Ozone therapy and the role of the glutathione pathway

Oxygen-ozone therapy (OOT) represents a multi-target intervention that engages redox modulation, endothelial repair, nitric oxide bioavailability, and immune reprogramming. In contrast, intravenous glutathione (IV-GSH) provides only transient antioxidant support without activating upstream adaptive pathways. Using an ODE-based mechanistic model, we evaluated the contribution of the GSH/GSSG system against other ozone-activated networks. Sensitivity analysis demonstrated that GSH/GSSG accounts for only a minor fraction of the therapeutic benefit (< 10% in adults, ~ 2% in elderly), while endothelial/NO and Nrf2-driven adaptive responses dominate. Forecasted recovery trajectories over six months showed ozone rapidly drives near-complete recovery, whereas IV-GSH plateaus at negligible improvements. These results highlight that OOT is not a simple antioxidant therapy but a systemic bioregulatory treatment, particularly effective in immune, inflammatory, nociceptive, and degenerative disorders. Glutathione plays a supportive role but cannot substitute ozone's multi-pathway efficacy.