Neuronal injury: folate to the rescue? http://www.jci.org/articles/view/40764 Interestingly, the authors found an inverted U-shaped relationship between the therapeutic effect of folic acid and the dose administered, with peak therapeutic effects observed at 80 μg/kg (7). A similar biphasic increase and subsequent decrease in spinal cord global methylation was observed in response to increasing doses of folate. Notably, the magnitude of de novo DNMT protein expression also followed an inverted U-shaped pattern over the dose range of folic acid treatment Paradoxical folate insufficiency by another name still stinks the same. So maybe they will one day put a horse with paradoxical folate deficiency from folic acid and a mouse with paradoxical folate deficiency from folic acid together and realize humans have that problem with folic acid also. They would not have found this effect with L-methylfolate unless the layer they were studying was one not activated in a donut hole paradoxical folate deficiency. The paradoxical nature of all this is missed by many researchers and not understood at all. The important thing in this paper is that they became aware that more folic acid is a worse performer than less folic acid. They don't know any of the rest of it. And they are speaking of rodent studies. The whole idea of paradoxical folate deficiency/insufficiency in humans is not recognized, noticed, studied or understood by the research or medical community. There is not a single peer reviewed paper concerning the subject that I can find.