|
|
||||||||

* German Institute of Human Nutrition, Bergholz-Rehbrücke, Germany; and
Department of Nutrition and Food Management, Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97330, USA
1Correspondence: German Institute of Human Nutrition, Arthur Scheunert-Allee 114116, D-14558 Bergholz-Rehbrücke, Germany.
Although vitamin E has been known as an essential nutrient for
reproduction since 1922, we are far from understanding the mechanisms
of its physiological functions. Vitamin E is the term for a group of
tocopherols and tocotrienols, of which
-tocopherol has the highest
biological activity. Due to the potent antioxidant properties of
tocopherols, the impact of
-tocopherol in the prevention of chronic
diseases believed to be associated with oxidative stress has often been
studied, and beneficial effects have been demonstrated. Recent
observations that the
-tocopherol transfer protein in the liver
specifically sorts out RRR-
-tocopherol from all
incoming tocopherols for incorporation into plasma lipoproteins, and
that
-tocopherol has signaling functions in vascular smooth muscle
cells that cannot be exerted by other forms of tocopherol with similar
antioxidative properties, have raised interest in the roles of vitamin
E beyond its antioxidative function. Also,
-tocopherol might have
functions apart from being an antioxidant. It is a nucleophile able to
trap electrophilic mutagens in lipophilic compartments and generates a
metabolite that facilitates natriuresis. The metabolism of vitamin E is
equally unclear. Excess
-tocopherol is converted into
-CEHC and
excreted in the urine. Other tocopherols, like
- and
-tocopherol,
are almost quantitatively degraded and excreted in the urine as the
corresponding CEHCs. All rac
-tocopherol compared to
RRR-
-tocopherol is preferentially degraded to
-CEHC. Thus, there must be a specific, molecular role of
RRR-
-tocopherol that is regulated by a system that
sorts, distributes, and degrades the different forms of vitamin E, but
has not yet been identified. In this article we try to summarize
current knowledge on the function of vitamin E, with emphasis on its
antioxidant vs. other properties, the preference of the organism for
RRR-
-tocopherol, and its metabolism to
CEHCs.Brigelius-Flohé, R., Traber, M. G. Vitamin E:
function and metabolism.
This article has been cited by other articles:
![]() |
M. Matringe, B. Ksas, P. Rey, and M. Havaux Tocotrienols, the Unsaturated Forms of Vitamin E, Can Function as Antioxidants and Lipid Protectors in Tobacco Leaves Plant Physiology, June 1, 2008; 147(2): 764 - 778. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Ravaglia, P. Forti, A. Lucicesare, N. Pisacane, E. Rietti, F. Mangialasche, R. Cecchetti, C. Patterson, and P. Mecocci Plasma tocopherols and risk of cognitive impairment in an elderly Italian cohort Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1306 - 1313. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Siekmeier, C. Steffen, and W. Marz Role of Oxidants and Antioxidants in Atherosclerosis: Results of In Vitro and In Vivo Investigations Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2007; 12(4): 265 - 282. [Abstract] [PDF] |
||||
![]() |
S. W. Leonard, J. D. Joss, D. J. Mustacich, D. H. Blatt, Y. S. Lee, and M. G. Traber Effects of vitamin E on cholesterol levels of hypercholesterolemic patients receiving statins Am. J. Health Syst. Pharm., November 1, 2007; 64(21): 2257 - 2266. [Abstract] [Full Text] [PDF] |
||||
![]() |
Q. Jiang, H. Freiser, K. V. Wood, and X. Yin Identification and quantitation of novel vitamin E metabolites, sulfated long-chain carboxychromanols, in human A549 cells and in rats J. Lipid Res., May 1, 2007; 48(5): 1221 - 1230. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R. Fernandez-Santos, F. Martinez-Pastor, V. Garcia-Macias, M. C. Esteso, A. J. Soler, P. Paz, L. Anel, and J. J. Garde Sperm Characteristics and DNA Integrity of Iberian Red Deer (Cervus elaphus hispanicus) Epididymal Spermatozoa Frozen in the Presence of Enzymatic and Nonenzymatic Antioxidants J Androl, March 1, 2007; 28(2): 294 - 305. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. G Traber Heart disease and single-vitamin supplementation Am. J. Clinical Nutrition, January 1, 2007; 85(1): 293S - 299S. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Frank, A. Budek, T. Lundh, R. S. Parker, J. E. Swanson, C. F. Lourenco, B. Gago, J. Laranjinha, B. Vessby, and A. Kamal-Eldin Dietary flavonoids with a catechol structure increase {alpha}-tocopherol in rats and protect the vitamin from oxidation in vitro J. Lipid Res., December 1, 2006; 47(12): 2718 - 2725. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Sattler, L. Mene-Saffrane, E. E. Farmer, M. Krischke, M. J. Mueller, and D. DellaPenna Nonenzymatic Lipid Peroxidation Reprograms Gene Expression and Activates Defense Markers in Arabidopsis Tocopherol-Deficient Mutants PLANT CELL, December 1, 2006; 18(12): 3706 - 3720. [Abstract] [Full Text] [PDF] |
||||
![]() |
B.-L. Song and R. A. DeBose-Boyd Insig-dependent Ubiquitination and Degradation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Stimulated by {delta}- and {gamma}-Tocotrienols J. Biol. Chem., September 1, 2006; 281(35): 25054 - 25061. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Minehira-Castelli, S. W. Leonard, Q. M. Walker, M. G. Traber, and S. G. Young Absence of VLDL secretion does not affect {alpha}-tocopherol content in peripheral tissues J. Lipid Res., August 1, 2006; 47(8): 1733 - 1738. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. S. Chen and P. G. Wells Enhanced tumorigenesis in p53 knockout mice exposed in utero to high-dose vitamin E Carcinogenesis, July 1, 2006; 27(7): 1358 - 1368. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Delanian, R. Porcher, J. Rudant, and J.-L. Lefaix Kinetics of Response to Long-Term Treatment Combining Pentoxifylline and Tocopherol in Patients With Superficial Radiation-Induced Fibrosis J. Clin. Oncol., December 1, 2005; 23(34): 8570 - 8579. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Khanna, S. Roy, A. Slivka, T. K.S. Craft, S. Chaki, C. Rink, M. A. Notestine, A. C. DeVries, N. L. Parinandi, and C. K. Sen Neuroprotective Properties of the Natural Vitamin E {alpha}-Tocotrienol Stroke, October 1, 2005; 36(10): e144 - e152. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Maeda, Y. Sakuragi, D. A. Bryant, and D. DellaPenna Tocopherols Protect Synechocystis sp. Strain PCC 6803 from Lipid Peroxidation Plant Physiology, July 1, 2005; 138(3): 1422 - 1435. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Wolf The Discovery of the Antioxidant Function of Vitamin E: the contribution of Henry A. Mattill J. Nutr., March 1, 2005; 135(3): 363 - 366. [Full Text] [PDF] |
||||
![]() |
S. M. Lippman, P. J. Goodman, E. A. Klein, H. L. Parnes, I. M. Thompson, A. R. Kristal, R. M. Santella, J. L. Probstfield, C. M. Moinpour, D. Albanes, et al. Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT) J Natl Cancer Inst, January 19, 2005; 97(2): 94 - 102. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. L. Hall, Y. M. Jeanes, and J. K. Lodge Hyperlipidemic Subjects Have Reduced Uptake of Newly Absorbed Vitamin E into Their Plasma Lipoproteins, Erythrocytes, Platelets, and Lymphocytes, as Studied by Deuterium-Labeled {alpha}-Tocopherol Biokinetics J. Nutr., January 1, 2005; 135(1): 58 - 63. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. K. LODGE, W. L. HALL, Y. M. JEANES, and A. R. PROTEGGENTE Physiological Factors Influencing Vitamin E Biokinetics Ann. N.Y. Acad. Sci., December 1, 2004; 1031(1): 60 - 73. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. GOHIL, R. GODZDANKER, E. O'ROARK, B. C. SCHOCK, R. R. KAINI, L. PACKER, C. E. CROSS, and M. G. TRABER {alpha}-Tocopherol Transfer Protein Deficiency in Mice Causes Multi-Organ Deregulation of Gene Networks and Behavioral Deficits with Age Ann. N.Y. Acad. Sci., December 1, 2004; 1031(1): 109 - 126. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. GILLE, W. GREGOR, K. STANIEK, and H. NOHL Oxidized Vitamin E and Ubiquinone: Competition for Binding Sites of the Mitochondrial Cytochrome bc1 Complex? Ann. N.Y. Acad. Sci., December 1, 2004; 1031(1): 341 - 343. [Full Text] [PDF] |
||||
![]() |
C. C. McCormick and R. S. Parker The Cytotoxicity of Vitamin E Is Both Vitamer- and Cell-Specific and Involves a Selectable Trait J. Nutr., December 1, 2004; 134(12): 3335 - 3342. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Zhou, M. M. Tabb, A. Sadatrafiei, F. Grun, and B. Blumberg TOCOTRIENOLS ACTIVATE THE STEROID AND XENOBIOTIC RECEPTOR, SXR, AND SELECTIVELY REGULATE EXPRESSION OF ITS TARGET GENES Drug Metab. Dispos., October 1, 2004; 32(10): 1075 - 1082. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. M. Jervis and B. Robaire The Effects of Long-Term Vitamin E Treatment on Gene Expression and Oxidative Stress Damage in the Aging Brown Norway Rat Epididymis Biol Reprod, October 1, 2004; 71(4): 1088 - 1095. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Hofius, M.-R. Hajirezaei, M. Geiger, H. Tschiersch, M. Melzer, and U. Sonnewald RNAi-Mediated Tocopherol Deficiency Impairs Photoassimilate Export in Transgenic Potato Plants Plant Physiology, July 1, 2004; 135(3): 1256 - 1268. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Sattler, L. U. Gilliland, M. Magallanes-Lundback, M. Pollard, and D. DellaPenna Vitamin E Is Essential for Seed Longevity and for Preventing Lipid Peroxidation during Germination PLANT CELL, June 1, 2004; 16(6): 1419 - 1432. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. C.-Y. Soo, A. S. Haqqani, N. Hidiroglou, J. E. Swanson, R. S. Parker, and H. C. Birnboim Dose-Dependent Effects of Dietary {alpha}- and {gamma}-Tocopherols on Genetic Instability in Mouse Mutatect Tumors J Natl Cancer Inst, May 19, 2004; 96(10): 796 - 800. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. W Leonard, C. K Good, E. T Gugger, and M. G Traber Vitamin E bioavailability from fortified breakfast cereal is greater than that from encapsulated supplements Am. J. Clinical Nutrition, January 1, 2004; 79(1): 86 - 92. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. C. Min, R. A. Kovall, and W. A. Hendrickson Crystal structure of human {alpha}-tocopherol transfer protein bound to its ligand: Implications for ataxia with vitamin E deficiency PNAS, December 9, 2003; 100(25): 14713 - 14718. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. C. Wong, R. J. Lambert, Y. Tadmor, and T. R. Rocheford QTL Associated with Accumulation of Tocopherols in Maize Crop Sci., November 1, 2003; 43(6): 2257 - 2266. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Khanna, S. Roy, H. Ryu, P. Bahadduri, P. W. Swaan, R. R. Ratan, and C. K. Sen Molecular Basis of Vitamin E Action: TOCOTRIENOL MODULATES 12-LIPOXYGENASE, A KEY MEDIATOR OF GLUTAMATE-INDUCED NEURODEGENERATION J. Biol. Chem., October 31, 2003; 278(44): 43508 - 43515. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Saito, Y. Yoshida, T. Akazawa, K. Takahashi, and E. Niki Cell Death Caused by Selenium Deficiency and Protective Effect of Antioxidants J. Biol. Chem., October 10, 2003; 278(41): 39428 - 39434. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Cheng, S. Sattler, H. Maeda, Y. Sakuragi, D. A. Bryant, and D. DellaPenna Highly Divergent Methyltransferases Catalyze a Conserved Reaction in Tocopherol and Plastoquinone Synthesis in Cyanobacteria and Photosynthetic Eukaryotes PLANT CELL, October 1, 2003; 15(10): 2343 - 2356. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Gumustekin, K. Altinkaynak, H. Timur, S. Taysi, N. Oztasan, M F. Polat, F. Akcay, H. Suleyman, S. Dane, and M. Gul Vitamin E but not Hippophea rhamnoides L.prevented nicotine-induced oxidative stress in rat brain Human and Experimental Toxicology, August 1, 2003; 22(8): 425 - 431. [Abstract] [PDF] |
||||
![]() |
T. A. Thompson and G. Wilding Androgen Antagonist Activity by the Antioxidant Moiety of Vitamin E, 2,2,5,7,8-Pentamethyl-6-chromanol in Human Prostate Carcinoma Cells Mol. Cancer Ther., August 1, 2003; 2(8): 797 - 803. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Sattler, E. B. Cahoon, S. J. Coughlan, and D. DellaPenna Characterization of Tocopherol Cyclases from Higher Plants and Cyanobacteria. Evolutionary Implications for Tocopherol Synthesis and Function Plant Physiology, August 1, 2003; 132(4): 2184 - 2195. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Papucci, N. Schiavone, E. Witort, M. Donnini, A. Lapucci, A. Tempestini, L. Formigli, S. Zecchi-Orlandini, G. Orlandini, G. Carella, et al. Coenzyme Q10 Prevents Apoptosis by Inhibiting Mitochondrial Depolarization Independently of Its Free Radical Scavenging Property J. Biol. Chem., July 18, 2003; 278(30): 28220 - 28228. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. F. Carroll and D. S. Schade Timing of Antioxidant Vitamin Ingestion Alters Postprandial Proatherogenic Serum Markers Circulation, July 8, 2003; 108(1): 24 - 31. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Takahashi, K. Okumura, H. Matsui, Y. Saburi, H. Kamiya, K. Matsubara, T. Asai, M. Ito, and T. Murohara Impact of {alpha}-tocopherol on cardiac hypertrophy due to energy metabolism disorder: the involvement of 1,2-diacylglycerol Cardiovasc Res, June 1, 2003; 58(3): 565 - 574. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. L Stone, I. LeClair, T. Ponder, G. Baggs, and B. B. Reis Infants discriminate between natural and synthetic vitamin E Am. J. Clinical Nutrition, April 1, 2003; 77(4): 899 - 906. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Collakova and D. DellaPenna Homogentisate Phytyltransferase Activity Is Limiting for Tocopherol Biosynthesis in Arabidopsis Plant Physiology, February 1, 2003; 131(2): 632 - 642. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. De Caterina, F. Cipollone, F. P. Filardo, M. Zimarino, W. Bernini, G. Lazzerini, T. Bucciarelli, A. Falco, P. Marchesani, R. Muraro, et al. Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F2-Isoprostane Formation in Hypercholesterolemic Subjects: No Further Effect of Vitamin E Circulation, November 12, 2002; 106(20): 2543 - 2549. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Christen, Q. Jiang, M. K. Shigenaga, and B. N. Ames Analysis of plasma tocopherols {alpha}, {gamma}, and 5-nitro-{gamma} in rats with inflammation by HPLC coulometric detection J. Lipid Res., November 1, 2002; 43(11): 1978 - 1985. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Birringer, P. Pfluger, D. Kluth, N. Landes, and R. Brigelius-Flohe Identities and Differences in the Metabolism of Tocotrienols and Tocopherols in HepG2 Cells J. Nutr., October 1, 2002; 132(10): 3113 - 3118. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. J. Sontag and R. S. Parker Cytochrome P450 omega -Hydroxylase Pathway of Tocopherol Catabolism. NOVEL MECHANISM OF REGULATION OF VITAMIN E STATUS J. Biol. Chem., July 5, 2002; 277(28): 25290 - 25296. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. R. Rocheford, J. C. Wong, C. O. Egesel, and R. J. Lambert Enhancement of Vitamin E Levels in Corn J. Am. Coll. Nutr., June 1, 2002; 21(90003): 191S - 198. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Mardones, P. Strobel, S. Miranda, F. Leighton, V. Quinones, L. Amigo, J. Rozowski, M. Krieger, and A. Rigotti {alpha}-Tocopherol Metabolism Is Abnormal in Scavenger Receptor Class B Type I (SR-BI)-Deficient Mice J. Nutr., March 1, 2002; 132(3): 443 - 449. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. M. Attia, A. M. G. Verhagen, E. S. G. Stroes, E. E. van Faassen, H.-J. Grone, S. J. De Kimpe, H. A. Koomans, B. Braam, and J. A. Joles Vitamin E Alleviates Renal Injury, but Not Hypertension, during Chronic Nitric Oxide Synthase Inhibition in Rats J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2585 - 2593. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. RICCIARELLI, J.-M. ZINGG, and A. AZZI Vitamin E: protective role of a Janus molecule FASEB J, November 1, 2001; 15(13): 2314 - 2325. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Collakova and D. DellaPenna Isolation and Functional Analysis of Homogentisate Phytyltransferase from Synechocystis sp. PCC 6803 and Arabidopsis Plant Physiology, November 1, 2001; 127(3): 1113 - 1124. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Devaraj, I. Hugou, and I. Jialal {{alpha}}-Tocopherol decreases CD36 expression in human monocyte-derived macrophages J. Lipid Res., April 1, 2001; 42(4): 521 - 527. [Abstract] [Full Text] |
||||
![]() |
M. L. O'Brien, T. P. Twaroski, M. L. Cunningham, H. P. Glauert, and B. T. Spear Effects of Peroxisome Proliferators on Antioxidant Enzymes and Antioxidant Vitamins in Rats and Hamsters Toxicol. Sci., April 1, 2001; 60(2): 271 - 278. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Packer, S. U. Weber, and G. Rimbach Molecular Aspects of {{alpha}}-Tocotrienol Antioxidant Action and Cell Signalling J. Nutr., February 1, 2001; 131(2): 369S - 373. [Abstract] [Full Text] |
||||
![]() |
K. Kline, W. Yu, and B. G. Sanders Vitamin E: Mechanisms of Action as Tumor Cell Growth Inhibitors J. Nutr., January 1, 2001; 131(1): 161S - 163. [Full Text] |
||||
![]() |
E. Giovannucci {{gamma}}-Tocopherol: a New Player in Prostate Cancer Prevention? J Natl Cancer Inst, December 20, 2000; 92(24): 1966 - 1967. [Full Text] [PDF] |
||||
![]() |
W. Witt, I. Kolleck, H. Fechner, P. Sinha, and B. Rüstow Regulation by vitamin E of the scavenger receptor BI in rat liver and HepG2 cells J. Lipid Res., December 1, 2000; 41(12): 2009 - 2016. [Abstract] [Full Text] |
||||
![]() |
S. B. Lotito and C. G. Fraga Catechins Delay Lipid Oxidation and {alpha}-Tocopherol and {beta}-Carotene Depletion Following Ascorbate Depletion in Human Plasma Experimental Biology and Medicine, October 1, 2000; 225(1): 32 - 38. [Abstract] [Full Text] |
||||
![]() |
Q. Jiang, I. Elson-Schwab, C. Courtemanche, and B. N. Ames gamma -Tocopherol and its major metabolite, in contrast to alpha -tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells PNAS, September 22, 2000; (2000) 200357097. [Abstract] [Full Text] |
||||
![]() |
J. K. Sandhu, A. S. Haqqani, and H. C. Birnboim Effect of Dietary Vitamin E on Spontaneous or Nitric Oxide Donor-Induced Mutations in a Mouse Tumor Model J Natl Cancer Inst, September 6, 2000; 92(17): 1429 - 1433. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Asmis and J. Jelk Vitamin E Supplementation of Human Macrophages Prevents Neither Foa |