Dietary flax seed in prevention of hypercholesterolemic atherosclerosis


Prasad, K. 1997. Atherosclerosis.   132:60-76.


Oxygen free radicals have been implicated in the development of hypercholesterolemic atherosclerosis, and are produced via several mechanisms including the biosynthesis of prostaglandins and leukotrienes through arachidonic acid metabolism. Flax seed is a rich source of the omega-3 fatty acid, alpha-linolenic acid, and is the richest source of plant lignans, which have several beneficial effects. Lignans are antagonists of platelet-activating factor (PAF) and ALA suppresses production of interleukin-1, tumor necrosis factor (TNF) and reduces production of inflammatory mediator and leukotriene B4, and free radical release. One of the flax lignans, secoisolariciresinol diglucoside (SDG) has been shown to have antioxidant activity. Because of its high lignan and omega-3 fatty acid content, flax seed is thought to be able to prevent or retard the development of hypercholesterolemic atherosclerosis and production of oxygen free radicals by polymorphonuclear leucocytes (PMNLs). This study examined the effects of dietary flax seed on high cholesterol diet-induced atherosclerosis, lipid profiles and oxygen free radical-producing activity of PMNLs in rabbits. The control rabbits were fed rabbit laboratory chow pellets and the treated group received flax seed or cholesterol or cholesterol plus flax seed in addition to rabbit chow. Flax seed was fed orally at a dose of 7.5 g/kg body weight. Assessment of atherosclerotic plaques was done after eight weeks, and measurements of triglycerides, total cholesterol and chemiluminescent activity of PMNLs were done after four and eight weeks. The high cholesterol diet produced an increase in total cholesterol and no change in serum triglyceride. Serum total cholesterol was higher in rabbits fed a high cholesterol diet and flax seed compared to a high cholesterol diet alone, while flax seed alone produced a slight rise in serum total cholesterol. Previous studies in rats showed a higher flax seed diet for 90 days decreased serum total cholesterol, which could be due to a higher dose of flax seed and the long duration of treatment. In humans, flax seed has also been shown to decrease cholesterol, although perhaps not significantly. Based on studies to date, flax seed does not lower the risk factor for coronary artery disease. The severity of the atheromatous plaques in the aorta was associated with hypercholesterolemia. Flax seed reduced the development of hypercholesterolemic atherosclerosis by 46%, which could be attributed to the lignan and alpha-linolenic acid content. Decrease in the levels of IL-1 and TNF could also be due to suppression of their production by alpha-linolenic acid. Reduction in LTB4, IL-1 and TNF and anti-PAF activity would result in decreased activation of PMNLs and monocytes and decreased production of oxygen free radicals. Dietary n-3 fatty acids in flax seed further reduces the levels of oxygen free radicals by suppressing their production. SDG scavenges hydroxyl radicals thus further decreasing the amount of oxygen free radicals. Reduced levels of oxygen free radicals would decrease the chances of development of hypercholesterolemic atherosclerosis. Thus, dietary flax seed could be beneficial in preventing hypercholesterolemic atherosclerosis. The authors conclude that flax seed reduces hypercholesterolemic atherosclerosis by 46% without lowering serum cholesterol. Hypercholesterolemia is a risk factor for development of heart attack and stroke. Flax seed may be beneficial to prevent/reduce hypercholesterolemia-induced ischemic heart disease and stroke and could also be beneficial in peripheral vascular disease.