title: Adequate iron stores and the 'Nil nocere' principle.
abstract: There is a need to change the policy of unselective iron supplementation during periods of life with physiologically increased cell proliferation. 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 adaptations developed through millions of years by sophisticated and precisely coordinated regulation of iron absorption, utilization and storage. Recent data suggest that the chelatable intracellular iron pool regulates the expression of proteins with central importance in cellular iron 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 (IRF). This factor is simultaneously a sensor and a regulator of iron levels. The reduction 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 pathogens 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 malignant processes by iron binding to DNA and by the iron-catalysed release of free radicals. Oxygen radicals were shown to damage critical biomolecules leading, apart from cancer, to a variety of human disease states, including inflammation and atherosclerosis. They are also involved in processes of aging and thrombosis. Recent clinical trials have suggested that the use of iron-chelators, natural and synthetic antioxidants, and anti-TfR monoclonal antibodies can contribute in retarding malignant cell proliferation. Hypoferraemia during pregnancy is--like haemodilution--an adaptation to the risks involved in the natural hypercoagulable state of pregnancy. It may also serve to prevent the risk of infections and mutagenicity in the highly proliferating tissues of the foetus. Blunted erythropoiesis has been revealed during the first 30 weeks of pregnancy by the use of the newly developed method of determining the soluble serum transferrin receptor. The lack of increase in erythropoietin levels proves that there is no hypoxia. Decreases in Hb and iron levels are parts of a physiological adaptation. As a consequence 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 health effects of the recommended change in a national policy.
authors.affiliation: National Institute of Haematology, Blood Transfusion and Immunology, Budapest.
authors.forename: S
authors.initials: S
authors.lastname: Hollán
authors.forename: K S
authors.initials: KS
authors.lastname: Johansen
mesh_terms: D000328:Adult; D000747:Anemia, Hypochromic / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D000818:Animals; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology; D002648:Child; D005260:Female; D005293:Ferritins / Q000502:physiology; D005527:Food, Fortified; D006801:Humans; D015994:Incidence; D007223:Infant; D007225:Infant Food; D007239:Infections / Q000378:metabolism; D007408:Intestinal Absorption; D007501:Iron / Q000009:adverse effects / Q000493:pharmacokinetics / Q000502:physiology* / Q000627:therapeutic use; D008297:Male; D009369:Neoplasms / Q000378:metabolism; D009751:Nutritional Requirements; D011247:Pregnancy; D015995:Prevalence; D051381:Rats; D012016:Reference Values; D014168:Transferrin / Q000502:physiology
chemical_list: D014168:Transferrin; D005293:Ferritins; D007501:Iron