For DEEP IMMUNE SUPPORT, evidence confirms that iron is fundamental for normal immune function and development. It is necessary for healthy maturation of lymphocyte immune cells, and for a balanced gut microbiome which strongly influences immunity. The chelate form, especially iron bisglycinate, is most effective for rebuilding the body’s iron stores. Iron is essential for red blood cells, which are key to strong immune activity. Also, iron has a direct role in the immune system’s ability to vanquish infection or clear damaged cells.
Research in recent decades overwhelmingly shows that iron deficiency impedes the body’s ability to mount an adequate immune response. It has long been recognized that low iron status can increase susceptibility to infectious disease. Conversely, infection and inflammation can disrupt iron balance in the body.1, 2
Metal ions, like the mineral iron, are crucial components of all living organisms and essential to maintain life. Iron, specifically, is required by most organisms as an essential cofactor in numerous important biochemical reactions of immune and non-immune cells. But iron can also be used by pathogens. Thus, a careful balance of iron in the body must be finely regulated to protect the host and deprive unwanted invaders of iron.
The links between iron’s roles, immune function, and risk of infection have been recognized since the 1970s:
- Iron is essential for microbial growth and metabolism, and for maintaining a healthy composition of the intestinal microbiota, an essential part of good immune function.
- Many of the genes involved in iron homoeostasis prevent noxious bacteria from utilizing iron for growth.
- Cells of the innate immune system including monocytes, macrophages, microglia and lymphocytes, are able to combat bacteria by carefully controlling their iron fluxes. Lymphocytes play an important role in adaptive immunity.
- A healthy inflammatory response requires iron to properly respond to bacterial insult.
- Iron is the crucial element for red blood cell formation. Long assumed to be just oxygen carriers, red cells are emerging as important for the innate immune response. They scavenge and bind pathogens they encounter in the circulatory system.
Immunity refers to the body’s ability to defend against infection and disease. The human immune system is broadly divided into two components: innate and adaptive immunity. Innate immunity is an inborn, natural, immediate response to foreign invaders. The innate immune response is primed and ready to fight at all times. Adaptive immunity requires more time as the body develops complex responses and memorization of pathogens. The adaptive immune response mounts a more gradual response to threats and infections. The adaptive immune system includes B cells and T cells, which are lymphocytes derived from specific stem cells. Because the adaptive immune system can learn and remember specific pathogens, it provides long-lasting defense against recurrent infections. When the adaptive immune system is exposed to a new threat, the specifics of the foreign material or antigen are memorized to prevent the disease from developing again. Adaptive immune B and T cells only function if they are able to control their correct iron content and balance.
Iron is crucial in red blood cells and in muscle cells, which all store oxygen. It also has key roles for energy production enzymes and for DNA formation. In the human body, much of the iron entering the circulation is recycled from aged red blood cells; a smaller amount is absorbed from the diet. When old red blood cells die, the body usually retrieves their iron, and recycles it into the next generation of red cells. If this retrieval process fails, the levels of iron and of its storage protein ferritin both drop. This happens faster if blood loss outstrips the amount of iron ingested; anemia with low hemoglobin can follow.
Poor iron levels reduce the body’s immune activity and ability to make red blood cells. Ferritin, the iron-storage protein, drops to low levels with iron deficiency. Low iron and hemoglobin levels can lead to poor oxygenation of tissues, resulting in immune dysfunction, frequent colds or flu, fatigue, or weakness. Taking an absorbable form of iron can boost immune resistance, rebuild ferritin iron stores, and improve fatigue.
Studies indicate that low iron can influence the course of infection in one of two ways: directly by impeding the body’s control of bacterial multiplication. In this case, alterations in the expression of molecules that transport or seize iron can have direct effects on pathogen growth. Secondly, poor iron indirectly leaves the immune system less able to mount an effective inflammatory response to defend against pathogens.3
Good iron availability plays an important role in healthy immune function and calming chronic inflammatory conditions. Iron-chelating molecules have a pivotal place in keeping iron levels stable. Iron sequestration is a strategy used by the body to restrict pathogen proliferation. Macrophages play a central role in this process, as they are involved in removing aged red blood cells to recycle iron. Under healthy inflammatory conditions, macrophages retain iron in ferritin. At the same time, iron export is inhibited due to inflammation-mediated events and release of a substance called hepcidin. Hepcidin binds to the iron-export protein ferroportin and breaks it down, to starve pathogens of iron.4
If iron supplements are not in an absorbable form, iron can pass through the intestine without being assimilated, and enter the colon where pathogenic bacteria utilize it for growth. The vast majority of microbes in the gut require iron for growth, and they have formulated many strategies to acquire this nutrient. Noxious bacteria make use of a continuous supply of micronutrients, including iron, for metabolism and replication. There is constant competition for iron between various bacteria.
A 2019 study investigated the effect of iron availability on human gut microbes. This in vitro study found that chelating iron to decrease its availability cut the abundance of pathogens within the gut bacterial community. Pure culture studies with pathogenic bacteria confirmed this observation. Taken together, these data suggest that undigested iron could feed potentially pathogenic bacteria within the colon. The findings highlight the necessity for well-absorbed iron. The relationship between iron availability and the human gut microbiome is still being discovered, and ongoing research will clarify improved methods for maintaining gut microbial homeostasis.5
In our clinic, we find that iron in a chelate form such as bisglycinate has major advantages over other formulations of iron. It is almost always non-constipating, and very rarely affects the frequency or texture of bowel movements, even for patients with a history of slow digestion or chronic constipation. Secondly, the iron is in a chelate form, attached to a derivative of the amino acid glycine, which is a protein building block, and so the body easily recognizes the combination. Iron chelates are especially well absorbed, far better than inorganic sulfate. This prevents colon pathogens from taking up iron, and leads to better hemoglobin and ferritin formation, and more effective immune boosting. We track our patients’ iron store by measuring blood levels of ferritin. If ferritin levels are low, only a highly absorbable iron will help, or months of supplement-ingesting would be ineffective. We aim for blood levels between 45 to 150 ng/mL.
Recommendation: Iron bisglycinate or chelate 25mg one to three times daily, with any meals, or as directed by your healthcare provider. The absorption of iron is gently enhanced in the presence of a mild food acid, such as citrus or balsamic vinegar.
- Wessling-Resnick M. Iron homeostasis and the inflammatory response. Annu Rev Nutr. 2010;30:105–22.
- Schaible UE, Kaufmann SH. Iron and microbial infection. Nat Rev Microbiol. 2004;2:946–53.
- Cherayil, Bobby J. “The role of iron in the immune response to bacterial infection.” Immunologic research 50.1 (2011): 1-9.
- Chieppa, Marcello, and Gianluigi Giannelli. “Immune cells and microbiota response to iron starvation.” Frontiers in medicine 5 (2018): 109.
- Parmanand, Bhavika A., et al. “A decrease in iron availability to human gut microbiome reduces the growth of potentially pathogenic gut bacteria; an in vitro colonic fermentation study.” The Journal of nutritional biochemistry 67 (2019): 20-27.
- Ward, Roberta J., et al. “Iron and the immune system.” Journal of neural transmission 118.3 (2011): 315-328.
- Soyano, Andres, and Miguel Gomez. “Role of iron in immunity and its relation with infections.” Archivos latinoamericanos de nutricion 49.3 Suppl 2 (1999): 40S-46S.
- Kuvibidila, S. R., et al. “The role of iron in immunity and inflammation: implications for the response to infection.” Diet, Immunity and Inflammation. Woodhead Publishing, 2013. 193-220.