FROM OXIDATIVE SIGNALING TO CLINICAL PRACTICE: THE ROLE OF OZONE THERAPY IN SKIN HEALTH

Abstract

Ozone (O₃) is a highly reactive triatomic gas whose bent molecular structure and strong oxidizing capacity underpin its broad biological activity. In physiological systems, O₃ is produced by activated leukocytes and functions as part of antimicrobial defense. Clinically, its instability requires in situ generation, typically via corona discharge applied to medical-grade oxygen. Upon dissolution in aqueous media, O₃ reacts rapidly with polyunsaturated fatty acids, producing hydrogen peroxide (H₂O₂) and lipid oxidation products (LOPs), which act as early and late biological messengers. These compounds activate controlled oxidative pathways that modulate cellular redox status. Therapeutically, O₃ induces mild, transient oxidative stress that activates the Nrf2–ARE pathway, enhances endogenous antioxidant defenses, and downregulates NF-κB–mediated inflammation. Its potent antimicrobial activity arises from oxidation of microbial membrane components, demonstrating efficacy against bacteria, fungi, viruses, and antibiotic-resistant strains. O₃ also promotes wound repair by improving oxygenation, stimulating growth factors (VEGF, TGF-β, FGF2, PDGF), and enhancing fibroblast activation and epithelial–mesenchymal transition. Ozonated oils further support tissue regeneration through sustained release of reactive intermediates. In aesthetic and metabolic applications, O₃ exhibits lipolytic effects through cleavage of fatty acid double bonds, triggering lipid peroxidation and adipocyte breakdown. Clinical studies report reductions in body mass index, waist circumference, submental fat, and lipoma size. Additional benefits include improvements in acne, pigmentary disorders, and photoaging, with increased collagen type I deposition. Despite promising therapeutic potential, standardized protocols remain lacking, and optimal concentrations, dosing frequency, and long-term safety require clarification. Methodological limitations, heterogeneous study designs, and insufficient follow-up hinder definitive conclusions. Precise dosing is critical, as excessive concentrations are toxic while insufficient doses may be ineffective. Overall, O₃ therapy functions as a biomodulatory intervention with antimicrobial, anti-inflammatory, regenerative, and metabolic effects, representing a minimally invasive complementary approach across diverse clinical contexts.

DOI: https://doi.org/10.56238/sevened2026.009-005