Who doesn't benefit from acetylcholine supplements?

[Paw]

An intriguing new study finds that blockading acetylcholine activity can reverse mitochondrial dysfunction and promote nerve repair.

I take acetylcholine supplements purely on faith, since they're generally considered important for ME treatment. But I've only been able to take small doses because they seem to trigger burning, fatigue, and flu-like symptoms.

This study focuses on diabetic neuropathy, but researchers found that tamping down acetylcholine signalling allows proper oxygenation of cells AND promotes small-fiber nerve regeneration. (Small-fiber neuropathy is often linked to, or equated with, fibromyalgia.)

Importantly, acetylcholine antagonism must be selective, according to the study. Non-selective antagonists, like Benadryl (which I also don't tolerate), are not effective. Specifically, M1R antagonists like Pirenzepine (?) -- which are supposedly readily available -- seem to unambiguously promote neurological healing.

Unless I'm misreading the literature, this seems like a promising avenue of exploration for some of us. Maybe it also points to a delineation between those of us with FM-caused CFS and ME? The study suggests other factors (such as stress and injury) can lead to nerve damage, perhaps from too much acetylcholine activity.

One of the study's many intriguing conclusions:

Ongoing cholinergic signaling via the M1R constrains mitochondrial maximal respiratory capacity, which will restrict mitochondrial ATP generation under conditions of high demand.

 

[Cort]

An intriguing new study finds that blockading acetylcholine activity can reverse mitochondrial dysfunction and promote nerve repair.

I take acetylcholine supplements purely on faith, since they're generally considered important for ME treatment. But I've only been able to take small doses because they seem to trigger burning, fatigue, and flu-like symptoms.

This study focuses on diabetic neuropathy, but researchers found that tamping down acetylcholine signalling allows proper oxygenation of cells AND promotes small-fiber nerve regeneration. (Small-fiber neuropathy is often linked to, or equated with, fibromyalgia.)

Importantly, acetylcholine antagonism must be selective, according to the study. Non-selective antagonists, like Benadryl (which I also don't tolerate), are not effective. Specifically, M1R antagonists like Pirenzepine (?) -- which are supposedly readily available -- seem to unambiguously promote neurological healing.

Unless I'm misreading the literature, this seems like a promising avenue of exploration for some of us. Maybe it also points to a delineation between those of us with FM-caused CFS and ME? The study suggests other factors (such as stress and injury) can lead to nerve damage, perhaps from too much acetylcholine activity.

One of the study's many intriguing conclusions:

That's interesting. I would have thought the opposite as well - that they would help given the PNS problems. The body is obviously VERY complex. I don't hear much about acetylcholine antagonists. It sounds like maybe we should be hearing more about them....

 

[Paw]

I'd like to experiment on myself. First step is to eliminate acetylcholine supplementation. But the tough part will be getting my hands on some pirenzepine (or equivalent).

BTW, while trying to determine how greatly ALCAR promoted acetylcholine I stumbled across this Phoenix Rising thread and found I'm not the only one who responds negatively to acetylcholine -- or who continues to take it just because we're told how good it is.

The thread raises various theories of why some of us respond badly (mostly having to do with over-dosing), but this new research raises new questions about proactively blocking the receptors. I read somewhere else that antagonists will soon cause up-regulation in the acetylcholine receptors, which raises questions of treatment longevity (although the researchers sound hopeful that antagonism might permanently heal diabetic neuropathy; perhaps the treatment stops after nerve regeneration?)

 

[Paw]

I see they've already announced a three-phase drug trial for this. The researchers are excited, saying this is the first time, as far as they know, that they've actually seen regrowth of damage in neuropathy cases. HIV-, diabetes-, and chemically-caused peripheral neuropathies are the target, but it seems to me there's a lot of hope for fibromyalgia and other small-fiber neuropathic conditions.

I've ordered the trial drug, pirenzepine (gastrozepin) from an overseas pharmacy. It's supposedly safe and effective for acid reflux, peptic ulcers, irritable bowels, and possibly even muscle tremors -- so maybe I'll benefit from it as a medicine even if it doesn't reverse my neuropathies. Its anti-muscarinic properties are supposedly helpful to some of us who are having trouble maintaining a proper dopamine/acetylcholine balance. Since I've always had a paradoxical response to dopamine agents, this makes me hopeful.

I'll update after I've had a chance to evaluate my own personal trial. So far, I've eliminated acetylcholine supplements (namely ALCAR, alpha GPC, and alpha lipoic acid). Possibly I'm sleeping better and experiencing less RLS, burning, etc, but I haven't yet experienced less fatigue.

 

[AquaFit]

Paw, this is a subject I've been reading a LOT about and experimenting on myself. Cort's right, it is complex. Researchers have found that too.

Please check with your doctor before taking that medicine!

I've come to view ME/CFS as a matter of homeostasis. And acetylcholine, as our major neurotransmitter in the brain and body, can affect our cognition, memory, and the whole ANS. Rather than the view that we'll always need more or less of something, it seems that if our acetylcholine production or receptors are malfunctioning, then we need more or less of it at certain times. The problem seems to be that many of us are unaware of when our acetylcholine is being lowered or raised by drugs, inhaled chemicals, food and other sources. Modern medicine has reduced our concept of whole health to thinking that there is one simple solution to be applied to one simple problem.

For example; I was exposed to organophosphate as a fetus. Which leads to a buildup of acetylcholine at the time of the poisoning. https://en.wikipedia.org/wiki/Organophosphate_poisoning Acetylcholine is needed for the body to make collagen. Probably why I have great skin and look younger. Probably also why I have EDS features - not so great.

So one would think that now I need anti-cholergenics, right? Not so much for me. I actually need supplementation, but I only needed the supplements you mentioned for a few months. After that I felt wired and now my diet is sufficient. I look for foods, spices and herbs with high choline and phenolic acids and no organophosphates or hormones. But, sometimes I need a "hit" of a nightshade plant which will lower acetylcholine. Organic chocolate covered almonds and coconut water help immensely too; magnesium lowers acetylcholine in theory but maybe it's more complex than that. Maybe magnesium boosts something that regulates acetylcholine whichever way our body needs it, up or down.

Now for another "but". But foods themselves don't make the acetylcholine unless we get our heart rate up periodically even for a short time so that our metabolism can synthesize nutrients. I used to think low impact slow exercise was good but I discovered it's more tiring. I exercise in a pool in intervals (1 minute hard jogging, one minute rest, etc.) and it makes a huge difference.

Organophosphates are in fuel oil - The air in airplane cabins comes directly from the jet engines. We're exposed to unknown amounts every plane ride.

Anticholinergics are pervasive in medicine, even eye drops (which are organophosphates). Many anti histamines, pain meds, anesthesia, antivirals, etc are anticholinergics which can be substituted and are for geriatric patients. http://www.health.harvard.edu/blog/...l-linked-increased-dementia-risk-201501287667 It's thought that the blood brain barrier is more permeable in geriatric patients only, but I wonder if it is for us as well. If so, then a lot of the drugs/antibiotics/antivirals given for ME/CFS may be making us worse. http://emedicine.medscape.com/article/812644-overview

 

[Paw]

this is a subject I've been reading a LOT about and experimenting on myself. Cort's right, it is complex. Researchers have found that too.

Thanks for this AquaFit. I have quickly come to think of you as an acetylcholine expert around here.

Yeah, I've done enough research and experimentation to get a taste of how complex these systems are. Even the terms "agonist" and "antagonist" can get pretty confusing because of paradoxical reactions in the chain. So, to a large degree, researchers are just trying a bunch of stuff on rats to see what happens.

In this case, if one believes their data, they have stumbled across a specific, safe anticholinergic (targeted, not sweeping) that actually heals certain neuropathies. That's a big f-ing deal (to paraphrase the great Joe Biden). I'm a good guinea pig since there's evidence that my FM/CFS stems from neuropathies, along with the anecdotal evidence that I've never responded well to cholinergic supplementation.

I'm certainly not trying to demonize acetylcholine! And I think it's likely I'll tolerate the pirenzepine no better than cholinergics, since, as you point out, it's likely malfunctions are throwing homeostasis out of whack -- not necessarily the volume of certain transmitters. But this is a pretty low-risk way I can modestly contribute to the overall body of internet research. You're welcome!

 

[AquaFit]

Thanks for this AquaFit. I have quickly come to think of you as an acetylcholine expert around here.

Yeah, I've done enough research and experimentation to get a taste of how complex these systems are. Even the terms "agonist" and "antagonist" can get pretty confusing because of paradoxical reactions in the chain. So, to a large degree, researchers are just trying a bunch of stuff on rats to see what happens.

In this case, if one believes their data, they have stumbled across a specific, safe anticholinergic (targeted, not sweeping) that actually heals certain neuropathies. That's a big f-ing deal (to paraphrase the great Joe Biden). I'm a good guinea pig since there's evidence that my FM/CFS stems from neuropathies, along with the anecdotal evidence that I've never responded well to cholinergic supplementation.

I'm certainly not trying to demonize acetylcholine! And I think it's likely I'll tolerate the pirenzepine no better than cholinergics, since, as you point out, it's likely malfunctions are throwing homeostasis out of whack -- not necessarily the volume of certain transmitters. But this is a pretty low-risk way I can modestly contribute to the overall body of internet research. You're welcome!

Thanks for your patience with me. I'd forgotten we'd already spoke about acetylcholine. Right, with IBS I see why you're interested in targeting the M1 muscarinic receptor. This is very interesting - so many studies have been done but it's a matter of knowing what might apply and then expanding on those studies.

Noted from other convos your small muscle fibre neuropathy. Found this study, for what it's worth - https://www.ncbi.nlm.nih.gov/pubmed/1892361

Let us know how it goes. Would be interesting if part of dividing us up in subgroups is having too low or too low baseline acetylcholine. We are just stumbling around learning scientific and medical terms as we go, but it's so necessary at this time.

Forgive me if I've asked you this before, my horrible memory: how did you first get ME/FM?

Editing this post tonight - https://en.wikipedia.org/wiki/Hermona_Soreq
"Today, Soreq is The Charlotte Schlesinger Professor of Molecular Neuroscience at the Silberman Institute for Life Sciences and a founding member of the Hebrew University’s Edmond and Lily Safra Center for Brain Sciences. Her research is focused on the mechanisms underlying malfunctioning of communication by the neurotransmitter acetylcholine in muscle, nerves and blood cells, which involves changes in pre-mRNA processing and microRNA regulators, and may be manipulated by Oligonucleotide-mediated therapeutics (successfully completed Phase II clinical trials for treating inflammatory bowel disease)[6][7] that can be also relevant for anxiety-related, neuromuscular and neurodegenerative (Parkinson's and Alzheimer's) diseases. She is the author of over 280 peer-reviewed journal articles and 8 books"

 

[Paw]

Would be interesting if part of dividing us up in subgroups is having too low or too low baseline acetylcholine. We are just stumbling around learning scientific and medical terms as we go, but it's so necessary at this time.

Yes, and of course we're making plenty of speculations along the way. But with so little research targeting our area we can't always wait for others to see if certain puzzle pieces fit.

Thanks for the Soreq link. More clues. If the pirenzepine doesn't fix me I'll try splicing RNA myself!

Interesting that your other link found acetylcholine was similar to histamine in its ability to aggravate neuropathy. We may be on to something.

Forgive me if I've asked you this before, my horrible memory: how did you first get ME/FM?

That's all right. My illness is idiopathic. There's no discernible cause of my neuropathies (which are causing FM, and, in turn, CFS -- if one believes my neurologist). And I can't confidently trace other external factors for ME, although I can speculate about past injuries, infections, and exposures -- just not convincingly. What feels most true is that I was predisposed to a disease that was activated by a decade of chronic extreme stress.

 

[WilliamDonati]

This might be useful. Do check this article http://www.raysahelian.com/acetylcholine.html

 

[Paw]

A quick update. I've been taking the pirenzepine for just a few days (50 mg, twice a day) so it's too early to say whether any impact is from a placebo effect, although my irritable bowels seem better than usual.

I did contact the lead researcher on the upcoming trials, Paul Fernyhough (see overview here), and he tells me the reason they will be using a topical pirenzepine cream in the study is to reduce the possibility of side effects from oral administration (mainly digestive concerns). So I remain optimistic that my own little trial might impact more systemic problems from FM and small-fiber neuropathy.

I plan to take the drug for 50 days if I don't have pronounced adverse reactions. Meanwhile, I'm starting to wonder if any of our acetylcholine experts around here (@AquaFit?) think there might be value at some point in my re-introducing supplements (such as Alpha GPC, alpha lipoic acid, and ALCAR) to boost acetylcholine in general while allowing the pirenzepine to block only M1R?

 

[Not dead yet!]

Actually as my illness got worse my muscle relaxer stopped working (baclofen) and I switched to Flexeril (anticholinergic via muscarine receptor). It works so well, I'm amazed how much better I feel.

I did notice this effect before, for example, before I had preventative migraine meds, I used to take a massive dose of several antihistamines to stop a migraine (and for me it worked, but kinda bad to do that 4 times a week, so...).

Anyone who has cared for an elderly parent knows the OTC anticholinergics, there are lists online if you didn't realize how ubiquitous they are. Some elderly people, you give them an antihistamine, and they're incoherent for days.

It might explain why some people spontaneously heal from CFS as they get elderly. Looks like acetylcholine is much more important for early and late in life. But sigh, so much science, so little funding.

 

[Paw]

Baclofen helps me sleep, but I notice in my CPAP data more breathing disturbances with it. Odd. Flexeril never made much of an impression; interesting to learn it's anticholinergic. Recently I've been having interesting -- mostly positive -- results from low-dose galantamine, which is said to "balance" acetylcholine.

Meanwhile I'm nearing the end of my pirenzepine trial, which has been revealing. I'll update in awhile.

I hadn't heard about elderly healing from CFS. I wonder if that means they go hang-gliding, etc. I'm 55, but I feel elderly -- in the sense that my life generally ain't so bad if I don't try to do much, lie down frequently, manage pain in multiple ways, and laugh off a foggy brain. In other words, I've retired early. If I were 80 living exactly like I do no one would bat an eye.

 

[AquaFit]

A quick update. I've been taking the pirenzepine for just a few days (50 mg, twice a day) so it's too early to say whether any impact is from a placebo effect, although my irritable bowels seem better than usual.

I did contact the lead researcher on the upcoming trials, Paul Fernyhough (see overview here), and he tells me the reason they will be using a topical pirenzepine cream in the study is to reduce the possibility of side effects from oral administration (mainly digestive concerns). So I remain optimistic that my own little trial might impact more systemic problems from FM and small-fiber neuropathy.

I plan to take the drug for 50 days if I don't have pronounced adverse reactions. Meanwhile, I'm starting to wonder if any of our acetylcholine experts around here (@AquaFit?) think there might be value at some point in my re-introducing supplements (such as Alpha GPC, alpha lipoic acid, and ALCAR) to boost acetylcholine in general while allowing the pirenzepine to block only M1R?

Hi Paw! I just got NDY's post in my email inbox a few days ago; yours didn't show up at all! Technology.

To answer your question, I don't know. Wish I was an acetylcholine expert! Give us another update if you have a minute. Interested if you tried.

So, my theory of our having more permeable blood/brain, gut and skin barriers due to messed up collagen/acetylcholine in the womb - I note that perenzine is cytoprotective. So maybe it's shoring up your gut mucosal barrier? There's other ways to achieve that. Some of us use fermented products like kimchee, kombuchu drinks, and drinking vinagers in water or club soda. (Japanese Genki-Su available on Amazon or Bragg's apple cider vinager). Sometimes I drink about /1/3 of a teaspoon baking soda (from the health food store, without aluminum) in about 1/3 cup water and chase it with 1/8 teaspoon sugar.

 

[Paw]

I've been meaning to give a final update on my little experiment, but wanted to give enough time to gauge the permanency of the changes. For me the results have been very interesting, mainly because they've been so conclusive.

What I can say conclusively is that some of my peripheral nerves have noticeably been altered, seemingly long-term (I had my last dose on 3/18). Specifically those in the typical problem areas: feet, toes, hands, and fingers. I am regularly reminded through the day that I have sensations that I didn't have prior to the pirenzepine. Most notable are areas that had been completely numb (no tingling, burning, etc). In general my left side has been the numb side, while my right side has been the more painful side. Now, standing in the kitchen (for example) I will notice the feeling of my left toes on the cool tile. Or, if I stub a toe, I will feel the pain.

On average, I have more pain than before in all the peripheral areas. About half-way through my trial I started noticing a deep aching in those areas, reminiscent of frostbite-type experiences. This was both in the numb areas as well as the more tingling/burning areas on the right. I continued the trial anyway, reasoning that if nerves were indeed coming back to life, as they did in the mice, that might not be such a pleasant sensation. Afterward, I again contacted the main researcher, who agreed that this was logical. To be clear, he was never guilty of supporting my experiment, but he was polite and concerned, telling me that if I was determined I should be especially wary of gastrointestinal impact.

So that's why, after 31 days, I aborted my mission early: what had started as a lot of stomach gurgling and mild irritable bowel syndrome (e.g, mild diarrhea), gradually turned to a constant, dull stomach ache on the far right side. That's now gone, and my bowels are performing pretty well -- perhaps a bit better than before. This is the only possible sign that the experiment might have affected small-nerve fibers. (Small-nerve fiber was my main interest, since the researchers are only focusing on peripheral nerves.)

In short, I have no idea what would have happened had I continued the experiment. Would the aching in the peripheral nerves have gradually turned to normal sensations? (I.e., did they get only partially restored?) Would small-nerve fibers been next, leading to an improvement in my fibromyalgia? I do hope my feedback was helpful in a small way to the researchers. When they start the human trial perhaps they will now be prepared for the possibility that their diabetic subjects will experience significant pain as the nerves get restored. I'm not at all sorry about my additional pain because it's not severe, and it's actually a kind of nice reminder that those toes are still alive and part of my body!

I note that perenzine is cytoprotective. So maybe it's shoring up your gut mucosal barrier? There's other ways to achieve that.

Your theories are interesting, AquaFit, and I've had some limited success with some of your ideas (I had a thriving kombuchu going for about a year). But only one thing has made a really significant improvement; maybe you can fit it into your knowledge base: After 10-15 years of severe IBS (I'm talking literally a dozen watery BMs every single day), when my neurologist prescribed duloxetine for my overall burning, it also improved my bowels by probably 75%. I attribute that to the fact that serotonin is so essential to digestion. Maybe it's cytoprotective too?

 

[Issie]

Several of my med potentially could affect acetylcholine levels. If this causes brain fog and memory issues... I'm thinking, I'd rather have my brain. On a new trial to increase acetylcholine. See if it helps.

Issie

 

[AquaFit]

I've been meaning to give a final update on my little experiment, but wanted to give enough time to gauge the permanency of the changes. For me the results have been very interesting, mainly because they've been so conclusive.

What I can say conclusively is that some of my peripheral nerves have noticeably been altered, seemingly long-term (I had my last dose on 3/18). Specifically those in the typical problem areas: feet, toes, hands, and fingers. I am regularly reminded through the day that I have sensations that I didn't have prior to the pirenzepine. Most notable are areas that had been completely numb (no tingling, burning, etc). In general my left side has been the numb side, while my right side has been the more painful side. Now, standing in the kitchen (for example) I will notice the feeling of my left toes on the cool tile. Or, if I stub a toe, I will feel the pain.

On average, I have more pain than before in all the peripheral areas. About half-way through my trial I started noticing a deep aching in those areas, reminiscent of frostbite-type experiences. This was both in the numb areas as well as the more tingling/burning areas on the right. I continued the trial anyway, reasoning that if nerves were indeed coming back to life, as they did in the mice, that might not be such a pleasant sensation. Afterward, I again contacted the main researcher, who agreed that this was logical. To be clear, he was never guilty of supporting my experiment, but he was polite and concerned, telling me that if I was determined I should be especially wary of gastrointestinal impact.

So that's why, after 31 days, I aborted my mission early: what had started as a lot of stomach gurgling and mild irritable bowel syndrome (e.g, mild diarrhea), gradually turned to a constant, dull stomach ache on the far right side. That's now gone, and my bowels are performing pretty well -- perhaps a bit better than before. This is the only possible sign that the experiment might have affected small-nerve fibers. (Small-nerve fiber was my main interest, since the researchers are only focusing on peripheral nerves.)

In short, I have no idea what would have happened had I continued the experiment. Would the aching in the peripheral nerves have gradually turned to normal sensations? (I.e., did they get only partially restored?) Would small-nerve fibers been next, leading to an improvement in my fibromyalgia? I do hope my feedback was helpful in a small way to the researchers. When they start the human trial perhaps they will now be prepared for the possibility that their diabetic subjects will experience significant pain as the nerves get restored. I'm not at all sorry about my additional pain because it's not severe, and it's actually a kind of nice reminder that those toes are still alive and part of my body!


Your theories are interesting, AquaFit, and I've had some limited success with some of your ideas (I had a thriving kombuchu going for about a year). But only one thing has made a really significant improvement; maybe you can fit it into your knowledge base: After 10-15 years of severe IBS (I'm talking literally a dozen watery BMs every single day), when my neurologist prescribed duloxetine for my overall burning, it also improved my bowels by probably 75%. I attribute that to the fact that serotonin is so essential to digestion. Maybe it's cytoprotective too?

Hi Paw, sorry for the delay...I really don't know. I came across this study, I don't understand what it means, thought I'd point it out to you: http://gut.bmj.com/content/53/7/952.short "Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea"

Another study but mentioning the bladder; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1751864/ "Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder"

Meds are the other side of the coin of chemical warfare agents, so a primer on how they work on humans; https://academic.oup.com/bjaed/article/6/6/230/287821/Chemical-warfare-agents

While we're at it, a webpage on metabolic poisons; the last paragraph talks about a poison that interferes with ATP synthase - wonder if this is a cause of fatigue; http://www.ruf.rice.edu/~bioslabs/studies/mitochondria/mitopoisons.html

How are you doing now?

 

[AquaFit]

Hi again Paw,

There's something posted I think you might find interesting to read; scroll down to the comment by LY re blood serum and adipose tissues; https://www.healthrising.org/blog/2...hronic-fatigue-syndrome-mecfs/#comment-744082

The link posted re ATP cells being made from adipose tissues also touch on acetylcholine.

 

[Paw]

Thanks for the links. I had no idea nerve warfare was cholinergic! Interesting that clonidine is one of the preferred treatments, since it's become one of my most reliable sleep aids.

How are you doing now?

Well, I can say with high-level confidence that some permanent changes have taken place (or, at least, long-lasting). The most notable may be that my bowels have not performed so consistently reliably in decades. Every poop reminds me of my youth.

Your link to the serotonin connection to rotavirus-induced irritable bowels was interesting (but pretty old). I too found that SNRIs improved my IBS by about 50% after I started taking them several years ago (their other main effect was to significantly reduce my neurological burning symptoms). But I can't tell if the researchers made any attempt to examine serotonin's effect on non-rotavirus-caused IBS cases. Also, it's not clear whether their attempts at muscarinic blocking were specific or sweeping.

The other seemingly permanent impact from my experiment has been that my left-side numbness profile has noticeably changed. There's more feeling in several areas (which is not always more comfortable). Certainly the peripheral neuropathy has not disappeared. Whether or not these researchers will find specific enough applications and dosages to help in the real world, I do believe they have discovered something antagonistic to neuropathy in more than just mice.

 

[Issie]

I posted this on another link, but it fits here too. You may find this interesting.

An alternative that doesn’t require a script is Huperzine A. It helps with acetylcholine in the body and crosses the blood brain to improve brain function. Helps with blood flows. And I can vouch that it helps the brain fog and seems to be helping my POTS and stamina. Other great help is pregnenolone.

Of course, those that have seen my comments know – I disagree with traditional treatments for POTS. In my case, supressing what most people call “symptoms” – I call “compensation”. Many of the things the body does may seem uncomfortable and may flag as an inappropriate lab – but, very well could be the bodies adjustment to try to stabilize itself. My trying to block these “compensations” was wrong for me. I found moderating things to a tolerable level and trying to work on “core” causes much more effective.

There are some really good studies showing effects with calcium channels – in particular N calcium channel receptors and some having antibody response here. For me, Using mast cell med that not only stable mast cells but also is a calcium channel blocker and vasodilate veins – has also been a big help for me. Tramadol also works on this.

There are also some POTS people being found to have antibodies to NMDR receptors – glutamate regulators. I recently heard that of someone who is being treated for this at Mayo.

https://www.ncbi.nlm.nih.gov/pubmed/11920920

Seems not only is POTS, but CFS has an autonomic nervous system malfunction. Maybe CFS people are having autoimmune issues too —-like some of us POTSies. My two best additions are Huperzine A and pregnenolone of recent.
https://www.ncbi.nlm.nih.gov/pubmed/20360246/

There is another antibody being found to have issues in CFS – TRPM3. if you note the above article pregnenolone helps with this. Here’s an article showing it’s connection in CFS.

http://onlinelibrary.wiley.com/doi/10.1111/cei.12882/full

Pregnenolone also helps with calcium and muscle contractions. Which would help with blood flow.

https://www.ncbi.nlm.nih.gov/pubmed/20360246/

Issie

 

[Remy]

Here is an interesting podcast dealing with choline and acetylcholine...I had no idea that estrogen, for example, turned on a gene in the liver to make more choline so men and post-menopausal women are at much greater risk for choline deficiency.

http://smartdrugsmarts.com/episode-177-kyn-acetylcholine/#comment-86530