Thread by @angryhacademic

Latest venture: Choline

THREAD: Mishmash of ideas and some inferences 🧵

#postvac #longcovid

1. Last year we found:
👉🏻severe B12 deficiency
✅low MMA after B12 replacement...
❌...but still elevated homocysteine
❔low-normal folate
❌no MTHFR gene variant
✅...but correction of homocysteine after folic acid supplementation

https://twitter.com/angryhacademic/status/1550472844089466881

this caused confusion because there is no obvious reason why i need so much folic acid to keep my homocysteine down

turns out, choline deficiency can elevate homocysteine
ncbi.nlm.nih.gov/pmc/articles/P…

and B12 deficiency might increase choline needs leading to depletion

Choline is found in highest quantities in animal products, so I have a naturally low choline diet:
nal.usda.gov/sites/default/…

Inference 1: i was low in choline, and this got further depleted by B12 deficiency. this could explain my oddly high folic acid needs

2. Choline is needed in part to make the neurotransmitter acetylcholine.

Acetylcholine has a lot of important functions, including (lowering) heart rate, blood pressure, saliva production, urination, muscle contractions, and adrenal hormone release
my.clevelandclinic.org/health/article…

it's also involved in memory, attention, and sleep

I have POTS (high heart rate), random orthostatic intolerance (low blood pressure), dry mouth/thirst, weakness, slowness, i pee ALL the time, have issues with some adrenal hormones, cognitive dysfunctions, insomnia & poor sleep

i think in my second appointment with the consultant after my vaccine, i asked for acetylcholinesterase inhibitors. I asked again at my recent neuro appointment. these are in POTS recommendations by the Heart Rhythm Society
ncbi.nlm.nih.gov/pmc/articles/P…

https://twitter.com/angryhacademic/status/1654177381731401728

Acetylcholinesterase inhibitors block the enzyme that breaks down acetylcholine, therefore your essentially get "more" acetylcholine.

Inference 2: AChE inhibitors were possible a good idea right at the beginning

3. From near the beginning of the pandemic, the interaction between the spike protein/SARS-CoV-2 and the cholinergic system was posited. I wrote about it potentially being important in a paper about thirst in 2020

https://twitter.com/angryhacademic/status/1283446678792609799

More recently, its role in #longcovid has been speculated:
ncbi.nlm.nih.gov/pmc/articles/P…

with some finding relief with cholinergic modulators like nicotine.

Follow #TheNicotineTest for a n-of-1 experiment:

https://twitter.com/Canal1point5/status/1657381904365113346

Inference 3: the cholinergic system is likely an important player in the pathogenesis of long COVID and similar vaccine injuries

4. Another thing that we are confused about in my case is my chronically elevated D-dimer.

In dogs given an endotoxin, choline attenuated the endotoxin-induced clotting
pubmed.ncbi.nlm.nih.gov/20410813/

In humans, the association is less clear and there's evidence high choline is associated with poor cardiovascular outcomes.

However, this paper *may* offer an explanation:
tandfonline.com/doi/full/10.15…

The paper suggests that choline is released from ischaemic tissues, which then increases serum choline concentrations. this elevated choline does a few things, one of which is increase platelet activation

Inference 4: the vaccine triggered clotting via inflammation and spike protein. I may have been predisposed to clotting due to elevated homocysteine which may have been partly due to low choline diet (also/mainly severe B12 deficiency)

clotting, specifically microclots, then caused widespread ischaemia. the ischaemia released my limited stores of choline, furthering depletion.

I am now 2 years in, and whilst there is peaks and troughs, my weakness, slowness, cognitive function etc are generally declining

To sum:
I have low dietary choline intake
B12 deficiency may have depleted choline, leading to higher folate needs
My symptoms fit signs of low acetylcholine
The spike protein has direct interaction with the cholinergic system
Ischaemia can also deplete choline

These are all inferences, but this is something that i clearly had in my mind for a long time. Choline in the right quantities is generally safe. Since I will struggle to get enough from diet, I will supplement, staying within the upper limit (I will aim for 3 grams/d)

There are different types of choline, I think I will go for Alpha GCP
mindlabpro.com/blogs/nootropi…

You can read the evidence for this in other populations here: examine.com/supplements/al…

This is not an extensive review and i still have a lot of questions, but i'd rather act now

If I am right, I predict this will help with symptoms like slowness, weakness, OI, tachycardia, fatigue, sleep, cognition. I *think* the effects should be notable fairly rapidly, within a few weeks

We shall see...

Ooh look, interactions between mast cells and the cholinergic system
jneuroinflammation.biomedcentral.com/articles/10.11…

Not entirely surprising considering the link between mast cells and nerves but nice to see it in writing for this context