Excess acetylcholine & methylation

[jwat87]

Found this post on reddit, this could explain a lot:

"It seems like excessive methylation results in the formation of Lyso-Phosphatidylcholine (Lyso-PC), a dopaminergic neurotoxin, similar to MPTP/MPP+. It displaces D1 and D2 dopamine receptors from the cell membrane, while simultaneously inhibiting dopamine reuptake - essentially causing restlessness/akathisia/irritability.

In fact, injecting a single extremely high dose of SAMe (body's endogenous methyl donor) into the brains of mice causes severe dopaminergic disruption - Parkinsonian-like phenotype. Theoretically, high doses of methyl donor supplements may lead to higher SAMe levels than normally achievable by dietary ingestion of methyl donors in natural, unprocessed foods.

CDP-Choline has been shown to block the conversion of Phosphatidylcholine to Lyso-Phosphatidylcholine (PLA2 inhibitor), so certain Choline supplements may attenuate the formation of this neurotoxin, which is increased by excessive S-Adenosyl-L-Methionine (SAMe), the body's methyl donor.

I am not aware of papers showing Choline, in the form it is in Lecithin (Phosphatidylcholine), also has that effect, so this might be unique to CDP-Choline."

 

[drmullin30]

@jwat87 thanks very much for this. I'm wondering if I've been having this problem just lately since increasing my alpha-lipoic acid intake. I have had this restless/shaky feeling for the last few days. I had assumed it was some kind of oxalate dumping symptom causing hypocalcemia (calcium deficiency) but I may need to consider reducing my ALA or mb12 intake to compensate. I guess as my oxalate and toxin burden comes down I'll need fewer methyl donors to keep the cycle working. Very interesting these symptoms are very similar to calcium and potassium deficiency.

 

[Cnew2this]

That’s very interesting @jwat87 There is a lot of Parkinson’s in my family, so whenever I read about something messing with dopamine it gets my attention. And, I definitely have some serious irritability going on. I glanced at the links, but need to go back and read more thoroughly.

I’m trying to figure out what is driving my potassium deficiency and have read that choline is an antagonist to potassium. The info you provided gives me even more reason to cut back on choline. And, like drmullin30, I have decided recently that I probably have some calcium deficiency too.

Oxalate dumping has been on my list of future reading material since I started hearing about it from @drmullin30. It is probably time for me to get on that too.

 

[Cnew2this]

@drmullin30 Off topic for this thread, but I’ve been meaning to ask if you have thoughts on arginine and ornithine. I know you are concerned with ammonia too, and Roberts (heartfixer) says ornithine helps lower it.

Then I read on Yasko’s website that arginine can help with low potassium. So, I rushed out and bought both (in combo), but with a nagging feeling that I had read somewhere that I shouldn’t take arginine. I found that source – it is Lynch. He says it is not advised for people with high homocysteine. But then he doesn’t explain why. Thoughts?

 

[drmullin30]

@Cnew2this I tried arginine and ornithine very early on when I started following Yasko but it only increased my anxiety. Probably because they were in aspartate form. I was never able to find a good brand of ornithine or arginine that wasn't in aspartate form or gluten contaminated. Aspartates literally set my brain on fire with glutamate toxicity causing full blown panic attacks so they are a no go for me. So I've never really had a good shot at arginine or ornithine and I've always had to be careful with amino acids converting to glutamate because of my myriad GAD1 SNPs. I also remembered reading this about arginine from Roberts site: http://heartfixer.com/AMRI-Nutrigenomics.htm

"This deficiency in BH4 predisposes eNOS (endothelial nitric oxide synthase) to convert arginine in to free radicals (superoxide and peroxynitrite) as opposed to nitric oxide (atheroprotective vasodilator), predisposing you to hypertension and cardiovascular and inflammatory disease states. Those of you with reduced function alleles for the antioxidant enzymes SOD (superoxide dismutase), CAT (catalase), GPX (glutathione peroxidase), and PON1 (paraoxonase) may be challenged dealing with this superoxide free radical burden. "​

He continues:

Here ½ (+/-) or all (+/+) of your MTHFR enzymes are having trouble converting folic acid (or more precisely 5,10-methylene tetrahydrofolate) into 5-methyl folate. Without 5-methyl-folate (which we will shorten to methyl-folate) MTR cannot methylate homocysteine in to methionine and SAMe regeneration will be compromised. Methyl folate has another role - it can neutralize peroxynitrite. When NOS (nitric oxide synthase) is not functioning normally (i.e. when BH4 is deficient or if eNOS reduced function alleles are present), arginine is converted not in to the vasoprotective molecule nitric oxide, but rather in to the damaging free radicals superoxide and peroxynitrite. Superoxide (neutralized by Vitamin C) can further degrade nitric oxide, while peroxynitrite degrades BH4 (stimulating a vicious cycle).
​

So I don't consider arginine a treatment option anymore and I don't have the same issues around ammonia since starting higher dose methyl folate.

 

[Cnew2this]

@drmullin30 Thanks, as always, for taking the time to give me such detailed info.

The arginine/ornithine sup I have is Solgar, and they are just in free form. So no aspartate. I do avoid supps in that form ever since I started following Yasko.

But it sounds like no matter what form, arginine is probably not a good idea. I’m pretty sure that I don’t need more free radicals in my life.

So, I guess I will file that bottle in the supplement archive bin(s). Thanks again.

 

[Cnew2this]

@jwat87 and @drmullin30 I finally read jwat’s articles, to the best of my abilities, and see that I initially jumped to the wrong conclusion about choline. CDP-Choline blocks the formation of Lyso-Phosphatidylcholine. A good thing, right?

Those articles are pretty technical for my tired brain, but basically what I think is being described is what can happen in an overmethylated situation. I know drm doesn’t like the term “overmethylated” but I sure can’t help but feel that I am sometimes. I think that I may cycle back and forth between too little and too much.

It just so happens that I do have some CDP-Choline in my “supplement archives”. At some point in the past I must have read that it was a good thing, then decided it wasn’t. Lately I’ve been taking 350 mg of regular choline and just a touch of PC, plus PS which is probably adding some more PC. Maybe I would be better off with CDP-Choline instead of all of those?

 

[Levant]

Btw, saw niacin mentioned a few times on this thread and thought I'd pull up this comment on the limitations of no-flush niacin:
https://www.health.harvard.edu/news...-niacin-as-effective-as-other-kinds-of-niacin

No-flush niacin doesn't contain either nicotinic acid or nicotinamide. Instead, it contains inositol hexaniacinate. In theory, the body should slowly convert this into nicotinic acid. In reality, it doesn't. An excellent study by researchers at the University of Washington School of Medicine showed that taking no-flush niacin generates virtually no free nicotinic acid, and has little or no effect on HDL. No-flush niacin lives up to the no-flush part of its name because it isn't providing the body with any niacin.

 

[Cozi]

Just wondering what people's thoughts are on niacinamide for providing niacin? I think I may be a bit low and tried taking the proper flushing stuff yesterday. Actually want to use it for anxiety and depression, so I took 50mg with food. Mistake. The flush was immense, my knees and elbows (the bony parts weirdly, not near the lymph nodes where you might expect) were bright red and burning, rest of my body very pale and I ended up feeling so bad that I passed out. (Should say I have bad circulation and quite low blood pressure)

Has anyone had a bad niacin reaction?

Not keen to experience this again so wondering if I could get the niacin from niacinamide instead? Thanks for any thoughts!

 

[Pyrrhus]

Just wondering what people's thoughts are on niacinamide for providing niacin?

I took 50mg with food. Mistake. The flush was immense, my knees and elbows (the bony parts weirdly, not near the lymph nodes where you might expect) were bright red and burning, rest of my body very pale and I ended up feeling so bad that I passed out.

Not keen to experience this again so wondering if I could get the niacin from niacinamide instead?

Yes, niacinamide (AKA nicotinamide) is generally seen as a perfectly good replacement for niacin.
Many people say it's preferable to niacin.

There has been a lot of discussion here about other forms of niacin/niacinamide, as well.

 

[hapl808]

Does anyone have a brain fog friendly link to a summary of Yasko and Fredd protocols?

I found this thread because lately I've been researching neurotransmitters, methylation, lithium, low glutamate diets, low histamine diets, etc. As I'm mostly housebound, lately I've focused on the awful PEM that I get even from mental stimulation or focus.

I've experimented a bit with simple daily P5P 1.5mg, 400mcg Quatrefolic, mB12 1000mcg. Also tried adding benfotiamine or extra P5P, magnesium, NAC, SAMe, TMG, etc. But since my symptoms of CFS in general vary so much day to day, it's been very hard to figure out what is doing what if anything.

I'm C677T A/A, so that may be relevant on why I have some of these issues and what might help them, but seems to be a ton of conflicting information (like so many things).

So for people who have already gone down this path, I'm curious your suggestions and links to those protocols that you seem to be following or modifying. I recently stopped all my supplements so I can start over and also added lithium for the first time (which if I'd been taking B12 for years seems like it could have gotten depleted from what Yasko has written).

Anyways, thanks for any help!

 

[drmullin30]

Hello @hapl808 I've attached a pdf that went around here a few years ago that summarizes the Freddd protocol fairly well and I've attached one of Yasko's public domain books that is fairly strait forward.

Hope these help.

 

[hapl808]

Thanks very much - I'll read through these. Since I take it their approaches vary a bit, have you found more help with one or the other?