Vitamin E, LDL, and endothelium: Brief oral vitamin supplementation prevents oxidized LDL-mediated vascular injury in vitro

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Abstract

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 α-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-α-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 Iag 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 α-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-α-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 α-tocopherol content, increases LDL resistance to oxidation, and decreases the cytotoxicity of oxidized LDL to cultured vascular endothelial cells.

Original languageEnglish (US)
Pages (from-to)1779-1789
Number of pages11
JournalArteriosclerosis and Thrombosis
Volume13
Issue number12
DOIs
StatePublished - 1993

Keywords

  • LDL
  • atherosclerosis
  • heme
  • iron
  • oxidized LDL
  • vitamin C
  • vitamin E

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