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Human biomarkers for measuring iron intake and status

Biomarkers of iron status have been developed to characterize the stages of increasingly severe degrees of iron deficiency that would occur in an individual whose iron intake does not meet his or her requirements. Three stages are generally recognized: storage iron depletion, iron-deficient erythropoiesis, and iron-deficiency anaemia. Currently available biomarkers make it possible to categorize the severity of iron deficiency in individuals. They are also employed in population studies to determine the prevalence of iron deficiency and to differentiate between iron-deficiency anaemia and anaemia due to infection and other factors (2).

An estimate of the prevalence of anaemia derived from the haemoglobin concentration alone does not allow the contribution of iron deficiency to anaemia to be estimated, and ignores the role of other causes of anaemia. Therefore, when assessing the prevalence of iron deficiency with or without anaemia, and to plan effective interventions to combat both iron deficiency and anaemia, there is an urgent need to have better information on the iron status of populations. This will enable the right interventions to be chosen and once programmes are in place, to have the right indicators to monitor their impact (1).

RECOMMENDATIONS FROM WHO ON ASSESSING THE IRON STATUS OF POPULATIONS

(extracted from World Health Organization. 2007. 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. 2nd ed., Geneva, Switzerland.)

Important information

Haemoglobin concentration should be measured, even though not all anaemia is caused by iron deficiency. The prevalence of anaemia is an important health indicator and when it is used with other measurements of iron status the haemoglobin concentration can provide information about the severity of iron deficiency.

Measurements of serum ferritin and transferrin receptor provide the best approach to measuring the iron status of populations. In places where infectious diseases are common, serum ferritin is not a useful indicator because inflammation leads to a rise in the concentration of serum ferritin because of the acute phase response to disease. If infectious diseases are seasonal, then the survey should be done in the season of lowest transmission. In general, the concentration of transferrin receptor does not rise in response to inflammation so that, when combined with the concentration of serum ferritin, it is possible to distinguish between iron deficiency and inflammation.

It can be useful also to measure the concentration of an acute phase protein, if funding is available. The most commonly measured acute phase protein is CRP, but there is evidence that AGP may better reflect the change in concentration of ferritin in serum and may be the most useful acute phase protein to measure. Several commercial assays are available for measuring these proteins but, except for CRP, there are no international reference standards available, resulting in reference ranges specific to each assay. In such circumstances, the threshold recommended by the manufacturer should be used.

Serum ferritin is the best indicator of a response to an intervention to control iron deficiency and should be measured with the haemoglobin concentration in all programme evaluations. In circumstances in which iron deficiency is the major cause of anaemia, the haemoglobin concentration may improve more rapidly than the serum ferritin concentration. In circumstances in which the serum ferritin concentration improves (even when inflammation is common) but the haemoglobin concentration does not, factors in addition to iron are likely to be the cause of anaemia.

If funding is available, it could also be useful to measure the concentration of one or both of the acute phase proteins CRP or AGP, to account for a high serum ferritin concentration caused by inflammation. Individuals with high values for the acute phase protein should be excluded from the analysis, if possible, depending on the limitations imposed by the sample size of the dataset and the consequent translation of the results to define the iron status of the general population. This is particularly important when repeated surveys are done and there is no control group for the intervention.

If funding is available, the transferrin receptor should be measured during repeated surveys to classify populations. The combination of serum ferritin and transferrin receptor may also be used to estimate body iron stores in populations (12). The calculation of body iron stores is not essential but can be useful to estimate the amount of iron that is absorbed during an intervention and to demonstrate a decrease in iron deficiency. However, since the method uses measurements of serum ferritin concentration, infection may again be a confounding factor, so an acute phase protein should be measured to exclude individuals with a high concentration.

OpeN-Global readers are directed to the following open-access publications for recommendations and advice on population iron status assessment and interpretation of survey data:

World Health Organization. 2007. 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. 2nd ed., Geneva, Switzerland.

Lynch S, Pfeiffer CM, Georgieff MK, Brittenham G, Fairweather-Tait S, Hurrell RF, McArdle HJ, Raiten DJ 2018 Biomarkers of Nutrition for Development (BOND)-Iron Review. J Nutr 148:1001S-1067S.

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Laboratory Methods

Laboratory methods of iron analysis and standard operating procedures will be uploaded to OpeN-Global when available. If you have any questions meanwhile, please contact us.

 

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