Objective—: Olive oil polyphenols have shown beneficial properties against cardiovascular risk factors. Their consumption has been associated with higher cholesterol content in high-density lipoproteins (HDL). However, data on polyphenol effects on HDL quality are scarce. We, therefore, assessed whether polyphenol-rich olive oil consumption could enhance the HDL main function, its cholesterol efflux capacity, and some of its quality-related properties, such HDL polyphenol content, size, and composition. Approach and Results—: A randomized, crossover, controlled trial with 47 healthy European male volunteers was performed. Participants ingested 25 mL/d of polyphenol-poor (2.7 mg/kg) or polyphenol-rich (366 mg/kg) raw olive oil in 3-week intervention periods, preceded by 2-week washout periods. HDL cholesterol efflux capacity significantly improved after polyphenol-rich intervention versus the polyphenol-poor one (+3.05% and −2.34%, respectively; P =0.042). Incorporation of olive oil polyphenol biological metabolites to HDL, as well as large HDL (HDL ₂ ) levels, was higher after the polyphenol-rich olive oil intervention, compared with the polyphenol-poor one. Small HDL (HDL ₃ ) levels decreased, the HDL core became triglyceride-poor, and HDL fluidity increased after the polyphenol-rich intervention. Conclusions—: Olive oil polyphenols promote the main HDL antiatherogenic function, its cholesterol efflux capacity. These polyphenols increased HDL size, promoted a greater HDL stability reflected as a triglyceride-poor core, and enhanced the HDL oxidative status, through an increase in the olive oil polyphenol metabolites content in the lipoprotein. Our results provide for the first time a first-level evidence of an enhancement in HDL function by polyphenol-rich olive oil.

Background: Olive oil polyphenols have shown protective effects on cardiovascular risk factors. Their consumption decreased oxidative stress biomarker