Ingredients

Selenomethionine

Health Conditions13

Table of contents

Other Names

(2S)-2-Amino-4-(methylselanyl)butanoic acid(2S)-2-amino-4-(methylseleno)butanoate(2S)-2-Amino-4-(methylseleno)butanoic acid(2S)-2-amino-4-(methylseleno)butyric acid(S)-2-Amino-4-(methylselanyl)butanoic acid(S)-2-Amino-4-(methylseleno)butanoic acid(S)-2-Amino-4-(methylseleno)butyric acid2S-amino-4-(methylseleno)-butanoic acidButanoic acid, 2-amino-4-(methylseleno)-, (2S)-D-SelenomethionineDL-SelenomethionineL-SelenomethionineL-selenomethionine zwitterionL-SelenomethioninumSe-MetSelenium-L-methionineSeleno-L-methionineSeMet

Synopsis

Selenomethionine: A Comprehensive Reference

1. Identity and Chemical Characterization

1.1 Names and Chemical Classification

Selenomethionine (SeMet) is a naturally occurring amino acid. Its systematic IUPAC name is 2-amino-4-(methylselanyl)butanoic acid; it is also formally designated as L-selenomethionine in its biologically active stereoisomeric form. The compound is structurally analogous to the sulfur-containing amino acid methionine, with selenium (Se) substituted in place of sulfur in the thioether side chain. Selenium and sulfur are chalcogens that share many chemical properties, so the substitution of methionine with selenomethionine may have only a limited effect on protein structure and function in many contexts.

The organic compounds (organoselenium compounds) are represented in living organisms, in particular, by the amino acids L(+)-selenomethionine, L(+)-methylselenocysteine, and L(+)-selenocysteine. L(+)-Selenomethionine is the main source of organic selenium in humans and animals. However, humans and animals are autotrophic for this amino acid, which can be obtained only through the diet.

1.2 Natural Sources

The L-selenomethionine enantiomer is the main form of selenium found in Brazil nuts, cereal grains, soybeans, and grassland legumes, while Se-methylselenocysteine, or its γ-glutamyl derivative, is the major form of selenium found in Astragalus, Allium, and Brassica species. Selenocysteine is predominantly formed in animals fed inorganic selenium, while selenomethionine is derived from dietary sources of plant origin.

Selenomethionine, which is estimated to account for at least half of the dietary selenium, is absorbed by the same mechanism as methionine, and its selenium is made available for selenoprotein synthesis when it is catabolized via the transsulfuration pathway. Brazil nuts, green vegetables, shiitake and button mushrooms, and various kinds of seeds, such as young barley seedlings, are excellent organic sources of selenium in regions with adequate selenium levels in the soil. Dietary exposure from these sources varies with geographical location, depending upon the selenium content in the soil.

Selenomethionine is the major seleno-compound found in cereal grains, in legumes, in animals, and in selenium-enriched yeast nutritional supplements. In countries such as England and Norway, cereals were previously an important source of selenium because these countries imported selenium-rich grains from the United States and Canada.

1.3 Common Forms and Preparations

Forms of selenium that are commonly found in dietary supplements include selenomethionine, selenium-enriched yeast, sodium selenite, and sodium selenate. Common forms include selenomethionine, selenium-enriched yeast (grown in a high-selenium medium, predominantly as selenomethionine), sodium selenite, and sodium selenate.

Because the L-isomer of selenomethionine (Se-met) is a major natural food-form of selenium, synthetic L-Se-met or enriched food sources thereof such as selenium yeast are appropriate supplemental forms of Se for humans; for animals, DL-Se-met is acceptable. Higher bioavailability and greater safety of preparations containing organic selenium differ from those with a content of inorganic selenium salts. Additional advantages are low cost and simple manufacturing process of yeast biomass rich in selenium.

Selenomethionine is commercially available as:

Pure synthetic L-selenomethionine capsules and tablets — typically standardized to contain 100–200 mcg of elemental selenium per dose.
Selenium-enriched yeast (Se-yeast) — yeast cultured in high-selenium media that incorporates selenium primarily as selenomethionine. In accordance with EU regulations, the production of dietary supplements containing selenium may utilize dietary supplements in the form of selenium-enriched yeasts (<2500 μg S/g).
Multivitamin/mineral complexes — Selenium is available in multivitamin/mineral supplements, in supplements that contain vitamin E and other ingredients, and as stand-alone supplements.

The doses of selenium in multivitamin/mineral supplements vary, but many contain 55 mcg. Supplements that combine selenium with vitamin E or other ingredients generally contain 50 to 200 mcg of selenium. Selenium-only supplements typically contain 100 to 400 mcg.

2. Historical and Scientific Discovery

2.1 Discovery of the Element Selenium

The element selenium was discovered in 1817 more or less by accident by Jöns Jakob Berzelius and Johan Gottlieb Gahn. In 1817, the Swedish chemists, Berzelius and Gahn, on roasting 200 kg of sulfur from a pyrite from the Falun mine, obtained about 3 g of a precipitate that they first wrongly identified as tellurium. Berzelius doubted this result and repeated the analysis some months later, realizing that a new element was in his hands, and he named this element Selenium (Greek: Selene, moon) in consideration of its resemblance to Tellurium (Latin: Tellus, earth).

Originally, selenium was considered a naturally occurring toxicant; however, this view changed following the unexpected discovery that selenium prevented liver necrosis in rats by Schwarz and Foltz in 1957. Another turning point in Se research came through the discovery of Se in the enzyme glutathione peroxidase (Rotruck et al., 1973; Behne and Kyriakopoulos, 2001). Since then, the essentiality of Se for animals and human beings came into the limelight, and it is considered as an essential nutrient in the human diet.

2.2 Selenomethionine as a Food-Form Selenium: Recognition of Nutritional Significance

For over four decades, selenium has been acknowledged as an essential nutrient for human health. The foundational work by Schwartz and Foltz in 1957 identified selenium as a crucial trace element, highlighting its significance in nutrition. Subsequent research progressively established selenomethionine specifically as the predominant organic form of selenium in human foodstuffs, distinguishing it from inorganic selenium compounds and from the selenocysteine present in selenoproteins. It was not until the latter decades of the 20th century that selenomethionine emerged as a preferred supplement form, motivated by both its high bioavailability and its identity with naturally occurring dietary selenium.

Note on Traditional Use: Selenomethionine is not associated with any independent traditional botanical or ethnopharmacological use. Selenium in food — including the selenomethionine it naturally contains in grains, nuts, and legumes — has been consumed by all food-consuming cultures throughout history, but this occurred as an incidental nutritional exposure rather than a deliberately identified or prepared therapeutic agent. The deliberate isolation and supplemental use of selenomethionine as a defined chemical entity is entirely a product of 20th- and 21st-century nutritional science.

3. Key Constituents, Metabolism, and Mechanisms of Action

3.1 Chemical Identity and Absorption

Selenomethionine (SeMet) is one of two key amino acids — along with selenocysteine — involved in various biochemical processes. All living organisms can convert inorganic Se into biologically active organic forms, with SeMet being the predominant form and a precursor for SeC production in humans and animals.

Selenomethionine is absorbed by the same mechanism as methionine, i.e., via active transport through amino acid transporters in the small intestinal epithelium. The bioavailability of selenium in the form of selenomethionine is greater than 90 percent. By contrast, selenate and selenite, two inorganic forms of selenium, have roughly equivalent bioavailability which generally exceeds 50 percent.

3.2 Metabolic Fates

Ingested Se-met is either metabolized directly to reactive forms of selenium or stored in place of methionine in body proteins. Se-met metabolism is closely linked to protein turnover. Three primary metabolic fates have been described:

Non-specific protein incorporation: Cells do not distinguish between methionine and selenomethionine during protein synthesis, so this natural selenoamino acid gets incorporated into the general body proteins (e.g., albumin) in place of methionine when methionine is or is not a limiting factor. This non-specific incorporation of Se into proteins likely accounts for the observed dose-dependent increase of tissue Se levels with selenomethionine-supplemented diets compared with diets supplemented with other chemical forms of Se.
Transsulfuration to active selenium: Its selenium is made available for selenoprotein synthesis when it is catabolized via the transsulfuration pathway.
Selenoprotein synthesis: After being metabolized to selenite in the liver, selenomethionine is used in the synthesis of selenoproteins. Selenoprotein P is the main form by which Se is transported to extrahepatic tissues and is responsible for 53% of the Se concentration in plasma.

Selenomethionine can be non-specifically incorporated into tissue proteins in place of methionine, with highest incorporation occurring in tissues with high rates of protein synthesis. This non-specific incorporation of selenomethionine effectively serves as a pool of selenium reserve with a long biological half-life. Highest total selenium content is typically found in the kidney and liver, with lesser amounts in all other tissues.

3.3 Selenoproteins: The Active Mediators

The human genome encodes 25 selenoprotein genes, which incorporate low-molecular-weight Se compounds in the form of selenocysteine. The principal selenoprotein families through which selenomethionine-derived selenium exerts its biological effects include:

Glutathione peroxidases (GPx): Se is essential for life and required for the proper enzymatic function of selenoproteins such as glutathione peroxidases (GPX) and thioredoxin reductases (TrxR). The selenium-dependent glutathione peroxidase 4 (GPX4) serves as the central regulator of ferroptosis through enzymatic reduction of phospholipid hydroperoxides (PLOOH). Selenium functions through selenoproteins, several of which are oxidant defense enzymes. The Recommended Dietary Allowance (RDA) for selenium is based on the amount needed to maximize synthesis of the selenoprotein glutathione peroxidase, as assessed by the plateau in the activity of the plasma isoform of this enzyme.
Thioredoxin reductases (TrxR): Mammalian thioredoxin reductase (TR) is itself a selenoenzyme with a catalytic selenocysteine residue. The presence of selenium improves the redox properties of a given protein (e.g., GPX family, thioredoxin reductase, selenoprotein P).
Selenoprotein P: Serves as the major plasma transporter of selenium to peripheral tissues, as noted above.
Iodothyronine deiodinases: These selenoproteins catalyze the conversion of thyroxine (T4) to its active form triiodothyronine (T3) and are essential for normal thyroid hormone metabolism.

3.4 Antioxidant Mechanisms

Selenomethionine's antioxidant activity arises from its ability to deplete reactive oxygen species. Selenium and methionine also play separate roles in the formation and recycling of glutathione, a key endogenous antioxidant in many organisms, including humans. Selenomethionine decomposes lipid peroxides and inhibits in vivo lipid peroxidation in tissues of vitamin E-deficient chicks.

A recently described mechanism involves selenomethionine's role as a ferroptosis inhibitor. Selenomethionine was identified as a novel resister of ferroptosis. Mechanistically, selenomethionine serves as a selenium donor for GPX4 biosynthesis beyond the transsulfuration pathway. The anti-ferroptosis activity of selenomethionine persists even after CRISPR-mediated GPX4 knockout, revealing a GPX4-independent mechanism that relies on direct redox modulation via selenium-mediated reactive oxygen species (ROS) scavenging.

4. Scientific Evidence by Health Area

4.1 Thyroid Health and Autoimmune Thyroid Disease

Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone synthesis and exerts antioxidant effects. Therefore, it may be of relevance in the management of HT.

A 2024 systematic review and meta-analysis of randomized clinical trials (RCTs) evaluated the effects of selenium supplementation specifically in Hashimoto thyroiditis. The authors screened 687 records and included 35 unique studies. Their meta-analysis found that selenium supplementation decreased TSH in patients without thyroid hormone replacement therapy (SMD −0.21 [CI −0.43 to −0.02]; 7 cohorts, 869 participants; I² = 0%). In addition, TPOAb (SMD −0.96 [CI −1.36 to −0.56]; 29 cohorts; 2358 participants; I² = 90%) and malondialdehyde (MDA; SMD −1.16 [CI −2.29 to −0.02]; 3 cohorts; 248 participants; I² = 85%) decreased in patients with and without thyroid hormone replacement therapy.

Based on the current evidence, selenium supplementation therapy might reduce serum TPOAb and TgAb levels after 6 months of treatment in patients with HT. Meanwhile, it was reasonable to speculate that patients with high serum antibody levels would benefit from selenium supplementation. However, these results did not mean that selenium supplementation must be routinely used in clinical treatment, because the reduction of antibodies did not mean the improvement of thyroid function.

A separate meta-analysis examining 21 RCTs totalling 1,610 subjects found: serum TPOAb was significantly reduced after Se supplementation at 3 months (SMD = −0.46, 95% CI: −0.74 to −0.18, P = .001) and 6 months (SMD = −0.80, 95% CI: −1.38 to −0.21, P = .008). Serum TgAb levels decreased at 3 months (SMD = −0.46, 95% CI: −0.79 to −0.12, P = .007) but not at 6 months.

The NIH Office of Dietary Supplements notes that a study examining selenium supplementation specifically for thyroid function showed different results when focusing on functional outcomes: results showed that selenium supplementation ranging from 80 to 200 mcg/day as selenomethionine or sodium selenite for 3 to 12 months did not affect TSH levels, thyroid echogenicity (ultrasound, a measure of hypothyroidism), or health-related quality of life.

An Italian trial found that supplementation with SeMet downregulated the IFN-γ–inducible chemokines (CXCL9 and CXCL10). A Polish study found that the addition of selenomethionine (SeMet) to levothyroxine treatment inhibited lymphocyte release of IL-2, IFN-γ, and TNF, which was accompanied by a reduction of CRP.

Regarding pregnancy, the NIH documents that a trial provided 83 mcg/day selenium as selenomethionine to 45 pregnant women who were TPOAb and/or TgAb positive. It reported reductions in these antibodies at 6 months postpartum compared with placebo. However, a trial that provided 60 mcg/day selenium as selenium yeast to TPOAb-positive pregnant women who were mild to moderately iodine deficient showed no reduction in TPOAb levels at delivery. In 2017, the American Thyroid Association issued a weak recommendation against the use of selenium supplementation for pregnant women who are TPOAb-positive based on moderate quality evidence.

Evidence strength: Moderate — multiple RCTs and meta-analyses show consistent reductions in thyroid autoantibodies (TPOAb), but improvement in clinically meaningful thyroid function outcomes (TSH normalization, quality of life) is less consistently demonstrated. The current evidence is not conclusive enough to support the routine addition of selenium in the management of patients with Graves' disease or Hashimoto's thyroiditis. The high heterogeneity (I² = 90% for TPOAb) in pooled analyses limits firm conclusions.

4.2 Cancer Prevention

The most consequential trials of selenomethionine in cancer prevention are the Nutritional Prevention of Cancer (NPC) Trial and the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Nutritional Prevention of Cancer (NPC) Trial: The NPC trial randomized 1,312 patients with a history of nonmelanoma skin cancer to 200 mcg selenium per day in selenized yeast or to a yeast placebo, and patients were treated and followed for an average of 7.4 years. Patients randomized to selenium experienced significantly decreased total cancer incidence, mainly of the lung, colon, and prostate; they also experienced significantly decreased total cancer incidence and mortality. The association of selenium supplementation with decreased risk was especially marked for prostate cancer, and the strongest association with decreased risk was noticed among subjects in the lowest tertile of baseline plasma selenium. An important caveat for the NPC findings is that these endpoints were secondary to the primary endpoint: non-melanoma skin cancer recurrence.

SELECT (Selenium and Vitamin E Cancer Prevention Trial): The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was one of the largest human cancer prevention trials ever undertaken. Its purpose was to assess the role of selenium and vitamin E in prostate cancer prevention, but SELECT found no decline in prostate cancer.

The SELECT intervention consisted of oral selenium (200 mcg/day from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/day of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years. Hazard ratios for prostate cancer were 1.13 (99% CI, 0.95–1.35) for vitamin E, 1.04 (99% CI, 0.87–1.24) for selenium, and 1.05 (99% CI, 0.88–1.25) for selenium + vitamin E vs 1.00 for placebo. SELECT clearly establishes that selenium in the form of l-selenomethionine, when administered to the diet of healthy American males fifty years of age and older, does not prevent prostate cancer.

Analysts have proposed several explanations for SELECT's null findings. Comparison of this study to other clinical trials involving selenium and to the results of animal studies suggests that the source of the selenium supplement, L-selenomethionine, and the relatively high initial levels of selenium in the enrolled men may have contributed to this outcome. Selenomethionine can be converted to methyl selenol, but is also non-specifically incorporated into proteins in place of methionine, diverting the selenium away from its active chemopreventive form. Other selenocompounds like selenocysteine, selenite, or selenate, are not used non-specifically in proteins and therefore are more likely to be converted to the potentially antitumorigenic metabolite methyl selenol.

The negative efficacy outcomes of double-blinded, randomized, placebo-controlled Phase III human clinical trials with selenomethionine (SeMet) and SeMet-rich selenized-yeast (Se-yeast) for prostate cancer prevention and Se-yeast for prevention of non-small cell lung cancer (NSCLC) in North America led to rejection of SeMet/Se-yeast for cancer prevention in selenium-adequate populations. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention.

Evidence strength: Negative, for selenomethionine specifically in selenium-adequate populations. The hypothesis that selenomethionine reduces cancer risk has been formally tested in large-scale Phase III RCTs and has not been supported. Evidence from the earlier NPC trial, which used selenium-enriched yeast (not pure selenomethionine), is not directly applicable, and expert analysis suggests the active chemopreventive compound may have been a different selenium species in that yeast preparation.

4.3 Male Fertility and Reproductive Health

A 3-month trial in Scotland in 69 men (mean age 33 years) with reduced sperm motility and low selenium plasma concentrations (mean 8.1 mcg/dL) found that administering 100 mcg/day selenium as selenomethionine improved plasma selenium concentrations, sperm motility, and the odds of conception compared with placebo.

Selenium deficiency can cause Keshan disease (a type of heart disease) and male infertility. If left untreated, selenium deficiency can cause various health issues, including impaired immune function, cardiovascular effects, reproductive and fertility problems, thyroid dysfunction, neurological symptoms, and musculoskeletal abnormalities.

Evidence strength: Preliminary — the male fertility evidence involves a small trial (n = 69) in selenium-deficient men. Selenomethionine at 100 mcg/day demonstrated improvements in sperm motility and conception odds in that specific population. There is insufficient evidence to generalize to selenium-replete individuals.

4.4 Selenium Deficiency Diseases: Keshan Disease and Kashin-Beck Disease

Selenium deficiency alone rarely causes overt illness, but it produces biochemical changes that might predispose people who experience additional stresses to develop certain illnesses. For example, Keshan disease is an endemic cardiomyopathy that was first identified in 1935 in parts of China where the soil is low in selenium. Adults in these areas had average selenium intakes of no more than 10 mcg/day; intakes of at least 20 mcg/day are needed to protect adults from the disease. Keshan disease mainly affects women of childbearing age and preschool children.

Keshan disease is a type of congestive cardiomyopathy characterized by symptoms like heart failure, cardiac enlargement, electrocardiogram (ECG) irregularities, gallop rhythm, and cardiogenic shock. This condition predominantly impacts children and women of reproductive age. Initially discovered in areas of China plagued by selenium deficiency, Keshan disease was associated with a significant morbidity rate of 50%, often accompanied by occurrences of mortality.

Patients receiving long-term total parenteral nutrition have developed selenium deficiency with muscle pain and tenderness that responded to a selenomethionine supplement.

In certain populations, selenium deficiency may trigger the development of conditions such as Keshan disease and Kashin-Beck disease. In addition, selenium deficiency may increase the risk of congenital hypothyroidism in infants by exacerbating iodine deficiency.

Evidence strength: Strong, in the context of demonstrable selenium deficiency. Selenium supplementation (including selenomethionine) is well-established as effective for the prevention and management of Keshan disease and for correcting nutritional selenium deficiency.

4.5 Cardiovascular Health

This section focuses on six diseases and conditions in which selenium might play a role: cancer, cardiovascular disease (CVD), cognitive decline and Alzheimer's disease (AD), HIV infection, male fertility, and thyroid disease. Epidemiological data suggest associations between selenium status and cardiovascular outcomes, but the causal role of selenomethionine supplementation in cardiovascular disease prevention has not been established in large-scale RCTs. There is a general agreement about the multiple positive roles of selenium on human health, and a general U-shaped non-linear relationship between selenium status and beneficial effects has been suggested. Overall, subjects with low selenium levels at baseline could benefit from supplementation; on the contrary, those with an adequate or high status might be negatively affected.

Evidence strength: Preliminary to insufficient for direct selenomethionine supplementation — mechanistic rationale (antioxidant selenoproteins) is established, but RCT evidence specifically for selenomethionine and hard cardiovascular endpoints is lacking.

4.6 Immune Function

Selenium has also been shown to affect the immune system. Selenium (Se) is an essential trace element crucial for human health that primarily functions as an immunonutrient. Observational studies have found an association between lower selenium concentrations in people with HIV and an increased risk of cardiomyopathy; worsening of disease progression; death; and, in pregnant women, HIV transmission to offspring and early death of offspring. However, randomized trials suggest that selenium supplementation has little effect on HIV disease progression or treatment.

Evidence strength: Moderate for biochemical immune markers; insufficient for hard clinical immune endpoints from selenomethionine supplementation specifically.

4.7 Cognitive Function

Chronic selenium deficiencies are correlated with cognitive decline. However, clinical trial data specifically for selenomethionine and cognitive outcomes are sparse and inconclusive. More research is needed to find out whether selenium dietary supplements might help reduce the risk of or treat cognitive decline. The NIH Consumer fact sheet notes that a study in the United States found no link between selenium levels and memory.

Evidence strength: Insufficient for selenomethionine specifically — epidemiological associations exist between selenium status and cognitive function, but robust clinical trial evidence is lacking.

5. Dosage: Forms and Amounts Reported in Studies

The following dosages are reported from specific studies and authoritative sources; they are presented as documented, not as personal dosage recommendations.

RDA (Recommended Dietary Allowance): The RDA for both men and women is 55 µg (0.7 µmol)/day.
Tolerable Upper Intake Level (UL), US/IOM: The Tolerable Upper Intake Level (UL) for adults is set at 400 µg (5.1 µmol)/day based on selenosis as the adverse effect.
Tolerable Upper Intake Level (UL), EFSA (2023 revision): A lowest-observed-adverse-effect-level (LOAEL) of 330 µg/day is identified from a large randomised controlled trial in humans (SELECT), to which an uncertainty factor of 1.3 is applied. A UL of 255 µg/day is established for adult men and women (including pregnant and lactating women). Note: this is more conservative than the US value.
SELECT trial: SELECT administered daily 200 micrograms of selenium in the form of pure l-selenomethionine.
Thyroid autoimmunity trials: Participants received 200 micrograms of Selenium over 60 days. Studies ranged from 80 to 200 mcg/day as selenomethionine or sodium selenite for 3 to 12 months.
Selenium/selenomethionine in pregnancy: One trial provided 83 mcg/day selenium as selenomethionine to 45 pregnant women who were TPOAb and/or TgAb positive.
Male fertility: 100 mcg/day selenium as selenomethionine over 3 months was studied in the referenced Scottish trial.
Multivitamin/mineral supplements: The doses of selenium in multivitamin/mineral supplements vary, but many contain 55 mcg.
Selenium-only supplements: Selenium-only supplements typically contain 100 to 400 mcg.

6. Body Systems and Health Areas Associated with Selenomethionine

Endocrine system (thyroid): Iodothyronine deiodinases are selenoproteins essential for thyroid hormone activation. Clinical trials document antibody reductions in Hashimoto thyroiditis.
Antioxidant/redox defense: GPx and TrxR enzyme families are direct effectors of selenium-dependent antioxidant protection.
Immune system: Selenium modulates both innate and adaptive immunity through selenoprotein-dependent pathways.
Reproductive system: Selenium is required for sperm motility and testicular function; deficiency is associated with male infertility.
Cardiovascular system: Keshan disease (cardiomyopathy) is the prototypic selenium deficiency cardiovascular disease; selenoproteins protect myocardial cells from oxidative damage.
Musculoskeletal system: Kashin-Beck disease (osteoarthropathy) is linked to selenium deficiency.
Central nervous system: Selenium deficiency correlates with cognitive decline in observational data; selenoproteins are expressed in neural tissue.
Liver: The liver is the principal site of selenium metabolism and selenoprotein synthesis after selenomethionine absorption.

7. Safety Considerations and Interactions

7.1 Selenosis: Toxicity from Excess Selenium

Selenosis is the result of chronically high intakes of selenium. It is most commonly characterized by hair loss and nail brittleness or loss, but other signs and symptoms can include a garlic odor in the breath, a metallic taste in the mouth, skin rash, nausea, diarrhea, fatigue, irritability, and nervous system abnormalities. The Tolerable Upper Intake Level for selenium is 400 mcg for adults, and it ranges from 45 mcg to 400 mcg for infants, children, and adolescents, depending on age.

Chronically high intakes of the organic and inorganic forms of selenium have similar effects. Early indicators of excess intake are a garlic odor in the breath and a metallic taste in the mouth.

There is a general U-shaped non-linear relationship between selenium status and beneficial effects. Overall, subjects with low selenium levels at baseline could benefit from supplementation; on the contrary, those with an adequate or high status might be negatively affected.

Real-world toxic events have been documented: A case series from 2012 retrospectively examined 9 patients who presented to a medical toxicology clinic with symptoms of selenosis after consuming a nutritional supplement. Analyses revealed that the supplement contained 200 times the reported amount of selenium. This resulted in an average Se intake of 1.3 g over 10–60 days. Symptoms of selenium toxicity began within 1 week of supplement intake and included alopecia, fingernail changes, GI symptoms, and memory loss. All patients survived and none required hospitalization.

7.2 Bioavailability and Storage Considerations

A specific pharmacokinetic feature of selenomethionine — distinct from inorganic selenium forms — is its non-specific incorporation into body proteins in place of methionine. This non-specific incorporation of selenomethionine effectively serves as a pool of selenium reserve with a long biological half-life. This means that chronic high-dose supplementation can lead to cumulative tissue accumulation that outlasts the supplementation period. A lowest-observed-adverse-effect-level (LOAEL) of 330 µg/day is identified from the SELECT trial, which used pure L-selenomethionine, underpinning EFSA's more conservative UL of 255 µg/day.

7.3 Risk in Populations with Adequate or High Selenium Status

A critical finding from the SELECT trial and its analyses is that selenomethionine supplementation in already selenium-adequate individuals not only lacks cancer-preventive benefit but may be associated with harm at higher doses. There is some evidence that high selenium levels may negatively impact glycemic indices, thus selenium supplementation may not be recommended in those at risk for diabetes and/or with a genetic makeup that induces higher than average levels of selenoproteins.

The recommended daily allowance (RDA) of selenium is 55 µg/day; the tolerable upper intake level (UL) is 400 µg/day selenium, considering selenosis as the adverse effect. This is generally related to the well-established pro-oxidant effects observed when using supra-nutritional doses of selenium.

7.4 Drug and Nutrient Interactions

Selenium exhibits synergy with vitamin E. The combined interaction of selenium and tocopherol gives the best results in the protection of organs against the destructive effects of free radicals. However, the SELECT trial found no benefit and potential harm from the selenium–vitamin E combination in cancer prevention.

Selenium interacts with a few categories of medication. If you take immunosuppressive drugs, particularly after an organ transplant, selenium can work against them. Selenium stimulates immune activity, which is the opposite of what those medications are designed to do.

The EFSA Panel on Nutrition, Novel Foods and Food Allergens evaluated the safety and bioavailability of various forms of selenium as a source of selenium for use in food supplements or addition to foods. The safety and bioavailability of selenium-enriched yeast (Se-yeast) as a source of selenium were established under the proposed conditions of use. The safety and bioavailability of l-selenomethionine (SeMet) were established for use in food supplements, under the proposed conditions of use.

7.5 Special Populations

In 2017, the American Thyroid Association issued a weak recommendation against the use of selenium supplementation for pregnant women who are TPOAb-positive based on moderate quality evidence.

People living with HIV often have low selenium concentrations, possibly due to malabsorption or inadequate selenium intakes. The prevalence of selenium deficiency in people living with HIV varies by country, reflecting the variable selenium content of the soil.