Can an infection decrease serum iron levels and percent transferrin saturation?

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From the Guidelines

Yes, an infection can lower serum iron levels and percent saturation. During infection, the body activates an immune response that includes the production of cytokines, which trigger a process called the acute phase response. This response includes the sequestration of iron within cells, particularly in the liver and macrophages, reducing circulating iron in the bloodstream. The body does this intentionally as a defense mechanism against pathogens, many of which require iron for growth and replication. Additionally, the liver increases production of hepcidin, a hormone that regulates iron metabolism by blocking iron absorption from the gut and iron release from storage sites. This results in decreased serum iron levels and reduced transferrin saturation percentage, a condition known as anemia of inflammation or anemia of chronic disease. These changes can occur rapidly, often within 24-48 hours of infection onset, and may persist throughout the duration of the infection. Once the infection resolves, iron parameters typically return to normal, though this may take several weeks depending on the severity and duration of the infection, as supported by the most recent study 1.

Some key points to consider:

  • Infection leads to increased hepcidin production, which reduces iron export from macrophages and decreases transferrin saturation, as noted in 1.
  • The acute phase response during infection causes sequestration of iron within cells, reducing circulating iron levels, as discussed in 1.
  • Serum ferritin levels may appear normal or elevated during infection due to its role as an acute phase protein, making it less reliable for diagnosing iron deficiency in this context, as explained in 1.
  • Transferrin saturation and serum iron levels are more directly affected by the acute phase response and hepcidin regulation during infection, as shown in 1.

Overall, the evidence suggests that infection can significantly impact iron metabolism, leading to decreased serum iron levels and percent saturation, primarily through the mechanisms of hepcidin regulation and the acute phase response.

From the Research

Infection and Iron Levels

  • Infections can lead to a decrease in serum iron and percent saturation due to the body's natural response to infection, which involves the sequestration of iron to limit its availability to pathogens 2, 3, 4.
  • The hormone hepcidin plays a key role in regulating iron homeostasis during infection, and its induction can lead to a decrease in serum iron and percent saturation 5, 2, 4.
  • Studies have shown that low serum iron and percent saturation are associated with a better prognosis in critically ill patients, particularly those with sepsis 3.

Mechanisms of Iron Sequestration

  • During infection, the body increases the production of hepcidin, which binds to the iron exporter ferroportin and reduces iron availability in the serum 5, 2, 4.
  • This reduction in iron availability limits the growth of pathogens and is an important mechanism of host defense 2, 6, 4.
  • However, chronic immune activation and inflammation can lead to anemia of chronic inflammation, which is characterized by low serum iron and percent saturation 4.

Clinical Implications

  • The relationship between iron and infection highlights the importance of considering iron homeostasis in the management of infectious diseases 2, 3, 4.
  • Iron supplementation should be used with caution in patients with infections, as it can potentially exacerbate the infection by providing iron to the pathogen 2.
  • Further research is needed to fully understand the complex interactions between iron and immunity, and to develop effective strategies for managing iron homeostasis in patients with infections 6, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Infections Associated with Iron Administration.

Metal ions in life sciences, 2019

Research

Iron in infection and immunity.

Molecular aspects of medicine, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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