Vitamin E

What does it do? Vitamin E is an antioxidant that protects cell membranes and other fat-soluble parts of the body, such as LDL cholesterol (the “bad” 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. However, other recent double-blind trials have found either limited benefit,⁶ 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

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

Rating	Health Concerns
	Anemia (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 Anemia (injections for thalassemia, orally for glucose-6-phosphate dehydrogenase deficiency [G6PD] anemia and anemia caused by kidney dialysis) Angina Atherosclerosis Athletic performance (for exercise recovery and high-altitude exercise performance only) Bronchitis Cold sores Dermatitis herpetiformis Diabetes (for glucose tolerance and prevention of diabetic retinopathy) Down's syndrome Dysmenorrhea Heart attack (at 400 to 800 IU of natural vitamin E) Leukoplakia Lung cancer (reduces risk) Osteoarthritis Pancreatic insufficiency Preeclampsia (in combination with vitamin C; for high risk only) Premenstrual syndrome Prostate cancer (reduces risk) Retinopathy (diabetic retinopathy and retrolental fibroplasia) Skin ulcers (oral vitamin E) Wound healing Yellow nail syndrome
	Abnormal pap 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 Goiter Halitosis (if gum disease and deficient) Hepatitis High cholesterol HIV support Hypoglycemia Infertility (female) Infertility (male) Insulin resistance syndrome (Syndrome X) Kidney stones (prevention) Liver cirrhosis Lupus Macular degeneration Menopause Menorrhagia (heavy menstruation) Osgood-Schlatter disease Parkinson’s disease (in combination with vitamin C) Photosensitivity Pre- and post-surgery health Restless legs syndrome Retinopathy (abetalipoproteinemia) Retinopathy (in combination with selenium, vitamin A and vitamin C) Shingles Sickle cell anemia Skin ulcers (topical vitamin E) Sprains and strains (for exercise-related muscle strain) Stroke 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. An herb is primarily supported by traditional use, or the herb or supplement has little scientific support and/or minimal health benefit.

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 labeled “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, labeled “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 researchers have hypothesized that alpha tocopherol might interfere with the activity of gamma tocopherol, although this idea remains unproven.

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,¹⁹ ²⁰ 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.

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.²³

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.²⁴ The reason for the discrepancy between reports is not known.

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.²⁵

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 medications may interact with vitamin E. Refer to the drug interactions safety check for a list of those medications.

References:

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. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.