...The reason why red blood cells are larger and contain more hemoglobin than normal in ME/CFS is that the cells in the bone marrow that produce new blood cells do not have enough folate. Certain forms of folate are needed to make DNA and RNA, which are needed to make new cells. Since the bone marrow is not able to make red cells in normal numbers, it stuffs more hemoglobin into each one it does make, and that raises both MCV (their size) and MCH (their hemoglobin content).
The reason why these cells do not have enough folates is that there is a partial block in methionine synthase, which links the methylation cycle to the folate metabolism. Because of this block, folates continue to be converted to methylfolate (this is called the "methyl trap" mechanism), but it cannot be used by the methionine synthase reaction. Instead, peroxynitrite, which rises because of the depletion of glutathione, breaks down the methylfolate, and that depletes the folates in general.
A vicious circle forms between the depletion of glutathione and the partial block in methionine synthase. This vicious circle is what makes ME/CFS a chronic disorder.
The good news is that this vicious circle can be broken by a methylation protocol...
