Question: In hemochromatosis, why would ferritin be low but transferrin saturation high?

Ferritin is your long-term iron storage. Transferrin is your short-term iron storage. The problem with hemochromatosis is that usually in a normal functioning system, there is a hormonal regulatory system that prevents you from absorbing iron from food when you have enough iron that when you have too much iron, shuttle the iron into ferritin which is protective both against pathogens eating the iron to grow and against oxidative stress, which free iron causes, which if you don't know the details about can be thought of as wear and tear on your tissues over time.

In hemochromatosis, normally the way you judge how much iron you have is in the circulating transferrin pool, which is your short-term storage. How full is it? The defect in hemochromatosis is that when the short-term storage, transferrin, starts getting fuller than usual, you don't notice it, so you don't stop absorbing iron from food that makes the transferrin saturation go up even further. But you don't shuttle the iron into ferritin. That makes ferritin lower.

What people get confused by is that historically, we have only paid attention to hemochromatosis when it's too late, when the person has been suffering for it from 30 or 40 years and they need organ transplants. What happens at that point is that the ferritin is very, very high. Why is the ferritin high? Not because you had too much iron. The person without hemochromatosis has the ferritin go up when they have too much iron. The defect in hemochromatosis is that you do not stop absorbing from food when you have enough, and you do not put the iron into ferritin when you have too much.

The reason that ferritin is high in someone who's had hemochromatosis for 30 or 40 years is not because they have too much iron. It is because they have oxidative stress and damage caused by that iron. Oxidative stress and damage cause ferritin to go up no matter how much iron you have. So does infection, no matter how much iron you have. Essentially, what you have is ferritin is not the fireman that he should be to put out the fire as it starts, and the smoke detectors go off. Ferritin hemochromatosis is the cleanup crew who got to the fire after the house burned down.

This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019

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