• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Wow. These symptoms look familiar....high ACh?

Messages
53
Symptoms of High Acetylcholine



Subdued or depressed mood
Anhedonia (inability to experience pleasure)
Difficulty concentrating
Difficulty with higher-order or complex thought processes
Mental fatigue
Mental confusion
Memory problems
Decreased motivation
Feeling overly sleepy or tired (particularly in the evening), despite adequate sleep and rest
Difficulty understanding or performing tasks
Pessimistic, negative ideation or rumination
Feelings of helplessnes and hopelessness
Fretfulness
Irritability or anger
Emotional heightening and lability
Sadness, tearfulness
Blurred vision
Headache
Dry mouth
Altered sense of smell; heighted sensitivity to odors; olfactory delusions
Stomach pain or discomfort
Intestinal gas or bloating
Diarrhea or constipation
Nausea, dizziness, and vomiting
Muscle pain or discomfort
Joint pain, discomfort, or swelling
Tooth or jaw pain or discomfort
Tingling or numbness in arms or legs
Muscle weakness
Increased urinary frequency or problems with bladder control
Flu or cold-like symptoms
Weakening of immune system and increased susceptibility to illness
Cough
Nasal discharge
Chills or sensation of cold
Cold feet, hands
Sleep disturbance
Introversion
Anxiety
More and vivid dreaming, and higher incidence of nightmares
Decreased levels in the brain of the neurotransmitters, serotonin, norepinephrine, and dopamine
Interference with the release of the above brain transmitters, because of higher inhibition

Note: There is an inverse, antagonistic relationship between acetycholine (ACh) and serotonin (SE) in the brain. In other words as the quantity of one increases, the quantity of the other decreases. A certain amount of ACh is necessary for normal, optimal brain function. Memory, motivation, higher-order thought processes, sexual desire and activity, and sleep (among other things) depend on ACh. In lower amounts, ACh can act like a stimulant by releasing norepinephrine (NE) and dopamine (DA). However, those brain chemicals are used up (depleted) in the process; and a deficiency can occur. Too much ACh relative to other brain chemicals such as SE, NE, and DA has an adverse effect on brain function. This is because in larger quantities ACh acts like an inhibitory neurotransmitter, causing increased nervous system inhibition (depression). Important to remember is that, in general, as ACh levels go up in the brain, the levels of the other brain transmitters go down.

In terms of mood, the combination of higher ACh and NE, together with lower SE, produces anxiety, emotional lability, irritability, anger, aggressiveness, negative rumination, impatience, and impulsiveness (among other things). When NE, DA, and SE are low and acetylcholine is high, the result is simply depression. SSRI antidepressants, by increasing serotonin, are able to lower acetylcholine levels, thereby lessening or eliminating the symptoms associated with high acetylcholine. However, the major drawback is that increasing serotonin also leads to a reduction of norepinephrine and dopamine in the brain. Therefore, long-term use of SSRI antidepressants will result in a high serotonin condition, which is actually another type of depression (see separate article on this site about serotonin). So, in spite of all of the publicity and common usage, SSRI antidepressants are really not the best choice (at least, not in the long run) for treating depression. Unless the problem of low NE and DA is also addressed, a high acetylcholine depression, in time, will merely be replaced by a high serotonin depression. This explains why SSRI antidepressants do not help everyone, lose their effectiveness over time, make some people more depressed, or cause intolerable side effects.

Generally, ACh levels in the brain will increase proportionately to the amount of choline in the diet. However, ACh levels will also become higher for other reasons. Whenever there is interference with the release of the other neurotransmitters, or their levels have fallen, ACh levels will automatically increase. This is due to the balancing effect between all of the brain transmitters, whereby a decrease in one resuts in a relative increase in the other.

Foods that significantly increase ACh: eggs, fish, soybean products, foods (wide variety) containing lecithin, wheat germ.

Supplements that significantly increase ACh: choline, lecithin, fish oil, flaxseed oil, other.

Other things that increase acetylcholine: MSG (monosodium glutamate), medications, chemicals, physical activity (exercise, work).

Note that some people are more sensitive to choline and, therefore, will experience greater problems than usual with the consumption of the above foods and supplements. Also, reaction to choline may be age-dependent, with older people generally experiencing more sensitivity.

For more information, see:

http://www.acnp.org/g4/GN401000095/CH.html

http://www.yalescientific.org/2013/05/uncovering-the-biochemical-basis-of-depression/
 

crypt0cu1t

IG: @crypt0cu1t
Messages
599
Location
California
I just found out that I have high AChR binding antibodies and salivary protein 1 antibodies.

Would this cause a high level of ACh or a low level?
 
Messages
53
Wow. Well, the good news is you likely don't have CFS, but you need to look up Myasthenia Gravis. Not that it is any better but at least Dr's should know what to target to help you.

Do you know which receptors? Nicotinic? Muscarinic?
How does benadryl make you feel in general?


AChR antibodies would block (possibly damage or destroy) your receptors which ACh acts upon...thus, decreasing the effectiveness of all the things that ACh does both inside and outside the brain (a lot). Body might normally try and compensate by creating more AChr and ACh in response due to the blocking of the receptor sites. So, your ACh levels might be normal or high even, but the net effect should be a functional deficiency in ACh transmission.

There are drugs called Acetylcholinesterase Inhibitors which inhibit the enzyme that breaks down ACh, thus keep it "alive" longer and increasing levels.

One of the problems is that ACh receptors are located both inside and outside the brain, and act differently and on different things.

Some of the top early symptoms of ACh deficiency are
  • “Brain fog”
  • Poor short term memory and recall
  • Trouble concetrating
  • Fatigue
  • Slow or confused thinking
  • Dry mouth
BUT THE BIG LIST IS MUCH MORE EXTENSIVE.

You can get something called Huperzine A on even Amazon or at Nootropics Depot. This is an acetylcholinesterase inhibitor that is supposed to keep its effects inside the brain without messing with some of the body effects.
Acetyl L carnitine increases the body's ability to convert choline into ACh.

REALLY THOUGH. DON'T LISTEN TO ME THAT MUCH ABOUT THIS AND DEFINITELY FIND A SPECIALIST. LOOK UP MYASTHENIA GRAVIS.

PLEASE CREATE A NEW POST ABOUT THIS SO THAT SOME SMARTER PEOPLE THAN I WILL SEE IT AND GIVE YOU MORE INPUT.

EDIT: ACCIDENTLY USE NMDA instead of AChR. NMDA is more of a glutamate thing.
 
Last edited:

crypt0cu1t

IG: @crypt0cu1t
Messages
599
Location
California
I'm pretty new to the forum, where is a good place to post my questions regarding my ACh issues?

Would you mind PMing me about this? It has me very intrigue.
 

Gingergrrl

Senior Member
Messages
16,171
I just found out that I have high AChR binding antibodies and salivary protein 1 antibodies.

@crypt0cu1t I know we've talked before (b/c we have the same doctor) but now I cannot remember, did you already know that you had these autoantibodies or is this a new discovery? I think the AChR is the myasthenia gravis autoantibody and the salivary protein is Sjogrens.

Do you know which receptors? Nicotinic? Muscarinic?
How does benadryl make you feel in general?

@Crash Davis I know you were not asking me, but my understanding (which could be wrong) is that the MG autoantibody is the Nicotinic receptors (which is what is tested in the US) vs. the anti-Muscarinic antibodies are only tested in Germany by Cell Trend Labs. I am negative on the MG/MuSk & Nicotinic autoantibodies but positive on the anti-Muscarinic (and many other autoantibodies).

It sounds like you have a good understanding of this issue by your question about Benadryl. I had a horrible reaction to Benadryl back in 2015 (when I was extremely ill overall) but at present, I tolerate Benadryl well as a pre-med for when I get Rituximab infusions (both 25 and/or 50 mg).

PLEASE CREATE A NEW POST ABOUT THIS SO THAT SOME SMARTER PEOPLE THAN I WILL SEE IT AND GIVE YOU MORE INPUT.

I'd be interested to read a post on this as well and wish I was one of the "smarter people" so I could give more feedback (...versus adding more questions to it ;)).
 

crypt0cu1t

IG: @crypt0cu1t
Messages
599
Location
California
@crypt0cu1t I know we've talked before (b/c we have the same doctor) but now I cannot remember, did you already know that you had these autoantibodies or is this a new discovery? I think the AChR is the myasthenia gravis autoantibody and the salivary protein is Sjogrens.



@Crash Davis I know you were not asking me, but my understanding (which could be wrong) is that the MG autoantibody is the Nicotinic receptors (which is what is tested in the US) vs. the anti-Muscarinic antibodies are only tested in Germany by Cell Trend Labs. I am negative on the MG/MuSk & Nicotinic autoantibodies but positive on the anti-Muscarinic (and many other autoantibodies).

It sounds like you have a good understanding of this issue by your question about Benadryl. I had a horrible reaction to Benadryl back in 2015 (when I was extremely ill overall) but at present, I tolerate Benadryl well as a pre-med for when I get Rituximab infusions (both 25 and/or 50 mg).



I'd be interested to read a post on this as well and wish I was one of the "smarter people" so I could give more feedback (...versus adding more questions to it ;)).
I just made a thread, hopefully its in the right place! Lol https://forums.phoenixrising.me/index.php?threads/new-test-results-need-some-help.60237/
 
Messages
53
It sounds like you have a good understanding of this issue by your question about Benadryl. I had a horrible reaction to Benadryl back in 2015 (when I was extremely ill overall) but at present, I tolerate Benadryl well as a pre-med for when I get Rituximab infusions (both 25 and/or 50 mg).

Benadryl is an anticholinergic agent. Specifically to the muscarinic receptors. Actually is a known cause of dementia in the elderly with chronic use.

Benadryl antagonizes the ACh muscarinic receptors. If you have antibodies already "antagonizing" them then you could wind up with cholinergic syndrome type symptoms.

You probably tolerate it now because you are being treated with immunosuppressants that are freeing the receptors back up. I wouldn't ever take benadryl outside of when you are being dosed. They are probably only giving it to you during dosage to counteract any allergic reactions during infusion.
 

Gingergrrl

Senior Member
Messages
16,171
Benadryl antagonizes the ACh muscarinic receptors. If you have antibodies already "antagonizing" them then you could wind up with cholinergic syndrome type symptoms.

You probably tolerate it now because you are being treated with immunosuppressants that are freeing the receptors back up. I wouldn't ever take benadryl outside of when you are being dosed. They are probably only giving it to you during dosage to counteract any allergic reactions during infusion.

Thank you so much @Crash Davis for this info, and I wish I understood it all as well as you do! Do you know if POTS, shortness of breath, or muscle weakness could be symptoms of a cholinergic type syndrome (or if they would be unrelated and due to all my other autoantibodies)?

I suspect, like you said, that the anti-muscarinic (as well as my other autoantibodies) are now freeing up the receptors because of my IVIG & Rituximab treatments. And you are correct that I only take IV Benadryl as a pre-med to prevent a potential allergic reaction to Rituximab. I do not take Benadryl at any other time (so just once every three months).

What is weird though (from a cholinergic perspective) is that I never at any point had any problem with Atarax, like I did with Benadryl (even though both are first generation anti-histamines). And I never had any problem with Zyrtec or other second generation antihistamines (for MCAS).

I apologize for so many questions, and don't want to take your thread off-track! I would love to hear your feedback or ask you via PM. I have tried to understand this topic in greater depth since 2015 (but it is very challenging with no science background to retain the information... although I keep trying)!
 
Messages
53
What is weird though (from a cholinergic perspective) is that I never at any point had any problem with Atarax, like I did with Benadryl (even though both are first generation anti-histamines). And I never had any problem with Zyrtec or other second generation antihistamines (for MCAS).

Benadryl blocks all the mACh subtypes across the board pretty equally it seems.
As for Atarax, it really just hits the H1 histamine receptor hard and doesn't jack with mACh.
From Wiki:
"Unlike many other first-generation antihistamines, hydroxyzine has very low affinity for the muscarinic acetylcholine receptors, and in accordance, has low or no propensity for producing anticholinergic side effects."

As for Zyrtec:
" The drug shows 20,000-fold or greater selectivity for the H1 receptor over the five muscarinic acetylcholine receptors, and hence does not exhibit anticholinergiceffects.["
 

Gingergrrl

Senior Member
Messages
16,171
Benadryl blocks all the mACh subtypes across the board pretty equally it seems.
As for Atarax, it really just hits the H1 histamine receptor hard and doesn't jack with mACh.
As for Zyrtec: "The drug shows 20,000-fold or greater selectivity for the H1 receptor over the five muscarinic acetylcholine receptors

Thank you and that absolutely matches with my autoantibodies and why I was not able to tolerate Benadryl but had absolutely no problems with Atarax or Zyrtec (or other H1 blockers).