Ozone Therapy as Adjuvant for Cancer Treatment: Is Further Research Warranted?

Abstract

Introduction This article provides an overview of the potential use of ozone as an adjuvant during cancer treatment. Methods We summarize the findings of the most relevant publications focused on this goal, and we include our related clinical experience. Results Over several decades, prestigious journals have published in vitro studies on the capacity of ozone to induce direct damage on tumor cells and, as well, to enhance the effects of radiotherapy and chemotherapy. Indirect effects have been demonstrated in animal models: immune modulation by ozone alone and sensitizing effect of radiotherapy by concurrent ozone administration. The effects of ozone in modifying hemoglobin dissociation curve, 2,3-diphosphoglycerate levels, locoregional blood flow, and tumor hypoxia provide additional support for potential beneficial effects during cancer treatment. Unfortunately, only a few clinical studies are available. Finally, we describe some works and our experience supporting the potential role of local ozone therapy in treating delayed healing after tumor resection, to avoid delays in commencing radiotherapy and chemotherapy. Conclusions In vitro and animal studies, as well as isolated clinical reports, suggest the potential role of ozone as an adjuvant during radiotherapy and/or chemotherapy. However, further research, such as randomized clinical trials, is required to demonstrate its potential usefulness as an adjuvant therapeutic tool.

Modulation of Oxidative Stress by Ozone Therapy in the Prevention and Treatment of Chemotherapy-Induced Toxicity: Review and Prospects

“…There is a rational support for a potential enhancing effect of the "chemotherapy + ozone" combination as we have described in a recent review, which merits further research [87]. However, this potential and controversial combination during cancer treatment should not be hugely relevant for patients in the following situations:…”

Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19

“…Among patients with pneumonia caused by SARS-CoV-2, fever was the most common symptom, followed by cough, malaise and dry cough at the prodromal phase [5]. Bilateral lung involvement with ground-glass opacity was the most common finding from computed clinical evidence to support the potential role of OT in the prevention and management of cytotoxicity induced by different drugs and diseases including viral diseases [21][22][23][24]. The main mechanism is related to the modulation of the oxidative stress and pro-inflammatory cytokines.…”

“…These byproducts of the reaction act as secondary messengers and induce a further adaptive hormetic responses [56][57][58]. Ozone at a therapeutic dose "only acts" as a modulator or pro-drug and, by inducing secondary messengers, will enhance subsequent adaptive responses [21].…”

“…In addition, 4-HNE also sends a signal of transient oxidative stress and its effects depend on concentration as well as cell/tissue origin. This pathway can activate the synthesis of several substances such as: γ-glutamyl transferase, γ-glutamyl transpeptidase, HSP-70, HO-1, and antioxidant enzymes such as SOD, GPx, CAT and glucose-6-phosphate dehydrogenase [21]. In addition, these pluripotent effects of 4-HNE can be explained by its concentration-dependent interactions with the cytokine networks and complex cellular antioxidant systems also showing cell and tissue specificities [59,63].…”

Ozone Therapy: Overview of its Potential Utility in Male Reproduction

“…In autohemotherapy, small amount of blood is collected from the patient, then exposed ex vivo to ozone then infused back into the patient (Smith et al, 2017). Because ozone is a potent oxidant and a highly reactive molecule, it has strong bactericidal, antiviral, anti-fungal and antiprotozoalactions (Duricic et al, 2015;Yamayoshi and Tatsumi, 1993;Sugita et al, 1992;Sato et al, 1990) as well as other therapeutic effects (Duricic et al, 2015;Yamayoshi and Tatsumi, 1993;Sugita et al, 1992;Sato et al, 1990;Clavo et al, 2018;Kashiwagi et al, 2001). Due to the advantage of its multifaceted route of administration, ozone has been used to treat several pathologies such as cancers (Clavo et al, 2018;Dogan et al, 2018), bad abscesses (Karatieieva et al, 2017;Li et al, 2018) and chronic wounds (Fitzpatrick et al, 2018), skin diseases[such as acne (Gloor and Lipphardt, 1976), eczema (Kosheleva and Kulikov, 2001) and psoriasis (Evstigneeva et al, 2018), HIV infection (Garber et al, 1991;Carpendale et al, 1993;Frankum and Katelaris, 1993;OPOI, 1994), fibromyalgia (Hidalgo-Tallon et al, 2013), asthma (Turner et al, 1989), inflammatory conditions (Kucukgul et al, 2016) including arthritis (Raeissadat et al, 2018;Manoto et al, 2018), cardiac conditions (Buyuklu et al, 2017), liver disorders (Safwat et al, 2014;Tezcan et al, 2018), eye disorders (Kaya et al, 2017), urinary tract pathologies (Tasdemir et al, 2013), dyslipidemia…”