Acetylcholine and antihistamines

Hi everyone! I haven’t posted here before but have learnt a lot from reading in the past few years - so thank you! (And please say if I’ve posted anything wrongly, hoping I haven’t!)


I’m hoping for some help on a couple of questions revolving around acetylcholine.


Quick background: I currently have severe ME and am practically bedbound. I also have MCAS, POTS, probable hEDS, amongst other fun labels I’m sure many of you have too!


So my questions are;

1. Can anyone help my understanding of the mechanisms of action of antihistamines (AH) on acetylcholine?

I'm on an H1 blocker (cetirizine) but have been told that Ketotifen and an H2 blocker would also help my MCAS symptoms, in particular famotidine. However, I've heard that this reduces stomach acid. Having had an Organic Acids Test I know that mine is low so I'm conscious of how that may affect me since it feels like I’d be helping one issue and creating another. I’m also conscious that although the antihistamines will stop the mast cells firing too much and causing inflammation, blocking them doesn’t feel like a great long-term solution because it’s not getting to the issue of why they’re activated in the first place. I’ve been on cetirizine for close to 10 years and my reactions have gradually gotten worse to the point I’m down to a few foods, so it’s not even keeping things at the same level, let alone helping fix things.


2. I have 1 (possibly 2, I’ve forgotten, thanks brain fog!) homozygous mutation in the PEMT gene which means I have a choline deficiency therefore affecting any process/system that relies on choline (eg. acetylcholine and PC). ​

I understand antihistamines block acetylcholine receptors and that magnesium also decreases your ability to get as much acetylcholine (both of which I’m taking). So in theory, I should presumably be taking any meds/supplements that increase acetylcholine to help balance the deficiency out.​

However, I briefly took Pyridostigmine (aka. Mestinon) and although I felt better on the day, I had a number of mild allergic-like reactions and had to stop. But I don’t understand why since presumably my body needs it - could anyone help explain this?​

Also, in theory, antihistamines and magnesium should make my muscles weaker if I can’t get as much acetylcholine, but magnesium seems to help them - can anyone help me understand why that is too please? Could it be that my muscles are hyperexcitable and need calming down, so that’s why things that block acetylcholine help? … But then I come back to the fact that I'm deficient in acetylcholine so how can that be good?! ​

Sorry for the ramblings! Any thoughts to help my understanding would be really appreciated… Thank you so much and apologies in advance if I’m slow to reply!