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Hydroxytyrosol (HT) plays a significant role in cardiovascular disease (CVD) protection, and its metabolites are able to protect from the endothelial dysfunction commonly present in atherosclerosis. This randomized double-blinded, placebo-controlled crossover trial determined the effect in healthy volunteers of two gastroresistant capsules containing 15 mg/day of HT, for a 3-week period (HTT). Evaluation of nutritional status, serum metabolites, oxidative stress biomarkers, and gene expression of 9 genes related to oxidative stress, inflammation, and CVDs was performed. Oxidation biomarkers like thiol group ( p  = 0.001), total antioxidant status (TAS) ( p  = 0.001), superoxide dismutase 1 (SOD1) (2 −ΔΔCt  = 3.7), and plasma concentration of HT (2.83  μ g·mL −1 ) were significantly increased, while nitrite ( p  = 0.001), nitrate ( p  = 0.001), and malondialdehyde (MDA) ( p  = 0.02) were drastically reduced after HTT. A significant reduction of body fat mass percentage ( p  = 0.01), suprailiac skinfold ( p  = 0.01), and weight ( p  = 0.04; Δ% = −0.46%) was observed after HTT. This study shows that regular intake of 15 mg/day of HT changed body composition parameters and modulated the antioxidant profile and the expression of inflammation and oxidative stress-related genes. However, it is advisable to personalize HT doses in order to exert its health benefits in CVD prevention and protection of LDL-C particles from oxidative damage. This trial is registered with ClinicalTrials.gov  NCT01890070 .

oxidative medicine and cellular longevity

Antioxidant Effects of a Hydroxytyrosol-Based Pharmaceutical Formulation on Body Composition, Metabolic State, and Gene Expression: A Randomized Double-Blinded, Placebo-Controlled Crossover Trial