Well I found out something very important about this disease : a lot if not all of my symptoms are mast cell related.
When I fell ill everything seemed to revolve around my digestive tract as a cause of my problems. From extremely mild symptoms in my youth to severe digestive tract problems during the peak of my disease the mind and body effects followed this exactly. And when I started to treat my disease in several ways as if it was a digestive tract problem caused by some micro-organism I actually got some results and made myself at least a bit better over time. I thought I had made some sort of overgrowth of an organism less that also happened to produce acetaldehyde and it was mainly the acetaldehyde which seemed to be the cause of all the crazy amount of extreme whole-body wide symptoms, including making me feel quite literally “half-drunk”. It all seemed to make so much sense at the time…
But now I am certain that all of this is actually a mast cell problem. There might not even be a micro-organism problem at all !
When I fell ill because of the symptoms of severe face-flushing / redness and diarrhea and because I could provoke these symptoms with food / drinks I had all the medical tests for things like carcinoid-syndrome and pheochromocytoma and such. And also the tryptase test for mastocytosis which was negative (and several more tryptase tests over a number of years were all negative and I now know that the tryptase test is actually pretty useless for this type of mast cell problem). Back then I definitely researched mast cells as just one other thing that could cause my disease but the symptoms related to them just never really added up and it was always about analphalactic reactions as the main symptom whenever I read about it. And I just didn’t seem to have that so I discarded mast cell problems as not applicable to my situation. There was also hardly any mentioning of mast cell activation syndrome (MCAS) yet as a variant of these mast cell disorders as a cause of extremely weird and far-ranging disease symptoms, this was all quite new and upcoming in those days.
Though at the peak of severity of my illness I might have had minor analphalactic reactions without me recognizing it as such this is not the most defining feature of this particular kind of mast cell problem. It is a general non-analphalactic permanently activated state of mast cells producing all kinds of mediators that cause all the problems. It is a special variant of these mast cell activations. They are 24 hours a day “turned on” permanently with a bit of variability depending on all sorts of factors, internally or externally, and they make me seriously ill and are the cause of all my brain and body symptoms. There is probably still a role for the acetaldehyde on its own too as a cause of some symptoms, how much is difficult to say, but I think the mast cells are the biggest problem.
It might be more complex but I sort of see 2 possibilities so far :
– There is an endogenous source of acetaldehyde to begin with and this is the initial cause of the mast cell activation. And maybe this in turn could even create the circumstances for even higher endogenous acetaldehyde levels. This by inhibiting processes that have to do with the clearance of endogenously produced acetaldehyde from the body or more actively by stimulating biological processes that create endogenous acetaldehyde. Maybe this causes even more mast cell activation in a back-feed loop process until some higher balanced state is achieved.
– The mast cells are in a permanently activated state through some other means (An over-active immune system stuck in the “on” position ? Still a micro-organism of some sort ? Something that triggers them permanently). They then actively create the higher endogenous acetaldehyde levels by themselves as a follow up result. This by inhibiting processes that have to do with the clearance of endogenously produced acetaldehyde from the body or more actively by stimulating biological processes that create endogenous acetaldehyde. Maybe this causes even more mast cell activation in a back-feed loop process as an extra because they are now also stimulated by the acetaldehyde too until some higher balanced state is achieved.
These days I sometimes think the latter is the most likely. As if the high endogenous acetaldehyde blood level that I measured is a result from mast cell activation. What I do know is that they have a strong relationship with each other as a cause for what is happening and the higher endogenous blood acetaldehyde level can be measured and used as a blood marker.
There are some clues to all the mast cell effects on body and brain hidden in the effects of alcohol and in all of the alcohol related research out there but I have the idea that they never really completely figured it out so far how that exactly works in practice, especially when it comes to the effects mast cells have on the brain.
Just some examples from 1999 “Alcohol-histamine interactions.” https://pubmed.ncbi.nlm.nih.gov/10344773/
“Alcohol and histamine metabolic pathways in the body have the common enzymes aldehyde dehydrogenase and aldehyde oxidase.” “…. the hypnotic effects of alcohol. “ “ …. the involvement of the brain histamine system in the mechanisms of the central actions of alcohol… “
People need to understand the importance of all of this but it is difficult for them because all they can imagine is a drunk person holding a glass of alcohol probably doing dumb things. And what has that got to to with mast cells / ME/ CFS / Autism and more ?
But the acetaldehyde and mast cell activation are connected to that however a person has to be able to see the follow-up results of the effects of alcohol as a separate thing on its own without the alcohol.
You see because I have been so incredibly half-drunk without any alcohol influence at all I now also understand something about the mechanism of getting drunk the normal way. The effects of alcohol on the body and brain are actually incredibly complex and varied if you think about it, there is almost nothing that is not affected in some way or another. But the alcohol (Ethanol) is only the start of a further follow up process in the body which gives all those effects that we think of when someone is under the influence of alcohol. And I have learned to recognize that it is actually those mast cells and/or the acetaldehyde that are responsible for a lot of those effects.
And that means that if you have that part endogenously on its own in a low-level form as an illness 24 hours a day without the alcohol well you still get a whole lot of very interesting but also highly problematic symptoms.
There is a slight possibility that for the same amount of mast cell activation that give problems on its own in the body the level of endogenously produced acetaldehyde may vary between persons (it may not be connected completely linear 1 to 1 and there might be more going on with all of these interactions and processes) however at its basis I still think we are looking at the same sort of process going on as a cause for all of these things and when it comes to the more permanent effects on the brain :
Autism / Spectrum Conditions and most likely many more brain differences are caused by something that can be described in a practical way as “endogenous half-alcoholism” caused by mast cell and/or acetaldehyde effects on the brain. It needs to be understood however that these are natural processes in itself and if it does not get out of hand too much are a completely normal part of how human beings turn out to be.
The difference in the end result is in the dosage…
When / how much / how long…