Selenium and Chemoprevention: What Did We Learn About Nutrient Status?
Often in science, different people look at the same data and walk away with different conclusions and interpretations, and the subsequent debate is what often leads to discovery and insight. Two publications released in the Journal of the National Cancer Institute on the relationship between selenium and prostate cancer are examples of this continued debate. What can we learn from these reports?
First off, the report by Kenfield and colleagues used data from the Health Professionals Follow-Up Study to examine the relationship between selenium supplement use following prostate cancer diagnosis and the risk of recurrence and mortality related to prostate cancer. In short, they found that high-dose supplementation (≥140 mcg/day) was associated with an increased risk of prostate cancer mortality in these patients. While it should be noted that this report can’t prove causality, if you were recently diagnosed with prostate cancer it might be best to hold off on taking a selenium mega-dose (to put this in perspective, the current RDA for adult men and women is 55 mcg/day, nearly 1/3 of the intake associated with adverse events in this study).
In an accompanying editorial entitled “Learning From History in Micronutrient Research”, Drs. Theodore Brasky and Alan Kristal take us through the often confusing history of nutritional chemoprevention research. They state “there is reasonable agreement on the intakes of micronutrients that are required to prevent clinical manifestations of deficiency and on intakes high enough to cause acute toxicity, but optimal micronutrient intakes are likely within narrow ranges between these two extremes…”. They go on to note the often confusing results of selenium chemoprevention trials and use these results as a case study for the risks of using nutrients in this regard. Ultimately, they conclude that use of selenium supplements above the current RDA should be discouraged, based on the results of the Kenfield et al. report and other previous trials (despite the fact that the Kenfield report involves prostate cancer patients rather than a healthy population so it’s not very appropriate to blend the results of trials from these heterogeneous populations together, but I digress).
In certain respects, I agree with Drs. Brasky and Kristal. Regular readers of Talking Nutrition are probably well aware of our stance on the importance of nutrient status, and why it is important to be aware of status both when considering the impact of nutrition interventions. Nutrition interventions, whether on a personal health level or in clinical trials, will only benefit those who need it. Rarely do you find a “one-size fits all” solution.
The abridged version of the selenium and prostate chemoprevention story is that supplementation trials have shown potential benefit for those who started with low selenium status, and a potential harm for those who already had adequate or high selenium status. In sum, the data suggests that we should aim to achieve an optimal selenium intake (and status) to maximize the health benefit associated with specific nutrients – selenium is no exception. In this respect, I am in complete agreement with Drs. Brasky and Kristal.
Where we differ is the latter half of their argument – that because of this potential for harm among those with high status, supplementation should be discouraged, particularly in the case of selenium. If you take the results of the Nutritional Prevention of Cancer (NPC) trial as gospel – that selenium supplementation significantly reduced prostate cancer among those with low selenium status (<123.3 ng/mL) – then this could have implications for a large part of the population. According to data from NHANES, approximately 25% of the US population has plasma selenium concentrations below a similar threshold (124 ng/mL). Meaning that 1 out of 4 males may stand to benefit from increasing their selenium intake through dietary changes or supplementation.
I believe the history of micronutrient research – and selenium research in particular - teaches us three big lessons. First is that the biggest determinant of a nutrient’s effect is an individual’s nutrient status. Second, nutrients aren’t necessarily going to provide a health benefit every person (especially if they have already been diagnosed with a major chronic disease like prostate cancer). And third, more of a nutrient isn’t always better than some. Let the debate continue.
Brasky TM, Kristal AR. Learning from history in micronutrient research. J Natl Cancer Inst 2015; (epub ahead of print).
Kenfield SA, et al. Selenium supplementation and prostate cancer mortality. J Natl Cancer Inst 2015; (epub ahead of print).
Duffield-Lillico AJ, et al. Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial. BJU Int 2003; 91(7): 608-612.
Laclaustra M, et al. Serum selenium and serum lipids in US adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004. Atherosclerosis 2010; 210(2): 643-648.
Author’s Note: A personal pet peeve is when people state or insinuate that the dietary supplement industry is unregulated. Brasky and Kristal state “Given the high prevalence of [dietary supplement] use, it is disappointing that the sale of supplements is ‘regulated’ under the ironically titled Dietary Supplements Health [And] Education Act (DSHEA) of 1994”. Dietary supplements aren’t “regulated” – dietary supplements are regulated. Period. There are no caveats to that statement. No finger quotes. No asterisk. No subheading. No exceptions. In the future, I would encourage interested parties to review the rules and regulations stipulated in DSHEA and subsequent guidance documents put forth by the FDA (and also by the FTC) for information, rather than simply relying on a second hand account of dietary supplement regulations stated in a commentary article.