Selenium and Selenoprotein P and Mortality

Higher all-cause mortality and higher mortality due to cancer, cardiovascular disease, gastrointestinal diseases, and respiratory disorders are associated with lower serum selenoprotein P concentrations in older German adults [Schöttker 2024].

Operation table
Death from all causes and death specifically caused by cancer, cardiovascular disease, gastrointestinal diseases, and respiratory disorders are strongly associated with low serum concentrations of the selenium-dependent selenoprotein P.

In plain English, lower blood concentrations of the selenium-dependent selenoprotein P are significantly associated with a higher risk of degenerative disease progression and with dying. Moreover, the data from the German study show that the risk of dying associated with low blood Selenoprotein P levels was more than double in men compared to women [Schöttker 2024].

In the Esther Study, German researchers assessed the association of measurements of serum Selenoprotein P concentrations with all-cause and cause-specific mortality data. They measured serum Selenoprotein P at baseline and again at a 5-year follow-up in 7,186 and 4,164 participants, respectively [Schöttker 2024]. read more

Selenium and the Thyroid Gland

The thyroid gland is the organ in the body that contains the most selenium per gram of tissue [Wang 2023].

Illustration of thyroid gland from Wikimedia Commons
The thyroid gland makes and releases hormones that control our metabolism, i.e., regulate how we use energy. Source:

In a 2023 review article, Wang et al summarize the reasons why adequate selenium intake and status are necessary for good thyroid health.

Humans cannot synthesize selenium: the daily intake of selenium depends on the contents of the individual’s diet.

  • The selenium content of food depends on the selenium content of the soil, which varies extensively from region to region of the world. Much of Europe has selenium-poor soil; much of the United States has soil considerably richer in selenium.
  • Selenium is a micronutrient that makes possible the body’s synthesis of some 25 identified selenoproteins containing the amino acid selenocysteine.
  • The best known selenoproteins – such as the glutathione peroxidases, the thioredoxin reductases, and the iodothyronine deiodinases – are expressed in the thyroid gland, where they contribute to thyroid hormone metabolism and to antioxidant defense.
  • A selenium deficiency will increase the risk of several kinds of thyroid diseases.

Selenium Supplementation and Thyroid Diseases

Wang et al [2023] report the following outcomes from clinical trials of selenium supplementation. They advise that we need more clinical evidence for the efficacy of selenium treatment of thyroid disorders.

  • Selenium supplementation slows the progression of Graves’ orbitopathy and improves the quality of the patients’ lives.
  • Selenium supplementation is associated with the decreased levels of anti-thyroid peroxidase antibodies and with improved thyroid ultrasound structure in patients with Hashimoto’s thyroiditis.
  • Selenium supplementation has shown variable anticancer activity in patients with thyroid cancer.

Strong Association Between Selenium and Thyroid Disease

Selenium and Graves’ disease

Wang et al [2023] reviewed the data from 11 clinical trials. Nine clinical trials showed that selenium supplementation results in faster achievement of normal thyroid function in patients with hyperthyroidism. Two clinical trials did not show the beneficial effect of selenium supplementation. The difference in outcomes may be related to differences in the form of the selenium supplementation, the dose, the duration of supplementation, and the nutritional status of the study participants. read more

Heart Failure Risk and Selenium Deficiency

Low plasma selenoprotein P levels are associated with a higher risk of heart failure in a Swedish population [Jujic 2023].

Heart rate
Selenium deficiency in heart failure patients is significantly associated with increased risk of cardiovascular mortality, impaired exercise capacity, and poorer quality of life [Bomer 2020].
Selenoprotein P is the primary protein transporter of selenium in the blood.

Plasma and serum selenoprotein P concentrations are useful biomarkers of selenium status in individuals with relatively low selenium intakes because selenoprotein P responds to different intake forms of selenium [Hurst 2010].

Selenium deficiency – defined as serum selenium concentrations below 70 mcg/L – has been associated with more severe symptoms of heart failure, poorer exercise capacity, and poorer quality of life. Sub-optimal serum selenium concentrations of 70–100 mcg/L have similar adverse associations, suggesting that values less than 100 mcg/L, might be considered abnormal [Bomer 2020]. read more

Chronic Fatigue Syndrome and Impaired Selenium Transport

In a considerable number of chronic fatigue syndrome patients, researchers have observed the presence of autoantibodies to the selenium transporter Selenoprotein P. These autoantibodies disturb the normal transport of selenium to the tissues  in the body. They cause lower than normal levels of the antioxidant selenoenzyme glutathione peroxidase and lower than normal levels of deiodinase enzyme activity [Sun 2023].

Tired young woman at computer
Chronic fatigue syndrome is a complicated disorder that causes abnormal fatigue lasting six months or longer. Impaired selenium transport may be a factor underlying chronic fatigue syndrome.

Note: Autoantibodies are antibodies produced by the immune system and directed against the individual’s own proteins, in this case against selenoprotein P proteins. In an earlier study, researchers have identified autoantibodies to selenoprotein P in patients with Hashimoto’s thyroiditis, in which case the autoantibodies also impair selenium transport and selenoprotein expression [Sun 2021]. read more

Selenium and Type 2 Diabetes

Type 2 Diabetes. Some news reports have suggested that high selenium intakes and status may be potential risk factors for the development of type 2 Diabetes mellitus. However, current data show that supplemental selenium does not cause diabetes [Schomburg 2020].

Diabetes symptoms
It seems likely that diabetes causes elevated blood selenium levels rather than the other way around [Schomburg 2020].
Two large randomized controlled trials using selenium supplements have shown no diabetes risk caused by 1) a selenomethionine product [Lippman 2009] and 2)   a selenium-enriched yeast product [Thompson 2016; Jacobs 2019]. In neither study was there any significant risk of diabetes  at the recommended dosage, not even among selenium-replete individuals of various ages and both genders [Schomburg 2020].

Moreover, in the Selenium Trial, the researchers saw no causal role for selenium in the development of insulin resistance or diabetes. Instead, they observed decreased fasting blood glucose levels in the selenium supplemented group compared to the control group [Jacobs 2019]. read more

Selenium Supplementation for Vegetarians and Vegans

Vegetarians and vegans, do they get enough selenium in their diets? It is an important question because the number of vegetarians around the world is growing for ethical and environmental reasons. How do we measure selenium status in various groups of people?

Vineyard in Germany with selenium-poor soil
The arable land in much of Europe contains a sub-optimal content of selenium, meaning that the plants grown there are also poor in selenium. Pictured: A vineyard in Germany.

Selenium is an essential trace element. Essential means that we have to get it from our food or from supplements. The human body does not synthesize selenium. What the body does synthesize is the selenoproteins, of which selenium in the amino acid selenocysteine is a key active component.

Particularly in much of Europe and the Middle East, the soil and the plants have relatively poor selenium content. In many countries, the farm animals are supplemented with selenium to improve their nutritional intakes and their health and to avoid selenium deficiency syndromes. read more

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

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

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

Breast Cancer Recurrence and Selenoprotein P Autoimmunity

Breast cancer prognosis is especially poor in patients with low serum selenium and serum selenoprotein P concentrations. Now, researchers have discovered natural autoantibodies with antagonistic properties to selenoprotein P uptake in breast cancer patients and  in patients with thyroid disease [Demircan 2022; Sun 2022].

Autoimmunity is the production of antibodies against the tissues or substances of one’s own body, resulting in an autoimmune disease or hypersensitivity reaction. Autoantibodies to Selenoprotein P impair the transport of the essential trace element selenium in breast cancer patients and in Hashimoto’s thyroiditis patients.

Selenium is an essential trace element that has numerous biological functions in the body, most of which are carried out by selenium-containing selenoproteins. Among the more important selenoproteins are selenoprotein P, the main transporter of selenium in the blood, and glutathione peroxidase 3 (GPX3), an important antioxidant.

The human body does not synthesize selenium. Human cells are dependent upon selenium sources in the diet. Unfortunately, the selenium content in the soil and in food varies considerably from region to region in the world. For example, the plasma selenium concentrations in people living in much of Europe are generally below, often well below, 80–90 mcg/L whereas people living in North America generally have plasma selenium levels above 120 mcg/L [Alehagen 2022]. read more