Selenium and Human Health

Immune system enhancement, cancer suppression, and cardiovascular disease reduction are all associated with increased dietary selenium (95–97). The chief biological function of selenium is as an essential cofactor to the enzyme GSHx (81). The antioxidant enzyme GSHx protects against oxidative stress by removing DNA-damaging hydrogen peroxide and lipid hydroperoxides. The chemopreventive action of selenium may come from its role in GSHx (98). Other protective qualities attributed to selenium, independent of GSHx activity, include repair of damaged DNA (99), reduction in DNA binding of carcinogens (100), and suppressing genetic mutations (101).

Selenium Deficiency and Toxicity in Humans

The average selenium intake by humans in most countries is sufficient to meet the United States' recommended daily allowances, and selenium deficiency in healthy humans is relatively rare (5,6). Selenium status in a population correlates highly with the selenium content of locally produced crops (7). In areas of the world with low soil selenium, addition of selenium in normal fertility regimes is practiced to avoid selenium deficiencies in humans and livestock (16). A significant inverse relationship between low-selenium status and increased risk of cancer mortality has been established for some rural counties of the United States (102).

The link between selenium deficiency and disease is associated with more than 40 different health conditions (103). The first reports of diseases linked to selenium status came from regions of China having extremely low soil selenium. Keshan disease, an endemic cardiomyopathy, and Kashin-Beck disease, a chronic and deforming arthritis, have been linked to selenium deficiency (104). Selenium deficiency also depresses the effectiveness of immune cells. Selenium deficiency was found to be an independent predictor of survival rates among patients infected with HIV (human immunodeficiency virus) (105). Increasing selenium intake in animals and human beings increases antitumorigenic activities (106), and selenium-dietary supplementation decreases severity of several viral diseases (107).

The United States National Academy of Sciences has identified selenium intake of up to 200 µg day^-1 as safe (108). However, sustained consumption of selenium levels exceeding 750 µg day^-1 can cause selenium poisoning or selenosis (109). Signs of human selenosis include morphological changes in fingernails and hair loss, with an accompanied garlicky breath odor. Human selenosis reports have come from regions in China, where extremely high levels of soil selenium caused human-dietary intake to be <900 µg day^-1 (110).

Anti-carcinogenic Effects of Selenium

There is perhaps no more extensive body of evidence for the cancer preventive potential of a normal dietary component than there is for selenium (106). Evidence for inverse associations between nutritional selenium status and cancer risk exist from epidemiological studies (111,112), experimental animal models (92,113), and most recently, clinical trials (5). Selenium supplementation resulted in a 63% reduction in the incidence of prostate cancer over a 10-year period in an at-risk group of men given 200 µg Se day^-1 (5). Experimental antitumorigenic effects of selenium are associated with supranutritional levels of at least 10 times those required to prevent clinical signs of selenium deficiency (106). These levels are higher than those experienced by most people, an amount which tends to be 150 to 200 µg Se day^-1. Anticarcinogenic activity of selenium may not involve its usual role as a nutrient because selenium-dependent enzyme activities are already at a maximum at levels of selenium below effective anticarcinogenic level and the forms of selenium that lack nutritional activity (not synthesized by Se-dependent enzymes) show good cancerpreventing activity (82). Therefore, for anticarcinogenic effects to be seen, supplementation of selenium in the diet is usually needed. Inorganic SeO₃^2- and yeast-derived Se-Met are the most common selenium supplements for human consumption.

Importance of Selenium Methylation in Chemopreventive Activity

Methylation is the best-known fate of selenium, and fully methylated metabolites are regarded as detoxified forms of selenium. Selenium methylselenocysteine has very high chemopreventive activity. This form of selenium is naturally occurring in plants enriched with selenium and does not get incorporated into proteins, thus minimizing excessive accumulation in body tissues. The metabolism of Se-methylselenocysteine produced monomethylated forms of selenium as excretory products (82). The potential activity of selenium can be enhanced in the course of being metabolized in plants, especially in those having specialized alkyl-group capabilities. Some plants such as alliums can transfer allyl groups to sulfur, or possibly, selenium. These allyl groups can undergo methylation to form highly chemopreventive alkylated derivatives (82). Selenium-enriched garlic (Allium sativum L.) had higher chemopreventive activity than regular garlic alone in animal models (113). Natural selenium products formed in plants are very active chemopreventive metabolites. They show higher activity in animals than the selenium compounds metabolized from inorganic selenium sources (82).