The role of salivary lactoferrin as a potential biomarker for periodontal disease: a systematic review and meta-analysis

Aim – To systematically review and meta-analyse the diagnostic potential of salivary lactoferrin for periodontal disease monitoring. Materials and methods – A comprehensive electronic search was conducted across five databases without time restrictions, up to January 2026. Studies quantifying lactoferrin in saliva or gingival crevicular fluid in individuals with clinically diagnosed periodontal disease were included. Eligible designs were case-control and longitudinal pre-post intervention studies. Risk of bias was assessed via the Newcastle-Ottawa Scale for case control studies and ROBINS-I tool for intervention studies, and evidence certainty was graded using GRADE. Meta-analysis with stratified subgroup analyses was performed to explore inter-study variability. Results – Nineteen studies were included and 11 contributed to the meta-analysis. Compared to periodontally healthy subjects, lactoferrin levels were significantly higher in individuals with periodontal disease: Ratio of Means (ROM) = 1.77 (95% CI: 1.44–2.24) in unstimulated saliva, ROM = 2.14 (95% CI: 1.38–3.32) in stimulated saliva, and ROM = 8.63 (95% CI: 2.68–27.87) in gingival crevicular fluid. Lactoferrin levels decreased after mechanical periodontal treatment, notably in gingival crevicular fluid. Considerable methodological heterogeneity and variable study quality were noted. Meta-analysis of intervention studies was not feasible due to inconsistent protocols and reporting. Conclusion – Elevated lactoferrin levels in periodontitis and their reduction post-treatment highlights its potential as a biomarker for periodontal disease monitoring. However, methodological standardization and robust studies are needed to confirm clinical applicability. Systematic Review Registration – identifier: CRD420251017848.