Alpha-Tocopherol Metabolites (The Vitamin E Metabolome) and Their Interindividual Variability during Supplementation
The metabolism of α-tocopherol (α-TOH, vitamin E) shows marked interindividual variability, which may influence the response to nutritional and therapeutic interventions with this vitamin. Recently, new metabolomics protocols have fostered the possibility to explore such variability for the differen...
| मुख्य लेखकों: | , , , , , , , , , , |
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| स्वरूप: | लेख |
| भाषा: | English |
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MDPI AG
2021-01-01
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| श्रृंखला: | Antioxidants |
| विषय: | |
| ऑनलाइन पहुंच: | https://www.mdpi.com/2076-3921/10/2/173 |
| _version_ | 1827598058781671424 |
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| author | Desirée Bartolini Rita Marinelli Danilo Giusepponi Roberta Galarini Carolina Barola Anna Maria Stabile Bartolomeo Sebastiani Fabiola Paoletti Michele Betti Mario Rende Francesco Galli |
| author_facet | Desirée Bartolini Rita Marinelli Danilo Giusepponi Roberta Galarini Carolina Barola Anna Maria Stabile Bartolomeo Sebastiani Fabiola Paoletti Michele Betti Mario Rende Francesco Galli |
| author_sort | Desirée Bartolini |
| collection | DOAJ |
| description | The metabolism of α-tocopherol (α-TOH, vitamin E) shows marked interindividual variability, which may influence the response to nutritional and therapeutic interventions with this vitamin. Recently, new metabolomics protocols have fostered the possibility to explore such variability for the different metabolites of α-TOH so far identified in human blood, i.e., the “vitamin E metabolome”, some of which have been reported to promote important biological functions. Such advances prompt the definition of reference values and degree of interindividual variability for these metabolites at different levels of α-TOH intake. To this end, a one-week oral administration protocol with 800 U RRR-α-TOH/day was performed in 17 healthy volunteers, and α-TOH metabolites were measured in plasma before and at the end of the intervention utilizing a recently validated LC-MS/MS procedure; the expression of two target genes of α-TOH with possible a role in the metabolism and function of this vitamin, namely pregnane X receptor (PXR) and the isoform 4F2 of cytochrome P450 (CYP4F2) was assessed by immunoblot in peripheral blood leukocytes. The levels of enzymatic metabolites showed marked interindividual variability that characteristically increased upon supplementation. With the exception of α-CEHC (carboxy-ethyl-hydroxychroman) and the long-chain metabolites M1 and α-13′OH, such variability was found to interfere with the possibility to utilize them as sensitive indicators of α-TOH intake. On the contrary, the free radical-derived metabolite α-tocopheryl quinone significantly correlated with the post-supplementation levels of α-TOH. The supplementation stimulated PXR, but not CYP4F2, expression of leucocytes, and significant correlations were observed between the baseline levels of α-TOH and both the baseline and post-supplementation levels of PXR. These findings provide original analytical and molecular information regarding the human metabolism of α-TOH and its intrinsic variability, which is worth considering in future nutrigenomics and interventions studies. |
| first_indexed | 2024-03-09T03:43:07Z |
| format | Article |
| id | doaj.art-1dd25ae6d17f482a94bc5909c7c84dba |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T03:43:07Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-1dd25ae6d17f482a94bc5909c7c84dba2023-12-03T14:36:29ZengMDPI AGAntioxidants2076-39212021-01-0110217310.3390/antiox10020173Alpha-Tocopherol Metabolites (The Vitamin E Metabolome) and Their Interindividual Variability during SupplementationDesirée Bartolini0Rita Marinelli1Danilo Giusepponi2Roberta Galarini3Carolina Barola4Anna Maria Stabile5Bartolomeo Sebastiani6Fabiola Paoletti7Michele Betti8Mario Rende9Francesco Galli10Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, ItalyDepartment of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, ItalyIstituto Zooprofilattico Sperimentale dell’Umbria e delle Marche “Togo Rosati”, 06126 Perugia, ItalyIstituto Zooprofilattico Sperimentale dell’Umbria e delle Marche “Togo Rosati”, 06126 Perugia, ItalyIstituto Zooprofilattico Sperimentale dell’Umbria e delle Marche “Togo Rosati”, 06126 Perugia, ItalyDepartment of Medicine, University of Perugia, 06126 Perugia, ItalyDepartment of Chemistry, Biology and Biotechnology, University of Perugia, 06126 Perugia, ItalyIstituto Zooprofilattico Sperimentale dell’Umbria e delle Marche “Togo Rosati”, 06126 Perugia, ItalyDepartment of Biomolecular Sciences, University of Urbino “Carlo Bo”, 61029 Urbino, ItalyDepartment of Medicine, University of Perugia, 06126 Perugia, ItalyDepartment of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, ItalyThe metabolism of α-tocopherol (α-TOH, vitamin E) shows marked interindividual variability, which may influence the response to nutritional and therapeutic interventions with this vitamin. Recently, new metabolomics protocols have fostered the possibility to explore such variability for the different metabolites of α-TOH so far identified in human blood, i.e., the “vitamin E metabolome”, some of which have been reported to promote important biological functions. Such advances prompt the definition of reference values and degree of interindividual variability for these metabolites at different levels of α-TOH intake. To this end, a one-week oral administration protocol with 800 U RRR-α-TOH/day was performed in 17 healthy volunteers, and α-TOH metabolites were measured in plasma before and at the end of the intervention utilizing a recently validated LC-MS/MS procedure; the expression of two target genes of α-TOH with possible a role in the metabolism and function of this vitamin, namely pregnane X receptor (PXR) and the isoform 4F2 of cytochrome P450 (CYP4F2) was assessed by immunoblot in peripheral blood leukocytes. The levels of enzymatic metabolites showed marked interindividual variability that characteristically increased upon supplementation. With the exception of α-CEHC (carboxy-ethyl-hydroxychroman) and the long-chain metabolites M1 and α-13′OH, such variability was found to interfere with the possibility to utilize them as sensitive indicators of α-TOH intake. On the contrary, the free radical-derived metabolite α-tocopheryl quinone significantly correlated with the post-supplementation levels of α-TOH. The supplementation stimulated PXR, but not CYP4F2, expression of leucocytes, and significant correlations were observed between the baseline levels of α-TOH and both the baseline and post-supplementation levels of PXR. These findings provide original analytical and molecular information regarding the human metabolism of α-TOH and its intrinsic variability, which is worth considering in future nutrigenomics and interventions studies.https://www.mdpi.com/2076-3921/10/2/173α-tocopherolvitamin Emetabolomicsnutrigenomicspregnane X receptorlipoxygenase-5 |
| spellingShingle | Desirée Bartolini Rita Marinelli Danilo Giusepponi Roberta Galarini Carolina Barola Anna Maria Stabile Bartolomeo Sebastiani Fabiola Paoletti Michele Betti Mario Rende Francesco Galli Alpha-Tocopherol Metabolites (The Vitamin E Metabolome) and Their Interindividual Variability during Supplementation Antioxidants α-tocopherol vitamin E metabolomics nutrigenomics pregnane X receptor lipoxygenase-5 |
| title | Alpha-Tocopherol Metabolites (The Vitamin E Metabolome) and Their Interindividual Variability during Supplementation |
| title_full | Alpha-Tocopherol Metabolites (The Vitamin E Metabolome) and Their Interindividual Variability during Supplementation |
| title_fullStr | Alpha-Tocopherol Metabolites (The Vitamin E Metabolome) and Their Interindividual Variability during Supplementation |
| title_full_unstemmed | Alpha-Tocopherol Metabolites (The Vitamin E Metabolome) and Their Interindividual Variability during Supplementation |
| title_short | Alpha-Tocopherol Metabolites (The Vitamin E Metabolome) and Their Interindividual Variability during Supplementation |
| title_sort | alpha tocopherol metabolites the vitamin e metabolome and their interindividual variability during supplementation |
| topic | α-tocopherol vitamin E metabolomics nutrigenomics pregnane X receptor lipoxygenase-5 |
| url | https://www.mdpi.com/2076-3921/10/2/173 |
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