Thiamin and acetylcholine

[Bart1]

I hope somebody smart can explain me in easy to understand words the following seemingly contradicting actions.

Peat has written about the dangers of acetylcholine, is positive about anticholinergics for (degenerative) brain issues.

However, thiamin which increases acetylcholine has also been implicated to help/cure pretty much every degenerate brain condition.

So what’s going on here? Can somebody explain me this?

 

[redsun]

I hope somebody smart can explain me in easy to understand words the following seemingly contradicting actions.

Peat has written about the dangers of acetylcholine, is positive about anticholinergics for (degenerative) brain issues.

However, thiamin which increases acetylcholine has also been implicated to help/cure pretty much every degenerate brain condition.

So what’s going on here? Can somebody explain me this?

B1 does many many things besides increase Ach synthesis. Other vitamins also increase acetyl-CoA formation not just B1. But they are all integral to make other neurotransmitters as well as ATP formation.

However in excess, B1 does seem to strongly increase Ach independent of everuthing else it does and it can cause severe debilitating depressive like symptoms for some people. In my experience it does this after a few days of high doses. There have been some who dealt with similae issues which I had to enlighten them because they were megadosing B1 because it is spoken of way too highly here and couldnt figure out why they had severe insomnia, depressive symptoms, histamine symptoms (B1 is a histamine liberator).

 

[Bart1]

B1 does many many things besides increase Ach synthesis. Other vitamins also increase acetyl-CoA formation not just B1. But they are all integral to make other neurotransmitters as well as ATP formation.

However in excess, B1 does seem to strongly increase Ach independent of everuthing else it does and it can cause severe debilitating depressive like symptoms for some people. In my experience it does this after a few days of high doses. There have been some who dealt with similae issues which I had to enlighten them because they were megadosing B1 because it is spoken of way too highly here and couldnt figure out why they had severe insomnia, depressive symptoms, histamine symptoms (B1 is a histamine liberator).

Interesting thanks, could this maybe also be caused by depleting methyl donors?

 

[mostlylurking]

Peat has written about the dangers of acetylcholine, is positive about anticholinergics for (degenerative) brain issues.

However, thiamin which increases acetylcholine has also been implicated to help/cure pretty much every degenerate brain condition.

So what’s going on here? Can somebody explain me this?

I think that this is a complicated issue and you can get into trouble if acetylcholine is too high and you can get into trouble if acetylcholine is too low. The central nervous system, including the autonomic nervous system need acetylcholine to function. It is found everywhere in the body. It's there for a reason.

Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various ...

www.ncbi.nlm.nih.gov

"1.1. Acetylcholine as Neurotransmitter​

The first neurotransmitter discovered ACh is neurotransmitter at all autonomic ganglia, at many autonomically innervated organs, at the neuromuscular junction, and at many synapses in the central nervous system. In the autonomic nervous system, ACh is the neurotransmitter in the preganglionic sympathetic and parasympathetic neurons, as well as at the adrenal medulla and serves as the neurotransmitter in all the parasympathetic innervated organs. ACh is also the neurotransmitter at the sweat glands, and at the piloerector muscle of the sympathetic autonomic nervous system. In the peripheral nervous system, ACh is the neurotransmitter at the neuromuscular junction between the motor nerve and skeletal muscle. In the central nervous system, ACh is found primarily in interneurons, and a few important long-axon cholinergic pathways have also been identified. Noteworthy is the cholinergic projection from the nucleus basalis of Meynert (in the basal forebrain) to the forebrain neocortex and associated limbic structures. Degeneration of this pathway is one of the pathologies associated with Alzheimer's disease (AD) [6, 7].

ACh is synthesized by a single step reaction catalyzed by the biosynthetic enzyme choline acetyltransferase and the presence of this enzyme is the "marker" that a neuron is cholinergic. The majority of the ACh in nerve endings is contained in clear 100 nm vesicles and a small amount is also free in the cytosol. The uptake of ACh into storage vesicle occurs through an energy-dependent pump that acidifies the vesicle [7]. During neurotransmission, ACh is released from the nerve into the synaptic cleft and binds to ACh receptors (nicotinic and muscarinic) on the post-synaptic membrane, relaying the signal from the nerve. AChE, also located on the post-synaptic membrane, terminates the signal transmission by hydrolyzing ACh. The liberated choline from the ACh decomposition is taken up again by the pre-synaptic nerve and the neurotransmitter is synthesized by combining with acetyl-CoA through the action of choline acetyltransferase (Fig. 11) [8, 9]."

This article covers how organo-phosphates throw a wrench into the cycle by blocking acetylcholinesterase (AChE) which normally breaks down acetylcholine, causing acetylcholine overload and severe problems. I think this is the perspective that Ray Peat focuses on.

More about acetylcholine:

Non-neuronal acetylcholine, a locally acting molecule, widely distributed in biological systems: Expression and function in humans

Acetylcholine acts as a neurotransmitter in the central and peripheral nervous systems in humans. However, recent experiments demonstrate a widespread…

www.sciencedirect.com

Abstract​

Acetylcholine acts as a neurotransmitter in the central and peripheral nervous systems in humans. However, recent experiments demonstrate a widespread expression of the cholinergic system in non-neuronal cells in humans. The synthesizing enzyme choline acetyltransferase, the signalling molecule acetylcholine, and the respective receptors (nicotinic or muscarinic) are expressed in epithelial cells (human airways, alimentary tract, epidermis). Acetylcholine is also found in mesothelial, endothelial, glial, and circulating blood cells (platelets, mononuclear cells), as well as in alveolar macrophages. The existence of non-neuronal acetylcholine explains the widespread expression of muscarinic and nicotinic receptors in cells not innervated by cholinergic neurons. Non-neuronal acetylcholine appears to be involved in the regulation of important cell functions, such as mitosis, trophic functions, automaticity, locomotion, ciliary activity, cell-cell contact, cytoskeleton, as well as barrier and immune functions. The most important tasks for the future will be to clarify the multiple biological roles of non-neuronal acetylcholine in detail and to identify pathological conditions in which this system is up- or down-regulated. This could provide the basis for the development of new therapeutic strategies to target the non-neuronal cholinergic system.

(B1 is a histamine liberator)

(source: Thiamine deficiency and Histamine Intolerance. Is there a link?)
Histamine Intolerance Originates in the Gut
Histamine Intolerance Originates in the Gut
And...
All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases
All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases


Thiamine has been scientifically shown to modulate mast cell degranulation.

Increased mast cell degranulation within thalamus in early pre-lesion stages of an experimental model of Wernicke's encephalopathy
Increased mast cell degranulation within thalamus in early pre-lesion stages of an experimental model of Wernicke's encephalopathy - PubMed
"These data suggest that mast cell degranulation is a very early response induced by TD (Thiamine Deficiency)..."
And...
Regional changes in brain histamine levels following dietary-induced thiamine deficiency in rats
Regional changes in brain histamine levels following dietary-induced thiamine deficiency in rats - PubMed
"These data present a new finding that thiamine deficiency affects the central histaminergic neuron system as well as other monoaminergic systems."

And...
Effects of thiamine administration on hypothermia and hypothalamic histamine levels in dietary-induced thiamine deficient rats
Effects of thiamine administration on hypothermia and hypothalamic histamine levels in dietary-induced thiamine deficient rats - PubMed
"...the increased histamine levels in the hypothalamus, especially those in its anterior region, are closely related to the hypothermia in thiamine-deficient rats."

"What does the hypothalamus do?"
Hypothalamus: Function, hormones, and disorders

 

[Bart1]

I think that this is a complicated issue and you can get into trouble if acetylcholine is too high and you can get into trouble if acetylcholine is too low. The central nervous system, including the autonomic nervous system need acetylcholine to function. It is found everywhere in the body. It's there for a reason.

Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various ...

www.ncbi.nlm.nih.gov

"1.1. Acetylcholine as Neurotransmitter​

The first neurotransmitter discovered ACh is neurotransmitter at all autonomic ganglia, at many autonomically innervated organs, at the neuromuscular junction, and at many synapses in the central nervous system. In the autonomic nervous system, ACh is the neurotransmitter in the preganglionic sympathetic and parasympathetic neurons, as well as at the adrenal medulla and serves as the neurotransmitter in all the parasympathetic innervated organs. ACh is also the neurotransmitter at the sweat glands, and at the piloerector muscle of the sympathetic autonomic nervous system. In the peripheral nervous system, ACh is the neurotransmitter at the neuromuscular junction between the motor nerve and skeletal muscle. In the central nervous system, ACh is found primarily in interneurons, and a few important long-axon cholinergic pathways have also been identified. Noteworthy is the cholinergic projection from the nucleus basalis of Meynert (in the basal forebrain) to the forebrain neocortex and associated limbic structures. Degeneration of this pathway is one of the pathologies associated with Alzheimer's disease (AD) [6, 7].

ACh is synthesized by a single step reaction catalyzed by the biosynthetic enzyme choline acetyltransferase and the presence of this enzyme is the "marker" that a neuron is cholinergic. The majority of the ACh in nerve endings is contained in clear 100 nm vesicles and a small amount is also free in the cytosol. The uptake of ACh into storage vesicle occurs through an energy-dependent pump that acidifies the vesicle [7]. During neurotransmission, ACh is released from the nerve into the synaptic cleft and binds to ACh receptors (nicotinic and muscarinic) on the post-synaptic membrane, relaying the signal from the nerve. AChE, also located on the post-synaptic membrane, terminates the signal transmission by hydrolyzing ACh. The liberated choline from the ACh decomposition is taken up again by the pre-synaptic nerve and the neurotransmitter is synthesized by combining with acetyl-CoA through the action of choline acetyltransferase (Fig. 11) [8, 9]."

This article covers how organo-phosphates throw a wrench into the cycle by blocking acetylcholinesterase (AChE) which normally breaks down acetylcholine, causing acetylcholine overload and severe problems. I think this is the perspective that Ray Peat focuses on.

More about acetylcholine:

Non-neuronal acetylcholine, a locally acting molecule, widely distributed in biological systems: Expression and function in humans

Acetylcholine acts as a neurotransmitter in the central and peripheral nervous systems in humans. However, recent experiments demonstrate a widespread…

www.sciencedirect.com

Abstract​

Acetylcholine acts as a neurotransmitter in the central and peripheral nervous systems in humans. However, recent experiments demonstrate a widespread expression of the cholinergic system in non-neuronal cells in humans. The synthesizing enzyme choline acetyltransferase, the signalling molecule acetylcholine, and the respective receptors (nicotinic or muscarinic) are expressed in epithelial cells (human airways, alimentary tract, epidermis). Acetylcholine is also found in mesothelial, endothelial, glial, and circulating blood cells (platelets, mononuclear cells), as well as in alveolar macrophages. The existence of non-neuronal acetylcholine explains the widespread expression of muscarinic and nicotinic receptors in cells not innervated by cholinergic neurons. Non-neuronal acetylcholine appears to be involved in the regulation of important cell functions, such as mitosis, trophic functions, automaticity, locomotion, ciliary activity, cell-cell contact, cytoskeleton, as well as barrier and immune functions. The most important tasks for the future will be to clarify the multiple biological roles of non-neuronal acetylcholine in detail and to identify pathological conditions in which this system is up- or down-regulated. This could provide the basis for the development of new therapeutic strategies to target the non-neuronal cholinergic system.



(source: Thiamine deficiency and Histamine Intolerance. Is there a link?)
Histamine Intolerance Originates in the Gut
Histamine Intolerance Originates in the Gut
And...
All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases
All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases


Thiamine has been scientifically shown to modulate mast cell degranulation.

Increased mast cell degranulation within thalamus in early pre-lesion stages of an experimental model of Wernicke's encephalopathy
Increased mast cell degranulation within thalamus in early pre-lesion stages of an experimental model of Wernicke's encephalopathy - PubMed
"These data suggest that mast cell degranulation is a very early response induced by TD (Thiamine Deficiency)..."
And...
Regional changes in brain histamine levels following dietary-induced thiamine deficiency in rats
Regional changes in brain histamine levels following dietary-induced thiamine deficiency in rats - PubMed
"These data present a new finding that thiamine deficiency affects the central histaminergic neuron system as well as other monoaminergic systems."

And...
Effects of thiamine administration on hypothermia and hypothalamic histamine levels in dietary-induced thiamine deficient rats
Effects of thiamine administration on hypothermia and hypothalamic histamine levels in dietary-induced thiamine deficient rats - PubMed
"...the increased histamine levels in the hypothalamus, especially those in its anterior region, are closely related to the hypothermia in thiamine-deficient rats."

"What does the hypothalamus do?"
Hypothalamus: Function, hormones, and disorders

thanks for this!

I agree it's a complicated issue. Acetylcholine is the neurotransmitter used by the vagus nerve.

D. Lonsdale

"The cholinergic anti-inflammatory pathway is part of the parasympathetic nervous system and it can be also entitled as an anti-inflammatory reflex. Stopping production of pro-inflammatory cytokines is its major task. Acetylcholinesterase terminates the neurotransmission, so cholinesterase inhibitors can be beneficial by the prolongation of the reflex. It depends on termination of the vagus nerve into blood, and the release of acetylcholine. Acetyl CoA, used for the synthesis of acetylcholine, is derived from mitochondrial pyruvate dehydrogenase and there is a small pool of choline with cholinergic nerve endings available for acetylcholine synthesis."

vagus nerve Archives - Hormones Matter

www.hormonesmatter.com

 

[mostlylurking]

thanks for this!

I agree it's a complicated issue. Acetylcholine is the neurotransmitter used by the vagus nerve.

D. Lonsdale

"The cholinergic anti-inflammatory pathway is part of the parasympathetic nervous system and it can be also entitled as an anti-inflammatory reflex. Stopping production of pro-inflammatory cytokines is its major task. Acetylcholinesterase terminates the neurotransmission, so cholinesterase inhibitors can be beneficial by the prolongation of the reflex. It depends on termination of the vagus nerve into blood, and the release of acetylcholine. Acetyl CoA, used for the synthesis of acetylcholine, is derived from mitochondrial pyruvate dehydrogenase and there is a small pool of choline with cholinergic nerve endings available for acetylcholine synthesis."

vagus nerve Archives - Hormones Matter

www.hormonesmatter.com

you're welcome.

I've found Dr. Lonsdale's articles and his book very helpful.

 

[Kray]

you're welcome.

I've found Dr. Lonsdale's articles and his book very helpful.

For someone just jumping in here, what is the verdict? Try to get B1 from diet and avoid the potential problems of too much B1 via supplements?

 

[mostlylurking]

For someone just jumping in here, what is the verdict? Try to get B1 from diet and avoid the potential problems of too much B1 via supplements?

I'm taking high dose thiamine which is considered a "pharmaceutical" dose. I have had a lot of very long term health issues resolve by taking it (2 grams/day of thiamine hcl). I have not experienced any negative effects from taking it. I've been taking this high dose for about 18 months. I'm female, 72, with a high load of heavy metals (including lead).

The official recommended daily dosage for thiamine is around 1.5mg/day. I have no idea how the Powers that Be came up with that miserly recommended dose.

There are many things that will cause the need for additional thiamine: a genetic issue having to do with enzymes that use thiamine as a cofactor; heavy metal poisoning (like lead); too much sugar/refined carbs in the diet; coffee and tea consumption; consuming foods that are high in thiaminase; many pharmaceutical drugs including some antibiotics; being low in gut bacteria that make thiamine; being high in gut bacteria that consume thiamine; gut absorption problems. I'm sure there's more but I just wanted to quickly list the ones that I'm aware of.

I'll post some videos for you:

View: https://www.youtube.com/watch?v=rjVXFqiPDwE



View: https://www.youtube.com/watch?v=BkKmiZkiEPI


View: https://www.youtube.com/watch?v=mG3m3tbEGU0

 

[ealomz]

Interesting thanks, could this maybe also be caused by depleting methyl donors?

I am also interested in knowing the answer to this question. Can anyone enlighten?

 

[artist]

I get severe depression from B1, even small doses, regardless of form. It also kills my appetite (like, can barely eat 200 calories a day) and drives my histamine levels up. I know everyone says to push through but I honestly think that would end in suicide for me, srs. I really wanted B1 to be the panacea it is for some people, but I don’t think everyone suffers from B1 as their missing piece. Conversely, B2 makes me feel great. If anyone is suffering B1 depression, I highly suggest Benadryl while you ride it out, and stop taking the B1. I do think the problem is acetylcholine driven.

 

[reality]

I get severe depression from B1, even small doses, regardless of form. It also kills my appetite (like, can barely eat 200 calories a day) and drives my histamine levels up. I know everyone says to push through but I honestly think that would end in suicide for me, srs. I really wanted B1 to be the panacea it is for some people, but I don’t think everyone suffers from B1 as their missing piece. Conversely, B2 makes me feel great. If anyone is suffering B1 depression, I highly suggest Benadryl while you ride it out, and stop taking the B1. I do think the problem is acetylcholine driven.

I think Isolated b vitamins can also deplete or increase the need for others, and b2 is one of them

 

[Bart1]

I get severe depression from B1, even small doses, regardless of form. It also kills my appetite (like, can barely eat 200 calories a day) and drives my histamine levels up. I know everyone says to push through but I honestly think that would end in suicide for me, srs. I really wanted B1 to be the panacea it is for some people, but I don’t think everyone suffers from B1 as their missing piece. Conversely, B2 makes me feel great. If anyone is suffering B1 depression, I highly suggest Benadryl while you ride it out, and stop taking the B1. I do think the problem is acetylcholine driven.

You might need more B5 and B2 first like @reality says. Also B1 affect serotonin and normalises it in the longer term, but short term it can have adverse symptoms