Novel metabolites and roles for α-tocopherol in humans and mice discovered by mass spectrometry-based metabolomics

Caroline H. Johnson, Ondřej Slanař, Kristopher W. Krausz, Dong Wook Kang, Andrew D. Patterson, Jung Hwan Kim, Hans Luecke, Frank J. Gonzalez, Jeffrey R. Idle

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


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. Design: Human volunteers (n = 10) were fed almonds for 7 d and then an a-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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)818-830
Number of pages13
JournalAmerican Journal of Clinical Nutrition
Issue number4
StatePublished - Oct 1 2012

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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