title: Human plasma and tissue alpha-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E.
abstract: We report a comparison of natural and synthetic vitamin E in humans using deuterium labeling to permit the two forms of vitamin E to be measured independently in plasma and tissues of each subject. Differences in natural and synthetic vitamin E concentrations were measured directly under equal dosage conditions using an equimolar mixture of deuterated RRR-alpha-tocopheryl acetate and all-rac-alpha-tocopheryl acetate. Two groups of five adults took 30 mg of the mixture as a single dose and as eight consecutive daily doses, respectively. After a 1-mo interval the schedule was repeated but with a 10-fold higher dose (ie, 300 mg). In each case, the ratio of plasma d3-RRR-alpha-tocopherol to d6-all-rac-alpha-tocopherol (RRR:rac) increased from approximately 1.5-1.8 to approximately 2 after dosing ended. In an elective surgery study in which 22 patients were given 150 mg/d for up to 41 d before surgery, the RRR:rac in tissues was lower than in plasma and the percentage of deuterated alpha-tocopherol was lower in all tissues except gallbladder and liver. In a terminally ill patient given 30 mg/d for 361 d, plasma and tissue (x+/-SD) RRR-rac ratios (and % deuterated alpha-tocopherol) at autopsy were 2.06 (6.3%) and 1.71+/-0.24 (5.9+/-2.2%), respectively. In a second terminally ill patient given 300 mg/d for 615 d, the corresponding values were 2.11 (68%) and 2.01+/-0.17 (65+/-10%), respectively. The results indicated that natural vitamin E has roughly twice the availability of synthetic vitamin E. This 2:1 ratio is significantly higher than the currently accepted RRR:rac of 1.36:1.00. Gamma-Tocopherol, expressed as a fraction of total unlabeled tocopherols in 15 elective surgery patients, was 1.4-4.6 (mean: 2.6) times greater in adipose tissue, muscle, skin, and vein than in plasma, which is a substantially larger fraction than had been recognized previously.
authors.affiliation: Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Ontario. gburton@ned1.sims.nrc.ca
authors.forename: G W
authors.initials: GW
authors.lastname: Burton
authors.forename: M G
authors.initials: MG
authors.lastname: Traber
authors.forename: R V
authors.initials: RV
authors.lastname: Acuff
authors.forename: D N
authors.initials: DN
authors.lastname: Walters
authors.forename: H
authors.initials: H
authors.lastname: Kayden
authors.forename: L
authors.initials: L
authors.lastname: Hughes
authors.forename: K U
authors.initials: KU
authors.lastname: Ingold
mesh_terms: D000328:Adult; D003903:Deuterium; D017558:Elective Surgical Procedures; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D009928:Organ Specificity; D013237:Stereoisomerism; D019452:Terminally Ill; D024505:Tocopherols; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
chemical_list: D014810:Vitamin E; D003903:Deuterium; D024502:alpha-Tocopherol; D024505:Tocopherols