of trial subjects. In addition, the UL is not meant to apply to individuals who receive iron under medical supervision.
Iron is a redox-active transition metal. In health, it is carried from one tissue to another bound to transferrin and stored in cells in the form of ferritin or hemosiderin. These proteins hold iron in the ferric state. Kinetic restrictions prevent the iron from being reduced by cellular reductants, and it is thus shielded from unwanted participation in redox reactions (McCord, 1996). If the transport and storage mechanisms are overwhelmed, the free iron will immediately be chelated by cellular compounds, such as citrate or adenosyl diphosphate, that readily participate in redox reactions catalyzing the formation of highly toxic free radicals or the initiation of lipid peroxidation.
Acute Effects. There are reports of acute toxicity resulting from overdoses of medicinal iron, especially in young children (Anderson, 1994; Banner and Tong, 1986; NRC, 1979). Accidental iron over-dose is the most common cause of poisoning deaths in children under 6 years of age in the United States (FDA, 1997). Vomiting and diarrhea characterize the initial stages of iron intoxication. With increasing time after ingestion, at least five organ systems can become involved: cardiovascular, central nervous system, kidney, liver, and hematologic (Anderson, 1994). The severity of iron toxicity is related to the amount of elemental iron absorbed. Symptoms occur with doses between 20 and 60 mg/kg with the low end of the range associated primarily with gastrointestinal irritation while systemic toxicity occurs at the high end (McGuigan, 1996). These data, however, are not used because acute intake data are not considered in setting a UL.
Iron-Zinc Interactions. High intakes of iron supplements have been associated with reduced zinc absorption as measured by changes in serum zinc concentrations after dosing (Fung et al., 1997; Meadows et al., 1983; O’Brien et al., 2000; Solomons, 1986; Solomons and Jacob, 1981; Solomons et al., 1983). However, plasma zinc concentrations are not considered to be good indicators of body zinc stores (Whittaker, 1998). Studies using zinc radioisotopes showed reduced zinc absorption when both minerals were administered in the fast-