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
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

Selenium Exposure Studies

Selenium exposure in the diet and in supplements: in this review article, we summarize the key outcomes of the best selenium exposure studies.

Optimal Selenium Intake and Status

In his review of the available research literature, Professor Urban Alehagen, Linköping University, Sweden, concluded that a daily intake of 100–150 mcg of selenium per day is required.

This is the intake level that enables an optimal expression of the important selenoprotein P that transports selenium from the liver to peripheral tissues [Alehagen 2022].  For other selenoproteins to be optimized, i.e., to be fully expressed, Prof. Alehagen argues that selenium status of approximately 120 mcg/L when measured in red blood cells is necessary [Alehagen 2022]. read more

Hashimoto’s Disease Patients Benefit from Selenium Supplementation

Hypothyroidism is the medical condition caused by an underactive thyroid gland that is not producing sufficient quantities of thyroid hormones. It is the failure of the thyroid gland to function normally.

Jan Olav Aaseth
Endocrinologist Jan Aaseth, M.D., Ph. D., ERT, explains that, in Norway, the diagnosis of Hashimoto’s disease is made after a clinical examination that involves determination of the patient’s circulating levels of the thyroid hormone thyroxine (T4), thyroid stimulating hormone, and thyroperoxidase antibodies [Aaseth 2022].
The most common form of hypothyroidism is related to Hashimoto’s disease. Hashimoto’s disease is an autoimmune disorder most common among middle-aged women. Symptoms include anxiety, dry skin, fatigue and lethargy, muscle aches and muscle stiffness, negative mood, sensitivity to cold, slow thinking and poor memory.

The standard treatment for Hashimoto’s disease is twofold:

1) treatment with a synthetic hormone called levothyroxine, which works like the T4 hormone that is naturally produced by the thyroid gland read more

Serum Selenium Levels Predict Breast Cancer Prognosis

Research done in southern Sweden shows that three blood biomarkers of selenium availability correlated inversely with mortality from breast cancer. The lower the three selenium biomarker levels, the higher the mortality [Demircan 2021].

Breast cancer awareness
Assessment of selenium status at the time of breast cancer diagnosis identifies patients at exceptionally high risk for a poor prognosis. They are breast cancer patients with low levels of selenium, selenoprotein P, and glutathione peroxidase in their blood.

The blood biomarkers are:

  • Total selenium
  • Selenoprotein P
  • Glutathione peroxidase 3

Breast cancer patients with blood concentrations of these three selenium biomarkers in the highest quintile had significantly better chances of survival compared with patients whose blood levels of these substances were in the lowest quintile [Demircan 2021].

Breast cancer patients with low selenium status according to these three biomarkers had the highest mortality risk with an overall survival probability of approximately 50% after 8 years. The difference in survival between the breast cancer patients in the lowest selenium quintile compared to breast cancer patients with at least one biomarker in the highest quintile was especially notable [Demircan 2021]. read more

Selenium Supplementation for Senior Citizens

Health benefits of daily supplementation of senior citizens with a combination of selenium and Coenzyme Q10:

  • improved heart function as shown on echocardiograms
  • reduced risk of death from heart disease
  • improved health-related quality of life
Professor Urban Alehagen
In the KiSel-10 Study, Prof. Urban Alehagen and the research team administered 200 mcg/day of selenium and 2 x 100 mg/day of Coenzyme Q10 for 48 months to elderly Swedish citizens whose serum selenium status at baseline was quite low (mean: 67.1 mcg/L). The duration of the study was 48 months. The benefits of the supplementation were improved heart function and reduced risk of death from heart disease.

The combined supplementation seems to work by reducing the extent of oxidative stress, systemic inflammation, and fibrosis in the study participants [Alehagen 2022a].

Now, data from the KiSel-10 Study show the following effects of the combined supplementation with respect to Fibroblast Growth Factor 23 concentrations in blood:

  • Supplementation decreased concentrations of FGF-23 hormones.
  • The study showed a relationship between the circulating level of the FGF-23 and atrial fibrillation.
  • The study showed an association between the concentration of FGF-23 and death from heart disease.
  • The study showed an effect of reduced FGF-23 levels on the risk of death from heart disease that is independent of the level of the cardiac wall tension bio-marker NT-proBNP.
  • There exists a close interrelationship between FGF-23 concentrations and kidney function.
Why are FGF-23 Concentrations Important?

Prof. Alehagen explains that FGF-23 is a hormone that is secreted into the blood circulation. One of its primary functions is the regulation of the vitamin D metabolism and of the phosphorous metabolism in the kidneys.

However, there seems to be an association between FGF-23 activity and cardiovascular mortality even in the absence of kidney disease. Experimental data show that FGF-23 may act as a mediator for cardiac hypertrophy, cardiac fibrosis, and cardiac dysfunction [Alehagen 2022b]. read more

Selenium and Toxic Metals and the Ageing Kidney

In individuals older than 50-60 years, the kidneys’ glomerular filtration rate decreases with increasing age. The glomerular filtration rate is a measure of how well your kidneys are working. In your kidneys, there are tiny filters (called glomeruli) that remove waste and excess fluid from the blood.

Jan Aaseth
Jan Aaseth is a Norwegian physician and professor who has done extensive research in endocrinology, toxicology, and medical biochemistry. Here we summarize his review of the relationship between selenium status, heavy metal toxicity, and the kidneys.

Exposure to toxic metals – mercury, cadmium, lead – can be detrimental to kidneys of normal adults. Accordingly, exposure to toxic metals can affect individuals with reduced glomerular filtration rates even more adversely.

Professor Jan Aaseth and a team of researchers have reviewed the available research data. Their findings show the following relationships [Aaseth 2021]:

Elderly Individuals More Susceptible to Toxic Metal Exposure

Healthy elderly individuals are capable, for the most part, of maintaining normal kidney function. However, especially after the age of 70 years, physiological changes occur in the kidneys. read more

Selenium Status and Covid-19 Patients

In cases of severe Covid-19 disease, patients have significantly lower concentrations of selenium and selenoprotein P and significantly higher levels of oxidative stress. That is to say, there is a more intense formation of harmful free radicals in patients with severe Covid-19 disease [Skesters 2022].

Corona virus
An adequate supply of selenium and zinc and vitamin D is essential for resistance to the corona viruses and to other viral infections. Here, Skesters er al show that Covid-19 patients have significantly lower levels of plasma selenium and selenoprotein P and significantly higher levels of oxidative stress.

Note: Oxidative stress is the bio-medical term for an imbalance between harmful free radical activity and protective antioxidant activity. Selenium is a key component of antioxidant selenoproteins such as the glutathione peroxidases and the thioredoxin reductases.

Role of Selenium and Selenoprotein P in Covid-19 Disease

Researchers have been investigating the role that selenium may play in reducing the severity and mortality of Covid-19 infections. Studies have shown a close relationship between low selenium status, Selenoprotein P deficiency, oxidative stress level, and Covid-19 disease incidence, severity, and prognosis [Skesters 2022]. read more

Antioxidant Action of Selenium and Selenoproteins

Antioxidants. Several selenoproteins play important roles as antioxidant enzymes in the protection of the cells and the mitochondria against the oxidative damage caused by harmful free radicals. Prominent among the antioxidant seleno-enzymes are the glutathione peroxidases and the thioredoxin reductases [Alehagen 2022].

Professor Urban Alehagen
Professor Urban Alehagen, the lead researcher on the KiSel-10 Study, estimates that a daily selenium intake of 110-150 mcg per day is necessary to achieve optimal expression of selenoprotein P, one of the most important selenoproteins in the plasma and the main transporter of selenium in the blood [Alehagen 2022].
Note: Oxidative stress is the bio-medical term for an imbalance in the relationship of 1) harmful free radicals, mostly of the reactive oxygen species, and 2) protective antioxidants, which should neutralize the harmful free radicals.

In many regions of the world, notably in much of Europe and the Middle East, there is selenium-poor soil and selenium-poor foodstuffs. In Sweden, for example, the average daily intake of selenium among senior citizens
is approximately 35 mcg/day, well below the amounts (110–150 mcg/day) needed for an optimal expression of the selenoprotein antioxidants [Alehagen 2022].
read more

Impact of Selenium Status on Ageing

Selenium is an essential trace element. Essential means that sufficient selenium is necessary for normal cell functioning and that our bodies cannot synthesize selenium for us. We must get it from our diets. Trace element means selenium is a micronutrient that is needed in very small quantities, in microgram quantities. It may be an important element to slow the ageing process.

Elderly couple
Selenium as a component in protective enzymes helps to keep us healthier longer in life. It helps to suppress oxidative stress and to decrease inflammation, to remove misfolded proteins, to decrease DNA damage, and to promote telomere length.

Sufficient selenium status plays an important role in the prevention of cardiovascular diseases, inflammation, and infections. Prof. Margaret P. Rayman, University of Surrey, estimates that serum/plasma selenium status of around 125 mcg/L is optimal for human health [Rayman 2020].

The beneficial work of selenium in the cells and tissues is done by selenoproteins that contain the amino acid selenocysteine in the active center. Among the selenoproteins known to have an antioxidant effect in the body are the glutathione peroxidases (GPX1-4 and GPX6) and the thioredoxin reductases (TXNRD1-3) [Alehagen 2021]. read more

Selenium Supplementation and Preeclampsia Risk

Selenium supplementation of pregnant women at a high risk of preeclampsia has shown beneficial effects on 1) serum selenium levels, 2) some metabolic profiles, 3) uterine artery pulsatility index, and 4) mental health, compared to placebo. The study compared the effect in 60 pregnant women of supplementation with 200 mcg/day for 12 weeks with the effect of placebo for the same period.

Pregnant woman
Preeclampsia is a serious hypertensive condition of pregnancy. It is associated with high risk of maternal and fetal morbidity and mortality. Selenium intake and status have been linked to the occurrence of preeclampsia.

The supplementation took place for 12 weeks starting in weeks 16 to 18 of pregnancy. No side effects related to the intake of 200 mcg of selenium per day by pregnant women at high risk of preeclampsia were reported throughout the duration of the study  [Mesdaghinia 2022].

Selenium Supplementation Compared to Placebo

How did the selenium supplementation compare with the placebo supplementation in the pregnant women? read more