"The O2-O3 therapy is a non-invasive, non-pharmacological, no-side effect and low-cost procedure applied in medicine for the treatment of more than 50 pathological processes, whose alterations in endogenous oxidative-antioxidative balance play a crucial role . Different clinical trials evidenced the effectiveness of this therapy in the treatment of degenerative disorders such as multiple sclerosis (Smith et al., 2017, Delgado-Roche et al., 2017, Ameli et al., 2019), but also cardiovascular, peripheral vascular, neurological, orthopedic, gastrointestinal and genitourinary pathologies (Bocci, 2011, Elvis, Ekta, 2011, Re et al., 2008, Bocci, 2012, Smith et al., 2017, Braidy et al., 2018); fibromyalgia (Moreno -Fernandez et al., 2019, Tirelli et al., 2019); skin diseases / wound healing (Fitzpatrick et al., 2018, Wang, 2018); diabetes / ulcers (Martinez-Sanchez et al., 2005, Guclu et al. ., 2016, Rosul, Patskan, 2016, Izadi et al., 2019, Ramirez-Acuna et al., 2019); infectious diseases (Smith et al., 2017, Mandhare et al., 2012, Song et al., 2018), including the recent global pandemic disease of coronavirus disease 2019 (COVID-19) (Zheng et al., 2020); dentistry (Isler et al., 2018, Khatri et al., 2015, Srikanth et al., 2013, Azarpazhooh et al., 2009); lung diseases (Hernandez Rosales et al., 2005); osteomyelitis (Bilge et al., 2018). The potential role of O2-O3 as an adjuvant therapy for cancer treatment has been also suggested in in vitro and animal studies as well as in isolated clinical reports (Clavo et al., 2018).
At present, we have commenced a randomized double-blind clinical trial with the aim to test the efficacy of this therapy in a cognitive frailty cohort, a grant approved by the Italian Minister of Health (RF-2016-02363298). This pilot study will permit to validate the O2-O3 therapy in an early phase of cognitive decline, when it is still possible to intervene, before to develop a potential neurodegenerative pathology.
To date, the O2-O3 therapy acquires a further prestigious significance, after the medicine Nobel prize for "discovery of how cells sense oxygen" in 2019. Indeed, O2 is the most vital element required for human life and it is the key to good health; O3 is O2 with an extra molecule added. The O2 availability affects genes expression of different factors (HIFs, Hypoxia Inducible Factors), leading to the activation of trophic proteins (VEGF, Vascular Endothelial Growth Factor; PDGF, Platelet-derived growth factor) and consequently to specific biological processes, including erythropoiesis, angiogenesis and anaerobic glucose metabolism (Zhou et al., 2019). O3 plays a role of cellular adapter to hypoxia, because it is well known its effects in increasing the levels of VEGF, PDGF, HIF (Curro et al., 2018, Zhang et al., 2014, Re et al., 2010), exactly as the cell does when there is no O2 available ".