Associations of urinary caffeine and caffeine metabolites with metabolic syndrome in U.S. adults

Abstract

Abstract The relationship between caffeine and metabolic syndrome (MetS) has only been evaluated from the perspective of caffeine intake, however, the association between urinary caffeine and MetS is still unclear. This study examines the associations between urinary caffeine and its metabolites and MetS and its components among adults. Data from the US National Health and Nutrition Examination Survey (NHANES) 2011–2014 was analyzed. NHANES is a stratified, multi-stage survey of all non-institutionalized persons in the United States. A total of 2394 subjects without missing data and aged ≥18 years were selected in this study. Urinary caffeine and 14 of its metabolite levels are quantified by the use of high-performance liquid chromatography-electrospray ionization-tandem quadrupole mass spectrometry (HPLC-ESI-MS/MS) with stable isotope-labeled internal standards. We performed principal components analysis (PCA) to investigate the underlying correlation structure of these fifteen features of urinary caffeine and its metabolites and used these principal components (PCs) as independent variables to conduct logistic regression analysis with or without restricted cubic splines (RCS) terms to explore the associations between caffeine metabolites and MetS. Two main PCs that derived from PCA explained 90.67% of the total variance of caffeine and its metabolites. The first PC (PC1, strongly correlated with 1-MU, 1,3-DMU, 1,7-DMU, 1,3,7-TMU, 1-MX, 1,3-DMX, 1,7-DMX, 1,3,7-TMX and AAMU) was positively correlated with risk of MetS (OR=1.27, P<0.001) and all its components (all ORs>1, all P-values<0.001) in the unadjusted models, while in the adjusted models, it was positively correlated with MetS (OR=1.16, P=0.042) and central obesity (OR=1.22, P<0.001). In the unadjusted model, there were significant associations between the second PC (PC2, correlated with 3-MU, 7-MU, 3,7-DMU, 3-MX, 7-MX and 3,7-DMX) and MetS (OR=1.11, P=0.030) and central obesity (OR=1.16, P<0.001), while in the adjusted models, PC2 was positively associated with MetS (OR=1.15, P=0.035) and central obesity (OR=1.15, P=0.005), and negatively associated with raised triglycerides (TG) (OR=0.84, P=0.008). Moreover, we observed U-shaped associations between PC1 and the risk of raised TG both in unadjusted (Pnon-linear = 0.017) and adjusted (Pnon-linear = 0.014) models. Urinary caffeine metabolites were positively associated with the risk of MetS and its components through a variety of linear or non-linear patterns. Excessive consumption of coffee increases the risk of developing MetS and its related diseases.