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

Eline H Van Roekel ,Rosario Tumino,Fulvio Ricceri,David Achaintre,Marion Carayol,Miren Dorronsoro,Johan Malm,Vittorio Krogh,Laura Trijsburg,Sabina Rinaldi,Nada Assi,Anne Tjønneland,Mattias Johansson,Augustin Scalbert,Heiner Boeing,Neil Murphy,Gianluca Severi,Mazda Jenab,Anders Håkansson,Khalid Iqbal,Elio Riboli,Domenico Palli,Kim Overvad,Pietro Ferrari,Anna Karakatsani,Tilman Kühn,Salvatore Panico,Elisabete Weiderpass,Rudolf Kaaks,Antonia Trichopoulou,Eva Ardanáz ,Marie Christine Boutron-Ruault ,Αnastasia Kotanidou ,Konstantinos K Tsilidis ,Matty P Weijenberg ,Petra H.m Peeters ,J Ramón Quiŕos ,Elena Molina‐Portillo ,Leila Luján-Barroso ,Ruth C Travis ,José María Huerta ,Agnetha Linn Rostgaard-Hansen ,Magdalena Stępień ,Marc J Gunter ,Julie A Schmidt ,Bas Bueno‐De‐Mesquita

doi:10.3390/nu10050654

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.

Highlights

The harmful use of alcohol is among the main modifiable risk factors for human morbidity, disability, and mortality worldwide [1]
Results of prostate cancer (PC)-PR2 analysis indicated that sub-study, lifestyle, and laboratory variables combined explained 41.9% of the total variability in metabolite concentrations (Figure 1)
In this study, which is one of the largest to explore the associations between circulating metabolites and alcohol consumption, alcohol intake was related to several phospho- and sphingolipids

Summary

Introduction

The harmful use of alcohol is among the main modifiable risk factors for human morbidity, disability, and mortality worldwide [1]. It has been associated with over 200 health conditions including neuropsychiatric conditions, liver cirrhosis, several cancers, hypertensive heart disease, fetal alcohol syndrome, and infectious diseases [1]. 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 (e.g., through identification of pharmacotherapy targets). It may help to identify biomarkers of alcohol consumption facilitating early preventive strategies in individuals at risk of developing alcohol-related morbidities

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