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 (R² = 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.

Keywords: Alcohol; fatty acids; metabolic profiling; metabolomics; risk factors.

Figure 1.

Cross-sectional and longitudinal associations between alcohol consumption and lipoprotein lipid measures. Left: cross-sectional associations of alcohol intake with lipid measures meta-analysed for three cohorts of young adults (n = 9778). Right: changes in lipid concentrations associated with change in alcohol intake after 6-year follow-up for 1466 individuals. All associations were adjusted for age and sex. Error bars denote 95% confidence intervals. Association magnitudes in absolute concentration units are listed in Supplementary Table S1 and continuous shapes of the metabolic associations with alcohol intake are shown in Supplementary Figure S2 (available as Supplementary data at IJE online).

Figure 2.

Cross-sectional and longitudinal associations between alcohol consumption and fatty acids. Left: cross-sectional associations of alcohol intake with circulating fatty acids meta-analysed for three cohorts of young adults (n = 9778). Right: changes in fatty acid levels associated with change in alcohol intake after 6-year follow-up for 1466 individuals. All associations were adjusted for age and sex. Error bars denote 95% confidence intervals.

Figure 3.

Cross-sectional and longitudinal associations of alcohol consumption with low-molecular-weight metabolites and hormonal measures. Left: cross-sectional associations of alcohol intake with metabolite and hormonal measures meta-analysed for three cohorts of young adults (n = 9778). Right: changes in metabolite and hormone levels associated with change in alcohol intake after 6-year follow-up for 1466 individuals. All associations were adjusted for age and sex. Error bars denote 95% confidence intervals.

Figure 4.

Consistency between metabolic associations with alcohol intake at a single time point with the corresponding metabolic changes associated with 6-year change in alcohol consumption. The resemblance between the overall association patterns was quantified by the linear fit between the cross-sectional and longitudinal associations with alcohol intake (red dashed line).

Figure 5.

Lipid and metabolite concentrations as a function of alcohol consumption for 12 selected metabolic measures (n = 9978). The shaded curves denote the 95% confidence intervals of the local polynomial regression fits. Associations were adjusted for age, sex and cohort. The continuous shapes of associations for all 86 metabolic measures are shown for men and women in Supplementary Figure S2, available as Supplementary data at IJE online.