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.

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.

The timing of food intake has been associated with obesity and adverse metabolic outcomes, independently of the amount or content of food intake and activity level. However, the impact of the variability in the timing of food intake between weekends and weekdays on BMI (body mass index) remains unexplored. To address that, we propose to study a marker of the variability of meal timing on weekends versus weekdays (denominated as ‘eating jet lag’) that could be associated with increments in BMI. This cross-sectional study included 1106 subjects (aged 18–25 years). Linear regression models were used to examine the associations of eating jet lag with BMI and circadian related variables (including chronotype, eating duration, sleep duration, and social jet lag). Subsequently, a hierarchical multivariate regression analysis was conducted to determine whether the association of eating jet lag with BMI was independent of potentially confounding variables (e.g., chronotype and social jet lag). Moreover, restricted cubic splines were calculated to study the shape of the association between eating jet lag and BMI. Our results revealed a positive association between eating jet lag and BMI (p = 0.008), which was independent of the chronotype and social jet lag. Further analysis revealed the threshold of eating jet lag was of 3.5 h or more, from which the BMI could significantly increase. These results provided evidence of the suitability of the eating jet lag, as a marker of the variability in meal timing between weekends and weekdays, for the study of the influence of meal timing on obesity. In a long run, the reduction of the variability between meal timing on weekends versus weekdays could be included as part of food timing guidelines for the prevention of obesity among general population.

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvención con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 ± 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (>70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) >35 kg/m² reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c.