Selenium: what it is and how it works

Selenium is a trace element that the body needs in very small amounts, but without it key antioxidant enzymes and the activation of thyroid hormones do not work. At the same time, selenium has one of the narrowest “safety windows” of all nutrients. The editorial team explains what selenium is, how it is incorporated into proteins, where we get it from, and why there are so many contradictory data around it.

What selenium is

Selenium is a chemical element of group 16 of the periodic table, close in properties to sulfur. It was discovered by the Swedish chemist Jöns Jacob Berzelius in 1817, and the element got its name from the Greek word “selene” — the Moon. For a long time selenium was considered only a toxic substance, because poisonings of livestock on pastures with a high selenium content in the soil were known.

The view changed in the mid-20th century, when it turned out that selenium prevents some forms of liver necrosis in animals. In the 1970s it was discovered that selenium is part of the enzyme glutathione peroxidase, and later it became clear that selenium deficiency is associated with an endemic cardiomyopathy — Keshan disease, described in China in regions with selenium-poor soils.

Today selenium is recognized as an essential trace element: the body cannot synthesize it and must obtain it from food. The selenium content in foods largely depends on the soil on which the plants were grown or the animals grazed. That is why selenium sufficiency differs several-fold across countries (Rayman, 2012).

For sports nutrition, selenium is interesting primarily as a component of antioxidant defense and a regulator of thyroid function. However, as we will see below, “more” here does not at all mean “better.”

Selenoproteins: how selenium works in the cell

The biological action of selenium is realized almost entirely through selenoproteins — proteins containing the special amino acid selenocysteine. It is often called the 21st amino acid: it is encoded in the genetic code by the codon UGA, which usually means “stop,” and the cell uses special machinery to incorporate it. Twenty-five selenoprotein genes have been described in the human genome.

The best-known selenoproteins are the glutathione peroxidases. They neutralize hydrogen peroxide and lipid peroxides, using glutathione as an electron donor. This is one of the main lines of defense of cell membranes against oxidation, in particular during intense physical exercise, when the formation of reactive oxygen species increases.

The second important group is the thioredoxin reductases. They keep the protein thioredoxin in a reduced state, which regulates the cell’s redox balance, DNA synthesis and the activity of many signaling molecules. The third group is the iodothyronine deiodinases, which convert thyroxine (T4) into active triiodothyronine (T3) or inactivate thyroid hormones.

A special place is occupied by selenoprotein P — a plasma transport protein that delivers selenium from the liver to other tissues, in particular the brain and testes. Another selenoprotein, GPX4, is necessary for normal spermatogenesis. All this explains why selenium deficiency can affect such different systems — from the heart to reproductive function.

Absorption, transport and stores

Selenium in food is present mainly in organic forms — selenomethionine (in grains, nuts, yeast) and selenocysteine (in animal products). Supplements also use inorganic salts — sodium selenite and selenate. All these forms are well absorbed in the intestine, although their subsequent metabolism differs.

The body does not distinguish selenomethionine from ordinary methionine, so part of it is nonspecifically incorporated into the proteins of muscles and other tissues. This creates a kind of selenium store that is released during protein breakdown. Inorganic forms do not accumulate this way: what is not used for selenoprotein synthesis is excreted faster (Schrauzer, 2000).

Excess selenium is converted by the body into methylated compounds, which are excreted in the urine, and at high doses — also in exhaled air. It is dimethyl selenide that gives the breath a characteristic garlic smell, considered one of the early signs of excessive intake.

To assess selenium status, the concentration of selenium in plasma or serum, the level of selenoprotein P and the activity of glutathione peroxidase are used. Selenoprotein P is considered one of the most sensitive markers, because its concentration plateaus when the body’s needs are met (Combs, 2015).

Sources and intake norms

The richest sources of selenium are Brazil nuts, seafood, fish, offal, meat and eggs. Grains and legumes contain selenium in an amount that depends on the soil. Brazil nuts are a special case: the selenium content in them can differ several-fold even between nuts from the same batch, so they should not be regarded as a precise source of a dose.

• Fish and seafood:tuna, sardines, shrimp, mussels.
• Meat and offal:liver, kidneys, beef, poultry.
• Eggs and dairy products:a moderate but stable source.
• Nuts and grains:Brazil nut, whole grain products (content depends on the soil).

The recommended intake for adults, according to the US Institute of Medicine, is 55 mcg per day; the upper tolerable limit is 400 mcg. The European agency EFSA set adequate intake at 70 mcg, and in 2023 revised the upper tolerable limit for adults down to 255 mcg per day, taking into account data on the adverse effects of long-term supplementation.

Deficiency and excess: a narrow window

The classic manifestations of selenium deficiency are Keshan disease (cardiomyopathy) and Kashin-Beck disease (damage to joints and cartilage), described in regions of China with poor soils. In Europe severe deficiency is rare, but suboptimal selenium status occurs more often than in the USA, where the soils are generally richer in this element.

On the other hand, chronic selenium excess causes selenosis: garlic breath, brittle nails and hair, hair loss, skin rashes, digestive disorders, fatigue and neurological symptoms. In 2008 in the USA a mass poisoning was recorded through a liquid supplement that contained hundreds of times more selenium than declared on the label (MacFarquhar et al., 2010).

Large randomized studies have shown that selenium supplements do not provide the expected benefit to people who already have adequate status. In the SELECT trial selenium did not reduce the risk of prostate cancer, and in the NPC trial a repeat analysis found a higher risk of type 2 diabetes in the selenium group (Stranges et al., 2007). Rayman (2012) describes the dependence of selenium’s effects on status as U-shaped: harm is possible both with deficiency and with excess.

That is why the editorial team emphasizes: selenium is not the nutrient to “top up with a reserve.” First it is worth assessing the diet and, if possible, the status, and considering supplements when intake is truly low.

Editorial conclusions

Selenium works through selenoproteins — enzymes of antioxidant defense, redox regulation and activation of thyroid hormones. Its requirement is small, and the range between the norm and the upper limit is narrow.

Most people with a varied diet that includes fish, meat, eggs and grains get enough selenium from food. Supplements are appropriate when intake is low, but not as an “antioxidant insurance” for everyone.

We also recommend reading our articles “The benefits of Selenium for athletes: the evidence base,” “Side effects of Selenium” and “How to take Selenium: dosage, timing, duration.”

References

1. Rayman MP. Selenium and human health. Lancet. 2012;379(9822):1256–1268.
2. Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press; 2000.
3. EFSA Panel on Nutrition, Novel Foods and Food Allergens. Scientific opinion on the tolerable upper intake level for selenium. EFSA J. 2023;21(1):7704.
4. Schrauzer GN. Selenomethionine: a review of its nutritional significance, metabolism and toxicity. J Nutr. 2000;130(7):1653–1656.
5. Combs GF Jr. Biomarkers of selenium status. Nutrients. 2015;7(4):2209–2236.
6. MacFarquhar JK, Broussard DL, Melstrom P, et al. Acute selenium toxicity associated with a dietary supplement. Arch Intern Med. 2010;170(3):256–261.
7. Stranges S, Marshall JR, Natarajan R, et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med. 2007;147(4):217–223.
8. 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.