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By Ralph Hall, MD
Emeritus Professor of Medicine
University of Missouri-Kansas City School of Medicine
What do you really know about the vitamin E you have been prescribing or perhaps taking? Many cardiologists take vitamin E for its antioxidant properties to prevent cardiovascular disease. What kinds of vitamin E are they taking? Are they taking natural vitamin E? But what is natural vitamin E? All of this now becomes important since increased amounts of alpha-tocopherol in plasma are associated with a decreased incidence and mortality from prostate cancer.
But consider this: In a recent study published in the Journal of The National Cancer Institute, by Kathy Helzlsouer, MD, MHS, and associates from Johns Hopkins University School of Hygiene and Public Health in Baltimore, alpha-tocopherol was shown to be only protective if it is associated with greater than average amounts of gamma-tocopherol in the plasma. Alpha- and gamma-tocopherols are two of the most active of the eight molecular forms of vitamin E that occur naturally in food.1
The study was done "because a protective effect of selenium and alpha-tocopherol, the major form of vitamin E in supplements, against prostate cancer had been observed in clinical trials. The trials had been designed to test the efficacy of these nutrients against skin and lung cancer."
They observed that "little attention had been paid to the possibility that gamma-tocopherol, a major component in the U.S. diet and the second most common tocopherol in human serum, might also be important in the development of prostate cancer," wrote the researchers.
The study involved 10,556 male residents of Washington County, MD, who donated blood for a specimen bank. The relationships between alpha- and gamma-tocopherol and selenium were studied.
The most significant finding was that for gamma-tocopherol, men in the highest fifth of the distribution had a fivefold reduction in the risk of developing prostate cancer than men in the lowest fifth. (P = 0.002). Since this was the first study to examine this relationship, the researchers concluded that future investigations should be designed to study the combined effects of alpha- and gamma-tocopherol.
If you have been taking only alpha-tocopherol, as most people have, what does this do to your plasma levels of gamma-tocopherol? This means that we need to know a bit more about vitamin E. Many patients have been told only to take natural vitamin E. Is that the best advice?
Maret Traber, PhD, principal investigator at the Linus Pauling Institute at Oregon State University in Corvallis, is the author of a chapter on vitamin E, in the textbook Modern Nutrition in Health and Disease.2 In the chapter, she notes that "vitamin E is the collective name for molecules that exhibit the biological activity of alpha-tocopherol." Vitamin E occurs naturally in eight different forms: four tocopherols and four tocotrienols. Tocotrienols differ from tocopherols in that the former have unsaturated side chains.
Each group of four is labeled:
Unlike other vitamins, chemically synthesized alpha-tocopherol is not identical to the natural form. The naturally occurring and most biologically active form, formerly called d-alpha-tocopherol, still is labeled in that manner on many supplements. As noted, it is only one of eight stereoisomers of tocopherol.
According to Traber, the richest dietary sources of vitamin E are vegetable oils. The alpha-tocopherols are especially high in wheat germ and safflower and sunflower oils. Soybean and corn oils contain predominately gamma-tocopherol. Cottonseed oil and palm oil contain both the alpha- and gamma-tocopherols in equal proportion. Meats, vegetables, and nuts also contain vitamin E.
Interestingly, the DASH (Dietary Approaches to Stop Hypertension) diet, which so effectively lowers blood pressure, and the Mediterranean diet, which is associated with a lower incidence of both cancer and heart disease, both contain large amounts of vitamin E.3 Vitamin E is sold as supplement pills: The natural form is labeled d-alpha-tocopherol, and the synthetic form is labeled dl alpha-tocopherol. Vitamin E functions in vivo as an antioxidant, which prevents propagation of free-radical damage in biological membranes. Anemia and neuropathies can occur with vitamin E deficiency, which is rare except in genetic disease and malabsorption syndromes.
In an accompanying editorial, Edward Giovannucci, MD, ScD, a researcher at Channing Laboratory, Brigham and Women’s Hospital, and Harvard Medical School, all in Boston, lists a host of studies done with selenium and alpha-vitamin E.4 These studies, although promising, have yielded conflicting results. On balance, the results have shown some benefits, especially in smokers. However, the relationship between gamma- and alpha-tocopherol has not been studied previously.
This has raised other questions about vitamin E. In the past, most of the benefits have been attributed to the antioxidant properties of alpha-tocopherol. Now more is known about the function of the other tocopherols, which have specific actions that inhibit nitrogen oxide and other agents that are important in setting the stage for many types of cancer.5
Giovannucci’s editorial concludes: "There are a number of compounds, known to trap highly reactive compounds [which may promote cancer] for which there are varying degrees of evidence for protection against prostate cancer. Some of their benefits may be synergistic or complementary, and potential displacement effects, which have been shown to occur, such as the displacement of gamma-tocopherol by large doses of alpha-tocopherol, may be important."
The American Heart Association (AHA) in Dallas does not recommend vitamin E supplementation along with its dietary recommendations.6 It is the AHA’s opinion that the evidence for vitamin E’s protective effects against arteriosclerotic cardiovascular disease are not strong enough to support such a recommendation.
How then should we use this information? If the AHA expert committee contends that the evidence is not strong enough to recommend using vitamin E supplements to prevent heart disease, how can we recommend using it for cancer prevention, for which there is even less, often conflicting evidence? Our best option seems to be making wise choices in the food we eat and recommend to our patients.
How do we proceed from here? It seems prudent not to take vitamin E supplements. There currently is no convincing evidence that it prevents cardiovascular disease or that it reduces the incidence of cancer. There is evidence that the DASH diet lowers blood pressure substantially, and therefore it is likely that the diet will reduce the incidence of stroke and heart disease. The Mediterranean diet, which is high in fruits and vegetables, olive oil, and fish, also is likely to reduce both the incidence of vascular disease and stroke. Those two diets are very similar and contain adequate amounts of foods with high levels of both alpha- and gamma-vitamin E.
1. Helzlsouer K, Huang H, Aslberg A. Association between alpha-tocopherol, gamma-tocopherol and selenium and subsequent prostate cancer. J Natl Cancer Inst 2000; 92:2,018-2,023.
2. Shils M, Shike M, Olson J, et al, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore: Lippincott, Williams and Wilkins; 1998, pp. 347-362.
3. Sacks F, Svetkey L, Vollmer, W. Effects on blood pressure of reduced sodium and dietary approaches to stop hypertension (DASH) diet. N Engl J Med 2000; 344:3-10.
4. Giovannucci E. Alpha-tocopherol: A new player in prostate cancer prevention. J Natl Cancer Inst 2000; 92:1,966-1,967.
5. Woodall C, Shigenaga M. Gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha tocopherol: Physiological implications. Proc Natl Acad Sci U S A 1997; 94:3,217-3,222.
6. Krauss R, Eckel R, Barbara H, et. al. AHA dietary guidelines revision 2000: A statement for healthcare professionals from the nutrition committee of the American Heart Association. Circulation 2000; 102:2,284-2,299.