Selenium: Go Nuts

Go nuts (well, 3*) for selenium

Selenium (Se) is a trace mineral that plays a major role in immune function, reducing cancer incidence and maintaining the redox homeostasis in our cells. Plants accumulate the inorganic form (selenate, selenite) from the soil and convert it to the organic form (selenomethione, selenocysteine). 

Originally discovered in 1817(1) by Jöns Jacob Berzelius and Johan Gottlieb Gahn (2) at the Gripsholm Chemical Factory in Sweden, selenium (Se) sits between sulphur and tellurium in column 16 of the periodic table – part of the chalcogens (or oxygen family). Sweden has a long history of mining and assaying, so it should come as no surprise that a total of 19 elements were discovered there.

Berzelius chose the name selenium (Ancient Greek: Σελήνη(selènè), moon) for the newly discovered element and noted its resemblance to tellurium – well, the odour when burnt anyway. 

Since its discovery, research was initially directed towards toxicity and later for improving commercial animal production. It would take 140 years before selenium was shown to be essential for all mammalian life. From 1943-1969, Se went from a possible carcinogenic risk to anti-carcinogen (3). In 1979 selenium was recognised as being essential to human health. The RDA was established in 1989.

 

What has selenium done for you lately?

Selenium is primarily used in the form of selenocystine (SeCys) – also known as the 21st amino acid – and incorporated in selenoproteins, of which there could be in excess of 30 – these are the ones we know:

Glutathione peroxidase

There are at least 8 selenocysteine-containing glutathione peroxidase isoenzymes (enzymes that differ in amino acid sequence but catalyse the same reaction) in humans. Their job is to help protect our cells from the ravages of oxidative stress (4) in the area of the body where their particular gene is expressed:

GPx1 is expressed in many tissues throughout the body acting as an antioxidant enzyme reducing hydrogen peroxide to water, limiting its harmful effects (5). GPx1 is poorly expressed when selenium levels are low.

GPx2 is another hydrogen peroxide-reducing enzyme localised in the cytoplasm in the epithelium of the gastrointestinal tract.

Gpx3 expresion is higher in the kidneys and epididymis were it similarly reduces hydrogen peroxide (6).                                         

GPx4 and GPx5 help protect the lipid membranes of spermatozoa (7).

Gpx6 expression is restricted to embryos and adult olfactory epithelium. 

Thioredoxin Reductase

In all mammals, there are three selenocysteine-containing  thioredoxin reductase (TrxR) isoenzymes. These ubiquitous isoenzymes are to be found in the cytosol (TrxR-1) and the mitochondria (TrxR-2) of eukaryotic cells. A third isoenzyme (TrxR-3) is found in the testis. TxrR isoenzymes play a key role in antioxidant defense system as part of the thioredoxin system (8,9).

Iodothyronine Deiodinase (Thyroid Hormone Deiodinase)

A selenoenzyme involved in the regulation of levels of thyroid hormones T3 (triiodothyronine) and T4 (thyroxine). This deiodinase enzyme – as the name suggests – removes one iodine atom from the inactive T4 to produce the active T3 (10,11).

Selenoprotein P

The “P” denotes this selenoproteins presence in plasma. Unlike other selenoproteins – with their one atom of selenium(Se) – selenoprotein P (SeP) is thought to contain ten atoms of Se as selenocysteine. SeP is believed to be a free radical scavenger and Se transporter: provinding the all important Se to the frontline selenoproteins in our cells antioxidant defense system – from the brain to the testes (12).

Selenoprotein W

A relatively small protein (87 amino acids) – that comes in four forms – with one selenocysteine residue. This selenoprotein has  its highest level of expression in skeletal muscle and the heart. It has been suggested that SeW acts as a scavenger for reactive oxygen species (such as hydrogen peroxide) during muscle and nervous system development (13). 

Selenophosphate synthetase 2

There is no free pool of the amino acid selenocysteine within cells. So, SPS2 is the catalyst for generating selenophosphate: the onsite donor for selenocysteine where it is incorporated into elongating selenorpoteins (14).

Methionine-R-sulfoxide reductase B1 (formerly selenoprotein R)

During oxidative stress, methionine is oxidsed – by ROS – to methionine-R-sulfoxide. Methionine-R-sulfoxide reductase B1 (MsrB1) reduces it back to methionine (15).

15 kDa selenoprotein

Expressed in the endoplasmic reticulum (ER) – the transportation system of the eukaryotic cell, 15 kDa selenoprotein (Sep15) is believed to be involved in cancer prevention as Sep15 expression was seen to be lowered in malignant lung, breast, prostate and liver cancer cell lines (16).

Selenoprotein S

This selenocysteine-containing selenoprotein is also expressed in the endoplasmic reticulum (ER) where it has roles in ER function and inflammation. Selenoprotein S (SelS) also participates in quality control of proteins by aiding in the transfer of misfolded proteins from the ER to the cytosol, where they are destroyed.

Selenium requirements and recommended dietary intakes

EAR = Estimated Average Requirement
RDA = Recommended Dietary Allowance
AI = Adequate Intake
UL = Tolerable Upper Intake Level
NR = normative requirement estimate
PRI = population reference intake

Toxicity

Both deficiency and excess can lead to health problems.

Selenium intoxication (selenosis) can occur through dietary intake in areas with selefinerous soil – naturally occurring and contaminated by industry and mining (28). There is also evidence for intoxication through exposure to air-born pollutants (arsenic, flourine, and selenium) from the use of indoor coal burners in China (32).

The other route to toxic overexposure is through supplementation. In the eastern United States, in 2008, a misformulated batch of dietary supplement labelled as suitable for the “entire family” contained 40 800μg of selenium – more than 100 times the UL for adults. And, although no-one died, 201 met the definition for selenium poisoning (29). It’s not only humans that have fallen prey to poor pharmaceutical practices; in 2009, 21 ponies at the U.S. Open Polo Championship dropped dead a few hours after a supplement injection that contained a massive dose of selenium (30).

Interestingly, the population of communities along the selenium-rich, Lower Tapajós River of the Brazilian Amazon showed no symptoms of selenosis when tested in 2006 (31). Their traditional diet including Brazil nuts, chicken, game meat and certain fish meant their B-Se (Blood) and P-Se (Plasma) were at levels that would be considered toxic. Similar observations have been made in Inuit populations, whose traditional diet is exceptionally rich in Se, consisting principally of marine mammals (33).

Where to get your daily fix of selenium?

Selenium is a rare element on this planet which is unevenly distributed; where the average concentration is much higher in sedimentary rocks (especially shales and coal) than in igneous rocks. There is also a high correlation between soil concentrations of Se and iodine. Atmospheric transport of iodine and Se mean that the soils in humid coastal regions are better supplied – by rain and snow –  than dryer inland regions (17).

The richest sources of selenium in the diet are: brazil nuts (<1.6 – 29μg per gram fresh weight), organ meats and seafoods (0.4 – 1.5μg per gram fresh weight), followed by muscle meat (0.1 – 0.4μg per gram fresh weight), cereals and grains (<0.1 – 0.8μg per gram fresh weight), dairy products (<0.1 – 0.3μg per gram fresh weight), and lastly fruits and vegetables (<0.1μg per gram fresh weight). All depending on the soil where the crop/ feed was grown (18).

It is thought that between 0.5 and 1 billion people worldwide have a serious selenium deficiency. Which means there is a far greater number consuming less than is required for optimal production of those all important selenoenzymes.

Maps showing the distribution of selenium in soil around the globe have existed for some time now (19). Soil is considered selenium-poor if has a concentration below 0.5mg per Kg. As I sure you would expect, some countries are rather better mapped than others: the U.S. Department of the Interior have produced an extensive map of the whole country, down to individual counties (20). Which is really useful if you live there – or can track your food back to there!

The United States is in fact one place where you needn’t worry about suboptimal selenium intake. In counties with a poorer concentration of Se in soil, you could simply refer to the extensive USDA National Nutrient Database for Standard Reference (Release 28) and adjust your diet accordingly.

In Europe, Se intake declined after Se-rich wheat imports from North America were swapped for European wheat grown in grown in poorer European soil. The British diet declined from 65 to 35μg a day after this switch.

Finland on the other hand, geochemistry has marked it out as a selenium deficient country. During the1960’s, several diseases associated with a serious selenium deficiency were observed in domestic animals. These were eliminated with the introduction of selenium supplementation and medication in 1969. The 1970’s saw an extensive study of the Se content in foods which showed a daily dietary intake of 25μg. In 1984, the decision was made to supplement the fertilisers with Se in the form of sodium selenate. Since then, the population’s Se intake has risen to the present plateau of 80μg (21). As a result, only vegans are recommended to supplement their Se intake.

China incorporates areas of low dietary selenium (3 – 22μg per day), areas affected by Keshan disease, and areas affected with endemic human selenosis (3200 – 6690μg per day): due to the soil being contaminated with selenium leached from highly seleniferous coal fly ash – from coal-fired power stations (18).

Nuts from Brazil?

The Brazil nut tree (Bertholletia excelsa), or castanheira-do-Pará in Brazilian, grows wild in the Amazon forest. Sometimes towering above the forest canopy, the Brazil nut tree can reach heights of 30 metres. After pollination of its flowers by the large female long-tongued orchid bee, attracted by the tree’s resident orchids (22), the fruit starts to form and grow. It takes 15 months to ripen before falling to the forest floor. The Brazil nut pods are then collected and cracked open to reveal 8 to 24 Brazil nuts (the seeds). Due mainly due to deforestation, this Amazon forest giant is threatened with extinction in all but 2 of the 9 Amazonian countries (Brazil, Peru, Colombia, Ecuador, Bolivia, Guyana, Suriname, Venezuela and French Guyana)(23,24).                                                         

Growing up in the UK, I was used to Brazil nuts being part of the Christmas spread. I was used to calling them Brazil nuts and believed they came from Brazil. The thick polyhedron shells would grace Christmas tables up and down the land. These days your Brazil nuts will come from the world’s largest exporter: Bolivia. And they will arrive shell-less due to an EU Directive requiring all unshelled Brazil nuts to be tested for aflatoxins – a potent carcinogen, produced by naturally occurring moulds that affect numerous commodities from figs to peanuts (25).

As soil concentration of selenium affects the Se in plants and therefore their fruits; the average Se concentration in Brazil nuts varies according to where they grew(26):

N.South America ~101μg (per 5g nut)

Peru ~32.5μg (per 5g nut)

Brazil  ~18μg (per 5g nut)

Bolivia ~8μg (per 5g nut)

Due the great variation in the possible Se concentration in Brazil nuts, it is advisable to stick to 3 nuts per day.

JAMx

References

1. Journal für Chemie und Physik, XXI (1817) pages 342-344. https://archive.org/details/journalfrchemie80unkngoog/page/n351/mode/2up?view=theater
2. Chemistry International September-October 2011. http://publications.iupac.org/ci/2011/3305/5_trofast.html
3. A brief history of selenium research: From alkali disease to prostate cancer (from poison to prevention); J. E. Oldfield. https://www.asas.org/docs/default-source/midwest/mw2020/publications/oldfieldhist.pdf?sfvrsn=b5eefff0_0
4. Glutathione Peroxidase in Health and Diseases. Eren Sarikaya, Selami Doğan. https://www.intechopen.com/chapters/70955
5. Glutathione Peroxidase-1 in Health and Disease: From Molecular Mechanisms to Therapeutic Opportunities. Edith Lubos, Joseph Localzo, Diane E.Handy. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159114/
6. Extracellular Glutathione Peroxidase GPx3 and Its Role in Cancer. Caroline Chang, Beth L.Worley, Rébécca Phaëton, Nadine Hempel. https://www.mdpi.com/2072-6694/12/8/2197/htm
7. Mammalian glutathione peroxidases control acquisition and maintenance of spermatozoa integrity. E. Chabory, C. Damon, A. Lenoir, J. Henry-Berger, P. Vernet, R. Cadet, F. Saez, and J. R. Drevet. https://www.researchgate.net/profile/Joel-Drevet/publication/40819534_Mammalian_glutathione_peroxidases_control_acquisition_and_maintenance_of_spermatozoa_integrity/links/5de0e1f792851c836451e6f7/Mammalian-glutathione-peroxidases-control-acquisition-and-maintenance-of-spermatozoa-integrity.pdf
8. Thioredoxin reductase. D. Mustacich and G. Powis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220815/
9. Thioredoxin and Thioredoxin Target Proteins: From Molecular Mechanisms to Functional Significance. Samuel Lee, Soo Min Kim, Richard T. Lee. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579385/
10. Selenium, the Thyroid, and the Endocrine System J.Köhrle, F.Jakob, B.Contempré, J.E.Dumont. https://academic.oup.com/edrv/article/26/7/944/2355177
11. Defining the Roles of the Iodothyronine Deiodinases: Current Concepts and Challenges. Donald L. St. Germain, Valerie Anne Galton, Arturo Hernandez. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654746/
12. Selenoprotein P: Its Structure and Functions. Yoshiro Saito and Kazuhiko Takahashi. https://www.researchgate.net/publication/266456194_Selenoprotein_P_Its_Structure_and_Functions
13. Selenoprotein W in development and oxidative stress. Chrissa Kioussi, Philip D.Whanger. https://link.springer.com/chapter/10.1007/0-387-33827-6_12
14. Selenophosphate synthetase 2 is essential for selenoprotein biosynthesis. Xue-Ming Xu, Bradley A. Carlson, Robert Irons, Heiko Mix, Nianxin Zhong, Vadim N. Gladyshev, Dolph L. Hatfield. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868833/
15. Methionine Sulfoxide Reduction in Mammals: Characterization of Methionine-R-Sulfoxide Reductases. Hwa-Young Kim, Vadim N.Gladyshev. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC363075/
16. Roles of the 15-kDa Selenoprotein (Sep15) in Redox Homeostasis and Cataract Development Revealed by the Analysis of Sep 15 Knockout Mice. Marina V. Kasaikina, Dmitri E. Fomenko, Vyacheslav M. Labunskyy, Salil A. Lachke, Wenya Qiu, Juliet A. Moncaster, Jie Zhang, Mark W. Wojnarowicz, Jr., Sathish Kumar Natarajan, Mikalai Malinouski, Ulrich Schweizer, Petra A. Tsuji, Bradley A. Carlson, Richard L. Maas, Marjorie F. Lou, Lee E. Goldstein, Dolph L. Hatfield, Vadim N. Gladyshev. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190948/
17. How to use the world’s scarce selenium resources efficiently to increase the selenium concentration in food. Anna Haug, Robin D.Graham, Olav A.Christopherson, Graham H.Lyons. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556185/  – https://www.tandfonline.com/doi/full/10.1080/08910600701698986
18. Modern Nutrition in Health and Disease. 11th Edition. A. Catherine Ross, Benjamin Caballero, Robert J.Cousins, Katherine L.Tucker, Thomas R.Ziegler. https://treatment.tbzmed.ac.ir/uploads/User/47/nutrition/1394/modern%20nutrition.pdf
19. Selenium World Atlas Updated Edition (2002). James E.Oldfield. http://docplayer.net/28499873-Selenium-world-atlas-updated-edition-professor-james-e-oldfield-oregon-state-university-corvallis.html
20. Selenium in Counties of the Conterminous States. U.S. Department of the Interior. https://mrdata.usgs.gov/geochem/doc/averages/se/usa.html
21. Effects of nationwide addition of selenium to fertilizers on foods, and animal and human health in Finland. From deficiency to optimal selenium status of the population. Journal of Trace Elements in Medicine and Biology 31. Georg Alfthan, Merja Eurola, Päivi Ekholm. https://www.researchgate.net/publication/262452930_Effects_of_nationwide_addition_of_selenium_to_fertilizers_on_foods_and_animal_and_human_health_in_Finland_From_deficiency_to_optimal_selenium_status_of_the_population
22. Pollination ~ the Brazil nut tree, the orchid & the orchid bees. https://brazilnuttree.co.uk/bees.html
23. The Brazil nut tree: grandiose and threatened. WWF. https://www.wwf.org.br/?26235/The-Brazil-nut-tree-grandiose-and-threatened
24. Brazil Nuts and the Amazon Rainforest: A Story of Sustainability, Livelihood, and Conservation. INC international Nuts & Dried Fruit. https://www.nutfruit.org/industry/publications/inc-magazine/articles/detail/brazil-nuts-and-the-amazon-rainforest-a-story-of-sustainability-livelihood-and-conservation
25. Aflatoxins and Their Impact on Human and Animal Health: An Emerging Problem. Eva G.Lizárraga-Paulin, Ernesto Moreno-Martínez, Susana P.Miranda-Castro. https://www.researchgate.net/publication/221917629_Aflatoxins_and_Their_Impact_on_Human_and_Animal_Health_An_Emerging_Problem
26. Concentrations of selenium, barium, and radium in Brazil nuts. P.P. Parekh, A.R. Khan, M.A. Torres, M.E. Kitto. https://www.researchgate.net/publication/223715605_Concentrations_of_selenium_barium_and_radium_in_Brazil_nuts
27. USDA National Nutrient Database for Standard Reference (Selenium). Release 28. https://ods.od.nih.gov/pubs/usdandb/Selenium-Content.pdf
28. Selenosis – Signs, Symptoms and Causes of Toxic Selenium Exposure. INTERNATIONAL JOINT COMMISSION HEALTH PROFESSIONALS ADVISORY BOARD PRACTITIONERS’ GUIDE. https://ijc.org/sites/default/files/2020-09/HPAB_Selenosis_Signs_Symptoms_Causes_Toxic_Selenium_Exposure_EN.PDF
29. Acute Selenium Toxicity Associated With a Dietary Supplement. Ms. Jennifer K. MacFarquhar, RN, MPH, Dr. Danielle L. Broussard, PhD, MPH, Dr. Paul Melstrom, PhD, Mr. Richard Hutchinson, Ms. Amy Wolkin, MPH, Ms. Colleen Martin, MPH, Dr. Raymond F. Burk, MD, Dr. John R. Dunn, DVM, PhD, Dr. Alice L. Green, MS, DVM, Dr. Roberta Hammond, PhD, Dr. William Schaffner, MD, and Dr. Timothy F. Jones, MD. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225252/
30. Mystery solved: Polo ponies probably died of selenium overdose. Scientific American. https://blogs.scientificamerican.com/news-blog/mystery-solved-polo-ponies-probably-2009-04-30/
31. No evidence of selenosis from a selenium-rich diet in the Brazilian Amazon. Mélanie Lemire, Aline Philibert, Myriam Fillion, Carlos José Sousa Passos, Jean Rémy Davée Guimarães, Fernando Barbosa Jr., Donna Mergler. https://core.ac.uk/download/pdf/132284445.pdf
32. Health effects of arsenic, fluorine, and selenium from indoor burning of Chinese coal. Liu Guijian  1 , Zheng Liugen, Nurdan S Duzgoren-Aydin, Gao Lianfen, Liu Junhua, Peng Zicheng. https://pubmed.ncbi.nlm.nih.gov/17193737/
33. Selenium Status in Greenland Inuit. Jens C Hansen, Bente Deutch, Henning Sloth Pedersen. https://pubmed.ncbi.nlm.nih.gov/15325150/
34. Assessment of requirements for selenium and adequacy of selenium status: a review. C.D.Thomson. https://www.nature.com/articles/1601800

35. Dietary Reference Intakes. Government of Canada. https://www.canada.ca/en/health-canada/services/food-nutrition/healthy-eating/dietary-reference-intakes/tables/reference-values-elements-dietary-reference-intakes-tables-2005.html

Terms of Use

The contents of this website are for educational purposes and are not intended to offer personal medical advice. You should seek the advice of your doctor or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. EatingJAM does not recommend or endorse any commercial products.