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 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.