Vitamin E supplementation and atherosclerosis : Epidemiological studies in smokers and elderly

The antioxidant vitamin E may have beneficial effects on several indicators of human health. We studied the impact on atherosclerosis, immune response and total mortality in smokers and elderly people, who are at risk for increased oxidative stress. Vitamin E may exert its effect on atherosclerosis by protecting low density lipoprotein (LDL) against lipid peroxidation. Moreover, lipid peroxidation may also negatively influence the immune response. In addition to its antioxidant function, vitamin E may be beneficial through effects on cellular function, e.g., by preserving endothelium-dependent vaso-relaxation or decreasing cytokine production.<strong>Observational studies</strong> . In a cross-sectional study among 158 male lifelong smokers aged 50 to 75 years, adjusted vitamin E intake and plasma levels were not associated with intima media wall thickness (IMT) of the common carotid artery. IMT ,which is a marker for atherosclerosis, was measured non-invasively by using the B-mode ultrasound technique. In a prospective study among 638 independently living elderly aged 65 to 85, no significant association was observed between cholesterol adjusted serum levels of vitamin E and 7.2 years total mortality. (Hazard ratio for lowest tertile vs. highest of 1.11, 95% confidence interval 0.74 to 1.65).<strong>Intervention trials.</strong> In a randomized placebo-controlled double-blind trial among 218 lifelong male smokers, 400 IU (364 mg) vitamin E was administered daily for two years. A non significant (p=0.34) reduced progression of carotid IMT by 47% was observed compared to a significant spontaneous progression in the placebo group of 0.030 mm (p=0.006). Results were adjusted for initial IMT values and traditional CVD risk factors. Vitamin E significantly reduced the in vitro susceptibility of LDL to oxidation, which was not related to progression.In this trial results were stratified by genetic predisposition. Smokers lacking the detoxifying enzyme activity of glutathion S -transferase µ (genotype GSTM1- 0 ) were compared with those with the positive genotype (GSTM1- 1 ). In the GSTM1- 0 group vitamin E reduced the proportion of smokers with increased carotid IMT by 62% (p=0.06) for the left posterior and by 73% (p=0.01) for the left anterior wall. No effects were observed for the IMT at the right side.In a 3-month randomized double-blind placebo-controlled trial among 83 apparently healthy elderly, aged 67-87 years, 100 mg vitamin E supplementation significantly decreased the percentage of oxidized linoleic acid in LDL (10.4%) compared to the placebo group (4.6%). In this trial vitamin E supplementation did not affect the cellular and humoral immune response.<strong>In conclusion</strong> , no supportive evidence is provided that vitamin E supplementation has beneficial effects on atherosclerosis and immune response among smokers and elderly. The observations for GSTM1- 0 genotype needs further confirmation. The protective effect of vitamin E on LDL oxidation in vitro lacks validation in vivo. Research on biomarkers of lipid oxidation and arterial damage needs priority to more adequately assess the clinical relevance and optimal intake of vitamin E