To investigate the relations between caffeine-derived metabolites (methylxanthines) and plasma lipids, by using population-based data from two European countries.
Participants and Methods:
Families were randomly selected from the general population of Northern Belgium (FLEMENGHO), from August 12, 1985, until November 22, 1990, and three Swiss cities (SKIPOGH), from November 25, 2009, through April 4, 2013. We measured plasma (FLEMENGHO, SKIPOGH) and 24h urinary excretions (SKIPOGH) of four methylxanthines: caffeine, paraxanthine, theobromine, and theophylline, using ultra-high performance liquid chromatography tandem mass spectrometry. We used enzymatic methods to estimate total, HDL cholesterol, and triglycerides, and Friedewald equation for LDL cholesterol in plasma. We applied sex-specific mixed models to investigate associations between methylxanthines and plasma lipids, adjusting for major confounders.
In both FLEMENGHO (N=1987, 53% females) and SKIPOGH (N=990, 53% females), total, LDL cholesterol, and triglycerides increased across quartiles of plasma caffeine, paraxanthine, and theophylline (total cholesterol by caffeine quartiles–FLEMENGHO, males: 5.01±0.06, 5.05±0.06, 5.27±0.06, 5.62±0.06; females 5.24±0.06, 5.15±0.05, 5.25±0.05, 5.42±0.05). Similar results were observed using urinary methylxanthines in SKIPOGH (total cholesterol by caffeine-males: 4.54±0.08, 4.94±0.08, 4.87±0.08, 5.27±0.09; females 5.12±0.07, 5.21±0.07, 5.28±0.05, 5.28±0.07). Furthermore, urinary caffeine and theophylline were positively associated with HDL in SKIPOGH males.
Plasma and urinary caffeine, paraxanthine, and theophylline were positively associated with plasma lipids, whereas the associations involving theobromine were less clear. We postulate that the positive association between caffeine intake with plasma lipids may be related to the sympathomimetic function of methylxanthines, mitigating the overall health-beneficial effect of caffeine intake.