Effects of short-term walnut consumption on human microvascular function and its relationship to plasma epoxide content

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.