No abstract

The evidence for a reduction In cardiovascular mortality from fish oil is based on epidemlologic 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 flsh-oll concentrate dally and compared them to a control group fed un8upplemented rabbit chow. Serial cholesterol and trlglyceride levels were monitored as were plasma llpld hydroperoxldes. 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 trlglyceride levels were noted between the two groups. Fatty acid hydroperoxlde levels were also similar and were noted to Increase from weaning (1.0±0.7/£M) to the time of sacrifice (1.8± 1.5/xM, 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, llpld hydroperoxldes, or aortic atherosclerosis In WHHL rabbits. The hypothesis that fish oil protects against atherosclerosis was not supported by this study. I n the past several years, there has been a heightened interest in the possible cardioprotective effects of dietary fish oil. Initiated by the observation of a low incidence in cardiac disease-related mortality in the Greenland Eskimo, 1 a population whose diet is high in fish consumption, this interest has been strengthened by studies suggesting that fish-oil ingestion may reduce atherosclerosis, possibly via a mechanism that relates to its influence on eicosanoid metabolism. 234 Other studies have suggested that circulating lipid hydroperoxldes represent a chronic oxidant stress that is capable of promoting atherogenesis directly or indirectly via the stimulation of intracellular hydroperoxides.5 There is evidence, as well, that omega-3 fatty acids can decrease the rate of generation of hydroperoxides by cyclooxygenase 8 or decrease the amount of oxidants produced locally by leukocytes via a reduction in eicosanoid biosynthesis.7 If the omega-3 fatty acids found in fish oil affect eicosanoid synthesis or lower peroxide levels, then increasing the consumption of fish oil in a population that is prone to atherosclerosis (such as the U.S. adult population) might prevent or retard the development of atherosclerotic heart disease, independent of serum cholesterol levels or genetic predisposition.The protective effect of chronic fish-oil ingestion on naturally occurring atherosclerosis has been based on supposition, however. No necropsy studies have been published on the Greenland Eskimos, and the presumed low incidence of atherosclerosis attributable to fish oil has been extrapolated from observations comparing populations with high and low fish consumption. 8 ...