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High histamine = undermethylation, but B12 raises histamine...?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by PeterPositive, Jan 2, 2014.

  1. PeterPositive

    PeterPositive Senior Member

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    There seem to be a consensus that high histamine can be related to a state of under-methylation, which is my case, for instance.

    However taking methyl-B12 causes an even higher release of histamine. I experience this all the times, especially on an empty stomach. I noticed it this morning once again, I took a smallish dose (300mcg) and bam... pins and needles all over my skin.

    Dibencozide doesn't seem to cause the same effect, at least not with the same intensity.
    Is it a sign that I should avoid Methyl-B12? Being MTR(+/-) and MTRR(+/-) I don't think it's a good idea. Right?

    Thanks
    Thinktank likes this.
  2. Thinktank

    Thinktank Senior Member

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    Interesting, i'd like to know as well because i'm dealing with the same problem.
    High histamine and PGE2 (Excessive mast cell degranulation?)
    Low B12
    Same MTR / MTRR heterozygous mutations.

    I didn't try Dibencozide or any other form of B12 yet except mb12 because i've just started to explore the world of methylation. high dose Mb12 gives me the same feeling as a histamine overload. Little bit of "pins and needles" and flushing but more of an anxious, panicky, psycho overstimulated effect. The only thing that works with such an episode is xanax or a high dose anti-histamin with mast-cell stabilizing properties to calm me down.

    Have you tried niacin yet? It's often used when over-methylated but i guess you already knew that. Some say it's easy to switch between undermethylation and overmethylation.
  3. PeterPositive

    PeterPositive Senior Member

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    hi Thinktank,
    yes methyl-B12 can also increase anxiety especially at high dosages (1mg +). I started with 250mcg but at the time even that dose would trigger some anxiety. Eventually the effect declined and I was able to increase to around 1000-1500mcg. You may experience the same.

    Niacin for me causes even more flushing so I usually take low doses. Not more that 200% the RDA.

    What is PGE2?
    Last edited: Jan 2, 2014
  4. caledonia

    caledonia

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    Reduce the dose to a level to where you're not increasing histamine. See the Start Low and Go Slow document in my signature. For example, I'm taking 16mcg methylcobalamin so I don't feel metal detox.

    If you're taking methylcobalamin, you need adenosylcobalamin (dibencozide) to go along with it. Adenosyl works on the mitos and not so much on methylation.
    katim and Thinktank like this.
  5. PeterPositive

    PeterPositive Senior Member

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    Thanks caledonia.
    Indeed I should take adenosyl-b12 as well. The only product I have at hand also contains folic acid so I am staying away from it since my 23andme results came back with the MTHFRC677T +/+

    I have ordered Dr.Lynch's b12/folate product which has both forms of b12 and 800mcg of active folate but it usually takes a while to receive those products in Europe.
  6. PeterPositive

    PeterPositive Senior Member

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    Oh, I almost forgot that SAMe might help with the excess histamine.
    I have taken it for short periods of times but it's not easy on my stomach, 200 to 400mg is all I can take.
  7. PeterPositive

    PeterPositive Senior Member

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    One more question: do you find your histamine problems worsen during winter, possibly even more with low humidity? This is a constant for me, when talking to doctors they usually give me a strange look or raise an eyebrow :D

    With a rapid search I've found this: http://www.ncbi.nlm.nih.gov/pubmed/12932227
    At least I share the same problem with mice o_O
    aaron_c likes this.
  8. GenDylan

    GenDylan

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    Methyl B12 gives a histamine reaction when its in your blood stream because it lowers cortisol(by raising melatonin). cortisol is basically the biggest histamine fighter in your body, along w/ adrenaline.
    in general tho, b12 should lower histamine if you have a methyl trap going on ;if so it allows 5mTHF to turn into THF which degrades histamine.(this is how histamine is "methylated")
    if you can, take some more 5mthf w/ ur mb12 and your histamine reaction will decrease.
    shah78, Star-Anise and Gloria H like this.
  9. PeterPositive

    PeterPositive Senior Member

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    Good point. I actually need quite a bit of 5mthf as I have the mthrf c677t +/+ mutation.
    Thanks
  10. GenDylan

    GenDylan

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    yes, but im 100% sure that your issue w/ b12 is cortisol. licorice root around timed for the b12 dose would also help.
  11. Ema

    Ema Senior Member

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    Everything I've read suggests mB12 suppresses melatonin which is perhaps one way if affects the sleep wake cycle and helps with alertness.

    It would make sense that lower melatonin would also mean higher cortisol, but this one study at least suggests it has no impact on cortisol.

    http://www.nature.com/npp/journal/v15/n5/full/1380492a.html
    aaron_c likes this.
  12. aaron_c

    aaron_c

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    Here is Rich Van K on histamine:

    So while THF is necessary to metabolize histamine, it metabolizes it into glutamate, an excitatory neurotransmitter. While this is a problem for those of us deficient in folates, or else experiencing a methyl-trap (where the folates are trapped as 5MTHF), for those of us taking the right supplements, this shouldn't be an issue.

    For the rest of us, the methyltransferase pathway that Rich alluded to is the main way methylation (SAMe, in this case) contributes to lowering histamine. This is the first step of the histamine deactivation pathway in the central nervous system.

    Here is a thread with a good diagram. Although I disagree with the idea that higher-than-moderate doses of niacin might be helpful.

    But GenDylan is right, in that raising 5MTHF and/or mB12 would increase both THF and SAMe, which should help with histamine issues in the central nervous system. If the issues are outside of the CNS, as it sounds like yours might have been, @PeterPositive , my understanding is that it might be more of a DAO issue, genetic, and/or cofactor related. As Rich wrote, those cofactors are B6 and Copper.

    All of this, however, does not explain why mB12 would cause histamine release. I have one possible answer: Methylmercury. Rich Van K's hesitation around mB12 was that, if it was not bound to a carrier protein, it would donate it's methyl group to inorganic mercury, forming organic mercury (methylmercury). I do not know the details about organic vs inorganic mercury toxicity, but Rich Van K's concern was at least that methylmercury could enter the brain. Here is an article on what methylmercury does to mast cell degranulation: Basically, it seems to increase histamine release initially, and then it decreases it. So it seems like mercury *could* be part of the equation. Have you been tested for heavy metals, Peter?

    @Thinktank : Where are you with all this? Do you still attribute the mB12 reaction to histamine?

    Well, here's hoping I haven't yelled "fire" for no reason. I do hope the whole mB12 raises histamine thing ends up being more benign.

    Aaron C
    bertiedog likes this.
  13. PeterPositive

    PeterPositive Senior Member

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    Interesting. I have had problems with L-glutamine adding extra anxiety, which I thought was due to a screwed-up conversion. Now that I take 2g methylfolate I can take glutamine up to 2-3g without problems. Maybe there's a connection between the two, as you suggest. Would this make sense? I haven't looked into the the glutamate cycle.


    Thanks. I have experimented with oral SAMe but it doesn't work very well with my digestion. So now I am working of fixing the methylation cycle and making my own. Which is probably best anyways.

    I think you're right. When I wrote this post (~ 6 months ago) I was still taking a relatively low dose of B12 and folate, at least for my needs. This was confirmed also by the results of a methylation panel which showed low SAMe, high SAH and bad SAM/SAH ration.

    I have now doubled the dose of both supplements and added Adeno-B12, and I seem to be doing better. I have also raised zinc and B6 which were also too low. ( I recently discovered I have high KPU/HPL which worsens the situation for those two cofactors )

    Yes. I monitor heavy metals almost every year. In the last 3-4 years mercury has been elevated, before it wasn't but in terms of symptoms there is no correlation.

    I have also done the porphyrin tests a couple of times as an extra marker for Hg toxicity but it came back negative both times.

    cheers

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