Ozone in Medicine. The Low‐Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases

Renate Viebahn‐Haensler, and Olga Sonia León Fernández

Abstract: Low‐dose ozone acts as a bioregulator in chronic inflammatory diseases, biochemically characterized by high oxidative stress and a blocked regulation. During systemic applications, “Ozone peroxides” are able to replace H2O2 in its specific function of regulation, restore redox signaling, and improve the antioxidant capacity. Two different mechanisms have to be understood.
Firstly, there is the direct mechanism, used in topical treatments, mostly via radical reactions. In systemic treatments, the indirect, ionic mechanism is to be discussed: “ozone peroxide” will be directly reduced by the glutathione system, informing the nuclear factors to start the regulation. The GSH/GSSG balance outlines the ozone dose and concentration limiting factor. Antioxidants are regulated, and in the case of inflammatory diseases up‐regulated; cytokines are modulated, here downregulated.
Rheumatoid arthritis RA as a model for chronic inflammation: RA, in preclinical and clinical trials, reflects the pharmacology of ozone in a typical manner: SOD (superoxide dismutase), CAT (catalase) and finally GSH (reduced glutathione) increase, followed by a significant reduction of oxidative stress. Inflammatory cytokines are downregulated. Accordingly, the clinical status improves.
The pharmacological background investigated in a remarkable number of cell experiments, preclinical and clinical trials is well documented and published in internationally peer reviewed journals. This should encourage clinicians to set up clinical trials with chronic inflammatory diseases integrating medical ozone as a complement.

Keywords: ozone therapy; bioregulation; redox balance; chronic inflammation; biological medicine;
complementary medicine

[rml_read_more]. When and if the H2O2 concentration is too high, regulation is blocked and degenerative processes begin, as in the case of chronic inflammatory diseases.
This key position of hydrogen peroxide is then likely to be assumed by the “ozone peroxide” formed from ozone, as seen in Figure 1a,b. Here, we will demonstrate this on a molecular and biochemical basis, supported by preclinical and clinical data using a prime example of a chronic inflammatory disease, rheumatoid arthritis.


Figure 1. (a) Hydrogen peroxide as key redox regulator in the biological system modified acc. to [1,2]. (b). Low‐dose ozone as bioregulator.

1.2. Indications and Applications of Systemically Administered Ozone
Over the last three decades, the pharmacology and molecular mechanisms of ozone in medical use have been widely investigated and well confirmed. In the 1980s and 1990s its influence on the RBC (red blood cell) metabolism with an improvement of oxygen release as final result [3–5], while the impact of ozone on immunocompetent cells was the
main subject of Bocci’s ozone research in the 1990s, e.g., [6,7], expanding the knowledge and understanding of immunomodulation.
The first paper on ozone as a bioregulator of the redox balance in a biological system was published by León and her group in 1998 followed by an intensive research program all over the world until today [8].

On this basis and with standardized forms of ozone treatments, such as major autohemotherapy (MAH) and rectal insufflation (RI) as low‐risk systemic ozone applications (see Figure 2a,b), the indications of medical ozone have been established, mainly chronic inflammations or diseases associated with chronic inflammatory conditions [9]. Following
the low‐dose ozone concept, medical ozone can be successfully integrated into a complementary medical system in angiopathia, rheumatoid arthritis, or chronic intestinal diseases as examples, see Table 1. They all have one phenomenon in common: high oxidative stress, measured as ROS (reactive oxygen species) and a suppressed antioxidant capacity as well as an immune disbalance …

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