Document Detail


gamma-Tocopherol biokinetics and transformation in humans.
MedLine Citation:
PMID:  14703735     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The uptake and biotransformation of gamma-tocopherol (gamma-T) in humans is largely unknown. Using a stable isotope method we investigated these aspects of gamma-T biology in healthy volunteers and their response to gamma-T supplementation. METHODS: A single bolus of 100 mg of deuterium labeled gamma-T acetate (d(2)-gamma-TAC, 94% isotopic purity) was administered with a standard meal to 21 healthy subjects. Blood and urine (first morning void) were collected at baseline and a range of time points between 6 and 240 h post-supplemetation. The concentrations of d(2) and d(0)-gamma-T in plasma and its major metabolite 2,7,8-trimethyl-2-(b-carboxyethyl)-6-hydroxychroman (-gamma-CEHC) in plasma and urine were measured by GC-MS. In two subjects, the total urine volume was collected for 72 h post-supplementation. The effects of gamma-T supplementation on alpha-T concentrations in plasma and alpha-T and gamma-T metabolite formation were also assessed by HPLC or GC-MS analysis. RESULTS: At baseline, mean plasma alpha-T concentration was approximately 15 times higher than gamma-T (28.3 vs. 1.9 micromol/l). In contrast, plasma gamma-CEHC concentration (0.191 micromol/l) was 12 fold greater than alpha-CEHC (0.016 micromol/l) while in urine it was 3.5 fold lower (0.82 and 2.87 micromol, respectively) suggesting that the clearance of alpha-CEHC from plasma was more than 40 times that of gamma-CEHC. After d(2)-gamma-TAC administration, the d(2) forms of gamma-T and gamma-CEHC in plasma and urine increased, but with marked inter-individual variability, while the d(0) species were hardly affected. Mean total concentrations of gamma-T and gamma-CEHC in plasma and urine peaked, respectively, between 0-9, 6-12 and 9-24 h post-supplementation with increases over baseline levels of 6-14 fold. All these parameters returned to baseline by 72 h. Following challenge, the total urinary excretion of d(2)-gamma-T equivalents was approximately 7 mg. Baseline levels of gamma-T correlated positively with the post-supplementation rise of (d(0) + d(2)) - gamma - T and gamma-CEHC levels in plasma, but correlated negatively with urinary levels of (d(0) + d(2))-gamma-CEHC. Supplementation with 100 mg gamma-TAC had minimal influence on plasma concentrations of alpha-T and alpha-T-related metabolite formation and excretion. CONCLUSIONS: Ingestion of 100mg of gamma-TAC transiently increases plasma concentrations of gamma-T as it undergoes sustained catabolism to CEHC without markedly influencing the pre-existing plasma pool of gamma-T nor the concentration and metabolism of alpha-T. These pathways appear tightly regulated, most probably to keep high steady-state blood ratios alpha-T to gamma-T and gamma-CEHC to alpha-CEHC.
Authors:
Francesco Galli; Rosalind Lee; Jeffrey Atkinson; Ardesio Floridi; Frank J Kelly
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Free radical research     Volume:  37     ISSN:  1071-5762     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2004-01-05     Completed Date:  2004-08-13     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1225-33     Citation Subset:  IM    
Affiliation:
Lung Biology, School of Health and Life Sciences, King's College, London, UK. f.galli@unipg.it
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MeSH Terms
Descriptor/Qualifier:
Adult
Chromans / metabolism
Chromatography, High Pressure Liquid
Female
Gas Chromatography-Mass Spectrometry
Humans
Kinetics
Male
Middle Aged
Propionic Acids / metabolism
Tocopherols
Vitamin E / metabolism
alpha-Tocopherol / analogs & derivatives*,  blood,  metabolism,  urine
gamma-Tocopherol / blood,  pharmacokinetics*,  urine
Chemical
Reg. No./Substance:
0/Chromans; 0/Propionic Acids; 0/gamma-Tocopherol; 1406-18-4/Vitamin E; 1406-66-2/Tocopherols; 178167-77-6/2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman; 59-02-9/alpha-Tocopherol

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