Although I have seen a lot of this mentioned in passing, I haven't been able to find a thread specifically on this, so I thought I'd open one up. In a nutshell, B6 makes me feel amazing for about a day, then makes me feel terrible for the rest of the days I take it. I am curious about the role of CBS mutations in this--is it because I have built up too much sufites? Or is ammonia? Or something else? And what have other people experienced? And if you know, what is your CBS C699T status? A very brief primer on CBS and the C699T mutation: CBS causes homocysteine to enter the transulfuration pathway. Yasko thinks the C699T mutation will do this at at an increased rate, which would end up producing an excess of ammonia and sulfites that need to be tackled. The CBS enzyme uses B6 as a cofactor. Yasko believes C699T mutation increases the frequency that this occurs I think maybe 20-fold(?). There seems to be some controversy around how important this mutation is. To begin, a short history: I've been sick with chronic fatigue for maybe ten years, depending how you count it. Near the beginning of my attempts to fix this medically, I took a lot of supplements, including regular folate (I am MTHFR C677T ++) and B6 (probably 100mg / day). I felt better than I had ever felt, and it lasted maybe a month, followed by maybe a month and a half that were progressively worse, until I became...nonfunctional, because my thoughts were so speedy that one would begin before the last one ended, and so nothing made much sense. I ended up stopping supplementation, and I subsequently got...well my thoughts became the normal sludgy. Subsequently, I was treated (successfully, I hope) for heavy metal toxicity. In the last year I began doing the Yasko protocol. Having begun pretty much everything she indicated I do, I inadvertently started taking a supplement with B6 in it (up till then, I had taken none) Suddenly, things got better. Beautiful things looked beautiful, and songs actually touched me. I felt so much more human! But within a day, maybe three, it was gone, to be replaced by a fairly deep depression. Two or three weeks later, I figured out that I was taking B6, and stopped. The depression lifted back up to the usual plodding grey. Notice that the first time I used B6, the good times lasted at least a month, and the decent took at least a month and a half, while the second (and other times) I have tried it, the good times last a day, maybe three, and the descent takes about the same amount of time before hitting the bottom. I'm not concerned that hitting bottom meant racing thoughts the first time and severe depression the second--I was taking lots of stuff the first time, so I would expect a different effect. But why the difference in timing? I have started taking Molybdenum to help convert sulfites into sulfates. Perhaps I had high molybdenum stores the first time, and their depletion was a major mediator of my slow crash? Any other ideas? Similar experiences? Thank yall so much.