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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Selenium and statin medications and selenoproteins

Adequate synthesis of several selenoproteins – including the various glutathione peroxidases and thioredoxin reductases and Selenoprotein P – is important for the anti-oxidative defense of the cells. Professor Urban Alehagen and a group of Swedish researchers observed significantly reduced death from heart disease in a 10-year follow-up of healthy elderly study participants who were given four years of combined high-selenium yeast and Coenzyme Q10 supplementation.

In a recent article on the web-site q10facts.com, I have posted a summary of an article in which researchers discuss the various ways in which statin medications may increase patients’ risk of atherosclerosis and heart failure.  Yes, the Japanese and American researchers say, the statin medications do lower cholesterol levels [Okuyama].  

But, the guidelines for the use of statin medications need to be re-examined.  The researchers say: There has been a remarkable increase in the incidence of heart failure in the same period that statin medications have been used [Okuyama].

Furthermore, there are known mechanisms by which statin medications could be causing an increase in the incidence of atherosclerosis and heart failure.

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Mercury’s neurotoxicity and disruption of selenium biochemistry

The brain is particularly vulnerable to oxidative damage in the absence of adequate antioxidant selenoprotein protection for a variety of reasons: the brain has limited antioxidant enzyme pathways, the brain has high iron content, and the brain contains many long-chain polyunsaturated fatty acids, which are vulnerable to lipid oxidation. Oxidative damage to the brain results in structural and functional damage to brain cells and tissues. A selenium yeast supplement has proven effective at reducing the levels of bio-markers of lipid peroxidation and oxidative damage to DNA. An exclusively selenomethionine supplement was not effective [Richie 2014].
Selenium containing antioxidant selenoproteins play an important role in the prevention and reversal of oxidative damage in the brain.  This role has generally been underestimated in studies of the toxicity of elemental mercury and methylmercury.  The common understanding has been that selenium helps to prevent mercury toxicity by binding with mercury and rendering the mercury inactive.

This chemical binding and inactivation of mercury does take place.  Mercury has a great affinity for selenium, estimated to be approximately one million times stronger than mercury’s affinity for sulfur.  So, selenium’s binding with mercury in the tissues does keep the mercury from getting into mischief in the brain and spinal cord, peripheral nervous system, and endocrine system.

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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 and Coenzyme Q10 and heart protection

Healthy aging is the goal of us all. We want to remain physically active and mentally alert as long as we can. A study of the supplementation of elderly Swedish citizens has shown that daily supplementation with high-selenium yeast tablets and Coenzyme Q10 capsules significantly reduced the rate of death from heart disease. Depicted here: symptoms of heart attack.

Leading cardiologists in Sweden conducted a four-year study — the KiSel-10 study — of 443 of the elderly Swedish citizens and found that a prophylactic treatment with 200 micrograms of high-selenium yeast and 200 milligrams of Coenzyme Q10 daily reduces the risk of dying from heart disease by over 50 per cent.  This is an immensely interesting study result because heart disease is the number one killer in Western countries.

The KiSel-10 Study

The KiSel-10 clinical trial — a randomized, double-blind, placebo-controlled study–  investigated the effect of a combination of high-selenium yeast tablets and Coenzyme Q10 capsules, as compared with matching placebo capsules and tablets, on the following outcomes:

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