Ozone: a natural bioactive molecule with antioxidant property as potential new strategy in aging and in neurodegenerative disorders
Scassellati C, Galoforo AC, Bonvicini C, et al. Ageing Research Reviews, 2020.
- Study type
- Review
- People studied
- No participants of its own (review)
- Published
- 2020, Ageing Research Reviews
- Identifiers
- PMID 32810649, DOI 10.1016/j.arr.2020.101138
What the authors reported
A review arguing that ozone, through the Nrf2 antioxidant system, could be a new strategy in aging and to delay neurodegeneration. Through what it calls a meta-analytic approach, it reports significant modulation by ozone of endogenous antioxidant-Nrf2 (OR 1.71) and vitagene-Nrf2 (OR 1.80) systems.
What limits this result
A hypothesis-generating review, not a clinical trial. Its pooled odds ratios combine before-and-after marker levels, from human studies for the antioxidant markers and from human, animal, and cell samples for the vitagene markers, with high heterogeneity (I² 97% and 66%); no human outcome links ozone to slower aging. One of its two co-first authors lists the ozone-therapy society SIOOT.
How ozone acts on blood and cells, how blood filters work, the laboratory and device-development studies behind the EBOO circuit, and studies that measure markers in the blood rather than how patients fare. None of these shows whether EBO2 helps patients. One study rarely settles a medical question; our guides weigh each paper against the rest of the evidence.
How the study was done
- Design
- Review presenting scientific background on ozone (O3) as a potential new strategy to delay neurodegeneration
Based on this rationale, in this review we present wide scientific background indicating how a natural bioactive molecule with antioxidant property such as the ozone (O3) can be indicated as a potential new strategy to delay neurodegeneration.
- Setting
- Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy (first author's affiliation)
- Read from
- Read from the full text of the paper. Read on September 28, 2026.
What it measured
- Meta-analysis of the effect of O3 on endogenous antioxidant-Nrf2 and vitagene-Nrf2 systems
- Significant modulation: endogenous antioxidant-Nrf2 p < 0.00001, OR = 1.71 (95%CI 1.17-2.25); vitagene-Nrf2 p < 0.00001, OR = 1.80 (95%CI 1.05-2.55)
Through a meta-analytic approach, we found a significant modulation of O3 on endogenous antioxidant-Nrf2 (p < 0.00001, Odd Ratio (OR) = 1.71 95%CI:1.17-2.25) and vitagene-Nrf2 systems (p < 0.00001, OR = 1.80 95%CI:1.05-2.55).
- Basis of the meta-analyses of oxidative-stress biomarkers
- Performed for these biomarkers on human studies where available (see supplementary material)
- Single-marker results in the endogenous antioxidant-Nrf2 meta-analysis
- Similar results for single markers, except GR (Z = 1.04; p = 0.30) and GSH (Z = 0.80, p = 0.42)
- Heterogeneity across the studies in the meta-analyses
- High heterogeneity in effect size (P < 0.00001, I2 = 97%)
- Heterogeneity across the studies pooled for Nrf2, HO-1 and Hsp70 expression
- High heterogeneity (p < 0.0001, I2 = 66%), attributed to different sources of samples (human, cell and animal models) and different methodology
- Other reported actions of O3
- Activates immune and anti-inflammatory signalling and proteasome, releases growth factors, improves blood circulation, has antimicrobial activity, with potential effects on gut microbiota
- Clinical trial of O2-O3 therapy in a cognitive frailty cohort
- Authors state they have commenced a randomized double-blind clinical trial to test the efficacy of the therapy
- Authors' conclusion
- Further studies are needed; the review reports scientific evidence for building a rationale of using O2-O3 therapy to delay aging processes and neurodegeneration
Safety as reported
The review states that side effects are minimal and that the World Federation of Ozone therapy (WFOT) estimates the incidence of complications at 0.0007%
Source: Full text on PubMed Central
Funding and conflicts
Supported by grants from the Italian Ministry of Health (Ricerca Corrente and RF-2016-02363298)
Source: Full text on PubMed Central
Where we cite this study
Does EBO2 (EBOO) Work? The Evidence, Study by Study
Every study in our EBO2 (EBOO) library in one place: design, size, what was measured and found, its limits, and a check for any study a clinic cites.