# 11.4 Selenium
## 11.4.1 Sources

Selenium can be found in animal based foods, plant based foods and in a dietary supplement. For animal based foods, a good source of selenium is found in organ meats, such as the liver, and seafood (Sunde). Selenium can also be found in plant based food such as nuts and grains. The highest source of selenium is found in Brazil Nuts. Brazil Nuts contains about 544 mcg of selenium per serving (Thomson et al., 2008). This amounts to over 700% of the daily value established by the FDA. A poor source of selenium containing foods are found in vegetables, fruit and diary (Tinggi et., 1992).
The concentration of selenium found in plant based food is effected by several environmental factors. The pH and selenium concentration of the soil influence the selenium concentration in food (Rayman, 2008). Thus the amount of selenium found in food is a variable of geographical location. In areas that are low in selenium concentrations, farmers will add selenium into their fertilizer or livestock feed to increase selenium concentration.
There are different chemical forms of selenium found in food. The chemical forms are characterized as organic or inorganic compounds. The organic and most abundant forms found in food are selenocysteine and selenomethionine (“7 Selenium”). Selennocysteine is found in animal selenoproteins. Selenomethionine is found inside the muscle tissue of animals. However it is initially synthesized inside plants. Humans are incapable of producing selenomethionine, it must be consumed from food. About 90 percent or more of Selenomethionine is absorbed into the body (Swanson et al., 1991). This form of selenium is predominantly found in animal and plant based products. The two major inorganic forms are selenites and selenates. Selenates (SeO42-) has a high absorption rate. Almost all of it is absorbed into the body, however a significant amount is loss and excreted with urine. On the other hand, Selenites ( SeO32-) does not have as high of an absorption rate as selenates, but it does have a higher retention rate (Thomson and Robinson, 1986). In contrast to selenomethionine, only about 50% of selenites is absorbed by the body. (Thomson and Robinson, 1986). Selenites and selenates are traditionally found in animal feeds and dietary supplements.
All three major forms of selenium, selenomethionine, selenates and selenites are found in dietary supplements.
A list the top 10 Selemium containing foods is listed below:
Brazil nuts Yellow fin Tuna Halibut Sardines Ham Canned shrimp Enriched macaroni Beef steak Turkey Beef liver
Note: This list is compiled from the USDA National Nutrient Database for Standard Reference, Release 25
Reference page:
"7 Selenium." National Research Council. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: The National Academies Press, 2000.
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, DC, 2000.
Sunde RA. Selenium. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:225-37
Swanson CA, Reamer DC, Veillon C, King JC, Levander OA. 1983. Quantitative and qualitative aspects of selenium utilization in pregnant and nonpregnant women: An application of stable isotope methodology . Am J Clin Nutr 38:169–180
Thomson CD, Chisholm A, McLachlan SK, Campbell JM. Brazil nuts: an effective way to improve selenium status. Am J Clin Nutr. 2008 Feb;87(2):379-84. [PubMed abstract]
Tinggi U, Reilly C, Patterson CM. Determination of selenium in foodstuffs using spectrofluorometry and hydride generation atomic absorption spectrometry. J Food Comp Anal. 1992;5:269–80
Rayman MP. Food-chain selenium and human health: emphasis on intake. Br J Nutr 2008;100:254-68
U.S. Department of Agriculture, Agricultural Research Service. USDA National Nutrient Database for Standard Reference, Release 25. Nutrient Data Laboratory Home Pageexternal link disclaimer, 2012

## 11.4.2 Functions

Selenium, a micronutrient, plays a vital role within the enzymatic function of the human body and is linked to aiding in the stimulation of antibody production (which are disease-fighting organisms within the human body) following a vaccination ("Selenium.", n.d.). Selenium is also linked to aiding in male fertility and is also considered an antioxidant (Mangiapane, 2014). Selenium may work alongside other antioxidants (like vitamin C and E) in order to protect the cells of the body against reactive oxygen species or “free radicals”, which are linked to the development of various cancers and heart disease ("Selenium.", n.d.). Selenium protects against these free radicals by aiding to prevent the formation of these highly unstable and volatile molecules ("Selenium.", n.d.).
Selenium has a wide range of varying functions, which are mainly due in large part to the amino acid Selenocysteine. This amino acid is found in twenty-five proteins (also known as Selenoproteins) (Kurokawa, n.d.). Within the human genome, there are twenty-five identified genes that code for Selenoproteins (Kurokawa, n.d.). Of these twenty-five, the following have known functions:
* 5 Glutathione Peroxidases
* 3 Thioredoxin Reductases
* 3 Iodothyronine Deiodinases
* 1 Methionine Sulfoxide Reductase B1
The twelve above are among the most well known Selenoproteins, along with their main functions which have been identified within various research publications.
Various research publications have gradually begun to uncover all of the potential metabolic functions of all of the present and identified human selenoproteins (Olson, 2008). The Selenoproteins with identified functions include the following:
* Glutathione peroxidases
* Thioredoxin reductases
* Iodothyronine deiodinases (thyroid hormone deiodinases)
* Selenoprotein P
* Selenoprotein W
* Selenophosphate synthetase 2
* Methionine-R-sulfoxide reductase B1 (formerly selenoprotein R)
* 15 kDa selenoprotein
* Selenoprotein S
Glutathione peroxidases have five different identified selenium-containing types:
* GPx1- which is a cytosolic GPx
* GPx2- which is a epithelial cell-specific GPx expressed in intestinal lining and lungs
* GPx3- which is highly expressed in thyroid gland and kidneys
* GPx4- which is a phospholipid-hydroperoxide GPx or PHGPx
* GPx6- which is expressed in the epithelium of the olfactory
GPx isoenzymes are all antioxidant enzymes, that are linked with the reduction of all potentially damaging reactive oxygen species (ROS) through the oxidation-reduction coupling using glutathione. Selenoprotein P aids in spermatogenesis and male fertility using GPx4 (Boitani, n.d.). In the testes, GPx4 reduces phospholipid hydroperoxides, which in turn protects the immature spermatozoa cells against oxidative stress (Boitani, n.d.).
Thioredoxin reductases have three identified Selenocysteine-containing thioredoxin reductase (TrxR) isoenzymes (Arner, 2009):
* TrxR- which is in the cytosol
* TrxR3- which is in the mitochondria
* Thioredoxin glutathione reductase (or TGR)- which is testes-specific
Iodothyronine deiodinases have three identified selenium-dependent iodothyronine deiodinases (DIO) isoenzymes:
* Selenium-dependent Iodothyronine Deiodinases (DIO type 1)
* Selenium-dependent Iodothyronine Deiodinases (DIO type 2)
* Selenium-dependent Iodothyronine Deiodinases (DIO type 3)
Iodothyronine deiodinases (thyroid hormone deiodinases) catalyze the removal of an atom of from T4 (inactive form of thyroid hormone, or T3 precursor) in order to generate majority of the biologically active T3 within the human circulation and on the inside of cells (Schomburg, 2012).
Selenoprotein has three identified selenium-dependent isoenzymes (Olson, 2008):
* Selenoprotein P (SEPP1)
* Selenoprotein W (SEPW or SelW)
* Selenoprotein S (SEPS1 or SelS)
Selenoprotein P (or SEPP1) is predominately produced by the liver, and works as an antioxidant to protect cells from oxidative damage or stress. SEPP1 enables the full activity of thioredoxin reductases and glutathione peroxidases by providing an adequate supply of selenium to all of the other extrahepatic tissues (Arner, 2009). Selenoprotein W (SEPW or SelW) plays a role in redox regulation specifically in the brain, providing protection against oxidative stress which could induce neuronal cell death (Olson, 2008). Selenoprotein S (SEPS1 or SelS) is involved in the cell’s response to ER stress, which is triggered by the presence of misfolded proteins (Olson, 2008). SEPS1 contributes to the removal and transfer of these misfolded proteins from within the lumen of the ER to the cytosol. This is where proteins are then tagged with ubiquitin in order to be degraded later on (Olson, 2008). Selenophosphate synthetase 2 is a selenium donor that catalyzes the synthesis of selenophosphate using hydrogen selenide.
Methionine-R-sulfoxide reductase B1 (previously known as Selenoprotein R) has three identified selenium-dependent isoenzymes:
* Methionine sulfoxide reductases (MsrA)
* Methionine sulfoxide reductases (MsrB1, 2, or 3)
MsrB1 is linked to the regulation of redox reactions of certain proteins, particularly in macrophages, where chemotaxis and phagocytosis rely heavily on the reorganization of the actin cytoskeleton to occur. Therefore, this regulation requires a MsrB1-dependent reduction of methionine-R-sulfoxide residues within the actin.
15 kDa selenoprotein (Selenoprotein 15 or SEP15) is highly expressed in various organs such as the prostate, kidney, testes, liver, and brain (Hill, 2012). Although the function of this Selenoprotein is unknown, SEP15 possess a thioredoxin-like catalytic site and therefore it is presumed that it either regulates the activity of UGGT or the redox state of the UGGT substrates (Hill, 2012). This aspect is said to be critical to this Selenoprotein’s quality control system in regard to the protein folding in the lens of the eye, as well as why it is implicated in various anti-cancer mechanisms (Hill, 2012).
* Arner ES. Focus on mammalian thioredoxin reductases—important selenoproteins with versatile functions. Biochim Biophys Acta. 2009;1790(6):495-526. (PubMed)
* Boitani C, Puglisi R. Selenium, a key element in spermatogenesis and male fertility. Adv Exp Med Biol. 2008;636:65-73. (PubMed)
* Hill KE, Wu S, Motley AK, et al. Production of selenoprotein P (Sepp1) by hepatocytes is central to selenium homeostasis. J Biol Chem. 2012;287(48):40414-40424. (PubMed)
* Kurokawa, Suguru; Berry, Marla J. (2013). Astrid Sigel, Helmut Sigel and Roland K. O. Sigel, ed. Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences 13. Springer. pp. 499–534 Selenium. Role of the Essential Metalloid in Health. doi:10.1007/978-94-007-7500-8_16.
* Lu J, Holmgren A. The thioredoxin antioxidant system. Free Radic Biol Med. 2014;66:75-87. (PubMed)
* Mangiapane E, Pessione A, Pessione E. Selenium and selenoproteins: an overview on different biological systems. Curr Protein Pept Sci. 2014;15(6):598-607. (PubMed)
* Olson GE, Winfrey VP, Hill KE, Burk RF. Megalin mediates selenoprotein P uptake by kidney proximal tubule epithelial cells. J Biol Chem. 2008;283(11):6854-6860. (PubMed)
* Rayman MP. The importance of selenium to human health. Lancet. 2000;356(9225):233-241. (PubMed)
* "Selenium." Sentry Health Monitors. Sentry Health Monitors, Inc., n.d. Web.
* S. J. Lippard, J. M. Berg "Principles of Bioinorganic Chemistry" University Science Books: Mill Valley, CA; 1994. ISBN 0-935702-73-3.
* Schomburg L. Selenium, selenoproteins and the thyroid gland: interactions in health and disease. Nat Rev Endocrinol. 2012;8(3):160-171. (PubMed)

## 11.4.3 Requirements

Selenium deficiency can lead to a heart disease called Keshan disease (Whitney, 2013). This disease is prevalent in China where the soil lacks selenium. Side effects of selenium deficiency include poor immunity and impaired cognation. Selenium deficiency also causes male infertility, could exacerbate iodine deficiencies and is potentially associated with Kashin-Beck disease. Kashin-Beck disease is a type of osteoarthritis. Adequate amounts of selenium are important because it is an antioxidant nutrient. This means having an adequate intake of selenium may help prevent cancer. The recommended daily allowance is 55 micrograms per day. The side effects associated with the toxicity of selenium include brittleness of hair and nails, garlic breath odor, and nervous system abnormalities. These side effects cause selenium to have an UL of 400 micrograms per day. Pregnant and lactating females are recommended an extra 60 or 70 micrograms of selenium per day. Also, the older a human gets, the more selenium they should consume.
Whitney, E., & Rolfes, S. (2013). Understanding nutrition (14th ed.). Belmont, CA: Wadsworth.
Selenium. (2103, July 1). Retrieved December 3, 2015, from https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/

## 11.4.4 Imbalance

Selenium Toxicity High doses of the trace mineral Selenium is quite toxic so the recommended maximum daily intake of Selenium for adults is 0.0004 grams a day. A high intake of Selenium at one time can result in acute or fatal toxicities and small doses of Selenium over long periods of time can result in chronic selenium toxicity, also known as selenosis. Selenosis is noticeable from hair and nails becoming brittle or breaking away, a garlic like odor on breath, or in some severe cases, nervous system abnormalities. Other possible symptoms of Selenium toxicity may include skin rashes, fatigue, gastrointestinal disturbances, and irritability.
Selenium Deficiency
Impaired cognition, susceptibility to psychological stress, and a poor immune system are symptoms of Selenium deficiency. Several selenium responsive enzymes such as iodothyronine deiodinases, selenoprotein W, glutathione peroxidases may be negatively affected with an insufficient selenium intake. Bariatric surgery or severe gastrointestinal conditions like that of Crohn’s disease can increase the risk of acquiring a selenium deficiency. The heart disease known as the Keshan disease is also tied to prolonged Selenium deficiency, though it is believed that Keshan is primarily caused by a virus or a toxin. Keshan is a fatal form of dilated cardiomyopathy that is found most rampant in places like China where there is not a sufficient amount of Selenium found in the food or soil. An enlargement of the heart which causes it to work insufficiently is a key factor in the chronic form of the Keshan disease along with the middle layer of muscle tissue in the wall of the heart being replaced by fibrous tissue while the acute form of the Keshan disease is observed to contain sudden onsets of cardiac insufficiency. Even still, an adequate amount of Selenium helps in preventing Keshan while not obtaining enough Selenium will actually increase the likelihood of contracting Keshan. Now selenium supplements such as sodium selenite has the ability to prevent people from developing the Keshan disease, but it is unable to reverse any of the damage done to the heart muscles. Another disease that also affects low selenium communities like North Korea and central China is the Kashin-Beck disease. The Kashin-Beck disease results in the degeneration of articular cartilage between joints that may lead to joint deformities. Some of the most severe forms of the disease have led to dwarfism. Children as young as two years old have been known to be affected by the Keshan-Beck disease.
Whitney, E., & Rolfes S. R. 2013. Understanding Nutrition. Stamford, C.T.: Cengage Learning.
Hidgon, J., Drake V. J., Delage B., & Tsuji P. A. 2001. Micronutrient Information Center: Selenium. Retrieved from http://lpi.oregonstate.edu/mic/minerals/selenium#deficiency.
Ehrlich S. D. 2013. University of Maryland Medical Center: Selenium. Retrieved from https://umm.edu/health/medical/altmed/supplement/selenium
Selenium toxicity or deficiency are uncommon here in the United States. Since foods such as whole wheat bread, chicken, tuna, brown rice, oatmeal, and mushrooms are all high in selenium, Americans often consume more than enough selenium in their diet (“Top 10 Foods Highest in Selenium”). Since selenium is a trace mineral, only small amounts of it are required in a person’s diet, with the recommended dietary allowance for both men and women being 55 micrograms a day. There is also a “Tolerable Upper Level Intake Level” of 400 micrograms a day to avoid selenium toxicity (“7 Selenium”) Selenium deficiency is rare in the United States due to it being found in a majority of foods in our diet and because farmers also add selenium to the fertilizer they use and to livestock feed. A deficiency in selenium can be common if someone is following a vegetarian diet, since most vegetables are a poor source of selenium if it is not added to the soil. Also people who are undergoing kidney dialysis very often also have low levels of selenium because during this process some selenium is removed from the blood. People living with HIV have low levels of selenium possibly due to malabsorption. It can also be related to a poor diet in developing countries (“Selenium”). People fed intravenously for long periods of time may also suffer from selenium deficiency (“Selenium in Diet”)”). Selenium deficiency could eventually lead to Keshan’s disease, a cardiomyopathy disease that was first noted in Keshan County in Northeast China before a government sponsored selenium supplementation program was created in 1970 (“Keshan’s Disease”). This has been the only confirmed disease linked to a deficiency in selenium, but it has also been associated with male infertility and Kashin-Beck disease. Kashin-Beck is a joint and bone disease (“Selenium in diet”). Selenium Imbalance 4
Selenium toxicity could cause selenosis that included symptoms such as skin rash, fingernail loss, fatigue, weight loss, irritability, vomiting, diarrhea, and skin lesions. People suffering from selenosis will also notice a strange garlic odor in their breath. This disease could potentially also cause nerve damage (“Chandler”). Selenium toxicity can be caused by eating too many foods that are high in selenium, such as Brazilian nuts that have 1917 micrograms of selenium per 100 grams of nuts (“Top 10 Foods Highest in Selenium”). It could also be caused by overusing dietary supplements or by dietary supplements that are mislabeled. For example, a dietary supplement may say that they have just the adequate amount of selenium where instead it may have 300 times that amount (“Selenium”).
“Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids" at NAP.edu." 7 Selenium. The National Academies Press, n.d. Web. 01 Dec. 2015. "Top 10 Foods Highest in Selenium." HealthAliciousNess. N.p., n.d. Web. 01 Dec. 2015. "Selenium." Dietary Supplement Fact Sheet: — Health Professional Fact Sheet. National Institue of Health, n.d. Web. 01 Dec. 2015. "What Is the Danger of Too Much Selenium in the Body?" Healthy Eating. Stephanie Chandler, n.d. Web. 01 Dec. 2015. "Selenium in Diet: MedlinePlus Medical Encyclopedia." U.S National Library of Medicine. U.S. National Library of Medicine, n.d. Web. 01 Dec. 2015. "Keshan Disease." Wikipedia. Wikimedia Foundation, n.d. Web. 01 Dec. 2015.