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

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

Research output: Contribution to journalArticle

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Abstract

Background: Beta-carotene is one of the most commonly used compounds in clinical trials of chemopreventive agents in various neoplastic diseases. Animal studies, including our own, have documented that dietary beta-carotene can reduce plasma alpha-tocopherol (vitamin E) levels, but few published studies have examined the clinical or pharmacokinetic ramifications of long-term, high-dose beta-carotene regimens on other fat-soluble vitamins such as alpha-tocopherol. Purpose: This study was designed to determine the effects of long-term beta-carotene supplementation on plasma concentrations of alpha-tocopherol in normal human subjects and in an experimental C3H/HeN mouse model. Methods: In a double-blind study, 45 normal subjects were randomly assigned to receive 0 (placebo), 15, 30, 45, or 60 mg of oral beta-carotene daily for approximately 9 months. Monthly plasma samples were collected. Thirty-five C3H/HeN mice were fed a basal diet with or without beta-carotene and treated topically with or without alpha-tocopherol, 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 high-performance 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) month of dosing, with a decrease of 40% from baseline. All oral beta-carotene doses (15-60 mg/d), however, resulted in similar decreases in steady-state plasma levels of alpha-tocopherol and in only small differences in beta-carotene plasma levels. Conclusion: Long-term oral administration of beta-carotene decreased steady-state plasma concentrations of alpha-tocopherol. The lack of a significant dose-response effect between doses of beta-carotene and alpha-tocopherol plasma levels is not unexpected, given the small differences in steady-state beta-carotene plasma levels in the four beta-carotene dose groups. Implications: Studies are needed to determine how long-term beta-carotene dosing influences tissue distribution of dietary alpha-tocopherol. Careful surveillance for this and other potentially harmful nutrient interactions should become part of all long-term intervention studies.

Original languageEnglish (US)
Pages (from-to)1559-1565
Number of pages7
JournalJournal of the National Cancer Institute
Volume84
Issue number20
StatePublished - Oct 21 1992

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beta Carotene
alpha-Tocopherol
Skin
Oral Administration
Mouse
Plasma
Plasmas
Dose
Decrease
Human
Carotenoids
Inbred C3H Mouse
Vitamins
Dose-response
Pharmacokinetics
High-performance Liquid Chromatography
Ramification
Nutrients
Clinical Trials
Surveillance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging

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Reduction in plasma or skin alpha-tocopherol concentration with long-term oral administration of beta-carotene in humans and mice. / Xu, M. J.; Plezia, P. M.; Alberts, David S; Emerson, S. S.; Peng, Y. M.; Sayers, S. M.; Liu, Y.; Ritenbaugh, C.; Gensler, H. L.

In: Journal of the National Cancer Institute, Vol. 84, No. 20, 21.10.1992, p. 1559-1565.

Research output: Contribution to journalArticle

Xu, MJ, Plezia, PM, Alberts, DS, Emerson, SS, Peng, YM, Sayers, SM, Liu, Y, Ritenbaugh, C & Gensler, HL 1992, 'Reduction in plasma or skin alpha-tocopherol concentration with long-term oral administration of beta-carotene in humans and mice', Journal of the National Cancer Institute, vol. 84, no. 20, pp. 1559-1565.
Xu, M. J. ; Plezia, P. M. ; Alberts, David S ; Emerson, S. S. ; Peng, Y. M. ; Sayers, S. M. ; Liu, Y. ; Ritenbaugh, C. ; Gensler, H. L. / Reduction in plasma or skin alpha-tocopherol concentration with long-term oral administration of beta-carotene in humans and mice. In: Journal of the National Cancer Institute. 1992 ; Vol. 84, No. 20. pp. 1559-1565.
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title = "Reduction in plasma or skin alpha-tocopherol concentration with long-term oral administration of beta-carotene in humans and mice",
abstract = "Background: Beta-carotene is one of the most commonly used compounds in clinical trials of chemopreventive agents in various neoplastic diseases. Animal studies, including our own, have documented that dietary beta-carotene can reduce plasma alpha-tocopherol (vitamin E) levels, but few published studies have examined the clinical or pharmacokinetic ramifications of long-term, high-dose beta-carotene regimens on other fat-soluble vitamins such as alpha-tocopherol. Purpose: This study was designed to determine the effects of long-term beta-carotene supplementation on plasma concentrations of alpha-tocopherol in normal human subjects and in an experimental C3H/HeN mouse model. Methods: In a double-blind study, 45 normal subjects were randomly assigned to receive 0 (placebo), 15, 30, 45, or 60 mg of oral beta-carotene daily for approximately 9 months. Monthly plasma samples were collected. Thirty-five C3H/HeN mice were fed a basal diet with or without beta-carotene and treated topically with or without alpha-tocopherol, 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 high-performance 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) month of dosing, with a decrease of 40{\%} from baseline. All oral beta-carotene doses (15-60 mg/d), however, resulted in similar decreases in steady-state plasma levels of alpha-tocopherol and in only small differences in beta-carotene plasma levels. Conclusion: Long-term oral administration of beta-carotene decreased steady-state plasma concentrations of alpha-tocopherol. The lack of a significant dose-response effect between doses of beta-carotene and alpha-tocopherol plasma levels is not unexpected, given the small differences in steady-state beta-carotene plasma levels in the four beta-carotene dose groups. Implications: Studies are needed to determine how long-term beta-carotene dosing influences tissue distribution of dietary alpha-tocopherol. Careful surveillance for this and other potentially harmful nutrient interactions should become part of all long-term intervention studies.",
author = "Xu, {M. J.} and Plezia, {P. M.} and Alberts, {David S} and Emerson, {S. S.} and Peng, {Y. M.} and Sayers, {S. M.} and Y. Liu and C. Ritenbaugh and Gensler, {H. L.}",
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T1 - Reduction in plasma or skin alpha-tocopherol concentration with long-term oral administration of beta-carotene in humans and mice

AU - Xu, M. J.

AU - Plezia, P. M.

AU - Alberts, David S

AU - Emerson, S. S.

AU - Peng, Y. M.

AU - Sayers, S. M.

AU - Liu, Y.

AU - Ritenbaugh, C.

AU - Gensler, H. L.

PY - 1992/10/21

Y1 - 1992/10/21

N2 - Background: Beta-carotene is one of the most commonly used compounds in clinical trials of chemopreventive agents in various neoplastic diseases. Animal studies, including our own, have documented that dietary beta-carotene can reduce plasma alpha-tocopherol (vitamin E) levels, but few published studies have examined the clinical or pharmacokinetic ramifications of long-term, high-dose beta-carotene regimens on other fat-soluble vitamins such as alpha-tocopherol. Purpose: This study was designed to determine the effects of long-term beta-carotene supplementation on plasma concentrations of alpha-tocopherol in normal human subjects and in an experimental C3H/HeN mouse model. Methods: In a double-blind study, 45 normal subjects were randomly assigned to receive 0 (placebo), 15, 30, 45, or 60 mg of oral beta-carotene daily for approximately 9 months. Monthly plasma samples were collected. Thirty-five C3H/HeN mice were fed a basal diet with or without beta-carotene and treated topically with or without alpha-tocopherol, 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 high-performance 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) month of dosing, with a decrease of 40% from baseline. All oral beta-carotene doses (15-60 mg/d), however, resulted in similar decreases in steady-state plasma levels of alpha-tocopherol and in only small differences in beta-carotene plasma levels. Conclusion: Long-term oral administration of beta-carotene decreased steady-state plasma concentrations of alpha-tocopherol. The lack of a significant dose-response effect between doses of beta-carotene and alpha-tocopherol plasma levels is not unexpected, given the small differences in steady-state beta-carotene plasma levels in the four beta-carotene dose groups. Implications: Studies are needed to determine how long-term beta-carotene dosing influences tissue distribution of dietary alpha-tocopherol. Careful surveillance for this and other potentially harmful nutrient interactions should become part of all long-term intervention studies.

AB - Background: Beta-carotene is one of the most commonly used compounds in clinical trials of chemopreventive agents in various neoplastic diseases. Animal studies, including our own, have documented that dietary beta-carotene can reduce plasma alpha-tocopherol (vitamin E) levels, but few published studies have examined the clinical or pharmacokinetic ramifications of long-term, high-dose beta-carotene regimens on other fat-soluble vitamins such as alpha-tocopherol. Purpose: This study was designed to determine the effects of long-term beta-carotene supplementation on plasma concentrations of alpha-tocopherol in normal human subjects and in an experimental C3H/HeN mouse model. Methods: In a double-blind study, 45 normal subjects were randomly assigned to receive 0 (placebo), 15, 30, 45, or 60 mg of oral beta-carotene daily for approximately 9 months. Monthly plasma samples were collected. Thirty-five C3H/HeN mice were fed a basal diet with or without beta-carotene and treated topically with or without alpha-tocopherol, 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 high-performance 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) month of dosing, with a decrease of 40% from baseline. All oral beta-carotene doses (15-60 mg/d), however, resulted in similar decreases in steady-state plasma levels of alpha-tocopherol and in only small differences in beta-carotene plasma levels. Conclusion: Long-term oral administration of beta-carotene decreased steady-state plasma concentrations of alpha-tocopherol. The lack of a significant dose-response effect between doses of beta-carotene and alpha-tocopherol plasma levels is not unexpected, given the small differences in steady-state beta-carotene plasma levels in the four beta-carotene dose groups. Implications: Studies are needed to determine how long-term beta-carotene dosing influences tissue distribution of dietary alpha-tocopherol. Careful surveillance for this and other potentially harmful nutrient interactions should become part of all long-term intervention studies.

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