A Mediterranean diet enriched with olive oil lowers CETP activity and improves multiple HDL functions in the year-long PREDIMED trial (Circulation 2017)

Original title: Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals: A Randomized Controlled Trial

Circulation · 14 February 2017 · 6

Hernáez Á, Castañer O, Elosua R, Pintó X, Estruch R, Salas-Salvadó J, Corella D, Arós F, Serra-Majem L, Fiol M, Ortega-Calvo M, Ros E et al.

In 296 volunteers from the PREDIMED randomized controlled trial at high cardiovascular risk, researchers compared a traditional Mediterranean diet enriched with virgin olive oil (n=100) or nuts (n=100) against a low-fat control diet (n=96) over one year, assessing HDL reverse-cholesterol-transport function, antioxidant properties, and vasodilatory capacity. Both Mediterranean diets increased cholesterol efflux capacity relative to baseline (P=0.018 and P=0.013). The olive-oil-enriched diet specifically decreased CETP activity relative to baseline (P=0.028) and, relative to the control diet, increased HDL's ability to esterify cholesterol, paraoxonase-1 arylesterase activity, and HDL vasodilatory capacity (P=0.039, P=0.012, and P=0.026 respectively). All three diets increased the percentage of large HDL particles relative to baseline (P less than 0.001), with the olive-oil Mediterranean diet showing the broadest improvement in HDL atheroprotective function.

Original abstract

Background: The biological functions of high-density lipoproteins (HDLs) contribute to explaining the cardioprotective role of the lipoprotein beyond quantitative HDL cholesterol levels. A few small-scale interventions with a single antioxidant have improved some HDL functions. However, to date, no long-term, large-scale, randomized controlled trial has been conducted to assess the effects of an antioxidant-rich dietary pattern (such as a traditional Mediterranean diet [TMD]) on HDL function in humans.

Methods: This study was performed in a random subsample of volunteers from the PREDIMED Study (Prevención con Dieta Mediterránea; n=296) after a 1-year intervention. We compared the effects of 2 TMDs, one enriched with virgin olive oil (TMD-VOO; n=100) and the other enriched with nuts (TMD-Nuts; n=100), with respect to a low-fat control diet (n=96). We assessed the effects of both TMDs on the role of HDL particles on reverse cholesterol transport (cholesterol efflux capacity, HDL ability to esterify cholesterol, and cholesteryl ester transfer protein activity), HDL antioxidant properties (paraoxonase-1 arylesterase activity and total HDL antioxidant capacity on low-density lipoproteins), and HDL vasodilatory capacity (HDL ability to induce the release of nitric oxide in endothelial cells). We also studied the effects of a TMD on several HDL quality-related characteristics (HDL particle oxidation, resistance against oxidative modification, main lipid and protein composition, and size distribution).

Results: Both TMDs increased cholesterol efflux capacity relative to baseline (P=0.018 and P=0.013 for TMD-VOO and TMD-Nuts, respectively). The TMD-VOO intervention decreased cholesteryl ester transfer protein activity (relative to baseline, P=0.028) and increased HDL ability to esterify cholesterol, paraoxonase-1 arylesterase activity, and HDL vasodilatory capacity (relative to control, P=0.039, P=0.012, and P=0.026, respectively). Adherence to a TMD induced these beneficial changes by improving HDL oxidative status and composition. The 3 diets increased the percentage of large HDL particles (relative to baseline, P<0.001).

Conclusions: The TMD, especially when enriched with virgin olive oil, improved HDL atheroprotective functions in humans.

Clinical Trial Registration: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.