title: Novel metabolites and roles for α-tocopherol in humans and mice discovered by mass spectrometry-based metabolomics.
abstract: BACKGROUND
  Contradictory results from clinical trials that examined the role of vitamin E in chronic disease could be a consequence of interindividual variation, caused by factors such as xenobiotic use. Cometabolism of vitamin E with other pharmaceutical products could affect the bioavailability of the drug. Thus, it is necessary to understand fully the metabolic routes and biological endpoints of vitamin E.
  
  
  OBJECTIVE
  The objective was to uncover novel metabolites and roles of vitamin E in humans and mouse models.
  
  
  METHODS
  Human volunteers (n = 10) were fed almonds for 7 d and then an α-tocopherol dietary supplement for 14 d. Urine and serum samples were collected before and after dosing. C57BL/6 mice (n = 10) were also fed α-tocopherol-deficient and -enriched diets for 14 d. Urine, serum, and feces were collected before and after dosing, and liver samples were collected after euthanization. Ultraperformance liquid chromatography electrospray ionization time-of-flight mass spectrometry and multivariate data analysis tools were used to analyze the samples.
  
  
  RESULTS
  Three novel urinary metabolites of α-tocopherol were discovered in humans and mice: α-carboxyethylhydroxychroman (α-CEHC) glycine, α-CEHC glycine glucuronide, and α-CEHC taurine. Another urinary metabolite, α-CEHC glutamine, was discovered in mice after α-CEHC gavage. Increases in liver fatty acids and decreases in serum and liver cholesterol were observed in mice fed the α-tocopherol-enriched diet.
  
  
  CONCLUSIONS
  Novel metabolites and metabolic pathways of vitamin E were identified by mass spectrometry-based metabolomics and will aid in understanding the disposition and roles of vitamin E in vivo.
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Johnson
authors.forename: Ondřej
authors.initials: O
authors.lastname: Slanař
authors.forename: Kristopher W
authors.initials: KW
authors.lastname: Krausz
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kang
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Patterson
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Hans
authors.initials: H
authors.lastname: Luecke
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Idle
mesh_terms: D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000737:chemistry / Q000652:urine; D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D002839:Chromans / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D020719:Glucuronides / Q000737:chemistry / Q000652:urine; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D013045:Species Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D013654:Taurine / Q000031:analogs & derivatives / Q000737:chemistry / Q000652:urine; D014811:Vitamin E Deficiency / Q000097:blood / Q000378:metabolism / Q000652:urine; D055815:Young Adult; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D002839:Chromans; D020719:Glucuronides; C483420:carboxyethyl-hydroxychroman; D013654:Taurine; D002784:Cholesterol; D024502:alpha-Tocopherol