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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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Abstract

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.

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Abbreviations

AUC:

Area under the curve

CI:

Confidence interval

COSY:

Correlation spectroscopy

d:

Doublet

EtG:

Ethyl glucuronide

FFQ:

Food frequency questionnaires

FM:

Food metabolome

IQR:

Interquartile range

J:

J-coupling

m:

Multiplet

ROC:

Receiver operating characteristic

s:

Singlet

t:

Triplet

U:

Unassigned compound

WIS:

Wine interventional study

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Acknowledgments

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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Authors and Affiliations

  1. Biomarkers and Nutrimetabolomic Lab. Nutrition and Food Science Department, XaRTA, INSA, Torribera Campus, Pharmacy Faculty, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain

    Rosa Vázquez-Fresno, Rafael Llorach, Mireia Urpi-Sarda, Olha Khymenets & Cristina Andres-Lacueva

  2. INGENIO-CONSOLIDER Program, Fun-C-Food CSD2007-063, Ministry of Science and Innovation, Barcelona, Spain

    Rosa Vázquez-Fresno, Rafael Llorach, Mireia Urpi-Sarda, Olha Khymenets & Cristina Andres-Lacueva

  3. Human Nutrition Unit, Biochemistry and Biotechnology Department and Hospital Universitari de Sant Joan de Reus, Institut d‘Investigació Sanitària Pere Virgili, Universitat Rovira I Virgili, Reus, Spain

    Mònica Bulló

  4. CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain

    Mònica Bulló, Dolores Corella, Montserrat Fitó, Miguel Angel Martínez-González & Ramon Estruch

  5. Department of Preventive Medicine and Public Health, University of Valencia, Valencia, Spain

    Dolores Corella

  6. Cardiovascular Epidemiology Unit, Municipal Institute for Medical Research (IMIM), Barcelona, Spain

    Montserrat Fitó

  7. Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

    Miguel Angel Martínez-González

  8. Department of Internal Medicine, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain

    Ramon Estruch

Authors
  1. Rosa Vázquez-Fresno
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  2. Rafael Llorach
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  3. Mireia Urpi-Sarda
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  4. Olha Khymenets
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  5. Mònica Bulló
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  6. Dolores Corella
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  7. Montserrat Fitó
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  8. Miguel Angel Martínez-González
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  9. Ramon Estruch
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  10. Cristina Andres-Lacueva
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Corresponding authors

Correspondence to Rafael Llorach or Cristina Andres-Lacueva.

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Vázquez-Fresno, R., Llorach, R., Urpi-Sarda, M. et al. An NMR metabolomics approach reveals a combined-biomarkers model in a wine interventional trial with validation in free-living individuals of the PREDIMED study. Metabolomics 11, 797–806 (2015). https://doi.org/10.1007/s11306-014-0735-x

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