Vitamin E

Also indexed as: Alpha Tocopherol, Tocopherol, Tocopheryl (Acetate, Succinate)

What is it?

Vitamin E is an antioxidant that protects cell membranes and other fat-soluble parts of the body, such as low-density lipoprotein (LDL; “bad” cholesterol) cholesterol, from damage.

Only when LDL is damaged does cholesterol appear to lead to heart disease, and vitamin E is an important antioxidant protector of LDL.¹ Several studies,² ³ including two double-blind trials,⁴ ⁵ have reported that 400 to 800 IU of natural vitamin E per day reduces the risk of heart attacks. Other recent double-blind trials have found either limited benefit⁶ or no benefit at all from supplementation with synthetic vitamin E.⁷ One of the negative trials used 400 IU of natural vitamin E⁸ —a similar amount and form to previous successful trials. In attempting to make sense of these apparently inconsistent findings, the following is clear: less than 400 IU of synthetic vitamin E, even when taken for years, does not protect against heart disease. Whether 400 to 800 IU of natural vitamin E is, or is not, protective remains unclear.

Vitamin E also plays some role in the body’s ability to process glucose. Some, but not all, trials suggest that vitamin E supplementation may eventually prove to be helpful in the prevention and treatment of diabetes.

In the last ten years, the functions of vitamin E in the cell have been further clarified. In addition to its antioxidant functions, vitamin E is now known to act through other mechanisms, including direct effects on inflammation, blood cell regulation, connective tissue growth, and genetic control of cell division.⁹

Where is it found?

Wheat germ oil, nuts and seeds, whole grains, egg yolks, and leafy green vegetables all contain vitamin E. Certain vegetable oils should contain significant amounts of vitamin E. However, many of the vegetable oils sold in supermarkets have had the vitamin E removed in processing. The high amounts found in supplements, often 100 to 800 IU per day, are not obtainable from eating food.

Vitamin E has been used in connection with the following conditions (refer to the individual health concern for complete information):

Science Ratings	Health Concerns
	Anaemia (if deficient) Burns (in combination with vitamin C for prevention of sunburn only) Epilepsy (for children) Immune function (for elderly people) Intermittent claudication Rheumatoid arthritis Tardive dyskinesia
	Alzheimer’s disease Anaemia (injections for thallasaemia, orally for glucose-6-phosphate dehydrogenase deficiency [G6PD] anaemia and anaemia caused by kidney dialysis) Angina Atherosclerosis Athletic performance (for exercise recovery and high-altitude exercise performance only) Bronchitis Cold sores Dermatitis herpetiformis Down’s syndrome Dysmenorrhoea Endometriosis (in combination with vitamin C) Hay fever Heart attack (at 400 to 800 IU of natural vitamin E) High blood pressure Leukoplakia Lung cancer (reduces risk) Osgood-Schlatter disease Osteoarthritis Pancreatic insufficiency Parkinson’s disease (in combination with vitamin C) Preeclampsia (in combination with vitamin C; for high risk only) Premenstrual syndrome Prostate cancer (reduces risk) Radiation therapy (side-effect prevention in people with cancer of the oral cavity) Retinopathy (diabetic retinopathy and retrolental fibroplasia) Skin ulcers (oral vitamin E) Type 1 and Type 2 diabetes (for glucose tolerance and prevention of diabetic retinopathy) Wound healing Yellow nail syndrome
	Abnormal cervical smear Age-related cognitive decline (ARCD) Alcohol withdrawal support Burns (minor) (topical) Cataracts Childhood diseases Colon cancer (reduces risk) Cystic fibrosis Dupuytren’s contracture Epilepsy (for adults) Fibrocystic breast disease Fibromyalgia Goitre Halitosis (if gum disease and deficient) Hepatitis High cholesterol HIV support Hypoglycaemia Infertility (female) Infertility (male) Insulin resistance syndrome (Syndrome X) Kidney stones (prevention) Liver cirrhosis Lupus Macular degeneration Menopause Menorrhagia (heavy menstruation) Photosensitivity Pre- and post-surgery health Restless legs syndrome Retinopathy (abetalipoproteinemia) Retinopathy (in combination with selenium, vitamin A, and vitamin C) Shingles Sickle cell anaemia Skin ulcers (topical vitamin E) Sprains and strains (for exercise-related muscle strain) Stroke Type 2 diabetes (for abetalipoproteinemia) Vaginitis
Reliable and relatively consistent scientific data showing a substantial health benefit. Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit. For a herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

Who is likely to be deficient?

Severe vitamin E deficiencies are rare. People with a genetic defect in a vitamin E transfer protein called thrombotic thrombocytopenic purpura (TTP) have severe vitamin E deficiency, characterised by low blood and tissue levels of vitamin E and progressive nerve abnormalities.¹⁰ ¹¹

Low vitamin E status has been associated with an increased risk of rheumatoid arthritis¹² and major depression.¹³ Women with preeclampsia have been found to have lower blood levels of vitamin E than women without the condition.¹⁴

Very old people with type 2 diabetes have shown a significant age-related decline in blood levels of vitamin E, irrespective of their dietary intake.¹⁵

Which form is best?

The names of all types of vitamin E begin with either “d” or “dl,” which refer to differences in chemical structure. The “d” form is natural (also known as RRR-alpha tocopherol) and “dl” is synthetic (more correctly known as all-rac-alpha tocopherol). The natural form is more active and better absorbed. Little is known about how the “unnatural” “l” portion of the synthetic “dl” form affects the body, though no clear toxicity has been discovered.

In theory, when a vitamin E supplement is labelled “400 IU” it should have the same level of activity regardless of its source. This is purportedly achieved by using more synthetic vitamin E to reach the same potency as a lesser amount of natural vitamin E. For example, 100 IU of vitamin E requires about 67 mg of the natural form but closer to 100 mg of the synthetic. However, a recent review of the scientific evidence suggests that natural vitamin E probably has greater activity in the body than indicated on the label.¹⁶ Natural vitamin E may be as much as twice as bioavailable as synthetic vitamin E, not 1.36 times as is generally accepted.¹⁷ Many doctors advise people to use only the natural, the “d” form, of vitamin E.

After the “d” or “dl” designation, often the Greek letter “alpha” appears, which also describes the structure. Synthetic “dl” vitamin E is found only in the alpha form—as in “dl-alpha tocopherol.” Natural vitamin E may be found either as alpha—as in “d-alpha tocopherol”—or in combination with beta, gamma, and delta, labelled “mixed”—as in mixed natural tocopherols.

Little is known about the importance of the beta and delta forms of vitamin E, but a debate has arisen concerning gamma tocopherol. In a test tube study, gamma tocopherol was found to be more effective than alpha tocopherol in protecting against certain specific types of oxidative damage.¹⁸ In addition, some research has shown that supplementation with large amounts of alpha tocopherol (such as 1,200 IU per day) increases the breakdown, and decreases blood levels, of gamma tocopherol.¹⁹

Human trials with vitamin E have almost always been done with the alpha (not gamma) form. Historically the synthetic “dl” form was used in most trials, but some trials are now using the natural form. The issue of alpha vs. gamma form requires more research before it can be fully understood.

Almost all vitamin E research shows that, when positive results are obtained, hundreds of units per day are required—an amount easily obtained with supplements but impossible with food. Therefore, switching to food sources, as suggested by some researchers, is impractical. On the other hand, the vitamin E occurring naturally in food contains gamma tocopherol and other tocopherols. Thus, it possibly may turn out to be more effective than the vitamin E taken in supplement form. Additional research is needed in this area.

Vitamin E forms are listed as either plain “tocopherol” or tocopheryl followed by the name of what is attached to it, as in “tocopheryl acetate.” The two forms are not greatly different. However, plain tocopherol may be absorbed a little better, while tocopheryl attached forms have a slightly better shelf life. Both forms are active when taken by mouth. However, the skin utilizes the tocopheryl forms very slowly,²⁰ ²¹ so those planning to apply vitamin E to the skin should buy plain tocopherol. In health food stores, the most common forms of vitamin E are d-alpha tocopherol and d-alpha tocopheryl acetate or succinate. Both of these d (natural) alpha forms are frequently recommended by doctors. Although the succinate form is slightly weaker than the acetate form, more milligrams of the succinate form are added to supplements to compensate for this small difference in potency. Therefore, 400 IU of either form should have equivalent potency.

How much is usually taken?

The recommended dietary allowance for vitamin E is low, just 15 mg or approximately 22 International Units (IU) per day. The most commonly recommended amount of supplemental vitamin E for adults is 400 to 800 IU per day. However, some leading researchers suggest taking only 100 to 200 IU per day, since trials that have explored the long-term effects of different supplemental levels suggest no further benefit beyond that amount. In addition, research reporting positive effects with 400 to 800 IU per day has not investigated the effects of lower intakes.²² For tardive dyskinesia, the best results have been achieved from 1,600 IU per day,²³ a large amount that should be supervised by a doctor.

Are there any side effects or interactions?

Vitamin E toxicity is very rare and supplements are widely considered to be safe. The National Academy of Sciences has established the daily tolerable upper intake level for adults to be 1,000 mg of vitamin E, which is equivalent to 1,500 IU of natural vitamin E or 1,100 IU of synthetic vitamin E.²⁴

In a double-blind study of healthy elderly people, supplementation with 200 IU of vitamin E per day for 15 months had no effect in the incidence of respiratory infections, but increased the severity of those infections that did occur.²⁵ For elderly individuals, the risks and benefits of taking this vitamin should be assessed with the help of a doctor or nutritionist.

In contrast to trials suggesting vitamin E improves glucose tolerance in people with diabetes, one trial reported that 600 IU per day of vitamin E led to impairment in glucose tolerance in obese people with diabetes.²⁶ The reason for the discrepancy between reports is not known.

In a double-blind study of people with established heart disease or diabetes, participants who took 400 IU of vitamin E per day for an average of 4.5 years developed heart failure significantly more often than did those taking a placebo.²⁷ Hospitalizations for heart failure occurred in 5.8% of those in the vitamin E group, compared with 4.2% of those in the placebo group, a 38.1% increase. Considering that some other studies have shown a beneficial effect of vitamin E against heart disease, the results of this study are difficult to interpret. Nevertheless, individuals with heart disease or diabetes should consult their doctor before taking vitamin E.

A review of 19 clinical trials of vitamin E supplementation concluded that long-term use of large amounts of vitamin E (400 IU per day or more) was associated with a small (4%) but statistically significant increase in risk of death.²⁸ Long-term use of less than 400 IU per day was associated with a small and statistically nonsignificant reduction in death rates. This research has been criticized because many of the studies on which it was based used a combination of nutritional supplements, not just vitamin E. For example, the adverse effects reported in some of the studies may have been due to the use of large amounts of zinc or synthetic beta-carotene, and may have had nothing to do with vitamin E. It is also possible that long-term use of large amounts of pure alpha-tocopherol may lead to a deficiency of gamma-tocopherol, with potential negative consequences. For that reason, some doctors recommend that people who need to take large amounts of vitamin E take at least part of it in the form of mixed tocopherols.

Patients on kidney dialysis who are given injections of iron frequently experience “oxidative stress.” This is because iron is a pro-oxidant, meaning that it interacts with oxygen molecules in ways that may damage tissues. These adverse effects of iron therapy may be counteracted by supplementation with vitamin E.²⁹

A diet high in unsaturated fat increases vitamin E requirements. Vitamin E and selenium work together to protect fat-soluble parts of the body.

Are there any drug interactions?
Certain medicines may interact with vitamin E. Refer to drug interactions for a list of those medicines.

References
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1. Balz F. Antioxidant vitamins and heart disease. Presented at the 60th Annual Biology Colloquium, Oregon State University, Corvallis, Oregon, February 25, 1999.

2. Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993;328:1450–6.

3. Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary heart disease in women. N Engl J Med 1993;328:1444–9.

4. Stephens NG, Parsons A, Schofield PM, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996;347:781–6.

5. 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;356:1213–8.

6. GISSI-Prevenzione Investigators. 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; 354:447–55.

7. Collaborative Group of the Primary Prevention Project (PPP). Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomized trial in general practice. Lancet 2001;357:89–95.

8. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:154–60.

9. Azzi A, Breyer I, Feher M, et al. Specific cellular responses to a-tocopherol. J Nutr 2000;130:1649–52.

10. Traber MG. Vitamin E. In: Shils ME, Olsen JA, Shike M, Ross AC (eds). Modern Nutrition in Health and Disease. Baltimore: Williams & Wilkins, 1999, 347–62.

11. Cavalier L, Ouahchi K, Kayden HJ, et al. Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families. Am J Hum Genet 1998;62:301–10.

12. Knekt P, Heliovaara M, Aho K, et al. Serum selenium, serum alpha-tocopherol, and the risk of rheumatoid arthritis. Epidemiology 2000;11:402–5.

13. Maes M, De Vos N, Pioli R, et al. Lower serum vitamin E concentrations in major depression. Another marker of lowered antioxidant defenses in that illness. J Affect Disord 2000;58:241–6.

14. Kharb S. Total free radical trapping antioxidant potential in pre-eclampsia. Int J Gynaecol Obstet 2000;69:23–6.

15. Polidori MC, Mecocci P, Stahl W, et al. Plasma levels of lipophilic antioxidants in very old patients with type 2 diabetes. Diabetes Metab Res Rev 2000;16:15–9.

16. VERIS Research Information Service. Summary finds superiority of natural vitamin E supplements over synthetic forms. Townsend Letter for Doctors & Patients 1999;July:100–5 [review].

17. Acuff RV, Thedford SS, Hidiroglou NN, et al. Relative bioavailability of RRR- and all-rac-alpha-tocopheryl acetate in humans: studies using deuterated compounds. Am J Clin Nutr 1994;60:397–402.

18. Christen S, Woodall AA, Shigenaga MK, et al. Gamma-tocopherol traps mutagenic electrophiles such as NO+ and complements alpha-tocopherol: physiological implications. Proc Natl Acad Sci 1997;94:3217–22.

19. Morinobu T, Yoshikawa S, Hamamura K, Tamai H. Measurement of vitamin E metabolites by high-performance liquid chromatography during high-dose administration of alpha-tocopherol. Eur J Clin Nutr 2003;57:410–4.

20. Beijersbergen van Henegouwen GM, Junginger HE, de Vries H. Hydrolysis of RRR-alpha-tocopheryl acetate (vitamin E acetate) in the skin and its UV protecting activity (an in vivo study with the rat). J Photochem Photobiol B 1995;29:45–51.

21. Norkus EP, Bryce GF, Bhagavan HN. Uptake and bioconversion of alpha-tocopheryl acetate to alpha-tocopherol in skin of hairless mice. Photochem Photobiol 1993;57:613–5.

22. Rimm E. Micronutrients, coronary heart disease and cancer: should we all be on supplements? Presented at the 60th Annual Biology Colloquium, Oregon State University, February 25, 1999.

23. Hashim S, Sajjad A. Vitamin E in the treatment of tardive dyskinesia: a preliminary study over 7 months at different doses. Int Clin Psychopharmacol 1988;13:147–55.

24. Panel on Dietary Antioxidants and Related Compounds, Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, D.C.: National Academy Press, 2000, 249–59.

25. Graat JM, Schouten EG, Kok FJ. 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.

26. Skrha J, Sindelka G, Kvasnicka J, Hilgertova J. Insulin action and fibrinolysis influenced by vitamin E in obese type 2 diabetes mellitus. Diabetes Res Clin Pract 1999;44:27–33.

27. Zoler ML. Supplemental vitamin E linked to heart failure. Fam Pract News 2003 (October 1):28 [News report].

28. Miller ER III, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142:37–46.

29. Roob JM, Khoschsorur G, Tiran A, et al. Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis. J Am Soc Nephrol 2000;11:539–49.

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The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or chemist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires March 2007.