Hi Everyone, In a nutshell, I seem to be having success limiting methyl-group sensitivity by limiting my daily riboflavin-5-phosphate (R5P—the active form) supplemental intake to about 35 mg. This does not seem to work via limiting 5-MTHF synthesis via MTHFR, as taking even large amounts of 5-MTHF has not causes “overmethylation” symptoms. Perhaps methyl groups are the usual limiting factor in the synthesis of some catecholamines, but having added extra methyl groups R5P becomes the limiting factor? Here is the only salient study I could find, reporting that “Riboflavin deficiency induced decreases in liver epinephrine and norepinephrine, and in brain norepinephrine, but not in the adrenal glands or spleen.” I am interested to hear if anyone else finds this to be true. Perhaps this is the reason that people on Freddd's protocol do not suffer from “overymethylation” (he recommends limiting R5P to 50 mg per day, I believe).* Here is the longer story, for those interested: I recently “stepped down” from using large amounts of mB12 and 5-MTHF, more or less according to Freddd's protocol. Part of this protocol involves keeping B1, B2 and B3 supplementation under 50 mg per day. I had experienced some benefits, but I wanted to experiment with higher levels of magnesium supplementation, and the magnesium seemed to be interacting with the B12 unfavorably. In attempting to find a lower amount of methylfolate and methylb12 that I would take, I accidentally found that taking the multi-B complex I had used while on Freddd's protocol prevented overmethylation symptoms (alertness without extra physical energy stores, followed by insomnia and exhaustion but still with a “caffeinated” feeling.) I added B1 without inducing over-methylation symptoms, which only left B2 as the culprit, as all other vitamin intakes had been the same when I got overmethylated and when I was not. Assuming this works roughly like I suggest, there would be further questions to answer: Where are the extra methyl groups going? Are we at risk of over-methylating genes? Do the answers to these questions depend on COMT status? Although I feel I a need to point out the possible risks, I should also say that this discussion probably overlaps with discussion on possible risks of Freddd's protocol. Having acknowledged some of the risks involved, I would also like to point out the advantages I see: This allows me to use as much lecithin as I would like, both for liposomal nutrients and to repair my gut and mitochondrial membranes in general. It allows me to add more methylfolate and b12 into the mix, which does seem to improve my general wellbeing up to a point. In sum, it eliminates the precise balancing act I had been subject to in regard to methyl groups, and allows me to take (more of) some helpful supplements. I am very curious to hear from anyone suffering from methyl sensitivity who tries or has experience with this (I believe Pure Encapsulation's B-Complex Plus should limit b2 to an acceptable amount.) But as stated, I am unsure of the medium-to-long-term consequences of this.** Finally, I wonder if anyone has insight into what mechanism might be driving this (assuming that this works as I imagine, and I have not missed something!) Hooray for you if you have gotten this far, and thank you so much from me. Warmly, Aaron C *This could also, as Rich Van K pointed out, be attributable to increased conversion of sarcosine into glycine and THF into 5, 10 methylene-THF via SDH. Or perhaps they arrived at an entirely different conclusion? I haven't read much on that particular question. ** I am not a medical practitioner in any way, just a person with ME.