Absorption, Distribution and Excretion
... Lambs were orally administered a single dose of selenium as either sodium selenite or selenomethionine and were monitored for 7 days, after which they were euthanized and necropsied. ... Analysis of liver, kidney cortex, heart, blood, and serum revealed linear, dose-dependent increases in selenium concentration. However, tissue selenium concentration in selenomethionine-treated lambs were significantly greater than that in lambs treated with equivalent doses of sodium selenite.
Se-Methylated selenoamino acids, Se-methylselenocysteine (MeSeCys) and selenomethionine (SeMet), are chemically inert storage forms of selenium in selenium-accumulators, and a nutritional and supplemental source. ... Male Wistar rats were depleted of endogenous natural abundance selenium with a single (80)Se-enriched isotope, and then (76)Se-MeSeCys, (77)Se-SeMet and (82)Se-selenite were orally administered simultaneously at 25 ug Se/kg body weight each. Organs and body fluids were obtained at 3, 6, 9 and 12 hr, and 1 and 2 days later, and subjected to speciation analysis. The main characteristics of the metabolism were as follows; MeSeCys was incorporated into selenoprotein P slightly more than or at a comparable level to that of SeMet but less than that of selenite. MeSeCys and SeMet but not selenite was taken up by organs in their intact forms. MeSeCys and SeMet were delivered specifically to the pancreas and present in a form bound to an identical or similar protein. Trimethylselenonium (TMSe) was only produced from MeSeCys, i.e., not from SeMet or selenite, in the kidneys. Both selenosugars A and B of MeSeCys, SeMet and selenite origin were detected in the liver but only selenosugar B in the kidneys...
... Rats were depleted of endogenous natural abundance selenium by feeding a single selenium stable isotope ((82)Se-selenite) and then administered (76)Se-selenite and (77)Se-selenomethionine ((77)Se-SeMet)simultaneously. Biological samples were subjected to quantification and speciation analysis by HPLC-ICPMS. Metabolites of the labeled (76)Se and (77)Se and interaction with endogenous selenium were traced and examined without interference from the corresponding endogenous natural abundance isotopes. Differences in the distribution and metabolism among organs and between the two nutritional selenocompounds were compared under exactly identical biological and analytical conditions: (1) selenite was distributed more efficiently than SeMet in organs and body fluids except the pancreas. (2) SeMet was taken up by organs in its intact form. (3) Selenium of SeMet origin was distributed selectively in the pancreas and mostly bound to a protein together with intact SeMet. (4) Selenosugars A and B but not trimethylselenonium (TMSe) were detected in the liver. (5) Selenosugar B and TMSe were detected in the kidneys.
... More than 80% of orally administered selenomethionine ... is absorbed by rats.
For more Absorption, Distribution and Excretion (Complete) data for SELENIUM METHIONINE (15 total), please visit the HSDB record page.

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Metabolism / Metabolites
Most dietary selenium is in the form of selenomethionine ... or selenocysteine, both of which are well absorbed. Other forms of selenium include selenate and selenite, which are not major dietary constituents, but are commonly used in fortified foods and dietary supplements. Two pools of reserve selenium are present in the body. The first is as selenomethionine, which is not known to have a physiological function separate from that of methionine. The second reserve pool is the selenium found in liver glutathione peroxidase. Ingested selenite, selenate, and selenocysteine are all metabolized directly to selenide, the reduced form of selenium. Selenomethionine can also be metabolized to selenide.
To obtain quantitative information on human metabolism of selenium, ... selenium speciation analysis /was performed/ by HPLC/ICPMS on samples of human urine from one volunteer over a 48-hour period after ingestion of selenium (1.0 mg) as sodium selenite, L-selenomethionine, or DL-selenomethionine. The three separate experiments were performed in duplicate. Normal background urine from the volunteer contained total selenium concentrations of 8-30 ug Se/L (n=22) but ... only about 30-70% could be quantified by HPLC/ICPMS. The major species in background urine were two selenosugars, namely methyl-2-acetamido-2-deoxy-1-seleno-beta-D-galactopyranoside (selenosugar 1) and its deacylated analog methyl-2-amino-2-deoxy-1-seleno-beta-D-galactopyranoside (selenosugar 3). Selenium was rapidly excreted after ingestion of the selenium compounds: the peak concentrations (approximately 250-400 ug Se/L, normalized concentrations) were recorded within 5-9 hours, and concentrations had returned to close to background levels within 48 hours, by which time 25-40% of the ingested selenium, depending on the species ingested, had been accounted for in the urine. In all experiments, the major metabolite was selenosugar 1, constituting either approximately 80% of the total selenium excreted over the first 24 hours after ingestion of selenite or L-selenomethionine or approximately 65% after ingestion of DL-selenomethionine. Selenite was not present at significant levels (<1 ug Se/L) in any of the samples; selenomethionine was present in only trace amounts (approximately 1 ug/L, equivalent to less than 0.5% of the total Se) following ingestion of L-selenomethionine, but it constituted about 20% of the excreted selenium (first 24 hours) after ingestion of DL-selenomethionine, presumably because the D form was not efficiently metabolized. Trimethylselenonium ion, a commonly reported urine metabolite, could not be detected (<1 ug/L) in the urine samples after ingestion of selenite or selenomethionine. Cytotoxicity studies on selenosugar 1 and its glucosamine isomer (selenosugar 2, methyl-2-acetamido-2-deoxy-1-seleno-beta-D-glucosopyranoside) were performed with HepG2 cells derived from human hepatocarcinoma, and these showed that both compounds had low toxicity (about 1000-fold less toxic than sodium selenite). The results support earlier studies showing that selenosugar 1 is the major urinary metabolite after increased selenium intake, and they suggest that previously accepted pathways for human metabolism of selenium involving trimethylselenonium ion as the excretionary end product may need to be re-evaluated.
When selenium is consumed as selenomethionine or other organic forms that occur naturally in foods, it is released as selenite by postabsorptive catabolism.
A major source of selenium in the diet is selenomethionine. Once ingested by an animal, it enters the methionine pool and is not distinguished from methionine. Thus, much of the selenium in animal tissues is selenomethionine that is non-specifically incorporated in proteins at methionine positions. When selenomethionine is catabolized, its selenium becomes available to the selenium metabolic.
For more Metabolism/Metabolites (Complete) data for SELENIUM METHIONINE (6 total), please visit the HSDB record page.

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Biological Half-Life
The long term fate of an oral dose of (75)Se selenomethionine has been studied in 4 women. Intestinal absorption amounted to 95-97% of the dose, the first 2-wk urinary excretion accounted for 6-9% & after 8 wk, the whole body retention of (75)Se decreased exponentially with a half life of 207-290 days. ... (75)Se selenomethionine was found to be more completely absorbed and had a greater body retention of (75)Se with smaller urinary and fecal losses than (75)Se from (75)Se selenite.
The half life of selenium methionine is 234 days.

Interactions
Lethal toxicity of mercury chloride (20 umol/kg ip) was lowered in rats by concomitant sc injection of 10 umol/kg selenomethionine.
Male Wistar rats received two intraperitoneally (i.p.) administrations, either methylmercury (MeHg) (1.5mg/kg body weight), selenium methionine (SeMet) alone (1mg/kg body weight) or combined MeHg and SeMet, followed by 3 weeks of rat urine collection and neurobehavioural assays. The effects of different administrations were investigated by the quantification of total mercury in kidney and brain, analysis of urinary porphyrins, determination of hepatic GSH and evaluation of motor activity functions (rearing and ambulation). MeHg exposure resulted in a significant increase of urinary porphyrins during the 3 weeks of rat urine collection, where as it caused a significant decrease in motor activity only at the first day after cessation of rat exposure. Additionally, SeMet co-exposure was able to normalize the porphyrins excretion, and a tendency to restore rat motor activity was observed, on the first day after cessation of exposure. Brain and kidney mercury levels increased significantly in rats exposed to MeHg; however, in co-exposed rats to SeMet no significant changes in Hg levels were found as compared to rats exposed to MeHg alone. Hence, /this/ study shows that urinary porphyrins are sensitive and persistent indicators of MeHg toxicity and demonstrates ... that SeMet reduces its formation. Finally, these results confirm that the mechanism of interaction between SeMet and MeHg cannot be explained by the reduction of Hg levels in target organs and suggestions are made to clarify the interference of SeMet on MeHg toxicity.
The chemopreventive efficacies of selenate, selenite, selenium dioxide, selenomethionine and selenocystine were examined during the promotion phase of carcinogenesis in the 7,12-dimethylbenz(a)anthracene induced mammary tumor model in rats. Each agent was added to the diet of a final concentration of 3 ppm selenium. In general, there was no significant difference in the potency of these five selenium compounds in inhibiting the development of mammary tumors. The interaction of vitamin E (500 ppm) with either selenite or selenomethionine was further characterized in a second carcinogenesis study. Results of this experiment suggested that vitamin E enhanced the protective effect of selenite but not that of selenomethionine. In an attempt to explore the synergistic mechanism of selenium and vitamin E, the effects of these two agents on mitogen induced blastogenesis and natural killer cytotoxic activity were also investigated. No consistent changes in these in vitro immune functions were detected resulting from supranutritional feeding of either selenite or vitamin E or both. ...
The objectives of this study were a) to compare the efficacy of inorganic or organic selenium compounds in protecting against mammary tumorigenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA); in rats and b) to study the interaction of vitamin C with either selenite (inorganic) or seleno-DL-methionine (organic) in chemoprevention. Control Sprague Dawley rats were fed a purified 5% corn oil diet containing 0.1 ppm selenium. Selenite or seleno-DL-methionine was added to the basal diet in concentrations of 2, 3, or 4 ppm starting 1 week after DMBA administration. The inhibitory response in mammary tumorigenesis with selenium supplementation was dose dependent. Both selenium compounds were found to be equally efficacious in prophylaxis, although at the 4 ppm level a slight reduction in growth was observed.
For more Interactions (Complete) data for SELENIUM METHIONINE (13 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat ip 11 mg/kg
LD50 Mouse iv 22 mg/kg
LD50 Mouse intracervical 13 mg/kg

Therapeutic Uses
Radioactive form of /selenomethionine/ as diagnostic aid (pancreas function determination); radioactive agent.
Available forms of /nutritional/ supplements include high selenium yeast, L-selenomethionine, sodium selenate and sodium selenite. /L-selenomethionine/
/Experimental Therapy/ ... Squamous dysplasia, the accepted histological precursor for esophageal squamous cell carcinoma, represents a potentially modifiable intermediate end point for chemoprevention trials in high-risk populations. ...Aa randomized, controlled trial of selenomethionine 200 ug daily and/or celecoxib 200 mg twice daily (2 x 2 factorial design) among residents of Linxian, People's Republic of China. Subjects had histologically confirmed mild or moderate esophageal squamous dysplasia at baseline. Esophagogastroduodenoscopy was performed before and after a 10-month intervention. Per-subject change (regression, stable, or progression) in the worst dysplasia grade was defined as the primary end point. Results were compared by agent group (selenomethionine vs placebo; celecoxib vs placebo). ... Two hundred sixty-seven subjects fulfilled all eligibility criteria, and 238 (89%) completed the trial. Overall, selenomethionine resulted in a trend toward increased dysplasia regression (43% vs 32%) and decreased dysplasia progression (14% vs 19%) compared with no selenomethionine (P = .08). In unplanned stratified analyses, selenomethionine favorably affected a change in dysplasia grade among 115 subjects with mild esophageal squamous dysplasia at baseline (P = .02), but not among 123 subjects with moderate esophageal squamous dysplasia at baseline (P = 1.00). Celecoxib status did not influence changes in dysplasia grade overall (P = .78) or by baseline histology subgroup. ... After a 10-month intervention, neither selenomethionine nor celecoxib inhibited esophageal squamous carcinogenesis for all high-risk subjects. However, among subjects with mild esophageal squamous dysplasia at baseline, selenomethionine did have a protective effect...
/Experimental Therapy/ ... Studies were carried out on nude mice bearing human colorectal carcinoma SW480 cell line xenografts 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 by IP injection for 21 days. ... The pathologic changes and the cell apoptosis in tumor tissue /were observed/ by HE staining and TUNNEL assay after HSSe and SeMet treatment. GSH level and antioxidant enzyme GPX activity in tumor tissues were assessed. In addition, Western blotting was used to detect the expression of apoptosis-related proteins. The results suggested that HSSe and SeMet had significantly inhibited tumor growth in vivo. ... GSH level was a bit increased but the GPX activity was reduced. Moreover, SSe and SeMet treatment downregulated the expression of the protein Bcl-xL, increased the expression of Bax, Bad, and Bim, and activated caspase-9. SSe and SeMet may be the selective, low-toxic anticancer agents to treat human colorectal carcinoma cancer.
/Experimental Therapy/ ... Based on clinical findings and recent studies in selenoprotein gene-modified mice, it is likely that the antioxidant function of one or more selenoproteins is responsible for the chemopreventive effect of Se. Furthermore, upregulation of phase 2 enzymes by Se has been implicated as a possible chemopreventive mechanism at supranutritional dietary levels. Se-methylselenocysteine (SeMSC), a naturally occurring organic Se product, is considered as one of the most effective chemopreventive selenocompounds...

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Drug Warnings
The ability of selenomethionine (SeMet) to be incorporated into the body proteins in place of methionine (Met) furthermore provides a means of reversible Se storage in organs and tissues. This property is not shared by any other naturally occurring selenoamino acid and thus could be associated with a specific physiological function of SeMet. Since higher animals cannot synthesize SeMet, yet from it all needed forms of Se are produced, SeMet meets the criteria of an essential amino acid. Accordingly, SeMet, or enriched food sources thereof, are appropriate forms of Se for human nutritional Se supplementation. However, while SeMet or Se yeast are already widely used in over-the-counter nutritional supplements, infant formulas and parenteral feeding mixtures still contain Se in the form of sodium selenate or sodium selenite, even though these are not the normal nutritional forms of Se. In animal nutrition, these inorganic selenium salts are increasingly replaced by food sources of SeMet such as Se yeast. Synthetic SeMet could also be employed as a feed additive, but its regulatory status is as yet undetermined. The optimal nutritional levels of SeMet for different animal species still need to be determined. The expectation is that lower additions to feedstock of equivalent levels of SeMet will suffice to achieve adequacy than currently approved maximum levels of Se in the form of inorganic Se salts.
SELECT stands for the Selenium and Vitamin E Cancer Prevention Trial, a clinical trial to see if one or both of these substances prevent prostate cancer when taken as dietary supplements. ... Enrollment for the trial began in 2001 and ended in 2004. More than 400 sites in the United States, Puerto Rico, and Canada took part in the study. Over 35,000 men participated in SELECT. SELECT was initially planned for a follow-up of a minimum of seven years and a maximum of 12 years. However, the independent Data and Safety Monitoring Committee (DSMC) for the trial met on September 15, 2008, to review SELECT study data and found that selenium and vitamin E, taken alone or together did not prevent prostate cancer. They also determined that it was unlikely selenium and vitamin E supplementation would ever produce a 25 percent reduction in prostate cancer, as the study was designed to show. As a result, SELECT participants were told in October 2008 to stop taking their study supplements. Although there were no statistically significant differences (in other words, these differences could have occurred by chance alone) in the rates of prostate cancer between the four groups in the trial, there was a larger number of cases in men taking only vitamin E. The difference does not prove that vitamin E causes prostate cancer and may be due to chance. ... deaths combined, or the overall incidence of cardiovascular events between the study groups. Based on data reported from the beginning of the trial, there were more new cases of diabetes in men taking only selenium (10 percent of these men) as compared to the men taking placebo (9.3 percent). This finding was not statistically significant, does not prove an increased risk from selenium and may be due to chance. /Selenium containing preparations/
The most frequently reported adverse reactions of selenosis or chronic selenium toxicity are hair and nail brittleness and loss. Other symptoms include skin rash, garlic-like breath odor, fatigue, irritability and nausea and vomiting. /Selenium containing preparations/
Intakes of selenium less than 900 ug daily (for adults) are unlikely to cause adverse reactions. Prolonged intakes of selenium of doses of 1,000 ug (or 1 mg) or greater daily may cause adverse reactions. /Selenium containing preparations/
Pregnant women and nursing mothers should avoid selenium intakes greater than Recommended Dietary Allowance amounts. /Selenium containing preparations/

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.)