Cardiovascular benefits of phenol-enriched virgin olive oils: new insights from the virgin olive oil and HDL functionality (VOHF) study

[Scope] The main findings of the “Virgin Olive Oil and HDL Functionality” (VOHF) study and other related studies on the effect of phenol‐enriched virgin olive oil (VOO) supplementation on cardiovascular disease are integrated in the present work.[Methods and results] VOHF assessed whether VOOs, enriched with their own phenolic compounds (FVOO) or with those from thyme (FVOOT), improve quantity and functionality of HDL. In this randomized, double‐blind, crossover, and controlled trial, 33 hypercholesterolemic subjects received a control VOO (80 mg kg−1), FVOO (500 mg kg−1), and FVOOT (500 mg kg−1; 1:1) for 3 weeks. Both functional VOOs promoted cardioprotective changes, modulating HDL proteome, increasing fat‐soluble antioxidants, improving HDL subclasses distribution, reducing the lipoprotein insulin resistance index, increasing endogenous antioxidant enzymes, protecting DNA from oxidation, ameliorating endothelial function, and increasing fecal microbial metabolic activity. Additional cardioprotective benefits were observed according to phenol source and content in the phenol‐enriched VOOs. These insights support the beneficial effects of OO and PC from different sources.[Conclusion] Novel therapeutic strategies should increase HDL‐cholesterol levels and enhance HDL functionality. The tailoring of phenol‐enriched VOOs is an interesting and useful strategy for enhancing the functional quality of HDL, and thus, it can be used as a complementary tool for the management of hypercholesterolemic individuals.This work was supported by grants: the VOHF Study (AGL2009-13517- C03) and the MEFOPC Project (AGL2012-40144-C03) from the Spanish Ministry of Education and Science. The authors wish to acknowledge the support of the IISPV, the EURECAT-CTNS, and the COS; Reus, Spain. M.C.L.H has predoctoral student grant from the Universitat de Lleida. A.P. has Torres Quevedo contract (Subprograma Estatal de Incorporaci´on, Plan Estatal de Investigaci´on Cient´ıfica y T´ecnica y de Innovaci´on). L.R. and M.F. have Sara Borrell postdoctoral grants (CD14/00275, 2015–2017;CD17/00233, 2018–2021). M.F. was also supported by a joint contract of the ISCIII and Health Department of the Catalan Government (CES12/025; CB06/03/0028). U.C. has a PERIS post-doctoral grant ´ (SLT002/16/00239; Catalunya, Spain). NFOC-Salut group is a consolidated research group of Generalitat de Catalunya, Spain (2017 SGR 522).CIBERDEM and CIBEROBN are initiatives of ISCIII of Spain which is supported by FEDER funds (CB06/03).Peer reviewe