Selenium intakes and type-2 diabetes

In many regions of the world, it may not be possible to get an optimal amount of selenium from meals. The content of selenium in our food depends on the availability of selenium in the soil. Known selenium-poor areas are found in much of Europe and the Middle East, China, Korea, Japan, and New Zealand. In the United States, the coastal areas tend to have lower selenium content than the middle of the country does.

In 2013, Dr. Margaret Rayman, University of Surrey, United Kingdom, reviewed the published reports of randomized controlled trials in which a selenium supplement had been used as a single-agent treatment option and in which there had been a follow-up or sub-group analysis of the effect of the selenium supplementation on the risk of type-2 diabetes.

Dr. Rayman found 5 such studies.  I want to summarize Dr. Rayman’s review, and then I want to see what studies have been done since 2013.

Selenium and diabetes studies
Nutritional Prevention of Cancer (NPC) study
In 2007, Dr. Saverio Stranges published the results of a post hoc analysis of the data from the Nutritional Prevention of Cancer study.  In the NPC study, supplementation for an average of 4.5 years with 200 micrograms of a high selenium yeast preparation resulted in significant reductions in the risk of lung cancer, colon cancer, and prostate cancer [Clark 1996].  The age of most participants in the study was 63 years, plus or minus 10 years.

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Selenium and HIV and opportunistic infections

Individuals infected by the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) commonly have low selenium status. Selenium supplementation can prevent or delay the decline of immune system function and can protect against opportunistic infections.

Selenium supplements – especially selenium supplements as a component of a multi-micronutrient cocktail – can help to delay the decline of the immune system and can reduce the risk of death in HIV-infected patients.  Most of the data that we have comes from randomized controlled studies carried out in African countries, but the results are relevant to the United States and Europe.  Moreover, the results from studies of HIV-infected patients speak to the issue of the anti-microbial protection and antioxidant protection that comes with adequate selenium status.

Selenium and HIV and CD4 counts
CD4 cells are white blood cells that are part of the immune system.  Specifically, the CD4 cells fight infections in the body.  The HIV virus kills CD4 cells.  When a person has fewer CD4 cells, he or she is at greater risk of contracting an infection.

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Selenium and the risk of pre-eclampsia

Pre-eclampsia is a serious condition that causes high blood pressure in pregnant women who did not have high blood pressure prior to their pregnancies. The high blood pressure typically develops after the 20th week of pregnancy. Research studies show that a daily selenium supplement can reduce the risk of pre-eclampsia.

There is a clear relationship between a pregnant woman’s selenium status and her risk of pre-eclampsia.   Observational studies show that low selenium status is associated with a greater risk of pre-eclampsia.  Studies of selenium supplementation have shown reduced incidence of pre-eclampsia [Xu].

What is pre-eclampsia?
Pre-eclampsia is a complex condition characterized by the onset, around week 20 of the pregnancy, of the following symptoms:

  • abnormally high protein levels in the urine (indicating possible damage to the kidneys)
  • systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg when measured twice with an interval of at least 4–6 hours and not more than 7 days apart [Uzan]
  • severe headaches
  • blurred vision
  • decreased platelet levels in the blood [Mayo Clinic]

Pre-eclampsia seems to be caused by an abnormal development of the new blood vessels that are needed to carry blood to the placenta.  The new blood vessels are narrower than they should be, and they respond differently to hormonal signaling [Mayo Clinic].

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Selenium and male infertility

The selenium containing selenoprotein glutathione peroxidase 4 (GPx4) is present in sperm cells at surprisingly high levels. Biochemists say that GPx4 carries out two functions in sperm cells. It protects the developing sperm calls against oxidative damage caused by toxic peroxides, and it contributes later to the structural integrity of the mature sperm cells [Strauss].
Here is a little-known fact.  Human testicles contain high concentrations of one of the important selenium containing antioxidant enzymes, the selenoprotein glutathione peroxidase number 4 (GPx4).  Furthermore, the testicles have special receptors for another of the important selenoproteins, the selenoprotein P [Rayman 2012].

Adequate intakes of selenium for the synthesis of the selenoproteins are necessary to produce mature and viable sperm.  The selenoprotein GPX4 seems to be indispensable:

  • to the development and maturation of the sperm cells
  • to the antioxidant protection of the sperm cells
  • to the structural cohesiveness of the sperm cells
  • to the motility and viability of the sperm cells [Foresta]

Selenium and semen quality
What are we talking about here?  Let’s define some terms that are relevant to male fertility.

Our bodies produce semen by combining sperm cells from the testicles with various fluids from the seminal vesicles, the prostate, and the two small glands called Cowper’s glands.  The semen needs to contain high counts of sperm cells – perhaps 200 million plus – and needs to contain sperm cells capable of good motility if one of the sperm cells is to succeed in reaching and fertilizing the mature female egg.

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Selenium and thyroid disorders

The thyroid is the little endocrine gland at the base of our necks.  It produces hormones that affect nearly every organ in our bodies.  Specifically, the thyroid hormones regulate our cells’ metabolism. Both iodine and selenium are needed in adequate amounts for optimal thyroid functioning.

Iodine is an essential component of the thyroid hormones.  After iodine, selenium is arguably the micronutrient most important to the thyroid gland. Proportionally, there is more selenium in the thyroid gland than there is selenium in any other organ in the body. There are good reasons for the presence of selenium in the thyroid gland.  Iodine and selenium are both required for thyroid hormone synthesis and function.

Our bodies do not make selenium. We must get the selenium that we need from our food and from supplements. The selenium that we absorb is incorporated into the amino acid selenocysteine. Selenocysteine, then, is a necessary component of some 25 selenoproteins that are needed for various biological functions.

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How much selenium every day?

Yes, good health depends on good genes. But it also depends on good diet, good exercise, good sleep, and adequate intakes of essential bio-nutrients such as selenium and Coenzyme Q10.

The proper daily dosage of selenium for normal people?   Normal people?  How many of us are approximately normal?  68 percent of us, perhaps?  Yes, we humans are more the same in many ways than we are different.  However, there is considerable biochemical variation amongst us humans.  So, it is difficult to say who is average and normal and then suggest an ideal daily dosage of selenium.

What do the numbers from selenium studies say?
Let’s look at the numbers from published research and see what sense we can make of them.  Remember: we humans need adequate plasma selenium concentrations for optimal antioxidant and anti-viral and anti-carcinogenic protection [Schrauzer 2009].

Putative beneficial range for plasma selenium status
Hurst and Fairweather-Tait et al, researchers based at Norwich Medical School, University of East Anglia, in the United Kingdom have suggested that the “putative beneficial range” lies between 120 and 150 nanograms of selenium per milliliter of plasma [Hurst 2010].

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Selenium and the prostate

Next to skin cancer, prostate cancer is the most common cancer in men in the United States. It is a leading causes of cancer death among men of all races and ethnic backgrounds. Low selenium status is associated with increased risk of prostate cancer.

There have been some recent research results relating to selenium supplementation and prostate gland tissue.  Researchers in The Netherlands have published results showing that a five-week daily intervention with a high-selenium yeast supplement, 300 micrograms daily, is associated with a down-regulation of genes that are involved with cellular growth and proliferation, with cellular immune response, and with inflammation processes.  Also down-regulated by the selenium supplementation is the activity of genes involved with wound-healing [Kok 2017].

The Dutch study was a randomized, double-blinded, placebo-controlled study.  Interestingly, the researchers saw the opposite effect in the placebo group.  In the placebo group, there was an up-regulation of the genes involved in cellular immune response [Kok 2017].

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Prostate cancer risk and selenium status

Selenium supplements in the form of organic high-selenium yeast tablets provide the best cancer chemo-protection. These supplements are made using the yeast species Saccharomyces cerevisiae in a selenium-enriched growth medium. The yeast cells that produce the high selenium yeast tablets are rendered inactive. They are killed off by a heating process. Strains of the same yeast species are used to brew beer and bake bread.

Selenium supplementation and the risk of prostate cancer?  What do we know?  We need to be careful in interpreting the research results that we have (and we need more research), but, yes, there is evidence for an inverse association between prostate cancer risk and selenium status [Hurst 2012].

As of this writing (April 2017), the protective effect of selenium supplementation against prostate cancer seems to be found in a relatively narrow range of plasma selenium status [Hurst 2012].  Furthermore, there seems to be a U-shaped relationship between selenium status and protection against prostate cancer.

If the concentrations of selenium in the plasma are too low, there is increased risk of prostate cancer.  This is a serious concern in many regions of the world.

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Selenium and reduced risk of cancer

The results of Dr. Larry Clark’s Nutritional Prevention of Cancer trial showed the efficacy of selenium supplementation in reducing the risk of colon cancer, lung cancer, and prostate cancer. Now, a meta-analysis of 69 studies shows that higher selenium exposure is associated with reductions in the risk of breast cancer, lung cancer, and prostate cancer.

Authors of a recent meta-analysis of 69 studies of selenium exposure and cancer risk have concluded that high selenium exposure can reduce cancer risk, especially high selenium exposure that is reflected in high plasma or serum selenium status and/or in high toenail concentrations [Cai 2016].  Admittedly, higher selenium intakes (as compared to lower selenium intakes) can affect different forms of cancer differently.  We still need more research to sort out which forms and dosages of dietary and supplemental selenium are most effective at reducing cancer risk.  In this article, I want to summarize the findings of Dr. Xianlei Cai and colleagues.

What is a meta-analysis of selenium exposure and cancer risk?
A meta-analysis is a research method of combining the data from several selected research studies to reach conclusions that have greater statistical power.  In the present case, Cai et al selected 69 studies that met their inclusion criteria.  Each one of the 69 selected studies had the following characteristics:

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Selenium and heart disease

A study of serum selenium levels and supplementation with a patented organic selenium yeast preparation shows an association between serum selenium concentrations and the rate of deaths from heart disease in healthy elderly study participants.

There have been two noteworthy discoveries from a recent randomized controlled trial conducted by Dr. Urban Alehagen of Linköping University (Sweden) and his colleagues.

Firstly, people with low concentrations of selenium in their blood were found to be at significantly higher risk of death from heart disease.

Secondly, a combination of a patented high selenium yeast supplement and a proven Coenzyme Q10 supplement taken daily for four years provided significant protection against heart disease in people with low serum selenium status.

The KiSel-10 study of cardiovascular mortality
The study enrolled 668 healthy elderly individuals aged 70-80 years.  The study was well-designed and well-executed.  One group of 219 randomly selected individuals received 200 micrograms of selenized yeast tablets and 200 milligrams of Coenzyme Q10 capsules daily for four years. A second randomly assigned group of 222 individuals received matching placebos.  The remaining group of 227 individuals received no treatment at all.

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