Journal Mobile Options
Table of Contents
Vol. 48, No. 3, 2004
Issue release date: May–June 2004
Ann Nutr Metab 2004;48:169–188
(DOI:10.1159/000079555)

Gamma-Tocopherol – An Underestimated Vitamin?

Wagner K.-H. · Kamal-Eldin A. · Elmadfa I.
aInstitute of Nutritional Sciences, University of Vienna, Vienna, Austria; bDepartment of Food Science, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

The main research activities of the last decades on tocopherols were mainly focused on α-tocopherol, in particular when considering the biological activities. However, recent studies have increased the knowledge on γ-tocopherol, which is the major form of vitamin E in the diet in the USA, but not in Europe. γ-Tocopherol provides different antioxidant activities in food and in-vitro studies and showed higher activity in trapping lipophilic electrophiles and reactive nitrogen and oxygen species. The lower plasma levels of γ- compared to α-tocopherol might be discussed in the light of different bioavailability, but also in a potential transformation from γ- into α-tocopherol. From the metabolism end product, only that of γ-tocopherol (2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman), but not that of α-tocopherol, was identified to provide natriuretic activity. Studies also indicate that only the γ-tocopherol plasma level served as biomarker for cancer and cardiovascular risk. Therefore, this paper provides a comprehensive review on γ-tocopherol with emphasis on its chemistry, biosynthesis, occurrence in food, different intake linking to different plasma levels in USA and Europe, absorption and metabolism, biological activities, and possible role in human health.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Evans H, Bishop KS: On the existence of hitherto unrecognized dietary factor essential for reproduction. Science 1922;56:650–651.
  2. Evans H, Emerson OH, Emerson GA: The isolation from wheat-germ oil of an alcohol, α-tocopherol, having the properties of vitamin E. J Biol Chem 1936;113:319–332.
  3. Karin-Herbers: Vitamin production in transgenic plants. J Plant Physiol 2003;160:821–829.

    External Resources

  4. Leth T, Sondergaard H: Biological activity of all-rac-α-tocopherol and RRR-α-tocopherol determined by three different rat bioassays. Int J Vitam Nutr Res 1983;53:297–311.
  5. Bieri JG, Evarts RP, Gart JJ: Relative activity of α-tocopherol and γ-tocopherol in preventing oxidative red cell hemolysis. J Nutr 1976;106:124–127.
  6. Landvogt C, Elmadfa I: Effect of α- and γ-tocopherol as well as cholesterol on lipid peroxidation. Z Ernährungswiss 1986;25:47–62.
  7. Horwitt MK: Interrelationship between vitamin E and polyunsaturated fatty acids in adult men. Vitam Horm 1962;20:541–558.

    External Resources

  8. Schäfer H, Elmadfa I: Relative bioactivity of α- and γ-tocopherol calculated from respiration parameters in rat liver mitochondria. Ann Nutr Metab 1984;28:297–304.
  9. El-Sohemy A, Baylin A, Spiegelman D, Ascherio A, Campos H: Dietary and adipose tissue γ-tocopherol and risk of myocardial infarction. Epidemiology 2002;13:216–223.
  10. Traber MG, Kayden HJ: Preferential incorporation of α-tocopherol versus γ-tocopherol in human lipoproteins. Am J Clin Nutr 1989;49:517–526.
  11. Food and Nutrition Board, Institute of Medicine, USA: Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, National Academy Press, 2000.
  12. Combs GF: The Vitamins. Fundamental Aspects in Nutrition and Health, ed 2. New York, Academic Press, 1998.
  13. Brubacher G, Weiser H: Tocopherole. Wiss. Veröff. Dtsch. Ges. Ernährung. Darmstadt, Steinhoff, 1967, vol 16, pp 1–50.
  14. Leth T, Sondergaard H: Biological activity of vitamin E compounds and natural materials by the resorption-gestation test, and chemical determination of the vitamin E activity in foods and feeds. J Nutr 1977;107:2236–2243.
  15. Elmadfa I, Bosse W: Vitamin E. Stuttgart, Wissenschaftliche Verlagsgesellschaft, 1985.
  16. Weimann BJ, Weiser H: Functions of vitamin E in reproduction and in prostacyclin and immunoglobulin synthesis in rats. Am J Clin Nutr 1991;53:1056S–1060S.
  17. Jiang Q, Ames BN: Gamma-tocopherol, but not α-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats. Faseb J 2003;17:816–822.
  18. Gysin R, Azzi A, Visarius T: Gamma-tocopherol inhibits human cancer cell cycle progression and cell proliferation by down-regulation of cyclins. Faseb J 2002;16:1952–1954.
  19. Appenroth D, Karge E, Kiessling G, Wechter WJ, Winnefeld K, Fleck C: LLU-α, an endogenous metabolite of γ-tocopherol, is more effective against metal nephrotoxicity in rats than γ-tocopherol. Toxicol Lett 2001;122:255–265.
  20. Jiang Q, Elson-Schwab I, Courtemanche C, Ames BN: Gamma-tocopherol and its major metabolite, in contrast to α-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proc Natl Acad Sci USA 2000;97:11494–11499.
  21. Tomasch R, Wagner KH, Elmadfa I: Antioxidative power of plant oils in humans: The influence of α- and γ-tocopherol. Ann Nutr Metab 2001;45:110–115.
  22. Li D, Saldeen T, Mehta JL: Gamma-tocopherol decreases ox-LDL-mediated activation of nuclear factor-κB and apoptosis in human coronary artery endothelial cells. Biochem Biophys Res Commun 1999;259:157–161.
  23. Saldeen T, Li D, Mehta JL: Differential effects of α- and γ-tocopherol on low-density lipoprotein oxidation, superoxide activity, platelet aggregation and arterial thrombogenesis. J Am Coll Cardiol 1999;34:1208–1215.
  24. Duthie GG, Gonzalez BM, Morrice PC, Arthur JR: Inhibitory effects of isomers of tocopherol on lipid peroxidation of microsomes from vitamin E-deficient rats. Free Radic Res Commun 1991;15:35–40.
  25. Furuya T, Yoshikawa T, Kimura T, Kaneko H: Production of tocopherols by cell cultures of safflower. Phytochemistry 1987;26:2741–2747.
  26. Shintani D, DellaPenna D: Elevating the vitamin E content of plants through metabolic engineering. Science 1998;282:2098–2100.
  27. Grusak MA: Genomics-assisted plant improvement to benefit human nutrition and health. Trends Plant Sci 1999;4:164–166.
  28. DellaPenna D: Nutritional genomics: Manipulating plant micronutrients to improve human health. Science 1999;285:375–379.
  29. Bramely PM, Elmadfa I, Kafatos A, Kelly FJ, Manios Y, Roxborough HE, Schuch W, Sheehy PJA, Wagner KH: Vitamin E. J Sci Food Agric 2000;80:913–938.
  30. Osuna-Garcia JA, Wall MM, Waddell CA: Endogenous levels of tocopherols and ascorbic acid during fruit ripening of New Mexican-type chile (Capsicum annuum L.). J Agric Food Chem 1998;46:5093–5096.
  31. Kallio HP, Yang B, Peippo P: Effects of different origins and harvesting time on vitamin C, tocopherols, and tocotrienols in sea buckthorn (Hippophaë rhamnoides) berries. J Agric Food Chem 2002;50:6136–6142.
  32. Dolde D, Vlahakis C, Hazebroek J: Tocopherols in breeding lines and effects of planting location, fatty acids composition, and temperature during development. J Am Oil Chem Soc 1999;76:349–355.
  33. Kamal-Eldin A, Anderson R: A multivariate study of the correlation between tocopherol content and fatty acid composition in different vegetable oils. J Am Oil Chem Soc 1997;47:375–380.

    External Resources

  34. Wyatt CJ, Pérez S, Méndez RO: Alpha- and γ-tocopherol content of selected foods in the Mexican diet: Effect of cooking losses. J Agric Food Chem 1998;46:4657–4661.
  35. Lampi AM, Kamal-Eldin A, Piironen V: Tocopherols and tocotrienols from oil and cereal grains; in Shi J, Mazza G, Le Maguer M (eds): Functional Foods. Boca Raton, CRC Press, 2002, vol 2, pp 1–38.
  36. Murphy SP, Subar AF, Block G: Vitamin E intakes and sources in the United States. Am J Clin Nutr 1990;52:361–367.
  37. Schneider R: Qualität pflanzlicher Erzeugnisse: Ergebnisse der Nationalen Verzehrsstudie. Kongressband 1993 Hamburg. Vortrage zum Generalthema des 105 VDLUFA-Kongress vom 20.–25.9.1993 in Hamburg: Qualität und Hygiene von Lebensmitteln in Produktion und Verarbaitung, pp 441–444.
  38. Gascon-Vila P, Ribas L, Garcia-Closas R, Farran Codina A, Serra-Majem L: Dietary sources of vitamin A, C, E and β-carotene in a adult Mediterranean population. Gac Sanit 1999;13:22–29.
  39. Heinonen M, Piironen V: The tocopherol, tocotrienol, and vitamin E content of the average Finnish diet. Int J Vitam Nutr Res 1991;61:27–32.
  40. Elmadfa I, Freisling H, König J, Blachfelner J, Cvitkovich-Steiner H, Genser D, Grossgut R, Hassan-Hauser C, Kichler R, Kunze M, Majchrzak D, Manafi M, Rust P, Schindler K, Vojir F, Wallner S, Zilberszac A: Österreichischer Ernährungsbericht 2003 (Austrian Nutrition Report 2003). Wien, Bundesministerium für Gesundheit und Frauen, 2003.
  41. Bieri JG, Evarts RP: Tocopherols and fatty acids in American diets. J Am Diet Assoc 1973;62:147–151.
  42. Dial S, Eitenmiller RR: Tocopherols and tocotrienols in key foods in the US diet; in Ong ASH, Niki E, Packer L (eds): Nutrition, Lipids, Health, and Disease. Champaign, AOCS Press, 1995, pp 327–342.
  43. Putnam JJ, Allshouse JE: Food consumption, prices, and expenditures, 1970–97. Washington, Food and Rural Economics Division, Economic Research Service, US Department of Agriculture, 1999 (Statist Bull No 965).
  44. Alaimo K, McDowell MA, Briefel RR, Bischof AM, Caughman CR, Loria CM, Johnson CL: Dietary intake of vitamins, minerals, and fiber of persons ages 2 months and over in the United States: Third National Health and Nutrition Examination Survey, Phase 1, 1988–91. Adv Data 1994;258:1–28.

    External Resources

  45. Swanson JE, Ben RN, Burton GW, Parker RS: 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 1999;40:665–671.
  46. El-Sohemy A, Baylin A, Ascherio A, Kabagambe E, Spiegelman D, Campos H: Population-based study of α- and γ-tocopherol in plasma and adipose tissue as biomarkers of intake in Costa Rican adults. Am J Clin Nutr 2001;74:356–363.
  47. FAO/WHO: Fats and oils in human nutrition report of a joint expert consultation. Food and Agriculture Organization of the United Nations and the World Health Organization. FAO Food Nutr Pap 1994;57:1–147.
  48. Sanders TAB: Polyunsaturated fatty acids in the food chain in Europe. Am J Clin Nutr 2000;71:176–178.
  49. Burton GW, Traber MG, Acuff RV, Walters DN, Kayden H, Hughes L, Ingold KU: Human plasma and tissue α-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E. Am J Clin Nutr 1998;67:669–684.
  50. Handelman GJ, Epstein WL, Peerson J, Spiegelman D, Machlin LJ, Dratz EA: Human adipose α-tocopherol and γ-tocopherol kinetics during and after 1 year of α-tocopherol supplementation. Am J Clin Nutr 1994;59:1025–1032.
  51. Traber MG, Kayden HJ, Green JB, Green MH: Absorption of water-miscible forms of vitamin E in a patient with cholestasis and in thoracic duct-cannulated rats. Am J Clin Nutr 1986;44:914–923.
  52. Traber MG, Kayden HJ: Preferential incorporation of α-tocopherol vs. γ-tocopherol in human lipoproteins. Am J Clin Nutr 1989;49:517–526.
  53. Lee R, Galli F, Kelly FJ: γ-Tocopherol metabolism and its relationship with α- tocopherol in humans; in Packer L, Traber MG, Kraemer K, Frei B (eds): The Antioxidant Vitamins C and E. Champaign, AOCS Press, 2003, pp 180–194.
  54. Handelman GJ, Machlin LJ, Fitch K, Weiter JJ, Dratz EA: Oral α-tocopherol supplements decrease plasma γ-tocopherol levels in humans. J Nutr 1985;115:807–813.
  55. Baker H, Handelman GJ, Short S, Machlin LJ, Bhagavan HN, Dratz EA, Frank O: Comparison of plasma α- and γ-tocopherol levels following chronic oral administration of either all-rac-α-tocopheryl acetate or RRR-α-tocopheryl acetate in normal adult male subjects. Am J Clin Nutr 1986;43:382–387.
  56. Lykkesfeldt J, Christen S, Wallock LM, Chang HH, Jacob RA, Ames BN: Ascorbate is depleted by smoking and repleted by moderate supplementation: A study in male smokers and nonsmokers with matched dietary antioxidant intakes. Am J Clin Nutr 2000;71:530–536.
  57. Kaempf-Rotzoll DE, Traber MG, Arai H: Vitamin E and transfer proteins. Curr Opin Lipidol 2003;14:249–254.
  58. Hosomi A, Goto K, Kondo H, Iwatsubo T, Yokota T, Ogawa M, Arita M, Aoki J, Arai H, Inoue K: Localization of α-tocopherol transfer protein in rat brain. Neurosci Lett 1998;256:159–162.
  59. Copp RP, Wisniewski T, Hentati F, Larnaout A, BenHamida M, Kayden HJ: Localization of α-tocopherol transfer protein in the brains of patients with ataxia with vitamin E deficiency and other oxidative stress-related neurodegenerative disorders. Brain Res 1999;822:80–87.
  60. Fechner H, Schlame M, Guthmann F, Stevens PA, Rustow B: Alpha- and δ-tocopherol induce expression of hepatic α-tocopherol-transfer-protein mRNA. Biochem J 1998;331:577–581.
  61. Stocker A, Zimmer S, Spycher SE, Azzi A: Identification of a novel cytosolic tocopherol-binding protein: Structure, specificity, and tissue distribution. IUBMB Life 1999;48:49–55.
  62. Dutta-Roy A, Leishman D, Gordon M: Identification of a low molecular mass (14.2 kDa) α-tocopherol-binding protein in the cytosol of rat liver and heart. Biochem Biophys Res Commun 1993;196:1108–1112.
  63. Brigelius-Flohe R, Kelly FJ, Salonen JT, Neuzil J, Zingg JM, Azzi A: The European perspective on vitamin E: Current knowledge and future research. Am J Clin Nutr 2002;76:703–716.
  64. Simon EJ: The metabolism of vitamin E. II. Purification and characterization of urinary metabolites of α-tocopherol. J Biol Chem 1956;221:807–817.
  65. Simon EJ, Gross CS, Milhorat AT: The metabolism of vitamin E. The absorption and excretion of d-α-tocopheryl-5-methyl-C14-succinate. J Biol Chem 1956;221:797–805.
  66. Stahl W, Graf P, Brigelius-Flohe R, Wechter W, Sies H: Quantification of the α- and γ-tocopherol metabolites 2,5,7,8-tetramethyl-2-(2′-carboxyethyl)-6-hydroxychroman and 2,7,8-trimethyl-2-(2′-carboxyethyl)-6-hydroxychroman in human serum. Anal Biochem 1999;275:254–259.
  67. Traber MG, Elsner A, Brigelius-Flohe R: Synthetic as compared with natural vitamin E is preferentially excreted as α-CEHC in human urine: Studies using deuterated α-tocopheryl acetates. FEBS Lett 1998;437:145–148.
  68. Wechter WJ, Kantoci D, Murray ED Jr, D’Amico DC, Jung ME: A new endogenous natriuretic factor: LLU-α. Proc Natl Acad Sci USA 1996;93:6002–6007.
  69. Parker RS, Sontag TJ, Swanson JE: Cytochrome P4503A-dependent metabolism of tocopherols and inhibition by sesamin. Biochem Biophys Res Commun 2000;277:531–534.
  70. Kamal-Eldin A, Pettersson D, Appelqvist LA: Sesamin (a compound from sesame oil) increases tocopherol levels in rats fed ad libitum. Lipids 1995;30:499–505.
  71. Sontag TJ, Parker RS: Cytochrome P450 ω-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. J Biol Chem 2002;277:25290–25296.
  72. Yamashita K, Nohara Y, Katayama K, Namiki M: Sesame seed lignans and γ-tocopherol act synergistically to produce vitamin E activity in rats. J Nutr 1992;122:2440–2446.
  73. Behrens WA, Madere R: Mechanisms of absorption, transport and tissue uptake of RRR-α-tocopherol and D-γ-tocopherol in the white rat. J Nutr 1987;117:1562–1569.
  74. Hattori A, Fukushima T, Imai K: Occurrence and determination of a natriuretic hormone, 2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman, in rat plasma, urine, and bile. Anal Biochem 2000;281:209–215.
  75. Stone WL, Papas AM, LeClair IO, Min Q, Ponder T: The influence of dietary iron and tocopherols on oxidative stress in the colon. Cancer Detect Prev 1998;22:S110.
  76. Yamashita K, Takeda N, Ikeda S: Effects of various tocopherol-containing diets on tocopherol secretion into bile. Lipids 2000;35:163–170.
  77. Stone WL, Papas AM: Tocopherols and the etiology of colon cancer. J Natl Cancer Inst 1997;89:1006–1014.
  78. Campbell S, Stone W, Whaley S, Krishnan K: Development of γ-tocopherol as a colorectal cancer chemopreventive agent. Crit Rev Oncol Hematol 2003;47:249–259.
  79. Emmel VM, Celle PL: Observations concerning intestinal absorption of γ-tocopherol and its conversion to α-tocopherol. Anat Rec 1959;133:376.
  80. Elmadfa I, Kim SW, Reutlinger M, Siewert R: The transformation of γ-tocopherol to α-tocopherol in the animal organism; a generational study in rats (in German). Z Ernährungswiss 1989;28:36–48.
  81. Goh SH, Hew NF, Khor HT, Choo YM, Yap SC, Ong SH: An apparent in vivo conversion of tocotrienols to tocopherols in the rabbit. Malaysian Oil Sci Technol 1992;1:56–59.
  82. Clement M, Dinh L, Bourre JM: Uptake of dietary RRR-A- and RRR-γ-tocopherol by nervous tissues, liver and muscle in vitamin-E-deficient rats. Biochim Biophys Acta 1995;1256:175–180.
  83. Clement M, Bourre JM: Graded dietary levels of RRR-γ-tocopherol induced a marked increase in the concentrations of α- and γ-tocopherols in nervous tissues, heart, liver and muscle of vitamin E-deficient rats. Biochim Biophys Acta 1997;1334:173–181.
  84. Qureshi AA, Pearce BC, Nor RM, Gapor A, Peterson DM, Elson CE: Dietary α-tocopherol attenuates the impact of γ-tocotrienol on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in chickens. J Nutr 1996;126:389–394.
  85. Farwer SR, der Boer BC, Haddeman E, Kivits GA, Wiersma A, Danse BH: The vitamin E nutritional status of rats fed on diets high in fish oil, linseed oil or sunflower seed oil. Br J Nutr 1994;72:127–145.
  86. Behrens WA, Madere R: Mechanisms of absorption, transport and tissue uptake of RRR-α-tocopherol and d-γ-tocopherol in the white rat. J Nutr 1987;117:1562–1569.
  87. Khor HT, Chieng DY, Ong KK: Tocotrienols inhibit HMG-CoA reductase activity in the guinea pig. Nutr Res 1995;15:537–544.
  88. Qureshi AA, Sami SA, Salser WA, Khan FA: Synergistic effect of tocotrienol-rich fraction (TRF25) of rice bran and lovastatin on lipid parameters in hypercholesterolemic humans. J Nutr Biochem 2001;12:318–329.
  89. Kamal-Eldin A, Appelqvist LÅ: The chemistry and antioxidant properties of the tocopherols and tocotrienols. Lipids 1996;31:671–701.
  90. Kamal-Eldin A, Görgen S, Pettersson J, Lampi AM: Normal-phase high-performance liquid chromatography of tocopherols and tocotrienols: Comparison of different chromatographic columns. J Chromatogr 2000;881:217–227.
  91. Wright JS, Carpenter DJ, McKay DJ, Ingold KU: Theoretical calculation of substituent effects on the O-H bond strength of phenolic antioxidants related to vitamin E. J Am Chem Soc 1997;119:4245–4252.
  92. Fuster MD, Lampi AM, Hopia A, Kamal-Eldin A: Effects of α- and γ-tocopherols on the autooxidation of purified sunflower triacylglycerols. Lipids 1998;33:715–722.
  93. Wagner KH, Elmadfa I: Effect of tocopherols and their mixtures on oxidative stability of olive oil and linseed oil under heating. Eur J Lipid Sci Technol 2000;102:624–629.
  94. Yanishlieva NV, Marinova EM, Toneva AG, Kamal-Eldin A: Kinetic study of the antioxidant activity of α- and γ-tocopherols in sunflower and soybean triacylglycerols. Eur J Lipid Sci Technol 2002;104:262–270.
  95. Bowry VW, Ingold KU, Stocker R: Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant. Biochem J 1992;288:341–344.
  96. Christen S, Hagen TM, Shigenaga MK, Ames BN: Chronic inflammation, mutation, and cancer; in Parsonnet J (ed): Microbes and Malignancy: Infection as a Cause of Human Cancers. New York, Oxford University Press, 1999, pp 35–88.
  97. Ames BN, Shigenaga MK, Hagen TM: Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 1993;90:7915–7922.
  98. Christen S, Jiang Q, Shigenaga MK, Ames BN: Analysis of plasma tocopherols α, γ, and 5-nitro-γ in rats with inflammation by HPLC coulometric detection. J Lipid Res 2002;43:1978–1985.
  99. Christen S, Gee P, Ames BN: Mutagenicity of nitric oxide in base pair-specific Salmonella tester strains: Ta7000 series. Methods Enzymol 1996;269:267–278.
  100. Brown KM, Morrice PC, Arthur JR, Duthie GG: Effects of vitamin E supplementation on erythrocyte antioxidant defence mechanisms of smoking and non-smoking men. Clin Sci (Lond) 1996;91:107–111.
  101. Cooney RV, Franke AA, Harwood PJ, Hatch-Pigott V, Custer LJ, Mordan LJ: Gamma-tocopherol detoxification of nitrogen dioxide: Superiority to α-tocopherol. Proc Natl Acad Sci USA 1993;90:1771–1775.
  102. Hoglen NC, Waller SC, Sipes IG, Liebler DC: Reactions of peroxynitrite with γ-tocopherol. Chem Res Toxicol 1997;10:401–407.
  103. Christen S, Woodall AA, Shigenaga MK, Southwell-Keely PT, Duncan MW, Ames BN: Gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements α-tocopherol: Physiological implications. Proc Natl Acad Sci USA 1997;94:3217–3222.
  104. Sjöholm A, Berggren PO, Cooney RV: Gamma-tocopherol partially protects insulin-secreting cells against functional inhibition by nitric oxide. Biochem Biophys Res Commun 2000;277:334–340.
  105. Williamson KS, Gabbita SP, Mou S, West M, Pye QN, Markesbery WR, Cooney RV, Grammas P, Reimann-Philipp U, Floyd RA, Hensley K: The nitration product 5-nitro-γ-tocopherol is increased in the Alzeimer brain. Nitric Oxide 2002;6:221–227.
  106. Evans JC, Kodali DR, Addis PB: Optimal tocopherol concentrations to inhibit soybean oil oxidation. J Am Oil Chem Soc 2002;79:47–51.
  107. Isnardy B, Wagner KH, Elmadfa I: Effects of α-, γ-, and δ-tocopherols on the autoxidation of purified rapeseed oil triacylglycerols in a system containing low oxygen. J Agric Food Chem 2003;51:7775–7780.
  108. Yi OS, Han D, Shin HK: Synergistic antioxidative effects of tocopherol and ascorbic acid in fish oil/lecithin/water system. J Am Oil Chem Soc 1991;68:881–883.
  109. Kourimska J, Pokorny J, Reblova Z: Phospholipids as inhibitors of oxidation during food storage and frying. Prehrambeno-Technol. Biotechnol Rev 1994;32:91–94.
  110. Schwartz K, Frankel EN, German JB: Partition behaviour of antioxidative phenolic compounds in heterophasic systems. Fett/Lipid 1996;98:115–121.
  111. Wagner KH, Isnardy B, Elmadfa I: Gamma- and δ-tocopherol are more effective than α-tocopherol on the autoxidation of a 10% rapeseed oil triacylglycerol-in-water emulsion with and without a radical initiator. Eur J Lipid Sci Technol 2004;106:44–51.
  112. Saldeen T, Li D, Mehta JL: Differential effects of α- and γ-tocopherol on low-density lipoprotein oxidation, superoxide activity, platelet aggregation and arterial thrombogenesis. J Am Coll Cardiol 1999;34:1208–1215.
  113. Elmadfa I, Park E: Impact of diets with corn oil or olive/sunflower oils on DNA damage in healthy young men. Eur J Nutr 1999;38:286–292.
  114. Shi H, Noguchi N, Niki E: Comparative study on antioxidant activity of α- and γ-tocopherols in mouse brain homogenates (abstract). Free Radic Biol Med 1999;27:S44.

    External Resources

  115. Helzlsouer KJ, Huang HY, Alberg AJ, Hoffman S, Burke A, Norkus EP, Morris JS, Comstock GW: Association between α-tocopherol, γ-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst 2000;92:2018–2023.
  116. Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens CH, Stampfer MJ: Lower prostate cancer risk in men with elevated plasma lycopene levels: Results of a prospective analysis. Cancer Res 1999;59:1225–1230.
  117. Nomura AM, Stemmermann GN, Lee J, Craft NE: Serum micronutrients and prostate cancer in Japanese Americans in Hawaii. Cancer Epidemiol Biomarkers Prev 1997;6:487–491.
  118. Nomura AM, Ziegler RG, Stemmermann GN, Chyou PH, Craft NE: Serum micronutrients and upper aerodigestive tract cancer. Cancer Epidemiol Biomarkers Prev 1997;6:407–412.
  119. Huang HY, Alberg AJ, Norkus EP, Hoffman SC, Comstock GW, Helzlsouer KJ: Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer. Am J Epidemiol 2003;157:335–344.
  120. Sato R, Helzlsouer KJ, Alberg AJ, Hoffman SC, Norkus EP, Comstock GW: Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2002;11:451–457.
  121. Palli D, Masala G, Vineis P, Garte S, Saieva C, Krogh V, Panico S, Tumino R, Munnia A, Riboli E, Peluso M: Biomarkers of dietary intake of micronutrients modulate DNA adduct levels in healthy adults. Carcinogenesis 2003;24:739–746.
  122. Moyad MA, Brumfield SK, Pienta KJ: Vitamin E, α- and γ-tocopherol, and prostate cancer. Semin Urol Oncol 1999;17:85–90.
  123. Wolf G: Gamma-tocopherol: An efficient protector of lipids against nitric oxide-initiated peroxidative damage. Nutr Rev 1997;55:376–378.
  124. Jones KH, Liu JJ, Roehm JS, Eckel JJ, Eckel TT, Stickrath CR, Triola CA, Jiang ZC, Bartoli GM, Cornwell DG: Gamma-tocopheryl quinone stimulates apoptosis in drug-sensitive and multidrug-resistant cancer cells. Lipids 2002;37:173–184.
  125. Calviello G, Di Nicuolo F, Piccioni E, Marcocci ME, Serini S, Maggiano N, Jones KH, Cornwell DG, Palozza P: Gamma-tocopheryl quinone induces apoptosis in cancer cells via caspase-9 activation and cytochrome c release. Carcinogenesis 2003;24:427–433.
  126. WHO: The World Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva, WHO, 2002.
  127. Yochum LA, Folsom AR, Kushi LH: Intake of antioxidant vitamins and risk of death from stroke in postmenopausal women. Am J Clin Nutr 2000;72:476–483.
  128. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC: Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993;328:1444–1449.
  129. Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick RM: Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med 1996;334:1156–1162.
  130. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P: Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:154–160.
  131. GISSI: Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet 1999;354:447–455.
  132. Kontush A, Spranger T, Reich A, Baum K, Beisiegel U: Lipophilic antioxidants in blood plasma as markers of atherosclerosis: The role of α-carotene and β-tocopherol. Atherosclerosis 1999;144:117–122.
  133. Öhrvall M, Tengblad S, Vessby B: Tocopherol concentrations in adipose tissue: Relationships of tocopherol concentrations and fatty acid composition in serum in a reference population of Swedish men and women. Eur J Clin Nutr 1994;48:212–218.
  134. Morton LW, Ward NC, Croft KD, Puddey IB: Evidence for the nitration of γ-tocopherol in vivo: 5-Nitro-γ-tocopherol is elevated in the plasma of subjects with coronary heart disease. Biochem J 2002;364:625–628.
  135. Kaminskas A, Zieden B, Elving B, Kristenson M, Abaravicius A, Bergdahl B, Olsson AG, Kucinskiene Z: Adipose tissue fatty acids in men from two populations with different cardiovascular risk: The LiVicordia study. Scand J Clin Lab Invest 1999;59:227–232.
  136. Sabate J, Haddad E, Tanzman JS, Jambazian P, Rajaram S: Serum lipid response to the graduated enrichment of a step I diet with almonds: A randomized feeding trial. Am J Clin Nutr 2003;77:1379–1384.
  137. Fuster V, Badimon L, Badimon JJ, Chesebro JH: The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992;326:242–250.
  138. Liu M, Wallmon A, Olsson-Mortlock C, Wallin R, Saldeen T: Mixed tocopherols inhibit platelet aggregation in humans: Potential mechanisms. Am J Clin Nutr 2003;77:700–706.
  139. Li D, Saldeen T, Romeo F, Mehta JL: Relative effects of α- and γ-tocopherol on low-density lipoprotein oxidation and superoxide dismutase and nitric oxide synthase activity and protein expression in rats. J Cardiovasc Pharmacol Ther 1999;4:219–226.
  140. Mishima K, Tanaka T, Pu F, Egashira N, Iwasaki K, Hidaka R, Matsunaga K, Takata J, Karube Y, Fujiwara M: Vitamin E isoforms α-tocotrienol and γ-tocopherol prevent cerebral infarction in mice. Neurosci Lett 2003;337:56–60.
  141. Jiang Q, Christen S, Shigenaga MK, Ames B: γ-Tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am J Clin Nutr 2001;74:714–722.
  142. Gao R, Stone WL, Huang T, Papas AM, Qui M: The uptake of tocopherols by RAW264.7 macrophages. Nutr J 2002;1:2.
  143. Jiang Q, Lykkesfeldt J, Shigenaga MK, Shigeno ET, Christen S, Ames BN: Gamma-tocopherol supplementation inhibits protein nitration and ascorbate oxidation in rats with inflammation. Free Radic Biol Med 2002;33:1534–1542.
  144. Jiang Q, Ames BN: Gamma-tocopherol, but not α-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats. Faseb J 2003;17:816–822.
  145. Lyle BJ, Mares-Perlman JA, Klein BE, Klein R, Palta M, Bowen PE, Greger JL: Serum carotenoids and tocopherols and incidence of age-related nuclear cataract. Am J Clin Nutr 1999;69:272–277.
  146. Olmedilla B, Granado F, Southon S, Wright AJ, Blanco I, Gil-Martinez E, Berg H, Corridan B, Roussel AM, Chopra M, Thurnham DI: Serum concentrations of carotenoids and vitamins A, E, and C in control subjects from five European countries. Br J Nutr 2001;85:227–238.
  147. Wallstrom P, Wirfalt E, Lahmann PH, Gullberg B, Janzon L, Berglund G: Serum concentrations of β-carotene and α-tocopherol are associated with diet, smoking, and general and central adiposity. Am J Clin Nutr 2001;73:777–785.
  148. Walda IC, Tabak C, Smit HA, Rasanen L, Fidanza F, Menotti A, Nissinen A, Feskens EJ, Kromhout D: Diet and 20-year chronic obstructive pulmonary disease mortality in middle-aged men from three European countries. Eur J Clin Nutr 2002;56:638–643.
  149. Brunner E, Stallone D, Juneja M, Bingham S, Marmot M: Dietary assessment in Whitehall II: Comparison of 7-day diet diary and food-frequency questionnaire and validity against biomarkers. Br J Nutr 2001;86:405–414.
  150. Beitz R, Mensink GB, Fischer B, Thamm M: Vitamins – Dietary intake and intake from dietary supplements in Germany. Eur J Clin Nutr 2002;56:539–545.
  151. Capita R, Alonso-Calleja C: Intake of nutrients associated with an increased risk of cardiovascular disease in a Spanish population. Int J Food Sci Nutr 2003;54:57–75.
  152. Block G, Norkus E, Hudes M, Mandel S, Helzlsouer K: Which plasma antioxidants are most related to fruit and vegetable consumption? Am J Epidemiol 2001;154:1113–1118.
  153. Sato R, Helzlsouer KJ, Alberg AJ, Hoffman SC, Norkus EP, Comstock GW: Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2002;11:451–457.
  154. Cooney RV, Custer LJ, Okinaka L, Franke AA: Effects of dietary sesame seeds on plasma tocopherol levels. Nutr Cancer 2001;39:66–71.
  155. Ruiz Rejon F, Martin-Pena G, Granado F, Ruiz-Galiana J, Blanco I, Olmedilla B: Plasma status of retinol, α- and γ-tocopherols, and main carotenoids to first myocardial infarction: Case control and follow-up study. Nutrition 2002;18:26–31.
  156. Palli D, Masala G, Vineis P, Garte S, Saieva C, Krogh V, Panico S, Tumino R, Munnia A, Riboli E, Peluso M: Biomarkers of dietary intake of micronutrients modulate DNA adduct levels in healthy adults. Carcinogenesis 2003;24:739–746.
  157. Kristenson M, Kucinskiene Z, Schafer-Elinder L, Leanderson P, Tagesson C: Lower serum levels of β-carotene in Lithuanian men are accompanied by higher urinary excretion of the oxidative DNA adduct, 8-hydroxydeoxyguanosine. The LiVicordia study. Nutrition 2003;19:11–15.
  158. Fuchs J, Weber S, Podda M, Groth N, Herrling T, Packer L, Kaufmann R: HPLC analysis of vitamin E isoforms in human epidermis: Correlation with minimal erythema dose and free radical scavenging activity. Free Radic Biol Med 2003;34:330–336.
  159. Meylan WM, Howard PH: Atom/fragment contribution method for estimating octanol-water partition coefficients. J Pharm Sci 1995;84:83–92.
  160. Brigelius-Flohe R: Vitamin E and drug metabolism. Biochem Biophys Res Commun 2003;305:737–740.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50