Introduction

Recently, much medical research has been devoted to studying the possibility that supplementing the diet with larger amounts of certain nutrients may help prevent and even treat many diseases. Over the past several decades, much experimental and clinical evidence have demonstrated the positive benefits of nutrient supplementation. In particular, nutrients such as vitamin E, vitamin C, and beta-carotene, are now recognized for their strong antioxidant potential, meaning they effectively quench the harmful by-products of metabolism called"free radicals".

For some time, researchers believed free radicals may be involved in the genesis and progression of a large number of diseases, including heart disease, cancer, cataracts, and aging, to name a few. According to this theory, free radicals interfere with genetic processes, activate inappropriate immune attacks against the body's own cells, cause otherwise healthy cells to self-destruct, and begin chain-reactions which cause an avalanche of more free radicals to be produced. Quite a messy picture, to be sure!

The body has numerous defenses and repair mechanisms against free radical damage, collectively known as antioxidants. For instance, powerful antioxidant enzymes are constantly quenching free radicals. Many of these enzymes require co-nutrients such as selenium and zinc in order to be produced and/or function. Besides enzymes, the body also uses antioxidant nutrients such as vitamin E, vitamin C, and beta-carotene to neutralize free radicals. These nutrients must come from ingestion via food or extra supplementation, since the body is not able to make them.

In the free-radical theory of disease, a very reasonable line of thought goes like this:

a. Excessive amounts of free radicals may cause significant cellular damage.

b. Significant cellular damage may accumulate and manifest itself as certain kinds of disease.

c. Antioxidant enzymes and nutrients effectively neutralize free radicals.

d. Sufficient antioxidant levels should thus prevent the cellular damage which may have resulted due to excessive free radical activity.

e. Thus, sufficient antioxidant levels should prevent or even reverse the diseases which may be caused by excessive free radical damage.

Based on this reasoning, numerous studies, including in vitro (test-tube) studies, live animal studies, epidemiological (large population) life-style/nutrition studies, and human clinical trials, have been conducted to test the free radical theory of disease. Mostly, the results are very encouraging and positive, supporting the idea that dietary antioxidants in food and supplements offer significant health benefits. While the results of some studies are less supportive and even negative, closer consideration of the methods or assumptions used in the particular study often reveals what may have caused the difference. Certainly, we still do not have an entirely consistent picture and many gaps in our understanding exists. More research is needed to this end. Encouragingly, current results do justify confidence in the free-radical picture of certain diseases and the effectiveness of antioxidant therapies, including supplementation, in their prevention and treatment.

In this article, we focus mainly on the positive benefits found from vitamin E in recent studies on certain human diseases. While the emphasis is on vitamin E, it is important to remember vitamin E is a part of a larger family of antioxidant nutrients, including vitamin C and beta-carotene. Indeed, many studies suggest for maximum effectiveness, the antioxidant nutrients should be taken together. Biochemically, this makes sense, because each nutrient plays a unique role in a rather complex process, the overall goal of which is to neutralize free radicals. Numerous interactions and interrelationships exist, and a popular term to describe such interdependency is"synergy".

On the other hand, vitamin E could be more difficult to obtain through the average western diet. The main sources of vitamin C and beta-carotene are fruits and vegetables, generally more popular in the diet than nuts, seeds, and fresh oils, the main sources of vitamin E. A life-long diet of vitamin E-poor foods may result in a condition where supplementation of the single nutrient would restore optimal, synergistic levels and could significantly improve antioxidant mechanisms. Nevertheless, research using single antioxidant nutrients as well as in combination with other antioxidants is important to find the most effective approach.

Because of the diverse and numerous studies on vitamin E in the current medical literature, this article is presented in a way to emphasize the essential details and findings of representative studies in eight categories: the heart, diabetes, neurology, immunology, exercise, the eye, cancer, and other benefits. Both negative and positive results are reported to fairly represent the current state of knowledge, including what is not yet well understood. Each study is succinctly summarized in the tables for quick reference. Full references are provided, and with modern access to the Internet, readers can find most of these studies on-line in their full length through such services as PubMed or other health related search engines.

(A note about vitamin E units:

Amounts of vitamin E can be expressed in term of weight (mg) or international units (IU). The difference arises because not all vitamin E forms are equivalent. The most recent ruling by the Food and Nutrition Board of the Institute of Medicine recognizes only alpha-tocopherol as having vitamin E activity, excluding the other tocopherols and tocotrienols, since only alpha-tocopherol binds to a specific liver protein believed essential in transporting vitamin E. Alpha-tocopherol can come from natural sources, such as soy oil, or chemically synthesized. The molecular form of natural-source alpha-tocopherol is a single"right-handed" stereoisomer (RRR). In addition to RRR-alpha-tocopherol, the synthetic form has 3 more right-handed stereoisomers (RSR, RRS. RSS) plus 4"left-handed" ones (SSS, SSR, SRR, SRS). All the right-handed stereoisomers have 100% vitamin E activity, but the left-handed stereoisomers have none. Thus, by weight, synthetic vitamin E has less bioactivity than the natural-source. The IU system helps equilibrate the expression of potency. That is, 100 mg of RRR- alpha-tocopherol has roughly 50% greater vitamin E activity compared to 100 mg of synthetic alpha-tocopherol. But when expressed in terms of IU, the difference in potencies by weight are taken into account and re-expressed as an effective value. For instance, the conversion factor for RRR-alpha-tocopherol is 1 IU / 0.67 mg and synthetic is 1 IU / 1.00 mg. Then, 100 IU of vitamin E can mean either 67 mg of natural-source RRR-alpha-tocopherol or 100 mg of synthetic alpha-tocopherol, and in either case, both provide the same bioavailability of vitamin E. Where specified in the articles, the form of vitamin E is included in the following summaries. For a more complete discussion on the forms and potency of vitamin E, please refer to the Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids, National Academy Press, Washington, D.C. 2000.)