BACKGROUND: Selenium is a central determinant of antioxidative glutathione 
peroxidase 1 (GPx-1) expression and activity. The relevance of selenium 
supplementation on GPx-1 in coronary artery disease (CAD) needs to be 
established. We assessed the effect of selenium supplementation on GPx-1 in cell 
culture and on endothelial function in a prospective clinical trial.
METHODS: Human coronary artery endothelial cells were incubated with 5.78 to 578 
nmol/L sodium selenite, Se-methyl-selenocysteine hydrochloride, or 
seleno-l-methionine. Glutathione peroxidase 1 mRNA and protein expression and 
activity were measured. Coronary artery disease patients (n = 465) with impaired 
endothelial function (flow-mediated dilation [FMD] <8%) were randomly assigned 
to receive 200 or 500 microg sodium selenite daily or matching placebo during a 
12-week period. We tested the effect on red blood cell GPx-1 activity and 
brachial artery FMD. Furthermore, differences in biomarkers of oxidative stress 
and inflammation were measured.
RESULTS: Sodium selenite and Se-methyl-selenocysteine hydrochloride increased 
GPx-1 protein and activity in a dose-dependent manner (P < .0001). The 
intention-to-treat groups comprised 433 CAD patients. Glutathione peroxidase 1 
activity increased from 37.0 U/gHb (31.3-41.7) to 41.1 U/gHb (35.2-48.4) (P < 
.0001) in the 200 microg and from 38.1 U/gHb (33.2-43.8) to 42.6 U/gHb 
(35.0-49.1) (P < .0001) in the 500 microg sodium selenite group treated for 
12-weeks. No relevant changes were observed for FMD or biomarkers of oxidative 
stress and inflammation.
CONCLUSIONS: Sodium selenite supplementation increases GPx-1 activity in 
endothelial cells and in CAD patients. Future studies have to demonstrate 
whether long-term CAD outcome can be improved.