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

    Selenium Deficiency A Big Risk Factor for Heart Disease

    Ash tray with cigarette butts
    In the Italian study (Giacconi et al. 2021), only smoking ranked above selenium deficiency as a risk factor for heart disease. Age, BMI, cholesterol and triglyceride levels, and gender all ranked lower than selenium deficiency as risk factors for heart disease.

    Results from an Italian study have added to the evidence that adequate selenium status is necessary to prevent heart disease, especially in elderly individuals.

    The Italian study data showed that study participants with plasma selenium concentrations below 60 micrograms per liter were 1.9 times more likely to suffer from cardiovascular disease compared to study participants with higher selenium status [Giacconi 2021].

    Reduced plasma selenium status was associated with elevated levels of biomarkers of inflammation, increased expression of cytokines, and down-regulation of sirtuins in peripheral blood mononuclear cells [Giacconi 2021].

    Selenium Status and Risk of Cardiovascular Disease

    The KiSel-10 Study Results

    In a clinical trial with combined selenium and Coenzyme Q supplementation of elderly citizens, average age: 78 years, with low selenium status (mean: 67.1 micrograms per liter), for 48 months, researchers found reduced cardiovascular mortality after 10 and 12 years of follow-up [Alehagen 2018, 2015). read more

    Selenium as a Nutritional and Preventive Medicine Substance

    Berlin Brandenburger Tor
    Professor Dr. Lutz Schomburg, affiliated with the Charité Institute of Experimental Endocrinology and with both the Humboldt University and the Free University in Berlin, has analyzed the research literature on selenium supplementation. He concludes that current data show that selenium supplementation does not cause diabetes.

    The long-time selenium researcher Professor Dr. Lutz Schomburg has reviewed the nutritional and preventive medicine aspects of selenium supplementation. In his mind, a selenium deficiency in and of itself constitutes a health risk that should be corrected by dietary measures or by supplemental selenium intake [Schomburg 2020].

    He interprets the available evidence for positive health effects of selenium supplement as the outcome of correcting a deficiency or insufficiency of selenium.

    His review of the research literature indicates that selenium supplement does not cause diabetes. Instead, the current evidence suggests that the development of type 2 diabetes with low insulin levels and high glucose levels may be causing increases in selenium levels; hence, the perceived association between the incidence of diabetes and the higher selenium status [Schomburg 2020]. read more

    Plasma Selenium Levels and the Risk of a First Stroke

    A Chinese study has shown that there is a significant negative association between plasma selenium concentrations and the risk of a first stroke in males but not in females. This is not the first time that sex differences have been reported relative to selenium metabolism. More on that later.

    Picture of the brain
    Typically, there were many more cases of first ischemic stroke, usually caused by a blood clot, than there are cases of first hemorrhagic stroke, usually caused when a blood vessel leaks or breaks open). Adequate selenium supply to the brain may protect against the risk of stroke.

    Plasma Selenium Levels and the Risk of a First Stroke

    The Chinese researchers analyzed the results from a nested case-control study with 1255 first stroke cases and 1255 matched controls [Hu 2021].

    N.B. In this study,  there were many more cases of first ischemic stroke (n=1079) than there are cases of first hemorrhagic stroke (n=171). Five cases were of uncertain origin.

    Evidence from Other Studies of Selenium Level and Stroke Risk

    The results from studies of selenium level and stroke risk have been somewhat confusing to date: read more