Introduction
- Selenium is a vital trace element nutrient with multiple roles in the growth and functioning of living cells in higher animals and humans. This element is unevenly distributed in the earth’s crust. Almost all of the selenium in animal tissue is found in the proteins. Some of these proteins contain stoichiometric quantities of selenium and are known as selenoproteins. Other proteins contain variable amounts of selenium (which substitutes sulfur randomly in the original protein) and are known as selenium-binding proteins
- The selenoproteins in animal tissues are enzymes that control oxidation-reduction processes. At the molecular level, selenium (as selenocysteine) is an essential component of the active sites of the enzymes glutathione peroxidase, iodothyronine 5′-deiodinase and mammalian thioredoxin reductase, and is also present in several other mammalian selenoproteins. Both glutathione peroxidase and thioredoxin reductase catalyze reactions essential to the protection of cellular components against oxidative and free radical damage. Glutathione peroxidase protects cell membranes from oxidative damage by hydrogen peroxide and a variety of hydroperoxides and supplements the protective action of the antioxidant enzyme superoxide dismutase in quenching free oxygen radicals. Selenium is molecularly integrated at the active sites of these enzymes and it was found that replacing the selenium with sulfur caused marked reduction in the activity of these enzymes
- The primary nutritional source is the soil from which it is absorbed by plants and enters the food chain. Geographical variations in the selenium status of populations therefore exist, necessitating selenium supplementation. The recommended levels for selenium supplementation in humans are 50-200 mcg/day. The recommended daily dietary allowance for selenium is 55 mcg. This recommendation also suggests that intake of selenium from all sources should not exceed 400 mcg
- Recent research including laboratory studies, clinical evaluations, and observational data highlights selenium’s important role in supporting overall health. Selenium is recognized for its involvement in the body’s antioxidant enzyme systems, which help protect cells from oxidative stress. Adequate selenium levels have been associated with support for healthy immune function, cardiovascular wellness, normal inflammatory responses, and general cellular health. These findings underscore the importance of selenium as a key nutrient in maintaining long-term well-being.
- Historically, Selenomethionine was definitely identified in plant proteins in the 1950s-1960s. It was also demonstrated that the compound could be produced by yeast, E.coli, rumen bacteria and algae grown in selenium-enriched media. The isotope Selenomethionine was used as a pancreatic radioimaging agent. The use of Selenomethionine as a nutritional supplement was established in the 1970s when researchers determined in metabolic studies that the compound is well absorbed and retained in the body. Concurrently, selenium yeast was introduced as a food source of Selenomethionine. In 1984, L-(+)-Selenomethionine was produced and considered to be comparable to selenium yeast as a source of selenium
- Plants absorbing selenium from the soil usually convert it to the organic forms. Selenium is present as selenomethionine in wheat and other cereals. Selenomethionine therefore represents the major food form of selenium. If ingested in this form, selenium substitutes sulfur in the body proteins in animals and humans. Selenomethionine is thus the predominant storage form of selenium and can be considered as an essential amino acid – as with methionine, selenomethionine cannot be efficiently synthesized by humans and monogastric animals. As in the case of amino acids, natural materials contain Selenomethionine in the L-(+) form. The significance of this fact in selenium supplementation, will be explored in a later section
The biological significance of chirality in Selenomethionine
- In general, the transport of a drug or nutritional compound from the site of administration to the target tissue or organ depends upon the properties and structure of the drug or nutrient molecule. Biologically active agents are known to have discriminatory capacity with regard to their molecular sites of action. Both the sugars and the amino acids have mirror image isomers. Humans can use only one set of these isomers. The preference is based on the enzymatic reactions that are essential to the functions of a living cell. While D-sugars and L-amino acids can bind to the active sites of these enzymes, their mirror images cannot. Thus enzymes are stereoselective.
- The form of selenomethionine that the body can use is L-(+)-Selenomethionine. L-(+)-Selenomethionine is better absorbed and better incorporated into body components than any other known form of selenium. This may be understood by the fact that selenomethionine is incorporated into the body proteins including the antioxidant enzymes.
- In the formation of a protein molecule such as an enzyme, amino acids bond to form chains of peptides. A protein may consist of one or more polypeptide chain twisted, wound and folded into an unique 3D macromolecule. This is known as the native conformation of the protein, that determines its function and activity. In most cases the function of a protein relies on binding or recognizing or interacting with another molecule (enzyme-substrate, antibody-antigen (foreign material), hormone-receptor). It is the unique conformation of the protein that results in this specificity of function
- Primary level structure relates to the sequence of amino acids in the polypeptide chain. Secondary level structure looks at the initial folding and stabilization of the polypeptide chain and assumes several forms such as an alpha-helix, beta-pleated sheet or a random coil, through hydrogen bonding or ionic/electrostatic interactions. Tertiary structure relates to the further stabilization of the conformation by the bonding between the variable side chains of the amino acids in the polypeptide chain. Hydrogen bonds, ionic bonds and hydrophobic interactions may form weak interactions which help to maintain the conformation. Additionally disulfide bridges may form strong covalent bonds between adjacent -SH groups (as from reduced cysteine viz., cystine). Large numbers of amino acids are folded into distinct regions called domains that are responsible for specific functions of the proteins
- Quaternary structure is the formation of proteins from multiple polypeptide chains or subunits. Some proteins consist of two or more polypeptide chains. Each polypeptide chain is called a subunit and the quarternary structure is the relationship between the subunits, held together by hydrogen bonds, ionic bonds, hydrophobic interactions and disulfide bridges
- Thus the protein molecule has a three-dimensional structure. It is evident that the configuration of Selenomethionine would be important in determining its incorporation into this structure
Research from the University of Edinburgh suggests that adequate selenium levels may support the skin’s natural defenses against UV-related oxidative stress
New role for selenium
- “New research from the University of Edinburgh suggests that adequate selenium intake may help support the skin’s natural defenses against UV-induced oxidative stress.”
- Recent news and analyses highlight growing scientific interest in selenium, including reviews on functional nutrition, studies exploring its potential to support prostate and bladder health, and research identifying seafood as a naturally rich dietary source. Additional reports examine new insights into selenium’s biological activity and note that many British consumers may not be getting adequate selenium in their diets.
- Human skin cell studies suggest that adequate selenium levels may help reduce oxidative stress, a factor associated with unwanted cellular changes and imbalance.
- Selenium is an antioxidant, but many nutritionists believe that the average British diet contains less than the ideal amount of this essential trace element, found in Brazil nuts, bread, fish, meat and eggs
- A study published in the Journal of Food Sciences and Agriculture last year confirmed that levels of selenium in British bread-making wheats are up to 50 times lower than their American and Canadian counterparts and levels of selenium in the blood of the British population has been dropping since the 1970s. This is when grain began to be sourced from EU countries where soil is depleted of selenium
- Dermatologist Roddie McKenzie, leading the Edinburgh team, has suggested that people should take selenium supplements as a preventative measure
- “According to Dr. McKenzie, the findings suggest that maintaining adequate selenium levels year-round may be beneficial as part of overall wellness practices, alongside common sun-protective measures such as using sunscreen. The researcher noted that observational studies have linked low selenium status with reduced immune function and other health concerns, indicating the importance of sufficient dietary intake for general well-being.”
- Selenium has been the subject of scientific review by regulatory and expert groups, including the UK Expert Group on Vitamins and Minerals. In the United States, the Food and Drug Administration has issued a qualified health claim acknowledging that some scientific evidence suggests selenium may play a supportive role in overall health. The FDA notes that this evidence remains limited and not conclusive, and any such claims must be accompanied by appropriate disclaimers.
- The new study findings are published this month in Clinical and Experimental Dermatology and the British Journal of Dermatology
Selenium and Prostate Cell Health: Emerging Scientific Findings
- 05/02/03 – Research indicates that dogs receiving selenium-supplemented diets showed improved markers of prostate cellular health, including lower levels of DNA damage, compared with those on unsupplemented diets.
- A study published in the Journal of the National Cancer Institute reported that selenium supplementation was associated with reduced cellular changes linked to prostate health, suggesting a potential protective role for maintaining normal prostate function.
- David J. Waters, of Purdue University in West Lafayette, Indiana, and his colleagues randomly assigned 49 elderly male dogs to a normal diet or one of four diets supplemented with different amounts of selenium
- After seven months, dogs receiving selenium-supplemented diets showed lower levels of DNA damage in prostate tissue compared with those on a standard diet. The supplemented group also demonstrated a higher number of prostate cells undergoing apoptosis, a natural cellular process that helps the body remove damaged cells and maintain normal tissue health.
- The authors conclude that “selenium may benefit the aging prostate by decreasing the accumulation of DNA damage in epithelial cells even before these cells show cytotoxic
changes suggestive of malignancy” - The researchers noted that selenium was associated with helping maintain healthy cellular function in the prostate, including supporting the body’s natural defenses against oxidative stress and DNA damage. These findings relate to cellular health and do not establish any disease-related effects.
- Glucose regulation was assessed by standard intravenous glucose tolerance tests after an overnight fast. Memory was assessed by a series of tests in which patients were asked to recall paragraphs and, overall cognitive function was measured on a test called the Mini Mental Status Examination (MMSE)
- The researchers demonstrated that poorer glucose regulation was associated with lower memory performance and smaller hippocampal volumes, which were adjusted for head size. These results were independent of age or overall cognitive performance, meaning that these variables did not affect the results, and suggest that delivery of glucose may influence hippocampal structure and function. Dr Convit stressed however that the observations needed to be confirmed by other investigators
- He said: “If our results are confirmed then they may have significant treatment implications given that diabetes and obesity are reaching epidemic proportions in the United States and there are a large number of middle aged and elderly individuals with impaired glucose metabolism and memory dysfunction.”
- The study was supported by grants from the National Institutes of Health/National Institute on Aging and the General Clinical Research Center (GCRC) at the NYU School of Medicine.
- Related news analyses
Recently published on the site
-Seafood as a Source of Selenium
-Research Explores Selenium’s Role in Cellular Health
-Are British Consumers Meeting Selenium Intake Recommendations?
-Daily Supplements and Ear Wellness: Review of Emerging Research
-Rice Bran–Based Probiotics and Gastrointestinal Support
Source: Proceedings of the Nationa! Academy of Science
Research Explores Potential Link Between Selenium Status and Esophageal Health
- 21/05/03 – A new study reports that higher selenium status may be associated with slower progression of Barrett’s oesophagus, a condition that can precede esophageal cancer.
- Researchers in the US observed an association between lower blood selenium levels and a higher likelihood of progressing to more advanced cellular changes in individuals with Barrett’s oesophagus. These findings do not establish causation but highlight the importance of maintaining adequate selenium status as part of overall nutritional health.
- A research team from the Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine evaluated how blood selenium levels relate to changes in oesophageal tissue that reflect more advanced stages of cellular alteration. The findings describe an association and do not establish that selenium prevents or treats any disease.
- However, the researchers emphasized that higher intakes of selenium do not equate to better outcomes. They noted that, based on laboratory findings, excessive selenium intake may have adverse effects, and very high doses could be unsafe. Therefore, using extremely high or “mega-dose” levels of selenium supplements is not recommended. These findings describe associations only and do not imply that selenium prevents or treats Barrett’s oesophagus or any other disease.
- Related News & Analyses Recently published on the site
– New role for selenium
– High doses of vitamins are dangerous. UK report
– A functional team
-Selenium supplements and prostate health research
-Selenium and bladder health findings
-Scientific insights into selenium’s actions at the cellular level - The US recommended dietary allowance for selenium is 55 micrograms (mcg) for adults, while the UK’s Expert group on Vitamins and Minerals recently recommended no more than 0.35mg in daily supplement intake. The average multivitamin is thought to contain up to 20 mcg. Fish, meat and nuts are also good sources, while bread tends to have much less in Europe than in the US, due to lower levels of the mineral in the soil
- Research in humans has explored the potential role of selenium in supporting overall cellular health, including studies investigating its impact on various types of cancer. Some clinical trials have reported associations between selenium intake and reduced risk or mortality in certain cancers, such as prostate and colorectal, and emerging findings have examined its role in skin health. Selenium is believed to help maintain normal cellular function by supporting antioxidant activity, aiding in the protection of cells from oxidative stress, and assisting natural processes such as healthy cell turnover. While these findings are encouraging, they are not conclusive, and selenium should not be interpreted as a treatment or cure for any disease. Further research is needed to fully understand its role in human health.
- In the study, researchers analyzed data from individuals with Barrett’s oesophagus and observed that participants with higher circulating selenium levels were less likely to exhibit certain biological markers associated with progression toward more advanced cellular changes compared to those with lower selenium levels.
- Individuals with higher selenium levels were observed to have fewer indicators of advanced cellular changes. These included markers such as dysplasia (abnormalities in cell size, shape, or growth pattern), loss of heterozygosity at 17p (a partial loss of chromosome 17 that can affect normal cell-regulation pathways), aneuploidy (cells with abnormal amounts of DNA, reflecting significant genetic imbalance), and an increased 4N fraction (a higher number of cells with twice the typical chromosome content, which may suggest irregularities in cell division). While these findings highlight associations seen in research settings, additional studies are needed to further clarify selenium’s role in supporting overall cellular health.
- Research findings indicated that individuals with higher circulating selenium levels showed a lower likelihood of certain cellular changes. In particular, higher selenium status was associated with reduced incidence of markers such as aneuploidy, cellular dysplasia, and loss of the p53 gene. These observations highlight a scientific association, though additional research is needed to better understand selenium’s role in supporting normal cellular processes.
- Selenium appeared to have the greatest effect on markers associated with advanced progression of Barrett’s, which suggests that the nutrient might be most beneficial for people with later-stage disease, they reported
- According to the researchers, blood selenium levels were not linked with the earliest biological markers of Barrett’s progression. However, individuals with selenium levels in the middle or upper end of the normal range were observed to have fewer advanced precancerous changes compared with those with lower selenium levels. These findings reflect an association, and additional studies are needed to clarify selenium’s role in supporting overall cellular health.
- Rudolph and colleagues noted that selenium may help support healthy cellular processes by maintaining the activity of proteins involved in normal cell regulation, including the p53 tumor-suppressor pathway. Their observations suggest that adequate selenium status may play a role in supporting the body’s natural defenses against further cellular changes. These findings are based on associations, and additional research is needed to clarify selenium’s specific role in this area.
- While the results are promising, more research is needed, Rudolph said. A limitation of the study is its cross-sectional design; the analysis was based on data collected from Barrett’s patients at a single point in time, representing an isolated snapshot of biological activity
- Rudolph noted that continued follow-up of participants over time will help clarify how selenium and other dietary factors relate to precancerous progression. She added that, if future longitudinal studies and randomized controlled trials confirm these findings, the potential public-health implications could be meaningful.
Fast facts – Selenium study
- Lead investigators: Dr. Scott Lippman, MD Anderson Cancer Center and Dr. Charles Coltman, Jr., Chairman, Southwest Oncology Group (SWOG)
- Subjects: US multi-center population of 32,000 men with an average age of 55 years old. The confirmatory trial will involve 5 years, with active intervention lasting between 7 – 12 years, with an average of 8 – 9 years. Recruitment began in January, 2001
- Dosages: The study will consist of four groups of equal size, with one group receiving 200 ug per day elemental Selenium alone, another 400 mg per day vitamin E alone, the third both Selenium and Vitamin E and the fourth an identical looking placebo
L–, D- and DL forms of Selenomethionine – A brief explanation
A molecular model for Selenomethionine is shown below:
L-(+)-Selenomethionine
From above structure, that the Carbon atom indicated is attached to four different chemical groups and is “asymmetric”. The molecule, therefore, has one chiral center at this point and exhibits “chirality”.
Chirality
- Chiral compounds are chemical compounds that exist in two forms (enantiomers) that are non-superimposable mirror images of each other, and so are asymmetrical. The word “Chiral” comes from a Greek word meaning hand, applied here because our hands are mirror images of one another
- Chiral center (asymmetric atom, stereocenter): Appears in compounds that lack reflection symmetry. For organic compounds, the presence of four different moieties about a central carbon atom, constitutes the chiral center
- Enantiomers: Non-superimposable mirror images that must contain a chiral center
- Racemic Mixture (Racemate): A 1:1 mixture of enantiomers
- The Selenomethionine molecule has one chiral center, similar to amino acids such as methionine. Because one carbon atom is asymmetric, Selenomethionine can occur as two optical isomers (enantiomers). These isomers rotate the plane of polarization of plane-polarized light in opposite directions
- Optical activity (quantified by the rotation of the plane of polarized light as it passes through a substance) was measured long before the three dimensional structure of molecules could be determined by methods such as X-ray Crystallography. Based on experimental results for the direction of rotation of plane-polarized light, optical activity was then symbolized with the letter “d” or the “+” sign (for dextrorotatory, right handed or clockwise rotation of the plane of polarized light when viewed toward the light source) and “l” or “-” (for levorotatory, left hand or counterclockwise rotation)
- Later the “D” and “L” symbols were associated with absolute configuration based on the arbitrary, but correct assignment of the absolute configuration of the dextrorotatory and levorotatory forms of glyceraldehyde. Here, absolute configuration is based on chemical synthesis with glyceraldehyde as the starting material and optical activity is specified using the “+” and “-” notation. Thus L-Selenomethionine is dextrorotatory (+) and D-Selenomethionine is levorotatory (-). L -amino acids are found in naturally produced proteins. D and L amino acids as well as the racemic DL- mixture can be synthetically produced.
Enantiomers of Selenomethionine
Selenium supplementation
- Adequate selenium intake plays an important role in supporting normal immune function, particularly the body’s cell-mediated immune responses. Research indicates that selenium works together with vitamin E to help protect immune cells from oxidative stress. Because selenium levels in soil vary widely around the world, certain regions have historically shown lower dietary selenium intake. In these areas, low selenium status has been associated with various health challenges observed in both humans and animals. Infants may be especially sensitive to inadequate intake due to higher biological demands. Since the total selenium content of a food does not always reflect how well the body can use it, supplemental selenium is often provided in forms known for better bioavailability to help support overall health and normal physiological function.
- The inorganic salts and chelates are not normal dietary forms of selenium. Selenium derived from selenite and selenate cannot be stored in significant amounts in the body proteins. These compounds also failed to raise blood
- Selenium levels in human subjects. Sodium selenite is chemically unstable and is degraded to elemental selenium by ascorbic acid. It is important to note that elemental selenium is not bioavailable and may have toxic effects at levels only four to five times the amounts normally ingested in the human diet. Sodium selenate is almost completely absorbed, but a significant fraction is lost in the urine before it can be incorporated into the body tissues
- L-(+)-Selenomethionine is a form of selenium in which the mineral is naturally integrated into the amino acid structure, allowing it to be incorporated into proteins in place of methionine without altering normal protein function. Studies suggest that when selenium occupies this position, it may help support the body’s natural defenses against oxidative stress, including the protection of DNA. Because the carbon-selenium bond is more readily broken during photochemical reactions than the carbon–sulfur bond in methionine, L-(+)-Selenomethionine can preferentially absorb excess energy from light. This characteristic has been explored for its potential to help support the skin’s ability to manage environmental stressors, including exposure to ultraviolet light.
- Research indicates that supplementation with L-(+)-Selenomethionine, including forms derived from selenium-enriched yeast, can effectively raise selenium levels in the body. In one study, selenium levels in red blood cells increased significantly—approximately doubling—after 16 weeks of supplementation, while inorganic forms such as selenite and selenate did not produce comparable changes. Because L-(+)-Selenomethionine is efficiently incorporated into proteins, it is widely recognized as a highly bioavailable and well-tolerated form of selenium for use in nutritional supplements and functional foods, including those designed for sensitive populations. Selenium-enriched yeast containing L-(+)-Selenomethionine has also been studied for its potential role in supporting overall cellular health. Together, these findings support the use of L-(+)-Selenomethionine as a preferred form of selenium supplementation.
- In the preparation of selenium yeast, Saccharomyces species are grown on selenium-enriched media, so that their protein contains selenomethionine and 90+% of the total selenium is in the form of L-(+)-Selenomethionine. Saccharomyces cerevisiae may accumulate up to 3000 mcg/g selenium
Metabolism of L-(+)- Selenomethionine
- More than 90% of L-(+)-Selenomethionine which is the major dietary form of selenium, is absorbed by a mechanism similar to that for the essential amino acid, methionine. L-(+)-Selenomethionine has the sulfur atom in L-(+)-Methionine replaced by selenium. It is converted to selenocysteine in the body. Selenocysteine is then incorporated into selenoproteins. The sequence is schematically represented in the Figures and the metabolism of all forms of selenium supplementation is presented in Figure 3. However, if Selenomethionine is supplied in the form of pure selenomethionine or selenium yeast, it is important to ascertain that the selenium is present in the form of L-(+)-Selenomethionine. Good commercial samples of selenium yeast typically contain 1000-2000 ppm of selenium, most of which is in the form of L-(+)-Selenomethionine. However, some samples may contain substantial amounts of inorganic selenium compounds instead of L-(+)-Selenomethionine. Similarly, some commercial samples of “pure” Selenomethionine may actually be mixtures of inorganic selenium salts with methionine or could contain selenomethionine in the DL- or D- forms that do not provide efficient supplementation.