Key Takeaways (expand)
- Selenium is a trace mineral needed by all mammals to sustain life.
- Selenium serves as component of two amino acids, selenocysteine and selenomethionine; rather than being used to build proteins, these amino acids are added to proteins during post-translational modifications.
- The body stores most selenium in the form of selenomethionine, with large quantities present in muscle tissue.
- Selenium helps form over two dozen proteins (called selenoproteins), which play various roles in thyroid hormone metabolism, reproduction, DNA synthesis, and immunity.
- In the form of selenoproteins, selenium also has antioxidant functions; in fact, up to 30 different enzymes require selenoproteins in order to protect the brain and other tissues from oxidative damage!
- Selenium plays an important role in thyroid function, particularly the conversion of the thyroid hormone T4 into T3.
- Through its involvement in thyroid hormone production, selenium helps regulate a variety of biological processes—including metabolism, carbohydrate absorption, fatty acid release, growth, development, and reproductive function.
- Selenium is an essential player in immunity—helping regulate the migration, activation, differentiation, proliferation, and optimal function of immune cells.
- Selenoproteins also play a role in producing eicosanoids, lipid mediators involved in inflammatory responses.
- Selenium helps regulate iodine homeostasis, and helps regenerate vitamins C and E from their oxidized state.
- Higher selenium take is associated with a reduced risk of cancer-related death, bladder cancer, prostate cancer, colon cancer, and potentially breast cancer; however, controlled trials haven’t confirmed the cancer-protective effects seen observationally.
- If selenium does have anti-cancer activity, it’s likely due to reducing DNA damage, helping regulate immunity, protecting against oxidative stress, and directly destroying cancer cells.
- For HIV-positive patients, supplementing with selenium may help increase immune cell count, reduce the rate of hospital admissions, and protect against viral load progression.
- Selenium may also play a preventative role in asthma and inflammatory bowel disease—although more controlled human trials are needed here.
- For people with sepsis, septic shock, or systemic inflammatory response syndrome (SIRS), intravenous selenium can significantly reduce the risk of mortality.
- Due to its role in thyroid hormone metabolism, selenium may support thyroid health, protect against goiter, and improve autoimmune thyroid disease.
- Selenium has a protective effect against mercury toxicity, due to mercury’s high affinity for binding to selenium; this allows selenium to prevent mercury from accumulating in nerve cells.
- Observational studies suggest selenium could help protect against heart disease, although controlled trials of selenium supplementation haven’t shown a clear cardiovascular benefit.
- About one billion people globally are selenium deficient.
- Selenium deficiency doesn’t always produce obvious symptoms, but can reduce the activity of selenium-dependent enzymes and lead to immune dysfunction, autoimmune disorders, and increased risk of infection.
- Chronic selenium deficiency can produce a form of cardiomyopathy called Keshan disease, and a chronic bone and joint condition called Kashin-Beck disease.
- The richest food source of selenium is Brazil nuts; it’s also found in organ meats, seafood, muscle meat, and mushrooms.
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Selenium is a trace mineral that all mammals need to survive. But, it had a long road from its initial discovery to its recognition as an essential nutrient! It was first identified in 1817, when Swedish chemist Jöns Jacob Berzelius was trying to pinpoint a toxic substance that was causing illness among workers in a sulfuric acid plant—which turned out to be selenium. (He initially thought the substance was an already-known element called tellurium, which was named after the Latin word for earth (tellus); when he realized it was actually a brand new element, he named it after the Greek word for moon—selene!)
In 1937, selenium’s reputation was further tarnished when an agricultural report named selenium as the culprit for livestock poisoning (animals were eating toxicity-inducing levels of this nutrient from foraging on wild Astragalus, which accumulates high amounts of selenium from the soil, and suffering physical ailments as a result). It wasn’t until the 1950s that selenium became known as a biologically essential mineral rather than just a health scourge: in 1954, a biochemist named Jane Pinsent observed that selenium was needed for the growth of E. coli, and in 1957, another biochemist named Klaus Schwarz discovered that feeding rats torula yeast (which is selenium-deficient) caused them to develop liver necrosis, while feeding them baker’s yeast (which contains selenium) allowed the rats to thrive. The discovery of this selenium-responsive liver disease led to selenium officially being recognized as an essential trace mineral!
Selenium serves as component of two amino acids, and is a constituent of over two dozen selenoproteins involved in thyroid hormone metabolism, reproduction, DNA synthesis, and immunity. It also helps protect against oxidative damage.
Food sources of selenium include Brazil nuts (a single Brazil nut contains nearly double the daily requirement for this nutrient!), seafood, organ meats, muscle meat, and mushrooms (especially shiitake and button).
The Biological Roles of Selenium
Selenium is a component of two unusual amino acids: selenocysteine and selenomethionine. These amino acids aren’t used as building blocks for proteins, but instead, are added to proteins during post-translational modifications (which can impact enzyme and neurotransmitter activity). The body stores most selenium in the form of selenomethionine, with the muscles being particularly important storage sites (holding about 28 to 46% of all the selenium in the body!). Meanwhile, proteins containing selenocysteine are called selenoproteins, and they act as catalysts for various enzymatic reactions and antioxidant defense (selenoproteins are required for the activity of up to 30 different enzymes that protect the brain and other tissues from oxidative damage). In all, scientists have identified 25 genes that code for selenoproteins.
Although many more exist that we don’t know much about, the best-characterized selenoproteins include five glutathione peroxidases (enzymes that reduce potentially harmful reactive oxygen species to harmless products like water and alcohols); three thioredoxin reductases (enzymes that help reduce a number of different substrates, serve as electron donors for antioxidant regeneration, and help regulate cell growth and survival); one methionine sulfoxide reductase (which helps protect against oxidative stress); and three iodothyronine deiodinases (enzymes critical for thyroid hormone production—more on that shortly!).
Additional selenoproteins include selenoprotein P, which is the major form of selenium transport to peripheral tissues in the body (and is critical for maintaining selenium homeostasis in the brain and testes); selenoprotein W, which is concentrated in the heart and skeletal muscles and plays a role in redox regulation; selenophoshate synthetase 2, which catalyzes the synthesis of selenophosphate from hydrogen selenide; 15 kDA selenoprotein, which is highly expressed in the prostate, testes, kidney, brain, and liver and is thought to be involved in anticancer mechanisms and protein folding in the lens of the eye; and selenoprotein S, which plays a role in regulating inflammatory and immune responses.
One of this nutrient’s most important roles is in thyroid function—specifically, the production of thyroid hormones! First, the thyroid gland pulls iodine from the blood and integrates it into a glycoprotein called thyroglobulin, which then gets hydrolyzed by lysosomal enzymes to create thyroid hormones: thyroxine, or T4 (the most abundant circulating thyroid hormone) and triiodothyronine, or T3 (the physiologically active thyroid hormone that can regulate gene expression by binding to thyroid receptors in cell nuclei). Iodine plays a major structural role here, comprising over half the molecular weight of both T4 and T3. After being produced, these thyroid hormones are stored and released into circulation whenever they’re needed, mostly in the form of inactive T4. Next, selenium steals the show: target tissues in the body (particularly the liver and brain) use selenium-dependent enzymes called iodothyronine deiodinases to convert that T4 into T3, by removing one iodine atom from T4. Two of these selenium-containing enzymes (deiodinases type 1 and 2) are able to catalyze the T4 to T3 conversion, while a third selenium-containing enzyme (deiodinase type 3) can turn both T3 and T4 into inactive metabolites.
From there, thyroid hormones are able to regulate a variety of processes in the body: they act upon gene transcription mechanisms to regulate metabolism (thyroid hormone deficiency can reduce the basal metabolic rate by up to 50%!), they act on small intestine cells to increase carbohydrate absorption, they act upon adipocytes (fat cells) to induce fatty acid release, and they play major roles in growth, development, and reproductive function!
Selenium also plays an essential part in the immune system—specifically, regulating the migration, differentiation, proliferation, activation, and optimal function of immune cells. As a result, selenium influences T-cell immunity, B-cell dependent antibody production, and innate immunity. Likewise, selenoproteins appear to play a role in the production of lipid mediators called eicosanoids, which are involved in inflammatory responses.
Interactions with Other Nutrients
Selenium has some noteworthy interactions with other nutrients. Along with its collaborative role with iodine in thyroid hormone synthesis, selenium-dependent enzymes may help regulate iodine homeostasis, and selenium deficiency appears to exacerbate the effects of iodine deficiency. Selenium also acts synergistically with the antioxidant vitamins C and E by regenerating them from their oxidized state.
Selenium in Health and Disease
Observational research suggests a link between higher selenium intake and protection against cancer—possibly due to selenium’s ability to reduce DNA damage, boost immunity, combat oxidative stress, and directly destroy cancer cells; however, controlled trials haven’t shown a clear anti-cancer benefit from selenium supplements. Likewise, while observational research suggests a protective role of selenium for cardiovascular disease, asthma, and inflammatory bowel disease, controlled human trials are lacking. More reliable evidence suggests that selenium can help reduce mortality rates in patients with sepsis, protect against mercury toxicity, and benefit HIV-positive individuals by increasing immune cell count and reducing viral load progression. Getting enough selenium is also important for protecting against preeclampsia during pregnancy.
Selenium and Cancer
Selenium has been studied for its potential role in cancer prevention in both humans and other animals. A number of observational studies on selenium and cancer risk suggest a protective effect of this nutrient, with meta-analyses indicating that higher versus lower selenium status (as measured by markers of selenium exposure, like selenium content of the blood and toenails) is associated with a 40% reduced risk of cancer-related death and a 31% lower risk of cancer at any site (as well as a lower risk of bladder and prostate cancer, specifically!).
Some (but not all) studies have found an inverse relationship between serum selenium levels and breast cancer risk. Intervention trials have also given weight to a cause-and-effect role of selenium on cancer development, with research showing that selenium supplementation was able to reduce the risk of liver cancer by 35% in populations prone to hepatitis B infection (a major liver cancer risk factor); that supplementation with 200 micrograms daily of selenium-enriched yeast reduced incidence of prostate cancer by 52% (particularly among men with baseline low selenium status); and that supplementation with 200 micrograms daily of selenium (but, interestingly, not 400 micrograms!) reduced total cancer incidence by 25%, along with specific reductions in lung cancer, colon cancer, and breast cancer risk. Likewise, the majority of animal model experiments looking at selenium and cancer (over 100 studies and counting!) have shown that selenium supplementation significantly reduces tumor incidence.
However, other research on the selenium-cancer relationship has been contradictory. One study found that selenium supplementation appeared to increase the risk of squamous cell carcinoma (a form of skin cancer) by 25%, and contrary to other interventions, potentially increase the risk of high-grade prostate cancer. Similarly, a major meta-analysis of randomized trials failed to find a beneficial effect of selenium supplementation on cancer when including only the highest-quality studies. It’s possible that the protective effect of selenium seen in observational research, too, is confounded by other dietary or lifestyle factors related to selenium-rich foods or selenium-abundant geographical regions. However, via its role in selenoproteins, selenium has very plausible anti-cancer mechanisms—such as by reducing DNA damage, protecting against oxidative stress, helping regulate immunity, and even directly destroying cancer cells. So, more research is needed to explore the role selenium plays in cancer!
Selenium and Immunity
Preliminary evidence also suggests that among HIV-positive patients, supplementing with selenium may help increase immune cell count and protect against viral load progression. Experiments have shown that HIV could reduce the levels of some important selenoproteins (especially thioredoxine reductases and glutathione peroxidases), in turn disrupting the normal antioxidant defenses of infected T-cells; likewise, through their antioxidant activity, selenoproteins appear to prevent HIV-infected immune cells from replicating. As a result of these mechanisms, several trials have been conducted testing whether selenium supplementation could benefit HIV-infected individuals, with promising results—including significantly reduced rate of hospital admissions, improved CD4 lymphocyte T-cell count, and reduced viral load progression (all resulting from supplementation of 200 micrograms of selenium daily). One trial also found that a combination of selenium and multivitamins (B, C, and E) reduced the risk of immune decline in HIV patients more effectively than either the selenium or the multivitamins alone.
Through its influence on immunity and inflammation, selenium may also play a preventative role in asthma and inflammatory bowel disease—although randomized controlled trials are needed to explore this possibility. And, selenium may help protect against sepsis and related conditions, with randomized controlled trials showing that intravenous selenium supplementation in people with sepsis, septic shock, or systemic inflammatory response syndrome (SIRS) can significantly reduce the risk of mortality.
Selenium and Thyroid Health
Not surprisingly, given its importance in thyroid hormone metabolism, selenium may support thyroid health and even help improve autoimmune thyroid disease. Observational studies show an inverse relationship between selenium levels in the blood and risk of goiter and thyroid volume, particularly among women with iodine deficiency. And, several randomized trials have reported a beneficial effect of selenium supplementation in patients with Hashimoto’s disease (including a reduction in circulating antibodies) and Grave’s disease (including enhanced quality of life, improvements in eye health, and a slower progression of symptoms).
Selenium and Mercury Toxicity
Fascinatingly, selenium also has a protective effect against mercury toxicity! Mercury has a very high affinity for binding to selenium—up to a million-times higher affinity than for sulfur, mercury’s second-best binding partner. Studies have shown that selenium-enriched diets not only help prevent mercury toxicity, but can also quickly reverse some of the most severe symptoms. Mechanistically, animal models show that selenium prevents mercury from accumulating in nerve cells, in turn protecting against the muscular and nervous system dysfunctions seen with mercury poisoning.
Selenium and Cardiovascular Disease
And, some evidence suggests selenium could help protect against heart disease. Across numerous observational studies, higher selenium status (as measured by blood selenium concentrations) has been associated with a significantly lower risk of developing cardiovascular disease—per one meta-analysis, a 15% risk reduction for every 10 mcg increase in blood levels. But, randomized controlled trials haven’t shown a consistent benefit for selenium supplementation on heart disease during long-term followups, so it’s unclear whether these observational trends are due to dietary selenium intake or other diet, lifestyle, or genetic factors.
Health Effects of Selenium Deficiency
About one billion people around the world are estimated to have selenium deficiency, often due to regional agricultural conditions (the selenium content of plant foods depends on how much selenium is in the soil they’re grown in, and some areas are notoriously deficient—including Eastern Europe, China, New Zealand, and areas in the American Midwest near the Great Lakes!). But, selenium deficiency can also occur in people with compromised intestinal function (such as from Crohn’s disease), people undergoing kidney dialysis, patients reliant on parenteral nutrition, elderly adults aged 90 and above, and people on certain restrictive diets that limit typical sources of selenium (such as low-protein diets for treating phenylketonuria).
Although selenium deficiency doesn’t usually cause obvious symptoms of illness, it can negatively impact the activity of selenium-dependent enzymes (especially glutathione peroxidases, selenoprotein W, methionine-R-sulfoxide reductase B1, and iodothyronine deiodinases)—which in turn can affect different body systems. Long-term selenium deficiency may contribute to the development of two health conditions:
- a fatal form of cardiomyopathy called Keshan disease, which can either be acute (sudden-onset cardiac insufficiency) or chronic (ongoing heart enlargement with varying levels of cardiac insufficiency); and
- a chronic bone and joint condition called Kashin-Beck disease, characterized by the degeneration of cartilage between joints, leading to joint deformities and severe functional limitation (selenium deficiency is thought to play a role here due to reducing antioxidant protection).
Over time, selenium deficiency can also contribute to a variety of health conditions related to immunity and inflammation. For example, selenium deficiency has been linked with immune dysfunction, autoimmune thyroid disorders, pemphigus vulgaris (a rare group of autoimmune diseases affecting the skin and mucous membranes), and lichen planus (a more common condition that causes swelling and irritation on the skin or mouth). People with insufficient selenium intake also appear more prone to infections and illness.
Although selenium is sold in the form of dietary supplements, there’s no evidence that extra selenium offers added health benefits among people who aren’t at high risk of deficiency.
Problems From Too Much Selenium
It’s worth noting that although small amounts of selenium are vital for health, consuming excess selenium—such as by chronically ingesting doses above the tolerable upper intake level of 400 micrograms daily, or taking a very high selenium dose (thousands of micrograms) all at once—can cause selenium toxicity, also known as selenosis. Symptoms of selenosis include hair loss, fingernail loss, fatigue, irritability, a garlicky breath odor, gastrointestinal disorders, and skin rashes. Cases of selenosis have been reported in regions with very high selenium content in the soil, as well as from manufacturing errors that produced mislabeled selenium supplements (causing people to ingest much more than the packaging indicated).
Even at less-than-toxic doses, some evidence suggests that high selenium levels in the blood can adversely impact blood sugar control. This finding mostly comes from observational studies, with some data showing that people with the highest versus lowest blood selenium concentrations have an elevated risk of type 2 diabetes, have higher levels of glycated hemoglobin, and have higher levels of plasma glucose. A randomized trial similarly found that among people with the highest baseline levels of blood selenium, supplementing with 200 micrograms daily led to a significantly higher risk of developing type 2 diabetes over the course of years. It’s possible that some selenoproteins interfere with insulin action and glucose homeostasis, but it’s also possible that the causation is reversed (with impaired glucose metabolism affecting selenoprotein expression and selenium homeostasis)—so, more research is definitely needed! For now, selenium supplementation doesn’t appear dangerous for most people, but those with high selenium status and those at risk of developing type 2 diabetes are advised to avoid supplementing this nutrient.
How Much Selenium Do We Need?
The recommended dietary allowance (RDA) for selenium is 55 micrograms per day for all adolescents and adults. Due to the potential side effects of excessive selenium intake, be sure to seek the medical advice of a health professional before supplementing with high doses.
Best Food Sources of Selenium
The following foods have high concentrations of selenium, containing at least 50% of the recommended dietary allowance per serving, making them our best food sources of this valuable mineral!
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