Acetyl-Choline Overload

GreenMachineX

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I'm now convinced that I have an issue with choline build up causing many symptoms. Does anyone else have an issue with this? The worst symptom it gives me is horrendous insomnia. For years, I've thought it was too much or too little b12/methylfolate, norepinephrine overload, etc, but the reality is my pulse is just 60 when I'm laying there at 3am wide awake, sometimes hands and feet are sweaty but 100% completely calm (no anxiety, but maybe irritated). When I do sleep, it's terribly light like I'm basically awake but unconscious.

So far, all I've come up with is to take Lipoic Acid (just bought Na-R-ALA but it won't be here for a few days). Is there anything else? I have on hand hydroxyzine, but I've read I can't mix lemon balm with antihistamines (stopped the lemon balm last night). Anyone have any thoughts?
 

Pyrrhus

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Since choline synthesis in the body consumes a large percentage of the body's methyl donors, taking supplemental choline should free up a large percentage of the body's methylation capacity, perhaps more than 50%. Therefore, choline supplements can come with the same negative start-up effects as other supplements that boost the body's methylation capacity.

If you're interested, various patient experiences with choline are described in these discussions:

In my own personal case:
In my own personal case, a single dose of 300mg glycero-phospho-choline (GPC) caused temporary start-up effects of headache, weakness, worsened brain fog, worsened light/sound sensitivity, depression/irritability, preceded by a brief burst of energy and appetite loss.

Over a few weeks, these start-up effects faded and I was able to tolerate two daily doses of 300mg GPC without any problems.

Hope this helps.
 

GreenMachineX

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Since choline synthesis in the body consumes a large percentage of the body's methyl donors, taking supplemental choline should free up a large percentage of the body's methylation capacity, perhaps more than 50%. Therefore, choline supplements can come with the same negative start-up effects as other supplements that boost the body's methylation capacity.

If you're interested, various patient experiences with choline are described in these discussions:



In my own personal case:



Hope this helps.
Well, maybe I'm less convinced now it's choline as an issue. I'm so lost. Thanks though. Definitely helpful.

I guess an easy way to test choline as a problem would be to just take a dose of choline bitartrate and see what happens.
 

Mary

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High cortisol middle of the night causes severe insomnia for me. And I don't always feel anxious. Seriphos is very helpful to me when this happens, but I have to take it in the morning - taking it before bed causes horrible insomnia for me. Note: seriphos is phosphorylated serine, not to be confused with phosphatidyl serine, which does not work nearly as well. Unfortunately, it seems to be out of stock just about everywhere right now (like so many things!)

Magnesium also helps me with sleep, I take it before bed and middle of the night. I can't get completely away from middle of the night insomnia but take a couple of things which sometimes help - niacin (the kind that makes you flush, both before bed and middle of the night), taurine (before bed), glycine (before bed), gotu kola (before bed). Also, epsom salt bath before bed can help too. Some things help a lot initially, but my body seems to adapt to them pretty quickly and then I have to find something new - it seems my body is determined not to sleep!

This product by Swanson Vitamins was very powerful initially, but after a relatively short time became less effective, though I still take it before bed and middle of the night: Chamomile Flower Extract Supplement - Swanson Health Products (swansonvitamins.com)

And box or 4-sided breathing sometimes helps me go back to sleep, if I do it for at least 15 minutes or so when I can't sleep: How To De-Stress In 5 Minutes Or Less, According To A Navy SEAL (forbes.com)

When I do it, I'll inhale for a count of five, hold my breath for a count of 8 or 9 (had to build up to that), exhale slowly to count of 8 or 9, and hold again for 8 or 9. All the inhale and exhaling is done through your nose - keep your mouth closed the whole time.

I keep thinking if I ever can start sleeping naturally or normally without any support, it will be a sign that maybe I'm recovering! or at least getting started on it - can only hope!

Also, grounding helps when it's warm enough to sit outside with my feet on the ground, but I have to do it at least for an hour to make a difference, and the longer the better. I only have cement and rocks where I live (high desert) but the cement works. I read that as long as it's not sealed it should be effective. I didn't know if it was sealed or not but tried it anyways, and it does help.
 

GreenMachineX

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High cortisol middle of the night causes severe insomnia for me. And I don't always feel anxious. Seriphos is very helpful to me when this happens, but I have to take it in the morning - taking it before bed causes horrible insomnia for me. Note: seriphos is phosphorylated serine, not to be confused with phosphatidyl serine, which does not work nearly as well. Unfortunately, it seems to be out of stock just about everywhere right now (like so many things!)

Magnesium also helps me with sleep, I take it before bed and middle of the night. I can't get completely away from middle of the night insomnia but take a couple of things which sometimes help - niacin (the kind that makes you flush, both before bed and middle of the night), taurine (before bed), glycine (before bed), gotu kola (before bed). Also, epsom salt bath before bed can help too. Some things help a lot initially, but my body seems to adapt to them pretty quickly and then I have to find something new - it seems my body is determined not to sleep!

This product by Swanson Vitamins was very powerful initially, but after a relatively short time became less effective, though I still take it before bed and middle of the night: Chamomile Flower Extract Supplement - Swanson Health Products (swansonvitamins.com)

And box or 4-sided breathing sometimes helps me go back to sleep, if I do it for at least 15 minutes or so when I can't sleep: How To De-Stress In 5 Minutes Or Less, According To A Navy SEAL (forbes.com)

When I do it, I'll inhale for a count of five, hold my breath for a count of 8 or 9 (had to build up to that), exhale slowly to count of 8 or 9, and hold again for 8 or 9. All the inhale and exhaling is done through your nose - keep your mouth closed the whole time.

I keep thinking if I ever can start sleeping naturally or normally without any support, it will be a sign that maybe I'm recovering! or at least getting started on it - can only hope!

Also, grounding helps when it's warm enough to sit outside with my feet on the ground, but I have to do it at least for an hour to make a difference, and the longer the better. I only have cement and rocks where I live (high desert) but the cement works. I read that as long as it's not sealed it should be effective. I didn't know if it was sealed or not but tried it anyways, and it does help.

Thanks Mary. I've also wondered if the issue is cortisol and even histamine. My concern with something like Seriphos, is that I believe my day time cortisol is already too low. I don't know how it happens, but it seems like my diurnal rhythm is flipped. I've been having mild success taking 3mg melatonin, 200mg theanine and 50-100mg niacin which puts me back to sleep for roughly an hour or 2 and I do that 3 times per night. I do take 300mg magnesium right before bed and another 150mg middle of night. How much niacin do you use?

Lemon balm seems to have lost effectiveness, but I also have magnolia bark and cbd/cbg, and I have inositol on the way. I'm on telmisartan for blood pressure so I've been hesitant to use the magnolia bark for fear of interactions (also why I haven't used the hydroxyzine yet).

Methyl b12 and methylfolate are definitely part of this equation for me as well, but having trouble figuring out the right combo. What used to work for me was 300mcg methyl b12, 600mcg methylfolate, and 5 whole welland Eggland Best eggs with 100g Shonen which provided 120% folate from food. That worked for years but now that makes me feel terrible and worsens the insomnia.

I do have recent bloodwork showing bottom of normal range b12 and folate just above normal range. Maybe I finally fixed folate deficiency (had terrible angular cheilitis, zero nail growth, water weight gain, etc) and now maybe this is b12 deficiency or folate trap? That blood work was 2 or 3 days drawn after any supplemental vitamins. One thing is I cannot try Fred's methylation protocol because I'm too sensitive to methyls. I've been to the ER too many times fire trying it and similar things. I seem to respond to low doses of any b vitamin. I do have some r5p b2 here that in the past felt like a sedative, but that was at 10mg capsule (and I only used half!), now the only thing I've found was 36mg and afraid to try to weigh out only 5mg from that.

I forgot to add that it also seems like some things meant for sleep keep me awake, Chamomile being one of them. I'll look into grounding as well, but sadly that breathing technique doesn't work for me as I've tried it and other various ways before. Taurine and glycine are a couple others that wake me up at 1am, then I'm up for hours.


Any thoughts on any of that?
 
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Learner1

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My concern with something like Seriphos, is that I believe my day time cortisol is already too low. I don't know how it happens, but it seems like my diurnal rhythm is flipped.
That's exactly what Seriphos is good for, flipping the diurnal cortisol pattern. Try taking a capsule about an hour before bed for a month and see if it helps.

You should also do a 24 hour saliva or cortisol test if that doesn't work. Also, Seriphos is different than other phosphatidyl serine supplements, do make sure you get the actual product.
I've also wondered if the issue is cortisol and even histamine.
Have you had histamine checked? Prostaglandin D3 or F2?
50-100mg niacin which puts me back to sleep for roughly an hour or 2 and I do that 3 times per night. I do take 300mg magnesium right before bed and another 150mg middle of night. How much niacin do you use?
What kind of magnesium do you take? Magnesium glycinate is good for sleep.
I do have recent bloodwork showing bottom of normal range b12 and folate just above normal range. Maybe I finally fixed folate deficiency (had terrible angular cheilitis, zero nail growth, water weight gain, etc) and now maybe this is b12 deficiency or folate trap? That blood work was 2 or 3 days drawn after any supplemental vitamins. One thing is I cannot try Fred's methylation protocol because I'm too sensitive to methyls. I've been to the ER too many times fire trying it and similar things. I seem to respond to low doses of any b vitamin. I do have some r5p b2 here that in the past felt like a sedative, but that was at 10mg capsule (and I only used half!), now the only thing I've found was 36mg and afraid to try to weigh out only 5mg from that.
You need more than folate and B12 for methylation. Vitamin B6 (in the form of pyridoxal-5-phosphate) is used in methylation and 100 other biochemical processes. R5P is needed too. Also, magnesium, zinc, and potassium. Then you need ample glycine, glutamine and cysteine (NAC) to make glutathione and C to recycle the glutathione. And B1 and molybdenum to make the transsulfuration pathway work. And you need NAD+.



Additionally, have you looked into ammonia? Too much can really disturb sleep. Lack of BH4, citrulline and ornithine can be causes, so supplementing with any or all may help.
 

Violeta

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Cortisol increases your heart rate, and your heart rate is only 60 when you are experiencing these symptoms.

So what might actually be happening is you are tanking on neurotransmitters such as norepinephrine. This is just a possibility to think about while everyone is brainstorming. This is what was happening with me. So now when I can't sleep things like tyrosine or Butcher's Broom can help.

One morning before figuring it out my heart rate was 53 while lying in bed, I felt like I couldn't move but knew I had to. That was happening so frequently, but isn't nearly as bad now.
 
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GreenMachineX

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That's exactly what Seriphos is good for, flipping the diurnal cortisol pattern. Try taking a capsule about an hour before bed for a month and see if it helps.

You should also do a 24 hour saliva or cortisol test if that doesn't work. Also, Seriphos is different than other phosphatidyl serine supplements, do make sure you get the actual product.
Have you had histamine checked? Prostaglandin D3 or F2?
What kind of magnesium do you take? Magnesium glycinate is good for sleep.

You need more than folate and B12 for methylation. Vitamin B6 (in the form of pyridoxal-5-phosphate) is used in methylation and 100 other biochemical processes. R5P is needed too. Also, magnesium, zinc, and potassium. Then you need ample glycine, glutamine and cysteine (NAC) to make glutathione and C to recycle the glutathione. And B1 and molybdenum to make the transsulfuration pathway work. And you need NAD+.



Additionally, have you looked into ammonia? Too much can really disturb sleep. Lack of BH4, citrulline and ornithine can be causes, so supplementing with any or all may help.
I should've mentioned that I take 1 Thorne 2 Per Day which is where I get the b12 and other vitamins. I was using Thorne Men 50+ for about a year, but I think that's what led me to this current problem.

I'll look into Seriphos...thanks!

I haven't had those blood tests done, but I know my doctor won't do it. Is there a place you recommend I can buy it myself?

I use magnesium citrate because Glycinate gives me horrible insomnia too.

I have NAC, but haven't used it yet. Used it years ago in a previous life, but since I react to everything these days, I've been nervous about that too.

Citrulline I just started again because I use it pre-workout, and began attempting to work out again. Nothing like I used to do sadly, but it's something.

For what it's worth, this is what I take:
1 capsule of Thorne 2 Per Day
5000iu vitamin D
2g EPA/DHA fish oil
450-600mg magnesium citrate
8g citrulline malate (or 4g citrulline)
2g vitamin C
600-800mg theanine
150mg nicotinic acid
3-9mg melatonin
2tbsp ground flaxseed
125mcg synthroid (all thyroid labs look good with this oddly enough)
40mg telmisartan
400mg Ecdysterone
TRT

Thanks all to who are replying!
 

GreenMachineX

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Cortisol increases your heart rate, and your heart rate is only 60 when you are experiencing these symptoms.

So what might actually be happening is you are tanking on neurotransmitters such as norepinephrine. This is just a possibility to think about while everyone is brainstorming. This is what was happening with me. So now when I can't sleep things like tyrosine or Butcher's Broom can help.

One morning before figuring it out my heart rate was 53 while lying in bed, I felt like I couldn't move but knew I had to. That was happening so frequently, but isn't nearly as bad now.
So low amounts of neurotransmitters like norepinephrine cause insomnia??? Definitely thought it would be the opposite. I was thinking maybe I'm also low on serotonin, which if I recall correctly is the neurotransmitter responsible for feeling satisfied (which is never for me) while dopamine is the drive for pleasure which I have plenty of (so junk like video games never satisfy, or never enough food, etc). This is where inositol could come into play, right? Due to the sweaty palms and anxiety during the day, in addition my heart rate staying elevated all day long, I figured my norepinephrine was too high all the time. My resting heart rate can go to 57-58, but when I stand up and walk around it jumps to 80-90. Then moderate exercise it goes to 140 which doesn't make sense I don't think on a light jog.

For the record, today I took 1 Thorne 2 per day, and ate about zero vegetable folate with breakfast with 4 whole brown organic eggs and this is the most *normal* I've felt in weeks...maybe months! Maybe I'm on to something about not enough b12 for the amount of folate I have and eat typically...
 
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It sounds like you and I have similar reactions to supplements and I’ve been trying to figure out my insomnia lately too, which started with me taking a prescription that enhances cholinergic transmission.

So, that led me to suspect acetylcholine but it‘s confusing because in the past, things that increase acetylcholine (like mestinon) haven’t caused this… taking citi-choline did make me feel bad but I don’t remember how.

I also thought of histamines so I tried taking a weaker antihistamine (it doesn’t cross the bbb as much as diphenhydramine or hydroxyzine), cetirizine, which only makes me very slightly drowsy. For 2 nights I’ve slept better with it but I still have some trouble falling asleep initially.

My brain also feels a little calmer during the day which is helpful because I’ve had terrible brain fog.

Cetirizine is only a weak anticholinergic, so I don’t know if it’s the histamine or choline situation that it’s helping (or maybe I’m just feeling better with a little more sleep?)? It might not be the answer to my problems but we’ll see.

Lemon balm used to help me too and it supposed to increase acetylcholine (decrease its breakdown).

My thought is that maybe it’s an increase in choline (increasing methylation like mentioned) causing the problem and not acetylcholine. Or it’s histamine… Or I also liked @Violeta ’s suggestion of tanking neurotransmitters, that makes sense to me too :lol:
 

GreenMachineX

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It sounds like you and I have similar reactions to supplements and I’ve been trying to figure out my insomnia lately too, which started with me taking a prescription that enhances cholinergic transmission.

So, that led me to suspect acetylcholine but it‘s confusing because in the past, things that increase acetylcholine (like mestinon) haven’t caused this… taking citi-choline did make me feel bad but I don’t remember how.

I also thought of histamines so I tried taking a weaker antihistamine (it doesn’t cross the bbb as much as diphenhydramine or hydroxyzine), cetirizine, which only makes me very slightly drowsy. For 2 nights I’ve slept better with it but I still have some trouble falling asleep initially.

My brain also feels a little calmer during the day which is helpful because I’ve had terrible brain fog.

Cetirizine is only a weak anticholinergic, so I don’t know if it’s the histamine or choline situation that it’s helping (or maybe I’m just feeling better with a little more sleep?)? It might not be the answer to my problems but we’ll see.

Lemon balm used to help me too and it supposed to increase acetylcholine (decrease its breakdown).

My thought is that maybe it’s an increase in choline (increasing methylation like mentioned) causing the problem and not acetylcholine. Or it’s histamine… Or I also liked @Violeta ’s suggestion of tanking neurotransmitters, that makes sense to me too :lol:
Our situations do sound similar.

Aren't choline and acetylcholine basically the same thing though?

In another day or 2 I'll try the hydroxyzine if this doesn't resolve by then.
 

Mary

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I do take 300mg magnesium right before bed and another 150mg middle of night. How much niacin do you use?
It looks like we've tried many of the same things! I used to take 400 mg magnesium glycinate before bed and 300 mg more middle of the night. Now I spread it more throughout the day, 100 mg with breakfast and lunch, 200 mg with dinner, 200 mg before bed and 200 mg middle of the night.

For niacin, I take 400 mg before bed and 300 mg middle of the night. I found the kind that makes you flush works the best. I tried it once in the morning but it made me tired - I think probably slowed down methylation, but it helps me sleep at night.
I forgot to add that it also seems like some things meant for sleep keep me awake, Chamomile being one of them. I'll look into grounding as well, but sadly that breathing technique doesn't work for me as I've tried it and other various ways before. Taurine and glycine are a couple others that wake me up at 1am, then I'm up for hours.


Any thoughts on any of that?
Afraid not - Sorry! It's crazy that so many of us have paradoxical reactions to various things. And I'm really not an expert on Freddd's protocol or methylation. All I know is that folate has helped my energy quite a bit, but it also caused potassium deficiency, and I've had to supplement with potassium for over 10 years now, but that's fine - it works and I'm able to keep taking folate.

About Seriphos - it worked best for me taking it in the morning. But I don't think my cortisol pattern is flipped so I think trying it at night is worth a try, as @Learner1 suggested. When I took it at night, it gave me horrible insomnia.

I am having a conundrum I'm trying to sort out right now - it's my paradoxical reaction to l-citrulline and possibly beet juice. This is tangentially related to sleep so hopefully not too off-topic. I tried l-citrulline for energy and to lower BP, . It worked really well for energy, but then raised my BP alarmingly high (in the 180's). I tried it again the other day after not taking it for a year - it gave me a little energy, but my BP spiked again. It's supposed to be a vasodilator and lower BP, not raise it.

Anyways, I drank some beet juice the other night (to lower my BP from the l-citrulline) and it helped, and also, I slept pretty well that night. I didn't make the connection until last night I was wrestling again wtih middle of the night insomnia and remembered the beet juice from the other night. So I opened a can of beets and drank the juice and was back to sleep within 15 - 30 minutes, and slept the rest of the night - only my BP was higher this morning instead of lower! arrggghhh!!! I have to experiment some more - but the beet juice really did seem to help my sleep a lot. So you might give it a try. There are a lot of powdered beet supplements but they didn't do much for me. I want to experiment some more with this - I believe it all has to do with NO, and now am looking into Martin Pall's protocol, thanks to @Learner1 .

Anyways, you might look into NO (nitric oxide) and sleep. btw, beet juice has lowered my BP before so I hope last night was just an anomaly, but have to experiment some more.

ETA: Beets are high in oxalates, which doesn't seem to be a problem for me though it is for many people.
 

GreenMachineX

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It looks like we've tried many of the same things! I used to take 400 mg magnesium glycinate before bed and 300 mg more middle of the night. Now I spread it more throughout the day, 100 mg with breakfast and lunch, 200 mg with dinner, 200 mg before bed and 200 mg middle of the night.

For niacin, I take 400 mg before bed and 300 mg middle of the night. I found the kind that makes you flush works the best. I tried it once in the morning but it made me tired - I think probably slowed down methylation, but it helps me sleep at night.

Afraid not - Sorry! It's crazy that so many of us have paradoxical reactions to various things. And I'm really not an expert on Freddd's protocol or methylation. All I know is that folate has helped my energy quite a bit, but it also caused potassium deficiency, and I've had to supplement with potassium for over 10 years now, but that's fine - it works and I'm able to keep taking folate.

About Seriphos - it worked best for me taking it in the morning. But I don't think my cortisol pattern is flipped so I think trying it at night is worth a try, as @Learner1 suggested. When I took it at night, it gave me horrible insomnia.

I am having a conundrum I'm trying to sort out right now - it's my paradoxical reaction to l-citrulline and possibly beet juice. This is tangentially related to sleep so hopefully not too off-topic. I tried l-citrulline for energy and to lower BP, . It worked really well for energy, but then raised my BP alarmingly high (in the 180's). I tried it again the other day after not taking it for a year - it gave me a little energy, but my BP spiked again. It's supposed to be a vasodilator and lower BP, not raise it.

Anyways, I drank some beet juice the other night (to lower my BP from the l-citrulline) and it helped, and also, I slept pretty well that night. I didn't make the connection until last night I was wrestling again wtih middle of the night insomnia and remembered the beet juice from the other night. So I opened a can of beets and drank the juice and was back to sleep within 15 - 30 minutes, and slept the rest of the night - only my BP was higher this morning instead of lower! arrggghhh!!! I have to experiment some more - but the beet juice really did seem to help my sleep a lot. So you might give it a try. There are a lot of powdered beet supplements but they didn't do much for me. I want to experiment some more with this - I believe it all has to do with NO, and now am looking into Martin Pall's protocol, thanks to @Learner1 .

Anyways, you might look into NO (nitric oxide) and sleep. btw, beet juice has lowered my BP before so I hope last night was just an anomaly, but have to experiment some more.

ETA: Beets are high in oxalates, which doesn't seem to be a problem for me though it is for many people.
It does look like we've tried many of the and things!

Also looks like I need to up my niacin! I've been nervous about going to high but your doses blow mine away. If I have insomnia again tonight, I'll try 150mg.

How high is your blood pressure? How high does it go?

One thing I forgot to mention that occasionally works is 500mg Celtic sea salt or pink salt in some water. That works particularly well when I've done something wrong and have overmethylation/overstimulation.

That's very interesting that citrulline made your bp go up. I feel nothing from it and it does bring my BP down just a few points. Citrulline malate on the other hand does nothing for my BP but does increase exercise performance (but again, no energy that I can feel). Beet juice...nervous about things that are strong blood pressure reducers like that. Maybe I just need to come off the telmisartan so I can use all this other stuff. On the flip side, I like the covid protection it offers...

Today still is the best day I've had in a long time, as in, feeling almost normal. I have high hopes for sleep tonight!
 
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I forgot to add that it also seems like some things meant for sleep keep me awake, Chamomile being one of them.
Like you, I seem to have a determined paradoxical response to a lot of the herbal things that help others in PR, but give me anxiety, twitchiness, and insomnia. Valerian is the worst, but passion flower, chamomile, hops, and several others get trophies, too.


So you're not alone, for what that's worth.
I use magnesium citrate because Glycinate gives me horrible insomnia too.
I've been using magnesium glycinate for a couple of years now, in very high amounts. For some reason, and in spite of sensitivity to glutamate, it doesnt seem to bother me. Which is fortunate, because mag citrate sends me screaming to the bathroom almost instantaneously. But we're all different, so if it works for you, rock on !!!!
 

GreenMachineX

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Does anyone else who has posted in here get out of breath at weird times? I can exercise just fine most of the time but then occasionally (usually after breakfast or lunch) I get super winded going up the stairs. Or sometimes when I lay down in the middle of the night after using the restroom (but fine going to the restroom)...? This out-of-place shortness of breath always comes when I'm also dealing with insomnia, oddly enough.