Biomarkers of Nutrition for Development (BOND)-Iron review

Sean Lynch, Christine M. Pfeiffer, Michael K. Georgieff, Gary Brittenham, Susan Fairweather-Tait, Richard F. Hurrell, Harry J. McArdle, Daniel J. Raiten

Research output: Contribution to journalReview articlepeer-review

185 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1001S-1067S
JournalJournal of Nutrition
StatePublished - Jun 1 2018

Bibliographical note

Funding Information:
Published in a supplement to The Journal of Nutrition. The Biomarkers of Nutrition for Development (BOND) project was developed by the nutrition program staff of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the NIH within the US Department of Health and Human Services (DHHS). The initial 6 nutrients selected, iodine, vitamin A, iron, zinc, folate, and vitamin B-12, were chosen for their high public health importance. Expert panels on each nutrient were constituted and charged with developing comprehensive reviews for publication in the BOND series. The BOND program received its core funding from the Bill & Melinda Gates Foundation, PepsiCo, the Division of Nutrition Research Coordination (DNRC, NIH), the Office of Dietary Supplements (ODS, NIH), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD, NIH). The Supplement Coordinators for this supplement were Daniel J Raiten (NICHD, NIH) and Jenica Abram, Academy of Nutrition and Dietetics (AND). Supplement

Funding Information:
Coordinators disclosures: no conflicts of interest. Publication costs for this supplement were defrayed in part by the payment of page charges. This publication must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact. The opinions expressed in this publication are those of the authors and are not attributable to the sponsors or the publisher, Editor, or Editorial Board of The Journal of Nutrition. Funding for the BOND project was provided, in part, by the Bill and Melinda Gates Foundation, the PepsiCo, the Office of Dietary Supplements (ODS), National Institutes of Health (NIH), the Division of Nutrition Research Coordination (DNRC), NIH and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH. The iron review was written in response to an invitation from NICHD, NIH within the US Department of Health and Human Services (DHHS). The content represents the views of the Iron Expert Panel (I-EP) and other invited contributors and does not necessarily reflect the official position of the NICHD, the NIH, the CDC/the Agency for Toxic Substances and Disease Registry, or the DHHS. In addition, individual members of © 2018 American Society for Nutrition. This work is written by (a) US Government employee(s) and is in the public domain in the US. Manuscript received March 31, 2017. Initial review completed May 27, 2017. Revision accepted November 7, 2017. First published online June 7, 2018; doi:

Funding Information:
the EP may not endorse all statements in this report. The original EP consisted of SL (chair), CMP, MG, GB, SFT, RFH, HJM, and DJR. The BOND project thanks the European Recommendations Aligned (EURRECA) program, the Micronutrient Genomics Project (MGP), the WHO and the CDC for their partnership. Author disclosures: SL, CMP, MKG, GB, SF-T, RFH, HJM, and DJR, no conflicts of interest. Supplemental Table 1 is available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at Address correspondence to DJR (e-mail: Abbreviations used: ACD, anemia of chronic disease; ACT, α1-antichymotrypsin; AGP, α1-acid glycoprotein; AOAC, Association of Official Analytical Chemists; APP, acute-phase protein; APR, acute-phase response; BMP, bone morphogenetic protein; BOND, Biomarkers of Nutrition for Development; BRINDA, biomarkers reflecting inflammation and nutrition determinants of anemia; CHr, reticulocyte hemoglobin content; CNPase, cyclic nucleotide 3-phophohydrolase; CRP, C-reactive protein; DCYTB, duodenal cytochrome b; DMT-1, divalent metal transporter 1; DR, dietary record; EFSA, European Food Safety Authority; EP, erythrocyte protoporphyrin; ERFE, erythroferrone; EuroFIR, European Food Information Resource; EURRECA, European Recommendations Aligned; FAO, Food and Agriculture Organization of the United Nations; FEP, free erythrocyte protoporphyrin; FPN, ferroportin; GAIN, Global Alliance for Improved Nutrition; HAMP, gene encoding hepcidin; HbE, hemoglobin E; Hct, hematocrit; HFE, human hemochromatosis; HIF-1, hypoxia inducible factor 1; HIF2α,hypoxia inducible factor 2α; HJV, hemojuvelin; ICSH, International Council for Standardization in Haematology; IDA, iron-deficiency anemia; I-EP, Iron Expert Panel; INSPIRE, Inflammation and Nutrition Science for Program/Policy and Interpretation for Research Evidence; IRIDA, iron-refractory iron-deficiency anemia; IRE, iron-responsive element; IRP, iron-regulatory protein; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; mTOR, mechanistic (mammalian) target of rapamycin; NaFeEDTA, sodium iron ethylene diamine tetraacetic acid; NRAMP2, natural resistance-associated macrophage protein 2; PSC, preschool children; PT, proficiency testing; QA, quality assessment; QC, quality control; RAS/RAF MAPK, rapidly accelerated fibrosarcoma mitogen-activated protein kinase; RDW, red blood cell distribution width; Ret He, reticulocyte hemoglobin equivalent; RNI, recommended nutrient intake; SF, serum ferritin; sHJV, soluble hemojuvelin; sTfR, serum (soluble, plasma) transferrin receptor; SMAD, sons of mothers against decapentaplegic; TB, tuberculosis; TfR, transferrin receptor; TIBC, total iron-binding capacity; TSAT, percentage transferrin saturation; T3, tri-iodothyronine; T4, thyroxine; TTSP, type-two transmembrane serine protease; UIBC, unsaturated iron binding capacity; WRA, women of reproductive age; ZPP, zinc protoporphyrin; ZPP/H, zinc protoporphyrin/heme ratio.

Publisher Copyright:
© 2018 American Society for Nutrition.


  • Iron
  • Iron biology
  • Iron biomarkers
  • Iron nutrition
  • Iron status assessment


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