Scientific Name(s): Alpha-tocopherol
Common Name(s): Vitamin E
Routine use of high-dose vitamin E for cancer, cardiovascular disease, diabetes, and epilepsy is not recommended. Vitamin E supplementation may have a role in treating age-related macular degeneration, dysmenorrhea, preeclampsia, rheumatoid arthritis, and tardive dyskinesia. Topical use of vitamin E has been investigated for the reduction of scarring.
Doses in clinical trials range from 400 to 1,600 units/day. The established safe upper limit is 1,000 mg/day (1,500 units/day), but consequent to the findings from meta-analyses, a lower safe dosage of 150 to 200 units/day has been suggested.
Contraindications have not been identified.
Trials have been conducted in pregnant women (see Uses and Pharmacology). The majority of trials report no increase in negative fetal outcome, but results regarding birth-weight are conflicting. Considering the evidence of harm (all-cause mortality), high-dose vitamin E supplementation, should be used with caution. Natural food sources are preferred.
Orlistat may reduce vitamin E absorption. Vitamin E may increase the anticoagulant effect of warfarin and may decrease the benefits of atorvastatin therapy.
Meta-analyses of trials investigating high-dose vitamin E supplementation have found evidence of harm. Low-dose vitamin E supplementation (150 mg/day) does not appear to have any serious adverse reactions. High doses of vitamin E may prolong bleeding time.
Vitamin E is a known antioxidant. However, it may be a pro-oxidant, causing oxidation and consequent damage to cells. The use of high-dose vitamin E supplementation may increase the risk of cancer in certain populations and also increase mortality.
Vitamin E was discovered in 1922 when reproductive abnormalities in rats reared on a basic diet were cured by a substance isolated from vegetable oils. A pure fraction was chemically identified in 1938 and named tocopherol after the Greek words tokos and phero meaning “child birth” and “to bring forth.” 1
Vitamin E is a generic term for a group of tocol and tocotrienol derivatives. It is a fat-soluble vitamin that exists in a variety of forms in many foods (eg, asparagus, mangoes, nuts, olives, spinach, sunflower seeds, vegetable oils, wheat germ, whole-wheat breads). Its most common form in a Western diet is alpha-tocopherol. 2 The most important chemical characteristic is its antioxidant property.
Vitamin E is fairly stable to heat and acids, but unstable to alkalis, ultraviolet light, and oxygen. It is destroyed when in contact with rancid fats, lead, and iron. Esters of tocopherol are more stable, with tocopherol acetate accounting for the most common, naturally occurring form. 1
Uses and Pharmacology
Vitamin E has been extensively studied for several decades, with the large number of clinical trials making animal experiments largely redundant.
A number of meta-analyses and systematic reviews have found no positive effect of vitamin E on mortality in cardiovascular disease or cancer. 3 , 4 , 5 , 6 Furthermore, high-dose vitamin E supplementation has been associated with increased risk of morbidity and mortality. 3 , 4 , 6 , 7 A Cochrane meta-analysis of all randomized clinical trials evaluating the effect of antioxidant supplements on primary and secondary disease prevention found that antioxidants had no significant effect on all-cause mortality (relative risk [RR] 1.02; 95% confidence interval [CI] = 0.99 to 1.06). Supplementation with vitamin E alone in trials with a low risk of bias showed significantly increased mortality (RR 1.04; 95% CI = 1.01 to 1.07). 6Age-related macular degeneration and visual loss
Systematic reviews report the effects of vitamin E on the prevention and progression of age-related macular degeneration. 8 , 9 The majority of trials were conducted by the Age-Related Eye Disease Study Research Group. 10
The analyses conclude that vitamin E supplementation has a modest, borderline protective effect (odds ratio [OR] 0.83; 95% CI = 0.69 to 1.01), 9 and people with moderate to severe degeneration may experience a slight delay in progression of disease with antioxidant supplementation. 8 Harm from long-term use should be considered. 8
A similar, small study investigated the effect of 4 months of therapy with high-dose vitamin E (1,600 units/day) for uveitis-associated macular edema. Supplementation did not affect visual acuity or retinal thickening, and the study was terminated early. 11Cancer
Despite epidemiological studies suggesting favorable outcomes with vitamin E supplementation in reducing the risks and mortality of cancer, meta-analyses of clinical trials 12 , 13 , 14 , 15 , 16 , 17 , 18 found no beneficial effect and suggest evidence for harm. 3 , 4 , 5 , 6 , 7 , 19 , 20
A role in reducing the risk of prostate cancer is possible, with limited smaller trials showing a protective, but not statistically significant, effect. 21 , 22 The SELECT (Selenium and Vitamin E Cancer Prevention Trial) study was halted earlier than planned because of a lack of positive effect. 22 Among Finnish smokers, a high baseline alpha-tocopherol level was associated with a lower total mortality risk, 23 despite negative findings for pancreatic cancer from the same trial. 15 In the Women's Health Study, vitamin E 600 units on alternate days did not increase the risk of cancer or death from cancer, nor did it increase total mortality. 24
In vitro studies are directing attention to the role of vitamin E analogs, especially alpha-tocopheryl succinate, on inducing apoptosis of malignant cells, but clinical trials are lacking. 25 , 26 , 27 , 28 , 29 , 30 Complications from chemotherapy, such as mucositis 31 , 32 and paclitaxel-induced peripheral neuropathy, 33 may benefit from vitamin E supplementation, but data from quality trials are limited.Cardiovascular disease
Despite epidemiological studies in favor of vitamin E supplementation in reducing the risks of cardiovascular disease 4 , 34 , 35 , 36 and as a plausible mechanism for antioxidant action, 37 , 38 , 39 , 40 meta-analyses of landmark trials 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 found no evidence for effect and suggested evidence for harm. 3 , 4 , 5 , 6 , 34 , 35 , 50 The American Heart Association does not support the routine use of antioxidants in people with cardiovascular disease. 51
Trials evaluating subgroup populations subsequent to the Cochrane meta-analysis 6 have found varying effects. In men and women with hypercholesterolemia, no effect documented cardiovascular risk despite a variety of tocotrienol isomers tested. 52 In smokers 50 years of age or older, ultrasound showed no effect on atherosclerosis after 5 years of vitamin E supplementation. 35 In the Women's Antioxidant and Cardiovascular Study, no impact from supplementation on total mortality was observed in women at high risk for cardiovascular events, but a marginal effect was reported in women with a previous cardiovascular event. 53 A null effect was documented in another study for vitamin E supplementation, with increased mortality in certain disease groups and a reduced risk in others. 54CNS effects/Alzheimer disease/Mild cognitive impairment
Animal experiments and epidemiological studies suggest a correlation between low-serum vitamin E levels and memory performance in elderly patients. 55 However, clinical trials demonstrate equivocal results. A trial evaluating vitamin E supplementation (2,000 units/day) showed no difference in conversion from mild cognitive impairment to Alzheimer disease over 2 years compared with donepezil or placebo 56 , 57 ; other trials found a prolonged time to end point for vitamin E but no improvement in cognitive tests. 55 , 58 A Cochrane review reported few trials meeting the inclusion criteria. In 1 trial, fewer patients on vitamin E supplementation reached end point (death, institutionalization, or loss of 2 out of 3 basic activities) within 2 years but experienced more falls. Overall, the review revealed no statistically significant difference compared with placebo, in the probability of progression from mild impairment to Alzheimer disease. 59 If vitamin E supplementation is considered beneficial (versus the potential for harm), then low-dose supplementation is recommended. 60Amyotrophic lateral sclerosis/Motor neuron disease
Conflicting evidence exists. Epidemiological data suggest vitamin E supplementation taken for longer than 10 years is associated with a 50% decreased risk of death from amyotrophic lateral sclerosis than in those individuals not taking supplementation. 55 However, a review of available data found poor methodology and insufficient evidence for antioxidants in general for motor neuron disease. 61Epilepsy
A Cochrane review of trials from 1966 through 2006 discuss poor trial methodology and did not find sufficient evidence to support routine use of vitamin E in the management of epilepsy. 62Parkinson disease
Animal studies have produced conflicting results. In humans receiving alpha-tocopherol 2,000 units/day, no benefit was demonstrated in 1 trial, whereas high-dose vitamin E (3,200 units/day) with vitamin C (3 g/day) delayed the progression of Parkinson disease by 2.5 years. 55Tardive dyskinesia
A meta-analysis of neuroleptic-induced tardive dyskinesia, including 10 studies from 1966 through 2001, showed that vitamin E protected against deterioration but did not improve the symptoms of tardive dyskinesia. 63 A trial evaluating vitamin E 1,200 units/day versus placebo over 12 weeks reported a mean improvement in Abnormal Involuntary Movements Scale (AIMS) scores. 64 In combination with vitamin C 200 mg/day, vitamin E 1,800 mg/day reduced tardive symptoms in a small trial (N = 8). Theoretically, the combination reduces vitamin E radicals formed when vitamin E scavenges oxygen radicals. 65Diabetes mellitus
The role of vitamin E in diabetes was not determined in any of the major meta-analyses 3 , 5 , 6 ; however, the risk of harm raised in these analyses should not be overlooked. A number of clinical trials found no effect of vitamin E on outcomes, 66 , 67 , 68 , 69 , 70 while others showed unexpected increases in blood pressure. 71 , 72 Some small trials have reported improvements in surrogate outcomes. 47 , 48 , 70 The American Diabetes Association does not consider the evidence to be sufficient to support routine use of antioxidants in people with diabetes. 73Dysmenorrhea
A few trials demonstrated a reduction in menstrual pain, with maximum effect after 3 months of vitamin E at dosages up to 200 units for 5 days, when starting 2 days prior to menses. 74 , 75 A meta-analysis confirms evidence for effect. Harm or adverse reactions, however, were not reported. 76 , 77Pregnancy and preeclampsia
As a consequence of earlier trials and a meta-analysis revealing a reduction in the risk of preeclampsia, 78 , 79 , 80 several large multicenter and international trials have been or are being conducted to investigate the effect of antioxidant supplementation on the rate of preeclampsia. 81 , 82 Of the available data, vitamin E 400 units in combination with vitamin C 1,000 mg does not affect the risk of preeclampsia versus placebo. 83 , 84 , 85 , 86 A meta-analysis of trials from 2006 found no effect of antioxidant supplementation on the rate of preeclampsia versus placebo. 87
Varying results on fetal outcomes have been obtained from these trials, with most showing no effect. 83 , 84 , 85 , 86 A study investigating the effect of maternal concentrations of alpha-tocopherol on fetal growth suggested a positive relationship, with a decreased risk for small-for-gestational-age births. 88 A negative association was suggested for wheeze (in the absence of a cold) in the second year of life in children of mothers who took vitamin E supplements during pregnancy. 89 A follow-up at 5 years exposed an association between childhood asthma and low maternal vitamin E intake. 90 Similarly, a negative association for childhood eczema and maternal vitamin E intake was found. 89Preterm infants
The use of vitamin E for the prevention of morbidity and mortality in preterm infants has been investigated. A meta-analysis concluded that routine use of vitamin E supplementation via the intravenous route is not supported by evidence because of the increased risk for harm. 2 , 91 A small study evaluated the effects of vitamin E supplementation (50 units/day) on erythropoiesis in premature infants. No effect was reported at that dosage, and no increased harm was detected. 92Rheumatoid arthritis
Clinical trials present conflicting results. 49 , 93 , 94 Overall, vitamin E supplementation exhibits a low level of evidence for effectiveness in rheumatoid arthritis. The value of vitamin E may only be evident in patients with increased oxidative stress or at dosages higher than the 400 units/day. 95Other
Vitamin E has been evaluated for use in immuno-deficient states and for topical use in reducing scarring. 96
Deficiencies in vitamin E are uncommon, and dietary sources are preferred over supplementation. 97
The established safe upper limit is 1,000 mg/day (1,500 units/day), 97 but consequent to the findings from meta-analyses, a lower safe dosage of 150 to 200 units/day has been suggested. 3 , 6 The American Heart Association's guidelines for prevention of heart disease and stroke in women advise against antioxidant use, and the Alzheimer's Association recommends use only under the care of a health care provider. 97
Trials have been conducted in pregnant women (see Uses and Pharmacology). The majority of trials report no increase in negative fetal outcome, but results regarding birth-weight are conflicting. 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90
Vitamin E at 400 units/day impaired the positive endothelial effects of low-dose atorvastatin in a trial of patients with heart failure. 98Orlistat
Orlistat administration may reduce the biologic and therapeutic effect of vitamin E by decreasing GI absorption of the vitamin. In 12 healthy subjects receiving Orlistat (120 mg 3 times daily for 4 days), administration of vitamin E (400 units alpha-tocopheryl acetate) on the fourth day of Orlistat treatment decreased the area under the curve and peak plasma level of vitamin E 60% and 43%, respectively, compared with placebo. 99 , 100Warfarin
Vitamin E may interfere with vitamin K-dependent clotting factors, adding to the anticoagulant effects of warfarin. A markedly prolonged prothrombin time and bleeding occurred in a 55-year-old man stabilized on warfarin for 2 months after he started taking vitamin E supplementation (1,200 units/day or less). Taking more than vitamin E 400 units/day may cause additive hypo-prothrombinemic effects to occur. 101 , 102
High levels of vitamin E can adversely affect the absorption of vitamins A and K. Long-term use of high doses may cause nausea, diarrhea, blurred vision, and prolonged bleeding time. 103
Vitamin E is a known antioxidant. However, it may be a pro-oxidant, causing oxidation and consequent damage to cells. 7 The use of high-dose vitamin E supplementation may increase the risk of cancer in certain populations 7 and also increase mortality. 6
Bibliography1. Mahan LK, Arlin MT. Krause's Food, Nutrition, & Diet Therapy . 8th ed. Philadelphia, PA: WB Saunders Co; 1992.
2. Kaegi E. Unconventional therapies for cancer: 5. Vitamins A, C and E. The Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. CMAJ . 1998;158(11):1483-1488.
3. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med . 2005;142(1):37-46.
4. Brown BG, Crowley J. Is there any hope for vitamin E? JAMA . 2005;293(11):1387-1390.
5. Huang HY, Caballero B, Chang S, et al. The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health state-of-the-science conference. Ann Intern Med . 2006;145(5):372-385.
6. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev . 2008;(2):CD007176.
7. Slatore CG, Littman AJ, Au DH, Satia JA, White E. Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer. Am J Respir Crit Care Med . 2008;177(5):524-530.
8. Evans JR. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev . 2006;(2):CD000254.
9. Chong EW, Wong TY, Kreis AJ, Simpson JA, Guymer RH. Dietary antioxidants and primary prevention of age related macular degeneration: systematic review and meta-analysis. BMJ . 2007;335(7623):755.
10. Age-Related Eye Disease Study Research Group. 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. 9. Arch Ophthalmol . 2001;119(10):1439-1452.
11. Nussenblatt RB, Kim J, Thompson DJ, et al. Vitamin E in the treatment of uveitis-associated macular edema. Am J Ophthalmol . 2006;141(1):193-194.
12. Blanke CD, Stipanov M, Morrow J, et al. A phase I study of vitamin E, 5-fluorouracil and leucovorin for advanced malignancies. Invest New Drugs . 2001;19(1):21-27.
13. Cascinu S, Ligi M, Del Ferro E, et al. Effects of calcium and vitamin supplementation on colon cell proliferation in colorectal cancer. Cancer Invest . 2000;18(5):411-416.
14. Albanes D, Malila N, Taylor PR, et al. Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland). Cancer Causes Control . 2000;11(3):197-205.
15. Rautalahti MT, Virtamo JR, Taylor PR, et al. The effects of supplementation with alpha-tocopherol and beta-carotene on the incidence and mortality of carcinoma of the pancreas in a randomized, controlled trial. Cancer . 1999;86(1):37-42.
16. Virtamo J, Edwards BK, Virtanen M, et al. Effects of supplemental alpha-tocopherol and beta-carotene on urinary tract cancer: incidence and mortality in a controlled trial (Finland). Cancer Causes Control . 2000;11(10):933-939.
17. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group. New Engl J Med . 1994;330(15):1029-1035.
18. Mooney LA, Madsen AM, Tang D, et al. Antioxidant vitamin supplementation reduces benzo(a)pyrene-DNA adducts and potential cancer risk in female smokers. Cancer Epidemiol Biomarkers Prev . 2005;14(1):237-242.
19. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev . 2004;(4):CD004183.
20. Senior K. More negative results for vitamin E. Lancet Oncol . 2005;6(5):261.
21. Coulter ID, Hardy ML, Morton SC, et al. Antioxidants vitamin C and vitamin E for the prevention and treatment of cancer. J Gen Intern Med . 2006;21(7):735-744.
22. http://www.crab.org/select/ . Accessed December 2, 2008.
23. Wright ME, Lawson KA, Weinstein SJ, et al. Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Clin Nutr . 2006;84(5):1200-1207.
24. Buring JE. Aspirin prevents stroke but not MI in women; vitamin E has no effect on CV disease or cancer. Cleve Clin J Med . 2006;73(9):863-870.
25. Neuzil J, Tomasetti M, Mellick AS, et al. Vitamin E analogues: a new class of inducers of apoptosis with selective anti-cancer effects. Curr Cancer Drug Targets . 2004;4(4):355-372.
26. Tomasetti M, Andera L, Alleva R, Borghi B, Neuzil J, Procopio A. Alpha-tocopheryl succinate induces DR4 and DR5 expression by a p53-dependent route: implication for sensitisation of resistant cancer cells to TRAIL apoptosis. FEBS Lett . 2006;580(8):1925-1931.
27. Sylvester PW. Vitamin E and apoptosis. Vitam Horm . 2007;76:329-356.
28. Wang XF, Dong L, Zhao Y, Tomasetti M, Wu K, Neuzil J. Vitamin E analogues as anticancer agents: lessons from studies with alpha-tocopheryl succinate. Mol Nutr Food Res . 2006;50(8):675-685.
29. Kline K, Lawson KA, Yu W, Sanders BG. Vitamin E and cancer. Vitam Horm . 2007;76:435-461.
30. Hampton T. Vitamin E derivative packs anticancer punch. JAMA . 2006;296(1):32.
31. Worthington HV, Clarkson JE, Eden OB. Interventions for preventing oral candidiasis for patients with cancer receiving treatment. Cochrane Database Syst Rev . 2002;(3):CD003807.
32. Wadleigh RG, Redman RS, Graham ML, Krasnow SH, Anderson A, Cohen MH. Vitamin E in the treatment of chemotherapy-induced mucositis. Am J Med . 1992;92(5):481-484.
33. Argyriou AA, Chroni E, Koutras A, et al. Preventing paclitaxel-induced peripheral neuropathy: a phase II trial of vitamin E supplementation. J Pain Symptom Manage . 2006;32(3):237-244.
34. Eidelman RS, Hollar D, Hebert PR, Lamas GA, Hennekens CH. Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med . 2004;164(14):1552-1556.
35. Magliano D, McNeil J, Branley P, et al. The Melbourne Atherosclerosis Vitamin E Trial (MAVET): a study of high dose vitamin E in smokers. Eur J Cardiovasc Prev Rehabil. 2006;13(3):341-347.
36. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet . 2002;360(9326):23-33.
37. Thomson MJ. Puntmann V. Kaski JC. Atherosclerosis and oxidant stress: the end of the road for antioxidant vitamin treatment? Cardiovasc Drugs Ther . 2007;21(3):195-210.
38. Siekmeier R, Steffen C, März W. Role of oxidants and antioxidants in atherosclerosis: results of in vitro and in vivo investigations. J Cardiovasc Pharmacol Ther . 2007;12(4):265-282.
39. Tribble DL. AHA Science Advisory. Antioxidant consumption and risk of coronary heart disease: emphasison vitamin C, vitamin E, and beta-carotene: A statement for healthcare professionals from the American Heart Association. Circulation . 1999;99(4):591-595.
40. Simons LA, Von Konigsmark M, Balasubramaniam S. What dose of vitamin E is required to reduce susceptibility of LDL to oxidation? Aust N Z J Med . 1996;26(4):496-503.
41. No authors listed. 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):447-455.
42. 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(3):154-160.
43. Dagenais GR, Yusuf S, Bourassa MG, et al. HOPE Investigators. Effects of ramipril on coronary events in high-risk persons: results of the Heart Outcomes Prevention Evaluation Study. Circulation . 2001;104(5):522-526.
44. de Gaetano G. Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project. Lancet . 2001;357(9250):89-95.
45. Rapola JM, Virtamo J, Ripatti S, et al. Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet . 1997;349(9067):1715-1720.
46. Rapola JM, Virtamo J, Ripatti S, et al. Effects of alpha tocopherol and beta carotene supplements on symptoms, progression, and prognosis of angina pectoris. Heart . 1998;79(5):454-458.
47. Riemersma RA, Wood DA, Macintyre CC, Elton RA, Gey KF, Oliver MF. Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene. Lancet . 1991;337(8732):1-5.
48. Boaz M, Smetana S, Weinstein T, et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet . 2000;356(9237):1213-1218.
49. Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet . 1996;347(9004):781-786
50. Antioxidant vitamins did not reduce death, vascular events, or cancer in high-risk patients. ACP J Club . 2003;138(1):3.
51. Kris-Etherton PM, Lichtenstein AH, Howard BV, Steinberg D, Witztum JL; Nutrition Committee of the American Heart Association Council on Nutrition, Physical Activity, and Metabolism. Antioxidant vitamin supplements and cardiovascular disease. Circulation . 2004;110(5):637-641.
52. Mustad VA, Smith CA, Ruey PP, Edens NK, DeMichele SJ. Supplementation with 3 compositionally different tocotrienol supplements does not improve cardiovascular disease risk factors in men and women with hypercholesterolemia. Am J Clin Nutr . 2002;76(6):1237-1243.
53. Cook NR, Albert CM, Gaziano JM, et al. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study. Arch Intern Med . 2007;167(15):1610-1618.
54. Hayden KM on behalf of Cache County Investigators. Risk of mortality with vitamin E supplements: the Cache County study. Am J Med . 2007;120(2):180-184.
55. Ricciarelli R, Argellati F, Pronzato MA, Domenicotti C. Vitamin E and neurodegenerative diseases. Mol Aspects Med . 2007;28(5-6):591-606.
56. Fleisher AS, Sowell BB, Taylor C, Gamst AC, Petersen RC, Thal LJ; Alzheimer's Disease Cooperative Study. Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology . 2007;68(19):1588-1595.
57. Small BJ, Gagnon E, Robinson B. Early identification of cognitive deficits: preclinical Alzheimer's disease and mild cognitive impairment. Geriatrics . 2007;62(4):19-23.
58. Ames D, Ritchie C. Antioxidants and Alzheimer's disease: time to stop feeding vitamin E to dementia patients? Int Psychogeriatr . 2007;19(1):1-8.
59. Isaac M, Quinn R, Tabet N. Vitamin E for Alzheimer's disease and mild cognitive impairment. Cochrane Database of Syst Rev : Reviews 2000 Issue 4 John Wiley & Sons, Ltd Chichester, UK DOI: 10.1002/14651858. CD002854
60. Ancelin ML, Christen Y, Ritchie K. Is antioxidant therapy a viable alternative for mild cognitive impairment? Examination of the evidence. Dement Geriatr Cogn Disord . 2007;24(1):1-19.
61. Orrell RW, Lane RJ, Ross M. Antioxidant treatment for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev . 2007;(1):CD002829.
62. Ranganathan LN, Ramaratnam S. Vitamins for epilepsy. Cochrane Database Syst Rev . 2005;(2):CD004304.
63. Soares KVS, McGrath JJ. Vitamin E for neuroleptic-induced tardive dyskinesia. Cochrane Database of Syst Rev : Reviews 2001 Issue 4 John Wiley & Sons, Ltd Chichester, UK DOI: 10.1002/14651858.CD000209
64. Zhang XY, Zhou DF, Cao LY, Xu CQ, Chen DC, Wu GY. The effect of vitamin E treatment on tardive dyskinesia and blood superoxide dismutase: a double-blind placebo-controlled trial. J Clin Psychopharmacol . 2004;24(1):83-86.
65. Michael N, Sourgens H, Arolt V, Erfurth A. Severe tardive dyskinesia in affective disorders: treatment with vitamin E and C. Neuropsychobiology . 2002;46 (suppl 1):28-30.
66. Liu S, Lee IM, Song Y, et al. Vitamin E and risk of type 2 diabetes in the women's health study randomized controlled trial. Diabetes . 2006;55(10):2856-2862.
67. McQueen MJ, Lonn E, Gerstein HC, Bosch J, Yusuf S. The HOPE (Heart Outcomes Prevention Evaluation) Study and its consequences. Scand J Clin Lab Invest Suppl . 2005;240:143-156.
68. Giannini C, Lombardo F, Curro F, et al. Effects of high-dose vitamin E supplementation on oxidative stress and microalbuminuria in young adult patients with childhood onset type 1 diabetes mellitus. Diabetes Metab Res Rev . 2007;23(7):539-546.
69. Engelen W, Manuel-y-Keenoy B, Vertommen J, De Leeuw I, Van Gaal L. Effects of micronized fenofibrate and vitamin E on in vitro oxidation of lipoproteins in patients with type 1 diabetes melitis. Diabetes Metab . 2005;31(2):197-204.
70. Fardoun RZ. The use of vitamin E in type 2 diabetes melitis. Clin Exp Hypertens . 2007;29(3):135-148.
71. Ward NC, Wu JH, Clarke MW, et al. The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. J Hypertens . 2007;25(1):227-234.
72. Economides PA, Khaodhiar L, Caselli A, et al. The effect of vitamin E on endothelial function of micro- and macrocirculation and left ventricular function in type 1 and type 2 diabetic patients. Diabetes . 2005;54(1):204-211.
73. American Diabetes Association, Bantle JP, Wylie-Rosett J, Albright AL, et al. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care . 2008;31(suppl 1):S61-78.
74. Rasgon NL, Yargin KN. Vitamin E for the treatment of dysmenorrhea. BJOG . 2005;112(8):1164.
75. Ziaei S, Faghihzadeh S, Sohrabvand F, Lamyian M, Emamgholy T. A randomised placebo-controlled trial to determine the effect of vitamin E in treatment of primary dysmenorrhoea. BJOG . 2001;108(11):1181-1183.
76. Vitamin E for dysmenorrhoea. Bandolier . http://www.jr2.ox.ac.uk/bandolier/band136/b136-6.html . Accessed June 2008.
77. Proctor ML, Murphy PA. Herbal and dietary therapies for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev . 2001;(3):CD002124.
78. Rumbold A, Duley L, Crowther C, Haslam R. Antioxidants for preventing pre-eclampsia. Cochrane Database Syst Rev . 2005;(4):CD004227.
79. Fraser WD, et al.The vitamin E debate: implications for ongoing trials of pre-eclampsia prevention. BJOG . 2005;112(6):684-688.
80. Romero R, Garite TJ. Unexpected results of an important trial of vitamins C and E administration to prevent preeclampsia. Am J Obstet Gynecol . 2006;194(5):1213-1214.
81. Banerjee S, Chambers AE, Campbell S. Is vitamin E a safe prophylaxis for preeclampsia? Am J Obstet Gynecol . 2006;194(5):1228-1233.
82. Jeyabalan A, Caritis SN. Antioxidants and the prevention of preeclampsia—unresolved issues. N Engl J Med . 2006;354(17):1841-1843.
83. Spinnato JA 2nd, Freire S, Pinto E Silva JL, et al. Antioxidant therapy to prevent preeclampsia: a randomized controlled trial. Obstet Gynecol . 2007;110(6):1311-1318.
84. Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robinson JS; ACTS Study Group. Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med . 2006;354(17):1796-1806.
85. Poston L, Briley AL, Seed PT, Kelly FJ, Shennan AH; Vitamins in Pre-eclampsia (VIP) Trial Consortium. Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Lancet . 2006;367(9517):1145-1154.
86. Beazley D, Ahokas R, Livingston J, Griggs M, Sibai BM. Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial. Am J Obstet Gynecol . 2005;192(2):520-521.
87. Polyzos NP, Mauri D, Tsappi M, et al. Combined vitamin C and E supplementation during pregnancy for preeclampsia prevention: a systematic review. Obstet Gynecol Surv . 2007;62(3):202-206.
88. Scholl TO, Chen X, Sims M, Stein TP. Vitamin E: maternal concentrations are associated with fetal growth. Am J Clin Nutr . 2006;84(6):1442-1448.
89. Martindale S, McNeill G, Devereux G, Campbell D, Russell G, Seaton A. Antioxidant intake in pregnancy in relation to wheeze and eczema in the first two years of life. Am J Respir Crit Care Med . 2005;171(2):121-128.
90. Devereux G, Turner SW, Craig LC, et al. Low maternal vitamin E intake during pregnancy is associated with asthma in 5-year-old children. Am J Respir Crit Care Med . 2006;174(5):499-507.
91. Brion LP, Bell EF, Raghuveer TS. Vitamin E supplementation for prevention of morbidity and mortality in preterm infants. Cochrane Database Syst Rev . 2003;(4):CD003665.
92. Pathak A, Roth P, Piscitelli J, Johnson L. Effects of vitamin E supplementation during erythropoietin treatment of the anaemia of prematurity. Arch Dis Child Fetal Neonatal Ed . 2003;88(4):F324-F328.
93. Brand C, Snaddon J, Bailey M, Cicuttini F. Vitamin E is ineffective for symptomatic relief of knee osteoarthritis: a six month double blind, randomised, placebo controlled study. Ann Rheum Dis . 2001;60(10):946-949.
94. Wang Y, Prentice LF, Vitetta L, Wluka AE, Cicuttini FM. The effect of nutritional supplements on osteoarthritis. Altern Med Rev . 2004;9(3):275-296.
95. Chrubasik S. Vitamin E for rheumatoid arthritis or osteoarthritis: low evidence of effectiveness. Z Rheumatol . 2003;62(5):491.
96. Young GL, Jewell D. Creams for preventing stretch marks in pregnancy. Cochrane Database Syst Rev . 2000;(2):CD000066.
97. Easy does it with vitamin E. Swallowing an amber-colored vitamin E capsule has long been a daily ritual for millions of American women. It may be time to stop. Harv Womens Health Watch . 2005;12(7):1-3.
98. Tousoulis D, Antoniades C, Stefanadis C. Statins and antioxidant vitamins: should co-administration be avoided? J Am Coll Cardiol . 2006;47(6):1237-1238.
99. Melia AT, Koss-Twardy SG, Zhi J. The effect of orlistat, an inhibitor of dietary fat absorption, on the absorption of vitamins A and E in healthy volunteers. J Clin Pharmacol . 1996;36(7):647-653.
100. Corrigan JJ Jr, Marcus FI. Coagulopathy associated with vitamin E ingestion. JAMA . 1974;230(9):1300-1301.
101. Schrogie JJ. Letter: Coagulopathy and fat-soluble vitamins. JAMA . 1975;232(1):19.
102. Corrigan JJ Jr, Ulfers LL. Effect of vitamin E on prothrombin levels in warfarin-induced vitamin K deficiency. Am J Clin Nutr . 1981;34(9):1701-1705.
103. Hathcock JN. Vitamin and Minerals Safety . 2nd ed. Council for Responsible Nutrition (CRN). 2004.
Copyright © 2009 Wolters Kluwer Health
More about vitamin e
- Side Effects
- During Pregnancy
- Dosage Information
- Drug Interactions
- Support Group
- 5 Reviews – Add your own review/rating
- Drug class: vitamins
Other brands: Aquasol E