Administration of effective doses of iron in the treatment of iron deficiency anemia is complicated by the fact that iron compounds are not innocuous. Toxicity experiments on dogs and rabbits are here summarized; they showed that the concentration of iron attained in the animal's serum determined the severity of the acute symptoms. Iron in the form of ferrous sulfate or ferrous gluconate raised the serum iron level higher, and caused more intense symptoms of intoxication, than did equivalent doses of iron choline citrate. Presenting the iron to the system as a chelate complex caused less adverse effects than the use of ionized or readily ionizable preparations. Test doses containing 120 mg. of iron were given orally to five volunteer subjects, first as ferrous sulfate solution, then two weeks later as iron choline citrate solution; determinations of serum iron before and after each administration showed that the sulfate caused a higher and less sustained rise in serum iron than did the complex. Given orally in tablet form thrice daily to 131 patients in doses ranging from 120 to 240 mg. of iron per day for a total of 3,303 treatment days, iron choline citrate caused gastrointestinal symptoms in only six patients, and in these it was possible to continue the medication since all symptoms presently disappeared. The clinical responses, both symptomatically and from a laboratory viewpoint, were entirely satisfactory and were comparable to those previously attained from other iron preparations utilized under similar circumstances.
Franklin M, Rohse WG, Huerga JDL, Kemp CR. CHELATE IRON THERAPY. JAMA. 1958;166(14):1685–1693. doi:10.1001/jama.1958.02990140019004
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