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

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 alpha-tocopherol dietary supplement for 14 d. Urine and serum samples were collected before and after dosing. C57BL/6 mice (n = 10) were also fed alpha-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 alpha-tocopherol were discovered in humans and mice: alpha-carboxyethylhydroxychroman (alpha-CEHC) glycine, alpha-CEHC glycine glucuronide, and alpha-CEHC taurine. Another urinary metabolite, alpha-CEHC glutamine, was discovered in mice after alpha-CEHC gavage. Increases in liver fatty acids and decreases in serum and liver cholesterol were observed in mice fed the alpha-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. Am J Clin Nutr 2012;96:818-30.