Background information:
The effects of ozone and ionizing radiation involve the generation of reactive oxygen species (ROS) such as superoxide or hydroxyl radicals and singlet oxygen as well as free radicals (e.g., atoms, molecules, or ions that have an unpaired valence electron). Free radicals and ROS are chemically reactive compounds which induce oxidative stress and their effects are partially palliated by antioxidants
In 1980 another prestigious journal, Science, described how, as a function of concentration, ozone could selectively inhibit (in cell cultures) the growth of different human tumor cells (lung, breast, and uterus) without affecting nontumor cell lines. More recently, ozone was described as having a direct cytotoxic effect in human colon cancer cells, and ozone boosted the effect of cisplatin and 5-fluorouracil
Evidence:
In 2008, two different preclinical studies in mice were published in the same article. In the first study, cells of Ehrlich ascitic tumor and sarcoma 37 tumor were implanted in the ocular plexus of mice. After implantation, the animals were treated with ozone via rectal insufflation over 12 sessions using different ozone concentrations. In both tumors, a significant decrease in the numbers of lung metastases was observed, with lower numbers of tumor cells per mice at higher ozone concentrations. In the second preclinical study, varying ozone concentrations were applied intraperitoneally for 15 days. Twenty-four hours after the last ozone treatment, Lewis lung carcinoma cells were inoculated via subcutaneous route. Relative to the control group, all the ozone pretreated groups showed a delay in tumor volume increase and the kinetics of tumor development, with a trend to better results when lower ozone concentrations had been used. Additionally, at 16 days after tumor cell inoculation, all animals in the control group had tumor development, while in the ozone-treated groups there were animals without signs of tumor growth, even after 35 days
The O3T was administered intraperitoneally, i.e., the route that is frequently employed in small animals as being an approximation to the intravenous route in humans. In the group receiving O3T, 7 of the 14 rabbits survived and, of them, all but one showed complete response (complete disappearance of the tumor).
The studies demonstrate that ozone can modulate the production of various cytokines (such as interleukins and interferon) and, as such, modulate the activity of the immune system which is responsible for the defense of tumor cells.
Treatment plan:
As a result, monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4), the programmed death-1 receptor (PD-1), and its ligand (PD-L1) have been approved by the European Medicines Agency (EMA) and/or the Food and Drug Administration (FDA) for the treatment of several tumors, especially melanoma and non-small cell lung cancer [27].
Immune modulation produced by O3T is nonspecific. The mode of action differs in relation to the activity of different types of lymphocytes and on the production of different types of cytokines. The extent of activity depends on environment, functional status, and ozone concentration. Indeed, several years ago Bocci et al. proposed the hypotheses that low-medium ozone concentrations could upregulate cytokines produced by CD4+ TH1 lymphocytes enhancing TH1/TH2 ratio while higher ozone concentrations could decrease this ratio. Additionally, there could be considerable clinical gain in combining monoclonal antibody therapy and O3T.
In 2012, a report on 40 patients with advanced non-small cell lung cancer was communicated. The patients were treated with and without concomitant O3T by autohemotherapy (once a week for 12 weeks) and subcutaneous injection of Viscum album fermentatum (a species of mistletoe, a phytocompound used in northern Europe since Celtic times). Patients treated simultaneously with ozone and extracts of Viscum album showed a significantly better quality-of-life score measured by the quality-of-life questionnaire-core 30 (QLQ-C30). Additionally, this patient group showed a significant decrease in plasma values of reactive species metabolites and an increase in biological antioxidant potential
Treatment effect:
Further, ozone can (1) improve the flexibility of erythrocytes membranes and the rheological properties of blood and diminish blood viscosity [48, 49]; (2) induce the production of nitric oxide by vascular endothelial cells and, thus, produce vasodilation at the microcirculation level. These two effects decrease peripheral vascular resistance, which, as a result, gives rise to an increase in blood flow according to Poiseuille’s law.
Despite not being observed in all cases, in tumors in which O3T does increase tumor oxygenation, the effects of RT and CT could be enhanced, especially if this oxygenation increase is produced in zones of tumor hypoxia, i.e., in those that are most radio resistant. Theoretically, more oxygenation (lower hypoxia) could inhibit HIF-1α activity in tumors, and this effect could reduce tumor-neoangiogenesis and further metastases. However, more studies are needed to address specifically whether an increase in O2 delivery to hypoxic tumors can downregulate HIF-1α.
Also in 2003, a Russian study reported the potential usefulness of adding parenteral ozone therapy to the standard treatment in 90 patients with hepatic dysfunction secondary to cancer-related obstructive jaundice. O3T facilitated a more rapid arrest of hepatic dysfunction and endogenous intoxication
Wound healing:
Although we are not aware of published works focusing on the treatment of delayed wound healing in patients awaiting anticancer treatment, the application of ozonated water or ozonated oil represents a viable option. The oxidation products generated following the reactivity of ozone with fatty acids and other substrates can act as germicide and/or tissue restoration agents. The biological activities and stability of ozonized oils enable the development of standard formulations that deliver the benefits of ozone, with longer storage time (it remains stable for two years if kept refrigerated) [79]. The mechanism-of-action of ozonized oil in wound healing may be related, at least in part, to its antimicrobial effect and, as well, to its ability to activate local antioxidant mechanisms and promotion/liberation of growth factors and tissue reparation.
Considerations:
O3T should not be used as a substitute for any other oncological treatment (never as “alternative” medicine).
O3T should always be “complementary” to conventional treatment (complementary medicine and/or integrative) in collaboration with the oncologists and other specialists responsible for the patient.
Always have detailed and truthful information provided to the patient highlighting the studies that have suggested potential usefulness, but also that data from randomized clinical trials are lacking.
Fully informed written consent must be obtained.
The use of O3T as adjuvant for the management or prevention of cancer treatment toxicity has higher levels of scientific evidence and clinical justification. With this approach, O3T could be readily accepted because of its great potential in amplifying the administration of RT or CT in patients who may not be candidates because of their poor clinical status. This could include patients with poor renal, hepatic, pulmonary, and cardiac function, or when the option to apply the treatment is associated with high-risk toxicity. However, wider explanations of these topics would require a different review article.
To date, no RCTs have been conducted and so high level of evidence is lacking for the systematic use of O3T during anticancer treatment. However, many non-RCT reports do highlight the potential enhancement of RT and/or CT. Also, encouraging preclinical results have been described for intraperitoneal administration of ozone.
Therefore, as to the initial question of “ozone therapy as adjuvant for cancer treatment: is further research warranted?” we believe that the answer is an emphatic “yes”.
References:
Clavo, B., Santana-Rodríguez, N., Llontop, P., Gutiérrez, D., Suárez, G., López, L., Rovira, G., Martínez-Sánchez, G., González, E., Jorge, I., Perera, C., Blanco, J., Rodríguez-Esparragón, F., (2018) Ozone Therapy as Adjuvant for Cancer Treatment: Is Further Research Warranted? Evidence Based Complement Alternate Medicine doi: 10.1155/2018/7931849 Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151231/
What does this all mean to you:
- The use of Ozone has been noted in scientific labs to shrink tumors by increasing oxygen and blood allowing body’s own defense mechanism to seek and destroy cancer cells.
- Other treatments may be required to fully eradicate the any cancers but there is strong clinical evidence that Ozone through MAH’s (Intravenously) is an excellent way to manage some cancers including Melanoma.
- The use of Ozone for those with poor renal, hepatic, pulmonary, and cardiac function, or when the option to apply the treatment is associated with high-risk toxicity. (meaning a safer option)
- Discussing the use of IV Ozone and extracts of Viscum album with Dr. Kilgore to assess her thoughts on this practice of treating Cancer cells – This treatment showed a significant decrease in plasma values of reactive species metabolites and an increase in biological antioxidant potential.
- Topical Ozone has been clinically proven to increase wound healing. Use on areas that have been compromised due to skin removal to aid in increased healing.