Are varnishes based on other fluoride sources more efficacious in preventing or treating dental caries than NaF-based varnish? – A systematic review and meta-analysis

Purpose: this systematic review evaluated the efficacy of fluoride varnishes containing alternative fluoride sources compared with conventional NaF varnish. Methods: two independent reviewers searched seven databases and gray literature up to February 15, 2025. Eligible studies included randomized and non-randomized clinical trials assessing varnishes in primary or permanent teeth for caries prevention or treatment. Risk of bias was assessed with Cochrane RoB2 tool, and certainty of the evidence graded using GRADE. Random-effects meta-analyses estimated the relative risk of lesion inactivation and mean difference in lesion size reduction. Results of 4,290 records screened, ten studies met the inclusion criteria, and two were suitable for meta-analysis. Six studies presented high risk of bias, three moderate, and one low. Alternative fluoride sources identified were difluorosilane, TiF₄, and ammonium fluoride. Only studies comparing TiF₄ with NaF varnish were included in meta-analysis, using ICDAS and QLF outcomes. NaF varnish showed greater efficacy in promoting remineralization (OR = 1.33; 95% CI: 1.03–1.72; I² = 0%; p = 0.03) and inhibiting caries progression (OR = 1.44; 95% CI: 1.04–2.00; I² = 0%; p = 0.03). No significant differences were observed in QLF (OR = 0.17; 95% CI: -0.56–0.90; I² = 65%; p = 0.65). Conclusions NaF appears more efficacious than TiF₄ varnish in preventing caries progression and enhancing remineralization in permanent teeth, although certainty of evidence remains low.