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Selenoprotein P – Selenium Transport Protein and Biomarker of Selenium Status

Selenium and selenoproteins are essential to human health [Rayman 2012]. However, selenium intakes from food vary considerably from region to region in the world, depending on how rich or poor the soil and the foodstuffs are.

Selenium researcher Professor Urban Alehagen
Professor Urban Alehagen realized that the low selenium content of the soil in Sweden and in much of Europe results in wide-spread low dietary selenium intake and selenium deficiency. In the Swedish KiSel-10 Study, the average serum selenium concentration was a quite low 67 mcg/L.

For example, widespread suboptimal selenium status has been reported throughout Europe, the UK, and the Middle East [Stoffaneller & Morse 2015]. In contrast, the soil and the foodstuffs in much of the United States and Canada have a much higher selenium content than is the case in Europe. Serum selenium levels of US citizens are generally above 120 mcg/L. In many European countries, the corresponding serum selenium levels are 90 mcg/L on average [Alehagen 2016].

  • The best estimate for serum selenium status that is sufficient for good health is around 125 mcg/L [Winther 2020, fig. 3].
  • Serum selenium levels below 70 mcg/L are indicative of selenium deficiency [Bomer 2020].
  • Serum selenium levels below 100 mcg/L are indicative of sub-optimal selenium status [Al-Mubarak 2021].
Selenoprotein P as the Major Selenium Transport Protein

Dietary selenium is incorporated into the amino acid selenocysteine, which becomes an integral component of 25 selenoproteins. The best known selenoproteins are the glutathione peroxidases, thioredoxin reductases, and
iodothyronine deiodinases [Schomburg 2019]. read more

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Selenium Supplementation Increases Serum Sirtuin1 Concentrations

Daily supplementation with 200 mcg of selenium and 200 mg of Coenzyme Q10 for four years has resulted in significant increases in serum SIRT1 concentrations. In the parallel placebo group, the serum SIRT1 concentrations decreased significantly [Opstad, Alehagen 2023].

Selenium Researcher Professor Jan Aaseth
Professor Jan Olav Aaseth, Inland Norway University of Applied Sciences, is the guest author on this review article. Dr. Aaseth has written extensively about selenium in health and disease. He is one of the co-authors on the Sirtuin1 study summarized here.

This is the latest evidence from the KiSel-10 Study in which researchers randomly assigned elderly community-living Swedish men and women, average age: 76 years, 49% female, to a combined selenium and Coenzyme Q10 treatment group or to a placebo group [Alehagen 2013].

In earlier papers, the KiSel-10 Study researchers have reported beneficial effects of the combined supplementation of the elderly Swedish citizens with low baseline selenium levels [Alehagen 2022; Opstad 2022]: read more

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Selenium Supplementation and Chemotherapy in Cervical Cancer Patients

Selenium yeast supplementation administered concurrently with chemotherapy and radiation therapy effectively increased blood selenium levels in cervical cancer patients with inadequate selenium status. The selenium yeast supplementation was used as an adjuvant treatment to the standard chemotherapy and radiation therapy. It significantly decreased the hematologic toxicity of the chemoradiotherapy [Yang 2023].

Cancer and selenium
Each year, worldwide, half a million women are diagnosed with cervical cancer, and 300 000 die from the disease. In most cases, the human papilloma virus is the cause of the disease [Cohen 2019]. The trace element selenium has antiviral properties. Cell studies and mouse studies of cervical cancer have shown that different selenium species have anticancer effects in cervical cancer induced by human papilloma virus or by chemical carcinogens [Jablonska 2021].
In a randomized controlled trial, researchers randomly assigned 104 patients diagnosed with stage IIB cervical cancer receive 100 mcg selenium yeast tablets (n=50) or matching placebos twice daily (n=54) for five weeks [Yang 2023].

All patients in both groups received the standard treatment including pelvic external irradiation, concurrent five cycles of chemotherapy, and brachytherapy [Yang 2023]. read more

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Selenium Status and the Risk of Gestational Diabetes

Lower selenium status during pregnancy means there is a greater risk of developing gestational diabetes [Hamdan 2022; Xu 2022]. Three different selenium biomarkers in early and late pregnancy show a quite strong association of selenium with 1) the risk of developing gestational diabetes mellitus and 2) the birth of large for gestational age offspring [Demircan 2022].

Storks on a nest
Low maternal selenium status is strongly associated with an increased risk of gestational diabetes and with an increased risk of large for gestational age offspring.

The Mayo Clinic defines gestational diabetes as being diagnosed with diabetes for the first time during pregnancy. Gestational diabetes is like other forms of diabetes in that it affects how well the cells use glucose. It causes high blood sugar levels that can affect the mother’s health and the baby’s health [Mayo Clinic 2023]. read more

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Selenium and a Longer Healthier Life

The micronutrient selenium has antioxidant and anti-aging properties. Specifically, numerous selenoproteins, in which selenium is an essential component, have antioxidant, anti-inflammatory, and immunostimulating effects [Bjørklund 2022].

Why is this important?

Old people
Biological aging involves the gradual worsening of the composition of our cells and organelles. It involves the slowing down of our body functions. Aging is typically accompanied by wrinkled skin and thinner skin, by a loss of body mass and bone density, and by poorer eyesight. The older we get, the more vulnerable we are to loss of cognitive function and dementia, heart trouble, osteoporosis, renal failure, viral infections, etc. Eventually death comes.

The aging process is characterized by the following inevitable physiological developments [Alehagen 2021]:

Selenium and selenoproteins and antioxidant protection

One theory of biological aging is that oxidative stress and chronic low-grade inflammation play an important role in aging-related physical and mental decline. Harmful reactive oxygen species – popularly known as free radicals – overwhelm the ability of the available antioxidants to neutralize them. The harmful free radicals cause oxidative damage to the cells and to the DNA, lipids, and proteins in the cells [Bjørklund 2022]. read more

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Selenium and Mitochondrial Disorders and Telomere Attrition

Selenium supplements may be beneficial as an adjuvant treatment for patients with mitochondrial disorders. This is especially true in many parts of Europe and the Middle East where the soil and the foodstuffs have poor selenium content [Stoffaneller & Morse 2015]. Specifically, individuals with mitochondrial dysfunction need the antioxidant and anti-inflammation effects of selenium-dependent selenoproteins [Alehagen 2021; Opstad 2022].

Prof Jan Aaseth
The mitochondria are the organelles in our cells that generate the ATP energy that our cells need to function. They are our essential mini power plants. However, mitochondrial dysfunction is associated with generation of toxic oxygen, telomere shortening, cell death, and biological aging. Pictured: Prof. Jan Aaseth, MD, PhD, Innlandet Hospital & Inland Norway University of Applied Sciences.

Mitochondrial dysfunction can be defined as the diminished capacity of the mitochondria in the cells to convert sugars into energy, i.e., the diminished capacity of the cells to generate ATP energy [Miwa 2022].

Mitochondrial dysfunction is closely associated with biological aging and with cell senescence (the cessation of cell division) [Miwa 2022]. read more

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Selenium Status and Immune Function

Selenium is one of the micronutrients known to have an important and specific impact on immune system activity.

T-helper cell
Administration of selenium enhances the immune response of T-helper 1 cells and the stimulation of T cells. Depicted here: T-helper cell. Selenium also acts as a co-factor to achieve a more effective immune response to COVID vaccination.

In a 2022 review, Munteanu and Schwartz summarize the relevant research data on the modulation of immune function by micronutrients, including selenium and zinc [Munteanu 2022].

For selenium, the authors find the following evidence of a beneficial effect of selenium on immune system function:

  • Selenium, as a component of the amino acid selenocysteine, improves the synthesis of inflammatory mediators.
  • Selenium treatment leads to a decline in the gene expression of the pro-inflammatory cytokines IL-1 and TNF-alpha. This indicates that selenium has an anti-inflammatory effect in the body.
  • Selenium enhances the immune response of T-cells and T-helper 1 cells. T-cells work to destroy cells that have been infected by bacteria or viruses. Th1 cells are also responsible for fighting against bacteria and viruses.
  • Selenium supplementation increases the concentration of antibodies that enhance vaccine effects.
  • Selenium acts as a co-factor in the immunity that is mediated by the influenza vaccine. Selenium also serves as a co-factor to achieve a more effective immune response to COVID vaccination.
  • Selenium contributes to the defense against bacterial and vital pathogens through its effects on redox signaling activities.
  • -Selenium supplementation of patients with cancer increases antibody concentrations of the immunoglobulins IgA and IgG as well as increases the number of neutrophils.

Selenium – A Crucial Micronutrient for a Functional Immune System

Munteanu & Schwartz [2022] make the following additional points about an adequate supply of selenium:

  • Selenium improves not only in the functioning of the immune system but also the functioning of thyroid metabolism and the functioning of the cardiovascular system.
  • Selenium may play a role in the prevention of some forms of cancers.

Selenium and COVID-19

Munteanu & Schwartz [2022] report that selenium together with zinc exerts a protective role in COVID-19 patients. The combination of selenium and zinc is associated with a higher chance of survival. read more

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Thyroid Disorders and Selenium Supplementation

Thyroid disorders.

Many clinicians treating autoimmune thyroid diseases are using selenium supplementation as one treatment modality even though, in the official guidelines, selenium supplementation is recommended only in the treatment of mild Graves orbitopathy [Winther 2020].

Thyroid gland
The thyroid gland is the butterfly-shaped organ in the front part of the neck. Thyroid hormones regulate body temperature, heart rate, and weight gain or loss. Autoimmune thyroid disorders occur when immune system cells attack thyroid gland cells. Autoimmune thyroid disorders cause overproduction of thyroid hormones (hyperthyroidism) and underproduction of thyroid hormones (hypothyroidism). Graves’ disease is the most common autoimmune hyperthyroidism. Hashimoto’s thyroiditis is the most common autoimmune hypothyroidism.

Some clinicians consider supplementation with selenium to be a pharmaceutical action that should be taken only with thyroid disorder patients with well-defined symptoms in order to alleviate the symptoms, to improve the course of the disease, or to provide a cure. Typically, in such cases, the selenium treatment is conducted for short periods, and the health benefits and side effects are evaluated and weighed [Schomburg 2020].

Other clinicians consider supplementation with selenium in a more holistic way and use selenium supplementation as a way to correct a nutritional deficiency of selenium, which is associated with thyroid disorders [Schomburg 2020]. read more

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HIV Infection and Selenium Supplementation

HIV infection is associated with a higher risk of tuberculosis and death.  Selenium deficiency is associated with an increased risk of HIV infection. Several trials have shown that selenium supplementation of patients with HIV is associated with beneficial outcomes [Muzembo 2022].

HIV symptoms
HIV = human immunodeficiency virus.

Muzembo et al conducted a systematic review of six randomized controlled trials of selenium supplementation of HIV-infected patients. They reached the following conclusions [Muzembo 2022]:

  • Daily supplementation with 200 mcg selenium slowed the loss of CD4 cells in HIV-infected patients.
  • The length of selenium supplementation and HIV infection studies varied from 9 to 24 months.
  • The selenium supplements were well tolerated in all six studies.
  • Further investigation of the effects of daily selenium supplementation of HIV-infected patients is warranted.

Note: CD4 cells are a particular type of white blood cells that help the immune system fight infections. CD4 cells are also known as CD4 lymphocytes and helper T cells [MedlinePlus 2022].

If untreated, the HIV infection will destroy many CD4 cells, and the immune system will not be able to fight off opportunistic infections [MedlinePlus 2022]. read more

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Selenium Supplementation and Alzheimer’s Disease

Clinical studies show a clear correlation between Alzheimer’s Disease and low selenium status.  Lower selenium status is associated with worse cognitive decline [Aaseth 2016].

In many regions of Europe and the Middle East, there is poor selenium content in the soil and, accordingly, lower intake of selenium from food sources [Stoffaneller & Morse 2015; Winther 2020].

Woman with Alzheimer's
Adequate levels of selenium are essential for brain function; in fact, the brain is one of the organs that is supplied with selenium at the expense of other organs and tissues in times of low selenium intake. Selenoprotein P plays a special role in delivering selenium to the brain and the neurons. Some of the glutathione peroxidase and thioredoxin reductase selenoenzymes are important intracellular antioxidants in neurons and glia cells of the central nervous system.

The daily intake of selenium from food in many European countries is well below the amount needed for optimal function of important selenoproteins. The needed intake of selenium from food is  estimated to be at least 105 mcg per day [Winther 2020, fig. 2].

Using evidence from human studies in various countries, Prof. Jan Aaseth and colleagues have documented the association between lower selenium  status and Alzheimer’s Disease and/or cognitive impairment [Aaseth 2016]. read more