An NMR metabolomics approach reveals a combined-biomarkers model in a wine interventional trial with validation in free-living individuals of the PREDIMED study
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The development of robust biomarkers of consumption would improve the classification of participants with regard to their dietary exposure. In addition, validation of them in free-living individuals remains an important challenge. The aim of this study is to assess wine intake biomarkers using an NMR metabolomic approach to measure the utility of these biomarkers in a wine interventional study (WIS, n = 56) and also to evaluate them in a free-living individuals (PREDIMED study, n = 91). Nine metabolites showed a significantly higher presence in urinary excretion in WIS after wine intake: five food metabolome metabolites (tartrate, ethyl glucuronide [EtG], 2,3-butanediol, mannitol, and ethanol); one related to the endogenous response to wine exposure (3-methyl-2-oxovalerate) and three unidentified compounds. Receiver operating characteristic (ROC) curve for each single metabolite were evaluated and exhibited areas under the curves (AUC) between 67.4 and 86.3 % when they were evaluated individually. Then, a logistic regression model was fitted to generate a combined-biomarkers model using these metabolites. The model generated which included tartrate-EtG, showed an AUC of 90.7 % in WIS. Similarly, the AUC in the PREDIMED study was 92.4 %. Results showed that a model combining tartrate-EtG is more useful for evaluating exposure to wine than single biomarkers, both in interventional studies and epidemiological data. To our knowledge, this is the first time that a combined-biomarker model using an NMR platform in wine biomarkers’ research has been generated and reproduced in a free-living population.
KeywordsBiomarkers Nutrimetabolomics NMR Wine Interventional study Cohort study
Area under the curve
Food frequency questionnaires
Receiver operating characteristic
Wine interventional study
Supported by the Spanish National Grants from Ministry of Economy and Competitiveness (MINECO) and cofounded by FEDER (Fondo Europeo de Desarrollo Regional): AGL2006-14228-C03-02/ALI, AGL2009-13906-C02-01, AGL2010-10084-E, the CONSOLIDER INGENIO 2010 Programme, FUN-C-FOOD (CSD2007-063), CIberOBN, as well as PI13/01172 Project, (Plan N de I+D+i 2013-2016) by ISCII-Subdirección General de Evaluación y Fomento de la Investigación. We also thank the award of 2014SGR1566 from the Generalitat de Catalunya’s Agency AGAUR. R.V.-F, O.K, M.U.-S and R. Ll. would like to thank the FPI fellowship, the “Juan de la Cierva” and the “Ramon y Cajal” programmes of the Spanish Government and the Fondo Social Europeo. We thank the participants for their collaboration in the study.
Conflict of interest
All the authors declare no competing financial interest.
Compliance with ethical requirements
WIS study. The study received the ethical approval Institutional Review Board of the Hospital Clinic of Barcelona. All participants had signed an informed consent. This trial has been registered in the Current Controlled Trials in London, International Standard Randomized Controlled Trial Number (ISRCTN88720134).
PREDIMED study. The trial protocol was conducted according to the Declaration of Helsinki and was approved by the institutional review boards of all the centres involved. All participants had signed an informed consent. This trial has been registered in the Current Controlled Trials in London, International Standard Randomized Controlled Trial Number (ISRCTN35739639).
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