Hi All, I'm a long term (18 year) ME/CFS patient, but was just diagnosed a couple of years ago. I tested positive (hetero) for both MTHFR 677 and 1298, so thought methylation would be very worthwhile to try. I don't know what other SNPs I might have (I've bought the 23 and me kit, but won't get results for awhile). This is the list of supplements I'm taking, with brand names: Direct supplements to support methylation: "B-Right" multi-b complex -- 2 pills a day Solgar Folate as Metafolin -- 6 x 800 mcg = 4.8 mg B12 Infusion by Enzymatic Therapy (methylcobalamin) -- 2 x 1 mg = 2 mg (sublingual) Anabol Naturals Dibencoplex (cobamamide dibencozide) = 2 mg (sublingual) Doctor's Best L-Carnitine Fumarate = 855 mg Potassium chloride -- 4 x 99 mg = 400 mg Lecithin (Whole Foods) = 2400 mg One note: I take so much Metafolin because if I take less than that to my current amount of b12s, then I get continuous migraines and worsening of the normal level of my other CFS symptoms Other supportive supplements: Selenium (Whole Foods) = 100mcg Vitamin D3 (Whole Foods) = 5000 iu Vitamin K (Carlson) = 5 mg Vitamin C (Solaray) = 2000 mg Magnesium malate (Source Naturals) = 300 mg Zinc picolinate (Bluebonnet) = 50 mg I also take Amour Thyroid (1.5 grains) I've been on the protocol for over a month, and while there were about 6 days where I started to think, wow, this is really going somewhere, most of the time I feel just as bad as usual. Am I missing something crucial? How long should it take for me to start feeling better, if the methylation is something that will help me at all? I mean, how long a try should I give it until it's clear that it isn't the answer for me? Should I just try raising the folate and B-12s? I titrated up to the amounts shown above, but have been staying at these levels for the past 3 weeks or so. Actually, I'm not sure why I stopped titrating up. I guess it's because the methylfolate is already high. EDITED TO ADD: I remember why I stopped titrating up. I was getting intense and unrelenting anxiety and inflammation in my joints. 5 days ago I started taking Progest-E (a progesterone suspended in E oil) and that has calmed down the anxiety, but I still have some inflammation happening. I figured that the anxiety was due to excitotoxicity from driving the methylation cycle. Not really sure though. Also, I don't know why I'm getting so much inflammation. One weird thing is that my core body temperature went up significantly on those few good days. Normally, I run a degree (fahrenheit) too cool (on average), and on the days I was feeling good my temp was probably even a little too hot (it got over 99.0 fahrenheit several times--it actually felt great, because I'm used to being too cold, which is really unpleasant). Thank you for your help or advice!