Susceptibility of human LDL to oxidative modification. Effects of variations in beta-carotene concentration and oxygen tension.

Epidemiological studies suggest that beta-carotene supplementation may decrease atherosclerotic events. Because beta-carotene is transported in low-density lipoprotein (LDL), one mechanism by which this protective effect may occur is through direct inhibition of LDL oxidation. Addition of beta-carotene to LDL in vitro inhibits the susceptibility of LDL to oxidation. In contrast, we have shown that feeding large doses of beta-carotene results in beta-carotene-enriched plasma LDL (16- to 35-fold), but such LDL does not show increased resistance to oxidation. Potential criticisms of our initial study relate to the unique antioxidant properties of beta-carotene. Beta-Carotene provides better quenching of some free radicals, such as singlet oxygen, than others. Additionally, since beta-carotene can easily autooxidize, forming metabolites that can also generate free radicals, it has been argued that at sufficient concentrations in vivo the antioxidant effect of beta-carotene may be diminished. It has thus been suggested that in our initial study we may have failed to properly assess the unique antioxidant effects of beta-carotene by our selection of oxidizing conditions and/or failed to achieve antioxidant activity because of excessive enrichment of LDL with beta-carotene. We now report the effects of feeding lower doses of beta-carotene on the susceptibility of LDL to oxidation and test whether any antioxidant activity of beta-carotene can be detected when different modes of initiating oxidation are used. Because the antioxidant activity of beta-carotene is reputedly most pronounced in low-oxygen environments, we also investigated its effect on LDL oxidation under conditions of reduced oxygen tension.(ABSTRACT TRUNCATED AT 250 WORDS)