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Betaine and TMG are the same substance. Betaine HCl has a hydrochloric acid molecule bound to it. Yes, if you take betaine HCl, you will also have the benefit of TMG. However, note that TMG stimulates the alternative BHMT pathway from homocysteine to methionine in the liver and kidneys. TMG will promote production of SAMe, but it can shunt flow away from the methionine synthase enzyme, which is partially blocked in ME/CFS. It's important to get this enzyme going, because it is linked to the folate metabolism, which is needed to make new DNA and RNA, and also because it regulates the entire sulfur metabolism. In Amy Yasko's protocol, she recommends starting with some TMG, and then after the B12 and folate have been built up some, to add DMG, which will inhibit the BHMT reaction by product inhibition, and that will push more of the homocysteine through the methionine synthase reaction. The benefit of doing TMG first is that it can increase the level of SAMe, and that is needed by the methionine synthase reductase reaction, which rescues the cobalamin coenzyme of methionine synthase when it becomes oxidized, thus restoring it to the +1 oxidation state and giving it a methyl group, so that it is a functional methylcobalamin molecule again. I don't know what dosage of betaine HCl will interfere with the methionine synthase reaction. Some people use the Allergy Research Group's dilute HCl solution to augment their stomach acid, and then there is no TMG (betaine) involved. Others use lemon juice (note that it is important to use a drinking straw and to flush the teeth with water afterward, because the citric acid in lemon juice chelates calcium and can damage the enamel on the teeth over time).
TMG stimulates the BHMT (betaine homocysteine methyltransferase) reaction, as it is a reactant for it. This reaction takes place in the liver and kidneys. It is an alternative pathway for converting homocysteine into methionine, and it will help to produce SAMe in those organs.
There are a couple of ways that it might produce symptoms. One is that it will initially lower the flow of homocysteine into the transsulfuration pathway, so the rate of production of glutathione may drop lower initially. So symptoms could be caused by initially making the glutathione depletion somewhat more severe.
Another possible mechanism is that it can also take homocysteine away from the main methionine synthase pathway initially, and that will impact the folate metabolism, since the conversion of methylfolate to tetrahydrofolate will decrease in the liver and kidneys.
A little TMG is often helpful when methylfolate and B12 supplementation are started, because it can help to raise SAMe, needed for recycling methyl B12. After these supplements are well underway and methionine synthase is coming up in activity, the TMG can be stopped, or DMG can be added to counter the BHMT pathway, so as to route more of the homocysteine to the methionine synthase pathway and the transsulfuration pathway.
In order to drain the homocysteine produced from taking SAMe, it would be correct to supplement B6,Folate and B12 along with the SAMe,right?
So TMG is performing the opposite task as SAMe. SAMe is producing homocysteine whereas TMG is clearing it away. Then why at many places it is said that TMG is a good alternative to SAMe. Considering a methylation cycle such as here: http://babyfoodsteps.files.wordpress.com/2012/05/methylation-cycle.jpg
It can be seen that SAMe when taken directly will convert to homocysteine. TMG when taken directly will help in converting homocysteine to methionine, thereby fulfilling the two purposes: production of methionine(which SAMe also tends to do), and clearing up of homocysteine.
Please tell if my understanding is correct and share your views.
Thanks.
And I would never use B6, folate or B12, but only P5P, mfolate, and mB12. In particular, too much B6 causes neuropathy and B6 does not protect the kidneys from glycation, whereas P5P protects the kidneys from glycation, and can be taken in higher doses, in fact I have never heard that one can take too much. P5P also helps the CBS +/+ defect to work correctly in a large percentage of people...
...I take exception to the thought that taking TMG may reduce the transsulfuration pathway and lower glutathione temporarily...firstly homocysteine is a nerve toxin and is never intended to build up and so you NEED TMG to keep it from postprandial buildup in your system because the transsulfuration pathway is SLOW and the mB12+mflate pathway is SLOW. While it is true that if you let homocysteine build up to do its deleterious damage it may eventually process through the transsulfuration pathway but that is not the way to raise glutathione. If you keep homocysteine from building up by recycling, then instead of injuring your nerves while waiting to drain by that path it will be (and is supposed to be) cycled THREE times through the methyl cycle making SAMe for use throughout the body, and THEN it will drain through that pathway to make glutathione (or not) EXACTLY as it would have done anyway but w/o the nerve ad blood vessel damage. It was deermied that the people who ate the most amount of TMG through diet eat 2g/day.
So all I know is that this is what gets my homocysteine perfect:
2/day Thorne Basic B
1 Solgar Metafolin (800 mcg)
50mg P5P
2g TMG (Soloray 1g pills)
I do not take mB12 except as is in the Thorne Basic B.
However note:
I do take 50,000 D/week and D is known to improve the methyl cycle.
The methyl cycle enzymes need both zinc and copper. I have to supplement both.
I take high dose anti-oxidants, as free radicals negatively impact the methyl ccyle.
I take DHEA and studies say the testosterone it makes corrects my CBS defects and the DHEA or something it makes also improves my ability to make or conserve BH4 (so maybe I am saying the same thing because it is CBS +/+ that uses up BH4 so fast, although it could be the MTHFR 1298AC it corrects although I never read that it did so). Beaware that BH4 is also destroyed by oxidative stress, hence the many benefits of antioxidants.
DanHi triffid,
5. Finally -- did you add the Thorne Basic B after you had the methyl donors, etc., in place? It looks like a pretty decent formulation, but seems to have (like so many), quite high levels of niacinamide/niacin, which as said to act as 'methyl sponges'.
THANKS IN ADVANCE,
Dan