Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort

Abstract

Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (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 alcohol consumption with 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 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions.

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

“…Diet, fitness level, alcohol intake and body mass index might be modifiable determinants of these metabolites. [22][23][24][25][26] The current results on phosphatidylcholines and sphingomyelins (treelet component 1) and risk are broadly consistent with those of other prospective studies investigating individual metabolites, including our previously published results, 6 which were conducted in a subset (~35%) of the current study population. For example, we previously reported inverse associations of many individual phosphatidylcholines, all of which were included with positive loadings in treelet component 1 or 3, with risk of advanced stage prostate cancer, and some associations remained when restricting the analysis to aggressive prostate cancer.…”

“…Our previous study in EPIC also suggested inverse associations of acylcarnitines and taurine with advanced prostate cancer . There are also some published data on dietary and lifestyle correlates of the metabolites in treelet component 2 …”

“…In line with our results, treelet transform applied to untargeted metabolomics and lipidomics data from EPIC‐Potsdam also identified a pattern characterized by positive loadings on a sphingomyelin, three phosphatidylcholines and other glycerophospholipids (a class including phosphatidylcholines). Diet, fitness level, alcohol intake and body mass index might be modifiable determinants of these metabolites …”

“…6 There are also some published data on dietary and lifestyle correlates of the metabolites in treelet component 2. 23,26,37,38 Altered levels of phosphatidylcholines, lysophospholipids (mostly lower), sphingomyelins, acylcarnitines, glutamate, ornithine (mostly lower) and taurine in postdiagnostic samples from prostate cancer patients have been reported. 4,39,40 The most recent of these studies, used Mendelian randomization to assess the causality of cross-sectionally observed associations between 14 serum metabolites (including tyrosine), measured using nuclear magnetic resonance spectroscopy, and overall risk of prostate cancer, detected via prostate-specific antigen test.…”

Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium

“…Alcohol intake and fasting status have been suggested to potentially influence the concentration of certain metabolites, such as acylcarnitines and phosphatidylcholines. 21,22,36 We were not able to take these factors into account, because of incomplete or unavailable data in our cohorts. The issue of reverse causality should also be considered in our study because disease-related lifestyle behaviors or advanced tumor characteristics, such as lymph node involvement or disturbed liver metabolism resulting from metastases, may also be responsible for altered plasma metabolite profiles.…”