Cell study links iron to certain cancer markers

By Tim Cutcliffe contact

- Last updated on GMT

Ferric citrate and ferric EDTA, are often used in dietary supplements and as a food additive respectively, in worldwide markets including the USA and the EU. (Picture credit: Yen Strandqvist/Chalmers University of Technology)
Ferric citrate and ferric EDTA, are often used in dietary supplements and as a food additive respectively, in worldwide markets including the USA and the EU. (Picture credit: Yen Strandqvist/Chalmers University of Technology)
The increased formation of a known biomarker for colon cancer has been linked to two forms of iron in commonly used supplements, say researchers.

The cell line study found increased levels of a recognised cancer biomarker known as amphiregulin when human colon cancer cells were treated with ferric citrate and ferric ETDA (ethylenediaminetetraacetic acid) in laboratory conditions.

According to the team - a collaboration between Chalmers University, Gothenburg, the UK Medical Research Council and Cambridge University - the effect occurred even at low doses of the two ferric compounds.

However, as no increase in amphiregulin was found using ferrous sulphate, said the researchers who emphasised that the potential carcinogenic effect was not due to iron itself.

"We can conclude that ferric citrate and ferric EDTA might be carcinogenic, as they both increase the formation of amphiregulin, a known cancer marker most often associated with long-term cancer with poor prognosis,"​ commented first author Nathalie Scheers, Assistant Professor at Chalmers University of Technology.


Previous mouse studies have shown that the two ferric compounds increase the formation of tumours in mice with colon cancer. The researchers therefore wanted to identify whether iron citrate and iron EDTA had the same effect in human colon cancer cells.

Ferric citrate has been marketed as gentler on the stomach and more bioavailable than ferrous sulphate, the most common supplementary form of iron. Ferric EDTA is used globally in iron-fortified foods and in some countries in medicines to treat iron deficiency.

Although the study is preliminary, the findings warrant further scrutiny of safe oral iron use, the researchers emphasised.

"First, we must bear in mind that the study was done on human cancer cells cultured in the laboratory, since it would be unethical to do it in humans. But, the possible mechanisms and effects observed still call for caution. They must be further investigated," ​said Scheers.

"At the moment, people should still follow recommended medical advice. As a researcher, I cannot recommend anything: - that advice needs to come from the authorities. But speaking personally, if I needed an iron supplement, I would try to avoid ferric citrate,"​ she added.

Type of iron critical

"Many stores and suppliers don't actually state what kind of iron compound is present - even in pharmacies. Usually it just says 'iron' or 'iron mineral', which is problematic for consumers​," explained Scheers.

The importance of differentiating between different types of iron is therefore essential.

“Most importantly, researchers and authorities need to start to distinguish between this form of iron and that form of iron. We need to consider that different forms can have different biological effects,"​ Scheers concluded.

Source: Oncotarget
Volume 9, pages 17066-17077, published online, doi: 10.18632/oncotarget.24899
“Ferric citrate and ferric EDTA but not ferrous sulfate drive amphiregulin-mediated activation of the MAP kinase ERK in gut epithelial cancer cells”
Authors: Nathalie M. Scheers, Dora I.A. Pereira, Nuno Faria and Jonathan J. Powel

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