Chasing iron deficiency

Programs to eliminate iron deficiency have had limited success because of the lack of epidemiologic methods to identify iron deficiency. Anemia, per se, is a poor indicator for iron deficiency because it is often mild and because in developing countries, the prevalence of anemia associated with malnutrition and infection may exceed iron deficiency anemia. In this issue, Cook and colleagues (page3359) describe a method for measuring body iron that relies on the ratio of serum transferrin receptor to serum ferritin measurements, translated into body iron stores in milligrams per kilogram of body weight. This method provides a continuum of values ranging from normal, to storage iron depletion, and finally to tissue iron deficiency (anemia). The original method has been validated in volunteers subjected to quantitative phlebotomy (Skikne et al, Blood. 1990;75:1870-1876).

In the present study the method was applied to a large number of samples collected in the NHANES III survey, a study of iron supplementation in pregnant women in Jamaica, and a study of iron fortification in anemic Vietnamese women. The results obtained are remarkable. A single normal distribution of body iron has been obtained for US men and pregnant Jamaican women. In trials of iron supplementation and fortification, it was possible to calculate the absolute amount of iron absorbed over time in individual subjects. This was achieved using minute volumes of serum suitable for collection by capillary specimens, a procedure highly suitable for large-scale field studies. The pitfalls and limitations of the method were carefully defined. It is unsuitable for subjects with inflammation or hepatocellular injury because of their effect on serum ferritin. Moreover, for ethical reasons, the phlebotomy validation cannot be applied to children and pregnant women, the groups at highest risk of nutritional iron deficiency. Nevertheless, the paper by Cook et al represents a major step forward in the development of suitable methodology for effective interventional programs to address a major global health problem.