High-dose α-tocopherol therapy does not affect HDL subfractions in patients with coronary artery disease on statin therapy

Background: Subfractions of HDL, particularly large HDL (HDL2), are inversely correlated with the severity of coronary artery disease (CAD). α-Tocopherol (AT) is the main lipid-soluble antioxidant in plasma. Results of a previous small study (n = 44) suggested that either a combination of an antioxidant cocktail [800 IU/day 2R,4′R,8′R-(RRR)-AT plus 1 g vitamin C, 25 mg β-carotene, and 100 μg selenium] or individual antioxidant vitamins combined with simvastatin-niacin (S-N) therapy attenuated the protective increase in HDL2 seen with S-N alone. Few data are available on the effect of AT therapy alone on HDL subfractions, which we addressed in this study. Methods: In a prospective placebo-controlled study, we randomized 127 patients with stable CAD to receive high-dose RRR-AT (1200 IU/day for 2 years) or placebo. HDL subfractions (small, medium, and large HDL particles) were analyzed by nuclear magnetic resonance spectroscopy. Results: AT concentrations significantly increased in the AT arm but not with placebo. No differences were noted between AT and placebo groups in concentrations of total cholesterol, triglyceride, LDL-cholesterol, or HDL-cholesterol. AT therapy did not affect total, small, medium, or large HDL particles compared with baseline or placebo. Furthermore, serum apolipoprotein A1 concentrations did not change after 2 years AT therapy as compared with baseline. Conclusions: High-dose AT therapy administered for a 2-year period does not negatively affect either HDL subfractions or apolipoprotein A1 in patients with CAD on statin therapy. Thus the negative interaction previously proposed between antioxidant cocktail and statin therapy cannot be attributed to AT.