Effect of fish oil on atherosclerosis and lipoprotein metabolism

This review primarily covers work on the effects of dietary n-3 fatty acids on lipoprotein metabolism and atherosclerosis that has been done in a nonhuman primate model, the African green monkey, and puts it in context with work of others using humans and other experimental animals. Detection of effects of n-3 fatty acids in the monkey model was facilitated by a considerable enrichment of dietary fat with fish oil (about 20% of dietary calories came from menhaden oil in the fish oil group or about 5 g/1000 cal of n-3 fatty acids). This group was compared with a group fed lard isocalorically substituted for fish oil, such that the percentage of saturated fatty acids was essentially equivalent in the 2 dietary groups. Cholesterol concentrations in whole plasma, LDL and HDL were about 1/3 lower in the fish oil group, as was apo A-I concentration, but apo B concentration was not different. The fish oil group had plasma LDL particles that were smaller, contained fewer cholesteryl ester molecules and had lower cholesteryl ester transition temperatures due to a relative enrichment of n-3 fatty acids in the CE fraction. In addition, hepatic cholesterol and cholesteryl ester concentrations were significantly lower in the animals fed fish oil. Liver perfusion was used to show that hepatic secretion of cholesterol and triglyceride was lower in the fish oil group, although the number of cholesterol and triglyceride enriched apo B-containing particles secreted was not different. We also demonstrated a lower plasma LCAT reactivity for the plasma phospholipids of the animals fed fish oil. Taken together, these findings clearly demonstrate important effects of n-3 fatty acids on cholesterol metabolism in a primate model that have not been previously recognized. In addition, the monkeys fed fish oil had less atherosclerosis in the coronary arteries and in the aorta. Thus, these findings indicate that, in addition to the many other effects of fish oil in eicosanoid production, fish oil effects on cholesterol metabolism, per se, can have an important role in limiting atherosclerosis.