Development of atherosclerosis in genetically hyperlipidemic rabbits during chronic fish-oil ingestion

The evidence for a reduction in cardiovascular mortality from fish oil is based on epidemiologic observations. To test whether fish-oil supplementation influences the development of atherosclerosis, we treated Watanabe heritable hyperlipidemic rabbits (WHHL), an inbred strain that spontaneously develops atherosclerosis, with 2.5 ml of MaxEPA fish-oil concentrate daily and compared them to a control group fed unsupplemented rabbit chow. Serial cholesterol and triglyceride levels were monitored as were plasma lipid hydroperoxides. The animals were given fish oil from the time of weaning until 1 year of age, when they were sacrificed and their aortas were compared for the extent of atherosclerosis. No significant differences in the cholesterol or triglyceride levels were noted between the two groups. Fatty acid hydroperoxide levels were also similar and were noted to increase from weaning (1.0 ± 0.7 μM) to the time of sacrifice (1.8 ± 1.5 μM, p < 0.01). Fish oil had no influence on the extent of aortic atherosclerosis (25% ± 14% surface area for controls vs. 28% ± 19% for treated, p = NS), plaque thickness, or plaque volume after 1 year. We conclude that fish oil does not reduce the levels of serum cholesterol, lipid hydroperoxides, or aortic atherosclerosis in WHHL rabbits. The hypothesis that fish oil protects against atherosclerosis was not supported by this study.