Overview
Selenium is an essential trace mineral required for synthesizing selenoproteins, a family of proteins with critical antioxidant and metabolic functions. The most well-known selenoproteins include glutathione peroxidases (antioxidant enzymes) and deiodinases (thyroid hormone conversion enzymes).
Dietary sources include Brazil nuts (extremely high - a single nut can provide the entire daily requirement), seafood, meat, eggs, and grains (selenium content varies by soil selenium levels).
Critical characteristic: Selenium has a narrow safety margin. The difference between the recommended daily amount (~55-70 mcg) and toxic levels (~400+ mcg) is smaller than for most nutrients, making over-supplementation risky.
Primary applications focus on thyroid hormone metabolism (particularly T4 to T3 conversion), antioxidant defense through selenoproteins, immune function support, and potentially reducing oxidative stress and inflammation.
Evidence quality is strong for selenium's essential role in thyroid function and antioxidant systems, though clinical benefits of supplementation in selenium-sufficient individuals are limited.
Safety concerns center on the narrow therapeutic window with chronic excess causing selenosis (selenium toxicity) characterized by hair loss, nail problems, neurological issues, and other serious symptoms.
What it means
Selenium is essential trace mineral for making selenoproteins (proteins with critical antioxidant and metabolic functions). Most known: glutathione peroxidases (antioxidant enzymes) and deiodinases (thyroid hormone conversion enzymes). Found in Brazil nuts (extremely high - single nut can provide entire daily requirement), seafood, meat, eggs, grains (selenium content varies by soil). CRITICAL: narrow safety margin - difference between recommended (~55-70 mcg) and toxic (~400+ mcg) smaller than most nutrients, over-supplementation risky. Used for thyroid hormone metabolism (T4 to T3 conversion), antioxidant defense (selenoproteins), immune function, potentially reducing oxidative stress/inflammation. Evidence strong for essential role in thyroid/antioxidant systems but clinical benefits in sufficient individuals limited. Safety concerns: narrow window - chronic excess causes selenosis (toxicity: hair loss, nail problems, neurological issues, serious symptoms).
Mechanisms of Action
Selenoprotein synthesis is selenium's sole essential function. Selenium is incorporated as selenocysteine (the 21st amino acid) into approximately 25 selenoproteins in humans.
Glutathione peroxidases (GPx) are selenium-dependent antioxidant enzymes that neutralize hydrogen peroxide and lipid peroxides, protecting cells from oxidative damage. This is a primary antioxidant defense system.
Thioredoxin reductases are selenoproteins involved in redox regulation, protein folding, and cellular antioxidant defense.
Deiodinases convert thyroid hormones between forms. Type 1 and Type 2 deiodinases convert T4 (the inactive form produced by thyroid) to T3 (the active form). Without adequate selenium, thyroid hormone activation is impaired.
This explains why selenium deficiency causes hypothyroid-like symptoms even when the thyroid gland produces adequate T4 - the conversion to active T3 is blocked.
Selenoprotein P transports selenium in the blood and delivers it to tissues, particularly brain and reproductive organs which have high selenium priority.
Immune function involves selenium-dependent processes including T cell proliferation and function, antibody production, and natural killer cell activity.
DNA protection and repair mechanisms involve several selenoproteins, potentially explaining some cancer prevention research findings.
What it means
Selenium's only essential function: selenoprotein synthesis - incorporated as selenocysteine (21st amino acid) into ~25 selenoproteins in humans. Glutathione peroxidases (GPx) selenium-dependent antioxidant enzymes neutralizing hydrogen peroxide and lipid peroxides - protect cells from oxidative damage, primary antioxidant defense. Thioredoxin reductases selenoproteins for redox regulation, protein folding, cellular antioxidant defense. Deiodinases convert thyroid hormones. Type 1 and 2 deiodinases convert T4 (inactive, thyroid-produced) to T3 (active form). Without adequate selenium, thyroid hormone activation impaired. Explains why selenium deficiency causes hypothyroid-like symptoms even when thyroid makes adequate T4 - conversion to active T3 blocked. Selenoprotein P transports selenium in blood, delivers to tissues (especially brain, reproductive organs with high selenium priority). Immune function: selenium-dependent T cell proliferation/function, antibody production, NK cell activity. DNA protection/repair involve several selenoproteins - explains some cancer prevention research findings.
Effects and Benefits
Thyroid Function
For those with selenium deficiency, supplementation improves thyroid hormone conversion and resolves hypothyroid symptoms caused by impaired T4-to-T3 conversion.
Research shows selenium supplementation in autoimmune thyroiditis (Hashimoto's disease) reduces thyroid antibody levels and might slow disease progression. A meta-analysis by van Zuuren et al. (2013) found selenium supplementation reduced thyroid peroxidase antibodies in autoimmune thyroiditis.
However, benefits for thyroid function in selenium-sufficient individuals without autoimmune disease are minimal.
Antioxidant Defense
Selenium-dependent glutathione peroxidases provide critical antioxidant protection. Deficiency impairs this system, increasing oxidative stress.
Supplementation in deficient individuals restores antioxidant capacity. In sufficient individuals, additional selenium doesn't meaningfully enhance antioxidant status beyond optimal levels.
Immune Function
Selenium deficiency impairs immune responses. Supplementation in deficient populations improves immune function and reduces infection severity.
Some research suggests selenium supplementation might reduce respiratory infection severity, though evidence is mixed and depends on baseline selenium status.
Cancer Prevention
Observational studies show inverse associations between selenium status and certain cancer risks (particularly prostate, lung, colorectal).
However, large randomized trials (SELECT trial for prostate cancer) found selenium supplementation did NOT prevent cancer in selenium-sufficient men and might have increased diabetes risk at high doses.
Current evidence does NOT support selenium supplementation for cancer prevention in adequately nourished populations.
Cardiovascular Health
Selenium deficiency is associated with Keshan disease, a cardiomyopathy endemic to low-selenium regions of China. Supplementation prevents this condition.
For cardiovascular health in selenium-sufficient populations, evidence for benefits is weak and inconsistent.
Cognitive Function and Mood
Selenium deficiency might impair cognitive function and mood. Small studies suggest supplementation in deficient elderly improves mood and cognitive measures.
Evidence for cognitive enhancement in selenium-sufficient individuals is lacking.
What it means
For thyroid (when deficient), supplementation improves hormone conversion, resolves hypothyroid symptoms from impaired T4→T3 conversion. Research: selenium in autoimmune thyroiditis (Hashimoto's) reduces thyroid antibodies, might slow progression. 2013 meta-analysis: selenium reduced thyroid peroxidase antibodies in autoimmune thyroiditis. But benefits for thyroid in sufficient individuals without autoimmune minimal. For antioxidant defense, selenium-dependent glutathione peroxidases provide critical protection - deficiency impairs system, increases oxidative stress. Supplementation in deficient restores capacity. In sufficient, additional selenium doesn't meaningfully enhance beyond optimal. For immunity, deficiency impairs responses - supplementation in deficient improves function, reduces infection severity. Some research: might reduce respiratory infection severity (mixed evidence, depends on baseline). For cancer prevention, observational studies show inverse associations (prostate, lung, colorectal). BUT large randomized trials (SELECT for prostate) found selenium did NOT prevent cancer in sufficient men, might have increased diabetes risk at high doses. Evidence does NOT support supplementation for cancer prevention in adequately nourished. For heart, deficiency associated with Keshan disease (cardiomyopathy in low-selenium China regions) - supplementation prevents. For heart in sufficient populations, evidence weak, inconsistent. For cognition/mood, deficiency might impair function/mood - small studies suggest supplementation in deficient elderly improves. Evidence for enhancement in sufficient lacking.
Dosing and Timing
Recommended dietary allowance (RDA): Adults 55 mcg daily. Pregnant women 60 mcg. Breastfeeding women 70 mcg.
Upper tolerable limit (UL): 400 mcg daily for adults. Chronic intake above this significantly increases selenosis risk.
Most people in developed countries get adequate selenium from diet. Typical dietary intake in the US is 80-120 mcg daily, well above RDA.
Populations potentially at risk for deficiency: Those in low-selenium soil regions (parts of Europe, China, New Zealand), strict vegans not consuming Brazil nuts or selenium-rich foods, people with malabsorption conditions, and those on long-term dialysis.
Brazil nuts are the richest dietary source. A single Brazil nut contains approximately 70-90 mcg selenium (varies by source). Eating 1-2 Brazil nuts daily provides adequate selenium without supplementation.
However, Brazil nuts from high-selenium regions can contain much more (~200 mcg per nut), making it possible to exceed safe limits by eating just a few daily. This variability makes Brazil nuts both an excellent selenium source and potential over-supplementation risk.
Supplement forms include selenomethionine (organic, well-absorbed), sodium selenite (inorganic), and selenium yeast (mix of forms). Selenomethionine is most common and bioavailable.
Typical supplement doses: 50-200 mcg daily. Many multivitamins contain 55-70 mcg.
For Hashimoto's thyroiditis, research typically uses 200 mcg daily. This should be done under medical supervision given proximity to upper limit.
Timing doesn't significantly affect absorption. Selenium can be taken with or without food.
Testing selenium status: Plasma or serum selenium measures current status. Selenoprotein P is a functional marker. Most people don't need testing - dietary sources suffice.
What it means
RDA: adults 55 mcg daily. Pregnant 60 mcg. Breastfeeding 70 mcg. Upper limit: 400 mcg daily - chronic intake above significantly increases selenosis risk. Most in developed countries get adequate from diet. Typical US intake 80-120 mcg, well above RDA. At-risk populations: low-selenium soil regions (parts of Europe, China, New Zealand), strict vegans not eating Brazil nuts/selenium foods, malabsorption conditions, long-term dialysis. Brazil nuts richest source - single nut ≈ 70-90 mcg (varies by source). 1-2 nuts daily provides adequate without supplements. But nuts from high-selenium regions can have much more (~200 mcg per nut) - possible to exceed safe limits eating just few daily. Variability makes Brazil nuts excellent source AND potential over-supplementation risk. Supplement forms: selenomethionine (organic, well-absorbed), sodium selenite (inorganic), selenium yeast (mix). Selenomethionine most common, bioavailable. Typical supplement doses: 50-200 mcg daily. Many multivitamins have 55-70 mcg. For Hashimoto's, research uses 200 mcg daily - should be under medical supervision (near upper limit). Timing doesn't affect absorption - with or without food. Testing: plasma/serum selenium measures current. Selenoprotein P functional marker. Most don't need testing - dietary suffices.
Safety and Interactions
Selenosis - CRITICAL WARNING
Chronic selenium excess causes selenosis, a toxicity syndrome with serious symptoms.
Symptoms of selenosis include: garlic odor on breath and skin (from volatile selenium compounds), hair loss and brittle nails, nail discoloration and deformity, fatigue and irritability, nausea and GI distress, skin rashes and lesions, neurological problems (peripheral neuropathy, mood changes), and in severe cases, respiratory distress, heart failure, and death.
Selenosis typically results from chronic intake above 400 mcg daily, though individual susceptibility varies. Acute toxicity from massive doses (thousands of mcg) has occurred from contaminated supplements.
This is why casual high-dose selenium supplementation is dangerous. The margin between RDA (55 mcg) and toxicity threshold (400+ mcg) is relatively narrow - only about 7-fold, compared to 50-100 fold for many nutrients.
Type 2 Diabetes Risk
The SELECT trial found higher selenium levels and supplementation associated with increased type 2 diabetes risk. Other research supports this concern in selenium-sufficient populations.
Mechanism might involve selenium's effects on insulin signaling. This adds another reason to avoid unnecessary supplementation in adequate populations.
Medication Interactions
Anticoagulants: Very high selenium doses might have mild anticoagulant effects. Those on warfarin should use caution with high-dose supplements.
Chemotherapy drugs: Selenium might interfere with certain chemotherapy agents. Cancer patients should discuss selenium supplementation with oncologists.
Statins: Some research suggests selenium might reduce statin effectiveness, though evidence is limited.
Nutrient Interactions
Vitamin C: High-dose vitamin C (multiple grams) might reduce selenium absorption. Separate by several hours if taking both at high doses.
Iodine: Selenium and iodine work together in thyroid function. Selenium deficiency with iodine supplementation can worsen thyroid problems. Ensure adequate selenium before addressing iodine deficiency.
Population Considerations
Pregnancy and breastfeeding: Moderate supplementation (60-70 mcg) is safe and recommended if dietary intake is inadequate. Avoid high doses.
Children: RDA for children is lower (20-55 mcg depending on age). Adult doses can cause toxicity in children.
Autoimmune thyroid disease: Some evidence supports selenium supplementation (200 mcg daily) for Hashimoto's thyroiditis under medical supervision. However, consult endocrinologist before using.
What it means
SELENOSIS WARNING: chronic selenium excess causes toxicity with serious symptoms. Symptoms: garlic breath/skin odor (volatile selenium compounds), hair loss and brittle nails, nail discoloration/deformity, fatigue/irritability, nausea/GI distress, skin rashes/lesions, neurological problems (peripheral neuropathy, mood changes), severe cases: respiratory distress, heart failure, death. Typically from chronic intake above 400 mcg though individual susceptibility varies. Acute toxicity from massive doses (thousands mcg) happened with contaminated supplements. This is why casual high-dose selenium dangerous. Margin between RDA (55 mcg) and toxicity (400+ mcg) relatively narrow - only ~7-fold vs 50-100 fold for many nutrients. For diabetes, SELECT trial found higher selenium and supplementation associated with increased type 2 diabetes risk - other research supports in sufficient populations. Mechanism might involve insulin signaling effects. Another reason avoid unnecessary supplementation. Anticoagulants: very high selenium might have mild anticoagulant effects - caution with warfarin at high doses. Chemotherapy: might interfere with certain agents - cancer patients discuss with oncologists. Statins: some research suggests might reduce effectiveness (limited evidence). Vitamin C: high-dose (multiple grams) might reduce selenium absorption - separate hours if both at high doses. Iodine: selenium and iodine work together in thyroid - selenium deficiency with iodine supplementation can worsen thyroid. Ensure adequate selenium before addressing iodine deficiency. Pregnancy/breastfeeding: moderate (60-70 mcg) safe, recommended if dietary inadequate - avoid high doses. Kids: RDA lower (20-55 mcg by age) - adult doses toxic in children. Autoimmune thyroid: some evidence supports selenium (200 mcg) for Hashimoto's under medical supervision - consult endocrinologist first.
Research Strength and Limitations
Selenium research quality is strong for its essential biochemical roles with selenoprotein functions well-established through decades of research.
The benefits of correcting deficiency are unequivocal, particularly for thyroid function and antioxidant systems.
However, research on supplementation benefits in selenium-sufficient populations is disappointing. Large trials for cancer prevention, cardiovascular health, and other outcomes generally show no benefits and some risks (diabetes) in adequately nourished populations.
The narrow therapeutic window creates challenges - optimal intake appears to be in a relatively narrow range where both deficiency and excess cause problems.
Geographic variation in soil selenium creates variable dietary intake globally, making population-level recommendations challenging.
Individual variation in selenium metabolism and requirements likely exists but isn't well-characterized, making personalized recommendations difficult.
What it means
Research quality strong for essential biochemical roles - selenoprotein functions well-established through decades. Benefits of correcting deficiency unequivocal (especially thyroid/antioxidant systems). But research on supplementation in sufficient populations disappointing - large trials for cancer prevention, cardiovascular, other outcomes generally show NO benefits and some risks (diabetes) in adequately nourished. Narrow therapeutic window creates challenges - optimal intake in relatively narrow range where both deficiency and excess cause problems. Geographic soil selenium variation creates variable dietary intake globally - population recommendations challenging. Individual variation in metabolism/requirements likely exists but not well-characterized - personalized recommendations difficult.
Practical Considerations
Selenium supplementation makes sense only for those with documented deficiency, specific medical conditions (Hashimoto's under supervision), or living in known low-selenium regions without dietary access to selenium-rich foods.
For most people in developed countries: Dietary selenium from normal food sources is adequate and supplementation is unnecessary.
Simple dietary approach: Eat 1-2 Brazil nuts several times weekly. This provides adequate selenium without supplementation risks. Just don't overdo it - eating a jar of Brazil nuts daily can cause selenosis.
Who might need supplementation: Those in documented low-selenium regions (specific parts of Europe, China), people with Hashimoto's thyroiditis (under medical supervision), strict vegans avoiding nuts and selenium-rich foods, and those with malabsorption conditions causing deficiency.
Who should avoid high-dose supplementation: Anyone with adequate dietary intake (which is most people), those at risk for type 2 diabetes, anyone without documented deficiency, and those already taking multivitamins containing selenium.
Product selection: If supplementing, choose selenomethionine at modest doses (50-100 mcg). Check multivitamin labels - you might already be getting 55-70 mcg, making additional supplementation unnecessary or excessive.
Brazil nut variability: Recognize that Brazil nut selenium content varies widely. Use them as selenium source but don't consume excessive quantities daily assuming more is better.
Thyroid health optimization: If dealing with thyroid issues, ensure both iodine AND selenium adequacy. They work together. Discuss with endocrinologist rather than self-treating.
Cancer prevention: Do NOT use selenium supplements for cancer prevention based on current evidence. Observational associations haven't translated to intervention benefits.
Selenium exemplifies "essential but not more is better." Get enough through diet, avoid casual supplementation, respect the narrow safety margin.
What it means
Selenium supplementation makes sense only for documented deficiency, specific medical conditions (Hashimoto's under supervision), or known low-selenium regions without dietary access to selenium foods. For most in developed countries: dietary selenium from normal food adequate, supplementation unnecessary. Simple approach: eat 1-2 Brazil nuts several times weekly - provides adequate without supplementation risks. Just don't overdo - eating jar daily can cause selenosis. Might need supplementation: documented low-selenium regions (specific Europe/China parts), Hashimoto's thyroiditis (medical supervision), strict vegans avoiding nuts/selenium foods, malabsorption causing deficiency. Avoid high-dose: adequate dietary intake (most people), type 2 diabetes risk, no documented deficiency, already taking multivitamins with selenium. Product selection: if supplementing, choose selenomethionine at modest (50-100 mcg). Check multivitamin labels - might already get 55-70 mcg, additional unnecessary or excessive. Brazil nut variability: selenium content varies widely - use as source but don't consume excessive quantities daily assuming more is better. Thyroid optimization: if thyroid issues, ensure both iodine AND selenium adequacy - work together. Discuss with endocrinologist vs self-treat. Cancer prevention: do NOT use selenium for this based on current evidence - observational associations didn't translate to intervention benefits. Selenium exemplifies "essential but not more is better." Get enough through diet, avoid casual supplementation, respect narrow safety margin.
References
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.
Rayman MP. Selenium and human health. Lancet. 2012;379(9822):1256-1268.
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.