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 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.
Schnabel
Renate
R
Department of Medicine II, Johannes Gutenberg-University, Mainz, Germany.
Lubos
Edith
E
Messow
Claudia M
CM
Sinning
Christoph R
CR
Zeller
Tanja
T
Wild
Philipp S
PS
Peetz
Dirk
D
Handy
Diane E
DE
Munzel
Thomas
T
Loscalzo
Joseph
J
Lackner
Karl J
KJ
Blankenberg
Stefan
S
D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000201:enzymology; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D016566:Organoselenium Compounds / Q000008:administration & dosage*; D011446:Prospective Studies; D017279:Selenocysteine / Q000031:analogs & derivatives; D012645:Selenomethionine / Q000008:administration & dosage*; D018038:Sodium Selenite / Q000008:administration & dosage*; D014664:Vasodilation / Q000187:drug effects
D000975:Antioxidants; D016566:Organoselenium Compounds; D017279:Selenocysteine; D012645:Selenomethionine; D005979:Glutathione Peroxidase; D018038:Sodium Selenite; D003545:Cysteine; C002979:selenomethylselenocysteine