@dannybex I didn't know that. I always assumed that we didn't have enough acetylcholine (ACh), probably just because of my own experience: Whenever I remove one of the pieces of ACh synthesis from my supplement regimen I gradually (or suddenly) become unable to concentrate.
Can you remember what dose of B5 was thought to cause anxiety et? Admittedly, I am asking partly in defense of the idea that a much lower dose of B5 than had been mentioned on this thread might be helpful (50 mg vs 500 mg)
Not knowing anything about this I read a little bit. Please forgive the pedantic tone when you didn't really ask a question. I just learn best this way.
It sounds to me like the whole ACh in ME/CFS issue is pretty muddy. The
MRI study finding high choline in the brain might be unrelated to ACh. Here is an excerpt from an
article talking about the kind of MR spectroscopy used (emphasis added):
NAA is a neuronal marker and decreases with any disease that adversely affects neuronal integ-rity. Creatine provides a measure of energy stores. Choline is a measure of increased cellular turnover and is elevated in tumors and inflammatory processes. The observable MR metabolites provide powerful information, but unfortunately, many notable metabolites are not represented in brain MR spectra. DNA, RNA, most proteins, enzymes, and phospholipids are missing. Some key neurotransmitters, such as acetylcholine, dopamine, and serotonin, are absent.
So the findings of high choline in the CNS of people with CFS (PWCFS) wasn't suggestive of high ACh. That's not to say that they ruled out high ACh or sensitivity to ACh in the CNS--but neither of those were tested for, and indeed, ACh couldn't be tested for, not with an MRI. The choline they saw was probably the result of inflammation.
I did read one
study that dealt more directly with ACh, although it measured it in the blood where it is a vasodilator and not the CNS where it also effects mood and memory. The study found that ACh-induced vasodilation was more long-lived in PWCFS, and that while cholinesterase levels had an impact on "ACh-stimulated blood flow recovery" in healthy people, it did not in the PWCFS. Their explanation for this is that cholinesterases aren't functioning properly in PWCFS, possibly because of herpes or lymphocytic choriomeningitis, both of which can inhibit acetylcholinesterase.
But the authors finish sounding less sure about the ramifications of their study: They remind us that "endothelial cholinergic activity ... may or may not be applicable to other more widespread neurotransmitter functions of ACh." And they cite three case studies of PWCFS who had (appeared to have?) autoantibodies targeting one of the types of acetylcholine receptors, where treatment with cholinesterase
inhibitors "might well be therapeutic."
The takeaway from this limited review of two studies (as far as I am concerned):
1. Some, perhaps many PWCFS cannot break down ACh quickly enough. Maybe this is from a hidden infection. Maybe this just happens in some parts of our body, maybe everywhere. Interestingly, it didn't seem to happen in people with CFS/Gulf War Syndrome or people with CFS/organophosphate poisoning. Maybe this lends credence to the hidden infection thing.
2. I didn't find any data on ACh levels in PWCFS. My own experience suggests to me that I, at least, probably don't have enough of it in my brain. Maybe I have autoantibodies to muscarinic (acetylcholine) receptors. Maybe I have difficulty producing enough acetylcholine because of a deficiency in phosphatidylcholine and acetyl-CoA...I really don't know.
3. As Dannybex said above, some people can get too much ACh.
