What are the risks of iron supplementation?

Iron is an essential micronutrient for all living beings. When we battle infectious diseases, both pathogens and our own immune cells need iron to reproduce and carry out their functions. Locking the iron away from micro-organisms is an effective strategy for defending our bodies, but pathogens aren't amateurs, either: over millions of years they have developed countless mechanisms to access the body's iron stores, and their success in doing so greatly determines the effectiveness of the infection. So there is a constant battle going on within our bodies for this precious micronutrient, and it is partly the outcome of this battle that determines how long a disease lasts.

Iron deprivation is an important defense mechanism of the immune system

To prevent pathogens from gaining a foothold in our bodies, our iron metabolism ensures in advance that most of the stored iron is stored in a place where microorganisms have a hard time gaining access to it. (1)

Hemoglobin and transferrin

Most of the iron in our bodies is found inside cells, in hemoglobin, but certain pathogens have developed the ability to extract iron from it. (2,3) To do this, they have to compete with the body's own proteins, which quickly seek it out and recycle it. Interestingly, much of the iron we need comes from recycled hemoglobin, not from food. (4)  

Another factor that limits the availability of iron to invading pathogens is the lack of free extracellular iron. Extracellular iron is bound by transferrin, which is typically less than 50% saturated with iron in healthy humans.

Ferritin and hepcidin

We also store a significant amount of iron within cells in the form of ferritin.  Its levels increase significantly during infections and inflammation. 

During infections, iron retention is increased by a substance called hepcidin. (1) This is produced by the liver and even by immune cells themselves to further reduce iron availability to pathogens during infections or other inflammation, and to prevent the increased oxidative load of inflammation from causing as much damage to tissues. Iron levels are a key determinant of this, which explains why too much iron is so detrimental to various chronic diseases. (5,6)

Lactoferrin

Lactoferrin, a component of breast milk, has been found to be effective against bacteria, viruses and even fungal infections. (7,8) Like transferrin, it is highly effective at binding free iron, thereby depriving microorganisms of it.(1) It is therefore present in high concentrations in the mucus membrane, the body's protective layer against the environment, and is also produced locally by immune cells themselves at the site of infection and inflammation.

Human colostrum contains 7 g of lactoferrin per liter, which is necessary for the healthy development of the intestinal flora of babies and to prevent the proliferation of pathogens. (9) 

The real effectiveness of lactoferrin is illustrated by a recent meta-analysis showing that its supplementation reduced the incidence of upper respiratory tract infections by almost half. (10)

In addition to these, many other substances have now been discovered that also play an important role in the fight for iron, but their biochemical processes will not be discussed here. The point is that in the case of infections, host-driven iron deprivation inhibits the growth of pathogens, which is an important part of our natural immunity. Unfortunately, when the immune response is chronically activated due to prolonged chronic infections, autoimmune diseases or malignant tumors, it no longer only deprives pathogens, autoimmunity-inducing lymphocytes and tumor cells of iron, but also our own healthy cells. (11) This can lead to anemia over time, which is a feature of many chronic inflammatory diseases.

Iron replacement can add fuel to the fire

It follows from the above that iron supplementation alone is often not a good solution, even if your blood work shows a slight iron deficiency, as this may be simply a result of your natural defense mechanism and in supplementing iron supplementation we counteract its protective effects.

This is more than mere theory, as it has been confirmed in human studies where oral iron supplementation has been shown to increase the risk and worsen the course of diverse infections. (12,13) In contrast, mild iron deficiency has been shown to be protective. (14) Iron supplementation has been most studied in malaria, but has also been shown to be detrimental in bacterial and viral infections. (15,16)

According to a meta-analysis published in 2021, intravenous iron supplementation also increased the risk of infections, and many studies compared it to oral iron, not a placebo. (17) 

This is not to say that iron supplementation should never be used, as it is justified in some cases and may even be life-saving. But it demands caution and should only be used when no other solution proves effective.

In the other two articles on iron, I mentioned several nutritional strategies (and lactoferrin supplementation) that may in many ways be safer and even more effective than conventional iron supplementation. It is important to note, however, that it can take weeks/months to replenish iron stores in this way, so don't expect significant improvement in a few days and check your levels frequently.

It's also worth trying these first, because iron supplementation can cause a lot of side effects, such as unpleasant digestive symptoms, (18) while not always being effective. 

It's also important to remember that iron deficiency is not the only cause of anemia; a range of other nutrient deficiencies or health problems can be behind it - yet many people start taking iron straight away which fails to improve their condition.
Iron deficiency itself can also be caused by, for example, a lack of vitamin B2, (19) which is also worth investigating, especially if higher iron intake does not improve our levels.

Summary

To stay healthy it's important to get enough iron, but rather than going straight for iron supplements in some cases, make sure the deficiency is not caused by an infection. If necessary, try safer alternatives first. Rash iron supplementation can do us a lot of harm by upsetting the delicate balance of our immune system's defense against pathogens.

If you are genetically predisposed to iron accumulation, it is a good idea to donate blood regularly; otherwise you may develop problems due to excess iron.