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Published on: April 22, 2022
Semi-targeted Metabolomics Analysis of Biomarkers of Low to Moderate Alcohol Intake in the Postmenopausal Women's
Yukiko Yano1, Paul S Albert1, Siddharth Roy1
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, United States.
Background:
Epidemiologic studies of the health impact of alcohol consumption have mostly been based on self-reported measures of intake. Objective markers may provide better measures of alcohol intake and its biologic effects, potentially elucidating mechanisms of disease. However, there are currently no validated biomarkers to assess low to moderate drinking.
Objectives:
To apply semi-targeted metabolomics to identify biomarkers of low to moderate alcohol consumption using plasma samples collected in the Postmenopausal Women's Alcohol Study (WAS), a randomized controlled crossover feeding study.
Methods:
In the WAS, postmenopausal women (n = 51) were randomly assigned to consume 0, 15, or 30 g of alcohol/d (equivalent to 0, 1, or 2 drinks/d) for 8 wk each as part of a controlled diet, with washout periods between treatments. Metabolites were measured in baseline, washout, and post-treatment fasting plasma samples. Linear mixed-effects models were used to identify metabolites significantly altered by alcohol intake.
Results:
A total of 1422 metabolites were measured, of which 150 were previously reported to be correlated with alcohol in observational studies. Alcohol intake significantly altered plasma levels of 46 metabolites, including xenobiotics directly related to alcohol, ethyl glucuronide and ethyl α-glucopyranoside; α-hydroxyisovalerate; 2-aminobutyrate; androgenic steroids; and multiple phosphatidylcholines. Top-ranking metabolites displayed clear dose-response relationships with alcohol dose-most notably, ethyl α-glucopyranoside, which showed a strong positive relationship (461% and 900% change for 15 and 30 g of alcohol/d, respectively, compared with no alcohol). We replicated associations for 14 alcohol-related metabolites identified in previous studies and discovered a number of new potential biomarkers.
Conclusions:
In a tightly controlled feeding study, consumption of 1 or 2 alcoholic drinks/d changed plasma levels of 46 metabolites, suggesting their utility as biomarkers of low to moderate alcohol consumption, with opportunities to conduct etiologic research in cohorts with metabolomics data.
