Ozone therapy

Short history
Ozone therapy is a form of treatment used for more than a century, with the purpose to increase tissue oxygenation. The main effects of the therapy are those of improving the metabolism, detoxification, stimulation of the immune function and of the repair mechanisms of the body.

Ozone was discovered in 1840 by German chemist Christian Friedrich Schonbein. For over 150 years, ozone has been used for curative and palliative purposes worldwide.

In 1904, the US public health service approved the publication of a manual for the use of ozonated water and olive oil. In 1930, the Journal of The American Medical Association published an article entitled "Therapeutic use of oxygen in coronary thrombosis." In 1931, the German doctor Otto Warburg wan the Nobel Prize for his discoveries in oncology: he proved that the occurrence of cancer is conditioned almost entirely by the lack of adequate oxygenation of cells. Specifically, a 60% decrease in oxygen intake causes the first cancer cells to appear. This occurs through the accumulation of toxic substances inside and around the cell, accumulation that blocks and damages the processes of cellular respiration. Dr. Warburg's initial research has been confirmed in time, proving that the deficit and the subsequent accumulation of toxins represent the leading cause of degenerative diseases, including cancer.

Over the last 5 years, more than 3000 references of millions of uses have been registered in the German medical literature, which show the efficiency and safety of ozone administration in patients diagnosed with various diseases. The International Ozone Association, together with the manufacturers of medical equipment used in ozone therapy, report that, in Europe alone, there are more than 7000 physicians who, for more than 40 years, have been using this form of therapy.

How does it work in the body
Ozone therapy represents the enrichment of blood and, implicitly, of cells with a mixture of oxygen and ozone (O2/O3).
Red blood cells transport oxygen from lungs to cells, through the capillaries. The diameter of the capillaries may be smaller than the diameter of red cells, and their flexibility is therefore a vital characteristic. Ozone therapy improves the flexibility of red blood cells, thus improving blood flow and the amount of oxygen that reaches the cells.
Likewise, ozone therapy stimulates the production of 2,3-DGP of red cells. This molecule allows red cells to release oxygen into the cells, its synthesis being directly related to the volume of oxygen directed to the cells.
Another effect of ozone therapy is the stimulation of mitochondrial function. Mitochondria are cellular organisms specialized in producing the energy that a cell needs to function. The more energy produced, the greater the capacity of any cell in the body to regenerate and maintain within normal operating parameters.
Researchers such as Velio Bocci in Italy and Silvia Menendez in Cuba have shown that ozone also modulates the activity of the immune system. More precisely, in places in the body where excess inflammatory processes occur, ozone decreases the intensity of the inflammatory process, promoting healing of the respective tissues. Therefore, the effect of ozone on the immune system is of balancing. Inflammation is necessary in the body's fight against pathogens and toxins, but when it is not kept under control, it becomes harmful. As regards joints, for instance, the modulation of the inflammatory processes through ozone may generate immediate results.

Ozone and its metabolism products have a direct toxic effect on pathogens. More precisely, these compounds immediately pierce through the membrane of bacteria, causing their destruction. By comparison, compounds of disinfectants act 100 times more slowly.

Medical procedure
Medical ozone is obtained by means of a medical device where electrical impulses break down the oxygen into atoms, thus forming a mixture of ozone and oxygen, of the intended concentration. Only standardized medical generators are used, that produce ozone by using medicinal oxygen. Medical ozone is always made up of a mixture of pure ozone and pure oxygen (0.05% - max. 5%). Ozone generators are made of stainless steel, glass or Teflon. Normal air is not used in the generation of ozone because toxic nitrogen dioxide (N2O2) is formed. Ozone therapy is carried out only by specialized medical personnel.
Major autohemotherapy is one of the most used and effective methods of ozone administration. The process involves the extraction, in special sterile containers, of 50 - 150 mL of blood from the patient's cubital vein. Once collected, ozone is injected into the container and mixed with the blood, shaking slightly. Then the ozonated blood is re-perfused to the patient, and the entire procedure lasts for approximately 30-40 minutes.
Other procedures used in ozone therapy are: minor autohemotherapy (with ozonation of 10 - 15 mL of blood, followed by intramuscular re-injection), direct injection into the tumor (ozonopuncture), rectal insufflation, skin infiltration, intra-articular infiltration, topical administration of oil or creams.
The therapy consists of 10 sessions, depending on the pathology, and it may be repeated 2 or 3 times (20-30 sessions).

Recommendations
Ozone is used to treat the following disorders:
• Tendon and ligament disorders
• Circulatory disorders (high blood pressure, poor circulation, arthritis, heart pains)
• Dermatological disorders (acne, burns, boils, herpes, psoriasis, dermatitis, etc.)
• Allergies
• Crohn's disease
• Lyme disease
• Autoimmune diseases
• Cancer
• Candidiasis
• Cystitis
• Colitis
• Senile dementia
• Diabetes
• Dyslipidemias
• Fibromyalgia
• Chronic hepatitis
• Disc hernias
• Chronic infections
• Vaginal infections
• Insomnia
• Lumbosciatica
• Alzheimer's disease
• Migraine
• Chronic fatigue
• Osteoarthritis
• Rheumatoid polyarthritis
• Chronic sinusitis
• Trauma (fractures, sprains, muscle tears)
• Ulcers
• Shingles

Benefits
Some of the benefits of ozone therapy explained through the mechanisms of action of ozone and its metabolites, once they reach the body:

It destroys bacteria, viruses, fungi, protozoa. Research has shown that ozone eliminates microorganisms by destroying their outer membranes or capsules. In addition, unlike human cells that contain enzymes which are able to restore the affected DNA, pathogenic microorganisms do not have this protective capacity; this is another strategy by which ozone acts selectively on pathogens encountered in the body, without affecting healthy cells. Repeated treatments with ozone are necessary because certain forms of viruses and fungi are more susceptible to the effect of ozone at different stages of their development. There are microorganisms with a higher resistance than others, therefore longer treatment is required. Viruses that contain more lipids in the outer capsule are more susceptible to ozone action: herpes, mumps, measles, influenza, rabies, HIV, Epstein Barr virus, Coxsackie virus, cytomegalovirus. In vitro studies have proven the ability of ozone to completely inactivate the HIV virus, and the concentration used in experiments does not have cytostatic effects on the healthy cells. Subsequent tests indicated that this inactivation is due to the ability of ozone to reduce p24 protein synthesis, essential for maintaining the integrity of the virus.

It stimulates basal metabolism. Ozone determines the increase of red blood cell metabolism, by increasing the production of 2,3-DPG, a molecule that is directly involved in the transfer of oxygen from red cells to all the tissues of the body. Ozone also increases the production of cellular ATP (energy), by stimulating the oxidative carboxylation of pyruvate, and it stimulates the production of enzymes that play a role in defense and in the elimination of free radicals. Moreover, the production of molecules with antioxidant protective role (glutathione peroxidase, catalase, superoxide dismutase) is activated.

Its helps forming peroxides. When ozone is introduced into the body, it is metabolized, thus forming compounds called peroxides. They have beneficial effects because they are "drawn" towards the weak or unhealthy cells, reacting with the lipids from their cell membranes. By interacting with the unsaturated fatty acids of the lipid bi-layer, ozone forms hydroperoxides. The enzymes from the healthy, intact cell membranes prevent the intracellular penetration of these peroxides. Thus, peroxides selectively attack cells that contain parasites, viruses, etc., cells that are weakened by toxins or by abnormal, cancerous cells.

It improves blood circulation. When, in the capillaries, the red blood cells no longer circulate normally, building up and obstructing the normal blood flow, the amount of oxygen reaching the cells is diminished. Ozone reduces or eliminates these build-ups of red cells, restoring their flexibility and thus improving the blood viscosity and facilitating the easy crossing of the capillaries, followed by increased tissue oxygenation.

It helps with the oxidation of arterial plaques. Ozone produces prostacyclin, a vasodilator of the arteries, which decreases the risk of myocardial infarction.

It activates the immune system. The administration of medical ozone increases the production of interferon and interleukins, which, on their turn, trigger an entire series of immunological reactions. The results of an in vitro study demonstrated the effectiveness of ozone in reducing the concentrations of Acinetobacter baumannii, Clostridium difficile and Methicillin-Resistant Staphylococcus Aureus (MRSA), validating its use at least as disinfectant.

Influence on chronic infections. Ozone has been successfully used in the treatment of Lyme disease, hepatitis C, hepatitis B, herpes simplex infections.

Influence on autoimmune disorders. Ozone has proven its efficiency in alleviating the symptoms of diseases such as multiple sclerosis, lupus, chronic fatigue, scleroderma, rheumatoid arthritis.

It renders drugs more efficient. The effects of drug treatments administered at the same time as ozone therapy are enhanced. Moreover, as regards chemotherapy, ozone reduces the intensity and incidence of side effects.

Ozone therapy may be successfully applied in the treatment of any painful syndrome.

Anti-tumor effect
Ozone affects and inhibits the metabolism of cancer cells, oxidizing the outer lipid layer of the cell membrane and achieving its lysis. According to the data published by the American Society of Clinical Oncology, the death rate of patients in the last stage of cancer has not decreased since 1950, when chemotherapy was rarely used, until present time, and this is a reality that proves that, in many advanced cancer cases, this therapy is little effective. Cancer is a complex disease that requires an integrative, holistic approach. The use of oxygen by cells and the immune function must be maximal for the body to fight the disease. Ozone therapy, as part of an integrative oncological treatment, increases tissue oxygenation and stimulates the actions of the immune system, improving cell viability.

As regards the different forms of cancer, besides increasing the oxygen concentration at cellular level, ozone also stimulates the function of the mitochondria, and it is a well known fact that the impairment of the proper functioning of these cellular organelles is a key factor in the occurrence of this pathology.

The tumor tissue is characterized by hypoxia and acidosis, conditions that determine the activation of the KRAS oncogene, with the increase of the HIF1A transcription and subsequently of the production of glycolytic enzymes (hexokinases, aldolases, phosphofructokinases, lactate dehydrogenase). The activity of all these enzymes accelerates the glycolytic flow and lactic fermentation, processes that maintain the hypoxic acid environment of the tumor. In addition, HIF1A also determines the transcription of angiogenic factors, with the proliferation of endothelial cells and new blood vessels.
Recent studies (2014, 2016) have shown that HIF1A plays a role in increasing tumor resistance to chemo- and radiotherapy. Research has shown that tumor tissue hyperoxygenation directly causes HIF1A inhibition, a factor which has a high value in most forms of cancer. Additionally, ozone may induce the synthesis of various classes of pro-inflammatory cytokines, which will in turn activate macrophages, thus triggering a vast reaction of the immune system. Consequently, ozone therapy is able to improve the antitumor activity of T lymphocytes and of the natural killer (NK) cells. By inhibiting the action of HIF1A factor, ozone-induced hyperoxia enhances the effect of chemotherapy, reducing tumor resistance to treatment, also enhancing the hemorheologic properties, facilitating drug access to the hypoxic tumor center. These two actions also determine the decrease of the administered doses of chemotherapeutics, reducing toxicity and the related side effects: reduced cardiac effects of doxorubicin, reduced infection rate, by stimulating the immune function, increasing hemoglobin concentration, decreasing fatigue, reducing the incidence of dizziness and vomiting caused by chemotherapy. The concomitant administration of ozone with chemotherapy reduces by ¼ to ¾ the administered amount of drugs. Also, in chelation therapies, their effect is enhanced, which has a positive impact on the mental state of the patients as well.

Consequently, as regards cancer, the reversal of local hypoxia-inducing processes has a stopping effect on tumor tissue growth.

The effect of ozone on cancer, hypoxic cells, is a specific one. It "attacks" the abnormal, unhealthy cells, which divide chaotically, identifying them according to their lack of certain membrane proteins. Thus, ozone selectively destroys the cancer cells, not interfering with the activity of the normal cells, as in the conventional anticancer therapies, where there is no differentiation between the types of cells that they destroy.

A clinical study conducted in Spain in 2015 shows that ozone therapy is effective in reducing the side effects caused by radiation therapy in prostate cancer patients, without causing side effects during its administration.
The results of another clinical study conducted in Russia in 2017, on 100 patients with forms of uterine and endometrial cancer, showed that this therapy increases the anti-tumor function of the immune system.
As regards the secondary lymphedema, clinical studies have shown that ozone therapy significantly reduces (p <0.05) the swelling of the affected area and improves the lymphatic circulation in patients diagnosed with breast cancer.

Clavo B et al. Evidence-Based Complementary and Alternative Medicine 2004; 1(1):93-98.
Bocci V, Larini A, Micheli V. The Journal of Alternative and Complementary Medicine 2005; 11(2): 257-265.
Clavo B. et al. Evidence-Based Complementary and Alternative Medicine 2015, article ID 480369, 7 pg, doi:10.1155/2015/480369.
Smith AJ et al. Open Journal of Molecular and Integrative Physiology 2015; 5:37-48.
Kiziltan HȘ et al. Alternative Therapies in Health and Medicine2015; 21(2):24-29.
Yanchenko OS et al. Revista Española de Ozonoterapia 2017; 7(1):77-81.
Waked IS, Nagib SH, Omar MH. Cancer and Clinical Oncology 2013; 2(2):93.
Ai Z, Lu Y, Qiu S, Fan Z. Cancer Letters 2016; 373:36-44.
Delgado-Roche L et al. Sultan Qaboos University Medical Journal 2014; 14:e342-348.
Hatfield SM et al. Sci Transl Med 2015; 7:277ra30.
Coppola L et al. Int J Geriatr Psychiatry 2010; 25: 208-213.

Side effects and contraindications
Ozone therapy is a method characterized by the lack, almost entirely, of side effects, as it is used complementary to the standardized medical treatments. Before initiating the treatment, basic blood tests, such as coagulation, must be carried out.
The use of ozone, in compliance with the required medical standards, is absolutely safe and without side effects. An analysis carried out in Germany among doctors and practitioners authorized to use ozone for therapeutic purposes showed that for 5,579,238 treatments carried out for 384,775 patients, a rate of 0.0007% of side effects was recorded, side effects that had a minor character and that did not endanger the patients’ life.

Selective action. Research has shown that ozone does not act on the healthy cells of the body, differentiating them depending on the specific electrical charge and strong membrane enzymatic barrier. This is why ozone therapy is also called "targeted therapy" - ozone only identifies and destroys the cells that are sick. For example, the complications associated with diabetes are attributed to the state of oxidative stress present in the body. Studies have shown that ozone activates antioxidant systems in the body, helping to lower blood sugar and free radical levels. In addition, by normalizing the concentration of organic peroxide, as a result of stimulating superoxide dismutase activity, ozone reduces and prevents the installation of oxidative stress.

The main side effect of ozone is the "Herxheimer Reaction". It may occur when, after administration, a strong detoxification reaction occurs in the body. The membranes of the destroyed pathogenic bodies release endotoxins, thus "validating" the effectiveness of the treatment. The symptoms of the Herxheimer reaction are similar to those of influenza (joint pain, sweating, dizziness, vomiting), they are an indicator of the reaction of the pathogens that ozone is fighting in the body. This reaction may last from several hours to several weeks. Once the pathogens are eliminated from the body, these symptoms disappear.

Ozone therapy is contraindicated to people suffering from favism (a deficit of a fraction of glucose), hyperthyroidists, pregnant women and patients with essential hypertension.

Selective references
Clavo B et al. Evidence-Based Complementary and Alternative Medicine 2004; 1(1):93-98.
Bocci V, Larini A, Micheli V. The Journal of Alternative and Complementary Medicine 2005; 11(2): 257-265. 
Clavo B. et al. Evidence-Based Complementary and Alternative Medicine 2015, article ID 480369, 7 pg, doi:10.1155/2015/480369.
Smith AJ et al. Open Journal of Molecular and Integrative Physiology 2015; 5:37-48.
Kiziltan HȘ et al. Alternative Therapies in Health and Medicine2015; 21(2):24-29.
Yanchenko OS et al. Revista Española de Ozonoterapia 2017; 7(1):77-81.
Waked IS, Nagib SH, Omar MH. Cancer and Clinical Oncology 2013; 2(2):93.
Ai Z, Lu Y, Qiu S, Fan Z. Cancer Letters 2016; 373:36-44.
Delgado-Roche L et al. Sultan Qaboos University Medical Journal 2014; 14:e342-348.
Hatfield SM et al. Sci Transl Med 2015; 7:277ra30.
Coppola L et al. Int J Geriatr Psychiatry 2010; 25: 208-213.