Alpha-tocopherol protects against diet-induced atherosclerosis in New Zealand white rabbits

Dawn C. Schwenke, Lawrence L. Rudel, Mary G. Sorci-Thomas, and Michael J. Thomas

Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1016

Corresponding Author: mthomas{at}wfubmc.edu

In this study, we asked the question "does $alpha$ -tocopherol supplementation prevent an increase in total plasma cholesterol (TPC) and reduce the amount of cholesterol deposited in arterial plaques of rabbits fed a nutritionally adequate, atherogenic diet." Isocaloric diets containing 0.1% cholesterol to induce atherosclerosis were enriched in one of three fats: saturated fats (SAT), monounsaturated fats (MONO), or n-6 polyunsaturated fats (POLY). Half of each of the three diets were supplemented with 2500 IU $alpha$ -tocopherol/kg-diet (+VE). Unsupplemented diets contained 25 IU $alpha$ -tocopherol/kg-diet. Rabbits fed diets with $alpha$ -tocopherol supplementation had plasma $alpha$ -tocopherol concentrations 10-fold higher and an average TPC 31%, p=0.017, lower than rabbits fed unsupplemented diets. The TPC of POLY fat-fed animals supplemented with 2500 IU $alpha$ -tocopherol/kg-diet was 54% lower than POLY fat-fed animals at low levels of $alpha$ -tocopherol, p=0.041. Rabbits fed the POLY fat diet with the low $alpha$ -tocopherol level had a lower plasma HDL cholesterol concentration, p * 0.0001, than the other groups. There was no significant difference in the HDL cholesterol concentration among the diet groups with 2500 IU $alpha$ -tocopherol/kg-diet. Rabbits fed $alpha$ -tocopherol at 2500 IU/kg-diet had an average arterial $alpha$ -tocopherol level that was 3.5-fold greater than that measured when rabbits were fed diets with 25 IU $alpha$ -tocopherol/kg-diet. There was less cholesterol in the artery tissue from MONO fat animals fed 25 IU $alpha$ -tocopherol/kg-diet than in SAT fat animals fed the same $alpha$ -tocopherol level, p = 0.006. Rabbits fed $alpha$ -tocopherol at 2500 IU/kg-diet had artery cholesterol concentrations in the POLY fat group that were approximately equal to that of the MONO fat group. This study shows that in groups fed high pharmacological doses of $alpha$ -tocopherol, the TPC concentration was lower for all diet groups. These results suggest that high $alpha$ -tocopherol supplementation can diminish atherosclerosis in situations where the plasma cholesterol concentrations are also significantly lower.

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