Key findings:
Flaxseed consumption has shown dramatic antihypertensive effects, however the mechanisms responsible for these effects remain unknown. This study showed that the effects of flax may be mediated in part through the alteration of a group of compounds called oxylipins. Oxylipins are derived from fatty acids and exert powerful actions in the body. Here both the type of levels of plasma oxylipins were altered and were strongly associated with reductions in systolic and mean arterial blood pressure. Further research is required to ascertain the role of individual oxylipins on vascular tone and blood pressure.
ABSTRACT:
In a randomized, double-blinded, controlled clinical trial, participants with peripheral arterial disease (75% hypertensive) consumed 30 g of milled flaxseed/d for 6 months. The flaxseed group exhibited significant reductions in systolic (-10 mm Hg) and diastolic (-7 mm Hg) blood pressure. Flaxseed contains the n-3 fatty acid alpha-linolenic acid. Plasma alpha-linolenic acid increased with ingestion of flaxseed and was inversely associated with blood pressure. However, the antihypertensive mechanism was unclear. Oxylipins derived from polyunsaturated fatty acids regulate vascular tone. Therefore, the objective was to examine whether flaxseed consumption altered plasma oxylipins in a manner that influenced blood pressure. Plasma of FlaxPAD (Flaxseed for Peripheral Arterial Disease) participants underwent solid phase extraction and high-performance liquid chromatography-mass spectrometry/mass spectrometry analysis. The flaxseed group exhibited significant decreases in 8 plasma oxylipins versus control. Six of these (5,6-, 8,9-, 11,12-, 14,15-dihydroxyeicosatrienoic acid and 9,10- and 12,13-dihydroxyoctadecenoic acid) were products of soluble epoxide hydrolase, a pharmacological target for antihypertensive treatment. Patients exhibiting a decrease in total plasma soluble epoxide hydrolase-derived oxylipins, exhibited a significant decrease in systolic blood pressure (mean [95% confidence interval], -7.97 [-14.4 to -1.50] mm Hg) versus those who exhibited increased plasma soluble epoxide hydrolase-derived oxylipins (+3.17 [-4.78 to 11.13] mm Hg). These data suggest that a flaxseed bioactive may have decreased blood pressure via soluble epoxide hydrolase inhibition. Using a soluble epoxide hydrolase inhibitor screening assay, increasing concentrations of alpha-linolenic acid decreased soluble epoxide hydrolase activity (P=0.0048; ρ=-0.94). In conclusion, alpha-linolenic acid in flaxseed may have inhibited soluble epoxide hydrolase, which altered oxylipin concentrations that contributed to the antihypertensive effects in patients with peripheral arterial disease. ( Authors Abstract)
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