Background and Purpose: Iron supplementation in iron deficiency is recognized as important for maintaining organ/cell function in chronic heart failure and renal failure. In the elucidation of these organ function effects of iron supplementation, there is little research information on mechanisms other than anemia improvement. In this study, intravenous iron infusion therapy was conducted to patients with iron deficiency anemia who complained of (1) symptoms of pagophagia (craving or chewing ice) and (2) fatigue, and the multifaceted effects of iron replacement were explored by analyzing the time course of improvement of the two symptoms and improvement of anemia-related blood examination data.

Subjects and Methods: The subjects were 10 patients with glacial symptoms and fatigue. Hb was 8.7±1.6 g/dL, MCV was 74.2±8.0 fL, and Ferritin was 2.8±3.9 ng/mL. One infusion of ferric carboxymaltose 500 mg was administered and evaluated 1 month later.

Results: Glacial symptoms resolved in all 10 patients. Fatigue was also remarkably improved in all patients (including disappearance). Anemic status showed significant changes with Hb 11.2±1.6 g/dL, MCV 81.8±6.9 fL, and Ferritin 38.6±25.5 ng/mL, but 7 patients were still anemic (Hb<12.0 g/dL) and required continued iron supplementation.

Discussion: Some studies have reported that glacial eating is directly caused by anemia (Woods SC, Science 1334-1336, 169, 1970). However, in our analysis, the disappearance of glacial symptoms (as well as fatigue) occurred earlier than the time of improvement in anemia, suggesting that there are biological effects of iron that are distinct from erythropoiesis. These results may provide important information for the elucidation of iron-related organ/cell functions in many diseases including chronic heart failure and renal failure.