I have the exact same problem, in fact I'm just coming out of a week-long Phosphatidylcholine, TMG and possibly Betaine HCL induced depressed week where I go into complete freak-out and tunnel vision mode and seem to lose enough of my brainpower to no longer be able to see the very obvious, heh. Doesn't help that the amount of pain I then experience goes up to nearly unbearable proportions (low dopamine!).
I share a bit of the same SNPs (MAO A, MTRR, CBS, SOD2 but not MTHFR) but I don't know how important that is, I like to be guided by responses in the first place over theoretical stuff although we need theory to figure stuff like this out of course.
What I understand so far (which is common knowledge around here but still, want to spell this out so we can crack this and if anyone spots something wrong, please do correct me):
- Phosphatidylcholine becomes TMG after oxidation
- TMG is Glycine with three methyl groups attached
- TMG 'stimulates' the BHMT pathway which is the 'backup' or 'short' route to recycle Homocysteine into Methione
- Betaine HCL is TMG with HCL attached so will contribute to the TMG-'pool'
- Taking TMG will spare (and thus increase) Choline since less Phosphatidylcholine needs to be oxidized into TMG
Stuff that I've gathered over the past months that is less clear to me or from less reliable sources:
- Taking TMG raises Carnitine levels
- Taking TMG raises the need for Methylfolate
- Increasing BHMT pathway activity lowers the amount of homocysteine available for the 'main' or 'long' route to recycle homocysteine to methionine via methionine synthase (MTR) and methionine synthase reductase (MTRR).
*Insert commercial break*
Pondering about this I've reviewed my documentation which pointed me to this pubmed article:
http://www.ncbi.nlm.nih.gov/pubmed/6115113
And this has me intrigued: "
5-methyl-THF, the form in which almost all folate is transported in human plasma,
must react with intracellular
homocysteine before it can be retained by the cell as a polyglutamate. Since homocysteine is derived entirely from methionine,
methionine deficiency will cause
intracellular folate deficiency, and the rate of
mitosis of rapidly dividing cells will be
reduced"
Thus by taking anything that stimulates the BHMT pathway we in effect create a Folate deficiency on a cellular level. It doesn't matter how much Methylfolate (or Methylcobalamin) you take at that (/a certain) point since that's not the main issue, it's a lack of Homocysteine (/Methionine) that causes the issue!
So that means Homocysteine isn't just a waste product but a necessary part of proper Folate metabolism!?! You mean Homocysteine isn't the boogie man I thought it was?!? Awww
In hindsight this is just what the whole methylation cycle does but it's obvious it wasn't clear to me how it worked exactly! In my mind Homocysteine was just the thing being recycled by Methylfolate and Methylcobalamin, not contributing to Folate metabolism itself!
So that would mean anything that increases Homocysteine would help here which means:
- Taking Methionine
- Taking things that spare Methionine:
- Cysteine (might increase urea excretion so not the best idea initially) (hello NAC btw, although that would contradict your experience, maybe exactly because it increases the urea burden EDIT: NAC lowers homocysteine, see my post below)
- Carnitine which is methionine + lysine
- Taking SAMe
- Taking things that spare SAMe:
- Creatine
- Increasing absorption of Methionine from food via a properly working digestive system:
- Digestive enzymes to break down protein
- Stimulate bile so endogenous enzymes are released
- Increasing stomach acid if low since bile is released in response to correct acidity of food
- SAMe is know to increase bile...
- Eating a protein rich diet, preferably meat
- Making the CBS pathway function normally since it otherwise might be a drain on homocysteine as well
One other thing that I think (hope) is related to this is that I have issues taking Magnesium and Carnitine (Fumarate). I've had great results with Boron and Manganese (and Calcium) and then being able to take Magnesium but I can never sustain it. After a while I have to stop taking it as it causes increased pain and depression and/or just a general crash of everything. Maybe Boron, Manganese and Calcium were just increasing my need for Magnesium and thus reducing availability of it for other processes. Hmm.
Now I'm wondering if Magnesium is such an issue because it is increasing ATP production and then leading to a Methionine deficiency because that is what is used to convert Methionine into SAMe? Or it's because of an overall increase in metabolism.
Not sure why Carnitine would be such a problem at the moment, maybe because it would spare TMG and thus in effect increase available TMG for the BHMT pathway? Unsure of TMG - Carnitine connection though.
I guess I'll find out when I try it all! Something tells me I'll finally experience hypokalemia symptoms which I haven't with taking Methylfolate, Methylcobalamin, Adenosylcobalamin or Carnitine.
So to summarize:
TMG induces a
Homocysteine deficiency and thus
induces a Folate deficiency when there is
insufficient Homocysteine(/Methionine) to feed both pathways which leads to several issues like depression and, you know, basically everything we're trying to solve with methylation!?!
I know this has been mentioned and done before (trying Methionine etc.) but I've never seen it's relation to TMG spelled out like I did above.
I've got some SAMe on the way, as well as several amino acids including Methionine as wel as digestive aids. I guess some part of me was still functioning when I ordered it all last week
But as always; the proof is in the pudding!