A Two-Phase Translational Framework for Personalized Ozone Therapy: From Baseline Clinical Redox Screening to Individualized Ex Vivo Concentration Selection

Background: Medical ozone therapy traditionally relies on standardized concentration protocols. However, interindividual variability in baseline oxidative stress and antioxidant capacity suggests that uniform dosing may be biologically suboptimal. Objective: To evaluate baseline redox heterogeneity in patients with musculoskeletal disorders and investigate whether an ex vivo graded ozone exposure framework using the FRAS5 system can identify personalized optimal redox response. Methods: In Phase 1 (Clinical Screening), baseline derivatives of reactive oxygen metabolites (d-ROMs), plasma antioxidant test (PAT), and the Oxidative Stress Index (OSI REDOX) were profiled in 11 symptomatic participants presenting with active pain. In Phase 2 (Ex Vivo Evaluation), whole blood samples from 9 consecutive participants were exposed to graded ozone concentrations (10–40 μg O3/mL O2) to map individual response curves. Results: Phase 1 revealed profound baseline heterogeneity despite identical clinical pain presentations, with OSI REDOX values varying nearly threefold (41–108), confirming highly divergent homeostatic starting points. Phase 2 ex vivo titration demonstrated non-linear, participant-specific redox trajectories. Multiple participants exhibited classic bi-phasic (hormetic) responses, achieving optimal OSI REDOX scores at intermediate concentrations (20–25 μg O3/mL O2), while higher concentrations triggered oxidative rebound or loss of antioxidant defense. Conclusion: Fixed ozone protocols fail to account for distinct individual redox profiles. Integrating baseline screening with ex vivo prospective profiling might offer a clinically accessible translational framework for biomarker-guided, personalized ozone concentration selection, after being confirmed in a larger cohort study.