Zhen Tang, Yunzhen Deng, Gang Guo
Periodontitis is a chronic inflammatory disease driven by dysbiosis and oxidative stress (OS). While various antioxidants have been proposed as adjuncts to non-surgical periodontal therapy (NSPT), individual meta-analyses have reported conflicting results. This umbrella meta-analysis aimed to synthesize the evidence from existing meta-analyses to evaluate the efficacy of local and systemic antioxidants on clinical periodontal outcomes. A systematic search was conducted across PubMed, Scopus, Embase, and Web of Science through May 2026. Meta-analyses of human studies investigating the effects of antioxidants (e.g., curcumin, melatonin, CoQ10, vitamins) on plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were included. A random-effects model was used to calculate the overall effect size, while heterogeneity and publication bias were formally evaluated using established statistical methods. Methodological quality was assessed using the AMSTAR2 tool. A total of 14 meta-analyses were included following systematic screening of 495 retrieved records. Overall, subgroup analyses indicated a significant reduction in GI with melatonin and significant effects for curcumin on CAL on PD. However, no statistically significant improvements were observed on PI (ES = 0.13 (95% CI: - 0.14 to 0.41), GI (ES = 0.046, 95% CI: -0.211 to 0.303), PD (ES = 0.064, 95% CI: -0.341 to 0.468), or CAL (ES = 0.056, 95% CI: -0.269 to 0.280). Subgroup analyses indicated a significant reduction in GI with melatonin and significant effects for curcumin on CAL and PD. Publication bias analyses suggested potential small-study effects for PD and mild asymmetry for GI and CAL, although adjusted estimates remained non-significant. In contrast, antioxidant supplementation significantly reduced BOP (ES = 0.57, 95%CI: 0.44-0.69). Heterogeneity was formally assessed, and sensitivity analyses demonstrated that the overall conclusions remained robust despite attenuation of some pooled estimates after trim-and-fill adjustment. Antioxidants as adjuncts to NSPT provide a significant anti-inflammatory benefit by reducing BOP, but they do not consistently improve structural periodontal outcomes such as PD or CAL. Due to high heterogeneity and the low methodological quality of existing evidence, antioxidants should be considered supportive rather than primary therapeutic agents. Future high-quality, long-term randomized controlled trials are needed to establish standardized protocols for specific antioxidant formulations.