Effects of Antioxidant Vitamins C and E on Atherosclerosis in Lipid-Fed Rabbits

Abstract

Background: Antioxidant vitamins are hypothesized to help prevent atherosclerosis by blocking lipoprotein oxidation. We investigated the effects of dietary vitamins C and E on atherosclerosis in rabbits. Methods and Results: Forty New Zealand male rabbits were divided into 4 groups: 0.3% cholesterol diet with (LV) and without vitamin (LC), and 0.5% cholesterol diet with (HV) and without vitamins (HC). The treated groups consumed 137 ± 8 mg/day vitamin C and 80 ± 4 mg/day vitamin E for 10 weeks. Vitamin treatment did not significantly affect serum lipids. α-Tocopherol values were significantly higher in both serum (mg/dl) and omental fat (µg/g) among the treated rabbits (3.9 ± 0.5 and 31.6 ± 2.1 for LV, 1.7 ± 0.2 and 12.1 ± 1.9 for LC, 5.6 ± 0.8 and 51.3 ± 9.3 for HV and 1.9 ± 0.3 and 8.2 ± 0.4 for HC; p < 0.001). Vitamin treatment did not affect the percent of surface lesions in the aorta and pulmonary artery (23.8 ± 5.2 and 20.1 ± 3.3% for LV, 19.8 ± 5.6 and 23.2 ± 3.5% for LC, 28.1 ± 6.5 and 51.1 ± 4.2% for HV and 32.4 ± 5.5 and 43.7 ± 3.9% for HC, respectively; p = 0.981 and p = 0.562. Conclusions: Although significantly higher values of α-tocopherol were found in both serum and omental fat, antioxidant vitamins C and E did not demonstrate a significant protective effect on atherosclerosis in lipid-fed rabbits during the 10-week study period.

Study of the Effects of Total Flavonoids of Astragalus on Atherosclerosis Formation and Potential Mechanisms

“…In support of our findings, a double-masked placebo-controlled randomized clinical trial has shown that long-term supplementation of nondepleted men with a reasonable dose of vitamin E alone or in combination with slow release vitamin C reduces lipid peroxidation [20]. However, in previous reports by Kinlay et al [21] and by Sun et al [22], they did not demonstrate a significant protective effect on lipids in human and animal. Thus, it is plausible that the effects of TFA and the combination of vitamin E plus C on lipid metabolism might be involved in other mechanisms in addition to the antioxidant.…”

Vulnerable Atherosclerotic Plaque Morphology in Apolipoprotein E–Deficient Mice Unable to Make Ascorbic Acid

“…The results have been conflicting, ranging from increased fatty streaks in vitamin C-deficient guinea pigs 15 to no effects of vitamin C supplementation in cholesterol-fed rabbits. 16 LDL oxidation in Apoe Ϫ/Ϫ mice occurs in vivo as demonstrated by increased amounts of circulating autoantibody against oxidized LDL, 17 and antioxidants, such as vitamin E and N,N-diphenyl 1,4-phenylenediamine, have been shown to reduce atherosclerosis in Apoe Ϫ/Ϫ mice. 18,19 In support of a role for vitamin E, Apoe Ϫ/Ϫ mice that also lack vitamin E transfer protein and have vitamin E deficiency (Ͻ10% normal in plasma) had modest but significant increases in atherosclerosis.…”

Effect of Vitamin E on Lipid Parameters in Ovariectomized Rats

“…Elevation of total cholesterol in male mongrel rabbits fed a high fat diet was also markedly suppressed by vitamin E, which was attributed to the higher levels of 7␣-hydroxylase, an enzyme involved in the conversion of cholesterol to bile acids. 19 On the other hand, supplementation with vitamin E did not reduce hypercholesterolemia in New Zealand rabbits 28,29 and hamsters. 30 One explanation put forth by Shen et al 30 for the inconsistent effect of vitamin E on plasma cholesterol, at least in hamsters, is that the effect of vitamin E is only manifested under conditions of high cholesterol feeding, which sets the stage for vitamin E-induced alterations in the generation of cholesteryl ester transfer protein activity from adipose tissue.…”

“…While there are studies that have shown a hypocholesterolemic effect of vitamin E, [18][19][20][21][22] certain studies have shown no effect of vitamin E on serum lipids. [28][29][30] For example, findings by Phonpanichrasamee et al 18 show that oral supplementation with 2,100 IU vitamin E/week lowered cholesterol by 50% after 8 weeks of supplementation. Elevation of total cholesterol in male mongrel rabbits fed a high fat diet was also markedly suppressed by vitamin E, which was attributed to the higher levels of 7␣-hydroxylase, an enzyme involved in the conversion of cholesterol to bile acids.…”