Borrowing from an iron forum summary:
First on Ferritin:
Serum ferritin is a test that was formerly thought to be directly related to the amount of tissue ferritin, and thus, something that could be used to measure the amount of stored iron, which was believed to always be stored bound to ferritin. Today, modern research has shown that actually, serum ferritin levels are not related to tissue ferritin levels, and that iron is only stored bound to ferritin in tissues that produce ferritin, like the liver, and is stored in free molecule form in other tissues, like cardiac muscle, that do not produce ferritin. There is no required serum ferritin level; you do not need to be concerned about “depleting” it.
Transferrin Saturation %:
Transferrin saturation is the indicator of excess iron storage, and needs to be below 40% in everyone, more especially those individuals who have HH. When transferrin saturation is over
40%, which indicates that iron storage sites around the body have reached their normal capacity, two things happen. One, is the liver releases the HFE protein (starting when %TS is over 20%),
which is supposed to bind with receptors in other cells, stimulating the release of hepcidin, which in turn binds with receptors in intestinal cells, halting the absorption and release into the blood stream of iron molecules. The second one is the reason that 40% was chosen as the threshold - at 40%, there’s not enough transferrin to bind with all of the iron being secreted to the bloodstream by the intestinal cells, causing free iron molecules to circulate in the bloodstream, getting deposited wherever they can, where they act as free radicals, causing damage
When deironing, the removal of red blood cells via phlebotomy results in increased RBC manufacture in the bone marrow, which picks up iron from the transferrin and uses it to make hemoglobin. This results in a temporary lowering of %TS - which then rises again as tissues release stored iron, which binds with the transferrin, once again increasing saturation. As phlebotomies continue during de ironing, this continues to occur until finally all excess stored iron is gone from tissues. In order to coax all of the excess stored iron out, the transferrín saturation must be low - which is why the target during de ironing is 20% or lower. Once deironed, the thing to watch out for is transferrin saturation over 40%, which signals the start of iron loading and damage from free iron molecules. Some people with HH (wonky iron genes) have adverse reactions once transferrin saturation enters the “normal reference range”, which starts at 15% for women, 20% for men. Which is why, those with HH, should try to keep my %TS as low as possible. It’s also important to note that there is no such thing as a too low %TS. Instead, you would do a CBC to check the Red Blood Cell counts, and hemoglobin levels - if they are normal, then RBC manufacturing is taking place normally which means your body has sufficient iron for its use.
