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MethylB12 - how much is too much ?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by globalpilot, Jan 24, 2011.

  1. globalpilot

    globalpilot Senior Member

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    Ontario
    this question is for Rich.

    I like to take methylb12 instead of the hydroxy because I have mutations in the MTRR enzyme which could limit the conversion of cobalamin to methylcobalamin.

    Is there a danger in taking too much methylb12. I know about the issue with mercury but is there any other reason one couldn'ttake 2000 mcg of mb12 instead of hydroxyb12 if the MTRR mutations are present ?

    Global Pilot
  2. richvank

    richvank Senior Member

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    Hi, Global Pilot.

    My concern about methylB12 is related only to its possible potential for methylating inorganic mercury that may be in the body, primarily from exposure to mercury vapor, as is released continuously from amalgam fillings in the teeth. Methyl mercury is readily able to cross the blood-brain barrier and enter the brain, where it apparently then reacts with enzymes containing selenium (and to a lesser extent, sulfur) and acts as a neurotoxin, with a residence time in the brain measured in years.

    I do not have proof that this will actually occur in humans with the inventories of inorganic mercury that are actually present and the dosages of methyl B12 that are used in treating ME/CFS.

    My concern comes from the fact that there are published papers indicating that methyl B12 is able to react and donate a methyl group to inorganic mercury, and in fact, it is one of the only substances in biological systems that is able to do this. The reason is that inorganic mercury exists as a doubly positive mercuric ion (Hg++). In order for a substance to donate a methyl group to it, the substance must be negatively charged. methyl B12 forms a carbanion, which is able to do this.

    It is known that the way methylmercury enters fish is that bacteria in aquatic environments use methyl B12 and other similar substances to methylate mercury, and then are eaten and travel up the food chain to the larger fish. Apparently the bacteria methylate the mercury as a means of exporting it to their outer surfaces and so protecting themselves from its toxicity. It can have some toxic effects on fish (see first abstract below) and when people eat fish containing methylmercury, it can be toxic to them, especially if their bodies are low in selenium (see second abstract below). Methylmercury dumped as waste into the ocean in a fishing area was responsible for the Minimata disease disaster in Japan in the late 1950s, and methylmercury used to treat grain seed that was unfortunately later eaten by people caused a disaster in Iraq as well.

    There have been experiments in guinea pigs in which it was found that methylation of mercury occurred in their bodies. It is not clear whether this methylation occurred within their own metabolism, or whether it was carried out by bacteria in their gut.

    As far as I'm concerned, this is an issue that has not yet been resolved. I'm aware that people with certain polymorphisms will benefit more in terms of helping their methylation cycle by taking methyl B12 rather than hydroxo B12. I know that there are people who are taking dosages of methyl B12 of several milligrams per day, sublingually, and some are reporting benefits. I don't know what their body burdens of inorganic mercury might be. Unfortunately, there is no good way of evaluating it, short of doing autopsies, which isn't very helpful for people who want to keep living for a while!

    It may be that supplementing with selenium will give sufficient protection from methylmercury toxicity. This approach is actually used by marine animals and birds, who eat seaweed, containing selenium, together with fish containing methylmercury. Some whales have been found to have large deposits of selenium-mercury compound in their livers. This is very chemically stable, and makes them both non-bioavailable. It should be noted, however, that selenium is toxic in large amounts as well, and the Institute of Medicine has placed a recommended upper limit on selenium supplementation of 400 micrograms per day. Some have argued that this limit is too conservative. The safe upper limit for an individual probably depends on a number of factors, the body burden of mercury being one of them, but it is difficult to determine what it should be on an individual basis. The Institute of Medicine attempts to set a limit with a safety factor that will apply to the general population.

    I wish I could give you a more definitive answer to your question, but that's as much as I know. It's possible that I am being overly cautious in raising this issue, but I really do not want people to be harmed.

    Best regards,

    Rich


    J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009 Oct;27(4):212-25.
    Reproductive, developmental, and neurobehavioral effects of methylmercury in fishes.

    Weis JS.

    Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA. jweis@andromeda.rutgers.edu
    Abstract

    In the decades since the Minamata tragedy in Japan, there has been a considerable body of research performed on effects of methylmercury in fishes. The studies have revealed that some of the most sensitive responses seen in fishes are reminiscent of the symptoms experienced by the Minamata victims. This article reviews the literature, with a focus on mercury's effects on fish reproduction (hormone levels, gametogenesis, fertilization success), embryonic development (morphological abnormalities, rate), the development of behavior, and neurobehavioral effects in adults. Both experimental exposures and epidemiological approaches are included. There have been many studies demonstrating delayed effects of mercury exposure in that exposures during one life history stage can produce effects much later during different life history stages. For example, exposure of maturing gametes can result in abnormal embryos, even though the embryos were not themselves exposed to the toxicant. Exposures during sensitive embryonic periods can produce long-lasting effects that can be seen in adult stages. The existence of these manifold delayed effects renders the practice of short-term toxicity testing particularly unhelpful for understanding the effects of this (and other) toxicants.

    PMID: 19953396 [PubMed - indexed for MEDLINE]



    Toxicology. 2010 Nov 28;278(1):112-23. Epub 2010 Jun 16.
    Dietary selenium's protective effects against methylmercury toxicity.

    Ralston NV, Raymond LJ.

    Energy & Environmental Research Center, University of North Dakota, 15 North 23rd Street, Grand Forks, ND 58202, USA. nralston@undeerc.org
    Abstract

    Dietary selenium (Se) status is inversely related to vulnerability to methylmercury (MeHg) toxicity. Mercury exposures that are uniformly neurotoxic and lethal among animals fed low dietary Se are far less serious among those with normal Se intakes and are without observable consequences in those fed Se-enriched diets. Although these effects have been known since 1967, they have only lately become well understood. Recent studies have shown that Se-enriched diets not only prevent MeHg toxicity, but can also rapidly reverse some of its most severe symptoms. It is now understood that MeHg is a highly specific, irreversible inhibitor of Se-dependent enzymes (selenoenzymes). Selenoenzymes are required to prevent and reverse oxidative damage throughout the body, particularly in the brain and neuroendocrine tissues. Inhibition of selenoenzyme activities in these vulnerable tissues appears to be the proximal cause of the pathological effects known to accompany MeHg toxicity. Because Hg's binding affinities for Se are up to a million times higher than for sulfur, its second-best binding partner, MeHg inexorably sequesters Se, directly impairing selenoenzyme activities and their synthesis. This may explain why studies of maternal populations exposed to foods that contain Hg in molar excess of Se, such as shark or pilot whale meats, have found adverse child outcomes, but studies of populations exposed to MeHg by eating Se-rich ocean fish observe improved child IQs instead of harm. However, since the Se contents of freshwater fish are dependent on local soil Se status, fish with high MeHg from regions with poor Se availability may be cause for concern. Further studies of these relationships are needed to assist regulatory agencies in protecting and improving child health.
    Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

    PMID: 20561558 [PubMed - indexed for MEDLINE]
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  3. Freddd

    Freddd Senior Member

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    Hi Globalpilot,

    I want to stress that mb12, or hycbl for that matter, needs to be taken with all the needed cofactors for the best possibility of effectiveness. In the case of the methylb12 and adb12, brand can make as big a difference in effectiveness as type of b12 can. If one uses one of the 5 star brand of mb12s plus adb12 it is usually massively more effective from the first hour than hycbl. There is no reason at all not to take 2000mcg. If 2000mcg of mb12 is allowed to linger 45-120 minutes under your lip generally from 15-25% is absorbed. That generally means that a 5mg sublingual can be about as effective as a 1mg injection sc injection.
  4. Binky123

    Binky123

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    Fredd/Rich

    Currently I am taking 5g methylcobalmin twice daily, under the tongue for 45 minutes (jarrow brand), along with 800-1200 mcg of methylfolate.

    I know this is a lot, but I have had some success - including the single best day since I've been sick.

    I had my mercury filings removed a year ago, but I do eat a decent amount of fish. Mostly fish that are low in mercury (salmon, sardines, shrimp). I noticed that I felt absolutely terrible after eating salmon in fairly large quantities the other day, so I may need to cut down.

    Assuming I stay mostly away from Mercury, do either of you see problems with this dosage? Thanks again for your help - these b12/methylation protocols really seem to have some potential for me.
  5. richvank

    richvank Senior Member

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    Hi, Binky.

    I'm guessing that you meant 5 MILLIgrams of methylcobalamin twice daily.

    I don't actually know how much would be too much. My suggestion would be to pay attention to how you feel. If you develop symptoms that are neurological in nature, such as pain or changes in cognition, memory or mood, that could be a warning sign.

    Best regards,

    Rich
  6. slayadragon

    slayadragon Senior Member

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    twitpic.com/photos/SlayaDragon
    One thing that we don't talk about enough is the importance of people with ME/CFS taking into consideration the point that they are at in their own recoveries rather than following a one-size-fits-all strategy.

    For example, in November 2007, when I was living in my moldy house, even a speck of FolaPro and 1000 mcg of hydroxy B12 were enough to make me so ill that I am listed in the "adverse effects" section of Rich's paper.

    Three years later, I have become able to take extremely high doses of these supplements -- 7.5 mg of Deplin (equal to 36x the amount of FolaPro in Rich's simplified protocol) and 10 mg injections of methyl B12.

    I have found this to be one of the most helpful things I've done recently, as I've moved towards full wellness. My body feels more resilient, my brain is working better, and I feel much calmer and stronger.

    This dose, of course, would be enough to kill someone with severe ME/CFS. It only works for me because I have already done a great number of other things to improve my health over these last years -- including pursuing extreme biotoxin avoidance, taking over a year of full-dose Famvir and full-dose Valcyte (another treatment that could kill really sick ME/CFS patients), doing extremely intensive detox with cholestyramine, addressing other pathogens in a variety of ways, starting with small amounts of these supplements and working up, supplementing with co-factors (including extremely high dose P-5-P, zinc and lithium with the knowledge that I have kryptopyrroluria issues), and a variety of other things.

    I think of this whole thing as peeling away the layers of an onion. Many people with ME/CFS are so sick that there isn't anything that they can do to make improvements -- detoxing and killing pathogens (both of which seem to be necessary) are too much. At that point, avoidance of biotoxins and other triggers may be the only place to start.

    As time goes on, more aggressive treatments can be tolerated. I recently have been corresponding with a patient who got extremely sick while living for a relatively brief time in Lake Tahoe (I believe from the outdoor biotoxin that is especially prevalent there), but who has made extremely fast progress since moving away as a result of high-dose daily methyl B12 injections (he was using 25 mg), FolaPro, and Lyme/pathogen treatments.

    Mike Dessin has repeatedly warned people on this board about doing anything to promote detox (such as using glutathione or any methyl B12) when really sick; now that he is close to full wellness, he's started using methyl B12 himself.

    Judy Mikovits recently mentioned Deplin as a potential treatment to help patients to use antiretrovials more effectively. Implying that this might be an appropriate treatment for all ME/CFS sufferers seems to me to be a real mistake, however. Many people who are considering antiretrovirals (especially, I believe, those living in bad environments) are extremely ill and are being made even more sick from the "inflammatory flare" of the drugs; adding something else stressful on top of them is hardly what they need. On the other hand, someone who is further along in the recovery process -- and who is living in a good environment -- might benefit from both of them, as I have benefited from Valcyte/Famvir and methylation support. Again, a one-size-all strategy serves none of us well.

    So I think it's a real mistake for people here to ask Rich or anyone else what dosage of any supplement is safe. It all depends on where we are at in terms of our recoveries. Perhaps a really good doctor could make such a recommendation for a particular patient at a particular point in time (my own longtime physician, Dale Guyer, recommended to me the 10 mg methyl B12 injections after evaluating in detail my current status), but in lieu of that, self-knowledge and trial-and-error seems necessary.

    As for the idea of moving mercury into the brain: it's my belief that most of us have (as a result of Stachybotrys exposure) blood-brain barriers that are full of perforations that basically let anything in. This would include all forms of mercury. My own assumption is that any substance I encounter will go right into my brain, which is part of why avoidance of bad substances (insofar as my body can't detoxify them easily) seems to be a good thing.

    I would agree with the idea that doing everything possible to make sure that toxins that are loosened up or converted are removed efficiently from the body (e.g. by looking at intestinal binding, co-factors, etc.) is important as well.

    Best, Lisa
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  7. kurt

    kurt Senior Member

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    Lisa, I have a similar experience to yours. Methylfolate plus B12 made me very sick when I lived in a house and area with mold problems. After moving to a dry climate I now do well with both. We do have many layers to peel back.

    globalpilot, I am taking three forms of B12 and have learned I need them all, Methyl, Adenosyl and Hydroxy. There is no logic that will expose a person's individual needs in my experience, you have to try them out. And if they don't work, try some other things (peel back other layers) then try again. What they appear to do for me, the Methyl helps me detox and gives me energy, the Adenosyl improves my muscle strength and endurance, and the Hydroxy reduces brain fog and helps my clarity of thought. I know this due to experimenting with B12 and many supporting nutrients over months and months.
  8. Freddd

    Freddd Senior Member

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    Hi Binky,

    Those doses, and I assume you mean 5mg of methylb12, apeaqr quite adequate until there is other evidence. The more important thing for you now is to add Country Life Dibencozide (adebosylb12) 3MG at a dose of somewhere between 1 per week and 1 per day, establish the basics, like b-complex, a, d, E, minerals (calcium, magnesium, potassium, etc). omega3 oils (of critical importance for neurological healing), enough zinc, say perhaps 50mg/day, and then after all these basics are established then try the critical cofactors, such as l-carnitine fumarate, especially if there are still some not fully responsive symptoms.

    If you have neurological damage already then as healing starts, and it might be kicked off by any of the basics or critical cofactors, symptoms will intensify. That is completely normal. The difference is that they frequently unwind backwards in order. S if a nerve has totally stopped transmitting and it doesn't cause a large area of numbness you might not even be aware of it, the first thing that might happen is jolting pain, the most intense tingling you might have ever felt, all sorts of paresthesias and so on. These things usually progress pretty rapidly compared to how they came on over years and decades, the reversal may be packed into weeks or months. It is normal to feel energized beyond "normal" levels while the internal "thermostat" down-regulates and this can occur because of mitochondria in muscles and neurons come back to functioning and as nerves begin transmitting signals better. As there are at least 4 or 5 distinct things that may be occurring this energized feeling has multiple aspects and can occur in stages. I had it occur for mb12, adb12, l-carnitine fumarate, SAM-e, zinc, Metafolin and a few other things to much lesser extents. These are what you are aiming for. They are your feedback that healing is beginning or continuing.

    Shifting food sensitivities and chemical sensitivities, often extreme to start with, frequently occur during b12 deficiencies, methylfolate deficiency and the healing of these things. Again, symptoms are intensified and shift, often rapidly. The things that kick up the most flak also appear to heal most rapidly and completely with continued use of the b12 etc.

    The potentially most dangerous (potentially fatal) side effect is the sudden reduction of potassium from your body abruptly starting to generate cells by healing. This can manifest in mood changes and sudden severe spasms, especially legs, while relaxed, such as in bed at night among other things. This happens frequently with the active b12 protocol. Have potassium on hand either as a supplement, a prescription or "Losalt" salt substitute from the supermarket. Other induced deficiencies caused by healing stop or limit healing abruptly often.

    Hypokalemia (potassium shortage) as a direct result of sudden healing is mentioned as a "rare" side effect with hydroxycbl and cyanocbl but is fairly common with methylb12/adnosylb12/methylfolate. I have experienced it multiple times as I have added certain critical cofactors that increased healing and when I resumed healing after glutathione (precursors) trashed my body.

    Good luck.
  9. Freddd

    Freddd Senior Member

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    Hi Kurt,

    A lot of people have mentioned the mold connection. It is possibly the most common environmental factor I have heard mentioned. Also, pealing back in layers is also my own experience, one layer after another is revealed only by peeling back the one covering it. However, when one looks at a lot of people and the EXACT things they have done and the order they do it (yes, order can be important, there are a lot of dependencies) there is considerable logic to it all.
  10. Binky123

    Binky123

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    Thanks for the response Fredd! I didn't detail this in the original post, but I am also taking the following:

    - AdenosylB12 (country life 3mg) - I don't notice nearly as strong a response to ADb12 as I do to methylb12
    - Magnesium malate and citrate
    - zinc
    - Herb complex for immune support (reishi, astragalus, etc.)
    - Curcumin
    - jarrow b-right
    - rhodiola
    - vit D 5000 iu
    - cod liver oil (with 4000iu + vit A)
    - probiotics (jarrowdophilus)
    - alpha lipoic acid 100 mg w/ biotin
    - Vitamin K2 (rotating between MK-7 and MK-4)
    - then of course methylb12 (5-10mg) and methyl folate (800-1200 mcg)

    I am adding in your last cofactor vitamin E (Now gamma E) soon. The first time I took this I felt terrible, but I'm not entirely sure if it was the vit E.

    I eat a lot of bananas (averaging 3 per day) and other fruit for potassium. I do not have a calcium supplement currently - I will probably take a low does if I add this as vitamin D already increases the absorption.

    Methylb12 is very interesting for me. A while ago, I took it alone without any cofactors, and was feeling great. As with most of my CFS treatments, the success did not last.

    For now, I seem to be quite volatile. I had what was probably the best day of my CFS life on Sunday, and this even continued into Monday morning. Then, I took 10mg of MB12 (2 doses of 5 mg for 2+ hours) and everything got worse. I am hoping that I reach some sort of stability soon - work is taking quite a toll on me lately.

    Thanks for all your help Fredd.
  11. Freddd

    Freddd Senior Member

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    Hi Binky,

    "Feeling awful" can certainly describe some of the startup responses to mb12. This is a healing journey of 10,000 steps for each part of your body. The problem is when you get half way there, 5000 steps, it has just been 5000 other ways to feel bad with 5000 more ahead of you. Feeling good doesn't happen until some item actually heals. For me for instance, I had immediate energization and intensification of all symptoms in gruesome detail. The added energy felt euphoric after 17 years of zero energy. Everything hurt a lot worse. After 10 days my bladder stopped burning as badly as did my mouth and tongue. However it took another 3 months to complete that tissue healing so they hovered back and forth for a while. When my neurology started healing that was intensely painful and for the CNS produced volatile mood shifts which took 9 months to mellow out, for the better, much better.

    The adb12 only is directly involved in 2 things and we can only feel one of them directly. Mb12 is said to be involved in 600 and who knows how many of then we feel, a lot I would say. Taken without cofactors, while it improves some things it leaves a lot undone and stalled becasue of some other limiting factor.

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