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

Lipid Clinic at the Endocrinology and Nutrition Service, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.
Circulation (Impact Factor: 14.95). 05/2004; 109(13):1609-14. DOI: 10.1161/01.CIR.0000124477.91474.FF
Source: PubMed

ABSTRACT 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 alpha-linolenic acid, a plant n-3 fatty acid.
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 approximately 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 alpha-linolenic acid and LDL gamma-tocopherol content, and changes of endothelium-dependent vasodilation correlated with those of cholesterol-to-HDL ratios (P<0.05 for all).
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.

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Available from: Elena Casals, Sep 03, 2015
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    • "In the 1-year, randomized PREDIMED (n = 516), adults consuming a Mediterranean diet with either extra virgin olive oil or mixed nuts (walnuts, almonds, and hazelnuts) versus a low fat diet had lower intercellular adhesion molecule-1 (ICAM-1), interleukin (IL)-6, tumor necrosis factor (TNF)R60, and TNFR80 levels (P < 0.05) [22]. Hypercholesterolemic men and women (n = 21) following a Mediterranean diet with walnuts replacing foods high in monounsaturated fatty acids (32% of energy) compared to a Mediterranean diet for 4 wk in a crossover randomized trial were found to have lower levels of vascular cell adhesion molecule-1 (VCAM-1) (P < 0.05), but similar levels of ICAM-1, C-reactive protein (CRP), homocysteine, and oxidation biomarkers [23]. Nuclear factor κB (NF-κB) level also was shown to decrease with a Mediterranean versus Western diet (P < 0.05), with no significant differences between the Mediterranean and high-ALA diet (walnuts were not specified in this study) [24]. "
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    • "The crossover design eliminated the effect of individual differences on response to treatments and reduced the required sample size. Endothelial function was found to be significantly changed in studies with a crossover or a parallel design over a period of four weeks following dietary intervention, indicating that the study design and the duration of the current study is appropriate for detecting changes in endothelial function [43,44]. Moreover, an acute study that measured endothelial function by FMD four hours after a high-fat meal supplemented with either 25 g olive oil or 40 g of shelled walnut in hypercholesterolemic subjects [34] also showed significant changes. "
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