Is it iron deficiency anaemia, or something else?

Iron deficiency and iron deficiency anaemia

If you do a Google search for Iron, you will likely come up with lots of commentary on iron deficiency (ID), iron deficiency anaemia (IDA) and how this is the most common nutrient deficiency in the world, significantly contributing to the global burden of disease. This is what I was originally taught and is the continuing assumption by most doctors and health practitioners worldwide.

Dysregulated iron?

However, based on accumulating evidence; an improved understanding of iron balance is emerging, along with the need to reevaluate how we diagnose and treat ID. Although there are situations where ID and IDA do exist, for many of us, particularly adult men, and post-menopausal women, what we are experiencing is dysregulated iron that has led to an iron imbalance. When dysregulated, we have plenty of iron in our bodies, it’s just not available for use.

Our iron system in operation

Most of our iron comes from the iron recycling system that provides about 25mg/day. Although our dietary intake of iron is approximately 10-20 grams per day, we only absorb 1-3grams of this.  Processing the iron from food and recycling involves complex biochemical pathways with many steps that are dependent on enzyme and hormone function along with an adequate supply of synergistic nutrients. The key steps that regulate iron balance include intake, absorption, transport, storage, use, and loss.

Intake and absorption

From a dietary perspective, haem and non-haem iron are absorbed differently, with haem the most bioavailable. Animal sourced foods provide haem iron along with a combination of other nutrients that enhance iron uptake and transport. Plant nutrients often come in different forms different from what the body can use, (such as non-haem iron) and have to be converted into bioactive forms. The anti-nutrient properties in many plant foods, also make it more difficult to absorb and convert iron and other nutrients into forms the body can use effectively.

The recycling system

The iron recycling system revolves around the reuse of old and damaged RBC’s. Macrophages (think of these as big eaters), consume the RBC’s and break open the haem, so the iron is released. This iron is then transported to the bone marrow to make new RBC’s. We need to make about 200 billion RBC’s every day – 2000 every second.

Iron regulation

Because there is no regulatory mechanism to control the loss of iron, balance is managed by a hormone called Hepcidin. Hepcidin controls iron intake by acting as a doorman, determining how much iron is needed and deciding how much can enter into the circulation. When Hepcidin senses the body has too much iron or is inflamed for some reason, it will reduce the amount of iron absorbed from the diet.

Iron Transport

Once the iron from digestion and recycling is ready to enter the bloodstream another series of complex processes occur. Because free iron is highly toxic, it must be bound to proteins to be transported or stored safely in the body. Imagine, free iron as a bunch of school kids with hammers, who can do a lot of damage if they are allowed to run around unsupervised.  

The transport protein for iron is called transferrin – that makes it easy to remember! Transferrin is like a boat that travels through the red river (bloodstream), with 2-seats for its iron passengers. Magnesium, amino acids and insulin are important building blocks for transferrin. When these are low, we can’t make enough boats to transport the iron.

Nutrients such as vitamin A, magnesium and copper act as the dockworkers and crane operators that load the iron onto the boats. The supervisor is an antioxidant protein called Ceruloplasmin, that is very dependent on copper to function properly.

If these nutrients aren’t available then iron won’t be loaded onto the boats, even when there is plenty of iron available in the body. This will decrease the production of new RBC, Hgb and transferrin saturation. Transferrin saturation refers to how many seats in each of the boats are filled with iron, how “saturated” the boats are. When you’re low in these nutrients, you may appear to be iron deficient, whereas you may be iron dysregulated instead.

Storing iron

Another situation that confuses the iron balance picture is ferritin. This is a storage protein for iron. Remember, when free iron runs rampant, it gets into cells and causes oxidative damage to the body. To prevent this, surplus iron is stored in the pantry (called ferritin) for later use. This system works well unless there is inflammation in the body.

Anaemia of chronic inflammation

Any long-term medical condition can lead to anaemia of chronic inflammation, including cancer, autoimmune diseases, infections and diabetes. 

Remember the doorman Hepcidin, who decides how much iron can enter the circulation. Pathogens, such as viruses, bacteria and cancer cells all need iron to survive and thrive, just like we do. When the body senses inflammation or an increase in these “invaders” it responds by increasing Hepcidin and locking the doors; preventing iron from entering the bloodstream. This helps to keep us safe from pathogens, by stunting their growth and reducing their ability to reproduce.

This iron that hasn’t been able to exit the cells, is also stored in ferritin for safe keeping. The problem is, as the ferritin stores begin to overflow, some of this iron manages to find its way into the circulation and penetrates into cells. Remember those kids being let loose with their hammers? Free iron in cells leads causes damage that injures DNA, membranes, mitochondria, lipids, and organs such as heart, liver and brain and so on. This is a situation we want to avoid as much as possible.

Serum ferritin

There are different types of ferritin stored in different organs. Serum ferritin is found in the blood and is commonly used as a blood test to check how much iron is in storage. However, current research is reassessing the use of serum ferritin as a marker of iron status. There are questions around optimal serum ferritin levels and what level indicates inflammation. It’s important not to rely on serum ferritin as a sole marker of iron status.

Haemochromatosis

Some people have a genetic iron overload condition that results in a failure to regulate iron absorption and to control iron release into the circulation. Most of these hereditary disorders result from low Hepcidin production and dangerous levels of iron accumulation in vital organs. This condition needs proper medical management and therapeutic blood donations.

Using iron

Iron is used by every cell in the body. Along with its role in RBC production and oxygen transport, iron is used in the mitochondria to make energy and is an important building block of many enzymes and plays a role in their function.

Losing iron

The amount of iron we lose is not regulated by physiological mechanisms. The most common reason for iron loss is through blood loss. Women with heavy menstrual bleeding are at a greater risk of iron deficiency. Chronic GI bleeding is another cause of iron loss. A very small amount of iron is lost each day through skin, sweat, kidney and in the faeces. On average iron loss is between 1-2 mg/day, that is balanced with absorption.

Diet

Animal foods offer the most bioavailable source of iron along with the other nutrients that are important for iron absorption, recycling and transport. Remember, we only absorb about 1-2 mg each day from our diet. Organ meats (or supplements) provide an excellent source of all the important nutrients including vitamin C. Other animal and seafood are dense in bioavailable nutrients.

Despite what the TV adverts tell us, plant foods are not a very bioavailable source of iron and don’t have any vitamin B12, an essential vitamin for life.

Whether you’re iron deficient or iron dysregulated, improving iron balance requires attention to all the synergist nutrients in our diet.