iron metabolism

There is a brilliant review of iron metabolism and the implications for deficiency in the Lancet
Zimmermann and Hurrell Nutritional iron deficiency 2007 Lancet 370, 511-20
Estimates of iron deficiency in developed countries are usually derived from specific indicators of iron status. These are expensive so in developing countries estimates are often based on haemoglobin alone which does not allow for other causes of anaemia , eg vitamin A deficiency), infectious disorders (particularly malaria, HIV disease, and tuberculosis), haemoglobinopathies, and ethnic differences in normal haemoglobin distributions.
WHO estimates that 39% of children younger than 5 years, 48% of children between 5 and 14 years, 42% of all women, and 52% of pregnant women in developing countries are anaemic, with half having iron deficiency anaemia. Iron deficiency is also common in women and young children in industrialised countries. In the UK, 21% of female teenagers between 11 and 18 years, and 18% of women between 16 and 64 years are iron deficient.. Other countries have similar figures.
Human beings are unable to excrete iron actively, so its concentration in the body must be regulated at the site of iron absorption in the proximal small intestine . Diets contain haem and non-haem (inorganic) iron; each form has specific transporters. There is an intestinal haem iron transporter which is upregulated by iron deficiency, which may also transport folate. Transport of non-haem iron from the intestinal lumen into the enterocytes is mediated by the divalent metal ion transporter 1 which transports only ferrous iron, but most dietary iron that enters the duodenum is in the ferric form. Therefore, ferric iron must be first reduced to ferrous iron, possibly by the brush border ferric reductase, duodenal cytochrome b or by other reducing agents, eg ascorbic acid. Inside the enterocyte, iron may be stored as ferritin or crosses the basolateral membrane into the blood, controlled by the transport protein ferroportin 1, and the iron oxidase, hephaestin.
When red cell are old they are broken down in the spleen and the freed iron binds to transferrin , which binds to transferrin receptors in the bone marrow and this iron is incorporated into new red cells.
Within cells, iron status upregulates or downregulates ferritin and transferring receptors important in iron homeostasis by binding at the post-transcription level iron regulatory proteins to specific non-coding sequences in their mRNAs, called iron-responsive elements. Various genes are modulated by iron status, many of these genes are not directly related to iron metabolism.
During gestation, the fetus stores about 250 mg of iron which is used during breastfeeding, as breastmilk supplies only about 0-15 mg of absorbed iron per day, whereas requirements for absorbed iron are about 0-55 mg per day. Low birth weight infants do not store sufficient iron and are at risk of developing iron deficiency while being breastfed. During growth in childhood, about 0-5 mg of iron per day is absorbed in excess of body losses; adequate amounts of iron during growth typically results in a 70-kg man accumulating about 4 g of body iron. About 2-3 g of body iron is within haemoglobin and about 1 g is stored as ferritin or haemosiderin, mainly in the liver. Men absorb and excrete about 0-8 mg of iron per day, and women, during childbearing years, should absorb almost twice as much (1 -4mg per day) to cover menstrual losses. The usual diet of a population strongly affects iron bioavailabiiity,so that recommended intakes for iron depend on diet characteristics.
Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations eating plant-based diets with little meat. In meat, 30-70% of iron is haem iron, 15-35% of which is absorbed.” However, in plant-based diets most dietary iron is non-haem iron, and its absorption is often less than 10%. The absorption of non-haem iron is increased by meat and ascorbic acid, but inhibited by phytates, polyphenols, and calcium.The needs for iron increase in infants and young children, adolescents, and in menstruating and pregnant women.
Increased blood loss from gastrointestinal parasites aggravates dietary deficiencies in many developing countries.
During the first two trimesters of pregnancy, iron deficiency anaemia increases the risk for preterm labour, low birthweight, infant mortality, and predicts iron deficiency in infants after 4 months of age. Data for the adverse effects of iron deficiency on cognitive and motor development in children are equivocal because environmental factors limit their interpretation
There are three main strategies for correcting iron deficiency in populations, alone or in combination: education combined with dietary modification or diversification, or both, to improve iron intake and bioavailability; iron supplementation (provision of iron, usually in higher doses, without food); and iron fortification of foods. A new approach is biofortification through plant breeding or genetic engineering. Although dietary modification and diversification is the easiest , changing dietary practices and preferences is difficult, and foods that provide highly bioavailable iron (such as meat) are expensive.
For oral supplementation, ferrous iron salts (ferrous sulphate and ferrous gluconate) are preferred as they are cheap and have high bioavailability. Standard therapy for iron deficiency anaemia in adults is a 300-mg tablet of ferrous sulphate (60 mg of iron) three or four times per day.
Iron fortification is probably the most practical, sustainable, and cost-effective long-term solution to control iron deficiency at the national level. Fortification of foods with iron is more difficult than it is with other nutrients, such as iodine in salt and vitamin A in cooking oil. The most bioavailable iron compounds are soluble in water or diluted acid, but often react with other food components to cause flavour, and colour changes, fat oxidation, or both.Thus, less soluble forms of iron, although less well absorbed, are often chosen for fortification to avoid unwanted sensory changes.

Martin Eastwood
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