The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
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Excess TMG and methylation...

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by dannybex, Jan 11, 2015.

  1. dannybex

    dannybex Senior Member

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    Can "too much" trimethylglycine (TMG) cause problems? And if so, how does this excess TMG affect the rest of the methylation cycle?

    I ask because I've been taking betaine HCL for more than a decade, and wondering if or how it's affected folate and b12, etc.?

    Thanks in advance.
     
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  2. Sherpa

    Sherpa Ex-workaholic adrenaline junkie

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    I'm not sure, since I've never taken TMG.. but this recent article on TMG by Dr. Lawrence Wilson has some detailed info that should interest you.
     
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  3. dannybex

    dannybex Senior Member

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  4. caledonia

    caledonia

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    Yes, I managed to get into overmethylation in the BHMT pathway using lecithin (which is much milder than straight up TMG) - even though I have many BHMT SNPs. There was a person on here who had accidentally OD'd on TMG and had horrible overmethylation.

    Niacin was helpful in both cases.

    It seems like if you had the secondary (BHMT) pathway running fast, it might take way from the long way around (primary folate/B12 pathway).
     
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  5. dannybex

    dannybex Senior Member

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    Thank you @caledonia. That's my understanding as well. But in doing so, do you know if it drains or depletes folate in the process? Niacin never helps when I feel 'overmethylated'.
     
  6. caledonia

    caledonia

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    Hi Dannybex, I've never been able to find out what happens to folate except it never makes it around the cycle to make methyl groups. Maybe it backs up and becomes UnMetabolized Folic Acid :eek:

    See this post by Rich Vank (about halfway down the page). http://forums.prohealth.com/forums/...hvank-question-re-tmg-and-methylation.176467/
     
  7. dannybex

    dannybex Senior Member

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    Thanks @caledonia. I stumbled across an October 2010 email from Rich, after I told him I was taking 6-7 betaine HCLs with each meal, where I think he's saying kind of the same thing:

    "The betaine will stimulate the alternative BHMT pathway in the liver and kidneys, and that may make it difficult to lift the partial block in the methionine synthase pathway, which is linked to the folate metabolism, and which needs to be operating normally to bring glutathione up and also get the folate metabolism back to normal. So if you don't notice much change after being on the simplified treatment approach for a couple of months or so, then you could consider adding some DMG (dimethylglycine), which will slow down the BHMT pathway and hopefully shift more of the flow to the methionine synthase pathway. I think this has to be done by trial and error, because different people may respond differently, based on genetics."

    Interesting from your link, he says: "(DMG) forces more of the flow through the parallel methionine synthase pathway, provided that the B12 and folate have been built up prior to this."

    So I have a feeling I've indeed been cluelessly either draining whatever folate I may have eaten/taken, and/or almost completely bypassing any fix of the methionine synthase pathway with such an excess of betaine HCL.

    sigh.
     
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  8. Critterina

    Critterina Senior Member

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    The block of the methionine synthase pathway you're talking about here - that would be not enough homocysteine, right? That's the substrate that TMG uses up in the BHMT pathway, the substrate that MTR also competes for. So, this total argument/suggestion to take DMG to encourage the MTR makes no sense to me! DMG does indeed slow down the BHMT reaction, but other than making more homocysteine available, I can't see it doing anything to encourage the folate cycle. The problem most people have with the folate and methionine cycles is NOT too little homocysteine. Am I missing something here?
     
  9. caledonia

    caledonia

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    I think I found it.

    http://en.wikipedia.org/wiki/Methionine_synthase


    MTR = methionine synthase

    MTR is used both to convert folate and make methionine out of homocysteine. So shunting some extra homocysteine over to MTR should also help folate conversion (assuming you have some folate which needs converting).

    Cobalamin (B12) is also a co-factor in the reaction. So that's why Rich is saying to have B12 and folate built up prior to using DMG.
     
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  10. kyzcreig

    kyzcreig Senior Member

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    I've been taking TMG aggressively for a few months because I found it helped my sleep, if what I'm understanding is right that's a bad idea with a methionine block.

    Is there any way to detect a methionine block? Or is that implied in a functional folate deficiency.

    For the record I'm also taking 20-30mg of folate (and corresponding amounts of b6 and b12 depending on if I feel over methylated).
     
  11. Critterina

    Critterina Senior Member

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    There is no "shunting" going on here. From a chemical point of view, homocysteine is available for the MTR or the BHMT reaction. If you don't use it for one, yes, it's available for the other. But only if it's a limiting factor does not using it for BHMT make any difference in the MTR pathway. BOTH routes convert homocysteine to methionine through methylation, letting the methyl cycle run.
    If someone has a folate cycle problem, homocysteine tends to build up, so there is too much of it. Too much homocysteine is associated with ill health (cardiovascular disease and other). So doctors are not happy to find high homocysteine. If that person takes DMG, the BHMT pathway essentially slow down, so the only way for the methyl cycle to run is through the already-less-than-efficient MTR pathway (MTHFR C677T and MTRRA66G are the specific SNPs I'm talking about). So by taking DMG, the person is forcing their body to use the broken pathway. I can't imagine a world where this is a good idea.
     
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  12. dannybex

    dannybex Senior Member

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    I'm definitely no expert, that's why I was asking for guidance. But doesn't the BHMT pathway only affect homocysteine levels in the liver, not the rest of the body?
     
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  13. caledonia

    caledonia

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    Right - not a good idea unless you're also supporting MTHFR and MTRR with folate and B12, essentially bypassing the broken pathway.
     
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  14. kyzcreig

    kyzcreig Senior Member

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    so how do you know if you've adequately built up folate and b12?

    Early on Tmg is tremendously effective in getting methylation kickstarted, is this supposed to diminish over time? How would you know, just based on sympyoms?

    Speaking just for myself i feel terrible if I don't take copious amounts of Tmg. Does that mean I should keep taking it until it's no longer so effective and then switch to DMG?


    I'm just trying to make sense of this all, any insight would be much appreciated
     
  15. soccer_dude

    soccer_dude

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    Hi,

    I was an under-methylator. I have been taking TMG 600mg-1200mg daily in the mornings, and 5000mcg of Active B12, etc....Is it possible to start over-methylating? I was feeling REALLY good for a while, but now I'm feeling over stimluated, like I've had too much caffeine. I don't feel any anxiety/panic, but just feel stimulated. And I also have some excess nervousness, and/or butterfly feelings in my stomach, but again, I don't have any anxiety/panic. I might get nervous easy going into a meeting or a party, but I look forward to going and usually have a good time although I'm feeling really uncomfortable with this stimluation feeling. My heart rate is normal, I'm not sweating like a pig, just this uncomfortable stimulation feeling. And it has caused severe insomnia as I'm just very alert/wired.

    I thought I had some adrenal fatigue. And there's warning about taking B12 as you could feel good for a while then crash your adrenals. Yet, I've heard you need B12 to keep your energy going so that your adrenals don't have to compensate.

    I am MTRR++, so I require Methly-B12.

    I did have some extra stressors that seemed to kind of trigger some of this, but I have to wonder how much of this is due to being over methlyated and being suspectable to being easily stressed?

    I'm also on 300mg of St. John's Wort, so it's possible I'm making too much of a particular neurotransmitter. But....

    I could try 500mg Niacin and see if this feeling shuts off. If it does, then maybe I need to lower my dose of B12 and/or TMG....

    Any thoughts? Thank you!!!
     
  16. ahmo

    ahmo Senior Member

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    @soccer_dude If it were me, I'd start w/ reducing the TMG. or eliminating it for a day or 2, see what happens. Are you taking folate?
     
  17. ebethc

    ebethc Senior Member

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    What does overmethylation feel like? I take betaine hcl every day, and I have +/+ BHMT 2 & 8
     
  18. ebethc

    ebethc Senior Member

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    What does homocysteine do in the liver? I always have normal levels of homocysteine
     
  19. dannybex

    dannybex Senior Member

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    I'm still not an expert -- 2 1/2 years later -- but in general, I believe you would feel overstimulated in general. I'm still taking betaine HCL, but 3 or sometimes four caps w/a meal instead of 6-7. Trying to eventually cut it out completely though and get my stomach to naturally produce it's own hydrochloric acid. Obviously haven't figured that out yet, but am starting to try high-dose probiotics and/prebiotics...
     
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  20. dannybex

    dannybex Senior Member

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    I have no idea, sorry @ebethc.
     
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