Why is Iron so Important for your Immune System?

Iron is the most common element by mass on earth, and it’s required by all forms of life for a vast range of cellular processes. 

You’ve likely heard that iron is an essential component of hemoglobin, the substance in red blood cells that transports oxygen from your lungs to the rest of your body. This is why fatigue is a common symptom of iron deficiency because, without enough iron, you simply aren’t getting enough oxygen to all your cells.

A less publicized fact is that iron is also vital for your immune system. One scientific review concluded that “almost every effector of the immune response is limited in number or action by experimental iron deficiency.” (1) In other words, every aspect of your immune system will be impaired by inadequate iron levels in your body.

Iron is fundamental for the growth and development of individual immune cells, such as white blood cells. (2) It is also essential for many other cellular functions within your immune system. What follows are some of these essential functions and how iron is involved.

Enzyme Function

Iron is a critical component of certain enzymes that are required for immune cells to work properly.

For example, neutrophils are the most common type of white blood cell, making up 55 to 70 percent of your total white blood cell count. (3) Neutrophils are “first responders” that constantly circulate throughout your body. They will actively attack pathogens and help coordinate an immune response when a pathogen or injury is detected. 

One of their specialized tools for killing pathogens is an enzyme called myeloperoxidase. When neutrophils find a pathogen, they will attach themselves to the outside of the invading cell and inject a slurry of toxic chemicals that will quickly kill the cell. Myeloperoxidase is essential to this process. It assists with the synthesis of many of the toxic chemicals needed to kill the pathogen. (4)

Perhaps it’s no surprise that iron is a vital component of myeloperoxidase. Studies have shown that iron deficiency reduces the activity of myeloperoxidase, which reduces the ability of neutrophils to kill pathogens. (5)

In similar ways, a wide variety of other immune cells require iron-containing enzymes to function properly.

Regulation of Oxidation

Oxidation is a natural process throughout your body, but it can become harmful when it gets out of balance.

Oxidation refers to the chemical process of atoms losing electrons. When an atom has been oxidized, it simply means that it has lost an electron, which has been taken by another atom. 

Chemical reactions are continuously going on throughout your body, which includes an ongoing exchange of electrons between atoms to maintain balance. Atoms that remain unbalanced, with an uneven number of electrons, are known as free radicals. Free radicals are more reactive in your body due to their electron imbalance, and too many of them can start damaging your tissues and lead to chronic disease over time.

Iron is one of many elements that help regulate electron exchange and maintain balance during these reactions, including within your immune system.

Iron is particularly well-suited to help regulate electron exchange because it can exist in two different oxidation states in your body. An iron atom can exist as ferrous iron (Fe2+) or ferric iron (Fe3+). Ferrous iron has one more electron than ferric iron. And because it exists in these two forms, iron can accept or donate electrons to other atoms in your body when needed. (6)

This allows iron to assist chemical reactions and prevent the creation of excessive free radicals. In turn, this helps support a vast number of cellular functions and protects tissues from free radical damage.

Nutritional Immunity

The fact iron can have two different electrical charges is beneficial for balancing chemical reactions. But iron’s reactivity can become harmful when you have too much.

Excessive iron atoms in your body essentially act like free radicals and can be toxic to cells. This is why iron levels are strictly regulated in your body. Your body includes a complex system of checks and balances to maintain your iron balance, also known as homeostasis. 

A primary strategy to prevent excessive accumulation of iron is to regulate iron’s entry into your system. (7) This is one reason why many of us struggle to absorb iron from food and supplements because your body actively prevents the absorption of iron to help maintain balance.

Although, your body’s ability to tightly regulate iron levels is also an important part of your immune system. Like all living things, pathogens require iron for healthy development and functioning. 

When your immune system detects an infection, it immediately starts to remove circulating iron from the infection site to make it unavailable to the pathogen. At the same time, your body also ensures that iron remains available for all vital immune functions. This finely-tuned immune process is known as nutritional immunity, and it’s shown to be quite effective for controlling infections. (8)

Restricting iron from an invading pathogen is so effective, iron supplementation has actually been shown to be potentially detrimental for immunity. For example, a scientific review on how iron affects malaria concluded, “In humans, iron deficiency appears to protect against severe malaria, while iron supplementation increases risks of infection and disease.” (9) 

Iron supplementation has been shown to benefit those who are iron deficient, and supplementation lowers their risk of becoming infected with malaria. But those who take iron supplements when they are not iron deficient actually have an increased risk of infection. (10)

This shows the importance of iron homeostasis in your body, as well as the significant effect iron can have on the function of your immune system.

Conclusion

Iron is involved in nearly every aspect of your immune system, from the creation of white blood cells to supporting the function of essential enzymes.

Iron can also act as an antioxidant, assisting chemical reactions in your body and immune system and preventing the creation of harmful free radicals.

Your immune system can also use iron as a type of defense by regulating how much iron is available to invading pathogens, a process known as nutritional immunity.

Iron is vital for proper immune function, but for those who eat a primarily plant-based diet, certain compounds in grains and other seeds can bind to iron and prevent its absorption. 

Click here for more information on how you can make sure you’re absorbing all the iron possible in plant-based foods.

 

References

(1) Beard JL. Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr. 2001;131(2):568S-580S.

(2) Beard JL. Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr. 2001;131(2):568S-580S.

 (3) American Society of Hematology. Blood Basics. American Society of Hematology Website. https://www.hematology.org/Patients/Basics. Accessed January 20, 2020.

(4) Klebanoff SJ. Myeloperoxidase: friend and foe. J Leukoc Biol. 2005;77(5):598–625. 

(5) Spear AT, Sherman AR. Iron deficiency alters DMBA-induced tumor burden and natural killer cell cytotoxicity rats. J Nutr.1992;122(1):46–55.

(6) Cassat JE, Skaar EP. Iron in infection and immunity. Cell Host Microbe. 2013;13(5):509–519. 

(7) Hallberg L, Hulthen L. Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. Am J Clin Nutr. 2000;71(5):1147-60.

 (8) Cassat JE, Skaar EP. Iron in infection and immunity. Cell Host Microbe. 2013;13(5):509–519. 

 (9) Spottiswoode N, Duffy PE, Drakesmith H. Iron, anemia and hepcidin in malaria. Front Pharmacol. 2014;5:125. 

 (10) Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ, Dutta A, Dhingra U, et. al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet. 2006;367(9505):133-43.