Effects of White Wine and Tyrosol on Circulating Ceramides in Individuals at Cardiovascular Risk

Abstract Objectives Ceramides (Cer) are a class of bioactive lipids that are receiving increasing attention as biomarkers of cardiometabolic diseases. Tyrosol (Tyr) is a phenolic compound present in olive oil and wine. Once ingested, it is partially biotransformed into hydroxytyrosol (HOTyr). Tyr and its partial biotransformation into HOTyr promote cardiovascular health-related benefits in humans. The aim of this study was to evaluate the effects of white wine and Tyr on circulating Cer. Methods Thirty-three participants (12 women and 21 men) at cardiovascular risk (age 65 ± 6 years; BMI, 32.6 ± 4.2 kg/m2, LDL cholesterol 118 ± 34 mg/dL) received either white wine (females 1, males 2 standard drinks/days), white wine plus tyrosol capsules (one 25 mg capsule per drink) and water (control, ad libitum) according to a randomized-controlled cross-over design. Each intervention lasted 4 weeks and was preceded by a 3-week washout period. Arterial stiffness biomarkers were measured before and after each intervention. Fasting blood samples were collected before and after each intervention period. The plasma levels of seven Cer (C14:0, C16:0, C18:0, C20:0, C22:0, C24:0, and C24:1) were measured by LC/MS/MS. Results Amongst the three interventions, only white wine plus Tyr significantly altered the levels of circulating ceramides (P < 0.05). White wine plus Tyr decreased the Cer C16:0/C24:0 ratio (P = 0.0018), Cer C18:0/C24:0 ratio (P = 0.040), and Cer C24:1/C24:0 ratio (P = 0.005), compared to white wine alone or water interventions. The final values of Cer ratios after the white wine plus Tyr intervention correlated with arterial stiffness biomarkers (endothelin 1 and augmentation index), which in turn were decreased by this intervention (P < 0.05). Conclusions The Cer ratios C16:0/C24:0, C18:0/C24:0, and C24:1/C24:0 (which had been previously reported to be cardiovascular and mortality risk factors) were decreased by the administration of dietary doses of white wine plus Tyr. Reductions in these ceramides correlated with improvements in arterial stiffness biomarkers. These results, which were not observed after white wine alone, provide new insights on the cardiovascular protective activity of Tyr and its partial conversion into HOTyr. Funding Sources Funded by the Instituto de Salud Carlos III. JRM acknowledges a Sara Borrell contract.