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Slow methylator? Methyl B12 intolerance?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by justy, Nov 18, 2011.

  1. justy

    justy Senior Member

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    Hi, i posted about my problems with side effects from taking Methyl B12 daily injections (500mcg a day)
    The symptoms are agitation, increased anxiety and face/head pain as well assome good effects - less sick feeling and more energy.

    The agitation is not something i can put up with so iam trying every 3 days instead at the same dosage.

    My question is that on the other thread Willow suggested it could be because i was intolerant to the Methyl B12 due to being a "slow methylator" and i just want to understand more about what this means and wht the implications are.
    Thanks, Justy
  2. merylg

    merylg Senior Member

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    Hi justy,

    I am also having problems with the "Methyls"....(Jarrow) Methyl-B12 5000 mcg sub-lingual, Methylmate B (Calcium L5-methyltetrahydrofolate) 200 mcg sub-lingual, and Solgar Metafolin 800 mcg (L-methylfolate) tablets.

    The symptoms I get are those of a sicca syndrome, like Sjogren's Syndrome, very dry eyes, nose, other mucous membranes, noticeable on waking. It is as if the Methyls provoke an autoimmune response, or add to a pre-existing one :eek:

    I am now trialling Methyl B12 100 mcg by tablet, every second day.

    I also tolerate Hydroxy B12, Adenosyl B12 (Dibencozide) and Folinic Acid (as Calcium Folinate).

    meryl
  3. Ocean

    Ocean Senior Member

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    Interesting Merylg. I also got severe dryness when trying sublingual B12 and eventually stopped taking it because of that.
  4. justy

    justy Senior Member

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    Hi Meryl, i was ok with Methyl B12 oral tabs, i cant remember the dose now im afraid. But maybe they werent doing anything as i seem to have absorption issues.
    I havent had a shot for 2 days now and the agitation has subsided. Dr Myhill said that B12 can be "stimulating" I have also read from Autism papers that Methyl B12 injections can have side effects of increased agitation. hyperactivity etc, but that if the side effects are tolerable then you should just ride them out and after a month or so they will subside.

    I really wish i could take it more as i felt the best i have in months taking it. Thge other thing i noticed is that the effects seemed to be cumulative as i felt nothing for a week, then felt a bit better, then a lot better, then anxious and horrible.
    Its so frustrating because everything Dr M has prescribed for me i seem to have problems with.:(
  5. richvank

    richvank Senior Member

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    Hi, justy.

    Taking B12 orally will allow the body to absorb only a small amount, a few micrograms. If you inject it or take it sublingually, much larger dosages can be put into the blood. In treating ME/CFS, we have found that the dosage needs to be fairly high, usually of the order of a milligram (1000 micrograms) or more.

    The concept of being a "slow methylator" comes from Dr. Amy Yasko. She finds that if a person has inherited certain genetic variations (SNPs) in the genes that code for the COMT (catechol-O-methyltransferase) enzyme and the VDR (vitamin D receptor), then their body will not be able to utilized methyl groups at as high a rate as normal. According to her, if such a person takes supplements containing methyl groups, they can experience symptoms such as you have described. I don't think this has been independently confirmed by other researchers, but Dr. Yasko has been giving this guidance for several years now. It is included in her book "Autism, Pathways to Recovery," and she advises many people (mostly mothers of autistic children) about this in her internet forum at www.ch3nutrigenomics.com which now has over 12,000 members. She advises people who are slow methylators to take hydroxocobalamin rather than methylcobalamin, and to minimize other supplements that have methyl groups.

    You may have built up excess methyl groups over time. Perhaps lower dosages, skipping days, or shifting to hydroxocobalamin would help.

    Best regards,

    Rich
  6. justy

    justy Senior Member

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    Thank you so much Rich for taking the time to reply on both my threads. This is all making much more sense to me now, i'll just have to see how it goes.
    Considering my reaction to the B12 would that make it more likely that i would have a problem with the full (simplified) protocol? or does it not work like that. Currently the only part of the protocol i am using is the B12. i'm only taking the methyl form because it is what Dr Myhill now prescribes, i will ask her if we can try the hydroxy if the lower dose doesnt work out.
    Once again many thanksw, Justy.
  7. Dreambirdie

    Dreambirdie work in progress

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    Questions for Rich:

    I just went through several days of *horrific detox and agitation*---to the point that I felt like a "METH" head. (Pun intended.)

    I had been taking the methylmate 200mcg and both the hydroxy 1000 mcg. and less frequently the methyl B12 500 mcg. For about 5 weeks I had little in the way of adverse symptoms, but also not much in the way of a positive change either. Then last Thursday I developed really bad flashing and a huge floater in my right eye, to the point that I thought I had a detached retina. I saw an eye doctor and it panned out that it was/is probably a vitreous detachment, so at least I don't need laser surgery. After the eye went berserk, I began to have an intensification of detox symptoms, with the severe agitation peaking this week. I hadn't made a connection that it was the B12 causing this, until Jenbooks mentioned it to me on another thread. I stopped the B12 and took some Chinese herbs to assist neutralization and elimination of toxins, and I already feel better. BUT... I don't know if I can handle any more of the B12 for now. The strange thing is how it crept up in a cumulative way. I see that I am not the only one this happened to.

    If I take just the hydroxy and take it only 3 days a week, will that still be effective to repair the glutathione depletion? And what is the easiest way to split a drop of hydroxy in 2--will it lose potency if left in water for a day or two?


    Thanks Justy for starting this thread.
  8. richvank

    richvank Senior Member

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    Hi, justy.

    You're welcome. It's hard to say how you would respond to the full simplified protocol. People seem to differ a lot in that respect. However, the simplified protocol, as you probably know, uses hydroxocobalamin. It tends to be gentler, because it can't be used to support methionine synthase until it gets a methyl group and becomes methylcobalamin. This takes some time, and it is also controlled by the cell. Say hi to Dr. Myhill for me!

    Best regards,

    Rich
  9. richvank

    richvank Senior Member

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    Hi, DB.

    I'm sorry that you had this awful experience, and I hope that your eye problem will resolve. When you say "vitreous detachment," do you mean an ordinary floater, though a big one?

    Yes, I think that going lower and slower is called for in your case. B12 has a long residence time in the body, so I don't think you will lose by doing this. I think this long residence time is the reason you experienced a cumulative effect.

    Yes, hydroxocobalamin is pretty stable in water at room temperature. Putting in the dark will make it even more stable. I would suggest using only a small amount of water, so that you can take it sublingually. If you have so much water that you have to drink it, the amount of hydroxocobalamin that will be absorbed into the blood will be quite small.

    Best regards,

    Rich
  10. drex13

    drex13 Senior Member

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    Mehtyl mate B formula change

    Hi Rich,
    I went to re-order my supply of hydroxy b-12 and methylmate b the other day and noticed the methyl mate B had a "new and improved" formula. Uh-oh. It now contains glutathione. Any thoughts on this ?

    Thanks
    Drex
  11. richvank

    richvank Senior Member

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    Hi, Drex.

    Thanks for this news. I hadn't heard about the change, and I haven't heard from anyone who has tried it. I think the glutathione should be O.K. It might help to lower the excitotoxicity symptoms that many people have, especially at first, on this protocol. One of the ultimate biochemical goals of this protocol is to get glutathione back up to normal, so I think this is O.K.

    Best regards,

    Rich
  12. suzanne

    suzanne Senior Member

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    Hi Drex,

    For what it is worth I am one of those (like fredd) that has had really bad reacions to even the tiniest doses of glutathione. reactions to glutahtione seem to differ from one person to another, so maybe it is just a trial and error thing. my dr was convinced that glutathione would be a good thing for me and I tried it in various forms orally, transderaml cream, sub lingual- all made me feel really sick at the tiniest of doses- my dr could hardly believe that anyone could react to such a small dose. It just made me feel really ill.

    I realise that there are others that feel better on this.
  13. richvank

    richvank Senior Member

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    Hi, Suzanne.

    Thanks for reporting this.

    I'm sorry to hear that your body also responds badly to glutathione. I would like to understand why this happens in some cases. I think that in Freddd's case, this is due to an inherited mutation in the cblC (MMACHC) gene, and that this same mutation is what causes his cells not to be able to use hydroxocobalamin or cyanocobalamin, but to need large dosages of the two coenzyme forms of B12: methylcobalamin and adenosylcobalamin, taken either sublingually or by injection. If this type of mutation is present, I think that what happens is that glutathione reacts with the available B12 to form glutathionylcobalamin, and that makes it inaccessible to the metabolism, because the MMACHC protein is not able to retrieve the cobalamin and pass it on to form the two coenzyme B12 forms, as it normally does. This would worsen B12 deficiency symptoms.

    Dr. Cheney believes that the reason some PWMEs are not able to tolerate glutathione supplementation is that their bodies are low in NADPH, and thus are not able to recycle oxidized glutathione back to reduced glutathione via the glutathione reductase reaction, which requires NADPH as the reducing agent. This would cause the redox environment to become more oxidizing over time. There seems to be a buildup of symptoms over time if glutathione is taken and this problem is present. He has measured and found low NADPH in quite a few patients. I don't know what would cause this. NADPH is normally regenerated by the pentose phosphate shunt on the glycolysis pathway, so some glucose is needed to feed this shunt, and a normal glucose-6-phosphate dehydrogenase enzyme is needed to regulate the activity of this shunt. Low glucose or a deficiency in G6PD would thus be possibilities to explain this, and apparently a G6PD deficiency is more common than is realized in the population. A niacin (vitamin B3) deficiency would also cause low NADPH, because niacin is needed to make NADP.

    In any case, if glutathione makes a person feel worse, I think it is best avoided. Fortunately, it is still possible to obtain methylfolate without added glutathione.

    Best regards,

    Rich
  14. therron

    therron

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    Slow methylator

    Hello Slow Methylators
    Like many of you, making progress with methylation is very slow for me. I would like to share my recent experiences since they are similar to messages posted in this thread. Because I have such extreme excitotoxicity reactions to most supplements, I have had to start methylation with extremely slow doses. I started with about 100 mcg or less of Jarrow sublingual Methyl B12 (Solgar), and have worked up to 500 mcg over a 6 month period. I have tried subcutaneous injections in the past, but they back up in my body within a few days, and then continue to make me worse and worse each day. Low and slow sublingual has helped me avoid extreme reactions, but quite honestly, have not provided much in the way of gains....until I started taking a second and equal dose of mB12, mFolate, and TMG in the afternoon. I had huge gains and no negative reactons.............until about day 10. At this point, I got a big floater in my eye one day, the next day my insomnia was back, and then the gut pain started much worse than it has been since I started taking Olive Leaf Extract a year and a half ago. Within a couple more days, congnitive improvements were gone as well. So............I'm back to the original dose, and trying to climb out of this hole, but slowly increase my dose, since obviously, my body needs more. I am curious about hydroxycobalamin. I have a bottle here, but haven't tried it yet. Hmmmmmmmmmmmmmm......
  15. lampkld2

    lampkld2

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    Hi Rich. Can supplementing NADPH lead to detox, restarting of the methylation cycle or depletion of cofactors? I want to start on it for energy, but I am not ready to actually have my methylation cycle restarted at this point as I had a very bad reaction in the past after one day of increased energy and hedonia.
  16. richvank

    richvank Senior Member

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    Hi, lampkld2.

    I'm sorry about your bad experience. That one good day doesn't sound as though it was worth it.

    I don't know that NADPH is available as a supplement, is it? I know that Enada is (NADH). Anyway, I don't think that supplementing either of them would lead to detox.

    Best regards,

    Rich
  17. lampkld2

    lampkld2

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    Thank you Rich.

    I did mean NADH.

    Yes it was not worth it, but it did give me hope that I can feel better... I just have to sort out some things first.
  18. lampkld2

    lampkld2

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    Thanks Rich. I did mean NADH.


    It was not worth it, but it did give me hope that I can feel better if I Just sort out some things first.
  19. DrD

    DrD

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    hi Rich i had mentioned the NADPH theory last year in the Freddd wrong diagnosis thread, but no one replied and I assumed no one was interested in the information. This is clearly spelled out in Pangborn and Baker's cautionary status on glutathione as a supplement for autistics (section 5, p 303 in the paperback version). I think that this explanation for the adverse reactions to glutathione are much more viable and occur much more frequently (for people other than Freddd), than the Freddd mutation in MMACHC.

    Theor explanation points, in particular, to infused and even oral GSH administration. NADPH is depleted as GSSG to GSH conversion is occurring

    They also mention external GSH might very well have different effects than what GSH inside the cell does (ie, detoxifying mercury and other toxins from the cell). He speculates that external GSH might actually cause toxins to flow into the cells if there are toxins present external to the cells.

    They also mention the possibility of insulin getting decreased to critical levels. I don't know that rationale behind this theory.

    The NADPH theory seems to be the most likely explanation. Also, wouldn't a massive and rapid decrease in NADPH severely affect the folate metabolism as well, thus increasing the severity and complexity of the "crash" symptoms ? (hence supplementing with increased dosages of methyl-folate, etc might help the recovery process, as it did in Freddd's case)
  20. Malachy

    Malachy

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    Taking Jarrow methylcobalamin 1000mg for two days made me feel like I'd just spent a big night out at a dodgy chinese restaurant. I woke up on the third day feeling like I have MSG poisoning. Is that what is meant by excitotoxicity ?

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