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COMT++ MTR++ MTRR -+

Discussion in 'Genetic Testing and SNPs' started by GimmeAdrenaline, Oct 8, 2018.

  1. GimmeAdrenaline

    GimmeAdrenaline

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    I will include a snapshot of my gene snps below, brought to you by Nutrahacker. I’m fairly new to the understandings of gene mutations, but have come a long way. I’m in my mid 30’s and have dealt with chronic-sometimes debilitating health issues since around the age of 17. Two years ago I decided to stop utilizing pharmaceuticals, benzos and opiates, and put myself on a track to wellness; only...it didn’t quite work like that. Anxiety, chronic pain, insomnia, phlegm, sinus issues, migraines, depression, bowel issues...the list is baffling and mostly boring. This is my first post, so go easy on me. From what I’ve read, it seems that some of these mutations are more less “benign”, but my health speaks otherwise. Any insight or personal experience would be much appreciated.
     

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  2. kurt

    kurt Senior Member

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    These are not benign mutations. What I say should not be construed as medical advice, but your result is similar to my own and several members of my family. And we are using methylfolate, in fact one family member was told by an MD who knows about physiology that he should definitely be taking methylfolate. So he started, with a small dose, and it was way too much. so he had to start with a tiny dose and is still working up. Basically, you need more information about your results. The COMT is hard to treat, but there are some good websites for that. The MTHFR, well, that's obvious, the methylfolate. And most people recommend B12 and magnesium and sometimes other B vitamins. I suggest doing some research into your results, there is some good information out there. But go slow.
     
  3. Learner1

    Learner1 Forum Support Assistant

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    Methylation is essential to proper function of.multiple body systems, so you are wise to look into this angle. Unfortunately, you have other genes, aa well as envurinmental factors which impact how your genes are expressed, so its imporyamt yo know what's actually going on, rather than what could be going on.

    A comprehensive test, like a Genova Diagnostics NutrEval, can identify where you need to supplement to optimize your methylation. Guessing leads to unpleasant symptoms, which can include depression, anxiety, irritability, a intestinal symptoms, headache, etc
     
  4. GimmeAdrenaline

    GimmeAdrenaline

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    Thanks for the reply, Kurt.
    I've started some methylfolate, seem to be tolerating it ok. I've also started some hydroxy12/adeno, also thus far tolerated. I'm not entirely sure I "feel" better, or different yet, but I'm hopeful that with time they will prove to be beneficial. I think getting a complete nutritional work up is probably vital for me, so I know what's going on. Yes, the COMT seems to be complicated. Magnesium seems to work, but it usually takes a heck of a lot...and for some strange reason the results vary with use. I've found a couple of other things that offer varying degrees of help. I think sleep and anxiety are the main players. With less sleep comes more anxiety, and more anxiety comes less sleep; always stuck in the cycle.
     
  5. GimmeAdrenaline

    GimmeAdrenaline

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    Awesome! Thanks for the reply. I will definitely look into this test. I've made an appointment with an ND, so I shall run it by him. How accurate is this test?
     
  6. Hip

    Hip Senior Member

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    While it's interesting to know one's SNPs, and it might give you a few clues as to which supplements to try, there are very few, if any, stories on this forum of patients who actually improved their health as a result of this knowledge.

    Most ME/CFS patients develop ME/CFS after a viral infection, and studies show the presence of ongoing viral infection in the tissues of ME/CFS patients. Thus the causes of ill-health may not necessarily be found in your genes, but in these exogenous infectious agents that are using your body as their home.
     
  7. alicec

    alicec Senior Member

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    Nutrahacker is not a reliable source of information. It cuts and pastes stuff from all over the internet, sometimes contradictory, usually without any real understanding of the SNPs and their effect.

    A good illustration of one of the various misleading features of their reports is treating the two +/+ COMT SNPs as equivalent. The first is a synonymous variant - ie the protein produced by the variant gene is identical to the one produced by the wildtype gene. This variant has no effect.

    The second COMT variant does alter the protein and this variant protein does have a lower activity than the wildtype protein. This is not a pathogenic variant however and is widespread in the population. Approx 20% are +/+, 50% are +/- and 30% are -/-. So approx 70% of the population has a least one copy of the variant - it is not the cause of disease.

    The effects of the variant have been widely studied and the slower and faster versions of the enzyme simply confer different advantages and disadvantages. Neither is "better" or "riskier" than the other.

    The red flagged MTR variant does change the protein structure of the enzyme but it is not clear from research if this has consequences. There are even disputed claims about whether the variant has increased or decreased activity. In other words, if there is any effect, it is small.

    There is also some suggestion that the combination with the MTRR variant rs1801394, of which you have 1 copy, may increase the effect of the MTR variant. Again the effect is small.

    So neither of these very common variants are the cause of your health problems. At best they might be making a small contribution.

    Simply ensure you have adequate magnesium, the cofactor for COMT, to ensure the enzyme is properly stimulated and supplement B12 to reinforce MTR activity. Whatever form of B12 you best tolerate is fine. It is a myth that COMT +/+ means sensitivity to methyl donors. Finally, if you supplement B12 make sure you also supplement folate, either as methylfolate or folinic - again whichever you tolerate best.

    If you are interested in pursuing possible genetic contributions to your health problems, you will not find smoking guns in these common populations variants that billions of people live with and compensate for perfectly adequately, despite all the exaggerated internet claims. At best some combinations of these common SNPs might suggest that you pay particular attention to intake of certain nutrients because you have mild processing problems.

    Genetic contributions to you in particular will be found in much rarer variants and these you have to search for. You may not find any smoking guns here either. Some do, many don't.

    By all means consider tests like Nutraeval. These may give important insights into aspects of metabolism that are inadequate and which you may be able to shore up. This reflects the complexity of cellular function, not individual SNPs.
     
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  8. GimmeAdrenaline

    GimmeAdrenaline

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    Alice,
    Thank you so much for the very detailed and thorough response to my thread, appreciate you taking your personal time.

    In reference to the snp’s, yes, that was my assumption; that beyond keeping a close eye on my nutrition, and possibly adding commonplace supplements-I might not be able to do a whole lot. I think myself like many other cfs sufferers, we’re looking for the culprit and the panacea in order to return the old life.

    As for seeking out the rarer variants to find possible answers, will qualified physicians know from symptoms what snps to dig for, or is this mostly my journey to later take my homework to them? I know it’s a bit of a silly question, but I’ve only recently been able to afford to see a doctor out of my pocket, so I’m unaware of how to not spin my wheels.
    Again, many thanks.
     
    Last edited by a moderator: Oct 10, 2018
  9. GimmeAdrenaline

    GimmeAdrenaline

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    Hip,

    Thanks for the follow up.
    Geez. That’s not promising. Still, I’d rather have vast truth over false hope.
    With your experience, what’s the best place to begin looking for solutions?

    Seems like I’ve tried every diet from paleo, keto, Vegan, fasting, time restricted. I can find small victories via mild exercise and sauna, but, ultimately-sleep seems to be the biggest pedictor of a decent day; those are slim to none. It’s like heaven though when they show up.
    Thanks again!
     
    Last edited by a moderator: Oct 10, 2018
  10. Hip

    Hip Senior Member

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    Yeah, from reading some of the threads about 23andme SNP testing on this forum, you can come away with the impression that everything in your health can be explained by your SNPs, and that illnesses can be rectified simply by finding the relevant SNP mutations and then addressing them with compensatory supplements.

    But in reality, having been reading these forums for nearly 10 years, in spite of all the exploration and tweaking that people have tried on their SNPs, you rarely find anyone saying: "Ah, it turns out that all my health problems were due to SNP mutations X, Y and Z, and once I started taking supplements A, B and C to address these, I felt a lot better". Unfortunately that usually does not happen.

    I don't regret paying the $100 or so for my 23andme results, because I found it very interesting, and would do it again. But if I were down to my last $100, 23andme would not be what I would spend it on.



    The main use of 23andme results on this forum tends to be in an attempt to fine-tune the methylation protocol devised by Rich Van Konynenburg (which involves taking the B12, folate, etc supplements Konynenburg detailed here).

    Konynenburg devised a one-size-fits-all methylation protocol which some have found helps their ME/CFS, and so this may be worth trying. Then you get a few people trying to optimize this methylation protocol using their SNP data. But before you get into all that SNP complexity (which probably will not yield any additional benefit anyway), you might just want to try the simple one-size-fits-all methylation protocol to see if that helps.

    Many people on this forum get their methylation-related SNPs interpreted by uploading their raw 23andme data to Genetic Genie, which provides a free interpretation (similar to your Nutrahacker results above).

    Your Nutrahacker results already provide some suggestions for which supplements to try and which to avoid. It's your double mutations (shown in red on your Nutrahacker report) that you mainly want to focus on. When you only have a single mutation (shown in yellow), the effect of that mutation is assumed to be much less. Double mutations are also called homozygous, and single mutations heterozygous.

    You might also like to search this forum for people who have the same double mutations as you, and see what they say. Your double mutations are:

    COMT H62H (rs4633) — forum search
    COMT V158M (rs4680) — forum search
    MTR A2756G (rs1805087) — forum search



    As an aside, a very new theory about the genetic contributions to disease has been proposed, called RCCX theory. This is purely a hypothesis at this stage, but it's something worth keeping an eye one. Mutations in the RCCX group of genes are not picked up by 23andme, and indeed the RCCX region of the human genome is a largely unexplored area, but which may have implications for diseases like ME/CFS.

    But even with these RCCX region mutations, diseases may only manifest if you catch certain viruses or bacteria, which in combination with some RCCX genetic susceptibility and other factors may lead to disease.
     
    Last edited: Oct 11, 2018
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  11. Mary

    Mary Moderator

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    @kurt, @GimmeAdrenaline - it's generally not recommended to take folate without B12, because folate can mask symptoms of a B12 deficiency, which could lead to severe neurological problems among other things. https://www.nutraingredients-usa.co...Folate-fortification-may-mask-B12-deficiency# This article is mainly about elderly people but applies to everyone of course.

    Also, you should be aware of the very likely possibility of potassium levels tanking when starting B12 and/or folate. It's happened to many on this board and can cause severe fatigue, arrhythmia, muscle cramps and twitching, among other things - you can google symptoms. The folate and/or B12 will increase the need for potassium as cells begin to divide more rapidly and do what they're supposed to, thus inducing a functional potassium deficiency. Symptoms can be quite severe and a banana or 2 may not be enough to help. Low-sodium V8 is high in potassium and drinking several glasses can often tell you if low potassium is the reason for symptoms that may develop after starting folate/B12. And if it helps, then you can decide where to go from there - e.g., whether to take a potassium supplement. https://forums.phoenixrising.me/ind...ded-in-methylation-treatmt.18670/#post-291422
     
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  12. alicec

    alicec Senior Member

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    Unfortunately the latter, in the first instance at least. 23andme themselves indicate that any pathogenic variants identified be confirmed by further testing by a clinical genetics laboratory - ie think of 23andme as an initial screening device. Once you have identified potentially serious variants, you might then be able to get a doctor interested in follow up.

    This initial screening process is not an easy undertaking. Perhaps you might be able to find someone you can pay to do the searching through your 23andme data looking for rare likely pathogenic variants but it would be a fairly expensive exercise I imagine. I'm not referring to the many services like Nutrahacker, Genetic Genie etc that look at a very few common SNPs and make all kinds of ridiculous recommendations based on them. I mean finding a proper genetics researcher.

    Alternatively you can search yourself using Promethease and Enlis (I suggest both). You can do this in several ways. First use their filters to look for rare variants - say 1% incidence or less. Then you would need to follow up on each of the identified variants to see what is known about them, what effect they have and whether you think they might have some relevance to you.

    Alternatively you can search by disease/condition and concentrate on the rarer variants.

    Or as your knowledge increases and you come across genes that you think might be relevant, you can search gene by gene.

    None of this is easy, particularly if you don't have some scientific background. You may need to take some sort of basic genetics course.

    Is it worth doing? Only you can decide how much effort you want to put into something that may not lead to anything much.

    There is the possibility that you might find something that suggests you don't have ME/CFS but something else that could have better targeted treatment options.

    Here, here and here are threads about a couple of people identifying mitochondrial disease along with some guidance in using Enlis.

    I know another person who had observed that his very serious symptoms responded strongly to B12. By searching gene by gene for every enzyme involved in B12 uptake and processing (using Promethease), he eventually identified several newly identified pathogenic variants in both of the B12-dependent enzymes and in two processing enzymes. These are real smoking guns which need to be followed up.

    Or even if you find nothing related to your symptoms, you might find a variant with serious consequences for your health for which you can take preventative action.

    More likely though you will find nothing much - just a few things that increase risk for various conditions. It's entirely up to you how much effort you put into this.
     
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  13. GimmeAdrenaline

    GimmeAdrenaline

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    Hip,
    Thanks for the additional info. Will let you know how it goes.
     
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  14. GimmeAdrenaline

    GimmeAdrenaline

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    Thanks! Will definitely keep on eye on my potassium.
     
  15. GimmeAdrenaline

    GimmeAdrenaline

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    Yeah, I think this is most likely going to become a passion project for me. I’m one of those persons who firmly believes that the body, when unhealthy, is merely asking for some very small things it’s not currently getting (and/or plus avoidance), so I’m determined to find the link. It’s very possible that it’s a cumulative effect. At any rate. I’m just going to have to slowly increase my genetic I.Q., as I’m sure almost all of us do.
    I have done Promethease, but later switched to Nurtahacker and geneticgenie as an easier solution of break down. Now that I’m aware of the common snp’s I’m dealing with, I’ll probably dig back into Prethease for some insight/answers.
    Thanks
     

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