Abstract

Oral iron supplementation constitutes the first line treatment for iron deficiency anemia (IDA), with daily doses between 80 mg and 200 mg of elemental iron. Ferrous salts, such as ferrous sulphate (FeSO4), while efficacious, frequently give rise to gastrointestinal side effects. In the present paper we attempted to directly compare the efficacy of an alternative to the FeSO4 formulation, which presents a better tolerability profile, iron protein succinylate (Ferplex®). In a diet-induced anemia model, rats were treated by oral gavage with vehicle, FeSO4, or Ferplex® at a human-dose equivalent of 80 mg and 200 mg of elemental iron. We evaluated the change in anemia-related hematological and biochemical parameters, conducting a histological examination of the intestine at sacrifice. Results indicate that both types of iron supplementation are equally effective in the treatment of IDA, restoring hemoglobin, hematocrit, erythrocytes, free iron and transferrin levels in 15 days, with no statistical differences between treated groups and control. The impact of anemia on body weight was also attenuated following treatment with both iron supplements. Thrombocyte and reticulocyte levels, altered by the anemic condition, returned to homeostasis after 15 days of either FeSO4 or Ferplex® treatment. Importantly, the lower and higher doses of iron were equally effective, thus supporting the current school of thought which states that lower therapeutic doses are sufficient for management of IDA. In addition, the study shows for the first time that oral treatment with Ferplex® does not increase serum hepcidin. Finally, Ferplex® induced minimal iron depositions in the intestinal tissue compared to FeSO4.

Highlights

  • IntroductionIron deficiency is the principal cause of anemia [1] and can be produced by malnutrition, blood loss (gastrointestinal or menstruation bleeding) or by chronic diseases, including inflammatory bowel disease, chronic kidney disease or cancer [2]

  • Iron deficiency is the principal cause of anemia [1] and can be produced by malnutrition, blood loss or by chronic diseases, including inflammatory bowel disease, chronic kidney disease or cancer [2]

  • In a diet-induced anemia model, rats were treated by oral gavage with vehicle, FeSO4, or Ferplex® at a human-dose equivalent of 80 mg and 200 mg of elemental iron

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Summary

Introduction

Iron deficiency is the principal cause of anemia [1] and can be produced by malnutrition, blood loss (gastrointestinal or menstruation bleeding) or by chronic diseases, including inflammatory bowel disease, chronic kidney disease or cancer [2]. Ferrous sulphate (FeSO4) is the gold standard among iron treatments for anemia. It frequently produces adverse effects in the gastrointestinal tract such as nausea, vomiting, constipation and diarrhea [6,7]. The average duration of treatment is 3–6 months, but common side effects result in a non-adherence to therapy in up to 50% of patients, preventing effective correction of iron deficiency anemia. Unabsorbed iron is generally deemed to be the cause of these gastrointestinal side effects [7]

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