Caffeine and caffeine metabolites in relation to hypertension in US adults

Background/Objectives Most studies assessing the association between coffee consumption and hypertension ascertained caffeine intake in terms of number of cups per days, and yield mixed results. Although the inter-individuals variability in the caffeine metabolism is known, the relation of caffeine metabolites with hypertension remains unsettled. We examined the association of caffeine and 13 direct and indirect caffeine metabolites with hypertension in U.S. adults. Methods Using data from 2009-2010 National Health and Nutrition Examination Survey, we included 2278 individuals aged 18 to 80 years. Urinary methyluric acids (MU) and methylxanthines (MX) products of caffeine metabolism were measured using high performance liquid chromatography-electrospray ionization-tandem quadrupole mass spectrometry. We used multivariate logistic regression to model hypertension (systolic blood pressure >= 130 mmHg or diastolic blood pressure >= 80 mmHg) as functions of urinary coffee metabolites. Results The odds of hypertension decreased across quartiles of 3-MU, 7-MU, 3-MX and 7-MX, with 7-MU being the more powerful metabolite. Compared with adults in the bottom quartile of 7-MU, the odds of hypertension decreased by 81% (95% CI: -90 to -22%) in those in the upper quartile. In contrast, the odds ratio for being hypertensive from the bottom to the upper quartile were 4.47 (95% CI: 1.21-16.50) for 1,3-dimethyluric acid, 4.45 (95% CI: 1.48-13.39) for 1,3-dimethylxanthine, and 5.08 (95% CI: 1.11-23.36) for 1,7-dimethylxanthine. Neither insulin resistance nor abdominal obesity were moderators in these associations. Conclusions Final metabolites of caffeine (namely 3-MU, 7-MU, 3-MX and 7-MX), but not caffeine, significantly reduce the odds for hypertension in this population.