Causal effects of serum nutrients and macronutrient intake on periodontitis: A Mendelian randomization study

Observational studies suggest an association between diet and periodontitis, but causality remains unclear. This study employed a Mendelian randomization analysis to investigate the causal effects of nutrients (UK Biobank, N = 64,979; 5 trace elements and 4 vitamins) and dietary patterns (Social Science Genetic Association Consortium, N = 2,68,922; relative carbohydrate intake [E%] (CHO), relative fat intake [E%], relative protein intake [E%]) on periodontitis (gene-lifestyle interactions in dental endpoints, N = 45,563). Using the inverse variance weighted method as the primary model, supplemented by multiple sensitivity analyses to validate robustness. Additionally, potential mechanisms were explored using multivariable Mendelian randomization and mediation analysis. The results indicate causal associations between specific nutrients and reduced periodontitis risk: serum magnesium levels (odds ratio [OR] = 0.900, 95% confidence interval [CI] = 0.829-0.977, P = .011), vitamin B12 levels (OR = 0.881, 95% CI = 0.780-0.994, P = .039), and CHO (OR = 0.728, 95% CI = 0.582-0.910, P = .005). The effects of other exposures were non-significant, and sensitivity analyses supported the robustness of these findings. Multivariable Mendelian randomization further demonstrated that CHO (OR = 0.868, 95% CI = 0.765-0.985, P = .029) remained significantly inversely associated with periodontitis risk after adjusting for other factors. Notably, mediation analysis revealed that body mass index may mediate approximately 23.1% of the effect between CHO and periodontitis. These findings provide evidence relevant to the development of dietary guidelines for the prevention of periodontitis.