Question about how cypro induces weight gain

[OliviaD]

It can help some people temporarily. In the end it is not a permanent solution, no drug is. It will help those with excess histamine and high serotonin levels the most. The rest it will do nothing or make them worse.

I never understood the use of antihistamines unless you have severe allergic reactions and chronically high, insane histamine levels and the symptoms to go along with it. That is the only reason I would ever recommend its temporary use. In that case it should be used while the diet and micronutrient intake is fixed and optimized and the histamine levels are brought down to more controllable levels through use of methyl donors such as TMG.

Then it should be stopped to allow the homeostasis to return because make no mistake it is not normal homeostasis to depend on an antihistamine and blocking all these receptors that cypro blocks is not good for the body in the long run. It should not be taken while the appropriate steps to lower histamine levels and promote healthy adrenal activity are not being taken. Its like treating someone with ADHD with just adderall and never taking the necessary steps through diet and lifestyle to make it so not only could their medication work better but eventually they won't need it.

Yes, I agree with all that.
I kind of 'think out loud" as I wrote to someone else on here - I probably should word things more carefully - i.e. "i don't understand the rationale for the cypro" - other than for the high histamine... or something like that :) It probably doesn't matter anyway :) . More appropriate - would I want to take this?

Worded a bit differently - there is no magic pill, I'm too tired now to write eloquently - but you put that so well re: manipulating receptors and neurotransmitters for long periods of time - because physiology is so intricate - changing one thing always creates a domino effect.

And yes, adderall - it sure would be nice if that was done or is possible.

 

[OliviaD]

Your right its not black and white but blanket recommendations by Peat or anyone for that matter is rarely useful and can be even harmful for some people. Lets take the OP of this thread for example. Do you know what happened to him? Turns out he did in fact just need choline. I suspected The genetic issue he mentioned where due to his SNPs his choline requirement was tripled and this is what was causing all his symptoms. I ended up having a private conversation with him.

He started taking large doses of choline as sunflower lecithin and it quite literally fixed all his issues. This includes his autistic behaviors (stimming), anxiety, nervousness, cold extremities,he was able to dream again, he was able to feel emotions again, he became social and was able to make jokes with his friends again. Basically he felt human again. All because of repleting choline. Thats all he did. He didnt need cypro or anything else for that matter. And then he told me now that he is better is just going to get off this forum and live his life and that's what he did.

And you see that's great and all, an amazing recovery story. But you see it also infuriated me because I imagined if I didn't get to this guy first basically he would have been screwed but advice from the rest of the users here.

So many of the peaters try to help others but in the end they do so in vain because their advice is not specific to the individual, 99% of their advice comes from Peat or some other authority figure. If I had let this slide and never got into this thread and let the Peaters get their hands on him, I guarantee you that this guy would still have all his problems and probably new ones, and he still would be advised to be taking cypro and who knows what else at this point. All he needed was ******* choline and that would never be suggested or even thought of by 99.9% of the people here. Because the suggestions come purely from Peat's articles and his podcasts and Peat himself speaks mostly ill (and wrongly) of acetylcholine/choline. Parroting info while not digesting and understanding what is going on in each specific person is a major error that many here who try to help make regularly.

This is a severe weakness of this community, and every community that clings too strongly to one expert or one major way of thinking and understanding. Most of the users here truly refuse to appreciate the depth of knowledge there actually is that can be used to help people on this forum. Peat's articles and podcasts discuss maybe 1% of it. If anyone wants to truly help people, they need to read. And read a lot. Read, and watch and learn from every expert even if they seem ridiculous. Use your judgment and intuition. Take what makes sense and do your best to be sensible. Scientific articles on pubmed and similar are the best resources if you actually want to understand something with as little bias as possible.

I can't help every single newbie thread unfortunately, and I can't hold everyone responsible and correct them for senseless and possibly harmful advice. I wish I could but I am just one person. And still even now this kind of irresponsibility occurs daily here. I implore everyone that truly wants to help others to write less, read more. Read from everyone and everything. Ponder, make connections, and then read more into those connections. If you are truly inspired and fascinated by biochemistry, this will be easy for you. It just takes time.

This is a great comment. I'm too tired to comment on it in any detail - but some important points you bring out 1. individual differences and 2. never ever make any human your God or Guru. I mostly loved "got off this forum and went on to live his life" !! How wonderful! Because I do believe - ultimately, we don't want to be this obsessed with our health - in fact, the 'healthiest' people I know aren't at all.

One question I have - I am so cynical re: research after learning about so much fraud, manipulation, distortion, cherry picking and results being so controlled based on for instance, what pharmaceutical companies are pushing - I'm not sure how much faith to have in scientific publications.. Just thinking out loud as usual.

 

[OliviaD]

Glad things are going well for you.

@deliciousfruit This post made me realize that your past intake of niacin could be the issue. Excess niacin intake depletes methyl donors which are needed to make endogenous choline for acetylcholine synthesis. You could have severely undermethylated yourself.

Low Ach can not only lead to ADHD symptoms, but it will also feel like your whole body is falling apart because Ach is needed for all parasympathetic and sympathetic processes. Digestion and stomach acid secretion is also dependent on Ach signalling. From what I understand in the other thread you do not eat meat or animal protein in general right? Also do you eat any eggs? Dairy has almost no choline. You should examine your choline intake in your diet. You likely are not even reaching close to the bare minimum needs for choline.

You likely are very deficient in choline if you do not consume much animal protein at all. And if this is the case, digestion will weak or nonexistent. Likely you need to try and supplement phosphatidylcholine from sunflower lecithin. PointOutside also supplemented it for different reasons but in your case it seems the low choline issue can definitely apply to you because of a history of a low animal protein diet, and high dose niacin which depletes methyl groups used to make endogenous choline.

So it may be a mineral issue, or it may not be that at all and you just choline so your acetylcholine levels can increase to properly signal normal digestive functions.

I am still reading this entire thread (and trying to digest it) - I'm suspecting I am likely deficient in choline, perhaps for a long long time.. and definitely low in Ach. My whole body has been falling apart, for sure. (most likely lots of other things -but this intrigues me). Seems like there could be little harm in supplementing sunflower lecitin. Is there a brand you recommend - dose - or somewhere to look into that?

You seem very knowledgeable. I do agree I should be able to figure this all out myself. My struggle is that I have been very sick for a long time, and don't have a lot of time, energy , and ability to concentrate available to study as fast as I feel I may need to help myself (and I have some background). i.e there is so much to learn - that I do feel it is helpful to rely a bit on those who have studied more than I - provided I can trust them as reliable sources :)

 

[redsun]

I am still reading this entire thread (and trying to digest it) - I'm suspecting I am likely deficient in choline, perhaps for a long long time.. and definitely low in Ach. My whole body has been falling apart, for sure. (most likely lots of other things -but this intrigues me). Seems like there could be little harm in supplementing sunflower lecitin. Is there a brand you recommend - dose - or somewhere to look into that?

You seem very knowledgeable. I do agree I should be able to figure this all out myself. My struggle is that I have been very sick for a long time, and don't have a lot of time, energy , and ability to concentrate available to study as fast as I feel I may need to help myself (and I have some background). i.e there is so much to learn - that I do feel it is helpful to rely a bit on those who have studied more than I - provided I can trust them as reliable sources :)

Send me a PM with your symptoms and issues and what your diet looks like to so we can start to fill in your dietary gaps. Ideally if you can avoid supplements you should but sunflower lecithin is safe.

Sunflower lecithin because it doesnt contain just phosphatidylcholine its hard to find actually how much you are getting. It is simpler to use choline bitartrate or cdp choline because you can look up by percentage how much actual choline you are getting per serving so this way you know more accurately what you get.

I never said you should figure things out yourself. If you want to help others you need to learn and figure many things out yourself but if you need help this is completely different.

Not everyone can help themselves and there is nothing wrong with that. Some people's problems are too complex and their cognition is too poor due to their poor health for them to figure it out alone within a reasonable amount of time.

 

[InChristAlone]

Your right its not black and white but blanket recommendations by Peat or anyone for that matter is rarely useful and can be even harmful for some people. Lets take the OP of this thread for example. Do you know what happened to him? Turns out he did in fact just need choline. I suspected The genetic issue he mentioned where due to his SNPs his choline requirement was tripled and this is what was causing all his symptoms. I ended up having a private conversation with him.

He started taking large doses of choline as sunflower lecithin and it quite literally fixed all his issues. This includes his autistic behaviors (stimming), anxiety, nervousness, cold extremities,he was able to dream again, he was able to feel emotions again, he became social and was able to make jokes with his friends again. Basically he felt human again. All because of repleting choline. Thats all he did. He didnt need cypro or anything else for that matter. And then he told me now that he is better is just going to get off this forum and live his life and that's what he did.

And you see that's great and all, an amazing recovery story. But you see it also infuriated me because I imagined if I didn't get to this guy first basically he would have been screwed but advice from the rest of the users here.

So many of the peaters try to help others but in the end they do so in vain because their advice is not specific to the individual, 99% of their advice comes from Peat or some other authority figure. If I had let this slide and never got into this thread and let the Peaters get their hands on him, I guarantee you that this guy would still have all his problems and probably new ones, and he still would be advised to be taking cypro and who knows what else at this point. All he needed was ******* choline and that would never be suggested or even thought of by 99.9% of the people here. Because the suggestions come purely from Peat's articles and his podcasts and Peat himself speaks mostly ill (and wrongly) of acetylcholine/choline. Parroting info while not digesting and understanding what is going on in each specific person is a major error that many here who try to help make regularly.

This is a severe weakness of this community, and every community that clings too strongly to one expert or one major way of thinking and understanding. Most of the users here truly refuse to appreciate the depth of knowledge there actually is that can be used to help people on this forum. Peat's articles and podcasts discuss maybe 1% of it. If anyone wants to truly help people, they need to read. And read a lot. Read, and watch and learn from every expert even if they seem ridiculous. Use your judgment and intuition. Take what makes sense and do your best to be sensible. Scientific articles on pubmed and similar are the best resources if you actually want to understand something with as little bias as possible.

I can't help every single newbie thread unfortunately, and I can't hold everyone responsible and correct them for senseless and possibly harmful advice. I wish I could but I am just one person. And still even now this kind of irresponsibility occurs daily here. I implore everyone that truly wants to help others to write less, read more. Read from everyone and everything. Ponder, make connections, and then read more into those connections. If you are truly inspired and fascinated by biochemistry, this will be easy for you. It just takes time.

I agree that ANY blanket statement can be harmful. Someone with anxiety and depression could have opposite neurochemistry as someone else with anxiety and depression, that's what I mean by it not being black and white. It's useful this guy had his DNA tested so it gave you an idea of what may be going on but many don't have that information. Then what?

I was eating 3 eggs a day for a few months when I started having severe anxiety. That surely was plenty of choline when you add on one serving of meat a day. My dreams were so annoying I was waking up everyday thinking what's wrong with me! I felt everything intensely. So I had anxiety and adrenaline just like the guy who started this thread but my chemistry seems opposite and an anticholinergic drug seems like a godsend. (And I still dream vividly on it, but not as heavily). Just like someone with ADHD who takes Ritalin for the first time might say why didn't I do this sooner? And I agree with you using drugs is a bandaid. My son could easily be diagnosed with ADHD, but we are trying out dietary and parenting approaches first and foremost. We also know in the back of our mind unmedicated ADHD has risks. They have a higher likelihood of drug addiction and unemployment. We seemed to have gotten his craving for caffeine under control (he stopped having most caffeine sources over a yr ago) but he's really struggling with reading and math and boredom, he can't tolerate sitting at home for too long. We are about to try zinc with him as we have heard from many other parents that zinc helped relax their hyperactive kid. Anyway not to derail the thread but this kind of nutrition is very complex I've been trying to figure it out for many yrs. The Peat stuff was mostly a disaster for me, I was breastfeeding this son while heavily into stimulants, dairy and sugar. He was addicted to caffeine and chocolate at an early age and I was stupid and let him eat junk, Peat gave me the freedom to eat all the things I like! Lol.

What I find frustrating about biochemistry is it's not usually as simple as getting one nutrient. Though I wish it were and maybe the zinc will change my son's chemistry in a positive way. We also use mag oil on him before bed, seems to have made some impact on his aggression.

 

[redsun]

I agree that ANY blanket statement can be harmful. Someone with anxiety and depression could have opposite neurochemistry as someone else with anxiety and depression, that's what I mean by it not being black and white. It's useful this guy had his DNA tested so it gave you an idea of what may be going on but many don't have that information. Then what?

I was eating 3 eggs a day for a few months when I started having severe anxiety. That surely was plenty of choline when you add on one serving of meat a day. My dreams were so annoying I was waking up everyday thinking what's wrong with me! I felt everything intensely. So I had anxiety and adrenaline just like the guy who started this thread but my chemistry seems opposite and an anticholinergic drug seems like a godsend. (And I still dream vividly on it, but not as heavily). Just like someone with ADHD who takes Ritalin for the first time might say why didn't I do this sooner? And I agree with you using drugs is a bandaid. My son could easily be diagnosed with ADHD, but we are trying out dietary and parenting approaches first and foremost. We also know in the back of our mind unmedicated ADHD has risks. They have a higher likelihood of drug addiction and unemployment. We seemed to have gotten his craving for caffeine under control (he stopped having most caffeine sources over a yr ago) but he's really struggling with reading and math and boredom, he can't tolerate sitting at home for too long. We are about to try zinc with him as we have heard from many other parents that zinc helped relax their hyperactive kid. Anyway not to derail the thread but this kind of nutrition is very complex I've been trying to figure it out for many yrs. The Peat stuff was mostly a disaster for me, I was breastfeeding this son while heavily into stimulants, dairy and sugar. He was addicted to caffeine and chocolate at an early age and I was stupid and let him eat junk, Peat gave me the freedom to eat all the things I like! Lol.

What I find frustrating about biochemistry is it's not usually as simple as getting one nutrient. Though I wish it were and maybe the zinc will change my son's chemistry in a positive way. We also use mag oil on him before bed, seems to have made some impact on his aggression.

Well zinc is really important for the development and function of the neocortex which is the main area in the brain involved in learning and language. And yes it can reduce hyperactivity but really it should help with his learning and brain development most importantly. And acetylcholine also is heavily involved in the learning process. It helps trigger glutamate and dopamine release in the the cerebral cortex and is needed for the hippocampus to function properly. So I would try zinc just avoid large doses for the child as zinc can cause nausea. Also zinc potentiates and upregulates cholinergic receptors in the brain.

Rarely is it just one nutrient or mineral. Often there needs to be many changes that need to be made though sometimes a singular change does make a massive difference. It was fortunate in OPs case it in fact was. But that is the point if it can be solved like this (figuring out glaring issues in the diet, genetic testing can also help) it should be.

I hope you don't get a lot of choline in the late afternoon. B vitamin supplementation as well as too much sodium in the late afternoon will all synergistically raise acetylcholine activity, leading to vivid, wild dreams at night. But B-vitamins linger in the body so it can still keep Ach high at night even if taken in the morning. Salt and choline however will have an acute effect if you have a significant amount of either in the later afternoon, last meal. The choline you have in the morning shouldnt affect choline activity much at night because choline is quickly metabolized out of the blood and into tissues. At night though, the acute elevation of choline and/or sodium in the blood if you have too much will lead to elevated Ach activity at night.

The rate-limiting step in Ach synthesis is actually the reuptake of choline back into the synapse after acetylcholine is broken down to choline and acetate. This transporter is sodium and chloride dependent. This is why too much salt is a problem for Ach levels, especially at night.

Did you know if he has a major source of iodine in his diet or if you supplement? It is vital and intake has been shown to be related to IQ. So I would look into that as well. Eggs have some but very little, not enough on their own. Milk tends to have a decent amount. Otherwise seafoods, iodized salt, or kelp/iodine supplements...

High-affinity choline transporter - PubMed

The cholinergic neurons have long been a model for biochemical studies of neurotransmission. The components responsible for cholinergic neurotransmission, such as choline acetyltransferase, vesicular acetylcholine transporter, nicotinic and muscarinic acetylcholine receptors, and acetylcholine...

pubmed.ncbi.nlm.nih.gov

 

[InChristAlone]

Well zinc is really important for the development and function of the neocortex which is the main area in the brain involved in learning and language. And yes it can reduce hyperactivity but really it should help with his learning and brain development most importantly. And acetylcholine also is heavily involved in the learning process. It helps trigger glutamate and dopamine release in the the cerebral cortex and is needed for the hippocampus to function properly. So I would try zinc just avoid large doses for the child as zinc can cause nausea. Also zinc potentiates and upregulates cholinergic receptors in the brain.

Rarely is it just one nutrient or mineral. Often there needs to be many changes that need to be made though sometimes a singular change does make a massive difference. It was fortunate in OPs case it in fact was. But that is the point if it can be solved like this (figuring out glaring issues in the diet, genetic testing can also help) it should be.

I hope you don't get a lot of choline in the late afternoon. B vitamin supplementation as well as too much sodium in the late afternoon will all synergistically raise acetylcholine activity, leading to vivid, wild dreams at night. But B-vitamins linger in the body so it can still keep Ach high at night even if taken in the morning. Salt and choline however will have an acute effect if you have a significant amount of either in the later afternoon, last meal. The choline you have in the morning shouldnt affect choline activity much at night because choline is quickly metabolized out of the blood and into tissues. At night though, the acute elevation of choline and/or sodium in the blood if you have too much will lead to elevated Ach activity at night.

The rate-limiting step in Ach synthesis is actually the reuptake of choline back into the synapse after acetylcholine is broken down to choline and acetate. This transporter is sodium and chloride dependent. This is why too much salt is a problem for Ach levels, especially at night.

Did you know if he has a major source of iodine in his diet or if you supplement? It is vital and intake has been shown to be related to IQ. So I would look into that as well. Eggs have some but very little, not enough on their own. Milk tends to have a decent amount. Otherwise seafoods, iodized salt, or kelp/iodine supplements...

High-affinity choline transporter - PubMed

The cholinergic neurons have long been a model for biochemical studies of neurotransmission. The components responsible for cholinergic neurotransmission, such as choline acetyltransferase, vesicular acetylcholine transporter, nicotinic and muscarinic acetylcholine receptors, and acetylcholine...

pubmed.ncbi.nlm.nih.gov

Thank-you, yeah so would someone like my son do better with higher choline? He is the type to not want eggs and meat so much (though he always has one serving of meat a day). He has gone through periods of having more in his diet and it didn't seem to help during those periods. I think the greatest thing that has helped him is quitting the coffee, sodas, and cocoa. I know ADHD people do well with caffeine but he was someone that it would just make him go crazy high energy and not eat enough. And with that we thought Ritalin would be a disaster but apparently it's the opposite for people? I don't understand that. How can a stimulant be calming? Is he really actually low dopamine and noradrenaline? He gets up in the morning easily has lots of motivation for things he likes to do and generally has a good outlook for his life. And is way more of a go getter and helper in our family than the asperger son who'd rather just check out of life altogether and is depressive. I guess he's not the typical apathetic ADHD.

He does love certain seafood but seafood is pricey so we don't do it very often. He loves imitation crab sushi from Publix. He just had that this morning actually despite being pretty picky! Though he does drink milk every few days. So I guess iodine would be pretty good.

So about my vivid annoying dreams.. you said chloride and then I immediately thought about how I've been doing mag chloride on my body before bed every night for the last 3 yrs just out of habit because I used to have severe clenching problems that causes horrific TMJ pain. I tried the magnesium on my face and it mostly cleared up. I wonder if I get too much chloride now. I don't supplement b vitamins because they are overly stimulating to me (except niacinamide but I just don't supp much at all other than vit C).

 

[redsun]

Thank-you, yeah so would someone like my son do better with higher choline? He is the type to not want eggs and meat so much (though he always has one serving of meat a day). He has gone through periods of having more in his diet and it didn't seem to help during those periods. I think the greatest thing that has helped him is quitting the coffee, sodas, and cocoa. I know ADHD people do well with caffeine but he was someone that it would just make him go crazy high energy and not eat enough. And with that we thought Ritalin would be a disaster but apparently it's the opposite for people? I don't understand that. How can a stimulant be calming? Is he really actually low dopamine and noradrenaline? He gets up in the morning easily has lots of motivation for things he likes to do and generally has a good outlook for his life. And is way more of a go getter and helper in our family than the asperger son who'd rather just check out of life altogether and is depressive. I guess he's not the typical apathetic ADHD.

He does love certain seafood but seafood is pricey so we don't do it very often. He loves imitation crab sushi from Publix. He just had that this morning actually despite being pretty picky! Though he does drink milk every few days. So I guess iodine would be pretty good.

So about my vivid annoying dreams.. you said chloride and then I immediately thought about how I've been doing mag chloride on my body before bed every night for the last 3 yrs just out of habit because I used to have severe clenching problems that causes horrific TMJ pain. I tried the magnesium on my face and it mostly cleared up. I wonder if I get too much chloride now. I don't supplement b vitamins because they are overly stimulating to me (except niacinamide but I just don't supp much at all other than vit C).

His appetite for animal protein will probably increase from taking some zinc. This in turn will allow him to eat a bit better and get the nutrition he needs. I would not recommend choline supplementation for a child. The zinc may be the key to unlock other doors so to speak. Just keep to 5-10mg a day maximum.

Yeh it seems contradictory that a stimulant can be calming but what it tends to do is provide natural internal stimulation that you miss when baseline monoamine activity is too low. Dopamine also promotes the release of acetylcholine and GABA. Norepinephrine promotes the uptake of glutamate so it can deal with negative effects of uncontrolled glutamate. It is way more complicated then this, it also has to do with how dopamine and norepinephrine affect endogenous endorphin activity and other things which then affect our ability to sustain attention and be productive and organize our lives.

Acetylcholine is a natural depressant and reduces overstimulation and adrenal hyperactivity. So there is different ways to deal with ADHD and it depends on whats going on in each person. Rarely is dopamine activity too low in young adults and children despite what many want to think. Unless you were severely iron and protein deficient or had folate deficiency. Those are some very clear reasons for true dopamine deficiency. But it sounds like your son is otherwise fine and low DA and NE clearly does not apply to him and just may benefit from more zinc to hopefully increase his appetite for proteins and thus get the choline and other things he needs to learn better. So yes I do think he will benefit from more choline in his diet but this should improve itself from zinc increasing appetite for animal proteins.

Occasional milk and seafood does not sound like enough iodine. A simple solution to make sure your children get enough is to use iodized salt in cooking. Its estimated that currently 2 billion people suffer with iodine deficiency while only 50 million people show obvious signs of it. Its too vital to just hope he is getting enough from the occasional iodine containing food because I honestly think he is not. So thats what I would recommend in regards to that. That way you don't need to be spending money on pricey food when you can simply add iodine to anything they eat.

Most people get tons of chloride. Its not really an issue of chloride. But the transporter is also sodium dependent so the extra chloride will not do anything on its own. Magnesium itself may potentiate or inhibit acetylcholine. There is evidence for both and its probably context dependent.

High doses of vitamin C can also enhance acetylcholine synthesis and it also has been shown to increase acetylcholine receptor density. I have experienced more dream vividness from the times I used a lot of vitamin C so I would be wary of that. I dont know how much niacinamide you take, but it has been shown to reduce how much choline is transported out of the brain.

Selective effects of ascorbic acid on acetylcholine receptor number and distribution - PubMed

Ascorbic acid in soluble extracts of neural tissue can account for the increase in surface acetylcholine receptors (AChR's) seen on L5 myogenic cells treated with crude brain extract (Knaack, D., and T. R. Podleski, 1985, Proc. Natl. Acad. Sci. USA., 82:575-579). The present study further...

pubmed.ncbi.nlm.nih.gov

 

[InChristAlone]

His appetite for animal protein will probably increase from taking some zinc. This in turn will allow him to eat a bit better and get the nutrition he needs. I would not recommend choline supplementation for a child. The zinc may be the key to unlock other doors so to speak. Just keep to 5-10mg a day maximum.

Yeh it seems contradictory that a stimulant can be calming but what it tends to do is provide natural internal stimulation that you miss when baseline monoamine activity is too low. Dopamine also promotes the release of acetylcholine and GABA. Norepinephrine promotes the uptake of glutamate so it can deal with negative effects of uncontrolled glutamate. It is way more complicated then this, it also has to do with how dopamine and norepinephrine affect endogenous endorphin activity and other things which then affect our ability to sustain attention and be productive and organize our lives.

Acetylcholine is a natural depressant and reduces overstimulation and adrenal hyperactivity. So there is different ways to deal with ADHD and it depends on whats going on in each person. Rarely is dopamine activity too low in young adults and children despite what many want to think. Unless you were severely iron and protein deficient or had folate deficiency. Those are some very clear reasons for true dopamine deficiency. But it sounds like your son is otherwise fine and low DA and NE clearly does not apply to him and just may benefit from more zinc to hopefully increase his appetite for proteins and thus get the choline and other things he needs to learn better. So yes I do think he will benefit from more choline in his diet but this should improve itself from zinc increasing appetite for animal proteins.

Occasional milk and seafood does not sound like enough iodine. A simple solution to make sure your children get enough is to use iodized salt in cooking. Its estimated that currently 2 billion people suffer with iodine deficiency while only 50 million people show obvious signs of it. Its too vital to just hope he is getting enough from the occasional iodine containing food because I honestly think he is not. So thats what I would recommend in regards to that. That way you don't need to be spending money on pricey food when you can simply add iodine to anything they eat.

Most people get tons of chloride. Its not really an issue of chloride. But the transporter is also sodium dependent so the extra chloride will not do anything on its own. Magnesium itself may potentiate or inhibit acetylcholine. There is evidence for both and its probably context dependent.

High doses of vitamin C can also enhance acetylcholine synthesis and it also has been shown to increase acetylcholine receptor density. I have experienced more dream vividness from the times I used a lot of vitamin C so I would be wary of that. I dont know how much niacinamide you take, but it has been shown to reduce how much choline is transported out of the brain.

Selective effects of ascorbic acid on acetylcholine receptor number and distribution - PubMed

Ascorbic acid in soluble extracts of neural tissue can account for the increase in surface acetylcholine receptors (AChR's) seen on L5 myogenic cells treated with crude brain extract (Knaack, D., and T. R. Podleski, 1985, Proc. Natl. Acad. Sci. USA., 82:575-579). The present study further...

pubmed.ncbi.nlm.nih.gov

Ok sounds good, yeah he doesn't seem to suffer from low neurotransmitters and thus Ritalin would just cause side effects like not being able to fall asleep, they typically have to give kids a blood pressure drug to help them sleep on stimulants. I will think more about the iodine, I definitely think it's important.

Didn't take the cypro last night I was already super sleepy I didn't need it. Had some cool dreams towards morning lol. They aren't usually enjoyable but say from day 7 of my cycle til I'm producing progesterone from the corpus luteum I tend to have more enjoyable dreams. I think there is something to MAO being slower during this time thus more dopamine and noradrenaline around providing some pleasure which would make sense biologically when a woman is gearing up to ovulate she needs to want sex and thus needs to experience pleasure to get it. It's not so necessary once the corpus luteum is producing progesterone. So I think Peat is short sighted on how the whole system works. Relying on exogenous progesterone is very strange when if you are healthy enough ovulation should be taking place 12 times a yr providing plenty of progesterone to counteract all of the estrogen. But without the estradiol a woman will feel very low motivation, low drive, dryness in the vagina, and depression. Oh and joint pain.

Yeah I think ascorbic acid has it's downsides. I am going to try just going off soon and see what happens. Weaning off didn't work. Cold turkey might speed up the progress. And if my nervous system doesn't adjust well that stinks! I haven't taken any niacinamide in a while. I test it out here and there. I don't need anything that promotes free fatty acids.

 

[redsun]

Ok sounds good, yeah he doesn't seem to suffer from low neurotransmitters and thus Ritalin would just cause side effects like not being able to fall asleep, they typically have to give kids a blood pressure drug to help them sleep on stimulants. I will think more about the iodine, I definitely think it's important.

Didn't take the cypro last night I was already super sleepy I didn't need it. Had some cool dreams towards morning lol. They aren't usually enjoyable but say from day 7 of my cycle til I'm producing progesterone from the corpus luteum I tend to have more enjoyable dreams. I think there is something to MAO being slower during this time thus more dopamine and noradrenaline around providing some pleasure which would make sense biologically when a woman is gearing up to ovulate she needs to want sex and thus needs to experience pleasure to get it. It's not so necessary once the corpus luteum is producing progesterone. So I think Peat is short sighted on how the whole system works. Relying on exogenous progesterone is very strange when if you are healthy enough ovulation should be taking place 12 times a yr providing plenty of progesterone to counteract all of the estrogen. But without the estradiol a woman will feel very low motivation, low drive, dryness in the vagina, and depression. Oh and joint pain.

Yeah I think ascorbic acid has it's downsides. I am going to try just going off soon and see what happens. Weaning off didn't work. Cold turkey might speed up the progress. And if my nervous system doesn't adjust well that stinks! I haven't taken any niacinamide in a while. I test it out here and there. I don't need anything that promotes free fatty acids.

Yeh putting kids on BP meds just so they can take ADHD meds is ridiculous and who knows what the long term implications of that are.

That is an interesting experience about how hormonal cycles affect dreams.

It may help to have calcium and magnesium on hand so you can take them. They are generally sedative so will help you out when you do decide to get off vitamin C. But the "withdrawal" symptoms should only last a few days at most.

 

[InChristAlone]

Yeh putting kids on BP meds just so they can take ADHD meds is ridiculous and who knows what the long term implications of that are.

That is an interesting experience about how hormonal cycles affect dreams.

It may help to have calcium and magnesium on hand so you can take them. They are generally sedative so will help you out when you do decide to get off vitamin C. But the "withdrawal" symptoms should only last a few days at most.

I said the same thing! Ridiculous!! But parents absolutely have to be figuring out how to improve a child's ability to tolerate non-preferred tasks and obviously look at their diet or when they are older it could be disasterous for them. There are probably loads of people in jail right now with undiagnosed ADHD.

Yeah magnesium chloride oil has been helpful for me at bedtime so I hesitate to try to stop that anytime soon. I've been getting way more calcium lately and I think it's been good for my nervous system. One thing I think Peat got right about dairy lol.

 

[OliviaD]

Ok sounds good, yeah he doesn't seem to suffer from low neurotransmitters and thus Ritalin would just cause side effects like not being able to fall asleep, they typically have to give kids a blood pressure drug to help them sleep on stimulants. I will think more about the iodine, I definitely think it's important.

Didn't take the cypro last night I was already super sleepy I didn't need it. Had some cool dreams towards morning lol. They aren't usually enjoyable but say from day 7 of my cycle til I'm producing progesterone from the corpus luteum I tend to have more enjoyable dreams. I think there is something to MAO being slower during this time thus more dopamine and noradrenaline around providing some pleasure which would make sense biologically when a woman is gearing up to ovulate she needs to want sex and thus needs to experience pleasure to get it. It's not so necessary once the corpus luteum is producing progesterone. So I think Peat is short sighted on how the whole system works. Relying on exogenous progesterone is very strange when if you are healthy enough ovulation should be taking place 12 times a yr providing plenty of progesterone to counteract all of the estrogen. But without the estradiol a woman will feel very low motivation, low drive, dryness in the vagina, and depression. Oh and joint pain.

Yeah I think ascorbic acid has it's downsides. I am going to try just going off soon and see what happens. Weaning off didn't work. Cold turkey might speed up the progress. And if my nervous system doesn't adjust well that stinks! I haven't taken any niacinamide in a while. I test it out here and there. I don't need anything that promotes free fatty acids.

Hi - just want to say that I am enjoying following this discussion - there are many topics being brought up, so I hope I'm not going to get to tangental. I appreciate that you and redsun are trying to look at things objectively rather than having to assume that RP is correct or has the answer for everything. I think he is brilliant and I have great respect for him, but I always think it isn't wise to consider anyone a 'guru'. Anyway, I think discussion and looking at things from as many angles as possible can only be helpful.

* It seems that cypro might be a thing to use once in awhile for sleep? better than some things, I know some people use benedryl that way.

* I hope I'm not getting too tangental on this thread, let me know - but your comments re: estrogen. I was all ready to have a consult re: having some estrogen (and I'd want the combo with progesterone) replacement therapy), but after discovering RP and binge listening and reading him, I got the 'estrogen bad' message in my head, and cancelled that appointment. After more time and thought - I've been questioning whether 'estrogen always bad" is true or practical. It's obviously a hormone we need! I think issues are usually more a problem of imbalance vs. "all good or all bad", and I wonder if perhaps estrogen has become too vilified in his philosophy. As you say, in a healthy pre menopausal woman, things should be in balanced. I guess one theory is that there are environmental factors increasing estrogen, OR if a woman is supplementing estrogen via birth control, imbalance might develop.

However, I experience most of the symptoms that are attributed to lack of estrogen after after menopause (I realize most of these can be caused by many different things). One size does not fit all. I know many women who have gotten dramatic relief from HRT with estrogen - even just the cream for the vaginal dryness is a big help to many. I have even read some women comment on this forum that estrogen replacement is what really helped them. So, I'm re-thinking this and wondering if you or anyone else here has any thoughts. My theory is that is something is gong to help - it will, and very soon; so it would be easy enough to try and discontinue if there is no benefit or negatives. I don't know. Sometimes I feel the more I read and learn the more confused I get :). Interesting that you mention low motivation and drive as symptoms of lacking/low estradiol (assuming you are referring to 'general' not just related to sex. These is how I would most characterize my mood overall - lack of motivation to do anything, more so than depression, per se. I realize the 2 are closely related. I have had some significant personal losses recently I believe feeling a little 'depressed' would be normal now. I do not feel it is pathological. The lack of motivation was present before, and a little worse.

*It seems like just about anything has pros and cons.

 

[PeskyPeater]

Next to Bupropion, I think you can use Rhodiola Rosea with cyproheptadine to reduce cravings by increasing brain noradrenaline and dopamine.
Citrus aurantium and Rhodiola rosea in combination reduce visceral white adipose tissue and increase hypothalamic norepinephrine in a rat model of diet-induced obesity

In addition, C aurantium + R rosea administration resulted in an elevation (+15%) in hypothalamic norepinephrine and an elevation (+150%) in frontal cortex dopamine compared with the pair-fed group. These initial findings suggest that treatments of C aurantium + R rosea have actions on central monoamine pathways and have the potential to be beneficial for the treatment of obesity.

Bupropion inhibits the reuptake of dopamine and norepinephrine and reduces appetite through stimulating POMC neurons. Naltrexone blocks the effect of beta-endorphins secreted from POMC neurons.270

 

[PeskyPeater]

By the way Cyproheptadine blocks serotonin 5-ht2c. I think this is probably the main way it increases appetite. Not much you can do about this, so perhaps then boosting brain norepinephrine or dopamine could inhibit appetite.

Abstract​

Obesity is primarily a consequence of consuming calories beyond energetic requirements, but underpinning drivers have not been fully defined. 5-Hydroxytryptamine (5-HT) neurons in the dorsal Raphe nucleus (5-HT DRN) regulate different types of feeding behavior, such as eating to cope with hunger or for pleasure. Here, we observed that activation of 5-HT DRN to hypothalamic arcuate nucleus (5-HT DRN → ARH) projections inhibits food intake driven by hunger via actions at ARH 5-HT2C and 5-HT1B receptors, whereas activation of 5-HTDRN to ventral tegmental area (5-HT DRN → VTA) projections inhibits non-hunger-driven feeding via actions at 5-HT2C receptors. Further, hunger-driven feeding gradually activates ARH-projecting 5-HT DRN neurons via inhibiting their responsiveness to inhibitory GABAergic inputs; non-hunger-driven feeding activates VTA-projecting 5-HT DRN neurons through reducing a potassium outward current. Thus, our results support a model whereby parallel circuits modulate feeding behavior either in response to hunger or to hunger-independent cues.

5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding - Molecular Psychiatry

 

[InChristAlone]

Hi - just want to say that I am enjoying following this discussion - there are many topics being brought up, so I hope I'm not going to get to tangental. I appreciate that you and redsun are trying to look at things objectively rather than having to assume that RP is correct or has the answer for everything. I think he is brilliant and I have great respect for him, but I always think it isn't wise to consider anyone a 'guru'. Anyway, I think discussion and looking at things from as many angles as possible can only be helpful.

* It seems that cypro might be a thing to use once in awhile for sleep? better than some things, I know some people use benedryl that way.

* I hope I'm not getting too tangental on this thread, let me know - but your comments re: estrogen. I was all ready to have a consult re: having some estrogen (and I'd want the combo with progesterone) replacement therapy), but after discovering RP and binge listening and reading him, I got the 'estrogen bad' message in my head, and cancelled that appointment. After more time and thought - I've been questioning whether 'estrogen always bad" is true or practical. It's obviously a hormone we need! I think issues are usually more a problem of imbalance vs. "all good or all bad", and I wonder if perhaps estrogen has become too vilified in his philosophy. As you say, in a healthy pre menopausal woman, things should be in balanced. I guess one theory is that there are environmental factors increasing estrogen, OR if a woman is supplementing estrogen via birth control, imbalance might develop.

However, I experience most of the symptoms that are attributed to lack of estrogen after after menopause (I realize most of these can be caused by many different things). One size does not fit all. I know many women who have gotten dramatic relief from HRT with estrogen - even just the cream for the vaginal dryness is a big help to many. I have even read some women comment on this forum that estrogen replacement is what really helped them. So, I'm re-thinking this and wondering if you or anyone else here has any thoughts. My theory is that is something is gong to help - it will, and very soon; so it would be easy enough to try and discontinue if there is no benefit or negatives. I don't know. Sometimes I feel the more I read and learn the more confused I get :). Interesting that you mention low motivation and drive as symptoms of lacking/low estradiol (assuming you are referring to 'general' not just related to sex. These is how I would most characterize my mood overall - lack of motivation to do anything, more so than depression, per se. I realize the 2 are closely related. I have had some significant personal losses recently I believe feeling a little 'depressed' would be normal now. I do not feel it is pathological. The lack of motivation was present before, and a little worse.

*It seems like just about anything has pros and cons.

Yeah it's hard to say whether a woman should take estrogen post menopause. I'd tend to think no and I don't think just using progesterone is that great either, it may even prolong menopause cause breakthru bleeding spotting and possibly even start the cycle again. We should just go back to how we were before puberty. But problem is our fatty tissue does produce the bad kind of estrogen and as we get older it's harder to get rid of that circulating estrogen. The key would be to make sure you eat things that bind up your bile acids. This is where hormones are excreted. As far as vaginal dryness I wonder if that has to be a thing of one doesn't use hormones. Haven't looked into it yet.

 

[Limon9]

Glad things are going well for you.

@deliciousfruit This post made me realize that your past intake of niacin could be the issue. Excess niacin intake depletes methyl donors which are needed to make endogenous choline for acetylcholine synthesis. You could have severely undermethylated yourself.

Low Ach can not only lead to ADHD symptoms, but it will also feel like your whole body is falling apart because Ach is needed for all parasympathetic and sympathetic processes. Digestion and stomach acid secretion is also dependent on Ach signalling. From what I understand in the other thread you do not eat meat or animal protein in general right? Also do you eat any eggs? Dairy has almost no choline. You should examine your choline intake in your diet. You likely are not even reaching close to the bare minimum needs for choline.

You likely are very deficient in choline if you do not consume much animal protein at all. And if this is the case, digestion will weak or nonexistent. Likely you need to try and supplement phosphatidylcholine from sunflower lecithin. PointOutside also supplemented it for different reasons but in your case it seems the low choline issue can definitely apply to you because of a history of a low animal protein diet, and high dose niacin which depletes methyl groups used to make endogenous choline.

So it may be a mineral issue, or it may not be that at all and you just choline so your acetylcholine levels can increase to properly signal normal digestive functions.

Sorry about the necro, but this whole thread was very refreshing to read. I concur with what's said about acetylcholine - Peat's learned helplessness article is one of his subtler and more implicatory, yet has been taken as a knock-out blow against acetylcholine, as if this neurotransmitter was not obligatory for intestinal motility (people love high-dose thiamine - maybe they should see what it's used for!) For me the qualia of all these things - cyproheptadine, high-dose niacinamide or other methyl depletors, and so on - are identical, all tending to an anhedonic, mentally coagulated and zombie-like state, possibly brought on by homocysteine derangement and certainly by low acetylcholine. Again, similarly to others, this is relieved with B6, reduced consumption of liver, and dietary choline. People like to journal their illness, but I find it more productive to log the exceptionally good days.

Besides price, what difference would there be in using saturated phosphatidylcholine derived from MitoLipin as compared to sunflower lecithin? I suppose the concomitant vitamin E would aid its synthesis, but lecithin is not a specialty, and I have never used it.

 

[PeskyPeater]

You could also add betaine HCL, not TMG, "It is a protonated form of TMG, meaning it will give up or transfer a proton and a chloride ion in an aqueous solution (liquid). This makes betaine HCl a very good dietary source of hydrochloric or gastric acid"

Betaine taken together with choline sources, can prevent TMAO formation better than using pure choline, if that is a risk for you, but that has been found to be overrated issue.

Betaine supplementation will spare methionine and choline and helps to improve their usage in the biosynthesis pathway to form phosphatidylcholine. Because of that Betaine can reduce homocysteine levels back no normal. Unless when one is overdosing >100mg niacinamide that stears betaine away to act as the main methyldonor. Probably why Dr Peat recommends 50mg niacinamide.

"choline to serve as a methyl donor, it needs first to be converted to betaine. Dietary betaine can act as a direct replacement for choline, saving the organism of one metabolic step, and of course sparing dietary choline itself."

"In regards to methionine, the transfer of a methyl group depends on the activation of methionine to S-adenosyl methionine (SAM). This compound transfers then the methyl group to an acceptor for the synthesis of substances such as creatine, carnitine, phosphatidylcholine and epinephrine. Following the transmethylation, SAM is degraded to S-adenosyl homocysteine (SAH) and subsequently to homocysteine, which can have two distinct fates, one involving betaine."

A little warning about using Nootropic, they can affect the availablity of choline for the liver, reduces levels of choline available for the liver.
Perhaps one can circumvent this problem whith a water soluble nootropic powder and absorbed it sublingual to avoid first pass to the liver, that's how I always used oxiracetam. Oxiracetam is mainly cleared renally and approximately 84% is excreted unchanged in the urine

Sorry about the necro, but this whole thread was very refreshing to read. I concur with what's said about acetylcholine - Peat's learned helplessness article is one of his subtler and more implicatory, yet has been taken as a knock-out blow against acetylcholine, as if this neurotransmitter was not obligatory for intestinal motility (people love high-dose thiamine - maybe they should see what it's used for!) For me the qualia of all these things

edit- Calcium channel blockers like Kumis Kutjing may be able to reduce the release of acetylcholine and noradrenaline to easy gut symptoms. Also dopamine inhibits the release of acetylcholine in the gut, some licorice tea blocking the breakdown of dopamine (MOA-B) might prove useful, a non laxative dose cascara has similar MAO-B blocking effects.

- cyproheptadine, high-dose niacinamide or other methyl depletors, and so on - are identical, all tending to an anhedonic, mentally coagulated and zombie-like state, possibly brought on by homocysteine derangement and certainly by low acetylcholine. Again, similarly to others, this is relieved with B6, reduced consumption of liver, and dietary choline. People like to journal their illness, but I find it more productive to log the exceptionally good days.

in the brain, there is a paradox effect going on with choline - acetylcholine, becasue they dont function with re-uptake tranporters.
When you starve the uptake of choline into the brain the acetylcholine metabolism is affected, is not broken down and turnover is deceased, causing a stressed like state. But if you restore the available choline, then proper operational turnover and metabolism is restored. By splitting the acetylcholine from choline and acetate, the transported choline is later on rejoined with acetylcholine, etc. So you should focus to improve the uptake of choline and the degredation process of acetylcholine to improve cognition.

Then Cyproheptadine that blocks Muscarinic m2 cells could worsen cognition when the altered turnover of acetylcholine has been affecting the M2:

"One possible explanation for limited therapeutic efficacy of AChE inhibitors might be that besides stimulating the postsynaptic cholinergic receptors, higher levels of baseline ACh levels at the cholinergic synapses may also stimulate presynaptic autoreceptors, such as muscarinic M2 receptors, which may shut down the recruitment of cholinergic inputs during information processing (Decossas et al., 2005). " link

And then that pesky serotonin increases acetylcholine buildup, disturbing its breakdown and may well be affecting cognition. see below:

"The release of cerebral acetylcholine from terminals in the cerebral cortex has been shown to be regulated by 5-hydroxytryptamine (5-HT) but it is not known which subtype of the 5-HT receptor is involved. 5-HT receptor agonists increase acetylcholine levels in vivo, indicating a reduced turnover, and reduce release of acetylcholine from striatal slices in vitro. Depleting 5-HT by inhibiting synthesis or by destroying the neurons containing 5-HT potentiates acetylcholine release, and increases acetylcholine turnover in the cerebral cortex and hippocampus. Selective antagonists for the 5-HT3 receptor subtypes which seem to have effects on mood and activity may exert their effect through the regulation of acetylcholine release in the cortex and limbic system. Radioligand binding studies show a high density of 5-HT3 receptors in the cholinergic-rich entorhinal cortex and we provide evidence that a reduction in cortical cholinergic function can be effected in vitro by 5-HT3 receptors. " link

 

[redsun]

Sorry about the necro, but this whole thread was very refreshing to read. I concur with what's said about acetylcholine - Peat's learned helplessness article is one of his subtler and more implicatory, yet has been taken as a knock-out blow against acetylcholine, as if this neurotransmitter was not obligatory for intestinal motility (people love high-dose thiamine - maybe they should see what it's used for!) For me the qualia of all these things - cyproheptadine, high-dose niacinamide or other methyl depletors, and so on - are identical, all tending to an anhedonic, mentally coagulated and zombie-like state, possibly brought on by homocysteine derangement and certainly by low acetylcholine. Again, similarly to others, this is relieved with B6, reduced consumption of liver, and dietary choline. People like to journal their illness, but I find it more productive to log the exceptionally good days.

Besides price, what difference would there be in using saturated phosphatidylcholine derived from MitoLipin as compared to sunflower lecithin? I suppose the concomitant vitamin E would aid its synthesis, but lecithin is not a specialty, and I have never used it.

I dont think it makes much of a different either way but I always recommend food for choline before supplements.

Niacinamide induced anhedonia would not really be from loss of methyl groups. It depletes betaine but it doesnt deplete choline directly actually and research has shown it keeps more choline in the nervous system. But niacinamide agonizes GABA-A which can lead to anhedonia as gaba activity can reduce the activity of the major neurotransmitters involved in emotional function, glutamate and dopamine. Keep in mind NAD is used for a lot of processes including making many NTs, ATP production, antioxidant recycling, so NAD has use despite loss of methyl. Also, supplementing B3 spares tryptophan use for serotonin, this is why research has shown it increases serotonin. And too much serotonin can also contribite to anhedonia. But the negative effects would be temporary.

 

[PeskyPeater]

I dont think it makes much of a different either way but I always recommend food for choline before supplements.

Niacinamide induced anhedonia would not really be from loss of methyl groups. It depletes betaine but it doesnt deplete choline directly actually and research has shown it keeps more choline in the nervous system. But niacinamide agonizes GABA-A which can lead to anhedonia as gaba activity can reduce the activity of the major neurotransmitters involved in emotional function, glutamate and dopamine. Keep in mind NAD is used for a lot of processes including making many NTs, ATP production, antioxidant recycling, so NAD has use despite loss of methyl. Also, supplementing B3 spares tryptophan use for serotonin, this is why research has shown it increases serotonin. And too much serotonin can also contribite to anhedonia. But the negative effects would be temporary.

Bingo

Ventral tegmental area GABA neurons mediate stress-induced blunted reward-seeking in mice - Nature Communications

Abstract​

Decreased pleasure-seeking (anhedonia) forms a core symptom of depression. Stressful experiences precipitate depression and disrupt reward-seeking, but it remains unclear how stress causes anhedonia. We recorded simultaneous neural activity across limbic brain areas as mice underwent stress and discovered a stress-induced 4 Hz oscillation in the nucleus accumbens (NAc) that predicts the degree of subsequent blunted reward-seeking. Surprisingly, while previous studies on blunted reward-seeking focused on dopamine (DA) transmission from the ventral tegmental area (VTA) to the NAc, we found that VTA GABA, but not DA, neurons mediate stress-induced blunted reward-seeking. Inhibiting VTA GABA neurons disrupts stress-induced NAc oscillations and rescues reward-seeking. By contrast, mimicking this signature of stress by stimulating NAc-projecting VTA GABA neurons at 4 Hz reproduces both oscillations and blunted reward-seeking. Finally, we find that stress disrupts VTA GABA, but not DA, neural encoding of reward anticipation. Thus, stress elicits VTA-NAc GABAergic activity that induces VTA GABA mediated blunted reward-seeking. link

 

[redsun]

Bingo

Ventral tegmental area GABA neurons mediate stress-induced blunted reward-seeking in mice - Nature Communications

Abstract​

Decreased pleasure-seeking (anhedonia) forms a core symptom of depression. Stressful experiences precipitate depression and disrupt reward-seeking, but it remains unclear how stress causes anhedonia. We recorded simultaneous neural activity across limbic brain areas as mice underwent stress and discovered a stress-induced 4 Hz oscillation in the nucleus accumbens (NAc) that predicts the degree of subsequent blunted reward-seeking. Surprisingly, while previous studies on blunted reward-seeking focused on dopamine (DA) transmission from the ventral tegmental area (VTA) to the NAc, we found that VTA GABA, but not DA, neurons mediate stress-induced blunted reward-seeking. Inhibiting VTA GABA neurons disrupts stress-induced NAc oscillations and rescues reward-seeking. By contrast, mimicking this signature of stress by stimulating NAc-projecting VTA GABA neurons at 4 Hz reproduces both oscillations and blunted reward-seeking. Finally, we find that stress disrupts VTA GABA, but not DA, neural encoding of reward anticipation. Thus, stress elicits VTA-NAc GABAergic activity that induces VTA GABA mediated blunted reward-seeking. link

Yeh GABA isnt all good. Its great to control anxiety and hyperstimulation, but too much and then you don't care about anything and your emotional function is all in impaired.