Biological Effects of Ozone

Unlike oxygen, ozone reacts immediately when dissolved in biological water (physiological saline, plasma, lymph, urine), acting the atomic oxygen as a highly reactive radical. Immediately, due to its high reactivity, ozone reacts with compounds such as antioxidants, protein, carbohydrate, and preferably polyunsaturated fatty acids (PUFA), ascorbic acid and uric thionic compounds with-SH groups such as cysteine, reduced glutathione (GSH ) and albumin which are in a high percentage in the fluid and cellular structures of the body. All these compounds act as electron donors and are oxidized.

In these reactions, organic peroxides, hydrogen peroxide (H2O2), ozone and aldehydes are generated, which in adequate and controlled quantities exert different biological actions that give ozone a set of therapeutic properties.


The reaction of ozone with such a variety of molecular compounds involves:

Initial stage of reaction in which, despite much of the ozone being consumed by antioxidants present in plasma, forms a number of ROS reactive oxygen species, capable of firing several biochemical pathways (although these ROS are neutralized 0 , 5-1 nm by the antioxidant systems, converting the ozone in water) and one

Late stage at which lipid oxidation products POL, such as: peroxyl radical complex mixtures of final products of low molecular weight aldehydes (maloniladdehyde) and alquenales and also, H2O2 (not a radical oxidant, including within ROS). This and the POL are responsible for the therapeutic and biological late effects of ozone.

The novelty of ozone therapy is that its functions are directed to restore and improve the metabolism of oxygen, together with sugars and fats to produce energy, through normal metabolic pathways of controlled combustion:

  • Glycolysis
  • Respiratory chain
  • Fatty acid cycle
  • Glucose 6 phosphate dehydrogenase
  • Oxidative decarboxylation of pyruvate. .


Since ozone is an extremely reactive and unstable gas, it suggests that the mechanisms of action of this agent is related to the generation of secondary products in their selective interaction with the double carbon-carbon bonds present in organic compounds found in the plasma and cell membranes.

Ozone interacts with polyunsaturated fatty acids, which are in a high percentage of the body, generating organic peroxides, aldehydes, hydrogen peroxide and ozone, which in adequate and controlled quantities exert different biological actions by giving ozone a series of therapeutic properties:



    • Improves oxygen metabolism.
  • Modulates biological oxidative stress.
    • Modulates the immune system.
  • Participates in the synthesis and/or release of autacoids.
    • It regulates the metabolism.
  • Germicidal effect.
    • Platelet aggregation.

The various biological effects generated by ozonetherapy achieve therapeutic results when the gas is applied at proper doses and through a way not harmful to the body, producing no adverse reactions or genotoxic damage.

The wide range of various effects allow its application in various specialties in medicine.

Effects of ozone on oxygen metabolism

In cases of impairment of oxygenation can be explained by the effects of ozone, given its direct and indirect actions on the following reactions:

  • Through a change in the rheological properties of blood.
  • By an increased rate of glycolysis in the erythrocyte.
  • By activating the mitochondrial respiratory chain.

The erythrocytes which are broken down and softened are more able to absorb and transfer oxygen, among other things, over the increased surface free contact and deformability. The arterial oxygen pressure increases and the pressure for venous oxygen decreases (Bohr effect), improving cell oxygenation in ischemic tissues. There is an increase of 2.3 DPG (Diphospho glycerol), which facilitates the transfer of oxygen trapped in the oxyhemoglobin in red blood cells.


Obviously, a single autohemotherapeutic treatment has minimal effect, and therapeutic efficacy becomes subjective and objectively evident after about 12 to 16 treatments, if performed at a rate of 2-3 per week. In other words, we need to ozonate at least 2.5 to 4 liters of blood within 30-60 days. During this period, the POL act as repetitive stressors on the bone marrow, and these frequent stimuli produce the adaptation of erythrocytes of the erythrogenesis because of the ozone stress with regulation of antioxidant enzymes.

There is evidence that new generation erythrocytes have a G-6PD activity (glucose 6-dehydrogenase) greater than that of old erythrocytes, and are considered “gifted erythrocytes”. The typical erythrocyte agglomeration of the occlusive arterial diseases is reversed by ozonetherapy with these changes in the erythrocyte membrane.

Occlusive arterial diseases are related to the potential loss of normal red cell plasma membrane, the normalization of ion exchange for ozone and its products, promotes the restoration of the normal potential, so that the generation of normal electrical conditions for the membrane favours to regain flexibility and plasticity of erythrocytes, improving the rheological properties of blood, favoring the transport of oxygen.

The increased velocity of glycolysis in the erythrocyte is accompanied by an increase in the exchange of sodium and potassium ions, being these responsible for maintaining the electrical potential of the membrane, standardizing the exchange of these ions.

Ozone as a modulator of oxidative stress

Although the production of reactive oxygen species such as: radical hydroxyl, superoxide anion and non-radical species such as hydrogen peroxide, and hypochlorous acid are part of the normal biological metabolism and is also a necessary phenomenon for the proper functioning of vital processes as phagocytosis. On the other hand, the uncontrolled growth of these products are closely related to aging.


In the body antioxidant defence mechanisms are present which are able to maintain an adequate balance against these powerful agents through antioxidant enzyme systems, where enzymes are the main sources of protection. Therefore, the excessive production of oxygen metabolites or inadequate defence to counter their accumulation in the body, with consequent tissue injury, promotes or accelerates the development of multiple pathological processes, being the mechanism of signal transduction for activation or repression of transcription specific genes are the cornerstone of the mechanism of action for modulation of oxidative stress.

Ozone possesses the property of stimulating certain antioxidant enzyme systems, dynamically regulating antioxidant and prooxidant processes, through molecular and physiological mechanisms. This has been demonstrated in a preclinical and clinical manner.

Ozone as a modulating agent of the immune response

Ozone has been considered an ideal cytokine inducing agent, its immunizing effectiveness allows its application not only in the deficiencies but also in autoimmune diseases.


Immunological action of ozone is guided by monocytes and T lymphocytes, which once induced, release small amounts of all the cytokines and interferon gamma, with the release of cytokines as endogenous. It is believed that during treatment with ozone, the release of antagonists of cytokines such as interleukin and transforming growth factor beta 1 type can be increased, capable of suppressing cytotoxicity autorrectiva, so that the induction of cytokines would not exceed necessary levels once activated counter regulatory elements.


Effects of ozone on the synthesis and / or release of autacoids

The word autocoids derives from the Greek “auto” (own), and “akos” (medicinal agent or remedies) and is considered as such a group of endogenous substances with various physiological and pharmacological actions which are involved in many physiological events. Two different families of autacoids derived from cell membrane phospholipids have been identified. Eicosanoids formed from certain polyunsaturated fatty acids (mainly arachidonic acid) which include prostaglandins, prostacyclin, thromboxane A2 and leukotrienes, and other phospholipids represented by the Platelet Activating Factor.

During ozone treatment, studies in patients with asthma, retinitis pigmentosa, glaucoma, senile dementia, it has been found a significant increase in the ratio prostacyclin / thromboxane at the end of treatment; ozone principal role would be in maintaining the proper balance between eicosanoids with beneficial effects and those which cause harmful effects.

Effect of ozone as a metabolic regulator

In various studies it has been established the regulatory action of ozone on different biochemical parameters, such as glucose, cholesterol, triglycerides, creatinine, being normalized at the end of the cycle and those with normal values were maintained over it. Ozone through endogenous mechanisms tries to normalize the functioning of the body.

Germicidal effect of ozone

Ozone is recognized as a powerful germicide against viruses, bacteria and fungi. This property has been useful in infectious diseases of varying etiology thanks to its direct action towards the microorganism, as well as the immune response that it can trigger.

Effect of ozone over platelet activation

Researches (Matsuno K, 1997) have found that the platelet-rich plasma (PRP) and suspension of washed platelet, treated with ozone, it has been observed the inhibition of platelet aggregation; apparently the ozone inhibited the increase of calcium concentration induced by collagen and thrombin, in turn inhibiting the signal transduction between the inductor and platelet activation.

Similar results were obtained in a study conducted at the Institute of Angiology and Vascular Surgery in Cuba (Cuban Rev. Invest. Biomed 2001; 20 (1):42-4

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