Darryl mentioned SELECT recently, in the context of being careful what we put into our mouths. I might add that researchers should be careful how they spend their money.
& SELECT was expensive. 35,533 men for a planned 12 year intervention trial.
Four arms: 200 µg/day L-selenomethionine &/or 400 IU/day of all rac-α-tocopheryl acetate, or placebo.
"supplements were discontinued ... at a planned 7-year interim analysis because the evidence convincingly demonstrated no benefit from either study agent"
"Potential limitations of SELECT include that it did not test different formulations or doses of selenium and vitamin E and that it did not definitively assess results in subgroups of men who may have responded differently than did the overall population. Because of active annual screening with PSA and DRE and early detection, SELECT could not assess effects in reducing advanced or fatal prostate cancer, which recent data suggest may be a potential benefit of vitamin E and selenium. SELECT also could not assess intervention effects in a population deficient in vitamin E and/or selenium (since our trial population was well-nourished at baseline)".
When I first reviewed the selenium-PCa literature in 2004, I was struck by the fact there appeared to be no dose advantage once one had risen above deficiency.
In a 2000 U.S. paper [2]:
"The association between selenium and prostate cancer risk was in the protective direction with individuals in the top four fifths of the distribution having a reduced risk of prostate cancer compared with individuals in the bottom fifth".
The wording is significant. Normally, extreme quintiles would be compared, but Q2 was as good a place to be as Q5.
Mark Moyad, commenting on SELECT in 2002 [3], made this comment about previous studies:
"Selenium supplements provided a benefit only for those individuals who had lower levels of baseline plasma selenium. Other subjects, with normal or higher levels, did not benefit and may have an increased risk for prostate cancer."
More recently (Jan [04]):
"In this paper, we summarize the translational significance of research results gained from dog studies on selenium and prostate cancer risk. Our discovery of a U-shaped dose-response between toenail selenium concentration and prostatic DNA damage in dogs remarkably parallels data on the relationship between selenium status and prostate cancer risk in men. Notably, the dog U-curve provides a plausible explanation for the unanticipated increase in prostate cancer incidence among men with highest baseline selenium who received selenium supplementation in the largest-ever prostate cancer prevention trial (SELECT)."
The distribution of selenium in the soil varies tremendously. Americans are fortunate, in that a food staple - wheat - is grown in selenium-rich soil. This is also true for Canadian wheat. When the U.K. entered the Common Market 45 years ago, it switched to European wheat which is low in selenium.
"It is generally recognised that Se intakes across Europe are low, reflecting inadequate soil levels, particularly in Eastern Europe. Se intake in the UK has declined since the 1970s, and previous government surveys indicate low Se intake across a wide age range of the UK population". [5]
IMO, SELECT results for selenium would have been quite different had it been conducted in the U.K.
Instead, "our trial population was well-nourished at baseline".
Why plan a massive intervention study for a nutrient, knowing that the population is predominantly not deficient? What benefit might be expected?
One half of the 35,533 men received 200 µg/day L-selenomethionine regardless of their selenium status - regardless of whether they were already supplementing.
The small percentage of deficient men were likely to benefit, but men with a high intake of selenium might have been put at risk.
I have a pet peeve about selenomethionine. Methionine is an essential amino acid & selenomethionine will readily be used by the body when making protein. "the substitution of methionine with selenomethionine may have only a limited effect on protein structure and function. However, the incorporation of selenomethionine into tissue proteins and keratin in horses causes alkali disease." Perhaps it doesn't matter, but how does one determine a therapeutic dose of selenomethionine when the supplement is being hijacked for protein building?
Note that PCa cells want to be hypermethylated. When this happens, the promoter regions for tumor suppressor genes become silenced. Methionine is an important source of methyl. I would be inclined to avoid selenomethionine. Although it is inorganic, I prefer sodium selenite.
-Patrick
[1]
[2] ncbi.nlm.nih.gov/pubmed/111...
[3] ncbi.nlm.nih.gov/pubmed/119...
[4] ncbi.nlm.nih.gov/pubmed/293...
My father was selected it in the Lu-177 trial 
Iodine as a Prostate Cancer Preventative
Vitamin E for hot flashes?
Selective Cancer Cell Killing and Tumor Suppression? (article)
