Novel metabolites and roles for α-tocopherol in humans and mice discovered by mass spectrometry–based metabolomics
Open accessAbstract
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 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.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.
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New metabolites formed from nutrients and other food constituents are continuously being identified, even for widely studied compounds.
“new metabolites formed from nutrients and other food constituents are continuously being identified, even for widely studied compounds (101, 179).”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [179]
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- Authors
- Johnson, C. H., Slanař, O., Krausz, K. W., Kang, D. W., Patterson, A. D., Kim, J.-H., Luecke, H., Gonzalez, F. J., & Idle, J. R.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 96
- Issue
- 4
- Pages
- 818-830
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC3441109
- OpenAlex
- W2159860375
- Cited by
- 58
- References
- 29
- Citations by year
- 2026: 3 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 8 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 9 · 2013: 3 · 2012: 2
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- alpha-tocopherol, vitamin E metabolism, novel metabolites, urinary metabolites, glucuronidation, taurine conjugation, dietary vitamin E, almond, cholesterol, liver fatty acids, vitamin E bioavailability, xenobiotic interactions, vitamin E deficiency
- MeSH terms
- Adolescent, Adult, Amino Acids, Animals, Cholesterol, Chromans, Chromatography, High Pressure Liquid, Female, Humans, Liver, Male, Mice, Inbred C57BL, Species Specificity, Taurine, Vitamin E Deficiency, Molecular Structure, Glucuronides, Spectrometry, Mass, Electrospray Ionization, alpha-Tocopherol, Mice, Metabolomics, Young Adult
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