Iron fortification: health risks of excessive iron intake

Iron is an essential mineral required for many bodily functions, including the formation of hemoglobin, but it can be harmful when taken in excess. One of the suggested methods of treating iron deficiency anemia is the enrichment of food with iron. Typically, a chosen staple food such as wheat or rice, or even salt, is fortified to provide up to two-thirds (10 mg/day) of adult women’s iron needs and nearly all of men’s daily iron needs. Therefore, excessive consumption of iron can occur if you habitually consume a balanced quality diet to start with or if you exceed the limits for the consumption of the fortified food (as can happen with staple foods such as rice or wheat) or if you consume two fortified foods.

Additionally, when combined with additional iron supplemental interventions such as weekly iron folic acid supplements (as in the National Iron Plus Initiative program), this can lead to excess iron intake for women. There is a defined level of iron intake beyond which the risk of adverse events begins to increase. This is called the tolerable upper limit of intake and is set at 40 mg/day.

While this is relevant for populations with normal iron stores, it may be particularly deleterious for populations that have iron overload states such as patients with thalassemia and other hemolytic anemias, hemochromatosis, and chronic liver disease, who have mechanisms of iron excretion compromises.

Once iron is absorbed, its excretion is thought to be constant and very little, except when bleeding occurs, as in the case of menstrual bleeding. Therefore, women can excrete iron from the body, but men cannot, unless they have some form of pathological or abnormal bleeding. This makes men especially vulnerable to excessive iron intake.

Iron transactions in the body are complex. Recent studies using stable isotope iron to accurately understand iron balance (absorption and excretion), conducted in the United States and Africa, have shown that with fortification there is an increase in iron excretion in children, such that the body tries to get rid of the excess absorbed iron. It is not known exactly how, or by what route, this extra excretion occurs. for excretion or through urine. We do not know the consequences of this form of body iron loss, nor of the crosstalk between body iron stores and this excretion. However, beyond excess reserves, the net effect of iron intake through enrichment on hemoglobin formation is likely to be less than thought.

As stated earlier, to the extent the body can, it will try to regulate iron absorption. However, excess iron in the fortified diet can remain unabsorbed. Typically, only 5-10% of ingested iron, from the added iron salt, is expected to be absorbed. The remainder passes through the intestines and reaches the large intestine (colon) before excretion. Studies have shown that unabsorbed iron can lead to inflammation in the gastrointestinal lining and disrupt the colonic microbiota with long-term consequences. This is due to a proliferation of living iron bacteria in the colonic microbiome and a reduction of beneficial strains such as lactobacteria, with the emergence of some bacterial strains that may be pathogenic. This lining irritation may present clinically as abdominal cramps, constipation, or diarrhea.

In addition, mucosal irritation can also lead to gastrointestinal blood loss, as has been described in endoscopic studies of patients receiving iron supplementation. An excess of iron in the gastrointestinal tract can impair the absorption of other minerals such as zinc and copper, which are also essential for the body and lead to other deficiencies.

A more pressing concern is that excess iron has been closely linked to many chronic comorbidities such as diabetes. The risk of diabetes is increased in people with higher dietary iron intakes and higher iron stores (represented by high levels of a storage molecule called ferritin) even in the absence of markers of inflammation. This is attributed to many causes including oxidative damage and destruction of beta cells by reactive oxygen species (ROS) which could lead to decreased insulin secretion. Iron can generate ROS and lead to oxidative stress in the body.

Oxidative stress can, in turn, lead to damage to cells, proteins and DNA with long-term consequences. This chronic oxidative stress leads to impaired mitochondrial oxidation of long-chain fatty acids. This abnormal fat oxidation leads to excessive serum triglycerides and excessive accumulation of triglycerides in muscle and liver tissues. This is relevant to India.

An analysis of data on blood biomarkers of chronic disease risk (such as glucose and lipids) from the Comprehensive National Nutritional Survey in Indian adolescents aged 10 to 19 years showed that for every 10 mcg/L increase in ferritin serum, reflecting the storage status of iron, the risk of having elevated fasting blood glucose, total cholesterol, triglycerides and hypertension increased proportionately. A scenario analysis of these data showed that if an additional 10 mg of iron/day was provided (by fortification), the prevalence of elevated fasting serum glucose levels could increase by 2-14% across socioeconomic groups.

In very high amounts, iron also has a role to play in the activation of hepatic stellate cells (HSCs) and excessive extracellular matrix deposition in the liver. This can lead to liver fibrosis, with subsequent progression to cirrhosis. When the liver iron concentration (LIC) exceeds a threshold of 60 mol/g, HSC function begins to deteriorate, and cirrhosis can occur at LIC levels above 250 mol/g.

Even though iron fortification has been successful in addressing iron deficiency, it’s important to consider the dangers of consuming too much iron. Rather than adopting mandatory iron fortification programs where unsupervised high iron intakes are instituted in a diverse population, it is imperative to develop individualized strategies and ensure thorough monitoring to detect any adverse events at the earliest. There’s no question that some segments of the population need extra iron in their diets, but not all.

Ultimately, accuracy in public health is essential if we are to avoid the risk of iron overload and the potential for long-term chronic disease from excess iron. As a public health strategy, the pendulum should not swing completely the other way.

(Anura Kurpadis Professor of Physiology and Jananee Muralidharanis Assistant Professor of Medicineat St. Johns Medical College, Bangalore. The opinions expressed are personal.)