Coffee and Cholinesterase (AChE)

[Sitaruîm]

In Ray's article about learned helplessness, arguably his most important article, one of the main points seems to be that low cholinesterase leads to overexcitation of the nerves and to cell death. He cites articles that show that rats living in idyllic environments have high levels of cholinesterase in their brain. There are two types of cholinesterase enzymes, AChE and BChE, and caffeine is known to inhibit AChE.
How do you guys think Ray would argue in favor of coffee given his posture on cholinesterase? Does low choline consumption in the diet lower cholinergic activity in the brain, which could logically lead us to conclude that inhibiting cholinesterase would be a positive outcome? Could caffeine be harmful in the presence of high amounts of choline in the diet? I'd be particularly interested in hearing @redsun 's opinion on this, since his view seems to be that most people don't meet the daily requirement of choline.

 

[redsun]

In Ray's article about learned helplessness, arguably his most important article, one of the main points seems to be that low cholinesterase leads to overexcitation of the nerves and to cell death. He cites articles that show that rats living in idyllic environments have high levels of cholinesterase in their brain. There are two types of cholinesterase enzymes, AChE and BChE, and caffeine is known to inhibit AChE.
How do you guys think Ray would argue in favor of coffee given his posture on cholinesterase? Does low choline consumption in the diet lower cholinergic activity in the brain, which could logically lead us to conclude that inhibiting cholinesterase would be a positive outcome? Could caffeine be harmful in the presence of high amounts of choline in the diet? I'd be particularly interested in hearing @redsun 's opinion on this, since his view seems to be that most people don't meet the daily requirement of choline.

We know Rays stance on coffee. Coffee mechanisms of action is not only on AChE. Caffeine stimulates the release of several neurotransmitters such as catecholamine, glutamate, histamine activity. Caffeine is definitely not harmful if the diet is also high choline. The effect of caffeine is quite weak.

Yes, low choline intake would reduce cholinergic activity in the brain. But choline's function is not just for use as raw material to make acetylcholine. Its needed for phospholipid synthesis, methylation and cholesterol metabolism.

You would need to be eating tons of choline plus consuming a significant amount of AChE inhibitors to possibly cause problems. And those problems would be mild cholinergic toxicity symptoms. Racetams, which often work through acetylcholine in some fashion, are popular in nootropics communities. I doubt it would be so popular if they caused bad side effects easily.

I think its way too simplistic to suggest simply blocking AChE will increase learned helplessness. Too little acetylcholine activity will reduce stress tolerance just like too much will. I don't think its that easy to get excessive acetylcholine for the vast majority of the population just by eating high choline foods like eggs and the solanine that is present in potatoes in the normal quantities most people consume.

Its not my view that most people don't get enough choline, thats what the research shows. At least in the US, its estimated about 90% dont even meet the RDA for choline. Pre-menopausal women are generally protected from choline deficiency due to estrogen increasing phosphatidylcholine synthesis by inducing PEMT.

 

[moa]

I've learned so much about acetylcholine from redsun. This is how i discovered i was low on it.

when i was very young, 15 years ago i used piracetam almost every day for maybe 10 months, with cafein pills. back than i was eating very bad and low calorie, and very low choline.

I'm not sure if this has resulted in my acetylcholine deficiency 15 years later, but i know eating too much liver and vitamin A along not enaught zinc, and choline and b5 was surely the short term cause.

regarding having too much choline, with depression it learned helplessness, i think having a good copper/zinc balance is much more important than avoiding acetylcholine, as low dopamine (caused by low copper, etc) is the real cause of learned helplessness and tiredness, more than acetylcholine. more acetylcholine will require more GABA and more dopamine and not every system is able to cope with the requirement. the real learned helplessness hormone is high serotonin with low dopamine.

I'm not sure if redsun agree with this, but i find Peat's view on acetylcholine not very accurate.

coffee may raise glutamate and histamine, I'm not sure, maybe that's why it causes anxiety and insomnia. but long term usage of coffee will upregulate GABA and acetylcholine receptors if i remember well.

so coffee is better used long term for the health benefits.