Acetylcholine caused crash

[Gingergrrl]

And the problem with Parasym is that you increase availability of ACh (via Alpha GPC), while inhibiting the breakdown of it (via Huperzine A) at the same time. So this will cause a huge increase in ACh that can't be cleared from the synapse.

You are definitely correct about the Parasym. The way that it was marketed in the interview I read made it seem so harmless, but it is incredibly potent and I wish that I would have been more cautious.

I agree it is marketed as harmless but depending on the person's ability to tolerate cholinergic meds/supps, it could be extremely dangerous. I suspect this kind of supplement would injure or even kill me based on past experience of micro doses of cholinergic/anti-cholinergic meds giving me akathesia and respiratory depression. I might be unique in that level of extreme reactions though.

 

[picante]

I don't think anyone knows. The theory is that the spike in ACh is followed by long-term suppression. The same probably goes for cortisol, since the HPA is activated by ACh. There could be immune system changes, etc. Also, ACh overload is neurotoxic.

Perhaps topping up the Ach with mild boosters would help. Or perhaps suppressing ACh even more would allow the system to swing back. But these are just guesses.

No one has mentioned CDP choline (Citicoline). Is that a "mild booster"? Or would it have the potential to cause this AchE upregulation you're talking about?

I'm on my second trial of Citicoline; the first was over a year ago, and I couldn't tell what caused my cognitive drop at that time, but I attributed it to methylfolate/MeB12 supplementation and/or thiamine deficiency caused by taking a lot of potassium.

I decided to try it again based on 1) two homozygous snps in MTHFD1 and 2) Alzheimer's in my family.

I started Citicoline a month ago, and it helped initially, but now I wonder if that's what is draining my brain and my energy, and making me groggy.

 

[adreno]

I use CDP-choline and don't find it as strong as ALCAR or Alpha GPC, but I have seen reports from others on the forum that it was too much for them. I hesitate to call it mild.

 

[picante]

I use CDP-choline and don't find it as strong as ALCAR or Alpha GPC, but I have seen reports from others on the forum that it was too much for them. I hesitate to call it mild.

What dose do you use? Do you cycle off of it sometimes?

 

[Sidereal]

Man, I took 1 gram of PC today and I feel like shit, a bunch of old symptoms flooding back. Messing around with cholinergic supplements is most definitely not harmless or risk-free in this patient population.

 

[picante]

ALCar doesn't contain any choline, though. It has to combine with choline, right?

I've been using ALCar as part of the deadlock quartet, since LCF didn't seem to have any effect. This made sense to me when I looked up my NAT2 snps. I have rs1799930, rs1041983, and rs1495741 all +/+, making me an "ultra-slow acetylator".

Perhaps either the ALCar or the Citicoline would be fine for me, but taking both creates too much acetylcholine? Would that make sense?

I was taking Citicoline mainly as a methyl donor, thinking it would give me fewer problems than methylfolate (which makes me depressed and exhausted).

 

[ahmo]

This made sense to me when I looked up my NAT2 snps. I have rs1799930, rs1041983, and rs1495741 all +/+, making me an "ultra-slow acetylator".

I'm AA, TT, AA for these. Is that what you mean by ++? ALCAR did nothing for me in terms of methylation, but was helpful when I employed it as an antioxidant.

I'm now happily using both citicoline and AlphaGPC. I'd been worried about reacting poorly to both. I've read that the efficacy is increased when taking with caffeine. certainly the pleasure is.

 

[picante]

I'm AA, TT, AA for these. Is that what you mean by ++? ALCAR did nothing for me in terms of methylation, but was helpful when I employed it as an antioxidant.

Yes, those are my results, too. I had to do some digging to find these snps, since Sterling's report doesn't have two of them.

 

[ahmo]

an "ultra-slow acetylator".

So does this imply we need need extra because it's utilized too slowly? Or less, because it's hanging around longer? I'm also using lecithin, extra when I'm hot or otherwise stressed.

 

[adreno]

What dose do you use? Do you cycle off of it sometimes?

250mg /day. No cycling.

 

[adreno]

ALCar doesn't contain any choline, though. It has to combine with choline, right?

ALCAR is not a source of choline, but it still enhances cholinergic transmission.

 

[JPV]

The theory is that the spike in ACh is followed by long-term suppression.

I found a few discussions on the LongeCity forum that relate to this exact topic. I'm assuming these are some of the message threads that @Xander5 was talking about...

Can severe stress cause anticholinergic symptoms?

I ran across this paper which suggests an acute trauma may induce chronic changes in acetylcholine expression:
Acute stress facilitates long-lasting changes in cholinergic gene expression
I haven't read the full text, but they imply that the surge in acetycholine that occurs during acute stress (perhaps this is the cause of "life flashing before one's eyes"??) leads to epigenetic changes leaving one in a chronically hyperexcitable state. However, they associate these symptoms with AChE inhibitors, i.e. a surplus of ACh.

So I've got all these symptoms, and a lot of other people have some or all these symptoms (and some I don't) associated with diverse chronic conditions such as

• CFS/ME
• The morass known as "Adrenal fatigue"
• Post acute benzodiazepine withdrawal
• Chronic Lyme
• Gulf War Syndrome
• PTSD
• MG, Sjogren's, other autoimmune diseases
• More?

Rather than posting 50 studies, just google "stress acetylcholine", and other similar combinations, and you can find various research articles. The gist is that stress floods the brain (not sure about the periphery, but I would imagine there too, since you'd need to be able to flex your muscles) with ACh, which upregulates AChE for a several day period... which somehow messes everything else up indefinitely.

Could it be so simple that so many symptoms of chronic conditions arise as a malfunction of the longest-known neurotransmitter -- a sort of hyperactive sympathetic and anemic parasympathetic nervous system? Or perhaps even stress-induced autoantibodies, a sort of functional myasthenia gravis? I'm guessing no, but still ... cofactors such as B5 are popular in adrenal fatigue treatment, and B1 megadoses have a decent response rate in CFS/ME.

What are all the possible symptoms of acetylcholine overload?

Summary: The result of acute, severe stress or short-term acetylcholine overload is the same. Gene expression of acetylcholinesterase is upregulated and that of VAChT and ChAT is downregulated, leaving you with a paradoxical long-term deficit of ACh and concomitant cognitive and physical problems. The pathway through which the gene expression changes is c-Fos, a gene which is turned on, generally speaking, as a result of oxidative stress. As for c-Fos inhibitors, I take fisetin with good effect, though there are others: curcumin, gastrodin, mollugin, quercetin.

 

[JPV]

A light bulb went off in my head while reading this thread. After years of minor lingering malaise, the major onset of my ME/CFS symptoms came on very suddenly while taking methamphetamines in my mid 30's. In addition to brain fog and fatigue I also suffer from neurological issues such as a burning sensation in my legs and, what I would probably refer to as, excitotoxicity. I assume some biochemical system got overdriven by the drugs and then became stuck into a permanent state. Like a switch that was turned on and never got turned off.

My mother had a similar neurologic condition, to mine, with the sudden onset of severe burning sensations in her legs. I believe they diagnosed it as Reflex Sympathetic Dystrophy but this may have been a misdiagnosis for all I know. Her doctor performed a procedure to sever the nerves in her lower back because he couldn't figure out any other way to fix the problem. So I'm assuming that I must have some sort of genetic predisposition.

This puts a lot of the discussions about Jay Goldstein's rapid remission treatments into a very interesting context. It seems that he came up with numerous ways, through trial and error, to flip these genetic switches back into their normal positions.

I now strongly feel that issues with acetylcholine/acetylcholinesterase dysfunction is the main problem that I'm dealing with. Many of those with ME/CFS talk about a stressful incident, or accident of some sort, that triggered the onset of their illness. I wonder if they're dealing with similar issues.

This seems to me to be a very important direction to keep exploring.

 

[knackers323]

Has anyone managed to find something effective for this issue?

 

[picante]

I'd be interested in hearing from people who've used bacopa monnieri, since I just ordered some powder.

 

[adreno]

I'd be interested in hearing from people who've used bacopa monnieri, since I just ordered some powder.

Bacopa monnieri is an acetylcholinesterase inhibitor.

 

[picante]

Bacopa monnieri is an acetylcholinesterase inhibitor.

Yes. So that means it would slow the rate of acetylcholine breakdown and theoretically raise acetylcholine levels. I was looking at this quote from JPV above:

Gene expression of acetylcholinesterase is upregulated and that of VAChT and ChAT is downregulated, leaving you with a paradoxical long-term deficit of ACh and concomitant cognitive and physical problems.

If that is what's going on, then an AChE inhibitor might help, ¿no?

 

[adreno]

If that is what's going on, then an AChE inhibitor might help, ¿no?

If that's the case, then yes.

 

[charlie1]

It seems most of those on this thread are looking for help with dysautonomia symptoms other than as a help for constipation which Parasym Plus is also supposed to help with. My POTS and Dysautonmia has almost entirely been resolved now but slow GI motility continues despite now starting a motility drug.. Motilium (Domperidone).

Dr. Diane believes that those like myself with Ehlers Danlos (hypermobility type) who experience chronic C can be helped with her product. I think this is because she feels it is the overly lax ligaments that are contributing to the C and that PP's ingredients work on the Vagus Nerve issue where (my) problem probably initiates from. At least that's my interpretation of her thinking on this ... and I may be wrong.

Until reading this thread, I was interested in trialing PP for the C issue but now I'm more likely to trial individual supplements of the ingredients....

Question: Where improved motility is concerned, would the success of Parasym Plus be less likely due to the effects of the Alpha GPC and more likely due to the effects of the Huperzia (since Mestinon, also a cholinesterase inhibitor, is known to increase GI motility/peristalsis )?
And If that's correct, would the fact that long acting daily supplementation with Mestinon helped with my POTS (initially) but didn't improve my C, mean that I shouldn't be looking into the PP ingredients as an aid for increased peristalsis anyway?

Thanks, Charlie
ps. Magnesium supplements makes no difference but Mirulax does help although I'd like to discontinue if possible.
I realize I'll have to find another thread for that but wanted to know first if I should close the Parasym Plus door for the C issue.

 

[MissCB]

It seems most of those on this thread are looking for help with dysautonomia symptoms other than as a help for constipation which Parasym Plus is also supposed to help with. My POTS and Dysautonmia has almost entirely been resolved now but slow GI motility continues despite now starting a motility drug.. Motilium (Domperidone).

Dr. Diane believes that those like myself with Ehlers Danlos (hypermobility type) who experience chronic C can be helped with her product. I think this is because she feels it is the overly lax ligaments that are contributing to the C and that PP's ingredients work on the Vagus Nerve issue where (my) problem probably initiates from. At least that's my interpretation of her thinking on this ... and I may be wrong.

Until reading this thread, I was interested in trialing PP for the C issue but now I'm more likely to trial individual supplements of the ingredients....

Question: Where improved motility is concerned, would the success of Parasym Plus be less likely due to the effects of the Alpha GPC and more likely due to the effects of the Huperzia (since Mestinon, also a cholinesterase inhibitor, is known to increase GI motility/peristalsis )?
And If that's correct, would the fact that long acting daily supplementation with Mestinon helped with my POTS (initially) but didn't improve my C, mean that I shouldn't be looking into the PP ingredients as an aid for increased peristalsis anyway?

Thanks, Charlie
ps. Magnesium supplements makes no difference but Mirulax does help although I'd like to discontinue if possible.
I realize I'll have to find another thread for that but wanted to know first if I should close the Parasym Plus door for the C issue.

Did you end up trying the individual ingredients or Parasym Plus? I'm curious as to your experience with it. I have Alpha GPC which always eases my POTS symptoms and improves my motility but then is followed my a tingling/ clenching feeling in my brain around 12 hours later.

I'm curious if maybe taking an inhibitor or PP may correct this issue.