Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 143, Issue -, Pages 471-481Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2019.08.032
Keywords
CYP2A6; CYP2D6; Endothelial function; Hydroxytyrosol; Tyrosol; Wine
Funding
- Instituto de Salud Carlos III [PI14/00072]
- DIUE of Generalitat de Catalunya [2107 SGR 138]
- PFIS predoctoral fellowship from the Instituto Carlos III [PFIS-FI16/00106]
- Centro de Informacion Cerveza y Salud, Fundacion Manuel de Oya
- Marie Sklodowska-Curie grant [712949]
- ACCIO
- Canada Research Chair in Pharmacogenomics
- Canadian Institutes of Health Research [FDN-154294]
- Rio Hortega fellowship from the Instituto Carlos III [CM17/00024]
- Marie Curie Actions (MSCA) [712949] Funding Source: Marie Curie Actions (MSCA)
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Introduction: The simple phenol hydroxytyrosol (OHTyr) has been associated with the beneficial health effects of extra virgin olive oil. Pre-clinical studies have identified Tyr hydroxylation, mediated by cytochrome P450 isoforms CYP2A6 and CYP2D6, as an additional source of OHTyr. Aim: We aimed to (i) confirm Tyr to OHTyr bioconversion in vivo in humans, (ii) assess the cardiovascular benefits of this bioconversion, and (iii) determine their interaction with a polygenic activity score (PAS) from CYP2A6 and CYP2D6 genotypes. Methods: Randomized, crossover, controlled study. Individuals at cardiovascular risk (n = 33) received: white wine (WW) (females 1, males 2 standard drinks/day), WW plus Tyr capsules (WW + Tyr) (25 mg Tyr capsule, one per WW drink), and water (control) ad libitum. Participants were classified by a PAS as low versus normal activity metabolizers. Results: OHTyr recovery following WW + Tyr was higher than after other interventions (P < 0.05). Low PAS individuals had lower OHTyr/Tyr ratios compared to individuals with normal PAS. WW + Tyr improved endothelial function, increased plasma HDL-cholesterol and antithrombin IIII, and decreased plasma homocysteine, endothelin 1, and CD40L, P65/RELA, and CFH gene expression in peripheral blood mononuclear cells (p < 0.05). Combining Tyr capsule(s) with WW abolished the increase in iNOS, eNOS, VEGFA, and CHF expressions promoted by WW (p < 0.05). Conclusions: Tyr, and its partial biotransformation into OHTyr, promoted cardiovascular health-related benefits in humans after dietary doses of Tyr. The study design allowed the health effects of individual phenols to be singled out from the dietary matrix in which they are naturally found.
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