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LNN

Tourettes and Histamine...and methylation

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This crossed my radar yesterday:

 

In a study published Wednesday in the journal Neuron, the researchers say a genetic mutation that blocks histamine also leads to Tourette syndrome http://www.ctnow.com/health/connecticut/hc-tourette-0109-20140108,0,6843310.story

 

A second study, published last summer, follows the same family identified in the above article

Journal of Medical Genetics Support of the Histaminergic Hypothesis in Tourette Syndrome - Association of the Histamine Decarboxylase Gene in a Large Sample of Families
The theory is that people who suffer from tics may have histamine levels that are too low. You need proper levels of histamine to support the methylation cycle. Pfeiffer and co., in their limited knowledge of the 70s, say the same thing - overmethylators tend to have histamine levels that are too low.
For reasons I cannot yet wrap my head around, increased folinic acid - and possibly niacin - seem to be involved in the solution. Any geek parents with ticcers with 23andMe results care to delve into this with me? I could use a sounding board. An eye tic is DS's only remaining issue - and it ironically appeared last summer when I adjusted his supplements based on 23andMe results. Prior to that, he'd been tic-free for almost 2 yrs. Yet, the change in supps brought all around goodness in most every other way. So I think I'm just missing a small puzzle piece and a geek pal or two to help me out. (DS has normal MTHFR).

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I've been thinking on this but I'm no geek and I'm not sure how to think about it. My son is compound hetero. He's not a primary ticcer but he will tic when things flare up. He also has diagnosed allergies from skin prick testing and takes 10 mg of Claritin everyday which is an antihistamine. I'm stumped. I was hoping you were going to shed some light:)

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I haven't recieved my 23&ME results yet. But, when I was looking at the pfieffer histamine info (a long time ago), I was struck by the fact that, my child didn't fit. Trying to remember, but it seems like she fit the profile behaviorally for high histamine, but, I've always thought she had low histamine because antihistamines really ramp up aggressive/ragey behaviors, her IgE is almost nonexistant, and she has low IgA, IgG4&2. She is compound hetero MTHFR from blood test, and 7.5mg of methylfolate (w/ MB12, and P5P B6) does wonders for her. I have not tested her Ig levels since we've been supplementing w/ the methyls, nor have I tried antihistamines...

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I remember when dr T tested my highly ticcing son for a bunch of blood levels. He commented at the time that his Histamine level was zero which was an indication of what he had was really pandas. I did really understand because he suffers from seasonal allergies but j guess that those are other histamine levels. In any case, for my son it was all about Antiinflammatories I played with many if them. That's what brought the tics down and what I use whenever they flare.

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LLM -- You are pretty much THE "geekiest" among us here, in my estimation (and very high esteem), though there are probably a few among us (like kimballout or dut, perhaps) who can contribute at a higher intellectual level than the likes of me! I am almost always at least 5 paces behind you on any given train of inquiry, if not 5 miles! :P

 

Like Peglem, I brought up my Pfeiffer methylation/histamine chart to refresh my memory on the particulars. My DS, as you know, isn't much of a ticcer . . . it wasn't until many months after the fact and much reading and exchange on this forum that I came to realize that he ever ticked at all, and that was only at the height of his PANDAS and relatively short-lived. And by nearly every Pfeiffer criteria, he's an under-methylator: allergy-prone, OCD, perfectionistic, competitive, highly motivated, high-achiever academically, responds well to antihistamines and antidepressants (at appropriate doses), B6 and zinc. His reaction to B12 (methyl or non), meanwhile, is not good.

 

The genetic piece of things . . . I've got nothing. Toyed with the idea of 23andme, but have been holding off due to some concern over privacy issues.

 

Do you have the paper titled "Histamine in the Nervous System" by Haas, Sergeeva and Selbach? There's a section there about movement disorders (they reference Parkinsons rather than TS), as well as one about the immune system. Some interesting segments:

 

- Histamine-deficient animals show elevated levels of proinflammatory cytokines, tumor necrosis factor and leptin.

- Meanwhile, deficiency in different histamine receptors (H1, H2, H3 and H4) can result in very different behavioral and mood results

- Beginning on Page 1186 of my copy of the study, there's a lengthy discussion of methylation, metabolism and synthesis with respect to histamine. It mentions that histamine methylation requires S-adenosyl-methionine as the methyl donor, but most of this is Greek to me, though it will certainly make more sense to you. There's some discussion of the role of GABA and histamine on Page 1193; are you dosing GABA currently? Maybe that will be of some interest.

- Mice lacking histamine or H1R display "altered ambulatory activity."

 

Looks like a treasure trove, just lying in wait for your "geekiness"! :D

Edited by momwithocdson

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Well, I figured this would be a swamp and I also figured the majority here would have undermethylators. Sigh.

Like every neurotransmitter, even our nemesis glutamate, none are pure evil. They're all necessary. It's just about balance. I'd always ignored the discussions about Histamine receptors because they never applied to DS and while DD has high histamine, hers was under control.

 

When I saw these TS studies, it made me realize that the very cycles that were affecting DD could also be affecting DS - in the exact opposite ways. So I went on a google fest looking for ways to increase histamine and of course, the majority of ink is spent on how to decrease it. There are histamine supplements but I hesitate on that - not sure it's a matter of adding more histamine. Histamine is methylated into two components - histadine and glutamate. Certainly don't need to be adding more glutamate. What I want to focus on is that road junction where the body decides how much histadine it can make and I'm just not sure that adding more of the raw ingredient is the right place to focus. That's what I'm hoping someone can help me with.

 

There are 4 types of histamine receptors, as far as I can tell. And things like Pepcid and zyrtec seem to work by blocking particular receptors, rather than actually reducing the raw supply of histamine. I "think" quercetin and lutein act upstream, actually reducing the amount of histamine released by mast cells. But all these things are reducers in one way or another. How do you upregulate the release of histamine? Niacin does this briefly - that's one reason why you get a "flush" from it - it's the small capillaries releasing histamine and prostaglandins (something else I need to learn about). But once that histamine is released, you've temporarily depleted the supply. I need to figure out how to increase the supply - but at the right point in the cycle. Not by necessarily dumping more raw material into the pot and hoping it gets sorted out correctly. Where is the roadblock? This is, I think, where the tic is originating.

 

Walsh, Pfeiffer & co. are vague on this, as they are on many specifics of their work. One one hand, I'm amazed at how insightful they were 40-50 years ago and how on target their basic theories are. On the other hand, Walsh's work continues to be based on general symptoms and forces you to put yourself into one bucket or the other (under or over methylator) when in reality, you can be an undermethylator at one point in the chemical highway but an overmethylator at another point and knowing your gene status at these various junctions can be really informative. This is the piece I'm searching for. I can't throw spaghetti at the wall to see what sticks and add x, y, and z. when 23andMe and my own experience tells my that too much x and y send DS into orbit.

 

I need some help identifying what x, y and z are and then I want to systematically adjust one at a time. So far, it "seems" that increasing "folate" (and Pfeiffer uses this term without recognizing that different forms of "folate" can have major differences because MTHFR wasn't well studied back then) would be helpful, along with the right form of B12 and some niacin. But this needs to be done in a way that doesn't add too many methyl donors b/c DS is already an overmethylator (thus DS needs to avoid SAMe like the plague even tho it plays a role in histamine regulation).

 

I think this weekend's experiment will be to add some folinic acid and add some additional niacin to DS's mix. I'll keep you posted...

 

Nicklemama and Peglem - just an fyi on the antihistamines - switching now to a story about my daughter. She has MTHFR +/- and terrible allergies. So she's taken Zyrtec and various antihistamines her whole life. Three times now we've had severe reactions because of antihistamines. When she was 4, the minute clinic dr. told me her flu wasn't the flu but an allergy and I should give an antihistamine. She then spiked a fever and antihistamines can lower your seizure threshold. She had a febrile seizure as a result. Then when she was 7, she had a cold and I was dosing cold medicines every 6 hrs as directed - but for many days in a row. It provoked an anti-cholinergic response with horrible tremors, spastic movements, spaciness. We ended up needing an EEG a few weeks later (which was thankfully normal). But I realized I could never again rely on steady doses of cold meds. Then recently, she'd been taking a nightly Zyrtec for fall & winter allergies and she started having tachycardia (150 bpm) for 2 hrs at a time and having whole body tremors. This would happen several days in a row, several times a month. When it finally dawned on me that it felt similar to her anti-cholinergic episode from the cold meds, I stopped the zyrtec and the symptoms went away.

 

Googling taught me that antihistamines block choline receptors and can provoke tremor/seizure like symptoms. DD also did a spectracell test that showed a choline deficiency. I've started giving her choline (100mg daily) and surprisingly, the body itchiness and allergy symptoms that were prompting me to give her zyrtec in the first place have stopped. So it seems she was 1. already deficient in choline and then 2. I was blocking choline receptors and this was depleting the system even more. So peglem - Allie's response may have something to do with a choline deficiency. To anyone using daily allergy meds - just a word of caution. Indefinite daily dosing can trigger some adverse effects that look like tremors and POTS. Check choline deficiency as a possible issue.

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Seems a bit of a paradox to what many on the TS board have noted...that their kids actually tic LESS when given anti-histamines like benadryl etc.

 

FWIW..........My son cannot tolerate high histamine foods (and has genetic TS)

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peglem - Allie's response may have something to do with a choline deficiency. To anyone using daily allergy meds - just a word of caution. Indefinite daily dosing can trigger some adverse effects that look like tremors and POTS. Check choline deficiency as a possible issue.

You are so dang smart! Allie has, in the past, had an excellent response to cholinergic agonist (bethanechol). But it seems to have an immediate short term effect, then makes no difference. I wonder though, if I started messing w/ something else that may have nullified the effect. Lots of spaghetti on these walls! So, maybe I'll try bethanechol for a few days and see what happens....

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From what I can tell from a 10 sec. look, bethanechol stimulates certain choline related channels. If it doesn't help, or help for a long time, maybe look into a choline supplement. DD is using citicholine (started 2 weeks ago). Supposed to be a nootropic and an intermediate that turns into phosphatidylcholine. Jury is still out but as I said, her itchiness and allergy symptoms are decreasing, without the use of antihistamines. But won't know long term results for another month or two. Just something to consider...

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I'm not sure about the folinic acid but the histamine portion of the article does bring something to mind. If you have a DAO mutation then there are issues with metabolizing extracellular histamine. If it isn't metabolized then more histamine hanging around. DAO is not reported on Genetic Genie. You have to put your raw data through Sterlings app on the MTHFRSupport page. Also through that app or any app that reports Allergy sections if you have several positive SNPS under the IgE section then that is an indicator that you produce more histamine and have higher levels of Inflamation and potential for "leaky cells" (think leaky gut). Just my thoughts.

 

Dedee

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Dee - can you send me the DAO snp rs id#s Sterling uses? I could then just look them up in the raw data.

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Sorry, just now getting back to the board. There are 3 DAO's, rs2070586, rs2111902, and rs3741775. According to Dr. Jess Armine, they all work to metabolize extra cellular histamine. One other thing that may be helpful because you said somehow this may be related to folinic acid.........Check theses rs numbers as well: rs2071010, rs651933, rs7925545, and rs7926875. This group are the FOLR mutations and deal with blocking folate receptors. Those with FOLR mutations (the more mutations the more severe), are unable to move folates into the cells leaving a high amount of active reduced folate in the blood which is supposed to be a bad thing. Ok, that is the full extent of my contribution.

 

Dedee

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It has been awhile since I've visited and now that I have this post has me intrigued as the mother of a 16 yo daughter who vocal and motor tics. We've been doing CBT once every week for the past 9 months for the OCD and the therapist had me convinced that the tics were all OCD related. Now I'm not so sure.

 

The full new study in the Neuron journal can be viewed here. Just X out of the download prompt.

 

http://www.academia.edu/4581915/Histidine_decarboxylase_deficiency_causes_Tourette_syndrome_parallel_findings_in_humans_and_mice._Neuron_81_2014_77-90

 

The mutation in the histidine decarboxylase gene (HDC) is W317X. I haven't a clue how to figure out via the 23andMe data how to tell if you have it. Nothing comes up in a search on their site. I put in a support request asking about it. Google doesn't give much about it either except for the studies on it. I browsed my family's HDC gene SNPs and my son, husband, and myself are all the same but my tic'g daughter had several homozygous differences we didn't have so I Live Wello'd them and they were

 

HDC rs2238292 T TT +/+ HDC rs2853766 T TT +/+ HDC rs854151 G GG +/+ HDC rs854158 G GG +/+ HDC rs860526 T TT +/+

 

Does anyone know what to do when you have a histidine decarboxylase deficiency? There's not a lot of info on that. One of the articles said that although this study helps figure out what is wrong it will take several years for them to figure out how to address it. She has taken an L-Histidine supplements in the past and we both remember that it seemed to help but we didn't stay with it long enough. We have also tried the H1 and H2 blockers. I seem to remember that either an H3 or H4 blocker seemed like it would be more helpful but they weren't available.

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Studies I had read said the dose for L-Histidine was 2-3 grams a day. Last night my daughter took 1800mg (three 600mg capsules) of the Montiff L-Histidine. When I asked her tonight about it she said it made her feel very crazy and didn't want to take it again. There can be that much histidine in a few chicken eggs. I wish this epigenetics was easier.

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