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

We hypothesized that human plasma alpha- and gamma-tocopherol concentrations reflect differences in their kinetics, especially influenced by gamma-tocopherol metabolism. Vitamin E kinetics were evaluated in humans (n = 14) using similar to 50 mg each of an equimolar ratio of d(6)-alpha- and d(2)-gamma-tocopheryl acetates administered orally. Mass spectrometry was used to measure deuterated plasma tocopherols, as well as plasma and urinary vitamin E metabolites, alpha- and gamma-carboxyethylhydroxychromans (CEHCs). Plasma d(2)-gamma-tocopherol fractional disappearance rates (FDR; 1.39 +/- 0.44 pools/day, mean +/- SD) were more than three times greater than those of d(6)-alpha-tocopherol (0.33 +/- 0.11, p < 0.001). The d(2)gamma-tocophcrol half-life was 13 +/- 4 h compared with 57 +/- 19 for d(6)-alpha-tocopherol. Whereas neither plasma nor urinary d(6)-alpha-CEHC was detectable (limit of detection 1 nmol/L), gamma-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 d(2)-gamma-CEHC represented 54 +/- 4% of plasma gamma-CEHC. Women compared with men had a greater d(2)-gamma-tocopherol FDR (p < 0.004) and a greater maximal plasma d(2)-y-CEHC concentration (p < 0.02) and CEHC FDR (p < 0.007), as well as excreting four times as much d(2)-gamma-CEHC (p < 0.04) in urine. Thus, gamma-tocopherol is rapidly metabolized to gamma-CEHC, and to a greater degree in women than in men, whereas alpha-tocopherol is maintained in the plasma and little is metabolized to alpha-CEHC. (c) 2004 Elsevier Inc. All rights reserved.