Background and Relevant Pharmacokinetics
Selenium is an essential trace element that enters the food chain through incorporation into plants from the soil. Selenium is mainly present in the form of selenite in acid soils, which is poorly assimilated by crops, whereas for alkaline soils, it is in the form of selenate, which is more soluble and assimilated by crops. When taken in supplement form, animal and human trials demonstrate that bioavailability of organic forms of selenium (Se-methionine and Se-cysteine) is higher than that obtained for inorganic forms (selenite and selenate).
The variation in selenium content of adult humans living in different parts of the world is testimony to the influence of the natural environment on the selenium content of soils, crops and human tissues. According to a WHO report, adults in New Zealand have approximately 3 mg selenium in their bodies compared with 14 mg in some Americans (WHO 2002).
Selenium is readily absorbed, especially in the duodenum but also in the caecum and colon. Vitamins A, E, and C can modulate selenium absorption, and there is a complex relationship between selenium and vitamin E that has not been entirely elucidated for humans. Selenium enters the body in two major forms: Se-methionine, which is derived from plants, and Se-cysteine, which is mainly derived from animal selenoproteins. Metabolism is complex and occurs via several routes for the different selenoproteins. Se-methionine enters the methionine pool where it undergoes the same fate as methionine until catabolised. Once the selenium from Se-methionine is liberated by the trans-sulfu ration pathway in the liver or kidney, it is able to be used by peripheral cells. Ingested selenite, selenate and selenocysteine are metabolised to selenide. Urinary excretion accounts for 50-60% of total excretion of selenium and homeostasis is achieved through regulation in the kidney. Volatile forms of selenium are exhaled when intake is very high and presents a significant route of excretion at this level.
During his travels in the 13th century, Marco Polo first reported what is thought to be selenium toxicity in grazing animals. He observed that certain grazing areas in China were associated with horses developing diseased hooves. It is now known that parts of China have the highest selenium soil concentrations in the world and diseased hooves were likely to be due to selenium toxicity. It was not until nearly 500 years later, in 1817, that selenium was actually discovered and the fact that it is essential in mammals was not discovered until 1957. In 1979, the importance of selenium in human nutrition was further reinforced when Chinese researchers reported that selenium supplementation prevented the development of Keshan disease, a cardiomyopathy seen in children living in selenium replete areas, and New Zealand workers reported a clinical response to selenium supplementation in a selenium-depleted patient.
In human tissues, it is found as either L-selenomethionine or L-selenocysteine.
The most concentrated food sources are brewer’s yeast, wheatgerm, meats, fish and seafood, brazil nuts, garlic and organ meats.
Selenium: Deficiency Signs and Symptoms
Selenium deprivation reduces the activity of selenium-dependent enzymes and has widespread effects. Characteristic signs of selenium deficiency have not been described in humans, but very low selenium status is a factor in the aetiologies of a juvenile cardiomyopathy (Keshan disease) and a chondrodystrophy (Kashin-Beck disease) that occur in selenium-deficient regions of China. Low selenium status has been associated with:
• loss of immunocompetence
• increased risk of developing certain cancers
• reduced male fertility
• poorer prognosis in HIV infection and AIDS
• compromised thyroid hormone metabolism (particularly when iodine deficiency is also present)
• asthma and atopy
• rheumatoid arthritis
• possibly, increased inflammatory processes
• changes to drug metabolising enzymes including the cytochrome P450 system, with some activities increasing and others decreasing.
Low selenium status may contribute to the aetiology of several diseases, while in others this state exacerbates disease progression, such as in HIV infection.
People at risk of marginal selenium deficiency include those living in areas of low environmental selenium, such as some regions of New Zealand, people receiving long-term TPN, alcoholics, and those with liver cirrhosis, malabsorption syndromes, cystic fibrosis, coeliac disease and AIDS.