Interesting Case Study of Pyridoxine-Responsive Megaloblastic Anemia

Here's an article [Hines and Harris, 1964: (http://www.ajcn.org/cgi/reprint/14/3/137) (http://www.ncbi.nlm.nih.gov/pubmed/14127943?dopt=Abstract)] describing people who had begun treatment for megaloblastic anemia (which "should," according to the strict definitions, have only been responsive to folic acid or cobalamin or both) with folic acid (15 mg/d, among other dosages) but who ultimately required both folic acid and pyridoxine (100 mg/d, among other dosages) to completely resolve the anemia. These were elderly people who did not have inherited, X-linked sideroblastic anemia. They describe, in the article, the way they kept decreasing the dose of pyridoxine, thinking one patient would only need it for a few days or something, and the person's hematocrit fell every time they tried stopping it. That's common in these case studies. The dosage keeps getting reduced, and the person has a recurrence of anemia or gradual rise in intracranial pressure, etc. I'm not saying there's anything wrong with peripheral blood smears, but there's a lot that isn't known about hematology. I suppose the pyridoxine-responsivity of the megaloblastic anemia could be explained in terms of the PLP-dependence of serine hydroxymethyltransferase activity (a folate-cycle enzyme that's part of the so-called "thymidylate cycle," produced by the "cyclic" activities of the cytosolic enzymes dihydrofolate reductase, cytosolic serine hydroxymethyltransferase (cSHMT), and thymidylate synthase). cSHMT activity is essential for thymidine biosynthesis, and a reduction in thymidine biosynthesis in reticulocytes is a major cause of megaloblastic anemia due to folate-depletion or cobalamin depletion. But it's probably more complicated than that and could have something to do with amino acid metabolism or alcohol intake, etc.