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Selenium Supplementation: No Adverse Effect on Insulin Resistance

Researchers at the Arizona Cancer Center report study results that do not support any significant adverse effect of daily supplementation with 200 micrograms/day of selenized yeast on beta-cell function or insulin sensitivity. High-selenium yeast preparations contain more selenium species with more biological functions than the 100% selenomethionine preparations do.

Researchers at the University of Arizona Cancer Center in Tucson have reported interesting findings with respect to selenium supplementation [Jacobs 2019]:

  • Supplementation with 200 micrograms/day of a selenized yeast preparation for 2.9 years had no effect on insulin sensitivity or beta-cell function as compared with the placebo group.
  • Further stratification of the data by sex and age showed no effect modification in response to the selenium supplementation.

The Take-Home Message from this Selenium Research

  • The Arizona Cancer Center research does not support the idea of a major role for selenium in insulin sensitivity or beta-cell function.
  • The University of Arizona researchers write that their results provide key information for clinicians to convey to patients in the USA about the use of selenized yeast dietary supplements.

The Selenium Supplementation Research Design

The researchers analyzed the data from a subset of 400 individuals who were participating in the Selenium Trial, a randomized, double-blind, placebo-controlled trial of the effect of selenium supplementation at 200 micrograms per day on colorectal adenomatous polyps [Jacobs 2019].

The data included the fasting plasma glucose and insulin measured both before randomization and within 6 months of completing the intervention.

The researchers compared changes in the homeostasis model assessment-beta cell function (HOMA2-%beta) and insulin sensitivity (HOMA2-%S) between the active selenium treatment group and the placebo control group. read more

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Selenium Intake and Status Related to Health

The quantity of selenium in foodstuffs may be inadequate in many parts of the world.  Sub-optimal selenium status is reported to be widespread throughout Europe, the UK, and the Middle East [Stoffaneller & Morse]. Coastal regions in the US tend to have selenium-poor soil. Vast regions in China, Korea, Siberia, Tibet, and New Zealand are low selenium regions. Low selenium status is associated with increased risk of cancer and cardiovascular disease and thyroid disorders [Tolonen].
The research evidence to date suggests that there is a U-shaped relationship between selenium intake and health.  According to a recent report by the long-time selenium researcher Professor Dr. Margaret P. Rayman, University of Surrey, UK, both selenium deficiency and selenium excess have been associated with adverse health effects.

Conditions Indicating a Need for Selenium Supplementation

Professor Rayman lists a number of conditions that have been associated in the research literature with selenium deficiency:

  • Keshan disease (a heart muscle disease caused by a selenium deficiency together with a strain of Coxsackie virus)
  • Kashin-Beck disease (a bone disease for which selenium deficiency is a factor)
  • Increased viral virulence
  • Increased mortality
  • Poorer immune function
  • Problematic fertility/reproduction
  • Thyroid autoimmune disease
  • Cognitive decline/dementia
  • Type-2 diabetes
  • Prostate cancer risk
  • Colo-rectal cancer risk (in women)
  • Increased risk of tuberculosis in HIV patients

Professor Rayman does not specify a plasma/serum selenium level for selenium deficiency. 

She does mention a US National Health and Nutrition Examination Survey that measured the serum selenium levels in 13,887 adult participants and then followed up for mortality for up to 18 years.  The mortality in that study showed a U-shaped association between serum selenium and death, with a serum selenium concentration of 135 micrograms per liter at the bottom of the U [Rayman 2019]. read more

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Selenium and Autoimmune Diseases

Autoimmune diseases are conditions in which the person’s immune system mistakenly attacks parts of the person’s own body such as his or her joints or skin. There are as many as 14 common autoimmune diseases. Some attack only one organ; others attack the entire body. Through its role in the maintenance of thyroid function and its role in the antioxidant defense of cells and DNA, selenium may have a critical protective effect in the management of autoimmune diseases. More clinical research is needed.

Selenium is a micronutrient that plays an important role in the oxidative defense of cells and DNA against damage by harmful free radicals.  Selenium is the main component of the selenoproteins that play important roles in reproductive function, immune system modulation, and thyroid hormone synthesis [Sahebari].

Low Serum Selenium Levels and Autoimmune Diseases

Decreased serum selenium levels have been associated with increased incidence of some autoimmune diseases.  Furthermore, low levels of selenium may be a risk factor for systemic inflammation and for the initiation of some autoimmune diseases [Sahebari]:

  • Rheumatoid arthritis
  • Sjögren syndrome
  • Behcet’s diseases
  • Scleroderma (systemic sclerosis)

Selenium Supplementation and Autoimmune Diseases

Selenium supplementation has been shown to have beneficial effects in the management of rheumatoid arthritis and scleroderma [Sahebari]. read more

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Selenium Supplementation for Premature Neonates

Preterm neonates are babies born more than three weeks before the normal term, i.e. born before the 37th week of gestation. Sepsis – the condition caused by harmful bacteria entering the blood circulation – is one of the complications associated with premature birth. Selenium supplementation can reduce the risk of late-onset sepsis in preterm neonates.

Selenium supplementation reduces the risk of sepsis in premature babies.

Three studies carried out in low-selenium countries – Australia, New Zealand, and India – have shown a positive effect of selenium supplementation in reducing the incidence of sepsis in premature babies [Daniels; Darlow; Aggarwal].

Selenium supplementation – both selenium fed orally and selenium fed parenterally – significantly improved the selenium status of premature babies and reduced the incidence of “late onset” sepsis [Darlow].

In none of the three clinical studies were there any adverse reactions to the selenium supplementation [Daniels; Darlow; Aggarwal].

Increased Risk of Sepsis in Premature Babies Without Selenium Supplementation

“Late onset” sepsis presents, typically, one week or more following birth and is caused by exposure to infection in the hospital.  A “late onset” sepsis occurs in about one out of five premature babies with a birth weight below 1500 grams (about 3 pounds and five ounces). read more

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Selenium Supplementation and HIV Infections

Selenium supplementation of HIV-infected patients can slow the progression of the virus, improve CD4 cell counts, and reduce the risk of mortality. The form and the dosage of the selenium supplementation needs to be researched further. At present, supplementation with 200 micrograms of high-selenium yeast daily seems most promising, but the dosage will vary according to regional variation in the selenium content in the soil and food.

Humans with low blood selenium concentrations are more likely to have impaired immune function and rapid mutation of benign variants of RNA viruses to virulent forms.  Low blood selenium concentrations are concentrations less than 1 micromol of selenium per liter of blood = less than 78 micrograms of selenium per liter of blood [Harthill].

If a virus-infected, selenium-deficient human host is supplemented with selenium, the mutation rate of the virus tends to decrease, and the immune function tends to improve [Harthill].

Thus, the selenium status of the human host can have a profound effect on the development of a virus infection.  In cases of selenium deficiency, a normally non-virulent virus can become virulent.  A virus can become pathogenic by replicating in a nutritionally deficient human host [Beck]. read more

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Selenium Supplementation and Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) occurs in 5 to 10% of women. It is the most common cause of infertility in women. PCOS is typically described by the presence of common symptoms: mild obesity, irregular periods or absence of a period, and signs of excessive androgen such hirsutism and acne. Most PCOS patients will have multiple cysts in the ovaries. More research into the effects of selenium supplementation on PCOS is needed.

Polycystic ovary syndrome (abbreviated PCOS) is a hormonal disorder with a prevalence of 5 – 10% in women of reproductive age.

  • The exact cause of PCOS is unknown.
  • Symptoms of PCOS include irregular periods, increased levels of male hormone, and failure of the ovaries to function regularly.
  • Excess insulin production and low-grade inflammation are thought to have an effect on the development of PCOS [Mayo Clinic].

Selenium: Effect on Mental Health, Hormonal Profile, Inflammation, and Oxidative Stress in Patients with PCOS

In a randomized controlled trial enrolling 60 women aged 18 – 40 years, daily co-administration of a probiotic supplement and 200 micrograms of selenium for 12 weeks was associated with the following outcomes [Jamilian 2018]:

  • significant improvement in Beck Depression Inventory scores, general health questionnaire scores, and depression anxiety and stress scale scores compared with the placebo
  • significantly reduced total testosterone levels, hirsutism, high-sensitivity C-reactive protein levels (a bio-marker for inflammation), and malondialdehyde levels (a bio-marker for oxidative stress) as well as significantly increased total antioxidant capacity and total glutathione (GSH) levels compared with the placebo

The researchers concluded that the co-administration of probiotics and selenium for 12 weeks to women with PCOS had beneficial health effects.

Selenium: Effect on Metabolic Profile in Patients with PCOS

In a randomized controlled trial enrolling 70 women aged 18 – 40 years, daily supplementation with 200 micrograms of selenium for 8 weeks was associated with the following outcomes compared with placebo [Jamilian 2015]: read more

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Selenium in Body Tissues and Physiological Processes

Professor Gerhard N. Schrauzer was the director of the Biological Trace Element Research Institute in San Diego, California. He led the way in the study of the biological functions of selenium, especially in relation to selenium’s cancer protective properties.

The biology of selenium in humans is complex.  What is known is that selenium is widely distributed in body tissues and in physiological processes [Wrobel].

Particularly of interest is the preferential maintenance of selenium concentrations in the brain, even in circumstances in which selenium stores are deleted in other organs such as the liver and kidneys [Wrobel].

What Does Selenium Do in the Body?

Dr. Wrobel, University of Miami Department of Biochemistry and Molecular Biology, lists the following functions of selenium and selenoproteins in the body:

  • Adequate levels of selenium are needed to modulate the function of the thyroid gland.
  • Selenium plays an important role in male and female fertility.
  • Selenium deficiency is associated with cardiac and skeletal muscle disorders, with changes in muscle fibers leading to the impairment of muscle contraction and to muscle atrophy.
  • Low levels of selenium are associated with impaired cognitive function and neurological disorders.
  • There exists an inverse relationship between selenium concentrations and the risk of coronary heart disease and the risk of certain types of cancer.
  • Low selenium levels are associated with high HIV mortality.
  • Selenium supplementation reduced the number of hospital admissions for HIV patients.

Selenium and the Prevention of Cancer

Epidemiological studies show generally that higher exposure to selenium is associated with a reduced risk of most forms of cancer.  For example, people living in higher soil selenium regions tend to have lower incidence of cancer [Wrobel]. read more

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Selenium and Brain Function

Brain cells are especially vulnerable to oxidative stress, which could be a factor in the pathology of neurodegenerative disorders. The danger of oxidative damage caused by free radicals (oxygen reactive species) is great because 1)  the neurons use large quantities of oxygen, 2) the brain has high iron content, 3) neuronal mitochondria produce large quantities of hydrogen peroxide, and 4) neuronal membranes are full of polyunsaturated fatty acids, which are susceptible to oxidative stress [Shichiri, 2014]. Adequate supply of selenium and synthesis of antioxidant selenoproteins are necessary to counteract the harmful effects of oxidative stress.
A review of the research literature on selenium and selenoprotein function in brain disorders reveals that selenium deficiency is associated with impaired cognitive function and impaired motor function [Pillai].

It is interesting to note that selenium concentrations are preferentially maintained in the brain even when the selenium concentrations in the blood circulation, in the liver, and in the skeletal tissues are depleted [Pillai].

Selenium supplementation may help to reduce the progression of the pathology of neurodegenerative diseases: Alzheimer’s, Huntington’s, and Parkinson’s [Pillai].

Selenium and Selenoproteins

What do we know about the trace element selenium and its incorporation into selenoproteins? read more

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Selenium and Coenzyme Q10 for Senior Citizens

Professor Urban Alehagen, Linköping University, Sweden, was one of the key researchers on the Q-Symbio clinical trial and has been the lead researcher on the KiSel-10 clinical trial. He has shown that joint selenium and Coenzyme Q10 supplementation of senior citizens with low selenium status reduces the risk of cardiovascular mortality and improves heart function.

The Swedish KiSel-10 Study provides randomized controlled trial evidence that a daily combination of an organic high-selenium yeast supplement and a pharmaceutical-grade Coenzyme Q10 supplement can reduce cardiovascular mortality, improve heart function, and increase health-related quality of life in senior citizens [Alehagen 2013].

Low blood selenium concentrations and higher risk of heart disease

Professor Urban Alehagen and a team of researchers from Linköping University investigated the blood selenium levels in 688 Swedish senior citizens.  The mean blood selenium level was 67.1 micrograms per liter, which is quite low but not surprising, given that Sweden is a country with selenium-low soil and selenium-poor foodstuffs [Alehagen 2016].

When the researchers adjusted for gender, smoking, coronary artery disease, diabetes, chronic obstructive pulmonary disease, and impaired heart function, they found that the quartile of senior citizens with the lowest level of blood selenium had a 43% higher risk of all-cause mortality and a 56% higher risk of cardiovascular mortality [Alehagen 2016]. read more

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Blood selenium concentrations and high-grade prostate cancer

A 2012 meta-analysis and systematic review has shown an inverse association between plasma/serum selenium levels and prostate cancer advanced prostate cancer in particular. Denmark is in a low-selenium region of the world, and the Danish population as a whole has low selenium intakes and sub-optimal blood selenium levels. Danish researchers have, accordingly, investigated the association between pre-diagnostic selenium levels and the risk of total, advanced, and high-grade prostate cancer. Pictured here: the Dannebrog, Denmark’s national flag.

Higher blood selenium concentrations and higher blood selenoprotein P concentrations are significantly associated with reduced risk of high-grade prostate cancer [Outzen].

The researchers defined “advanced” prostate cancer as ≥T3 or with a Gleason-score ≥7.  They defined “high-grade prostate cancer” as cancers having a Gleason score equal to or greater than 8.

Furthermore, in survival analyses, a higher pre-diagnostic level of plasma selenium is significantly associated with a lower risk of all-cause mortality in prostate cancer patients [Outzen].

Selenium and prostate cancer in the “Diet, Cancer, and Health” cohort

These are the conclusions from an analysis of the data from the Danish “Diet, Cancer, and Health” cohort.  The cohort consists of 27,179 men living in the greater metropolitan areas of Copenhagen and Aarhus who were recruited into the study.  They were aged 50 – 64 years and had no previous record of cancer at the time of recruitment [Outzen]. read more