Vitamin E

The α-tocopherol form of vitamin E.

Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols.^[1] There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet.^[2] γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings.^[3][4] α-Tocopherol, the most biologically active form of vitamin E, is the second most common form of vitamin E in the North American diet. This variant of vitamin E can be found most abundantly in wheat germ oil, sunflower, and safflower oils.^[4][5] It is a fat-soluble antioxidant that stops the production of reactive oxygen species formed when fat undergoes oxidation.^[6][7][8]

Health effects

Vitamin E does not decrease mortality, even at large doses,^[9] and may slightly increase it.^[10] It does not improve blood sugar control in an unselected group of people with diabetes mellitus^[9] or decrease the risk of stroke.^[11] Daily supplementation of vitamin E does not decrease the risk of prostate cancer and may increase it.^[12]

Deficiency

Main article: Vitamin E deficiency

Vitamin E deficiency can cause:

• spinocerebellar ataxia^[13]
• myopathies^[4]
• peripheral neuropathy ^[14][15][16]
• ataxia^[14][15][16]
• skeletal myopathy^[14][15][16]
• retinopathy^[14][15][16]
• impairment of the immune response^[14][15][16]

α-Tocopherol

α-Tocopherol is an important lipid-soluble antioxidant. It performs its functions as antioxidant in what is known by the glutathione peroxidase pathway^[17] and it protects cell membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction.^[13][7] This would remove the free radical intermediates and prevent the oxidation reaction from continuing. The oxidized α-tocopheroxyl radicals produced in this process may be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol.^[18] However, the importance of the antioxidant properties of this molecule at the concentrations present in the body are not clear and it is possible that the reason why vitamin E is required in the diet is unrelated to its ability to act as an antioxidant.^[19] Other forms of vitamin E have their own unique properties; for example, gamma-tocopherol is a nucleophile that can react with electrophilic mutagens.^[20]

Vitamin E has many biological functions. The antioxidant function is considered to be the most important function of vitamin E and is the one it is best known for.^[21] However, there are other functions that have also been recognized to be of importance. α-Tocopherol has a regulatory effect on enzymatic activities. For instance, protein kinase C (PKC), which plays a role in smooth muscle growth, can be inhibited by α-tocopherol. α-Tocopherol has a stimulatory effect on the dephosphorylation enzyme, protein phosphatase 2A, which in turn, cleaves phosphate groups from PKC leading to its deactivation, bringing the smooth muscle growth to a halt.^[22] Vitamin E also has an effect on gene expression. Macrophages rich in cholesterol are found in the atherogenetic tissue. Scavenger receptor CD36 is a class B scavenger receptor found to be up-regulated by oxidized low density lipoprotein (LDL) and binds it.^[23] Treatment with alpha tocopherol was found to down regulate the CD36 scavenger receptor gene expression as well as the scavenger receptor class A (SR-A).^[23] In addition to the effect it has been shown to have on SRA and CD36, α-tocopherol also has an effect on expression of the connective tissue growth factor (CTGF).^[24][25] CTGF gene, when expressed, is responsible for the repair of the wounds and regeneration of the extracellular tissue that is lost or damaged during atherosclerosis.^[25] Moreover, vitamin E also plays a role in neurological functions,^[26] and inhibition of platelet aggregation^[27][28][29] and it has even been suggested that the most important function of vitamin E is as a signaling molecule, and that it has no significant role in antioxidant metabolism.^[30][31]

So far, most studies about vitamin E have supplemented using only alpha-tocopherol, but doing so leads to reduced serum gamma- and delta-tocopherol concentrations. Moreover, a 2007 clinical study involving alpha-tocopherol concluded that supplementation did not reduce the risk of major cardiovascular events in middle aged and older men.^[32]

Tocotrienols

Compared with tocopherols, tocotrienols are sparsely studied.^[33][34][35] Less than 1% of PubMed papers on vitamin E relate to tocotrienols.^[36] Current research direction is starting to give more prominence to the tocotrienols, the lesser known but more potent antioxidants in the vitamin E family. Some studies have suggested that tocotrienols have specialized roles in protecting neurons from damage^[36] and cholesterol reduction^[37] by inhibiting the activity of HMG-CoA reductase; delta-tocotrienol blocks processing of sterol regulatory element‐binding proteins (SREBPs).

Oral consumption of tocotrienols is also thought to protect against stroke-associated brain damage in vivo.^{[citation needed]} Until further research has been carried out on the other forms of vitamin E, conclusions relating to the other forms of vitamin E, based on trials studying only the efficacy of alpha-tocopherol, may be premature.^[38]

Recommended daily intake

The Food and Nutrition Board at the Institute of Medicine report the following dietary reference intakes for vitamin E:^[39]

Infants

• 0 to 6 months: 4 mg/day
• 7 to 12 months: 5 mg/day

Children

• 1 to 3 years: 6 mg/day
• 4 to 8 years: 7 mg/day
• 9 to 13 years: 11 mg/day

Adolescents and Adults

• 14 and older: 15 mg/day

One IU of Vitamin E is 0.67 mg of RRR-alpha-tocopherol, or 0.45 mg of all rac-alpha-tocopherol

Dietary sources and supplements

The following foods are rich in vitamin E:^[40]

• Wheat germ oil
• Sunflower oil
• Safflower oil
• Nuts and nut oils, like almonds and hazelnuts
• Green leafy vegetables, like lettuce, spinach, turnip, beet, collard, and dandelion greens
• Tomato products
• Pumpkin
• Sweet potato (0.26 mg/100 g^[41] so it corresponds to 5.8 kg of potatoes per day of the recommended intake for adults)
• Rockfish
• Mangoes
• Asparagus
• Broccoli
• Papayas
• Avocados
• Kiwifruit

History

The first use for vitamin E as a therapeutic agent was conducted in 1938 by Widenbauer. Widenbauer used wheat germ oil supplement on 17 premature new born infants suffering from growth failure. Eleven out of the original 17 patients recovered and were able to resume normal growth rates.^[42] Later on, in 1948, while conducting experiments on alloxan effects on rats, Gyorge and Rose noted that the rats receiving tocopherol supplements suffered from less hemolysis than those that did not receive tocopherol.^[43] In 1949, Gerloczy administered all-rac-α-tocopheryl acetate to prevent and cure edema.^{[citation needed]} Methods of administration used were both oral, that showed positive response, and intramuscular, which did not show a response.^[42] This early investigative work on the benefits of vitamin E supplementation was the gateway to curing the vitamin E deficiency caused hemolytic anemia described during the 1960s. Since then, supplementation of infant formulas with vitamin E has eradicated this vitamin’s deficiency as a cause for hemolytic anemia.^[42]

References

1. ^ Brigelius-Flohe, B; Traber (1999). "Vitamin E: function and metabolism". FASEB 13: 1145–1155. 
2. ^ Traber, MG (1998). "The biological activity of vitamin E". The Linus Pauling Institute. http://lpi.oregonstate.edu/sp-su98/vitamine.html. Retrieved Mar 6, 2011. 
3. ^ Bieri, JG; Evarts (1974). "γ-Tocopherol: metabolism, biological activity and significance in human vitamin E nutrition". American Journal of Clinical Nutrition 27 (9): 980–986. PMID 4472121. 
4. ^ ^{a b c} Brigelius-Flohé R, Traber MG (1 July 1999). "Vitamin E: function and metabolism". FASEB J. 13 (10): 1145–55. PMID 10385606. http://www.fasebj.org/cgi/pmidlookup?view=long&pmid=10385606. 
5. ^ Reboul E, Richelle M, Perrot E, Desmoulins-Malezet C, Pirisi V, Borel P (2006 Nov 15). "Bioaccessibility of carotenoids and vitamin E from their main dietary sources". Journal of Agricultural and Food Chemistry 54 (23): 8749–8755. doi:10.1021/jf061818s. PMID 17090117. 
6. ^ National Institute of Health (5/4/2009). "Vitamin E fact sheet". http://ods.od.nih.gov/factsheets/VitaminE.asp. 
7. ^ ^{a b} Herrera; Barbas, C (2001). "Vitamin E: action, metabolism and perspectives". Journal of Physiology and Biochemistry 57 (2): 43–56. doi:10.1007/BF03179812. PMID 11579997. 
8. ^ Packer L, Weber SU, Rimbach G (February 2001). "Molecular aspects of α-tocotrienol antioxidant action and cell signalling". Journal of Nutrition 131 (2): 369S–73S. PMID 11160563. http://jn.nutrition.org/cgi/content/full/131/2/369S. 
9. ^ ^{a b} Abner, EL; Schmitt, FA, Mendiondo, MS, Marcum, JL, Kryscio, RJ (2011 Jul). "Vitamin E and all-cause mortality: a meta-analysis.". Current aging science 4 (2): 158–70. PMID 21235492. 
10. ^ Bjelakovic, G; Nikolova, D, Gluud, LL, Simonetti, RG, Gluud, C (2008 Apr 16). "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.". Cochrane database of systematic reviews (Online) (2): CD007176. PMID 18425980. 
11. ^ Bin, Q; Hu, X, Cao, Y, Gao, F (2011 Apr). "The role of vitamin E (tocopherol) supplementation in the prevention of stroke. A meta-analysis of 13 randomized controlled trials.". Thrombosis and haemostasis 105 (4): 579–85. PMID 21264448. 
12. ^ Haederle, Michael. "Vitamin E Supplements Raise Risk of Prostate Cancer". Health Discovery. AARP. http://www.aarp.org/health/drugs-supplements/info-10-2011/vitamin-e-supplements-raise-prostate-cancer-risk-health-discovery.html. Retrieved 11 November 2011. 
13. ^ ^{a b} Traber; Atkinson, J (2007). "Vitamin E, Antioxidant and Nothing More". Free radical biology & medicine 43 (1): 4–15. doi:10.1016/j.freeradbiomed.2007.03.024. PMC 2040110. PMID 17561088. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2040110. 
14. ^ ^{a b c d e} Office of Dietary Supplements. "Vitamin E Professional Fact Sheet". National Institutes of Health. http://ods.od.nih.gov/factsheets/vitamine.asp#h3. Retrieved 14 August 2010. 
15. ^ ^{a b c d e} Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000.
16. ^ ^{a b c d e} Kowdley KV, Mason JB, Meydani SN, Cornwall S, Grand RJ (June 1992). "Vitamin E deficiency and impaired cellular immunity related to intestinal fat malabsorption". Gastroenterology 102 (6): 2139–42. PMID 1587435. 
17. ^ Wefers, H; Sics (1988). "The protection of ascorbate and glutathione against microsomal lipid peroxidation is dependent on Vitamin E". European Journal of Biochemistry 174 (2): 353–357. doi:10.1111/j.1432-1033.1988.tb14105.x. PMID 3383850. 
18. ^ Wang; Quinn, PJ (1999). "Vitamin E and its function in membranes". Progress in lipid research 38 (4): 309–36. doi:10.1016/S0163-7827(99)00008-9. PMID 10793887. 
19. ^ Brigelius-Flohé (2009). "Vitamin E: the shrew waiting to be tamed". Free radical biology & medicine 46 (5): 543–54. doi:10.1016/j.freeradbiomed.2008.12.007. PMID 19133328. 
20. ^ Brigelius-Flohé; Traber, MG (1999). "Vit amin E: function and metabolism". The FASEB journal : official publication of the Federation of American Societies for Experimental Biology 13 (10): 1145–55. PMID 10385606. 
21. ^ Bell, EF (1987). "History of vitamin E in infant nutrition". Am. J. Clin.Nutr 46 (1 Suppl): 183–186. PMID 3300257. 
22. ^ Schneider, C (2005). "Chemistry and biology of vitamin E". Mol Nutr Food Res 49 (1): 7–30. doi:10.1002/mnfr.200400049. PMID 15580660. 
23. ^ ^{a b} Devaraj, S; Hugou, I., Jialal, I. (2001). "-Tocopherol decreases CD36 expression in human monocyte-derived macrophages". J Lipid Res 42 (4): 521–527. PMID 11290823. 
24. ^ Azzi, A; Stocker, R. (2000). "Vitamin E: non-antioxidant roles". Prog Lipid Res 39 (3): 231–255. doi:10.1016/S0163-7827(00)00006-0. PMID 10799717. 
25. ^ ^{a b} Villacorta, L.; Graca-Souza, A. V., Ricciarelli, R., Zingg, J. M., Azzi, A (2003). "α-Tocopherol induces expression of connective tissue growth factor and antagonizes tumor necrosis factor-α-mediated downregulation in human smooth muscle cells". Circ. Res. 92 (1): 104–110. doi:10.1161/01.RES.0000049103.38175.1B. PMID 12522127. 
26. ^ Muller, D.P. (2010). "Vitamin E and neurological function. Review". Mol. Nutr. Food Res 54 (5): 710–718. doi:10.1002/mnfr.200900460. PMID 20183831. 
27. ^ Dowd, P; Zheng, Z. B. (1995). "On the mechanism of the anticlotting action of vitamin E quinone". Proc Natl Acad Sci U S A. 92 (18): 8171–8175. doi:10.1073/pnas.92.18.8171. PMC 41118. PMID 7667263. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=41118. 
28. ^ Brigelius-Flohé; Davies, KJ (2007). "Is vitamin E an antioxidant, a regulator of signal transduction and gene expression, or a 'junk' food? Comments on the two accompanying papers: "Molecular mechanism of alpha-tocopherol action" by A. Azzi and "Vitamin E, antioxidant and nothing more" by M. Traber and J. Atkinson". Free radical biology & medicine 43 (1): 2–3. doi:10.1016/j.freeradbiomed.2007.05.016. PMID 17561087. 
29. ^ Atkinson; Epand, RF; Epand, RM (2008). "Tocopherols and tocotrienols in membranes: a critical review". Free radical biology & medicine 44 (5): 739–64. doi:10.1016/j.freeradbiomed.2007.11.010. PMID 18160049. 
30. ^ Azzi (2007). "Molecular mechanism of alpha-tocopherol action". Free radical biology & medicine 43 (1): 16–21. doi:10.1016/j.freeradbiomed.2007.03.013. PMID 17561089. 
31. ^ Zingg; Azzi, A (2004). "Non-antioxidant activities of vitamin E". Current medicinal chemistry 11 (9): 1113–33. PMID 15134510. 
32. ^ Sesso, H. D.; Buring, J. E.; Christen, W. G.; Kurth, T.; Belanger, C.; MacFadyen, J.; Bubes, V.; Manson, J. E. et al. (2008). "Vitamins E and C in the Prevention of Cardiovascular Disease in Men: The Physicians' Health Study II Randomized Trial". JAMA: the Journal of the American Medical Association 300 (18): 2123–33. doi:10.1001/jama.2008.600. PMC 2586922. PMID 18997197. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2586922. 
33. ^ Traber, MG; Packer, L (1995). "Vitamin E: beyond antioxidant function". American Journal of Clinical Nutrition 62 (6): 1501S–1509S. PMID 7495251. http://www.ajcn.org/cgi/content/abstract/62/6/1501S. 
34. ^ Traber; Sies, H (1996). "Vitamin E in humans: demand and delivery". Annual review of nutrition 16: 321–47. doi:10.1146/annurev.nu.16.070196.001541. PMID 8839930. 
35. ^ Sen; Khanna, S; Roy, S (2004). "Tocotrienol: the natural vitamin E to defend the nervous system?". Annals of the New York Academy of Sciences 1031: 127–42. doi:10.1196/annals.1331.013. PMID 15753140. 
36. ^ ^{a b} Sen; Khanna, S; Roy, S (2006). "Tocotrienols: Vitamin E Beyond Tocopherols". Life sciences 78 (18): 2088–98. doi:10.1016/j.lfs.2005.12.001. PMC 1790869. PMID 16458936. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1790869. 
37. ^ Das; Lekli, I; Das, M; Szabo, G; Varadi, J; Juhasz, B; Bak, I; Nesaretam, K et al. (2008). "Cardioprotection with palm oil tocotrienols: comparison of different isomers". American journal of physiology. Heart and circulatory physiology 294 (2): H970–8. doi:10.1152/ajpheart.01200.2007. PMID 18083895. 
38. ^ Sen, C; Khanna, S; Roy, S (2007). "Tocotrienols in health and disease: the other half of the natural vitamin E family". Molecular Aspects of Medicine 28 (5–6): 692–728. doi:10.1016/j.mam.2007.03.001. PMC 2435257. PMID 17507086. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2435257. 
39. ^ Institute of Medicine. Food and Nutrition Board. (2000). Dietary Reference Intakes: Applications in Dietary Assessment. Washington, DC: National Academy Press. p. 289. OCLC 45618946. 
40. ^ Office of Dietary Supplements • National Institutes of Health: Health Professional Fact Sheet - Vitamin E, http://ods.od.nih.gov/factsheets/vitamine.asp
41. ^ USDA nutritional database, sweet potato, raw
42. ^ ^{a b c} Bell, EF (1987). "History of vitamin E in infant nutrition". American Journal of Clinical Nutrition 46 (1 Suppl): 183–186. PMID 3300257. 
43. ^ Gyorgy, P.; Rose (1948). "Effect of dietary factors on early mortality and hemoglobinuria in rats following administration of alloxan". Science 108 (2817): 716–718. doi:10.1126/science.108.2817.716. PMID 17752961. 

Further reading

• Brigelius-Flohe, Regina; Kelly, F; Salonen, J; Neuzil, J; Zingg, J; Azzi, A (2002). "The European perspective on vitamin E: current knowledge and future research". American Journal of Clinical Nutrition 76 (4): 703–16. PMID 12324281. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=12324281. 

External links

• Vitamin E Medline Plus, Medical Encyclopedia, U.S. National Library of Medicine
• Vitamin E Office of Dietary Supplements, National Institutes of Health
• Jane Higdon, "Vitamin E", Micronutrient Information Center, Linus Pauling Institute, Oregon State University