Use of vitamin E associated with increased risk of prostate cancer

In a trial that included about 35,000 men, those who were randomized to receive daily supplementation with vitamin E had a significantly increased risk of prostate cancer, according to a study in the October 12 issue of JAMA.

Men who took 400 international units (I.U.) of vitamin E daily had more prostate cancers compared to men who took a placebo, according to an updated review of data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The findings showed that, per 1,000 men, there were 76 prostate cancers in men who took only vitamin E supplements, vs. 65 in men on placebo over a seven-year period, or 11 more cases of prostate cancer per 1,000 men. This represents a 17 percent increase in prostate cancers relative to those who took a placebo. This difference was statistically significant and therefore is not likely due to chance. The results of this update appeared Oct. 12, 2011, in the Journal of the American Medical Association.

SWOG, an international network of research institutions, carried out SELECT at more than 400 clinical sites in the United States, Puerto Rico, and Canada. SELECT was funded by the National Cancer Institute (NCI) and other institutes that comprise the National Institutes of Health.

"Based on these results and the results of large cardiovascular studies using vitamin E, there is no reason for men in the general population to take the dose of vitamin E used in SELECT as the supplements have shown no benefit and some very real risks," said Eric Klein, M.D., a study co-chair for SELECT, and a physician at the Cleveland Clinic. "For now, men who were part of SELECT should continue to see their primary care physician or urologist and bring these results to their attention for further consideration."

The SELECT study began in 2001 and included over 35,000 men. It was started because earlier research had suggested that selenium or vitamin E might reduce the risk of developing prostate cancer. However, based on an independent safety monitoring review in autumn 2008, participants were told to stop taking their study supplements because it had become clear that the trial would never produce the 25 percent reduction in prostate cancer the study was designed to show with the use of these supplements. In 2010, the study sites were closed and over half of the participants consented to have their health monitored via mail questionnaires. Now, because of this latest finding, researchers are encouraging all participants to consider taking part in long-term study follow-up so investigators can continue to track outcomes.

SELECT was undertaken to substantiate earlier, separate findings from studies in which prostate cancer risk was not the primary outcome. A 1998 study of male smokers in Finland who took 50 I.U. of vitamin E daily to prevent lung cancer, showed 32 percent fewer prostate cancers in men who took the supplement. A 1996 study of men and women with a history of skin cancer who took selenium for prevention of disease recurrence showed that men who took the supplement had 52 percent fewer prostate cancers than men who did not take the supplement.

Based on these and other findings, men were recruited to participate in SELECT. They were randomly assigned to take one of four sets of supplements or placebos, with more than 8,000 men in each group. One group took both selenium and vitamin E; one took selenium and a placebo that looked similar to vitamin E; one took vitamin E and a placebo that looked similar to selenium; and the final group received placebos of both supplements. Men who took selenium alone or vitamin E and selenium together were also more likely to develop prostate cancer than men who took a placebo, but those increases were small and possibly due to chance.

"SELECT has definitively shown a lack of benefit from vitamin E and selenium supplements in the prevention of prostate cancer and has shown there is the potential for harm," said Lori Minasian, M.D., study co-author and acting director of NCI's Division of Cancer Prevention. "Nevertheless, this type of research has been critically important to understanding the potential benefits and risks from supplements."

SELECT researchers are now measuring the amount of vitamin E, selenium, and other nutrients in the blood of participants when they joined the trial, to see if the effect of the supplements depended upon this baseline level of micronutrient. Other researchers are looking at single nucleotide polymorphisms, which are DNA changes known as SNPs, to see if a change in one or more genes could affect cancer risk or perhaps increase a man's risk of developing prostate cancer while taking vitamin E.

The participant samples come from the study biorepository of blood and toe nail clippings which, when coupled with the extensive clinical information on participants, is a vital resource for further study. "SWOG is soliciting proposals from researchers nationwide to use the SELECT biorepository to help answer the biological question of why vitamin E increased risk instead of decreasing it," said Laurence Baker, D.O., study co-author and chairman of SWOG. "There are many more questions raised by these study results than we have answers for, and thus the need for further investigation."

Except for skin cancer, prostate cancer is the most common type of cancer in men in the United States. The current lifetime risk of prostate cancer for American men is 16 percent. In 2011, there will be an estimated 240,890 new cases of prostate cancer and 33,720 deaths from this disease in the United States.

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More information: JAMA. 2011;306[14]:1549-1556
Provided by JAMA and Archives Journals
Citation: Use of vitamin E associated with increased risk of prostate cancer (2011, October 11) retrieved 16 October 2019 from
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Oct 11, 2011
Thats a great test, "hey guys take this and get prostate cancer"

Oct 11, 2011
This latest study is flawed. The original 1998 Fins volunteers took only 50 I.U daily, whereas this study uses 400 I.U. More is not better, in some case it has the opposite effect, as with vitamin A, alcohol, even water. Yes, you can die from drinking too much water.

Oct 12, 2011
What kind of Vitamin E were these men given? There are four forms of Vitamin E that occur naturally, and a safe Vitamin E supplement should be a mixture containing all four forms of Vitamin E. Many of the old (or cheap) Vitamin E supplements contain only the Alpha form, usually produced synthetically. For at least the past 5 years it has been understood that supplements containing only the Alpha Vitamin E were likely to do more harm than good. (The other forms of Vitamin E are effective against some dangerous free radicals that are not combatted by Alpha Vitamin E. Heavy supplementation by the Alpha form tends to displace the other forms from the body.) Since this study began in 2001, it is likely that they were only using the Alpha Vitamin E, but the article does not discuss this issue.

Oct 12, 2011
You are exactly right. It took me a while, but I was able to find their study and confirm that they used dl-Alpha-Tocopherol which has been shown to be ineffective, to say the least. The other forms of Vitamin E, called Tocotrienols, are very effective against cancer and this claim can be confirmed by looking at the research papers available on the NIH abstract website. I think it was very irresponsible to release this information without making that distinction in the public release.

Oct 12, 2011
@Mrmajestic - Thank you for the information. I was unable to find it anywhere without paying $30 to JAMA. I agree that it was very irresponsible to release the report without noting that they were only using dl-Alpha-Tocopherol in the experiment.

I hope they didn't deliberately hide this information. This was an expensive government-funded study, and NIH could be embarassed that their study was testing a supplement that was already discredited by the more reputable manufacturers of Vitamin E.

Oct 12, 2011
I am not a medic but I have known to avoid any products containing dl-alpha-tocopherol, the synthetic (and cheaper) form of vitamin E (alpha type). What is the point of running a study with this form? Perhaps it was not known at the time that this form was not just ineffective but would cause damage.

In any case, I find it really "unscientific" when scientific sites/papers/articles just say "vitamin E" without mentioning the type. This is unacceptable.

This article seems to be part of a recent onslaught of poorly-written articles demonizing supplements and trying to create panic among the public. It would seem prudent to skeptical of any studies pointing the finger at supplements without providing all the details and particularly if the studies show poor design or if any conflicts of interest are present.

Oct 14, 2011
BIG PROBLEM with this study. The vitamin E used was likely derived from GENETICALLY ENGINEERED SOY. C'mon. Another farcical no doubt big pharma funded project.

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