Chapter 198: Iron

INTRODUCTION

Iron supplements are widely available, particularly in homes with small children and young women. Women of childbearing age with iron available at home are at risk of intentional iron overdose due to the impact of maternal stress. The attractiveness of the brightly colored sugar-coated tablets and improper storage of iron make children susceptible to ingestion, serious toxicity, and death.¹ The 1997 federal requirement that all preparations containing >30 milligrams of elemental iron be distributed only in blister packs and the implementation of mandated warning labels from the U.S. Food and Drug Administration coincided with the reduction of pediatric iron poisonings and deaths.^2,3 Despite the rescindment of the blister pack requirement in 2003, serious iron poisonings in children have remained low.⁴

PHARMACOLOGY

Excess iron in overdose may saturate the body’s mechanisms for iron homeostatis, allowing for unbound (“free”) iron to cause organ toxicity. Due to its reactivity with oxygen, iron is always bound to a carrier molecule under normal circumstances. Carrier molecules include transferrin (serum protein), ferritin (intracellular storage), and iron-containing proteins (hemoglobin, myoglobin, cytochromes, and other enzymes and cofactors). The body cannot directly excrete iron, so regulation of GI iron uptake and limitation of absorption by sloughing of mucosal cells containing surplus iron are the principal mechanisms for maintaining physiologic iron concentrations.

The oral bioavailability of iron depends on the formulation ingested (Table 198-1) along with body iron stores (increased with iron deficiency anemia) and ingestion with food or fasting (increased in fasting state). The bioavailability of ionic iron preparations is low, about 10% to 15% for ferrous (Fe²⁺) salts and about 5% for ferric (Fe³⁺) salts. Most dietary iron is in the ferric form chelated to a heme moiety. Following ingestion, the ferric ion is separated from heme and reduced to ferrous iron by a brush border ferrireductase. Iron chelated with heme, such as that found in meat, is more readily absorbed than tablets of ionic iron or nonheme iron in plants. Commercially available formulations of iron chelated with amino acids (e.g., glycinate) mimic dietary meat, with bioavailability about twice that of ferrous sulfate.