Does iron deficiency cause low immunity?

Does Iron Deficiency Cause Low Immunity?

Yes, iron deficiency impairs both innate and adaptive immunity, leading to compromised immune function that increases susceptibility to infections and reduces vaccine responses. 1

Impact on Innate Immunity

Iron deficiency significantly compromises the body's first-line defense mechanisms:

• Iron is essential for the antimicrobial oxidative burst inside neutrophils, which is critical for killing pathogens. 1
• The binding activity of proinflammatory transcription factors requires adequate iron, affecting the inflammatory response needed to combat infections. 1
• Macrophage polarization and differentiation during infection depend on iron availability, impairing the ability to mount effective responses against invading microbes. 1

The innate immune system relies on iron for "nutritional immunity"—the host defense mechanism that limits iron availability to invading microbes through the hepcidin-ferroportin axis. 1 When iron deficiency exists, this delicate balance is disrupted, potentially compromising the body's ability to withhold iron from pathogens while maintaining adequate immune cell function.

Impact on Adaptive Immunity

The adaptive immune system is particularly vulnerable to iron deficiency:

T Cell Dysfunction

• Iron deficiency in both adults and children is associated with reduced proportions of mature T cells and impaired T cell activation and proliferation. 1
• Most iron intervention studies show beneficial effects of iron supplementation on T cell percentage, suggesting that correcting iron deficiency can restore impaired T cell responses. 1
• Lymphocytes express transferrin receptor 1 (TfR1) to import iron, and blocking this receptor inhibits proliferation and differentiation during early T cell development. 1
• A rare genetic mutation in TfR1 caused combined immunodeficiency with compromised T and B cell proliferation, demonstrating that the adaptive immune system is highly compromised when lymphocytes cannot acquire iron. 1

B Cell and Antibody Responses

• Recent studies demonstrate the importance of serum iron levels for primary and memory B cell responses, which directly influences vaccine efficacy. 1
• Iron-deficient mice show impaired B cell proliferation and attenuated antibody responses compared with control mice. 1
• A randomized birth cohort study in Kenyan infants showed that anemia and iron deficiency at time of vaccination predicted decreased responses to diphtheria, pertussis, and pneumococcal vaccines. 1
• Iron supplementation improved the primary response to measles vaccines in the same cohort. 1

Clinical Implications

The relationship between iron deficiency and immunity has important practical consequences:

• Iron deficiency can increase susceptibility to infections through impaired immune cell function. 2
• Vaccine responses may be suboptimal in iron-deficient individuals, particularly affecting protection against diphtheria, pertussis, pneumococcal disease, and measles. 1
• Iron supplementation in iron-deficient patients can boost immunity and improve vaccine responses. 1

Important Caveats

While iron deficiency impairs immunity, the evidence shows methodological heterogeneity and quality issues in many studies, including inadequately powered designs, absence of placebo groups, and potential confounding by baseline iron status and comorbidities. 1 This makes it difficult to draw unequivocal conclusions about the quantitative relationship between iron deficiency and immune dysfunction. 1

The body's iron-withholding response during infection is a protective mechanism, and excessive iron supplementation during active infection could theoretically provide iron to pathogens. 3 However, this concern applies primarily to excess supplementation rather than correction of deficiency. 3

Practical Approach

When evaluating patients with recurrent infections or poor vaccine responses:

• Assess iron status using ferritin, transferrin saturation, and hemoglobin to identify iron deficiency. 1
• Consider iron supplementation in iron-deficient patients to restore immune function, particularly before vaccination. 1
• Monitor for improvement in T cell percentages and clinical infection rates after iron repletion. 1
• In malaria-endemic regions, balance iron supplementation with antimalarial interventions, as oral iron has been associated with increased clinical malaria in some studies. 4