Oxidative stress and antioxidant markers in oral leukoplakia: a systematic review and meta-analysis

Objective Oral leukoplakia (OLK) is a common possibly malignant condition of the oral cavity, oxidative stress (OS) are intrinsically linked to the initiation and progression of carcinogenesis. However, previous studies on the changes of various OS and antioxidant markers in patients with OLK and their diagnostic value have been inconsistent, and there is a lack of systematic comparison and evaluation. This study aims to systematically evaluate and compare the status of OS and antioxidant markers in patients with OLK versus healthy controls to identify potential biomarkers for early diagnosis. Methods A comprehensive electronic search was conducted across PubMed, Embase, Web of Science, and the Cochrane Library to identify case–control studies investigating antioxidant and OS markers in OLK patients compared to healthy individuals from database inception to May 1, 2025. Results Twelve studies were selected for inclusion in this meta-analysis. The analysis focused on five pro-oxidant substances and antioxidant state markers. Our findings revealed that the level of malondialdehyde (MDA) higher in patient with OLK (MD: 0.26, 95% CI: 0.22 to 0.3, p 0.02, I 2 = 63%), while the levels of key antioxidants, including serum glutathione (GSH, MD: −8.6, 95% CI: −12.97 to −4.23, p 0.00001), superoxide dismutase (SOD, MD: −6.25, 95% CI: −11.45 to −1.05, p = 0.02), glutathione peroxidase (GPx, MD: −9.27, 95% CI: −15.72 to −2.82, p = 0.005), and catalase (CAT, MD: −25.71, 95% CI: −40.09 to −11.33, p = 0.0005), were lower in patient with OLK. Conclusion This meta-analysis suggests that OS may be involved in the pathogenesis of OLK. The pooled analysis indicates a potential disruption of redox balance in patients with OLK. These findings provide a basis for further investigation into the mechanisms linking OS to OLK pathogenesis. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/#myprospero , CRD42025642682.