Dietary marine oil supplements fail to affect cholesterol metabolism or inhibit atherosclerosis in rabbits with diet-induced hypercholesterolemia

Dietary marine oil supplements may protect against atherosclerosis, although their influence on plasma lipids, in vivo cholesterol metabolism, and aortic cholesterol accumulation remains uncertain. The effects of daily administration of marine oil-delivering 100 mg of eicosapentaenoic acid, 59 mg of docosahexaenoic acid, and 221 mg of omega-3 fatty acids per kilogram-were assessed in 33 New Zealand white rabbits. Six animals (group I) were immediately killed. In the remaining animals stable hypercholesterolemia was induced with a 0.25% cholesterol-enriched diet. After 7 weeks on this diet, six animals were killed (group II). Total plasma cholesterol had increased significantly (982 ± 119 mg/dl vs. 55.6 ± 7.1 mg/dl, mean ± SEM, p < 0.001). The remaining animals randomly received a tap-water placebo (group III, n = 12) or marine oil (group IV, n = 9) daily. After 3 months, total plasma cholesterol was similar (p = NS) among group II (982 ± 119 mg/dl), group III (965 ± 54 mg/dl), and group IV (913 ± 46 mg/dl). No significant differences in HDL cholesterol, LDL cholesterol, VLDL cholesterol, or triglyceride levels developed between the placebo and marine oil groups. Two-hour, hepatic total lipid, neutral steroid, fatty acid, bile acid, and cholesterol synthesis rates were not significantly affected by marine oil treatment. Thoracic aortic cholesterol content increased during cholesterol feeding (5.7 ± 0.9 mg/gm vs. 1.1 ± 0.05 mg/gm, group II vs. group I, p < 0.05). Marine oil supplementation had no effect on the progressive accumulation of cholesterol in the thoracic aorta (28.8 ± 2.5 mg/gm vs. 29.4 ± 1.8 mg/gm, group IV vs. group III, p = 0.84). The abdominal aortic cholesterol contents were also similar. These results do not support the use of dietary marine oil supplements for the amelioration of lipid metabolism or the prevention of atherosclerosis.