Habitual Coffee, Tea, and Caffeine Consumption, Circulating Metabolites, and the Risk of Cardiometabolic Multimorbidity.

CONTEXT Cardiometabolic multimorbidity (CM) is an increasing public health concern. Previous observational studies have suggested inverse associations between coffee, tea, and caffeine intake and risks of individual cardiometabolic diseases; however, their associations with CM and related biological markers are unknown. METHODS This prospective study involved 172 315 (for caffeine analysis) and 188 091 (tea and coffee analysis) participants free of any cardiometabolic diseases at baseline from the UK Biobank; 168 metabolites were measured among 88 204 and 96 393 participants. CM was defined as the coexistence of at least 2 of the following conditions: type 2 diabetes, coronary heart disease, and stroke. RESULTS Nonlinear inverse associations of coffee, tea, and caffeine intake with the risk of new-onset CM were observed. Compared with nonconsumers or consumers of less than 100 mg caffeine per day, consumers of moderate amount of coffee (3 drinks/d) or caffeine (200-300 mg/d) had the lowest risk for new-onset CM, with respective hazard ratios (95% CIs) of 0.519 (0.417-0.647) and 0.593 (0.499-0.704). Multistate models revealed that moderate coffee or caffeine intake was inversely associated with risks of almost all developmental stages of CM, including transitions from a disease-free state to single cardiometabolic diseases and subsequently to CM. A total of 80 to 97 metabolites, such as lipid components within very low-density lipoprotein, histidine, and glycoprotein acetyls, were identified to be associated with both coffee, tea, or caffeine intake and incident CM. CONCLUSION Habitual coffee or caffeine intake, especially at a moderate level, was associated with a lower risk of new-onset CM and could play important roles in almost all transition phases of CM development. Future studies are warranted to validate the implicated metabolic biomarkers underlying the relation between coffee, tea, and caffeine intake and CM.