The role of omega-3 polyunsaturated fatty acids in the non-surgical management of periodontitis: a systematic review and meta-analysis

Aim: Omega-3 polyunsaturated fatty acids (PUFA) possess anti-inflammatory and pro-resolving properties, suggesting potential benefits as adjuncts to non-surgical periodontal therapy (NSPT). This systematic review and meta-analysis aimed to evaluate the clinical efficacy of Omega-3 PUFA supplementation, with or without acetylsalicylic acid (ASA), in patients with periodontitis. Methods: Electronic and manual searches were conducted across MEDLINE (PubMed), the Cochrane Central Register of Controlled Trials, and Google Scholar up to September 2025. Randomized controlled trials (RCTs) assessing NSPT combined with Omega-3 supplementation for ≥1 month were included. Primary outcomes were changes in clinical attachment level (CAL) and probing pocket depth (PPD); data were pooled using random-effects models, and risk of bias was assessed with the Cochrane RoB 2 tool. Results: Sixteen RCTs met the inclusion criteria, and nine were included in the quantitative synthesis. Meta-analysis revealed significant improvements in CAL [mean difference (MD) = −0.49 mm; 95% CI −0.75 to −0.23] and PPD (MD = −0.44 mm; 95% CI −0.62 to −0.25) at 3 months, favoring NSPT + Omega-3 over NSPT alone. At 6 months, differences remained favorable and statistically significant for both CAL (MD = −0.58 mm; 95% CI −0.96 to −0.21) and PPD (MD = −0.45 mm; 95% CI −0.76 to −0.14). Conclusions: Adjunctive Omega-3 PUFA supplementation improves short-term periodontal healing following NSPT, yielding modest but clinically meaningful benefits in CAL and PPD. Despite promising results, further standardized RCTs are needed to confirm long-term efficacy and clarify the potential synergistic role of ASA co-administration. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024508208, PROSPERO CRD42024508208.