Impact of Consuming Extra-Virgin Olive Oil or Nuts within a Mediterranean Diet on DNA Methylation in Peripheral White Blood Cells within the PREDIMED-Navarra Randomized Controlled Trial: A Role for Dietary Lipids

Ana Arpón, Fermín I Milagro, Cristina Razquin, Dolores Corella, Ramón Estruch, Montserrat Fitó, Amelia Marti, Miguel A Martínez-González, Emilio Ros, Jordi Salas-Salvadó, José-Ignacio Riezu-Boj, J Alfredo Martínez, Ana Arpón, Fermín I Milagro, Cristina Razquin, Dolores Corella, Ramón Estruch, Montserrat Fitó, Amelia Marti, Miguel A Martínez-González, Emilio Ros, Jordi Salas-Salvadó, José-Ignacio Riezu-Boj, J Alfredo Martínez

Abstract

DNA methylation could be reversible and mouldable by environmental factors, such as dietary exposures. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in extra-virgin olive oil (MedDiet + EVOO) and the other one in nuts (MedDiet + nuts), was influencing the methylation status of peripheral white blood cells (PWBCs) genes. A subset of 36 representative individuals were selected within the PREvención con DIeta MEDiterránea (PREDIMED-Navarra) trial, with three intervention groups in high cardiovascular risk volunteers: MedDiet + EVOO, MedDiet + nuts, and a low-fat control group. Methylation was assessed at baseline and at five-year follow-up. Ingenuity pathway analysis showed routes with differentially methylated CpG sites (CpGs) related to intermediate metabolism, diabetes, inflammation, and signal transduction. Two CpGs were specifically selected: cg01081346-CPT1B/CHKB-CPT1B and cg17071192-GNAS/GNASAS, being associated with intermediate metabolism. Furthermore, cg01081346 was associated with PUFAs intake, showing a role for specific fatty acids on epigenetic modulation. Specific components of MedDiet, particularly nuts and EVOO, were able to induce methylation changes in several PWBCs genes. These changes may have potential benefits in health; especially those changes in genes related to intermediate metabolism, diabetes, inflammation and signal transduction, which may contribute to explain the role of MedDiet and fat quality on health outcomes.

Keywords: DNA methylation; Mediterranean diet; blood cells; nuts; olive oil.

Conflict of interest statement

The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Representation of significant methylation changes of cg01081346. (a) Methylation mean and SD of each dietary group at baseline and at 5 years. Statistical analysis was performed by a Student-t test between 5 years and baseline for each diet. (b) Methylation changes (Mean and SD) for each participant and diet. Statistical analysis of differences in methylation changes among diets was performed by ANOVA (+Tukey’s multiple comparison test). Significance is considered * p < 0.05, *** p < 0.001. (c) Regression graph representing the relation between methylation changes and nuts intake at 5 years. Dot lines on both sides of the solid line (linear regression line) represent 95% confidence band. MedDiet: Mediterranean diet.
Figure 2
Figure 2
Representation of significant methylation changes of cg17071192. (a) Methylation mean and SD of each dietary group at baseline and at 5 years. Statistical analysis was performed by a Student-t test between 5 years and baseline for each diet. (b) Methylation changes (Mean and SD) for each participant and diet. Statistical analysis of differences in methylation changes among diets was performed by ANOVA (+Tukey’s multiple comparison test) or Kruskal-Wallis (+Mann-Whitney’s U), when appropriate. Significance is considered * p < 0.05, ** p < 0.01. EVOO: extra-virgin olive oil; MedDiet: Mediterranean diet.
Figure 3
Figure 3
Regression graph between cg01081346 methylation and polyunsaturated fatty acids (PUFA) consumption at five years. Dot lines on both sides of the solid line (linear regression line) represent 95% confidence band.

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