| gamma-Tocopherol biokinetics and transformation in humans. | |
MedLine Citation:
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PMID: 14703735 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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:
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Francesco Galli; Rosalind Lee; Jeffrey Atkinson; Ardesio Floridi; Frank J Kelly |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Free radical research Volume: 37 ISSN: 1071-5762 ISO Abbreviation: Free Radic. Res. Publication Date: 2003 Nov |
Date Detail:
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Created Date: 2004-01-05 Completed Date: 2004-08-13 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9423872 Medline TA: Free Radic Res Country: England |
Other Details:
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Languages: eng Pagination: 1225-33 Citation Subset: IM |
Affiliation:
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Lung Biology, School of Health and Life Sciences, King's College, London, UK. f.galli@unipg.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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