The trace element selenium (Se) is an essential part of the human diet; moreover, increased health risks have been observed with Se deficiency. A sufficiently high Se status is a prerequisite for ...adequate immune response, and preventable endemic diseases are known from areas with Se deficiency. Biomarkers of Se status decline strongly in pregnancy, severe illness, or COVID-19, reaching critically low concentrations. Notably, these conditions are associated with an increased risk for autoimmune disease (AID). Positive effects on the immune system are observed with Se supplementation in pregnancy, autoimmune thyroid disease, and recovery from severe illness. However, some studies reported null results; the database is small, and randomized trials are sparse. The current need for research on the link between AID and Se deficiency is particularly obvious for rheumatoid arthritis and type 1 diabetes mellitus. Despite these gaps in knowledge, it seems timely to realize that severe Se deficiency may trigger AID in susceptible subjects. Improved dietary choices or supplemental Se are efficient ways to avoid severe Se deficiency, thereby decreasing AID risk and improving disease course. A personalized approach is needed in clinics and during therapy, while population-wide measures should be considered for areas with habitual low Se intake. Finland has been adding Se to its food chain for more than 35 years—a wise and commendable decision, according to today’s knowledge. It is unfortunate that the health risks of Se deficiency are often neglected, while possible side effects of Se supplementation are exaggerated, leading to disregard for this safe and promising preventive and adjuvant treatment options. This is especially true in the follow-up situations of pregnancy, severe illness, or COVID-19, where massive Se deficiencies have developed and are associated with AID risk, long-lasting health impairments, and slow recovery.
Next year (2017), the micronutrient Selenium (Se) is celebrating its birthday-i.e., 200 years after first being identified by the Swedish chemist Jöns Jakob Berzelius. Despite its impressive age, ...research into the functions of this essential trace element is very alive and reaching out for new horizons. This special issue presents some recent fascinating, exciting, and promising developments in Se research in the form of eight original contributions and seven review articles. Collectively, aspects of Se supply, biochemical, physiological, and chemotherapeutic effects, and geobiological interactions are covered by leading scientists in the areas of nutritional, basic, and clinical research. It is obvious from the contributions that the bicentennial anniversary will celebrate a micronutrient still in its infancy with respect to being understood in terms of its biomedical importance.
In the last two years, there has been a surge in the number of publications on the trace element selenium (Se) and selenocysteine-containing selenoproteins in human health, largely due to the ...pandemic and the multiple roles that this micronutrient and Se-dependent selenoproteins play in various aspects of the disease ....
The expression of selenoproteins is controlled on each one of the textbook steps of protein biosynthesis, i.e., during gene transcription, RNA processing, translation and posttranslational events as ...well as via control of the stability of the involved intermediates and final products. Selenoproteins are unique in their dependence on the trace element Se which they incorporate as the 21st proteinogenic amino acid, selenocysteine. Higher mammals have developed unique pathways to enable a fine-tuned expression of all their different selenoproteins according to developmental stage, actual needs, and current availability of the trace element. Tightly controlled and dynamic expression patterns of selenoproteins are present in different tissues. Interestingly, these patterns display some differences in male and female individuals, and can be grossly modified during disease, e.g. in cancer, inflammation or neurodegeneration. Likewise, important health issues related to the selenium status show unexpected sexual dimorphisms. Some detailed molecular insights have recently been gained on how the hierarchical Se distribution among the different tissues is achieved, how the selenoprotein biosynthesis machinery discriminates among the individual selenoprotein transcripts and how impaired selenoprotein biosynthesis machinery becomes phenotypically evident in humans. This review tries to summarize these fascinating findings and highlights some interesting and surprising sex-specific differences.
The trace elements iodine and selenium (Se) are essential for thyroid gland functioning and thyroid hormone biosynthesis and metabolism. While iodine is needed as the eponymous constituent of the two ...major thyroid hormones triiodo-L-thyronine (T3), and tetraiodo-L-thyronine (T4), Se is essential for the biosynthesis and function of a small number of selenocysteine (Sec)-containing selenoproteins implicated in thyroid hormone metabolism and gland function. The Se-dependent iodothyronine deiodinases control thyroid hormone turnover, while both intracellular and secreted Se-dependent glutathione peroxidases are implicated in gland protection. Recently, a number of clinical supplementation trials have indicated positive effects of increasing the Se status of the participants in a variety of pathologies. These findings enforce the notion that many people might profit from improving their Se status, both as a means to reduce the individual health risk as well as to balance a Se deficiency which often develops during the course of illness. Even though the underlying mechanisms are still largely uncharacterised, the effects of Se appear to be exerted via multiple different mechanisms that impact most pronounced on the endocrine and the immune systems.
SARS-CoV-2 infections underlie the current coronavirus disease (COVID-19) pandemic and are causative for a high death toll particularly among elderly subjects and those with comorbidities. Selenium ...(Se) is an essential trace element of high importance for human health and particularly for a well-balanced immune response. The mortality risk from a severe disease like sepsis or polytrauma is inversely related to Se status. We hypothesized that this relation also applies to COVID-19. Serum samples (
= 166) from COVID-19 patients (
= 33) were collected consecutively and analyzed for total Se by X-ray fluorescence and selenoprotein P (SELENOP) by a validated ELISA. Both biomarkers showed the expected strong correlation (
= 0.7758,
< 0.001), pointing to an insufficient Se availability for optimal selenoprotein expression. In comparison with reference data from a European cross-sectional analysis (EPIC,
= 1915), the patients showed a pronounced deficit in total serum Se (mean ± SD, 50.8 ± 15.7 vs. 84.4 ± 23.4 µg/L) and SELENOP (3.0 ± 1.4 vs. 4.3 ± 1.0 mg/L) concentrations. A Se status below the 2.5th percentile of the reference population, i.e., Se < 45.7 µg/L and SELENOP < 2.56 mg/L, was present in 43.4% and 39.2% of COVID samples, respectively. The Se status was significantly higher in samples from surviving COVID patients as compared with non-survivors (Se; 53.3 ± 16.2 vs. 40.8 ± 8.1 µg/L, SELENOP; 3.3 ± 1.3 vs. 2.1 ± 0.9 mg/L), recovering with time in survivors while remaining low or even declining in non-survivors. We conclude that Se status analysis in COVID patients provides diagnostic information. However, causality remains unknown due to the observational nature of this study. Nevertheless, the findings strengthen the notion of a relevant role of Se for COVID convalescence and support the discussion on adjuvant Se supplementation in severely diseased and Se-deficient patients.
Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual's zinc status. The total serum zinc concentration, which is presently the most commonly ...used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body's zinc status, and its suitability as a future biomarker for an individual's zinc status.
The habitual intake of selenium (Se) varies strongly around the world, and many people are at risk of inadequate supply and health risks from Se deficiency. Within the human organism, efficient ...transport mechanisms ensure that organs with a high demand and relevance for reproduction and survival are preferentially supplied. To this end, selenoprotein P (SELENOP) is synthesized in the liver and mediates Se transport to essential tissues such as the endocrine glands and the brain, where the “SELENOP cycle” maintains a privileged Se status. Mouse models indicate that SELENOP is not essential for life, as supplemental Se supply was capable of preventing the development of severe symptoms. However, knockout mice died under limiting supply, arguing for an essential role of SELENOP in Se deficiency. Many clinical studies support this notion, pointing to close links between health risks and low SELENOP levels. Accordingly, circulating SELENOP concentrations serve as a functional biomarker of Se supply, at least until a saturated status is achieved and SELENOP levels reach a plateau. Upon toxic intake, a further increase in SELENOP is observed, i.e., SELENOP provides information about possible selenosis. The SELENOP transcripts predict an insertion of ten selenocysteine residues. However, the decoding is imperfect, and not all these positions are ultimately occupied by selenocysteine. In addition to the selenocysteine residues near the C-terminus, one selenocysteine resides central within an enzyme-like environment. SELENOP proved capable of catalyzing peroxide degradation in vitro and protecting e.g. LDL particles from oxidation. An enzymatic activity in the intact organism is unclear, but an increasing number of clinical studies provides evidence for a direct involvement of SELENOP-dependent Se transport as an important and modifiable risk factor of disease. This interaction is particularly strong for cardiovascular and critical disease including COVID-19, cancer at various sites and autoimmune thyroiditis. This review briefly highlights the links between the growing knowledge of Se in health and disease over the last 50 years and the specific advances that have been made in our understanding of the physiological and clinical contribution of SELENOP to the current picture.
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•Selenoprotein P (SELENOP) in the blood has transport functions to target tissues.•SELENOP protects certain tissues from Se loss in deficiency via SELENOP cycling.•SELENOP binds heavy metals and heparin with unclear physiological significance.•Enzymatic activity of SELENOP is described in vitro, while clinical evidence is lacking.•SELENOP concentrations and autoantibodies to SELENOP associate with health risks.
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