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Just got my Methylation and Detox Profile Results: can the Experts Kindly Provide Commentary Please

Discussion in 'Genetic Testing and SNPs' started by Hip, Mar 12, 2013.

  1. ktred

    ktred

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    Does anyone know where there's information on interpreting the detox profile?
     
  2. Hip

    Hip Senior Member

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    Caledonia, it's very interesting that all the 40 or 50 ME/CFS patients whose methylation results you saw had MTHFR mutations. Since you say these MTHFR mutations are common in the general population (40% of people have them), you'd expect many ME/CFS patients to have MTHFR mutations; but not all ME/CFS patients.

    Your observations tend to indicate a causal connection between MTHFR mutations and ME/CFS.

    I wonder if research has been done that links MTHFR mutations to ME/CFS?
     
  3. caledonia

    caledonia

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    I don't think any formal research has been done yet. I could see this happening soon via 23andme and their partnership with (darn can't ever remember the name) a health site.They have a grant from the NIH which is why they dropped their price through Dec. They hope to get 1 million samples in their database, which will be awesome for research.

    My naturopath at one point had said that everyone who walked into his practice had MTHFR mutations. So I guess you can take that for whatever it's worth.
     
  4. Lotus97

    Lotus97 Senior Member

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    Betaine HCL is the same thing as TMG. On that note, I just found out there's over 600 mg of TMG in 100 g of quinoa, but maybe a lot of that is lost in cooking.
     
  5. Hip

    Hip Senior Member

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    Betaine is the same thing as TMG (trimethylglycine), but betaine HCl is a different substance, as it has an additional HCl added, HCl being the hydrochloric acid molecule which boosts stomach hydrochloric acid levels.

    Betaine = TMG = C5H11NO2
    Betaine HCl = C5H11NO2HCl

    This I guess makes betaine HCl a doubly useful supplement for ME/CFS patients with low stomach acid levels, as the HCl part boosts stomach acid, and the betaine part acts as a methyl donor to boost the methylation cycle.
     
  6. Lotus97

    Lotus97 Senior Member

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    I don't understand this chemistry stuff too well. Is there any way to know what the equivalent dosage is between TMG and Betaine HCL as far as being a methyldonor? Since Betaine HCL has extra stuff would that mean that 500 mg of TMG would be stronger than 500 mg of betaine HCL?
     
  7. Hip

    Hip Senior Member

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    I have just done a quick molecular weight calculation, and it turns out that 76% of the weight of betaine HCl is the betaine component. So if you took 500 mg of betaine HCl, that would give you 76% x 500 mg = 380 mg of betaine.
     
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  8. Hip

    Hip Senior Member

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    Over this last week, I just started to experience significant depression symptoms after beginning a regimen of taking betaine HCl daily with my meals (a total of 1800 mg daily).

    This betaine HCl (a hydrochloric acid supplement) did noticeably improve my digestion, so there is no doubt I have low stomach acid, but I think the betaine component of this supplement seems to have caused depression in me, presumably by activating my methylation cycle.

    In the past, I have also noticed that SAMe and betaine (= trimethylglycine) supplements — both methyl donors — make me depressed.

    So for the moment, I have stopped taking betaine HCl (and my depression quickly cleared).


    Can anyone hazard a guess as to whether this depression I experienced from betaine HCl is a temporary Herxheimer reaction as methylation kicks in, or whether this depression has some other cause?

    Also, if this depression is due to methylation kicking in, how long might it take before the depression clears? I find depression symptoms like this very hard to bear, and I don't think I go through more than a few days like this.
     
  9. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    That is indeed useful - I burp for England (or should that be Cornwall?) when I take bicarb!
     
  10. caledonia

    caledonia

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    In practice, I'm not so sure about betaine hydrochloride = TMG. At least when I tried them, the betaine worked on stomach acid as it was supposed to and didn't give me any energy. The TMG presumably helped the secondary pathway like it's supposed to and has given me a bit of energy.

    I have both CBS and BHMT mutations. I was getting anxiety/stress reactions to methyl donors (this is what is predicted if your CBS is expressed). When I overdid TMG, I got a revved up anxious feeling. Some niacin calmed it back down. So everything for me is working as predicted.

    Do you have COMT mutations by any chance? Getting too many methyl donors can cause mood swings.
     
  11. Hip

    Hip Senior Member

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    I am heterozygous for two COMT SNP's, as you can see here.
     
  12. caledonia

    caledonia

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    Do you also get the depression if you take mB12 or mfolate?
    The solution is to be careful how many methyl donors you take. If you're having mood problems, it's too much, so you need to lower the dose to something you can tolerate.
     
  13. Hip

    Hip Senior Member

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    No, I am always fine with B12 methylcobalamin, even if I take as much as 30 mg sublingually. I am also fine with methylfolate.

    It is just TMG that seems to cause depression (either as pure TMG, or as betaine HCl). The other supplement that causes me to get some mild depression is SAMe (aka: S-adenosyl-L-methionine). I know SAMe is supposed to act as an antidepressant, but for me, it in fact causes some mild depression.
     
  14. caledonia

    caledonia

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    Then I'm not sure why they would cause depression. Maybe something to do with BH4 as a guess, but I'm not very familiar with that end of the pathway. At any rate, if they make you feel worse, I would avoid them or at least cut back to something you can tolerate.
     
  15. Lotus97

    Lotus97 Senior Member

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    If TMG causes depression in you then it sounds like that's probably the reason for the betaine HCL to cause the same symptoms (although I have no idea why since you say you can tolerate methylfolate and methylcobalamin fine), but it could be from die-off. Starting 4 months ago I've been getting depression from supplements that cause die-off (including probiotics). I also find the depression very difficult to bear. I had my depression pretty much handled with Prozac until a few months ago. As far as betaine hcl causing die-off, I found a few accounts
    http://www.remedyspot.com/showthread.php/1011121-Can-Betaine-Hcl-cause-die-off
    http://curezone.org/forums/am.asp?i=1479233
     
  16. Hip

    Hip Senior Member

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    I think I may have worked out why TMG and SAMe cause me to feel depressed: because both of these supplements increase the alpha interferon response, and interferon can cause depression. Ref: 1.


    The way this interferon-induced depression arises is as follows:

    • Low serotonin can cause depression or irritability.
    • Tryptophan is needed to make serotonin.
    • Tryptophan is broken down by the enzyme IDO (indoleamine-2-3-dioxygenase).
    • Interferon stimulates the activity of the IDO enzyme, causing increased tryptophan breakdown.
    • Hence interferon can cause depression or irritability.

    Since interferon gamma is generated when the immune system is in Th1 mode, the use of Th1 boosting supplements may also cause increased tryptophan breakdown, leading to depression or irritability.

    And indeed, I find several Th1 boosting supplements tend to cause me to get noticeably depressed, particularly the following Th1 supplements: Epicor (Saccharomyces cerevisiae), Astragalus, inosine, beta sitosterol, and transfer factor.

    This is very unfortunate, because of course the Th1 mode, and interferon gamma, are part of the body's antiviral response, and are needed to help fight the viruses thought to underpin ME/CFS.


    Dr Chia used to use interferon for his enterovirus-associated ME/CFS patients, but stopped doing so because of the bad depression side effects of interferon (and the fact that after the interferon treatment, the patients that gained remission would crash back into ME/CFS some months later, so in fact interferon was not a permanent cure).



    Interestingly, in the case of herpes family viruses, this interferon-induced breakdown of tryptophan has an antiviral effect, because herpes family viruses depend on tryptophan for replication.

    Although for some reason, only the tryptophan breakdown triggered by interferon gamma has an antiviral effect for herpes family viruses; but the tryptophan breakdown triggered by interferon alpha or interferon beta does not seem to result in an antiviral effect against herpes family viruses. So the antiviral effects of interferon alpha and interferon beta against herpes family viruses come from mechanisms other than tryptophan breakdown. Refs: 1, 2.
     
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  17. Lotus97

    Lotus97 Senior Member

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    I have a question about this and then some comments. You said you've taken methylfolate and high doses of methylcobalamin without a problem. So what's the difference between the SAMe produced through methylation and SAMe from TMG?

    I've traced my recent depression over the past 4 months to inflammatory cytokines. I'm trying to fit all the pieces together and this information seems to help. I believe that my Lyme infection has reactivated due to my relapse and/or Lyme being part of the cause of my relapse (chicken vs. eggo_O). Anyway, Lyme can cause the Th1 immune system to become overactive. I also happened to be taking a lot of immune system supplements. Some of which can shift from Th2 to Th1 and/or stimulate Th1 responses.

    I think there's more to building a healthy immune response than just stimulating Th1 and/or shifting from Th2 to Th1. With Lyme, the illness suppresses certain aspects of the Th1 system so that an activated Th1 response isn't necessarily effective. In general, with viruses and infections associated CFS/ME Rich talked about how glutathione depletion can cause natural killer cells and CD8 cytoxic T lymphocytes (both associated with Th1 responses) to be unable to function properly.
    http://forums.phoenixrising.me/inde...lls-perforin-and-glutathione-depletion.17603/
    Natural killer cells normally kill cells that are infected with viruses. They do this by secreting a substance called perforin, which makes a hole in the cell membrane, and then injecting granzymes, which induce the cell to undergo apoptosis (programmed cell death). The CD8 cytotoxic T cells operate in the same way in terms of their killing mechanism.

    Some years ago, Dr. Kevin Maher, who was in Dr. Nancy Klimas's group, reported that the natural killer cells in PWMEs are low in perforin. It was also found that the CD8 cytoxic T lymphocytes were also low in perforin. This would, of course, inhibit their cytotoxic activity.

    I suggest that this new result is consistent with the mechanism I have proposed for low perforin in ME/CFS. It indicates that the NK cells and CD8 cells are "trying hard" to produce perforin by boosting the transcription of the PRF1 gene to messenger RNA, but the protein synthesis process is at least partially blocked and cannot respond. If glutathione is somewhat depleted in the NK cells and CD8 cells, the protein synthesis process would indeed be partially blocked.

    I continue to propose, as I did in 2007, that other features of the observed immune dysfunction in ME/CFS can also be explained by the GD-MCB hypothesis. These include the shift to Th2 immune response, the elevated RNase-L and formation of the low-molecular-weight RNase-L, the elevated inflammation, the failure of lymphocytes to proliferate when stimulated with mitogens, the reactivation of viruses and intracellular bacteria, and the accumulation of pathogens over time.

    Best regards,

    Rich
     
  18. Hip

    Hip Senior Member

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    Did you mean to say: "So what's the difference between the SAMe produced through methylation and SAMe from a supplement?" If so, I don't know for sure, but possibly supplemental SAMe will raise your SAMe levels higher than the levels achieved through the methylation cycle.

    You might consider cutting out the Th2 to Th1 shifting supplements for two or three days, and if your depression lifts, then it indicates these supplements were the cause of your depression. I have found that Th2 to Th1 shifting supplements cause me to have depression literally just a few hours after taking them; but equally, this depression will go away by the next day if I stop these supplements.

    Certainly. The immune system has hundreds of facets.

    I find it interesting that coxsackievirus B, when it infects cells, down-regulates the expression of certain proteins on the cell surface, making CVB-infected cells invisible to CD8 T cells (ref: 1). So even boosting or modulating immune system, you are still going to find it hard to target these infected cells, that are invisible to the immune system.
     
  19. Lotus97

    Lotus97 Senior Member

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    I was just referring to SAMe produced from TMG/betaine HCL (and not taking SAMe directly) vs. SAMe from methylation. Based on your experience, it sounds like there is a difference between SAMe produced through methylation and SAMe produced from TMG and betaine HCL. And also that there are similarities between supplemental SAMe and SAMe produced from TMG/betaine HCL. I suppose we'd need more information to come to any conclusion. I also wonder if supplementing with methionine would cause the same issues since that's also converted to SAMe.
     
  20. Lotus97

    Lotus97 Senior Member

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    In that thread I linked to, there's a discussion about interferon (mostly on page 2 of the thread). Interesting what he said about cold and flus. I don't think I've had the flu or a cold in over 15 years. Maybe just coincidence, but maybe not.
     
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