According to a media release issued by the Fred Hutchinson Cancer Research Center late last Friday, “high-dose supplementation with both the trace element selenium and vitamin E increase the risk of high-grade prostate cancer. But importantly, this risk depends upon a man’s selenium status before taking the supplements.”
This conclusion is based on a re-analysis of data from the SELECT trial, which began in 2001 and was stopped early in 2008. Initial data from the trial were reported by Lippman et al. in 2008, and the final results by Klein et al. in 2011. The new report by Kristal et al. (“Effects of selenium and vitamin E supplementation on prostate cancer risk differ by selenium status”) has been published in the Journal of the National Cancer Institute.
The complete and updated summary of the results and recommendations issued by the National Cancer Institute and based on the SELECT study clearly includes the latest findings from the paper by Kristal et al. (which is listed in the references). The new information that is being emphasized as a consequence of the paper by Kristal and his colleagues boils down to two primary facts:
- Men who started the SELECT trial with high levels of selenium, as assessed by measures of selenium in their toenail clippings, doubled their risk of developing a high-grade prostate cancer by taking selenium supplements.
- Men who had low levels of selenium at the start of the SELECT trial doubled their risk of high-grade prostate cancer by taking vitamin E.
These two findings re-emphasize the original findings of the trial … that neither selenium, nor vitamin E, nor the combination of the two had any beneficial effects in the prevention of prostate cancer, and for most men came with some increase in risk.
Quoted in the media release issued by the Fred Hutchinson Cancer Research Center, Dr. Kristal is blunt in his statement about the implications of the data:
Men using these supplements should stop, period. Neither selenium nor vitamin E supplementation confers any known benefits – only risks.
He continues, more generally, by stating:
While there appear to be no risks from taking a standard multivitamin, the effects of high-dose single supplements are unpredictable, complex and often harmful. Taking a broad view of the recent scientific studies there is an emerging consistency about how we think about optimal intake of micronutrients. There are optimal levels, and these are often the levels obtained from a healthful diet, but either below or above the levels there are risks.
There may, perhaps, be a role for selenium supplementation in men with well-documented, sub-normal levels of selenium in their blood, but based on the currently available data, that decision is one that should only be taken in careful consultation with one’s doctors.
Many men and women do take over-the-counter (OTC) vitamins and supplements of a wide variety, but products like vitamin E and selenium are among the most popular — particularly among men. The problem is there is no medical evidence of benefit associated with this type of behavior unless there is a clear medical problem that needs to be addressed. Neither selenium nor vitamin E supplements appear to have any clear and documented benefit for the vast majority of men (or women).
Filed under: Management, Prevention, Risk | Tagged: over-the-counter, Prevention, risk, selenium, supplement, vitamin E |
THE "NEW" PROSTATE CANCER INFOLINK 
DEVIL IN THE DETAILS?
There are various kinds of both selenium and vitamin E, and the SELECT trial focused on one specific version of each. As stated in the Lippman paper, “Oral selenium (200 µg/day from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/day of all rac-α-tocopheryl acetate)” were the types used.
There was serious doubt in some quarters prior to trial launch whether the type of vitamin E was right, with research suggesting that gamma-tocopherol was the key to more likely benefit, and more than a suggestion that too much alpha-tocopherol depleted gamma-tocopherol, a line of thought suggesting increased risk from the use of alpha-tocpherol. Also, the dose, at 400 units, was found after trial start to be too high from a bleeding safety standpoint. I have stopped taking vitamin E, mainly because I have not had time to reassure myself that gamma- or mixed tocopherol with a lot of gamma may be safe at a dose of 200 units or less, but I suspect that may be the case.
Similarly, selenium comes in a number of forms, with some quite toxic and at least one regularly used in feed for animals in areas where selenium is deficient in the soil. There was concern while the trial was being launched that the wrong kind of selenium was being used.
My take from these analyses is that the forms of selenium and vitamin E used in the trial are problematic for men, but that we do not really know how the other forms would stand up.
I really dislike media coverage where the level of differentiation in addressing a topic is inadequate. To me, that is sloppy thinking, and I wish the researchers had been more precise in addressing the differences in types of vitamin E and selenium.
With the report of this trial some years back, it appeared that selenium at 20 mg and vitamin E (as alpha-tocopherol/AT) at 400 IU not only served no purpose in prevention or management of prostate cancer, but actually can play a small but definite role in prostate cancer development. The information from this trial was recently (2014) resurrected. But with that resurrection, now comes this much more recent paper published in rebuttal of this resurrection and the SELECT results:
and
This now leaves us with the question as to just what is an appropriate and safe level of vitamin E in either natural d-alpha-tocopherol form or the synthetic d,l-alpha-tocopherol form to still serve as an important antioxidant, since apparently “high dosage” is the problem, not low dosage, that can alter the good effect of gamma-tocopherol and enhance prostate cancer development? One patient remarked that the synthetic d,l-alpha tocopherol form may not be as effective as the natural d-alpha tocopherol form. For those trying to make a decision, I’ll let you be the judge of which form you would prefer, and only suggest that a reduced daily measure of < 400 IU would be the consideration to still serve its importance as an antioxidant along with gamma-tocopherol in the hopeful prevention of the diagnosis of prostate cancer, and as control of prostate cancer growth for those already diagnosed. A reasonable “low dose” appears to be somewhere < 400 IU daily, and from the earlier trial that found alpha-tocopherol as d,l-alpha-tocopherol effective as an antioxidant that dose was only 50 IU daily. More often than not we find vitamin E on the shelves in d,l-alpha tocopherol form at 400 IU. It is likely available in lower dosage in drug departments, so you may want to see if so available. I happen to take the synthetic form of one 400 IU capsule every-other day and since I have been “living” with continued prostate cancer for over 21 years, have no idea if this dosage aids my experience of control and management of my cancer as an antioxidant in company with the medications I am prescribed; it apparently is not causing me any problem in that control.
Dear Jim and Chuck:
While I appreciate that there are all sorts of hypothetical possibilities related to the precise dose of selenium and the precise dose and formulations of vitamin E that could be used as dietary supplements, the fact remains that — as of now — no specific dose or formulation of either vitamin E or selenium has been categorically shown to have any preventive or therapeutic benefit in the management of prostate cancer.
Furthermore, in the case of vitamin E, this lack of preventive or therapeutic benefit has been replicated in the case of several other forms of cancer. Why would one take something that has no demonstrated benefit? And why would one recommend that to others?
June Chan first published this set of results in the Journal of Clinical Oncology in August 2009. TNPCI revisited this in a post on 7/4/2012.
The bottom line is that men need to know their levels of selenium and vitamin E before they decide to supplement … whatever dose is appropriate.
I have heard the argument that the type of vitamin E was wrong. But it was the type that was in publications by quite a few well-known physicians that this was the type that prevented prostate cancer. They were wrong. So wrong that the SELECT trial was stopped prematurely as data suggested quite the opposite of the claims.
As the Patient Advocate for the SWOG GU committee that performed the SELECT trial, I asked about other types of vitamin E. The answer is that these hypotheses can potentially be dangerous to men. We know that the types in the trial performed similarly in increasing risks for high-grade disease. To have another trial testing various types would come with full knowledge that if these hypotheses are wrong again, that all the trial would do is knowingly expose men to the risks confirmed in the SELECT trial. There is no need for a future trial as the data in SELECT is pretty solid.
As far as selenium goes, it had no effect on prevention. And high doses of anything can and will likely be harmful to liver, kidney, and who knows what over time. Anyone who wants to question the SELECT trial results can do so. But I would question them on where they get their data.