Pharmacokinetics of Oral Selenium-Enriched Yeast Supplements

The Danish researchers Niels Hadrup and Gitte Ravn-Haren have published a comprehensive study of the absorption, distribution, metabolism, and excretion of selenium obtained from food and from nutritional supplements [Hadrup 2021].

Selenium supplements come in many forms, both organic and inorganic. The advantage of the selenium-enriched yeast preparations is that they contain 20-30 different species of selenium in addition to selenomethionine. Some of these selenium species may have important biological effects.

Here we summarize their findings with respect to selenium in selenium-enriched yeast supplements. We do this for two reasons:

Absorption of selenium from selenium-enriched yeast preparations

In a 2008 paper, researchers reported having given healthy elderly individuals 100, 200 or 300 mcg selenium in a selenium-enriched preparation daily for a period of 5 years. The supplementation resulted in mean plasma levels of 165, 221, and 260 mcg/L, respectively. In the control group, given a placebo for 5 years, the plasma selenium concentration was 92 mcg/L [Ravn-Haren 2008]. read more

Selenium and Patients with Autoimmune Thyroid Disease

Sufficient selenium status is necessary for good thyroid health.

A woman's neck
Selenium-containing drugs are effective for treating patients with autoimmune thyroid disorders [Zuo 2021].
Zuo et al [2021] have investigated selenium status and the effects of selenium supplementation in patients with autoimmune thyroid disease.

They analyzed the data from 17 journal articles based on studies of 1,911 subjects. Their meta-analysis results showed the following statistically significant associations:

  • Serum free triiodothyronine (FT3) levels in patients were reduced after selenium supplementation compared to placebo treatment.
  • Serum free thyroxine (FT4) levels and anti-thyroid peroxidase antibody (TPOAb) levels were reduced after selenium supplementation compared to placebo treatment.
  • Anti-thyroid peroxidase antibody (TPOAb) levels were decreased after selenium supplementation compared to placebo treatment.

However, the thyroid stimulating hormone (TSH) levels
and the anti-thyroglobulin antibody (TGAb) levels were not significantly different between the selenium treatment group and the control group.

The researchers concluded that selenium-containing drugs were effective in treating patients with autoimmune thyroid disease and greatly reduced
the levels of free triiodothyronine, free thyroxine, and anti-thyroid peroxidase antibody in these patients. read more

Selenium Status and Risk of Non-Alcoholic Fatty Liver Disease

Data from an observational study done in the United States have shown the following relationships [Reja 2020]:

Upper right abdomen pain
Liver pain is usually felt as a dull, throbbing pain in the upper right abdomen. NAFLD is the most common form of liver disease. It is characterized by the storing of too much fat in liver tissues, by inflammation, and by fibrosis. Liver fibrosis is a degenerative disease in which liver tissue is damaged and replaced by scar tissue.

Higher serum selenium status is correlated with lower risk of advanced liver fibrosis.

  • This correlation is especially strong in liver disease patients who are elderly, who are non-Hispanic white, or who are female.
  • The patients with non-alcoholic fatty liver disease (NAFLD) who had higher serum selenium levels also had a 28% lower hazard ratio of death from all causes compared to the NAFLD patients with the lowest serum selenium levels.
  • Serum Selenium Levels and the Risk of Advanced Liver Fibrosis and All-Cause Mortality in NAFLD Patients
    What was the study based on?

    The data analyzed in the study came from 33,944 NAFLD patients identified in the Third National Health and Nutrition Examination Survey (NHANES). read more

    Serum Selenium Status and Cancer Risk

    On its Selenium: Fact Sheet for Health Professionals website, the US Office of Dietary Supplements, an agency of the National Institutes of Health, writes that selenium might play a role in the prevention of cancer for the following reasons:

    • selenium’s role in DNA repair
    • selenium’s role in apoptosis
    • selenium’s role in the endocrine and immune systems
    • the antioxidant properties of certain selenoproteins
    Cancer prevention ribbons
    It is not possible to draw any conclusions regarding a causal link between selenium exposure/status and the prevention of cancer. However, numerous observational studies show an inverse relationship between serum selenium status and the risk of cancer.
    Different Selenium Compounds Have Different Effects on Cancer

    The evidence from scientific research into the effect of selenium on cancer prevention can be confusing. Two observations about selenium supplementation may help to explain the confusing results from existing selenium and cancer studies:

    1. Different selenium containing compounds differ widely in their ability to prevent cancer. Study results may vary according to the form of the selenium supplement tested.

    2. Selenium supplementation may be more effective at cancer prevention in study participants with low baseline selenium status (below 100 mcg/L) and less effective in study participants with high baseline selenium status (above 135 mcg/L). read more

    Selenium Supplementation and Male Infertility

    Clinical studies show that daily supplementation with selenium can improve male fertility [Moslemi et al.; Safarinejad & Safarinejad; Scott et al.].

    Stork bringing baby
    Sperm motility is a parameter of sperm analysis used to evaluate the ability of sperm to move in a forward direction. Poor sperm motility is associated with diminished male fertility. Adequate serum selenium status (> 90-100 mcg/L) is associated with improved sperm quality and improved sperm motility.
    Selenium Supplementation of Men in Iran in 2009

     In a 2009 study lasting 26 weeks, researchers in Teheran randomly assigned infertile men, average age 31 years, range 25-48 years, to the following groups [Safarinejad & Safarinejad]:

    1. selenium supplementation group (n=116; dosage = 200 mcg/day)
    2. N-acetyl-cysteine group (n=118; dosage = 600 mg/day)
    3. selenium supplementation group (n=116; dosage = 200 mcg/day) plus N-acetyl-cysteine (dosage = 600 mg/day)
    4. placebo group (n=118)
    Outcomes of the 2009 Iranian selenium study:
    •  All semen parameters significantly improved with the selenium treatment and with the N-acetyl-cysteine treatment.
    • Administering selenium plus N-acetyl-cysteine resulted in additive beneficial effects.
    • There was a significant positive correlation between the seminal plasma concentrations of selenium and N-acetyl-cysteine and the semen parameters.
    • There was a strong correlation between the sum of the selenium and N-acetyl-cysteine concentrations and the mean sperm concentration, sperm motility, and percentage of normal morphology sperm.
    Selenium Supplementation of Men in Iran 2011

    In an open-label study of 690 infertile men, average age 28.5 years, range 20-45 years, who received a daily selenium supplement (200 mcg) together with a daily synthetic vitamin E (400 units, α-tocopherol) for at least 100 days, the researchers concluded that supplemental selenium and vitamin E improve semen quality and have beneficial effects on sperm motility [Moslemi et al.]. read more

    Selenium and Heart Failure Risk

    Cardiologists at the University of Groningen in The Netherlands have published a comprehensive review of the current knowledge about selenium deficiency and the role of selenoproteins in heart failure patients [Al-Mubarak 2021].

    Heart failure is a form of heart disease with high morbidity and mortality and with increasing prevalence. It is estimated that there are more than 26 million heart failure patients worldwide. Suboptimal selenium intakes and status adversely affect heart muscle function.

    The key points in their review are as follows:

    • Selenium is an essential micronutrient. It is incorporated into 25 different selenoproteins that have many biological functions in the body.
    • Suboptimal selenium intakes and status lead to the impaired cellular synthesis of these selenoproteins and to the diminished function of selenoproteins, which may aggravate oxidative stress and inflammation, both of which are associated with greater severity of heart failure.
    • 70% of patients diagnosed with heart failure have suboptimal serum selenium levels (below 100 micrograms per liter).
    • The heart failure patients with suboptimal serum selenium concentrations have lower exercise capacity, lower quality of life, and a worse prognosis than heart failure patients with serum selenium concentrations above 100 mcg/L.
    • Clinical trials of the efficacy of selenium supplementation in patients with heart failure have shown improved clinical symptoms such as improvements in NYHA function class, in left ventricular ejection fraction, and in lipid profile.
    Selenium Deficiency and Heart Failure
    Observational Studies of Selenium Concentration and Heart Failure

    Three meta-analyses have provided evidence of a relationship between selenium status and the risk of heart disease:

    Studies of Selenium Supplementation – the KiSel-10 Study

    The most interesting clinical study is the KiSel-10 study in which elderly community living citizens, average age 78 years, with low selenium status (mean baseline status: 67.1 mcg/L), were treated with a combination of 200 mcg of an organic high-selenium yeast preparation and 200 mg of Coenzyme Q10 daily for four years. read more

    Selenium Deficiency and Covid-19 Infection

    Selenium is a natural trace element that has an important role in the functioning of the immune system (summarized in an earlier article).

    Corona virus
    Individuals with low serum selenium concentrations, e.g. below 70 mcg/L, are at greater risk of contracting Covid-19 and at greater risk of a more severe outcome. Selenium supplementation may give therapeutic benefits.

    SARS-CoV-2 is a single-stranded RNA virus responsible for COVID-19 infections. Covid-19 infections have a complex metabolism that is comparable to RNA virus infections such as coxsackievirus, influenza virus, Hanta virus, and HIV virus infections.

  • Selenium deficiency is associated with a higher susceptibility to RNA viral infections and with more severe disease outcomes [Hiffler 2020].
  • Selenium deficiency is associated with increases in the mutation, replication, and virulence of RNA viruses [Hiffler 2020].
  • There may be a protective effect of selenium supplementation against the susceptibility to and the severity of Covid-19 infections in selenium deficient individuals [Hiffler 2020].
  • Selenium Deficiency Promotes Mutations, Replication, and Increased Virulence of RNA Viruses

    Selenium deficiency – frequently defined as serum selenium status below 70 mcg/L – increases the risk of infection with RNA viruses: read more

    Selenium and Good Immune System Response

    In people with selenium deficiency (variously defined as serum selenium status below 60 mcg/L or 70 mcg/L), the responses of the innate and adaptive immune systems may be impaired.

    Immunity spelled with Scrabble pieces
    Selenium intake and status play a big role in the functioning of the immune system. Selenoproteins help to lower oxidative stress, reduce inflammation, and strengthen immune response to pathogens.

    Selenium deficiency can lead to an immune-incompetence that is associated with increased susceptibility to infections [Avery & Hoffmann 2018; Hiffler et al. 2020].

    In cell culture models, in rodent models, in livestock and poultry studies, and in human studies, researchers have found evidence that adequate levels of dietary selenium and the efficient incorporation of selenium into selenoproteins are important for immune system function [Avery & Hoffmann 2018].

    Studies of selenium supplementation to boost immunity against pathogens have not provided entirely clear-cut results; however, selenium and selenoproteins do play a role in regulating immune cell functions. Dysregulation of these immune cell processes can lead to inflammation and immune-related diseases [Avery & Hoffmann 2018]. read more

    Selenium and Inflammatory Bowel Disease: A Review

    Herewith the conclusions from a review of the available research literature about selenium and inflammatory bowel disease [Ala & Kheyri 2021].

    • Selenium deficiency is a common finding in Inflammatory Bowel Disease (IBD) patients, and there is a correlation between increasing selenium deficiency and disease severity.
    • Selenium contributes to effective function of antioxidant systems
      and alleviates colitis.

      Diagram of gastrointestinal tract
      Inflammatory Bowel Disease comprises two sub-types: ulcerative colitis and Crohn’s disease. IBD is a very complex disease that is difficult to manage. One estimate is that 1 million citizens in the US and 2.5 million residents in Europe suffer from IBD. These patients must contend with the high price of medication, social stigma, and diminished quality of life. IBD patients suffer from malabsorption and commonly have a deficiency of selenium and other micronutrients.Selenium deficiency is a common finding in Inflammatory Bowel Disease (IBD) patients, and there is a correlation between increasing selenium deficiency and disease severity.Selenium supplementation alleviates colitis (inflammation of the large intestine, the colon).
    • Selenium aids healing of the intestinal mucosa through modification of immune response.
    • Selenium may improve the activity of gut protective microbiota, which are decreased in IBD.
    • Selenium may reduce the risk of colorectal cancer by modulating several signaling pathways.  

    How does Adequate Selenium Status Help Inflammatory Bowel Disease patients?

    Adequate intakes of selenium are needed for the biosynthesis of selenoproteins, which contribute to antioxidative protection of cells and to the effective functioning of the immune system.

    • Selenium through the action of selenoproteins is known to have anti-inflammatory properties.
    • Adequate selenium status supports protective gut microbiota, which indirectly improves the management of IBD.
    • Selenium may block some of the tumorigenesis pathways under investigation in colitis-associated colorectal cancer.
    Intake of Selenium Varies from Region to Region

    The dietary intake and individuals’ serum level of selenium varies from region to region. For example, the US population has higher serum level of selenium (ca. 124 – 193 mcg/L) compared to most of the European and Middle Eastern populations (ca. 50-120 mcg/L) simply because the soil in many regions of North America is rich in selenium. read more

    Sex Differences in Selenium Metabolism and Selenoproteins

    Couple on the beach
    Males and females are different in ways that go beyond the morphology of their sex organs. This sexual dimorphism affects critical aspects of the selenium metabolism in animals and humans. Here Seale et al. review the available information on the influence of biological sex parameters on selenium metabolism and the effect of selenium and selenoproteins on sex hormones.

    One thing that the Covid-19 infections have taught us is that biological sex differences affect the way we respond to the virus. The Johns Hopkins University biologist Dr. Sabra Klein says that men are more likely to die from Covid-19 and more likely to be hospitalized with severe cases of the disease.

    This seems to hold true even though women are just as likely to be infected and even when researchers control for the effect of factors such as age and region.

    Women seem to have a stronger immune response to pathogens – bacteria, viruses, parasites – and to have a higher antibody production after vaccination. On the other hand, women are at greater risk for the development of auto-immune diseases. read more