibition of Parkinson’s disease.

Kusuda Y, Takemura A, Nakano M, Ishihara A (2018) Mild hyperbaric oxygen inhibits the decrease of dopaminergic neurons in the substantia nigra of mice with MPTP-induced Parkinson’s disease. Neurosci Res 132:58–62

In another study performed on 64 parkinsonian patients, 29 men and 35 women ranging in age from 37 to 78 years. (3 individuals from 37-39 years; 12 individuals from 40-49 years; 27 individuals from 50-59 years; and 22 individuals 60 and above). The duration of the illness ranged from 1 to 15 years, but up to 5 years in the majority of patients.

The effectiveness of HBOT was higher in vascular parkinsonism than in the encephalitic form. Significant regression of the akinetic-rigid syndrome was observed in patients with the use both of low (I.3-1.5 ATA).

Analysis of the history of 36 patients showed that the therapeutic effect achieved by the use of M-HBOT was maintained up to six months. The course of treatment was repeated at a frequency of two times per year in order to stabilize the patients’ condition.

Can we treat Infertility with mild hyperbaric oxygen therapy (M-HBOT)?

Hyperbaric oxygen therapy, an established medical treatment usually conducted under conditions of 2.0–3.0 ATA with 100% oxygen, has been investigated for improving female and male infertility. However, several side effects, including barotrauma and excessive production of reactive oxygen species, associated with hyperbaric oxygen therapy, have been reported.

Low metabolism in the uterus and ovaries may be a factor responsible for infertility since the former reduces the ability of fertilized eggs to remain in the uterus. Exposure to mild hyperbaric oxygen has been suggested to enhance oxygen supply to cells and tissues, thus improving oxidative metabolism, without barotrauma and excessive production of reactive oxygen species.

In a recent study, 37 women with intractable infertility, who had previously received over 5 embryo transfers with a low clinical pregnancy rate (4.9%) and without birth, were exposed to mild hyperbaric oxygen before receiving any further embryo transfer. As a result, 13 women achieved clinical pregnancy with a rate of 13.8%; 5 women gave birth after in vitro fertilization treatment. Two women achieved natural conception and gave birth. However, 1 woman had an extra-uterine pregnancy, and 5 women had miscarriages.

Yoshikawa F, Netsu Y, Shimizu T, Ishihara A (2019) Mild hyperbaric oxygen improves the outcome of infertility treatment. J Reprod Med (accepted)

Perspectives on exposure to mild hyperbaric oxygen

Exposure to mild hyperbaric oxygen is effective for elderly people, those with physical disability, as well as injured athletes, since no special movement needs to be performed under mild hyperbaric oxygen conditions. In the near future, exposure to mild hyperbaric oxygen may be investigated for: prevention and improvement of dementia, improvement of functional imbalances of autonomic (sympathetic and parasympathetic) nerves, e.g., menopausal disorders and emotional instability, maintenance and improvement of immunity, health, and physical fitness, and early recovery from an injury. Further studies are required to solve these problems and define a useful protocol for exposure to mild hyperbaric oxygen.