Protective effect of homovanillyl alcohol on cardiovascular disease and total mortality: virgin olive oil, wine, and catechol-methylation

  • Am J Clin Nutr. 2017 Jun;105(6):1297-1304. doi: 10.3945/ajcn.116.145813.
Rafael De la Torre  1  2  3 ,  Dolores Corella  4  3 ,  Olga Castañer  1  3 ,  Miguel A Martínez-González  5  3 ,  Jordi Salas-Salvado  6  3 ,  Joan Vila  1  3 ,  Ramón Estruch  7  3 ,  José V Sorli  4  3 ,  Fernando Arós  8  3 ,  Miquel Fiol  9  10  3 ,  Emili Ros  11  3 ,  Lluís Serra-Majem  12  3 ,  Xavier Pintó  13  3 ,  Enrique Gómez-Gracia  14  3 ,  José Lapetra  15  3 ,  Miguel Ruiz-Canela  5  3 ,  José Basora  6  3 ,  Eva Maria Asensio  4  3 ,  Maria Isabel Covas  1  16  3 ,  Montserrat Fitó  17  3
Affiliations
  • 1. Hospital del Mar Research Institute, Barcelona, Spain.
  • 2. Department of Experimental and Health Sciences, University Pompeu Fabra, Barcelona, Spain.
  • 3. CIBER of Obesity Physiopathology and Nutrition, Madrid, Spain.
  • 4. Genetic and Molecular Epidemiology Unit, University of Valencia, Valencia, Spain.
  • 5. Preventive Medicine and Public Health, University of Navarra-Navarra Institute of Sanitary Research, Navarra, Spain.
  • 6. Department of Biochemistry and Biotechnology, Human Nutrition Unit, Hospital Universitari Sant Joan de Reus, Reus, Spain.
  • 7. Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain.
  • 8. Department of Cardiology, University Hospital of Álava, Álava, Spain.
  • 9. Health Sciences Research Institute, University of Balearic Islands, Islas Baleares, Spain.
  • 10. Hospital Son Espases, Islas Baleares, Spain.
  • 11. Lipid Clinic, Endocrinology and Nutrition Service, Hospital Clinic, University of Barcelona, Barcelona, Spain.
  • 12. University of Las Palmas de Gran Canaria, Las Palmas, Spain.
  • 13. Lipids and Vascular Risk Unit, Internal Medicine, University Hospital of Bellvitge, Barcelona, Spain.
  • 14. Department of Preventive Medicine, University of Málaga, Málaga, Spain.
  • 15. Department of Family Medicine Research Unit, Sanitary District Primary Care Sevilla, Sevilla, Spain; and.
  • 16. Nutritional Projects Assessment (NUPROAS) Handesbolag, Nacka, Sweden.
  • 17. Hospital del Mar Research Institute, Barcelona, Spain; [email protected].
PMID: 28446500 DOI: 10.3945/ajcn.116.145813
Abstract

Background: Hydroxytyrosol is a phenolic compound that is present in virgin olive oil (VOO) and wine. Hydroxytyrosol-related foods have been shown to protect against Cardiovascular Disease (CVD).Objective: We investigated the associations between hydroxytyrosol and its biological metabolite, 3-O-methyl-hydroxytyrosol, also known as homovanillyl alcohol (HVAL), with CVD and total mortality.Design: We included 1851 men and women with a mean ± SD age of 66.8 ± 6 y at high risk of CVD from prospective cohort data. The primary endpoint was a composite of myocardial infarction, stroke, and death from cardiovascular causes; the secondary endpoint was all-cause mortality. Twenty-four-hour urinary hydroxytyrosol and HVAL and catechol-O-methyltransferase (COMT) rs4680 genotypes were measured.Results: After multivariable adjustment, all biomarkers were associated, as a continuous variable, with lower CVD risk, but only HVAL showed a strong inverse association (HR: 0.44; 95% CI: 0.25, 0.80) for the comparison between quintiles. Only HVAL, as a continuous variable, was associated with total mortality (HR: 0.81; 95% CI: 0.70, 0.95). Individuals in the highest quintile of HVAL compared with the lowest had 9.2 (95% CI: 3.5, 20.8) and 6.3 (95% CI: 2.3, 12.1) additional years of life or years free of CVD, respectively, after 65 y. Individuals with the rs4680GG genotype had the highest HVAL concentrations (P = 0.05). There was no association between COMT genotypes and events or interaction between COMT genotypes and HVAL concentrations.Conclusions: We report, for the first time to our knowledge, an independent association between high urinary HVAL concentrations and a lower risk of CVD and total mortality in elderly individuals. VOO and wine consumption and a high metabolic COMT capacity for methylation are key factors for high HVAL concentrations. The association that stems from our results reinforces the benefits of 2 key components of the Mediterranean diet (wine and VOO). This trial was registered at www.predimed.es as ISRCTN35739639.

Keywords
cardiovascular; homovanillyl alcohol; hydroxytyrosol; traditional Mediterranean diet; virgin olive oil.
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