Dietary Antioxidants Do Not Reduce Fatty Streak Formation in the C57BL/6 Mouse Atherosclerosis Model

Department of Veterinary Pathology and Public Health, Massey University (J.S.M., K.G.T., B.W.M.) and New Zealand Institute for Crop and Food Research Limited (K.A.C.J.), Palmerston North, New Zealand.

E-mail jsmunday{at}massey.ac.nz

Abstract—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.

Key Words: atherosclerosis • antioxidants • BHT • vitamin E • mice

This article has been cited by other articles:

				D. C. Schwenke, L. L. Rudel, M. G. Sorci-Thomas, and M. J. Thomas {alpha}-Tocopherol protects against diet induced atherosclerosis in New Zealand white rabbits J. Lipid Res., November 1, 2002; 43(11): 1927 - 1938. [Abstract] [Full Text] [PDF]

				X.-L. Niu, X. Yang, K. Hoshiai, K. Tanaka, S. Sawamura, Y. Koga, and H. Nakazawa Inducible Nitric Oxide Synthase Deficiency Does Not Affect the Susceptibility of Mice to Atherosclerosis but Increases Collagen Content in Lesions Circulation, February 27, 2001; 103(8): 1115 - 1120. [Abstract] [Full Text] [PDF]

				R. Asmis and J. Jelk Vitamin E Supplementation of Human Macrophages Prevents Neither Foam Cell Formation Nor Increased Susceptibility of Foam Cells to Lysis by Oxidized LDL Arterioscler Thromb Vasc Biol, September 1, 2000; 20(9): 2078 - 2086. [Abstract] [Full Text] [PDF]

				G. J. Schroepfer Jr. Oxysterols: Modulators of Cholesterol Metabolism and Other Processes Physiol Rev, January 1, 2000; 80(1): 361 - 554. [Abstract] [Full Text] [PDF]

				J. M. UPSTON, A. C. TERENTIS, and R. STOCKER Tocopherol-mediated peroxidation of lipoproteins: implications for vitamin E as a potential antiatherogenic supplement FASEB J, June 1, 1999; 13(9): 977 - 994. [Abstract] [Full Text]

				A. Shaish, J. George, B. Gilburd, P. Keren, H. Levkovitz, and D. Harats Dietary ß-Carotene and {alpha}-Tocopherol Combination Does Not Inhibit Atherogenesis in an ApoE–Deficient Mouse Model Arterioscler Thromb Vasc Biol, June 1, 1999; 19(6): 1470 - 1475. [Abstract] [Full Text] [PDF]

				P. K. WITTING, K. PETTERSSON, A.-M. ÖSTLUND-LINDQVIST, C. WESTERLUND, A. W. ERIKSSON, and R. STOCKER Inhibition by a coantioxidant of aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice FASEB J, April 1, 1999; 13(6): 667 - 675. [Abstract] [Full Text]