L-Selenocysteine

• Antioxidant protection
• Immune system support
• Thyroid function regulation

• Detoxification support
• Cardiovascular health
• Cognitive function
• Cancer risk reduction

L-Selenocysteine (Sec) is a unique amino acid that contains selenium in place of the sulfur found in cysteine. Often referred to as the ’21st amino acid,’ selenocysteine is genetically encoded and incorporated into proteins through a specialized translation mechanism that repurposes the UGA stop codon when a specific RNA structure (Selenocysteine Insertion Sequence or SECIS element) is present. The primary mechanisms of action for L-selenocysteine revolve around its incorporation into selenoproteins, which are responsible for most of selenium’s biological effects. The selenium atom in selenocysteine has unique chemical properties that distinguish it from sulfur in cysteine: it has a lower pKa (5.2 compared to 8.3 for cysteine), making it predominantly ionized at physiological pH, and it has higher nucleophilicity and redox potential.

These properties make selenocysteine-containing enzymes particularly efficient catalysts for redox reactions. In the human proteome, 25 selenoproteins have been identified, with selenocysteine being crucial for their biological activity. The major mechanisms through which selenocysteine exerts its effects include: 1) Antioxidant defense: Selenocysteine is the active site residue in glutathione peroxidases (GPx), which catalyze the reduction of hydrogen peroxide and organic hydroperoxides, protecting cells from oxidative damage. The selenol group (-SeH) in selenocysteine cycles between reduced and oxidized states, efficiently neutralizing reactive oxygen species at rates several orders of magnitude faster than similar reactions with cysteine.

2) Thyroid hormone metabolism: Selenocysteine is essential for the function of iodothyronine deiodinases (DIOs), enzymes that activate or inactivate thyroid hormones by removing specific iodine atoms. These enzymes regulate the conversion of thyroxine (T4) to the more active triiodothyronine (T3) or to inactive reverse T3, thus controlling cellular thyroid hormone activity. 3) Redox signaling and regulation: Thioredoxin reductases (TrxRs) contain selenocysteine and play crucial roles in maintaining cellular redox homeostasis by reducing oxidized thioredoxin, which in turn reduces disulfide bonds in various proteins. This system influences numerous cellular processes including DNA synthesis, gene expression, and apoptosis.

4) Protein folding and quality control: Selenocysteine is found in selenoprotein K, selenoprotein S, and selenoprotein N, which are involved in endoplasmic reticulum-associated protein degradation (ERAD) and protection against endoplasmic reticulum stress. 5) Selenium transport and storage: Selenoprotein P (SELENOP) contains multiple selenocysteine residues (up to 10) and serves as the primary plasma selenium transport protein, delivering selenium from the liver to peripheral tissues, particularly the brain and testes. 6) Immune function modulation: Selenoproteins influence various aspects of immune function, including the regulation of inflammatory responses, leukocyte migration, and cytokine production. Selenocysteine-containing enzymes help control oxidative burst in activated immune cells and modulate redox-sensitive transcription factors like NF-κB.

7) Metal detoxification: Some selenoproteins participate in the detoxification of heavy metals by forming complexes with mercury, cadmium, and other toxic elements, reducing their bioavailability and toxicity. Unlike many other supplements, L-selenocysteine is not typically consumed directly but is instead incorporated into proteins through dietary selenium intake. The body uses various forms of dietary selenium (selenomethionine, selenite, selenate) to synthesize selenocysteine, which is then incorporated into selenoproteins. The biological activity of selenocysteine is therefore dependent on adequate selenium intake and the proper functioning of the selenoprotein synthesis machinery.

L-Selenocysteine is not directly available as a supplement due to its instability and specialized incorporation mechanism in proteins. Instead, selenium supplementation in various forms (selenomethionine, sodium selenite, selenium yeast) provides the raw material for the body to synthesize selenocysteine and incorporate it into selenoproteins. The Recommended Dietary Allowance (RDA) for selenium is 55 μg/day for adults, which is sufficient to support selenoprotein synthesis under normal conditions. For therapeutic purposes, selenium supplementation typically ranges from 100-200 μg/day, with most clinical studies using this range to achieve optimal selenoprotein expression and function.

It’s important to note that selenium has a narrow therapeutic window, with the tolerable upper intake level set at 400 μg/day. Exceeding this amount may lead to selenosis (selenium toxicity) with symptoms including garlic breath, hair loss, nail brittleness, gastrointestinal disturbances, and in severe cases, neurological effects.

L-Selenocysteine itself is not typically consumed directly as a supplement due to its instability and specialized incorporation mechanism in proteins. Instead, the body synthesizes selenocysteine from other forms of selenium and incorporates it into selenoproteins through a unique translation process. The bioavailability of selenocysteine therefore depends on the absorption and metabolism of various dietary selenium forms. Organic selenium forms like selenomethionine (found in plants and selenium yeast) have higher bioavailability (approximately 90-95%) compared to inorganic forms like selenite and selenate (50-70%).

Once absorbed, these selenium compounds enter different metabolic pathways. Selenomethionine can be non-specifically incorporated into proteins in place of methionine or metabolized to selenocysteine. Inorganic selenium forms are reduced to hydrogen selenide (H₂Se), which serves as a precursor for selenocysteine synthesis. The synthesis of selenocysteine occurs on its specific tRNA (tRNA[Ser]Sec), where serine is first attached and then converted to selenocysteine.

This unique tRNA then delivers selenocysteine for incorporation into selenoproteins at specific UGA codons (normally stop codons) when a Selenocysteine Insertion Sequence (SECIS) element is present in the mRNA. The efficiency of this process is regulated by selenium availability, with priority given to essential selenoproteins like glutathione peroxidase 1 and 2 during selenium limitation. Excess selenium is excreted primarily through urine, with some elimination through breath (as dimethylselenide, giving the characteristic garlic odor in cases of high intake) and feces.

Organic selenium forms: Using organic selenium sources like high-selenium yeast or selenomethionine provides better bioavailability than inorganic forms, leading to more efficient selenocysteine synthesis and incorporation into selenoproteins., Adequate protein intake: Since selenocysteine is incorporated into proteins, ensuring adequate protein intake supports optimal selenoprotein synthesis., Vitamin E co-supplementation: Vitamin E works synergistically with selenium-dependent enzymes in antioxidant defense systems, potentially enhancing the functional effects of selenocysteine-containing proteins., Balanced intake of other minerals: Maintaining appropriate levels of other minerals like zinc and copper helps optimize selenium metabolism, as these minerals are involved in related antioxidant systems., Probiotics: Some research suggests that certain probiotic strains may enhance selenium absorption and metabolism, potentially improving selenocysteine incorporation into proteins., Avoiding excessive intake of competing minerals: High doses of zinc, iron, or calcium taken simultaneously with selenium supplements may reduce selenium absorption through competition for transporters or binding sites., Selenium-enriched foods: Consuming selenium-enriched foods (grown in selenium-rich soil or specially cultivated) may provide selenium in forms that are more readily used for selenocysteine synthesis than some supplements.

Since L-selenocysteine is not directly supplemented but rather synthesized in the body from other selenium forms, timing recommendations relate to the intake of selenium supplements or selenium-rich foods. For optimal absorption of selenium supplements, taking them with a meal containing some fat may enhance absorption, particularly for organic forms like selenomethionine. However, very high-fat meals might slightly delay absorption. Selenium supplements are generally well-absorbed at any time of day, but consistent timing helps maintain steady selenium levels.

For individuals taking multiple mineral supplements, separating selenium from high-dose zinc, iron, or calcium supplements by at least 2 hours may reduce potential competition for absorption. There is some evidence that selenium supplementation in the morning may better support the body’s antioxidant defense systems, which face increased challenges during daytime activities and exposure to environmental stressors. For those taking selenium specifically for immune support, consistent daily dosing is more important than specific timing. When selenium is taken for thyroid support, morning administration may be beneficial as this coincides with the natural peak in thyroid hormone production.

For individuals with gastrointestinal sensitivity, taking selenium supplements with food rather than on an empty stomach may reduce the potential for mild digestive discomfort. It’s worth noting that the body maintains selenium stores, primarily in the liver and kidneys, which help buffer short-term variations in intake. This means that occasional timing inconsistencies are unlikely to significantly impact selenium status or selenoprotein function in most individuals.

• Garlic-like breath and body odor (at high doses)
• Metallic taste in mouth
• Nausea and digestive discomfort
• Hair loss (with chronic excessive intake)
• Nail changes and brittleness
• Skin rashes or lesions (in selenosis)
• Fatigue
• Irritability
• Nervous system abnormalities (at very high doses)
• Potential increased risk of type 2 diabetes with long-term high-dose supplementation

• Known hypersensitivity to selenium compounds
• Existing selenium toxicity (selenosis)
• Concurrent use of medications with high selenium content
• Severe kidney disease (may impair selenium excretion)
• Pregnancy and breastfeeding (except under medical supervision)
• Individuals scheduled for surgery within two weeks (due to potential anticoagulant effects)
• Individuals with certain genetic variations affecting selenium metabolism (rare)

• Anticoagulants and antiplatelet drugs: Selenium may enhance the blood-thinning effects of these medications, potentially increasing bleeding risk.
• Statins: Some evidence suggests that high-dose selenium supplementation might reduce the effectiveness of certain statin medications.
• Niacin: Concurrent use of high-dose niacin and selenium may increase the risk of insulin resistance.
• Barbiturates: These may increase the metabolism and excretion of selenium, potentially reducing its effectiveness.
• Chemotherapy drugs: Selenium may interact with certain chemotherapy agents, either enhancing or interfering with their effects. Medical supervision is essential.
• Gold compounds: Used in rheumatoid arthritis treatment, these may compete with selenium in the body.
• Thyroid medications: Since selenium affects thyroid function, it may alter the requirements for thyroid medications. Monitoring is recommended.

The Tolerable Upper Intake Level (UL) for selenium is set at 400 μg per day for adults by the Institute of Medicine. This limit includes selenium from all sources—food, water, and supplements. Exceeding this amount regularly increases the risk of adverse effects, particularly selenosis (selenium toxicity). Acute selenium toxicity can occur at much higher doses (approximately 5 mg or 5,000 μg), with severe toxicity possible at doses above 10-20 mg.

Chronic intake above the UL but below acutely toxic levels (typically 750-1000 μg daily) may lead to gradual onset of selenosis symptoms, including garlic breath, hair loss, nail changes, and skin lesions. These symptoms are generally reversible when selenium intake is reduced. Some research suggests that long-term intake of selenium at doses of 200-300 μg daily may be associated with increased risk of type 2 diabetes and certain other adverse effects in some populations, particularly those with already adequate selenium status. This has led some researchers to suggest that the optimal range for supplementation may be narrower than previously thought, especially for individuals with adequate dietary selenium intake.

It’s worth noting that selenium requirements and tolerance may vary based on individual factors including genetics, overall health status, and geographical location (as selenium content in foods varies widely by region). For therapeutic purposes, selenium doses above the RDA but below the UL (typically 100-200 μg daily) are commonly used and generally considered safe for most individuals when used appropriately.

L-Selenocysteine itself is not directly regulated as a supplement ingredient by the U.S. Food and Drug Administration (FDA), as it is not typically available in this form due to instability issues. Instead, the FDA regulates various selenium compounds that the body can use to synthesize selenocysteine. Selenium is recognized as an essential nutrient with an established Recommended Dietary Allowance (RDA) of 55 μg/day for adults and a Tolerable Upper Intake Level (UL) of 400 μg/day.

The FDA allows selenium to be used in dietary supplements, typically as sodium selenite, sodium selenate, selenomethionine, or selenium-enriched yeast. These selenium compounds are regulated under the Dietary Supplement Health and Education Act (DSHEA) of 1994. Qualified health claims for selenium supplements are limited. In 2003, the FDA authorized a qualified health claim for selenium and cancer risk reduction, but with significant disclaimers about the limited and mixed nature of the evidence.

This claim states: ‘Selenium may reduce the risk of certain cancers. Some scientific evidence suggests that consumption of selenium may reduce the risk of certain forms of cancer. However, FDA has determined that this evidence is limited and not conclusive.’ Following the results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT), which did not show cancer prevention benefits, the FDA has been more conservative regarding selenium health claims. Selenium is also permitted as a nutrient in food fortification and in medical foods for specific conditions, subject to relevant regulations for these categories.

The European Food Safety Authority (EFSA) has established a Population Reference Intake (PRI) for selenium of 70 μg/day for adults and a tolerable upper intake level of 300 μg/day. EFSA regulates selenium compounds rather than selenocysteine directly, with approved forms for food supplements including sodium selenate, sodium selenite, sodium hydrogen selenite, selenomethionine, and selenium-enriched yeast. EFSA has evaluated and approved several health claims related to selenium, including: ‘Selenium contributes to the normal function of the immune system’ ‘Selenium contributes to normal thyroid function’ ‘Selenium contributes to the protection of cell constituents from oxidative damage’ ‘Selenium contributes to normal spermatogenesis’ ‘Selenium contributes to the maintenance of normal hair’ ‘Selenium contributes to the maintenance of normal nails’ These claims can be used for foods and supplements that contain at least 8.25 μg of selenium per 100 g, 100 ml, or per package if the package contains only a single portion. EFSA has rejected other proposed claims related to selenium and cognitive function, anxiety reduction, and joint health due to insufficient scientific evidence.

The European Union has also established maximum levels for selenium in certain food categories to prevent excessive intake.

Health Canada recognizes selenium as an essential nutrient with a Recommended Dietary Allowance (RDA) of 55 μg/day for adults and a Tolerable Upper Intake Level (UL) of 400 μg/day. Selenium compounds, rather than selenocysteine directly, are regulated as Natural Health Product (NHP) ingredients under the Natural Health Products Regulations. Approved selenium forms include sodium selenate, sodium selenite, selenomethionine, and selenium-enriched yeast. Health Canada permits certain health claims for selenium supplements, including its role in antioxidant function, immune support, and thyroid health, when products provide at least 3.5 μg of selenium per day.

Products must not exceed the established upper limit of 400 μg per day. Selenium supplements require a Natural Product Number (NPN) before they can be legally sold in Canada. Health Canada has specific labeling requirements for selenium supplements, including cautionary statements for products providing more than 100 μg per day.

The Therapeutic Goods Administration (TGA) of Australia regulates selenium compounds rather than selenocysteine directly. Selenium is recognized as an essential nutrient with a Recommended Dietary Intake (RDI) of 70 μg/day for adults and an upper limit of 400 μg/day. Approved forms of selenium for use in listed complementary medicines include sodium selenate, sodium selenite, selenomethionine, and selenium-enriched yeast. The TGA permits certain health claims for selenium supplements related to antioxidant function, immune support, and thyroid health when products provide appropriate doses.

Products containing more than 150 μg of selenium per day are classified as Pharmacist Only Medicines in Australia, requiring pharmacist intervention for sale. Selenium supplements must be included in the Australian Register of Therapeutic Goods (ARTG) before they can be marketed. The TGA has specific labeling requirements for selenium supplements, including warnings about potential toxicity at high doses.

Japan: The Japanese Ministry of Health, Labour and Welfare recognizes selenium as an essential nutrient with a recommended intake of 30 μg/day for adult men and 25 μg/day for adult women. Selenium is permitted in Foods with Health Claims, including Foods for Specified Health Uses (FOSHU) and Foods with Nutrient Function Claims (FNFC). China: The Chinese Nutrition Society recommends a daily selenium intake of 60 μg for adult men and 60 μg for adult women, with an upper limit of 400 μg/day. Selenium supplementation is closely monitored in China due to the country’s complex geography of selenium distribution, with both selenium-deficient and selenium-excessive regions.

Russia: The Russian Federation has established a recommended daily intake of 70 μg for selenium with an upper limit of 300 μg/day. Selenium is approved for use in dietary supplements and specialized foods. Brazil: ANVISA (Brazilian Health Regulatory Agency) has established a recommended daily intake of 34 μg for selenium with an upper limit of 400 μg/day. Selenium supplements require registration before marketing.

India: The Indian Council of Medical Research recommends a daily selenium intake of 40 μg for adults. Selenium supplements are regulated under the Food Safety and Standards Authority of India (FSSAI). In developing countries, particularly those with known selenium deficiency regions, national fortification programs sometimes include selenium addition to fertilizers or staple foods, representing a different regulatory approach focused on population-level intervention rather than individual supplementation.

L-Selenocysteine itself is not available as a prescription medication. Various selenium compounds used to support selenocysteine synthesis and selenoprotein production are generally available as over-the-counter supplements in most countries, subject to dose limitations. In most jurisdictions, selenium supplements providing up to 200 μg per day are available without prescription. Higher doses may have restricted access: In Australia, selenium supplements containing more than 150 μg per day are classified as Pharmacist Only Medicines, requiring pharmacist intervention for sale.

In some European countries, high-dose selenium supplements (typically >200 μg per day) may require a prescription or pharmacist consultation. For clinical conditions requiring therapeutic selenium doses, such as severe selenium deficiency or certain specialized applications in cancer supportive care, medical supervision is recommended even if not legally required. Selenium injections, sometimes used in clinical settings for severe deficiency, typically require a prescription in all jurisdictions. It’s worth noting that while high-dose selenium supplementation may not always legally require a prescription, medical guidance is strongly recommended due to the narrow therapeutic window of selenium and potential for toxicity at high doses.

L-Selenocysteine itself is not directly available as a supplement due to its instability and specialized incorporation mechanism in proteins. Instead, various selenium compounds that the body can use to synthesize selenocysteine are available in supplement form. Basic selenium supplements (typically sodium selenite or selenate) range from $5-$15 for a 30-day supply at standard doses (50-200 μg daily). Higher quality organic forms like selenomethionine or selenium-enriched yeast typically cost $15-$30 for a 30-day supply.

Premium selenium formulations, often including synergistic nutrients like vitamin E or specialized delivery systems, range from $25-$50 for a 30-day supply. Specialized high-selenium yeast products with standardized selenomethionine content can cost $30-$60 for a 30-day supply. Food-based selenium supplements, derived from sources like selenium-enriched garlic or mushrooms, typically range from $20-$40 for a 30-day supply. It’s worth noting that many multivitamin/mineral formulations include selenium (typically 50-200 μg), making dedicated selenium supplements unnecessary for many individuals.

These multivitamins range widely in price from $10-$50 for a 30-day supply, depending on quality and formulation.

Compared to other essential minerals: Selenium supplements are moderately priced compared to other essential mineral supplements. They are generally more expensive than basic minerals like zinc or magnesium but less expensive than specialized mineral formulations like chelated iron or lithium orotate. The relatively low required dose of selenium (micrograms rather than milligrams) contributes to its reasonable cost-efficiency. Compared to other antioxidants: As a component of antioxidant enzymes, selenium provides good value compared to many direct antioxidant supplements.

While dedicated antioxidants like astaxanthin or specialized vitamin E formulations can cost $30-$80 monthly, selenium supplements supporting endogenous antioxidant systems typically cost $10-$30 monthly. Compared to obtaining selenium from food sources: Brazil nuts provide exceptional value as a selenium source, with a single nut containing approximately 70-90 μg selenium at a cost of about $0.10-$0.20. However, the selenium content can vary widely based on growing region, and consistent daily consumption of exactly one nut is impractical for most people. Other selenium-rich foods like seafood provide good nutritional value but at a higher cost than supplements if consumed solely for selenium content.

Selenium-enriched foods (like selenium-enriched garlic or mushrooms) are typically more expensive than basic supplements but may provide additional beneficial compounds. Overall value consideration: The value proposition of selenium supplements is strongest for: 1) Individuals living in regions with low soil selenium content; 2) Those with increased selenium needs due to certain health conditions or medications; 3) People with dietary patterns that limit selenium-rich foods (e.g., some vegetarian diets); 4) Those seeking targeted selenoprotein support for specific health goals like thyroid or immune function.

Purchasing larger containers of selenium supplements (90-180 day supply) typically offers savings of 15-25% compared to 30-day supplies. Subscription services from many brands provide recurring shipments at a discount of approximately 10-20% compared to one-time purchases. Some manufacturers offer significant discounts (20-30%) for multi-bottle purchases. Professional-grade supplement suppliers sometimes offer larger package sizes with better per-dose pricing for healthcare practitioners.

For those who consume selenium regularly, these bulk purchasing options can substantially improve cost-efficiency over time. However, given the potential for selenium toxicity with excessive intake, bulk purchasing should be approached with caution, particularly for higher-dose formulations.

Selenium supplements are generally not covered by conventional health insurance plans in most countries. In the United States, selenium supplements may be eligible expenses for Health Savings Accounts (HSAs) or Flexible Spending Accounts (FSAs) if prescribed by a healthcare provider for a specific medical condition, though this is uncommon in practice. In some cases, high-dose selenium prescribed for specific medical conditions (such as severe deficiency) may be covered by insurance, particularly in countries with national healthcare systems. Some specialized healthcare plans focused on integrative medicine may offer limited reimbursement for supplements including selenium when recommended by an in-network provider, but this is the exception rather than the rule.

Medicare, Medicaid, and most national healthcare systems do not cover selenium supplements unless they are prescribed as medical foods for specific conditions, which is rare. In regions with endemic selenium deficiency, some public health programs may provide selenium supplements at reduced or no cost to vulnerable populations, though such programs are limited.

L-Selenocysteine itself is highly unstable in its free form due to the reactive nature of the selenol group (-SeH), which is readily oxidized in the presence of oxygen. For this reason, pure L-selenocysteine is not typically available as a dietary supplement. Instead, various selenium compounds that the body can use to synthesize selenocysteine are used in supplements. The shelf life of these selenium compounds varies: Sodium selenite and sodium selenate are relatively stable inorganic forms with shelf lives of 2-3 years when stored properly in sealed containers.

Selenomethionine and selenium-enriched yeast typically have shelf lives of 1-2 years under recommended storage conditions. Liquid selenium supplements generally have shorter shelf lives of 6-12 months once opened due to increased exposure to oxygen and potential microbial contamination. The stability of selenium compounds in multivitamin/mineral formulations may be affected by interactions with other ingredients, particularly minerals and reducing agents, potentially shortening their effective shelf life. For selenium-rich foods, proper storage is essential to maintain selenium content.

Brazil nuts, for example, can become rancid if stored improperly, which may affect both palatability and selenium bioavailability.

For selenium supplements (providing raw material for selenocysteine synthesis):, Store in a cool, dry place, ideally between 15-25°C (59-77°F), Protect from direct sunlight and UV radiation, Keep container tightly closed to protect from moisture and oxygen, Avoid storage in bathrooms or other high-humidity environments, For liquid selenium supplements, refrigeration after opening is often recommended, Keep away from strong oxidizing or reducing agents that might alter the selenium species, For selenium-rich foods:, Store Brazil nuts in the refrigerator or freezer to prevent rancidity, Keep selenium-enriched grains and seeds in airtight containers in cool, dry conditions, Minimize cooking time and water volume when preparing selenium-rich foods to reduce losses, For selenium yeast products:, Follow manufacturer’s storage recommendations precisely, Some products may require refrigeration, particularly after opening, Protect from moisture, which can activate yeast enzymes and potentially degrade selenium compounds

Oxidation: The selenol group in selenocysteine is highly susceptible to oxidation, forming selenocystine (the diselenide) or other oxidized forms, Heat: Elevated temperatures accelerate most degradation reactions of selenium compounds, Light: UV and visible light can catalyze oxidation reactions involving selenium compounds, Moisture: Can promote hydrolysis, microbial growth, and other degradation pathways, pH extremes: Most selenium compounds have optimal stability in specific pH ranges, Metal ions: Certain metals can interact with selenium, potentially altering its chemical form and bioavailability, Reducing agents: Can convert selenium between different oxidation states, potentially affecting stability and bioactivity, Enzymatic activity: In food matrices or certain supplement formulations, enzymes may alter selenium compounds, Microbial contamination: Can lead to degradation of selenium compounds, particularly in liquid formulations or foods

L-Selenocysteine is highly unstable in aqueous solution due to the reactive nature of the selenol group, which is readily oxidized to form selenocystine (the diselenide) and other oxidation products. In oxygenated solutions at physiological pH, the half-life of free selenocysteine can be as short as minutes to hours, depending on temperature, pH, and the presence of other compounds. For this reason, selenocysteine is not typically used in solution form for supplementation. Other selenium compounds used in supplements show varying stability in solution: Inorganic forms like selenite and selenate are generally more stable in solution than organic forms, though they may interact with other components in the solution.

Selenomethionine shows moderate stability in solution but can gradually oxidize over time. The stability of all selenium compounds in solution is enhanced under acidic conditions and reduced under alkaline conditions. The presence of reducing agents like ascorbic acid can affect the stability of selenium compounds in solution by altering their oxidation state. For liquid selenium supplements, manufacturers typically use various stabilizers, pH adjusters, and preservatives to extend shelf life, though specific formulation details are often proprietary.

Once prepared, solutions containing selenium compounds should ideally be used promptly or stored according to manufacturer recommendations, typically in airtight containers protected from light and heat. In biological systems, selenocysteine is stabilized by its incorporation into the peptide chain of selenoproteins and by the local protein environment, which protects the reactive selenol group from premature oxidation.

Natural Sources

Synthetic Production Methods

Quality Indicators

Sustainability Considerations

L-Selenocysteine itself was not specifically identified or utilized in traditional medicine systems, as its discovery and characterization occurred only in the modern scientific era. However, selenium-rich foods and remedies containing selenium have been used traditionally in various cultures, often without knowledge of the specific active compounds involved. In traditional Chinese medicine, certain herbs grown in selenium-rich regions were valued for their health-promoting properties, particularly for conditions that we now recognize might be related to oxidative stress or immune function. These include Astragalus membranaceus and certain medicinal mushrooms that can accumulate selenium from the soil.

In parts of Europe with selenium-rich soil, certain plants were traditionally used for their medicinal properties, though the connection to selenium content was not understood at the time. Some Native American tribes living in the Great Plains region, where soil selenium levels are naturally high, incorporated selenium-accumulating plants into their traditional medicines, particularly for skin conditions and wound healing. In regions of China with endemic selenium deficiency (Keshan disease areas), there are historical records of people traveling to trade for foods from other regions, which may have been an inadvertent way of obtaining selenium. While these traditional applications did not specifically target selenocysteine or selenoproteins, they represent historical recognition of the health benefits of selenium-containing foods and medicines, which we now understand work in part through selenocysteine incorporation into functional selenoproteins.

The discovery and characterization of L-selenocysteine represents a fascinating chapter in biochemistry that challenged conventional understanding of protein synthesis. Selenium was discovered as an element in 1817 by Jöns Jacob Berzelius, but its biological importance wasn’t recognized until much later. In the 1950s, selenium was identified as an essential trace element for mammals, primarily through the work of Klaus Schwarz and Calvin Foltz, who demonstrated that selenium could prevent liver necrosis in vitamin E-deficient rats. The first selenoprotein, glutathione peroxidase, was discovered in 1973 by Rotruck and colleagues, who demonstrated that selenium was an essential component of this antioxidant enzyme.

However, the exact form of selenium in the enzyme was not immediately clear. The breakthrough in understanding selenocysteine came in the 1980s through the work of several research groups. In 1984, Thressa Stadtman and her colleagues at the NIH determined that the selenium in certain bacterial enzymes was present as selenocysteine, not merely bound to the protein but actually incorporated into the peptide chain. This was a revolutionary finding, as it suggested a novel amino acid beyond the canonical 20 amino acids.

The genetic code for selenocysteine incorporation was elucidated in the late 1980s, revealing that the UGA codon, typically a stop codon, could be recoded to specify selenocysteine when a specific RNA structure (later named the Selenocysteine Insertion Sequence or SECIS element) was present. This discovery established selenocysteine as the ’21st amino acid’ and revealed a previously unknown expansion of the genetic code. In 1991, the complete pathway for selenocysteine biosynthesis and incorporation was described, showing that selenocysteine is not directly incorporated from free selenocysteine but is synthesized on its specific tRNA through a series of enzymatic reactions starting with serine. The human selenoproteome, consisting of 25 selenoproteins, was fully characterized in the early 2000s through genomic approaches, revealing the diverse roles of selenocysteine-containing proteins in human health.

The understanding and application of selenocysteine and selenium in health has evolved significantly over the past several decades. In the 1960s and 1970s, following the recognition of selenium as an essential nutrient, selenium supplementation was primarily focused on preventing overt deficiency conditions like Keshan disease (a cardiomyopathy) in selenium-deficient regions. The discovery of selenoproteins, particularly glutathione peroxidase, in the 1970s shifted the focus toward selenium’s antioxidant functions and its potential role in preventing conditions associated with oxidative stress. The 1980s and 1990s saw increased research on selenium’s role in cancer prevention, sparked by promising epidemiological studies and the discovery of additional selenoproteins involved in redox regulation.

This led to large-scale clinical trials like the Nutritional Prevention of Cancer (NPC) trial and later the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The identification of the complete selenoprotein synthesis pathway and the human selenoproteome in the 1990s and early 2000s expanded the understanding of selenium’s biological roles beyond simple antioxidant functions to include thyroid hormone metabolism, immune function, and various aspects of cellular signaling. This broader understanding led to more targeted applications of selenium supplementation for specific health conditions. Recent decades have seen a more nuanced approach to selenium supplementation, recognizing the importance of baseline selenium status, genetic variations affecting selenoprotein function, and the potential for both beneficial and harmful effects depending on dosage and individual factors.

The concept of an optimal selenium intake range, rather than simply preventing deficiency or maximizing intake, has become central to recommendations. Current research focuses on personalized approaches to selenium supplementation based on individual selenoprotein genotypes, specific health conditions affecting selenium metabolism, and interactions with environmental factors like heavy metal exposure. There is also growing interest in developing selenium compounds with targeted effects on specific selenoproteins or cellular pathways, moving beyond simple selenium supplementation toward more sophisticated interventions based on selenoprotein biology.

Selenium Supplementation and Prostate Cancer Prevention (SELECT) Follow-up Study – Long-term follow-up of participants from the original SELECT trial to assess late effects of selenium supplementation on prostate cancer risk, Selenium and Vitamin E for Chemoprevention of Colorectal Adenomas – Investigating whether selenium and vitamin E supplementation can prevent colorectal adenoma recurrence, Selenium Supplementation in Patients with Autoimmune Thyroiditis – Evaluating the effects of different selenium dosages on thyroid antibody levels and quality of life, Selenium Supplementation in Critical Illness – Assessing the impact of high-dose selenium on outcomes in critically ill patients with systemic inflammatory response syndrome, Selenium and Cognitive Function in the Elderly – Investigating whether selenium supplementation can slow cognitive decline in older adults with low selenium status, Selenium Supplementation in HIV-Positive Patients on Antiretroviral Therapy – Evaluating the effects of selenium on immune recovery and viral suppression in the context of modern antiretroviral therapy