A new study finds that two iron compounds, which are used in supplements and food additives, raise levels of a cancer biomarker — even when consumed in low amounts.
iron supplements
Certain iron supplements may raise the risk of colorectal cancer, a study shows.

The new research comes from the Chalmers University of Technology in Gothenburg, Sweden, in collaboration with the United Kingdom Medical Research Council and the University of Cambridge, also in the U.K.

The scientists — led by Nathalie Scheers, an assistant professor at the Chalmers University of Technology — explain that their research was prompted by older studies that showed that two compounds, called ferric citrate and ferric EDTA, promote tumors in mice.

But, these previous studies did not reveal “whether all forms of ‘bioavailable’ iron exacerbate gut cancer cells,” or whether different forms of iron display the same mechanism.

So, in the new study, Scheers and colleagues examined the effect of these two compounds on the growth of human colorectal cancer cells. Additionally, they tested another widely available iron compound called ferrous sulfate.

In their experiment, the researchers used levels of the compounds that might realistically be found in the gastrointestinal tract after taking the supplement.

To their knowledge, Scheers and colleagues are the first to study the effect of these compounds on human cells. The researchers published their findings in the journal Oncotarget.

Ferric citrate, EDTA may be carcinogenic

Scheers and her team used a range of techniques, including cell proliferation assays and Western blot analysis, to carry out their investigation.

The study revealed that even in low amounts, both ferric citrate and ferric EDTA raised cellular levels of a cancer biomarker called amphiregulin and its receptor. By contrast, ferrous sulfate had no such effect on the cells.

“[S]pecific iron compounds affect cell signaling differently, and some may increase the risk of colon cancer advancement in an amphiregulin-dependent fashion,” the authors write.

Scheers comments on the findings, saying, “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.”

However, Scheers adds, “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.”

The problem with iron supplements

Ferric citrate, often marketed as Auryxia, is a widely available iron supplement used to treat anemia in people with chronic kidney disease.

In some countries, ferric EDTA is sometimes added to cereals, flour, or powdered drinks. In the United States, the Food and Drug Administration (FDA) approved the use of ferric EDTA as a food additive to a variety of sauces, including soy sauce, sweet and sour sauces, teriyaki, and fish sauce.

Iron supplements are used medically by pregnant women, people who have lost blood, and patients with chronic kidney disease, among others. The researchers warn that these groups of people might be at a higher risk of consuming harmful levels of the carcinogenic chemical.

The authors caution that consumers may find it difficult to discern between iron supplements because “[m]any 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,” Scheers adds. “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.”

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.”

Nathalie Scheers

“But, speaking personally, if I needed an iron supplement, I would try to avoid ferric citrate,” she concludes.