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LLM - Digital Humanities 16

ERROR: type should be string, got "https://doi.org/10.1007/s12011-021-02716-z\nBiological Trace Element Research (2022) 200:971–987 https://doi.org/10.1007/s12011-021-02716-z\nBiological Trace Element Research (2022) 200:971–987 Abstract Selenium (Se) is an important microelement with numerous positive effects on human health and diseases. It is important to\nspecify that the status and consumption of Se are for a specific community as the levels of Se are extremely unpredictable\nbetween different populations and regions. Our existing paper was based on the impacts of Se on human health and disease along\nwith data on the Se levels in Middle Eastern countries. Overall, the findings of this comprehensive review show that the\nconsumption and levels of Se are inadequate in Middle Eastern nations. Such findings, together with the growing awareness\nof the importance of Se to general health, require further work primarily on creating an acceptable range of blood Se concen-\ntration or other measures to determine optimal Se consumption and, consequently, to guarantee adequate Se supplementation in\npopulations at high risk of low Se intake. Keywords Selenium . Selenoproteins . Human health . Middle East . GPx A Comprehensive Review on Selenium and Its Effects on Human\nHealth and Distribution in Middle Eastern Countries Marek Kieliszek1\n& Iqra Bano2 & Hamed Zare3 Received: 22 February 2021 /Accepted: 8 April 2021\n# The Author(s) 2021\n/ Published online: 21 April 2021 * Marek Kieliszek\nmarek_kieliszek@sggw.edu.pl; marek-kieliszek@wp.pl Introduction by Swedish scientist Jöns Jakob Berzelius in 1818 during the\nproduction of sulphuric acid [2]. Initially, it was considered to\nbe toxic to humans, until its vital function was evidenced in\nthe last decade [3]. Se plays an important role in preserving\nmany natural body functions; therefore, interest in Se research\nhas grown in many areas for public health improvement over\nthe past few decades. The biological function of Se is related\nto its incorporation through selenocysteine (SeCys) into the\nstructure of proteins important for metabolism [4]. Naturally,\nSe is present in both organic and inorganic forms. The organic\nform is the Se contained in amino acids termed as\nselenomethionine (SeMet) and SeCys, while the inorganic\nforms include selenate, selenite, selenide, and elemental Se,\nrespectively [5]. The inorganic form of Se is a major source of\ndietary Se in the human population. Animals who are raised\non Se-containing soil are a rich source of selenoproteins\n(SePs). To distribute Se across a whole country, animals\nshould be raised in fields where there is a proper concentration\nof Se in soil [6]. Due to the large differences in Se detection\nmethodologies among different laboratories, it is difficult to\ncompare Se levels in different countries [7]. It is very impor-\ntant to identify the status and intake of Se in a particular pop-\nulation as the levels of Se are highly variable between diverse\ncommunities and regions. Throughout Middle Eastern coun-\ntries, very little has been known about the level of Se intake\n[8]. Available research shows that the level of Se is highly\nheterogeneous, with some states deficient, and others Human body cells require appropriate nutrition for the main-\ntenance of homeostasis. Micronutrients, such as trace min-\nerals, antioxidants, and vitamins, are crucial for performing\nvarious regenerative processes, managing oxidative stress,\nand developing immunity against pathogens [1]. Selenium\n(Se) is one of the trace minerals that is required to maintain\nvarious functions of the body (Fig. 1). 1\nDepartment of Food Biotechnology and Microbiology, Institute of\nFood Sciences, Warsaw University of Life Sciences-SGGW,\nNowoursynowska 159C, 02-776 Warsaw, Poland Selenoproteins (SePs) SePs are considered to be proteins and perform critical biological\nroles [9] (Fig. 2). They were discovered by a Dr William\nHoekstra of the University of Wisconsin in 1973 [10]. To date,\n30 mammalian SePs have been identified from 25 genes. Structurally, they are composed of 21 amino acids [11]. During\nthe initial phases of the analysis of SePs, recognition of SePs was\nmainly dependent on experimental techniques that included pro-\ntein studies for Se through spectrometry and radioactivity analy-\nsis [12]. The largest group of selenoproteins is involved in the\nprocesses of protecting cells against the effects of reactive oxy-\ngen species (ROS). Generally, SePs perform their activities Introduction It was first discovered * Marek Kieliszek\nmarek_kieliszek@sggw.edu.pl; marek-kieliszek@wp.pl\nIqra Bano\niqrashafi05@yahoo.com\nHamed Zare\nhamed.zare1363@gmail.com\n1\nDepartment of Food Biotechnology and Microbiology, Institute of\nFood Sciences, Warsaw University of Life Sciences-SGGW,\nNowoursynowska 159C, 02-776 Warsaw, Poland\n2\nDepartment of Veterinary Physiology and Biochemistry, Shaheed\nBenazir Bhutto University of Veterinary & Animal Sciences\nSakrand, Sindh 67210, Pakistan\n3\nCellular and Molecular Research Center, Birjand University of\nMedical Sciences, Birjand, Iran 1\nDepartment of Food Biotechnology and Microbiology, Institute of\nFood Sciences, Warsaw University of Life Sciences-SGGW,\nNowoursynowska 159C, 02-776 Warsaw, Poland 2\nDepartment of Veterinary Physiology and Biochemistry, Shaheed\nBenazir Bhutto University of Veterinary & Animal Sciences\nSakrand, Sindh 67210, Pakistan 3\nCellular and Molecular Research Center, Birjand University of\nMedical Sciences, Birjand, Iran 972 Kieliszek et al. Fig. 1 Functions of selenium in various organisms Fig. 1 Functions of selenium in various organisms within cells, acting as enzymes such as deiodinases and\nthioredoxin, and also as antioxidants including glutathione per-\noxidase (GPx), which is regarded as the first animal SePs to be\ndiscovered [10]. SeP synthesis is crucial for Se maintenance and\ndisorders occurring due to disturbance of homeostasis [13]. Both\nSeCys and SeMet are crucial forms of SePs and are present\nnaturally in various sources. SeCys is found in animal tissues\nand in Se-containing proteins, whereas SeMet is obtained from\nyeast, algae, bacteria, and plants respectively [5]. Details about\nsome SePs are given below. oversufficient. The current review is based on the biological\nfunctions of Se and selenoproteins, the health benefits\nof Se, and diseases concerned with deficiency of this\ntrace mineral along with its distribution in Middle\nEastern countries including Saudi Arabia, Jordan,\nTurkey, Libya, Egypt, Iran, and Qatar. Selenoprotein-P (SelP) The\nassumption that SelP is secreted into the bloodstream, as well as\nseveral SeCys sequences that are found in its structure, indicates\nthat SePs can become a source of Se for peripheral tissues [20, 21]. Moreover, when a SelP-knockout mouse was fed a normal Se diet,\nit wasmarkedby asubstantial reductionin Selevels, particularlyin\nthe central nervous system and testes, while Se content was only\nslightly affected in the kidneys and other organs and tissues. In the Selenoprotein-P (SelP) SelP is a glycoprotein that was discovered in 1993 and is one\nof the most abundant SePs, representing some 50% of the Se\nin the blood. Research has shown that SelP plays a major role\nin selenium metabolism [5]. The reduction of systemic SelP\nexpression is associated with Se deficiency in the diet. The\nconsequence of these processes is the formation of oxidative\nstress and the occurrence of various disease states. Thus, Se A Comprehensive Review on Selenium and Its Effects on Human Health and Distribution in Middle Eastern... 973 deficiency reduces the content of SelP [14]. It was found that\nafter administration of Se, the concentration of SelP increases\nfirst and only then does the concentration of other Se-\nliver, Se was also improved by removing the SelP gene and by\nincreasing urinary excretion of Se residues [22]. Fig. 2 Examples of selenoproteins and their functions in organisms Fig. 2 Examples of selenoproteins and their functions in organisms Fig. 2 Examples of selenoproteins and their functions in organisms liver, Se was also improved by removing the SelP gene and by\nincreasing urinary excretion of Se residues [22]. deficiency reduces the content of SelP [14]. It was found that\nafter administration of Se, the concentration of SelP increases\nfirst, and only then does the concentration of other Se-\ndependent proteins increase [15]. SelP is produced in hepato-\ncytes [13]. The activity of this protein has been noted in var-\nious tissues of the body, including in plasma. It is composed of\ntwo domains: the larger N-terminal, which is responsible for\nmaintaining the redox potential in the cell, and the smaller C-\nterminal, which mediates Se transport [16]. This protein is highly\nexpressed in the testes, the brain, and liver tissues. It is considered\ntobe a marker of Se concentrationin thebody. It plays a major role\nin the transport of Se within tissues and maintains homeostasis. SelP is the first protein discovered to contain more than one Se\natom in the form of SeCys. It has also been shown that P-\nselenoprotein protects lipoproteins against oxidation by removing\nthe peroxynitrite molecule that is formed due to oxidative stress\nwithin cells as a result of the reaction between superoxide ions\nwith nitric oxide molecules at sites of inflammation [17–19]. Thioredoxin Reductase This element is found primarily in parent rocks,\nsedimentary rocks of volcanic origin, and also enters to the\nsoil together with rainfall resulting from the evaporation of\nwater from the seas and oceans. Worldwide, its content in soil\nis about 0.4 mg/kg [44, 46]. Soils with a high concentration of\nthis element are found in: North America, Ireland, Australia,\nand Israel. In turn, the areas poor in Se include, among others,\nsome provinces of China (72% of the areas in China), New\nZealand, and a large part of Europe [47]. Moreover, elevated\nSe concentrations appear in soils rich in iron compounds and\norganic matter in saline soils. The geochemical properties of\nthis element will be present in the given area. Selenides and\nselenium sulphides occur mainly in acidic, oil-rich soils with a\nhigh content of organic matter. On the other hand, in soils with\nmedium oxidation conditions and neutral pH, selenites (IV)\npredominate, which are easily soluble after combination with\nalkali metals. The environment is dominated by combinations\nof oxides with iron hydroxides (iron oxide adsorbed and fixed\nSe(IV)), which show low bioavailability in the soil. The third\ngroup are selenates (VI), which are found in well-oxidized\nalkaline soils. Selenates (VI) cannot be combined with iron\ncompounds; therefore, they are easily available. It should be\nnoted that individual forms of Se are easily transformed under\nthe influence of changes in the soil environment, and inorgan-\nic forms of Se may undergo the process of biomethylation to\nvolatile forms of Se: an example is dimethylselenide:\n(CH3)2Se. The distribution of individual compounds allows\nthe natural geochemical cycle of this element to be preserved\n[48]. The constant cycle of Se in the environment relies on the\nbiomethylation of elements by microbes and decomposition\nof the organic material present in it. As a result, volatile Se\ncompounds are synthesized that include dimethyl selenium\n(DMSe), dimethyldiselenide (DMDSe), selenium oxide\n(SeO2), and hydrogen selenide (H2Se). The Se is present in\nthe form of selenates and selenites in water [49]. In aqueous\nsolutions, Se occurs most often in the form of selenite\n(SeO2\n−3) Se (IV), selenate (SeO2\n−4) Se (VI), biselenin\n(HSeO−3), and selenic acid (H2SeO3) [50]. The concentration\nof Se is elevated in groundwater as compared to seawater. The Thioredoxin Reductase Se is a very common element on Earth and is present in the\nlithosphere, atmosphere, hydrosphere, and biosphere respec-\ntively [43]. It is released into the atmosphere via volcanic\ngases. An important factor is also the emission of this element\nto the atmosphere from industrial sources (burning coal, crude\noil) [44]. The content of Se in the atmosphere depends primar-\nily on anthropogenic activity. Human activity releases the el-\nement into the atmosphere, making up 37.5–40.6% of total\natmospheric emissions. In addition, the content of this element\nin the atmosphere in urban areas ranges from 1 to 10 ng/m3\nand mainly comes from the combustion of coal and crude oil\n[45]. Se is unevenly distributed and concentrated in the\nEarth’s crust. This element is found primarily in parent rocks,\nsedimentary rocks of volcanic origin, and also enters to the\nsoil together with rainfall resulting from the evaporation of\nwater from the seas and oceans. Worldwide, its content in soil\nis about 0.4 mg/kg [44, 46]. Soils with a high concentration of\nthis element are found in: North America, Ireland, Australia,\nand Israel. In turn, the areas poor in Se include, among others,\nsome provinces of China (72% of the areas in China), New\nZealand, and a large part of Europe [47]. Moreover, elevated\nSe concentrations appear in soils rich in iron compounds and\norganic matter in saline soils. The geochemical properties of\nthis element will be present in the given area. Selenides and\nselenium sulphides occur mainly in acidic, oil-rich soils with a\nhigh content of organic matter. On the other hand, in soils with\nmedium oxidation conditions and neutral pH, selenites (IV)\npredominate, which are easily soluble after combination with\nalkali metals. The environment is dominated by combinations\nof oxides with iron hydroxides (iron oxide adsorbed and fixed\nSe(IV)), which show low bioavailability in the soil. The third\ngroup are selenates (VI), which are found in well-oxidized\nalkaline soils. Selenates (VI) cannot be combined with iron\ncompounds; therefore, they are easily available. It should be\nnoted that individual forms of Se are easily transformed under\nthe influence of changes in the soil environment, and inorgan-\nic forms of Se may undergo the process of biomethylation to\nvolatile forms of Se: an example is dimethylselenide:\n(CH3)2Se. The distribution of individual compounds allows\nthe natural geochemical cycle of this element to be preserved\n[48]. Selenoprotein W (SepW) SepW is one of the most abundant SePs in mammals. This\nsmall 9-kDa SeP is found in the cytosol and has a high muscle\nand brain concentration [23]. Generally, SepW is required for\nmuscle metabolism in animals. However, the role of this pro-\ntein is still unknown. It has been revealed by some studies that\nits concentration was increased in animal tissues when Se was\nincreased in the diet [24]. Moreover, skeletal muscle calcifi-\ncation during white muscle disease was also prevented\nthrough Se supplementation in cattle and sheep [25]. Various studies on the relationship between SepW and human\nmuscle disease have been carried out and some researchers\ncontinue to working on this to observe SepW’s further effects\non human muscle metabolism [26]. Some studies have re-\nvealed that SepW is a part of the stress-related commu-\nnity of SePs as its expression is heavily influenced by\ndietary availability of Se [27]. Another study has re-\nvealed that when excised from rat skin, a glutathione\ncomplex was found in native SepW [28]. 974 Kieliszek et al. Thioredoxin Reductase The constant cycle of Se in the environment relies on the\nbiomethylation of elements by microbes and decomposition\nof the organic material present in it. As a result, volatile Se\ncompounds are synthesized that include dimethyl selenium\n(DMSe), dimethyldiselenide (DMDSe), selenium oxide\n(SeO2), and hydrogen selenide (H2Se). The Se is present in\nthe form of selenates and selenites in water [49]. In aqueous\nsolutions, Se occurs most often in the form of selenite\n3\n4 Thioredoxin comprises three main enzymes, including TR1,\nTR2, and TR3. They all act as intracellular antioxidant mole-\ncules by regulating redox reactions. These also act as a major\nfactor for apoptosis and DNA synthesis [29]. Thioredoxin acts\nas a key enzyme for the metabolism of Se compounds by\nproviding selenide for the synthesis of SePs [30]. Moreover,\nthis SeP is known to activate the tumor suppressor p53 gene,\nand TR1 is highly expressed in many carcinoma cells and\ntumors [31]. Furthermore, the inhibition of TR1 in cancerous\ncell lines contributed to diminishing the proliferation of cell\nand cancer progression by administering knockdown TR1\ncells into mice as compared to a control cell line [32]. TR1\ncan therefore have two conflicting functions in the develop-\nment and progression of cancer. TR1 can aid cancer preven-\ntion by preserving cell redox balance and lowering the inci-\ndence of mutations that trigger the development of tumors. TR1 is also essential for tumor progression because cancer\ncells are highly sensitive to oxidative damage [33]. TR1 has\nrecently been involved in mediating the essential role of Se in\nthe immune system and prevention of HIV infection, as well\nas its involvement in cancer [34]. Se is a very common element on Earth and is present in the\nlithosphere, atmosphere, hydrosphere, and biosphere respec-\ntively [43]. It is released into the atmosphere via volcanic\ngases. An important factor is also the emission of this element\nto the atmosphere from industrial sources (burning coal, crude\noil) [44]. The content of Se in the atmosphere depends primar-\nily on anthropogenic activity. Human activity releases the el-\nement into the atmosphere, making up 37.5–40.6% of total\natmospheric emissions. In addition, the content of this element\nin the atmosphere in urban areas ranges from 1 to 10 ng/m3\nand mainly comes from the combustion of coal and crude oil\n[45]. Se is unevenly distributed and concentrated in the\nEarth’s crust. Glutathione Peroxidase (GPx) Glutathione peroxidase (GPx) group SePs are common\nin all three domains of life (archaea, bacteria, and\neukarya) [35]. The bacteria, protozoa, fungi, and terres-\ntrial plants also contain SeCys-containing GPx sequence\nhomology. GPx carries out a variety of biological roles\nin cells, including the regulation of hydrogen peroxide\n(H2O2), hydroperoxide detoxification, and the mainte-\nnance of cell redox homeostasis [36]. GPx1 is present\nthroughout the body but highly expressed in red blood\ncells, kidneys, lungs, and liver [37]. It works as an\nantioxidant enzyme and is thought to be affected by\nSe deficiency [38]. GPx2 is present in the gastrointesti-\nnal tract and protects against oxidative stress [39]. GPx3\nis present in plasma and the extracellular fluid of the\nbody and contributes to 10–30% of the Se present in\nthe blood. It is also present in the breast, kidneys,\nlungs, liver, thyroid glands, heart, testes, and also in\nthe placenta. It reduces the production of lipid hydro-\nperoxides in plasma [40]. GPx4 is widely spread in the\nbody but strongly expressed in the testes. It resides in\nmitochondria, cytosol, and the nucleus of cells. It is\nessential for sperm maturation and motility and has a\nhighly effective impact on male fertility improvement\n[41]. GPx5 is mainly present in the olfactory epithelium\nand embryo cells [30]. The functions of GPx6, 7, and 8\nare still thought to be unknown [42]. A Comprehensive Review on Selenium and Its Effects on Human Health and Distribution in Middle Eastern... 975 Table 1 Selenium\ncontent in different\nhuman feeds\nFeeds\nSe content (mg/kg)\nBeef\n0.042–0.142\nLamb\n0.033–0.260\nChicken\n0.081–0.142\nPork\n0.032–0.198\nDairy products\n<0.001–0.11\nCereal\n0.01–0.31\nPasta\n0.01–0.10\nRice\n0.05–0.08\nPotatoes\n0.12\nTuna\n5.6\nCod\n1.5\nOnions\n<0.5\nLentils\n0.24–0.36 Se concentration in Poznań (Poland) is approximately 0.17–\n0.44 μg/L [51]. According to Stefaniak et al. [52], 8% of\n3,000 samples of tap water showed an Se content exceeding\nthe standards of the Environmental Protection Agency. The\nconcentration of Se in polluted water may vary between 400–\n700 μg/L [53]. The content of Se in water depends on the\ngeochemical environment and environmental pollution, as\nwell as the leaching of this element from the rocks. The ac-\nceptable threshold of Se in drinking water is 10 μg/L accord-\ning to World Health Organization (WHO) guidelines and the\nOffice of Environmental Health Hazard Assessment\n(OEHHA) [46]. Glutathione Peroxidase (GPx) It is worth noting that Se present in soils is\nabsorbed by plants. The absorption of this element by plants is\nconditioned by its chemical forms and concentration in soils. Some of these plants are identified to be present in China,\nwhich contains approximately 20.000 ppm Se concentration\n[54]. More than 20 seleniferous plants have been identified,\none of them being the Astragalus species [55]. Astragalus\nincludes A. bisulcatus, A. racemosus, A. praelongus,\nA. pectinatus, and A. thephorosides [54]. According to re-\nsearchers, the concentration of Se is higher in green grasses\nthan in leguminous plants [56, 57]. Plants take up Se in the\nform of selenite or selenate. Selenate is less absorbed by soil\nminerals and more easily absorbed by plants than selenite. Moreover, selenite, selenate, and selenium nanoparticles\n(SeNPs) in plant cells are reduced to organic compounds such\nas selenium amino acids (selenocysteine (SeCys)) [58]. The\nmain consumers of Se from plants are herbivores, which are\nthen consumed by humans. The excess or deficiency of this\nelement at this stage of the food chain may affect the health of\nhumans and animals. That is why it is important to monitor\nsupplementation of this element [59]. methods for determining the concentration of Se include anal-\nysis of biological samples including urine, hair, and finger-\nnails. The enteral formulas and parenteral nutrition formulas\nfor dietary Se intake have been published since 1980 by the\nfood and nutrition board of the US National Research\nCouncil. For parenteral solutions, sodium selenate is the best\nchoice to be considered. The recommended amount of Se in\nparenteral solutions for adults is 50–70 μg/day (Table 2),\nwhile for neonates and children younger than 5 years it is 2–\n3 μg/day/kg weight, and for adolescents and older children the\nrecommended dose of Se is 30–40 μg/day [65]. Nowadays, in several countries, a revolutionary technolog-\nical process focused on the processing of Se-rich food items\nincluding eggs, meat, and dairy has been successfully imple-\nmented [68]. Pork and chicken enriched with Se are vailable in\nKorea, whereas eggs fortified with Se are now on the market\nof 25 countries across the globe. When reviewing research\nstudies on the development of functional foods, it also seems\nclear that eggs enriched with Se could be used to supplement\nmicronutrient deficiencies and to sustain the body’s metabolic\nstability [69]. An egg or chicken meat with a Se content of can Se and Inflammatory Response supply 50% of the recommended daily intake for this ingredi-\nent [70]. Many research centers around the world are actively\nworking to acquire food items that are sources of Se. The most\nattractive attribute is to have the maximum bioactivity of or-\nganic shapes of Se in food items. Moreover, the use of organic\nSe supplementation of yeast origin in terms of shortage has\nmultiple beneficial effects on health [71]. The effect of Se on inflammatory responses was first identi-\nfied in diabetic rats [80]. According to some studies, it has\nbeen proved that Se can influence inflammatory responses\nby inducing inhibition of NF-kB series, which promotes the\nproduction of tumor necrosis factors and interleukins [81]. Some studies suggest that there is a sex-specific impact of\nSe on inflammatory responses, as there is an degree of sexual\ndimorphism among the distribution of Se in organs of the\nbody that affects Se status and arrangement related to body\nfunction [82]. Chronic inflammatory syndromes are usually\nlinked with a reduction in Se status and some studies have\nrevealed that patients with cystic fibrosis [39, 83], inflamma-\ntory bowel diesease, and acne [84] may have a lower status of\nSe than healthy controls. SelS (selenocysteine-containing pro-\nteins), whose secretions from liver cells and human serum\nrecognition have also been published, is one of the SePs in-\nvolved in immune responses [85, 86]. The correct supply of\nSe influences the process of transcription of the gene respon-\nsible for the synthesis of immunoglobulins (Ig), which plays a\nsignificant role in regulating the activity of the immune sys-\ntem. The Se level also influences the differentiation of macro-\nphages. In conditions of Se deficiency, more pro-\ninflammatory macrophages M1 are formed, while in condi-\ntions of Se excess, mainly antiinflammatory macrophages M2\nare formed. This model of action allows the induction of a pro-\ninflammatory cellular immune response against viral and bac-\nterial pathogens by Th1 lymphocytes [71]. It is also worth\nemphasizing that the release of various mediators of inflam-\nmatory reactions in the body may trigger the occurrence of\nvarious disease states. Lowering the activity of selenoproteins\nmay be associated with abnormalities in the functioning\nof the entire antiradical system in the body. SelS is\nregulated by inflammatory markers and extracellular\nsugar levels in liver cells [87]. Moreover, SelS has an\nantitumorigenic function in the systemic macrophages\nand brain astrocytes, decreasing stress [88]. Se and Human Health Se plays a very important role in the maintenance of\nvarious physiological processes in the human body\n[72]. It also plays a crucial role in the pathogenesis\nand pathophysiology of various disorders due to its an-\ntioxidant properties, such as oxidative stress, inflamma-\ntion, apoptosis, reproductive disorders, diabetes, thyroid\nissues, cancer, and immune responses [8]. Rising Se\ndeficiency in various parts of the world is leading to\nmany pathological disorders [73]. According to the lit-\nerature, it has been proved that people consuming a\nspecial diet (due to phenylketonuria) are especially vul-\nnerable to the adverse effects of Se deficiency [74]. Patients with liver cirrhosis, celiac disease, rheumatoid\narthritis, and other degenerative diseases have very low\nlevels of Se [74]. Furthermore, individuals exposed to\nadvanced chemotherapy, and patients who have already\nundergone radiation therapy, are susceptible to reduced\nexpression of this microelement in the system [75]. Se\ndeficiency leads to many other diseases, such as asthma\ndue to impaired GPx activity; it also promotes impaired\ncirculation, irregular heartbeats, coma, or sudden infant\ndeath syndrome [5, 6]. Keshan disease is another con-\ndition that is associated with Se deficiency. This is pe-\ndiatric cardiomyopathy that occurs mainly in young\nwomen of reproductive age and children around 2–10\nyears old [76]. While excess dietary Se commonly\ncauses food poisoning complications such as diarrhea,\nnausea, and vomiting [77, 78]. Many cases of excessive\nSe in people and livestock present in a particular geo-\ngraphic region are usually affected by large concentra-\ntions of Se in the soils. Animal grazing in fields in\nwhich the Se concentration is greater than 5 μg/g must\nbe considered hazardous to consumer health. The Se\nderivatives are characterized by various levels of toxic-\nity. Inorganic forms of Se have greater efficacy com-\npared to organic versions [79]. These findings all sug-\ngest that both excessive and insufficient levels of this\nelement have various impacts on the health of human. A range of diseases and conditions associated with Se\nintake or deficiency and involvement in pathogenesis\nare described below. The Dietary Se and Human Requirements Food enrichment with Se must be conducted in a careful and\nregulated manner to avoid serious impacts that are the inverse\nof the expected effect, since Se is among the most toxic ele-\nments in relatively small amounts, while at the very same\nbeing a vital nutrient with a significant biological role. The\ndifference between the required quantity of Se and the toxic\ndose is very small [4, 60, 61]. Other sources of Se for humans\nare dairy products, cereals, rice, and tuna (Table 1). Table 2\nRecommended dietary allowances (RDAs) for selenium intake\n[66, 67]\nGroup\nSelenium content (μg/day)\nInfants\n10–15\nChildren 1–3\n15–20\nChildren 4–8\n20–30\nChildren 9–13\n40–45\nAdults (men, women)\n55–70\nPregnant women\n60\nLactating women\n60–75 Table 2\nRecommended dietary allowances (RDAs) for selenium intake\n[66 67] The level of Se within human tissue depends on dietary\nintake, which it related to Se availability in the soil and its\ngeographical distribution [62]. One of the most critical prob-\nlems in analytical epidemiological studies based on Se is the\ndifficulty of measuring Se uptake from the diet [63]. According to some studies, the marker for adequate Se intake\nis the measurement of GPx enzyme activity, which was mea-\nsured in erythrocytes, because the activity of this enzyme is\ndirectly proportional to dietary intake of Se [64]. The other 976 Kieliszek et al. Se and Cancer It has been proved by some studies that\nSec insertion sequences (SECIS: selenocysteine insertion se-\nquence) of the open reading frame for mammalian SePs re-\nsemble that of the CD4 gene [92]. Such reading frames can\nencode amino acid sequences within potential selenoproteins. It is worth noting that the accumulation of UGA codons in\nopen reading frames for selenoproteins may refer to the exis-\ntence of specific sequences within the untranslated mRNA\nregion responsible for the insertion of selenocysteine\n(SeCys) in place of another cysteine amino acid (Cys) during\nthe biosynthesis of various proteins. In this way, the resulting\nproteins containing Se in their structure show biological activ-\nity [93]. Hence, Se is important for T-cell protein formation\nand its normal function [94]. Moreover, thioredoxin reductase\npurified from human T-cells plays an important role in reduc-\ning tumor cell growth [95]. The effects of Se status on prostate\ncancer are superior for secondary infections and diseases, sug-\ngesting an inhibitory effect on the spread of tumor [94]. The\nprocess of angiogenesis requires growth factors such as vas-\ncular endothelial cells, growth factors, and metalloproteinases\nfor the degradation of proteins residing in the extracellular\nmatrix. The metalloproteinases cause a reduction in the level\nof growth factors and proteins via methyl selenol (CH3SeH)\nprecursor [95], whereas the selenite suppresses the invasion of\nhuman fibroids by reducing expression of metalloproteinases-\n2 and metalloproteinases-9 [96]. Moreover, bladder cancer\ndevelopment is affected by the genotype of GPx1 which sug-\ngests that GPx1 is relevant to bladder cancer progression [97]. Various methods from numerous areas including China and\nthe USA have verified that low Se consumption is related to\nthe occurrence of lung, thyroid, prostate, mammary and colo-\nrectal carcinomas [98]. The association between Se and risk of\ngastric or esophageal cancer is still unclear. Meanwhile, hu-\nman experiments have been conducted with Se doses of\naround 50 mg/day along with a blend of additional supple-\nments [99, 100]. To date, various compounds of Se\nhave been tested to induce apoptosis involving various\nsignaling pathways [101]. The results revealed that Se\nsupplementation via organic Se decreased metastasis\nboth in vivo and in vitro, suggesting that Se acts as\nan antimetastatic compound by suppressing angiogene-\nsis, cancer cell migration, and invasion [102]. Se and Alzheimer’s Disease Alzheimer’s disease (AD) is a common type of dementia and\nsubsequent development of disease characterized by a pro-\ngressive loss of memory, expression, and recognition of indi-\nviduals or objects, along with more managerial, or alert be-\nhavioral changes [112]. For many years, there has been in-\ncreased interest in the role of Se in medical and neurological\ndisorders such as AD. Furthermore, it was stated in a some\nanimal studies that changes in the level of Se-containing com-\npounds affect the metabolic activity of neurotransmitters\n[113]. This seems very significant in the study of AD because\nseveral neurotransmitters are defective in this disease. However, the most important role of Se in AD is the antiox-\nidant role of distinct seleno-enzymes. Furthermore, the links\nbetween Se and AD risk factors have also been noted. Interactions between Se and apolipoprotein E (ApoE) and\npresenilin 2 are both considered to be heritable genetic factors\nfor AD [114]. Many postmortem studies involving human\nbrain autopsy and tissue biopsies from AD patients and con-\ntrol subjects have explored whether AD is related to altered\nlevels of Se [115]. Epidemiological and clinical studies on Se\nhave indicated stratified consequences in primary and second-\nary prevention of AD. Considered collectively, multiple re-\ncent studies have suggested that modification of Se is a cause Se and Cancer The prevention of cancer by the use of Se in humans, as well\nas in animals, has been indicated by various epidemiological\nstudies. A recent study conducted on 1312 cancer patients\nsupplemented with almost 200 μg Se on a daily basis showed\na decrease in tumor size in prostate cancer, lung cancer, and\ncolon cancer of up to 63%, 58%, and 46% respectively [89,\n90]. The mechanism of action is still unknown but is thought\nto be through two key Se-dependent redox systems (glutathi-\none peroxidase and thioredoxin) within cells. The specific\ncells that facilitate the extermination of toxin compounds\nand mutated cells in blood circulation are T-lymphocytes, A Comprehensive Review on Selenium and Its Effects on Human Health and Distribution in Middle Eastern... 977 Both small and large amounts of Se have been found to se-\nverely impact the cardiovascular system. A trial was under-\ntaken in Eastern USA, with a 7.6-year follow-up to evaluate\nthe impact of Se intake on CVD prevention. The occurrence of\nmyocardial infarction, complete cerebrovascular injuries, and\nCVD were evaluated, and the findings showed that there is no\noverall advantage of applying 200 μg/day of Se to avoid CVD\n[108]. In general, in the context of cardiovascular physiology,\nthe GPx family belongs to the strongest known SePs. Studies\nthat concentrated on the significance of Se deficiency in heart\ndisease development lacking infectious origin have already\nshown that correlation between an inadequate intake of Se\nand cardiac dysfunctions may arise from oxidative stress, as\nwell as its complications. Animal experiments utilizing vari-\nous medications and formulas of Se, as well as trials in GPx\nmouse models, reported an important role in neutralizing re-\nactive oxygen and nitrogen molecules, ultimately restricting\norgan injury following myocardial reperfusion. In addition to\nthe GPx subtypes, thioredoxin reductase is assumed to have\nspecific duties in the cardiovascular system by oxidizing in-\ntraspecific and extracellular signaling molecules via an influ-\nence on adaptive responses such as remodeling [109, 110]. Moreover, some experiments based on animal models have\nrevealed that Se deficiency has proved the down gradation of\nlowdensity lipoprotein (LDL) receptor, which is essential for\nregulating plasma cholesterol levels [111]. and it is thought that Se is required for activation of T-\nlymphocytes [91]. Se and Cancer It has been proved by some studies that\nSec insertion sequences (SECIS: selenocysteine insertion se-\nquence) of the open reading frame for mammalian SePs re-\nsemble that of the CD4 gene [92]. Such reading frames can\nencode amino acid sequences within potential selenoproteins. It is worth noting that the accumulation of UGA codons in\nopen reading frames for selenoproteins may refer to the exis-\ntence of specific sequences within the untranslated mRNA\nregion responsible for the insertion of selenocysteine\n(SeCys) in place of another cysteine amino acid (Cys) during\nthe biosynthesis of various proteins. In this way, the resulting\nproteins containing Se in their structure show biological activ-\nity [93]. Hence, Se is important for T-cell protein formation\nand its normal function [94]. Moreover, thioredoxin reductase\npurified from human T-cells plays an important role in reduc-\ning tumor cell growth [95]. The effects of Se status on prostate\ncancer are superior for secondary infections and diseases, sug-\ngesting an inhibitory effect on the spread of tumor [94]. The\nprocess of angiogenesis requires growth factors such as vas-\ncular endothelial cells, growth factors, and metalloproteinases\nfor the degradation of proteins residing in the extracellular\nmatrix. The metalloproteinases cause a reduction in the level\nof growth factors and proteins via methyl selenol (CH3SeH)\nprecursor [95], whereas the selenite suppresses the invasion of\nhuman fibroids by reducing expression of metalloproteinases-\n2 and metalloproteinases-9 [96]. Moreover, bladder cancer\ndevelopment is affected by the genotype of GPx1 which sug-\ngests that GPx1 is relevant to bladder cancer progression [97]. Various methods from numerous areas including China and\nthe USA have verified that low Se consumption is related to\nthe occurrence of lung, thyroid, prostate, mammary and colo-\nrectal carcinomas [98]. The association between Se and risk of\ngastric or esophageal cancer is still unclear. Meanwhile, hu-\nman experiments have been conducted with Se doses of\naround 50 mg/day along with a blend of additional supple-\nments [99, 100]. To date, various compounds of Se\nhave been tested to induce apoptosis involving various\nsignaling pathways [101]. The results revealed that Se\nsupplementation via organic Se decreased metastasis\nboth in vivo and in vitro, suggesting that Se acts as\nan antimetastatic compound by suppressing angiogene-\nsis, cancer cell migration, and invasion [102]. and it is thought that Se is required for activation of T-\nlymphocytes [91]. Se and Fertility Se is a micronutrient that is important for male and female\nreproduction [137]. The primary factor in male fertility main-\ntenance is oxidative damage to sperm cells, while Se protects\nsperm cells from this destruction and as a result acts as a key\nfactor in the maintenance of male fertility [102]. Low Se con-\ncentration may increase sperm susceptibility to free radicals,\nwhich may disturb the biochemical processes taking place in\nthe acrosome [138]. It was found that lowering the Se concen-\ntration reduces sperm motility, results in damage to the central\npart of the sperm whip, and also increases abnormalities relat-\ned to the morphological structure (mainly with an abnormal\nsperm head or folded tail) [139]. A prominent occurrence of\nfree radicals and lipid peroxidation has been observed in male\nmice fed Se-lacking and improved Se-supplemented diets\n[140, 141]. The results proved that the Se-deficient diet leads\nto a decrease in motility ability and poor-quality semen as\ncompared to increased Se in the diet [142]. Furthermore, one\nstudy showed that Se deficiency can lead to decreased pro-\nduction of spermatozoa. Generally, the total amount of Se in\ntestes can be analyzed by observing the GPx4 concentration\nwithin them [143]. In another study, 69 infertile Scottish men\nreceived Se for 3 months combined with vitamins A, C, and E. A significant increase was found in sperm motility at the end of\nthe clinical trial as compared to control patients [144]. As report-\ned by Mintziori et al. [145], Se supplementation (<200 μg/day) is\nprobably beneficial for men in terms of improving sperm motil-\nity. In other studies, it was found that supplementing the diet with Se and Cardiovascular Diseases It is believed that an antioxidant plays an important role in\ndefending against atherosclerotic and cardiovascular disease\n(CVD) events [103]. Deprivation of Se was strongly correlat-\ned with cardiomyopathy occurring in countries with signifi-\ncantly reduced Se intake [104]. Multiple studies have been\nconducted to evaluate Se’s effect on CVD risk [105–107]. 978 Kieliszek et al. of the pathogenesis of AD. However, the differences in GPx\nactivity may not be unique to AD, because no differences in\nGPx activity were found when comparing the cerebrospinal\nfluid of patient subjects with cerebrovascular disease\n[116–118]. As another example, SelM (selenoprotein M),\nwhich is a SeP has been confirmed to lead to a decreased\ncalcium stream in neurons. SelM downregulation contributed\nto a spike in cytosolic calcium levels [119]. This is notable\nbecause shifts in calcium homeostasis are claimed to be in-\nvolved in AD pathogenesis [120, 121]. Clinically, it is impor-\ntant to evaluate the consequences of Se supplementation in the\nlong term and in comparison with other possible effects to\nbuild the clinical evidence that enables an effective under-\nstanding of the impact of Se on AD prevention [112]. iodine therapy. The results suggested that Se supplementation\nleads to a reduction in thyroid-stimulating hormone (TSH)\nconcentration in healthy children [131]. Another study re-\nvealed that the concentration of Se was recuced in Graves’\norbitopathy disease as compared with patients having only\nGraves’ disease [132]. This suggests that Se deficiency may\nform an independent risk factor for Graves’ orbitopathy. Moreover, in another study, there was no significant link\nfound between Se status and severity of Graves’ orbitopathy\n[133]. Another study suggests that Se deficiency elevates risks\nfor hyperthyroidism, either from nodular goiter or from\nGraves’ disease. The alteration in thyroid hormone levels\nwas only observed in males, signifying the sexual dimorphism\nconcerning Se status and thyroid abnormalities [134]. Significantly, new innovative trials in mutually acute infec-\ntious thyroiditis (AIT) and Graves’ illness have the potential to\nchange existing scientific practice where Se is an important\nelement [135]. The determination of Se status throughout ex-\nperiments and self-medication of patients is very impor-\ntant for clarification of outcomes. Clear recommenda-\ntions for appropriate use of Se as an international guide-\nline are urgently needed [136]. Se and Type 2 Diabetes Mellitus Several in vitro and in vivo experiments have already shown\nthat Se plays a key role in glucose homeostasis regulation. Se\nhas also been found to postpone diabetes development and\nprogression. It has also been reported that Se acts as mimetic\ninsulin in the form of selenite [122–124]. Some experiments\nhave associated concentrations of plasma Se above approxi-\nmately 140 ng/mL with enhanced type 2 diabetes (T2D) risk\n[125]. These results were based on the use of T2D-consistent\ntreatment unconfirmed with glucose, insulin, or hemoglobin\n(HbA1c) circulation tests. However, this has not yet been\nverified in other randomized Se controlled studies [126]. Some animal model experiments have provided positive re-\nsults. The link between a high level of Se exposure and insulin\nresistance and glucose intolerance in late gestation and off-\nspring was found by contrasts between supranutritional\n(>190 mg Se/kg) and nutritional (<50 mg Se/kg) dietary sup-\nplementation [127]. A similar experiment with pigs has been\nfound to show a higher circulating level insulin with a diet\ncontaining 3 mg Se/kg with natural glucose relative to dietary\nlevels [128]. The consequences of T2D can be identified brief-\nly as ineffective deposition and/or insulin sensitivity. SePs are\nessential physiological antioxidants capable of exercis-\ning insulin-like properties that may excessively impede\nthe signaling of insulin [88]. Moreover, pancreatic beta\ncells demonstrate the biological plausibility of Se\nplaying a role in T2D [129]. Se Status in the Kingdom of Saudi Arabia organic Se at an amount of 0.6 and 0.9 ppm increases sperm\nmotility and vitality in Thai-native chickens [146]. Moreover,\nanother study suggested that the level of mitochondrial glutathi-\none peroxidase (mGPx4) that becomes prominent during puberty\nneutralizes free radicals created throughout a succession of redox\nreactions along inside mitochondria. Furthermore, the increased\nlevel of mGPx4, manages the appearance and arrangement of the\nmitochondrial casing by creating a transverse connection through\nitself, as well as additional proteins [147]. When the mGPx4\nconcentration declinea, the structural consistency of sperms re-\nduces, resulting in infertility. Additionally, research has revealed\nthat a low amount of mGPx4 was present in infertile males [148]. Studies in the Kingdom of Saudi Arabia (KSA) studies have\nshown that soil Se levels and food which is grown in KSA\nregions have low to poor Se concentrations [152]. According\nto the data presented by Al-Saleh [154], the content of Se in\nthe soil in KSA (in Al-Kharj, which is located in close\nproximity to Riyadh city) ranges from 0.1 to 0.11 mg/kg. The KSA government is actively making efforts to ensure\nfood safety in the Kingdom by promoting home-grown items. Even so, food imports are a major part of the local supply,\nalmost all originating from the US, whose soil Se grades ap-\npear to be higher to adequate [153]. The main factors contrib-\nuting to Se consumption in KSA are cereals and baked prod-\nucts, followed by fish and meat products, and dairy products\n[155, 156]. With the aim of helping to increase Se consump-\ntion, a study has been conducted by students of King Abdul-\nAziz University study at Jeddah on the Se content of different\nfood items [157, 158]. The major food groups tested in the\nexperiment were cereal products, legumes, and meats. Moreover, for infants residing in KSA, the consumption of\nSe is achieved through infant formulas imported from\nEurope to ensure adequate intake of Se [159]. Conversely,\nmany breast-fed infants do not get enough Se [154]. Food\nchoices may vary among cities and suburbs and various areas\nof the state where there may be variations in the accessibility\nof some imported goods. This may have a significant effect on\nSe levels observed in the KSA community [152]. Se and Thyroid Gland Although the thyroid gland requires iodine for its normal func-\ntions, recent studies have suggested that Se status in the diet\naffects the volume of the thyroid gland [130]. The first ever\nstudy on Se and thyroid metabolism was carried out in central\nAfrica with Se deficient and Se-combined diet in addition to A Comprehensive Review on Selenium and Its Effects on Human Health and Distribution in Middle Eastern... 979 The Role of Se in Pregnancy The requirement for several nutrients increases during the gesta-\ntion period due to several metabolic changes in the body [149]. The reduced Se blood concentration during pregnancy is fre-\nquently associated with reduced activity of the GPx enzyme. Several authors have demonstrated that whole-blood and red\nblood cell enzyme activity decreases throughout pregnancy due\nto Se deficiency in the blood. According to previous studies, it\nhas been proved that the concentrations of Se throughout the\ngestation period were found to be strongly reduced. GPx activity\nwas found to be substantially reduced during the first trimester\nand this low level was sustained until the third trimester, with a\nslight drop during delivery of the fetus [150, 151]. Deficiencies\nof Se in pregnant women could harm the growth of fetus, espe-\ncially it affects the nervous system of growing fetus. Moreover,\ncase-control analysis of expectant mothers found a significant\nrelationship between lower levels of Se and neural tube disabil-\nities [8]. Oxidative stress is believed to arise due to Se deficien-\ncies throughout pregnancy, leading to miscarriages, premature\nbirth, cholestasis, intrauterine retardations, preeclampsia, thyroid\ndisorders, and diabetes mellitus [152]. Se Status in the Kingdom of Saudi Arabia It is worth\nnoting that the estimated Se consumption in Saudi Arabia in a\nstudy by Al-Ahmary [158] was 75–122 μg/person/day, and\nthis level was close to the recommended level (72 μg/person/\nday). It is worth noting that in the studies conducted by Al-\nOthman et al. [156] the daily Se consumption by Saudis in the\ncity of Riyadh was greater than for Sweden (44 μg/person/\nday) or Greece (39 μg/person/day). Nevertheless, it is impor-\ntant to carry out further research aimed at determining the\nbioavailability of Se in food in order to correctly determine\nthe value of this element in the diet. Se Status in Turkey The content of Se in soil in various regions of Turkey ranges\nfrom 0.01 to 0.08 mg/kg [167]. The consumption of bread in\nTurkey by the average person resident ranges from 150 to 450\ng/day, which is almost half of the dry diet [168, 169]. Bearing\nin mind that wheat is the staple food in this country, it seems\nthat the availability of dietary Se for humans will depend on\nthe content of this element in this plant [169]. The average\nlevels of Se in white, whole grain. and maize wheat bread\nwere respectively 1.149, 1.204, and 2.023 μg/kg [168]. The\nSe concentration was measured in the colostrum and mature\nbreast milk samples of the healthy lactating women in Turkey. It was found that the Se content was below the international\nreference range set at 18.5 μg/L among all the analyzed sam-\nples during the whole lactation period [152]. Furthermore,\nvarious samples from dairy milk products were also analyzed. The study found that goat milk had the highest Se content, and\ncow milk had the lowest content of Se [8]. All dairy products\nwere analyzed in another study, where it was revealed that Se\nconcentrations varied based on the type of food. Food samples\ncontaining butter and cheese had higher concentrations,\nwhereas other products such as milk, ice cream, and yogurt\nhad almost no Se [170]. Depending on the region, the daily Se\nintake generally ranges from 4 to 84 μg [169]. Different data\nprovided by Aras et al. [171] indicate that the daily intake of Se Status in Libya Libya is located on the North African coast, bordered by the\nMediterranean Sea to the north. In Libya, groundwater is the\nprimary source of water for drinking supplies and for agriculture\n[175]. Elemental analysis of fields from two distinct agricultural\nland sectors in Libya was performed to calculate the number of\ncertain trace elements utilizing their long-lived radioactive iso-\ntopes. This showed that the amount of Se in Libyan soil is much\nlower than in other countries. The average content of Se in the\nEarth’s crust is 0.4 μg/g. The findings of the experiment indicat-\ned that Se concentrations in Libyan clay surface soil (0.16–0.62\nμg/g) were greater than in sandy soil (0.09–0.22 μg/g) [176]. The\nSe content of various Libyan food items was calculated, includ-\ning a number of types of local and imported food, such as wheat,\nrice, bread, nuts, tea, coffee, and commonly used additives such\nas black and red pepper. The results suggested that the level of Se\nin imported products, such as rice, wheat, and wheat products,\nvaries significantly with both the species of plants, as well as the\ncondition of the lands in which they were grown. Moreover, the\ncalculated and analyzed dietary Se levels tend to be lower\nthroughout the Libyan community than is recommended. Dosing of Se in Libyan diets is strongly recommended through\nintroducing Se to Libyan fields as a fertilizer application, espe-\ncially for cereal schemes [177]. Se Status in Jordan The\napproximate daily average dose and noncarcinogenic hazard\nmeasurement values for Se exposure were below the level of\nconcern for negative health effects [165]. In conclusion, it\nshould be noted that the local grain harvest in Jordan is largely\ninsufficient to meet demand. That is why Jordan is dependent\non food imports. In addition, the presented data may not re-\nflect the actual nutritional status of the population of this coun-\ntry with regard to this trace element (Se) [166]; therefore, it is\nworth carrying out further research in this direction to deter-\nmine the level of this element in Jordan. Se is 20–53 μg/day. In the case of the estimated Se intake in\nchildren, this was reported as 30–40 μg/day [172]. Most stud-\nies from Turkey have shown that the community has an sub-\noptimal Se level [173, 174]. However, other studies docu-\nmented concentrations of plasma [70] and serum Se slightly\nabove 120 μg/L [173]. Se Status in Jordan Se status in Middle Eastern countries is widely variable, as Se\nis found less in some countries and more in others. This var-\niability is apparent even among provinces in the same country. These variations can be related to varying concentrations of\nthe Se in the soil where food is grown. In this section of the\nreview paper, we summarize the status of Se and its intake\namong Middle Eastern countries based on the available liter-\nature. Here, it should be noted that the majority of studies that\nassessed the concentrations of Se in biological samples were\ncase-controlled with small sample sizes, and cannot be gener-\nalized to the whole population. The experiments based on Se\naround the Middle East have various findings [153]. There are currently no scientific data on the Se content of soil\nin Jordan. Only the content of Se in the water has been deter-\nmined. A groundwater survey was carried out to assess Se\nlevels in several aquifers at Amman Zarqa Basin, which is\nregareded as the most populated and industrialized basin in\nJordan. Se levels ranged from 0.09 to 0.74 mg/L across dif-\nferent aquifers, with an average of 24 μg/L, which exceeds the\nWHO recommended drinking water threshold [160]. Another\npublication by Mistry et al. [161] states that the average con-\ntent of Se in water is 0.308 mg/L. Thus, it can be noted that the\ncontent of this element in soil and food grown in these areas 980 Kieliszek et al. may be very low. A later case-control analysis in patients with\ncolorectal cancer tested Se consumption (38.75 ±11.42 μg/\nday) which was significantly lower than the control (59.26\n±8.91 μg/day). It should be noted that the recommended daily\nallowances (RDA) for Se should be at the level of 60–70 μg/\nday [162]. Concentrations of Se have, however, been exam-\nined in two studies using samples of blood and hair [163]. Blood concentrations of about 187 μg/L were considered to\nbe comparatively large in nonsmokers [164]. According to the\nliterature, it has been revealed that in Jordan the assessment of\nseasonal trends in distributions of Se displayed greater levels\nduring the dry season. The strategy including all basic of po-\ntential sources and factors leading to the water content of Se\nhas been reviewed. Serious adverse risk analysis and exposure\namong residents using spring water was also estimated. Se Status in Junhuriyah Misr-Al-Arabiya\n(Egypt) Se is not mentioned in the Egyptian food formulation table. Therefore, limited studies have been undertaken to evaluate Se\nin various food groups, to support a formal decision on\nEgyptians’ dietary Se intake [178]. Consumption of 8.3 mg/day\namong healthy children in Egypt has been reported [179]. Case-\ncontrol studies were performed primarily in children living in\nEgypt and Se levels of 65–83 μg/L were documented [8]. It\nshould be noted that skilful research and processes aimed at\ndetermining the enrichment of this element in the diet will likely\nincrease Se supplementation by people living in Egypt. To sum\nup, the condition of proper human nutrition is complete coverage\nof the body’s energy requirements and individual nutrients need-\ned for physical and mental development and maintaining full\nhealth. Appropriate balancing of Se in the diet can help to min-\nimize the occurrence of various disease states. A Comprehensive Review on Selenium and Its Effects on Human Health and Distribution in Middle Eastern... 981 Declarations Competing Interests\nThe authors declare no competing interests. Open Access This article is licensed under a Creative Commons\nAttribution 4.0 International License, which permits use, sharing, adap-\ntation, distribution and reproduction in any medium or format, as long as\nyou give appropriate credit to the original author(s) and the source, pro-\nvide a link to the Creative Commons licence, and indicate if changes were\nmade. The images or other third party material in this article are included\nin the article's Creative Commons licence, unless indicated otherwise in a\ncredit line to the material. If material is not included in the article's\nCreative Commons licence and your intended use is not permitted by\nstatutory regulation or exceeds the permitted use, you will need to obtain\npermission directly from the copyright holder. To view a copy of this\nlicence, visit http://creativecommons.org/licenses/by/4.0/. Se Status in Qatar (Dawlat Qatar) In Qatar, there have been no direct studies to determine\nSe intake among the Qatari population. The concentra-\ntion of Se in soils is low (0.12–0.77 mg/kg) [186]. According to Qatar General Electricity & Water\nCompany (Kahramaa), Se is not believed to be present\nin the water system in Qatar [187]. However, studies\npresented by Sharm [186] showed that the selenium\ncontent in groundwater is from 0.6 to 80 μg/L [186]. Besides, in Qatar’s primary staple food plant, a survey\nof Se in imported rice concluded that rice makes up\nmore than 100% of the reference nutritive intake\n(RNI) of Se, which was 30 μg/day for Qatari citizens. However, for foreign residents of Qatar (more than 80%\nof the population) who ingested much less rice, the\npercentages varied with sex and rice variety, and all\nwere below 100% of RNI Se. Further research included\nrice-based infant cereals in Qatar, which were found to\nprovide approximately 63% of RNI Se based on the\ndaily portion recommended [8]. This may mean that\nthe use of rice in Qatar contributes greatly to daily\nintake of Se. Even so, Se status was not evaluated in\nany of the several available studies in Qatar. Se Status in Iran The content of soil-Se in Iran ranges from 0.04 to 0.45 mg/kg\n[180]. Considering that rice is one of the most important foods\nin Iran, it may be of interest to determine the content of Se in\nthis product. Rahimzadeh-Barzoki et al. [181] investigated the\nassociation between Se concentration in rice and the rate of\nesophageal malignancy in Golestan province, Iran. They mea-\nsured the Se content of various samples of rice. The mean Se\nlevel in rice samples was 0.229 mg/kg. Moreover, Se levels in\nIranian rice samples were significantly higher than in other\ncountries [178] (0.020 mg/kg and 0.05 mg/kg in Italy and\nKorea, respectively) [182]. Extensive studies on Se content\nin different groups including adolescents, adults, and the el-\nderly have been conducted in Iran [178, 180]. The intake in\nadults and children was found to be sufficient, whereas post-\nmenopausal women had a significantly lower intake than the\nRDA, which is 55 μg/day [180]. Another study revealed that\nthe serum selenium concentration ranged from 58 to 123 μg/L\nin infants, adults, and expectant mothers [183]. Mirzaeian\net al. [184] assess Se intakes in female students in Isfahan,\nIran. Food intake analysis indicated that the amount of Se\nwas 54.5 μg/day, which is not significantly different from\nthe recommended value (55 μg/day). According to other stud-\nies, it can be said that Se intake was found to be adequate in\nIranian children and adults [8, 152, 185]. Se is an important trace mineral for successful functionality of\nhuman and animal species. Unlike many other trace elements,\nit is an element with a very limited quantitative range of con-\ncentrations between deficiency and physiological status, as\nwell as toxic concentrations. Overall, the findings of this sys-\ntematic analysis show that the intake and status of Se are\ninadequate in Middle Eastern countries with much less con-\nsistency as per current measures of sustainability. These find-\nings, together with increasing awareness of the importance of\nSe to general health, require additional work, primarily on\nestablishing an accepted range of blood Se concentration or\nother indicators to determine appropriate Se consump-\ntion and, thereby, to guarantee adequate Se supplemen-\ntation in groups at risk of poor Se intake. More work\nshould be done on the evaluation of Se content in the\nMiddle Eastern population and its impacts on the health\nof individuals living in those countries. References 1. Bhattacharya PT, Misra SR, Hussain M (2016) Nutritional aspects\nof essential trace elements in oral health and disease: an extensive\nreview. Scientifica, Article ID 5464373. https://doi.org/10.1155/\n2016/5464373 2. 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