Effect of switching to combustion-free nicotine delivery systems on salivary c-reactive protein levels in smokers with gingivitis or mild periodontitis: a randomized controlled trial

Abstract

Abstract Background Smoking is a significant risk factor for periodontal disease and is associated with elevated salivary C-Reactive Protein (CRP), a marker of local inflammation. Combustion-free nicotine delivery systems (CFNDS) reduce exposure to certain combustion-derived toxicants compared with conventional cigarettes, but their effects on oral inflammatory biomarkers remain poorly characterized. Methods This parallel-group, open-label randomized controlled trial enrolled 37 adult smokers with gingivitis or mild periodontitis between July–December 2022. Participants were randomized 1:1 to either switch to CFNDS ( n = 22; RELX ® or IQOS ® ) or continue smoking conventional cigarettes ( n = 15). All participants underwent baseline professional scaling and oral hygiene instruction. The primary outcome was change in unstimulated salivary CRP measured by high-sensitivity ELISA at baseline and six months. Within-group changes were evaluated using paired t-tests; between-group differences were assessed with independent-samples t-tests and analysis of covariance. Results All 37 participants completed the study period with 100% retention of the analyzed sample. Baseline characteristics were comparable between groups, including age ( p = 0.408), gender distribution ( p = 1.000), and baseline exhaled carbon monoxide levels confirming active smoking status ( p = 0.966). Contrary to hypothesis, both groups demonstrated significant increases in salivary CRP: CFNDS group increased + 1.04 ± 1.09 ng/mL (t₂₁ = 4.483, p = 0.0002), control group increased + 0.64 ± 0.76 ng/mL (t₁₄ = 3.267, p = 0.0056). Between-group difference was not statistically significant (t₃₅ = 1.223, p = 0.2297; 95% CI: −0.263, 1.060). Analysis of covariance adjusting for baseline CRP confirmed no significant group effect (F₁,₃₄ = 3.53, p = 0.069). Conclusions Switching to CFNDS for six months was not associated with reduction in salivary CRP levels compared with continued combustible tobacco smoking. Both groups showed significant CRP increases, likely reflecting post-scaling rebound. These findings do not support CFNDS as an evidence-based strategy for reducing periodontal inflammatory burden in the short term. Longer-duration RCTs with clinical periodontal endpoints are warranted before any therapeutic claims can be made. Trial registration UMIN Clinical Trials Registry, UMIN000051684. Registered on 21 July 2023. Retrospectively registered.