selenium and vitamin E may increase risk of prostate cancer

New study in JNCI attempted to sort out diverse findings on prostate cancer development in men supplemented with selenium or vitamin D or both.  (see prostate cancer selenium vit e jnci 2014 in dropbox, or DOI:10.1093/jnci/djt456).  Previous data has shown:

 

        --From the selenium and vitamin E cancer prevention trial (SELECT) in 2001, a prospective study of 35,533 men randomized to one of 4 groups (selenium 200 mcg/d plus vitamin E 400 IU/d, vitamin E plus placebo, selenium plus placebo, or just placebo),  there was no  benefit from these interventions, and a significantly increased risk of prostate cancer by 17% with vitamin E supplementation alone

        --The nutritional prevention of cancer trial (NPC), a study of 928 men who lived in an area of the US with low soil selenium levels, found that men with moderate or low selenium levels and given supplementation with selenium had a decrease in prostate cancer risk by 75%.  This was not found in men who had high plasma selenium levels at baseline. 

 

this current study was a cohort study comparing 1739 men with prostate cancer (489 with Gleason 7-10) from the SELECT trial with a randomly selected subcohort of 3117 men, also a from the SELECT trial.  They assessed whether selenium and vitamin E supplementation effect on prostate cancer was conditional on baseline selenium status.  Findings:

 

        --Toenail selenium levels at baseline was not associated with prostate cancer risk

        --Supplementation with selenium only or selenium plus vitamin E had no effect on prostate cancer in men with low baseline selenium levels in their toenails, but found a 91%  increased risk of high grade prostate cancer in men with a higher baseline selenium status.

        --Vitamin E supplementation alone had no effect among men with high selenium status at baseline, the but had an increased risk of prostate cancer by 63% (total, low-grade, and high-grade) in men with lower selenium baseline status.

        --When these investigators assessed the data using the cutpoints of the NPC trial above for baseline selenium concentrations, they could not reproduce any positive effect of supplementation. (though note that the NPC study was much smaller than the SELECT one).

        --a couple of caveats to the current study: Toenail selenium concentrations are  not a perfect measure of actual selenium absorption and metabolism, and does not measure the functional activity of selenium-dependent proteins in prostate and other tissues.  Also there were very few black patients involved in the SELECT trial.

 

So, bottom-line, supplementation with selenium and vitamin E did not help, and in certain groups (e.g. selenium supplementation in those with high baseline selenium levels, and vitamin E supplementation alone in those with low selenium levels) was associated with increased prostate cancer risk.  We do know from many different studies that good nutrition is associated with lower levels of heart disease and cancer.  However, we repeatedly find in the studies that micronutrient supplementation often does not reproduce these results, and in some cases (e.g. beta-carotene and lung cancer in smokers) is harmful.  The issue here, as I pointed out in many prior e-mails/blogs about micro-nutritional supplementation, is that there is likely an important  interplay between the different nutritional components to foods as well as a balance of the amounts of each one, and there is been a long evolutionary history of humans consuming an array of appropriate vegetables, for example, which provide the appropriate mix.  The reductionist approach of trying to isolate specific micronutrients as a magic bullet to prevent disease and then supplementing with a supraphysiologic dose is therefore both conceptually problematic and typically clinically unsuccessful (with the possible exception to vitamin D, which is not largely nutritionally-derived, and deficiency may well create problems in those in untoward northern climates).