A novel soluble epoxide hydrolase inhibitor: Flaxseed alters the plasma oxylipin profile and reduces blood pressure in a randomized, double blinded, placebo controlled clinical trial

January 1, 2014 Human Health and Nutrition Data 0 Comments

A novel soluble epoxide hydrolase inhibitor: Flaxseed alters the plasma oxylipin profile and reduces blood pressure in a randomized, double blinded, placebo controlled clinical trial

Year: 2014
Authors: Caligiuri, S.P.
Publication Name: ISSFAL International Congress, Stockholm, Sweden June 28 – July 1
Publication Details: ID# Monday S8.04

Abstract:

Background: Previously, in the FlaxPAD trial, participants with peripheral arterial disease and hypertension consumed ground flaxseed every day for 6 months and exhibited significant reductions in systolic (10 mmHg) and diastolic (7 mmHg) blood pressure. The daily flaxseed dose equated to 6 g of the n3 fatty acid, alpha linolenic acid (ALA). An inverse relationship existed between plasma ALA and blood pressure; yet the mechanism of action remained unclear. Due to polyunsaturated fatty acids being precursors to oxylipins that regulate vascular tone, it was hypothesized that flaxseed consumption reduced vasoconstrictive oxylipins. Methods and Results: Plasma of FlaxPAD participants (n of 76) underwent solid phase extraction, analyzed with multiple reaction monitoring and HPLCMS MS and quantified with the stable isotope dilution method. After 6 months, the flax group compared to control exhibited significant decreases in 8 plasma oxylipins. Six of these (5,6, 8,9, 11,12, 14,15 dihydroxyeicosatrienoic acid, 9,10 and 12,13 dihydroxyoctadecenoic acid) were n6 fatty acid derived and products of soluble epoxide hydrolase (sEH), a pharmacological target for antihypertensive treatment. This suggested that a bioactive of flaxseed inhibited sEH. Using an sEH inhibitor screening assay, increasing physiological concentrations of ALA decreased sEH activity (p of 0.0048, ρ of 0.94). In contrast, neither increasing levels of linoleic acid nor other flaxseed bioactives, enterolignans, were associated with sEH inhibition (p>0.05). To confirm the relationship between sEH inhibition and blood pressure reduction, a binary analysis was performed. Patients exhibiting a decrease in total plasma she derived oxylipins, exhibited a significant decrease in systolic blood pressure [7.97 mmHg (14.4, 1.50)] versus those exhibiting increased plasma sEH derived oxylipins [plus 3.17 mmHg (4.78, 11.13)]. Specifically, only a reduction in plasma 9,10 dihydroxyoctadecenoic acid and 8,9 dihydroxyeicosatrienoic acid were significantly associated with blood pressure reduction. Conclusions: Flaxseed consumption decreased blood pressure by reducing oxylipins associated with inflammation and loss of vasodilation via an ALA induced sEH inhibition. (Authors abstract)



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