Efficacy of antioxidant treatment in the management of oral leukoplakia: systematic review

Abstract

Introduction: Oral leukoplakia is the most common potentially malignant disorder of the oral cavity. Its development and potential malignant transformation have been associated with oxidative stress. In this context, antioxidant treatments have been proposed as a therapeutic strategy to counteract oxidative damage and prevent lesion progression. Objectives: To evaluate the clinical and biochemical efficacy of antioxidant treatments in patients with oral leukoplakia. Material and Methods : A systematic review was conducted following the PRISMA guidelines. An electronic search was performed in the PubMed, Scopus, and Web of Science databases for studies published between 2000 and 2025. Randomized controlled trials, controlled clinical studies, and observational studies assessing the use of topical or systemic antioxidants in patients with oral leukoplakia were included. Results: A total of 11 studies involving 695 patients were included. The most studied antioxidants were lycopene, curcumin, vitamin A, and fenretinide. Most studies reported significant clinical improvements in terms of lesion size reduction or regression. On a biochemical level, a decrease in oxidative stress was observed, evidenced by reductions in LPO, MDA, and 8-OHdG levels, as well as increases in antioxidant enzymes such as catalase (CAT), vitamins C and E. Some studies reported higher apoptosis rates in altered epithelium. Results concerning superoxide dismutase (SOD) were variable. The heterogeneity in study design, dosage, and treatment duration limited direct comparison between studies. Conclusion: Antioxidants represent a promising therapeutic option for managing oral leukoplakia, not only for their ability to improve clinical outcomes but also due to their positive impact on oxidative stress biomarkers. Their inclusion in therapeutic protocols could help reduce the risk of progression to oral carcinoma, although further research is required.