For POTS or for digestion: Instead of Parasym Plus, increase acetylcholine at low cost & naturally

Hip

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The ingredients are:
https://www.amazon.com/forum/-/Tx1AKJRWUC0QKMH/ref=ask_dp_dpmw_al_hza?asin=B016J8FJYS
Alpha-Glyceryl Phosphoryl Choline, Aceytl-L-Carnitine HCL, Huperzia serrata leaf standardized extract 840 mg, Thiamin (as Thiamin HCI) 60 mg
The Huperzia serrata extract is huperzine A, which is an acetylcholinesterase inhibitor supplement. I think this is an important part of the formula. For those in Europe, a very cheap supplement supplier is healthmonthly.co.uk, who sell huperzine A — see here.

Galantamine is another acetylcholinesterase inhibitor supplement, but is more expensive than huperzine A.

A cheap supplier of acetyl-L-carnitine is here.
 

Lolinda

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Since the vagus nerve of the parasympathetic nervous system lies outside of the brain, you don't need to worry about passing through the blood-brain barrier.
Indeed. But the acetylcholine in the brain is useful too. as it is the main neurotransmitter of the parasymp, I expecta lot of good from increasing it in the brain. (this is my expectation, I do not yet have references on this!) This could be useful in particularly in people who have too much symp. as in some forms of pots as well as in people who have digestive issues because of too much symp. / low parasymp. Indeed, the nerves actually triggering the digestive system by acetylcholine will be peripheral. But if the brain has less symp. dominance that will be useful as all the digestion is steered from there and if your brain is as sympathetic as when you face a lion, then you will digest just that much as when facing a lion :D

All in all, I thank you a lot for pointing out this, because this was really poorly described in the first post in this thread. I did a quick fix right now, but more is needed. Essentially, the questions are
  • if much or little therapeutic utility can be achieved by increasing acetylcholine in the brain, and for which health issues
  • in particular, would increasing acetylcholine in the brain help to make the brain produce a bigger pparasympathetic outflow, or not
  • if peripheral or central nerves do take up acetic acid, or not

All what I described above are my own musings and should be underpinned or refuted by some good references. I hope I will be able to come up with some; or if sbdy has sthg on this, that would be wonderful!

update: research in support of the above
(hey @Gondwanaland and @Hip I guess you will be interested to know about this research)
I found the paper that within 6 hours after causing brain damage to mice, they developed leaky gut! and the really impressive thing: the leaky gut was prevented if the vagus nerve was electrically stimulated (as a substitute for parasympathicoutflow from the braIn):
http://www.ncbi.nlm.nih.gov/pubmed/20453760
For anyone less into science, an easy to read / listen description of this research is here:
https://chriskresser.com/the-healthy-skeptic-podcast-episode-9/
justsearch for "mice" or for "leaky gut".
In this Chris Kresser talk, there is also a lot of further useful info on vagus, leaky gut and brain inflammation. Btw in his talk, he not only says that the vagus is needed for good motility and lack of that causes bacteria to develop fast and they cause leaky gut. But he actually says the same as Dr Driscoll that low vagus input to the stomach and pancreas makes them produce less digestive juices. So there we go (anyone a paper for this?)

-> All this gives support to the above idea that increasing parasympathetic outflow from the brain may improve poor digestion. So it is not simply all about improving the effects of the vagus nerve by improving acetylcholine at its peripheral terminals. That is only one part.

-> The remaining question is now if acetylcholine does or does not increase parasympathic outflow from the brain.
 
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Hip

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I am not very clear if much or little utility can be achieved by increasing acetylcholine in the brain,
Not really related to ME/CFS, but I found choline bitartrate very effective for treating my social anxiety, a condition that appeared alongside my ME/CFS. It's known to help social anxiety. Social anxiety is a really weird one: it manifests as an unduly deep concern about how other people judge your words or actions.


For ME/CFS brain fog, I found the combination of piracetam and choline bitartrate very helpful. Piracetam is a positive allosteric modulator of acetylcholine receptors (makes the receptors more sensitive to acetylcholine).

You can buy piracetam as a supplement in many countries.
 

Lolinda

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Just one more thing that might be of interest: acetylcholinesterase breaks down acetylcholine into acetic acid (vinegar) and choline.
https://en.wikipedia.org/wiki/Cholinesterase
(ok, you guessed that... :) )
The interesting thing is that one can have too much of this, which the results in premature breakdown of acetylcholine. I just got tested for this. I post this just in case anyone wants to get tested. Btw this connects well to ME: this test is usually done in myasthenia gravis, the symptoms of which are essentially identical with ME. so you should not find it difficult to convince doctors to prescribe a test for this. (I do not have any ME any more, zero. but wanted to get tested anywise to find out if my issues could somehow be related to premature acetylcholine breakdown). One caveat might be that the acetylcholine esterase measured is in serum or in rbc and the acetylcholinesterase we are interested in is in the neurons / muscles. but I just trust them that they will know what they do... Screenshot_2016-08-11-00-23-38.png
 
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Lolinda

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The Huperzia serrata extract is huperzine A,

Galantamine is another acetylcholinesterase inhibitor supplement, but is more expensive than huperzine A.
Did you notice a difference in effect? Have you had side effects?
 

Lolinda

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thanks. and how about these?

piracetam and choline bitartrate
you say they worked well, but any side effects? (I ask such questions because I noted that side effects in a subgroup of patients such us here on PR have, more often than not, little in common with general lists of side effects)
 

Hip

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you say they worked well, but any side effects?
For me personally, piracetam increases my anhedonia, which is why I don't use piracetam much. I suffer from anhedonia as a comorbid condition to ME/CFS. But since most ME/CFS patients do not have anhedonia, this should be no problem. I have no other side effects.
 

bertiedog

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You may also want to think about lecithin. Its pretty cheap. Just going by the prices at the supermarket here in OZ (coles) 20g lecithin which would cost 56c would contain as much choline as $1.02 worth of the cheapest eggs or $2.40 worth of chicken liver.
I have the sympathetic overdrive causing my POTS but thankfully I am helped my 20 mg Propananol x 2 plus a small amount of Fludrocortisone especially if its hot. Unfortunately lecithin caused excessive bruising for me and also bad migraines and this is to do with the fact I have this huge tenancy to vasodilation.

Yesterday I had to go to a funeral and it was quite hot and that together with far too much standing set my legs off horribly. After about an hour and a half even though I was sitting I kept getting little stabs of dizziness and my legs started screaming at me so I left early and couldn't wait to get home, get my legs up, put on my tight leggings and go on my oxygen concentrator for 45 minutes. I had quite a lot of pain so took a NSAID and after another half an hour everything had improved and I could get a meal ok. I was also glad to be able to walk my dog around the block later in the evening. But if I hadn't taken all those measures I would have been very miserable and in agony.

I do add cider vinegar to my drinks at least 4 times a day and also have a boiled egg for breakfast every morning so it looks at least I am doing what I can.

One other thing I have so much trouble with due to vasodilation are loads of herbs that are often mentioned as beneficial. The vast majority are vasodilators so I end up with terrible migraines and if they are a blood thinner endless bruises too.

Pam
 

Lolinda

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@Lolinda When you said you can't tolerate eggs, what happens when you eat them? (what symptoms do they give you)
Unfortunately I dont remember any more, was quite a while ago that I tried last. But it was definitively digestion-related. Meanwhile, I have tried out several high choline foods:
- duck fat
- brain
- last year the eggs
All failed. All cause digestion probs. There is a post above by @Richard7 explaining that choline and carnitine feeds bad bacteria. And I do not tolerate carnitine either, so there is quite some evidence for "bad bugs eating stuff before I do".:):eek:

all in all, the experiment to naturally increase my choline failed completely. and the experiment to increase it transdermally first failed because I overdid it
http://forums.phoenixrising.me/inde...ng-our-innate-immune-system.8533/#post-751582

but now it works and rescued me from some misery.

if it is of interest I can describe all what I did in detail, how I failed on all attempts, why that was or how I succeeded in the end, whatever...
let me know what you need.
 
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Richard7

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@Lolinda, I will second @South

also you may find this interesting https://www.ncbi.nlm.nih.gov/pmc/articles/PMC436457/

It mentions that about 60% of the choline is not absorbed in the gut and available for bacterial consumption and shows less trimethylamines in the urine for people using lecithin than choline salts.

The authors also show that choline supplementation changed the composition of gut flora (growing more of the relevant bacteria) and that coadministration of antibiotics stopped the increase in trimethylamines.
 

ebethc

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I don't understand why you'd want to increase ACh, when all the evidence suggests dysregulation of the response to Acetylcholine, rather than deficiency? Acetylcholine suppresses NK Cell activity, Galanthamine Hydrobromide (an acetylcholinesterase inhibitor) was found to be ineffective in a blinded RCT (with some suggestion of increased adverse effects), overactivity of the response to Acetylcholine could explain the micro-vascular issues etc.
How do you know that ACh lowers NK Cells? Wouldn't that only matter if you have too much?

I took some Huperzine A yesterday and felt so much better... I've taken it before w/o as positive of a reaction, but I guess that's because nothing helps when I just need a lot of rest..
 

Lolinda

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My bumpy road towards increasing acetylcholine, finally with success

Thanks @South, @Richard7 and @Gondwanaland for all your interest in my experiences. That motivated me a lot to find some time in between of doctor's appointments to write it all down. Sorry for the long delay: Badly enough, I suffered a new setback: choline inhibited my motility. What? It is supposed to improve that. So I did not feel it would be responsible to announce my experiences when all I have to offer is risk and suffering. It should at least work for a single person, that is, me. Now, read below: I am glad to say this hurdle is taken and I am now happy with my new self-treatment.

References will follow:
To most things below I have meanwhile collected some research and will post it here as soon as I have a little time. My newest happy research find: increasing acetylcholine may increase alpha-msh, which is the gut's natural defense against pathogenic biofilms. So instead of going to Kenny De Meirleir and swallowing his well-intended antibiotics for many months, one has this natural antibiotic which accomplishes what the pills are not so good at: demolish biofilms. This however may also explain the bad chills I had at high doses. So, increasing natural alpa-msh may be no better at avoiding die-offs. But much better in so far as that antibiotics ruin also the healthy parts of the gut flora and one cannot take them forever. I red posts by people geting out of CFS on Meirleir's treatment and then gliding into CFS again after stopping antibiotics for a while. I appreciate De Meirleir for what he brought in such as popularizing the connection between CFS and gut bacteria. Highly appreciated! But do you want to keep De Meirleir treating you forever...? :eek:
- ok, this was just an appetizer. I need to do more work on this. Concrete research with references will follow.

1. I measured my choline intake from food using cronometer.com. Choline data is sometimes missing, so the nutritional tables posted in this thread (thanks to @Richard7 !) do help to doubly verify. I found my intake to be badly low. -> indication to increase choline. This is a widespread issue:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782876/
"A recent analysis of data from NHANES 2003–2004 revealed that for older children, men, women and pregnant women, mean choline intakes are far below the AI. Ten percent or fewer had usual choline intakes at or above the AI"

2. I take AGP choline (= alpha GPC = Alpha-Glyceryl Phosphoryl Choline). I do not know if any other choline would do better or worse. This is the form Dr Diana Driscoll uses in Parasym Plus and it is said to resorb well.

3. I take it transdermally. Oral intake from food or pills can grow bad bacteria
I open the capsule and sprinkle the powder on skin just anywhere, drip a tiny amount of water and rub it in until it becomes a layer that feels greasy. Choline is eaten by bad gut bacteria. One won't notice the bad effects immediately but would damage oneself. I have experience with carnitine, which has this same effect. I damaged myself for a year or so before I understood where my small but slowly accumulating deteriorations came from... :(
And before taking AGP choline transdermally, I tried eating duck fat and brain, both high in choline. I ran into digestive issues compatible with feeding bad bugs. This was my first try and my first setback on this acetylcholine path... I was not well and hope my experiences save you suffering.
As a precautionary measure to avoid changes in skin microbiome, I cycle the skin area (left thigh, right thigh, left calf, ...).

4. I apply it some 0-30 min before protein-rich meals only:
Acetylcholine and serotonine antagonise each other. When I took it before salad meals (no tryptophane to produce serotonine) It didn't improve but inhibited upper gut motility (that "wonderful" stone-in-the-stomach feeling). Good motility needs serotonine and acetylcholine.
Regarding the 0-30 min before meals, I did not experiment with other times. At the beginning when I started choline transdermally, I clearly noticed the effect coming. It came fast. So I know that it resorbs fast. I want the choline to arrive with the tryptophan from food. It is possible that smearing it right after the meal would be even better...?
All this attention to tryptophan - choline balance may be a particular issue in me: My 5hiaa was almost nonexistent already before taking choline. Maybe this is why I need to be so careful, maybe other people do not need to care about this.

5. It was good to start ridiculously low:
I started at 75 mg/day (no effect), then was unresponsible to increase to 600 mg/day (wonderful, but bad side effects, see below. Lost much time as I had to stop completely), then found my current optimum dosage at 1x150 mg/day. Other people take 600 or 1200mg doses:
https://examine.com/supplements/alpha-gpc/
Recommended daily choline intakes: 550 for men, 425 for women:
https://www.nrv.gov.au/nutrients/choline

6. Having found a well tolerated dosage, I plan to increase it only very slowly:
I found the body needs quite a while to adjust. My current dosage of 1x150mg/day I keep since 2 weeks and will increase only if everything feels fully settled. Concretely, I have sometimes small feelings as if a flu would start. I will wait until these do not come any more and increase only then.

7. No other experiment / changes at the same time:
Choline effects so many systems that one would never know what causes what. Just think of all the effects below...

8. Look out for the following effects:
- Now, on my current optimum dosage (1x150mg/day), I have the following. All these effects are mild, nothing big: more relaxed, better digestion, better gastric emptying, heart pumping more forcefully in a pleasant way, improved blood flow (I have poor intestinal blood flow, I can tell from symptoms that it improved), my too low nightly blood pressure improved as measured by 24h BP, more energy, less chills and less feeling cold.
negative: sometimes a bit of a body feeling as if a flu would be approaching (no chills, no throat issues). Seems to be mostly gone meanwhile.
- In me, when I overdid (600mg/day): surprising, strong and very pleasant deep relaxed peace inside, but then really bad die-offs (exactly the same as when I take anything that kills intestinal bugs in me. Mostly chills such that I need three pullovers in hot summer!)

9. i do not take huperzine A
I had my cholinesterase measured. It was in the lower normal range, see a few posts above for the numbers. Adding to this, I achieved already a good effect with increasing choline. So I do not want to take any huperzine A. Taking choline is a dietary thing. Taking a cholinesterase inhibitor is a poison. Poison can be medicine and yes, people feel better. But there are reports of people who suffered bad damage fom huperzine A:
http://forums.phoenixrising.me/index.php?threads/acetylcholine-caused-crash.43104/
All the positive reviews on amazon.com for Parasym Plus are from a short-time intake! Hippocrates was a wise guy to say: First, cause no harm.
My guess is that cholinesterase inhibitors are for people with increased cholinesterase, or for cases where increasing choline is exhausted. Why not exhaust first the low-risk treatment before going to the risky one?
 
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South

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@Lolinda Thank you for writing up this facinating experimentation! Wonderful that you have figured this out and that it is going so well.

I'm particularly interested in this idea of using the choline product transdermally. Swallowed choline of various types usually gives me strange side effects, so I have avoided it as a supplement, (and I don't like the taste of eggs, so diet never had much) and have long wondered if those bad effects are due to the wrong gut bacteria turning the choline into something bad.

And I have had slow gut motility for years.

Is the type of choline that you are using by any chance "Alpha GPC"?
 

Gondwanaland

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http://www.ncbi.nlm.nih.gov/pubmed/25784704
MBio. 2015 Mar 17;6(2):e02481. doi: 10.1128/mBio.02481-14.
Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide.

Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which upon absorption by the host is converted in the liver to trimethylamine-N-oxide (TMAO).
 

Lolinda

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Is the type of choline that you are using by any chance "Alpha GPC"?
Yes. AGP choline = alpha GPC = Alpha-Glyceryl Phosphoryl Choline.
Good that you asked. I added these infos in the long post above.

I use this product:
http://iherb.com/p/176
Jarrow Formulas, Alpha GPC 300, 300 mg, 60 Veggie Caps
I have chosen this one because it contains essentially nothing else than the choline. This wasimportant for me because I dont know if skin tolerates it well if there is any starch or lactose or whatever in it, maybe I would grow some mushrooms on my skin ;) :eek: :) ?
 
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cman89

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My bumpy road towards increasing acetylcholine, finally with success

Thanks @South, @Richard7 and @Gondwanaland for all your interest in my experiences. That motivated me a lot to find some time in between of doctor's appointments to write it all down. Sorry for the long delay: Badly enough, I suffered a new setback: choline inhibited my motility. What? It is supposed to improve that. So I did not feel it would be responsible to announce my experiences when all I have to offer is risk and suffering. It should at least work for a single person, that is, me. Now, read below: I am glad to say this hurdle is taken and I am now happy with my new self-treatment.

References will follow:
To most things below I have meanwhile collected some research and will post it here as soon as I have a little time. My newest happy research find: increasing acetylcholine may increase alpha-msh, which is the gut's natural defense against pathogenic biofilms. So instead of going to Kenny De Meirleir and swallowing his well-intended antibiotics for many months, one has this natural antibiotic which accomplishes what the pills are not so good at: demolish biofilms. This however may also explain the bad chills I had at high doses. So, increasing natural alpa-msh may be no better at avoiding die-offs. But much better in so far as that antibiotics ruin also the healthy parts of the gut flora and one cannot take them forever. I red posts by people geting out of CFS on Meirleir's treatment and then gliding into CFS again after stopping antibiotics for a while. I appreciate De Meirleir for what he brought in such as popularizing the connection between CFS and gut bacteria. Highly appreciated! But do you want to keep De Meirleir treating you forever...? :eek:
- ok, this was just an appetizer. I need to do more work on this. Concrete research with references will follow.

1. I measured my choline intake from food using cronometer.com. Choline data is sometimes missing, so the nutritional tables posted in this thread (thanks to @Richard7 !) do help to doubly verify. I found my intake to be badly low. -> indication to increase choline. This is a widespread issue:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782876/
"A recent analysis of data from NHANES 2003–2004 revealed that for older children, men, women and pregnant women, mean choline intakes are far below the AI. Ten percent or fewer had usual choline intakes at or above the AI"

2. I take AGP choline (= alpha GPC = Alpha-Glyceryl Phosphoryl Choline). I do not know if any other choline would do better or worse. This is the form Dr Diana Driscoll uses in Parasym Plus and it is said to resorb well.

3. I take it transdermally. Oral intake from food or pills can grow bad bacteria
I open the capsule and sprinkle the powder on skin just anywhere, drip a tiny amount of water and rub it in until it becomes a layer that feels greasy. Choline is eaten by bad gut bacteria. One won't notice the bad effects immediately but would damage oneself. I have experience with carnitine, which has this same effect. I damaged myself for a year or so before I understood where my small but slowly accumulating deteriorations came from... :(
And before taking AGP choline transdermally, I tried eating duck fat and brain, both high in choline. I ran into digestive issues compatible with feeding bad bugs. This was my first try and my first setback on this acetylcholine path... I was not well and hope my experiences save you suffering.
As a precautionary measure to avoid changes in skin microbiome, I cycle the skin area (left thigh, right thigh, left calf, ...).

4. I apply it some 0-30 min before protein-rich meals only:
Acetylcholine and serotonine antagonise each other. When I took it before salad meals (no tryptophane to produce serotonine) It didn't improve but inhibited upper gut motility (that "wonderful" stone-in-the-stomach feeling). Good motility needs serotonine and acetylcholine.
Regarding the 0-30 min before meals, I did not experiment with other times. At the beginning when I started choline transdermally, I clearly noticed the effect coming. It came fast. So I know that it resorbs fast. I want the choline to arrive with the tryptophan from food. It is possible that smearing it right after the meal would be even better...?
All this attention to tryptophan - choline balance may be a particular issue in me: My 5hiaa was almost nonexistent already before taking choline. Maybe this is why I need to be so careful, maybe other people do not need to care about this.

5. It was good to start ridiculously low:
I started at 75 mg/day (no effect), then was unresponsible to increase to 600 mg/day (wonderful, but bad side effects, see below. Lost much time as I had to stop completely), then found my current optimum dosage at 1x150 mg/day. Other people take 600 or 1200mg doses:
https://examine.com/supplements/alpha-gpc/
Recommended daily choline intakes: 550 for men, 425 for women:
https://www.nrv.gov.au/nutrients/choline

6. Having found a well tolerated dosage, I plan to increase it only very slowly:
I found the body needs quite a while to adjust. My current dosage of 1x150mg/day I keep since 2 weeks and will increase only if everything feels fully settled. Concretely, I have sometimes small feelings as if a flu would start. I will wait until these do not come any more and increase only then.

7. No other experiment / changes at the same time:
Choline effects so many systems that one would never know what causes what. Just think of all the effects below...

8. Look out for the following effects:
- Now, on my current optimum dosage (1x150mg/day), I have the following. All these effects are mild, nothing big: more relaxed, better digestion, better gastric emptying, heart pumping more forcefully in a pleasant way, improved blood flow (I have poor intestinal blood flow, I can tell from symptoms that it improved), my too low nightly blood pressure improved as measured by 24h BP, more energy, less chills and less feeling cold.
negative: sometimes a bit of a body feeling as if a flu would be approaching (no chills, no throat issues). Seems to be mostly gone meanwhile.
- In me, when I overdid (600mg/day): surprising, strong and very pleasant deep relaxed peace inside, but then really bad die-offs (exactly the same as when I take anything that kills intestinal bugs in me. Mostly chills such that I need three pullovers in hot summer!)

9. i do not take huperzine A
I had my cholinesterase measured. It was in the lower normal range, see a few posts above for the numbers. Adding to this, I achieved already a good effect with increasing choline. So I do not want to take any huperzine A. Taking choline is a dietary thing. Taking a cholinesterase inhibitor is a poison. Poison can be medicine and yes, people feel better. But there are reports of people who suffered bad damage fom huperzine A:
http://forums.phoenixrising.me/index.php?threads/acetylcholine-caused-crash.43104/
All the positive reviews on amazon.com for Parasym Plus are from a short-time intake! Hippocrates was a wise guy to say: First, cause no harm.
My guess is that cholinesterase inhibitors are for people with increased cholinesterase, or for cases where increasing choline is exhausted. Why not exhaust first the low-risk treatment before going to the risky one?
Do you mind telling me how you narrowed in on Acetylcholine as a main treatment modality? I am curious about this, but as I have tried many other vitamins that I now use, how did this end up leading to the results you are having? As opposed to other possible supplements...
 

Lolinda

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Do you mind telling me how you narrowed in on Acetylcholine as a main treatment modality?
I like your question!

I have two answers:

One one hand, I did not really narrow in. I just tried everything under the sun, one-by one. (And I did not mention in my post on how I got out of ME everything that helped me in some ways, but only the most important things most closely related to ME). I knew that multivitamins are bad for me. So I tried individual vitamins to have a chance to tell the good from the bad. The essential discovery was that transdermal vitamins and minerals and even amino acids resorb as well as oral. Some very fast, others slower. Here you find my experiences.
This was the essential discovery. Before that I would have failed all of them because Ihave SIBO and gut bugs love isolated nutrients and they fiest before I do. Here is all I tried:
  • I take them now, with success: borage oil, K2, Calcium, Chromium, B5, Mg-Cl. - I did not modify intake of these during the introduction of agp-choline, so I know that the new effects I perceive are really from the choline.
  • Failed transdermally: B6, B3 (because of neuropathy), B2 (increased potassium loss)
  • No effect noticed, hence dropped after a week: Manganese and Biotin
On the other hand, I do a slight preselection of things, so that vitamins, minerals or amino acids with some vague chance of doing good are tried first. In the case of choline, it was info I found here on PR on a product Parasym Plus. It boosts the parasymp. nervous system. I do have digestive issues and I do ( or rather did! ) have excessive sympathetic activation (some vague restlessness which is not psychological stress). If you read this thread from the beginning, you find in the very first posts information what parasym plus does. In particular I recommend the link to the patent on Parasym Plus. So that was it what sounded exactly like "This is what I want for me!!". In sum, my hopes got fulfilled.
 
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