This fat-soluble vitamin is commonly found in many foods and was thought to be one of the main antioxidants that humans ingest. As researchers began exploring the depths of antioxidant actions in any identified substance, vitamin E was targeted for multiple extensive clinical trials. On the surface, it seemed to be fairly straightforward. Many studies were based on the assumption that since vitamin E was a natural substance, required by the body, and an antioxidant, it would be unlikely that supplementation could be anything but beneficial.

Background

Vitamin E is ingested in foods and absorbed in the small intestine.1 Since it is a lipophilic molecule, vitamin E must be eaten in combination with fats to be assimilated into the bloodstream. From there, it travels to the liver for metabolism into several different forms of the tocopherol molecular structure.1 As an antioxidant, vitamin E helps protect cells from oxidative damage caused by oxygen-free radicals, but studies have shown that vitamin E is much more than an antioxidant: It has specific functions as a signaling molecule and as a coenzyme.2,3 Some theories depict the true role of vitamin E to be more of a catalyst for other protective processes than as an independent antioxidant.2,3

Science

Until recently, research focused on vitamin E’s potential for enhancing that antioxidative protective function. Although this protective action seemed logical, the results of several large clinical trials involving supplemental vitamin E have not validated that hypothesis. While select groups did have notably positive results, most trials yielded either outright negative results or inconclusive data.


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One trial followed more than 84,000 U.S. men aged 50 to 74 years for an average of five years.4 The men were randomized according to daily vitamin E supplementation levels ranging from zero to 400 IU or more.4 At the end of the trial, the hypothesis that vitamin E would have a protective influence against prostate cancer was not supported. No statistically significant difference existed between the nonusers and the daily users of any dose range in the development of prostate cancer.4 However, in the subcategory of men who either smoked or had recently quit smoking, there was a notable positive effect of vitamin E use.4 These results again led researchers to consider that the truly beneficial effects of vitamin E are beyond those of a typical antioxidant.

In a subgrouping of the Women’s Health Study trial, nearly 40,000 women using vitamin E supplementation, aspirin, or placebo were followed for 10 years.5 The participants were monitored for breast, lung, or colon cancer. At the end of the trial, no significant difference was found in the vitamin E supplementation cohort.5 This study also showed no definitive protective effect against cardiovascular disease for the vitamin E supplementation group.5

In a similar trial, nearly 15,000 U.S. physicians aged 50 years and older were randomized to either vitamin E or vitamin C supplementation.6 At an average eight years’ follow-up, neither vitamin supplementation showed any protection against the development of cardiovascular disease or mortality.6

The American Heart Association sponsored a decision analysis of all data published to that point using the quality-adjusted life year (QALY) as the determining factor.7 In this summary review, vitamin E supplementation not only failed to increase QALY in the participants, but, in some cases, actually reduced it.7

Other conditions considered to benefit from vitamin E supplementation include complications of pregnancy, neurodegenerative diseases, and certain vision disorders.8 Symptoms of confirmed vitamin E deficiency include cerebellar ataxia, peripheral neuropathy, impaired immune response, skeletal myopathy, and some forms of retinopathy.3 It is now assumed that the interaction vitamin E has with these systems is far different than that of a typical antioxidant.8

Dosage, safety, how supplied

Vitamin E supplements are typically found as an oil-filled gel capsule. Dietary experts, however, agree that the only effective way to increase vitamin E levels is by consuming foods high in the molecule. The Food and Nutrition Board at the Institute of Medicine has established a dietary reference intake of 15 mg/day for adults.3 Foods especially rich in vitamin E include nuts, seeds, enriched cereals, dark-green leafy vegetables, tomatoes, pumpkins, and sweet potatoes.3 When supplementation is determined to be necessary, vitamin E in its most bioavailable form that we know of—meaning the alpha-tocopherol form—is recommended at doses no higher than 400-600 IU/day.

Few drug interactions have been identified for vitamin E; however any antioxidant is considered a mild platelet aggregation inhibitor, so caution is advised when taken with other anticoagulants.

Summary

As much as clinicians have embraced vitamin E supplementation, it is possible to have too much of a good thing. The best assurance against vitamin E deficiency is a healthful diet.

References

1. National Institutes of Health. Dietary fact sheet: Vitamin E.

2. Zingg JM, Azzi A. Non-antioxidant activities of vitamin E. Curr Med Chem. 2004;11:1113-1133.

3. Linus Pauling Institute at Oregon State University. Micronutrient information center: Vitamin E. 

4. Rodriguez C, Jacobs EJ, Mondul AM, et al. Vitamin E supplements and risk of prostate cancer in U.S. men. Cancer Epidemiol Biomarkers Prev. 2004;13:378-382.

5. Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA. 2005;294:56-65.

6. 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;300:2123-2133.

7. Dotan Y, Pinchuk I, Lichtenberg D, Leshno M. Decision analysis supports the paradigm that indiscriminate supplementation of vitamin E does more harm than good. Arterioscler Thromb Vasc Biol. 2009;29:1304-1309. 

8. Brigelius-Flohé R, Kelly FJ, Salonen JT, et al. The European perspective on vitamin E: current knowledge and future research. Am J Clin Nutr. 2002;76:703-716.

All electronic documents accessed February 15, 2011