Progressive Increases in Dietary Iron Are Associated with the Emergence of Pathologic Disturbances of Copper Homeostasis in Growing Rats

Consumption of a high-iron diet causes copper deficiency in weanling rodents; however, the minimum amount of dietary iron that disrupts copper homeostasis has not been established. We tested the hypothesis that dietary iron at only several-fold above physiologic requirements would cause copper depletion. Weanling male Sprague-Dawley rats (n = 6/group) were fed AIN-93G-based diets with adequate (88 µg Fe/g = 1×), or excessive (4×, 9.5×, 18.5×, 38×, or 110×) iron content for 7 wk (110× group, due to notable morbidity) or 8 wk (all other groups). Copper-related physiologic parameters were then assessed. A hierarchy of copper-related, pathologic symptoms was noted as dietary iron concentrations increased. All statistical comparisons reported here refer to differences from the 1× (i.e., control) group. The highest iron concentration (110×) impaired growth (final body weights decreased ∼40%; P