Selenium is an essential mineral and micronutrient. It is fundamental to human health and found in many foods. It is found in meat, seafood (hence, selenium levels are high in populations with high intake of seafood, like the Inuit population), grain cereals, egg yolk, milk, brazil nuts, mushrooms and garlic. Concern has been raised for some years about falling levels of selenium intake and a possible relationship to the incidence of some diseases, including some cancers.
Selenoproteins are important constituents of a number of enzymes with a range of functions including antioxidant function, thyroid hormone metabolism, male fertility and immune mechanisms. A decline in blood selenium levels in the UK and other European countries has raised concern about possible public health implications, particularly in relation to cancer and cardiovascular disease. Whilst there is some understanding of the role of these proteins in health and disease (and some interesting theories and research), there are many unanswered questions and much debate about supplementation. More research is repeatedly called for. Deficiency is linked with Keshan disease but excessive intake can have toxic effects and may even be carcinogenic.
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How much selenium is recommended?
Dietary recommendations for selenium differ between countries. This is because there is uncertainty over what constitutes 'optimal selenium status'. The average daily intake of selenium in in the UK has been falling over a 30-year period. The recommended daily allowance (RDA) of 75 micrograms/day and 60 micrograms/day for men and women respectively in the UK differs from the US RDA of 55 micrograms/day for adults. The World Health Organization (WHO) RDA for selenium is 70 micrograms/day to 350 micrograms/day. Some are recommending supranutritional supplements of 200 micrograms/day to 800 micrograms/day. Toxic effects probably occur at around 40 x the RDA.
How are selenium levels measured?
Erythrocyte, serum and tissue levels of glutathione peroxidase (GP) can be measured to assess selenium status. Selenium in hair and nails can also be measured. Discuss with your laboratory before deciding which method to use.
Why is selenium essential?
Dietary recommendations were made over 15 years ago on the basis of blood levels of glutathione peroxidase (GP). This intracellular enzyme converts hydroxyl radicals or hydrogen peroxide into water and this requires selenium as a cofactor. Levels of this enzyme have thus been taken to correlate with selenium levels. Since then, over 30 new selenoproteins have been identified and about half of these have an identified biological function. These selenoproteins include:
- Four GP enzymes, a major class of functionally important selenoproteins and the first to be characterised:
- Classical GP x 1.
- Gastrointestinal GP x 2.
- Plasma GP x 3.
- Phospholipid hydroperoxide GP x 4.
- Thioredoxin reductase (TR), a selenocysteine-containing enzyme important in regulating metabolic activity.
- Selenoprotein P (60% of plasma selenium is held in this form) may have a role in the transport of selenium but also may have other functions.
- Several iodothyronine deiodinase enzymes. These are responsible for conversion of the prohormone thyroxine to the active thyroid hormones (triiodothyronine, or T3).
- Sperm capsule selenoprotein which may be responsible for maintaining integrity of the sperm flagella (and hence motility of sperm).
- Selenoprotein W. This is involved in muscle metabolism.
What harm does deficiency of selenium cause?
Deficiency of selenium may cause a variety of problems, but the health implications of a decline in selenium levels in the UK over 25 years have not been systematically investigated. In general, selenium is thought to be important in a number of varied aspects of health (for a healthy immune system, for a protective effect against some forms of cancer, to maintain and enhance male fertility, for a reduction in cardiovascular mortality and to regulate inflammatory markers in asthma). Research is in progress and there is a lot of interest in the results of this research. Although there are still many unanswered questions, so far selenium has been linked with:
- Keshan disease and Kashin-Bek disease (also often referred to as Keshan-Beck disease). These are both associated with selenium deficiency.
- Counteracting the development of virulence and inhibiting HIV progression to AIDS. Trials are small and results mixed but more research is called for.
- Enhancing sperm motility. Selenium-deficient rats have immotile deformed sperm and infertility. Although there is a rationale for this one RCT was not able to show such an effect.
- A possible role in preventing pre-eclampsia, although the Cochrane review suggests more trials are necessary.
- A possible relationship between mood disturbance and selenium deficiency.
- A possible association between elevated selenium intake and reduced cancer risk.The association between selenium status and cancer risk remains enigmatic and epidemiological studies have failed to consistently link low selenium levels with increased cancer risk in men and women. It is possible that there may be gender differences in susceptibility to cancer risk with men being more susceptible to the risk of low selenium. In the Nutritional Prevention of Cancer Trial, daily supplementation of selenium significantly reduced prostate cancer in men. It is thought that the greatest benefit from selenium supplementation will be in low selenium status populations, although the biggest primary and secondary prevention trials - SELECT (= Sel enium and Vitamin E C ancer Prevention T rials) - are underway in the USA (where selenium status is good). Some were predicting that the SELECT trial results in 2013 would show benefit. However, this trial was recently discontinued because there was no evidence of a benefit from either vitamin E or selenium on prevention of prostate cancer. Concern was also raised about a link between selenium supplementation and an increased risk of developing type 2 diabetes.
- In asthma, some epidemiological studies suggest that deficiencies of selenium, zinc and other nutrients (vitamins A, C, D, and E) may be associated with the development of allergic disorders and asthma. Although a number of trials suggest supplementation with selenium may help symptoms of chronic asthma, only one small trial, according to the Cochrane review, showed evidence of this.
- Cardiovascular disease. Deficiency is associated with cardiomyopathy. The hypotheses that low selenium concentrations are associated with increased cardiovascular disease and that selenium supplements prevent coronary heart disease are unproven. Selenium supplementation cannot currently be recommended for cardiovascular disease prevention.
- Deficiency in trauma and burns patients. One study reports improved recovery with selenium supplementation in trauma and burns patients.
- The thyroid gland is rich in selenium. Selenium deficiency may help to precipitate hypothyroidism and autoimmune thyroid disease and supplementation may contribute to prevention of these diseases.
Who is at risk of selenium deficiency?
Risk factors include:
- Poor dietary intake.
- Smoking. Smokers have lower levels of selenium compared with non-smokers.
- Socio-economic status. Lower levels have been found in people receiving state benefits or with lower educational attainment.
- The elderly living in residential or nursing homes had lower levels of selenium as did elderly hospital patients when compared with 'free-living' elderly patients.
- The elderly, particularly in areas where low intake is common.
- Where you live:
- Areas with a low selenium soil environment are associated with deficiency. Such areas include parts of China, Croatia, New Zealand, the Slovak Republic. The elderly in such areas are particularly at risk and one study from New Zealand recently demonstrated suboptimal levels of selenium in a significant proportion of 103 elderly New Zealand women.
- The levels of selenium are higher in the south of England than in the north. The selenium status may vary within countries according to factors such as the selenium in the local soil but is also affected by the levels of selenium in imported crops.
- Patients on total parenteral nutrition (TPN).
- Trauma and burns patients.
- Vegetarians in countries with low selenium status.
Indications for supplementation
Those at high risk of deficiency should have their selenium status measured. If deficient in selenium, such patients should certainly be given supplements. As with many nutritional components, distinction must be drawn between the basic nutritional requirement to prevent deficiency and supplementation to prevent, for example, chronic disease and cancer. According to recent research in the USA, 99% of over 17,000 subjects were 'selenium replete' according to plasma selenium levels and not in need of routine supplementation. There is widespread questioning of the use of RDAs and some questioning of methods of assessing deficiency in this as in other areas of nutrition. Evidence of benefit at supranutritional levels of dietary intake is needed to support what has been called the 'nutraceutical' approach to supplementation. Further studies are needed and are being undertaken to support such beneficial effects. If such evidence is forthcoming, then health professionals will need to use dietary and clinical assessment methods to ensure that those at risk of cancer, inflammatory or infectious disease be appropriately advised about selenium intake.
Further reading & references
- Hansen JC, Deutch B, Pedersen HS; Selenium status in Greenland Inuit. Sci Total Environ. 2004 Sep 20;331(1-3):207-14.
- Brown KM, Arthur JR; Selenium, selenoproteins and human health: a review. Public Health Nutr. 2001 Apr;4(2B):593-9.
- Rayman MP; Dietary selenium: time to act. BMJ. 1997 Feb 8;314(7078):387-8.
- Rayman MP; The importance of selenium to human health. Lancet. 2000 Jul 15;356(9225):233-41.
- Willett WC, Stampfer MJ; Selenium and cancer. BMJ. 1988 Sep 3;297(6648):573-4.
- Letavayova L, Vlckova V, Brozmanova J; Selenium: from cancer prevention to DNA damage. Toxicology. 2006 Oct 3;227(1-2):1-14. Epub 2006 Jul 25.
- Hurst R, Armah CN, Dainty JR, et al; Establishing optimal selenium status: results of a randomized, double-blind, Am J Clin Nutr. 2010 Apr;91(4):923-31. Epub 2010 Feb 24.
- Peng A, Yang C, Rui H, et al; Study on the pathogenic factors of Kashin-Beck disease. J Toxicol Environ Health. 1992 Feb;35(2):79-90.
- Zhang WH, Neve J, Xu JP, et al; Selenium, iodine and fungal contamination in Yulin District (People's Republic of China) endemic for Kashin-Beck disease. Int Orthop. 2001;25(3):188-90.
- Fang W, Wu P, Hu R, et al; Environmental Se-Mo-B deficiency and its possible effects on crops and Keshan-Beck disease (KBD) in the Chousang area, Yao County, Shaanxi Province, China. Environ Geochem Health. 2003 Jun;25(2):267-80.
- Kupka R, Msamanga GI, Spiegelman D, et al; Selenium status is associated with accelerated HIV disease progression among HIV-1-infected pregnant women in Tanzania. J Nutr. 2004 Oct;134(10):2556-60.
- Kaiser JD, Campa AM, Ondercin JP, et al; Micronutrient supplementation increases CD4 count in HIV-infected individuals on highly active antiretroviral therapy: a prospective, double-blinded, placebo-controlled trial. J Acquir Immune Defic Syndr. 2006 Aug 15;42(5):523-8.
- Irlam JH, Visser MM, Rollins NN, et al; Micronutrient supplementation in children and adults with HIV infection. Cochrane Database Syst Rev. 2010 Dec 8;(12):CD003650.
- Foresta C, Flohe L, Garolla A, et al; Male fertility is linked to the selenoprotein phospholipid hydroperoxide glutathione peroxidase. Biol Reprod. 2002 Sep;67(3):967-71.
- Hawkes WC, Turek PJ; Effects of dietary selenium on sperm motility in healthy men. J Androl. 2001 Sep-Oct;22(5):764-72.
- Waters DJ, Chiang EC, Cooley DM, et al; Making sense of sex and supplements: differences in the anticarcinogenic effects of selenium in men and women. Mutat Res. 2004 Jul 13;551(1-2):91-107.
- Waters DJ, Shen S, Glickman LT, et al; Prostate cancer risk and DNA damage: translational significance of selenium supplementation in a canine model. Carcinogenesis. 2005 Jul;26(7):1256-62. Epub 2005 Apr 7.
- Meyer F, Galan P, Douville P, et al; Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial. Int J Cancer. 2005 Aug 20;116(2):182-6.
- Rayman MP; Selenium in cancer prevention: a review of the evidence and mechanism of action. Proc Nutr Soc. 2005 Nov;64(4):527-42.
- Drake EN; Cancer chemoprevention: selenium as a prooxidant, not an antioxidant. Med Hypotheses. 2006;67(2):318-22. Epub 2006 Mar 30.
- Schmid HP, Fischer C, Engeler DS, et al; Nutritional aspects of primary prostate cancer prevention. Recent Results Cancer Res. 2011;188:101-7.
- Muecke R, Schomburg L, Buentzel J, et al; Selenium or no selenium--that is the question in tumor patients: a new Integr Cancer Ther. 2010 Jun;9(2):136-41. Epub 2010 May 11.
- Nurmatov U, Devereux G, Sheikh A; Nutrients and foods for the primary prevention of asthma and allergy: Systematic J Allergy Clin Immunol. 2011 Mar;127(3):724-733.e30. Epub 2010 Dec 24.
- Kanekura T, Yotsumoto S, Maeno N, et al; Selenium deficiency: report of a case. Clin Exp Dermatol. 2005 Jul;30(4):346-8.
- Flores-Mateo G, Navas-Acien A, Pastor-Barriuso R, et al; Selenium and coronary heart disease: a meta-analysis. Am J Clin Nutr. 2006 Oct;84(4):762-73.
- Berger MM; Antioxidant micronutrients in major trauma and burns: evidence and practice. Nutr Clin Pract. 2006 Oct;21(5):438-49.
- Duntas LH; Selenium and the thyroid: a close-knit connection. J Clin Endocrinol Metab. 2010 Dec;95(12):5180-8. Epub 2010 Sep 1.
- Bates CJ, Thane CW, Prentice A, et al; Selenium status and its correlates in a British national diet and nutrition survey: people aged 65 years and over. J Trace Elem Med Biol. 2002;16(1):1-8.
- Schmuck A, Roussel AM, Arnaud J, et al; Analyzed dietary intakes, plasma concentrations of zinc, copper, and selenium, and related antioxidant enzyme activities in hospitalized elderly women. J Am Coll Nutr. 1996 Oct;15(5):462-8.
- Dodig S, Cepelak I; The facts and controversies about selenium. Acta Pharm. 2004 Dec;54(4):261-76.
- de Jong N, Gibson RS, Thomson CD, et al; Selenium and zinc status are suboptimal in a sample of older New Zealand women in a community-based study. J Nutr. 2001 Oct;131(10):2677-84.
- Sheck L, Davies J, Wilson G; Selenium and ocular health in New Zealand. N Z Med J. 2010 Jun 11;123(1316):85-94.
- Madaric A, Kadrabova J, Ginter E; Selenium concentration in plasma and erythrocytes in a healthy Slovak population. J Trace Elem Electrolytes Health Dis. 1994 Mar;8(1):43-7.
- Ishida T, Himeno K, Torigoe Y, et al; Selenium deficiency in a patient with Crohn's disease receiving long-term total parenteral nutrition. Intern Med. 2003 Feb;42(2):154-7.
- Yusuf SW, Rehman Q, Casscells W; Cardiomyopathy in association with selenium deficiency: a case report. JPEN J Parenter Enteral Nutr. 2002 Jan-Feb;26(1):63-6.
- Alfieri MA, Leung FY, Grace DM; Selenium and zinc levels in surgical patients receiving total parenteral nutrition. Biol Trace Elem Res. 1998 Jan;61(1):33-9.
- Kadrabova J, Madaric A, Kovacikova Z, et al; Selenium status, plasma zinc, copper, and magnesium in vegetarians. Biol Trace Elem Res. 1995 Oct;50(1):13-24.
- Combs GF Jr; Impact of selenium and cancer-prevention findings on the nutrition-health paradigm. Nutr Cancer. 2001;40(1):6-11.
- Rayman MP, Rayman MP; The argument for increasing selenium intake. Proc Nutr Soc. 2002 May;61(2):203-15.
- Ryan-Harshman M, Aldoori W; The relevance of selenium to immunity, cancer, and infectious/inflammatory diseases. Can J Diet Pract Res. 2005 Summer;66(2):98-102.
- Burk RF; Selenium, an antioxidant nutrient. Nutr Clin Care. 2002 Mar-Apr;5(2):75-9.
- Neve J; Selenium as a 'nutraceutical': how to conciliate physiological and supra-nutritional effects for an essential trace element. Curr Opin Clin Nutr Metab Care. 2002 Nov;5(6):659-63.
- Neve J; New approaches to assess selenium status and requirement. Nutr Rev. 2000 Dec;58(12):363-9.
- Thomson CD; Assessment of requirements for selenium and adequacy of selenium status: a review. Eur J Clin Nutr. 2004 Mar;58(3):391-402.
|Original Author: Dr Richard Draper||Current Version: Dr Richard Draper||Peer Reviewer: Dr Adrian Bonsall|
|Last Checked: 19/10/2011||Document ID: 1699 Version: 22||© EMIS|
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