Hi, all, I'm hoping to get some advice regarding a couple methylation related issues. First, let me give a brief health background: Fatigue and weight control has been a long-standing issue for me. I learned how to cope with it in my teens, but a couple years ago, I "crashed". At the time, I was driving my body hard. Atkins-like diet, a lot of coffee, high-intensity interval training 2x a day, and some strong emotional stress. Fast forward a couple months and the crash didn't end. I was bedridden, not digesting anything, and unable to stand for more than 20 minutes at a time. Now, since then (2 years later), I've found substantial improvement by radically altering my diet and exercise regime and uncovering a long-standing thyroid issue. Digestion is solid, exercise tolerance is better, and fatigue levels are improving. Yet, I plateaued some months ago, and have been struggling with what I believe to be cellular thyroid resistance. T3-only keeps me somewhat stable, but there's clearly something else at work. Enter 23andme, and my pertinent (as I understand) results: BHMT-08 +/- CBS C699T +/+ COMT H62H +/+ COMT V158M +/+ MAO-A +/+ MTRR A66G +/- MTRR A664A +/- NOS2 +/+ NOS3 +/+ VDR Bsm +/- VDR Taq +/- I believe CBS, COMT, and MTRR to be my primary issues, based on a couple things: -My urinary sulfate levels are always >1200, despite being on a low thiol diet, incorporating all the SUOX support supplements, and avoiding methyl donors for almost 2 months. -Ammonia scavengers and limiting protein intake (to ~100g/day) greatly help me symptomatically (post-meal brain fog, sleep quality, muscle soreness, etc.). -I've always been very sensitive to B-complexes, and B12 is very potent, yet positive to my system. -I've relied on Mag-glycinate to get any semblance of sleep for the last 2 years. My sleep has been an issue since I was very little, and I believe this is due to COMT and the constant dopamine/norepinephrine imbalance. -My serum B12 levels have always been high, which as I understand it, could be pooling there from inadequate recycling (via MTRR). Now, a list of my current methylation-related supplements: HydroxoB12 (sublingual) - 500mcg, split into 2 doses ("stuck" at this dose for 6 weeks) AdoB12 (sublingual) - 375mcg, taken with morning HB12 (1 week, so far) Riboflavin 5 phosphate - 50mg (4 weeks) Molybdenum - 1000mcg, split into 2 doses (1 week at this amount, 6 weeks total) Vit E. Succinate - 400IU (6 weeks) Boron - 3mg (6 weeks) Yasko's Ammonia RNA (4 weeks) I'd love to really start cranking away at the methylation, but I'm concerned about: 1) The consistently high sulfate levels and ammonia issues 2) What I believe to be very expressive COMT SNPs So, some questions: a) Any advice on more ways to lower sulfate levels? How long should it take to lower? I've even cut out some of the high methionine foods I was consistently eating, but so far have not seen much improvement. Lowering protein intake further is just not gonna work for me. b) How about ammonia? Yasko's Ammonia RNA definitely helps, as does a daily bifido probiotic/resistant starch combo, but those don't quite do the trick. Activated charcoal flushes have a pretty negligible effect, as does post-meal Butyrate. I tried Yucca, and it was by far the most helpful (at 500mg split into 3 doses). However, I had to stop taking it as it caused somewhat frightening GI issues. These issues unfortunately flare up even at small (100mg) doses. I believe the saponins just do not agree with my system. c) Is it possible that the HB12 is actually contributing to my methyl load (via COMT)? I know a number of people indicate that HB12 really doesn't do much, but I've had a strong reaction to it - so much so that I've had trouble going from 500mcg to 750mcg. It's been mostly positive and is having an effect (evidenced by a much increased need for Potassium even before adding adoB12 and Niacin's ability to shunt the over-charged feeling when I take 750mcg+). Could there so many excess methyl groups from COMT that the HB12 is actually converting to MB12? I'll also say that AdoB12 has had a strongly positive effect. Muscle weakness has improved, muscle definition has improved, and sleep has been a bit smoother. I'm wondering, is it possible for AdoB12 to indirectly help ammonia detox by supporting the Krebs cycle? Based off of an organic acids panel I had done, I believe I've got blockages of sorts in both the Krebs and Urea cycle. Is this maybe why AdoB12 helps people like me? I haven't touched any methyl supplements; even grass-fed beef liver drives me up the wall. I've got some folinic acid that I want to try in the future, but again, I'm hesitant to start this process while sulfates and ammonia are still such an issue. Thanks in advance for any advice you can offer!