Effects of Resveratrol Supplementation as an Adjunct to Nonsurgical Periodontal Therapy: A Systematic Review and Meta-analysis

Background: Periodontitis is a chronic inflammatory disease often indicated by the gradual obliteration of the attachment apparatus of teeth. Nonsurgical periodontal therapy (NSPT) is substratum in the management of periodontitis, but adjunctive interventions can be an additive to treatment outcomes. A polyphenolic compound named resveratrol, with antioxidant, anti-inflammatory, and antimicrobial properties, has drawn attention for its potential advantages in periodontal therapy. Aim: This systematic review aims to investigate the effects of resveratrol supplementation as an adjunct to nonsurgical periodontal therapy, whether it improves periodontal parameters. Methods: This review was registered in PROSPERO (CRD420251028237) and follows PROSPERO 2020 guidelines. An extensive and systematic literature search was conducted from inception to September 25, 2024, across major electronic databases, including PubMed, EBSCO, Cochrane Library, and Google Scholar. Cochrane risk-of-bias 2 tool was utilized to evaluate the risk of bias. Randomized controlled studies assessing the impact of resveratrol supplementation in conjunction with NSPT on clinical parameters such as periodontal probing depth (PPD), clinical attachment level (CAL), bleeding on probing, and inflammatory markers included among periodontitis patients. Meta-analysis was evaluated using RevMan 5.4. Subgroup analyses were performed based on resveratrol dosage and patient condition (e.g., diabetes and smoking). Results: Seven RCTs ( n = 402 patients) met the inclusion criteria. Meta-analysis showed that adjunctive resveratrol significantly improved PPD (MD: –0.42 mm; 95% CI: –0.59 to -0.25; I ² = 99%), CAL (MD: –0.36 mm; 95% CI: –0.52 to –0.19; I ² = 98%) and IL-6 (MD: –0.40; 95% CI: –0.65 to –0.15; I 2 = 93%) compared to NSPT alone. Subgroup analysis indicated greater efficacy at dosages ≥480 mg/day and in patients with systemic conditions like diabetes. The risk of bias was low in four studies and had some concerns among three. GRADE assessment indicated moderate certainty of evidence. However, variations in study design, dosage, and follow-up duration necessitate cautious interpretation of results. Conclusion: Resveratrol as an adjunct appears to improve the efficacy of NSPT by improving clinical periodontal outcomes. While the current evidence is promising, further well-designed randomized controlled trials with standardized protocols are required to establish definitive clinical recommendations.