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

PeterPositive

Senior Member
Messages
1,426
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

Senior Member
Messages
1,640
Location
Europe
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.
 

PeterPositive

Senior Member
Messages
1,426
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?
 
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caledonia

Senior Member
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.
 

PeterPositive

Senior Member
Messages
1,426
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.
 

PeterPositive

Senior Member
Messages
1,426
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.
 
Messages
70
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.
 
Messages
70
yes, but im 100% sure that your issue w/ b12 is cortisol. licorice root around timed for the b12 dose would also help.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
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.

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

Senior Member
Messages
691
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")

Here is Rich Van K on histamine:

Histamine is made from histidine, and tetrahydrofolate is needed to metabolize histadine to glutamate. When there is a partial methylation cycle block, tetrahydrofolate is not being produced at a normal rate by the methionine synthase reaction (this is what produces the elevated Figlu on a urine organic acids test). It may be that more of the histidine goes into forming histamine when the conversion to glutamate is impeded by low tetrahydrofolate.

The other aspect to consider is the breakdown of histamine. If this is slow, histamine can build up. There are two main pathways for this. One is a methyltransferase pathway, and a partial methylation cycle block would be expected to interfere with it. The other is diamine oxidase, which requires vitamin B6 (actually its active form, P5P) and copper. If either of these is deficient, it could slow the breakdown of histamine and produce higher levels of it.

What can be done? Well, together with your physician, you might check the levels of copper and B6, and supplement if low. If copper is supplemented, zinc should also be supplemented at a dosage that is a factor of 10 or 15 higher, to keep them in proper balance. It's also important not to overdo the copper, because it can produce oxidative stress via the Fenton reaction.

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
 

PeterPositive

Senior Member
Messages
1,426
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.
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.


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.
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.

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.

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 )

So it seems like mercury *could* be part of the equation. Have you been tested for heavy metals, Peter?
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
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
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.

This study showed that methylb12 didn't lower cortisol, but did 'influence' melatonin.

http://www.ncbi.nlm.nih.gov/pubmed/8914118

And this one showed that methylb12 definitely lowered melatonin and adjusted sleep cycles:

http://www.ncbi.nlm.nih.gov/pubmed/1516676

Anyway, @GenDylan I'm curious if your histamine issues have been resolved, and what proportions of b12 and folate you're using now? Thanks.
 
Messages
2
Hi there,
I'm looking for some wisdom regarding Chronic Histamine Intol, affecting especially the central nervous system and causing food triggered migraines.
I've been suffering from such for the last 7 years and no regular doctor could shed a light on the way of the solution to my problem.

My symptoms are as follows:
Upon ingestion of most food groups, like any type of fruit, gluten and no gluten foods (bread, etc), chocolate, tea, soft drinks, sweeteners, milk, yogurts, Honey, caffeine, Kinua, grape juice and wine, etc....a metallic taste develops on the tip of my tong. Following, I develop black eyes (vasodilation effect) , asymptomatic hypotension (80 x 50 mmHg), and 6 to 8 hours later, a bad classic migraine.
Symptoms worsen along the day and build up the more food I eat. It seems to be dose dependant.
If I stay away from a particular food, like for instance a Coke, the reaction is milder, and as long as I keep exposing myself to the same drink, I tend to develop a stronger and faster reaction.

Eventually, if I insist in the same food, I develop a skin eczematous itchy rash that becomes elevated and warm.
Food that don't cause any reactions are meet, fish, chicken, rice, beans, salad, tomatoes, regular cheese.
I've been to a ton of tests and none have helped. Gluten intolerance was ruled out and even a biopsy was done to confirm that.

I've tried many migraine prophilactic medications but they did not help. The only medication that helped a little was Flunarizine, a Calcium channel blocker. After using it for a year in a very low dose, eventually It made me very tired and upon stopping it, the symptoms became worse again.

My symptoms are relieved by Triptans and I've been taking one of those every night and the following day, the same story starts again.

I've also developed a chronic constipation as it doesn't seem to be an easy way to help my bowels function properly. Recently I've started taking some Chia in the hopes it helps.
Chronic Histamine Intolerance affecting primarily the SNC seems to be a fairly reasonable diagnosis.

Is there I way to fix this.
I was thinking, histamine metabolizing probiotics, diaminooxidase, SAM-e to help my HMNT.
Can somebody let me know their thoughts?
 

aaron_c

Senior Member
Messages
691
Hi Pete,

I thought I'd copy and paste from our conversation on this topic, just to the get ball started.

First of all, I should say that I don't think I have all of the answers in this situation. To be honest, the symptoms you ascribe to histamine intolerance are not all familiar to me in that context.

Looking at the list of foods that a histamine-sensitive individual should and should not eat it does not look to me like your primary problem is histamine. Food allergies, however, can trigger a metallic taste on the tip of the tongue, so that seems more likely to me...although you mentioned testing that did not help. What kind of food allergy tests did you have done?

On the off-chance that histamine is a major player, this is a good post (and thread) on histamine and how to deal with it. I actually just prescribed this stuff to a friend today, and she is feeling better already.

My current thoughts on gut health are gravitating heavily towards the importance of both vitamin d and zinc. See my posts on the vitamin d thread for more detail--and there are more details. My hope would be that if your zinc and vitamins D and A (and possibly K and E) were normalized, your gut integrity would improve, and the improvement in D and A might also help balance the immune system--if that even plays an important part with your food issues.

As I said, these are mostly thoughts from the top of my head, and I am far from sure that I understand your situation well enough to have great confidence in my suggestions. Nonetheless, I hope this or another post can shed some light on your situation.

Best of Luck,

Aaron

PS: Too much zinc can inhibit cortisol, increasing inflammation. If taken orally, your body might be able to limit Zinc absorption, but with your gut issues, I am not sure that the normal rules apply. I would say that every item I mentioned that you might supplement carries risks, particularly if taken alone. The histamine-detox type supplements seem less risky as a whole, but as I said, I am far from sure this is your major problem. Perhaps the best advice, then, would be to take any change in supplements slowly.

PPS: I said this in our conversation, but it seems to have disappeared: As I imagine you are aware, I am not a physician, just a fellow sufferer of ME/CFS. As such, nothing I say should be construed as medical advice.
 
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aaron_c

Senior Member
Messages
691
@Pete Rav :

After looking around a little, I wonder if you have oxalate sensitivity. I know relatively little about this, but @Gondwanaland is dealing with this right now.

Here is a web site describing the oxalate contents of various foods. You will notice that most meats are fine to eat, while many fruits and vegetables are problematic. Calcium Oxalates are known to cause Vasodilation (Look in the text under the titles. Unfortunately, I think the text comes from the full articles that I cannot access). I am not sure about the hypotension, but I have read a few anecdotal accounts of oxalates causing migraines, including from Izzy (Gondwanaland). Hopefully Izzy will be able to direct you to another thread with more info...and also for the purposes of keeping this thread on topic and making it easier for other people to find the information they need.

Welcome to phoenixrising!
 

Timaca

Senior Member
Messages
792
@Pete Rav ~ I seem to have histamine intolerance. There are resources listed on my blog. You can read some of my blog posts too if interested. In addition to histamine intolerance, I also seem to have intolerance to many low histamine foods, especially grains. They don't cause me a typical histamine reaction (itching, headache, agitation, sleeplessness) but can give me either joint pain or GI issues.

You might try various probiotics to help with the constipation issue. I am experimenting with some probiotics now for a similar issue.....but most probiotics don't work for me.....either they cause more constipation or they give me histamine issues. If I find one that does work, I'll post about it!!!

I've been experimenting with DAO supplements. I am sensitive enough to histamines that I can't eat most meats or poultry. So, if in a restaurant, I will eat just a small amount of chicken (say 2 ounces) and take 4 DAO supplements, and *seem* to do reasonably Ok with that.

All the best,
 

Gondwanaland

Senior Member
Messages
5,092
I also seem to have intolerance to many low histamine foods, especially grains.
Have you ever looked into oxalates? http://www.lowoxalate.info/
Lists of recommended probiotics enclosed.
oxalate degradation commercial probiotics copy.jpg oxalate degration pure probiotics copy.jpg