EFSA establishes new safe level for iron intake

In a report published on June 12, EFSA's Panel on Nutrition, Novel Foods and Food Allergens (NDA)​ concluded there is not enough evidence to establish a TUI for iron—a maximum intake level that can be consumed daily over a lifetime without adverse health effects.

Instead, it has agreed on a 'safe level', which is the maximum amount it can confidently conclude poses no risk of adverse effects in the general population.

The level is based on the data related to the occurrence of black stools—an indication of significant unabsorbed iron in the GI tract and may be a first sign of iron metabolism dysfunction prior to iron overload and toxicity.

Data suggests that black stools do not occur at supplemental iron intakes of 20 to 25 mg/day (added to a background intake of 15 mg/day), therefore the panel established a safe level of intake for iron of 40 mg/day for adults (including pregnant and lactating women).

Allometric scaling was then used to confirm safe levels for children: 10 mg/day for those between the ages of 1 and 3 years; 35 mg/day for those between 15 and 17 years; and 5 mg/day for infants between 4 and 11 months, covering iron intakes from fortified food and food supplements but not from infant or follow-on formula.

These do not apply to individuals who receive iron under medical supervision as a treatment for iron deficiency anaemia.

The iron issue

Controlling anemia is a global health priority for the World Health Organization (WHO), which aims to cut anemia prevalence in women in half by 2025.

Iron deficiency anemia mainly affects premenopausal and pregnant women, growing children and the elderly, however, it is also increasingly recognized as a complication of multiple diseases associated with lifestyle and dietary patterns, such as obesity, inflammatory bowel disease, colorectal cancer or chronic kidney disease

There are many different types of oral iron supplements available but the most commonly prescribed oral iron is ferrous sulphate. Ferrous iron supplements are effective; however, they have a high frequency of side effects in comparison to ferric iron sources. In fact, up to 60% of people​ taking oral iron supplements report gastrointestinal side effects.

Common side effects include oxidative stress, stomach pains, constipation, diarrhea, loss of appetite, nausea and dark stools.

This is due to the poor bioavailability and excretory mechanism of iron supplements in the body, leading to a build-up and oxidative reactions. Long-term overdosing of the mineral has even been linked with colon cancer biomarkers​.

Nélida Leiva Eriksson, associate professor at Lund University, Sweden and founder of Ironic Biotech​, a start-up that aims to bring a truly bioavailable new source of iron to market, said this update raises awareness of the toxicity of iron supplements.

"This has been ignored for a long time, and that is why it is not uncommon to find pills of up to 360 mg on the market, and pregnant women receive doses higher than 60 mg."

Efforts to establish a safe limit​

In 2004, EFSA’s NDA Panel published a scientific opinion stating that the data available at that time were insufficient to establish an upper limit for iron.

The European Commission therefore requested a review of this scientific opinion based on newly available evidence.

The University of Copenhagen, in collaboration with the University of Oslo and the Karolinska Institutet, conducted a systematic literature review of human intervention and observational studies for EFSA. Based on this evidence, the panel assessed the potential negative impact on health related to high iron intake.

It again found insufficient data to determine an upper limit for iron and instead advised on the maximum amount that EFSA can confidently conclude poses no risk of adverse effects in the general population, referred to as the safe level of intake.

The panel also provided recommendations for the research community, suggesting the need to investigate: the effect of increasing doses of (haem and non-haem) iron on GI tract physiology, pathology and on the microbiome, the mechanisms of interactions between high intakes of iron and the absorption and metabolism of other minerals (such as copper, zinc, calcium and manganese), the physiological limits for iron homeostasis, and the level of iron absorption for high iron intakes over a prolonged period of time.