Absorption, Distribution and Excretion
Lambs were given a single oral dose of selenium, administered in the form of sodium selenite or selenomethionine, and monitored for 7 days before euthanasia and autopsy. Analysis of the liver, renal cortex, heart, blood, and serum showed a linear dose-dependent increase in selenium concentration. However, the tissue selenium concentration in lambs treated with selenomethionine was significantly higher than that in lambs treated with the same dose of sodium selenite. Selenylmethyl selenoamino acids, namely selenomethylcysteine (MeSeCys) and selenomethionine (SeMet), are chemically stable selenium storage forms in selenium-accumulating animals and are also a source of nutrition and supplementation. Male Wistar rats were depleted of their endogenous natural selenium abundance after treatment with a single Se enrichment isotope, 80Se. They were then orally administered 76Se-MeSeCys, 77Se-SeMet, and 82Se-selenite at doses of 25 μg Se/kg body weight. Organs and body fluids were collected at 3, 6, 9, and 12 hours post-administration, and on days 1 and 2, for morphological analysis. Key metabolic characteristics were as follows: MeSeCys incorporation into selenoprotein P was slightly higher than or comparable to that of SeMet, but lower than that of selenite. MeSeCys and SeMet were absorbed by organs in their intact form, while selenite was not absorbed. MeSeCys and SeMet were specifically delivered to the pancreas and existed in forms bound to the same or similar proteins. In the kidneys, trimethylselenoium (TMSe) is generated solely from MeSeCys, not from SeMet or selenite. MeSeCys, SeMet, and selenite-derived selenosaccharides A and B were detected in the liver, but only selenosaccharide B was detected in the kidneys… The endogenous natural abundance of selenium in rats was depleted by feeding them a single stable selenium isotope (Se-selenite), followed by simultaneous administration of Se-76-selenite and Se-selenomethionine (Se-SeMet). Quantitative and speciation analyses of the biological samples were performed using high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). The metabolites of labeled 76Se and 77Se and their interactions with endogenous selenium were tracked and studied without interference from the corresponding endogenous natural abundance isotopes. Under identical biological and analytical conditions, the distribution and metabolism of the two nutritional selenium compounds in different organs and body fluids were compared: (1) Selenite was distributed more efficiently than selenomethionine (SeMet) in all organs and body fluids except the pancreas. (2) SeMet was absorbed in its intact form by all organs. (3) SeMet-derived selenium was selectively distributed in the pancreas and primarily bound to proteins along with intact SeMet. (4) Selenose A and B were detected in the liver, but trimethylselenoselenium (TMSe) was not detected. (5) Selenose B and TMSe were detected in the kidneys. …Over 80% of orally administered selenomethionine… was absorbed by rats. For more complete data on the absorption, distribution, and excretion of selenomethionine (15 types), please visit the HSDB record page.

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Metabolism/Metabolites
Dietary selenium is primarily present as selenomethionine…or selenocysteine, both of which are readily absorbed. Other forms of selenium include selenates and selenites, which are not major dietary components but are commonly used in fortified foods and dietary supplements. There are two selenium reserves in the body. The first exists as selenomethionine, whose physiological function is currently unclear. The second selenium reserve is located in glutathione peroxidase in the liver. Ingested selenites, selenates, and selenocysteine can all be directly metabolized into selenides, the reduced form of selenium. Selenomethionine can also be metabolized into selenides. To obtain quantitative information on selenium metabolism in the human body, we performed high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC/ICPMS) analysis on selenium speciation in urine samples from a volunteer within 48 hours after ingestion of selenium (1.0 mg, in the form of sodium selenite, L-selenomethionine, or DL-selenomethionine). Three independent experiments were replicated. The total selenium concentration in the volunteer's normal background urine ranged from 8 to 30 μg Se/L (n=22), but only about 30-70% of the selenium could be quantified by HPLC/ICPMS. The main selenium compounds in the background urine were two selenosaccharides: methyl-2-acetamido-2-deoxy-1-seleno-β-D-galactopyranoside (selenosaccharide 1) and its deacylated analogue methyl-2-amino-2-deoxy-1-seleno-β-D-galactopyranoside (selenosaccharide 3). Following ingestion of selenium compounds, selenium is rapidly excreted from the body: peak concentrations (approximately 250-400 μg Se/L, standardized concentration) are reached within 5-9 hours and return to near-background levels within 48 hours. At this point, depending on the type of selenium compound ingested, 25-40% of the ingested selenium is excreted in the urine. In all experiments, the major metabolite was selenosyl 1 (SLE). Within 24 hours of ingestion of selenite or L-selenomethionine, SLE accounted for approximately 80% of total selenium excretion; after ingestion of DL-selenomethionine, SLE accounted for approximately 65%. No significant concentrations of selenite (<1 μg Se/L) were detected in any samples; after ingestion of L-selenomethionine, selenomethionine was present only in trace amounts (approximately 1 μg/L, equivalent to less than 0.5% of total selenium), but within 24 hours of ingestion of DL-selenomethionine, selenomethionine accounted for approximately 20% of total selenium excretion, possibly due to the low metabolic efficiency of D-selenomethionine. Trimethylselenodium ion is a common urinary metabolite, but it was not detected in urine samples (<1 μg/L) after ingestion of sodium selenite or selenomethionine. Cytotoxicity studies of selenosaccharide 1 and its glucosamine isomer (selenosaccharide 2, methyl-2-acetamido-2-deoxy-1-seleno-β-D-glucopyranoside) in the human hepatocellular carcinoma line HepG2 showed that both compounds had low toxicity (approximately 1000 times lower than sodium selenite). These results support previous research that selenosaccharide 1 is the major urinary metabolite after increased selenium intake and suggest that the previously accepted human selenium metabolism pathway with trimethylselenodium ion as the excretion end product may need to be reassessed. When selenium is ingested in selenomethionine or other naturally occurring organic forms in food, it is released as selenite through post-absorption catabolism. The main dietary source of selenium is selenomethionine. After ingestion in animals, selenomethionine enters the methionine pool and cannot be distinguished from methionine. Therefore, most of the selenium in animal tissues is selenomethionine, which is incorporated into the methionine sites of proteins in a non-specific manner. After the catabolism of selenomethionine, the selenium in it can be utilized by selenium metabolites.
For more complete data on the metabolism/metabolites of selenomethionine (a total of 6 metabolites), please visit the HSDB record page.

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Biological half-life
The long-term metabolism of (75)Se selenomethionine orally administered in 4 women has been studied. The intestinal absorption rate was 95-97%, the urinary excretion was 6-9% in the first 2 weeks, and after 8 weeks, the systemic retention of (75)Se decreased exponentially, with a half-life of 207-290 days. The study found that (75)Se selenomethionine was more completely absorbed, had a higher retention rate in vivo, and less (75)Se was excreted in urine and feces, while (75)Se was derived from (75)Se selenite. The half-life of selenomethionine is 234 days.

Interactions
In mice, concurrent subcutaneous injection of 10 μmol/kg selenomethionine reduced the lethal toxicity of mercuric chloride (20 μmol/kg, intraperitoneal injection). Male Wistar rats received two intraperitoneal injections (ip) of either methylmercury (MeHg) (1.5 mg/kg body weight), selenomethionine (SeMet) (1 mg/kg body weight), or a combination of MeHg and SeMet. Urine was collected afterward, and neurobehavioral tests were performed over a 3-week period. The effects of different administration regimens were investigated by quantifying total mercury levels in kidney and brain tissue, analyzing urinary porphyrins, measuring liver glutathione (GSH) levels, and assessing motor function (standing and walking). During the 3-week urine collection period, methylmercury (MeHg) exposure significantly increased urinary porphyrin levels, while a significant decrease in motor activity was observed only on the first day after cessation of exposure. Furthermore, co-exposure to selenomethionine (SeMet) restored porphyrin excretion to normal, and a trend toward recovery of kinetic activity was observed in rats on the first day after exposure cessation. Mercury levels in the brain and kidneys of rats exposed to MeHg were significantly elevated; however, mercury levels in rats co-exposed to SeMet did not change significantly compared to rats exposed to MeHg alone. Therefore, this study demonstrates that uroporphyrin is a sensitive and persistent indicator of MeHg toxicity and confirms that SeMet can reduce its production. Finally, these results confirm that the interaction mechanism between selenomethionine (SeMet) and methylmercury (MeHg) cannot be explained by a decrease in mercury (Hg) levels in target organs, and propose suggestions for elucidating the mechanism by which SeMet interferes with MeHg toxicity. In a 7,12-dimethylbenzanthracene (DMBA)-induced rat mammary tumor model, we examined the chemopreventive effects of selenate, selenite, selenium dioxide, selenomethionine, and selenocysteine during the carcinogenic promotion phase. Each reagent was added to the diet, with a final selenium concentration of 3 ppm. Overall, the five selenium compounds showed no significant difference in their efficacy in inhibiting breast tumor development. In another carcinogenicity study, we further investigated the interaction between vitamin E (500 ppm) and selenite or selenomethionine. Our results showed that vitamin E enhanced the protective effect of selenite but not that of selenomethionine. To explore the synergistic mechanism of selenium and vitamin E, this study also examined the effects of these two substances on mitogen-induced lymphoblast transformation and natural killer cytotoxic activity. The results indicated that hypertrophic levels of selenite, vitamin E, or both did not cause significant changes in these in vitro immune functions. ...
The objectives of this study were: a) to compare the efficacy of inorganic and organoselenium selenium compounds in preventing 7,12-dimethylbenzanthracene (DMBA)-induced breast tumor development in rats; and b) to investigate the interaction between vitamin C and selenite (inorganic selenium compound) or seleno-DL-methionine (organoselenium compound) in chemoprevention. Control group Sprague Dawley rats were fed a diet containing 0.1 ppm selenium in 5% purified corn oil. One week after DMBA administration, selenite or seleno-DL-methionine was added to the basal diet at concentrations of 2, 3, or 4 ppm. The inhibitory effect of selenium supplementation on mammary tumor development was dose-dependent. Both selenium compounds were comparable in efficacy for prevention, although a slight reduction in growth was observed at a concentration of 4 ppm. For more complete data on interactions of seleno-methionine (13 in total), please visit the HSDB record page. Non-human toxicity values: Rat intraperitoneal LD50: 11 mg/kg; Mouse intravenous LD50: 22 mg/kg; Mouse intracervical LD50: 13 mg/kg

Therapeutic Uses
Radioactive selenomethionine can be used as an adjunct to diagnosis (pancreatic function testing); a radioactive reagent. Available nutritional supplements include high-selenium yeast, L-selenomethionine, sodium selenate, and sodium selenite. L-Selenomethionine / Experimental Treatment / ... Squamous intraepithelial neoplasia is a recognized histological precursor of esophageal squamous cell carcinoma and a potentially modifiable intermediate endpoint in chemoprevention trials in high-risk populations. ... A randomized controlled trial conducted in residents of Linxian County, China, compared the effects of daily administration of 200 mcg selenomethionine and/or twice-daily administration of 200 mg celecoxib (2×2 factorial design). Subjects were histologically diagnosed with mild or moderate esophageal squamous intraepithelial neoplasia at baseline. All subjects underwent esophagogastric endoscopy before and after a 10-month intervention. The primary endpoint was defined as the change (regression, stabilization, or progression) in the degree of most severe dysplasia in each subject. Results were compared by drug group (selenomethionine vs. placebo; celecoxib vs. placebo). …A total of 267 subjects met all inclusion criteria, of whom 238 (89%) completed the trial. Overall, subjects treated with selenomethionine showed a trend toward increased dysplasia regression (43% vs. 32%) and decreased dysplasia progression (14% vs. 19%) compared with those not treated with selenomethionine (P = .08). In unplanned stratified analysis, selenomethionine had a positive effect on the dysplasia grade in 115 subjects with mild esophageal squamous dysplasia at baseline (P = 0.02), but no effect in 123 subjects with moderate esophageal squamous dysplasia at baseline (P = 1.00). Celecoxib status had no effect on changes in overall dysplasia grade (P = 0.78) or changes in baseline histological subgroups. …After 10 months of intervention, neither selenomethionine nor celecoxib inhibited esophageal squamous cell carcinoma in all high-risk subjects. However, selenomethionine did have a protective effect in subjects with mild esophageal squamous dysplasia at baseline…
/Experimental Treatment/…This study was conducted in nude mice carrying xenografts of human colorectal cancer SW480 cell line to evaluate the chemotherapeutic potential of selenium-containing compounds such as sodium selenite (SSe) and selenomethionine (SeMet). Three doses of anticancer drugs were used, including 0.1 mg/kg/day SSe (LSSe), 2 mg/kg/day SSe (HSSe), and 2 mg/kg/day SeMet…administered intraperitoneally for 21 days. …After HSSe and SeMet treatment, pathological changes and apoptosis in tumor tissues were observed by HE staining and TUNNEL assay. GSH levels and the activity of the antioxidant enzyme GPX in tumor tissues were assessed. Furthermore, the expression of apoptosis-related proteins was detected using Western blotting. Results showed that HSSe and SeMet significantly inhibited tumor growth in vivo. ...GSH levels were slightly increased, but GPX activity was decreased. In addition, SSe and SeMet treatment downregulated Bcl-xL protein expression, upregulated Bax, Bad, and Bim expression, and activated caspase-9. SSe and SeMet may be selective, low-toxicity anticancer drugs for the treatment of human colorectal cancer.
/Experimental Treatment/...Based on clinical findings and recent studies on selenoprotein gene-modified mice, the chemopreventive effect of selenium may be related to the antioxidant function of one or more selenoproteins. Furthermore, selenium upregulation of phase II enzyme expression is also considered a possible chemopreventive mechanism under supra-nutrition dietary levels. Selenomethionine (SeMSC) is a naturally occurring organic selenium product and is considered one of the most effective chemopreventive selenium compounds…

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Drug Warning
Selenomethionine (SeMet) can replace methionine (Met) and be integrated into human proteins, providing a pathway for the reversible storage of selenium in organs and tissues. No other naturally occurring selenoamino acid possesses this property, which may be related to the specific physiological functions of SeMet. Since higher animals cannot synthesize SeMet, but all essential forms of selenium are produced from it, SeMet meets the criteria for essential amino acids. Therefore, SeMet or food sources rich in SeMet are suitable forms of selenium supplementation for humans. However, although selenomethionine (SeMet) or selenium yeast is widely used in over-the-counter nutritional supplements, selenium is still present in infant formula and parenteral nutrition blends in the form of sodium selenate or sodium selenite, even though these are not the normal nutritional forms of selenium. In animal nutrition, these inorganic selenium salts are increasingly being replaced by food sources of selenomethionine, such as selenium yeast. Synthetic selenomethionine can also be used as a feed additive, but its regulatory status is yet to be determined. The optimal selenomethionine nutritional level for different animal species still needs to be determined. It is expected that adding an equal amount of selenomethionine to feed would achieve the same adequacy level as the currently approved maximum addition level for inorganic selenium salts.
SELECT stands for the Selenium and Vitamin E Cancer Prevention Trial, a clinical trial designed to investigate whether taking selenium, vitamin E, or both as dietary supplements could prevent prostate cancer. …Recruitment for the trial began in 2001 and ended in 2004. More than 400 research centers in the United States, Puerto Rico, and Canada participated in the study. More than 35,000 men participated in the SELECT trial. The initial planned follow-up period for the SELECT trial was at least 7 years and a maximum of 12 years. However, the trial's independent Data and Safety Monitoring Committee (DSMC) met on September 15, 2008, to review the SELECT study data and found that neither taking selenium alone nor in combination with vitamin E could prevent prostate cancer. They also concluded that selenium and vitamin E supplementation was unlikely to reduce the incidence of prostate cancer by 25%, as the study aimed to demonstrate. Therefore, participants in the SELECT trial were advised to stop taking the study supplement in October 2008. Although there was no statistically significant difference in the incidence of prostate cancer among the four groups in the trial (in other words, these differences may be purely coincidental), there were more cases in men taking only vitamin E. This difference does not prove that vitamin E causes prostate cancer and may simply be a coincidence. …Total deaths, or the overall incidence of cardiovascular events in each study group. According to data reported at the start of the trial, men taking only selenium (10% of these men) had more new cases of diabetes than men taking a placebo (9.3%). This finding was not statistically significant and does not prove that selenium increases the risk; it may simply be a coincidence. /Selenium-containing preparations/
The most common adverse reaction to selenium poisoning or chronic selenium poisoning is brittle and easily broken hair and nails, even loss. Other symptoms include rash, halitosis (similar to garlic odor), fatigue, irritability, and nausea and vomiting. Selenium-containing preparations
Adverse reactions are unlikely to occur in adults with a daily selenium intake of less than 900 micrograms. Long-term daily intake of 1000 micrograms (or 1 milligram) or more of selenium may cause adverse reactions. Selenium-containing supplements. Pregnant and lactating women should avoid exceeding the recommended dietary intake of selenium. Selenium-containing supplements.

C5H11NO2SE

196.1063

196.995

1464-42-2

L-SelenoMethionine;3211-76-5

15103

White to off-white solid powder

320.8±37.0 °C at 760 mmHg

267-269ºC

147.8±26.5 °C

0.0±1.5 mmHg at 25°C

-0.65

2

3

4

9

97

0

RJFAYQIBOAGBLC-UHFFFAOYSA-N

InChI=1S/C5H11NO2Se/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)

2-amino-4-methylselanylbutanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~12.5 mg/mL (~63.74 mM)

Solubility in Formulation 1: 10 mg/mL (50.99 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)