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Selenium and Selenoproteins and Viral Infections

Selenium is an essential micronutrient. Humans cannot synthesize it. Therefore, we must get it from our diets. The selenium content of our diets depends on the richness or poorness of the selenium in the soil and the food. In fact, there are surprisingly large differences in selenium content in various regions of the world [Zhang 2020a].

Woman sneezing
Selenium deficiency and reduced selenoprotein expression have been associated with the pathogenicity of several viruses.

Selenium through its incorporation into 25 known selenoproteins is necessary for a range of biological functions. Zhang et al [2020a] list the following biological functions of selenium and selenium-derived selenoproteins:

  • Antioxidant function
  • Anti-inflammatory function
  • Anti-viral function
  • Cellular redox function
  • Immune cell function
  • Protection of the cardiovascular system
Selenoprotein Functions Relevant to Viral Infections

Selenium and selenium-derived selenoproteins such as the glutathione peroxidases (GPXs), the thioredoxin reductases (TXNRDs), and the endoplasmic-reticulum-associated selenoproteins influence viral pathogenicity. Among other things, these antioxidant selenoenzymes reduce the extent of oxidative stress generated by viral pathogens. Failure to counteract oxidative stress can result in mutations in the viral genome from benign to highly virulent strains [Zhang 2020a]. read more

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Selenium and Anti-Aging Effects

Maintaining adequate selenium status is an acknowledged anti-aging strategy. We need selenium to live longer and to be healthier as we age. Adequate intakes of selenium and adequate bio-synthesis of selenoproteins contribute to healthy aging and to reduced vulnerability to various disorders. Selenium and selenoproteins are important for the following biological activity [Bjorklund 2022]:

  • antioxidant protection
  • enhancement of immune system function
  • metabolic homeostasis
Crowds of people
Bjorklund et al estimate that selenium deficiency affects about one billion people in the world and may have a significant adverse effect on human health.

One characteristic of aging is oxidative stress.

Oxidative stress is defined as an imbalance between the damage caused by harmful free radicals and the protection offered by antioxidants. Inadequate selenium status can reduce the longevity and the health of senior citizens by accelerating the aging process and/or increasing vulnerability to immune system dysfunction, cardiovascular disease, and cancer [Bjorklund 2022]. read more

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Blood Sugar Control and Selenium Supplementation

Blood sugar levels. Insulin sensitivity. Risk of diabetes. What, if anything, is the likely effect of selenium supplementation on glycemic control?

Blood sugar monitor
To maintain blood sugar levels within the normal range, the CDC recommends eating at regular times, not skipping meals, eating foods lower in calories, saturated fat, trans fat, sugar, and salt, drinking water instead of juice or soda, limiting alcohol intake, and exercising. Adequate intakes of selenium are also important.

Glycemic control is the maintenance of blood sugar levels within an acceptable range to prevent the adverse effects of low blood sugar and high blood sugar.

The best measure of glycemic control is the HbA1c test. This blood test HbA1C gauges the average glucose level in the blood over a period of approximately three months. It is considered a good predictor of diabetic complications.

Checking Blood Sugar

The US Center for Disease Control and Prevention suggests that logical times for testing blood sugar levels are as follows [CDC 2022]:

  • When first awake and before eating or drinking anything
  • Before a meal
  • Two hours after a meal
  • At bedtime
Target Blood Sugar Levels

The CDC suggests the following desirable blood sugar levels [CDC 2022]: read more

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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: https://www.nlm.nih.gov/medlineplus/.

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

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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

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Selenium-Enriched Yeast Supplementation Studies

The rationale for taking a selenium-enriched yeast preparation: one or more of the selenium compounds in the preparation other than selenomethionine may be the selenium species that has specific effects against cancer. This is an area for further research.

Glass of beer made using brewer's yeast
Selenium-enriched yeast preparations use Saccharomyces cerevisiae, commonly known as as brewer’s yeast. The yeast is grown in a selenium-enriched medium in which the yeast absorbs the selenium. The finished preparation is pasteurized, causing the yeast cells to die. Selenium-enriched yeast preparations contain many organic selenium compounds in addition to selenomethionine.

This week, we focus on studies conducted with a selenium-enriched yeast preparation containing at least 20 different species of selenium in addition to selenomethionine [Bendahl & Gammelgaard 2004].

Randomized, double-blind, controlled clinical trials are the gold standard method for testing the safety, absorption, and efficacy of nutritional supplements and medical drugs. Below, we summarize some of the important clinical trials of nutritional interventions using selenium-enriched yeast. read more

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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

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Selenium and Coenzyme Q10 Supplementation for Senior Citizens

In senior citizens, and delayed aging and longevity are associated with the antioxidant and anti-inflammatory protection derived  from daily supplementation with selenium and Coenzyme Q10 [Alehagen 2023].

Elderly couple dancing
Daily supplementation with selenium and Coenzyme Q10 seems to have a positive influence on longevity and delayed aging.

The KiSel-10 Study was a randomized, double-blind, placebo-controlled clinical trial of the effect of combined selenium and CoQ10 supplementation of senior citizens on cardiovascular mortality.

Researchers administered 200 micrograms of selenium in a selenium-rich yeast preparation and 200 milligrams of Coenzyme Q10 in the ubiquinone form or matching placebos to community living senior citizens daily for 48 months [Alehagen 2013].

Summary of Statistically Significant KiSel-10 Study Outcomes
  • reduction of cardiovascular mortality in the active treatment group vs. the placebo group (5.9% vs. 12.6%) and better cardiac function observed on echocardiograms in the active supplementation group compared to the placebo group [Alehagen 2013]
  • reduction of plasma levels of the N-terminal natriuretic peptide (NT-proBNP), a bio-marker for increased risk of heart failure [Johansson 2013]
  • improvement of health-related quality of life and fewer days in hospital [Johansson 2015]
  • reduction of cardiovascular mortality in senior citizens with low serum selenium status [Alehagen 2016a; Alehagen 2016b]
  • reduction of cardiovascular mortality that persisted after 10 and 12 years in the supplemented group and in subgroups with diabetes, hypertension, ischemic heart disease, and reduced functional capacity due to impaired cardiac function [Alehagen 2015a; Alehagen 2018]
  • reduction of plasma levels of two bio-markers for oxidative damage [Alehagen 2015c]
  • reduction of plasma levels of six bio-markers for systemic inflammation [Alehagen 2015b; Alehagen 2019b]
  • reduction of serum levels of seven bio-markers for fibrosis [Alehagen 2017b]
  • reduction of plasma levels of bio-markers for endothelial dysfunction [Alehagen 2020c]
  • increase in plasma levels of insulin-like growth factor-1, attenuating an age-related decline in IGF-1 concentrations [Alehagen 2017a]
  • reduction of fructosamine concentration compared with the concentration in the placebo group, which tended to increase, important because fructosamine concentration is positively associated with incidence of diabetes and increased blood glucose level [Alehagen 2020b]
  • improvement of renal function in elderly citizens deficient in selenium [Alehagen 2020a]
  • prevention of an increase in D-dimer levels, which are associated with increased risk of thrombotic disorders [Alehagen 2021]
  • association with significant changes in metabolic profiles and with significant changes in the pentose phosphate, the mevalonate, the beta-oxidation, and the xanthine oxidase pathways [Alehagen 2019a]
  • association with significant changes in circulating microRNA [Alehagen 2017c]
  • structural equation modelling that shows that antioxidant and anti-inflammatory effects are the primary underlying biological mechanisms to explain the success of the KiSel-10 study [Alehagen 2022b]
  • decrease in concentrations of fibroblast growth factor 23 (FGF-23) [Alehagen 2022a]
  • less shortening of leukocyte telomere length [Opstad 2022]
  • increase in serum SIRT1 concentrations [Opstad 2023]
  • improvement in serum free thiol levels, supporting a reduction in systemic oxidative stress [Dunning 2023]
  • positive effects on five age-related blood biomarkers – ICAM-1, adiponectin, leptin, stem cell factor, and osteoprotegerin – indicating an anti-aging direction compared to placebo [Alehagen 2023].
Conclusion: Delayed aging and longevity associated with Selenium and Coenzyme Q10 for senior citizens

Professor Urban Alehagen and Professor Jan Aaseth have explained an important biological interrelationship between selenium and Coenzyme Q10 and pointed to a theoretical advantage in using both substances in an intervention if there are deficiencies within the population [Alehagen 2015d]. read more

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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

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Selenium Protects Against Cadmium Poisoning and Atherosclerosis

Cadmium leaking from iron water pipes into drinking water may be a primary cause of increased risk of atherosclerosis – the increased risk of a buildup of plaque on the inside of the artery walls with inflammation as a consequence. This is the thesis of the Danish cardiologist Anton Dorph-Petersen.

Heart attack
Cadmium from drinking water accumulates in the body and causes damage to the layer of cells lining the inside of arteries, leading to a buildup of plaque and to increased risk of atherosclerosis and heart attack. Cadmium is a heavy metal that is found everywhere in the earth. Cadmium accumulates primarily in the liver and kidneys with toxic effects on the kidneys in particular. People with insufficient selenium and iron accumulate more cadmium. Cadmium takes a long time to be eliminated from the body. Iron water pipes and cigarette smoking are significant sources of cadmium in the body.

Dr. Dorph-Petersen asserts that the danger of cadmium toxicity is greatest in regions of the world in which the selenium content of the soil and plants is low and in regions of the world in which there is low dietary intake of selenium containing fish [Dorph-Petersen 2017].

Let me lay out Dr. Dorph-Petersen’s reasoning step by step. His hypothesis has not yet been verified by clinical trials.

However, we do know from a survey of 15,689 study participants in the US that low blood selenium and high blood cadmium are independent risk factors for heart failure. read more