Iron deficiency is one of the most common nutritional deficiencies worldwide. While in developing countries inadequate diet or low iron intake is the main reason behind iron deficiency, this cannot explain the high prevalence of this deficiency among overweight and obese children in developed countries. Possibly, the inflammation status related to the increased fat mass among these subjects may mediate the suboptimal iron levels and consequently increase the risk for iron deficiency and iron deficiency anaemia.
What is iron deficiency?
Iron deficiency is a state in which there is insufficient iron to maintain the normal physiological function of tissues and may lead in prolonged stage to iron deficiency anaemia.1,2 Insufficient iron status is most commonly due to inadequate diet intake, but also due to poor iron absorption from the gastrointestinal tract and increased iron loss usually via bleeding.3
The most common method for the assessment of iron deficiency is based on the assessment of serum ferritin, which is the main iron store. The generally accepted cut-off level for serum ferritin is 12 μg/L, below which iron deficiency is present in children younger than 5 years.1 As the ferritin’s diagnostic accuracy is rather limited especially in those cases where a person suffers from an infection or inflammation3 alternative methods are developed. The assessment of transferrin saturation, based on serum iron levels and total iron-binding capacity, has been proposed as a more reliable method, with levels lower than 16% reflecting iron deficiency.4 Further to low levels of transferrin saturation, if also haemoglobin or haematocrit levels are lower than 11g/dL and 33% respectively, iron deficiency anaemia is diagnosed among children younger than 5 years.1,4 Erythrocyte protoporphyrin and serum transferrin receptors are other reliable markers of iron deficiency and iron deficiency anaemia, but they are mainly used for research purposes so far.1,4 Consequences of iron deficiency in early childhood
Considering the central role of iron in the carriage of oxygen from the lungs to the tissues, as well as its importance for several enzyme systems, myelination and neurotransmitter production, poor iron status can potentially become detrimental for several physiological features in the body.1,5,6 All physiological changes induced by poor iron status are reflected in clinical symptoms that range from being completely asymptomatic to varying degrees of weakness, fatigue, irritability, headache, poor exercise tolerance and work performance or even pica and pagophagia.3 Consequently, special attention should be laid upon prevention and early treatment of iron deficiency, in an attempt to avoid any negative effect to cognitive function, healthy growth and development of young children.
The prevalence of iron deficiency and the role of obesity
Iron deficiency and iron deficiency anaemia remain one of the most common and important nutritional deficiencies worldwide. According to the World Health Organization (WHO), iron deficiency anemia affects approximately 39% of children younger than 5 years in non-industrialized countries (i.e. least-developed countries, developing countries and economies in transition) and approximately 20% in developed countries based on blood haemoglobin concentration.1 In a more recent study from the National Health and Nutrition Examination Survey (NHANES), in which iron deficiency was defined based on transferrin saturation, free erythrocyte protoporphyrin and serum ferritin, demonstrated that the prevalence of iron deficiency is much higher among obese toddlers reaching a level of 20.3%, while for overweight and normal weight toddlers it was 8.1% and 7.1% respectively.7 The same pattern has also been observed in older children, since overweight or obese schoolchildren and adolescents were found to have two to four times higher prevalence of iron deficiency and iron deficiency anaemia in comparison to their normal weight counterparts.8-11
While in underdeveloped and developing countries inadequate diet or low iron intake and especially low haemic iron intake is the main reason behind poor iron status, this cannot explain the different prevalence of iron deficiency and iron deficiency anaemia between obese or overweight children and normal weight children in developed countries, since no difference in iron intake has been observed among these subgroups during childhood10 or adulthood.12 Consequently, another possible underlying mechanism has been proposed related to the inflammation status and increased fat mass among overweight and obese children. Based on this hypothesis, cytokines, released due to obesity’s inflammatory state, activate the gene expression of hepcidin in the liver and adipose tissue. While hepcidin’s main role is the decrease of iron absorption as well as its release from ferritin, the higher levels of hepcidin observed in overweight and obese children may mediate the low serum iron levels and consequently iron deficiency and iron deficiency anaemia. 10,13,14
Figure 1. Prevalence of iron deficiency and weight status of toddlers7
Figure 2. Prevalence of iron deficiency and iron deficiency anaemia according to weight status of school aged boys and girls9
- World Health Organization. Dept. of Nutrition for Health and Development., Iron deficiency anaemia : assessment, prevention and control : a guide for programme managers. 2001, Geneva: World Health Organization. 114 p.
- Assessing the iron status of populations: including literature reviews : report of a Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the Assessment of Iron Status at the Population Level, Geneva, Switzerland, 6–8 April 2004. – 2nd ed.
- Liu, K. and A.J. Kaffes, Iron deficiency anaemia: a review of diagnosis, investigation and management. Eur J Gastroenterol Hepatol, 2012. 24(2): p. 109-16.
- Caballero, B., L. Allen, and A. Prentice, Encyclopedia of human nutrition. 2nd ed. / editor-in-chief, Benjamin Caballero ; editors, Lindsay Allen, Andrew Prentice. ed. 2005, Amsterdam ; London: Elsevier Academic Press.
- Joint FAO/WHO Expert Consultation on Human Vitamin and Mineral Requirements and World Health Organization. Dept. of Nutrition for Health and Development., Vitamin and mineral requirements in human nutrition. 2nd ed. 2005, Geneva: World Health Organization. 341 p.
- Beard, J.L. and J.R. Connor, Iron status and neural functioning. Annu Rev Nutr, 2003. 23: p. 41-58.
- Brotanek, J.M., et al., Iron deficiency in early childhood in the United States: risk factors and racial/ethnic disparities.Pediatrics, 2007. 120(3): p. 568-75.
- Nead, K.G., et al., Overweight children and adolescents: a risk group for iron deficiency. Pediatrics, 2004. 114(1): p. 104-8.
- Manios, Y., et al., The double burden of obesity and iron deficiency on children and adolescents in Greece: the Healthy Growth Study. J Hum Nutr Diet, 2012.
- Aeberli, I., R.F. Hurrell, and M.B. Zimmermann, Overweight children have higher circulating hepcidin concentrations and lower iron status but have dietary iron intakes and bioavailability comparable with normal weight children. Int J Obes (Lond), 2009. 33(10): p. 1111-7.
- Pinhas-Hamiel, O., et al., Greater prevalence of iron deficiency in overweight and obese children and adolescents. Int J Obes Relat Metab Disord, 2003. 27(3): p. 416-8.
- Menzie, C.M., et al., Obesity-related hypoferremia is not explained by differences in reported intake of heme and nonheme iron or intake of dietary factors that can affect iron absorption. J Am Diet Assoc, 2008. 108(1): p. 145-8.
- Zafon, C., A. Lecube, and R. Simo, Iron in obesity. An ancient micronutrient for a modern disease. Obes Rev, 2010. 11(4): p. 322-8.
- del Giudice, E.M., et al., Hepcidin in obese children as a potential mediator of the association between obesity and iron deficiency. J Clin Endocrinol Metab, 2009. 94(12): p. 5102-7.