Oxidized low-density lipoproteins and endothelium: oral vitamin E supplementation prevents oxidized low-density lipoprotein-mediated vascular injury.

Abstract

Vitamin E supplements may decrease the incidence of myocardial infarction by inhibiting LDL oxidation to atherogenic moieties. We previously reported that hemin is a potent and relevant lipophilic source of iron that can rapidly intercalate into LDL, catalyzing its oxidation and promoting its cytolysis of endothelium. The effects of oral vitamin E on heme-catalyzed LDL oxidation and resulting endothelial damage were studied in 10 volunteers who received daily 800 I.U. of vitamin E with or without vitamin C (1000 mg) for 2 weeks. Prior, during, and 2 weeks after supplementation, plasma LDL was isolated and its number of alpha-tocopherol molecules, resistance to heme-catalyzed oxidation, and ability to damage porcine aortic endothelial cells were assayed. Vitamin E supplementation doubled the lag phase of LDL peroxidation as compared to control (104 +/- 18 vs. 58 +/- 11 min; p < 0.001) accompanied by an increase in alpha-tocopherol content of LDL particles (26 +/- 6 vs. 11 +/- 2 mol/mol; p < 0.001). Most intriguingly, LDL-mediated endothelial cell cytotoxicity was prevented (3 +/- 2% vs. 42 +/- 12%; p < 0.001). After a 2-week washout period, LDL alpha-tocopherol content, the lag time of LDL oxidation, and oxidized LDL-mediated cytolysis all returned to baseline levels. To determine whether supplements of vitamin E and vitamin C beneficially synergize in these effects, we monitored several volunteers on daily vitamin E alone or vitamin C alone. Vitamin E alone (at doses as low as 400 I.U./day) affected all measurements in a manner identical to that when it was taken with vitamin C. Vitamin C alone had no significant effect on these measurements. We conclude: dietary vitamin E supplementation provides cytoprotection against LDL oxidation-mediated endothelial cell injury, but this salutary effect is rapidly lost after supplementation is stopped.