Vitamin E

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Vitamin E

Common Names

  • Tocopherol
  • Alpha-tocopherol
  • dl-tocopherol
  • Tocotrienol
  • RRR-alpha-tocopherol

For Patients & Caregivers

How It Works

A diet containing adequate amounts of vitamin E is important in maintaining general health, and may prevent against some forms of cancer. The ability of vitamin E to prevent or treat Alzheimer’s disease or heart disease requires further study.

Vitamin E, also known as alpha-tocopherol, is a natural antioxidant that is found in foods such as plant oils, eggs, nuts, green leafy vegetables, and whole grains. Its major function is to neutralize free radicals, meaning that it protects cells from their damaging effects. Therefore, vitamin E is being investigated in conditions such as Alzheimer’s disease and cancer, in which free radical damage is known to play a part.

Clinical trials show that vitamin E supplementation does not help prevent cardiovascular disease, and it may increase risk for a certain kind of stroke. Data on whether it can reduce cancer risk are also mixed, and under some circumstances taking vitamin E supplements may actually increase risk. For chronic disease prevention including conditions such as heart disease and cancer, a meta-analysis concludes that nutrients like vitamin E are best obtained from the diet.

Purported Uses
  • To prevent progression of Alzheimer’s disease One clinical trial showed that vitamin E reduced progression of Alzheimer’s disease. A few population-based studies suggest that high dietary intake of vitamin E may lower risk of developing Alzheimer’s disease.
  • To prevent cancer Data on whether Vitamin E supplementation can reduce cancer risk are mixed. Large population-based studies suggest it may reduce risk of prostate and colorectal cancers in male smokers. However, initial data from the SELECT Trial shows vitamin E taken alone or with selenium for 5 years did not reduce prostate cancer risk, and even increased risk after 7-year follow-up. Vitamin E also had no effect on lung, urinary tract, pancreas, mouth or stomach cancer risks. Another trial in patients with head and neck cancers found that patients who received vitamin E had a higher rate of second primary cancers compared with placebo, and that vitamin E may interfere with radiation therapy.
  • To manage cardiovascular disease Data from clinical trials show that vitamin E supplementation does not help prevent heart disease, and it may increase risk for a certain kind of stroke. For chronic disease prevention, a meta-analysis concludes that nutrients like Vitamin E are best obtained from the diet.
Patient Warnings
  • An analysis of commercially available vitamin E supplements found the actual content to vary considerably from the labeled dosage, from 41% less to 57% more than the labeled amounts.
  • This product is regulated by the FDA as a dietary supplement and is not required to be manufactured under specific standardized conditions. Therefore, it may not have been tested for safety or effectiveness, may not contain the labeled amount, or may be contaminated.
Do Not Take If
  • You are taking warfarin or other blood thinners: Doses of vitamin E greater than 400 IU per day may increase the risk of bleeding. PT and INR should be monitored if vitamin E is started or discontinued.
Side Effects
  • Symptoms of vitamin E toxicity from long-term consumption include fatigue, dizziness, weakness, rash, and vein inflammation due to a blood clot.
  • Vitamin E supplementation may increase stroke risk.
Special Point
  • Vitamin E supplements derived from plant oils contain d-alpha-tocopherol, which is believed to be the active form, while synthetic vitamin E supplements are a mixture of d-alpha-tocopherol and l-alpha-tocopherol (inactive forms).
  • It is controversial whether antioxidants like vitamin E can lessen or negate the effects of chemotherapy and radiation therapy. Because these therapies work by creating free radicals that kill cancer cells, some physicians have suggested that high levels of antioxidants can neutralize these free radicals and thereby protect cancer cells from these therapies. So what protects healthy cells may protect cancer cells as well. This question is still not fully understood and patients who are interested in taking more than the RDA of any antioxidant should consult with their doctor.
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For Healthcare Professionals

Scientific Name
d-alpha-tocopherol
Clinical Summary

Vitamin E is a fat-soluble vitamin derived from plants. Natural food sources include plant oils, wheat germ, eggs, green leafy vegetables, and whole grains (3). Vitamin E acts as an antioxidant and is thought to help prevent and treat many diseases. Although it is available in a variety of formulations, only the d-isomer is considered active (1).

Studies suggest Vitamin E may slow the progression of Alzheimer’s disease (9) (15) (16) (18). However, long-term supplementation did not reduce incidence of dementia (23) or slow cognitive deterioration (24), and another study does not support the utility of antioxidants (vitamin E, vitamin C, lipoid acid, and Coenzyme Q) for Alzheimer’s disease (43). It was also ineffective in arresting the development or progression of macular degeneration (14) and early Parkinson’s Disease (21).

Vitamin E did not decrease the incidence of acute respiratory tract infections (12), reduce mortality, or reduce the risk of cardiovascular death or cerebrovascular accident (26). When taken along with vitamin C, vitamin E may increase mortality and nonfatal myocardial infarction in patients with coronary artery disease (13). Further, findings from the recent Physicians’ Health Study II show that neither vitamin E nor C is beneficial in preventing cardiovascular events, and vitamin E may actually increase stroke risk (36). The Women’s Health Study also failed to find any benefit of vitamin E supplementation in lowering the risk of heart failure in healthy women (42). A meta-analysis showed that vitamin E increases the risk for hemorrhagic stroke but reduces the risk of ischemic stroke (38). Vitamin E may reduce symptoms of nonalcoholic steatohepatitis in adults (45), but not in children and adolescents (46).

Limited studies on Vitamin E to improve symptoms in cancer patients suggest it may help relieve hot flashes in breast cancer survivors (27) and reduce incidence of cisplatin-induced neurotoxicity (22) (25).

Data on whether Vitamin E supplementation can reduce cancer risk are mixed (19) (20) (37) (44) (49), and some studies even suggest it may increase cancer risk (28) (33) (48). In prostate cancer, data from the SELECT trial showed that vitamin E alone or with selenium for 5 years did not reduce prostate cancer risk (35), and significantly increased risk at 7 years’ follow-up (41). Vitamin E taken with soy and selenium also did not prevent prostate cancer progression (40).

Some studies suggest an association between dietary tocopherol and reduced risks for lung (38) (48) and liver (44) cancers. In addition, a meta-analysis supports dietary intake of various nutrients including alpha-tocopherol, but not antioxidant supplement use, for chronic disease prevention (50).

Toxicity may occur with chronic supplementation of vitamin E in doses greater than 800 IU. Daily supplementation over 400 IU may increase all-cause mortality (29). Vitamin E may also enhance the activity of warfarin. In a large study of patients treated with warfarin, higher serum vitamin E levels predicted hemorrhagic events (4).

Food Sources

Plant-derived oils (wheat germ, soybean, sunflower, almond, safflower, corn), wheat germ, liver, eggs, nuts and seeds, green leafy vegetables, whole grains (1) (2)

Purported Uses
  • Alzheimer’s disease
  • Cancer
  • Cardiovascular disease
Mechanism of Action

Vitamin E is a fat-soluble vitamin that acts as an antioxidant. The natural form of vitamin E is composed of 4 different tocopherols and 4 different tocotrienol homologues (alpha, beta, delta, and gamma). All 8 forms have antioxidant activity, but recent data indicate the different homologues have different activities unrelated to antioxidant effects (34).

Gamma-tocopherol is a stronger inhibitor of cyclooxygenase and traps reactive oxygen species more effectively than alpha-tocopherol. In vitro and in vivo, gamma-tocopherol exhibits antiproliferative and proapoptotic effects whereas alpha-tocopherol does not (34). While both alpha- and gamma-tocopherols exhibit anti-inflammatory effects in vitro and in vivo, gamma-enriched mixed tocopherols may have more activity than alpha-tocopherols. This may help explain the negative outcomes of recent large-scale intervention studies that used only the alpha homologue (34).

The d-alpha-tocopherol isomer is believed to be the active principle. Natural vitamin E supplements contain d-alpha-tocopherol derived from plant oil sources, whereas synthetic supplements are composed of a racemic mixture of d- and l-alpha-tocopherols. The major function of d-alpha-tocopherol is to prevent the propagation of free radical reactions by acting as a peroxyl radical scavenger and protecting polyunsaturated fatty acids (PUFAs) in membrane phospholipids and plasma lipoproteins. Alpha-tocopherol reportedly causes inhibition of protein kinase C activity, which is involved in cell proliferation and differentiation in smooth muscle cells, human platelets, and monocytes. Vitamin E enrichment of endothelial cells downregulates expression of intercellular and vascular cell adhesion molecules to decrease adhesion of blood cell components to the endothelium. Vitamin E also upregulates expression of cytosolic phospholipase A2 and cyclooxegenase-1, which leads to release of prostacyclin, a vasodilator and inhibitor of platelet aggregation in humans (3).

In an animal study, vitamin E increased lung cancer cell proliferation due to its antioxidant activity by reducing reactive oxygen species, DNA damage, and p53 expression (47).

Warnings

An analysis of commercially available vitamin E supplements found the actual content to vary considerably from the labeled dosage, from 41% less to 57% more than labeled amounts (5).

Adverse Reactions

Vitamin E supplementation may increase the risk of hemorrhagic stroke (36).

Toxicity: Thrombophlebitis; long-term consumption of doses greater than or equal to 400–800 IU per day may cause fatigue, dizziness, weakness, and rash (3) (6).

Herb-Drug Interactions

Warfarin: In a large study of patients treated with warfarin, higher serum vitamin E levels predicted hemorrhagic events (4).

Although many research protocols use milligrams of vitamin E, most commercial products are sold in international units (IU). One IU natural vitamin E equals 0.67 mg d-alpha-tocopherol and one IU of synthetic vitamin E equals 0.45 mg d-alpha-tocopherol.

Dosage (OneMSK Only)
References
  1. Packer L, Weber SU, Rimbach G. Molecular aspects of alpha-tocopherol antioxidant action and cell signaling. J Nutr 2001;131:369S-73S.
  2. Whitney EN, et al. Understanding Normal & Clinical Nutrition, 4th ed. Belmont (CA): West Publishing; 1994.
  3. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington (DC): National Academy Press; 2000.
  4. Pastori D, Carnevale R, Cangemi R, et al. Vitamin E serum levels and bleeding risk in patients receiving oral anticoagulant therapy: a retrospective cohort study. J Am Heart Assoc. Oct 28 2013;2(6):e000364.
  5. Feifer AH, Fleshner NE, Klotz L. Analytical accuracy and reliability of commonly used nutritional supplements in prostate disease. J Urol 2002;168:150-4.
  6. Roberts HJ. Thrombophlebitis associated with vitamin E therapy. With a commentary on other medical side effects. Angiology. Mar 1979;30(3):169-177.
  7. Corrigan JJ, Marcus FI. Coagulopathy associated with vitamin E ingestion. JAMA 1974;230:1300-1.
  8. Kim JM, White RH. Effect of vitamin E on the anticoagulant response to warfarin. Am J Cardiol 1996;77:545-6.
  9. Foley DJ, White LR. Dietary intake of antioxidants and risk of Alzheimer disease: food for thought. JAMA 2002;287:3261-3.
  10. Olmedilla B. et al. A European multicentre, placebo-controlled supplementation study with alpha-tocopherol, carotene-rich palm oil, lutein or lycopene; analysis of serum responses. Clin Sci (Lond) 2002;102:447-56.
  11. Preuss HG, et al. Randomized trial of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) on symptoms of benign prostatic hyperplasis (BPH). Int Urol Nephrol 2001;33:217-25.
  12. Graat J, et al. Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA 2002;288:715-21.
  13. Waters DD, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA 2002;288:2432-40.
  14. Taylor HR, et al. Vitamin E supplementation and macular degeneration: randomised controlled trial. BMJ 2002;325:11-16.
  15. Engelhart MJ, et al. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002;287:3223-9.
  16. Morris MC, et al. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 2002;287:3230-7.
  17. Yusuf S, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. N Eng J Med 2000;342:154-60.
  18. Sano M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. N Eng J Med 1997;336:1216-22.
  19. Heinonen OP, et al. Prostate cancer and supplementation with alpha-tocopherol and B-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998;90:440-6.
  20. Alpha-Tocopherol, Beta carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;330:1029-35.
  21. Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Eng J Med 1993;328:176-83.
  22. Pace A, Giannarelli D, Galiè E, et al. Vitamin E neuroprotection for cisplatin neuropathy: a randomized, placebo-controlled trial. Neurology. 2010 Mar 2;74(9):762-6.
  23. Kryscio RJ, Abner EL, Caban-Holt A, et al. Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer’s Disease by Vitamin E and Selenium Trial (PREADViSE). JAMA Neurol. May 1 2017;74(5):567-573.
  24. Sano M, Aisen PS, Andrews HF, et al. Vitamin E in aging persons with Down syndrome: A randomized, placebo-controlled clinical trial. Neurology. May 31 2016;86(22):2071-2076.
  25. Villani V, Zucchella C, Cristalli G, et al. Vitamin E neuroprotection against cisplatin ototoxicity: Preliminary results from a randomized, placebo-controlled trial. Head Neck. Apr 2016;38 Suppl 1:E2118-2121.
  26. Vivekananthan DP. Penn MS. Sapp SK. Hsu A. Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 2003;361(9374):2017-23.
  27. Barton D, et al. Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. J Clin Oncol 1998 Feb;16(2):495-500.
  28. Bjelakovic G, et al. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 2004;364:1219-28.
  29. Miller ER, et al. Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality. Annals of Internal Medicine 2005;142(1):37-46.
  30. Bairati I, et al. A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. J Natl Cancer Inst 2005;97(7):481-8.
  31. Kirsh VA, et al. Supplemental and dietary vitamin E, B-carotene, and vitamin C intakes and prostate cancer risk. J Natl Cancer Inst 2006;98(4):245-252.
  32. Peters U, Littman AJ, Kristal AR, et al. Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and lifestyle (VITAL) study cohort. Cancer Causes Control. 2008;19(1):75-87.
  33. Slatore CG, Littman AJ, Au DH, et al. 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):524-30.
  34. Reiter E, Jiang Q, Christen S. Anti-inflammatory properties of alpha- and gamma-tocopherol. Mol Aspects Med 2007;28(5-6):668-91.
  35. Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009 Jan 7;301(1):39-51.
  36. Sesso HD, Buring JE, Christen WG, et al. Vitamins E and C in the prevention of cardiovascular disease in men. The Physicians’ Health Study II Randomized Controlled Trial. JAMA. 2008;300(18):2123-2133.
  37. Jennifer Lin, Nancy R. Cook, Christine Albert, et al. Vitamins C and E and Beta Carotene Supplementation and Cancer Risk: A Randomized Controlled Trial. J Natl Cancer Inst 2009;101:14-23.
  38. Mahabir S, Schendel K, Dong YQ, et al. Dietary alpha-, beta-, gamma- and delta-tocopherols in lung cancer risk. Int J Cancer 2008;123(5):1173-80.
  39. Schürks M, Glynn RJ, Rist PM, et al. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ. 2010 Nov 4;341:c5702.
  40. Fleshner NE, Kapusta L, Donnelly B, et al. Progression From High-Grade Prostatic Intraepithelial Neoplasia to Cancer: A Randomized Trial of Combination Vitamin-E, Soy, and Selenium. J Clin Oncol. 2011 May 2.
  41. Klein EA, Thompson IM, Tangen CM, et al. Vitamin E and the Risk of Prostate Cancer. The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549-1556.
  42. Chae CU, Albert CM, Moorthy MV, Lee I-Min, Buring JE. Vitamin E Supplementation and the Risk of Heart Failure in Women. Circ Heart Fail. 2012 Mar 1;5(2):176-82.
  43. Galasko DR, Peskind E, Clark CM, et al; for the Alzheimer’s Disease Cooperative Study. Antioxidants for Alzheimer Disease: A Randomized Clinical Trial With Cerebrospinal Fluid Biomarker Measures. Arch Neurol. 2012 Jul;69(7):836-41.
  44. Zhang W, Shu XO, Li H, et al. Vitamin Intake and Liver Cancer Risk: A Report From Two Cohort Studies in China. J Natl Cancer Inst. 2012 Aug 8;104(15):1173-81.
  45. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010 May 6;362(18):1675-85.
  46. Lavine JE, Schwimmer JB, Van Natta ML, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA. 2011 Apr 27;305(16):1659-68.
  47. Sayin V, Ibrahim M, Larsson E, et al. Antioxidants Accelerate Lung Cancer Progression in Mice. Sci Transl Med. Jan 2014; 6:(221):ra15.
  48. Wu QJ, Xiang YB, Yang G, et al. Vitamin E intake and the lung cancer risk among female nonsmokers: a report from the Shanghai Women’s Health Study. Int J Cancer. 2015 Feb 1;136(3):610-7.
  49. Lance P, Alberts DS, Thompson PA, et al. Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention. Cancer Prev Res (Phila). Jan 2017;10(1):45-54.
  50. Aune D, Keum N, Giovannucci E, et al. Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective studies. Am J Clin Nutr. Nov 1 2018;108(5):1069-1091.
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