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α-Tocopherol does not Accelerate Depletion of γ-Tocopherol and Tocotrienol or Excretion of their Metabolites in Rats


From an enzyme kinetic study using rat liver microsomes, α-tocopherol has been suggested to accelerate the other vitamin E catabolism by stimulating vitamin E ω-hydroxylation, the late limiting reaction of the vitamin E catabolic pathway. To test the effect of α-tocopherol on catabolism of the other vitamin E isoforms in vivo, we determined whether α-tocopherol accelerates depletion of γ-tocopherol and tocotrienol and excretion of their metabolites in rats. Male Wistar rats were fed a γ-tocopherol-rich diet for 6 weeks followed by a γ-tocopherol-free diet with or without α-tocopherol for 7 days. Intake of γ-tocopherol-free diets lowered γ-tocopherol concentrations in serum, liver, adrenal gland, small intestine, and heart, but there was no effect of dietary α-tocopherol on γ-tocopherol concentrations. The level of urinary excretion of γ-tocopherol metabolite was not affected by dietary α-tocopherol. Next, the effect of α-tocopherol on tocotrienol depletion was examined using rats fed a tocotrienol-rich diet for 6 weeks. Subsequent intake of a tocotrienol-free diet with or without α-tocopherol for 7 days depleted concentrations of α- and γ-tocotrienol in serum and tissues, which was accompanied by a decrease in the excretion of γ-tocotrienol metabolite. However, neither the tocotrienol concentration nor γ-tocotrienol metabolite excretion was affected by dietary α-tocopherol. These data showed that dietary α-tocopherol did not accelerate the depletion of γ-tocopherol and tocotrienol and their metabolite excretions, suggesting that the positive effect of α-tocopherol on vitamin E ω-hydroxylase is not sufficient to affect the other isoform concentrations in tissues.

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Cytochrome P450


α-tocopherol transfer protein


  1. 1.

    Schultz M, Leist M, Petrzika M, Gassmann B, Brigelius-Flohé R (1995) Novel urinary metabolite of α-tocopherol, 2,5,7,8-tetramethyl-2(2′-carboxyethyl)-6-hydroxychroman, as an indicator of an adequate vitamin E supply? Am J Clin Nutr 62:1527S–1534S

    PubMed  CAS  Google Scholar 

  2. 2.

    Swanson JE, Ben RN, Burton GW, Parker RS (1999) Urinary excretion of 2,7, 8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman is a major route of elimination of γ-tocopherol in humans. J Lipid Res 40:665–671

    PubMed  CAS  Google Scholar 

  3. 3.

    Lodge JK, Ridlington J, Leonard S, Vaule H, Traber MG (2001) α- and γ-tocotrienols are metabolized to carboxyethyl-hydroxychroman derivatives and excreted in human urine. Lipids 36:43–48

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Sontag TJ, Parker RS (2002) Cytochrome P450 ω-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. J Biol Chem 277:25290–25296

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Bardowell SA, Duan F, Manor D, Swanson JE, Parker RS (2012) Disruption of mouse cytochrome p450 4f14 (cyp4f14 gene) causes severe perturbations in vitamin E metabolism. J Biol Chem 287:26077–26086

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Parker RS, Sontag TJ, Swanson JE (2000) Cytochrome P4503A-dependent metabolism of tocopherols and inhibition by sesamin. Biochem Biophys Res Commun 277:531–534

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    You CS, Sontag TJ, Swanson JE, Parker RS (2005) Long-chain carboxychromanols are the major metabolites of tocopherols and tocotrienols in A549 lung epithelial cells but not HepG2 cells. J Nutr 135:227–232

    PubMed  CAS  Google Scholar 

  8. 8.

    Abe C, Uchida T, Ohta M, Ichikawa T, Yamashita K, Ikeda S (2007) Cytochrome P450-dependent metabolism of vitamin E isoforms is a critical determinant of their tissue concentrations in rats. Lipids 42:637–645

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Ikeda S, Tohyama T, Yamashita K (2002) Dietary sesame seed and its lignans inhibit 2,7,8-trimethyl- 2(2′-carboxyethyl)-6-hydroxychroman excretion into urine of rats fed γ-tocopherol. J Nutr 132:961–966

    PubMed  CAS  Google Scholar 

  10. 10.

    Uchida T, Ichikawa T, Abe C, Yamashita K, Ikeda S (2007) Dietary sesame seed decreases urinary excretion of α- and γ-tocopherol metabolites in rats. J Nutr Sci Vitaminol 53:372–376

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Cooney RV, Custer LJ, Okinaka L, Franke AA (2001) Effects of dietary sesame seeds on plasma tocopherol levels. Nutr Cancer 39:66–71

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Lemcke-Norojärvi M, Kamal-Eldin A, Appelqvist LA, Dimberg LH, Ohrvall M, Vessby B (2001) Corn and sesame oils increase serum γ-tocopherol concentrations in healthy Swedish women. J Nutr 131:1195–1201

    PubMed  Google Scholar 

  13. 13.

    Wu WH, Kang YP, Wang NH, Jou HJ, Wang TA (2006) Sesame ingestion affects sex hormones, antioxidant status, and blood lipids in postmenopausal women. J Nutr 136:1270–1275

    PubMed  CAS  Google Scholar 

  14. 14.

    Frank J, Lee S, Leonard SW, Atkinson JK, Kamal-Eldin A, Traber MG (2008) Sex differences in the inhibition of γ-tocopherol metabolism by a single dose of dietary sesame oil in healthy subjects. Am J Clin Nutr 87:1723–1729

    PubMed  CAS  Google Scholar 

  15. 15.

    Sontag TJ, Parker RS (2007) Influence of major structural features of tocopherols and tocotrienols on their ω-oxidation by tocopherol-ω-hydroxylase. J Lipid Res 48:1090–1098

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939–1951

    PubMed  CAS  Google Scholar 

  17. 17.

    Kayden HJ, Traber MG (1993) Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. J Lipid Res 34:343–358

    PubMed  CAS  Google Scholar 

  18. 18.

    Traber MG, Sies H (1996) Vitamin E in humans: demand and delivery. Annu Rev Nutr 16:321–347

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Abe C, Ikeda S, Uchida T, Yamashita K, Ichikawa T (2007) Triton WR1339, an inhibitor of lipoprotein lipase, decreases vitamin E concentration in some tissues of rats by inhibiting its transport to liver. J Nutr 137:345–350

    PubMed  CAS  Google Scholar 

  20. 20.

    Traber MG, Arai H (1999) Molecular mechanisms of vitamin E transport. Annu Rev Nutr 19:343–355

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Hosomi A, Arita M, Sato Y, Kiyose C, Ueda T, Igarashi O, Arai H, Inoue K (1997) Affinity for α-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. FEBS Lett 409:105–108

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Uchida T, Abe C, Nomura S, Ichikawa T, Ikeda S (2012) Tissue distribution of α- and γ-tocotrienol and γ-tocopherol in rats and interference with their accumulation by α-tocopherol. Lipids 47:129–139

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Uchida T, Nomura S, Ichikawa T, Abe C, Ikeda S (2011) Tissue distribution of vitamin E metabolites in rats after oral administration of tocopherol or tocotrienol. J Nutr Sci Vitaminol 57:326–332

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Bardowell SA, Ding X, Parker RS (2012) Disruption of P450-mediated vitamin E hydroxylase activities alters vitamin E status in tocopherol supplemented mice and reveals extra-hepatic vitamin E metabolism. J Lipid Res 53:2667–2676

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Freiser H, Jiang Q (2009) Gamma-tocotrienol and gamma-tocopherol are primarily metabolized to conjugated 2-(beta-carboxyethyl)-6-hydroxy-2,7,8-trimethylchroman and sulfated long-chain carboxychromanols in rats. J Nutr 139:884–889

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Kiyose C, Saito H, Kaneko K, Hamamura K, Tomioka M, Ueda T, Igarashi O (2001) Alpha-tocopherol affects the urinary and biliary excretion of 2,7,8-trimethyl-2 (2′-carboxyethyl)-6-hydroxychroman, gamma-tocopherol metabolite, in rats. Lipids 36:467–472

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Machlin LJ, Keating J, Nelson J, Brin M, Filipski R, Miller ON (1979) Availability of adipose tissue tocopherol in the guinea pig. J Nutr 109:105–109

    PubMed  CAS  Google Scholar 

  28. 28.

    Ikeda S, Toyoshima K, Yamashita K (2001) Dietary sesame seeds elevate α- and γ-tocotrienol concentrations in skin and adipose tissue of rats fed the tocotrienol-rich fraction extracted from palm oil. J Nutr 131:2892–2897

    PubMed  CAS  Google Scholar 

  29. 29.

    Ikeda S, Tohyama T, Yoshimura H, Hamamura K, Abe K, Yamashita K (2003) Dietary α-tocopherol decreases α-tocotrienol but not γ-tocotrienol concentration in rats. J Nutr 133:428–434

    PubMed  CAS  Google Scholar 

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This work was supported in part by JSPS KAKENHI and a Sasakawa Scientific Research Grant from the Japan Science Society. We acknowledge a generous donation of vitamin E isoforms and CEHC from Eisai Food & Chemical and Eisai, respectively.

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Correspondence to Saiko Ikeda.

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Uchida, T., Nomura, S., Sakuma, E. et al. α-Tocopherol does not Accelerate Depletion of γ-Tocopherol and Tocotrienol or Excretion of their Metabolites in Rats. Lipids 48, 687–695 (2013).

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  • Carboxyethyl-hydroxychroman
  • Catabolism
  • Rat
  • Tocopherol
  • Tocotrienol
  • Vitamin E