Iron Deficiency

Reference from the joint report of FAO/WHO expert consultation on Human Vitamins and Minerals verbatim.

Populations at risk for iron deficiency

Worldwide, the highest prevalence of iron deficiency is found in infants, children, adolescents, and women of childbearing age, especially pregnant women. The weaning period in infants is especially critical because of the very high iron requirements in relation to energy requirements. Thanks to better information and access to fortified cereals for infants and children, the iron situation has markedly improved in these groups in most industrialized countries where the highest prevalences of iron deficiency today are observed in menstruating and pregnant women and adolescents of both sexes.

70. Hallberg, L. 1993. Screening for iron deficiency: an analysis based on bone-marrow examinations and serum ferritin determinations in a population sample of women. Br. J. Haematol., 85: 787-798.

In developing countries, however, the iron situation is very critical in many groups, especially in the weaning period. Iron nutrition is of great importance for the adequate development of the brain and other tissues such as muscles, which are finally differentiated early in life. Iron deficiency and iron deficiency anaemia are often incorrectly used as synonyms. A definition of these terms may clarify some confusion about different prevalence figures given in the literature (70).

 71. Wintrobe, M.M. 1981. Clinical Hematology. (Eighth ed.), Philadelphia, Lea & Febiger.

The cause of the problem is the very wide distribution of the haemoglobin concentration in healthy, fully iron-replete subjects (in women, 120–160 g/l; in men, 140–180g/l [71]). During the development of a negative iron balance in subjects with no mobilisable iron from iron stores (no visible iron in technically perfect bone marrow smears or a serum ferritin concentration <15 μg/l), there will be an immediate impairment in the production of haemoglobin with a resulting decrease in haemoglobin and different erythrocyte indexes (e.g., mean corpuscular haemoglobin and mean corpuscular volume). In turn this will lead to an overlap of the distributions of haemoglobin in iron-deficient and iron-replete women (Figure 25). 

The extent of overlap depends on the prevalence and severity of iron deficiency. In populations with more severe iron deficiency, for example, the overlap is much less marked. In women, anaemia is defined as a haemoglobin <120 g/l. For a woman who has her normal homeostatic value set at 150 g/l, haemoglobin level must decrease to 119 g/l (by 26 percent) before she is considered to be anaemic, whereas for a woman who has her normal haemoglobin set at 121 g/l, haemoglobin level must only decrease by 1.5 percent to 119 g/l.

72. Yip, R., Stolzfus, R.J. & W.K.S. 1996. Assessment of the prevalence and the nature of iron deficiency for populations: the utility of comparing haemoglobin distributions. In: Hallberg L, Asp, N-G., eds. Iron nutrition in health and disease. London, John Libby & Company Ltd. 

Iron deficiency anaemia is a rather imprecise concept for evaluating the single subject and has no immediate physiologic meaning. By definition, this implies that the prevalence of iron deficiency anaemia is less frequent than iron deficiency and that the presence of anaemia in a subject is a statistical rather than a functional concept. The main use of the cut-off value is in comparisons between population groups (72).

71. Wintrobe, M.M. 1981. Clinical Hematology. (Eighth ed.), Philadelphia, Lea & Febiger. 

In practical work, iron deficiency anaemia should be replaced by the functional concept of iron deficiency. Anaemia per se is mainly important when it becomes so severe that oxygen delivery to tissues is impaired. An iron deficiency anaemia which develops slowly in otherwise healthy subjects with moderately heavy work output will not give any symptoms until the haemoglobin level is about 80 g/l or lower (71). 

The reason for the continued use of the concept of iron deficiency anaemia is the ease of determining haemoglobin. Therefore, in clinical practice, knowledge of previous haemoglobin values in a subject is of great importance for evaluating the diagnosis. Iron deficiency being defined as an absence of iron stores combined with signs of an iron-deficient erythropoiesis implies that in a state of iron deficiency there is an insufficient supply of iron to various tissues. This occurs at a serum ferritin level <15 μg/l. Iron can then no longer be mobilised from iron stores and insufficient amounts of iron will be delivered to transferrin, the circulating transport protein for iron.

The binding sites for iron on transferrin will therefore contain less and less iron. This is usually described as a reduction in transferrin saturation. When transferrin saturation drops to a certain critical level, erythrocyte precursors, which continuously need iron for the formation of haemoglobin, will get an insufficient supply of iron. At the same time, the supply of iron by transferrin to other tissues will also be impaired. Liver cells will get less iron, more transferrin will be synthesised, and the concentration of transferrin in plasma will then suddenly increase. Cells with a high turnover rate are the first ones to be affected (e.g., intestinal mucosal cells with a short life span).

73. Harford, J.B., Röuault, T.A. & Klausner, R.D. 1994. The control of cellular iron homeostasis. In: Brock JH et al., eds. Iron metabolism in health and disease. p.123-149. London, W.B.Saunders Company Ltd.

74. Baker, E. & Morgan, E.H. 1994. Iron transport. In: Brock JH et al., eds. Iron metabolism in health and disease. p.63-95. London, W.B. Saunders Company Ltd.

The iron-transferrin complex is bound to transferrin receptors on cell surfaces and the whole complex is then taken up by special receptors on the surface of various cells and tissues. The uptake of iron seems to be related both to transferrin saturation and the number of transferrin receptors on the cell surface (73, 74). There is a marked diurnal variation in the saturation of transferrin because the turnover rate of iron in plasma is very high. This fact makes it difficultto evaluate the iron status from single determinations of transferrin saturation.