nutrients Review Selenium as a Bioactive Micronutrient in the Human Diet and Its Cancer Chemopreventive Activity Dominika Radomska 1 , Robert Czarnomysy 1,* , Dominik Radomski 1, Anna Bielawska 2 and Krzysztof Bielawski 1 1 Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland; [email protected] (D.R.); [email protected] (D.R.); [email protected] (K.B.) 2 Department of Biotechnology, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-85-748-5700; Fax: +48-85-879-5718 Abstract: This review answers the question of why selenium is such an important trace element in the human diet. Daily dietary intake of selenium and its content in various food products is discussed in this paper, as well as the effects of its deficiency and excess in the body. Moreover, the biological activity of selenium, which it performs mainly through selenoproteins, is discussed. These specific proteins are responsible for thyroid hormone management, fertility, the aging process, and immunity, but their key role is to maintain a redox balance in cells. Furthermore, taking into account world news and the current SARS-CoV-2 virus pandemic, the impact of selenium on the course of COVID-19 is also discussed. Another worldwide problem is the number of new cancer cases and cancer-related mortality. Thus, the last part of the article discusses the impact of selenium on cancer risk based on Citation: Radomska, D.; clinical trials (including NPC and SELECT), systematic reviews, and meta-analyses. Additionally, Czarnomysy, R.; Radomski, D.; this review discusses the possible mechanisms of selenium action that prevent cancer development. Bielawska, A.; Bielawski, K. Selenium as a Bioactive Micronutrient in the Keywords: selenium; cancer; prevention; cancer chemoprevention; molecular mechanisms; micronu- Human Diet and Its Cancer trients; essential nutrients; bioactive nutrients; nutrient sources; COVID-19 Chemopreventive Activity. Nutrients 2021, 13, 1649. https://doi.org/ 10.3390/nu13051649 1. Introduction Academic Editor: Lutz Schomburg In the 19th century, Swedish chemist Jöns Jakob Berzelius discovered selenium while researching a method of obtaining sulfuric acid from pyrites containing iron sulfide [1]. Received: 11 March 2021 Initially, it was regarded as a toxic element, and its role as an essential trace element in Accepted: 11 May 2021 the body was not established until 150 years after its discovery, in 1957 [2]. This was Published: 13 May 2021 determined by Klaus Schwartz and Calvin Foltz, who considered it a substance responsible for preventing lesions in blood vessels, the liver, and/or muscles in rats and chickens. Since Publisher’s Note: MDPI stays neutral then, its impact on the human body and the mechanisms involved have been thoroughly with regard to jurisdictional claims in studied. An important aspect was linking selenium deficiency, as well as its excess, with published maps and institutional affil- iations. disease occurrence and its impact on cancer development risk [3]. The aim of this review is to discuss the biological activity of selenium, i.e., its impact on the proper functioning of the body through various selenoproteins, which perform many important physiological roles [4]. They are responsible, among other things, for immunity, fertility, the aging process, and the management of thyroid hormones, but first Copyright: © 2021 by the authors. and foremost their main function is maintaining a redox balance in cells, which also affects Licensee MDPI, Basel, Switzerland. the aforementioned functions [5–9]. Moreover, the article addresses the issue of appropriate This article is an open access article selenium intake in the diet and the effects of its deficiency and excess in the body, and, very distributed under the terms and importantly, its association with cancer risk. The number of new cancer cases and cancer conditions of the Creative Commons Attribution (CC BY) license (https:// mortality are a worldwide problem [10]. For this reason, possible prophylactic measures creativecommons.org/licenses/by/ are being sought to prevent cancer development and thus reduce the number of new cases 4.0/). and deaths. The many studies associating cancer risk with selenium ingestion (and its Nutrients 2021, 13, 1649. https://doi.org/10.3390/nu13051649 https://www.mdpi.com/journal/nutrients Nutrients 2021, 13, 1649 2 of 25 levels in the body) indicate that this micronutrient may reduce this risk, which would be indicative of its chemopreventive properties [4]. The possible mechanisms responsible for this activity are also discussed in the last part of this review. 2. Dietary Intake of Selenium 2.1. Selenium in the Diet Selenium (Se) occurs as a trace element in the human body, performing a number of important biological functions, and is essential for life and health [11]. The main natural source of Se is food, but Se content varies. This is determined by the geographical location, soil quality in terms of Se concentration, and how much it is accumulated in plants. The climate and the way the food is cultivated and bred, and how we prepare it for consumption, are also important factors [3,12]. The richest sources of Se in the diet are Se-yeast (Se-enriched yeast), nuts, cereals, organ meats, fish, and seafood [13]. Brazil nuts (Bertholletia excelsa, family Lecythidaceae), a plant from the Amazon, have the highest known Se content among non-Se-enriched food [14]. Table1 gives the Se content in some examples of food products in our diet. Table 1. Examples of some food products and their selenium content. Food Typical Se Content (µg/g Fresh Weight) References Se-yeast 3000 [15] Broccoli (Se-enriched) 62.3 [16] Brazil nuts 0.85–6.86 [17] Shellfish 0.36–1.33 [18] Chicken 0.57 [19] Beef 0.35–0.47 [20] Lamb 0.4 [21] Salmon 0.21–0.27 [22] Eggs 0.17 [23] Milk products 0.1–0.55 [17] This microelement can exist in food in both chemical forms—as inorganic and organic compounds [24]. Mostly, Se is found in the form of organic compounds as selenomethionine (SeMet) and selenocysteine (Sec) in plant [25] and animal [26,27] tissues. However, the form of Se intake can affect its bioavailability in the body. Studies show that organic Se (e.g., SeMet) is more bioavailable than its inorganic compounds such as selenates or selenites [27–29]. Interestingly, the bioavailability of this element in the body is also modified by race. Richie et al. observed that in whites it is significantly higher than in blacks [30]. Nevertheless, the most important thing is a healthy and balanced diet that contains all the nutrients at the right levels. As far as Se and its recommended daily dose are concerned, it depends on the local content of this element in the cropland, as this affects its content in the food [31–33]. According to World Health Organization (WHO) standards, the recommended daily dose of Se for adults is 55 µg/day [13,34,35], while the maximum tolerable adult intake without side effects is set at 400 µg/day [13]. Of course, the requirement for Se depends on age and gender [13], as shown in Table2. Nutrients 2021, 13, 1649 3 of 25 Table 2. Recommended daily intakes of selenium for individuals in different age groups and genders. The Adequate Intake (AI) is equivalent to the mean selenium intake of healthy, breastfed infants from birth to 12 months of age, as established by the Food and Nutrition Board (FNB) [13]. Age Group Male (µg/d) Female (µg/d) Pregnancy (µg/d) Lactation (µg/d) Nutrients 2021, 13, x FOR PEER REVIEW Birth to 6 mths 15 * 15 * 3 of 26 7 to 12 mths 20 * 20 * 9 to 13 yrs 40 40 14 to 18 yrs 14 to55 18 yrs 5555 5560 6070 70 19 to 30 yrs 19 to55 30 yrs 5555 5560 6070 70 31 to 50 yrs 55 55 60 70 31 to 50 yrs 55 55 60 70 50 to 71 yrs 55 55 Above 71 yrs 50 to55 71 yrs 5555 55 * Adequate Intake (AI).Above 71 yrs 55 55 * Adequate Intake (AI). It is very important to maintain an adequate level of Se—both deficiency and excess can be dangerous forIt ishuman very importanthealth. What to maintain is important an adequate is that this level microelement of Se—both deficiency has a and excess narrow range ofcan safety be dangerous [36–38], so for one human should health. ensure Whatits optimal is important level in isthe that body. this For microelement has biomarkers of seleniuma narrow status range in of the safety body, [ 36measuring–38], so onethe activity should of ensure selenoproteins its optimal such level in the body. as glutathione peroxidaseFor biomarkers 3 (Gpx3) of selenium and selenoprotein status in theP (SelP, body, Sepp1) measuring in plasma the activity proves ofto selenoproteins be valuable becausesuch a as decrease glutathione of their peroxidase activity indicates 3 (Gpx3) directly and selenoprotein a deficiency of P (SelP,this trace Sepp1) in plasma element [39–41].proves The optimal to be valuable values of because Se in plasma a decrease have ofbeen their estimated activity indicatesat 90–120 directlyµg/L a deficiency (Figure 1), whichof thisis sufficient trace element to saturate [39–41 selenoproteins]. The optimal in values this liquid of Se inblood plasma component have been estimated at [40]. The limit below90–120 whichµg/L a(Figure deficiency1), which of this is sufficientelement is to found saturate is set selenoproteins at 85 µg/L [5,42], in this liquid blood while in Poland,component its concentration [40]. The in blood limit plasma below whichis below a deficiencythis value and of this is about element 50–55 is found is set at µg/L [43], which85 wouldµg/L suggest [5,42], while deficiencies in Poland, in the its inhabitants concentration of this in country.