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Selenium |
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Selenium is a semi-metal that is an important trace mineral for certain metabolic functions. It forms an essential part of certain enzymes and other proteins, called selenoproteins, which are very potent antioxidants. Some of the important selenoenzymes include glutathione peroxidase, thioredoxin reductase, and deiodinases. Antioxidants prevent cellular and tissue damage by free radicals that are produced during certain metabolic processes in the body. Apart from acting as an antioxidant, selenoproteins also protect the body from cardiac diseases and cancers that mainly occur due to free radicals. Some selenoproteins also help in thyroid metabolism by converting one form of thyroid protein to another and also in regulating the immune system.
Large doses of selenium can be toxic but micro quantities of this element are essential for proper functioning of the body. Selenium is known to be an important part of at least three enzymes that are important for proper thyroid gland functioning. Preliminary studies also indicate the preventive and therapeutic role of selenium in conditions like cancer, diabetes, HIV/AIDS, tuberculosis, cardiac disease, and mercury poisoning. Selenium also has anti-fungal properties that have been exploited in the formulation of many anti-dandruff shampoos and body lotions.
Selenium deficiency, though very rare, has been linked to certain heart diseases such as hypothyroidism. It is also reported that the immune system weakens in absence of selenium. Moreover, selenium deficiency can also make the body more susceptible to illness when individuals suffer from other nutritional and biochemical deficiencies.
Keshan's disease is an abnormal cardiac condition that leads to an enlarged heart and poor heart function, which occus in selenium-deficient children. Other diseases brought upon by selenium deficiency include Kashin-Beck's disease and Myxedematous endemic cretinism, leading to osteoarthropathy and mental retardation respectively. Since selenium is absorbed from the gastrointestinal tract, those individuals with gastrointestinal disorders (and an inability to absorb selenium) will be more susceptible to selenium deficiency.
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Selenium was first discovered in 1817 by Jons Jakob Berzelius in deposits within sulphuric acid chambers. Since then selenium has found applications in many chemical and electronics manufacturing industries, though the first report regarding the biological effect of selenium came only in 1996 when research first showed a positive link between selenium supplementation and cancer prevention. However, due to the micro-requirement of this element, there is no considerable demand in the supplement market.
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Antioxidant:
Selenium is an important part of enzyme glutathione peroxidase - a potent antioxidant. Glutathione peroxidase is responsible for converting hydrogen peroxide (produced during various oxidative metabolic reactions) to water. This enzyme also prevents the toxic free-radical reactions from occurring in cell membranes. Selenium deficiency has been linked to decreased levels of glutathione peroxidase and hence, increased free radical accumulation in cells. Selenium is also a part of another antioxidant, selenoprotein P that is responsible for neutralizing nitrogen-free radicals in blood vessels. Owing to its antioxidant property, selenium also seems to play a role in the aging process and relieves the symptoms of arthritis.
Anti-tumorigenic:
The health benefits of selenium became well recognized when the USFDA approved the health claim petition filed by Wellness Lifestyle Inc. regarding health benefits of selenium and its role in preventing cancers in 2003. The anti-cancer effect of selenium is well established in animals. However, there is very little supporting data for the same in humans. Studies are still being conducted to confirm the definitive role played by selenium in preventing cancers. However, selenium deficiency in humans has been implicated in cancers of the colon, rectum, prostate, breast, and leukocytes. Moreover, the preventive effects of selenium in cancer is more evident when antioxidants like carotenoids and vitamin E are low. A study conducted at the University of Arizona, Tuscon, showed that administration of 200 mcg of selenium per day reduced the risk of cancer by 32%, and reduced the risk of death due to cancer by 50%. Populations with low selenium concentrations in soil have been found to have a higher risk of cancer. However, recently it has been shown that selenium is ineffective in preventing and treating prostate cancers in men.
Anti-HIV:
Deficiency of selenium has been linked to a high risk of deaths due to HIV infection. Because of its immune-stimulating properties and antioxidant activities, selenium is reported to be important for preventing and delaying progression of HIV infection or AIDS. However, human clinical trials supporting the supplemental benefits of selenium in HIV infection need further substantiation.
Immune system booster:
Selenium is needed by specific cells of the immune system, called T-cells, that produce cytokines. Cytokines act as messengers within and between cells in cases of infections and inflammation. Selenium is also required by other cells of the immune system to fight against bacteria and fungi that enter the body and cause infections.
Pro-thyroid function:
Selenium is important for conversion of T4 thyroid hormone to its active T3 form. Deiodinase enzyme responsible for this conversion requires selenium at its active center. Hence, deficiency of selenium leads to low thyroid hormone levels resulting in hypothyroidism.
Anti-diabetic:
Selenium is also known to mimic the action of insulin and protect against diabetes and its complications. However, the exact mechanism of action of selenium is not yet known. It is believed that selenium stimulates glucose uptake and regulates metabolic processes like glycolysis and gluconeogenesis. However, many recent reports show that continuous administration of selenium supplements can lead to type 2 diabetes.
Cardiovascular support:
Selenium increases the ratio of good cholesterol to bad cholesterol. It also prevents clots in blood vessels, thus reducing the risk of heart attacks. Studies have shown that smokers and individuals who have had a stroke are benefited maximally by selenium supplementation.
Prevention of cataracts:
Though a direct link between selenium and cataract is yet to be established, selenium, along with glutathione, helps treat cataracts indirectly via glutathione peroxidase.
Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Systematic review: Primary and secondary prevention of gastrointestinal cancers with antioxidant supplements. Ailment Pharmacol Ther. 2008;28(6):689-703.
Canter PH, Wider B, Ernst E. The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: A systematic review of randomized clinical trials. Rheumatology (Oxford). 2007;46(8):1223-33.
Cocchi M, Venturi . Selenium and Iodide: ancient antioxidants of cellular membranes? 7th Internat Symp on Selenium in Biology and Medicine. Venice (Italy). Abs. 2000;P-88:134.
Combs G, Combs S. (1986). The role of selenium in nutrition., Orlando FL: Academic Press. 1986.
Combs G, Levander O, Spallholz I, et al. (Eds.) (1987). In 'Selenium in biology and medicine, Parts A and B'. New York NY: Van Nostrand Reinhold Co.
Duffield-Lillico AJ, Dalkin BL, Reid ME, et al. Nutritional prevention of Cancer Study Group. Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: An analysis of the complete treatment period of the nutritional prevention of cancer trial. B J U Int. 2003;91(7):608-12.
Hoekstra WG. (1974). In 'Trace element metabolism in animals'. Edited by Hoekstra WG, Suttie JW, Ganther HE, Mertz W. Baltimore MD:University Park Press. pp 61.
Schrauzer G, White D, Scheneider C. Cancer mortality correlation studies, III: Statistical associations with dietary selenium intakes. Bioinorg Chem. 1977;7:23-24.
Stapleton SR. Selenium: an insulin-mimetic. Cell Mol Life Sci. 2000;57(13-14):1874-9.
Venturi S, Venturi M. Evolution of dietary antioxidant defenses. European Epi-Marker. 2007;11(3):1-12.
Healthlink at Medical College of Wisconsin.
USFDA Selenium and Cancer Health Claim Petition by Wellness Lifestyle Inc.
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Sources and Forms of Selenium: |
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Selenium is generally an important component of soil, which is then absorbed by plants. Dried nuts, especially brazil nuts and walnuts, have the highest content of selenium. Meat, tuna, beef liver, calf liver, chicken, and turkey are also rich sources of selenium. Vegetarian sources of selenium include bread, oatmeal, noodles, milk, cheese, eggs, tofu, pinto beans, peanut butter and sunflower seeds. Natural sources of selenium include spinach, broccoli, carrots, potato, green beans, apples, oranges, avocados and strawberries.
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Recommended Dosage of Selenium: |
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The RDA for selenium is 55 micrograms (mcg)/day for individuals over 14 years of age. Pregnant and lactating women need 60 mcg/day. While infants require 15mcg/day, children aged up to 13 years require up to 40mcg/day. However, anti-cancer effects of selenium are evident only at levels closer to 200 mcg/day (the minimum concentration administered in human clinical trials). The Institute of Medicine has set the maximum limit for selenium intake at 400 mcg/day.
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Safety and Side Effects of Selenium: |
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Though most of the clinical studies have been done at a maximum concentration of 200 mcg/day, more than 400 mcg/day of selenium intake may lead to a condition called 'selenosis', which is characterized by gastrointestinal disorders, hair loss, white blotchy nails, and mild nerve damage. However, selenium toxicity is extremely rare.
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Frequently Asked Questions on Selenium: |
Is selenium really necessary for the body, even when its recommended daily allowance is 50 micrograms/day?
Yes. Selenium is extremely important for the body since many enzymes and proteins involved in metabolic processes require this trace element for proper functioning. Even though the RDA requirement of selenium is just 55 mcg/day, it is essential for proper metabolic functioning of the body and maintenance of inherent metabolic balance. Enzymes like glutathione peroxidase that is involved in antioxidation, deiodinase that is responsible for synthesis of active T3 thyroid hormone, and a specific nitrogen free radical scavenging selenoprotein P, require selenium in their active centers for their efficient activity. Selenium also increases good cholesterol in the body thus preventing obesity and related disorders. The antioxidant effect of selenium protects arteries and blood vessels from oxidative damage and may prevent cardiac disorders.
Gao S, Jin Y, Hall KS, et al. Selenium level and cognitive function in rural elderly Chinese. Am J Epidemiol. 2007;165(8):955-65.
Hawkes WC, Keim N. Dietary selenium intake modulates thyroid hormone and energy metabolism in men. J Nutr. 2003;133:3443-3448.
How effective is selenium in treating or preventing cancers?
Animal studies have shown that selenium supplementation decreased the risk of cancers. A study conducted by Clark and co-workers suggested that administration of as little as 200 mcg/day of selenium to non-melanoma skin cancer patients prevented recurrence of cancers and also decreased the occurrence of prostate and colon cancers. However, since these studies use selenium in much higher concentrations than physiological concentrations, human clinical trials have yet to confirm the results.
Until recently, selenium in conjunction with vitamin E, was believed to help prevent prostate cancer in men. However, the recent study by Lippman and colleagues at the Anderson Cancer Center, University of Texas showed that selenium was not effective in preventing prostate cancer, with or without vitamin E. Lippman and co-workers studied effect of selenium in preventing prostate cancers in more than 35,000 men aged 50 years and older, over a period of several years. This double-blind study divided the subjects into 4 groups and administered each group with selenium, or vitamin E, or a combination of selenium and vitamin E, or a placebo. The study concluded that selenium is not effective in preventing or treating prostate cancer.
Duffield-Lillico AJ, Slate EH, Reid ME, et al. Nutritional prevention of cancer study group. Selenium supplementation and secondary prevention of non-melanoma skin cancer in a randomized trial. J Natl Cancer Inst. 2003;95(19):1477-81.
Guan L, Han B, Li J, et al. Exposure of human leukemia NB4 cells to increasing concentrations of selenite switches the signaling from por-survival to pro-apoptotic. Ann Hematol. 2009 Jan 20.
Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: The selenium and vitamin E cancer prevention trial (SELECT). JAMA. 2009;301(1):39-51.
Reid ME, Duffield-Lillico LA, Slate E, et al. The nutritional prevention of cancer: 400mcg per day selenium treatment. Nutr Cancer. 2008;60(2):155-63.
Wallace K, Kelsey KT, Schned A, et al. Selenium and risk of bladder cancer: A population-based case-control study. Cancer Prev Res (Phila Pa). 2009;2(1):70-3.
How does selenium act as an antioxidant?
Selenium by itself does not act as an antioxidant but mediates its effects via many enzymes. One such enzyme is glutathione peroxidase - a selenium-containing, selenium-dependant enzyme. This enzyme comprises of glutathione molecules and selenium atoms and is responsible for scavenging free radicals produced by metabolic processes like lipid peroxidation, which can cause oxidative damage to the tissues. Moreover, it has been reported that administration of selenium stimulates synthesis of glutathione and enzyme glutathione peroxidase – both of which protects cells from oxidative stress.
Cocchi M, Venturi S. Selenium and Iodide: ancient antioxidants of cellular membranes? 7th Internat. Symp. on Selenium in Biology and Medicine. Venice (Italy). Abs. 2000;P-88:134.
Fischer A, Bosse A, Pallauf J. Effect of selenium deficiency on the antioxidative status and muscle damage in growing turkeys. Arch Anim Nutr. 2008;62(6):485-97.
Kutluhan S, Naziroglu M, Celik O, Yilmaz M. Effects of selenium and topiramate on lipid peroxidation and antioxidant vitamin levels in blood of pentylentetrazol-induced epileptic rats. Biol Elem Trace Res. 2009 Jan 6.
Venturi S, Venturi M. Evolution of dietary antioxidant defenses. European Epi-Marker. 2007;(3):1-12.
What is the current status of selenium in treating diabetes?
Though several preliminary reports suggest that selenium helps prevent diabetes by mimicking the action of insulin, other studies indicate that continued intake of selenium supplements may lead to type 2 diabetes. Hence, further studies and clinical trials are required to confirm the positive or negative relationship between selenium and diabetes.
Chandra A, Mahdi AA, Singh RK, Mahdi F, Chander R. Effect of INdian herbal hypoglycaemic agents on antioxidant capacity and trace elements content in diabetic rats. J Med Food. 2008;11(3):506-12.
Joachim B, Navas-Acien A, Eliseo G. Serum selenium and diabetes in US adults. Diab Care. 2007;30:829-834.
Zulet MA, Puchau B, Hermsdorff HH, Navarro C, Martinez JA. Dietary selenium intake is negatively associated with serum sialic acid and metabolic syndrome features in healthy young adults. Nutr Res. 2009; 29(1):41-8.
Is selenium capable of treating thyroid disorders?
There are no studies yet that show the therapeutic effects of selenium in treating thryoid disorders. However, there is some evidence that selenium deficiency may lead to thyroid disorders. Selenium is extremely important for activation of the deiodinase enzyme that is responsible for conversion of T4 thyroid hormone to active T3 form. Deficiency of selenium leads to an inactive enzyme and hence, an inactive thyroid hormone.
Micronutrient Information Center, Linus Pauling Institute at Oregon State University.
Stazi AV, Trinti B. Selenium deficiency in celiac diseases: risk of autoimmune thyroid disorders. Minerva Med. 2008;99(6):643-653.
Tan L, Sun W, Sang ZN, Zhang WQ. The effect of selenium on the expression of Fas/FasL in experimental autoimmune thyroiditis rats' thyroid with adequate iodine. Zhongua Yu Fang Yi Xue Za Zhi. 2008;42(9):640-3.
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Additional Research on Selenium: |
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Selenium and the Immune System
Kumar N, Garg AK, Mudgal V, Dass RS, Chaturvedi VK, Varshney VP. Effect of different levels of selenium supplementation on growth rate, nutrient
utilization, blood metabolic profile, and immune response in lambs. Biol Trace Elem Res. 2008 Dec;126 Suppl 1:S44-56.
Rayman MP. Selenoproteins and human health: Insights from epidemiological data. Biochim Biophys Acta. 2009 Mar 25.
Wardwell L, Chapman-Novakofski K, Herrel S, Woods J. Nutrient intake and immune function of elderly subjects. J Am Diet Assoc. 2008
Dec;108(12):2005-12.
Selenium and Thyroid Health
Gärtner R. Thyroid disorders during pregnancy. Dtsch Med Wochenschr. 2009 Jan;134(3):83-6. Epub 2009 Jan 13.
Keshteli AH, Hashemipour M, Siavash M, Amini M. Selenium Deficiency as a Possible Contributor of Goiter in Schoolchildren of Isfahan, Iran. Biol Trace
Elem Res. 2008 Dec 18.
Kubasova ED, Kubasov RV. Effect of trace elements on thyroid structural and functional state (a review). Gig Sanit. 2008 Sep-Oct;(5):79-81.
Selenium and Cataracts
Bartlett H, Eperjesi F. An ideal ocular nutritional supplement? Ophthalmic Physiol Opt. 2004 Jul;24(4):339-49.
Flohé L. Selenium, selenoproteins and vision. Dev Ophthalmol. 2005;38:89-102.
Li T, He T, Tan X, Yang S, Li J, Peng Z, Li H, Song X, Wu Q, Yang F, Xing Y. Prevalence of age-related cataract in high-selenium areas of China. Biol Trace
Elem Res. 2009 Apr;128(1):1-7.
Naziroglu M, Karaoğlu A, Aksoy AO. Selenium and high dose vitamin E administration protects cisplatin-induced oxidative damage to renal, liver and lens
tissues in rats. Toxicology. 2004 Feb 15;195(2-3):221-30.
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