Who doesn't benefit from acetylcholine supplements?

Do you notice benefits from acetylcholine supplementation?

  • I primarily have FM and notice benefits

    Votes: 0 0.0%
  • I primarily have FM and don't notice benefits

    Votes: 2 50.0%
  • I primarily have ME and notice benefits

    Votes: 1 25.0%
  • I primarily have ME and don't notice benefits

    Votes: 1 25.0%

  • Total voters
    4

Issie

Well-Known Member
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
Interesting. I just ordered CDP choline and am using Huperzine A and pregnenolone. Will be interesting to see if the choline makes even more difference. The other two have helped. Also got Gotu Kola coming. That should help with blood flows. Another supplement I use for blood thinning - since I'm positive for Lupus Anticoagulant - has Ginko in it. So I think I have all the bases on choline and cognitive function covered as well as I can. Only other one I know is Vinpocetine. Tried that one years ago and for some reason - didn't stick with it.
Issie
 

Paw

Well-Known Member
Very interesting, @Issie. I too have been enjoying the effects of pregnenolone every morning, along with galantamine, which I think has a lot of similar qualities to huperzine -- and no longer requires a prescription either.

Seems that "balancing" acetylcholine is more productive for me than merely adding supplements like ALCAR or alpha-GPC -- which I still don't tolerate.

Looking forward to reading your links, as well as checking out that podcast @Remy.
 

AquaFit

Active Member
Thanks for the info Issie and Remy. (I look forward to listening to that podcast too.) Paw, I'm glad that you've found something that works for you and that your experiment seems to have worked. Yes, I agree that in the human body balance or homeostasis is achieved individually and our needs differ according to genes, environment, aging, etc.

Further on the theory of acetylcholine - I've been finding that there are more connective tissue gene disorders other than EDS - from other ME/CFS patients! The whole lactic acid theory in muscles never really made sense to me. It seems so unrelated to the fatigue we experience for days after exertion (for me after a workout). What makes more sense to me is that during a workout we're putting strain on our connective tissues (including the fascia, the thin sheath that covers our muscles) and we just need to rest so the body can do the work of repairing microtears in connective tissue. (Which psychiatrists call "pacing for CFS" but they attribute it to brain signalling). So guess what! I just came across this article calling out the whole lactic acid theory completely and putting out the theory that the pain after a workout is from microtears in muscles! (Keeping in mind though that muscles are not connective tissue.) http://pbmassagetherapy.com/muscle-soreness-due-to-lactic-acid-build-up-not-quite/

Regarding multiple sclerosis which also has found drugs targeting nicotine/acetylcholine receptors: I also just read that an early feature is disruption of the blood/brain barrier. Researchers have also been looking at "...activation of local microglia...infiltration of immune cells..." (p.3 subheading "Whither non-pharmalogical MS research?) http://www.alisonmyrden.com/images/...to-ameliorate-multiple-sclerosis-symptoms.pdf It was also thought that MS was the result of a virus but that's no longer a theory I understand. I just don't see why more ME/CFS researchers don't look at connective tissue genetics. I think Dr. Peter Rowe may be the only one, and he's not doing lab work.
 

Paw

Well-Known Member
Paw, I'm glad that you've found something that works for you and that your experiment seems to have worked.
Ha, I'd hardly say that! All I can attest to is that blocking the acetylcholine has altered the patterns of my peripheral neuropathy -- so I think the researchers are probably on to something if they can figure out how to "weaponize" their findings effectively. So far I've seen no significant alleviation of any other symptoms (e.g. CFS).

That was an interesting blog post about micro-tears vs lactic acid. I'm not yet convinced it applies to me, though, as he was addressing healthy athletes with normally functioning systems who experience pain from hard workouts using eccentric muscle contractions; whereas I don't have to do anything close to micro-tearing to experience significant pain. While I do benefit from massage, my main evidence supporting the lactic acid theory is that additional exercise during pain does not typically lead to greater pain or injury. This was a big breakthrough for me -- when I realized my pain was not something to fear or protect myself from. In fact, further exercise (in moderation) often alleviates some pain.

Also, @Remy reminded me of the lactic acid theory behind certain heart issues. (I asked my cardiologist if she could do some lactic acid testing, but she refused.) So I'm not ready to throw the theory overboard just yet.
 

Paw

Well-Known Member
Wow, @Remy, that was an informative podcast! I learned a lot more about choline, epigenetics, etc. And I had the incidental realization that my post here might be construed as questioning the value of acetylcholine itself. Not so.

Just to be clear, my interest has been in trying to figure out why I don't respond well to it; i.e., what's weird with my particular wiring that supplementation worsens all my symptoms?

One very generalized possibility, which the podcast reinforced, is that choline promotes neural growth -- and since my issues are deeply related to neuropathy perhaps there's something in my bad nerves that gets irritated by the acetylcholine -- kind of like overfeeding a dying plant with tons of nitrogen. Taking standard amounts of ALCAR or alpha-gpc feels like mild poisoning to my system.

I've also wondered about signalling problems. What happens if a receptor is being blocked for some reason and then you flood the zone with the neurotransmitter? Could it lead to some of the symptoms Zeisel describes as resulting from choline overdoses?
 

Paw

Well-Known Member
@Issie, the TRPM3 studies on CFS/ME look very useful, from what I can understand of the write-ups. Glad they're going to continue digging deeper. I temporarily ran out of pregnenolone and felt significantly better when I replenished my supply. I've also been complementing those morning doses (50mg) with evening doses of "male" stuff: saw palmetto, tonkat root, horny goat weed, ginseng, etc. Does not worsen my sleep, and seems to improve next day's energy. Will have to order huperzine, as I'm now out of galantamine.

The cholesterol connection is interesting too. My cardiologist was not happy that I insisted on giving up statins, but their connection to increased soreness and overall dragged-down feelings was unequivocal. Apparently my body craves the regulation cholesterol provides.
 

Issie

Well-Known Member
http://www.medscape.com/viewarticle/752199
"septic patients with severe sublingual microcirculatory alterations had a bad prognosis in terms of outcome, with septic survivors showing a higher proportion of perfused capillaries than nonsurvivors.[49]Interestingly, these microcirculatory disturbances improved after the topical application of acetylcholine, highlighting that those changes might be reversible."

If we have endothelial dysfunction and issues with microcirculatory issues and acetylcholine helps reverse this - we probably need more of it not less.

Issie
 

Paw

Well-Known Member
If we have endothelial dysfunction and issues with microcirculatory issues and acetylcholine helps reverse this - we probably need more of it not less.
Yeah, my issue seems to be about how it's processed. Results from inhibitors like galantamine and huperzine are quite positive, while straight supplementation (like alpha GPC) is consistently negative (leading to "flu").

There seem to be conditions (such as the neuropathy the researchers are focusing on) that require at least a temporary respite from acetylcholine. This is what I've been attempting to explore -- not suggesting that this important transmitter is harmful in and of itself.
 

Issie

Well-Known Member
I just listened to a talk by Dr Ben Lynch on methylation and MTHFR mutations.
http://seekinghealth.org/gift/
He said that if we don't get the blockages cleared and get our methylation cycles going complete we could wind up with choline deficiency that could lead to Alzheimers and other neurological (neuropathy) and autoimmune issues. It's very important to have enough choline on board. But we may have to unblock the cycle before this, to have things used optimally. I've been addressing my MTHFR and other methylation mutations for awhile now. I don't seem to need to supplement with everything I was using and I don't take things daily any more. But yet I'm certain there is a choline issue as supplements are helping. I'm now finding that after a few weeks, I'm able to cut those back a little too. Not needing those daily now.

Issie
 

Issie

Well-Known Member
Update for me ---- Hyperzine A started causing me more brain fog. I think you need to take breaks from it. A few days off and I'm better. I also seemed to be a little more allergic to things while on it. Not sure if it affects histamine levels. I need to check into that. Maybe, it builds up. Still experimenting. Doing okay with adding Gotu Kola at night and still using CDP choline. Maybe was just too much with other.
Issie
 

Issie

Well-Known Member
Also appears that if you up acetylcholine too much it causes more histamine. Not a good thing for those of us with Mast Cell issues. Fine line between having better brain function and creating a "mast cell attack".
Issie
 

Jas1

New Member
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:

Paw--I'm new to this list so hopefully I am replying to your post and it gets to you. I noticed your thread on pirenzepine. Based upon a new trial by U. of San Diego and a Canadian university you said that you tried this medication. I'm curious if you crushed the tablets and put them into a cream? I have read about that study and am wondering if you might have tried it topically since that is what they are doing? Thank you.
 

Paw

Well-Known Member
I'm curious if you crushed the tablets and put them into a cream?
Not precisely. I did do that for a few weeks with my leftover tabs, but it didn't seem to affect what was already occurring with my oral experiment. Hard to say for sure. The researchers are targeting peripheral neuropathy only, so my experiment was focused on whether oral administration might impact small-fiber neuropathy globally (possibly easing my fibromyalgia).
Also appears that if you up acetylcholine too much it causes more histamine.
Yes, that's exactly what it feels like to me, even in small doses! I don't know if histamine is actually my issue, but it seems possibly tied to the flu-like symptoms that I frequently encounter (and are exacerbated by acetylcholine.

I still use huperzine with good effect, but I also take breaks every few days.
 

Issie

Well-Known Member
Yes, that's exactly what it feels like to me, even in small doses! I don't know if histamine is actually my issue, but it seems possibly tied to the flu-like symptoms that I frequently encounter (and are exacerbated by acetylcholine.

I still use huperzine with good effect, but I also take breaks every few days.
I gave up on Huperzine. Too many mast cell issues with it. Maybe I'm just allergic to that herb. Not sure. I will go back to trying CDP Choline - when I settle out. It may be something else I was using that was causing all the brain fog issues. I seem better last few days and have been cutting things out to see if there is an issue. My doc had me come off of magnesium, fish oil and Folate - he said it would feed mold/fungus and since we know I have an issue with it (similar to Valley Fever - different fungus - found in thyroid biopsy) my focus will be detox and clearing that out ---if it's possible. I also had environmental toxic mold exposure. These things can cause brain fog.
You are a little younger than me - not by much. We are to young for all this stuff........
Issie
 

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