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, 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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Selenium in combination with Coenzyme Q10

Selenocysteine, C3H7NO2Se, is known as the 21st amino acid. It contains selenium as a component. It is a constituent part of the 25 known selenoproteins and selenoenzymes found in the human body. The selenoproteins, in turn, play an important role in the body’s defense against cancer, cardiovascular disease, and neurodegenerative disease.

Selenium is an essential micronutrient for us humans.  It is a component of the selenoproteins that we need for antioxidant protection and for good immune system function.  The selenoproteins glutathione peroxidase, thioredoxin reductase, and selenoprotein P are arguably the most important selenoproteins [Alehagen 2014].

Variability of selenium content and intakes

The soil content of selenium and, thus, the dietary intake of selenium varies considerably around the world.  Consequently, the need for selenium supplementation differs from region to region of the world.  Generally, selenium intakes are lower in Europe than in the United States; there is, however, also considerable variation within the United States.  The safest thing to do is to get a plasma or serum selenium concentration test done.

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Low serum selenium status and increased mortality

Too few studies have investigated the relationship between low serum selenium status and negative health effects. Professor Urban Alehagen from Linköping University in Sweden has published the results of a study showing that low serum selenium status is significantly associated with increased cardiovascular and all-cause mortality.

During an almost seven-year follow-up period, elderly healthy Swedish citizens with low serum selenium concentrations had significantly increased cardiovascular mortality and total mortality rates compared to contemporaries with higher serum selenium concentrations.  Specifically, there was a 56% increased risk for cardiovascular mortality and a 43% increased risk for all-cause mortality.  Accordingly, the Swedish researchers suggested that selenium supplementation should be recommended to all Swedish citizens with a serum selenium concentration below 57 micrograms per liter [Alehagen 2016].

In fact, Professor Urban Alehagen and his team of researchers at Linköping University pointed out that the average serum selenium concentrations observed in the study of elderly Swedish citizens – 67.1 micrograms per liter – is not sufficient to achieve optimal function of the important selenoproteins that require selenium as a component [Alehagen 2016]:

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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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