Systemic and local oxidative stress biomarkers in periodontitis: an updated systematic review and meta-analysis

To update and extend our previously published 2019 systematic review by evaluating oxidative stress (OS) biomarkers in saliva, gingival crevicular fluid (GCF), and blood in relation to periodontitis. We systematically searched five electronic databases including PubMed, Scopus, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) up to May 2025. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were pooled to compare biomarker levels between periodontitis patients and healthy controls. A total of 62 studies were included. Notably, substantial between-study heterogeneity (most I 2 > 50%) was detected across pooled analyses. Total antioxidant capacity (TAOC) was significantly reduced in periodontitis patients across all sample types (blood: SMD = –1.94; saliva: SMD = –1.01; GCF: SMD = –2.30). Malondialdehyde (MDA) was elevated in blood (SMD = 1.06), saliva (SMD = 1.63), and GCF (SMD = 2.50). 8-Hydroxy-deoxyguanosine (8-OHdG) and nitric oxide (NO) were significantly elevated in saliva and GCF, and blood and saliva, respectively. Total oxidant status (TOS) was elevated in saliva and GCF but not in blood. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) did not show significant differences. Periodontitis is merely associated rather than causally linked with impaired antioxidant capacity and elevated oxidative stress, particularly in local biofluids. Although saliva and GCF show higher detection sensitivity than blood, such superiority needs further validated by well-designed comparative statistical studies.