Biomarkers of Nutrition for Development (BOND)-Iron Review

Abstract

This is the fifth in the series of reviews developed as part of the Biomarkers of Nutrition for Development (BOND) program. The BOND Iron Expert Panel (I-EP) reviewed the extant knowledge regarding iron biology, public health implications, and the relative usefulness of currently available biomarkers of iron status from deficiency to overload. Approaches to assessing intake, including bioavailability, are also covered. The report also covers technical and laboratory considerations for the use of available biomarkers of iron status, and concludes with a description of research priorities along with a brief discussion of new biomarkers with potential for use across the spectrum of activities related to the study of iron in human health.The I-EP concluded that current iron biomarkers are reliable for accurately assessing many aspects of iron nutrition. However, a clear distinction is made between the relative strengths of biomarkers to assess hematological consequences of iron deficiency versus other putative functional outcomes, particularly the relationship between maternal and fetal iron status during pregnancy, birth outcomes, and infant cognitive, motor and emotional development. The I-EP also highlighted the importance of considering the confounding effects of inflammation and infection on the interpretation of iron biomarker results, as well as the impact of life stage. Finally, alternative approaches to the evaluation of the risk for nutritional iron overload at the population level are presented, because the currently designated upper limits for the biomarker generally employed (serum ferritin) may not differentiate between true iron overload and the effects of subclinical inflammation.

FIGURE 1

Factors regulating hepcidin. Fpn, ferroportin. Reproduced with permission from reference .

FIGURE 2

Diagrammatic portrayal of the BBB and the iron transport proteins believed to play a role in iron movement into the brain. BBB, blood-brain barrier; CSF, cerebrospinal fluid; DMT1, divalent metal transporter 1; Frt, ferritin; FrtR, ferritin receptor; MTP, metal transport protein or ferroportin; Tf, transferrin; TfR, transferrin receptor. Reproduced with permission from reference .

FIGURE 3

Biomarkers of iron status during pregnancy and 6 wk postpartum in 31 apparently healthy Dutch women. The participants in this study were >18 y old with an expected normal pregnancy based on a normal hematologic blood count, renal function, and liver enzymes at their first visit. Iron supplements were not routinely prescribed and were reserved for those with hemoglobin concentrations <105 g/L and reduced mean cell volume (<80 fL) in accordance with national guidelines. Data are shown as medians with the IQR. Asterisks represent the significance in relation to first trimester values; analyzed with linear mixed models, *P < 0.05, **P < 0.001, ***P < 0.000. sTfR, soluble transferrin receptor; sTfR-index, sTfR divided by log ferritin; TIBC, total iron-binding capacity. Reproduced with permission from reference .