TY - JOUR
T1 - Cardiovascular benefits of tyrosol and its endogenous conversion into hydroxytyrosol in humans. A randomized, controlled trial
AU - Boronat, Anna
AU - Mateus, Julian
AU - Soldevila-Domenech, Natalia
AU - Guerra, Mercè
AU - Rodríguez-Morató, Jose
AU - Varon, Carlota
AU - Muñoz, Daniel
AU - Barbosa, Francina
AU - Morales, Juan Carlos
AU - Gaedigk, Andreas
AU - Langohr, Klaus
AU - Covas, Maria Isabel
AU - Pérez-Mañá, Clara
AU - Fitó, Montserrat
AU - Tyndale, Rachel F.
AU - de la Torre, Rafael
PY - 2019/11/1
Y1 - 2019/11/1
N2 - © 2019 Elsevier Inc. 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.
AB - © 2019 Elsevier Inc. 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.
KW - CYP2A6
KW - CYP2D6
KW - Endothelial function
KW - Hydroxytyrosol
KW - Tyrosol
KW - Wine
U2 - 10.1016/j.freeradbiomed.2019.08.032
DO - 10.1016/j.freeradbiomed.2019.08.032
M3 - Article
C2 - 31479717
SN - 0891-5849
VL - 143
SP - 471
EP - 481
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -