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COMT and methylfolate

Discussion in 'Genetic Testing and SNPs' started by drex13, Feb 14, 2013.

  1. drex13

    drex13 Senior Member

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    In the information from heartfixer and yasko etc.. mention is often made of those with COMT + status and their probable inability to handle methyl donors. In such cases they often advise that the patient would have difficulty tolerating methyl B-12 and would do better on hydroxy B-12. But, I have not found any mention of difficulty tolerating methylfolate. Wouldn't it make sense that if (in this theory) you can't tolerate methyl donors, and then can't tolerate methyl b-12, a patient would also have difficulty tolerating methylfolate, and therefore folinic acid may be a better option for that patient ? I admit, I don't have a thorough understanding of the methyl cycle or the interplay of all the various genetic SNP expressions, but this was just an idea that occurred to me, as I seem to have a very difficult, if not impossible time tolerating either MB12 or methylfolate, but hydroxy b12 seems ok. I am undecided on the the folinic acid, as I have never taken it without also being on methylfolate. I wondered if anyone else had a similar experience ?
     
  2. adreno

    adreno 3% neanderthal

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    Yes, it makes sense that you would be sensitive towards methyl donors in general in this case.
     
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  3. triffid113

    triffid113 Day of the Square Peg

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    And yet you cannot assume all the facts are in because I am COMT +/+ and am not at all sensitive to methyls:

    6 Homozygous:
    COMT V158M +/+
    COMT H62H +/+
    ACE Del16 +/+
    MTRR A66G +/+
    BHMT 1 +/+
    CBS C699T +/+

    12 Heterozygous:
    VDR Taq +/-
    VDR Fok +/-
    MAO A R297R +/-
    MTHFR A1298C +/-
    MTRR 11 +/-
    BHMT 8 +/-
    AHCY 1 +/-
    AHCY 2 +/-
    AHCY 19 +/-
    CBS A360A +/-
    SHMT C1420T +/-
    NOS D298E +/-

    You might note that I have MTHFR 1298AC, which means I have difficulty making BH4 and I have 2 CBS mutations which mean I use it up faster than normal (supposedly). At any rate, my father with MTHFR 1298CC (homozygous) and 2 CBS +/- died of kidney disease with no detectable level of BH4 (needed to make dopamine). My point is that there are many interactions not figured out yet. Your genes are only suggestive of things you should watch out for or test separately. Certainly the multitude of combinations have not been analyzed together.
     
  4. drex13

    drex13 Senior Member

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    I'm not assuming anything. I am asking a question. If the supposed idea that having a COMT mutation makes one sensitive to methyl groups (i.e. methyl b-12), then wouldn't one also be sensitive to methylfolate ? I never see this mentioned in the COMT information I've read, and just wondered if anyone found they couldn't tolerate either "methyl" supplement. Or if they could not tolerate mb12, but had no issue with methyl folate, then maybe COMT isn't the issue and doesn't matter at all ? So then maybe it isn't a "methyl " issue, but something else.
     
  5. LaurieL

    LaurieL Senior Member

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    It is my understanding that COMT relative to methyl donor sensitivity is related to dopamine levels of the individual in which COMT is responsible. But COMT status alone, would not be the determinate of sensitivity as other mutations also affect dopamine, such as VDR and CBS related sulfite toxicity. Sensitivity or tolerance is due to dopamine levels.
     
  6. Symptomatic

    Symptomatic Senior Member

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    I am wondering the same thing, I am COMT +/- (also CBS +/-) and trying to start some kind of methylation protocol. But I have concerns about methyl sensitivity too, and was also contemplating the methylfolate issue. I've been pointed to info from Yasko, who suggests that those with COMT rotate methyl donors. I have decided to start with hydroxycobalamin, then eventually add folinic acid one day and 5-MTHF the next, switching back and forth. I may or may not add TMG, depending on how I feel.
     
  7. Tom_Nightingale

    Tom_Nightingale

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    On this topic of dopamine levels, I MUST have higher dopamine levels since I can barely tolerate the majority of methyl donors. It's further corroborated by the fact I have to take an antipsychotic (read: dopamine receptor blocker) to prevent psychosis. I have been very frustrated in trying to supplement my methylation cycle. I just tried hydroxocobalamin for about 4 days, and it so affected my cognitive function that I had to stop if because I could hardly formulate a coherent thought. Are you aware of others here who probably have high dopamine levels because of their sensitivity? I'm desperately trying to find some help, as I constantly deal with fatigue and "brain fog" along with the threat of mood disorder.

    I've got 2 COMT (+/-) and MAOA (+). I started taking vitamin B2, riboflavin, as I was told it's a precursor for many enzymes like MAOA.
     
  8. Lotus97

    Lotus97 Senior Member

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    I don't want to take this thread off topic since it's about folate and not B12, but couldn't a COMT take methylcobalamin if it was just at a very low dose? I'm not necessarily saying that that is the best route to go, but I was curious. I don't know much about SNPs, but I'm trying to learn more.
     
  9. Lotus97

    Lotus97 Senior Member

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    Are there other reasons why a person can be sensitive to methylfolate? Even if someone is COMT and sensitive to methylfolate, do we know that that's the reason why? I know I'm sensitive to methylfolate and my symptoms seemed to be symptoms of overmethylation. I'll find out in a couple of weeks what my SNPs are, but I still want to raise the question as to why. I've heard some people suggest deficiency symptoms, but I'm not sure about that either.
     
  10. ktred

    ktred

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    I was researching studies relating to COMT +/+, it seems that it's not simply the levels of dopamine in the brain, but which part of the brain the dopamine is in. One study I read suggested that one of the COMT +/+ snp's tended to result in lower levels of dopamine in the frontal cortex but higher levels elsewhere. Low levels of dopamine in the frontal cortex are characteristic of ADD. Of course, not every study confirmed this, probably because they aren't accounting for the fact that COMT +/+ status plays out differently in various people due to all of their other snp's.

    I think I read somewhere that COMT +/+ people can have their dopamine excessively covert to noriephedrine, resulting in anxiety.

    I have 2 COMT +/+ snp's and do well with methyl folate. I am MTFR C699 +/+ so I really need the folate. It seems to be vary from individual to individual with COMT +/+ snp's how they handle methyl donors.
     
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  11. Lotus97

    Lotus97 Senior Member

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    I was talking to dbkita about why some people react so strongly to crumbs of methylfolate. I asked him if it had to do with SNPs and he didn't think that was necessarily the case and he wasn't sure about the deficiency angle either. It's just one person's opinion, but I do value his opinion.

    That's interesting. In my research of atypical antipsychotics (risperdal, seroquel, zyprexa) which I've taken for sleep there seemed to be some information about how they lower dopamine in part of the brain and raise it in another area.
     
  12. Lotus97

    Lotus97 Senior Member

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    Have you tried folinic since posting this? Someone told me they were able to tolerate methylation supplements better after taking folinic acid. I have no idea if that will help you though. I did have a bad experience with methylfolate last fall so I haven't taken any for a long time, but I've been taking folinic for the past month or so and seem to be doing ok so far.
     
  13. Star-Anise

    Star-Anise Senior Member

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    Hi all, what symptoms are you experiencing with methyl supplementation. I tried SAMe some time ago, and it worked very well for increased energy production, then there came a time when I just got very fatigued fom SAMe. I have been trying methylfolate, and methyl B12, and noticing an increase in fatigue. I know that I have read that with methyl supplementation one must go slow due to increase in detoxification, but this doesn't feel like a detox reaction. It's a return to that heavy fatigue. I am trying to figure out the underlying process. I plan on doing Yasko's testing, just saving money. I know for a fact that I have CBS issues, as I have followed the sulphur protocols and have found dramatic, mind-clearing, and increased energy results. Thanks in advance for any info you can provide, all the best :) Star.
     
  14. Lotus97

    Lotus97 Senior Member

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    Some people do get an energy boost at the beginning of methylation and then experience fatigue later on. I suppose there could be several reasons for this. One thing to rule out is low potassium. Also, some people who are in poor health are eventually going to burn out if they increase their activity level too much (due to the extra "energy" from methylation).

    I'd like to hear about how CBS is involved since I've just begun learning about SNPs. You said you experienced increased energy from a CBS protocol. Was this before starting methylation? If so, do you think methylation has made the CBS issues return?
     
  15. Star-Anise

    Star-Anise Senior Member

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    Thankyou Lotus97 for your feedback. Yes, I am aware of potential for low potassium, but not entirely sure of underlying mechanism of that. I crave bananas like crazy, and am taking Potassium supp to help with Kreb's cycle. It does seem to help with energy.
    re: CBS, well, I'm just starting to learn about this too.

    Short hx: sick since 2004 after trip to India x4mos with ++gut disturbances. Tried many things when I got home with little success. Major turnaround came when I did my 1st yeast cleanse using Biotics Research product AOR, emulsified oregano, instead of the standard fare of caprylic acid to kill yeast. At about same time I switched from vegetarian diet to slowly incorporating as much meat into my diet as possible. This improved my energy dramatically.
    Given CBS revelation, it makes sense to me that I felt better after yeast cleanse, as yeast is an ammonia producing organism, and those with CBS mutation struggle with eliminating ammonia as well as sulphur.
    I think I was so very deficient in amino acids, as I was starting to get sick before I went to India & didn't realize it. I think my adrenals have always been a bit weak, and I have a family history of diabetes. This combo combined with overtraining as I was training as a competitive runner, combined with life stress, some pre-existing yeast problems - aka the perfect storm, set the stage for what was going to be the worst 4 mos of my life in India. I was eating primarily a fruit based diet prior to going, and raw vegan prior to that for months. I think when I hit India due to a baseline of poor methylation my body just struggled to deal with the toxic overload of being in a 3rd world country. As well, when I got back I discovered I had blastocystis parasite, which I have now hopefully cleared up recently.

    RE: COMT, I know I have problems, as part of my healing over past few years I have found +++success with Tyrosine & Phenylalanine, Tryptophan, & 5-HTP supp


    I guess I wanted to provide some backstory, because I think for me, it wasn't just the CBS issue. I think that if I would have addressed the CBS issue prior to dealing with CBS issue right now, I wouldn't have had as much success. I think with my gut being healthier, and my adrenals being stronger, with my hypoglycemia under control, my body is more able to detoxify. It was almost magical, when I took the charcoal for first time, my brain cleared, and my energy improved by 10% daily. Now that I am supplementing with the Molybdenum and I have eliminated the sulphur supplements that I was taking (Maca, and previously a supp called Broccogen), my allergies have decreased substantially, and my energy is now improved almost to pre-India!

    I think this last piece is to figure out how to work with possible COMT mutation, & perhaps MTHFR, or other methylation problems, which I figure is my baseline prior to India, as I was having energy problems even then.

    My plan is to try to intro hydroxy-B12, as I have had this overdosed feeling with methyl supps before. As I said I did do well on SAMe, and methionine for several months (say 6mos), then it just seemed to make me fatigued. It seems possible to me that I was deficient in it, needed to top up, and now maybe have sufficient methyl available to bind. I dunno, if the hydroxy-B12 works that will confirm this suspicion.

    I'll just keep plugging away! Have to trial 'n error it until I get my testing done, which will be within next mos or two.

    All the best, Star :)
     
  16. Star-Anise

    Star-Anise Senior Member

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    Yay! Hydroxy-B12 did work, and for now, proved my hunch that I did have excess of methyl donors floating around, and voila! When combined with the hydroxy-B12, sucked them right up, and put it to work to produce energy for me :) I also eliminated the carnitine supp that I was on, @ least for me, seemed to related to overdriving the methylation cycle, so far now is off my shelf, same story for the Zinc I was taking. I also am going to experiment with cutting back on magnesium for a bit, as was still a bit buzzed last night a few hours after magnesium, which is uncharacteristic. Seems for me that with any of the methylation precursors I could have potential of overmethylating... lastly, slowly cutting back on my tyrosine/phenylalanine supps which I have been taking for almost one year now, as seems that my body may be resuming some of these functions itself now that possibly I have dealt with some of the sulphur issues and more BH4 is not taken up with ammonia detoxification and is available for neurotransmitter production. :) Fingers crossed!
    :)
     
  17. Lotus97

    Lotus97 Senior Member

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    Hydroxocobalamin uses up SAMe which is part of the reason it is tolerated better by people with COMT. Niacin/B3 has a similar effect. This is from Dr. Ben
     
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  18. Lotus97

    Lotus97 Senior Member

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    It turns out I am in fact COMT +/+ which might explain might reaction to methylfolate. I'm also MTHFR +/- so I could have also been deficient in methylfolate and that could have been partially why I reacted that way. However, I spoke to someone who is also COMT +/+ and they're taking 2400 mcg of methylfolate. I'm almost positive they meant 2400 mcg and not 2 x 400 mcg, but just for clarification Creekee

    I found this from Rich where he seemed to think that SNPs weren't always a good indicator of how a person reacts to methylation. This is from August 2012:
    (I think this was before 23andme lowered their price to $99. Maybe he would have the same answer, but the methylation pathways panel costs $299 which is why I mention it)
     
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  19. Lotus97

    Lotus97 Senior Member

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  20. Valentijn

    Valentijn Activity Level: 3

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    It also seems that the value of some of the results might be inaccurate or overstated. The MAO A showing up in the profiles (rs6323), for example, is saying that the most common variation (TT) is cause for concern. Is over half the population having trouble breaking down MOA to some extent? And if you throw in the +/- combination, that's 80-90% of people "malfunctioning" to some extent. It just seems very unlikely that that MAOA SNP is significant, especially by itself without knowing if/how it's interacting with other MAOA SNPs.
     
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