In HFE Hereditary Hemochromatosis, genes controlling iron absorption in the gut are permanently changed in a way leading to excess iron uptake into the body.
Seemingly a small change, a single protein is made differently when the HFE Gene is mutated on Chromosome 6. The location of the effect of the change is, perhaps, what makes this such a significant problem.
The effect is primarily upon the cells of the digestive system called enterocytes. Iron is normally absorbed by these enterocytes in the upper part of the gut known as the duodenum, similar to other minerals such as calcium, magnesium, and zinc.
Normally, the amount of iron absorbed is quite low–ranging from 5% to 35% given the circumstances of health and the body’s needs for iron.
If the iron needs of the body have been met, a complex feedback system should tell the GI system to reduce the amount of iron absorption from food and water.
However, in hemochromatosis, the feedback loop is broken because of a genetic mutation causing the continued absorption of iron. Even when the body is in a state of iron overload, the gut continues to absorb more and more iron.
If you recall, the process of iron overload is typically slow to develop and may not affect a person’s health until they are in their 30s, 40s, or even their 50s or 60s.
Symptoms of too much iron progressively worsen over time if the root cause (Hereditary Hemochromatosis) is not discovered.
This slow onset is descriptive of just how minimal this change is– at least at first. Typically, the body is very stingy about how much iron it absorbs because although normal levels of iron are critical for good health, excess iron is toxic.
Once we take iron into our bodies, we quickly bind it with proteins such as heme, ferritin, and transferrin so that we may put it to good use with hemoglobin to build Red Blood Cells.
Regardless whether we have hemochromatosis or not, the following are 2 of the primary ways our bodies control excess iron:
- Feedback Loops to Decrease Iron Absorption
- Iron-Binding Proteins
Yet over time, if we have hemochromatosis disease, our level of iron uptake slowly but steadily outpaces our body’s needs and our body’s ability to bind excess iron.
This makes it important to consider ways to block the absorption of iron:
Feedback loops play a major role in human health.
A substance increases in the body, and we respond in various ways to make sure levels remain healthy and not get too high. Essentially, our metabolism accomplishes one of the following tasks:
- Reduce Our Intake or Creation of that Substance
- Store It
- Use It or Metaboilze It
- Increase the Excretion of that Substance
In other words, one aspect of health is to avoid excessive toxins.
For example –> we want to avoid too much iron!
On the other hand…
A substance decreases in the body, and we respond in various ways to make sure levels remain healthy and not get too low. In this scenario, our metabolism attempts to:
- Increase Our Intake or Creation of that Substance
- Mobilize It From Storage
- Reduce the Use or Metabolism of It
- Reduce the Excretion of that Substance
Thus, another aspect of health is to avoid a deficiency of a nutrient.
In a nutshell, you can apply this to nearly any aspect of our health…
Water, Oxygen, Glucose, Carbohydrate, Protein, Fat, Vitamins, Minerals, Electrolytes, Hormones, Neurotransmitters, Red Blood Cells, White Blood Cells… and of course Iron!
In whichever manner we internalize a substance– whether we eat it, drink it, breathe it, absorb it, or metabolize it– feedback loops are so very vital and central to our health.
Hepcidin and Ferroportin
Excess iron absorption is the result of a broken feedback loop in Hereditary Hemochromatosis.
Hepcidin and Ferroportin are two terms central to understanding human iron absorption and metabolism.
Hepcidin is a hormone produced by the liver in response to several factors, including iron overload and inflammation. Its effect is to block the action of Ferroportin.
Ferroportin is a membrane protein that transports iron from the enterocytes into circulation. Ferroportin’s actions are assisted by another protein that causes the body to uptake iron into the bloodstream, Hephaestin.
Therefore, if hepcidin is low –> then ferroportin is high… and the result is that we absorb more iron than we should –> leading to iron overload.
Surely enough, individuals with Hereditary Hemochromatosis have low levels of hepcidin.
Researchers are currently hard at work trying to determine the role these substances play in Hemochromatosis. Scientists at UCLA are trying to develop a new medication to mimic the effects of hepcidin.
While the specifics are not completely understood at the present, we see the effects of excess iron absorption are in part due to the breakdown of the feedback loop including hepcidin, ferroportin, and hephaestin.
Regardless, the net effect is that we absorb too much iron which leads to iron overload in our body.
Continue reading the next part of the discussion here: Iron Overload: Excess Accumulation