Findings from a study published in the journal Oncotarget demonstrate that two iron compounds, ferric citrate and ferric EDTA, have the potential to induce the formation of a known cancer biomarker called amphiregulin. 

In the U.S., ferric citrate is commonly found in dietary supplements and ferric EDTA is often used as a food additive. In previous  studies, both chelated iron compounds have been shown to worsen tumor growth in murine models with colon cancer. For this study, researchers from Chalmers University of Technology, Sweden, examined the effect of normal supplement doses of these compounds on 2 types of cultured human colon cancer cells (Caco-2 and Hutu-80) and compared this effect with another common iron compound, ferrous sulfate.

The researchers observed increased levels of amphiregulin and its receptor (EGFr) with ferric citrate and ferric EDTA even at low doses while ferrous sulfate had no effect. In addition, the presence of ferric citrate and ferric EDTA resulted in activation of the MAP kinase pathway. 

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Lead author, Nathalie Scheers, said, “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.” She added that although the study was performed on cultured human cancer cells, “the possible mechanisms and effects observed still call for caution,” and additional studies are needed. 

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