Iron is essential for human biology, primarily functioning as the oxygen carrier in hemoglobin. It is also necessary for energy production, DNA synthesis, and numerous enzyme functions. Iron deficiency, or anemia, is a common global health issue leading to fatigue and impaired immune function. Despite this need, medical professionals typically withhold iron supplements during an active infection. This practice stems from a biological conflict between the human host and the invading pathogen over the limited supply of this metal.
Iron: An Essential Nutrient for Invading Pathogens
Nearly all living organisms, including the bacteria, fungi, and protozoa that cause disease, require iron for growth and survival. The metal’s ability to easily switch between its ferrous and ferric states makes it a necessary component in many fundamental metabolic processes. Pathogens use iron for energy generation, DNA synthesis, and cellular replication. The availability of iron can determine the severity of an infection.
The human body keeps the concentration of readily available iron extremely low, forcing microbes to develop complex strategies to obtain it. Bacteria, in particular, produce small, high-affinity molecules called siderophores. These compounds are secreted to chelate iron from host proteins and transport the nutrient back into the bacterial cell. The ability to produce these iron-scavenging molecules enhances a pathogen’s capacity to cause disease.
Nutritional Immunity: How the Body Hides Iron
The host’s defense strategy to limit the availability of essential nutrients to pathogens is known as nutritional immunity. Iron sequestration is the most well-studied example of this process, beginning almost immediately upon infection. The host achieves this by dramatically altering the systemic distribution of iron.
The central mechanism is the hormone hepcidin, produced in the liver. During infection, inflammatory signals stimulate its release, acting as the regulator of iron homeostasis. Hepcidin works by binding to and causing the breakdown of a protein called ferroportin, which is the sole known exporter of iron from cells.
By blocking ferroportin on cells like intestinal enterocytes and macrophages, hepcidin prevents dietary iron absorption and stops stored iron release into the bloodstream. This action effectively traps iron inside storage cells and rapidly lowers the concentration of free iron circulating in the blood, a condition called hypoferremia.
Other iron-binding proteins aid this sequestration effort, including transferrin, which tightly holds the majority of iron in the blood. Lactoferrin, a similar protein released by immune cells, also binds iron at sites of infection, making it inaccessible to microbes. This host-driven iron withholding is so effective that it causes a state known as “anemia of chronic inflammation” or “anemia of chronic disease,” which is a sign that the defense mechanism is functioning properly.
The Clinical Risk of Supplementing During Active Infection
Giving iron supplements during an active infection directly undermines the body’s natural defense strategy of nutritional immunity. By providing exogenous iron, the host’s careful sequestration efforts are bypassed, and the nutrient supply to the pathogen is increased. This influx of iron can accelerate microbial growth and enhance the expression of virulence factors, potentially worsening the infection.
Studies in animal models have demonstrated that administering intravenous iron can lead to higher morbidity and mortality in cases of severe infection. Clinical evidence suggests that iron supplementation, particularly intravenous iron, is associated with an increased risk of infection compared to no supplementation. A meta-analysis found that intravenous iron use was associated with a modest but significant increase in infection risk.
For this reason, major clinical guidelines recommend deferring iron administration until the acute infection is fully controlled with antimicrobial therapy. The practice of withholding iron is a safety measure based on sound biological principles that prioritize clearing the infection over correcting the anemia, which can be addressed once the patient has recovered.