Selenium is an essential element in humans that is required as a cofactor in a number of selenoproteins. Severe deficiency of selenium is not common, but when present results in the development of a form of childhood cardiomyopathy called Keshan disease, or in adults a number of different cancers including oesophageal squamous cell and gastric cardia cancer. Such selenium deficiency diseases are not common outside of certain provinces of China, but it is thought that a milder form of deficiency (often termed insufficiency or subclinical deficiency) is more prevalent in parts of Europe and North America. In the past, glutathione peroxidase, a selenium requiring enzyme and cellular antioxidant, has been researched as a marker for selenium intake. However, research using an onion meal as a source of selenium have found that glutathione peroxidase is not a sensitive marker for selenium status in normal healthy individuals, and that selenoprotein P is a better physiological marker.
In order to fully understand the best biomarker of selenium intake, researchers1 have investigated the optimal intake of selenium necessary to affect selenoprotein P levels. In a 40 week double blind placebo controlled study, 98 healthy Chinese subjects were assigned to randomly receive either 0, 21, 35, 55, 79, 102 or 125 µg of selenium as L-selenomethionine. At baseline the subjects were assessed and had a daily mean selenium intake of 14 µg. The optimisation of plasma levels of glutathione peroxidase, selenoprotein P and selenium were determined by a supplemental level that did not differ from the mean value of the individuals with larger intakes. The selenoprotein P levels were optimised by at week 40 by an intake of 35 µg, suggesting that 49 µg per day was sufficient (considering the 14 µg intake at baseline). However, in support of other studies, glutathione peroxidase activity was optimised at much lower intakes that selenoprotein P.
On the basis of these results, the authors concluded that an intake of ~75 µg per day was sufficient to allow full expression of selenoprotein P in most individuals, based on body weight and biochemical variation. The form of selenium used in this study was L-selenomethionine, which is known to be more bioavailable than the inorganic forms of selenium, selenate and selenite. Ingested selenomethionine can be stored in tissue proteins in place of methionine, creating a non-saturable store of selenium. As the proteins are catabolised, the selenomethionine within is released to the circulation, where it contributes to the production of selenoprotein P and glutathione peroxidase. Inorganic forms of selenium, such as selenate and selenite cannot enter this non-saturable pool, and instead enter the saturable pool in the plasma which is then used directly for whole body selenium homeostasis. Inorganic selenium is therefore less effective as a long term selenium solution.
It is suggested that glutathione peroxidase required a lower intake of selenium to be optimised because most glutathione peroxidase in plasma is synthesised in the proximal tubules of the kidney which has a priority over available plasma selenium due to specific receptors. This means that plasma glutathione peroxidase is not representative of whole body selenium homeostasis. In contrast, the liver synthesises most selenoprotein P and is also responsible for whole body selenium transport and homeostasis. Therefore selenoprotein P synthesis reflects more accurately the whole body status of selenium. At optimal plasma concentrations selenoprotein P and glutathione peroxidase contain around 90 µg/L of selenium, suggesting that plasma levels below 90 µg/L of selenium are not optimal and may lead to insufficiency. Plasma concentrations greater than 90 µg/L represent the sum of selenoprotein P, glutathione peroxidase plus additional selenomethionine, selenate or selenite, and may therefore represent sufficiency status.
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