Causal association of genetically determined caffeine intake from tea or coffee with bone health: a two-sample Mendelian randomization study

Background Relationship of caffeine intake and consumption of caffeinated beverages, such as tea and coffee, with bone health remains controversial. This study aimed to evaluate whether genetically determined caffeine intake from tea or coffee has causal effects on overall total body bone mineral density (TB-BMD) and fracture. We also assessed the association with TB-BMD in five age strata.Methods Using two-sample Mendelian randomization approach, summary statistics were retrieved from genome-wide association studies (GWAS)/GWAS meta-analyses of caffeine intake from tea (n = 395 866)/coffee (n = 373 522), TB-BMD (n = 66 628), and fracture (n = 426 795). Inverse variance weighted method was adopted as the main univariable analysis. Multivariable analysis was conducted to evaluate whether the causal effect is independent.Results In univariable analysis, genetically determined caffeine intake from tea had positive association with overall TB-BMD (per SD increase in genetically determined caffeine intake, beta of TB-BMD [in SD]: 0.166; 95% confidence interval (CI): 0.006-0.326) and inverse association with fracture (OR = 0.79; 95% CI: 0.654-0.954). Genetically determined caffeine intake from coffee was also positively associated with overall TB-BMD (beta = 0.231; 95% CI: 0.093-0.369). The association remained significant after adjustment for smoking in multivariable analysis. Genetically determined caffeine intake from tea or coffee was both positively associated with TB-BMD in the age strata of 45-60 years, but we lacked evidence of association in other strata.Conclusions Genetically, caffeine intake from tea or coffee may be beneficial to bone health. Due to the ascertainment method of caffeine intake from tea, our study also implied genetically higher tea consumption may improve TB-BMD and lower fracture risk. What is already known on this topic Published studies demonstrated controversial findings on the relationship of caffeine intake and consumption of caffeinated beverages, such as tea and coffee, with bone health. What this study adds This two-sample Mendelian randomization study demonstrated that genetically determined caffeine intake from tea or tea consumption was causally associated with improved overall TB-BMD and reduced fracture risk. Genetically determined caffeine intake from coffee was also positively associated with overall TB-BMD. How this study might affect research, practice or policy Caffeine and other active ingredients in tea may improve bone health. Tea may be included in the diet as a strategy to improve BMD and prevent osteoporosis-associated fracture.