Selenium supplementation improves antioxidant capacity in vitro and in vivo in patients with coronary artery disease: The SElenium Therapy in Coronary Artery disease Patients (SETCAP) Study

Background Selenium is a central determinant of antioxidative glutathione peroxidose 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 mu g sodium selenite daily or matching placebo during a 1 2-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 peroxidose 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 mu g and from 38.1 U/gHb (33.2-43.8) to 42.6 U/gHb (35.0-49.1) (P <.0001) in the 500 mu g 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. (Am Heart J 2008;156:1201.e1-1201.e11.)