The effects of consuming fatty acids from different sources on atherosclerotic development

Abstract

It is becoming increasingly evident that the development of atherosclerotic coronary heart disease (CHD) can largely be regulated by lifestyle and dietary choices. The type of fatty acids regularly consumed may promote or prevent atherogenesis. Flaxseed, the richest plant source of the omega-3 fatty acid alpha-linolenic acid (ALA) is thought to protect against atherosclerotic disease. However, the mechanism(s) by which flaxseed exerts these anti-atherogenic effects requires further investigation. Alternatively, there are dietary fatty acids that are thought to induce significant deleterious effects upon our cardiovascular health. Epidemiological evidence associates dietary trans fatty acids (TFAs) with atherosclerotic CHD. This evidence has largely focused on the main source of TFAs in the North American diet, industrially hydrogenated vegetable shortening (iTFAs). It is assumed that TFAs stimulate atherosclerosis but the only studies to date have shown no effect of TFAs on atherosclerosis. Even less is known of the impact of naturally occurring TFAs from dairy and meat products of ruminant animals (rTFAs) on atherosclerotic disease. We investigated the effects of flaxseed supplementation on atherosclerosis and vascular function in two animal models, the hypercholesterolemic rabbit and the cholesterol fed, low density lipoprotein receptor (LDLr-/-) deficient mouse. New Zealand White rabbits and LDLr-/- mice were fed a diet containing flaxseed in the absence or presence of dietary cholesterol for a period of 6 to 24 weeks. We found that dietary flaxseed inhibits the atherogenic effects of a high cholesterol diet in both animal models. The anti-atherogenic effect was achieved in the mouse model through a capacity to lower circulating cholesterol levels and at a cellular level by inhibiting cell proliferation and inflammation. This reduction is also associated with an improved vascular relaxation response as demonstrated in the rabbit model. We also investigated the effects of consuming TFAs from two sources, industrially hydrogenated iTFAs rich in elaidic TFA (C18:1t-9) or naturally-occurring ruminant rTFAs rich in vaccenic TFA (C18:1t-11), on atherosclerotic development in the LDLr-/- mouse in the presence or absence of elevated dietary cholesterol. Our results demonstrate that consuming iTFAs dose dependently initiates atherosclerotic development but not beyond the effects of dietary cholesterol alone. However, consuming rTFAs rich in vaccenic acid protects against hyperlipidemia and atherosclerosis in the presence or absence of dietary cholesterol. The effects of combining dietary flaxseed and iTFAs in the diet were also examined in this model. Adding whole ground flaxseed or flaxseed oil (ALA) to diets containing low and high doses of iTFAs completely prevented atherosclerotic development in the absence of dietary cholesterol. Flaxseed was also able to partially prevent atherosclerosis caused by iTFAs and cholesterol. Our results suggest that the omega-3 ALA fatty acid rich content of flaxseed is mainly responsible for the anti-atherogenic effects of flaxseed. Our results highlight potential mechanisms for the beneficial effects of dietary flaxseed and the mixed effects of TFAs on cardiovascular health and underscore the need for further basic and clinical investigations.