γ-Tocopherol biokinetics and transformation in humans

• Published in: Free radical research Vol. 37; no. 11; pp. 1225 - 1233
• Main Authors: Galli, Francesco, Lee, Rosalind, Atkinson, Jeffrey, Floridi, Ardesio, Kelly, Frank J.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.11.2003; Taylor & Francis
• Subjects: Adult; alpha-Tocopherol - analogs & derivatives; alpha-Tocopherol - blood; alpha-Tocopherol - metabolism; alpha-Tocopherol - urine; Carboxyethyl-hydroxychroman; CEHC; Chromans - metabolism; Chromatography, High Pressure Liquid; Female; gamma-Tocopherol - blood; gamma-Tocopherol - pharmacokinetics; gamma-Tocopherol - urine; Gas Chromatography-Mass Spectrometry; Humans; Kinetics; Male; Middle Aged; Propionates - metabolism; Tocopherols; Vitamin E; Vitamin E - metabolism; Vitamin E metabolites; γ-tocopherol
• ISSN: 1071-5762; 1029-2470
• DOI: 10.1080/10715760310001604125

Background: The uptake and biotransformation of γ-tocopherol (γ-T) in humans is largely unknown. Using a stable isotope method we investigated these aspects of γ-T biology in healthy volunteers and their response to γ-T supplementation. Methods: A single bolus of 100 mg of deuterium labeled γ-T acetate (d2-γ-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 d2 and d0-γ-T in plasma and its major metabolite 2,7,8-trimethyl-2-(b-carboxyethyl)-6-hydroxychroman (-γ-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 γ-T supplementation on α-T concentrations in plasma and α-T and γ-T metabolite formation were also assessed by HPLC or GC-MS analysis. Results: At baseline, mean plasma α-T concentration was approximately 15 times higher than γ-T (28.3 vs. 1.9 µmol/l). In contrast, plasma γ-CEHC concentration (0.191 µmol/l) was 12 fold greater than α-CEHC (0.016 µmol/l) while in urine it was 3.5 fold lower (0.82 and 2.87 µmol, respectively) suggesting that the clearance of α-CEHC from plasma was more than 40 times that of γ-CEHC. After d2-γ-TAC administration, the d2 forms of γ-T and γ-CEHC in plasma and urine increased, but with marked inter-individual variability, while the d0 species were hardly affected. Mean total concentrations of γ-T and γ-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 d2-γ-T equivalents was approximately 7 mg. Baseline levels of γ-T correlated positively with the post-supplementation rise of (d0 + d2) - γ - T and γ-CEHC levels in plasma, but correlated negatively with urinary levels of (d0 + d2)-γ-CEHC. Supplementation with 100 mg γ-TAC had minimal influence on plasma concentrations of α-T and α-T-related metabolite formation and excretion. Conclusions: Ingestion of 100mg of γ-TAC transiently increases plasma concentrations of γ-T as it undergoes sustained catabolism to CEHC without markedly influencing the pre-existing plasma pool of γ-T nor the concentration and metabolism of α-T. These pathways appear tightly regulated, most probably to keep high steady-state blood ratios α-T to γ-T and γ-CEHC to α-CEHC.