The Cause Of High Iron Saturation

Are you looking at your blood tests and wondering what's going on with your iron saturation? Maybe you see very high levels and you're worried that you might have some kind of chronic health condition. That's leading to high iron saturation.

My name's Dr. Terranella, and in this video we're going to look at the causes of high iron saturation. There are actually several causes of high iron saturation. We're going to look at four common causes for this. Some genetic factors that may be influencing it, diet, and other factors.
So in this video we want to look at the cause of high iron saturation. And as you may know, the cause of high iron saturation is more than just hemochromatosis. There are other causes of high iron saturation. But before we talk about the causes and its importance, we first want to look at this question:

What is iron saturation to begin with? What are we talking about here? So iron is carried around in our bodies via transport proteins. There are many steps involved in the absorption of iron, but once the iron is absorbed into the bloodstream, it's going to bind to a carrier protein called transferrin. Transferrin transports the iron throughout the body, delivering it to specific cells that require iron for their function, like bone marrow, for instance, that require iron to make red blood cells, but also other areas that may just be a little bit deficient in iron. For whatever reason. So when we talk about what is the cause of high iron saturation, what we're referring to is the saturation of this binding protein transferrin. There's only so much transferrin protein that our bodies make, and that's floating around in your blood. So with this, there's only so much binding capacity that those transferrin molecules have. So a high saturation means that there's not much binding capacity for the transferrin left. Why does this happen? Well, either there's too much iron coming in through the digestive tract, or too much in the system in general from other sources, which we'll discuss in just a minute. Or perhaps there's too little transferrin being made as well. Therefore, the transferrin saturation is high.
Let's look at some of the classic examples or common reasons for high transferrin.

So in looking at the cause for high transferrin, hemochromatosis is definitely one of those things that's going to be high on your list, something that you're going to want to rule out for sure. So what is hemochromatosis to begin with? It's a genetic disorder characterized by excessive absorption and accumulation of iron in the body. The primary cause for hemochromatosis is a genetic alteration or mutation in specific genes that control iron metabolism, and more specifically, absorption.

The most common of these mutations in hereditary hemochromatosis is caused by mutations in the HFE gene, specifically the C282Y and the H63D alterations. These alterations lead to a disruption of the normal regulatory process of iron absorption, which is somewhat regulated by the HFE protein.

The HFE protein interacts with transferrin in the body, and then goes on to signal to the liver how much hepcidin to make. So what is hepcidin? Well, hepcidin acts in the intestines and other places to reduce the amount of iron absorption into the body.
So when transferrin is elevated, the HFE should tell the liver to produce more hepcidin, thereby reducing the absorption of iron in the intestines. However, with hemochromatosis, and other liver conditions, this process is not working properly, and you end up with not enough hepcidin levels. They don't go up, and so the iron absorption continues even in the presence of a high iron saturation.

So in looking at the cause of high iron saturation, this is an important one. The second one, though, has to do more with iron overload disorders, and these are conditions such as thalassemia or sideroblastic anemia, and other conditions where the red blood cells are misshapen, and it leads to a higher turnover of those red blood cells.
So what ends up happening with that higher turnover is those red blood cells are being broken down at a higher frequency, leading to higher internal iron levels. That transferrin protein then needs to go grab those extra iron molecules. Otherwise, you end up with the iron running into and damaging other cells and tissues. So that's a second common cause for high iron saturation.
The third one has to do more with liver disease. Much any liver condition, if it goes on chronically, and you have ongoing elevations in liver enzymes, it can be a cause for high iron saturation, and there's a couple ways that that happens. One is through dysregulation of hepcidin production.