Vitamin E, LDL, and endothelium. Brief oral vitamin supplementation prevents oxidized LDL-mediated vascular injury in vitro.
In previously reported in vitro studies, we found that heme, a physiologically widespread hydrophobic iron compound, can rapidly generate oxidized low-density lipoprotein (LDL), which then becomes cytotoxic to cultured vascular endothelial cells; both LDL oxidation and endothelial cytotoxicity were inhibited by incubation with exogenous alpha-tocopherol (vitamin E) or ascorbic acid (vitamin C). Seeking relevance to in vivo conditions, we performed a study in which 10 human volunteers were given daily antioxidant supplements of 800 IU of DL-alpha-tocopherol acetate alone or in combination with 1000 mg of ascorbic acid for 2 weeks. LDL resistance to heme oxidation ex vivo, as measured by the lag time for conjugated-diene formation, increased by as much as threefold from a mean +/- SD of 58 +/- 11 to 104 +/- 18 minutes (P < .001); LDL alpha-tocopherol increased from 11 +/- 2 to 26 +/- 6 molecules per LDL particle (P < .001); and most impressively, cytotoxicity to porcine aortic endothelial cells incubated with LDL conditioned with heme plus H2O2 or with copper was completely prevented (cytotoxicity before supplementation was 42 +/- 12%, decreasing after supplementation to 3 +/- 2%, P < .001). These measurements reverted to their presupplement levels within 2 weeks after participants stopped taking antioxidant supplements and were reproduced in 4 subjects taking 800 IU of DL-alpha-tocopherol acetate supplements alone but not in the same subjects taking 1000 mg ascorbic acid supplements alone. In conclusion, oral vitamin E supplementation increases LDL alpha-tocopherol content, increases LDL resistance to oxidation, and decreases the cytotoxicity of oxidized LDL to cultured vascular endothelial cells.
Belcher
J D
JD
Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55454-1015.
Balla
J
J
Balla
G
G
Jacobs
D R
DR
Gross
M
M
Jacob
H S
HS
Vercellotti
G M
GM
D000328:Adult; D000818:Animals; D000975:Antioxidants; D001011:Aorta; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D006418:Heme / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013552:Swine; D024505:Tocopherols; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
D000975:Antioxidants; D017077:Culture Media, Conditioned; D008077:Lipoproteins, LDL; D014810:Vitamin E; D006418:Heme; D003300:Copper; D006861:Hydrogen Peroxide; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D024505:Tocopherols