Perturbed Vitamin A Status Induced by Iron Deficiency Is Corrected by Iron Repletion in Rats with Pre-Existing Iron Deficiency

Abstract

ABSTRACT Background Although iron deficiency is known to interrupt vitamin A (VA) metabolism, the ability of iron repletion to restore VA metabolism and kinetics in iron-deficient rats is not well understood. Objectives In the present study, we examined the effects of dietary iron repletion on VA status in rats with pre-existing iron deficiency. Methods Weanling Sprague-Dawley rats were fed a VA-marginal diet (0.35 mg retinol/kg diet) containing either a normal concentration of iron [35 ppm, control group (CN)] or reduced iron (3 ppm, iron-deficient group, ID−); after 5 wk, 4 rats/group were killed for baseline measurements. A 3H-labeled retinol emulsion was administered intravenously to the remaining rats (n = 6, CN; n = 10, ID−) as tracer to initiate the kinetic study. On day 21 after dosing, n = 5 ID− rats were switched to the CN diet, generating an iron-repletion group (ID+). Blood samples were collected at 34 time points ≤92 d after dose administration, when all rats were killed and iron and VA status were determined. Results At baseline, ID− rats had developed iron deficiency, with a reduced plasma VA concentration (0.67 compared with 1.20 μmol/L in ID− and CN rats, respectively; P < 0.01) and a tendency toward higher liver VA (265 compared with 187 nmol in ID− and CN rats, respectively; P = 0.10). On day 92, iron deficiency persisted in ID− rats, accompanied by 2-times higher liver VA (456 nmol compared with 190 nmol in ID− and CN rats, respectively; P < 0.001) but lower plasma VA (0.64 compared with 0.94 μmol/L in ID− and CN rats, respectively; P = 0.05). ID+ rats not only recovered from iron deficiency, but also exhibited less liver VA sequestration (276 nmol) and normal plasma VA (0.91 μmol/L, not different from CN rats). Conclusions Our results suggest that iron repletion can remove the inhibitory effect of iron deficiency on hepatic mobilization of VA and restore plasma retinol concentrations in iron-deficient rats, setting the stage for kinetic studies of VA turnover in this setting.