1 reply to this topic

[j87]

I have a problem with excess acetylcholine buildup I've been struggling to understand. I suspect it has something to do with a messed up methylation cycle.

For those who aren't familiar with acetylcholine, too much can cause depression https://www.pnas.org...tent/110/9/3573

I will reach a point where I have symptoms of excess acetylcholine- depression/anhedonia, poor working memory, fatigue. Diphenhydramine (Benadryl)
relieves these symptoms and allows me to feel normal again. Benadryl is an anticholinergenic. I've come across others on the internet who have this problem.

Some people have success with racetams (piracetam, aniracetam, etc) to use up excess acetylcholine, but these don't work for me. The only thing that helps is an anticholingernic drug such as benadryl, dramamine, or doxylamine.

I've received comments skeptical of the anticholinergic action, asking "How do you know it's not the antihistamine effect, or benedryl's effect on serotinin?" I know because other antihistamines with minimal anticholinergic activity do not help my symptoms at all. Also bendryl's effect on serotonin is extremely weak, and other supplements that effect serotonin do not help me at all.

There are several genetic mutations that influence how you break down acetylcholine. They can be found on 23andme. These articles list all of the mutations and go into detail.
https://www.geneticl...-risk-and-more/
https://www.geneticl...ks.com/choline/
https://sites.google...rase-inhibitors

Strangely, I've looked up the mutations listed, and mine are all normal.

Acetylcholinesterase (AChE) is the enzyme responsible for breaking down acetylcholine. If you take AChE inhibitors (such as huperzine, used for memory enhancement) it can cause buildup of excess acetylcholine. I've found that almost every herbal/plant extract out there has some degree of AChE inhibition. Plants have many components & chemicals in them, so it's likely at least one of the components in the extract has been shown to inhibit AChE to some degree.

These are some of the supplements, I've found to inhibit AChE and/or boost acetylcholine through some other mechanism, and make me feel worse:
black cumin seed oil
turmeric/curcumin
ginger
sulforaphane
fish oil
rhodiola
ginko bilboa
olive leaf
berberine
cbd oil
cannabis

Which is a shame because a lot of them also have antidepressant properties that initially make me feel good before the accumulation of choline occurs.


Excess methylation caused by taking too many methyl donors will cause acetylcholine overload. TMG and B12 (both hydroxy and methyl) cause me problems. I avoid TMG and only take hydroxyb12 is very small amounts when needed. I am careful not to get too many methylated B-vitamins.

Some people reported that taking niacin/niacinamide to slow down methylation has fixed their "excess choline" problem. This hasn't worked for me, though.

I have 2 Homozygous mutations: MTHFR A1298C and MAO-A R297R (warrior gene). I take small amounts of methylfolate and B2.

I've seen several reports of "Rebound problems" after taking methylfolate and methylb12, people feeling great the first day then it stops working, and they feel increasingly worse the following days. There are many causes for this (depending on individual genetics), but I believe acetylcholine overload is one of the overlooked factors involved in this.

[ibtisam_midlet]

yes anti-acetylcholine give me antidepressant effect and anti-anxiety effect, and i don't have high baseline acetylcholine system , just stick with benedryl its better to interact with the receptors directly to avoid strong tolerance from developing.