Benadryl & Acetylcholine

[Green Dot]

"A series of experiments that started at the University of California in 1960 found that rats that lived in larger spaces with various things to explore were better at learning and solving problems than rats that were raised in the standard little laboratory cages (Krech, et at, 1960). Studying their brains, they found that the enzyme cholinesterase, which destroys the neurotransmitter, acetylcholine, was increased. They later found that the offspring of these rats were better learners than their parents, and their brains contained more cholinesterase. Their brains were also larger, with a considerable thickening of the cortex, which is considered to be the part mainly responsible for complex behavior, learning and intelligence."

From a quick Google search: Diphenhydramine (e.g., Benadryl®) is a first-generation antihistamine medication. In addition to treating allergy and cold symptoms such as sneezing and watery eyes, it also blocks the actions of acetylcholine. This is a neurotransmitter that is important for brain functions including learning and memory.

Seems like they're under the impression that acetylcholine is beneficial though.

 

[Green Dot]

View: https://youtu.be/I3WuHjydbMU?t=975

 

[mostlylurking]

"A series of experiments that started at the University of California in 1960 found that rats that lived in larger spaces with various things to explore were better at learning and solving problems than rats that were raised in the standard little laboratory cages (Krech, et at, 1960). Studying their brains, they found that the enzyme cholinesterase, which destroys the neurotransmitter, acetylcholine, was increased. They later found that the offspring of these rats were better learners than their parents, and their brains contained more cholinesterase. Their brains were also larger, with a considerable thickening of the cortex, which is considered to be the part mainly responsible for complex behavior, learning and intelligence."

From a quick Google search: Diphenhydramine (e.g., Benadryl®) is a first-generation antihistamine medication. In addition to treating allergy and cold symptoms such as sneezing and watery eyes, it also blocks the actions of acetylcholine. This is a neurotransmitter that is important for brain functions including learning and memory.

Seems like they're under the impression that acetylcholine is beneficial though.

I've been interested in this subject and I've found some things about it. I think Peat is right about acetylcholine being a problem but there seems to be a lot of confusion about it. I've been looking into it in relationship to thiamine. This seems to be a complicated issue with multiple steps.

I found this article: Acetyl-CoA and acetylcholine metabolism in nerve terminal compartment of thiamine deficient rat brain - PubMed
the whole article is here: https://onlinelibrary.wiley.com/doi...JA7oPkyO7sk-1635255923-0-gqNtZGzNAjujcnBszQuR
quote:
"The decrease of pyruvate and ketoglutarate dehydrogenase complex activities is the main cause of energy and acetyl-CoA deficits in thiamine deficiency-evoked cholinergic encephalopathies. However, disturbances in pathways of acetyl-CoA metabolism leading to appearance of cholinergic deficits remain unknown. Therefore, the aim of this work was to investigate alterations in concentration and distribution of acetyl-CoA and in acetylcholine metabolism in brain nerve terminals, caused by thiamine deficits. They were induced by the pyrithiamine, a potent inhibitor of thiamine pyrophosphokinase. The thiamine deficit reduced metabolic fluxes through pyruvate and ketoglutarate dehydrogenase steps, yielding deficits of acetyl-CoA in mitochondrial and cytoplasmic compartments of K-depolarized nerve terminals. It also inhibited indirect transport of acetyl-CoA though ATP-citrate lyase pathway being without effect on its direct Ca-dependent transport to synaptoplasm. Resulting suppression of synaptoplasmic acetyl-CoA correlated with inhibition of quantal acetylcholine release (r = 0.91, p = 0.012). On the other hand, thiamine deficiency activated non-quantal acetylcholine release that was independent of shifts in intraterminal distribution of acetyl-CoA. Choline acetyltransferase activity was not changed by these conditions. These data indicate that divergent alterations in the release of non-quantal and quantal acetylcholine pools from thiamine deficient nerve terminals could be caused by the inhibition of acetyl-CoA and citrate synthesis in their mitochondria. They in turn, caused inhibition of acetyl-CoA transport to the synaptoplasmic compartment through ATP-citrate lyase pathway yielding deficits of cholinergic functions."

I think that Ray Peat is correct in that the problem is caused by a deficit of acetyl-CoA or its functional blockage, which makes acetylcholine get too high or work incorrectly. I am interested in the role of thiamine in this issue.

 

[CoconutEffect]

Very positive effects on depression and anxiety, and sleep.

 

[Mastodonhugger]

Are there any downsides with taking a Benadryl daily?

 

[InChristAlone]

My Mom has been taking benedryl everyday for like 20 yrs. No signs of dementia yet.

 

[crsnpalmer]

interested in lowering acetylcholine. Are there any foods that can help?

 

[aniciete]

Increasing acetylcholine makes me feel warmer and improves mood. Any anticholinergic leaves me feeling drained and constipated.

 

[redsun]

interested in lowering acetylcholine. Are there any foods that can help?

What symptoms do you have that you attribute to excess acetylcholine?

 

[crsnpalmer]

What symptoms do you have that you attribute to excess acetylcholine?

I am trying to improve my ability to relax at night. I hyperventilate most nights and cannot seem to stay in the parasympathetic state. Mind races a lot. I think it is related to estrogen, cortisol, serotonin, and acetylcholine.

Some symptoms are throat constriction, facial flushing, and occasional muscle twitching. I do not sweat often. Cold hands and feet have gone away with adequate caloric intake.

I had bouts of high stress growing up and throughout college. I’m on a vacation right now and seeing family members’ behavior patterns has been stressing me out. Alcoholism, terrible nutrition, etc. I tend to develop these states of learned helplessness on these trips.

I abused nicotine( Juul e vape) and THC( delta 8) in college. I do neither of these now. Makes me wonder if serotonin and acetylcholine are the culprits.

Diet:
Most days: eggs, coffee, honey, milk, OJ, red meat, gelatin, sugar, ice cream

1-2x a week: potatoes, oysters, shrimp, soda, carrot salad

Supplements: digestive enzyme, betaine HCL, and magnesium, b1, and creatine



Do you think this could be related to excess acetylcholine? I had a drink 2 nights ago and couldn’t forget how relaxed/good I felt. Stumbled upon an article from “F$%k Portion Control,” and it discussed how acetylcholine is inhibited by alcohol.

 

[redsun]

I am trying to improve my ability to relax at night. I hyperventilate most nights and cannot seem to stay in the parasympathetic state. Mind races a lot. I think it is related to estrogen, cortisol, serotonin, and acetylcholine.

Some symptoms are throat constriction, facial flushing, and occasional muscle twitching. I do not sweat often. Cold hands and feet have gone away with adequate caloric intake.

I had bouts of high stress growing up and throughout college. I’m on a vacation right now and seeing family members’ behavior patterns has been stressing me out. Alcoholism, terrible nutrition, etc. I tend to develop these states of learned helplessness on these trips.

I abused nicotine( Juul e vape) and THC( delta 8) in college. I do neither of these now. Makes me wonder if serotonin and acetylcholine are the culprits.

Diet:
Most days: eggs, coffee, honey, milk, OJ, red meat, gelatin, sugar, ice cream

1-2x a week: potatoes, oysters, shrimp, soda, carrot salad

Supplements: digestive enzyme, betaine HCL, and magnesium, b1, and creatine



Do you think this could be related to excess acetylcholine? I had a drink 2 nights ago and couldn’t forget how relaxed/good I felt. Stumbled upon an article from “F$%k Portion Control,” and it discussed how acetylcholine is inhibited by alcohol.

What about your heart rate? Is it elevated at night? Do you feel your heart pounding when trying to sleep?

Alcohol lowers glutamate and can actually increase nicotinic receptor activation as well as a bunch of other things which make you able to relax.

Hans has an article that goes more in depth on these effects:

Substituting/enhancing the effects of alcohol with these exceptional supplements » MENELITE

Alcohol is one of the most abused beverages out there. And why is that? Because it makes people feel amazing. It helps them calm down, remove their brakes that inhibit … Continue reading Substituting/enhancing the effects of alcohol with these exceptional supplements

men-elite.com

You probably have high glutamate. You need to try lowering that. But you also seem to have a control problem. Try to remember you are not responsible for you family members behavior and dietary habits. You should barely get bothered by it if at all. It makes no sense to get so riled by other people's choices. Everyone is their own conscious person who makes their own choices.

But regardless. Likely you don't have high acetylcholine but low and high adrenaline levels causing you to hyperventilate. Acetylcholine is the major parasympathetic neurotransmitter and it slows down the heart rate and ventilation rate so you don't breathe so hard.

Zinc in high doses can lower acetylcholine, and it also is a GABA-A antagonist. This means zinc in excess (very easy to get excess from oysters) can be anxiogenic and promote excessive stress and worry since gaba is vital for controlling glutamate and noradrenaline. Oysters are very high in zinc so I would avoid them completely for this reason.

Gelatin is high in glycine, and NMDA agonist. NMDA is a major glutamate receptor and too high glutamate can be making you tense and stressed. Some report less stress from glycine and gelatin, some get wired and insomnia from it.

I can see you barely eat starch. I would suggest incorporating white rice into your daily diet. Many people get constant adrenaline and stress reactions from a high sugar diet with little starch. I would replace some of the sugar your eating with starch. I would also try to get 700-800mg of choline daily. You eat eggs and meat, and there is some choline in milk so I would try to figure out how much you get and see if its enough. This will help reduce stress.

Coffee is an obvious issue because it is a stimulant. It really depends on how much you take and how far away from bed you take it. I would not consume more than 200mg of caffeine a day. If the other advice does not help enough then likely you may need to reduce caffeine intake.

 

[crsnpalmer]

What about your heart rate? Is it elevated at night? Do you feel your heart pounding when trying to sleep?

Alcohol lowers glutamate and can actually increase nicotinic receptor activation as well as a bunch of other things which make you able to relax.

I do feel my heart pounding some nights. My whoop band says my resting heart rate is around 47-52 bpm. I do not know if this is high or low?

You probably have high glutamate. You need to try lowering that. But you also seem to have a control problem. Try to remember you are not responsible for you family members behavior and dietary habits. You should barely get bothered by it if at all. It makes no sense to get so riled by other people's choices. Everyone is their own conscious person who makes their own choices.

But regardless. Likely you don't have high acetylcholine but low and high adrenaline levels causing you to hyperventilate. Acetylcholine is the major parasympathetic neurotransmitter and it slows down the heart rate and ventilation rate so you don't breathe so hard.

This is true. I need to become more self-aware of my need to control.

Gelatin is high in glycine, and NMDA agonist. NMDA is a major glutamate receptor and too high glutamate can be making you tense and stressed. Some report less stress from glycine and gelatin, some get wired and insomnia from it.

I can see you barely eat starch. I would suggest incorporating white rice into your daily diet. Many people get constant adrenaline and stress reactions from a high sugar diet with little starch. I would replace some of the sugar your eating with starch. I would also try to get 700-800mg of choline daily. You eat eggs and meat, and there is some choline in milk so I would try to figure out how much you get and see if its enough. This will help reduce stress.

Coffee is an obvious issue because it is a stimulant. It really depends on how much you take and how far away from bed you take it. I would not consume more than 200mg of caffeine a day. If the other advice does not help enough then likely you may need to reduce caffeine intake.

Glycine does make me wired sometimes!! Always wondered what was going on. I am going to incorporate more starches. I was avoiding them thinking endotoxin could be creating the symptoms.

Is 300-400mg of caffeine too much? I tend to stop after 11 am. and go to sleep around 10-11 pm.

I appreciate all of the insights redsun! lots of reading to do today.

 

[redsun]

I do feel my heart pounding some nights. My whoop band says my resting heart rate is around 47-52 bpm. I do not know if this is high or low?

This is true. I need to become more self-aware of my need to control.


Glycine does make me wired sometimes!! Always wondered what was going on. I am going to incorporate more starches. I was avoiding them thinking endotoxin could be creating the symptoms.

Is 300-400mg of caffeine too much? I tend to stop after 11 am. and go to sleep around 10-11 pm.

I appreciate all of the insights redsun! lots of reading to do today.

I think that band you are using is not accurately measuring your heart rate. That is quite low for a reading especially if you got that reading on nights you had heart pounding. Usually this signifies low acetylcholine activity in the heart which makes it difficult for your metabolism to slow down and for you to be able to calm down and sleep.

In my opinion that is a lot of caffeine, I would try to work your way down to 200mg or less. This can really be making your stress worse.

 

[crsnpalmer]

I think that band you are using is not accurately measuring your heart rate. That is quite low for a reading especially if you got that reading on nights you had heart pounding. Usually this signifies low acetylcholine activity in the heart which makes it difficult for your metabolism to slow down and for you to be able to calm down and sleep.

In my opinion that is a lot of caffeine, I would try to work your way down to 200mg or less. This can really be making your stress worse.

I will reduce my caffeine intake. The whoop band could definitely be off. I am incorporating white rice and more eggs into my diet today. Should I drop any of the supplements I listed?

 

[redsun]

I will reduce my caffeine intake. The whoop band could definitely be off. I am incorporating white rice and more eggs into my diet today. Should I drop any of the supplements I listed?

None of the things you mentioned are harmful in appropriate amounts, just avoid megadoses of stuff.

 

[Hesperian]

Are there any downsides with taking a Benadryl daily?

My Mom has been taking benedryl everyday for like 20 yrs. No signs of dementia yet.

I had frequent allergies growing up, so I took Benedryl regularly. Later I lived in a house with very poor air quality and would take Benedryl somewhat often. Around six or seven years ago I noticed Benedryl gives me dysphoria. Like clockwork, every single time. I tend to be depressed generally speaking, but after taking Benedryl there's a very noticeable and drastic change in mood for the worse.

 

[InChristAlone]

I had frequent allergies growing up, so I took Benedryl regularly. Later I lived in a house with very poor air quality and would take Benedryl somewhat often. Around six or seven years ago I noticed Benedryl gives me dysphoria. Like clockwork, every single time. I tend to be depressed generally speaking, but after taking Benedryl there's a very noticeable and drastic change in mood for the worse.

Yeah antihistamines can lower dopamine as well.

 

[Hesperian]

Yeah antihistamines can lower dopamine as well.

Didn't know that. Makes perfect sense though.

 

[Sapien]

I hear Benadryl promoted a lot in this community, but here is a reason it can be detrimental : acetylcholine is required for rem sleep, so Benadryl will inhibit rem sleep

 

[moa]

This means zinc in excess (very easy to get excess from oysters) can be anxiogenic and promote excessive stress and worry since gaba is vital for controlling glutamate and noradrenaline.

actually I've had very low acetylcholine levels with zinc deficiency, and i did felt the high glutamate, low GABA feeling for a few weeks, but i don't think it's bad signal.

i think when you raise acetylcholine from deficiency to normal levels, the body needs more GABA, and it takes some time to adapt to this new normal.

I've read studies that day the mechanism of raising GABA is by increased nitric oxide. Acetylcholine when it's getting higher than previous levels, it causes nitric oxide release and this will trigger, over the course of dozen days, a raise in GABA.

so i know Ray Peat had said acetylcholine is bad because it raises nitric oxide. actually it doesn't really do that in the long term, is the mechanism to trigger the increased GABA.

and for people who think it's good to have increased GABA, and it is, the way to everyone this may be with increased nitric oxide, as the main signaling for GABA increase.

avoiding all substances that increase nitric oxide, like acetylcholine, it's then not only counter productive, but also misunderstanding the good side of having high acetylcholine on the long term.

just be careful to go slow and allow the brain to adapt, otherwise you'll have a very bad day with anxiety, unable to stand loud noise, etc.

especially B5, don't take 500mg the first day like i did, start with 25 or 50mg, or you'll regret it badly.

once the body has resolved deficiency, you can take 500mg without symptoms, but you still don't need that much anyway.

acetylcholine is required for rem sleep, so Benadryl will inhibit rem sleep

indeed, i had so bad sleep until i raised my acetylcholine. actually i wasn't able to sleep deeply at all, only half awake and felt like wanting to move all night, restless legs syndrome awful.

once i suplemented zinc, choline, b5 it was better, but from experience, taking only 50mg b5 3h before sleep is the fastest way to have a good night regardless of other factors.