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expert reaction to study investigating low dose iron treatments and DNA damage in human cells

Publishing in the journal PLOS One a group of scientists have reported that low dose iron medical treatments could modify the cells that they looked at and brought about DNA damage.


Dr Claire Clarkin, Lecturer in Developmental Biology, University of Southampton, said:

“This is an early observation at a single cell level and more research is required to confirm if an entire blood vessel composed of many cell types behaves in the same way. In addition, this study has focussed most of its efforts on gene expression however this is not always linked to a cell changing its function, often gene expression changes can be quickly remedied and  go unnoticed. Furthermore, increased numbers of endothelial cell donors are required to repeat the study in more individuals.”


Prof. Susan Fairweather-Tait, Professor of Mineral Metabolism, University of East Anglia, said:

“I have two major concerns about this study. Firstly, the dose of iron (10 µmol/L) was too high, and secondly, the form of iron (Fe(II)citrate) does not represent the form found in non-transferrin bound iron (NTBI) in vivo. Previous studies observed much lower concentrations of NTBI both in patients with different iron-overload disorders (de Swart et al, 2016) and in healthy women given a 60 mg iron supplement (Brittenham et al, 2014). Therefore, the use of 10 µmol/L to treat primary human endothelial cells cannot be described as “low dose iron treatment”.

“Furthermore, non-transferrin bound iron (NTBI) is circulating iron not bound to transferrin, ferritin or heme and in the plasma it comprises several subspecies, which may be classified by their chemical composition, chemical reactivity or susceptibility to chelation. The chemical composition of NTBI is heterogeneous and it is thought that there are several circulating isoforms: Fe(III) bound to albumin and citrate and potentially to acetate, malate and phosphate. Citrate has the highest affinity for Fe(III), and under physiological conditions two isoforms dominate: monomeric and oligomeric Fe(III) complexes. The use of Fe(II) citrate in the cell studies is therefore non-physiological.

“This study needs to be repeated using an lower dose of iron, in the form of Fe(III) citrate. The data generated using high doses of Fe(II) citrate cannot be extrapolated to the human in vivo situation.”


Low Dose Iron Treatments Induce a DNA Damage Response in Human Endothelial Cells within Minutes’ by Mollet et al. published in PLOS One on Thursday 11th February. 


Declared interests

Dr Claire Clarkin: No conflicts of interest

Prof. Susan Fairweather-Tate: “I am employed as a Professor of Human Nutrition (Mineral Metabolism) at the Norwich Medical School, University of East Anglia, and have grant income from BBSRC, MRC and the EC. I also work for the European Food Safety Authority, where I am an appointed expert for the NDA Panel and also a member of two Working Groups (Dietary Reference Values for Minerals and Health Claims). None of these activities can be considered to be a conflict of interest.”

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