Published Online
on March 22, 2004

A more recent version of this article appeared on April 6, 2004

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Submitted on May 12, 2003
Revised on January 6, 2004
Accepted on January 12, 2004

A Walnut Diet Improves Endothelial Function in Hypercholesterolemic Subjects. A Randomized Crossover Trial

Emilio Ros MD^*, Isabel Núñez MD, Ana Pérez-Heras RD, Mercè Serra RD, Rosa Gilabert MD, Elena Casals MD, and Ramón Deulofeu MD

From the Lipid Clinic at the Endocrinology and Nutrition Service (E.R., A.P.-H., M.S.), Centre de Diagnòstic per l’Imatge (I.N., R.G.), and Centre de Diagnòstic Biològic (R.D., E.C.), Institut d’Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.

^* To whom correspondence should be addressed. E-mail: eros{at}clinic.ub.es.

Background--Epidemiological studies suggest that nut intake decreases coronary artery disease (CAD) risk. Nuts have a cholesterol-lowering effect that partly explains this benefit. Endothelial dysfunction is associated with CAD and its risk factors and is reversed by antioxidants and marine n-3 fatty acids. Walnuts are a rich source of both antioxidants and -linolenic acid, a plant n-3 fatty acid.

Methods and Results--To test the hypothesis that walnut intake will reverse endothelial dysfunction, we randomized in a crossover design 21 hypercholesterolemic men and women to a cholesterol-lowering Mediterranean diet and a diet of similar energy and fat content in which walnuts replaced 32% of the energy from monounsaturated fat. Participants followed each diet for 4 weeks. After each intervention, we obtained fasting blood and performed ultrasound measurements of brachial artery vasomotor function. Eighteen subjects completing the protocol had suitable ultrasound studies. Compared with the Mediterranean diet, the walnut diet improved endothelium-dependent vasodilation and reduced levels of vascular cell adhesion molecule-1 (P<0.05 for both). Endothelium-independent vasodilation and levels of intercellular adhesion molecule-1, C-reactive protein, homocysteine, and oxidation biomarkers were similar after each diet. The walnut diet significantly reduced total cholesterol (-4.4±7.4%) and LDL cholesterol (-6.4±10.0%) (P<0.05 for both). Cholesterol reductions correlated with increases of both dietary -linolenic acid and LDL -tocopherol content, and changes of endothelium-dependent vasodilation correlated with those of cholesterol-to-HDL ratios (P<0.05 for all).

Conclusions--Substituting walnuts for monounsaturated fat in a Mediterranean diet improves endothelium-dependent vasodilation in hypercholesterolemic subjects. This finding might explain the cardioprotective effect of nut intake beyond cholesterol lowering.

Key words: antioxidants • diet • endothelium • hypercholesterolemia • lipoproteins

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