The Effects of Dietary Flaxseed on Atherosclerotic Plaque Regression

Dietary flaxseed can retard the progression of atherosclerotic plaques. However,  it remains unclear whether these anti-atherogenic effects extend to plaque regression. The therapeutic potential of dietary flaxseed on atherosclerotic plaque regression and vascular contractile function is evaluated utilizing a novel rabbit model. Rabbits were randomly assigned to receive either a regular diet for 12 weeks (Group I) or a 1percent cholesterol-supplemented diet for 4 weeks followed by a regular diet for 8 weeks (Group II). The remaining experimental animals were treated as in Group II but were fed for an 52 additional 14 weeks with either a regular diet (Group III) or a 10percent flaxseed supplemented diet (Group IV). Animals in Group II showed clear evidence of plaque growth stabilization. Their vessels also exhibited significantly lower norepinephrine induced contraction and an impaired relaxation response to acetylcholine in comparison to Group I animals. Dietary flax-supplementation resulted in a significant 40percent reduction in plaque formation (P = 0.033). Both Group II and III animals displayed improved contraction and endothelial-dependent vessel relaxation. Dietary flaxseed is a valuable strategy to accelerate the regression of atherosclerotic plaques; however, the flaxseed intervention did not demonstrate a clear beneficial effect on vessel contractile response and endothelial-dependent vasorelaxation. (Auhtors abstract)

Although many studies have utilized nutritional interventions to induce plaque regression these studies have all prematurely initiated their interventions before there is clear evidence of the cessation of plaque growth.  The objective of the present study was to 1) identify a suitable dietary regimen in rabbits that showed clear evidence of plaque growth stabilization, 2) determine the ability of dietary flaxseed to induce or accelerate atherosclerotic plaque regression, and 3) discern whether flaxseed supplementation can reverse any cholesterol-induced vascular contractile abnormalities. It was hypothesized that flaxseed would accelerate the regression of atherosclerotic plaques and improve vascular abnormalities caused by cholesterol-supplementation.

Rabbits represent an ideal model in which to study atherosclerotic plaque regression because they 1) do not require genetic manipulation to create plaques, 2) develop atherosclerotic plaques after dietary cholesterol supplementation and 3) have similar lipoprotein transport mechanisms to humans. In the present study, a clear dissociation of circulating cholesterol levels from atherosclerotic plaque formation was found. The present study demonstrates that the deleterious effects of cholesterol feeding  on contractile function still persisted even after eight weeks of cholesterol withdrawal. The present findings show for the first time that the deleterious effects of cholesterol feeding on contractile function persist even eight weeks after the withdrawal of cholesterol from the diet. Flaxseed supplementation significantly accelerated the regression of atherosclerotic plaques. The high levels of n3 fatty acids detected within the aorta may account for the observed increases in plaque regression. Incorporation of n3 fatty acids into cell membranes quenches reactive oxygen species production, subsequently decreasing redox sensitive transcription factors, such as NF-κB, that regulates pro inflammatory and pro-atherogenic genes. Flaxseed also contains other functional components that have been implicated in mediating atherosclerosis. Flaxseed is a rich source of plant lignans such as cinnamic acid glucoside, hydroxymethylglutaric acid, and secoisolariciresinol diglucoside which are antioxidants. Oxidized lipoproteins may play a role in atherosclerosis.
In summary, the data demonstrate that dietary flaxseed can accelerate the regression of atherosclerotic plaques in rabbits. Further work is still required to definitively identify the mechanism(s) by which dietary flaxseed increases plaque regression. (Editors comments)