Selenium deficiency occurs in some patients with moderate-to-severe cirrhosis and can be corrected by administration of selenate but not selenomethionine: a randomized controlled trial.

BACKGROUND: Selenomethionine, which is the principal dietary form of selenium, is metabolized by the liver to selenide, which is the form of the element required for the synthesis of selenoproteins. The liver synthesizes selenium-rich selenoprotein P (SEPP1) and secretes it into the plasma to supply extrahepatic tissues with selenium. OBJECTIVES: We conducted a randomized controlled trial to determine whether cirrhosis is associated with functional selenium deficiency (the lack of selenium for the process of selenoprotein synthesis even though selenium intake is not limited) and, if it is, whether the deficiency is associated with impairment of selenomethionine metabolism. DESIGN: Patients with Child-Pugh (C-P) classes A, B, and C (mild, moderate, and severe, respectively) cirrhosis were supplemented with a placebo or supranutritional amounts of selenium as selenate (200 or 400 µg/d) or as selenomethionine (200 µg/d) for 4 wk. Plasma SEPP1 concentration and glutathione peroxidase (GPX) activity, the latter due largely to the selenoprotein GPX3 secreted by the kidneys, were measured before and after supplementation. RESULTS: GPX activity was increased more by both doses of selenate than by the placebo in C-P class B patients. The activity was not increased more by selenomethionine supplementation than by the placebo in C-P class B patients. Plasma selenium was increased more by 400 µg Se as selenate than by the placebo in C-P class C patients. Within the groups who responded to selenate, there was a considerable variation in responses. CONCLUSION: These results indicate that severe cirrhosis causes mild functional selenium deficiency in some patients that is associated with impaired metabolism of selenomethionine. This trial was registered at clinicaltrials.gov as NCT00271245.

Deletion of selenoprotein P upregulates urinary selenium excretion and depresses whole-body selenium content.

Deletion of the mouse selenoprotein P gene (Sepp1) lowers selenium concentrations in many tissues. We examined selenium homeostasis in Sepp1(-/-) and Sepp1(+/+) mice to assess the mechanism of this. The liver produces and exports selenoprotein P, which transports selenium to peripheral tissues, and urinary selenium metabolites, which regulate whole-body selenium. At intakes of selenium near the nutritional requirement, Sepp1(-/-) mice had whole-body selenium concentrations 72 to 75% of Sepp1(+/+) mice. Genotype did not affect dietary intake of selenium. Sepp1(-/-) mice excreted in their urine approximately 1.5 times more selenium in relation to their whole-body selenium than did Sepp1(+/+) mice. In addition, Sepp1(-/-) mice gavaged with (75)SeO(2-)(3) excreted 1.7 to 2.4 times as much of the (75)Se in the urine as did Sepp1(+/+) mice. These findings demonstrate that deletion of selenoprotein P raises urinary excretion of selenium. When urinary small-molecule (75)Se was injected intravenously into mice, over 90% of the (75)Se appeared in the urine within 24 h, regardless of selenium status. This shows that urinary selenium is dedicated to excretion and not to utilization by tissues. Our results indicate that deletion of selenoprotein P leads to increased urinary selenium excretion. We propose that the absence of selenoprotein P synthesis in the liver makes more selenium available for urinary metabolite synthesis, increasing loss of selenium from the organism and causing the decrease in whole-body selenium and some of the decreases observed in tissues of Sepp1(-/-) mice.

Effects of chemical form of selenium on plasma biomarkers in a high-dose human supplementation trial.

Intervention trials with different forms of selenium are under way to assess the effects of selenium supplements on the incidence of cancer and other diseases. Plasma selenium biomarkers respond to selenium administration and might be useful for assessing compliance and safety in these trials. The present study characterized the effects of selenium supplementation on plasma selenium biomarkers and urinary selenium excretion in selenium-replete subjects. Moderate (approximately 200 microg/d) to large (approximately 600 microg/d) selenium supplements in the forms sodium selenite, high-selenium yeast (yeast), and l-selenomethionine (selenomethionine) were administered. Subjects were randomized into 10 groups (placebo and three dose levels of each form of selenium). Plasma biomarkers (selenium concentration, selenoprotein P concentration, and glutathione peroxidase activity) were determined before supplementation and every 4 weeks for 16 weeks. Urinary selenium excretion was determined at 16 weeks. Supplementation with selenomethionine and yeast raised the plasma selenium concentration in a dose-dependent manner. Selenite did not. The increased selenium concentration correlated with the amount of selenomethionine administered. Neither glutathione peroxidase activity nor selenoprotein P concentration responded to selenium supplementation. Urinary selenium excretion was greater after selenomethionine than after selenite, with excretion after yeast being intermediate and not significantly different from either of the other two. We conclude that plasma selenium concentration is useful in monitoring compliance and safety of selenium supplementation as selenomethionine but not as selenite. Plasma selenium seems to reflect the selenomethionine content of yeast but not the other yeast selenium forms. As judged by urinary selenium excretion, selenium in the form of selenomethionine is better absorbed than selenite.