Does taking vitamin E increase your risk of prostate cancer? If you have seen the new study published in the Journal of the American Medical Association (JAMA) about the extended findings of the SELECT trial which stated that vitamin E can increase the risk of prostate cancer, don't panic. There are some important things you should know about the study and about vitamin E before you throw away your vitamin E supplements. The facts about vitamin E are:
•There are eight forms of vitamin E (see below), they are not all the same, and evidence to date has shown some forms can help with prevention of prostate cancer.
•The SELECT study used only one form of vitamin E -- alpha-tocopherol -- which research indicated years before the SELECT trial even began to be ineffective at preventing prostate cancer unless it was used along with another form of vitamin E, gamma-tocopherol.
•The gamma-tocopherol form of vitamin E was shown to be effective at reducing the risk of prostate cancer by researchers at Johns Hopkins School of Public Health before the SELECT trial began.
•Research from 1994 found that alpha-tocopherol robs cells of gamma-tocopherol, which is the form of vitamin E that offers more protection against prostate cancer.
•Limited studies of the tocotrienol forms of vitamin E have indicated they may also offer some protection against prostate cancer.
Therefore, to state that vitamin E increases the risk of prostate cancer without explaining the limitations of the study -- including the fact that SELECT used only one form of vitamin E -- is a misrepresentation of what scientists and researchers have discovered about vitamin E and prostate cancer to date.
What is vitamin E?
Vitamin E is a complex of eight different isoforms (alpha-, beta-, delta-, and gamma-tocopherol; and alpha-, beta-, delta-, and gamma-tocotrienol) that were discovered decades apart. When vitamin E was first discovered, one fraction seemed to be more potent and necessary for pregnancy, so the scientists named it alpha tocopherol -- "tocopherol" from the Greek meaning "to give birth." Subsequent research, however, revealed that other fractions of vitamin E were also beneficial.
Gamma-tocopherol, for example, was found to have anti-inflammatory and anticancer properties superior to those of alpha-tocopherol. More specifically, research showed gamma-tocopherol, especially in combination with other forms of vitamin E such as delta-tocopherol, prompted cell death in prostate cancer cells, while alpha-tocopherol alone did not have this impact.
The tocotrienols were first isolated in 1965, but their roles in the body were not established until 1980 when researchers reported tocotrienols and tocopherols had an ability to lower cholesterol levels. More recent studies have provided evidence that gamma-tocotrienols may be effective in targeting prostate cancer stem cells and that gamma-tocotrienol and delta-tocotrienol may be better at inhibiting the growth of prostate cancer cell lines than are gamma-tocopherol and delta-tocopherol.
Clearly, the take home message is that there is much more to vitamin E than just alpha-tocopherol, which was the focus of the SELECT study, and that the various forms of vitamin E offer important health benefits, including prevention of prostate cancer.
Alpha-tocopherol vs. gamma-tocopherol
Since alpha-tocopherol and gamma-tocopherol are the two forms of vitamin E we are most concerned with, you may be wondering what the difference is between the two in addition to their differing impact on prostate cancer cells. One difference is their chemical structure, which is similar yet varied enough so they have differing effects on the body. It appears that although the liver breaks down both forms of vitamin E, the body uses a special protein to place more alpha-tocopherol into the bloodstream to go to the tissues than it does gamma-tocopherol. This indicates alpha-tocopherol and gamma-tocopherol have differing roles in the body.
Another difference is their source: although both alpha-tocopherol and gamma-tocopherol are found in certain foods, such as oils (e.g., olive, canola, corn, soybean), almonds, hazelnuts and peanuts, there are significantly higher levels of gamma-tocopherol in corn, canola, and soybean oils (and margarines made with these oils), which are the main oils in the American diet. Therefore, gamma-tocopherol is the main natural dietary source of vitamin E among Americans.
Alpha-tocopherol is the form of vitamin E used in most vitamin E supplements. Supplements that contain alpha-tocopherol may have the form of vitamin E as (1) d-alpha-tocopherol, which is a natural source and so is more bioavailable to the body; or (2) dl-alpha-tocopherol, a synthetic form, which is less bioavailable.
About the SELECT trial
Before exploring the virtues of gamma-tocopherol, it's important to point out the design of the SELECT trial. SELECT (SELenium and vitamin E Cancer prevention Trial) originally ran from August 2001 through June 2004 and involved 35,000 men assigned to follow one of four different interventions per day: 200 micrograms (mcg) of L-selenomethione (selenium) plus a vitamin E placebo; 400 IU vitamin E (as alpha-tocopherol) plus a selenium placebo; 200 mcg selenium plus 400 IU vitamin E; or placebo of both.
The researchers ended the trial early because the participants were not displaying any benefits from taking selenium or vitamin E, either alone or combined. In fact, the investigators reported there was a slight increase in prostate cancer among men who took vitamin E only and a slight increase in diabetes among men who took selenium alone.
The original SELECT was planned to include at least a seven-year follow-up period, and this is where the results of the new JAMA study enter the picture. Authors of the study report that healthy men with an average risk of prostate cancer who took 400 IU vitamin E during SELECT demonstrated a significantly increased risk (17 percent) of prostate cancer when compared with men who took placebo.
Gamma-tocopherol and prostate cancer
Saying that vitamin E increases the risk of prostate cancer is like saying all cars get 25 miles per gallon: some types of cars get better mileage, some get worse. Some forms of vitamin E offer better anticancer benefits than others. This is true when it comes to alpha-tocopherol and gamma-tocopherol.
Let's return to the Johns Hopkins study mentioned earlier. A total of 10,456 men participated in the trial, in which researchers compared alpha-tocopherol, gamma-tocopherol, and selenium. They found that men who had the highest blood levels of gamma-tocopherol were five times less likely to get prostate cancer. Another important finding was that alpha-tocopherol and selenium protected against prostate cancer only when gamma-tocopherol intake was high. That means the alpha- and gamma-tocopherols have a synergistic effect when it comes to prostate cancer.
Then there was a review published in "Carcinogenesis" in 2010 in which the authors explained how many large-scale studies with alpha-tocopherol had not shown anticancer benefits. The authors suggested this lack of effect was caused by high doses of alpha-tocopherol, which reduced the body's levels of delta-tocopherols. They also noted that gamma-tocopherol had "strong anti-inflammatory" properties and that it "may be the more effective form of vitamin E in cancer prevention." They concluded by saying, "we propose that a gamma-tocopherol-rich mixture of tocopherols is a very promising cancer-preventive agent and warrants extensive future research."
Yet another study indicated that gamma-tocopherol can help protect against development of prostate cancer. From a total of approximately 20,000 men who donated blood samples for analysis of micronutrients and prostate cancer risk, the investigators found "potential chemopreventive effects of gamma-tocopherol on prostate cancer" and a weak association between alpha-tocopherol and prostate cancer risk.
Gamma-tocopherol: The other vitamin E
When you shop for vitamin E supplements, in most cases you will see "alpha-tocopherol" on the ingredient label. Alpha-tocopherol is also the form of vitamin E that is most often used in clinical studies. Given what scientists have discovered thus far about alpha-tocopherol and gamma-tocopherol, however, men should look to choose a mixed tocopherols vitamin E supplement that includes alpha- and gamma-tocopherols, and the reason is simple:
Alpha- and gamma-tocopherols work together: the alpha form inhibits the production of cell-damaging free radicals, while the gamma form captures and neutralizes them. If the level of alpha-tocopherol gets too high in the body, it tries to eliminate gamma-tocopherol in the cells. Therefore, both forms of vitamin E have to be kept in relative balance.
So before you throw away your vitamin E supplement based on the nightly news report, check the label. Chances are it contains alpha-tocopherol alone; if so, look for a brand that contains mixed tocopherols which includes alpha-tocopherol and gamma-tocopherol with a high gamma relative balance. Because among the facts about vitamin E is one that says some forms can help prevent prostate cancer.
Campbell SE et al. γ-tocotrienol induces growth arrest through a novel pathway with TGFβ2 in prostate cancer. Free Radic Biol Med 2011 May 15; 50(10): 1344-54
Christen S et al. Gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha-tocopherol: physiological implications. Proc Natl Acad Sci U S A 1997 Apr 1; 94(7):3217-22
Das S et al. Cardioprotection with palm oil tocotrienols: comparison of different isomers. Am J Physiol Heart Circ Physiol 2008 Feb; 294(2): H970-78
Handelman GJ et al. Human adipose alpha-tocopherol and gamma-tocopherol kinetics during and after 1 y of alpha-tocopherol supplementation. Am J Clin Nut 1994; 59(5): 1025-32.
Helzlsouer KJ et al. Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst 2000 Dec 20; 92(24):2018-23.
Huang HY et al. Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer. Am J Epidem 2003; 157(4): 335-44.
Jiang Q et al. Gamma-tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis. Proc Natl Acad Sci USA 2004 Dec 21; 101(51): 17825-30
Ju J et al. Cancer preventive activities of tocopherols and tocotrienols. Carcinogenesis 2010 Apr; 31(4): 533-42
Klein et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011 Oct 12; 306(14):1549-56.
Lippman et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009; 301(1):39-51.
Luk SU et al. Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population. Int J Cancer 2011 May 1; 128(9): 2182-91