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Clinical Trial
. 2008 Dec;156(6):1201.e1-11.
doi: 10.1016/j.ahj.2008.09.004.

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

Renate Schnabel  1 , Edith Lubos, Claudia M Messow, Christoph R Sinning, Tanja Zeller, Philipp S Wild, Dirk Peetz, Diane E Handy, Thomas Munzel, Joseph Loscalzo, Karl J Lackner, Stefan Blankenberg
Affiliations
Clinical Trial

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

Renate Schnabel et al. Am Heart J. 2008 Dec.

Abstract

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.

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Figures

Figure 1
Figure 1
Study design and patient sample of the SETCAP trial. ITT indicates intention to treat.
Figure 2
Figure 2
A, Glutathione peroxidase 1 protein in HCAEC after 4 days of sodium selenite treatment. B, Glutathione peroxidase 1 activity levels in HCAEC after 4 days of sodium selenite treatment. *P < .0001, #P < .05 vs no treatment (n = 8). C, Glutathione peroxidase 1 protein levels in HCAEC after 4 days of Se-methyl-selenocysteine hydrochloride or seleno-L-methionine. D, Glutathione peroxidase 1 activity levels in HCAEC after 4 days of Se-methyl-selenocysteine hydrochloride or seleno-L-methionine. *P < .0001 vs no treatment (n = 9). Data are expressed as mean ± standard error of the mean.
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