Alcohol consumption is a risk factor for numerous health conditions and an important cause of death. Identifying metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. The objective of this study is to investigate associations of alcohol consumption with circulating concentrations of 123 metabolites including amino acids, acylcarnitines, hexoses, biogenic amines, phosphatidylcholines, and sphingomyelins. For this purpose, the investigators use data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and applied a discovery and replication approach.

This study used data from 2,974 control participants from four case-control studies on colorectal (n=491), hepatobiliary (n=327), kidney (n=635), and prostate cancer (n=1,521) nested in the EPIC cohort, for which targeted metabolomics data had been acquired. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry using the BIOCRATES AbsoluteIDQTM p180 kit. Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of ln-transformed alcohol consumption with Z-standardized ln-transformed residual metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value<0.05) were further tested in the replication set (Bonferroni-corrected p-value<0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 metabolites were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Associations with acylcarnitines and phosphatidylcholines were generally positive, while mostly inverse associations were observed with citrulline and sphingomyelins.

This study adds novel knowledge regarding circulating metabolites associated with alcohol consumption, and provides leads for further studies into the underlying biological mechanisms. A better understanding of metabolic pathways affected by alcohol consumption may contribute to the development of mechanism-tailored intervention strategies to prevent and treat alcohol-related conditions. Furthermore, it may help to identify biomarkers of alcohol consumption facilitating early preventive strategies in individuals at-risk for developing alcohol-related morbidities.

Inclusion Criteria (for EPIC):

• Aged 30-70
• Healthy volunteers residing within defined geographical areas (where study centers are located). Different settings by centre; mostly general population with some exceptions: women of a health insurance company for teachers and school workers (France), women attending breast cancer screening (Utrecht-The Netherlands, and Florence-Italy), mainly blood donors (most centers in Italy and Spain) and a cohort consisting predominantly of vegetarians (the 'health-conscious' group in Oxford, UK).

Exclusion criteria (for this study):

• Individuals without metabolomics data
• Individuals without data on alcohol consumption at recruitment

Over 520,000 healthy men and women aged 25-85 were enrolled between 1992 and 2000 across 23 EPIC centres in 10 European countries including Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom.

This study used data from 2,974 control participants from four case-control studies on colorectal (n=491), hepatobiliary (n=327), kidney (n=635), and prostate cancer (n=1,521) nested in the EPIC cohort, for which targeted metabolomics data had been acquired.

Undecided.