Impact of systemic resveratrol on non-surgical periodontal treatment of smokers: A 12-month randomized clinical trial.

2025-08-30
Clinical oral investigations 29(9)
- Vanessa Haguihara Lucchesi
- Ana Paula Oliveira Giorgetti
- Mônica Grazieli Corrêa
- Vanessa G A Pecorari
- Bruno Braga Benatti
- Howard C Tenenbaum
- Fabiano Ribeiro Cirano
- Suzana Peres Pimentel
- Márcio Zafallon Casati

PubMed: 40884630
DOI: 10.1007/s00784-025-06517-9

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 19
Population: 38 smoking patients with periodontitis
Methods: Randomized, placebo-controlled, 180 days of systemic RSV (500 mg/day) or placebo adjunct to full-mouth ultrasonic debridement
Duration: 180 days
Funding: Unclear

Objective

Smoking patients demonstrate an elevated risk of periodontitis development and respond poorly to periodontal therapy as compared to nonsmokers, and resveratrol (RSV) demonstrated a positive effect in the reduction of periodontitis progression in both animal and clinical trials. However, to the authors' knowledge, no clinical study has assessed the impact of resveratrol under smoking conditions. Thus, this trial aimed to evaluate the effect of systemic administration (SA) of RSV adjunct to full-mouth ultrasonic debridement (FMUD) of periodontitis smoking patients (PSP).

Materials and methods

Thirty-eight individuals were randomly assigned to two groups:Placebo ( n = 19) -FMUD and placebo for 180 days; RSV ( n = 19) FMUD and RSV (500 mg/day) for 180 days. Clinical and immunoinflammatory outcomes were assessed at baseline, 3-, 6-, and 12-months post-therapy, and microbiological outcomes were evaluated at baseline, 3-, 6- months post-therapy.

Results

RSV appeared to induce lower PD [2.96 (0.41) - 3 months; 2.85 (0.40) - 6 months; 2.80 (0.35)- 12 months], CAL [4.02 (0.90) - 3 months; 4.04 (0.81) - 6 months; 3.87 (0.78) - 12 months], and PMG [2.20 (0.56) - 3 months; 2.28 (1.14) - 6 months; 2.32 (3.27) - 12 months] readings as compared to Placebo [PD: 3.22 (0.51) - 3 months; 3.07 (0.42) - 6 months; 3.02 (0.42) - 12 months; CAL: 4.43 (0.99) - 3 months; 4.24 ((0.89) - 6 months; 4.39 (0.93) - 12 months; PMG: 2.50 (0.50) - 3 months; 2.53 (0.45) - 6 months; 2.67 (0.46) - 12 months] throughout the time (p < 0.05). The concentration of Aggregatibacter actinomycetemcomitans (Aa) was significantly higher in moderate [2.29 (1.10); 1.61 (1.02) for PL and RSV, respectively] and deep PD [2.39 (1.14); 1.73 (0.90) for PL and RSV respectively] at 3 months for the Placebo group (p < 0.05). Additionally, Aa levels were lower at 6 months in the deep sites for the RSV group (p < 0.05) [1.77 (0.94); 2.23 (1.08) for PL and RSV, respectively]. Immunoinflammatory analysis showed lower levels of IL-1β at 3-month periods in deep sites in the RSV group [92.6 ± 84.2; 35.36 (52.92) for PL and RSV, respectively] and lower concentrations of IL-6 in the RSV group at 3 and 12 months in both moderate [8.11 (9.50); 4.67 (4.20) - 3 months for PL and RSV, respectively; 8.01 ± 3.52; 5.33 (4.14) - 12 months for PL and RSV, respectively]; and deep sites [4.69 (3.06); 3.57 (3.73) - 3 months for PL and RSV, respectively]; 3.50 (2.67); 2.10 (0.89) - 12 months for PL and RSV, respectively] (p < 0.05).

Conclusion

In conclusion, systemic administration of RSV improves clinical results and modulates IL-1β at 3 months, IL-6 at 3- and 6- months, in deep sites of smoking patients when associated with FMUD.

Trial registration

Rebec identifier https//ensaiosclinicos.gov.br/rg/RBR3gt65c.

Research Insights

Resveratrol→Improved Clinical Attachment
RSV appeared to induce lower ... CAL [4.02 (0.90) - 3 months; 4.04 (0.81) - 6 months; 3.87 (0.78) - 12 months] ... as compared to Placebo [CAL: 4.43 (0.99) - 3 months; 4.24 ((0.89) - 6 months; 4.39 (0.93) - 12 months] throughout the time (p < 0.05).
Effect
Beneficial
Effect size
Small
Dose
500 mg/day
Resveratrol→Reduced Aggregatibacter actinomycetemcomitans Level
The concentration of Aggregatibacter actinomycetemcomitans (Aa) was significantly higher in moderate [2.29 (1.10); 1.61 (1.02) for PL and RSV, respectively] and deep PD [2.39 (1.14); 1.73 (0.90) for PL and RSV respectively] at 3 months for the Placebo group (p < 0.05). Additionally, Aa levels were lower at 6 months in the deep sites for the RSV group (p < 0.05) [1.77 (0.94); 2.23 (1.08) for PL and RSV, respectively].
Effect
Beneficial
Effect size
Small
Dose
500 mg/day
Resveratrol→Reduced Interleukin-1 Beta Level
Immunoinflammatory analysis showed lower levels of IL-1β at 3-month periods in deep sites in the RSV group [92.6 ± 84.2; 35.36 (52.92) for PL and RSV, respectively] ... (p < 0.05).
Effect
Beneficial
Effect size
Moderate
Dose
500 mg/day
Resveratrol→Reduced Interleukin-6 Levels
lower concentrations of IL-6 in the RSV group at 3 and 12 months in both moderate [8.11 (9.50); 4.67 (4.20) - 3 months for PL and RSV, respectively; 8.01 ± 3.52; 5.33 (4.14) - 12 months for PL and RSV, respectively]; and deep sites [4.69 (3.06); 3.57 (3.73) - 3 months for PL and RSV, respectively]; 3.50 (2.67); 2.10 (0.89) - 12 months for PL and RSV, respectively] (p < 0.05).
Effect
Beneficial
Effect size
Moderate
Dose
500 mg/day
Resveratrol→Reduced Plaque Index
RSV appeared to induce lower ... PMG [2.20 (0.56) - 3 months; 2.28 (1.14) - 6 months; 2.32 (3.27) - 12 months] readings as compared to Placebo [PMG: 2.50 (0.50) - 3 months; 2.53 (0.45) - 6 months; 2.67 (0.46) - 12 months] throughout the time (p < 0.05).
Effect
Beneficial
Effect size
Small
Dose
500 mg/day
Resveratrol→Reduced Probing Depth
RSV appeared to induce lower PD [2.96 (0.41) - 3 months; 2.85 (0.40) - 6 months; 2.80 (0.35)- 12 months] ... as compared to Placebo [PD: 3.22 (0.51) - 3 months; 3.07 (0.42) - 6 months; 3.02 (0.42) - 12 months] throughout the time (p < 0.05).
Effect
Beneficial
Effect size
Small
Dose
500 mg/day