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

From Cardiovascular Risk and Nutrition Research Group (A.H., O.C., R.d.l.T, M. Fitó) and Cardiovascular Epidemiology and Genetics Research Group (R. Elosua), REGICOR Study Group, and Human Pharmacology and Neurosciences Research Group (R.d.l.T.), Hospital del Mar Medical Research Institute, Barcelona, Spain; PhD Program in Food Sciences and Nutrition (A.H.) and Department of Nutrition and Bromatology, Faculty of Pharmacy (M.C.L.-S.), Universitat de Barcelona, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (A.H., O.C., X.P., R. Estruch, J.S.-S., D.C., F.A., L.S.-M., M. Fiol, M.O.-C., E.R., M.A.M.-G., R.d.l.T., M.C.L.-S., M. Fitó); Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain (X.P.); Department of Internal Medicine, Institut d'Investigacions Biomèdiques August Pi I Sunyer, Hospital Clinic, University of Barcelona, Spain (R. Estruch, E.R.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d'Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Department of Preventive Medicine, Universidad de Valencia, Spain (D.C.); Department of Cardiology, Hospital Universitario de Álava, Vitoria, Spain (F.A.); Department of Clinical Sciences, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain (L.S.-M.); Hospital Son Espases, and Institute of Health Sciences (IUNICS), Palma de Mallorca, Spain (M. Fiol); Department of Family Medicine, Distrito Sanitario Atención Primaria Sevilla, Centro de Salud Las Palmeritas, Spain (M.O.-C.); and Department of Preventive Medicine and Public Health, Universidad de Navarra, Pamplona, Spain (M.A.M.-G.). From Cardiovascular Risk and Nutrition Research Group (A.H., O.C., R.d.l.T, M. Fitó) and Cardiovascular Epidemiology and Genetics Research Group (R. Elosua), REGICOR Study Group, and Human Pharmacology and Neurosciences Research Group (R.d.l.T.), Hospital del Mar Medical Research Institute, Barcelona, Spain; PhD Program in Food Sciences and Nutrition (A.H.) and Department of Nutrition and Bromatology, Faculty of Pharmacy (M.C.L.-S.), Universitat de Barcelona, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (A.H., O.C., X.P., R. Estruch, J.S.-S., D.C., F.A., L.S.-M., M. Fiol, M.O.-C., E.R., M.A.M.-G., R.d.l.T., M.C.L.-S., M. Fitó); Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain (X.P.); Department of Internal Medicine, Institut d'Investigacions Biomèdiques August Pi I Sunyer, Hospital Clinic, University of Barcelona, Spain (R. Estruch, E.R.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d'Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Department of Preventive Medicine, Universidad de Valencia, Spain (D.C.); Department of Cardiology, Hospital Universitario de Álava, Vitoria, Spain (F.A.); Department of Clinical Sciences, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain (L.S.-M.); Hospital Son Espases, and Institute of Health Sciences (IUNICS), Palma de Mallorca, Spain (M. Fiol); Department of Family Medicine, Distrito Sanitario Atención Primaria Sevilla, Centro de Salud Las Palmeritas, Spain (M.O.-C.); and Department of Preventive Medicine and Public Health, Universidad de Navarra, Pamplona, Spain (M.A.M.-G.). mfito@imim.es.

Circulation. 2017;(7):633-643
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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.

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Publication Type : Randomized Controlled Trial

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