Cardiovascular benefits of tyrosol and its endogenous conversion into hydroxytyrosol in humans. A randomized, controlled trial.

Anna Boronat, Julian Mateus, Natalia Soldevila-Domenech, Mercè Guerra, Jose Rodríguez-Morató, Carlota Varon, Daniel Muñoz, Francina Barbosa, Juan Carlos Morales, Andreas Gaedigk, Klaus Langohr, Maria-Isabel Covas, Clara Pérez-Mañá, Montserrat Fitó, Rachel F Tyndale, Rafael de la Torre

Journal: Free radical biology & medicine 2020;143():471-481

PMID: 31479717

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program, IMIM-Institut Hospital del Mar d'Investigacions Mèdiques, Dr. Aiguader 88, 08003, Barcelona, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra (CEXS-UPF), Dr. Aiguader 80, 08003, Barcelona, Spain.; Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program, IMIM-Institut Hospital del Mar d'Investigacions Mèdiques, Dr. Aiguader 88, 08003, Barcelona, Spain.; Department of Experimental and Health Sciences, Universitat Pompeu Fabra (CEXS-UPF), Dr. Aiguader 80, 08003, Barcelona, Spain.; Department of Experimental and Health Sciences, Universitat Pompeu Fabra (CEXS-UPF), Dr. Aiguader 80, 08003, Barcelona, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN, CB06/03/028), Monforte de Lemos 3-5, 28029, Madrid, Spain.; Department of Pharmacy, Vall d'Hebron Barcelona Hospital Campus, Passeig de Vall d'Hebron 119-129, 08035, Barcelona, Spain.; Cardiovascular Risk and Nutrition Research Group, IMIM (Hospital del Mar Research Institute), Dr. Aiguader 88, 08003, Barcelona, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN, CB06/03/028), Monforte de Lemos 3-5, 28029, Madrid, Spain.; CAP Barceloneta, Parc Sanitari Rovira Virgili, Passeig Marítim, 25 08003, Barcelona, Spain.; Department of Biochemistry and Molecular Pharmacology, Instituto de Parasitología y Biomedicina López Neyra, CSIC, PTS Granada, Avda. del Conocimiento 17, 18016, Armilla, Granada, Spain.; Children's Mercy Kansas City, Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, and University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA.; Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program, IMIM-Institut Hospital del Mar d'Investigacions Mèdiques, Dr. Aiguader 88, 08003, Barcelona, Spain; Department of Statistics and Operations Research, Polytechnic University of Catalonia, Barcelona, Spain.; Cardiovascular Risk and Nutrition Research Group, IMIM (Hospital del Mar Research Institute), Dr. Aiguader 88, 08003, Barcelona, Spain; NUPROAS Handesbolag (NUPROAS HB), Nacka, Sweden.; School of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain; Hospital Universitari Germans Trias i Pujol (IGTP), Badalona, Spain.; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Departments of Pharmacology & Toxicology, and Psychiatry, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.; Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program, IMIM-Institut Hospital del Mar d'Investigacions Mèdiques, Dr. Aiguader 88, 08003, Barcelona, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra (CEXS-UPF), Dr. Aiguader 80, 08003, Barcelona, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN, CB06/03/028), Monforte de Lemos 3-5, 28029, Madrid, Spain. Electronic address: [email protected].

DOI: 10.1016/j.freeradbiomed.2019.08.032

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MeSH Terms: Aged, Cardiovascular System, Case-Control Studies, Cross-Over Studies, Cytochrome P-450 CYP2A6, Cytochrome P-450 CYP2D6, Female, Gene Expression Regulation, Humans, Leukocytes, Mononuclear, Male, Phenylethyl Alcohol, Wine