(Burk et al., 1972). The excretory metabolites appear in the urine primarily, but when large amounts of selenium are being excreted, the breath also contains volatile metabolites (e.g., dimethylselenide) (McConnell and Portman, 1952).

Clinical Effects of Inadequate Intake

In experimental animals, selenium deficiency decreases selenoenzyme activities, but if the animals are otherwise adequately nourished, it causes relatively mild clinical symptoms. However, certain types of nutritional, chemical, and infectious stresses lead to serious diseases in selenium-deficient animals. For example, induction of vitamin E deficiency in selenium-deficient animals causes lipid peroxidation and liver necrosis in rats and pigs and cardiac injury in pigs, sheep, and cattle (Van Vleet, 1980). Another example of this phenomenon is the conversion of a nonpathogenic strain of coxsackie B3 virus to a pathogenic one that causes myocarditis when it infects selenium-deficient mice (Beck and Levander, 1998).

Keshan disease, a cardiomyopathy that occurs only in selenium-deficient children, appears to be triggered by an additional stress, possibly an infection or a chemical exposure (Ge et al., 1983). Clinical thyroid disorders have not been reported in selenium-deficient individuals with adequate iodine intake, but based on observations in Africa, it has been postulated that infants born to mothers deficient in both selenium and iodine are at increased risk of cretinism (Vanderpas et al., 1992).

Kashin-Beck disease, an endemic disease of cartilage that occurs in preadolescence or adolescence, has been reported in some of the low-selenium areas of Asia (Yang et al., 1988). It is possible that this disease, like Keshan disease, occurs only in selenium-deficient people. However, there has been no demonstration that improvement of selenium nutritional status can prevent Kashin-Beck disease, so involvement of selenium deficiency in its pathogenesis remains uncertain.

These considerations indicate that selenium deficiency seldom causes overt illness when it occurs in isolation. However, it leads to biochemical changes that predispose to illness associated with other stresses.

SELECTION OF INDICATORS FOR ESTIMATING THE REQUIREMENT FOR SELENIUM

A search of the literature revealed several indicators that could be considered as the basis for deriving an Estimated Average Require-



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