One studio reveals how it is possible to live with little oxygen in the highest city in the world, La Rinconada in Peru, which is located at 5,100 meters above sea level. Stefania Recalcati, Elena Gammella, Margherita Correnti and Gaetano Cairo (Iron Metabolism Laboratory at the Biomedical Health Sciences Department of the State University of Milan) investigated the link between iron metabolism and red blood cell formation (erythropoiesis) analyzing subjects residing in three areas of Peru: at sea level, at high altitude (Puno, 3,800 meters) and in La Rinconada (5,100 meters, the highest city in the world). The study, the result of extensive international collaboration, especially with French researchers at the University of Grenoble, was recently published in Hemasphere.
According to the study results, the human body adapts to the conditions of hypoxia induced by high altitudes by synthesizing large quantities of hemoglobin, necessary for the transport of oxygen. To make hemoglobin, red blood cells use large amounts of iron; the availability of iron is particularly crucial when the synthesis of red blood cells is very high (erythrocytosis), as occurs at high altitudes.
“The data obtained demonstrated that the progressive increase in erythroid parameters (i.e. the number of red blood cells and the mass of hemoglobin) is not accompanied by iron deficiency“, explains Stephanie Recalcati, research co-coordinator. “Me tooand extreme conditions observed in the inhabitants of La Rinconada, who have, for example, a hematocrit over 70% (due to a total red cell volume doubled from normal) do not lead to iron deficiency, as evidenced by unaltered ferritin and transferrin saturation. Only the additional erythropoietic stress present in subjects suffering from chronic altitude sickness caused the induction of erythroferrone and the repression of hepcidin (two systemic regulators of iron metabolism), in order to cope with the even higher need of erythroid cells”conclude Stephanie Recalcati.
Presumably, as demonstrated by the finding of higher levels of ceruloplasmin, a protein required for iron absorption and induced by oxygen deprivation, iron homeostasis reaches equilibrium with increased erythropoiesis. In this case, in fact, an efficient mobilization of iron from the intestinal lumen (absorption) to the erythroid compartment is promoted, thanks to the optimization of transport mechanisms.
These findings provide valuable insights into the aadjustment of iron homeostasis in response to chronically stimulated erythropoiesissuch as that of the more than 100 million people who live permanently above 2,500 metres, or of patients with respiratory pathologies involving severe chronic hypoxia or with haematological diseases such as polycythemia, characterized by a sharp increase in the amount of red blood cells.