Excess Urination, Hypovolemia, Erythropoeitin, & Iron—Rich Van Konynenburg—from the immunesupport.com CFS forum
Here's a possible explanation for why a person might need more iron after starting a treatment to lift the methylation cycle block: Many PWCs have a low total blood volume compared to normal, which I suspect is due to mild diabetes insipidus (not the same as diabetes mellitis). I think the diabetes insipidus in CFS is caused by glutathione depletion (secondary to methylation cycle block) in the cells of the hypothalamus that synthesize arginine vasopressin (antidiuretic hormone).
This causes the kidneys to excrete more water than normal into urine. This produces thirst and high fluid consumption, but it is unable to keep up with the excretion of water, so the total blood plasmas drops, and the person becomes hypovolemic (low blood volume). Now, I suspect that the kidneys then lower their production of erythropoeitin, which causes the bone marrow to slow the production of new red blood cells. If it didn't do that, the blood viscosity would rise, and that would cause problems with circulation.
PWCs also usually have a normal red blood cell count (sometimes a little low with somewhat large red blood cells (macrocytic), but usually still in the normal range). The blood count is a measure of the number of cells per unit volume of blood. So if the total volume is low and the RBC count is normal, that says that the total number of red cells is low, also.
Now, if the person treats to lift the methylation cycle block, the glutathione level in the hypothalamus should come up. This should raise the secretion of vasopressin, which should cut down on the daily urine volume. That should raise the volume of the blood serum, which in turn should cause the kidneys to put out more erythropoeitin, which will signal the bone marrow to produce new red blood cells at a faster rate. Since lifting the methylation cycle block also unblocks the folate cycle, there is now more of the particular folates needed to make new RNA and DNA, which are needed to make the precursors to red blood cells. The upshot of all this is that the rate of production of red blood cells will go up, which will demand a higher rate of production of hemoglobin. Hemoglobin, of course, requires iron. There's the increased demand for iron.
Excess iron is normally stored in the cells lining the gut, but if it isn't needed, it is excreted in the stools as the old cells slough off. If a person hasn't had a normal demand for iron for a long time, the inventory of iron stored in the cells lining the gut could be low. Thus, when the demand for iron suddenly goes up, these cells can become depleted. If that happens, the ferritin stores will drop, and eventually the actual iron level in the blood will go down, and the person may switch from the macrocytic anemia caused by the methylation cycle block to a microcytic anemia caused by low iron (iron deficiency anemia). So extra iron could certainly be needed in this situation.