title: Studies in humans using deuterium-labeled alpha- and gamma-tocopherols demonstrate faster plasma gamma-tocopherol disappearance and greater gamma-metabolite production.
abstract: 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 approximately 50 mg each of an equimolar ratio of d6-alpha- and d2-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 d2-gamma-tocopherol fractional disappearance rates (FDR; 1.39+/-0.44 pools/day, mean+/-SD) were more than three times greater than those of d6-alpha-tocopherol (0.33+/-0.11, p<0.001). The d2-gamma-tocopherol half-life was 13+/-4 h compared with 57+/-19 for d6-alpha-tocopherol. Whereas neither plasma nor urinary d6-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 d2-gamma-CEHC represented 54+/-4% of plasma gamma-CEHC. Women compared with men had a greater d2-gamma-tocopherol FDR (p<0.004) and a greater maximal plasma d2-gamma-CEHC concentration (p<0.02) and CEHC FDR (p<0.007), as well as excreting four times as much d2-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.
authors.affiliation: Linus Pauling Institute, Oregon State University, 571 Weniger Hall, Corvallis, OR 97331, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Leonard
authors.forename: Elaine
authors.initials: E
authors.lastname: Paterson
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Atkinson
authors.forename: Rajasekhar
authors.initials: R
authors.lastname: Ramakrishnan
authors.forename: Carroll E
authors.initials: CE
authors.lastname: Cross
authors.forename: Maret G
authors.initials: MG
authors.lastname: Traber
mesh_terms: D000328:Adult; D002839:Chromans / Q000097:blood / Q000652:urine; D003903:Deuterium; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D024502:alpha-Tocopherol / Q000097:blood* / Q000378:metabolism; D024504:gamma-Tocopherol / Q000097:blood* / Q000378:metabolism
chemical_list: D002839:Chromans; C483420:carboxyethyl-hydroxychroman; D024504:gamma-Tocopherol; D003903:Deuterium; D024502:alpha-Tocopherol