Vitamin E

• 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, rheumatoid arthritis, 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. The major function of vitamin E is to act as a free-radical scavenger, meaning that it neutralizes free radicals and 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. (See the Research Evidence section for more information about this.)

  Vitamin E also lessens the blood’s ability to clot by suppressing the number of adhesion molecules on the lining of the blood vessel walls. With fewer adhesion molecules, cells in the blood are less likely to “dock” on the blood vessel wall and start forming a clot. In addition, vitamin E causes the release of prostacyclin, which itself dilates the blood vessels and inhibits blood clotting. This may be helpful in patients with coronary artery disease, in which blood clots can form around atherosclerotic plaques in coronary arteries.

  Scientists think that vitamin E also inhibits a molecule called protein kinase C, which is involved in cell proliferation and differentiation in smooth muscle, platelets, and monocytes (a type of immune cell). Although in theory this would be helpful against cancer cells, this effect has not been strongly shown in humans. An animal study shows NAC can speed up the growth of lung cancer cells due to its antioxidant activity.

• Purported Uses
  • To prevent the progression of Alzheimer’s disease
    One clinical trial showed that vitamin E helped prevent progression of Alzheimer’s disease. A few population-based studies have suggested that high intake of vitamin E in the diet is associated with a lower risk of developing Alzheimer’s disease.
  • To treat arthritis
    One clinical trial suggested that vitamin E can relieve pain in patients with rheumatoid arthritis, but has no anti-inflammatory effect. No other clinical trials have tested this use.
  • To prevent cancer
    Large population-based studies in Finland found that taking vitamin E supplements reduced the risk of prostate and colorectal cancers in male smokers. However, initial data from the large-scale SELECT (Selenium and Vitamin E Cancer Prevention) Trial shows vitamin E taken alone or with selenium for five years, did not reduce the risk of prostate cancer. Vitamin E supplementation 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 those on placebo, and that vitamin E may interfere with radiation therapy.
  • To manage heart disease
    Data from clinical trials show that vitamin E does not help prevent heart disease.
  • To prevent cataracts
    Two clinical trials do not support this use
  • To prevent the cardiovascular complications of diabetes
    Several clinical trials have shown that vitamin E supplements may be helpful in preventing LDL oxidation in patients with diabetes, which may help prevent progression to atherosclerosis.
  • To treat liver diseases
  • Vitamin E can be used to treat fatty liver disease not caused by alcohol in adults
  • To stimulate the immune system
    No scientific evidence supports this use.
  • To prevent the progression of Parkinson’s disease
    Clinical trials do not support this use.
  • To improve wound healing
    No scientific evidence supports this use.
  • To reduce hot flashes
    A clinical trial showed that vitamin E reduces hot flashes in breast cancer survivors somewhat, but most patients did not prefer vitamin E over placebo at the end of the study and.
• Patient Warnings
  • A recent analysis of seven brands of commercially available vitamin E found their actual content to vary considerably from the labeled dosage, from 41% less than the labeled amount, to 57% more.
  • This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
• 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 of >400-800 IU per day include: fatigue, dizziness, weakness, headache, blurred vision, rash, and thrombophlebitis (inflammation of a vein due to a blood clot).
  • Vitamin E may increase the risk of stroke.
• Special Point
  • Natural vitamin E supplements that are 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.
• Scientific Name

  d-alpha-tocopherol

• Clinical Summary

  Vitamin E is a fat-soluble vitamin derived from plant. 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 available in a variety of formulations, only the d-isomer is considered active ⁽¹⁾.

  Studies evaluating vitamin E supplementation suggest that it may improve immune response in the elderly. Vitamin E may slow the progression of Alzheimer’s disease ^{(9) (15) (16) (18)}; however, conflicting data from another study do not support the utility of antioxidants (vitamin E, vitamin C, lipoid acid, and Coenzyme Q) ⁽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; vitamin E may actually increase the risk of stroke ⁽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 can reduce signs and symptoms of nonalcoholic steatohepatitis in adults ⁽⁴⁵⁾, but not in children and adolescents ⁽⁴⁶⁾ .

  Vitamin E was shown to reduce the risk of some cancers ^(19) (20). It may help to relieve hot flashes in breast cancer survivors ⁽²⁷⁾, and to reduce the incidence of cisplatin-induced neurotoxicity ⁽²²⁾. However, data suggest that supplementation with vitamins C, E, and beta carotene is not beneficial in preventing cancer incidence or affecting cancer mortality ⁽³⁷⁾. Furthermore, vitamin E when used alone or with other supplements did not prevent gastrointestinal cancer ⁽²⁸⁾. A large scale clinical Selenium and Vitamin E Cancer Prevention Trial (SELECT) evaluated the role of vitamin E in prostate cancer prevention. Initial review shows that vitamin E taken alone or with selenium for 5 years did not reduce the risk of prostate cancer ⁽³⁵⁾; observational data from 7 years of participant follow-up indicate a significant increase in the risk of prostate cancer with vitamin E supplementation ⁽⁴¹⁾. Vitamin E, when used together with soy and selenium, did not prevent prostate cancer progression ⁽⁴⁰⁾. Further, findings from other studies indicate vitamin E may actually increase risk of lung cancer ⁽³³⁾ and overall mortality ⁽²⁸⁾. At the same time, conflicting data suggest an association between dietary tocopherol and a reduction in risk of lung cancer ^(38) (48). Also, both dietary and supplemental form of vitamin E may reduce the risk of liver cancer ⁽⁴⁴⁾.

  Toxicity may occur with chronic supplementation of vitamin E with 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, but data are inconsistent ^(7) (8).

• 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
  • Arthritis
  • Cancer prevention
  • Cardiovascular disease
  • Cataracts
  • Diabetes
  • Hot flashes
  • Immunostimulation
  • Menopausal symptoms
  • Parkinson’s disease
  • Wound healing
• 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 that 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 anti-proliferative and pro-apoptotic effects where 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 be more potent compared to 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) within membrane phospholipids and in 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, down regulates the expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), thereby decreasing the adhesion of blood cell components to the endothelium. Vitamin E also upregulates the expression of cytosolic phospholipase A2 and cyclooxegenase-1, which leads to the release of prostacyclin, a potent 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 (ROS), DNA damage and p53 expression ⁽⁴⁷⁾.

• Warnings

  A recent analysis of 7 brands of commercially available vitamin E revealed actual content to vary considerably from the labeled dosage, from 59% to 157% of stated amount ⁽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, headache, blurred vision, and rash ^(3) (6).

• Herb-Drug Interactions

  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.

  Warfarin: It has been reported that vitamin E at doses greater than 400 IU per day may increase the effect of warfarin, although data are inconsistent ^(7) (8).

• 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, 4^th 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. Brody T. Nutritional Biochemistry. San Diego(CA):Academic Press; 1999.

  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. Pronsky ZM. Power’s and Moore’s Food-Medication Interactions, 11^th ed. Pottstown (PA): Food Medication Interactions; 2000.

  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. Edmonds SE, et al. Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial. Ann Rheum Dis 1997;56:649-55.

  24. Teikari JM, et al. Long-term supplementation with alpha-tocopherol and beta-carotene and age-related cataract. Acta Ophthalmologica Scandinavica 1997;75:634-40.

  25. Teikari JM, et al. Incidence of cataract operations in Finnish male smokers unaffected by alpha tocopherol or beta carotene supplements. Journal of Epidemiology & Community Health 1998;52:468-72.

  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. doi: 10.1002/ijc.29016.