New video: Is acetylcholine toxicity the cause of CFS?

[Gingergrrl]

Hi @Gingergrrl, my daughter's "condition" started with ACh toxicity as well. She also reacts badly to cholinergics. I was told that cetirizine would be safe for her to take, as it is not cholinergic. Cetirizine is a metabolite of hydroxyzine (Atarax) so perhaps it has the same qualities.

@Grey Owl thank you for your reply and I would love to learn more about what you said below. I actually take Cetirizine (Zyrtec) 2x/day for MCAS as one of my maintenance meds (along with Ketotefin) and have not had any problems with either. I think someone else once told me that Zyrtec is a metabolite of Atarax but I had forgotten. Atarax is much stronger than Zyrtec (at least for me) and it is my rescue med for strong MCAS reactions. For whatever reason, I do not tolerate Benadryl almost at all. In an emergency if I did not have access to Atarax, I could certainly take one Benadryl and it would not become toxic but if I were to try to take it every day again, I would quickly develop respiratory depression and other side effects.

My daughter also has respiratory issues with a restrictive pattern (and I know you struggle with this too) with a suspected DRESS reaction to benzoates (which we are still investigating). I'm interested in knowing what drug you reacted badly to originally. In my daughter's case, knowing that has helped us to put pieces together that we otherwise could not have done.

This is the part I am very curious about! Please respond via PM if you feel it is more appropriate but I would love to hear more about your daughter's restrictive breathing pattern (I assume you mean confirmed by spirometry or PFT test?) Does she also have MCAS, ME/CFS or dysautonomia issues? I did a very thorough TTT yesterday which confirmed 100% that I have POTS (in addition to prior 100% confirmation of the MCAS.) I am still unclear if I have true ME/CFS whatever that even means.

But I have failed four PFT tests showing a mild to moderate pulmonary restriction which my new doctor yesterday felt was very serious (although he does not yet know why I have this.) He also said he has seen patients with ME/CFS and severe dysautonomia who do not have the severe breathing problems or restrictive patterns on PFT's that I do so this piece remains a mystery that I hope to solve.

Does your daughter have a good pulmonologist? I realized I don't even know what country you live in but in case you live even remotely near me, I am curious! What is a DRESS reaction to benzoates? I have not heard of this and am too tired to Google at the moment but plan to tomorrow.

The medication that I originally reacted to was Levaquin (six years ago) but it was not an allergic reaction and was a neurotoxic reaction that was systemic and also nearly tore my right triceps tendon. Taking Levaquin was one of the biggest regrets of my life. There was no antidote at the time (and still is not) but glutathione can help reverse some of the damage and I have been using nebulized glutathione for about four months and it has been helpful- but I also had severe mold exposure so there were multiple triggers (as I am sure there were for all of us.)

 

[Deltrus]

@Deltrus Thanks for posting your story and I hope you don't mind a few questions...



I actually ended up getting a toxicity response to Benadryl but have an extremely positive response to Atarax. Have you ever taken Atarax and if so, what was your response?



What is Phenibut?



I also have pain/inflammation in my right shoulder, arm, neck and now often behind my right eye. I know what started this (an injury to a medication plus a car accident so it is not a mystery in my case) but would love to find something to alleviate this.



What dose Selenium do you take? I used to take 200 mcg a day (IIRC) for thyroid issues but stopped when I eliminated a whole bunch of supplements due to MCAS. Has selenium lowered your viral titers or made any noticeable differences for you?

I am convinced acetylcholine plays a huge role in my illness and just did some kind of antibody test but do not know the results yet or what to do for it. I seem to have a very small window of tolerance for meds that affect acetylcholine in either direction. But I do very well with Atarax as my rescue med for MCAS and have never had a single side effect from it and it has been a miracle drug that has saved me from never having to use the EpiPen.

I tried ceterizine, a h1 antagonist, which didn't do much, that is why I believe the good effects I get from diphenhydramine are from the anti-cholinergic effects. I don't believe Atarax has anti-cholinergic effects. But it does have some other interesting stuff, I'm not familiar with the drug tho so I can't really comment.

Phenibut is basically gabapentin that also has a slight very smooth dopamine effect. It relieves nerve pain and lowers inflammation, for me at least.

It is legal without a prescription. It also acts as a gaba b agonist but less so at lower doses. I've tried baclofen, which is only a gaba b agonist, and it doesn't give me the huge boost and antiinflammatory effect that phenibut does, so I assume that the inhibition of voltage gated calcium channels is the mechanism, like gabapentin.

Phenibut is famous for being an unsustainable drug for social events, it makes people very energetic, social and aware of social cues etc. But it gets tolerance fast and is addictive. You don't wanna take it more than once a week at normal doses.

I think I can say that phenibut has a synergistic effect with diphenhydramine in modulating the nervous system. I just tried 25 mg diphenhydramine and 500 mg phenibut, and it really helped me, when normally I have to take 1.2g+ of phenibut. I usually get tolerance to phenibut super fast so perhaps this way I can get more out of it.

Honestly don't look into the selenium too much, I actually haven't had success with it yet, but was just doing some theorycraft.

Today in addition to the phenibut / diphenhydramine stack, I used this device over my sacrum, and it actually gave me so much energy and clarity. The ICES pemf device seems to stimulate the nervous system in different ways depending on where you put it. If I put it around my neck, then I can feel pulses up my cranial nerves, but if I put it over my sacrum it gives a warm sensation around my pelvis and seems to energize me and give a nootropic boost. Some areas seem to pulse to my brain but I get better results putting it over areas that don't do that.

I think the way to fix sympathetic/parasympathetic nervous system imbalances would be to use an anti-cholinergic to lower the parasympathetic nervous system, or an adrenergic receptor antagonist to lower the sympathetic nervous system, and then use the ICES device to stimulate the underactive one of the two. Add in prednisone or phenibut/gabapentin to lower inflammation. I think the selfhacked guy has a higher sympathetic nervous system because he gets really good effects stimulating his vagus nerve with the device, which would increase the parasympathetic nervous system.

I'm still trying to figure out the best procedure for me. I don't know if diphenhydramine will get tolerance. I don't know if this lower dose of phenibut + diphenhydramine daily will get tolerance. I don't know if the ICES device will be reliable putting it in that spot. I'm still testing these things out. But I do know that at least this once I seem to be getting great effects. And phenibut at higher doses alone has given me fatigue relief around once a month for over a year. I only used it once a month because tolerance and withdrawal can be bad otherwise.

Oh and I also took uridine which normally gives me horrible fatigue, but it doesn't seem to give fatigue with the phenibut/diphenhydramine stack. Uridine is used for many things as seen here so I'm going to try to keep taking it.

I've been disappointed for 2 years trying different strategies to stop my CFS. A lot of times things get tolerance quickly (lavender and phenibut), or things only work once, or I think something is working and I'm just having a small remission. I know with this recent thing I'm getting a bit closer but I need at least 2 weeks testing to give a verdict. I probably shouldn't be posting about it at all until I test longer. Still it is worth noting that this protocol worked very well for at least 2.5 days.

If you got a bad response from benadryl then perhaps you would benefit from increasing the parasympathetic nervous system with the ICES pemf device on the vagus nerve like that selfhacked guy does. (since benadryl would normally decrease the parasympathetic nervous system)

ACTUALLY atarax is a α1-adrenergic (Ki = ~300 nM) receptor antagonist according to wikipedia. That means it should lower the sympathetic nervous system and make it easier for the parasympathetic nervous system to activate. That is something interesting to note.

It would be interesting if sympathetic / parasympathetic imbalance in either way causes CFS.

Too much sympathetic and the vagus nerve doesn't have enough anti-inflammatory stimulation, causing potential autoimmunity. Also, it doesn't get enough "rest and digest" mode to recover.

Too much parasympathetic and the vagus nerve constantly sends "rest and digest" signals and is vulnerable to infection from viruses because of how antiinflammatory acetylcholine is.

 

[Crux]

The disturbance in choline metabolism to produce acetylcholine may involve gut microbes that are highjacking choline, converting it to potentially toxic metabolites.

I suspect my OI was caused by some (unknown) microbes.

Here are some links, all of which have qualities that people may find objectionable....

http://mbio.asm.org/content/6/2/e02481-14.full
http://www.nejm.org/doi/full/10.1056/NEJMoa1109400#t=article
http://www.jci.org/articles/view/72335
http://mbio.asm.org/content/6/2/e00042-15.full

 

[Deltrus]

Sorry for making long posts guys.. I know most people here are too tired to read walls of text..

https://en.wikipedia.org/wiki/Sympathetic_nervous_system
https://en.wikipedia.org/wiki/Parasympathetic_nervous_system
https://en.wikipedia.org/wiki/Adrenergic_receptor
https://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptor

If you guys get a chance, read up on these pages, so much good information.

It seems that α receptors cause mostly negative things such as vasoconstriction and constipation. It causes vasoconstriction in the intestines, skin, etc in order to prepare for "fight or flight". It wants to shunt blood to the muscles.

β1 receptors seem to inhibit inflammation, cause relaxation, increase heart rate, improve insulin pathways, increase energy production pathways etc. If we keep going on the "fight or flight" mindset, the β1 receptor seems to be all about the "hunt", looking for food, stimulating hunger, and increasing energy output.

These two systems balance each other out. Too much α receptor activation and you get less β1 receptor activation.

https://en.wikipedia.org/wiki/Adrenergic_receptor#Roles_in_circulation

Epinephrine (adrenaline) reacts with both α- and β-adrenoreceptors, causing vasoconstriction and vasodilation, respectively. Although α receptors are less sensitive to epinephrine, when activated, they override the vasodilation mediated by β-adrenoreceptors because there are more peripheral α1 receptors than β-adrenoreceptors. The result is that high levels of circulating epinephrine cause vasoconstriction. At lower levels of circulating epinephrine, β-adrenoreceptor stimulation dominates, producing vasodilation followed by decrease of peripheral vascular resistance.

...

Increased cAMP will promote relaxation in smooth muscle, while promoting increased contractility and pulse rate in cardiac muscle.

Perhaps people with POTS have low cAMP due to α receptor overactivation and β1 receptor under activation. Vasoconstriction + lower heart rate is what results from low cAMP.
Gi inhibits cAMP so on those adrenergic / muscarinic wiki pages, whatever increases Gi would possibly cause POTS.

It seems that the muscarinic receptors have a lot of effect on cAMP and intracellular calcium. Phenibut lowers intracellular calcium.

The M3 muscarinic receptor can cause eye blurryness, gland oversecretion (ie salivation), vasoconstriction, and an increase in intracellular calcium. I suspect I have a lot of problems with this receptor. I have high amounts of salivation, eye blurryness and the rest.

Interestingly the activation of M4 causes decreased locomotion.

I think people can tell how much muscarinic receptor activation they get from how dry/wet their tongue is. A slightly damp tongue is the nice middle ground, it is what I get when I take diphenhydramine. Normally I have too much muscarinic receptor activation and it causes very wet tongue and high amounts of candida (furry tongue). My tongue when I take diphenhydramine has around 1/5th of that candida. If you have dry mouth then you probably have too little muscarinic receptor activation. Too little "rest and digest".

Perhaps people with sjorgen's have such low activation of these receptors that it causes salivary gland dysfunction and inflammation.

This is my 3rd day on my diphenhydramine / phenibut / ICES PEMF protocol and it seems to be working great still. I'm naturally moving and working on things, feels like my default state has momentum rather than my default state is walking uphill and getting constant reverse momentum. Please tolerance have mercy.

I think people with CFS need to experiment with substances trazodone/atarax to reduce α receptor signalling, diphenhydramine to reduce muscarinic signalling, anti-inflammatories/gabapentin/phenibut to reduce residual inflammation and ICES PEMF to stimulate the parts of the nervous system that you didn't inhibit. The parasympathetic and sympathetic nervous system seem to be integral to the pathology of CFS.

 

[Deltrus]

Adaptation to excess acetylcholine by downregulation of adrenoceptors and muscarinic receptors in lungs of acetylcholinesterase knockout mice.

According to this, increases in acetylcholine get a response of downregulation of acetylcholine receptors.

However according to this:
Direct Interaction of GABAB Receptors with M2 Muscarinic Receptors Enhances Muscarinic Signaling

Gaba b can re-upregulate muscarinic receptors after they have been downregulated. I bet other things can also re-upregulate the cholinergic system despite excessive acetylcholine.

I started getting my extrapyramidal symptoms after I took fasoracetam 2 months ago. Fasoracetam upregulates gaba b, and also similar to coluracetam increases HACU which is the rate limiting step in acetylcholine synthesis.

Rats given fasoracetam “showed [an] increase of ACh release from the cerebral cortex and the enhancement of HACU both in the cerebral cortex and hippocampus” Coluracetam mitigates learning deficits after a single dose and, even more fascinating, the improvements do not disappear with sudden cessation. This may be the result of comparatively long lasting alterations to HACU.

So already I was having chronic fatigue, most likely due to genetic/viral/autoimmune increase in peripheral cholinergic activity. Then, I take fasoracetam 2 months ago and it fucks everything up even more. Thus I get extrapyramidal symptoms and rare seizures from too much acetylcholine.



Another thing I'm going to try is inositol. It reduces both 5ht1a receptors and muscinergic receptor function.

 

[Gingergrrl]

I will write more later.

@GreyOwl Thank you for sharing all of that and I am so sorry for all your daughter has had to endure. I look forward to hearing more in this thread or via PM (whatever is easier for you!) especially re: the restrictive pulmonary part that they found and how it tied in (or didn't tie in) with the acetylcholine issues.

 

[Gingergrrl]

@GreyOwl

@Gingergrrl[/USER], thanks for reminding me...

No worries and I hope I did not rush you!

so, as part of the original ADR my daughter developed two types of terrible cough. It kept being dismissed as a virus but turns out it was a hypersensitivity reaction to the ingredients in the original drug she was given.

Can you remind me, was the very original ADR to the Benadryl or something else?

The cough was so bad and so prolonged that it has damaged my daughter's airways and she now has lung function at about 72% predicted with 6% improvement on BD.

Did the fact that she had a 6% improvement on bronchodilator make the doctor think she also had an obstructive airway disease or did they feel that percentage improvement was so small that it did not matter. I had no improvement with BD and have had four tests showing pulmonary restriction. I have now been told by all docs (ME/CFS docs, dysautonomia specialist, and really solid doctors) that my level of breathing difficulties and restriction exceed what they have seen in both ME/CFS and dysautonomia and I am hoping to see a good pulmonologist, I just cannot find one.

The curve is convex, which is a restrictive pattern. The respiratory specialist is not familiar with this presentation (as he's a paed specialist) but he does believe it's caused by the original ADR as it's not consistent with normal childhood respiratory illness and is consistent with the known drug effects.

Do you mean the flow volume loop curve or something else? It seems like all the specialists are familiar with obstructive lung disease but not restrictive. How did he determine it was from the original ADR? I am starting to wonder this in my case if the original ADR (which was horrific) weakened my lung muscles in addition to my arm muscles/tendons.

So, since the ADR, when my daughter has drugs containing benzoate preservatives she gets bronchitis and interstitial nephritis. Oh, and eosinophilia. The other ingredient gives her a funny type of delayed asthma.

This part is definitely different than my experience although at present I avoid preservatives due to my MCAS. It is possible I could tolerate them but I am not risking it yet.

I don't know whether this is helpful to you regarding your respiratory condition, but I believe, after many years, that my daughter's is a drug hypersensitivity-induced eosinophilic bronchitis which responds rapidly to inhaled steroids. Because benzoates are used as food preservatives, and also occur naturally in lots of food, there have been some food items that have triggered her so she's on a daily inhaled steroid which helps the cough, but not the eosinophilia or interstitial nephritis. It's an ongoing process to get a diagnosis let alone work out treatment for reasons I've previously mentioned.

It's very helpful to hear it and compare to my situation but it sounds different. I was not helped by inhaled steroids at all but I relate to the extreme difficulty in getting a diagnosis let alone treatment. Does your daughter's breathing condition change or worsen when she stands or is it unchanged by positional/postural changes? I can breath normally lying flat as long as I breath at my own pace but learned from recent autonomic testing that I cannot tolerate deep breathing at all.

After all that, the respiratory condition is not related to the ACh hypersensitivity/neuro condition, and because this was all triggered by drugs there is no viral re-activation with relapses, though she does get ++ - +++ enlarged nodes and red throat on the drug-injured side.

Does she have elevated viral titers on blood tests for things like EBV (or has this been tested?) I have high IgM titers but my throat and lymph nodes are totally normal.

How do they know that the Ach hypersensitivity is separate from the lung issue? Am just curious b/c it is so hard to sort it all out in my case- what is dysautonomia, what is the lung restriction, what is the ADR, what is viral or post-infectious, what is MCAS, what is mold exposure, etc. I am starting to doubt again that I ever will. And if I had a treatment that allowed me to breathe, I actually wouldn't even care about the cause but so far, I have no treatment (except some improvement with low dose Midodrine) that has helped my breathing.

Thank you again for sharing the info.

 

[Gingergrrl]

@GreyOwl

The original ADR was to something else, not an OTC preparation. That's about all I can say on that I'm sorry.

Thanks and I don't ever want you to post something you are not comfortable with. I apologize and was only curious if it was an FQ antibiotic like what happened to me.

6% improvement on BD is below the threshold for obstructive lung disease.

I agree and was told something similar on my test. Only one of my four tests involved trying an inhaled steroid by nebulizer (back in July) but it did not make any improvement in my case since it's restrictive not obstructive.

There are some other complicating factors which make diagnosing my daughter an unenviable task. Have you had a CT scan?

Mine is complicated as well and am so sorry your daughter is going through this at such a young age. I have had a high resolution cat scan which was normal and no ILD or fibrosis so they are saying the restriction is due to an extrapulmonary cause. However, the Neuro I saw last week, who was excellent, is questioning this since my V/Q scan was abnormal and he is the first doc to take it seriously when other docs blew it off as no big deal. He really wants me to see a good pulmo doc asap and I hope to make this happen somehow. My understanding of the V/Q scan is that it is different from the cat scan in that it showed areas of inadequate perfusion of blood and oxygen which is a different issue.

If you had an original ADR, and you're up to researching ADRs, I really suggest following that path as in my case it gave me the answers I was looking for. From what I've learned (from knowing nothing), a drug metabolite can trigger an immune response, and if that's the case, knowing what else uses that pathway might help you.

I wish I understood how to go about this and my science background is really lacking. I know that I will never take another med in this entire class of antibiotics which includes an anti-malarial and some other things but am not sure how to find out what else is in that group or pathway. Is there a website or way to search this? It is a great suggestion. My understanding is that there is no antidote for the damage that this med caused me although some have been helped by glutathione which I am currently nebulizing for the last 4-5 mos and find it helpful.

Thanks again!

 

[Gingergrrl]

@Gingergrrl, I've found these websites really helpful but it took me years to come *close* to understanding the info on them, and even then only for the specific case I'm interested in. Google has been my unfailing friend.

http://www.hmdb.ca/
http://www.genome.jp/kegg/

Thank you but the chances of me understanding these links are slim to none

I also found this article which may be interesting:
http://well.blogs.nytimes.com/2012/09/10/popular-antibiotics-may-carry-serious-side-effects/?_r=0
It mentions Dr. David Flockhart, an expert in fluoroquinolone side effects at the Indiana University School of Medicine, but he died last year. There may be someone else there you could talk to.

I had no idea that Dr. Flockhart died and am sad to hear that. There are few FQ side effects experts in the world and he was one of them. In 2010 I consulted with another expert (Dr. Jay Cohen) and also a tendonitis expert for my arm damage. Am debating if I want to try contacting either of them again to inquire if FQ's can cause lung damage.

My daughter's CT scan was also clear, so I'm interested in your V/Q scan...

Will post it here in case this can be of help to anyone else and my V/Q scan was done in a hospital on a cardiac unit in Sept 2014. In the "Findings" section it said:

"Ventilation images demonstrate mildly nonhomogeneous distribution of radionuclide in both lungs. Perfusion images reveal matched slightly nonhomogeneous distribution of macroaggregate in both lungs. The findings represent low probability for pulmonary embolism."

My cardio at time time said it was "normal" and no blood clot. I never actually thought that there was a blood clot but I felt the results were abnormal when I read them. I showed them to multiple other docs who all dismissed them as normal or "Nothing to worry about" in spite of my severe breathing difficulties.

Only the Neuro who I saw last week disagreed. I showed him the test expecting him to say it was normal like everyone else but he was alarmed and said that there should not be a nonhomogeneous distribution of blood or air and I had both. He said this meant there were areas of my lungs that were not getting adequate blood supply or ventilation (and this was back in 2014 when I could breathe better than now!) He did not know why I had these results, only that they were not normal.

This was the final thing that made him order an urgent pulmonary consult but it fell through (not his fault.) But it is making me very curious what it really means and why no other doctor felt they were abnormal. I told him that my cardio and a (horrible) pulmonary doc that I saw said they were normal and he immediately said, "Mrs. XXX, I strongly disagree and these results are not normal."

Did your daughter have a V/Q scan?

 

[Gingergrrl]

@Gingergrrl

No, I don't think nuclear medicine would be a good idea. One dose of paracetamol gives her two to three months of MCS, so who knows how she would handle it.

You're very lucky to have found a doctor who will stand up for you and disagree with colleagues. Good luck on your quest to find a good respiratory specialist.

Agreed V/Q scan probably not a good idea and I did it in 2014 before I had MCAS. I could never tolerate the dye now and it would be out of the question. Am very lucky to consult with the doc last week and wish he was not six hours away, it was a grueling trip! He felt many of my tests were abnormal but they were done at completely different hospitals so he was not directly disagreeing with colleagues or people he knew (but I agree it is rare to have a doctor disagree at all.) Thank you for the good wishes re: finding a pulmonary doc. Best wishes to your daughter as well.

 

[Deltrus]

I'm wondering if I jumped the gun and actually am getting a response from diphenhydramine, because it blocks the h1 receptor in the brain, and modulating something with inflammation. I compared the response to cetirizine, but cetirizine doesn't actually cross the BBB so the h1 receptor in the brain is still a large confounding factor. Acetylcholine probably lowered my twitches and stuff, but it is possible that the h1 receptor gave the increase in energy and mental clarity due to lowering inflammation. Or not, it could be the anti-cholinergic effect. No way to tell at the moment.

In other note, turns out h1 antagonists reduce gaba in the brain and reduce seizure threshhold. I have to stop taking diphenhydramine permanently because of this, I feel like my brain is so excitory that I'm bordering having siezures. I'm having strong reactions to sudden sounds, tinnitus, and I'm having trouble reading things.

 

[L Y]

Not sure if anyone is still watching this thread but in case you may be:
I've been looking at the angle of what does organophosphate poisoning, Ehlers Danlos Syndrome, POTS-low blood pressure, the vagal nerve, and multiple chemical sensitivities all have in common? I've found the answer so far is acetylcholine.

If a mother takes in organophosphate, which mothers in the 50s would do for pest control around the house or mosquito spray, or say as a agricultural worker, or eating pesticide laden food (non-organic) or in a myriad other ways her acetylcholine could be altered like this: http://pmep.cce.cornell.edu/profiles/extoxnet/TIB/cholinesterase.html The acetylcholine jams up and becomes excessive.

What happens to the fetus? Not sure but Myasthenis Gravis and Ehlers Danlos patients are studied and found to have a link between collagen and the acetylcholine pathways resulting in not enough acetylcholine or the receptors not being able to receive. MG for receptors themselves and ED perhaps for signalling though I'm not sure. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1377491/

Acetylcholine functions in the whole ANS, the sympathetic and the parasympathetic nervous system. Sent out by the vagus nerve in the PNS, it slows down heart rate. It tells the lungs to breathe. etc. The vagus nerve sends out signals through the cholinergic pathway to stop inflammation etc. http://mentalfloss.com/article/65710/9-nervy-facts-about-vagus-nerve

There's not much I can find on the relationship between acetylcholine and histamine except this one where small doses of acetylcholine reduced the response to histamine (guinea pig). I wonder if it's the lack of acetylcholine in our bodies which makes us so sensitive to our own histamine production. http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.1958.tb00183.x/pdf

Histamine is produced when we are poisoned, when we have a virus or bacteria invasion, etc. I think this may link all the so-called "subgroups" together. Having low acetylcholine from birth or from poisoning, managing ok, then eventually as we get older symptoms manifest from lifelong low acetylcholine or from low collagen in our bodies if that's the case. What about CFS from a virus? Anti-virals. People with low acetylcholine shouldn't take anticholinergenic drugs. Drugs for surgery, pain, antihistamines, antibiotics all may work but they'll deplete any acetylcholine we do have. I'm not sure why the effect is sometimes delayed and it doesn't explain all ME cases, but I think we should all make sure we don't have low acetylcholine before taking an "anti" drug.


Taking salt for POTS?
"1. In confirmation of the results of Mendel and Rudney, it has been shown that the optimum acetylcholine concentration for true cholinesterase is shifted to progressively higher levels by the addition of increasing concentrations of salt to the medium."
http://www.sciencedirect.com/science/article/pii/0003986152902087

What seems to be the giveaway for low acetylcholine is low blood pressure. Doctors think we're fine because we don't have high blood pressure, but there's problems associated with low blood pressure too.

 

[Gingergrrl]

Not sure if anyone is still watching this thread but in case you may be:

@L Y I am still following this thread and just bookmarked it for all of the great links that you included! I keep all references for the future in case I need them and thank you for all the work that you put into finding them.

I've been looking at the angle of what does organophosphate poisoning, Ehlers Danlos Syndrome, POTS-low blood pressure, the vagal nerve, and multiple chemical sensitivities all have in common? I've found the answer so far is acetylcholine.

Interesting. I wish I had a more sciency brain to make all of these connections.

If a mother takes in organophosphate, which mothers in the 50s would do for pest control around the house or mosquito spray

In my case, my mom was pregnant with me in the early 70's and was not exposed to any organophosphate or pest control to the absolute best of my knowledge.

Myasthenis Gravis and Ehlers Danlos patients are studied and found to have a link between collagen and the acetylcholine pathways resulting in not enough acetylcholine or the receptors not being able to receive.

I do not have MG or ED but I do have autoantibodies that are attacking the cholinergic-muscarinic receptors (vs. the nicotinic receptors in MG). I have some similar symptoms as far as muscle weakness and breathing weakness but am negative on the entire panel for Myasthenic Syndromes and MuSK from Mayo. But I am certain that these autoantibodies (even though they are not yet well known in the U.S.) are the key to my illness b/c as they are reducing with high dose IVIG, I am having improvements in my symptoms. Now whether these improvements are temporary or permanent, I have no idea.

Acetylcholine functions in the whole ANS, the sympathetic and the parasympathetic nervous system. Sent out by the vagus nerve in the PNS, it slows down heart rate. It tells the lungs to breathe. etc.

I have (TTT confirmed) POTS and am still confused how Acetylcholine relates to this except that my doctor said that based on my tests, I have "Autoimmune POTS" vs. another type.

There's not much I can find on the relationship between acetylcholine and histamine except this one where small doses of acetylcholine reduced the response to histamine (guinea pig). I wonder if it's the lack of acetylcholine in our bodies which makes us so sensitive to our own histamine production.

I have no idea but histamine became a HUGE problem for me in early to mid 2015 when I developed a near life-threatening case of MCAS but it went into remission with IVIG.

Histamine is produced when we are poisoned, when we have a virus or bacteria invasion, etc. I think this may link all the so-called "subgroups" together.

I would also add that in my case, the final trigger prior to developing MCAS was toxic mold exposure. I had viral exposure prior to the mold exposure but the mold tipped it over the edge and was the final trigger that my immune system could no longer fight. Am still unclear if I am in an ME sub-group or have a different illness.

People with low acetylcholine shouldn't take anticholinergenic drugs.

I did very poorly with Benadryl (and had a toxicity reaction) in 2015 but I do very well with Zyrtec and Atarax. I guess some are more anticholinergic than others (or don't cross the BBB)? I still take Zyrtec daily but now only take Atarax as one of my pre-meds for IVIG.

What seems to be the giveaway for low acetylcholine is low blood pressure. Doctors think we're fine because we don't have high blood pressure, but there's problems associated with low blood pressure too.

I have very low BP and it was in the 80's/50's daily prior to starting IVIG. It is now around 100/70 but again if I were to stop IVIG which I am now doing every three weeks, I suspect my BP would drop back down to very low numbers. And yes, most docs think it is fabulous that I have low BP and do not get that it has been a problem for me.

 

[L Y]

@L Y I am still following this thread and just bookmarked it for all of the great links that you included! I keep all references for the future in case I need them and thank you for all the work that you put into finding them.



Interesting. I wish I had a more sciency brain to make all of these connections.



In my case, my mom was pregnant with me in the early 70's and was not exposed to any organophosphate or pest control to the absolute best of my knowledge.



I do not have MG or ED but I do have autoantibodies that are attacking the cholinergic-muscarinic receptors (vs. the nicotinic receptors in MG). I have some similar symptoms as far as muscle weakness and breathing weakness but am negative on the entire panel for Myasthenic Syndromes and MuSK from Mayo. But I am certain that these autoantibodies (even though they are not yet well known in the U.S.) are the key to my illness b/c as they are reducing with high dose IVIG, I am having improvements in my symptoms. Now whether these improvements are temporary or permanent, I have no idea.



I have (TTT confirmed) POTS and am still confused how Acetylcholine relates to this except that my doctor said that based on my tests, I have "Autoimmune POTS" vs. another type.



I have no idea but histamine became a HUGE problem for me in early to mid 2015 when I developed a near life-threatening case of MCAS but it went into remission with IVIG.



I would also add that in my case, the final trigger prior to developing MCAS was toxic mold exposure. I had viral exposure prior to the mold exposure but the mold tipped it over the edge and was the final trigger that my immune system could no longer fight. Am still unclear if I am in an ME sub-group or have a different illness.



I did very poorly with Benadryl (and had a toxicity reaction) in 2015 but I do very well with Zyrtec and Atarax. I guess some are more anticholinergic than others (or don't cross the BBB)? I still take Zyrtec daily but now only take Atarax as one of my pre-meds for IVIG.



I have very low BP and it was in the 80's/50's daily prior to starting IVIG. It is now around 100/70 but again if I were to stop IVIG which I am now doing every three weeks, I suspect my BP would drop back down to very low numbers. And yes, most docs think it is fabulous that I have low BP and do not get that it has been a problem for me.

Thanks for the feedback! I see I need to link POTS and acetylcholine - I'll keep working on this. The vagus nerve uses acetylcholine as a neurotransmitter to signal our whole body to perform functions. If we don't have the right amount of acetylcholine or if our receptors are damaged, the signal is wonky. Diana Driscoll explains one connection here, just "find" acetylcholine on the page: http://thelowhistaminechef.com/dr-diana-driscoll-interview-vagus-nerve-and-potsmast-cell-activation/ and I just found this article: http://archive.naplesnews.com/commu...ressure-and-pots-ep-1210568570-331246791.html Regarding maternal exposure to organophosphates: could have been from a cat's flea collar, handling ant traps, bug spray.

 

[Muon]

Mechanism of choline deficiency and membrane alteration in postural orthostatic tachycardia syndrome primary skin fibroblasts

 

[Jjnz]

Might be interesting to check DNA fir rare mutations on RS1799807
It was once investigated for ehlers danlos too
All of my issues started about 6 weeks after quiting smoking, nicotine is an acetylcholine mimic and triggers alpha 7 Nicotinic receptors. Unsure exactly how this plays with acetylcholine levels.