Selenium is an essential trace mineral required for human health. Deficiency of selenium is associated the development of myalgia, cardiac myopathy, increased cell fragility and pancreatic degeneration, which can cause Keshan disease and Kashin-Beck’s disease. Selenium deficiency is rare in developed nations, but does still occur in developing nations, in regions with selenium poor soils. In recent decades a new classification of micronutrient status, the insufficiency, has come into common use as instrumentation and awareness of nutrient biochemistry has improved. The insufficiency is defined as a status below optimal, but at a level that prevents outright deficiency symptoms. Recent research suggests that while selenium deficiency is rare, selenium insufficiency might be common. Selenium insufficiencies may be responsible for many of the undiagnosed conditions that cause chronic ill health in large numbers of individuals, and may contribute to the development of serious disease.
Selenium insufficiency may increase the susceptibility of individuals to a number of diseases. Of particular interest is the role of selenium in the immune system. Selenium concentrations in immune tissue such as the spleen, liver and lymph nodes is significantly higher than other tissues, and insufficiency is known to impair immune system function in a number of ways. Supplementation of such individuals with selenium has been shown to replete immune tissue concentrations and improve immune response significantly. Although the exact mechanism of interaction between selenium and the immune system is not know, it appears that selenium is able to up-regulate the expression of interleukin-2 receptors on the surface of immune cells. This may sensitise the immune cells to the action of interleukin-2, a cytokine protein responsible for activation of blood cells in response to pathogens. Selenium insufficiency is also associated with virulence, occurrence and progression of some viral infections.
Selenium insufficiency may also affect reproductive functions in humans, although most of the evidence associating selenium depletion with poor reproductive function has come from animal studies. In humans, research has shown that women with first trimester miscarriages have significantly lower levels of selenium than controls, and that women with a history of miscarriages have lower selenium levels than control women. This may relate to the loss of DNA protection afforded by the selenium dependent protein glutathione peroxidise. However, as pregnancy can deplete maternal mineral supplies, the relevance of these results is not fully understood. In male fertility, selenium insufficiency may inhibit testosterone biosynthesis and spermatozoa formation. Serum selenium is associated with spermatozoa concentration and selenium insufficiency can lead to poor development and mobility, thus decreasing the chance of fertilisation. This may again relate to the presence of glutathione peroxidise, which protects the spermatozoa from oxidative stress.
Selenium insufficiency has been linked to brain abnormalities relating to mood and this has lead researchers to suggest that selenium is required for proper brain function. This is supported by studies reporting reduced rates of neurotransmitter turnover with selenium insufficiency. In addition, low levels of selenium are associated with dementia and accelerated cognitive decline in the elderly. Supplementation of selenium to individuals with insufficiency has been shown to improve mood and decrease depressive symptoms. Interestingly, high selenium intakes from supplements also appear to lift mood and decrease anxiety, depression and tiredness. Because selenium is required for thyroid hormone production sufficiency may compromise thyroid function. Supplementation of elderly individuals was shown to increase triiodothyronine (T3) and decrease thyroxine (tetraiodothyronine; T4) suggesting that increased concentrations of T4 had been converted to the more biologically active T3. Because thyroid hormone levels are related to mood, this may explain some of the mood enhancing effects of selenium.
One of the biggest concerns regarding selenium insufficiency in developing nations is an increased risk of cancer. This is illustrated in the seminal paper by Clark in 1996 (here), Data from this study showed that selenium insufficiency significantly increased the risk of developing a number of types of cancer. Selenium supplementation (200 µg selenium yeast) in this study decreased cancer morbidity and mortality by ~50 %. Protection from cancer may relate to higher cellular levels of glutathione peroxidise and to the general immune stimulatory effect of selenium. In addition, epidemiological data from regions with low selenium soil show an association between selenium intakes and cancer risk. Supplementation of individuals in these regions lowers cancer risk significantly. Much of the work on such trials has been performed in China in the Henan Province, were soil selenium is naturally low.
Selenium may also protect from cardiovascular disease, although the exact mechanism of action is not known, However, evidence suggest that the protective effects of selenium may relate to the cellular levels of glutathione peroxidise that decrease cellular oxidative stress and prevent the modifications to lipids that can result in platelet aggregation. The selenium dependent enzyme glutathione peroxidise is required for the metabolism of hydroperoxides formed during eicosanoid synthesis by the enzyme lipoxygenase and cyclo-oxygenase. If hydroperoxides are left to accumulate they can inhibit the enzyme prostacyclin synthetase, which may have vasodilatory actions. Selenium may therefore prevent cardiovascular disease by inhibiting platelet aggregation, and studies in men suggest that coronary artery disease and platelet aggregation are inversely related to selenium status.
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