The Usefulness of Ferrous Fumarate and Ferric Pyrophosphate as Food Fortificants in Developing Countries

Iron fortification of foods is usually considered the most cost-effective approach to prevent iron deficiency. However, iron is the most difficult mineral to add to foods. When added as water-soluble, highly bioavailable compounds such as ferrous sulfate, the soluble iron rapidly catalyzes fat oxidation resulting in rancid products. In addition, water-soluble iron compounds can cause unacceptable color reactions during storage and food preparation. Thus, food manufacturers are often obliged to use water-insoluble iron compounds to fortify foods and fortification compounds such as elemental Fe powder and ferric pyrophosphate are widely used to fortify cereal flours and infant cereals. However, these compounds never dissolve completely in the gastric juice and are usually far less well absorbed than ferrous sulfate (Hurrell 1997). Ferrous fumarate on the other hand, although almost insoluble in water, readily dissolves in the gastric juice and has been shown to have an equivalent absorption to ferrous sulfate in healthy, Western adults (Hurrell et al. 1989, 2000). Because it is non-water soluble, it causes relatively few sensory problems in the fortified foods and is therefore an interesting food fortificant. Iron absorption from ferrous fumarate has been demonstrated to be significantly higher than from ferric pyrophosphate in European infants (Davidsson et al. 2000) and this compound is currently used to fortify blended cereal flours for food aid programs and commercial infant cereals in Europe. However, based on our recent study in Bangladeshi children, there is now concern that due to lower gastric acid output, young children in developing countries may not be able to absorb ferrous fumarate as well as Western adults (Davidsson et al. 2001a, Sarker et al. 2001, 2003). Clearly, there is a need to evaluate the efficacy of water insoluble iron compounds to prevent the development of iron deficiency/iron deficiency anemia in infants and young children living in developing countries. The aim of this study is to evaluate the efficacy of ferrous fumarate and ferric pyrophosphate, as compared to ferrous sulfate, as food fortificants in preventing development of anemia/IDA in Bangladeshi infants and young children (part I).

A potential cause of low gastric acid secretion in Bangladesh and many developing countries is Helicobacter pylori infection. Although H. pylori-infection appeared to have no influence on absorption of ferrous fumarate in children, the impact of chronic H. pylori infection in adults could be expected to be more pronounced due to long time effects on the gastric mucosa, resulting in reduced gastric acid output. The other aim of the study is therefore, to assess of iron absorption and gastric acid output in adult women of child-bearing age with H. pylori infection (part II).

Two hundred and forty non-anemic Children (Hb>105 g/L) will be randomized to three study groups; ferrous fumarate, ferric pyrophosphate or ferrous sulfate (n=80 per group) in wheat flour- and cow milk-based infant formula and will be fed for 9 months. Hemoglobin, serum ferritin, and transferin receptor will be analyzed at baseline and after 4.5 and 9 months of intervention. Prevalence of anemia and iron deficiency during and after the intervention among the three groups will be compared (part I). We furthermore propose a complementary study to determine the relative absorption of ferrous fumarate (relative to ferrous sulfate) in H. pylori infected and non-infected adult Bangladeshi women (15 each) of 20-40 year of age with IDA using stable isotope technique based on the incorporation of iron stable isotopes into erythrocytes 14 days after administration. Assessment of gastric acid output will also be performed. Iron stature and absorption, and assessment of gastric acid output will be compared before and after therapy in H. pylori infected women (part II). The results of this study are expected to have implications in the prevention and treatment of iron deficiency anemia in developing countries