Selenium and its importance to human health

Selenium is a trace mineral that is essential for all living cells, however, its importance for human health was only discovered as recently as 1973.¹ It is well known for its role in immune health and thyroid hormone production but its functions extend well beyond this. In this blog, we will explore selenium’s functions including the health effects of sub-optimal intake and deficiency, food sources, research into supplementation and the different forms.

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Functions

Selenium is a potent antioxidant, it forms part of the amino acid selenocysteine which occurs in more than 25 selenocysteine-containing proteins known as selenoproteins. Selenium exerts most of its biological functions via these selenoproteins. Glutathione peroxidases (GPx), thioredoxin reductases and deiodinases are the most well-known selenoproteins:

• GPx – this enzyme is the body’s ‘master antioxidant’ protecting against oxidative damage/stress
• Thioredoxin reductases – these enzymes also act as antioxidants inside the cell
• Iodothyronine deiodinases (thyroid hormone deiodinases) – these enzymes are involved in the production of the active thyroid hormone triiodothyronine (T3) from thyroxine (T4)
• Selenoprotein P (SePP) – is essential for the transport and distribution of selenium, especially to the brain and testes². It also has antioxidant function

Selenium has a number of other roles (some of them structural) in human health including supporting the integrity of cell membranes.

Food sources

The selenium content of plants (crops, fruit and vegetables) is determined by its availability in the soil in which they are grown, therefore the content varies between countries and regions.² For example, the general dietary intake patterns in Canada and Finland are likely to be quite similar but cereals provided 75% of the 149ug/day intake of selenium in Canada compared with 10% of the total 30ug/day selenium in Finland before 1985, since then fertilisers in Finland have been fortified with selenium.³ Climate and genetics also impact the selenium content of plants. The richest sources are organ meats, seafood and muscle meats⁴. Cruciferous vegetables (such as broccoli and white cabbage), garlic, onions, mushrooms, asparagus and legumes such as lentils may have a high selenium content, depending on the quality of soil they were grown in. Brazil nuts (from selenium-rich soils) are also a good source, they contain 0.25 mg/kg of selenium.⁵

Early forms of agriculture were more sustainable than modern methods as plants were grown in soil to which excess plant waste and animal waste were returned. This process naturally re-mineralised and replenished the soil. Early ploughing techniques also helped to evenly distribute the natural fertiliser Mycorrhiza (a fungus living in plant roots that ‘biotransforms’ inorganic minerals into an organic form making minerals readily useable by plants thus ensuring good mineral uptake). However modern farming techniques focus on high yields to the detriment of soil quality;⁶ plants are harvested and shipped all over the world, deep ploughing destroys the Mycorrhiza and the standard use of N-P-K fertiliser (containing nitrogen, phosphorus and potassium) reduces nutrient content. These changes in farming mean that the selenium content of food has decreased in many countries⁷. There are only a couple of small pockets of land (e.g. Norfolk in the UK and Senegal in Africa), where the ground is still selenium-rich.⁸

Selenium’s interactions with other nutrients

Selenium is an essential component of the tetraiodothyronine 5’-deiodinase enzyme which plays a role in iodine metabolism hence there is a close interaction between iodine and selenium. A severe selenium deficiency alongside an iodine deficiency may increase stress on the thyroid gland. If an iodine deficiency is present, selenium supplementation on its own may exacerbate the iodine deficiency; however the interaction is only thought to be significant if the deficiency is severe so would not be relevant in the UK.⁵

Selenium interacts with other metals (studies in rats have shown that a copper deficiency can affect selenium utilisation in the body³) and vitamins C and E. For example, a selenium deficiency may exacerbate the effects of a vitamin E deficiency and vitamin E may prevent selenium toxicity. Selenium status affects the metabolism and thus the toxicities of some xenobiotics (foreign substances or chemicals that the body does not recognise e.g. drugs, chemicals).⁵

Research

Studies of selenium supplementation have demonstrated numerous possible clinical applications:

Infectious diseases such as AIDS/HIV – selenium appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS.⁹

Male and female fertility – selenium is needed for sperm motility and may reduce the risk of miscarriage⁹ in women.

Sepsis – more clinical trials are needed on selenium supplementation¹⁰ but initial research indicates that parenteral selenium supplementation may reduce risk of mortality in critically ill patients with sepsis.¹¹

Cardiovascular health – a small 4 year intervention trial of 200ug organic selenium yeast alongside CoQ10 supplementation reported reduced cardiovascular mortality which persisted during a 10 year follow-up period.¹²

Some research has indicated an association between selenium and cholesterol metabolism – a 2011 trial concluded that selenium supplementation may have modest beneficial effects on serum lipid levels in people with low selenium status but the clinical significance of the findings are unclear.¹³

Autoimmune thyroid disorders – a 2014 systematic review looking at selenium supplementation for Hashimoto’s thyroiditis concluded that taking selenium 200ug daily, singly or in combination with levothyroxine, may reduce thyroid antibodies compared with placebo but the reliability of the evidence was not sufficient to inform clinical decision-making.¹⁴

Selenium deficiency and requirements

Most people in the world today are selenium-depleted, most notably in some European populations and parts of China.¹ A 2013 paper reported that approximately 15% of the world’s population were selenium deficient.⁶

The European Nutrient Reference Value (NRV) and US Recommended Dietary Allowance (RDA) have been set at 55μg per day.⁸

The World Health Organisation recommends a selenium daily intake of 0.9μg/kg of body weight per day for adults¹⁵ (i.e. 63μg for a 70kg adult). The tolerable upper intake level (UL) for selenium is 400μg/day for adolescents and adults in the US⁴ and 300ug/day for adults in the EU.²³ The safe upper level recommended by the Expert Group on Vitamins and Minerals in the UK is 450μg a day.⁵

Selenium deficiency has been linked with a number of symptoms and health conditions:

• Keshan disease is an endemic cardiomyopathy that affects young women and children in selenium-deficient regions of China. The acute form of the disease is characterised by the sudden onset of cardiac insufficiency, while the chronic form results in moderate to severe heart enlargement with varying degrees of cardiac insufficiency. The incidence of Keshan disease is closely associated with low selenium soil status and hence very low dietary intakes of selenium and poor selenium nutritional status. Selenium supplementation has a prophylactic effect against Keshan disease³ but cannot reverse heart muscle damage once it occurs.

People in China who are susceptible to Keshan disease are ingesting 29μg/selenium per day – which is not much less than the 55μg/day target intake set for the UK population. It is also interesting to note that viruses are known to mutate in selenium-deficient individuals – and the first of these highly and rapidly-mutated viruses emerged as avian flu, again originating from Keshan. It is thought that low vitamin E levels alongside selenium deficiency may increase risk of Keshan disease³

• Kashin-Beck – is a type of osteoarthritis disease that occurs in certain areas of China, Tibet and Siberia,⁸ it mainly affects children. The advanced stage of the disease may be characterised by swollen and deformed joints caused by degeneration of cartilage in the joints. Further research needs to be conducted but it has been suggested that selenium supplementation may prevent Kashin-Beck disease
• Impaired/dysfunctional immunity – selenium deficiency is linked to impaired immunity (e.g. asthma, inflammatory response syndrome, decreased response to viral infections⁶), as selenoproteins impact on activation, differentiation and proliferation of immune cells¹³
• DNA damage, oxidative stress and chronic inflammation – in mice studies selenium deficiency has been found to be associated with genes that cause DNA damage and oxidative stress.¹⁶ Dietary selenium strongly influences inflammation¹⁷ through regulation of eicosanoid (immune system messengers) production¹⁷ so selenium supplementation may have a role to play in management of chronic inflammatory conditions such as asthma and inflammatory bowel diseases (IBDs)
• Mood and anxiety – selenium deficiency may have a detrimental effect on mood⁹

Who is most at risk of selenium deficiency and which individuals have increased requirements?

Selenium requirements should always be considered on an individual basis (taking into account factors such as age, sex etc.) but there are population groups who may be more at risk of deficiency or have increased requirements:

• Breastfeeding women – the selenium requirement in women increases duringlactation.³ The Committee on Medical Aspects of Food and Nutrition Policy (COMA) recommends 75μg selenium a day for lactating women⁵
• People (especially vegetarians) living in low-selenium areas – the problem of selenium deficiency is exacerbated in these areas if the diet consists largely of vegetables
• IBDs – serum selenium deficiency has been observed in patients with Crohn’s disease and ulcerative colitis due to impaired absorption¹⁸

Common forms of supplemental selenium and bioavailability

The amount of selenium available for uptake and assimilation by cells of the body depends on the form and concentration of selenium ingested.

Selenium exists in two forms; inorganic and organic (soil contains inorganic selenium that plants bioaccumulate and convert to organic forms):

• Inorganic selenium (selenite and selenate) – most commonly used to fortify foods and in selenium supplements

Organic selenium (selenomethionine, selenocysteine, selenium-methyl-selenocysteine, Y-glutamyl-selenium-methyl-selenocysteine). Selenium occurs in most foods as the amino acid derivatives selenomethionine and selenocysteine. Selenium-enriched yeast (grown in a high-selenium medium) is also an organic form containing selenium in the form of selenomethione and selenocysteine. Selenium is included in most multivitamin and mineral supplements or as a stand-alone product. Absorption of selenium in the small intestine is efficient but not closely regulated. Few studies have been conducted on the absorption and bioavailability of the different forms of selenium⁸ but it is known that 90% of selenomethionine (the major dietary form of selenium and the main form found in selenium-enriched yeast) is absorbed.¹⁹ Selenate is absorbed almost completely, but a significant proportion of it is lost in urine before it can be incorporated into tissues; absorption of selenite is about 50%.¹⁹ A small study in 2008 in men concluded that selenium from selenium-enriched yeast was well absorbed and retained by the body.²⁰

Selenium is distributed throughout the body but levels are slightly higher in the liver and kidneys than in other tissues. It is also found in breast milk. It is stored in the body as selenomethionine (this reserve is directly dependent on dietary intake of selenomethionine specifically) and as glutathione peroxidase in the liver. Selenium is mainly excreted via urine and faeces.

Precautions with selenium supplements

If your clients are taking several different supplements containing selenium, check that the total intake from supplements does not exceed 200µg per day (i.e. chronic, long-term supplementation); up to 400µg per day can be taken short-term.

If you have any questions regarding the topics that have been raised, or any other health matters please do contact me (Maddie) by phone or email at any time.

madelinet@cytoplan.co.uk, 01684 310099

Maddie Taylor and the Cytoplan Editorial Team

References

1. Foster LH et al. Selenium in health and disease: A review’. Crit Rev Food Sci Nutr. 1997;(3):221-228. https://www.tandfonline.com/doi/abs/10.1080/10408399709527773.
2. The British Nutrition Foundation. Selenium and health. Ann Clin Res. 1986;18(1):1-68. http://www.ncbi.nlm.nih.gov/pubmed/3717867.
3. WHO. Trace elements in human nutrition and health World Health Organization. World Heal Organ Geneva. 1996:1-360.
4. Institute LP. Selenium. https://lpi.oregonstate.edu/mic/minerals/selenium. Accessed November 13, 2018.
5. Expert Group on Vitamins and Minerals. Professor M J S Langman BSc, MD, FRCP, F Medici, University of Birmingham B. Safe Upper Levels for Vitamins and Minerals Expert Group on Vitamins and Minerals Contents. 2003;(May).
6. Garcia Moreno R, Burdock R, Díaz Álvarez MC, Crawford JW. Managing the selenium content in soils in semiarid environments through the recycling of organic matter. Appl Environ Soil Sci. 2013;2013. doi:10.1155/2013/283468
7. 268747422_Selenium_in_Agriculture_Water_Air_Soil_Plants_Food_Animals_and_Nanoselenium @ www.researchgate.net. https://www.researchgate.net/publication/268747422_Selenium_in_Agriculture_Water_Air_Soil_Plants_Food_Animals_and_Nanoselenium.
8. Selenium, Fact Sheet for Health Professionals. National Institutes for Health. https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/. Published 2018. Accessed November 13, 2018.
9. Rayman MP. The importance of selenium to human health. Lancet. 2000;356(9225):233-241.
10. Zhengdong K et al. Selenium supplementation for sepsis: a meta-analysis of randomized controlled trials. Am J Emerg Med. 2013;31(8):1170–1175. https://www.ajemjournal.com/article/S0735-6757(13)00251-9/fulltext.
11. Huang TS, Shyu YC, Chen HY, et al. Effect of Parenteral Selenium Supplementation in Critically Ill Patients: A Systematic Review and Meta-Analysis. PLoS One. 2013;8(1). doi:10.1371/journal.pone.0054431
12. Alehagen U, Aaseth J, Johansson P. Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens. PLoS One. 2015;10(12):e0141641. doi:10.1371/journal.pone.0141641
13. Rayman MP, Stranges S, Griffin BA, Pastor-barriuso R, Guallar E. Annals of internal medicine effect of supplementation with high-selenium yeast on plasma lipids. Ann Intern Med. 2011;154:656-665.
14. van Zuuren EJ, Albusta AY, Fedorowicz Z, Carter B, Pijl H. Selenium Supplementation for Hashimoto’s Thyroiditis: Summary of a Cochrane Systematic Review. Eur Thyroid J. 2014;3(1):25-31. doi:10.1159/000356040
15. Frisbie SH, Mitchell EJ, Sarkar B. Urgent need to reevaluate the latest World Health Organization guidelines for toxic inorganic substances in drinking water. Environ Heal A Glob Access Sci Source. 2015;14(1):1-15. doi:10.1186/s12940-015-0050-7
16. Ames BN. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci. 2006;103(47):17589-17594. doi:10.1073/pnas.0608757103
17. Hoffmann PR. The influence of selenium on immune responses. Mol Nutr Food Res. 2008;52(11):1273–1280. doi:10.1002/mnfr.200700330.The
18. Avinash K et al. Selenium and inflammatory bowel disease. AM J Physiol Gastrointest Liver Physiol. 2015;309(2):71-77. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504954/.
19. Intakes DR, Panel C, Antioxidants D, et al. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and Interpretation and Uses of DRIs, Standing Committee on the Scientif. Vol 529.; 2000. doi:10.1080/13664530.2013.813766
20. Bügel S, Larsen EH, Sloth JJ, et al. Absorption, excretion, and retention of selenium from a high selenium yeast in men with a high intake of selenium. Food Nutr Res. 2008;52:1-8. doi:10.3402/fnr.v52i0.1642
21. Natural Standards Database. Selenium. 2018.
22. Ogawa-Wong AN, Berry MJ, Seale LA. Selenium and metabolic disorders: An emphasis on type 2 diabetes risk. Nutrients. 2016;8(2). doi:10.3390/nu8020080
23. European Food Safety Authority Scientific Committee on Food, 2006. Tolerable Upper Intake Levels For Vitamins And Minerals. https://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=11&cad=rja&uact=8&ved=2ahUKEwikhbr5sYjfAhUmsaQKHdRlBVUQFjAKegQICRAC&url=http%3A%2F%2Fwww.efsa.europa.eu%2Fsites%2Fdefault%2Ffiles%2Fefsa_rep%2Fblobserver_assets%2Fndatolerableuil.pdf&usg=AOvVaw2NKoJnPses3xYq7UkiGFbs

Last updated on 20th October 2022 by cytoffice