Selenium Information Selenium: What Is It? What foods provide selenium? What is the recommended dietary intake for selenium? When can selenium deficiency occur? Who may need supplemental selenium? What are some current issues and controversies about selenium? What is the health risk of too much selenium? Selected food sources of selenium References Reviewers As a consumer, you need information you can trust to help you make thoughtful decisions about eating a healthful diet and using vitamin and mineral supplements. Registered dietitians at the Warren Grant Magnuson Clinical Center, the clinical research hospital at the National Institutes of Health (NIH) in Bethesda, MD developed this series of Fact Sheets in conjunction with the Office of Dietary Supplements in the Office of the Director of NIH to provide responsible information about the role of vitamins and minerals in health and disease and to help guide your decisions on the use of vitamin and mineral supplements. Each Fact Sheet in this series received extensive scientific review by recognized experts from the academic and research communities. The information is not intended to be a substitute for professional medical advice. It is important that you seek the advice of a physician about any medical condition or symptom. It is also important to seek the advice of a physician, registered dietitian, pharmacist, or other qualified health professional about the appropriateness of taking dietary supplements and their potential interactions with medications. Selenium: What Is It? Selenium is an essential trace mineral in the human body [1]. Minerals are elements found on earth, most often in soil and water, which are essential to life. Selenium is called a trace mineral because we need very small amounts to stay healthy. This nutrient is an important part of antioxidant enzymes that protect cells against the effects of free radicals. Free radicals are normal by-products of oxygen metabolism that can damage cells and may contribute to the development of some chronic diseases [2]. Scientists are researching the ability of selenium, as an anti-oxidant, to help prevent chronic diseases such as cancer and heart disease. Selenium is also essential for normal functioning of the immune system and thyroid gland [3-6]. What foods provide selenium? Plant foods are the major dietary sources of selenium in most countries throughout the world. The content of selenium in food depends on the selenium content of the soil where the plants are grown or the animals are raised. For example, researchers know that soils in the high plains of northern Nebraska and the Dakotas have very high levels of selenium. People living in those regions generally have the highest selenium intakes in the United States (U.S.) [7]. In the U.S., food distribution patterns across the country help prevent people living in low-selenium geographic areas from having low dietary selenium intakes. Soils in some parts of China and Russia have very low amounts of selenium and selenium deficiency is often reported in those regions. Selenium also can be found in some meats and seafood. Animals that eat grains or plants that were grown in selenium-rich soil have higher levels of selenium in their muscle. In the United States, meats and bread are common sources of dietary selenium [8,9]. Some nuts, in particular Brazil nuts, are also very good sources of selenium. Table 4: Selected Food Sources of Selenium (located at the end of this document) suggests many dietary sources of selenium. What is the recommended dietary intake for selenium? The latest recommendations for selenium are given in the Dietary Reference Intakes (DRIs) developed by the Institute of Medicine of the National Academy of Sciences [10]. Dietary Reference Intakes is the general term for a set of reference values used for planning and assessing nutrient intake for healthy people. Two important types of reference values included in the DRIs for each nutrient are the Recommended Dietary Allowance (RDA) and the Tolerable Upper Intake Level (UL). The RDA recommends the average daily intake that is sufficient to meet the nutrient requirements of nearly all (97-98%) healthy individuals in each age and gender group [10]. The UL, on the other hand, is the maximum level of daily nutrient intake that is unlikely to pose risks of adverse health effects in almost all individuals in a given age group [10]. Table 1 lists the RDAs for selenium, in micrograms, for children and adults. Table 1: Recommended Dietary Allowances (RDA) for Selenium for Adults and Children [10] Age (years) Males and Females (µg) Pregnancy (µg) Lactation (µg) 1-3 y 20 N/A N/A 4-8 y 30 N/A N/A 9-13 y 40 N/A N/A 14-18 y 55 60 70 19 y + 55 60 70 There is insufficient information on selenium to establish a RDA for infants. An Adequate Intake (AI) has been established that is based on the amount of selenium consumed by healthy infants who are fed breast milk [10]. Table 2 lists the AIs for selenium, in micrograms (ug), for infants. Table 2: Adequate Intake for Selenium, in micrograms, (µg) for Infants [10] Age (months) Males and Females (µg) 0-6 months 15 7-12 months 20 Results of the National Health and Nutrition Examination Survey (NHANES III-1988-94) indicated that diets of most Americans provide recommended amounts of selenium (11). When can selenium deficiency occur? Research indicates that selenium deficiency does not usually cause illness by itself. However, it can make the body more susceptible to illnesses caused by other nutritional, biochemical or infectious stresses [10]. Selenium deficiency is most commonly seen in parts of China where the selenium content of the soil is very low. Scientists believe that selenium deficiency is a major factor in Keshan disease, which is seen in large areas of the Chinese countryside [12]. The most common symptom of Keshan disease is cardiomyopathy, characterized by an enlarged heart and poor heart function [13]. In areas where this disease is found, dietary intake is less than 19 µg per day for men and less than 13 µg per day for women [14]. This intake is significantly lower than the current RDA for selenium. Selenium deficiency has been seen in people who rely on total parenteral nutrition (TPN) as their sole source of nutrition [15,16]. TPN is a method of feeding nutrients through an intravenous (IV) line to people whose digestive systems do not function. Forms of nutrients that do not require digestion are dissolved in liquid and infused through the IV line. It is important for TPN solutions to provide selenium in order to prevent a deficiency [17]. Physicians can monitor the selenium status of individuals receiving TPN to make sure they are receiving adequate amounts. Severe gastrointestinal disorders may decrease the absorption of selenium, resulting in selenium depletion or deficiency [18]. Gastrointestinal problems that impair selenium absorption usually affect absorption of other nutrients as well, and require routine monitoring of nutritional status so that physicians can recommend appropriate treatment [18]. Who may need supplemental selenium? Most cases of selenium depletion or deficiency are associated with severe gastrointestinal problems, such as Crohn's disease, or in individuals who have had over half of their small intestine surgically removed. These and other gastrointestinal disorders can impair selenium absorption [18]. Individuals with acute severe illness who develop inflammation and widespread infection often have decreased selenium in the blood [19]. Physicians will evaluate individuals who have gastrointestinal disease or severe infection for depleted blood levels of selenium and determine the need for supplementation. People with iodine deficiency may also benefit from selenium supplementation. Iodine deficiency is rare in the United States, but is still common in developing countries where access to iodine is limited [20]. Researchers believe that selenium deficiency may worsen the effects of iodine deficiency on thyroid function, and that adequate selenium nutritional status may help protect against some of the neurological effects of iodine deficiency [5-6]. As noted above, selenium supplementation is also essential for anyone relying on total parenteral nutrition (TPN) as the sole source of nutrition. Selenium supplementation during TPN administration is now routine [15-17]. While specific medical problems such as those described above indicate a need for selenium supplementation, evidence is lacking for recommending selenium supplements for healthy children and adults. Supplemental Selenium Selenium occurs in major staple foods such as corn, wheat, and soybean as selenomethionine [21]. Selenomethionine was first synthesized in the laboratory in 1984, and is now available in supplements. Selenium supplements also may contain sodium selenite and sodium selenate, two inorganic forms of selenium. Selenomethionine is generally considered to be the best absorbed and utilized form of selenium [10]. Selenium is also available as 'high selenium yeasts', which may contain as much as 1,000 to 2,000 micrograms of selenium per gram [21]. Most of the selenium in these yeasts is in the form of selenomethione. This form of selenium was used in the large scale cancer prevention trial in 1983, which demonstrated that taking 200 ug per day of supplemental selenium could lower the risk of developing prostate, lung, and colorectal cancer [22]. However, some yeasts may contain inorganic forms of selenium, which are not utilized as well by your body as selenomethione. A study conducted in 1995 suggested that the organic forms of selenium, including selenomethionine, increased blood selenium concentration to a greater extent than inorganic forms. However, it did not significantly improve the activity of the selenium-dependent enzyme, glutathione peroxidase [23]. Researchers are continuing to examine the effects of different chemical forms of selenium, but at this time the organic form appears to be the best choice. What are some current issues and controversies about selenium? Selenium and cancer Observational studies indicate that death from cancer, including lung, colorectal, and prostate cancers, is lower among people with higher selenium blood levels or intake [24-30]. In addition, the incidence of nonmelanoma skin cancer is significantly higher in areas of the United States with low soil selenium levels [27]. The effect of selenium supplementation on the recurrence of different types of skin cancers was studied in seven dermatology clinics in the U.S. from 1983 through the early 1990s. Supplementation with 200 µg selenium daily did not affect recurrence of skin cancer, but significantly reduced the occurrence of and death from, total cancers. In particular, the incidence of prostate cancer, colorectal cancer, and lung cancer was lower in the group given selenium supplements [31]. Research suggests that selenium affects cancer risk in two ways. As an anti-oxidant, selenium can help protect the body from damaging effects of free radicals. Selenium also may prevent or slow tumor growth. Certain breakdown products of selenium in the body are believed to prevent tumor growth by enhancing immune cell activity and suppressing development of blood vessels to the tumor [32]. However, not all studies have shown a relationship between selenium status and cancer. In 1982, over 60,000 participants of the Nurses Health Study, with no history of cancer, submitted toenail clippings for selenium analysis. Toenail analysis is thought to reflect selenium status over the previous year. After three and a half years, researchers compared the toenail selenium levels of nurses with and without cancer. Those nurses with higher levels of selenium in their toenails did not have a reduced risk of cancer [33]. Two important long-term studies, the Supplementation en Vitamines et Mineraux AntioXydants (SU.VI.MAX ) study in France and the Selenium and Vitamin E Cancer Prevention Trial (SELECT) study in the U.S., are now underway to further investigate the selenium/cancer prevention link. The SU.VI.MAX Study is a prevention trial looking at the effects of antioxidant vitamins and minerals (including selenium) on chronic disease such as cancer and cardiovascular diseases. Doses of the nutrients provided in the study are one to three times higher than recommended intakes, including a daily supplement of 100 µg selenium. The SU.VI.MAX study is following more than 12,000 adult men and women for eight years; results of the study are expected in 2003 [34]. The SELECT study, a long-term study sponsored by the NIH, is investigating whether supplemental selenium and/or vitamin E can decrease the risk of prostate cancer in healthy men. Past evidence as well as pre-clinical trials for the SELECT study suggests that these two nutrients may be effective in preventing prostate cancer. A supplement containing 200 µg of selenium will be given to individuals in the selenium-only study group, while the combined-nutrients groups will receive supplements with 200 µg selenium and 400 mg vitamin E. The study will include 32,400 healthy adult men and will run until 2013 [35]. Selenium and heart disease Some population surveys have suggested an association between lower antioxidant intake and a greater incidence of heart disease [36]. Additional lines of evidence suggest that oxidative stress from free radicals may promote heart disease [37-39]. For example, it is the oxidized form of low-density lipoproteins (LDL, often called "bad" cholesterol) that promotes plaque build-up in coronary arteries [38]. Selenium is one of a group of antioxidants that may help limit the oxidation of LDL cholesterol and thereby help to prevent coronary artery disease [37-39]. Currently there is insufficient evidence available to recommend selenium supplements for the prevention of coronary heart disease; however, the SU.VI.MAX study mentioned above is looking at the effects of antioxidant nutrients, such as selenium, on heart disease. Selenium and arthritis Surveys indicate that patients with rheumatoid arthritis, a chronic disease that causes pain, stiffness, swelling, and loss of function in joints, have reduced selenium levels in their blood [40,41]. In addition, some individuals with arthritis have a low selenium intake [42]. The body's immune system naturally makes free radicals that can help destroy invading organisms and damaged tissue, but that can also harm healthy tissue [43]. Selenium, as an antioxidant, may help to relieve symptoms of arthritis by controlling levels of free radicals [44]. Current findings are considered preliminary, and further research is needed before selenium supplements can be recommended for individuals with arthritis. Selenium and HIV HIV/AIDS malabsorption can deplete levels of many nutrients, including selenium. Selenium deficiency is associated with decreased immune cell counts, increased disease progression, and high risk of death in the HIV/AIDS population [45]. HIV/AIDS gradually destroys the immune system, and oxidative stress may contribute to further damage of immune cells. Antioxidant nutrients such as selenium are important in protecting cells from oxidative stress, thus potentially slowing progression of the disease [46]. Selenium also may be needed for the replication of the HIV virus, which could deplete host levels of selenium [47]. An examination of 125 HIV-positive men and women linked selenium deficiency with a higher rate of death from HIV [48]. In a small study of 24 children with HIV who were observed for five years, those with low selenium levels died at a younger age, which may indicate faster disease progression [49]. Results of research studies have led experts to suggest that selenium status may be a significant predictor of survival for those infected with HIV, due to the high correlation between selenium deficiency and death from HIV [50]. Researchers continue to investigate the relationship between selenium and HIV/AIDS, including the effect of selenium levels on disease progression and mortality. There is insufficient evidence to routinely recommend selenium supplements for individuals with HIV/AIDS, but physicians may prescribe such supplements as part of an overall treatment plan. It is also important for HIV+ individuals to consume recommended amounts of selenium. What is the health risk of too much selenium? High blood levels of selenium (greater than 100 µg/dL) can result in a condition called selenosis [51]. Symptoms of selenosis include gastrointestinal upsets, hair loss, white blotchy nails, garlic breath odor, fatigue, irritability, and mild nerve damage. Selenium toxicity is rare in the United States, even in areas with high levels of selenium in the soil. The few reported cases have been associated with industrial accidents and a manufacturing error that led to an excessively high dose of selenium in a supplement [52,53]. The Institute of Medicine of the National Academy of Sciences has set a tolerable upper intake level (UL) for selenium at 400 micrograms per day for adults to prevent the risk of developing selenosis [10]. Table 3 lists ULs for selenium, in micrograms, for infants, children, and adults. Table 3: Tolerable Upper Intake Levels for Selenium for Infants, Children, and Adults [10] Age Males and Females (µg) 0-6 months 45 7-12 months 60 1-3 y 90 4-8 y 150 9-13 y 280 14-18 y 400 19 y + 400 Selected food sources of selenium The 2000 Dietary Guidelines for Americans state, "Different foods contain different nutrients and other healthful substances. No single food can supply all the nutrients in the amounts you need" [54]. Table 4 lists some food sources of selenium in milligrams (mg) and percent Daily Value (%DV*) per portion. The selenium content of foods varies according to the growing area. Table 4 lists the selenium content of foods identified in the Total Diet Study [55] and in the USDA data bank [56]. For more information about building a healthful diet, refer to the Dietary Guidelines for Americans [54] and the US Department of Agriculture's Food Guide Pyramid [57]. Table 4: Selected Food Sources of Selenium [55,56] Food Selenium (µg) %DV* Brazil nuts, dried, unblanched, 1 ounce 840 1200 Tuna, canned in oil, drained, 3 ounces 50 70 Beef/calf liver, 3 ounces 47 70 Cod, cooked, dry heat, 3 ounces 32 45 Macaroni and cheese (box mix), 1 cup 32 45 Turkey, breast, oven roasted, 3 1/2 ounces 29 64 Spaghetti w/meat sauce, 1 cup 25 35 Chicken, roasted, meat only, 1/2 breast 24 35 Beef chuck roast, lean only, oven roasted, 3 ounces 23 35 Oatmeal, instant, fortified, cooked, 1 cup 19 25 Noodles, enriched, boiled, 1/2 cup 17 25 Macaroni, elbow, enriched, boiled, 1/2 cup 15 20 Egg, whole, 1 medium 14 20 Cottage cheese, low fat 2%, 1/2 cup 12 15 Bread, enriched, whole wheat, 1 slice 10 15 Bread, enriched, white, 1 slice 7 10 Rice, white, enriched, long grain, cooked, 1/2 cup 6 8 Walnuts, black, dried, 1 ounce 5 8 Cheddar cheese, 1 ounce 4 6 DV = Daily Value. DVs are reference numbers based on the Recommended Dietary Allowance (RDA). They were developed to help consumers determine if a food contains a lot or a little of a specific nutrient. The DV for selenium is 70 mcg. Most food labels do not list a food's selenium content. The percent DV (%DV) listed on the table above indicates the percentage of the DV provided in one serving. Percent DVs are based on a 2,000 calorie diet. Your Daily Values may be higher or lower depending on your calorie needs. Foods that provide lower percentages of the DV also contribute to a healthful diet. References National Research Council. Food and Nutrition Board. Recommended Dietary Allowances. 10th ed. Washington, DC: National Academy Press, 1989. Combs GF, Jr and Gray WP. Chemopreventive agents: Selenium. Pharmacol Ther 1998;79:179-92. McKenzie RC, Rafferty TS, Beckett GJ. Selenium: an essential element for immune function. Immunol Today. 1998;19:342-5. Levander OA. Nutrition and newly emerging viral diseases: An overview. J Nutr 1997;127:948S-950S. Arthur JR. The role of selenium in thyroid hormone metabolism. Can J Physiol Pharmacol 1991;69:1648-52. Corvilain B, Contempre B, Longombe AO, Goyens P, Gervy-Decoster C, Lamy F, Vanderpas JB, Dumont JE. Selenium and the thyroid: How the relationship was established. Am J Clin Nutr 1993;57 (2 Suppl):244S-248S. Longnecker MP, Taylor PR, Levander OA, Howe M, Weillon C, McAdam PA, Patterson KY, Holden JM, Stampfer MJ, Morris JS, Willett WC. Selenium in diet, blood, and toenails in relation to human health in a seleniferous area. Am J Clin Nutr 1991;53:1288-94. Pennington JA and Schoen SA. Contributions of food groups to estimated intakes of nutritional elements: Results from the FDA total diet studies, 1982-91. Int J Vitam Nutr Res 1996;66:342-9. Pennington JA and Young BE. Total diet study nutritional elements. J Am Diet Assoc 1991;91:179-83. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. 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Gramm HJ, Kopf A, Bratter P. The necessity of selenium substitution in total parenteral nutrition and artificial alimentation. J Trace Elem Med Biol 1995;9:1-12. Rannem T, Ladefoged K, Hylander E, Hegnhoj J, Staun M. Selenium depletion in patients with gastrointestinal diseases: Are there any predictive factors? Scand J Gastroenterol 1998;33:1057-61. Gartner R, Albrich W, Angstwurm MW. The effect of a selenium supplementation on the outcome of patients with severe systemic inflammation, burn, and trauma. Bio Factors 14 2001; 199-204. Berdanier, CD. Advanced Nutrition: Micronutrients. CRC Press 1998; 208-211. Schrauzer GN. Commentary: Nutrition selenium supplements: Product types, quality, and safety. J Am College of Nutr. 2001;20:1-4. Clark LC, Combs Jr GF, Turnbull BW, Slate EH, Chalker D, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL, Park HK, Sanders BB, Smith CL, Taylor JR. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. J Am Med Assoc 1996;276:1957-1963. Neve J. Human selenium supplementation as assessed by changes in blood selenium concentration and glutathione peroxidase activity. J Trace Elem Med Biol. 1995;9:65-73. Russo MW, Murray SC, Wurzelmann JI, Woosley JT, Sandler RS. Plasma selenium levels and the risk of colorectal adenomas. Nutr Cancer 1997;28:125-9. Patterson BH and Levander OA. Naturally occurring selenium compounds in cancer chemoprevention trials: A workshop summary. Cancer Epidemiol Biomarkers Prev 1997;6:63-9. Knekt P, Marniemi J, Teppo L, Heliovaara M, Aromaa A. Is low selenium status a risk factor for lung cancer? Am J Epidemiol 1998;148:975-82. Fleet JC. Dietary selenium repletion may reduce cancer incidence in people at high risk who live in areas with low soil selenium. Nutr Rev 1997;55:277-9. Shamberger RJ. The genotoxicity of selenium. Mutat Res 1985;154:29-48. Young KL and Lee PN. Intervention studies on cancer. Eur J Cancer Prev 1999;8:91-103. Burguera JL, Burguera M, Gallignani M, Alarcon OM, Burgueera JA. Blood serum selenium in the province of Merida, Venezuela, related to sex, cancer incidence and soil selenium content. J Trace Elem Electrolytes Health Dis 1990;4:73-77. Combs GF, Jr., Clark LC, Turnbull BW. Reduction of cancer risk with an oral supplement of selenium. Biomed Environ Sci 1997;10:227-34. Combs GF, Clark LC, Turnbull BW. An analysis of cancer prevention by selenium. BioFactors 14 2001; 153-159. Garland M, Morris JS, Stampfer MJ, Colditz GA, Spate VL, Baskett CK, Rosner B, Speier FE, Willett WC, Hunter DJ. Prospective study of toenail selenium levels and cancer among women. J Natl Cancer Inst 1995;87:497-505. Hercberg S, Galan P, Preziosi P, Roussel AM, Arnaud J, Richard MJ, Malvy D, Paul-Dauphin A, Briancon S, Favier A. 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Rheumatoid arthritis and metal compounds-perspectives on the role of oxygen radical detoxification. Analyst 1998;123:3-6. Look MP, Rockstroh JK, Rao GS, Kreuzer KA, Spengler U, Sauerbruch T. Serum selenium versus lymphocyte subsets and markers of disease progression and inflammatory response in human immunodeficiency virus-1 infection. Biol Trace Elem Res 1997; 56 (1):31-41. Romero-Alvira D and Roche E. The keys of oxidative stress in acquired immune deficiency syndrome apoptosis. Medical Hypotheses 1998; 51(2):169-73. Patrick L. Nutrients and HIV; Part One - - Beta carotene and selenium. Altern Med Rev 1999;4:403-13. Baum MK, Shor-Posner G, Lai S, Zhang G, Lai H, Fletcher MA, Sauberlich H, Page JB. High risk of HIV-related mortality is associated with selenium deficiency. J Acquir Immune Defic Syndr Hum Retrovirol 1997;15:370-4. Campa A, Shor-Posner G, Indacoche F, Zhang G, Lai H, Asthana D, Scott GB, Baum MK. Mortality risk in selenium-deficient HIV-positive children. 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USDA Nutrient Database for Standard Reference, Release 15. Nutrient Data Laboratory Home Page, http://www.nal.usda.gov/fnic/foodcomp Center for Nutrition Policy and Promotion, United States Department of Agriculture. Food Guide Pyramid, 1992 (slightly revised 1996). http://www.usda.gov/cnpp/pyramid2.htm

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