Selenium and prostate cancer: the toenail evidence

Meta-analyses have shown an inverse association between plasma/serum selenium concentrations and the risk of prostate cancer. The same inverse association has also been seen in three high-quality studies of toenail selenium concentrations and the risk of prostate cancer. The data from the Netherlands Cohort Study clearly show that higher toenail selenium is associated with significantly reduced risk of prostate cancer.

Analysis of data from the Netherlands Cohort Study shows that higher toenail selenium concentrations are associated with a substantial reduction in the risk of advanced prostate cancer.  Men in the highest quintile of toenail selenium had a statistically significant (p=0.001) 63% reduced risk of advanced (stage III-IV) prostate cancer compared to men in the lowest quintile of toenail selenium [Geybels].

Men in the highest quintile of toenail selenium concentrations had a toenail selenium level higher than 0.617 micrograms of selenium per gram of toenail.  Men in the lowest quintile of toenail selenium concentrations has a toenail selenium level lower than 0.469 micrograms of selenium per gram of toenail [Geybels].

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Selenium supplementation and insulin resistance: a clinical study

The latest clinical evidence shows that selenium supplementation of older adults with 200 micrograms of a high-selenium yeast preparation for up to three years does not adversely affect pancreatic beta-cell function or insulin sensitivity.

Results from a clinical trial comparing 200 micrograms of selenium supplementation with placebo supplementation show no effect of the selenium supplementation on measures of insulin secretion and insulin action [Jacobs]. 

These results can be regarded as important evidence that selenium supplementation for up to three years in older individuals has no diabetes causing effects in humans [Jacobs].

The researchers who conducted the selenium and insulin resistance study concluded that the results of the study do not show a causal role for selenium in the development of insulin resistance or in the development of type-2 diabetes [Jacobs].

Research design of the selenium and insulin resistance study

Background: In 2016, researchers at the Arizona Cancer Center in Tucson reported on the results of the Selenium Trial [Thompson].

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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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Circulatory selenium concentrations and Alzheimer’s disease

Brain tissue produces many free radicals (reactive oxygen species). The oxidative stress caused by an imbalance between potentially harmful free radicals and antioxidants to neutralize them is associated with ageing and with the onset of Alzheimer’s disease. Reduced levels of the selenium-dependent antioxidant enzyme glutathione peroxidase correlate strongly with cognitive decline and the risk of Alzheimer’s disease.

Blood selenium concentrations are significantly lower in patients with Alzheimer’s disease compared to healthy controls.  This reduction in selenium concentration is directly associated with the observed reduced levels of the important antioxidant selenoprotein, glutathione peroxidase, in Alzheimer’s disease patients.

These are the conclusions of the authors of a 2017 meta-analysis of 12 case-control studies of selenium concentrations in Alzheimer’s disease patients and healthy controls.  The 12 case-control studies comprised 594 Alzheimer’s disease patients and 472 healthy controls [Reddy].

Selenium and Alzheimer’s disease meta-analysis

The results of the systematic review and meta-analysis revealed the following associations:

  • Significantly decreased selenium levels were seen in the blood circulation of Alzheimer’s disease patients as compared to healthy controls.
  • Decreased selenium levels were also seen in the red blood cells and cerebrospinal fluid of Alzheimer’s patients as compared to healthy controls.  However, the difference in selenium concentrations did not reach the level of statistical significance.
  • Age matching between the Alzheimer’s disease patients and healthy controls showed decreased selenium levels regardless of the age of the patients.  This is interesting because advanced age is considered a risk factor for Alzheimer’s disease.
  • Controlling for socio-economic, geographical, and environmental differences also showed the decreased selenium levels in Alzheimer’s disease patients compared to the healthy controls.
  • A direct association was seen between decreased selenium levels and glutathione peroxidase levels in Alzheimer’s disease patients.

What is glutathione peroxidase, and why is it important?

The glutathione peroxidases (abbreviated GPx) are a family of antioxidant enzymes (selenoproteins) that reduce and thus neutralize potentially harmful radicals like hydrogen peroxide and lipid hydroperoxides.  In so doing, the GPx enzymes lessen the extent of oxidative stress damage.

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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, https://commons.wikimedia.org/w/index.php?curid=717159.

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.

Strange.

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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Low serum selenium levels and increased cardiovascular mortality

A recent study has found a relatively high mortality risk in elderly Swedish subjects with low selenium status. Supplementation with a high-selenium yeast supplement and a Coenzyme Q10 supplement for four years resulted in significantly reduced risk of death from heart disease, better maintained heart function, and better quality of life for senior citizens. The beneficial effect of the supplementation has persisted through the 12th year of follow-up.

Low plasma/serum selenium concentrations are associated with increased risk of death from heart disease and increased risk of death from all causes.  Professor Urban Alehagen and a team of researchers at Linköping University in Sweden have investigated the relationship between low selenium levels and the risk of heart disease.

Selenium supplements suggested for adults with very low Se levels

The Swedish study shows that adults with a serum selenium concentration below 57 micrograms per liter are at significantly higher risk of death from all causes (43% increased risk) and death from heart disease (56% increased risk) [Alehagen 2016].
57 micrograms of selenium per liter of serum.  Wow!  That’s low.

These significant associations remained solid even after the researchers had adjusted for the effects of possibly modifying factors:

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Long-term health protection of Selenium and Coenzyme Q10

The KiSel-10 study was done in Sweden, which is known to have selenium-poor soil and selenium-low foodstuffs. Consequently, daily supplementation with 200 micrograms of a high-selenium yeast preparations was appropriate. In geographical regions with higher levels of selenium in the soil and in the food, lesser selenium dosages may be needed. Selenium is an essential micro-nutrient, it has known antioxidant functions in the body, and it is associated with good thyroid health and good immune system defense.

Combining high-selenium yeast and Coenzyme Q10 supplements gives elderly people in low selenium regions good protection against heart disease.  That seems to be the take-home lesson from a 12-year follow-up analysis of the Swedish KiSel-10 study [Alehagen 2018].

Protective effects of selenium and CoQ10 persist 12 years

Originally, Professor Urban Alehagen and researchers at the University in Linköping enrolled 443 elderly Swedish citizens who were living in a community in which selenium intakes in the food were known to be low. They randomly assigned the study participants to take a combination of 200 micrograms of selenium in a high-selenium yeast tablet and 200 milligrams of Coenzyme Q10 daily or to take matching placebos.  The supplementation study lasted for four years [Alehagen 2013].

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Regional, age, and sex differences in serum selenium status

Selenocysteine is the 21st amino acid. The trace element selenium plays its important biological roles in the body as a component of selenocysteine. Selenocysteine is found in at least 25 selenoproteins including selenoprotein P and the various glutathione peroxidases, thioredoxin reductases, and iodothyronine deiodinases.

The results of clinical studies give us an estimate of what an individual’s optimal serum or plasma selenium status is.

  •  Plasma selenium status below 100 micrograms per liter  – also expressed as 100 nanograms per milliliter – is generally regarded as sub-optimal plasma selenium status [Hurst 2010].
  • Plasma selenium status of at least 110 – 118 micrograms per liter is considered necessary for the optimal expression of selenoprotein P [Hurst 2010]. 
  • Letsiou et al [2014] set the lower limit for optimal selenoprotein P activity at 120 micrograms per liter or higher.
  • Plasma selenium status of 120 up to 170 micrograms per liter is considered necessary for reducing the risk of prostate cancer [Hurst 2012].
  • Studies show that there are sex and age differences in the absorption and distribution of selenium taken in from the diet and from supplements [Letsiou 2014; Galan 2005].

Note: The Mayo Medical Laboratories report serum concentrations of 70 to 150 micrograms per liter as the adult reference range for residents of the United States.  The mean population serum concentration is 98 micrograms per liter [Mayo], but, remember, depending on the range and standard deviation of the data, the mean can be very little useful. The important thing about the United States is that there is regional variation in selenium intakes and status. See below.

Selenium intake and selenium status

The primary sources of selenium are the diet and supplements. The human body does not synthesize selenium.  It is difficult to calculate accurately how much selenium an individual gets from food.  It can also be difficult to know precisely how much selenium an individual absorbs from a supplement because of the variation in the form and formulation of the selenium supplements on the market.

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Serum selenium status and gestational diabetes

The prevalence of gestational diabetes varies from region to region of the world from below 5% of pregnancies to below 10% to as high as 20%. Gestational diabetes increases the risk of type 2 diabetes and metabolic syndrome for the mother and increases the risk of acute and long-term adverse metabolic disorders in the offspring. A recent meta-analysis reveals that women with gestational diabetes typically have significantly lower serum selenium concentrations.

Typically, the serum selenium concentration levels are significantly lower in women with gestational diabetes than in healthy pregnant women.  The differences are especially remarkable in non-Caucasian pregnant women and in pregnant women in the third trimester.  That is the finding of a recent meta-analysis and systematic review of the relevant literature from observational studies [Kong 2016].

Selenium and gestational diabetes

Gestational diabetes is defined as any degree of glucose intolerance that occurs with the onset of pregnancy.  A physiological insulin resistance beginning in the second trimester and progressing through the third trimester is fairly typical of pregnancies.  Expecting mothers generally need increased insulin secretion to maintain normal blood glucose levels.  Impairment of the needed compensatory increases in insulin secretion leads to a diagnosis of gestational diabetes [Kong 2016].

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The formulation of the high-selenium yeast supplement

Baker’s yeast, the yeast that feeds on sugars in flour and releases the carbon dioxide that makes the bread rise, that is the same yeast that the selenium is organically bound to in the production of high-selenium yeast supplements. In the production process, the selenium is  incorporated into selenium compounds: selenomethionine, methylselenocysteine, selenocysteine and numerous other organic selenium species. The high-selenium yeast supplement gives the best absorption, the best retention, and the best antioxidant, chemopreventive, and immunomodulating support.

We want stability, safety, and bio-availability from our selenium supplement.  The high-selenium yeast supplement – also known as the selenium-enriched yeast supplement – is the best formulation to achieve these goals.

High-selenium yeast supplements are produced using the selenium that has been grown with Saccharomyces cerevisiae yeast (baker’s yeast).  Those of us who take a daily high-selenium yeast supplement know that the yeast used in the making of the supplement is dead.  The yeast cells cannot get into our bodies and multiply because they are not alive.

Various forms of selenium supplements

There are both inorganic and organic forms of selenium in commercially available selenium supplements.  There are supplements made with inorganic forms containing selenium salts like sodium selenite and sodium selenate.  Their absorption is not nearly as good as the absorption of the best organic selenium-enriched yeast supplements.

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