ADEQUATE IRON STORES AND THE NIL-NOCERE PRINCIPLE

There is a need to change the policy of unselective iron supplementati on during periods of life with physiologically increased cell prolifer ation. Levels of iron stores to be regarded as adequate during infancy and pregnancy are still not well established. Recent data support the view that it is not justified to interfere with physiological adaptat ions developed through millions of years by sophisticated and precisel y coordinated regulation of iron absorption, utilization and storage. Recent data suggest that the chelatable intracellular iron pool regula tes the expression of proteins with central importance in cellular iro n metabolism (TfR, ferritin, and erythroid 5-aminolevulinic synthetase ) in a coordinately controlled way through an iron dependent cytosolic mRNA binding protein, the iron regulating factor (IR.F). This factor is simultaneously a sensor and a regulator of iron levels. The reducti on of ferritin levels during highly increased cell proliferation is a mirror of the increased density of TfRs. An abundance of data support the vigorous competition for growth-essential iron between microbial p athogens and their vertebrate hosts. The highly coordinated regulation of iron metabolism is probably crucial in achieving a balance between the blockade of readily accessible iron to invading organisms and yet providing sufficient iron for the immune system of the host. The most evident adverse clinical effects of excess iron have been observed in immunodeficient patients in tropical countries and in AIDS patients. Excess iron also increases the risk of initiation and promotion of mal ignant processes by iron binding to DNA and by the iron-catalysed rele ase of free radicals. Oxygen radicals were shown to damage critical bi omolecules leading, apart from cancer, to a variety of human disease s tates, including inflammation and atherosclerosis. They are also invol ved in processes of aging and thrombosis. Recent clinical trials have suggested that the use of iron-chelators, natural and synthetic antiox idants, and anti-TfR monoclonal antibodies can contribute in retarding malignant cell proliferation. Hypoferraemia during pregnancy is - lik e haemodilution - an adaptation to the risks involved in the natural h ypercoagulable state of pregnancy. It may also serve to prevent the ri sk of infections and mutagenicity in the highly proliferating tissues of the foetus. Blunted erythropoiesis has been revealed during the fir st 30 weeks of pregnancy by the use of the newly developed method of d etermining the soluble serum transferrin receptor. The lack of increas e in erythropoietin levels proves that them is no hypoxia. Decreases i n Hb and iron levels are parts of a physiological adaptation. As a con sequence they should neither be treated nor prevented. It is stressed that whenever a widespread and ingrained routine medical intervention has to be changed, it is essential to first monitor the potential heal th effects of the recommended change in a national policy.