Selenium in sepsis – substitution, supplementation or pro-oxidative bolus?

Sakr and colleagues report seemingly disappointing data on the effects of selenium in severe sepsis [1]. Mortality rates remained unaffected despite intensive selenium supplementation. The authors conclude that extra selenium above a basal supply of 100 μg/day provides no additional health benefit. However, there are good reasons for selenium supplementation in sepsis; the selenium status declines with the disease especially in nonsurvivors [2], reducing selenoprotein P levels [3], while supplemental selenium efficiently restores selenoprotein expression in experimental models [4]. Yet some major questions prevail. Is it sufficient to balance selenium decline (substitution)? Are larger dosages required for overcoming compromised selenoprotein biosynthesis (supplementation)? Are bolus dosages of selenite key to health benefits (pro-oxidative)? For me, the third option has been specifically disproven by the data [1].