Introduction_x000D_ The beneficial effects on human health derived from the consumption of ethanol at moderate doses could result, in part, from the interaction of ethanol with the oxidative metabolism of dopamine, leading to increased formation of the minor metabolite hydroxytyrosol (OHTyr or DOPET). OHTyr is the main antioxidant of olive oil and consumption of olive oil has shown to reduce lipid oxidation and prevent the occurrence of cardiovascular events. Wine, in addition to ethanol, contains phenols as tyrosol (Tyr) and minimal amounts of OHTyr._x000D_ Methods _x000D_ Objectives: (i) To establish the role of ethanol on OHTyr generation, (ii) to evaluate the relevance of the dose of ethanol on hydroxytyrosol endogenous generation. (iii) To establish the contribution of the different components of wine in OHTyr concentrations in the body and its biological effects. Healthy male volunteers aged from 18 to 55 years were selected. _x000D_ Two studies (DOPET 1 and 2) each composed of three pilot clinical trials and one definitive study were performed. Studies were all randomized, placebo-controlled and had a crossover design. 24 subjects were enrolled in the first study and different doses of pharmaceutical grade ethanol (0, 6, 12, 18, 24, 30 and 42 g) were administered. A total of 40 subjects were included in the second study where wine (13º or 8º), dealcoholized wine (0º), vodka (40º) and placebo (water) were administered. A study was subsequently designed in animals with several phenol precursors (tyramine, tyrosine, tyrosol) to better interpret the results in humans. The primary endpoint was urinary OHTyr excretion. Other variables measured were tyrosol and dopamine metabolites excretion in urine, blood ethanol concentrations, lipid profile, glucose, biomarkers of oxidation, inflammation and lipid peroxidation, ethanol subjective effects, vital signs and psychomotor performance. _x000D_ Results_x000D_ In DOPET 1 urinary OHTyr excretion increased with the dose of alcohol administered. In DOPET 2 OHTyr excretion was higher with wine in comparison with dealcoholized wine, which in turn was higher compared to vodka (alcohol) and finally alcohol excretion was higher relative to placebo. The recovery of OHTyr was 420% of the administered dose. In the animal study it was observed that Tyr administered was partially recovered as OHTyr. _x000D_ Conclusions _x000D_ Ethanol administration produces a change in dopamine metabolism, which leads, in a dose-dependent manner, to endogenous OHTyr formation. In turn, the various components of wine (phenols, ethanol) produce specific changes in OHTyr concentrations. The beneficial effects of drinking wine or alcohol at low doses may be partially explained by endogenous hydroxytyrosol production.
EL HIDROXITIROSOL COMO ANTIOXIDANTE DE ORIGEN ENDÓGENO Y NATURAL: MODULACIÓN POR LA INGESTA DE ALCOHOL.
Pérez Mañá, C. (Author). 4 Nov 2014
Student thesis: Doctoral thesis
Student thesis: Doctoral thesis