An essential trace element that is primarily protective in its biological roles. Unlike most metals covered in this wiki, selenium's toxicological significance lies more in the consequences of its deficiency than its excess. Selenium is the backbone of the selenoproteome -- a family of ~25 selenoproteins including glutathione peroxidases, thioredoxin reductases, and iodothyronine deiodinases -- that collectively defend against oxidative stress, regulate thyroid hormone metabolism, and modulate immune function.
Chemical Properties and Forms
- Metalloid (Group 16), incorporated into proteins as the amino acid selenocysteine (the "21st amino acid").
- Key organic forms: selenomethionine (dietary, supplement), selenocysteine (in selenoproteins), methylselenocysteine.
- Inorganic forms: selenite (SeO3 2-), selenate (SeO4 2-) -- used in some supplements.
- Narrow therapeutic window: deficiency below ~40 ug/day; toxicity (selenosis) above ~400 ug/day.
- The thyroid gland contains the highest concentration of selenium per gram of any organ in the body [brock 2015 selenium thyroid autoimmunity].
Sources of Exposure
Dietary
- Brazil nuts (highest natural source), seafood, organ meats, cereals (content varies by soil selenium).
- Geographic variation in soil selenium creates population-level deficiency zones (parts of China, Europe, New Zealand).
- Infant formula Se concentration: 130 ug/kg; exposure well below HBGV [hopfner 2025 infant formula dietary exposure elements germany].
Supplementation
- 200 ug/day selenomethionine or selenite commonly used in clinical trials [brock 2015 selenium thyroid autoimmunity].
- Combined selenomethionine + myoinositol reduced TSH and antithyroid antibodies at 6 and 12 months [kravchenko 2023 thyroid hormones minerals AITD].
Other Sources
- Tampons: Se detected in 98.3% of samples [shearston 2024 tampons metal exposure].
Key Selenoproteins
| Selenoprotein | Function | Disease Relevance |
|---|---|---|
| GPX1-4 (Glutathione peroxidases) | Reduce H2O2 and lipid hydroperoxides | Cancer, neurodegeneration, CKD |
| GPX4 | Specifically prevents lipid peroxidation | ferroptosis -- loss of GPX4 is the key trigger |
| TXNRD1/2 (Thioredoxin reductases) | Maintain thioredoxin in reduced state | Redox signaling, cancer |
| DIO1/2/3 (Iodothyronine deiodinases) | Convert T4 to T3 (DIO1/2) or inactivate T3 (DIO3) | Thyroid hormone metabolism |
| Selenoprotein P | Se transport and delivery; antioxidant | Se status biomarker |
Health Effects
Thyroid Autoimmunity
The selenium-thyroid axis is among the most clinically actionable findings in the wiki.
- Se deficiency is a risk factor for both Hashimoto's thyroiditis and Graves' disease [brock 2015 selenium thyroid autoimmunity].
- Hashimoto's thyroiditis RCTs: Se supplementation (200 ug) with levothyroxine significantly reduced anti-TPO antibodies; greatest reduction (40%) in those with anti-TPO >1200 IU/mL [brock 2015 selenium thyroid autoimmunity].
- Anti-TPO-positive euthyroid patients showed no reduction with Se supplementation, suggesting baseline thyroid function matters [brock 2015 selenium thyroid autoimmunity].
- Graves' ophthalmopathy: Double-blind RCT showed 200 ug Se/day for 6 months significantly decreased GO, improved quality of life; benefits persisted after withdrawal [brock 2015 selenium thyroid autoimmunity].
- Pregnancy: Selenomethionine 200 ug/day during pregnancy and postpartum decreased risk of permanent hypothyroidism and postpartum thyroiditis [brock 2015 selenium thyroid autoimmunity].
- Se builds deiodinases (DIO1/2/3) essential for T4 to T3 conversion; Se is a component of GPx protecting thyrocytes from oxidative damage during thyroid hormone synthesis [brylinski 2025 trace elements thyroid diseases].
- Se deficiency is an independent risk factor for Graves' ophthalmopathy development [brock 2015 selenium thyroid autoimmunity].
- Combined selenomethionine and myoinositol reduced TSH and antithyroid antibodies after 6 and 12 months [kravchenko 2023 thyroid hormones minerals AITD].
Cancer
Selenium depletion is one of the most consistent findings across cancer metallomic studies.
- Prostate cancer: Se significantly decreased (0.07 vs 0.13 ug/ml, p<0.005); low Se correlates with carcinogenesis risk through impaired antioxidant defense [saleh 2020 serum trace elements prostate cancer].
- Pan-cancer pattern: Se tends to decrease across cancer types in blood/serum/plasma, alongside Cu elevation and Zn depletion [zhang 2022 metallomics cancer review].
- Selenoprotein gene variants: GPX1, GPX4, TXNRD1/2 polymorphisms associated with cancer risk and susceptibility [zhang 2022 metallomics cancer review].
- Lung cancer/COPD: Se elevated 1.23-fold in COPD-LC transition group vs healthy; disrupted Zn-Se correlation (normally rho=0.69) in disease states [callejon leblic 2023 metallomic signatures lung cancer copd].
- Breast cancer: Decreased Se reported in multiple studies alongside elevated Cu [zhang 2022 metallomics cancer review].
Cardiovascular Disease
- Se decreased in AMI patients (90.31 vs 99.98 ng/mL, p<0.01), with persistent depression at 6 months post-event [lim 2023 plasma metallomics ami].
- Cu/Se ratio increased in AMI and showed significant longitudinal trajectory; identified as one of the most specific AMI biomarkers [lim 2023 plasma metallomics ami].
- Cu elevated and Se decreased represents a consistent cardiovascular risk signature [lim 2023 plasma metallomics ami].
Neurodegeneration
- Selenium deficiency associated with increased neurodegeneration risk; some studies suggest Se supplementation may have neuroprotective effects [doroszkiewicz 2023 common trace metals alzheimers parkinsons].
- Se deficiency in DLB primary visual cortex may compound effects of Cu loss by impairing GPx and TrxR activity [scholefield 2024 brain metallomics dementia].
- Se's role in GPX4 directly connects to ferroptosis resistance in neurons -- the same pathway implicated in PD dopaminergic neuron death.
Heavy Metal Protection
- Se plays a protective role against cadmium: binds Cd and facilitates biliary excretion [brock 2015 selenium thyroid autoimmunity].
- Se has an antagonistic relationship with mercury: demonstrated protective effect when Hg levels are elevated [brock 2015 selenium thyroid autoimmunity].
- In combined Se and iodine deficiency, normalizing Se without iodine worsens hypothyroidism; Se co-administration maintains GPx function during iodine repletion [brock 2015 selenium thyroid autoimmunity].
Mechanism of Action
1. Antioxidant defense: GPX enzymes reduce H2O2 and lipid hydroperoxides; TrxR enzymes maintain the thioredoxin system -- together they constitute the primary enzymatic antioxidant network.
2. Anti-ferroptotic activity: GPX4 specifically prevents lipid peroxidation in membranes; its loss triggers ferroptotic cell death [pendergrass 2026 microbial metallomics parkinsons ferroptosis].
3. Thyroid hormone activation: DIO1/2 convert inactive T4 to active T3; DIO3 inactivates T3 -- Se status directly controls thyroid hormone bioavailability [brock 2015 selenium thyroid autoimmunity].
4. Immunomodulation: Se supplementation increases GPx3 and selenoprotein P1; decreases MDA (oxidative stress marker); modulates anti-TPO antibody production [kravchenko 2023 thyroid hormones minerals AITD].
5. Heavy metal detoxification: Se-metal complexes (with Cd, Hg) are less toxic and more readily excreted than free metals.
Interactions with Other Metals
- Iron: Se and Fe cooperate through GPX4 -- Se provides the enzyme, Fe homeostasis determines the substrate (lipid peroxides from Fenton chemistry). Se deficiency amplifies iron-driven ferroptosis.
- Copper: Cu/Se ratio is a key AMI biomarker; Cu elevation + Se depletion is a consistent pathological signature in cancer and CVD [lim 2023 plasma metallomics ami].
- Zinc: Zn-Se correlation (rho=0.69) in healthy subjects is disrupted in lung cancer and COPD-LC, reflecting systemic dyshomeostasis [callejon leblic 2023 metallomic signatures lung cancer copd].
- Cadmium: Se binding facilitates Cd biliary excretion [brock 2015 selenium thyroid autoimmunity].
- Mercury: Se-Hg binding is protective; Se:Hg molar ratio determines net toxicity.
- Iodine: Two-way relationship; Se protects against both iodine excess and deficiency; combined Se+I deficiency requires careful sequential repletion [brock 2015 selenium thyroid autoimmunity].
Biomarkers
- Plasma/serum Se: Directly measurable; decreased in AMI (persistent at 6 months), prostate cancer, and other malignancies [lim 2023 plasma metallomics ami, saleh 2020 serum trace elements prostate cancer].
- Cu/Se ratio: Elevated in AMI; tracks longitudinally; incorporated into high-performing diagnostic models (AUC 0.942) [lim 2023 plasma metallomics ami].
- Selenoprotein P: Se-transport protein; emerging as functional Se status marker (reflects Se available for selenoprotein synthesis rather than total Se).
- GPX3 activity: Functional marker of Se-dependent antioxidant capacity [kravchenko 2023 thyroid hormones minerals AITD].
- Anti-TPO antibodies: Response to Se supplementation serves as clinical endpoint in thyroid autoimmunity trials [brock 2015 selenium thyroid autoimmunity].
Open Questions
- Whether population-level Se supplementation in Se-poor regions could reduce thyroid autoimmunity, cardiovascular events, and cancer incidence simultaneously.
- The optimal form and dose of Se supplementation across different disease contexts (selenomethionine vs selenite vs Se-enriched yeast).
- Why Se depletion is so consistently observed across cancer types -- is it cause (impaired antioxidant defense enabling carcinogenesis) or consequence (tumor Se consumption)?
- Whether Se status should be routinely measured in patients with autoimmune thyroid disease, cardiovascular risk, or cancer.
- The mechanism by which Se supplementation benefits Graves' ophthalmopathy but not necessarily euthyroid anti-TPO-positive individuals.
- How selenoprotein gene polymorphisms (GPX1, GPX4, TXNRD) modify individual cancer susceptibility and treatment response.
- Whether Se supplementation could enhance ferroptosis-based cancer therapies by selectively protecting normal cells while allowing tumor cell death.
Connections
- ferroptosis -- GPX4 is the master regulator; Se deficiency enables ferroptotic cell death
- thyroid autoimmunity -- Se supplementation reduces anti-TPO in Hashimoto's and improves Graves' ophthalmopathy
- Hashimotos thyroiditis -- 200 ug Se reduces anti-TPO antibodies, especially when >1200 IU/mL
- Graves disease -- Se deficiency as independent risk factor for ophthalmopathy
- iron -- Se-Fe cooperation through GPX4; Se deficiency amplifies iron-driven oxidative damage
- copper -- Cu/Se ratio as cardiovascular and cancer biomarker
- cadmium -- Se facilitates Cd detoxification via biliary excretion
- mercury -- Se-Hg binding provides protective effects
- oxidative stress -- selenoproteins are the primary enzymatic antioxidant network
- metallomics -- Se as key element in metallomic profiling of cancer, CVD, and neurodegeneration
- cancer -- consistent Se depletion across cancer types; selenoprotein gene variants modify risk
- acute myocardial infarction -- Se decreased with persistent depression at 6 months
- prostate cancer -- Se depletion associated with carcinogenesis risk
- nutritional immunity -- Se has no direct role in host-pathogen metal competition but supports immune function via selenoproteins