The analytical research group at the University of Graz has presented new results of a selenium speciation analysis on human urine from one volunteer over a 48-hour period after ingestion of 1.0 mg of selenium in three different forms in the recent issue of "Analytical and Bioanalytical Chemistry".
The group of researchers used HPLC/ICP MS for their speciation studies and carried out mass balance studies for quality assurance. Trimethylselenonium ion, a commonly reported urine metabolite generally thought to be produced as a way of excreting excess, potentially toxic selenium, could not be detected in normal (unsupplemented) human urine and in human urine collected after supplementation with selenite or selenomethionine. With respect to the obtained detection limit of 1 µg Se/L for TMSe, the group concluded that if at all present, this compound would account for < 0.5 % of the total selenium in those urine samples containing the highest selenium concentrations. This result is in accordance with recent results of the research group at the Danish University of Pharmaceutical Science but questions results obtained in some earlier studies.
The major Se species found in background urine were two selenosugars, namely methyl-2-acetamido-2-deoxy-1-seleno-ß-D-galactopyranoside (selenosugar 1) and its deacylated analog methyl-2-amino-2-deoxy-1-seleno-ß-D-galactopyranoside (selenosugar 3) (see below).
Other often reported selenium constituents of human urine such as selenite, selenate and selenomethionine could not be found in background urine. Quantification of identified species accounted for 30-70% of the total Se concentration of 11-18 g/L which in part was explained by the fact that concentrations of different species at background levels were close or below to limits of quantitation (1.5 µg/l).
After ingestion of 1.0 mg of selenium in the form of sodium selenite, L-selenomethionine or DL-selenomethionine, selenium was rapidly excreted, the peak concentrations (~250-400 µg Se/L) were recorded within 5 hours for the organoselium compounds and after 9 hours for the inorganic selenite. Concentrations returned back to background levels within 48 hours, by which time 25-40% of the ingested selenium had been excreted. The "missing" selenium is believed to be incorporated into essential proteins, excretion in the feces and losses via volatile respiratory products.
In all experiments, the major metabolite was selenosugar 1, constituting 65-80 % of the total selenium excreted over the first 24 hours after ingestion depending on the ingested compound. Other species detected were arsenosugar 3 (minor), arsenosugar 2 (traces) and some non-identified species (<10% of sum of species).
By spiking experiments it was confirmed that these non-identified species were not selenite, selenate, selenocystamine or trimethylselenonium. The researcher believe that the relative quantities of selenosugars 1 and 3 are dose-dependent, and thus might be relevant to a possible detoxification pathway for selenium. A possible explanation may involve transformation of excess selenium to selenosugar 1, which is then deacylated to selenosugar 3. At normal levels both species are present at similar concentrations, but at high exposure the deacylation steps is overloaded leading to a large excess of selenosugar 1. Both selenosugars were about a factor of 1,000 less toxic than selenite a finding that may reassure people on selenium supplements, that excess ingested selenium is excreted as nontoxic metabolites.
Selenomethionine was a significant species (20%) in the urine when DL-selenomethionine was ingested. It was speculated that unchanged selenomethionine results from the D-selenomethione in the ingested mixture, reflecting the selectivity for L-selenomethionine of enzymes involved in metabolism. This may be another hint, that naturally occuring "L" compounds, for example from selenized yeast, are better suited for Se-supplementation.
The original study:
Doris Kuehnelt, Norbert Kienzl, Pedro Traar, Nam Hoang Le, Kevin A. Francesconi, Takafumi Ochi, Selenium metabolites in human urine after ingestion of selenite, L-selenomethionine, or DL-selenomethionine: a quantitative case study by HPLC/ICP MS, Anal. Bioanal. Chem., 383/2 (2005) 235-246. DOI 10.1007/s00216-005-0007-8
Yasumitsu Ogra, Kazuya Ishiwata, Hiromitsu Takayama, Norio Aimi, Kazuo T. Suzuki, Identification of a novel selenium metabolite, Se-methyl-N-acetylseleno-hexosamine, in rat urine by HPLC-ICP MS and -electrospray ionization tandem mass spectrometry, J. Chromatogr. B, 767/2 (2002) 301-312. doi: 10.1016/S1570-0232(01)00581-5
Y. Kobayashi, Y. Ogra, K. Ishiwata, H. Takayama, N. Aimi, K.T. Suzuki, Selenosugars are key and urinary metabolites for selenium excretion within the required to low-toxic range, Proc. Natl. Acad. Sci. U.S.A., 99 (2002) 15932-36. doi: 10.1073/pnas.252610699
Yasumitsu Ogra, Toshitake Hatano, Masayoshi Ohmichi, Kazuo T. Suzuki, Oxidative production of monomethylated selenium from the major urinary selenometabolite, selenosugar, J. Anal. At. Spectrom., 18/10 (2003) 1252-1255. DOI: 10.1039/b306710f
Pedro Traar, Ferdinand Belaj, Kevin A. Francesconi, Synthesis of Methyl 2-Acetamido-2-deoxy-1-seleno-ß-d-gluco- and galacto-pyranoside: Selenium Metabolites in Human Urine, Aust. J. Chem., 57/11 (2004) 1051-1053. DOI: 10.1071/CH04176