1. Introduction
watery, cardiovascular disease, HT
CARDIOVASCULAR DISEASE, STILL, SECONDARY, BLOOD, OXIDATIVE STRESS
Table olives and olive oils are the main dietary sources of hydroxytyrosol (HT), a natural antioxidant compound that has emerged as a potential aid in protection against cardiovascular risk. Bioavailability studies with olive oils showed that HT is bioavailable from its free form and from conjugated forms such as oleuropein and its aglycone. Still, its low dietary intake, poor bioavailability, and high inter-individual variability after absorption through the gastrointestinal tract hamper its full benefits. In a randomized, controlled, blinded, cross-over study, we investigated the impact of HT metabolism and bioavailability by comparing two olive-derived watery supplements containing different doses of HT (30.58 and 61.48 mg of HT/dosage). Additionally, HT-fortified olive oil was used in the control group. To this aim, plasma and urine samples were evaluated in 12 healthy volunteers following the intake of a single dose of the supplements or fortified olive oil. Blood and urine samples were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 12 h after intake. HT and its metabolites were analyzed using UHPLC-DAD-MS/MS. Pharmacokinetic results showed that dietary HT administered through the food supplements is bioavailable and bioavailability increases with the administered dose. After intake, homovanillic acid, HT-3-Olive fruits (However, the olive phenolics relevant to health are not only contained in the oil but also in the water-soluble part of the olives. Indeed, HT is a polar molecule only slightly soluble in fats, a feature that hinders its passage through the lipid bilayer membrane in the small intestines. Clinical evidence related to HT metabolism is based primarily on human studies conducted with olive oils containing different concentrations of naturally present or added olive phenolic compounds [Vegetation water is a by-product of olive oil processing, i.e., the aqueous part of the olive that is separated from the oil. Such liquid by-product is rich in polar phenols, and typically contains 98% of the total phenols from the olive fruit [Our study investigates the bioavailability, disposition, and dose response of HT in humans after intake of the proprietary food supplements, To this end, a randomized, controlled human trial was conducted with 12 healthy volunteers. Kinetics and bioavailability were determined analyzing HT and Ole, as well as their metabolized oxidated-methylated, sulphated, and glucuronidated forms, in both plasma and urine at 0.5 h, 1 h, 1.5 h, 2 h, 4 h, and 12 h after taking 25 mL(one flask) of the liquid supplement, and evaluated as a change from baseline. HT and its metabolites were analyzed with UHPLC-DAD-MS/MS using pure reference standards. The results indicate that HT is dose-dependently absorbed after intake of the aqueous food supplements; it is metabolised mainly to HVA, HT-3-These results promise a good potential of both food supplements for oxidative stress control in vivo. We hypothesized that the food supplements rich in natural HT may provide benefits on risk factors for cardiovascular disease similar to those provided by high-phenolic extra virgin olive oils (EVOOs). Thus, further secondary outcomes of the present study [