Reduction in plasma or skin alpha tocopherol concentration with long-term oral administration of beta-carottene in humans and mice

M. J. Xu, P. M. Plezia, D. S. Alberts, S. S. Emerson, Y. M. Peng, S. M. Sayers, Y. Liu, C. Ritenbaugh, H. L. Gensler

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94 Scopus citations


Background: Beta-carotene is one of the most commonly used compounds in clinical trials of chemopreventive agents in various neoplastic diseases. Animal Studies, in cluding our own, have documented that dietary betacarotene can reduce plasma alpha-tocopherol (vitamin E) levels, but few published studies have examined the clinical of pharmacokinetic ramifications of long-term, high-dose beta -carotene regimens on other fat-soluble vitamines sugh as alpha-tocopherol. purpose: This study was designed to determine on plasma concentrations of alphatocopherol in normal human subjects and in an experimental C3H/HeH mouse model, Methods; In a doubleblind study, 45 normal subjects were randomly assigned to receive 0 (placebo), 15, 310, 45, or 60 mg of oral betacarotene daily for approximately 9 months. Monthly plasma samples were collected. Thirty-fie C3H/HeH mice were fed a basal diet with of without beta-carotene and treated topically with or without alpha-tocopherolo, except for the control mice, which received UV radiation for 27 weeks from week 3 to week 30. plasma and dorsal skin samples were taken after 40 weeks and were analyzed for alpha-tocopherol and /or beta-carotene by highperformance liquid chromatography. Results: Long-term dietary beta-carotene administration resulted in statistically significant reductions in levels of alpha-tocopherol in the skin and plasma of UV-irradiated mice. In the human study, the decrease in plasma alpha-tocopherol levels was progressive and significant between 6 and 9 months of beta-carotene dosing in all dosage groups. The greatest decrease was observed during the 9th (last) moths of dosing with a secrease of 40& from baseline. All oral betacarotene doses (15-60 mg/d, hoowever, resultedin similar and in only small differenses in beta-carotene plasma levels.Conclusion: Long-term oral adminiatration of beta carotene decreased steady-state plasma concentrations of alpha-tocopherol. The lack of a significant dose-responce effect between dose of beta-carotene and alpha-tocopherol plasma levels is not unexpected, given the small differences in steady-state beta-carotene plasma levels in the for beta-carotene dose groups. Implications: Studies are needed to determine how long-term beta-carotne dosing influences tissue distribution of dietary alphatopherol. Careful surveillance for this ad other potentially harmful nutrient interactions should become part of all long-term intervention studies.[J Natl Cancer Inst 84: 1559-1565, 1992]

Original languageEnglish (US)
Pages (from-to)1559-1565
Number of pages7
JournalJournal of the National Cancer Institute
Issue number20
StatePublished - Oct 21 1992

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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