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Need for massive amount of B12 and MTR A2756G polymorphism

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by kday, Dec 16, 2012.

  1. Freddd

    Freddd Senior Member

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    Hi Sea,

    No, I don't see from the results in your signature that there are complications to just jumoing in and correcting the deficiencies. Yes, you would have induced deficiencies most likely and deal with a lot of discomforts as things start coming back. I don't agree with what the interpreations are. Predictions made from 60 years of research and experience wirth folic acid, HyCbl and CyCbl in no way predict what happens with AdoCbl, MeCbl and l-methylfolate, with an LCF chaser. You can test the hypothesis very quickly. Of course if one were believe that neurological and mitochondrial and healing startup to be damaging to themself then they wouldn't correctly interpret the clues. People's working hypothesis controls what they try. When what can work appears counterintuitive to people they tend to avoid it.
     
  2. Sea

    Sea Senior Member

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    So what do you believe about the warnings Yasko and Heartfixer have about intolerance for methyl groups in those whose genetics reveal defects in COMT, TAQ, CBS? I am trying to understand the best way forward (with huge limitations in my ability to learn and remember)
     
    leela likes this.
  3. Freddd

    Freddd Senior Member

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    Hi Sea,

    I would suggest a visit to the Stages of Methylation thread at the end. There are 6 posts in the last few pages that have the symptoms by response nutrient(s). Take down all the nutrients groups for each symptom or sign of yours that matches these. That will let you see what this different interpretation is based upon. You will see that the groups of symptoms by reposive nutrients makes for sensible clusters. The may cluster by partial methylation block or maybe by methyltrap or partial ATP block, body and/or CNS and any combination of the 6. There are often additional problems people have, comorbidities. They aften become very clear as the background of these other symptoms recede. The combined biochemical processes are basically everuthong in the body between ATP and methylation problems. The details depend upon the balance of the deficiencies. Also make note of all thye symptoms left over that don't fit those descriptions.
     
    LaurieL likes this.
  4. Lotus97

    Lotus97 Senior Member

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    COMT tend to be overmethylators which is why taking hydroxocobalamin and limiting methyl donors is recommended. You're of course free to try any protocol you wish, but I would urge caution. Especially since Yasko has spent a lot more time dealing with SNPs than Freddd. I've heard the same recommendations from other members here regarding the COMT mutation.
     
    Sea likes this.
  5. xjhuez

    xjhuez Senior Member

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    Seems that folate insufficiency and IBS is a chicken and the egg type relationship. That is, one can cause the other, but how to tell which.
     
  6. dbkita

    dbkita Senior Member

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    I honestly don't see why the heterozygotes you have are a major concern. Their population frequencies are quite high. I don't know much about the AHCY gene though. You are hetero in the VDR haplotype but I don't necessarily buy what Yasko et al claim about those VDR SNPs since they believe the wild type baT haplotype is "defective".

    I would kill to have CBS heterozygotes. Of all the heterozygotes the A1298c has some significance as it affects BH4 levels directly and the ACAT which affects acetylcoa production, but that one needs additional things beyond simply mb12 and folate. Yes you have a heterozygote in MTRR, but I have five and I am on a methylation protocol. You have two BHMT heterozygote mutations, I have for example 4 homozygotes.

    Your homozygote COMT can be a cause for concern with have excess catecholamine levels based on stress response or high methylation but you have to find your own balance on that. People who tend to be awash in catecholamines anyways or have high inflammation from the outset may have rougher time starting methylation treatment. But it still has to be done. You have to find your balance and get through it.

    Perhaps a baseline check pre-support of your methylation pathway elements is in order, a la Doctor's Data or HDRI. Maybe your methylation status is better than you realize. What symptoms do you attribute to poor methylation or low mb12?
     
  7. Freddd

    Freddd Senior Member

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    HI Xjheuz,

    It is always part of a sequence. First I start retaining water. Then the area of the angular cheilitis starts burning, then the sores become open, then the IBS starts. The day it turns around I loose a big surge of water, then the IBS and cheilitis improve by the day for about 5 days. Then things are good until something triggers it all over again. It seems to follow a missed dose of folate. It has lessened since taking it separate from potassim and C but that is not a complete solution. Maybe something else starts it all I don't know. I have been working on this folate problem for about 5 years now. There are all sorts of cycles where it feeds itself in the word of b12 and folate. Both of them cause anorexia and/or nutrient specific anorexia. Until MeCbl all sorts of foods caused me prblems. After a year of healing, only milk and cheese and such cause me a problem now. And accidental folic acid or too much veggie folate can both be problems.
     
  8. Sea

    Sea Senior Member

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    I understand homozygote mutations are of more concern than hetero, but I don't think that means they can simply be dismissed. They may be completely irrelevant, they may not. I am trying to understand where there may be issues that can be addressed. The odds risks given for many illnesses make it clear that a hetero polymorphism can confer no risk, slightly increased risk or the same increased risk as a homo polymorphism.

    I don't quite know what to think regarding the population frequencies. 23andme test for common polymorphisms and SNPedia has more info on the common polymorphisms rather than the rare ones. The rare ones that I find have very little info and unknown significance. Also, that a polymorphism is common doesn't necessarily mean that it is insignificant. For example a polymorphism present in 40% of the general population is found in more that 95% of people diagnosed with Celiac who have been gene tested. That association is very significant even though it is not the whole picture.

    I don't know much about any of them really and the confusion and differences in claims make it even more difficult.

    I don't know how much effect these mutations have on any one individual. The combinations are endless and no doubt far beyond the few that we know about. I don't think you can do a simple comparison like I have 4 you only have 2 therefore you won't be as affected. It would certainly simplify things if it did work that way. Although MTRR polymorphisms need addressing I haven't heard that they are related to tolerance for methyl donors.

    I wish! Money is a scarce resource and I do not have a doctor who is keen to test more than the most basic of options.

    Maybe it is, maybe it isn't. Everything is a shot in the dark when you can't afford a lot of testing and don't have access to a helpful doctor. 23andme testing seemed like a reasonable outlay to see what polymorphisms I have. I have not been able to tolerate more than a few days of a vitamin B multi. Initially I get an increase in energy, followed by extreme irritability, wired but tired and insomnia. It would be nice to know whether this means it is good for me or bad for me, or whether it means folate is the missing link.

    I am very new to this and trying to avoid as many pitfalls as I can.
     
  9. dbkita

    dbkita Senior Member

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    Hi Sea,

    The 40% of the population SNP that shows up in 95% of Celiac's is because is part of a haplotype (multiple SNPs and I think on both alleles). There is a big logical difference between "necessary" and "sufficient". I.e. 95% of people with Celiac's have a marker. But the vast majority of people who have that marker do NOT have Celiac's. Ergo it is a part of the problem, ostensibly part of a haplotype.

    Please don't misunderstand I am not trying to belittle your health issues in any way. But I have seen a lot of people who report their SNPs and and all I meant is you show two homozygous SNPs on one gene (one SNP which is highly debatable as to utility) and even then that gene is not a core disaster one like some of the others. So maybe epigenetic stresses / triggers are a big factor? Or there are genetic aspects we do not understand. I don't know. I already wrote that I wager your ACAT could be a potential problem only because how critical that step is. I also wrote your three AHCY heterozygotes could put you into a bad combination (i.e. haplotype).

    I will stick firm though on my opinion about high frequency heterozygotes. And I think I have a fair reason to form such an opinion since I have worked in genomic, bioinformatics, and biopharmaceutical development for just shy of 20 years.We can choose to disagree. I think personally haplotypes are much bigger complex framework let alone gene networks. Single one shot SNPs for really complicated disorders are fool's gold in my profession.

    I think there are some medical professionals who do a real disservice to the public by looking at each individual SNP (especially heterozygotes unless they are a cluster swarm on a gene leading to a risky haplotype) and convincing people to focus on "correcting" those. That is really not kosher in my book.

    Still I am trying to figure out my own scenario. I have seven heterozygotes (four of them in MTRR, one in MTHFRa1298c) and seven homozygotes (three of them in BHMT, one in CBS, one in SHMT1). My BHMT gene is pretty torqued and combined with other measurements on the trans-sulfuration pathway, my CBS is a problem. I may have a risk haplotype with MTRR, would certainly explain some things. I still don't know what to make of my SHMT1 homozygote and since no one seems to know on the easily accessible parts of the Internet, I need to go trolling again through research papers like I did with VDR. I guess my point is I look for patterns, not single points.

    Btw your reaction to B-vitamins sounds like your neurotransmitters are out of whack especially NE and maybe GABA or serotonin. I used to have the same response a while back. It was miserable so I empathize.

    Good luck finding solutions to your health problems.
     
    Sea likes this.
  10. Lotus97

    Lotus97 Senior Member

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    I've heard from several people have a hypersensitivity to methylfolate. After taking too much for 5 weeks it caused a major relapse for me. I know of someone else who when they started methylation they had to wet a toothpick and pick up only a tiny bit of methylfolate and even that was too much. It's very possible that folate is the missing link, but regardless of why it's causing symptoms I'd recommend going slowly. Perhaps you could start by taking half a capsule or even 1/3 or less.
     
    Sea likes this.
  11. Freddd

    Freddd Senior Member

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    HI Sea,

    As a b-complex provides so many different possibilities for reactive causes it is difficult or impossible to say just what is going on. Chances are things may have shifted around running out of all sorts of things differently and so there you were, different imbalances. Things can be done differently so that it generates information for making changes.
     

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