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 (f200 Mg/d) to large (f600 Mg/d) selenium supplements in the forms sodium selenite, high-selenium yeast (yeast), and Lselenomethionine (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. (Cancer Epidemiol Biomarkers Prev 2006;15(4):804 -10)

SummaryDeletion 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 3 2− 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.

Objective: Our aim was to determine if a once-a-week folic acid supplement increases women's red blood cell folate to concentrations (4905 nmol/l) that are associated with a low risk of bearing a child with a neural tube defect. Design: Randomized control trial. Setting: General community. Subjects: In total, 114 nonpregnant women (18-40 y) volunteers, with red blood cell folate concentrations between 295 and 905 nmol/l at screening. Intervention: Women were randomized to receive a once-a-week 2800 mg folic acid supplement, a daily 400 mg folic acid supplement or a daily placebo for 12 weeks. Results: The mean (95% CI) red blood cell folate concentrations increased during the 12-week intervention from 608 (553-668) to 900 (828-978) in the weekly folic acid group (Po0.05) and from 615 (560-677) to 1053 (957-1158) nmol/l in the daily group (Po0.05) during the trial. At week 12, 49% of women ingesting the weekly folic acid supplement had red blood cell folate concentrations greater than 905 nmol/l compared to 74% of women ingesting the daily supplement. Conclusion: A once-a-week 2800 mg folic acid supplement can increase women's red blood cell folate to concentrations associated with a reduced risk of bearing a child with a neural tube defect, but is less effective than a 400 mg daily supplement. Use of a weekly folic acid supplement over at least 12 weeks before conception by women of child-bearing age may prevent neural tube defects.

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.

No abstract