Selenium and the prevention of prostate cancer: meta-analysis

There are many risk factors associated with the development of prostate cancer: age, family history, geographic region, insulin growth factor, nationality, and race. One risk factor that merits investigation is the relationship between blood selenium concentrations and prostate cancer risk.

Quote: “Selenium most probably has a protective role against the development of prostate cancer and its progression to advanced stages. Therefore, selenium supplementation can be proposed for prevention of prostate cancer.”

These words are taken from the conclusion of a 2018 systematic review and meta-analysis of studies of the association between selenium and prostate cancer [Sayehmiri].

The meta-analysis is based on the data from 38 journal medical articles that included 36,419 prostate cancer cases and 105,293 healthy controls. There were 22 case-control studies, 6 cohort studies, and 10 randomized controlled trials included in the meta-analysis [Sayehmiri].

Selenium levels associated with risk of prostate cancer

The pooled relative risk from the 38 studies of the association of selenium concentration and prostate cancer risk showed a statistically significant 14% risk reduction with higher levels of blood selenium or toe nail selenium.

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The importance of the selenium dosage

The world has only scarce selenium quantities from which to create selenium supplements for people in regions that have selenium-poor soils and selenium-poor foodstuffs. Selenium is not recyclable. The annual world production of selenium goes mostly to industrial production: metallurgical, glass, electrical, pigmentation, use in batteries, and soil fertilization. There is hardly enough selenium left over for nutritional supplementation purposes even though it is an essential trace element that the human body cannot produce itself. Attribution: CC BY-SA 2.0 uk,

The other day, I saw an interesting question: how can we make this boring trace element interesting?

The reference was to selenium, the element in the periodic table with the atomic number 34.  As a component of the selenium-dependent selenoproteins, selenium has numerous biological functions in the body:

  • Antioxidant protection of the cells against harmful free radical damage
  • Counteraction of DNA mutation
  • Inhibition of chronic low-grade inflammation
  • Optimal production of thyroid hormones
  • Proper reproduction of cells
  • Protection of lymph channels and blood vessel walls
  • Reduced risk of certain types of cancer
  • Reduced risk of cardiovascular disease
  • Regeneration of the antioxidant forms of vitamin C, vitamin E, and Coenzyme Q10

And, yet, hardly anyone has heard about selenium as an important bio-nutrient.  No one ever has a blood test done to see if he or she has adequate plasma selenium concentrations.


Selenium Supplementation Dosages

As with so many things, the form and the dosage is of supreme importance.

Proper selenium dosage requires attention.

  1. Selenium intakes vary considerably from region to region, from culture to culture, and certainly from diet to diet.  It is difficult to get a handle on how much selenium we get from our food.
  2. The amount of selenium we get from our food depends on the soil where the food was grown.  Generally, Americans living on the East Coast and in the Pacific Northwest get less selenium in their food than do Americans in the middle of the country.  But even that depends on the composition of the meals that the individuals eat.
  3. Selenium is essential in small amounts; however, at excessively high levels, it can be harmful in the long run.
  4. The human body does not synthesize selenium itself.  Without adequate selenium in the diet and from supplements, there will not be enough selenium for incorporation into the amino acid selenocysteine. Selenocysteine is, then, a necessary component for the synthesis in the body of the 25 known selenoproteins.

The Functions of the Selenoproteins

At present, we know of 25 genes that code for the synthesis of selenoproteins in the body.

*** There are eight known glutathione peroxidases, many of which have important antioxidant protection functions in various compartments of the body.

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Selenium for preventing cancer

A Cochrane review is a systematic review of research results in a field of human health care or health policy. The review’s authors summarize and analyze the evidence from observational studies and randomized controlled studies. Observational studies are studies in which the predictor variable (the study participants’ exposure to selenium) is not under the control of the researchers. In randomized controlled studies, the predictor variable (supplementation of some of the participants with selenium) is under the control of the researchers even though they are commonly blinded until the end of the study from knowing which study participants are receiving the active substance instead of the placebo substance.

Observational studies show predominantly and consistently an inverse association between selenium exposure and the risk of some cancer types [Vinceti 2018; Cai 2016].  The evidence from some 70 observational studies indicates that higher levels of exposure to selenium are associated with lower levels of cancer incidence and mortality [Vinceti 2018]. What the observational studies haven’t shown thus far is a systematic pattern suggesting specific dose-response relationships.   [Vinceti 2018].

The evidence from observational studies also indicates that there may be a U-shaped form to the relationship between selenium exposure and disease risk. For example, one study suggests that the best serum selenium range for protection against prostate cancer is between 119 and 137 micrograms per liter [Chiang 2010]. A second study shows that the risk of prostate cancer decreases gradually as the selenium concentrations increase in the range from 60 micrograms of selenium per liter of plasma up to 170 micrograms per liter.  Above 170 micrograms per liter, the protection ceases [Hurst 2012].

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Selenium supplementation in the Su.Vi.Max. study

Depicted above (A): apoptosis in normal cell division with a damaged cell (2) and programmed cell death (1). Depicted below (B): cancer cell division with uninhibited cell production and increasingly more dangerous cell mutations. Selenium supplementation can help normal healthy adults who have low selenium status with cancer chemo-prevention benefits, thyroid function benefits, and cognitive function benefits.

The Su.Vi.Max. study —  SUpplementation en VItamines et Minéraux AntioXydants — was a big randomized, double-blind, placebo-controlled study carried out with typical French efficiency.  Even though I have written the name of the study in French, there are so many English cognates that I am sure you can read the full name of the study.

The study was designed to test the health benefits of daily supplementation with a number of vitamins and minerals at nutritional dosages (roughly, one to three times the daily recommended dietary intakes) [Hercberg 1998]:

  • selenium, 100 micrograms
  • vitamin C, 120 mg
  • vitamin E, 30 mg
  • beta-carotene, 6 mg
  • zinc, 20 mg

In particular, the French researchers wanted to see the effect of the daily supplementation over a long period, approximately 7.5 years, from 1994 to 2002, on the prevention of cancer and cardiovascular disease, both of which have been linked to oxidative stress and oxidative damage and might, therefore, be affected by supplementation with antioxidants.

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Selenium and oral cancer

Because many cancers take so long to develop, research studies with cancer as the endpoint require a long period of observation and are very expensive. Focus on intermediate endpoints such as bio-markers for the development of cancer are useful for assessing the value of  selenium supplements for cancer prevention. Pictured here: a histo-pathologic image showing squamous cell carcinoma in a biopsy specimen.

When we test the efficacy of selenium supplementation in the prevention of cancer, we often look at the effect of the selenium supplementation on bio-markers for the development of cancer.  Bio-markers are substances whose presence in blood or tissue indicates the concurrent presence of a disease or an infection.

An Indian (sub-continent) research study has shown that supplementation with selenium, zinc, riboflavin, and vitamin A significantly inhibits the development of bio-markers for oral cancers [Prasad].

Okay, because the selenium was administered as one component in a micro-nutrient cocktail, we cannot attribute the outcome solely to the selenium supplementation.  But it is a good bet that the selenium – through its incorporation into antioxidant selenoproteins – was a major factor in the beneficial health effects.  There is support for the idea that antioxidant supplements are effective cancer chemopreventive agents [Prasad].

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Properties of a high-selenium yeast preparation

The element selenium is seldom found alone and unbound. In the body, it forms a part of the amino acids selenomethionine and selenocysteine and functions as a component of some 25 selenoproteins. The high-selenium yeast used in nutritional supplements is produced by enriching Saccharomyces cerevisiae yeast (also known as baker’s yeast or brewer’s yeast) with selenium. As the yeast grows, it absorbs the selenium. The result is an organic high-selenium yeast that has a relatively good absorption and bio-availability. It provides several species of selenium that are necessary for many cellular functions in the body. The yeast in the high-selenium yeast tablets is dead. It cannot cause yeast infections.

The evidence from clinical studies shows that high-selenium yeast preparations give the best health outcomes [Alehagen; Blot; Clark; Yu].

Today, I want to look at the documented properties of the high-selenium yeast preparation that was developed for use in the PRECISE studies.  PRECISE is the acronym for PREvention of Cancer by Intervention with SElenium.  The PRECISE studies were designed to test the effectiveness of selenium supplementation at preventing cancer.

The preparation is also the high-selenium yeast preparation used in the KiSel-10 study of combined selenium and Coenzyme Q10 supplementation of healthy elderly citizens to protect against heart disease.  Professor Urban Alehagen and the researchers at Linköping University in Sweden have written about the special interrelationship between selenium and Coenzyme Q10: our cells need adequate selenium status to obtain optimal concentrations of Coenzyme Q10, and our cells need adequate Coenzyme Q10 status to realize optimal selenoprotein function [Alehagen].

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Serum/plasma selenium status and protection against cancer

In cancer prevention, there seems to be a U-shaped response to selenium supplementation. The threat of adversity is greater at the lower and higher levels of serum/plasma selenium. For example, Emily Chiang and her colleagues posit that the optimal serum selenium level for the reduction of prostate cancer risk is between 119 and 137 micrograms per liter. (Graph for illustration purposes only)

The documentation in various systematic reviews and meta-analyses of selenium and cancer studies shows a significant inverse association between selenium intake and/or plasma/serum selenium status and cancer [Lee; Hurst; Cai].

There is some evidence of a U-shaped relationship between plasma/serum selenium status and protection against cancer [Hurst; Rayman].  Low plasma/serum selenium status clearly correlates with higher risk of cancer.  High plasma/serum selenium status correlates with no increased protective effect against cancer.  The key is to find the supplement doses and subsequent plasma/serum status that give the best protection in between the two extremes.

Evaluating the evidence from published studies is complicated.  We need to remember that the following factors affect the relationship between selenium status and/or intake and cancer risk:

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Selenium and antioxidants in combination against cancer

Nothing is clear-cut, it seems.  Yes, we want to eat fruits and berries for their antioxidant content.  But, fruits and berries are full of the sugar called fructose.  So, like everything else, we need to eat fruits and berries in moderation.  In this report, I focus on studies of selenium and antioxidant combinations to prevent cancer.

On the topic of cancer and selenium as a cancer chemo-preventive agent, we know some basic facts from published research:

  • selenium prevents or delays tumor development in animals [Schrauzer]
  • regions with low selenium intakes are regions with higher incidence of cancer [Schrauzer]
  • greater exposure to selenium is associated with lower incidence of cancer [Cai]
  • single interventions with high-selenium yeast preparations reduce the incidence of cancer [Clark; Yu; Li]

What do randomized controlled studies reveal about the efficacy of selenium and antioxidant combinations against the development of cancerous tumors, I wondered.

The first studies to come to mind were the Linxian Nutritional Intervention Studies, which are probably just as important in the history of selenium and cancer research as Professor Larry Clark’s Nutritional Prevention of Cancer study is.

Professor Blot’s Linxian Nutrition Intervention Studies in China

The Linxian studies were a very big research undertaking.  The researchers enrolled 29,584 study participants aged 40 to 69 years from four Linxian County municipalities.  The study participants lived in a region of China characterized by constantly low intakes of selenium and by high cancer mortality rates.

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Selenium as a single intervention for cancer prevention

In many regions of the world, low soil selenium levels result in the production of low-selenium wheat.  Then, the milling and processing of the wheat results in 14% less selenium in wheat flour than is found in the raw wheat.  The combined result is decreased intakes of dietary selenium and increased risk of cancer. Studies show that supplementation with high-selenium yeast preparations in low-selenium regions has a cancer preventive effect.

On this blog site,, we focus on the health and nutritional benefits of selenium supplementation.  We look at the following types of studies:

  • human studies more so than lab studies or animal studies
  • intervention studies more so than observational studies
  • randomized controlled studies whenever possible

Cancer and Selenium as a single intervention agent

The best studies of selenium as a single intervention to prevent or treat cancer show significant results in regions with low selenium intakes and/or high cancer risk.

Professor Clark’s NPC study

The big breakthrough came when Professor Larry Clark published the results of the Nutritional Prevention of Cancer (NPC) study in the prestigious journal JAMA: The Journal of the American Medical Association.

The NPC study was a multi-center randomized, double-blind, placebo-controlled study carried out in a selenium-poor region of the southeastern United States.  The study participants who took 200 micrograms of a high selenium yeast preparation over an average 4.5-year period showed significant health benefits (as compared to placebo):

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Selenium and liver cancer: the Qidong study results

China is a country with many selenium-poor regions. The people living in these regions have paid the price with high rates of heart disease, bone disease, and various forms of cancer. Selenium supplementation has proven beneficial in China.

Some 50 years ago now, Chinese researchers began to understand the health risks associated with low selenium status.  Cross-sectional studies showed an association between low selenium concentrations in cereal grains, the low selenium status of local citizens, and the incidence of Keshan disease, a heart disease with high death rates.  The administration of selenium supplements in intervention studies resulted in significant reductions in the incidence of Keshan disease [Chen 2012].  Selenium status is one of the main factors contributing to the development of Keshan disease.

Selenium and Kashin-Beck disease
Not long afterwards, Chinese researchers realized that Kashin-Beck disease, a disease of the bone, is prevalent in regions of China and Tibet that are poor in selenium.  The researchers saw that a deficiency of selenium and iodine was a common factor Kashin-Beck disease regions [Yao 2011].

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