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Methyl B12, Vit D increases excitotoxicity, what to do??

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by BFG, Jan 5, 2017.

  1. BFG

    BFG

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    Hi guys,

    I recently tested some of my nutrient status' due to my deteriorating condition and here are the results:

    serum b12: 215pg/mL (193-982)
    serum MMA: 149nmol/L (87-318)
    serum folate: 28.2 ng/mL (3.1-17.5) H
    RBC folate: 545ng/mL (>280) H
    homocysteine: 13.1 umol/L (3.2-10.7) H
    Vitamin B1 whole blood: 69 nmol/L (78-185) L
    Vitamin B2: <5.0 nmol/L (6.2-39.0) L
    Vitamin B6: 15.8 ng/m: (2.1-21.7)
    Vitamin D- 25 Hydroxy: 3 ng/mL (30-100) L

    So now my doctor says that I need to supplement vitamin D, b12 and b complex. I havn't taken those for a while due to either them causing me migraines and headaches or giving me diarrhea and other reactions. So now I'm at a loss of what to do...

    I purchased solgar, source naturals, jarrows sublingual methyl b12 and everytime I try to take even a crumb I end up getting headaches and migraines. It also increases my excitotoxictiy symptoms; ear ringing, eye flashes, anxiety, brain fog, can't sleep and I feel generally overall more inflamed. I don't know if this is due to the sugar alcohols or the b12 itself. I also tried taking vitamin D at a dose of 400 IU, which greatly increased my excitotoxicity and headaches.

    My doctor thinks my folate is good, but im not so sure. Can someone still be deficient with high serum and RBC folate levels?

    If MMA is normal and folate is high, what else can be causing my homocysteine to be elevated?

    Should I try to ask my doctor for subcutaneous injections of low dose methyl b12 and see if that also gives me a headache?

    Did anyone experience the same reactions to these supplements and did you find anything that helped?

    thanks.
     
  2. eljefe19

    eljefe19

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    Yes. In short, high folate levels actually show impaired folate absorption, and no, I have not had any side effects or otherwise from Vit D, folate, or b12, including any positive effects.
     
  3. Pippy2303

    Pippy2303

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    I had a bad reaction to Methylfolate and now on no B12 supplement. Dr Yasko methylation pathway analysis has info on which B12 suits you if you know your genes for COMT 158 (I think) and VDR Tak and some people are better on Hydroxycobalamin or Adenosylcobalamin. My daughter who also has MTHFR finds folinic acid helps her remarkably
     
  4. xrayspex

    xrayspex Senior Member

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    I can't remember why but in past couldnt tolerate b vitamins or rich's methylation protocol

    as far as vitamin d I am at a loss at what to do about that too, I have very low D and have ostepenia and bone pain etc and my doctor really wants me to supplement with it, but no matter what dose or form I take I feel awful from it, get insomnia and irritability.....am trying to work still and can't deal with that

    I also cannot go out in the sun with my autoimmune issue

    I am trying to experiment with diet to get it that way, dont feel good from salmon or tuna etc but seeing if can handle sardines and oysters etc sometimes
     
  5. drob31

    drob31 Senior Member

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    That's the lowest vitamin D level I've ever seen. The real question is, what is your active vitamin d level, 1,25 hydroxy?
     
    Paralee likes this.
  6. bertiedog

    bertiedog Senior Member

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    I cannot see how high folate in the blood shows poor absorption. If you had poor absorption is wouldn't be absorbed and therefore you would be low in it!

    Pam
     
  7. Valentijn

    Valentijn Senior Member

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    Have you tried hydroxoB12? A lot of people find it more tolerable than methylB12, myself included.

    I think it's possible that a B12 deficiency might result in elevated folate levels.

    Low B12 causes elevated homocysteine.
     
  8. PeterPositive

    PeterPositive Senior Member

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    I beat that. Mine was at zero. Literally.
    Yeah... It's not a competition :rolleyes:
     
  9. PeterPositive

    PeterPositive Senior Member

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    I had the same issues with vitamin D and solved with this:
    http://forums.phoenixrising.me/inde...ce-with-uvb-lamp-for-raising-vitamin-d.41202/

    Cheers
     
    xrayspex likes this.
  10. Hip

    Hip Senior Member

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    Excitotoxicity may not be the right word, because excitotoxicity (= death of neurons through overstimulation) occurs when there is NMDA receptor activation from really high levels of glutamate or other NMDA agonists. I am not sure if the glutamate levels in ME/CFS are high enough to cause actual excitotoxicity.

    However, higher levels of brain glutamate may be behind the "wired" symptoms of ME/CFS, and some ways to lower glutamate are given here:

    Five Ways To Reduce Your ME/CFS "Wired But Tired" Hyperaroused Brain State

    Possibly if you can reduce your glutamate levels (assuming that is your problem), you may be able to tolerate vitamin D and B12 better.



    What about getting vitamin D from sunlight / sunbathing? Does that cause you any problems?

    Have you tried supplements known to be useful for migraine, such as feverfew, riboflavin and magnesium? Ref: Supplements and Herbs for Migraine | The Migraine Trust
     
    xrayspex likes this.
  11. alicec

    alicec Senior Member

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    I think poor absorption into cells is meant, rather than poor absorption from the gut. In other words the vitamin is not being used and is accumulating in the blood.

    From the results posted by @BFG, however, RBC folate is high so the situation is not so simple.

    Nevertheless, I do think the results suggest that it is too simplistic to say that high folate means there is no problem with folate.

    High homocysteine suggests that there is a problem with the methionine synthase reaction. This in turn suggests a functional B12 deficiency.

    This could be the case despite normal serum B12 and MMA.

    Serum B12 is not a good measure of functional B12 status since it measures both B12 bound to haptocorrin and to transcobalamin II. Only the latter, which is a minor component of total B12, is actually taken up into cells for use with B12 dependant enzymes. This might be low but obscured by normal haptocorrin bound B12.

    Elevated MMA is a better measure since it reflects the activity of the adenosylB12-dependent enzyme methylmalonylCoA mutase. (MMA accumulates when this enzyme is not working well).

    Elevated homocysteine and MMA together are generally used to assess functional B12 status. You have only one of these but I can imagine a situation where your B12 status is marginal, perhaps not bad enough to show yet in elevated MMA, but beginning to manifest in a compromised methylB12-dependent methionine synthase reaction.

    The high folate could fit in here if we consider the concept of methyltrap.

    Methylfolate is the predominant form of natural folate in the blood. When it is taken up into cells it can be used only in the methionine synthase reaction. This converts it into THF, which is then funneled into the various other pathways of the folate cycle.

    When methylation is compromised (ie insufficent SAMe is being generated via methionine synthase) two things happen. First the body prioritises by suppressing other aspects of the folate cycle and concentrating on producing methylfolate.

    If B12 is limiting methionine synthase, this means that methylfolate may accumulate in the cell since it has nowhere else to go. This is the so-called methyltrap. There is plenty of folate in the cell but it can't be used because methionine synthase is not working properly.

    This could be the situation you are now in.

    The second thing that happens when too much methylfolate accumulates is that the cell expels it. This is methyl trap in action. Now marked folate deficiency symptoms are present but they can't really be resolved by folate supplementation. The problem is B12 deficiency.

    This could happen further down the track.

    What to do about it?

    Your sensitivities make the obvious answer of supplementation difficult.

    The reactions you describe are not unusual. Many people on PR have described similar things.

    Supplement sensitivities can have many causes, including problems with the gut. This is certainly worth considering.

    The other thing which may well be relevant to you is that at least some of the sensitivity reflects an even greater deficit in something else. Once the something else is supplied, the sensitivity settles down.

    Finding the something else (and of course this can be more than one thing) can take a lot of experimenting.

    Some people have reported tolerating B vitamins better once they had supplemented magnesium. For others it was sufficient B2/B6 which enabled magnesium to be tolerated.

    I had a slightly different experience but it may be relevant. I had no problems with B12/folate initially and derived a lot of benefit. Later the benefit petered out and I became very sensitive to both methyl and adenosylB12. Eventually I realised that I had depleted various trace minerals. Once I supplied these, I could tolerate and derive benefit from methylB12 again. Tolerating adenosylB12 is still a work in progress.

    In your case, given the "excitotoxic" type responses, magnesium might be a good place to start. You may need to experiment with magnesium types, or alternately, try topical magnesium.

    It could be worth experimenting with individual B vitamins rather than a B complex. It may be only one or two that are the problem. Perhaps getting a few on board may help tolerate the others.

    Trace minerals could be worth adding.

    When you've done a bit of this kind of experimenting it may be worth trying B12 again. By all means experiment with type, but there is no evidence for Yasko's claims that certain SNP's determine sensitivity to type.

    Here is a post about introducing B12/folate for a sensitive person. In your case you already know you are very sensitive so you need to be even more cautious.

    Hopefully though you may find introducing some minerals and other B vitamins first might make things a bit easier.
     
    Chocolove, Learner1 and xrayspex like this.
  12. bertiedog

    bertiedog Senior Member

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    I have this problem too. RBC over the range but the last OAT test I did showed I had a high need for folate. I think its to do with my genetics because I have a lot of SNPs which show impairment in the use of folate. I cannot take more folate because it seems to convert to excess glutamate which gives me horrendous migraines so I just carry on having plenty in my diet.

    My RBC B12 is also over the top of the range so I have stopped taking this too and the migraines have improved but in no way gone away.

    I do take lots of magnesium and tried extra minerals but none of it made any difference to the headaches/migraines. (I also have a problem in the conversion of glutamine to GABA). For me it seems to be an insolvable problem so after about 9 years of experimentation I have given up trying!).

    Pam
     
  13. xrayspex

    xrayspex Senior Member

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    good ideas..........I keep experimenting with nutrition to see if can figure it out....for me unfortunately the sun makes me feel bad,flares me, sort of like lupus, have sjogrens
    my doc wanted me to take the 50,000iu prescription to get D up but that is laughable since even 100 can make me feel more poorly

    It sure is a tangle to unravel the core deficiencies......I feel worse on most vitamins and minerals....but am trying various configurations of smoothies and soups now this winter to see where things improve or worsen

    am trying flaxseed oil again even tho in past number of times didnt like how i felt on it, going to try pulsing, its a good one for omega 3 which could help the d situation......fish oils are out for me
     
  14. BFG

    BFG

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    hi all, I appreciate all the suggestions, especially when energy is so scarce with us. Thank You.

    Im of the belief that methyl b12 is the form best used by the body. When I first came down with cfs/me I was taking 20 mg jarrows no problem and it healed a lot of my nerve and sensory issues. Now 4.5 years with cfs has taken its toll on my brain, gut, and ability to tolerate many things.

    Im curious what type of autoiimune issue do you have. I also cannot tolerate the sun.

    I tired hydroxy b12 in the past, but it scared me away when it gave me sudden nerve pains in my elbows, that didnt go away for about a couple of months.

    thanks for the suggestion, i was looking into the fda approved one since im in the US, but was wondering if it has fhe same effect as the sun? The sun also gives me headaches as does vit d supple,entation.

    I appreciate your posts hip, but unfortunatly supplements dont have strong enough effects on my excitotoxicity, neurotoxicity, kindling etc.

    I am on valium to barely control my anxiety, panic attacks, overstimulation, ears aching ringing sizzing hearling loss, neuropathy, secere brain fog, ability to focus, some days i just stare out of focus at my wall all day. It gets very scary sometimes.

    I cannot tolerate any calcium and sodium. They always make me super dizzy, headaches, increases my anxiety and especially my ear ringing, my theory is that they are increasing the nmda ampa influx of calcium and sodium increasing neuronal excitotoxicity. I cannot eat anymore proteins like beans, meats, eggs, becuases I beloeve the amino acids are already increasing the elevated levels already in my brain of glutamate further damaging neurons.
    It seems like im in a perpetual state of benzodiazapine withdrawal.

    To make matters worse im also withdrawing from a 18 year addiction to pornorgraphy. I have been struggling for years to quit, but I was in a cycle of abstinance and relapse, which I believe made my brain even more sensitive.I have been PMO (porn,masturbation,orgasm) free for 5 months now, but it has greatly increased all of my excitotoxic symptoms, similar to alcohol withdraw, which lowers seizure threshold, increases extracellular glutamate, and dysregulates glutamate homeostasis.

    Hi alicec, thanks for your thorough explanation and suggestions. I totally agree that my body is missing some cofactors or essential nutients maybe some amino acids, but cannot handle any protein. i feel better physically, but later will feel anxiety, anger, migraine, eye flashes, brain fog and crash. I am goign to take each b vitamin separtly and see what happens.

    I recenlt started methyl b12 subq injections of 500 mcg and it started up some pins and needles in my limbs and face, stabbing pains, which b1 cocarboxylase also did, but at least i can now tolerate some b12. I take magnesium ascorbate and potassium chloride just a pinch.

    Which trace minerals did you find that were helpful for your case?

    I also am probably deficient in essential fatty acids. But even after trying many fish oils, they also cause me headaches and exacerbates my diarrhea.

    I should have said in my original post that i have been eating only white rice and cabbage only for about a year, which are the only foods i seem to tolerate and this is what i believe has caused me so many vitamin deficiencies. Everything started getting worse when I made the decision to recover from my long addiction to porn. But now my brain has become severly damaged, but I feel it was also depleting me even thou it would temporarily make me feel good.

    Can anyone else relate?
     
  15. xrayspex

    xrayspex Senior Member

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    I have sjogrens (had antibody test) which can be as bad as lupus or any other AI altho a lot of md's just think of it as dry eyes not knowing it can cause bad fatigue and pain etc
    Sun and heat are my enemy, and showers and baths are too---but you can't tell by looking at me (and hopefully smell lol)

    fish oil also doesnt agree with me and the flax oil didnt work out , you might find this forum I linked below interesting, I was searching this weekend for other folks with AI and vitamin d intolerance and there are definitely others out there that feel bad if take d, go in sun, or even sun lamp, or take fish oil etc I havent tried sun lamp yet but I want to just because my d is like at a 7 and could be contributing to the pain I have in bones and teeth etc But obviously there is something about trying to raise it with the ways I mentioned that for some of us our bodies fight---that says to me there must be a reason we are low in D......I dont know if its related to ideas in Marshcall protocol, some sort of autoimmune response or something bout D being a hormone---Judy Mikovitz had noticed in her CFS research that a lot of us do not do well and get worse with certain hormones

    but I always want to know the mechanism and I also want to try to prevent my ostepenia and teeth from getting worse per my low vitamin D..........a friend of mine with psoriasis also felt awful on D and would get sort of bipolar flare from it, yell at people etc but she was determined to get rid of psoriais, she eats a lot of basil for the vitamin k and uses D cream and she cleared up her psoriasis, she had less negative effects with that protocol and took a lot of magnesium to help offset side effects and potentiate the medicinal part of it but it still effects her mood in those forms but not as bad as taking oral d etc

    http://www.healingwell.com/community/default.aspx?f=29&m=1766157

    oh and btw I eat mostly white rice (less hard on the gut than brown) with butter and cottage cheese and tolerate that great.....in the last 6-10 years (I am 57 and have had CFS or something like that for the last 27 years) I have gotten intolerant to an incredible amount of foods....I used to love to eat out....not so much anymore .....I have been experimenting with smoothies to get fruit and some other nutrients but can't do many supplements and lots of vegies bug me too
     
    Last edited: Jan 29, 2017
  16. Learner1

    Learner1 Professional Patient

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    If you've been eating only cabbage and rice for a year, you will likely have deficiencies in vitamins, minerals, amino acids, fatty acids, and phytonutrients.

    The problem you will run into in fixing this is starting with just one or two nutrients can't get entire pathways working properly...you need cofactors.

    From the info you've shared, it's likely you do need B12... you have folate backed up. But, you could need B2, B6, magnesium, methionine, trimethylglycine, etc. too. And glutamine, glycine, and cysteine to make glutathione, and the you'd need B1, molybdenum, and taurine.

    None of us can tell you what you're short of. It's just very complicated, and if you haven't been having normal nutrient intake, it'd be very hard to guess. Likely, you may have gut issues, too, perhaps an imbalance in your microbiome and malabsorption issues.

    You sound very motivated to work on this. Having a competent functional medicine doctor assist you with getting this fixed is important. They could run a test like a Genova Diagnostics NutrEval and a stool test to find out what's out of whack and fix it. And maybe testing for heavy metals like lead or mercury which can block pathways.

    Failing that, you might try a good dairy free probiotic, some digestive enzymes, and possibly some HCl to ensure whatever you're ingesting is absorbed.

    Then start with a high quality multivitamin in small doses, increasing gradually. Thorne Research makes good ones that are pretty allergy free, different ones depending on your age and sex.

    You might also try an amino acid powder to get some aminos into you, or something like Great Lakes Bovine gelatin powder.

    This will give you some cofactors for reactions.

    Then, try some B12. 20mg sounds like a huge amount. Start with a sublingual, maybe 3mg of methyl B12 to begin, and/or adenosyl12. It'll a topical oil. And a B complex to get enough B2 and B6, and magnesium glycinate (watch for arsenic contamination in magnesium supplements).

    Vitamin D needs cofactors, too, like calcium, magnesium, strontium, boron, etc. All of our pathways need cofactors...

    And your cell membranes need lipids...you might try something like NT Factor to help replenish them. B6 is needed, too. And a full palette of fats... try flax seed oil, avocados, MCT oil, evening primrose oil, cod liver oil. See what you can tolerate, and you'll likely need to try tiny amounts and add over time.

    Best wishes to you.
     
    Chocolove likes this.
  17. Basilico

    Basilico Florida

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    I second the suggestion to get your 1.25 D level checked. For some reason, doctors rarely check 1.25 (which is the active form) and is questionably a much better indicator of actual D status. A few years ago, my 0.25 D level was 33 while my 1.25 level was 99, which was multiple times the upper limit so supplementing with D would have been a very bad idea even though my 0.25 D level was on the low side.

    Have you ever tried Inositol? If not, It might be worth looking into- maybe it could help with the anxiety. There are some studies on pubmed showing it to be very effective (on par with prescription antidepressants) and beneficial for a wide range of mental/neurotransmitter issues. It's pretty cheap, too. I've only taken it once so far, but I think I already noticed some benefits from it.
     
  18. Crux

    Crux Senior Member

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    Many of these signs and symptoms are familiar, excepting the libido part, mine's mostly dead. :meh:

    I've had elevated serum folate, suspected gut bacterial overgrowth, treated it, now no negative reaction to folate supplements.

    The reaction to B12 may be because of its support of folate metabolism. ( I didn't have a negative reaction to B12.)

    The negative vitamin D reaction, I've had repeatedly. One issue is that it increases nitric oxide production, which can be neurotoxic if excessive.

    Another issue with vitamin D, is it inhibits the production of the hormone, hepcidin. The liver produces hepcidin to regulate iron metabolism. Hepcidin should increase when iron is high.

    So, low hepcidin can lead to excessive iron accumulation. This can cause oxidative stress, organ damage, and neurologic damage.

    http://jasn.asnjournals.org/content/25/3/564.full
     
  19. Konflict

    Konflict Senior Member

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    I've been dealing with severe symptoms that get worse with time (most notably joint instability body wide, including jaw, spine, neck and chest bone).

    Started getting these sides 5 weeks after stopping 5000mcg Methylcobalamin, 800mcg metafolin folate, and 33mg p5p. Was also taking 50mg riboflavin. At the same time I was taking vitamin E mixed tocopherols which are an Aromatase inhibitor tha directly binds to the estrogen receptor.

    2 weeks before my "crash" I had started taking vitamin K2 mk7 (which is also an Aromatase inhibitor by blocking new estrogen synthesis and raising intratesticular testosterone).

    So 5 weeks after stopping the B vitamins and vitamin E, and 2 weeks into taking vitamin K2 I crashed very hard and my symptoms keep getting worse. Dehydration, IBS, excessive urination, insomnia, joint pain/cracking/laxity, brain fog, heightened senses (smelling, hearing), body odor changes, fat/water weight loss, lowered body temperature. All of these symptoms are low estrogen related....but my E levels aren't too low I'm at 18pg/ml.

    I'm wondering if my body could crash 5 weeks after stopping the methyl Bs? Could this be a methyl trap? Or does this sound like something else going on? Keep in mind that I haven't taken any of these supplements in 2 months and these symptoms continue to worsen. If anyone has any input id appreciate it.
     
  20. Learner1

    Learner1 Professional Patient

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    Hi Konflict,

    Yes, the symptoms you have can be related to altering the balance in your methionine cycle.

    A very good functional medicine doctor could untangle you. Working with a less savvy doctor and getting some data would help. A Genova Diagnostics NutrEval test would help a lot in understanding what's going on. A Doctors Data provoked urine heavy metals test might be useful, too. And a CBC, complete metabolic panel and homocysteine level.

    You're a unique genetic individual with unique environmental factors, which is why a one size fits all approach doesn't work. I suspect the proportions of what you took threw your body dramatically out of balance... the proportions you report is extremely different than what my doctor has me on (like needing more P5P, B2, magnesium, and methionine...).

    This is just a guess, but you've probably mobilized toxins and your body is having trouble getting rid of them through your kidneys, intestines, and sweat. I've had many of the same symptoms working with my doctor over the past 5 years.

    While getting more info, so you can put together a comprehensive plan, you might try these ideas:

    - eating lots of vegetables and taking binders like charcoal, etc. Different binders bind different toxins, so you may want to research these and experiment

    - promoting glutathione with n-acetyl-cysteine, and adequate aminos, particularly glycine and glutamine

    - helping your transsulfuration pathway with more P5P, taurine, and molybdenum

    - FIR or dry sauna, starting in short intervals

    - ensuring you have enough potassium, magnesium, calcium, and sodium.

    Best wishes to you and I hope you can find a doctor who can help. What you're describing is not a do it yourself project and could be dangerous.
     

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