Studies in humans using deuterium-labeled α- and γ-tocopherols demonstrate faster plasma γ-tocopherol disappearance and greater γ-metabolite production

Scott W. Leonard, Elaine Paterson, Jeffrey K. Atkinson, Rajasekhar Ramakrishnan, Carroll E Cross, Maret G. Traber

Research output: Contribution to journalArticle

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Abstract

We hypothesized that human plasma α- and γ-tocopherol concentrations reflect differences in their kinetics, especially influenced by γ-tocopherol metabolism. Vitamin E kinetics were evaluated in humans (n = 14) using ∼50 mg each of an equimolar ratio of d6-α- and d2-γ-tocopheryl acetates administered orally. Mass spectrometry was used to measure deuterated plasma tocopherols, as well as plasma and urinary vitamin E metabolites, α- and γ-carboxyethylhydroxychromans (CEHCs). Plasma d2-γ-tocopherol fractional disappearance rates (FDR; 1.39 ± 0.44 pools/day, mean ± SD) were more than three times greater than those of d6-α-tocopherol (0.33 ± 0.11, p < 0.001). The d2-γ-tocopherol half-life was 13 ± 4 h compared with 57 ± 19 for d6-α-tocopherol. Whereas neither plasma nor urinary d6-α-CEHC was detectable (limit of detection 1 nmol/L), γ-CEHC (labeled plus unlabeled) increased from 129 ± 20 to 258 ± 40 nmol/L by 12 h and returned to baseline by 48 h; at 12 h d2-γ-CEHC represented 54 ± 4% of plasma γ-CEHC. Women compared with men had a greater d2-γ- tocopherol FDR (p < 0.004) and a greater maximal plasma d2- γ-CEHC concentration (p < 0.02) and CEHC FDR (p < 0.007), as well as excreting four times as much d2-γ-CEHC (p < 0.04) in urine. Thus, γ-tocopherol is rapidly metabolized to γ-CEHC, and to a greater degree in women than in men, whereas α-tocopherol is maintained in the plasma and little is metabolized to α-CEHC.

Original languageEnglish (US)
Pages (from-to)857-866
Number of pages10
JournalFree Radical Biology and Medicine
Volume38
Issue number7
DOIs
StatePublished - Apr 1 2005

Fingerprint

Tocopherols
Deuterium
Metabolites
Plasmas
Enzyme kinetics
Vitamin E
Plasma (human)
alpha-Tocopherol
Metabolism
Mass spectrometry
Half-Life
Limit of Detection
Mass Spectrometry
Urine

Keywords

  • α-CEHC
  • γ-CEHC
  • F-isoprostanes
  • Free radicals
  • Mass spectometry
  • Vitamin E kinetics

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Studies in humans using deuterium-labeled α- and γ-tocopherols demonstrate faster plasma γ-tocopherol disappearance and greater γ-metabolite production. / Leonard, Scott W.; Paterson, Elaine; Atkinson, Jeffrey K.; Ramakrishnan, Rajasekhar; Cross, Carroll E; Traber, Maret G.

In: Free Radical Biology and Medicine, Vol. 38, No. 7, 01.04.2005, p. 857-866.

Research output: Contribution to journalArticle

Leonard, Scott W. ; Paterson, Elaine ; Atkinson, Jeffrey K. ; Ramakrishnan, Rajasekhar ; Cross, Carroll E ; Traber, Maret G. / Studies in humans using deuterium-labeled α- and γ-tocopherols demonstrate faster plasma γ-tocopherol disappearance and greater γ-metabolite production. In: Free Radical Biology and Medicine. 2005 ; Vol. 38, No. 7. pp. 857-866.
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AU - Ramakrishnan, Rajasekhar

AU - Cross, Carroll E

AU - Traber, Maret G.

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AB - We hypothesized that human plasma α- and γ-tocopherol concentrations reflect differences in their kinetics, especially influenced by γ-tocopherol metabolism. Vitamin E kinetics were evaluated in humans (n = 14) using ∼50 mg each of an equimolar ratio of d6-α- and d2-γ-tocopheryl acetates administered orally. Mass spectrometry was used to measure deuterated plasma tocopherols, as well as plasma and urinary vitamin E metabolites, α- and γ-carboxyethylhydroxychromans (CEHCs). Plasma d2-γ-tocopherol fractional disappearance rates (FDR; 1.39 ± 0.44 pools/day, mean ± SD) were more than three times greater than those of d6-α-tocopherol (0.33 ± 0.11, p < 0.001). The d2-γ-tocopherol half-life was 13 ± 4 h compared with 57 ± 19 for d6-α-tocopherol. Whereas neither plasma nor urinary d6-α-CEHC was detectable (limit of detection 1 nmol/L), γ-CEHC (labeled plus unlabeled) increased from 129 ± 20 to 258 ± 40 nmol/L by 12 h and returned to baseline by 48 h; at 12 h d2-γ-CEHC represented 54 ± 4% of plasma γ-CEHC. Women compared with men had a greater d2-γ- tocopherol FDR (p < 0.004) and a greater maximal plasma d2- γ-CEHC concentration (p < 0.02) and CEHC FDR (p < 0.007), as well as excreting four times as much d2-γ-CEHC (p < 0.04) in urine. Thus, γ-tocopherol is rapidly metabolized to γ-CEHC, and to a greater degree in women than in men, whereas α-tocopherol is maintained in the plasma and little is metabolized to α-CEHC.

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KW - Mass spectometry

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