Source, application and pharmacological effect of selenium

Discovery

Selenium was discovered by Jöns Jacob Berzelius, a Swedish chemist, in the year 1817. He believed the element that was contaminating the sulphuric acid being produced at a factory in Sweden was tellurium. He realised he had found a new element. Berzelius suggested naming the element selenium; from the Greek word selene, for “moon” [1].

General description

Selenium is a trace element that is naturally present in many foods, added to others, and available as a dietary supplement. Selenium, which is nutritionally essential for humans, is a constituent of more than two dozen selenoproteins that play critical roles in reproduction, thyroid hormone metabolism, DNA synthesis, and protection from oxidative damage and infection [2].

Selenium exists in two forms: inorganic (selenate and selenite) and organic (selenomethionine and selenocysteine). Both forms can be good dietary sources of selenium [3]. Soils contain inorganic selenites and selenates that plants accumulate and convert to organic forms, mostly selenocysteine and selenomethionine and their methylated derivatives.

Sources of selenium

(1) Food

Brazil nuts, seafoods, and organ meats are the richest food sources of selenium. Other sources include muscle meats, cereals and other grains, and dairy products. The amount of selenium in drinking water is not nutritionally significant in most geographic regions. The major food sources of selenium in the American diet are breads, grains, meat, poultry, fish, and eggs [4].

(2) Dietary supplements

Selenium is available in multivitamin/multimineral supplements and as a stand-alone supplement, often in the forms of selenomethionine or of selenium-enriched yeast (grown in a high-selenium medium) or as sodium selenite or sodium selenate [5, 6]. The human body absorbs more than 90% of selenomethionine but only about 50% of selenium from selenite [7].

Application

Selenium (Se) is a chalcogenide element which possesses outstanding physical, chemical as well as biochemical properties. It is an essential trace element for human health and participates in numerous important life processes, for example, anti-cancer, anti-oxidation, enhancing human immunity, antagonizing harmful heavy metals and regulating protein synthesis. In addition, it can serve as the catalytic center of enzymes for biocatalysis. For example, glutathione peroxidase (GPx), an antioxidant enzyme with selenium cysteine as its catalytic center, plays an important role in maintaining intracellular redox balance [8]. Owning to its unique photoelectric property and photoconductivity, Se can serve as an excellent semiconductor component applied in various applications such as electrocatalysis, electrochemical sensors and solar cells. Due to its unique properties, selenium has attracted numerous attention. Selenium-based molecule compounds or polymers have been constructed as mimics of natural enzymes or probes for biological detection [9].

Pharmacological activities

The essential trace mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states [10]. Findings have been equivocal in linking selenium to cardiovascular disease risk although other conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. Selenium has additional important health effects particularly in relation to the immune response and cancer prevention, which are almost certainly not exclusively linked to these enzymic functions [11].

(1) Mood

There are a number of indications that selenium is important to the brain: during selenium depletion the brain receives a priority supply; the turnover rate of some neurotransmitters is altered in selenium deficiency; supplementation with selenium reduced intractable epileptic seizures in children; low plasma selenium concentrations in the elderly were significantly associated with senility. A beneficial effect of selenium status on mood has been shown, at least when selenium status is “marginal”. In three studies, low selenium status was associated with a significantly greater incidence of depression and other negative mood states such as anxiety, confusion, and hostility [12].

(2) Viral infection

Selenium seems to be a crucial nutrient for HIV-infected individuals. It is a potent inhibitor of HIV replication in vitro. The progress of HIV can be thought of as being synonymous with the progressive loss of CD4 helper T cells. More than 20 papers report a progressive decline in plasma selenium in parallel with the on-going loss of CD4 T cells in HIV-1. Selenium also appears to be protective in individuals infected with hepatitis virus (B or C) against the progression of the condition to liver cancer [13].

(3) Reproduction

Selenium has long been recognized in animal husbandry as being essential for successful reproduction. Idiopathic miscarriage has been shown to be associated with selenium deficiency Selenium supplements have been shown to prevent early pregnancy. Additionally, Selenium is essential for male fertility, being required for testosterone biosynthesis and the formation and normal development of spermatozoa. Selenium concentration of seminal plasma correlated positively with concentration of spermatozoa in a group of subfertile Norwegian men [14].

(4) Other oxidative-stress or inflammatory conditions

Selenium behaves both as an antioxidant and anti-inflammatory agent. This is because selenium in its antioxidant role, notably as GPx, can: reduce hydrogen peroxide, lipid and phospholipid hydroperoxides, thereby dampening the propagation of free radicals and reactive oxygen species; reduce hydroperoxide intermediates in the cyclo-oxygenase and lipoxygenase pathways diminishing the production of inflammatory prostaglandins and leukotrienes; and modulate the respiratory burst, by removal of hydrogen peroxide and reduction of superoxide production. Selenium supplementation may be of benefit in preventing ischaemia-reperfusion injury: a selenium-enriched diet had a significant effect (p<0·05) in preventing reperfusion-induced arrhythmias in an animal model [15].

Groups at risk of selenium inadequacy

(1) People undergoing kidney dialysis

Selenium levels are significantly lower in patients undergoing long-term hemodialysis than in healthy individuals. Hemodialysis removes some selenium from the blood. In addition, hemodialysis patients are at risk of low dietary selenium intakes due to anorexia resulting from uremia and dietary restrictions. Although selenium supplementation increases blood levels in hemodialysis patients, more evidence is needed to determine whether supplements have beneficial clinical effects in these individuals [16].

(2) People living with HIV

Selenium levels are often low in people living with HIV, possibly because of inadequate intakes (especially in developing countries), excessive losses due to diarrhea, and malabsorption. Observational studies have found an association between lower selenium concentrations in people with HIV and an increased risk of cardiomyopathy, death, and, in pregnant women, HIV transmission to offspring and early death of offspring. Some randomized clinical trials of selenium supplementation in adults with HIV have found that selenium supplementation can reduce the risk of hospitalization and prevent increases of HIV-1 viral load [17].

Health risks from excessive selenium

Chronically high intakes of the organic and inorganic forms of selenium have similar effects. Early indicators of excess intake are a garlic odor in the breath and a metallic taste in the mouth. The most common clinical signs of chronically high selenium intakes, or selenosis, are hair and nail loss or brittleness. Other symptoms include lesions of the skin and nervous system, nausea, diarrhea, skin rashes, mottled teeth, fatigue, irritability, and nervous system abnormalities [18].

References

[1] J. Trofast, Berzelius' discovery of selenium, Chemistry International 33(5) (2011) 16.

[2] M.E. Weeks, The discovery of the elements. VI. Tellurium and selenium, Journal of Chemical Education 9(3) (1932) 474.

[3] J. Chen, An original discovery: selenium deficiency and Keshan disease (an endemic heart disease), Asia Pacific journal of clinical nutrition 21(3) (2012) 320-326.

[4] W. Hu, C. Zhao, H. Hu, S. Yin, Food sources of selenium and its relationship with chronic diseases, Nutrients 13(5) (2021) 1739.

[5] D. Amouroux, P.S. Liss, E. Tessier, M. Hamren-Larsson, O.F. Donard, Role of oceans as biogenic sources of selenium, Earth and Planetary Science Letters 189(3-4) (2001) 277-283.

[6] R. Alimohamady, H. Aliarabi, A. Bahari, A.H. Dezfoulian, Influence of different amounts and sources of selenium supplementation on performance, some blood parameters, and nutrient digestibility in lambs, Biological trace element research 154(1) (2013) 45-54.

[7] U.C. Gupta, J. MacLeod, Effect of various sources of selenium fertilization on the selenium concentration of feed crops, Canadian journal of soil science 74(3) (1994) 285-290.

[8] E. Zoidis, I. Seremelis, N. Kontopoulos, G.P. Danezis, Selenium-dependent antioxidant enzymes: Actions and properties of selenoproteins, Antioxidants 7(5) (2018) 66.

[9] X. Zuo, J. Chen, X. Zhou, X. Li, G. Mei, Levels of selenium, zinc, copper, and antioxidant enzyme activity in patients with leukemia, Biological trace element research 114(1) (2006) 41-53.

[10] T.C. Stadtman, Selenium biochemistry, Annual review of biochemistry 59 (1990) 111-127.

[11] G. Combs Jr, S.B. Combs, The role of selenium in nutrition, Academic Press, Inc.1986.

[12] D. Benton, Selenium intake, mood and other aspects of psychological functioning, Nutritional neuroscience 5(6) (2002) 363-374.

[13] O.M. Guillin, C. Vindry, T. Ohlmann, L. Chavatte, Selenium, selenoproteins and viral infection, Nutrients 11(9) (2019) 2101.

[14] U. Ahsan, Z. Kamran, I. Raza, S. Ahmad, W. Babar, M. Riaz, Z. Iqbal, Role of selenium in male reproduction—A review, Animal reproduction science 146(1-2) (2014) 55-62.

[15] A. Rehman, P. John, A. Bhatti, Biogenic selenium nanoparticles: Potential solution to oxidative stress mediated inflammation in rheumatoid arthritis and associated complications, Nanomaterials 11(8) (2021) 2005.

[16] B. Dworkin, W.S. Rosenthal, L. Weiss, S. Weseley, E.M. Schwartz, Diminished blood selenium levels in renal failure patients on dialysis: correlations with nutritional status, The American journal of the medical sciences 293(1) (1987) 6-12.

[17] C.A. Stone, K. Kawai, R. Kupka, W.W. Fawzi, Role of selenium in HIV infection, Nutrition reviews 68(11) (2010) 671-681.

[18] M.P. Rayman, Selenium intake, status, and health: A complex relationship, Hormones 19(1) (2020) 9-14.