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Emergency, Please Help

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by joejack102, Oct 20, 2017.

  1. alicec

    alicec Senior Member

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    I have no doubt you are feeling extremely fatigued and unwell but thinking you are going to die suggests the possibility of some sort of panic reaction.

    Taking an excess of some nutrient is not going to cause you to die, you need to recognise this as an overreaction and try to calm down.

    One possible reason for the reduction of your sensitivities following choline supplementation is stimulation of histamine removal via the enzyme NHMT. In other words you may have increased methionine production via the enzyme BHMT, this in turn increased SAMe production which is the methyl donor for NHMT and so the enzyme was better able to act on removal of accumulated histamine.

    If this is the case it suggests that prior to the choline, your methyl cycle was sluggish. There could be many reasons for this. Some SNP combinations could perhaps be making a contribution but it is highly unlikely that you have some genetic blockage that is having dire effects. There is a great deal of hysteria on the net about SNPs and I urge you to be far more sceptical than you appear to be about claims for what SNPs do and don't do.

    The vast majority of the SNPs which generate a lot of popular internet chatter have little or no effect though a few do indeed have small to moderate effects. Furthermore, many are common variants that millions of people live with without too much difficulty.

    Strangely, the usually rare SNPs that can have very serious effects do not seem to be the ones that have captured the popular imagination.

    As for why the choline no longer seems to be beneficial and indeed why you seem to be unwell despite stopping it, consider that in stimulating these pathways you might have placed increased demands on one or more vitamin or mineral cofactors and have now depleted them. Multiple pathways have now become sluggish.

    Unfortunately there is no easy answer to which - it is something you would need to determine by trial and error.

    There is a thread on refeeding syndrome which might perhaps give some insight into the depletion phenomenon. Folate and potassium are usually the first nutrients to be depleted in this model, minerals come later.
     
    Asklipia, joejack102 and helen1 like this.
  2. joejack102

    joejack102

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    Over the weekend, I began looking over and over at all the Methylation charts and pathways. Staring. I was staring at them constantly. Thinking, thinking, thinking. I was asking myself, "What did the Choline do to make me not sensitive anymore to meds and made me so dangerously ill. And how do I reverse it?" My physical health was not just a "panic" reaction, but a very real one, because my body was starting to shut down.

    Then, I really started focusing on THIS on Saturday night!!!!

    FullSizeRender-2.jpg choline-2.jpg


    Mystery solved, I'm pretty sure. MAJOR BHMT pathway BLOCK. This Choline imbalance had not resolved itself in the slightest in over 8 years. Notice how after Choline, the Betaine leaves the Mitochondria, and it is supposed to return as DMG.

    Just started DMG (DiMethylGlycine) supplement and it appears to be working, but I'm waiting to see absolutely for sure before declaring, "it worked."

    Now, the real question is, why do I have a BHMT pathway block allegedly? And why is my ANA pattern speckled? Why have I had POTS Syndrome symptoms most if not all of my life? And how do I better understand and then attempt to cure the problem?
     
  3. joejack102

    joejack102

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    BHMT Gene
    • rs585800 - BHMT-01 (Risk Allele: T)
    • rs567754 - BHMT-02 (Risk Allele: T)
    • rs617219 - BHMT-04 (Risk Allele: C)
    • rs651852 - BHMT-08 (Risk Allele: A, 23andMe: T)
    The product the BHMT gene is central to the ‘short cut’ through the methylation cycle, again helping to convert homocysteine to methionine. The activity of this gene product can be affected by stress, by cortisol levels and may play a role in ADD/ADHD by affecting norepinephrine levels.

    Yasko believes that believes BHMT-02 and BHMT-04 play a role in the gut environment. Yasko also believes that BHMT-08 is related to the impact that psychological stress has on a patient's attention levels.


    NOTE: I also have ADHD.
     
  4. joejack102

    joejack102

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    I shouldn’t have made it seem like I know if DMG is working. I cannot tell yet. If not, who knows what I should try.
     
  5. alicec

    alicec Senior Member

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    Why conclude that. Choline oxidation to betaine occurs only in the mitochondrion. Maybe the problem lies with transport of choline into the mitochondrion. This would lead to shortage of betaine to act as substrate for BHMT1 in the cytosol.

    Increasing choline intake may have stimulated the transporters ultimately leading to more betaine to power BHMT1.

    Note there is a second form of BHMT (BHMT2) in the mitochondrion which uses SAMe rather than betaine to methylate homocysteine.

    Be careful - DMG is a potent inhibitor of BHMT.

    Yasko is not a reliable source of information on SNPs. Her claims often have no basis in any research or are contrary to research. The first three BHMT SNPs she lists have no reported effect. Her belief about the role in the gut of BHMT 02 and 04 is not backed by any studies.

    BHMT 08 does have a small effect but it is beneficial.

    Here is a thread about BHMT. As far as I'm aware there are no known serious genetic problems with this enzyme.
     
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  6. joejack102

    joejack102

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    THANK YOU ALICEC. I took one yesterday, and one this morning. But I am seriously doubting that it is working at this point!

    What should I try? What supplement has the BEST CHANCE?
     
  7. joejack102

    joejack102

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    Are you saying to try Betaine (TMG) or to try SAM-e (S-Adenosyl methionine) or what else?
     
  8. joejack102

    joejack102

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    What do you suggest I try? I've tried all the vitamins like B6, B12, Methyl-B12, Methyl-Folate, etc etc etc.

    Can you make a list of things that make sense to try and why they make sense?
     
  9. alicec

    alicec Senior Member

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    I could have been a good idea to substitute TMG for choline to see if it had the same effect. This would tend to confirm that the benefits of choline were due to its stimulation of BHMT (or at least predominantly so) rather than to some other aspect of choline metabolism.

    Now that choline no longer has the same effect, perhaps the TMG might not do anything.

    Still it could be worth a try to see if it does. It could give some clues that finding sustainable ways of stimulating the methylation cycle could be worthwhile.

    SAMe is a more difficult supplement and more expensive. I've never much seen the point of it though some people find it helpful.
     
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  10. alicec

    alicec Senior Member

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    I don't know enough about you or your background to make particular suggestions.

    I don't think any one nutrient is going to do it, it is probably combinations. After all, as the diagram you linked shows, many pathways are interdependent and they use a wide variety of vitamin and mineral cofactors.

    As an example of what you might need to consider, I suggest you look at threads started by people like Freddd on the range of cofactors that became necessary to gain consistent benefit from B12/folate, which of course is at the heart of the methylation cycle.

    What worked for him may not necessarily work for you but there is a lot of discussion on PR about peoples' experiments with stimulation of these pathways.
     
    joejack102 likes this.
  11. joejack102

    joejack102

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    So there is a chance that TMG (Betaine) could reverse the "permanent" effects of what the Choline did, hopefully?
     
  12. joejack102

    joejack102

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    IMG_0562.jpg

    Perhaps this is a new possibility. Perhaps the Betaine has a "reverse feedback" effect on the excessive Choline I took years ago?
     
  13. alicec

    alicec Senior Member

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    I have no idea really. If the problem is depletion of various cofactors, then no.

    If the problem is tied up with some other aspect of choline metabolism then maybe. You can but try.
     
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  14. alicec

    alicec Senior Member

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    Not a lot seems to be known about the CDH enzyme. I did a quick google about regulation. There is one reference to feedback inhibition of CDH by both betaine aldehyde and betaine - in oysters. Whether or not it happens in mammals I don't know, but this mechanism is a very common way of regulating many enzymes.

    If too much product accumulates for whatever reason, the high levels slow down the enzyme making it until levels drop below a certain level. Usually too, if product levels become too low, the enzyme is stimulated.

    This is just a normal regulatory mechanism. I don't see that it is particularly relevant to your problem.
     
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  15. joejack102

    joejack102

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    Perhaps it is an imbalance between Choline and TMG that is going on.

    Considering I've tried so many things which have zero effect on helping at all, I'm convinced it's a single chemical/ingredient that will reverse this for some reason.
     
  16. alicec

    alicec Senior Member

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    Well good luck with that. Let us know if you find the magical ingredient.
     
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  17. joejack102

    joejack102

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    I hope I do, but I also hope I am not across as closed minded. I'm desperate to fix this problem. I've got to find out how to reverse this so that I start being responsive to medicines and herbs again. Literally nothing works and everything makes me sick.

    You are so smart alicec, and if you have any other ideas/concepts or things I should be looking at, please let me know! I will investigate and consider ANY hypothesis! Is there anything else that might reverse the Choline problem and make me more sensitive to meds and herbs again?
     
  18. joejack102

    joejack102

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    7837CE12-6BBE-4156-A143-64730B4806E2.jpeg UPDATE:

    Since over the past 8 years I have tried EVERY ingredient it seems in the Methylation protocols extensively, I have another idea: AUTOIMMUNE.

    This condition is clearly an autoimmune condition. My Anti-Nuclear Antibody (ANA) test is positive. And I believe that since everything that has worked to reduced my sensitivities involved ACETYLCHOLINE, that somehow my immune system likes to attack my acetylcholine receptors or something like that. So somehow by taking so many Choline supplements, my sensitivities decreased over time. How can I reverse this by tricking my body to “attack” the opposite direction so to speak? I’ve been suffering for 8 years after taking Choline OTC, and it got worse after trying Choline again earlier this year.
     
    Last edited: Oct 26, 2017
  19. alicec

    alicec Senior Member

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    Sorry I was particularly unwell last week and unable to respond.

    I did have a thought yesterday - it is not a new concept since I still think depletion is the most likely explanation for your problems, but it helps to narrow things down a little.

    I was thinking about TMG and realised that, while in the past it might have been helpful to work out what was having the effect, now it would not be a good thing for you to try. It would probably make things worse.

    The reason for this is that by pushing the BHMT pathway so much with choline supplementation, you are depleting homocysteine. TMG would have the same effect.

    The consequence of homocysteine depletion is that the methionine synthase reaction is compromised (homocysteine is the substrate for the enzyme) and this is the only reaction in the cell that converts methylfolate (the major form of circulating folate) into THF, the form of folate which then feeds into the folate cycle.

    When methylfolate accumulates in the cell and can't be used, the cell responds by dumping it. You now have a profound folate deficiency within the cell. This is the so-called methyl trap. See this paper . It describes a slightly different situation from what might be happening in you though the principle holds.

    There was a thread some time ago that is very relevant. This post onwards goes into the detail. The effect of choline would be the same as TMG.

    So you say that you have tried various methylation supplements to no effect. I urge you to reconsider your strategy and consider that you may not have taken sufficient folate. Of course you need the whole gamut, but folate may be the key.

    The thread canvasses a lot of detail. It may be helpful to you and it is an easy enough strategy to try out. If it doesn't help then you know you need to look elsewhere.
     
    Helen likes this.
  20. alicec

    alicec Senior Member

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    That is not uncommon and may not mean much. See this post and this and read the whole thread. I would urge you not to jump to conclusions based on a test for an isolated antibody which is commonly found to be elevated in normal populations.

    There does seem to be an auto-immune subgroup in ME/CFS. There are threads discussing this on PR along with various tests for autoantibodies.
     

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