Nutritional iron deficiency: an evolutionary perspective

Abstract Iron deficiency, with or without iron-deficiency anemia, is so ubiquitous that it affects all populations of the world irrespective of race, culture, or ethnic background. Despite all the latest advances in modern medicine, improved nutrition, and the ready availability of cheap oral iron, there is still no good explanation for the widespread persistence of iron deficiency. It is possible that the iron deficiency phenotype is very prevalent because of many factors other than the commonly cited causes such as a decreased availability or an increased utilization of iron. Several thousand years ago, human culture changed profoundly with the agrarian revolution, when humans turned to agriculture. Their diet became iron deficient and new epidemic infections emerged due to crowding and lifestyle changes. There is convincing evidence that iron deficiency protects against many infectious diseases such as malaria, plague, and tuberculosis as shown by diverse medical, historical, and anthropologic studies. Thus, this change of diet increased the frequency of iron deficiency, and epidemic infections exerted a selection pressure under which the iron deficiency phenotype survived better. Multiple evolutionary factors have contributed in making iron deficiency a successful phenotype. We analyze some of the recent findings of iron metabolism, the theories explaining excessive menstruation in human primates, the unexplained relative paucity of hemochromatosis genes, the former medical practice of “blood-letting,” and other relevant historical data to fully understand the phenomenon of iron deficiency. We suggest that, due to a long evolutionary persistence of iron deficiency, efforts at its prevention will take a long time to be effective.