Selenium, vitamin E, soy, and prostate cancer prevention

A new Canadian study just reported in the Journal of Clinical Oncology has failed to find any significant benefit from the use of vitamin E, selenium, and soy protein supplements in the prevention of prostate cancer.

Fleshner et al. carried out a randomized, double-blind, Phase III trial of q combination of daily soy (40 g), vitamin E (800 IU), and selenium (200 μg) versus placebo in 303 men initially diagnosed with high-grade prostatic intraepithelial neoplasia (HG-PIN) at 12 Canadian centers.

HG-PIN is thought to be a precursor of prostate cancer. To be eligible for entry into this trial, patients had to have confirmed HG-PIN in at least one of two biopsies within 18 months of random assignment. Treatment was administered daily for 3 years. Follow-up prostate biopsies occurred at 6, 12, 24, and 36 months after randomization. The primary study endpoint was time to development of invasive prostate cancer.

The results of this study showed that:

  • The average (median) age of the patients at baseline was 62.8 years.
  • The patients’ median PSA level at baseline was 5.41 ng/ml.
  • The patients’ median total testosterone level at baseline was 13.4 nmol/l.
  • Invasive prostate cancer developed in 26.4 percent of patients.
  • The Gleason score distribution was similar in both groups of patients, and 83.5 percent of all cancers had a Gleason score of 6.
  • The risk of prostate cancer in patients receiving the nutritional supplements was not significantly different from the risk in patients receiving placebo (hazard ratio [HR] = 1.03).
  • The age, weight, PSA, and testosterone level at baseline did not predict for development of prostate cancer.
  • The nutritional supplement was well tolerated, with slightly more flatulence reported with greater frequency among men receiving micronutrients.

The authors conclude that this trial “does not support the hypothesis that combination vitamin E, selenium, and soy prevents progression” from HG-PIN to prostate cancer.

It should be noted that this study was only 3 years in length. As noted in a Reuters report about this trial, “The results don’t rule out that soy might be beneficial to those who eat it frequently for decades.” However, following the results of the SELECT study, reported in October 2008, there have now been two randomized trials showing that slenium and vitamin E fail to protect men from risk of prostate cancer.

5 Responses

  1. Strike two!

    Add the fish oil and you can take 1,200+ bucks a year out of your local supplement peddler’s pockets while doing no harm to your prostates. … I think it’s also getting to be time for some new editions of some very prominent prostate cancer books …

  2. I certainly agree, as I was on all three in high dosage a few years prior to cancer diagnosis (for something else, and they didn’t help that either).


    I’m sitting here as a patient who has never been enrolled in a medical course, observing at least one striking major flaw in another major North American study of selenium and vitamin E, this time with soy thrown into the mix. This follows not long after the profoundly flawed reports of the PLCO and ERSPC screening trials. Please help me understand what these prominent and respected researchers could have been thinking!

    I have read Sitemaster’s article above and the associated abstract, but not the full paper. The major concern I have is with the dose of vitamin E at 800 IU. I have looked three times just to make sure my eyes and mind are seeing that dose correctly, and they are. Why did they use that dose, which, as I understand it, is dangerously high according to published medical research indicating that there was a risk of excessive bleeding with a dose as high as 400 IU — just half the dose in the Canadian trial? My understanding, having read a number of articles and papers on the subject, is that the potential danger in the dose of vitamin E in the SELECT trial of 400 IU was the essential reason the SELECT trial was aborted. I’m going to be looking back to see when that happened, but I’m thinking it may have preceded the launch of the Canadian trial. Even if not, why did the Canadian trial continue after this problem with vitamin E became well known?

    I’m also wondering why that high dose was chosen, especially when earlier work suggested a benefit at just 50 IU.

    Another critical question, not covered in the abstract, is the form of vitamin E. Even before SELECT was launched the trialists were publicly defending the choice of alpha-tocopherol instead of gamma-tocopherol. Preliminary research was suggesting that gamma-tocopherol was potentially effective against prostate cancer, but that an excess of alpha-tocopherol was associated with depletion of gamma-tocopherol, potentially increasing risk of prostate cancer. I’m hoping that the Canadian trial at least was using gamma-tocopherol or a combination in which alpha-tocopherol was not predominant. Any insight there?

    I recall early research indicating that selenium and vitamin E interact. I’m wondering if the alpha-tocopherol form of vitamin E was used in the trial, and whether this could have derailed any benefit from selenium, and perhaps offset any benefit from soy.

    Regarding soy, after years with dwindling enthusiasm due to an absence of supportive research, Dr. Maha Hussain’s team found an apparent benefit in 2003, but at 200 mg daily. I have triple checked the dose in the Canadian study and have confirmed that the abstract shows a dose of 40 g! Wow! No wonder there was a flatulence issue, not to put too fine a point on it. Does anyone have insight into why such a high dose was used?

    These are my own immediate reactions, but I’m sure this paper will be receiving a lot more attention. I’m wondering if the Kantoff team’s research on a possible selenium benefit determined by genetics can be coupled with serum samples for this moderately large group of Canadian patients.

    For now, I’ll continue to take 200 IU of high gamma vitamin E daily, a dose which has never been associated with a concern with bleeding, 200 micrograms of Se daily, and a substantial dose of soy.

  4. With respect to selenium … At last year’s prostate cancer research symposium at UCSF, June Chan presented data suggesting that selenium can help or hurt depending on each man’s particular DNA. If deficient of a certain gene, a selenium supplement helps; if the gene is present, more can be detrimental.

    Her conclusion — we need to know our genetic make-up before using selenium.

  5. Jim,

    To me, I think it now is incumbent upon those that claim any of these supplements do work in the battle against prostate cancer to come up with evidence ~ other than opinion or anecdotal ~ to prove this claim. We can criticize all day long with what is wrong with the technical problems of these level 1 studies but the fact is that we have zero level 1 evidence they do anything at all for prostate cancer ~ other than maybe exacerbating the disease risk factors as shown in the selenium and Omega 3 trials (supplemented with fish oil). I don’t think some folks will accept any proof that they don’t help no matter what level of study proves they don’t. We really need to turn the table on those claiming it works and tell them to provide level 1 evidence proving the claim.

    With regards to Rick’s comment, it is possible that these things may work depending on genetic make-up but that is no reason for anyone to start slamming supplements with their POM juice. Just as genetics can open possibilities that some supplements do work, they also may cause problems depending on genetic make-up elsewhere in the human body. It is still a theory that has never been substantiated. Using the same logic, there are people that might have the right genetic make-up to benefit with these supplements for their prostate cancer ~ only to have another genetic make-up of their kidneys to not tolerate their long-term use, and to end up 10 years later on dialysis. This is just a possible example of playing the odds through genetics.

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