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Methyl B12 side effects?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by justy, Nov 14, 2011.

  1. MDL

    MDL

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    As I said, oxytosis, otherwise known as excitotoxicity or glutamate toxicity

    Hi Rich,

    In the last couple of days, I have been posting on the sulfur deficiency thread and elsewhere on this site about my work "Hypothesis: Chronic Fatigue Syndrome, Mitochondrial Hypo-function, and Hydrogen Sulfide"

    In part, I said:

    "A further known complication for some people is a CBS polymorphism. The body produces hydrogen sulfide through several enzymes, including cystathionine beta synthase (CBS). CBS produces H2S in the brain, where it modulates NMDA glutamate receptor function. H2S protects neurons from glutamate toxicity by increasing the production of glutathione. Long-term potentiation is altered in the absence of H2S, which suggests the involvement of H2S in synaptic activity, so looking more closely at CBS and H2S is very important."

    ...and earlier today I wrote another post on the same thread:

    "As for the neurons, we know that "H2S increases the glutathione levels, which normally decrease during the cell death cascade, by enhancing the activity of ?- glutamylcysteine synthetase and up-regulating cystine transport. Cystine (cysteine) is the rate- limiting substrate of glutathione synthesis. These observations reveal that H2S protects neurons from oxytosis by increasing the production of the antioxidant glutathione"." I then mentioned that I believe cysteine and NAC to be as important as B-12.

    Oxytosis, of course, is "excitoxicity" or glutamate toxicity, which results in nerve cell death.

    While your comments parallel mine (without any reference to them), I note that you didn't include the part about the role of H2S increasing the production of glutathione or protecting the neurons from glutamate toxicity. I believe this is critical for a full understanding of what is happening in the brains of people with ME/CFS. I am wondering, were you aware of the potential problem with glutamate toxicity prior to my postings? Have you written about this problem anywhere before, including the role that H2S plays? I think that glutamate toxicity is important for people to be aware of, particularly those with the CBS SNP.

    The astrocyte connection to the mitochondria is intriguing as I believe that ME/CFS is a mitochondrial disease and that hydrogen sulfide plays a critical role in the mitochondria as well. From what I have read, "the results seem to indicate that astrocytes provide neurons mainly with CSH (cysteine), rather than GSH (glutathione), as the antioxidant material for neuroprotection." (PMID: 21436138) Do you have the citation for what you have described? As always, I appreciate your time.

    Marian
  2. justy

    justy Senior Member

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    Hi Danny, im glad the agitation is decreasing for you. Mine has completely gone after a few days with no shots. Ive gone onto every other day, half the dose (so thats half of 0.1ml = 250mcg)
    I suggest you start a seperate thread with your question about metafolin and excitotoxicity, as i tend to find that all the people who are interested in the topic of this thread will have had a look in by now and tend not to come back to the discussion (i hope that makes sense?)

    Apart from lowering the dose of the Methyl B12, what else could be done to stop thios excitotoxicity? Also am interested in other drugs/supplements that make this happen as i can experience iot for all sorts of different reasons e.g co q10 and carnitine do this to me as do epsom salt baths and white wine (i dont drink now tho) I can also get a similar problem from general overstimulation (lights, noise, talking especially) and sugar overload. For a long time i accepted the GPs idea that this was anxiety, but i can see that it is not the same as anxiety at all. There is no worry or mental anguish attached to it, it is a purely physical, nasty sensation in the body which comes and goes according to what ive eaten or taken and sometimes comes on from not pacing well.
    All the best, Justy.

  3. Freddd

    Freddd Senior Member

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    :confused:
    Hi Justy,

    Very simple. That is your energy starting to return to normal. "Normal" feels abnormal at first. Leave it going and pretty soon it feels normal and you have you energy back. It is a MAJOR signpost that you are healing. Get rid of that and you will stop the healing or slow it down a lot.
  4. greenshots

    greenshots Senior Member

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    I sure loved methyl b 12 in the beginning but after 3-4 weeks I was sick as I'd ever been!
    In the beginning, it felt like what it must be like to be on speed & I have to say, I liked that!
    later, I just felt jittery, tense, and was sick, probably from the detox I had & didn't even realize.
    I had acne for the first time in 46 years and diarrea as well as sores down south!
    When I stopped, it all went away.

    I don't really understand most of what Dr. Vank wrote but I am a CBS so maybe thats why. I had my tests done at 23&me and know I have the MTHFR 1298 & the CBS 699 but can't seem to figure out the rest.
    Angela
  5. Freddd

    Freddd Senior Member

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    Hi Dan,

    I had a huge amount of muscle breakdown. It didn't slow down until adb12 was added and not reversed until l-carnitine fumarate was added a year after adb12, and then it was a whole new game. There had to be enough adb12 and functional mitochondria for my muscles to stop breaking down and start reparing and growing in response to exercise. At the time I reversed it, the top of my thigh muscle was the thickness of my thumb and now 9 times wider. I also was taking prescribed testosterone to bring my levels up to normal. That probably helped. However, as I had already been on testosterone for 5 years by that time and had continued to have muscle breakdown for the first 2 years of mb12 and 1 year of adb12. The last item added that suddenly reversed it was the l-carnitine fumarate.

    Lack of Adb12 and carnitine allows for tissue breakdown. This appears to be a possible cause of the neurological damage of Parkinson's. Interstingly it looks like it can aid neurological healing in at least some situations. The adb12 is essential for the formation of the myelin and the funtion of mitochondria. Carnitine for the function of the mitochondria and I don't know what else.

    Carnitine and AdeCbl were shown to promote cerebral mass growth, increase neocortical layer thickness and pyramidal neuron volume, and fully restore normal structure of the neocortex in an experimental model of anorexia nervosa.

    Now this whole "excitotoxicity" thing just doesn't work out with mb12. For instance, glutamate toxicity is a frequent cause of excitotoxicity. Mb12 is documented as protecting neurons form glutamate toxicity and and quite a few other toxins.


    MetCbl and AdeCbl have usually been administered in divided doses three times daily. These supplements have excellent tolerability and no known toxicity. AdeCbl has been administered safely during pregnancy. No rationale exists to suspect MetCbl would not also be safe during pregnancy.


    Trying to pin "excitotoxicity"on mb12 is about 180 degrees off. You are not going to find anything and will spend time and effort chasing something that isn't there. As our bodies, including mine, do manage to convert some mb12 into adb21 and start producing ATP, and the conversion of enough to make a noticable difference can take several days and as the adb12 once parked tends to stay in place and accumulate over several days, this can account for an accumulating effect of mb12 since all the other effects of mb12 start fading in 24 hours and symptoms return in 3 days. And if you are thinking adb12 in those terms, all it does is occupy the mitochondria and make ATP. Now, there seems to be a theme I'm seeing across quite a few people. I would like to ask a question that may actually get at something but I don't know what. If I did I wouldn't need to ask the question. Why do some people find ATP startup to be so intolerable?

    Now you had no problem when you had injections of methylb12 in 2003. The most likely dose was 1mg IM. And now you find a much smaller amount intolerable. So what happened in the last 8 years?

    One thing that comes to mind is that intensity of startup response appears to correlate directly with the severity of the deficiency. So what has worsened your deficiencies over time?

    Bhatt et al have suggested a transient response to OH-Cbl might be misleading and might subsequently impair the therapeutic response to AdeCbl. They further suggest AdeCbl be the cobalamin therapy of choice for individuals with biochemically uncharacterized methylmalonic acidemia.38

    How long have you been taking hydroxycbl? I noticed as soon as I started posting here how much worse many symptoms became for those on hydroxycbl and folic/folinic acid and then how much more severe the startup was. You appear to be an excellent example of this. I've mentioned this over and over but nobody wants to hear it. Now, once again you appear to be leading me to another BINGO but I don't quite have it yet. It hasn't gelled. I've gone back and forth multiple times as to whether it is the hycbl or folic/folinic or the combination and/or something else. In active b12 research through the years there have been hints that hycbl and cycbl did something not good, whether it was block mb12/adb12 somehow or damaged something or ??

    And the theraputic range of mb12? They have it pinned on the body effective dosage range but haven't gotten to the CNS effective threshold. The range should look to be familiar.

    A therapeutic dose for conditions requiring MetCbl would be a minimum of 1500 mcg and a maximum of 6000 mcg per day. No significant therapeutic advantage appears to occur from dosages exceeding this maximum dose; however, it is likely that beneficial physiological effects occur at dosages as low as 100 mcg per day, especially if this dose is given repetitively over time.

    The quotes in here are from http://forums.phoenixrising.me/showthread.php?15515-Two-active-B12-articles-with-footnotes-surveys-of-peer-reviewed-research which includes footnotes pointing to all the original research.
  6. Freddd

    Freddd Senior Member

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    Hi Angela,

    Sounds like induced deficiency(s).

    I just felt jittery, tense, and was sick, probably from the detox I had & didn't even realize.
    I had acne for the first time in 46 years and diarrea as well as sores down south!


    Sounds like reasonably severe folate deficiency.
  7. Freddd

    Freddd Senior Member

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    Hi Justy,

    Over stimulation is probably a good description. Excitotoxicity isn't going to get you anywhere. It isn't a productive idea for mb12. It is misleading. Fead my response to Dan and let's talk about these things. They are all problems to be solved.
  8. dannybex

    dannybex Senior Member

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    Hi Fred, and welcome back!

    I definitely want to solve these problems, but it's gonna take some more active listening on both sides.

    I agree that overstimulation, and even 'extreme agitation' are perhaps more accurate descriptions than "exicitoxicity" regarding the responses many folks have had to some of the methylation supplements. But it's important to acknowledge those as legitimately described by the other person, instead of negating their experiences by telling them that it's "just" startup and to just push through it. Some people need to start low and slow, and gradually ramp it up -- this has been found over and over on this forum, and on other sites as well. Many doctors stress this importance, docs who specialize in these genetic polymorphism issues.

    It's also very important to acknowledge that not everyone needs the massive daily doses that you require, although they may indeed need daily dosing. Some may not need daily dosing, and it may be harmful for them.

    I can't remember off-hand, but didn't you have problems when you take more than 200mgs (or 400mgs) of SAMe? And/or coq10 was it? I don't see anyone telling you that you need to push through it and take more...you know...just because they've found they need 800-1200mgs of SAMe. We're all different, and all require different amounts of different nutrients to address our individual biochemical issues, and I hope you'll respect that.

    (I don't mean to be insulting in ANY way, just trying to point out that we all have different reactions, and all are able to handle them in different ways. I know you're just trying to help. But you know that some have had to stop b12/folates completely and have done better on glutathione, while others like yourself and others cannot stop the b12/folates and cannot handle any glutathione.)

    Late this past year I was told I'm in adrenal burnout (different from adrenal exhaustion) where I'm putting out waaaay too much cortisol 2/3rds of the day -- and night -- and then it's way too low in the morning. It jumps up at noon too. Perhaps that's one of the reasons I had reactions to the mb12/folate...or perhaps it was something else. This practitioner also believes I have a hidden copper toxicity. I do know that my zinc is low, so am slowly increasing that. If I take too much, it lowers sodium, plus lowers cortisol (for 8 hours according to one study), so I have to time it, taking it in the early evening.

    I haven't been taking hydroxyb12 very much -- have just kind of restarted the adb12 very recently. I still have some mb12, (in a cold, dark closet), and will try small doses of that starting tomorrow morning.

    On another thread, I posted how my latest lab test showed low RBC folate, (and I didn't take much of that at all last year as I could not tell if it was causing (sorry) "extreme" reactions or not. In hindsight, I don't think it was, so I'm restarting both the metafolin in quarter tabs (and have seen increased agitation already) and also some folinic, as indicated by my test results. No folic at all.

    My medicaid doc even did a urinary MMA, which came out 'normal', and was alarmed at my high b12 levels, so she asked me to find out if b12 lowers folate. Rich replied, saying it doesn't, and in fact the reverse was true, that one needs b12 to keep folate from 'leaking out' of the cells.

    I don't know why I haven't tolerated mb12 as well as I did back in 2003. My cortisol levels were sky high back then throughout the 24 hour testing period, so perhaps that has something to do with it. But you're right -- it could be because I've been too deficient in it for way too long, so the reaction is stronger. But it was, literally, intolerable, early last year...it did get a little better during the summer. Perhaps the lack of folate is the problem...(along with the cortisol/adrenal burnout issue)......

    Okay, I'll shut up. Like I said, I'm all for solving this problem.

    Thanks Fred,

    Dan
  9. Freddd

    Freddd Senior Member

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    Hi Dan,

    I don't mean to be insulting in ANY way. I have been designing, writing and supporting software and consulting for decades. Something I can assure you is that when trying to get information from a person around a malfunction of the software they literally can never tell me what they actually did. I finally had to write a key capture routine to be able to know what they did, and all I mean is what they actually typed in rather than what they intended to type in. So in order to understand why the logic went wrong I had to know what they were giving it to chew on. So in all this all I'm trying to do is get precise information about what you are doing and have done in order to understand what your body's reactions and responses are actually caused by. Interpretation and hypotheses only lead that effort astray.

    I agree that overstimulation, and even 'extreme agitation' are perhaps more accurate descriptions than "exicitoxicity

    There is a massive difference between description and an interpretation and hypothesis such as "excitotoxicity". A commitment to "excitotoxicity" makes it difficult to consider other possiblities and creates counterproductive fear and anxiety. There are a lot of interpretative terms I never use because they close the mind off to other possibilities. So "over methylation" is a theoretical term that describes a potential but a person who is a depleted or blocked methylator is not sufferring from over methylation, they are sufferring from depleted or blocked methylation. It might be a possibilty after methylation is fully functional but it doesn't happen when methylation is shut down. So avoiding the startup of methylation in order to avoid "over methylation" doesn't get a person healthy. According to at least some research 50% of population are undermethylators, 30% potentially average and only 20% potentially over. However, as almost everybody here has an approximately equal number of over and under methylation defined symtpms and they can be exactly the same symptoms for BOTH (GIGO) and they are ALL b12 and folate deficiency symptoms so none of those pass the stink test. They completely lack internal consistancy. So I leave that whole idea alone because so far it has zero predictiveness of actual responses.


    I can't remember off-hand, but didn't you have problems when you take more than 200mgs (or 400mgs) of SAMe?

    Nope. Not at all. I take 200mg daily. If it was cheap I might take 400mg but more than 200mg doesn't do anything more so I elect to cut that expense 50%.

    And/or coq10 was it?

    In the first months of mb12 coq10 caused my blood pressure to go up to 190/110 in two hours with a hell of a headache. That was not true the years before or 1 year after starting mb12 which is also 3 months after adding adb12. Several others have had the similar resaponse to CoQ10 and the initial period on mb12. Cause is unknown but worth alerting folks to the possiblity. I take CoQ10 daily now with no problem at all.

    But it's important to acknowledge those as legitimately described by the other person, instead of negating their experiences by telling them that it's "just" startup and to just push through it.

    The stimulation or feeling of stimulation, as the mb12 might produce either or both depending upon whether the mb12 can be converted enough to cause ATP startup in addition to nervous system startup. When the person says same thing on adb12 then that is ATP -mito startup. Excitotoxicity that destroys neurons is dangerous. ATP startup is not TOXIC and helps stop the damaging of neurons which azre damaged by nonproduction of ATP. Increased perception of nervous sytstem signals, while uncomfortable, is not dangerous. It is perceptual changes, not neuron killing. Mb12 protects neurons from excitotoxicity from glutatmate and some other things and helps heal neurons. This healing can be uncomfortable. So calling it something it isn't to scare the shit out of people or self and stop them from doing that which can heal them is not a great thing. It causes a lot of unneeded anxiety and fear. It produces this contradiction in that a primary defining item in Chronic Fatigue Syndrome and FMS, FATIGUE, is caused by mitochondria shutdown. Starting up the mitochondria from very low levels of functionality is quite uncomfortable. However, I know of no way to start them up without starting them up. The sooner they are started up the less damage.

    metafolin in quarter tabs (and have seen increased agitation already) and also some folinic,

    My suggestion becasue you don't know if folinic is a problem or not and the potential is there is to avoid it for NOW until you are sucessively start up and then try adding the folinic and assess what it does when you have a sucessful basis for comparison. If you do both at once you will never know and yert could be sabotaging a successful startup.

    "My medicaid doc even did a urinary MMA",

    It can tell you that it is really really bad in total failure mode but not if you have enough adb12 and nothing at all about l-carnitine. Interpreting it that way limits treatment to perhaps 1 or 2 % of those who could benefit.

    which came out 'normal',

    worse than meaningless, misleading even. I posted research previously that told why it is useless and misleading.

    and was alarmed at my high b12 levels,

    IGNORANCE big time. Mine is estimated to average 200,000 pg/ml, the level needed to penetrate the CSF/CNS in somebody with tough to penetrate CSF/CNS such as is found in CFS/FMS. The high end of the scale is a statistical abstraction of 2 standard deviations of a population. It doesn't even mean asymptomatic. A peson can have a much higher serum level of cobalamin (not b12, cobalamin, all the inactive, unavailable and junk cobalamin counts too) and still have loads of symptoms, hundreds even, responsve to mb12 and adb12. In the USA (cycbl) and UK (hycbl) 160pg/ml is borderline "low" and in Japan (methylb12) 550 is low alert level. In Japan the alzheimer's rate is 20% of the USA and UK. Alzheimer's/ALS/MS/SupraNuclearPalsy all have difficult to enter CSF as does CFS/FMS.

    one needs b12 to keep folate from 'leaking out' of the cells.

    This is the "methyl trap" you have heard about. It is directly cause by glutathione and NAC (if it promotes glutathione in that person). This is NOT an enzyme reaction. It is a simple chemical reaction, like cyanide, the glutathione simply completely overwhelms the mb12/adb12 and causes it to be excreted from the body much faster than otherwise causing said methyltrap within a few hours or less.


    But you know that some have had to stop b12/folates completely

    People who have a "detox" reation to folic acid, folinic acid or sometimes also vegetable folate have to stop the folates because the folate deficiency becomes intolerable.

    and have done better on glutathione,

    Yes, there are those who will feel better on glutathione. I was very specific about who would be able to detect that they were having trouble with glutathione. The conditions are very specific and very exacting.

    1 - They had to have a strong response to mb12/adb12/methylfolate
    2 - The have to have considerable reversal of deficiency symptoms

    So who might feel better?

    1 - those who have the symptoms but have never had a strong reversal of the symptoms
    2 - Those who take hycbl and folic and/or folinic acid without a strong reversal of symptoms
    3 - Those who take mb12/adb12 and folic/folinic acid with paradoxical folate deficiency
    4 - Those who take mb12/adb12/metafolin but have paradoxical folate deficiency from vegetable folate and/or folic acid and/or folinic acid
    5 - unknown

    Those who feel worse after some while of feeling better are those who had milder folate deficiency symptoms that then worsen or have b12 deficincy symptoms added to the folate symptoms. Mb12 symptoms might show up starting in a couple of weeks and slowly worsen from there and adb12 deficiency symptoms increase after a couple of months and worsen from there.


    while others like yourself and others cannot stop the b12/folates

    Your language is non specific, ONLY mb12/adb12 and methylfolate can't be stopped by those who have had strong responses to it. Many would have had to stop folic acid and hadn't run into folinic acid yet.

    Failure to differentiate which folates (non-specific folate) and which cobalamins (nonspecific b12) causes faulty logic statements and hence faulty conclusions. Hycbl results or lack do NOT predict mb12 effects. Hycbl resutls or lack do NOT predict adb12 effects. Folic acid effects may NOT predict Metafolin effects and may be opposite. Folinic acid effect may NOT predict Metafolin results and may be opposite. Folic acid may block Metafolin. Folinic acid may block Metafolin. Vegetable folate may block Metafolin. Undenatured whey may block Metafolin

    Therefore, if any of the following; NAC, glutathione, undenatured whey, folic acid, folinic acid are continued while trying adb12/mb12/metafolin then if the trinity doesn't work you will never know why. As long as one or more of these are continued it may be sabotaging any possible results. You can never be sure unless all are eliminaqted and then added in after results are obtained or after a whole not obtained, to see if there are any resuts.

    None of these things say anything about quantities of mb12/adb12/metafolin. However, clinical research shows that Metafolin is more likely to be effective above about 4 mg (4000mcg), the approximate minimum amount in any of the prescription products. Clinical research on Deplin (pure Metafolin) 7.5mg and 15 mg doses find "no side effects different from placebo". Whereas Cerefolin with NAC has all sorts of nasty side effects and DANGEROUS side effects.

    In any case, this is a complicated multivariable problem and careful language and logic is required if we are going to figure out what works and what doesn't. The "general solution" will follow from a lot of individual solutions but each situation must be carefully specified. Good luck in starting up again. In general I would advise starting the the basics and the trinity, adding critical cofactors after you have something sucessful going to increase good results and questionable things one at a time only after good results are established.
  10. Rosebud Dairy

    Rosebud Dairy Senior Member

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    Start-up effects/agitation/ etc. etc.

    I am having good and bad effects from re-starting from a couple of years off---The more careful I have been about potassium and magnesium, the more the good has outweighed the bad.

    One of my docs checked my MTHFR, and being positive for a single C677T caused me to start up again.

    Start-up effects noticed:
    MUSCLE SPASMS -- were strong when I was doing JUST metafolin with no attention to potassium, magnesium or mb12's (now I have three of those). Greatly relieved when I am careful.
    ITCHING!!!! ----Not sure if this is related to my lower potassium intake days (basically, when I run out of bananas!). It is happening on higher dose bioidentical progesterone (transdermal) days.

    IBS - improving with occasional flares

    The itching occurs usually symmetrically -- for example yesterday -- the lower outside portion of both calves was itching like crazy. The day before that it was near the hip bone - both sides in the same place. Last night, it was hands. Something is happening, I just don't exactly what. I am mostly just making sure I don't run out of bananas!! I am being super careful (FOR NOW) about which supplements I put in my gut, as my IBS will flare from time to time, and I haven't always been able to figure out each and every one of them. -- FOR NOW, I think it is usually carbs that set me off, but I am willing to let me prove me wrong. BUT I have to pay attention.





    There has been a little bit of PMS mood swing type stuff, which is when I know I have to get my dose of progesterone.


    At this point, I just don't want to pin one particular symptom to one particular cause, and NOT always keep it in my mind as related........Maybe my PMS can get better related to my MTHFR protocol, not merely being treated by progesterone, for example, and I need to be open-minded enough to see when those related things take place.
  11. Freddd

    Freddd Senior Member

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    Hi Dan,

    One other thing has become very clear. The more often mb12 at least is started and stopped and started and stopped the worse the startup effects get. I had forgotten to mention that. That became clear after a number of people did do the stop and start and the effects got more intense each time. I don't know why. It was clearly occurring though. It wasn't one of my experiences becasue I didn't stop. Instead I used the startup effects as my aiming point and tried to find each supplement that would keep them going. They were signposts to healing rather than "awful side effects" as I have seen them called, that warrants stopping mb12. Of course I then had the opposite effect. I healed instead of staying sick. Looking back on your history it is possible that the worsening of the effects was because of the mb12 injections in 2003 and then stopping. That was the year I started this healing journey with mb12 too.


  12. dannybex

    dannybex Senior Member

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    Hi Fred,

    Thanks for the clarification. My point was that you did have a negative reaction to a supplement, yet no one (I don't think anyway) came along and told you to keep taking it or increase the dose or just push through it so that you'll feel better. Some things that others might be able to handle well other might have trouble with at first.

    Some good points, but (I say but a lot don't I?)...but...I would argue that in someone with adrenal burnout, or worse adrenal insufficiency, 'overstimulation' can potentially cause serious stress to already overtaxed adrenal glands, which MAY cause harm, even serious.

    Secondly, while mitochondrial 'shutdown' is certainly an issue to address, ME/CFS (and thus as you suggested, mitochondrial shutdown) it might be caused by other things besides mb12 and mb-folate deficiencies. A buildup of toxins to due chemical exposures, or heavy metals, just as two examples. There's been quite a discussion over the years as to what comes first and/or what should be addressed first -- the toxins which may impair methylation -- and should those be chelated for example first -- or should one start the B12's and folates to restart the 'blocked' methylation -- and in doing so, does this cause a 'dump' of toxins? I don't know, but just throwing that out there. [/QUOTE]

    Thanks...I will try that. I just had an email from a woman this morning who's child had terrible problems with mb12, so they stopped it for a couple weeks, slowly added and slowly increased methylfolate for a couple of weeks and then she was able to tolerate the mb12 just fine. :)

    Did you see my thread on zinc-deficiency and the reversed methylfolate trap? From a couple months ago. Don't have the energy to find it now, but I know I do have a zinc deficiency, but have to slowly increase that as well, or it will shut down cortisol production (for eight hours, according to a published study) and also release too much copper, according to my practitioner. I'm up to 16 mgs a day right now.

    Edit: Here's the link:

    http://forums.phoenixrising.me/show...ot-Methyl-Folate-Trap-quot-in-Zinc-Deficiency



    I understand the folic and possibly the folinic blocking methylfolate and thus perhaps causing a folate deficiency, but don't understand how vegetable folate can cause a folate deficiency. Didn't Rich have some study that suggested a possible explanation for this? Is it possible that too much mb12 could be causing it?

    And yet, some can tolerate it and even improve on it just fine...that should be pointed out as well shouldn't it?

    I did mean methylb12 and methylfolates -- I should've been more specific.

    Yes, very complicated and multivariable, compounded by the fact that many of us have a difficult time keeping these variables straight due to brain fog issues. Also some, like myself, can't tolerate the dosages of certain of the supporting nutrients or cofactors, because of one reason or another. Just as one more example, I can't tolerate more than one fish oil (EFA) pill a day without my gums bleeding. I used to not be able to tolerate much vitamin c, but am now able to tolerate more...on and on. :)

    Thanks Fred,

    Dan
  13. dannybex

    dannybex Senior Member

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    I have no idea Fred. I have a feeling it's a combination of things -- the severe adrenal burnout, the possible copper toxicity/zinc deficiency, just the fact of being so much weaker because of the stress (which contributed to the burnout) and the general lack of support/help that I've experienced over the last 3-4 years.

    Interestingly, I had a 24 hour salivary hormone test done back in August 2002, where it showed my cortisol was sky high throughout all four testing periods. And I started the mb12 in December 2002. Within a week or so, the b12 'deficiency' symptoms, if indeed they were that, went away, and I had a definite improvement over the next six months or so that I took it. But had no idea (because I was also taking quite a few other things) that it was due to the mb12. I only realized that in hindsight. I also nebulized glutathione for the first 2 months, which didn't seem to reverse any of the benefits of the mb12. I think I just stopped it because it was a hassle to use.

    Also back then, I didn't take any methylfolate -- don't think it was around back then? -- but still had a decent improvement for about a year and a half, maybe longer. I was also taking good ol' Country Life adb12 as well, which as you know contains folic acid. Not sure how I was able to tolerate that, am certainly not going to start that ever again.

    Amazingly, although my cortisol is now extremely low in the AM, it jumps up at noon (too high), and then again at midnight -- so I'm still putting out too much cortisol at times, so the adrenals need to stabilize. Hopefully the mb12 and metafolin will help, but I do have the zinc issue that I have to slowly increase, and also am supposed to avoid certain b vitamins as they stimulate adrenal hormone production which doesn't need stimulating right now. Just as one example, pantothenic acid (B5) stimulates the adrenals:

    http://www.ncbi.nlm.nih.gov/pubmed/18520055

    I won't be able to order more mb12 for about 10 days or so, so will use up the hydroxyb12 (injectable) that I have, and work on increasing my metafolin for now.

    d.
  14. Freddd

    Freddd Senior Member

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    Thanks...I will try that. I just had an email from a woman this morning who's child had terrible problems with mb12, so they stopped it for a couple weeks, slowly added and slowly increased methylfolate for a couple of weeks and then she was able to tolerate the mb12 just fine. :)



    Did you see my thread on zinc-deficiency and the reversed methylfolate trap? From a couple months ago. Don't have the energy to find it now, but I know I do have a zinc deficiency, but have to slowly increase that as well, or it will shut down cortisol production (for eight hours, according to a published study) and also release too much copper, according to my practitioner. I'm up to 16 mgs a day right now.

    Edit: Here's the link:

    http://forums.phoenixrising.me/show...ot-Methyl-Folate-Trap-quot-in-Zinc-Deficiency





    I understand the folic and possibly the folinic blocking methylfolate and thus perhaps causing a folate deficiency, but don't understand how vegetable folate can cause a folate deficiency. Didn't Rich have some study that suggested a possible explanation for this? Is it possible that too much mb12 could be causing it?



    And yet, some can tolerate it and even improve on it just fine...that should be pointed out as well shouldn't it?



    I did mean methylb12 and methylfolates -- I should've been more specific.

    Yes, very complicated and multivariable, compounded by the fact that many of us have a difficult time keeping these variables straight due to brain fog issues. Also some, like myself, can't tolerate the dosages of certain of the supporting nutrients or cofactors, because of one reason or another. Just as one more example, I can't tolerate more than one fish oil (EFA) pill a day without my gums bleeding. I used to not be able to tolerate much vitamin c, but am now able to tolerate more...on and on. :)

    Thanks Fred,

    Dan[/QUOTE]

    Hi Dan,

    I can't tolerate more than one fish oil (EFA) pill a day without my gums bleeding.

    That is a clue. Have you looked into why your gums are so prone to bleeding? Of course the number one thing that comes to mind Do you floss every day? Number two thought is about platelet count as that is and area that is associated with bleeding gums from Omega3 oils as they retard coagulation a little. That is an even bigger clue. B12 and or folate deficiency can cause that along with half a dozen other blood abnomalities yet all the focus is on MCV and yet that keeps on creeping up too.


    And yet, some can tolerate it and even improve on it just fine...that should be pointed out as well shouldn't it?

    Actually I could not say that yet. As 100% of those who did the trial had results of induced deficiencies and all shared success with active b12 protocol, there is more than one way to read that. People who still have all their folate and b12 deficincies intact and who benefit, would have no removed previous symtpoms to return. SO to say that people with bad deficiencies show improvment except on their deficiencies kay not sound that deisireable, That Cerefolin with NAC had no trouble at all having people develop acute folate deficiency symptoms completely unrecognized isn't reassurance. That people who don't take the active b12 protocol also have plenty of people who develop "Nac Detox" or "glutahtione detox" also induced folate deficiency leads me to beleive that the people who have benefits already have all the deficiency symptoms in place and hence show no detrimental changes from glutathione or NAC and may show benefits. Then there are those with folate deficiency but not b12 deficiencies that are obvious who show benefit at first and then develop the b12 deficiencies later and maybe a more sever folate deficiency later. There is no evidence yet that this is not the case and it is a hypothesis that fits the patterns so far. Time will tell. Glutathione combining with active b12s is like falling off a log, no enzyme and no ATP needed, it's as automatoic as with cyanide. If it doesn't happen in some people that would be very interesting. If that does happen but is not perceivable and only the good shows up, that is understandable and fits the hypothesis. There are some easy ways to test this with suitable size doses of b12 to see if the amountflushed from the body goes up the same for everybody or just some of us. So until we know that the only reason they don't notice it is that they are already that deficient or not, time will tell.

    but don't understand how vegetable folate can cause a folate deficiency

    That is very easy. Folinic acid from a pill or capsule is still the same folinic acid from a green leaf. If folinic blocks methyfolate why would the source matter?

    Didn't Rich have some study that suggested a possible explanation for this?

    I don't know but if he has it I would like to read it.


    Is it possible that too much mb12 could be causing it?

    Absolutely not. My paradoxical folate deficiency predates my consumption of vitamins by 20 years and my taking mb12 by 50+ years. People who take no vitamins can have it. It's just more obvious if people can try Metafolin because that gives them a basis of comparison for the first time in their lives to know what no folate deficiency is actually like.


    Did you see my thread on zinc-deficiency and the reversed methylfolate trap?

    No, I'll have to read it.

    Secondly, while mitochondrial 'shutdown' is certainly an issue to address, ME/CFS (and thus as you suggested, mitochondrial shutdown) it might be caused by other things besides mb12 and mb-folate deficiencies. A buildup of toxins to due chemical exposures, or heavy metals, just as two examples.

    In that case then those who have mito startup from active b12 protocol don't have shutdown for some other reasons. Wouldn't that be so? Perhaps that could account for those who don't have mito startup from adb12 and cofactors. Fortunately most do have mito startup from adb12 plus cofactors.
  15. SoniaR

    SoniaR

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    Hi, I am hoping that Fredd will see this post. I have posted on another thread but maybe this is the right thread..

    My 24 year old son has symptoms of Sub Acute combined degeneration of spinal cord since the past 1.5 years. However, repeated MRIs and nerve conduction study have been normal. He has been on B12 supplementation since the past 15 months - B12 (Methylcobalamin) injections - 500 mcg injection intra-muscular twice a week and sub-lingual Methylcobalamin lozanges (Jarrow). After 15 months he is about 50-60% better. He has also been taking some of the co-factors like omega 3, b-complex.

    His primary symptoms are:

    1. Loss pf proprioception in legs and arms - symptom intensifies on bending/ turning of back and neck
    2. Constant unsteadiness/ dizziness - symptom intensifies on bending/ turning of back and neck
    3. Weakness in arms and legs
    4. Neck stiffness
    5. General fatigue

    Even though he feels much better with more frequent injections, the neurologist has refused to prescribe more than 500 mcg Methylcobalamin per week. We did blood counts a week back and some of the results were a bit worrying:

    Red blood cell count 5.76 (Range 4.5 - 5.5)
    Hemoglobin 16 (Range 13 - 17)
    Hematocrit 47.9 (40-50)

    Platelet count 150 (150-410)

    The Red blood count, Hemoglobin and Hematocrit have been slowly increasing. The red blood cell count is slightly out of range. On seeing this result the doctor has asked us to stop all B12 supplementation for 6 weeks. After that my son's symptoms have started increasing even though he is still taking 2-3, 5000 mcg sublinguals of Methyl B-12 (Jarrow) a day. I recently read Mayo Clinic's report on the safety of B12 and I quote:

    "Use cautiously in patients with hematological concerns, as, according to case report data, treatment of vitamin B12 deficiency may lead to polycythemia vera, which is characterized by an increase in blood volume and the number of red blood cells".

    I am really stressed out and worried as on one hand my son feels better with more B12 injections and on the other hand his RBC count and Hemoglobin/ Hematocrit are increasing. Please can someone advise what to do. Many thanks, Sonia
  16. Freddd

    Freddd Senior Member

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    Hi Sonia,

    No amount of mb12 affected my red cells or platelets or anything. They were all abnormal. It took the addition of Metafolin to bring down the MCV and bring my platlets and everything back to normal.

    Japanese research suggested that doses in the range of 50mg daily of mb12 is needed to cause remission of brain and cord diseases. I and a a few others found that 30mg of mb12 subcutaneouisly injected daily as 4x7.5mg, 3x10mg or 2x15mg works, if it is a 5 star mb12 not exposed to light. I have been doing that for 5 years or so now.

    In reading up on the polycythemia vera bloodletting or donation can be used to control it.

    What is his MCV? What about multisegmented neutriphils? What about MCH?

    If you want to see what a 7.5-12.5mg injection is like, he can try a 50mg sublingual dose (Jarrow) over 3-4 hours with each tabley held 90-120 minutes and 3-4 at a time, adding 3 more each 30-40 minutes until 10 are reached. 15-30 minutes before this a dose of Metafolin of perhaps 8000mcg will aid absorbtion and distribution. It's a good idea if he also gets the adenosylb12, say 10mg of that added to the 50mg of mb12. In addition l-carnitine and omega3 fishoils are specifcally mentione in terms of neurological healing.

    Can you tell me how one so young has developed this subacute combined degeneration? It takes a severe CSF/CNS b12 deficiency.


    I have sucessfully reversed subacute combined degeneration sufficiently to regain full function. I have some feelining in my feet and can control my toes. I can stand on one foot. I don't trip over my toes any more. I know where my legs and feet are and don't fall. I even redid a roof which would have been impossible before healing. I am no longer intemmittantly incontinent. It was well established of 15 years duration before I was able to start reversing it.

    I used to have every symptom you mention. They are ALL gone or very diminished and the worst are controled. Does he have a multitude of other symptoms as well?

    Does he have angular cheilitis? What about IBS?
  17. SoniaR

    SoniaR

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    Hi Fredd,

    Thanks for your reply. It took a lot of consultations with different neurologists to come up with this diagnosis - based mainly on the symptoms, a positve Romberg's test and the fact that we are vegetarians. The MRI was normal.

    My son is extremely uncomfortable with his balance/ dizziness problems and the feeling that his arms and legs are not connected to his body . The sense of touch seems fine, proprioception seems to be affected most and there is a lack of strength in arms and legs.The worst symptom however is difficulty in focusing with the eyes and this constant feeling of waves of dizziness hitting the head, he says its very difficult not just to read but to even think, mind always seems overwhelmed. Any bending or turning of neck starts worsening these symptoms.

    But to an observer this discomfort is not apparent as his walk and appearance look normal. Except one, all neurologists who examined him said that there is no neurological sign. Is it common to have symptoms of Sub acute combined degeneration of spinal cord with a normal MRI?

    The reason that he has severe deficiency is may be because we are vegetarians and so probably the deficiency is due to lack of B12 in his diet. At the time we learnt about B12 we also found out that D3-25H was very low at 3.2 (almost negligible). After taking Calcerol Sachet (one per weak initially then twice a month and then once a month) this went to around 115 (Ref range 75-250).

    His complete blood count (December 2011) after 15 months of b12 therapy is as follows:
    Result Reference range
    Red blood cell count 5.76 4.5 - 5.5
    Hemoglobin 16.0 13-17 (was 14.90 eight months back)
    Hematocrit 47.9 40-50 (was 44.60 eight months back)
    MCV 83.2 83-101 (was 86 eight moths back)
    MCHgb 27.7 27-32 (was 28 eight months back)
    MCH concentration 33.3 31.5-34.5
    Red cell Dist Width 13 11.6-14.0
    Platelet count 150 150-410
    Mean Platelet volume 10.5 6.8-10.9
    WBC count 7.3 4-10
    Segmented Neutrophils 57 40-80
    Lymphocytes 33 20-40
    Monocytes 6 2-10
    Eosinophiles 4 1-6

    ESR 3 0-15
    Homocysteine 5.87 5.46-16.20 (down from 9.29 eight months back)
    Serum Zinc 73.51 (70-120) - Is this too low?
    Serum Ferritin 112 22-322
    Serum Iron 97 65-175
    Total Iron binding capacity 349 250-450
    % saturation 27.8 13-45

    Also, his AST and ALT are slightly raised for the past one year. We got a liver ultrasound done and he has grade 1 fatty liver. All other liver enzymes and kidney function tests are normal.
    AST 49 15-37
    ALT 115 30-65

    We will try the 50 mg test with Jarrow as suggested by you. So far he just takes about 1-2 lozenges of 5 mg of mb12 daily(Jarrow), 500 mcg Wockhardt intra muscular injection once a week, and one lozenge of adb12 (source Naturals) twice a week. In fact when we increased the frequency of injections to twice per week (500 mcg) with two 5mg lozenges every day life seemed more livable. But recently after being almost admonished by our hemotologist we have gone back to 1 injection per week & he says the symptoms become worse when this happened.We will add the other co-factors mentioned by you.

    He does not have angular cheilitis and IBS. The only stomach related symptom is frequent constipation if he does not consume fibre rich foods. His other symptoms were
    1. Muscle tremors in upper arms - this is nearly gone now
    2. Ulnar nerve sensitivity - better now
    3. All peripheral nerves sensitive - and limbs tend to become numb if some small pressure is applied for sometime.
    4. It seems like something is locked in the neck, can turn neck but for instance for reversing the car, he cannot turn enough to look back comfortably [could do this easily before the symptoms started].

    No doctor is ready to prescribe this dosage of mb12 here in India. Also, subcutaneous is not prescribed here but as you said this is the best method of injecting. We will try to get someone to teach us. Sorry for the long mail. I tried to give all the relevant information. Many thanks, Sonia
  18. Sallysblooms

    Sallysblooms P.O.T.S. now SO MUCH BETTER!

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    I had very bad deficiencies in B12 years ago after not eating red meat. I wish I could take it all back. I never would have done it. I saw a specialist and got back on meat as fast as I could. There are so many supplements you have to take if you do not eat meat. I thought I did it all right, but I sure had horrible problems. Vertigo, ataxia, IBS, and I was so ill. I hope you can get all of the supplements to help. Took a long time to recover.
  19. Freddd

    Freddd Senior Member

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    Hi Sonia,

    Being a vegetarian for 20+ years almost killed me. I look at the MCV and wonder why the MCV is so small, because of a concurrent low iron? I don't know if marginal low iron would do that or not. However, as many of us have learned the tough way that low CNS cobalamin without low body levels of cobalamin is very possible.

    MRI of brain won't show problems of cord. MRI of brain and cord can miss the demyelinations in any case. There is some guidance on line on how to set up the "weighting" on the MRI to see the lesions.



    Chances are reasonable that you can do this with the Jarrow sublinguals. You need to find the dose that increases the tingling in the numb areas or already affected tingling areas. This can be maintained on the Jarrow alone with a sufficient dose held for 2-3 hours. Sub cutaneous is real easy. Use an insulin syringe and find an area with a some subcutaneous fat, squeeze it into a lump and insert needle at 45 degrees and inject. It is almost painless. It takes longer to fullly difuse but maintains a serum peak longer. A 5mg Jarrow held for 2 hours under lip is equiv to 1mg injection approximately. 15mg of Jarrow plus 3mg of Enzymatic therapy held for 3 hours under lip will give a 5-6mg injection equivelent. If done daily and maintained for a couple of years it might actually fully heal the SCD enough that a maintenacne dose will keep it going. If he doesn't heal it soon it will become permanent and then he will gradually run down until it cripples him and then kills him. It's too bad that the docs are willing to sacrifice his neurologu y to a real ptroblem to save him from a theoretical problem that I have never actually heard of happening from mb12 injections depite hundreds of person years experince with myself and other people injecting up to 30mg of mb12 for years. My neurology is very damaged from long non treatment and it's all I can do to hold steady now. If I stopped I would be in diapers and a wheelchair in months with mood, personality changes and hallucinations to follow.

    Good luck.
  20. dannybex

    dannybex Senior Member

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    Seattle
    Hi Fred,

    Yes, I floss a couple times a day. I think there's a few possibilities -- like you say folate deficiency, which I know I have, is probably a biggie. Also vitamin C. I don't take very much at all, but am going to increase it as soon as I can get more, hopefully tomorrow. (I do get some in the adrenal supplement.)

    My MCV from a month ago was right at mid-range 'normal'.

    Dan

    p.s. Also, don't know if you noticed, but I found the link to the 'reverse' methyl-trap situation, and added it to my earlier post. Here it is again:

    http://www.ncbi.nlm.nih.gov/pubmed/18520055

    ???

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