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

Am Heart J. 2008 Dec;156(6):1201.e1-11. doi: 10.1016/j.ahj.2008.09.004.


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.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antioxidants / administration & dosage*
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / enzymology
  • Coronary Vessels / drug effects
  • Coronary Vessels / enzymology
  • Cysteine / administration & dosage
  • Cysteine / analogs & derivatives*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology
  • Erythrocytes / enzymology
  • Female
  • Glutathione Peroxidase / blood*
  • Humans
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Organoselenium Compounds / administration & dosage*
  • Prospective Studies
  • Selenocysteine / analogs & derivatives
  • Selenomethionine / administration & dosage*
  • Sodium Selenite / administration & dosage*
  • Vasodilation / drug effects


  • Antioxidants
  • Organoselenium Compounds
  • Selenocysteine
  • Selenomethionine
  • Glutathione Peroxidase
  • Sodium Selenite
  • Cysteine
  • selenomethylselenocysteine