Subject: iron/supplementation/bacteria
Haematologia (Budap) 1993;25(2):69-84
Adequate iron stores and the 'Nil nocere' principle.
Hollan S, Johansen KS
National Institute of Haematology, Blood Transfusion and Immunology,
Budapest.
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.
Publication Types:
* Review
* Review, tutorial
PMID: 8244202, UI: 94063698
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