Epidemiological and clinical studies have reported that olive oil reduces the incidence of cardiovascular disease. However, the mechanisms involved in this beneficial effect have not been delineated. The endothelium plays an important role in blood pressure regulation through the release of potent vasodilator and vasoconstrictor agents such as nitric oxide (NO) and endothelin-1 (ET-1), respectively, events that are disrupted in type 2 diabetes. Extra virgin olive oil contains polyphenols, compounds that exert a biological action on endothelial function. This study analyzes the effects of olive oil polyphenols on endothelial dysfunction using an in vitro model that simulates the conditions of type 2 diabetes. Our findings show that high glucose and linoleic and oleic acids decrease endothelial NO synthase phosphorylation, and consequently intracellular NO levels, and increase ET-1 synthesis by ECV304 cells. These effects may be related to the stimulation of reactive oxygen species production in these experimental conditions. Hydroxytyrosol and the polyphenol extract from extra virgin olive oil partially reversed the above events. Moreover, we observed that high glucose and free fatty acids reduced NO and increased ET-1 levels induced by acetylcholine through the modulation of intracellular calcium concentrations and endothelial NO synthase phosphorylation, events also reverted by hydroxytyrosol and polyphenol extract. Thus, our results suggest a protective effect of olive oil polyphenols on endothelial dysfunction induced by hyperglycemia and free fatty acids.

Oxidation of LDL is hypothesised as an early and critical event in atherogenesis. Oxidised LDL (oxLDL) favour the transformation of macrophages into foam cells, an important cell involved in atherosclerosis. Furthermore, oxLDL cause multiple changes in macrophage functions. Thus, oxLDL induces certain genes, suppresses others and alters cell lipid metabolism. Consumption of a Mediterranean diet is associated with a low incidence of atherosclerotic disease, but data about the specific dietary constituents involved and mechanisms conferring cardioprotection are still sparse. The aim of the present study was to determine the effect of representative minor components of wine and olive oil on reactive oxygen species and eicosanoid synthesis induced by oxLDL-stimulated macrophages. We observed that exposure to non-toxic oxLDL concentrations leads to the production of H₂O₂ by RAW 264.7 macrophages and this effect was reverted by apocynin, a NADPH oxidase inhibitor. Moreover, oxLDL induced arachidonic acid (AA) release, cyclo-oxygenase-2 overexpression and subsequent PGE₂ release. We observed that resveratrol and tyrosol revert H₂O₂ production induced by oxLDL as well as AA release and PGE₂ synthesis and that these effects were not as a consequence of these compounds interfering with the oxLDL binding to their receptors. Interestingly, β-sitosterol presence enhances these polyphenol actions. Thus, we found a synergistic action of polyphenols of olive oil and wine and β-sitosterol of olive oil led to the modulation of the effects of oxLDL on oxidative stress and PGE₂ synthesis.

Overweight and obesity have been steadily increasing in recent years and currently represent a serious threat to public health. Few human studies have investigated the relationship between polyphenol intake and body weight. Our aim was to assess the relationship between urinary polyphenol levels and body weight. A cross-sectional study was performed with 573 participants from the PREDIMED (Prevención con Dieta Mediterránea) trial (ISRCTN35739639). Total polyphenol levels were measured by a reliable biomarker, total urinary polyphenol excretion (TPE), determined by the Folin-Ciocalteu method in urine samples. Participants were categorized into five groups according to their TPE at the fifth year. Multiple linear regression models were used to assess the relationships between TPE and obesity parameters; body weight (BW), body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR). After a five years follow up, significant inverse correlations were observed between TPE at the 5th year and BW (β = −1.004; 95% CI: −1.634 to −0.375, p = 0.002), BMI (β = −0.320; 95% CI: −0.541 to −0.098, p = 0.005), WC (β = −0.742; 95% CI: −1.326 to −0.158, p = 0.013), and WHtR (β = −0.408; 95% CI: −0.788 to −0.028, p = 0.036) after adjustments for potential confounders. To conclude, a greater polyphenol intake may thus contribute to reducing body weight in elderly people at high cardiovascular risk.