Vitamin E (Tocopherol)
Description
Vitamin E actually constitutes a family of substances called tocopherols, which is furthered divided in four sub groups: alpha-tocopherol, beta-tocopherol, gamma-tocopherol and delta-tocopherol.
Alpha-tocopherol is the most common and most active form of vitamin E. gamma-tocopherol is also widely found in North-American diets and complements the activities of alpha-tocopherols.
Vitamin E activity appears to be particularly efficient when associated to selenium as well as vitamin C.
Function
Vitamin E is a fat-soluble vitamin that functions as a potent antioxidant. It prevents peroxidation of lipids in various parts of the body, prevents the formation of free radicals, and protects cell membranes against damages.
Vitamin E supplements have been used in the prevention of retrolental fibroplasia (a form of retinal disease affecting premature infants treated with high concentrations of oxygen) and for the treatment of hemolytic anaemia in premature infants.
Vitamin E antioxidant properties are also being studied for use in:
- protection against several important degenerative disorders (including Alzheimer's disease, certain cancers and heart disease)
- protection against some of the effects of ageing
- positive effects on immunity
In conclusion, sound clinical evidence supports the value of vitamin E supplementation. The RDA for vitamin E in adults ranges from 15-19 mg/day, while the average dietary intake of vitamin E among adults is less than 10 mg per day. Reported therapeutic benefits of vitamin E intake generally require supplementation of 200-800 mg per day.
Deficiency
Reported with some malabsorption disorders (e.g., cystic fibrosis or other malabsorption conditions), it may cause ataxia (neurological dysfunction) and premature destruction of red blood cells.
Sources
Natural sources include vegetable oils (especially wheat germ), nuts, seafood and whole grain cereals.
Of note is that the RDA for vitamin E in adults is 15mg (or 20IU) per day, and that the average dietary intake of vitamin E among adults in the US is less than 10 mg per day. However, in order to benefit from the potential therapeutic effects of vitamin E, amounts of ranging from 200 and 800 IU have been suggested. Reported therapeutic benefits of vitamin E intake generally require supplementation of 200-800 mg per day.
Levels of intake using supplements may vary between 200 and 1,600 IU although amounts between 400 and 800 IU are most commonly found.
Toxicity
Vitamin E toxicity is uncommon when taken orally and no toxicity is reported with amounts below 800 IU per day. However, in people deficient in vitamin K or on anticoagulant therapy, high levels of vitamin E (> 1,000 mg per day) may increase bleeding time.
Because vitamin E may interact with some prescribed drugs (e.g., anticoagulants, heart medication, insulin and some others), consult your physician before taking high doses of vitamin E if you are taking prescribed medication.
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Scientific References
Books
PDR for Nutritional Supplements. Hendler SS, Rorvik DR, eds. Montvale: Medical Economics Company, Inc; 2001.
Vitamin E. Traber MG. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease. Philadelphia: Lippincott Williams & Wilkiins; 2006:396-411.
Vitamin E. Traber MG. In: Bowman BA, Russell RM, eds. Present Knowledge in Nutrition. 9th ed. Volume Washington, D.C.: ILSI Press; 2006:211-219.
Vitamin E. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Food and Nutrition Board, Institute of Medicine. Washington D.C.: National Academy Press; 2000:186-28 (National Academy Press)
Scientific articles
Utilization of vitamin E. Traber MG. Biofactors. 1999;10(2-3):115-12
[Abstract]
Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation. Bruno RS, Leonard SW, Atkinson J, et al. Free Radic Biol Med. 2006;40(4):689-69
[Abstract]
Does vitamin E decrease heart attack risk? summary and implications with respect to dietary recommendations. Traber MG. J Nutr. 2001;131(2):395S-397S.
[Abstract]
Vitamin E regulatory mechanisms. Traber MG. Annu Rev Nutr. 2007;27:347-36
[Abstract]
Synthetic as compared with natural vitamin E is preferentially excreted as alpha-CEHC in human urine: studies using deuterated alpha-tocopheryl acetates. Traber MG, Elsner A, Brigelius-Flohe R. FEBS Lett. 1998;437(1-2):145-14
[Abstract]
gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha-tocopherol: physiological implications. Christen S, Woodall AA, Shigenaga MK, Southwell-Keely PT, Duncan MW, Ames BN. Proc Natl Acad Sci U S A. 1997;94(7):3217-322
[Abstract]
gamma-tocopherol decreases ox-LDL-mediated activation of nuclear factor-kappaB and apoptosis in human coronary artery endothelial cells. Li D, Saldeen T, Mehta JL. Biochem Biophys Res Commun. 1999;259(1):157-16
[Abstract]
Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. Helzlsouer KJ, Huang HY, Alberg AJ, et al. J Natl Cancer Inst. 2000;92(24):2018-202
[Abstract]
gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention. Jiang Q, Christen S, Shigenaga MK, Ames BN. Am J Clin Nutr. 2001;74(6):714-72
[Abstract]
Serum alpha-tocopherol status in the United States population: findings from the Third National Health and Nutrition Examination Survey. Ford ES, Sowell A. Am J Epidemiol. 1999;150(3):290-30
[Abstract]
Current status of vitamin E nutriture. Ahuja JK, Goldman JD, Moshfegh AJ. Ann N Y Acad Sci. 2004;1031:387-39
[Abstract]
Intake of alpha-tocopherol is limited among US adults. Maras JE, Bermudez OI, Qiao N, Bakun PJ, Boody-Alter EL, Tucker KL. J Am Diet Assoc. 2004;104(4):567-57
[Abstract]
Antioxidant vitamin intake and coronary mortality in a longitudinal population study. Knekt P, Reunanen A, Jarvinen R, Seppanen R, Heliovaara M, Aromaa A. Am J Epidemiol. 1994;139(12):1180-118
[Abstract]
Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick RM. N Engl J Med. 1996;334(18):1156-116
[Abstract]
Vitamin E consumption and the risk of coronary heart disease in men. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. N Engl J Med. 1993;328(20):1450-145
[Abstract]
Vitamin E consumption and the risk of coronary disease in women. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. N Engl J Med. 1993;328(20):1444-144
[Abstract]
High vitamin E plasma levels and low low-density lipoprotein oxidation are associated with the absence of atherosclerosis in octogenarians. Cherubini A, Zuliani G, Costantini F, et al. J Am Geriatr Soc. 2001;49(5):651-65
[Abstract]
Antioxidant vitamin status and carotid atherosclerosis in the elderly. Gale CR, Ashurst HE, Powers HJ, Martyn CN. Am J Clin Nutr. 2001;74(3):402-40
[Abstract]
Antioxidant vitamins and the risk of carotid atherosclerosis. The Perth Carotid Ultrasound Disease Assessment study (CUDAS). McQuillan BM, Hung J, Beilby JP, Nidorf M, Thompson PL. J Am Coll Cardiol. 2001;38(7):1788-179
[Abstract]
Erythrocyte, but not plasma, vitamin E concentration is associated with carotid intima-media thickening in asymptomatic men at risk for cardiovascular disease. Simon E, Gariepy J, Cogny A, Moatti N, Simon A, Paul JL. Atherosclerosis. 2001;159(1):193-20
[Abstract]
Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. Lee IM, Cook NR, Gaziano JM, et al. JAMA. 2005;294(1):56-6
[Abstract]
Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study. Glynn RJ, Ridker PM, Goldhaber SZ, Zee RY, Buring JE. Circulation. 2007;116(13):1497-150
[Abstract]
Vitamin E revisited: do new data validate benefits for chronic disease prevention? Traber MG, Frei B, Beckman JS. Curr Opin Lipidol. 2008;19(1):30-3
[Abstract]
Evidence for the use of nutritional supplements and herbal medicines in common eye diseases. West AL, Oren GA, Moroi SE. Am J Ophthalmol. 2006;141(1):157-16
[Abstract]
A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. Arch Ophthalmol. 2001;119(10):1439-145
[Abstract]
The Antioxidants in Prevention of Cataracts Study: effects of antioxidant supplements on cataract progression in South India. Gritz DC, Srinivasan M, Smith SD, et al. Br J Ophthalmol. 2006;90(7):847-85
[Abstract]
Vitamin E supplementation and cataract: randomized controlled trial. McNeil JJ, Robman L, Tikellis G, Sinclair MI, McCarty CA, Taylor HR. Ophthalmology. 2004;111(1):75-8
[Abstract]
Incidence of cataract operations in Finnish male smokers unaffected by alpha tocopherol or beta carotene supplements. Teikari JM, Rautalahti M, Haukka J, et al. J Epidemiol Community Health. 1998;52(7):468-47
[Abstract]
Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. Meydani SN, Meydani M, Blumberg JB, et al. JAMA. 1997;277(17):1380-138
[Abstract]
Vitamin E and infectious diseases in the aged. Han SN, Meydani SN. Proc Nutr Soc. 1999;58(3):697-70
[Abstract]
Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. Meydani SN, Leka LS, Fine BC, et al. JAMA. 2004;292(7):828-83
[Abstract]
Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer. Slatore CG, Littman AJ, Au DH, Satia JA, White E. Am J Respir Crit Care Med. 2008;177(5):524-53
[Abstract]
The role of vitamin E in the prevention of cancer: a meta-analysis of randomized controlled trials. Alkhenizan A, Hafez K. Ann Saudi Med. 2007;27(6):409-41
[Abstract]
Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. Heinonen OP, Albanes D, Virtamo J, et al. J Natl Cancer Inst. 1998;90(6):440-44
[Abstract]
SELECT: the next prostate cancer prevention trial. Selenum and Vitamin E Cancer Prevention Trial. Klein EA, Thompson IM, Lippman SM, et al. J Urol. 2001;166(4):1311-131
[Abstract]
National Cancer Institute. Review of Prostate Cancer Prevention Study Shows No Benefit for Use of Selenium and Vitamin E Supplements. [Web page]
Effect of supplementary antioxidant vitamin intake on carotid arterial wall intima-media thickness in a controlled clinical trial of cholesterol lowering.
Azen SP, Qian D, Mack WJ, et al. Circulation. 1996;94(10):2369-237
[Abstract]
Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ. Lancet. 1996;347(9004):781-78
[Abstract]
Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Boaz M, Smetana S, Weinstein T, et al. Lancet. 2000;356(9237):1213-121
[Abstract]
Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Rapola JM, Virtamo J, Ripatti S, et al. Lancet. 1997;349(9067):1715-172
[Abstract]
Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P. N Engl J Med. 2000;342(3):154-16
[Abstract]
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(9177):447-45
[Abstract]
Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. Lonn E, Bosch J, Yusuf S, et al. JAMA. 2005;293(11):1338-134
[Abstract]
In vivo formation of 8-iso-prostaglandin f2alpha and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation. Davi G, Ciabattoni G, Consoli A, et al. Circulation. 1999;99(2):224-22
[Abstract]
Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients. Paolisso G, D'Amore A, Giugliano D, Ceriello A, Varricchio M, D'Onofrio F. Am J Clin Nutr. 1993;57(5):650-65
[Abstract]
Pharmacological doses of vitamin E and insulin action in elderly subjects. Paolisso G, Di Maro G, Galzerano D, et al. Am J Clin Nutr. 1994;59(6):1291-129
[Abstract]
Daily vitamin E supplements improve metabolic control but not insulin secretion in elderly type II diabetic patients. Paolisso G, D'Amore A, Galzerano D, et al. Diabetes Care. 1993;16(11):1433-143
[Abstract]
Effects of Vitamin E on susceptibility of low-density lipoprotein and low-density lipoprotein subfractions to oxidation and on protein glycation in NIDDM. Reaven PD, Herold DA, Barnett J, Edelman S. Diabetes Care. 1995;18(6):807-81
[Abstract]
Effect of modest vitamin E supplementation on blood glycated hemoglobin and triglyceride levels and red cell indices in type I diabetic patients. Jain SK, McVie R, Jaramillo JJ, Palmer M, Smith T. J Am Coll Nutr. 1996;15(5):458-46
[Abstract]
Antioxidants and cognitive function. Meydani M. Nutr Rev. 2001;59(8 Pt 2):S75-80; discussion S80-72.
Vitamin E in neurodegenerative disorders: Alzheimer's disease. Kontush K, Schekatolina S. Ann N Y Acad Sci. 2004;1031:249-26
[Abstract]
A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Sano M, Ernesto C, Thomas RG, et al. N Engl J Med. 1997;336(17):1216-122
[Abstract]
Vitamin E and donepezil for the treatment of mild cognitive impairment. Petersen RC, Thomas RG, Grundman M, et al. N Engl J Med. 2005;352(23):2379-238
[Abstract]
Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Masaki KH, Losonczy KG, Izmirlian G, et al. Neurology. 2000;54(6):1265-127
[Abstract]
RRR-alpha-tocopheryl succinate-induced apoptosis of human breast cancer cells involves Bax translocation to mitochondria. Yu W, Sanders BG, Kline K. Cancer Res. 2003;63(10):2483-249
[Abstract]
Role of extracellular signal-regulated kinase pathway in RRR-alpha-tocopheryl succinate-induced differentiation of human MDA-MB-435 breast cancer cells. You H, Yu W, Munoz-Medellin D, Brown PH, Sanders BG, Kline K. Mol Carcinog. 2002;33(4):228-23
[Abstract]
Induction of cancer cell apoptosis by alpha-tocopheryl succinate: molecular pathways and structural requirements. Neuzil J, Weber T, Schroder A, et al. FASEB J. 2001;15(2):403-41
[Abstract]
The European perspective on vitamin E: current knowledge and future research. Brigelius-Flohe R, Kelly FJ, Salonen JT, Neuzil J, Zingg JM, Azzi A. Am J Clin Nutr. 2002;76(4):703-71
[Abstract]
Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo. Weber T, Lu M, Andera L, et al. Clin Cancer Res. 2002;8(3):863-86
[Abstract]
Vitamin E inhibits melanoma growth in mice. Malafa MP, Fokum FD, Mowlavi A, Abusief M, King M. Surgery. 2002;131(1):85-9
[Abstract]
Vitamin E succinate promotes breast cancer tumor dormancy. Malafa MP, Neitzel LT. J Surg Res. 2000;93(1):163-17
[Abstract]
Vitamin E succinate decreases lung cancer tumor growth in mice. Quin J, Engle D, Litwiller A, et al. J Surg Res. 2005;127(2):139-14
[Abstract]
Biokinetics in humans of RRR-alpha-tocopherol: the free phenol, acetate ester, and succinate ester forms of vitamin E. Cheeseman KH, Holley AE, Kelly FJ, Wasil M, Hughes L, Burton G. Free Radic Biol Med. 1995;19(5):591-59
[Abstract]
A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Berson EL, Rosner B, Sandberg MA, et al. Arch Ophthalmol. 1993;111(6):761-77
[Abstract]
Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Ann Intern Med. 2005;142(1):37-4
[Abstract]
Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease. Shekelle PG, Morton SC, Jungvig LK, et al. J Gen Intern Med. 2004;19(4):380-38
[Abstract]
Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Eidelman RS, Hollar D, Hebert PR, Lamas GA, Hennekens CH. Arch Intern Med. 2004;164(14):1552-155
[Abstract]
Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Lancet. 2003;361(9374):2017-202
[Abstract]
Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. JAMA. 2007;297(8):842-85
[Abstract]
Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. Brown BG, Zhao XQ, Chait A, et al. N Engl J Med. 2001;345(22):1583-159
[Abstract]
The MRC/BHF Heart Protection Study: preliminary results. Collins R, Peto R, Armitage J. Int J Clin Pract. 2002;56(1):53-5
[Abstract]
Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Lippman SM, Klein EA, Goodman PJ, et al. JAMA. 2009;301(1):39-5
[Abstract]
