Alpha-Tocopherol Supplementation in Healthy Individuals Reduces Low-Density Lipoprotein Oxidation but Not Atherosclerosis

Abstract

Background-Epidemiological studies have demonstrated an inverse relationship between vitamin E intake and cardiovascular disease (CVD) risk. In contrast, randomized controlled trials have reported conflicting results as to whether vitamin E supplementation reduces atherosclerosis progression and CVD events. Methods and Results-The study population consisted of men and women Ն40 years old with an LDL cholesterol level Ն3.37 mmol/L (130 mg/dL) and no clinical signs or symptoms of CVD. Eligible participants were randomized to DL-␣-tocopherol 400 IU per day or placebo and followed every 3 months for an average of 3 years. The primary trial end point was the rate of change in the common carotid artery far-wall intima-media thickness (IMT) assessed by computer image-processed B-mode ultrasonograms. A mixed effects model using all determinations of IMT was used to test the hypothesis of treatment differences in IMT change rates. Compared with placebo, ␣-tocopherol supplementation significantly raised plasma vitamin E levels (PϽ0.0001), reduced circulating oxidized LDL (Pϭ0.03), and reduced LDL oxidative susceptibility (PϽ0.01). However, vitamin E supplementation did not reduce the progression of IMT over a 3-year period compared with subjects randomized to placebo. Conclusions-The results are consistent with previous randomized controlled trials and extend the null results of vitamin E supplementation to the progression of IMT in healthy men and women at low risk for CVD.

Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans

“…A large percentage of both CR and comparison subjects were taking a variety of supplements. However, this should not interfere with the interpretation of our findings, because it has been shown that supplementation with antioxidant vitamins does not lower serum lipid and lipoproteins (29)(30)(31)(32)(33)(34) or BP (29). Moreover, a recent study, conducted in more than 20,000 subjects, found that vitamin E, vitamin C, and ␤-carotene supplementation resulted in small but significant increases in plasma Tchol, LDL-C, and TG concentrations (30).…”

Tocotrienols and Atherosclerosis

“…OxLDL can induce endothelial dysfunction (2) and expression of cytokines (3), growth factors, and several cell surface adhesion molecules (4) that are capable of recruiting circulating monocytes and T lymphocytes into the intima. OxLDL activates the development of monocytes into macrophages where the uptake of oxLDL via the scavenger receptor is rapid (5,6), and inhibits the migration of macrophages (8). OxLDL stimulates cell proliferation and transmigration of smooth muscle cells (7).…”

“…In contrast, clinical trials using this vitamin have been giving a more confused picture than expected, with results ranging from a significant protective action to the absence of any effect. Recent Vitamin E Atherosclerosis Prevention Study (VEAPS) study have demonstrated that ot-tocopherol supplecantly raised plasma vitamin E levels, reduced circulating oxLDL, and reduced LDL oxidative susceptibility, however, the progression of the intima-media thickness of common carotid artery was not reduced by the treatment [5].…”

Antioxidants and Atherosclerosis

“…In the Vitamin E Atherosclerosis Prevention Study (VEAPS), plasma levels of AT increased significantly in both the placebo group (33%) and the AT group, and thus it is hard to determine the effect of this on the primary endpoint. 12 Also, only 3 studies reported biomarkers of oxidative stress.…”