Dietary antioxidants do not reduce fatty streak formation in the C57BL/6 mouse atherosclerosis model

Epidemiological studies and animal trials have suggested that dietary antioxidants protect against atherosclerosis. To test this hypothesis, C57BL/6 mice were fed atherogenic diets supplemented with either vitamin E or butylated hydroxytoluene (BHT). Three groups of 20 mice were fed for 15 weeks on diets containing 1% cholesterol and 0.5% cholic acid. The diet of two groups was supplemented with either 2% vitamin E or 1% BHT. The control group received no antioxidant supplements. The lowest mean serum cholesterol concentration was measured in mice supplemented with vitamin E. Mean serum HDL cholesterol concentrations were highest in the control group, which also had the highest ratio of HDL cholesterol to total cholesterol. Mice fed BHT developed a significantly greater area of aortic fatty streak lesions than the other two groups. However, despite having a more atherogenic lipoprotein profile, mice fed vitamin E developed a level of fatty streak formation similar to the control group. At the end of the trial, mice consuming the vitamin E- and BHT-supplemented diets had higher serum total antioxidant levels than the control mice. Because of changes to lipid metabolism caused by both vitamin E and BHT, the results of this study cannot be used to support the hypothesis that antioxidants confer protection against atherosclerosis. The results do, however, raise the possibility that other studies demonstrating an antiatherogenic action of vitamin E and BHT may have been influenced by their effects on lipid metabolism.