Medical ozone: mechanisms, biological effects and clinical evidence—a narrative review

Medical ozone therapy has been increasingly explored as a potential adjunctive intervention across a range of clinical conditions. This narrative review aims to provide a critical overview of the biological mechanisms, biochemical interactions, and clinical applications of ozone therapy, with particular emphasis on the translational gap between experimental findings and clinical evidence. Ozone exerts its biological effects primarily through the generation of reactive oxygen species (ROS) and lipid ozonation products (LOPs), which act as secondary messengers influencing redox balance, immune responses, inflammation, and cellular metabolism. These mechanisms have been extensively characterized in vitro and in preclinical studies. However, their direct translation into clinically meaningful outcomes remains uncertain. Available clinical data suggest potential benefits of ozone therapy in selected contexts, including wound healing, musculoskeletal disorders, and infection control. Nevertheless, the majority of studies are small, heterogeneous, and often lack rigorous methodological design. High-quality randomized controlled trials are limited, and the overall level of evidence remains low to moderate depending on the indication. Recent systematic reviews and meta-analyses further emphasize the heterogeneity and methodological limitations of the available literature. Importantly, ozone therapy remains controversial within evidence-based medicine, with variability in regulatory acceptance across countries and limited endorsement from major health authorities. Safety data are also constrained by a lack of long-term studies and standardized treatment protocols. In conclusion, while ozone therapy demonstrates biologically plausible mechanisms and promising experimental effects, its clinical efficacy has not been conclusively established. At present, ozone therapy should be regarded as an investigational and adjunctive approach rather than a validated therapeutic modality, and further well-designed clinical trials are required to define its role in clinical practice.