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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    • "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.
    The Journal of nutritional biochemistry 09/2015; DOI:10.1016/j.jnutbio.2015.07.012 · 3.79 Impact Factor
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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.
    Nutrition research and practice 08/2014; 8(4):347-51. DOI:10.4162/nrp.2014.8.4.347 · 1.44 Impact Factor
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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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    ABSTRACT: The Canola Oil Multicenter Intervention Trial (COMIT) was a randomized controlled crossover study designed to evaluate the effects of five diets that provided different oils and/or oil blends on cardiovascular disease (CVD) risk factors in individuals with abdominal obesity. The present objective is to report preliminary findings on plasma fatty acid profiles in volunteers with abdominal obesity, following the consumption of diets enriched with n-3, n-6 and n-9 fatty acids. COMIT was conducted at three clinical sites, Winnipeg, Manitoba, Canada, Quebec City, Quebec, Canada and University Park, Pennsylvania, United States. Inclusion criteria were at least one of the followings: waist circumference (>=90 cm for males and >=84 cm for females), and at least one other criterion: triglycerides >=1.7 mmol/L, high density lipoprotein cholesterol <1 mmol/L (males) or <1.3 mmol/L (females), blood pressure >=130 mmHg (systolic) and/or >=85 mmHg (diastolic), and glucose >=5.5 mmol/L. Weight-maintaining diets that included shakes with one of the dietary oil blends were provided during each of the five 30-day dietary phases. Dietary phases were separated by four-week washout periods. Treatment oils were canola oil, high oleic canola oil, high oleic canola oil enriched with docosahexaenoic acid (DHA), flax oil and safflower oil blend, and corn oil and safflower oil blend. A per protocol approach with a mixed model analysis was decided to be appropriate for data analysis. One hundred and seventy volunteers were randomized and 130 completed the study with a dropout rate of 23.5%. The mean plasma total DHA concentrations, which were analyzed among all participants as a measure of adherence, increased by more than 100% in the DHA-enriched phase, compared to other phases, demonstrating excellent dietary adherence. Recruitment and retention strategies were effective in achieving a sufficient number of participants who completed the study protocol to enable sufficient statistical power to resolve small differences in outcome measures. It is expected that the study will generate important data thereby enhancing our understanding of the effects of n-3, n-6, and n-9 fatty acid-containing oils on CVD risks.Trial registration: NCT01351012.
    Trials 04/2014; 15(1):136. DOI:10.1186/1745-6215-15-136 · 1.73 Impact Factor
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