The Impact of Genetic Variability on the Relationship between Caffeine and Cardiometabolic Outcomes: A Systematic Review

The relationship between caffeine consumption and cardiometabolic health has been reported, albeit with heterogenous results. Discrepancies in study results may be due to inter-individual variability between study participants. This systematic review aimed to identify the impact of genetics on the relationship between caffeine consumption and cardiometabolic outcomes. Electronic databases (PubMed and EMBASE) were searched for studies published until July 2021. Selected studies were of both intervention and observational design and included: 1) analysis of at least one of the selected cardiometabolic outcomes (type 2 diabetes, glucose/insulin levels, cardiovascular disease, blood pressure or hypertension, blood lipids and catecholamines levels), 2) adults aged 18-65 and 3) genetic analysis of individuals consuming caffeine. Seventeen studies were included: four randomised controlled trials and an interventional and quasi-experimental study, six population-based prospective cohort studies, three cross-sectional studies and three case-control studies. CYP1A2 rs762551 and .ADORA rs5751876 were associated with glucose response when caffeine was consumed with carbohydrates. CYP1A2 rs762551 moderated the association between coffee intake and hypertension. Moreover, ADORA2A rs5751876 and the ADRA2B I variants moderated the associations between caffeine and blood pressure. Studies that investigated the effects of genetic variations on cardiovascular disease and caffeine consumption reported equivocal findings (CYP1A2) or warrant replication (COMT, ADORA, and TRIB1). Elucidating the extent to which these genes moderate the association between caffeine and cardiometabolic outcomes will enable caffeine consumption advice to be tailored to specific individuals to optimise health.