Metabolic profiling of alcohol consumption in 9778 young adults

ABSTRACT Background High alcohol consumption is a major cause of morbidity, yet alcohol is associated with both favourable and adverse effects on cardiometabolic risk markers. We aimed to characterize the associations of usual alcohol consumption with a comprehensive systemic metabolite profile in young adults. Methods Cross-sectional associations of alcohol intake with 86 metabolic measures were assessed for 9778 individuals from three population-based cohorts from Finland (age 24-45 years, 52% women). Metabolic changes associated with change in alcohol intake during 6-year follow-up were further examined for 1466 individuals. Alcohol intake was assessed by questionnaires. Circulating lipids, fatty acids and metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. Results Increased alcohol intake was associated with cardiometabolic risk markers across multiple metabolic pathways, including higher lipid concentrations in HDL subclasses and smaller LDL particle size, increased proportions of monounsaturated fatty acids and decreased proportion of omega-6 fatty acids, lower concentrations of glutamine and citrate (P<0.001 for 56 metabolic measures). Many metabolic biomarkers displayed U-shaped associations with alcohol consumption. Results were coherent for men and women, consistent across the three cohorts, and similar if adjusting for body mass index, smoking and physical activity. The metabolic changes accompanying change in alcohol intake during follow-up resembled the cross-sectional association pattern ( R 2 =0.83, slope=0.72±0.04). Conclusions Alcohol consumption is associated with a complex metabolic signature, including aberrations in multiple biomarkers for elevated cardiometabolic risk. The metabolic signature tracks with long-term changes in alcohol consumption. These results elucidate the double-edged effects of alcohol on cardiovascular risk. Key messages Alcohol intake in young adults associates with multiple novel metabolic biomarkers for the risk of cardiovascular disease and type 2 diabetes. The metabolic aberrations are mainly adversely related to cardiometabolic risk Prominent metabolic associations with alcohol consumption include monounsaturated fatty acids, omega-6 fatty acids, glutamine, citrate and lipoprotein particle size. Many of these cardiometabolic biomarkers were as strongly associated with alcohol intake as HDL cholesterol The strongest novel biomarkers of alcohol consumption followed linear association shapes, whereas many lipid measures displayed U-shaped associations The detailed metabolic signature of alcohol consumption tracked with long-term changes in alcohol use, suggesting that the observed metabolic changes are at least partly due to alcohol consumption The results provide improved understanding of the diverse molecular processes related to alcohol intake. Novel metabolic biomarkers reflecting both alcohol intake and cardiovascular risk could serve as intermediates that may help to bridge the complex relation between alcohol and cardiometabolic risk