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The effect of γ-tocopherol administration on α-tocopherol levels and metabolism in humans

European Journal of Clinical Nutrition volume 59, pages 900–905 (2005)Cite this article

Abstract

Background:

The bioavailability of γ-tocopherol and metabolites of vitamin E after γ-tocopherol administration is not well understood. We investigated the effect of γ-tocopherol administration on the levels and metabolism of α- and γ-tocopherol in healthy volunteers.

Methods:

We measured two metabolites of vitamin E (2,5,7,8-tetramethyl-2-(2′-carboxyethyl)-6-hydroxychroman (α-CEHC) and 2,7,8-trimethyl-2-(2′-carboxyethyl)-6-hydroxychroman (γ-CEHC)) in plasma and urine by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) during administration of γ-tocopherol. Two groups of volunteers were enrolled. The γ-tocopherol group received two γ-tocopherol capsules (each containing 186.4 mg of γ-tocopherol and 5 mg of α-tocopherol) for 28 days, while the control group received d-α-tocopherol at 5 mg/day, which was the same dose as that given to the γ-tocopherol group. Blood and urine samples were obtained on days 0, 14, 28, 35, 42, and 56 after the initiation of γ-tocopherol administration.

Results:

The plasma γ-tocopherol concentration increased markedly during administration of γ-tocopherol and the plasma γ-CEHC concentration increased along with that of γ-tocopherol. The plasma α-tocopherol concentration decreased significantly during γ-tocopherol administration. The plasma concentration of α-CEHC decreased significantly and urinary excretion of α-CEHC tended to increase in the γ-tocopherol group. Urinary sodium secretion was significantly increased at 1 week after the cessation of γ-tocopherol administration, but there was no significant difference of urine volume between the two groups.

Conclusion:

Metabolism of α-tocopherol is accelerated and the plasma α-tocopherol concentration is decreased during γ-tocopherol administration.

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References

  • Clement M & Bourre JM (1997): Graded dietary levels of RRR-γ-tocopherol induce a marked increase in the concentrations of α- and γ-tocopherol in nervous tissues, heart, liver and muscle of vitamin-E-deficient rats. Biochim. Biophys. Acta 1334, 173–181.

    Article  CAS  Google Scholar 

  • Galli F, Floridi AG, Floridi A & Buoncristiani U (2004): Accumulation of vitamin E metabolites in the blood of renal failure patients. Clin. Nutr. 23, 205–212.

    Article  CAS  Google Scholar 

  • Galli F, Lee R, Atkinson J, Floridi A & Kelly FJ (2003): γ-Tocopherol biokinetics and transformation in humans. Free Radic. Res. 37 (11), 1225–1233.

    Article  CAS  Google Scholar 

  • Galli F, Lee R, Dunster C & Kelly FJ (2002): Gas chromatography mass spectrometry anarysis of carboxyethyl-hydroxychroman metabolites of α- and γ-tocopherol in human plasma. Free Radic. Biol. Med. 32 (4), 333–340.

    Article  CAS  Google Scholar 

  • Grammas P, Hamdheydari L, Benaksas EJ, Mou S, Pye QN, Wechter WJ, Floyd RA, Stewart C & Hensley K (2004): Anti-inflammatory effects of tocopherol metabolites. Biochem. Biophys. Res. Commun. 319, 1047–1052.

    Article  CAS  Google Scholar 

  • Hattori A, Fukushima T & Imai K (2000a): Occurrence and determination of a natriuretic hormone, 2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxy chroman, in rat plasma, urine, and bile. Anal. Biochem. 281, 209–215.

    Article  CAS  Google Scholar 

  • Hattori A, Fukushima T, Yoshimura H, Abe K & Imai K (2000b): Production of LLU-a following an oral administration of γ-tocotrienol or γ-tocopherol to rats. Biol. Pharm. Bull. 23 (11), 1395–1397.

    Article  CAS  Google Scholar 

  • Hensley K, Benaksas EJ, Bolli R, Comp P, Grammas P, Hamdheydari L, Mou S, Pye QN, Stoddard MF, Wallis G, Williamson KS, West M, Wechter WJ & Floyd RA (2004): New perspectives on vitamin E: γ-tocopherol and carboxyethylhydroxychroman metabolites in biology and medicine. Free Radic. Biol. Med. 36 (1), 1–15.

    Article  CAS  Google Scholar 

  • Himmelfarb J, Kane J, McMonagle E, Zaltas E, Bobzin S, Boddupalli S, Phinney S & Miller G (2003): Alpha and gamma tocopherol metabolism in healthy subjects and patients with end-stage renal disease. Kidney Int. 64, 978–991.

    Article  CAS  Google Scholar 

  • 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 deteminant of the biological activities of vitamin E analogs. FEBS Lett. 409, 105–108.

    Article  CAS  Google Scholar 

  • Huang HY, Alberg AJ, Norkus EP, Hoffman SC, Comstock GW & Helzlsouer KJ (2003): Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer. Am. J. Epidemiol. 157, 335–344.

    Article  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • Jiang Q & Ames BN (2003): γ-Tocopherol, but not α-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats. FASEB J. 17, 816–822.

    Article  CAS  Google Scholar 

  • Jiang Q, Christen S, Shigenaga MK & Ames BN (2001): γ-Tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am. J. Clin. Nutr. 74, 714–722.

    Article  CAS  Google Scholar 

  • Jiang Q, Elson-Schwab I, Courtemanche C & Ames BN (2000): γ-Tocopherol and its major metabolite, in contrast to α-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proc. Natl. Acad. Sci. USA 97, 11494–11499.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Liu M, Wallmon A, Mortlock CO, Wallin R & Saldeen T (2003): Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms. Am. J. Clin. Nutr. 77, 700–706.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • Morinobu T, Yoshikawa S, Hamamura K & Tamai H (2003): Measurement of vitamin E metabolites by high-performance liquid chromatography during high-dose administration of α-tocopherol. Eur. J. Clin. Nutr. 57, 410–414.

    Article  CAS  Google Scholar 

  • Murray Jr ED, Wechter WJ, Kantoci D, Wang WH, Pham T, Quiggle DD, Gibson KM, Leipold D & Anner BM (1997): Endogenous natriuretic factors 7: biospecificity of a natriuretic γ-tocopherol metabolite LLU-α. J. Pharmacol. Exp. Ther. 282, 657–662.

    CAS  PubMed  Google Scholar 

  • Radosavac D, Graf P, Polidori MC, Sies H & Stahl W (2002): Tocopherol metabolites 2,5,7,8-tetramethyl-2-(2′-carboxyethyl)-6-hydroxychroman (α-CEHC) and 2,7,8,-trimethyl-2-(2′-carboxyethyl)-6-hydroxychroman (γ-CEHC) in human serum after a single dose of natural vitamin E. Eur. J. Nutr. 41, 119–124.

    Article  CAS  Google Scholar 

  • Resources Council, Science and Technology Agency (2000): Standard Tables of Food Composition in Japan, 5th Edition, Tokyo: National Printing Bureau (in Japanese).

  • Saito H, Kiyose C, Yoshimura H, Ueda T, Kondo K & Igarashi O (2003): γ-Tocotrienol, a vitamin E homolog, is a natriuretic hormone precursor. J. Lipid Res. 44 (8), 1530–1535.

    Article  CAS  Google Scholar 

  • Smith KS, Lee CL, Ridlington JW, Leonard SW, Devaraj S & Traber MG (2003): Vitamin E supplementation increases circulating vitamin E metabolites tenfold in end-stage renal disease patients. Lipids 38, 813–819.

    Article  CAS  Google Scholar 

  • Tamai H, Manago M, Yokota K, Kitagawa M & Mino M (1988): Determination of alpha-tocopherol in buccal mucosal cells using an electrochemical detector. Int. J. Vitam. Nutr. Res. 58, 202–207.

    CAS  Google Scholar 

  • Traber MG, Sokol RJ, Burton GW, Ingold KU, Papas AM, Huffaker JE & Kayden HJ (1990): Impaired ability of patients with familial isolated vitamin E deficiency to incorporate α-tocopherol into lipoproteins secreted by the liver. J. Clin. Invest. 85, 397–407.

    Article  CAS  Google Scholar 

  • Wechter WJ, Kantoci D, Murray Jr ED, D’Amico DC, Jung ME & Wang WH (1996): A new endogenous natriuretic factor: LLU-α. Proc. Natl. Acad. Sci. USA 93, 6002–6007.

    Article  CAS  Google Scholar 

  • Williamson KS, Gabbita SP, Mou S, West M, Pye QN, Markesbery WR, Cooney RV, Grammas P, Philipp UR, Floyd RA & Hensley K (2002): The nitration product 5-nitro-γ-tocopherol is increased in the Alzheimer brain. Nitric Oxide 6, 221–227.

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to Mitsuzou Yoshikawa and Yoshiko Nakamura, dietitian of Osaka Medical College, for the helpful dietary study on all the volunteers.

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Authors and Affiliations

  1. Department of Pediatrics, Osaka Medical College, Osaka, Japan

    S Yoshikawa & H Tamai

  2. Seikeikai Hospital, Osaka, Japan

    T Morinobu

  3. Section-3 Process Research Laboratories, Eisai Co Ltd, Ibaragi, Japan

    K Hamamura

  4. Division of Food Science, Independent Administrative National Institute of Health and Nutrition, Tokyo, Japan

    F Hirahara & T Iwamoto

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  1. S Yoshikawa
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  4. F Hirahara
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Correspondence to S Yoshikawa.

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Yoshikawa, S., Morinobu, T., Hamamura, K. et al. The effect of γ-tocopherol administration on α-tocopherol levels and metabolism in humans. Eur J Clin Nutr 59, 900–905 (2005). https://doi.org/10.1038/sj.ejcn.1602154

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