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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. kday

    kday Senior Member

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    I am homozygous for MTR A2756G (rs1805087) and I realized I failed to look at the details about this mutation carefully. If I did my calculations correctly from dbSNP, it appears that only 1.7% of Europeans are homozygous for this (I am 100% European). Pretty rare!

    http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?searchType=adhoc_search&type=rs&rs=rs1805087

    So my questions are, what more can I do about this them supplementing massive amounts of methyl-B12. I have added folate, P5P, etc, but it’s been pretty clear the last couple years that the biggest need is methyl-B12. In fact, I feel that I actually could die without it even thoiugh my lab results are >1999 for B12. It makes a huge difference. While not functional in terms of having a job, exercise, etc it helps me immensely compared to how I would be without it (incapacitated).
    http://en.wikipedia.org/wiki/5-Methyltetrahydrofolate-homocysteine_methyltransferase

    I have seen megoblastic anemia when I was feeling really sick or stopped B12 for a significant period of time.

    I also wanted to know how heavy metals would be implicated. On the diagram below, it looks like MTRR recycles B12. I also see with word “lead” there, and was wondering if the diagram is talking about lead as in the heavy metal. I am heterozygous for MTRR A66G, but I don’t know how much weight that has. But my question is, is this implying that I could have bioaccumulated lead my entire life if there wasn’t much methyl-B12 to be recirculated by MTRR.
    [​IMG]
    I have had depression a few times in my life. However, I was pretty healthy and very active until I suddenly got very sick one day in December 2008. It’s worth noting that the water company where I lived was seized by the government where I lived for high levels of inorganic arsenic and the whole infrastructure (including every single pipe that fed thousands of homes) had to be replaced. I drank the tap water (it was well water). I suffer from chronic infections, anxiety but not depression, chest pain, head pain, other pains that come and go, impaired cognitive processing (hard to drive a car), overstimulation, and so on.
     
  2. caledonia

    caledonia

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    I'm hetero for this as well as being hetero for 5 out of 6 Yasko MTR/MTRR SNPs (the other MTRR being unknown). I need a ton of mB12! You're lucky, you can actually take it. I can't because my CBS mutation sends everything down the CBS drain causing a lot of excitotoxicity. I'm working on resolving that.

    If lead is in the diagram, I think it means lead will gum up the works. Of course, if lead is gumming up the works, then more metals will accumulate because you can't detox them properly - a double whammy.

    The anxiety is probably from a GABA/glutamate imbalance. It looks like metals are implicated here too. I'm taking GABA or theanine for now until I can get things straightened out.

    I got tested for metals several years back and chelated them out. I had moderately high lead and mercury. Lead can come from leaded gasoline, lead in paints, industrial or hobby sources like solder. I recently found out that at least one industry in my area releases lead into the air. I was afraid to look at the rest of them and see what they're releasing- lol.

    Eventually, when I get to where I can detox better, I want to get a FIR sauna for regular detox of chemicals and metals.
     
    WoolPippi and kday like this.
  3. kday

    kday Senior Member

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    I bought TMG. Since I am homozygous for MTR and probably have significantly impaired methionine synthase, would it be of benefit to take it in combination with B12? Looking at the methylation diagram, I would think yes, but I'm not sure.

    caledonia - Did you have any changes with chelation. I am doing a non-provoked test (tomorrow) and then a provoked test so we can compare the two. I've avoided chelation because I didn't see many people get a whole lot better from it, and I'm concerned about the potential side effects and efficacy of IV or suppository EDTA.

    Thoughts anyone?
     
  4. Anteah

    Anteah Senior Member

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    Hi, Kday! Still waiting on my results here, but what I noticed when I started taking MethylB12 and especially when I added AdenosylB12 is that I started detoxing heavy metals. I tasted metal in my mouth, I had low bile production, excitotoxicity, sensitivity to light/sound, confusion, odd hearing, hard to control candida and so on, until just recently when whatever the amount of heavy metals I could detox with the amount of B12 I am taking has been excreted. I am sure if I upped my Adb12 I'd start pushing more metals out, but at 3mg of Adb12 per day (and 10mg of MethylB12/day) I feel that any more will be risky, I developed hypertension every time I attempted to go higher, even with adequate Potassium. I feel that I could use more Adb12, but have not found a way to add more with out raising blood pressure yet. So even at those doses I feel that this indicates a pretty hefty need for B12 (both forms but for different reasons). I second your insight about heavy metals. I am certain it is a huge part of our toxicity/adrenal/other issues.
     
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  5. Aileen

    Aileen Senior Member

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    yes and yes. if you go to http://www.holisticheal.com/autism-pathways-to-recovery-esp.html it has Dr. Yasko's book where it explains about how metals and microbes are held in the body.


    sounds like lead might not be the only toxic metal problem you may have.

    Here is a really great simplified presentation I just watched explaining the methylation cycle (part of it) and it specifically puts lead in there in one of the case studies presented. This is one of the most understandable presentations on methylation I've seen yet.


     
    PeterPositive and kday like this.
  6. kday

    kday Senior Member

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    Anteah, over the years I feel liked I detoxed a ton of metals too. I am a lot better than I used to be and had some good days recently. Just want to be more proactive to get back closer to where I was years ago.

    I have had bile/gallbladder/liver problems as well. And when taking too much B12, I induced elevated liver enzymes and an had an echo that looked like chronic liver disease. So I am a bit more careful now as I know it can be too much of a good thing.

    While I don't have proper metal testing results yet from my doctor, I have done hair analysis and we've looked at a few metals through LabCorp. I've also ordered do it yourself test kits that measured total excretion of metals (since I am kind of a geek I guess), and when I took B12, the excretion of metals was past the maximum level you can interpret with the kit. There was low-normal excretion without B12 for several days. It seems pretty obvious that I have/had a metals problem.

    It just seems like it may be a slow process to get rid of them (assuming I still have a heavy metal burden) considering I've been taking B12, other B's, Chlorella, etc for years now.
     
    Anteah likes this.
  7. kday

    kday Senior Member

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    Thanks Aileen for your input and the video.
     
  8. roxie60

    roxie60 Senior Member

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    In another of Kday's threads I mentioned a metals test and chelation, now reading this thread I think I meant to say 'provoked' and 'non-provoked' testing. I this the only way to do metals testing? If I may ask what test are you doing kday as I am also looking to do a metals test to see where I am.
     
  9. caledonia

    caledonia

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    Hi kday, sorry I missed your question. Anyway, I didn't feel any better from chelation, however, things looked much better on paper. My somewhat high thyroid antibodies came down to normal. This is supposed to be some kind of miracle. I still have to take Armour Thyroid though. However, I'm still at the same dose after 10 years. So maybe it helped keep things from getting worse?

    After chelation, I still had a couple mercury filings which I have just recently gotten out. So I'm guessing I may have to do another round. I will be getting some testing soon anyway to see whats up.
     
  10. Helen

    Helen Senior Member

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    Thank you all for interesting inputs.

    I got this answer from Dr. Neil Nathan (who made a study together with Rich)

    "mercury is a specific toxin for the methyl synthase enzyme that is critical in methylation. Even tiny amounts of mercury have been shown, by Dr. Richard Deth who is the dean of methylation chemistry, to poison the methylation cycle. While everyone is different, I suspect that everyone with mercury toxicity will have trouble to a greater or lesser degree with methylation."
    Neil

    It is also an experience among people in Sweden that have got sick from mercury that amalgam visible on X-ray has to be removed totally. That use to be a big step towards health, but some get into the CFS-club. Maybe because of genetic defects that increases the ability to make use of glutathione (GST-genes).
     
  11. Lotus97

    Lotus97 Senior Member

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    I unintentionally started taking methylfolate right after my tooth with an amalgam cracked. Until I learned about methylation I thought I had mercury toxicity due to my symptoms. Since then I have read other accounts of people having strong reactions to methylfolate so I'm not sure if I was exposed to much mercury or not, but my health has gotten significantly worse since that period. I still don't know why I'm so sick now. I do have Lyme and was sick before I got amalgams, but I've also heard accounts from people with metal toxicity having a rough time with methylation.
     
  12. Freddd

    Freddd Senior Member

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    Hi Kday,

    A lack of l-methylfoalte, AdoCbl and LCF each or all can prevent much MeCbl functioning. What kind of MeCbl are you taking and how much? Also. for many SAM-e added can make a huge difference.
     
  13. Freddd

    Freddd Senior Member

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    Hi Anteah,

    For me and some others hypertension was caused by CoQ10 during the first year or two of healing with even 1mg sublingual of active b12.. How do you explain AdoCbl "pushing more metals"? Which function of AdoCbl do you account for this by, processing fatty acids for myelin, ATP production or anti-inflammatory? Or are you caiming a new function for AdoCbl?

    And 1mg of mecury can destroy all active b12 a person may have in their body in 2 years.
    80% of the toxicity symptoms of the same as those of b12 deficiency. 30mg of mercury is theoretically enough to destroy all the active b12 in a persons body for the rest of their lives.
     
  14. Branston

    Branston

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    Could you clarify what you mean by "massive amounts of B12"......what type of B12 and how much ?
    Thanks.

     
  15. Lotus97

    Lotus97 Senior Member

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    Adenosylcobalamin can be converted into methylcoblamin which is then used for methylation. Methylation can cause toxins such as metals to be released.

    People who have tested positive for mercury toxicity have experienced adverse effects from taking methylcobalamin so I don't see how any of what you say is possible. They are obviously utilizing the B12 somehow.
     
  16. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Please supply references for the above.

    Sushi
     
  17. Freddd

    Freddd Senior Member

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    People who have tested positive for mercury toxicity have experienced adverse effects from taking methylcobalamin so I don't see how any of what you say is possible. They are obviously utilizing the B12 somehow

    People with mercury, and I had lots of it, can and do have toxic symptoms. 80% of the toxic symptoms of mercury are identical with b12 deficiency symptoms, or methyltrap symptoms ANDOR partial ATP block symptoms ANDOR partial methylation block (very possibly CAUSED by the mercury). Mercury converts MeCbl to inactive if and when it takes the methyl group. Taking the methyl group causes the now monomethylmercury to be excreted by the liver in the bile thereby ending up in the feces and not the body. Further it happens at a slow pace, less that 1% of MeCbl in the body. Using the research data I built a conversion and excretion model. The research data is actually very easy to model. The studies of methylmercury, toxicity and excretion are all quite consistant in peer reviewed literature.

    However, as mercury claims less than 1% of the avaialbe MeCbl on any given dose, that leaves plenty from any size dose, from 100mcg absorbed to 100mg injected and absorbed, for a person to have hypokalemia and folate insufficiency all at the same wonderfiul time of feeling awful sick. If mercury does steal the methyl group from MeCbl, one mg of mercury destroys about 7mg of MeCbl. There is zero doubt about that, simple math. Also 99% of the dose is excreted unchanged in the urine in 24 to 48 hours. Those are the "constraints of prior research", as Dbkita called them, along with others (parmacodynamics of various substances), put upon MeCbl and mercury. So, for 7mg of MeCbl to be destroyed rapidly by a given dose within those constraints, let's be generous and use a subcutaneous injection to give it more time for the two to get together at higher concentration, it would take a 700+mg injection to have the 7mg destroyed within the 1% constraint. Anything else would be fantasy in terms of the actual research that has been done. As it takes 30mg of mononmethylmercury in circulation to cause "barely noticable" toxic effects, according to peer reviewed research, the model I constructed attempted to get to conditions under which thayt could happen taking into account the pharmacodynmics of each of the substances. At any reasonable rate of MeCbl dosing, and I determined the amounts and posted the results of the model, such as 1-100mg of MeCbl absorbed per day, there is no way to get up to that threshold of toxic symptoms by taking MeCbl, not even close. I calculated the clearance time from the body of all sorts of levels of mercury, and the peak steady state monomethylmercury level in the body generated by MeCbl, if it can do that at all. Even that is debated in the peer reviewed papers.

    I'm a sceptic on lots of research, especially that which sounds like it was designed for marketing. Everybody researching the mercury is sufficiently disinterested that they can be trusted not to be bending the results to fit their theories which mostly they are still figuring out. I read all articles with large grains of salt. I saw no reason to distrust all the different studies involved in mercury that I read.

    So while you say " I don't see how any of what you say is possible" it might be a good idea for you to do some more reading sufficient to make your own models from the research info and let's discuss that. I trust the journals on mercury more than I trust the many belief systems on mercury that ignore all the scientific evidence. Show why the scientific evidence and all those journal articles are wrong. Are you going to after the chemistry? The pharmacodynamics? Or what?

    Adenosylcobalamin can be converted into methylcoblamin which is then used for methylation. Methylation can cause toxins such as metals to be released.


    At how much per day? At what percentage of sufficiency? As that is an uphill conversion it requires an enzyme and ATP which deosn't happen if there is not enough AdoCbl and LCF in the first place. For people in partial ATP block that just isn't going to happen. And even if 10mcg of AddoCbl does convert to MeCbland 100% of it goes towards mercury that amounts to 1.4mcg (MICROGRAMS, you know 1/1,000,000 of a gram) There is absolutely no evidence that 1.4mcg of methylmercury is toxic to a human. You hypotheses don't hold water and as far as I can see can't be made to hold water. So please, consider the scientific data that is avaialable.

    All of that said, whatever IS HAPPENING, has to have an explanation, just not that one.
     
  18. Freddd

    Freddd Senior Member

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    Hi Sushi,

    There is no one paper that says that. That is simply applying what a group of papers have to say in combination. There are hundreds of papers on serum halflife of the various cobalamins, early on the entire paper, and later, mention in passing confirming the earlier papers and building from there. The same goes on the pharmacoodynamics of monomethylmercury derived from studies of people accidently dosed with said monomethylmercury. There are no papers at all, at least last time this was all gone through on this forum, that establish that MeCbl and mercury have any interaction at in in vivo. The tests in vitro in high concetration of both reactants in a non bological system (testtube) show such activity but it has never been established in vivo. So I say "IF MeCbl and mercury react at all in very low concentration systems such as the body". I would be inclined to say that it does happen at a very low rate as people have lots of MeCbl responsive symptoms from mercury. A lof of the best research is in Japanese from the mercury poisoning disaster in the 50s. Japan is the only country that uses MeCbl as it's official B12 AND they set the highest minimum in the world at 550 pg/ml for alert. They also have Alzheimer's at 20% of the USA/UK rate.

    So if you can provide some papers showing the rate of in vivo monomethylmecury formation from mercury and MeCbl I would be very interested in seeing it. I would certainly adjust my models if I saw such. Howver, as I did a spectrum rate of conversion from 0.01% to 10% of MeCbl, despite all the evidenc that it is less than 1% for all uses in the body, I doubt that it will make much difference. If not I would be interested in seeing your synthesis of information after you read perhaps 100 or so foundational papers establishing the dynamics that are known.
     
  19. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Freddd

    I am just asking for clarity about what is a hypothesis and what has been commonly accepted in peer-reviewed research. It is confusing unless this is made clear.

    In a forum like this where there are varying degrees of scientific knowledge, this distinction is very important as many members are trying to make healthcare decisions and look to the forum for documented research.

    Sushi
     
  20. Freddd

    Freddd Senior Member

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    Hi Sushi,

    I think the whole things, the entire result set of the model is somewhere on this very methylation menu in a thread on a discussion of mercury. In 1978 I told the director of an HMO that we could get a lot of answers from the medical histories if we included some additional things. I was using the known need for the 3 vitamins to prevent neural tube defects. I was sure plenty of other things could also be found including different treatments that work.better with whatever side effects taken into account. They got bought in the rush to cash in on HMOs and hence destroy them. As soon as they were bought the health management part went down the drain and it was cash management.
     

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