FISH OILS AND LIPOPROTEIN METABOLISM

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The low incidence of cardiovascular diseases among fish-eating populations has led to the hypothesis that fish oils containing omega-3 fatty acids (w3 FA) may be protective agents. Clinical studies have shown that high intakes of fish oils cause total cholesterol and, particularly, triglyceride levels to fall in normals and hyperlipidemic patients. Although in these studies low density lipoprotein (LDL) cholesterol levels were reduced, recent studies utilizing more practical intakes of fish oil (less than 20 gm/day) have found significant elevations in LDL cholesterol levels, especially in patients with hypertriglyceridemia (HTG). Thus, the usefulness of fish oil may be limited in this population. We propose to study very low density lipoprotein (VLDL) and LDL apolipoprotein B metabolism in 32 HTG patients given fish oil vs. a vegetable oil control. They will receive 12, 1-gm capsules of the oils per day for 2, randomly assigned, 6-week periods. In 8 HTG patients with familial combined hyperlipidemia (FCHL) and 8 with familial hypertriglyceridemia (FHTG), the kinetics of 2 VLDL subfractions will be studied during each of the two treatment phases. In a different group of 8 FCHL and 8 FHTG patients, LDL kinetic studies will be done. Also, changes in the chemical composition of VLDL and LDL will be measured by combined ultracentrifugation and column chromatography in both groups of HTG patients and in a group of 8 normal subjects. We should be able to determine whether the increase in LDL cholesterol in HTG patients given fish oil supplements is the result of 1) increased conversion of large and/or small VLDL to LDL, 2) direct hepatic secretion of LDL, 3) decreased removal of LDL from the plasma because of increased competition from small VLDL for removal mechanisms, or 4) decreased removal of LDL because of a direct effect of w3 FA on receptor or non- receptor mediated pathways. These studies should reveal the mechanisms by which w3 FA supplements alter lipoprotein metabolism in HTG patients.