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 physiol ogically widespread hydrophobic iron compound, can rapidly generate ox idized low-density lipoprotein (LDL), which then becomes cytotoxic to cultured vascular endothelial cells; both LDL oxidation and endothelia l cytotoxicity were inhibited by incubation with exogenous alpha-tocop herol (vitamin E) or ascorbic acid (vitamin C). Seeking relevance to i n vivo conditions, we performed a study in which 10 human volunteers w ere given daily antioxidant supplements of 800 IU of DL-alpha-tocopher ol 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 l ag time for conjugated-diene formation, increased by as much as threef old from a mean+/-SD of 58+/-11 to 104+/-18 minutes (P<.001); LDL alph a-tocopherol increased from 11+/-2 to 26+/-6 molecules per LDL particl e (P<.001); and most impressively, cytotoxicity to porcine aortic endo thelial cells incubated with LDL conditioned with heme plus H2O2 or wi th copper was completely prevented (cytotoxicity before supplementatio n was 42+/-12%, decreasing after supplementation to 3+/-2%, P<.001). T hese measurements reverted to their presupplement levels within 2 week s after participants stopped taking antioxidant supplements and were r eproduced in 4 subjects taking 800 IU of DL-alpha-tocopherol acetate s upplements 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 ox idation, and decreases the cytotoxicity of oxidized LDL to cultured va scular endothelial cells.