Prostate cancer risk and selenium status

Selenium supplementation and the risk of prostate cancer?  What do we know?  We need to be careful in interpreting the research results that we have (and we need more research), but, yes, there is evidence for an inverse association between prostate cancer risk and selenium status [Hurst 2012].

As of this writing (April 2017), the protective effect of selenium supplementation against prostate cancer seems to be found in a relatively narrow range of plasma selenium status [Hurst 2012].  Furthermore, there seems to be a U-shaped relationship between selenium status and protection against prostate cancer.

If the concentrations of selenium in the plasma are too low, there is increased risk of prostate cancer.  This is a serious concern in many regions of the world.

If the concentrations of selenium in the plasma are too high, the protective effect against prostate cancer is no longer seen to the same extent.

Critical range of selenium status for prostate cancer protection
The protective effect of selenium against prostate cancer occurs in the plasma selenium concentration range from 120 nanograms per milliliter to 170 nanograms per milliliter [Hurst 2012].

Plasma selenium concentrations below 120 nanograms per milliliter are very likely to be associated with increased prostate cancer risk. And, the protective effect of selenium begins to decline at plasma selenium levels above 170 nanograms per milliliter.

Dose-response meta-analysis of selenium and prostate cancer
The evidence for the critical range of plasma selenium status comes from a systematic review and dose-response meta-analysis of research studies of the relationship between selenium status and the risk of prostate cancer.  Dr. Hurst and Dr. Fairweather-Tait and their research colleagues at Norwich Medical School, University of East Anglia, in the United Kingdom analyzed the data from 12 research studies enrolling 13,254 participants and involving 5007 cases of prostate cancer [Hurst 2012].

Note: The researchers focused on the bio-markers of selenium status – plasma or serum or toenail concentrations – rather than on selenium intakes because it is very difficult to get accurate measurements of long-term total dietary intakes of selenium.  The data from food-frequency questionnaires, diet records, and diet histories are just not reliable enough.  Studies in which selenium concentrations in plasma or serum or toenails are measured produce more reliable data.

Large randomized controlled trials of selenium and prostate cancer
Whenever we talk about selenium and prostate cancer, we think first of the big randomized controlled trials:

• Nutritional Prevention of Cancer Trial (NPC Trial)
• Selenium and Vitamin E Cancer Prevention Trial (SELECT Trial)

Nutritional Prevention of Cancer Trial
The NPC trial showed a statistically significant protective effect of a daily dose of 200 micrograms of a high-selenium yeast preparation in selenium-deficient at-risk group of men [Clark 1998].  This is exciting news.  The protective effect of the selenium supplementation was seen in men with a selenium status below 123.2 nanograms per milliliter [Duffield-Lillico 2003].

SELECT Trial
The SELECT Trial differed from the NPC Trial in at least two important respects:

• The baseline selenium concentrations of the study participants in the SELECT Trial (men = 136 nanograms per milliliter) were much higher than the baseline selenium concentrations in the NPC Trial (mean = 114 nanograms per milliliter).
• The preparation used in the SELECT Trial was a synthetic selenomethionine preparation as contrasted with the organic high-selenium yeast preparation used in the NPC Trial.

The selenium supplementation, using a selenomethionine preparation, of the selenium-replete study participants in the SELECT Trial did not show a protective effect against prostate cancer [Lippman].

Other studies of selenium and prostate cancer
There have been two large cross-sectional studies that have revealed a definite association between low selenium status and increased risk of prostate cancer.

• One study was done in Denmark and included data from 27,179 male participants [Outzen 2016].
• The other study was done in the Netherlands and analyzed data from 58,279 male participants [Geybels 2013].

The systematic review done by Hurst et al covered the research published in the period 2005 to 2010.  A previous systematic review done by Dr. Etminan analyzed results from cohort studies and case-control studies published in the period 1996 – 2005.

The compiled results from 16 studies showed a 26% reduction in the risk of prostate cancer in individual with higher selenium status.  Dr. Etminan’s analysis showed that increases in selenium status caused by selenium supplementation had a pronounced protective effect against prostate cancer [Etminan 2005].

The form of the selenium supplementation
Dr. Etminan’s analysis showed that the form of the selenium supplement is an important factor in the protective effect of the selenium [Etminan 2005].  This conclusion was later confirmed in a comparison study done by Dr. Richie and Dr. el-Bayoumy [Richie 2014].

They compared the results of supplementation with high-selenium yeast tablets and selenomethionine tablets on bio-markers of prostate cancer.  They reported the following results:

• The decreases in the risk of prostate cancer were greatest in study participants with low baseline plasma selenium concentrations (less than 127 nanograms per milliliter).
• Supplementation with high-selenium yeast preparations was positively correlated with significant reductions in oxidative stress biomarkers.
• The use of synthetic selenomethionine preparations was not positively correlated with any significant reductions in oxidative stress biomarkers.

Dr. Richie and Dr. el-Bayoumy suggested that there must be selenium-containing compounds in the high-selenium yeast preparations that lead to the reduction in oxidative stress.  Selenomethionine alone did not result in a reduction in oxidative stress [Richie 2014].

Bottom line

• Selenium supplementation has a potentially protective effect against the development of prostate cancer.
• The research to date shows that the most beneficial form of selenium supplement cancer chemoprevention is the yeast-based high-selenium supplement, which is also called selenium-enriched yeast and selenized yeast.
• When the nutritional supplement has been properly formulated and prepared for retail sale, it will contain l-selenomethionine and some 30 other species of selenium [Larsen].

Sources

Clark, L. C., Dalkin, B., Krongrad, A., Combs, G. J., Turnbull, B. W., Slate, E. H., & Rounder, J. (1998). Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. British Journal of Urology, 81(5), 730-734.

Duffield-Lillico, A. J., Dalkin, B. L., Reid, M. E., Turnbull, B. W., Slate, E. H., Jacobs, E. T., & Clark, L. C. (2003). 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 International, 91(7), 608-612.

Etminan, M., FitzGerald, J. M., Gleave, M., & Chambers, K. (2005). Intake of selenium in the prevention of prostate cancer: a systematic review and meta- analysis. Cancer Causes & Control: CCC, 16(9), 1125-1131.

Geybels, M. S., Verhage, B. J., van Schooten, F. J., Goldbohm, R. A., & van den Brandt, P. A. (2013). Advanced prostate cancer risk in relation to toenail selenium levels. Journal of The National Cancer Institute, 105(18), 1394-1401.

Hurst, R., Hooper, L., Norat, T., Lau, R., Aune, D., Greenwood, D. C., & Fairweather-Tait, S. J. (2012). Selenium and prostate cancer: systematic review and meta-analysis. The American Journal of Clinical Nutrition, 96(1), 111-122.

Larsen, E. H., Hansen, M., Paulin, H., Moesgaard, S., Reid, M., & Rayman, M. (2004). Speciation and bioavailability of selenium in yeast-based intervention agents used in cancer chemoprevention studies. Journal of AOAC International, 87(1), 225-232.

Lippman, S. M., Klein, E. A., Goodman, P. J., Lucia, M. S., Thompson, I. M., Ford, L. G., & Coltman, C. J. (2009). Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA, 301(1), 39-51.

Outzen, M., Tjønneland, A., Larsen, E. H., Friis, S., Larsen, S. B., Christensen, J., & Olsen, A. (2016). Selenium status and risk of prostate cancer in a Danish population. The British Journal of Nutrition, 115(9), 1669-1677.

Richie, J. J., Das, A., Calcagnotto, A. M., Sinha, R., Neidig, W., Liao, J., & El-Bayoumy, K. (2014). Comparative effects of two different forms of selenium on oxidative stress biomarkers in healthy men: a randomized clinical trial. Cancer Prevention Research (Philadelphia, Pa.), 7(8), 796-804.

Disclaimer: The information reported in this article is not intended as medical advice and should not be used as such.