Phenol-enriched olive oils modify paraoxonase-related variables: A randomized, crossover, controlled trial

Scope:Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels arecharacteristic of cardiovascular disease. Our aim was to assess short- and long-term effects ofvirgin olive oils (VOO), enriched with their own phenolic compounds (PC; FVOO) or with themplus complementary PC from thyme (FVOOT), on PON-related variables and the mechanismsinvolved.Methods and results:Two randomized, controlled, double-blind, and crossover interventionswere conducted. In an acute intake study, participants ingested three FVOOs differing in PCcontent. In a sustained intake study, participants ingested a control VOO and two differentFVOOs with the same PC content but differing in PC source. Acute and sustained intake ofVOO and FVOO decreased PON1 protein and increased PON1-associated specific activities,while FVOOT yielded opposite results. PON3 protein levels increased only after sustainedconsumption of VOO. Mechanistic studies performed in rat livers showed that intake of isolatedPC from VOO and from thyme modulate mitogen-activated protein kinases and peroxisomeproliferator-activated receptors regulating PON synthesis, while a combination of these PCscancels such regulation.Conclusion:This study reveals that the intake of phenol-enriched FVOOs modulates oxidativebalance by modifying PON-related variables according to PC content and source, and thismodulation can be perceived as beneficial.This study was supported by the Spanish Ministry of Econ-omy (MINECO) financing the projects AGL2009-13517-457-C03-01, C03-02 and C03-3, AGL2012-40144-C01-03, C02-03 and C03-03, and the FPI-fellowship (BES-2010-040766), byC©2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheimwww.mnf-journal.com 1600932 (11 of 13)S. Fern ́andez-Castillejo et al.Mol. Nutr. Food Res. 61,10, 2017, 1600932a contract from the Catalan Government, and by grants fromISCIII FEDER (CB06/03/0028), AGAUR(2014SGR240) andAGAUR (2014SGR783). AP is a Torres Quevedo contract (PTQ-15-08068; Subprograma Estatal de Incorporaci ́on, Plan Estatalde Investigaci ́on Cient ́ıfica y T ́ecnica y de Innovaci ́on). UC is aPERIS contract (SLT002/16/00239; Pla estrat`egic de recerca iinnovaci ́o en salut). LR is Sara Borell contract (CD14/00275)co-financed by and IISPV. OC was supported by a research con-tract of Carlos III (SCIII JR14/00008). Thanks to the Universityof Lleida for the M-CLH PhD. grant