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: 14.43). 05/2004; 109(13):1609-14. DOI: 10.1161/01.CIR.0000124477.91474.FF
Source: PubMed


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
    • "Besides the limited statistical power in our pilot, what else might help explain the difference in these results? While the trials by Ros et al.[31]and Cortes et al.[21]enrolled subjects with hypercholesterolemia, our samples had a lower prevalence of hypercholesterolemia, especially in the walnut group (38 %) vs. the control group (77 %). If the improvement of endothelial function was partially mediated by a reduction in cholesterol, then having fewer people with elevated cholesterol would make it harder to observe any benefits . "
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    ABSTRACT: The aim of this study was to obtain preliminary data to test the hypothesis that (1) a 12-week intervention with 28 g/day of walnuts improves endothelial function in people with type 2 diabetes mellitus (DM) and (2) intake of walnuts improves plasma adipokines after 12 weeks of intervention. In this pilot randomized, single-blinded, controlled trial of 26 adult subjects with prevalent DM, each subject was randomized to a usual diet with 28 g of walnuts per day or usual diet without walnuts (control group). Reactive hyperemia index (RHI), a measure of endothelial function, was measured non-invasively at baseline and after 12 weeks using Endo-PAT2000. We used linear regression to examine the effects of the intervention on RHI. The mean age at baseline was 64.8 ± 11.6 years; 61.5 % of participants were female, and 15.4 % had coronary artery disease. The standard error of RHI was 0.19. The difference in change in RHI during the intervention between the two groups was −0.029 (95 % confidence interval (CI) −0.52, 0.46, p = 0.23). Walnut intervention led to a suggestive increase in adiponectin, albeit non-statistically significant (difference 0.50 μg/ml (95 % CI −0.10, 1.09), p = 0.65). We demonstrated the feasibility of the proposed randomized trial and obtained needed standard deviations to calculate the required sample size to test proposed hypotheses in an efficacy trial.
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    • "Each participant received walnuts prepackaged into 5-or 40-g daily servings and were instructed to consume one serving daily for 4 weeks. The 40-g level of daily walnut intake was chosen based on the level of daily intake suggested in the 2004 Food and Drug Administration qualified health claim for walnuts and cardiovascular health [22], and also reflected the level and intake period (4 weeks) previously observed to improve postprandial vascular dysfunction induced by a high-fat meal [3]. The goal of the current study was to determine the vascular effects of walnuts when incorporated into the participant's habitual diet as a whole food. "
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    ABSTRACT: Improved vascular function after the incorporation of walnuts into controlled or high-fat diets has been reported; however, the mechanism(s) underlying this effect of walnuts is(are) poorly defined. The objective of the current study was to evaluate the acute and short-term effects of walnut intake on changes in microvascular function and the relationship of these effects to plasma epoxides, the cytochrome-P450-derived metabolites of fatty acids. Thirty-eight hypercholesterolemic postmenopausal women were randomized to 4 weeks of 5 g or 40 g of daily walnut intake. All outcomes were measured after an overnight fast and 4 h after walnut intake. Microvascular function, assessed as the reactive hyperemia index (RHI), was the primary outcome measure, with serum lipids and plasma epoxides as secondary measures. Compared to 5 g of daily walnut intake, consuming 40 g/d of walnuts for 4 weeks increased the RHI and Framingham RHI. Total cholesterol and low- and high-density cholesterol did not significantly change after walnut intake. The change in RHI after 4 weeks of walnut intake was associated with the change in the sum of plasma epoxides (r=0.65, P=.002) but not with the change in the sum of plasma hydroxyeicosatetraenoic acids. Of the individual plasma epoxides, arachidonic-acid-derived 14(15)-epoxyeicosatrienoic acid was most strongly associated with the change in microvascular function (r=0.72, P<.001). These data support the concept that the intake of walnut-derived fatty acids can favorably affect plasma epoxide production, resulting in improved microvascular function.
    Full-text · Article · Sep 2015 · The Journal of nutritional biochemistry
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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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    ABSTRACT: Inflammation is one mechanism through which cancer is initiated and progresses, and is implicated in the etiology of other conditions that affect cancer risk and prognosis, such as type 2 diabetes, cardiovascular disease, and visceral obesity. Emerging human evidence, primarily epidemiological, suggests that walnuts impact risk of these chronic diseases via inflammation. The published literature documents associations between walnut consumption and reduced risk of cancer, and mortality from cancer, diabetes, and cardiovascular disease, particularly within the context of the Mediterranean Diet. While encouraging, follow-up in human intervention trials is needed to better elucidate any potential cancer prevention effect of walnuts, per se. In humans, the far-reaching positive effects of a plant-based diet that includes walnuts may be the most critical message for the public. Indeed, appropriate translation of nutrition research is essential for facilitating healthful consumer dietary behavior. This paper will explore the translation and application of human evidence regarding connections with cancer and biomarkers of inflammation to the development of dietary guidance for the public and individualized dietary advice. Strategies for encouraging dietary patterns that may reduce cancer risk will be explored.
    Full-text · Article · Aug 2014 · Nutrition research and practice
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