Association Between Oxidative Stress Biomarkers and Periodontitis in Saliva and Gingival Crevicular Fluid: A Systematic Review and Meta-Analysis

Aim: This systematic review aimed to synthesize current observational evidence on the association between oxidative stress (OS) biomarker levels in saliva and gingival crevicular fluid (GCF) and periodontitis. Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched from 2000 to 2026. Two reviewers independently screened studies and extracted data. Inter-rater reliability was assessed using Cohen's kappa and percent agreement. Publication bias was investigated using Egger's test. Results: Out of 1695 records, 31 prospective studies and 54 cross-sectional studies met the inclusion criteria. In the primary analyses, periodontitis was associated with higher total oxidant status (TOS), malondialdehyde (MDA), and 8-hydroxy-deoxyguanosine (8-OHdG) levels and lower total antioxidant capacity (TAC) in both saliva and GCF. In GCF, superoxide dismutase (SOD) and glutathione (GSH) levels were lower, whereas glutathione peroxidase (GPX) was higher. No significant differences were found for salivary SOD, GSH, GPX, or glutathione reductase (GR) in the primary analyses. However, after trim-and-fill adjustment, the initially significant salivary TAC and 8-OHdG associations were no longer statistically significant. Substantial heterogeneity was observed among evaluated studies. Conclusions: This meta-analysis supports an association between periodontitis and altered OS biomarker levels in saliva and GCF. Trial Registration: PROSPERO: CRD420251154372.