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New video: Is acetylcholine toxicity the cause of CFS?

Lotus97

Senior Member
Messages
2,041
Location
United States
That might be acetylcholine overload since huperzine acts sort of like an SSRI, but for ACh. Especially if you're also getting a lot of choline from your diet. Unless you really want the algal based DHA, Swanson has the same thing for half the price. (If you're a first time customer PM me for a discount. Otherwise use SAVETODAY for 10% off $75 or more. Ends midnight 3/26) http://www.swansonvitamins.com/swanson-ultra-herbal-extract-memory-complex-60-caps
 

Sushi

Moderation Resource Albuquerque
Messages
19,935
Location
Albuquerque
That might be acetylcholine overload since huperzine acts sort of like an SSRI, but for ACh. Especially if you're also getting a lot of choline from your diet. Unless you really want the algal based DHA, Swanson has the same thing for half the price. (If you're a first time customer PM me for a discount. Otherwise use SAVETODAY for 10% off $75 or more. Ends midnight 3/26) http://www.swansonvitamins.com/swanson-ultra-herbal-extract-memory-complex-60-caps

Thanks for the link to the Swanson product. The dosing is slightly different--who knows what is best. As far as acetylcholine, I seem to be the opposite from most patients. I have already ordered the ProHealth product so I'll give it a try.

Sushi
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Thanks for the link to the Swanson product. The dosing is slightly different--who knows what is best. As far as acetylcholine, I seem to be the opposite from most patients. I have already ordered the ProHealth product so I'll give it a try.

Sushi
I'm not sure what you mean by opposite, but wasn't Rich saying that a deficiency in ACh is what causes the sensitivity? (assuming he's right of course). I haven't read through the entire thread, but here's what he said about it at the beginning.
For what it's worth, if my hypothesis about ME/CFS is valid, it is more likely that there will be a deficiency of acetylcholine, rather than too much, producing toxicity. The reason is that the production of phosphatidylcholine in the body, from which choline can be derived to make acetylcholine, is one of the two main users of methylation, and there appears to be a methylation deficit in most cases of ME/CFS, due to a partial block of methionine synthase in the methylation cycle.

I think that a deficiency of acetylcholine is consistent with the high sensitivity to acetylcholine that was observed by Vance Spence's group in Scotland a few years ago. I also think that the MRS experiments that were interpreted as showing elevation of choline in ME/CFS were misinterpreted by assuming that creatine is at normal levels. The problem is that creatine synthesis is the main user of methylation in the body, and creatine is also likely to be low.

Best regards,

Rich
 

sregan

Senior Member
Messages
703
Location
Southeast
For what it's worth, if my hypothesis about ME/CFS is valid, it is more likely that there will be a deficiency of acetylcholine, rather than too much, producing toxicity. The reason is that the production of phosphatidylcholine in the body, from which choline can be derived to make acetylcholine, is one of the two main users of methylation, and there appears to be a methylation deficit in most cases of ME/CFS, due to a partial block of methionine synthase in the methylation cycle.

This fits my experience. After my last 2 Amalgams were removed last June I have been experiencing a significant increase in symptoms including brain fog. Acetylcholine boosters have helped. I try to take as little as possible. DMAE is my first line of defense, then Pregnenolone if DMAE doesn't work. Pregnenolone is supposed to boost NMDA and helps if I believe I have too much GABA (after theanine).

I also want to add that since I've started on the SMP the brain Fog has significantly lessened.[/quote]
 

Lotus97

Senior Member
Messages
2,041
Location
United States
This fits my experience. After my last 2 Amalgams were removed last June I have been experiencing a significant increase in symptoms including brain fog. Acetylcholine boosters have helped. I try to take as little as possible. DMAE is my first line of defense, then Pregnenolone if DMAE doesn't work. Pregnenolone is supposed to boost NMDA and helps if I believe I have too much GABA (after theanine).
Too much GABA? What's that like?:lol:
 
Messages
83

Acetylcholine toxicity stimulates the sympathetic nervous system (fight or flight response) and the parasympathetic nervous system (rest and digest response)
The dysautonomia caused by this acetylcholine toxicity could explain the symptoms of CFS.

Symptoms of Parasympathetic Activation
Decreased heart rate
Pupil constriction
Blurred vision
Excess salivation
Lacrimation
Rhinorrhea
Bronchorrhea
Bronchospasm
Abdominal cramps
Nausea
Urinary retention

This is surely a heavy thread, having difficulties getting the big picture. I guess im extra tired today. But im wondering. If someone have problems with those symptoms, would it be beneficial with a supplement of citicholine ?

I know methionine is not working correctly, and the same goes for creatine as I dont feel strong in my muscles any longer.

I know many years ago when I was young I took creatine on a regular basis which I felt great from but with my history I believe that the creatine fueled the methylation in a way that would not last, consuming other pathways.

I have seen some positive effects of taking regular choline, but for some reasons it has not been helful the whole way, and I guess thats the way with a sluggish methylation.

So seeing some if only some positive effects I might see better ones with a stronger choline like citicholine.

Any suggestions or comments to my message?

Thanks
 
Messages
1
I have a pseudocholinesterase deficiency, homozygous.
I came upon this site because of your discussion thread. I believe my pervasive fatigue and diminished cognitive function (I taught grades7&8, all subjects for 25 years) is due to acetylcholine toxicity.

There is no family history of Alzheimer's or dementia in my family. I do not have depression.

Any thoughts?
 

lansbergen

Senior Member
Messages
2,512
I'm not sure what you mean by opposite, but wasn't Rich saying that a deficiency in ACh is what causes the sensitivity? (assuming he's right of course). I haven't read through the entire thread, but here's what he said about it at the beginning.
For what it's worth, if my hypothesis about ME/CFS is valid, it is more likely that there will be a deficiency of acetylcholine, rather than too much, producing toxicity.[/quote]

I agree with Rich but for other reasons
 

xks201

Senior Member
Messages
740
I have a pseudocholinesterase deficiency, homozygous.
I came upon this site because of your discussion thread. I believe my pervasive fatigue and diminished cognitive function (I taught grades7&8, all subjects for 25 years) is due to acetylcholine toxicity.

There is no family history of Alzheimer's or dementia in my family. I do not have depression.

Any thoughts?
What SNP?
 

xks201

Senior Member
Messages
740
DMAE is a false choline uptake substrate. It does not increase choline levels. It is used in experiments to block choline uptake.
 
Messages
4
Hi all,

I've got mild CFS like symptoms for almost 5 years. Can handle 50 hour work week desk job somewhat, but any sudden change in physical exertion will flare up symptoms pretty badly still.

After stumbling on this thread , I tried a nootropic supplement containing Huperzine A amongst other ingredients to see if it would be helped by it. At first I felt sleepy, had a nap, woke up feeling OK, but then gradually progressed into a flare up: headache, brain fog, nausea, irritability etc. It's been 9 hours and I'm feeling better now. Definitely did not have the effect it was supposed to have that's for sure!

Within the context of this thread , what am I to make of this?
 

sregan

Senior Member
Messages
703
Location
Southeast
Hi all,

I've got mild CFS like symptoms for almost 5 years. Can handle 50 hour work week desk job somewhat, but any sudden change in physical exertion will flare up symptoms pretty badly still.

After stumbling on this thread , I tried a nootropic supplement containing Huperzine A amongst other ingredients to see if it would be helped by it. At first I felt sleepy, had a nap, woke up feeling OK, but then gradually progressed into a flare up: headache, brain fog, nausea, irritability etc. It's been 9 hours and I'm feeling better now. Definitely did not have the effect it was supposed to have that's for sure!

Within the context of this thread , what am I to make of this?

Huperzine is a compound that helps Alzheimers patients by slowing down the breakdown of Acetylcholine. This would hopefully reduce brain fog and boost your mental functioning. Toward that end you could also take Lecithin, DHEA, Pregnenolone among others. Nootropics are usually geared toward this neurotransmitter.
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
After re-reading this tread, I came to the conclusion that we are not all the same...
It is necessary to distinguish between the different kinds of dysautonomia groups in ME/CFS.
I think that there are two main groups in ME/CFS: Sympathetic dominance (with a decreased parasympathetic tone) group and a underactive autonomic nervous system group.
I guess that most ME/CFS patients have an increased sympathetic tone and a decreased parasympathetic tone.

Symptoms of sympathetic dominance:
*Paleness (sympathetic dominance decreases skin blood flow)
*Gut problems (sympathetic dominance decreases gut blood flow which results in gastroparesis, malabsorption, dysbiosis and leaky gut)
*Immunosuppression
*Excessive sweating
*Anxiety
*Increased (nor)epinephrine
*Irritability
*Exacerbation of symptoms by stress, cold and exercise.

Therapy:
*Deep breathing, Meditation, Yoga (decrease sympathetic tone and increases parasympathetic tone)
*Muscarinic acetylcholine receptor agonist.
*Beta blockers
*Alpha 2 agonists
Therapies that increases acetylcholine will promote the parasympathetic tone (good thing) but also sympathetic tone (bad thing).
The therapeutic effect will depend on how much each systems is stimulated.

The second ME/CFS dysautonomia group, the underactive autonomic nervous system group:

Symptoms underactive parasympathetic nervous system:
*Urine retention
*Constipation
*Decreased salivation

Therapy:
*Urecholine
*Huperzine A
*Choline, Citicholine, L-Alpha Glycerylphosphorylcholine
*Cholinesterase inhibitor
*Alpha Lipoic Acid
*Acetylcarnitine

Symptoms underactive sympathetic nervous system:
*Orthostatic hypotension
*Decreased sweating

Therapy:
*Midodrine
*Amphetamines
*Yohimbine

I guess, it's best to be guided by your symptoms...

For more information:
http://www.ndrf.org/NDRFHandbook.htm

Thanks for this list @Emootje. I agree -- we're all different, and some (most) may lean more towards sympathetic dominance (th2), while others may be more on the parasympathetic side.

Most of my symptoms agree w/the sympathetic list (except that I'm all sweated out, for several years now). Anything, any food or supplement that contains choline revs me up and causes increased muscle twitching, agitiation, depression and anxiety.

Interesting that Rich suggested this may be due to methylation issues, as I found a study that found a connection between low B12 and decreased levels of acetylcholinesterase (the enzyme that breaks down acetylcholine):

http://www.ncbi.nlm.nih.gov/pubmed/18422

I'm a little confused though, as your list included acetylcarnitine and lipoic acid as things to avoid (?) yet this study found that (injected) l-carnitine normalized levels of acetylcholinesterase.

http://www.ncbi.nlm.nih.gov/pubmed/11253151

And this one found lipoic acid helped restore ACHe activity (also injected however):

http://www.ncbi.nlm.nih.gov/pubmed/16706642

???
 

Gingergrrl

Senior Member
Messages
16,171
@Emootje I know this is a really old thread but I saw you posted in it earlier this month so hoping you are still around. In your further research, did you find anything additional re: acetylcholine excess or toxicity as a cause of CFS? Are there any current links on this topic for non science people that I would be able to understand?

What is your understanding or opinion re: MCAS and histamine disorders in connection with acetylcholine? I don't want to say anything that could bias your answer but am trying to grasp this topic and currently very ill.
 

Emootje

Senior Member
Messages
356
Location
The Netherlands
Gingergrrrl, sorry to hear you are currently very ill.
I found some basic autonomic nervous system video's that I think non science people would be able to understand.

The man in the video's doesn't mention the acetylcholinesterase (the enzyme that breaks down acetylcholine) but it's not that hard. If you inhibit this enzyme, acetylcholine will build up in the preganglionic fibers resulting in a little bit stimulation of the sympathetic nervous system and huge stimulation parasympathetic nervous system resulting in SLUDGE symptoms.

The only link I could think of is that histamine and acetylcholine both stimulate nitric oxide production via eNOS. Nitric oxide in excess is neurotoxic and inhibits mitochondria function but it's roll in CFS is not clear. Some say there is to little nitric oxide in CFS.



 

dannybex

Senior Member
Messages
3,561
Location
Seattle
@Emootje I know this is a really old thread but I saw you posted in it earlier this month so hoping you are still around. In your further research, did you find anything additional re: acetylcholine excess or toxicity as a cause of CFS? Are there any current links on this topic for non science people that I would be able to understand?

What is your understanding or opinion re: MCAS and histamine disorders in connection with acetylcholine? I don't want to say anything that could bias your answer but am trying to grasp this topic and currently very ill.

@Gingergrrl, I'm not sure about MCAS, but there is a connection between nightshade vegetables and excess acetylcholine levels. Tomatoes, a nightshade veggie, in fact releases histamine.

The solanine in these vegetables inhibit the enzyme that breaks down acetylcholine. B12 and L-carnitine (and probably other things) help increase the activity of the enzyme.

Here's a list of solanine toxicity symptoms:

https://en.wikipedia.org/?title=Solanine#Symptoms

I used to be able to eat tomatoes, potatoes, etc., with abandon, but in hindsight, I wonder if in the long run I ate too many of these foods (especially sun dried tomatoes!) causing a deficiency of b12, etc?
 

Deltrus

Senior Member
Messages
271
Sorry the below post is a bit garbled but I feel like if I properly explain everything then people will just get bored because of post length and not read it.


I'm having a very good response to diphenhydramine (benadryl, an anticholinergic), the effect is getting tolerance but it seems like there is much less of a wall preventing me from interacting with the world. Phenibut is what normally makes me feel better, I think phenibut also prevents acetylcholine from working in the parasympathetic nervous system. Also last week, when I was on the tail end of a 1g phenibut dose, I had flu symptoms only on my right side, and my right side is what bothers me. My right shoulder, neck, eye, sacral area, all have nerve inflammation. These are all locations of parasympathetic nerves. I get extrapyramidal symptoms like parkinson's patients do, and they get treated with anti-cholinergics in order to calm down the parasympathetic nervous stem.

My theory is that a subset of people have high amounts of acetylcholine activation of their parasympathetic nervous system. In early childhood, they are always a bit more tired due to the "rest and digest" system being overly active. Then, because acetylcholine is very anti-inflammatory, a virus infects specifically the vagus nerve. Now the vagus nerve is overstimulated and itt also is prevented from sending out proper SOS messages because of the anti-inflammatory activity. Thus, only garbled and dysfunctional messages are sent out, whatever acetylcholine doesn't downregulate. These messages are still strong, but garbled. Thus, an inflammatory response that is very general is get sent out, and this inflammation just attacks the whole nerve, causing inflammation and damage. This fits in with the vagus nerve theory of chronic fatigue.

I'm going to try taking high dose selenium(antiviral booster), along with low dose (500mg daily) phenibut and diphenhydramine (just enough dose to get dry mouth, signalling the parasympathetic activity is low) to see if I can reproduce the right sided flu symptoms that I got. I use Phenibut to put out the fires of the self sustaining garbled neurotoxic immune response, anticholinergic to limit the anti-inflammatory activity in the parasympathetic nerves, and an viral immune booster to shove everything in the right direction. If I'm lucky, I should be able to trigger a proper immune response, then my nerves will repair and I can go off phenibut, and just keep the diphenhydramine.

I was dumb and last time I got the right side only flue response, I played some stressful video games and took some nicotine gum. That stopped that response, and my parasympathetic nerves got inflamed again. I will have to make sure to stay away from stress/nicotine next time.

EDIT: I also should add that my tongue, one of the areas that normally has nerve pain, is also normally covered in candida white gunk. Taking diphenhydramine, my tongue has 1/4 of that white gunk and is very slightly irritated, like it is having an immune response.
 
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Gingergrrl

Senior Member
Messages
16,171
@Deltrus Thanks for posting your story and I hope you don't mind a few questions...

I'm having a very good response to diphenhydramine (benadryl, an anticholinergic),

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?

Phenibut is what normally makes me feel better,

What is Phenibut?

My right shoulder, neck, eye, sacral area, all have nerve inflammation.

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.

I'm going to try taking high dose selenium(antiviral booster)

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.