elenium is an essential trace mineral required as a co-factor in a number of selenoproteins including selenoprotein P, thioredoxin reductase, and glutathione peroxidise. Of these glutathione peroxidise is particularly well researched with regard its cellular role, whereby it helps maintain intracellular reducing power by acting as a cytosolic water soluble antioxidant. In particular, glutathione peroxidase can catalyse the conversion of organic hydroperoxides (R-OOH) and hydrogen peroxide (H2O2) to water, using the tripeptide glutathione as a hydrogen donor (figure 1). The antioxidant effects of glutathione peroxidise are of interest because a growing body of evidence links low selenium intakes to cancers of various kinds. Low selenium status may lead to the development of cancer because free radical damage to cellular components may occur from hydrogen peroxide in the absence of high intracellular levels of glutathione peroxidase. This is worrying because selenium status of Western populations is dropping (here).
Figure 1. The conversion of hydrogen peroxide to water via the enzyme glutathione peroxidase. Following donation of a hydrogen group, two glutathione molecules combine. This oxidised glutathione (GSSG) can be recycled to reduced glutathione (GSH) by NADPH, which is produced in the pentose phosphate pathway
Studying patients receiving parenteral nutrition is useful because it allows a better understanding of the rates of depletion and repletion associated with varying selenium intakes. For example researchers1 investigated the time for plasma depletion of selenium in 5 patients aged 20 to 75 years who were undergoing parenteral nutrition. Plasma glutathione peroxidase took around 1 year to fall below the level that would be described as severely deficient (<15 % of the normal value of 0.32 u/mL). Red blood cell levels took around 1 to 2 years to decrease to the severely deficient range (<15 % of the normal value 24 U/g). This was despite some of the initial values being below the normal values at baseline. When the selenium status of the deficient individuals was checked the selenium status was also around 15 % of the normal values, suggesting a correlation between plasma and red blood cell selenium and glutathione peroxidase activity.
When the red blood cells and polymorphonuclear granulocyte of subjects were tested for their ability to metabolise hydrogen peroxide their glutathione perioxidase activity was found to be significantly diminished. When selenium was added to the parenteral nutrition at intakes between 100 and 400 µg/d as selenious acid there was an improvement in glutathione peroxidase activity of plasma within 6 hours and normal platelet values returned within 7 to 14 days. However, there was a significant variability between subjects. Polymorphonuclear granulocyte glutathione peroxidase activity took slightly longer to recover, but activity had retuned to normal levels after 2 to 3 week. However, no recovery of red blood cell glutathione activity was observed at 2 weeks after selenium repletion, with levels taking 3 to 4 months to recover to normal values. This is in agreement with other studies which show long periods of supplementation required to recover glutathione activity in red blood cells.
These data suggest that low intakes of selenium can cause low plasma selenium, and this in turn is associated with low cellular levels of glutathione peroxidase. Low levels of glutathione peroxidase subsequently reduced the ability of the cells to metabolise hydrogen peroxide. Selenium deficiency is rare in humans, and is only found in rural locations where selenium deficient soils are prevalent. However, a growing body of evidence suggests that selenium insufficiency, that is to say a chromic low status, is common amongst the populations of Western nations. Selenium supplementation at 200 µg/d has been shown to reduce the morbidity and mortality of cancer by 50 % (here). This suggests that the decrease in cellular reducing power seen with low selenium diets causes cellular damage due to the activity of hydrogen peroxide and hydroperoxides. Because selenium is deficient from foods, supplements are the best way to raise plasma levels.
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