Trouble understanding the Acetylcholine Antibodies thing

[Gingergrrl]

Main problem is my massive intolerances to foods, supplements, medications, smells.

Can you remind me what mast cell meds you are taking (prescription, OTC, and supplements) and which were helpful (if any) and which made it worse. I think you said you are only tolerating rice at the moment but might be mixing this up with an older thread.

 

[Malea]

Can you remind me what mast cell meds you are taking (prescription, OTC, and supplements) and which were helpful (if any) and which made it worse. I think you said you are only tolerating rice at the moment but might be mixing this up with an older thread.

I take low-dose Ativan and low-dose Cetirizine. I can’t take more of both because than the side-effects become unmanageable. Ativan is stabilizing me a littlebit overall but didn’t lead to better toleration of foods. The reason for that could be because my reactions are not primarily caused by mast cell degranulation but more by a typeIV-allergy from the t-lymphocytes. That’s at least what my doctor is thinking atm and it seems to make sense because reactions start slowly and delayed.

 

[Malea]

Oh and Ascorbic Acid was really helpful but I didn’t tolerate it in any buffered form, so had to stop using it because of GI-problems.

 

[kangaSue]

Oh and Ascorbic Acid was really helpful but I didn’t tolerate it in any buffered form, so had to stop using it because of GI-problems.

I'm having a real problem tolerating any form of ascorbic acid too and have major problems tolerating most foods, meds and supplements - sometimes from a slow reaction and sometimes it's an immediate thing. I have mostly severe GI problems (gatroparesis) and these intolerance problems probably relate back to my having Chronic Mesenteric Ischemia causing GI inflammation and malabsorption problems.

That in turn looks to be caused by an occluded left renal vein causing pelvic and abdominal (splanchnic) congestion - increased venous pressures can cause dysfunctional renin angiotension system (RAS) and mild adrenal insufficiency from increased pressures into the left adrenal gland (I have low, but "normal range" morning cortisol and aldosterone and elevated renin levels). Various other vessels can become dilated and cause subsequent inflammation, all of which can cause compression to other splanchnic organs and structures.

GI dysfunction and/or inflammation can be a cause of mast cell activation and can be something that can't be stabilised to any great degree with the usual mast cell meds until such time as the underlying cause of GI problems is fixed.

 

[Gingergrrl]

I take low-dose Ativan and low-dose Cetirizine. I can’t take more of both because than the side-effects become unmanageable.

Is it b/c the Cetirizine becomes too sedating or other side effects? My MCAS doctor has patients on huge doses of certain meds and said that he titrates up to the individual patient (although this is often to stop anaphylaxis risk so it is worth it). For about two years I was taking 2 Cetirizines per day (plus a ton of other stuff) until this whole thing went into remission.

Can you remind me if you tried Ketotifen? I hope I have not asked you this 50x already!

Ativan is stabilizing me a littlebit overall but didn’t lead to better toleration of foods. The reason for that could be because my reactions are not primarily caused by mast cell degranulation but more by a typeIV-allergy from the t-lymphocytes.

Is type IV allergy still mast cell mediated (or totally unrelated)? There can definitely be mast cell driven reactions that are delayed and they are not always immediate.

Oh and Ascorbic Acid was really helpful but I didn’t tolerate it in any buffered form, so had to stop using it because of GI-problems.

Is Ascorbic Acid the same as Vitamin C? If so, Vit C is also a mast cell stabilizer. Have you tried "Liposomal vitamin C"? This is just an example (Dr. Mercola's brand):

 

[kushami]

@Hip , your explanations in this thread are so helpful!

I know I have autoantibodies that are causing cerebral vasoconstriction; however, I am having trouble grasping which receptors might be involved.

A further complication is that I assume the autoantibodies might be either causing excessive vasoconstriction, or preventing normal vasodilation.

If you had any thoughts I would really appreciate it. At the moment I take vasodilators, and that helps, but maybe something that targets a receptor would be better.

 

[Hip]

I know I have autoantibodies that are causing cerebral vasoconstriction; however, I am having trouble grasping which receptors might be involved.

Unfortunately I have more difficulty doing online research now, ever since getting long COVID on top of my ME/CFS, which has increased brain fog and mental fatigue.

However, using the lazy approach, and asking the AI bot Perplexity the question: "Which adrenergic, muscarinic and nicotinic receptors are involved with blood vessel vasodilation and vasoconstriction?" I get the following answer:

Vasodilation​

• Endothelial M3 receptors (as well as M2 and M5) stimulate the production of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS), leading to vasodilation.
• Stimulation of vascular smooth muscle β2 adrenergic receptors causes vasodilation, especially in veins and bronchi.

Vasoconstriction​

• In the absence of endothelium or endothelial dysfunction, acetylcholine causes vasoconstriction by stimulating vascular smooth muscle M1 and M3 receptors, increasing vascular tone and blood pressure.
• Activation of vascular smooth muscle α1 adrenergic receptors mediates vasoconstriction by increasing intracellular calcium levels, leading to increased vasoreactivity and vascular tone.

Refs: here and here.

So assuming that is correct, if you had antibodies blocking muscarinic acetylcholine receptors, or equally antibodies blocking beta2 adrenergic receptors, this might be causing the vasoconstriction.



Asking the follow-up question "Which adrenergic, muscarinic and nicotinic receptors are involved with blood vessel vasodilation and vasoconstriction in the brain?" Perplexity answered:

Muscarinic receptors are primarily involved in vasodilation in the brain, while nicotinic receptors play a role in vasoconstriction.

Ref: here

And further questioning got the answer:

The M5 muscarinic acetylcholine receptor plays a crucial role in inducing vasodilation of cerebral blood vessels in the brain.

Ref: here

Looking to see what selective M5 muscarinic agonists are available, there does not seem to be much.



You might find this post of interest: it explains how carbon dioxide gas is a very potent brain blood vessel vasodilator, and details my experiments in breathing CO2 for cerebral vasodilation purposes.