Study: Selenium, Vitamin E may be Ineffective for Prostate Cancer Prevention

The government halted a major study that was testing whether vitamin E and selenium, either taken alone or together, may help prevent prostate cancer. An early review of the data showed that the supplements were ineffective and may possibly lead to health risks.

Two trends were found: slightly more men who took vitamin E alone developed prostate cancer, and slightly more men who took selenium alone developed type 2 diabetes. However, the results were not statistically significant, meaning they could just be coincidental.

More than 35,000 men aged 50 and older were taking supplements or placebos as part of the Selenium and Vitamin E Cancer Prevention Trial (SELECT). But now the participants are being informed about the findings and told to stop taking their supplements.

Although the participants will no longer take the supplements, the researchers will still monitor their health for the next three years.

The study was double-blinded, which means neither the researchers nor the participants knew which supplements (if any) they were taking. Those who want to know what supplements they were taking can ask the doctors. But according to the researchers, the data will be more accurate if the men wait to find out until the end of the follow-up period.

The National Cancer Institute (NCI), which provided most of the funding for SELECT, is sponsoring many other studies that are investigating the effects of different agents on prostate cancer. These agents include polyphenon E, green tea extract, lycopene, soy and di-indolylmethane (DIM), which is a compound found in Brassica vegetables such as broccoli and cauliflower.

Currently, there is a promising drug called finasteride that may help prevent prostate cancer. In 2003, the Prostate Cancer Prevention Trial found that finasteride reduced the risk of prostate cancer by 25 percent. However, finasteride has not been approved by the U.S. Food and Drug Administration for this use.

For more information about integrative therapies for prostate cancer prevention, please visit Natural Standard's Comparative Effectiveness database.

Comments

[suzanne adams, cytologist]

This study was highly flawed because the vitamin E used was the inactive synthetic form (dl-alpha tocopherol) and the amt. of selenium was too low (200 mcg). Also, they did not account for the effects of the drug, finasteride, that was introduced into the study, nor other drugs used by participants such as statin drugs, which are known to increase the risk of type 2 diabetes. It's yet another study to promote the use of synthetic drugs instead of natural biochemisty as a means to prevent cancer and related diseases.

Review PubMed's research abstracts on the two nutrients, and you will see a huge database of the effectiveness of these two nutrients in biochemical pathways that promote apoptosis and normal cell division and differentiation.

[Ann F.]

I criticized this study design when I heard about it back in 2002 at the first ever Frontiers in Cancer Prevention Research conference (AACR). Why? Because the substances being used were ALL artificial; the vitamin E was simply dl-alpha- tocopherol (which does not penetrate the nucleus of a cell) AFTER we KNEW that there were more elements to vitamin E (tocotrienols, gamma, delta, etc.); and there was nowhere near enough vitamin C being used (90 mgs from a multvitamin that was ALL artificial and synthetic).

I am sure now I had other criticisms but cannot recall. I spoke passionately - I was the only advocate in the room - and easily dismissed by the speakers.

I felt then -- as I often did and still do -- there are two different camps, and they do NOT speak or reference each other's work. And patients suffer ill effects from this problem (or fail to get appropriate, adequate and safe 'prevention' strategies tested). There are THOUSANDS of studies on vitamin therapies that show benefit. The benefit always comes when natural forms of vitamins are used. So why set up a multi-million dollar, long-term, very large, clinical trial with synthetic or artificial supplements? Whoops! We'll have to have a pharmaceutical product to use instead. I expect to see another such marketed soon. We already have finasteride.

Ann F.
Founder, President, The Annie Appleseed Project
www.annieappleseedproject.org

[PK]

While the Prostate Cancer Prevention Trial found that finasteride reduced the risk of prostate cancer by 25 percent, it also found that patients who did develop prostate cancer while taking finasteride developed high-grade tumors. High-grade tumors are more likely to grow rapidly and to spread to other parts of the body. At this time, finasteride is not recommended for prostate cancer prophylaxis because of this possible association with a more progressive form of the disease. Further research is being conducted to try to determine who might be appropriate candidates for finasteride prophylaxis.

[Mason]

I understand why the men who want to know what supplements they were taking were instructed to wait to find out after the follow-up period. However, at the same time, if I were enrolled and discovered the reasons to why this investigation was stopped, I would want to know what will happen to me (although they were only trends that were found). Prostate cancer or diabetes, both are important and serious conditions. If I knew I was taking the selenium, and diabetes was correlated with its use, I’d start modifying my diet and exercising more to lower my HbA1c.

[Luke]

What happened to the group that took the combination of vitamin E and selenium? Why did the trial have to be stopped even though the results were not statistically significant? Did selenium reduce prostate cancer at all? Could the trial be restarted with just selenium alone at a lower dose? What doses were given of each?

[lan]

I believe that this decision (halting the SELECT study) is wise since there is a link between the supplements (selenium and vitamin E) and health risks found during this trial. Even though the results were not statistically significant, the findings did point to serious effects of these supplements that need to be explored. What were the doses of selenium and vitamin E given in this study? I wonder if the finding in this study was due to giving doses higher than recommended for these supplements.

[Todd Y.]

Previous research has already shown that high doses of vitamin E may reduce the anticancer effects of conventional treatments such as radiation and chemotherapy. And there are many other antioxidants available, so I wonder why they chose to study vitamin E as a preventive against prostate cancer? On the other hand, selenium has been shown to have more beneficial antioxidant properties for humans, and a correlation between low levels of selenium and an increased risk of prostate cancer has already been researched. I’m glad to read that the National Cancer Institute is sponsoring other studies on prostate cancer, and I look forward to these results; cancer research is invaluable.

[joncancer]

Unfortunately, prostate cancer symptoms are not seen in the early stages when it can be curable. Decrease in food intake, lack of hunger, weight loss and softening of bone are the symptoms seen in advanced stages.

[FC]

This article is informative because vitamin E is a great supplement to take and so is selenium. Often, there are many supplements that should be taken together, as they work better that way. I often take all of my vitamins and supplements at once in the morning, but this article is going to have me look into whether I should space them out or not.

This article is an eye opener for men obviously but also for women as far as which supplements may be a health risk when combined.

[John]

The dose of selenium was not too low. The study used 200 mcg, which is the maximum daily recommended amount. The recommended daily allowance (RDA) is 80-200 mcgs, with 70 mcg for male adults. Also, the form of selenium used was selenomethionine, which is the organic form and has better bioavailability than other forms of selenium. Therefore, it may still be possible to reduce of dose of selenium to see if there are still any anti-cancer effects with fewer adverse effects.

[D.B.]

I didn't realize that the supplements used in this study were artificial forms of selenium and vitamin E. This makes me wonder whether supplements purchased at stored are usually synthetic? How do we check for this?

[liz]

I do not think adequate information is provided (such as other risk factors) in this study to associate the development of cancer and diabetes from taking these supplements.

[Becca]

Men who are older than 55, African American and have with a brother or father who had prostate cancer have the greatest risk of developing prostate cancer. Selenium and vitamin E are both antioxidants that help control the cell damage that leads to cancer. They are two nutrients that have shown strong initial evidence to prevent prostate cancer. Studies are showing that this may not be the case; in fact, taking selenium and vitamin E in supplemental form may cause adverse effects. Like anything, vitamin E and selenium should be taken in moderation.

Because prostate cancer is so common, the National Cancer Institute are placing priority on finding methods to reduce deaths and new cases of this disease. More research needs to be done, and there is not enough information about risk versus benefits for these nutrients for prostate cancer prevention.

[alocasia]

Informative post. Vitamins and supplements both are supportive to the body, but only to a certain extent. Excess amount may cause harm to the body, and you should also know whether they can be taken together or not. Also, I had no idea that vitamin E can cause prostate cancer.

[Andrew C.]

Before accepting published data, one has to evaluate the results and determine if the data are clinically significant. To do so, you should consider and ask yourself if the parameters and outcome measures make sense to you. Examine the intervention. As Suzanne pointed out, the amount of selenium used was too low than what would be used conventionally and the form of vitamin E was inactive. One should compare the interventions in a study to what is normally used or accepted/indicated for its use.

[Bob Cooney]

At most the SELECT study shows that an inappropriately high dose (400 mg) of synthetic vitamin E is not effective and may be harmful. Duh? The "scientists" that designed this travesty of a clinical trial should be banned from further public support for life and held accountable for this incredible waste of precious research funding. Everything we know about vitamin E is that it is essential, but there is much to be learned about its chemistry and biology. Studies such as the SELECT trial set back legitimate research by decades and mislead the public.

[Steve Q]

The results of this study do not surprise me in the least. It seems that for a long time, it was all the rage to take vitamin E as an antioxidant to promote cardiac health. As a patient with endothelial dysfunction, vitamin E supplements actually induce chest pains, and this research supports what my physiological response already knew. Selenium and Vitamin E are great examples of supplements that, although proved to have antioxidant effects, can have negative effects on systems and tissues that the public refuses to acknowledge. Is this because they do not require a prescription?

[william]

There might be some bias by having the National Cancer Institute (NCI) as the main financial contributor. Results obtained from the SELECT study are quite contrary to what is commonly believed of vitamin E and selenium. The study design needs to be thoroughly examined before drastic measures are taken against the use of selenium and vitamin E for the prevention of prostate cancer.

[Metu]

Vitamin E, while known as an antioxidant, has been found to exert pro-oxidant effects at high doses (in vitro). This increase in free radical formation is postulated to play a role in carcinogenesis. Thus, it really isn't surprising to hear that there was an increased risk of prostate cancer associated with the use of vitamin E alone.

Vitamin E has a plethora of biochemical actions; indeed, scientists are still in the process of deciphering its many effects. Furthermore, it was reported in a recent meta-analysis that intake of >150 IU/day of vitamin E increased all cause mortality. In fact, 400 IUs, which is the most common dose, was associated with a 10 percent higher risk of death, compared to people not taking vitamin E.

As one of my pharmacy professors used to say, "the dose makes the poison." The problem is that with many drugs (vitamins included), the amount that can cause harm is much smaller than people realize.

[KK]

This article left me wondering what doses were used in this study? Would the issue be the combination of the vitamin E and selenium or the high dose of selenium alone? Or could it be because of the source of the vitamins?

[George]

In response to Bob Cooney:

I agree with you that this trial was poorly designed, but I would not go as far as banning the researchers for life. The researchers should have at least done some preliminary studies of the dose of vitamin E and selenium in a small study group before using them at such a large scale. I would not go as far as banning them for life though. I would also like to point out that these adverse events were not considered statistically significant, but due to their severity, the trial was stopped.

[SUMA]

I was unable to access the full-text article, but I agree with Andrew on this one. When reviewing studies it is important to look at the following: objective, intervention (what products were used), quality testing on the product, adverse effects, parameters established for discontinuing the study, treatment adherence, study funding (any potential for bias), potential confounding factors and statistical analysis.

I must say that I find it hard to believe that the NCI would have any financial bias on this topic. Based on the abstract, the authors “comprehensively reviewed literature on the chemoprevention of prostate cancer with emphasis on the antioxidants vitamin E and selenium. The credible leads for the primary prevention of prostate cancer using selenium and vitamin E emerged as secondary findings from randomized controlled trials with corroborative evidence from observational and in vitro studies. Selenium and vitamin E are widely available compounds that are safe if taken in moderation, with relatively few adverse effects. The evidence in support of the antioxidants in the primary prevention of prostate cancer is promising, and the next step in definitively answering the question has been addressed by the investigators of SELECT. The SELECT study will define the role of the antioxidants selenium and vitamin E in the prevention of prostate cancer; complete data from the study will be available in 12 years.”

Based on this information, at the time of the initiation of the study, these two products were felt to be suitable choices. Unfortunately, sometimes outcomes do not always turn out to be what was expected. I do feel that the subjects should be notified of what they were taking in case lifestyle adjustments may help decrease their risk of developing either diabetes or prostate cancer.

[PK]

In response to John’s comment about the dose of selenium being at the high end of the Recommended Daily Allowance (RDA), I think a clarification is in order as to what exactly the RDA means. The RDA is defined as the amount needed for a healthy person to remain healthy. A patient who is deficient may require a higher dose, and a higher dose may be needed to prevent or treat a specific disease. The top range of an RDA is not an absolute dosing limit above which toxic effects are seen.

[PK]

William, while any financing can introduce bias, I fail to see what NCI could possibly gain by funding a study that did not show a way to prevent cancer. The purpose of conducting clinical trials is to establish evidence of the effectiveness of a treatment rather than to rely on historical beliefs. Oftentimes what is “commonly believed” is incorrect.

[daniella]

Suma, thank you for clarifying the RDA info. RDA is based on depletion/repletion studies, where the RDA is calculated following a fraction greater than what people need to not be deficient. This is not to say that RDA is a maximum; it’s really some fraction above the minimum on average. Some people require more than the RDA of a given vitamin/mineral.

[Thomas]

Were the patients’ nutritional statuses and family histories of prostate of cancer taken into account during this study? If not, then these parameters could be confounding variables that influenced the result of the study. The results of this study contradict what I have learned about selenium and vitamin E. Something seems wrong!

[Vince]

Thanks to the commentators who explained RDA. I never knew what it was based on. What is the RDA for vitamin E? People seem to be focusing on just selenium, but the prostate cancer study used both.

[Albert]

Metu,

That is really interesting that there is a 10 percent risk of all-cause mortality in people taking vitamin E 400IU daily compared to people who do not. Did the study present any ideas as to why? What was the vitamin E doing to cause these deaths? Was the difference statistically significant? Did anyone in the study die from cancer?

[Evan]

Synthetic? Real? But how does it make you feel? If a corn muffin is made out of plastic I will eat it if it cures me! Vitamin E is all but contraindicated in patients who have had heart attacks because for unknown reasons, it increases their risk of having a second one. Vitamin dEath it should be called. OK, maybe it should just have a warning, since it seems to help a lot of other people. As a cardiac patient who has not had an infarct, I still stay away from the stuff unless it shows up in a food product under my radar.

[Lynn]

DB, regarding artificial forms of selenium and vitamin E:

A natural source contains co-factors that come with the nutrient in nature. It is then carefully concentrated from its natural source. No extreme heat, pressure or possibly toxic solvents are used.

Synthetic vitamins, on the other hand, are made in a laboratory manufacturing setting. No co-factors are present (although co-factors aren't really needed, because we have our own). Synthetic vitamins are often cheaper to produce than natural vitamins.

It is also necessary to consider the differences in their molecular structures. I say if it is chemically the same, and there are no contaminants, it is the same; who cares if it is natural or synthetic? Do you want to pay $2.99 for vitamin C, or would you rather pay $8.99? (I'm just making these numbers up, so don't quote me on it.)

As for vitamin E, the d form is derived from vegetable oils and other natural sources; it is different from the racemic mixture dl- form (which is often called the synthetic form).

The human body uses only the d form. So when consuming the dl-form of vitamin E, you obtain an effective dose that is 1/2 of that reported on the label. The L form is excreted.

[Anna H.]

This is a very poorly conducted experiment, as only after administration of vitamin E and/or selenium, did the researchers find out that they could have led to possible health risks. This is a not expected from an institute of the caliber and reputation as the NCI. Moreover, the fact that both resources (i.e. even the researchers were unaware of the types of medicines being administered) is not understandable. It has already been proven in many clinical trials that vitamin E is an effective remedy for the prevention of prostrate cancer, and credit goes to the NCI for further exploring natural resources like brassica vegetables.

[beth]

That is scary news because vitamin E and selenium are going to be ingested through other forms other than supplements. How long did this study last before they started finding this information? Were these men other wise healthy?

[Janet]

When studies report results like these without providing the full story at the beginning, it only causes people to become overly worried. As many of you have mentioned, there are several factors here that should have been addressed by the authors. Inactive/synthetic forms of the vitamins were used, the results were not statistically significant, etc. Vitamins can provide benefit, but instead people become scared when things like this are reported inaccurately.

[Harrison]

This strikes me as a flawed study for a variety of reasons. First, after reading some of the comments, it has come to my attention that the researchers may not be using a chemically active form of vitamin E and selenium. If this is the case, vitamin E and selenium would not be able to exhibit any effects on the body.

Secondly, the risk of prostate cancer increases significantly after the age of 50. If the researchers of this study are following subjects after the age of 50 for three years, could it not be coincidental that many of their subjects would develop prostate cancer as statistics predict? I am unsure of whether the findings of this study are significant.