## 3 Organosehenium Compounds
### Selenium Species, Bioavailability, and Effects of Excess and Deficiency  
Selenium is an essential element with a narrow safety margin: essential to humans in trace amounts, but highly toxic when in excess. It has one of the narrowest ranges among all the elements between dietary deficiency (less than 40 \(\upmu\)g/day) and toxic levels (over 400 \(\upmu\)g/day) [140]. The recommended dietary allowance (RDA) of selenium for adults is 55 \(\upmu\)g/day, according to the Linus Pauling Institute [141]. The tolerable upper intake level advised by the USA is 400 \(\upmu\)g/day in the USA [142; 143] and 300 \(\upmu\)g/day in Europe [144]. However, the recommendations do not take into account that Se can be present in food (or food supplements) under different chemicals forms, organic or inorganic. These forms differ in bioavailability and therefore exert different effects on the organism [145; 146].  
To address this problem, several methods are used to determine selenium bioavailability. These include the measurement of plasma selenium concentration, measurement of glutathione peroxidase (GPx) activity, and absorption-retention tests following intake of a specific dose of a selenium compound [147]. Plasma selenium is the most commonly measured biomarker, reflecting different levels of Se exposure that also respond positively to intervention. According to the Mayo Clinic Laboratories, the normal concentration of Se in adult human blood serum is 70 to 150 micrograms per liter [148]. This is indicative of the adequate dietary intake, above which selenium supplementation is not recommended.  
When concentration of selenium is lower than the recommended 70 \(\upmu\)g/L, the selenium intake is inadequate, and there is a risk of diseases related to selenium deficiency. In this case, supplementation of this element is recommended. Conversely, excessive selenium intake leads to a serum concentration higher than the recommended Se (over 150 \(\upmu\)g/L\({}^{-1}\)), and there is an increased risk of diseases related to selenium excess. The U-shaped relationship between the concentration of selenium in human serum and the biological effects expressed as disease risk is particularly interesting [17]. The optimal selenium serum concentration (70-150 \(\upmu\)g/L) is indicative of the adequate dietary intake, in which case selenium supplementation is not recommended. Both the excess and deficiency of selenium have several common negative health effects, i.e., increased mortality, type 2 diabetes, and increased prostate cancer risk [18; 149; 150; 151].  
The complete list of the adverse health effects associated to an insufficient selenium intake and Se deficiency is wider and includes Keshan disease [152], Kashin-Beck disease [153], increased virus virulence [154], increased mortality [150], poor immune function [131], decreased fertility and reproductive health [17], thyroid autoimmune disease [155], cognitive decline and dementia [156], type-2 diabetes [149], prostate cancer risk [151], and colorectal cancer risk in women [157].  
A selenium overdose can occur during chronic exposure to high levels of selenium in food and water. This may occur, for example, during regular snacking on Brazil nuts, which may contain up to 90 \(\upmu\)g of selenium per nut, or participation in clinical trials where high doses of selenium are given for a long period of time [18], and overdose of Se food supplements [158]. The effects are similar for both organic and inorganic forms of selenium [144]. Symptoms of selenium overdose include hair loss, abnormal nails, nausea, vomiting, diarrhea, rash, fatigue, and nerve damage [159].  
To summarize, the beneficial and harmful effects of selenium depend on its dose and form (speciation). The introduction of the new forms of selenium (e.g., selenopolysacahrides) to be used as selenium supplementation or treatment of various diseases requires extensive studies on the bioavailability, absorption, and metabolism of this element.