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

Peter D. Reaven, Eric Ferguson, Mahamad Navab, Frank L. Powell

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Epidemiological studies suggest that β-carotene supplementation may decrease atherosclerotic events. Because β-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 β-carotene to LDL in vitro inhibits the susceptibility of LDL to oxidation. In contrast, we have shown that feeding large doses of β-carotene results in β-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 β-carotene. β-Carotene provides better quenching of some free radicals, such as singlet oxygen, than others. Additionally, since β-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 β-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 β-carotene by our selection of oxidizing conditions and/or failed to achieve antioxidant activity because of excessive enrichment of LDL with β-carotene. We now report the effects of feeding lower doses of β-carotene on the susceptibility of LDL to oxidation and test whether any antioxidant activity of β-carotene can be detected when different modes of initiating oxidation are used. Because the antioxidant activity of β-carotene is reputedly most pronounced in low-oxygen environments, we also investigated its effect on LDL oxidation under conditions of reduced oxygen tension. Dietary supplementation of 12 subjects with β-carotene over a 6-week period led to a gradual increase in their LDL β-carotene content (2.5- to 15-fold higher than in LDL from control subjects). Compared with LDL isolated from subjects taking placebo capsules, LDL from subjects receiving β-carotene was equally susceptible to both cell-mediated and non-cell-mediated oxidation and modification as measured by the formation of conjugated dienes and thiobarbituric acid-reactive substances and the change in electrophoretic mobility. Furthermore, no differences in extent of LDL oxidation were seen between study groups when oxidation reactions were performed at low oxygen tension. Addition of control LDL to cocultures of endothelial and smooth muscle cells led to an LDL modification that stimulated an increase in monocyte adhesion to endothelial cells and transmigration through Cocultures. When β-carotene-enriched LDL was added to the cocultures, monocyte adhesion and transmigration were similarly increased. In contrast, LDL added to cocultures that were preincubated with β-carotene did not increase monocyte adhesion and transmigration. Thus, oral β-carotene supplementation does not provide direct antioxidant protection to LDL particles, but β-carotene may inhibit the ability of cells to oxidize lipoproteins.

Original languageEnglish (US)
Pages (from-to)1162-1169
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number7
StatePublished - 1994
Externally publishedYes


  • Atherosclerosis
  • Cocultures
  • LDL
  • Lipid oxidation
  • Low oxygen tension

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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