Blood selenium concentrations and high-grade prostate cancer

A 2012 meta-analysis and systematic review has shown an inverse association between plasma/serum selenium levels and prostate cancer advanced prostate cancer in particular. Denmark is in a low-selenium region of the world, and the Danish population as a whole has low selenium intakes and sub-optimal blood selenium levels. Danish researchers have, accordingly, investigated the association between pre-diagnostic selenium levels and the risk of total, advanced, and high-grade prostate cancer. Pictured here: the Dannebrog, Denmark’s national flag.

Higher blood selenium concentrations and higher blood selenoprotein P concentrations are significantly associated with reduced risk of high-grade prostate cancer [Outzen].

The researchers defined “advanced” prostate cancer as ≥T3 or with a Gleason-score ≥7.  They defined “high-grade prostate cancer” as cancers having a Gleason score equal to or greater than 8.

Furthermore, in survival analyses, a higher pre-diagnostic level of plasma selenium is significantly associated with a lower risk of all-cause mortality in prostate cancer patients [Outzen].

Selenium and prostate cancer in the “Diet, Cancer, and Health” cohort

These are the conclusions from an analysis of the data from the Danish “Diet, Cancer, and Health” cohort.  The cohort consists of 27,179 men living in the greater metropolitan areas of Copenhagen and Aarhus who were recruited into the study.  They were aged 50 – 64 years and had no previous record of cancer at the time of recruitment [Outzen].

In the follow-years, 784 men in the cohort were diagnosed with prostate cancer.  Of these 784 men, 525 men were diagnosed with advanced prostate cancer (Gleason score > 7). Of the 525 men with advanced prostate cancer, 170 men had high-grade advanced prostate cancer (Gleason score > 8) [Outzen].

Toenail selenium concentrations and blood selenium concentrations

In our last article, we summarized the inverse association between toenail selenium concentrations and the risk of advanced prostate cancer as seen in the Netherlands Cohort Study [Geybels].  Here, we summarize the results of a study of the association between blood selenium levels and the risk of prostate cancer.

Toenail selenium concentrations are important because selenium content in toenails reflects longer term exposure to selenium, e.g. six months to one year, whereas serum and plasma selenium concentrations reflect shorter-term exposure on the order of a few weeks. The overall picture from toenail selenium studies shows an inverse relationship between selenium levels and the risk of prostate cancer [Outzen].

Blood selenium concentration levels and prostate cancer

The Danish population has a relatively low selenium intake, which is typical of the Scandinavian region except for Finland where selenium fertilization of the soil has improved selenium intakes [Stoffaneller & Morse].

Generally, the mean European blood selenium levels lie in the range from 70 to 80 micrograms per liter.  The mean Danish population blood selenium levels are thought to lie in the range from 90 to 100 micrograms per liter.  By comparison, the median US blood selenium concentrations lie between 105 and 140 micrograms per liter [Outzen].

A meta-analysis of studies examining the relationship between serum/plasma selenium levels and the risk of prostate cancer has found a gradual decline in risk with increasing selenium levels from 60 to 170 micrograms per liter. The association within this range was even stronger for the risk of advanced prostate cancer [Hurst 2012].

A study designed to establish optimal selenium intakes showed that a daily intake of approximately 55 micrograms of selenium from food and 50 micrograms of selenium from supplements over a ten-week period can raise the plasma selenium levels https://www.ncbi.nlm.nih.gov/pubmed/20181815 as follows [Hurst 2010]:

  • From a baseline mean of 95.7 micrograms per liter plus/minus 11.5 micrograms per liter to 118.3 plus/minus 13.1 micrograms per liter for participants taking 50 micrograms of selenium daily
  • From a baseline mean of 95.7 micrograms per liter plus/minus 11.5 micrograms per liter to 152.0 plus/minus 24.3 micrograms per liter for participants taking 100 micrograms of selenium daily

The importance of selenoprotein P in selenium and prostate cancer studies

Selenium is an essential micronutrient.  We do not need much of it, but what we do need is important.

Selenium is seldom found unbound in the body.  For the most part, it is a component of the selenomethionine and selenocysteine.

As a component of selenocysteine, it becomes part of some 25 known selenoproteins, some of them with antioxidant properties, for example, the glutathione peroxidases and the thioredoxin reductases [Steinbrenner].

Selenoprotein P is the most prevalent selenoprotein in the blood.  Its function is to deliver selenium to the tissues.  As such, it is thought to be an optimal marker of functional selenium in the body.  The maximum concentration of selenoprotein P is thought to be found at plasma selenium levels between 90 and 125 micrograms per liter [Outzen].

Conclusion: selenium supplementation and prostate cancer

The available evidence points in the direction of selenium supplementation’s having a role in delaying prostate cancer tumor progression.

A review of 17 observational studies of the relationship between selenium and the risk of prostate cancer showed a significantly lower risk of prostate cancer [Vinceti 2014].

Among the interventional studies, the outcome is mixed because of the lack of significant results in the SELECT Trial.  Two factors may account for the lack of a positive outcome in this trial:

  • the study participants were men with quite high baseline blood selenium levels (135 micrograms per liter)
  • the study participants were given a synthetic selenomethionine supplement [Lippman].

In the Nutritional Prevention of Cancer study, however, men with considerably lower baseline blood selenium concentrations (113 micrograms per liter) were given a natural organic high-selenium yeast preparation containing many different species of selenium including selenomethionine.

Daily supplementation with 200 micrograms of the high-selenium yeast was associated with a 52% decrease in prostate cancer incidence [Clark].

In addition to its role as a cancer prevention agent, selenium has antioxidant, anti-inflammatory, and anti-viral properties realized through the activity of the various selenoproteins into which selenium is incorporated.

For example, daily supplementation of senior citizens with a combined 200 micrograms of a high-selenium yeast preparation and 200 milligrams of a patented ubiquinone Coenzyme Q10 formulation has been associated with significantly reduced risk of cardiovascular mortality, improved heart function, and better quality of life.

In this study, the KiSel-10 study, the combined supplementation was associated with significantly reduced levels of bio-markers for oxidative stress and inflammation [Alehagen].

Sources

Alehagen, U., Aaseth, J., & Johansson, P. (2015). Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens. Plos One, 10(12), e0141641.

Clark, L.C., Combs, G.F., Jr., Turnbull, B.W., et al. (1996). Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA, 276(24):1957-1963.

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.

Hurst, R., Armah, C.N., Dainty J.R., Hart, D.J., Teucher, B., Goldson, A.J., Broadley, M.R., Motley, A.K., Fairweather-Tait, S.J.  (2010).  Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr, 91(4):923-31.

Lippman, S.M., Klein, E.A., Goodman, P.J., et al. (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.

Steinbrenner, H., Speckmann, B. & Klotz, L.O. (2016). Selenoproteins: Antioxidant selenoenzymes and beyond. Arch Biochem Biophys, 1;595:113-9.

Vinceti, M., Dennert, G., Crespi, C.M., et al. (2014). Selenium for preventing cancer. Cochrane Database of Systematic Reviews, Issue 3. Art. No.: CD005195.

The information provided in this review article is not intended as medical advice and should not be used as such.

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