59 replies to this topic

[PuzzleSolver]

I think the AChE inhibition by caffeine is a good point too - you could apply the same logic and ditch all caffeine as a precautionary measure based on the speculation of those articles. However, real studies show caffeine to be protective of neuronal health over the long-term.

Kewl, thanks for sharing that info... And I agree and say through experience, either ditch ALL caffeine consumption if you are considering taking Hup A or don't even use it and stick with caffeine

[aghonia]

Very good thread, subscribed. Now I wonder how to treat my Source Naturals 200mcg Hup.

Edited by aghonia, 21 August 2013 - 09:30 AM.

[Alexwkt]

I am new on here, but this is a very interesting discussion, a bit of history, I have mercury poisoning, many different tests have proved this to be the case, the damage has been widespread, vitamin and mineral balance is completely screwed I have to supplement with a significant amount of supplements each day just to stay on top of things, one thing I really suffered with was/is brain fog, sometimes cognitive ability goes down to a few minutes of study before my mind goes all over the place. Talking to my doctor who deals with these kind of issues he said I should take PC (phosphocholine) I said I was as is is part of soy lecithin when we worked out how much I was taking 3gm per day of PC he said I needed to significantly increase the levels.

I purchased PC as a supplement and was taking 10gm per day, the improvements were significant within a week zero brain fog concentration, cognitive function greatly improved, I spent 6 months on this dose and the effects were consistent across the period, I recently dropped the dose down to 3gm's and within a few days the brain fog is back, this time I looked at other routes, noocept was the first one to try, 30mg first thing in the morning I tried this for a month, the results were good but very short lived, I basically got about 2 hours clearer thought about an hour and a half after taking, then back to square one, and once I stopped it completely the brain fog is back, so Huperzine A is next, based on the discussion in this thread I have 200mcg tablets turning up, I will break these in half and dose once upon waking each day.

I have the benefit of a serious amount of study to do so I can see the effects within a few days.

Back to the mercury I am removing it but the process is causing a lot of neurological issues whilst it is being pulled out, so looking for something to help with the cognitive stuff whilst I remove it.

[mrnootropic]

Interesting thread!!

Very good thread, subscribed. Now I wonder how to treat my Source Naturals 200mcg Hup.

LOL, I also have some source naturals Huperzine A lying around.

If i take it, i take it once every few weeks if i need a brain boost, i find it very very strong..

Edited by Mr.Nootropic, 02 September 2013 - 07:01 PM.

[Ukko]

Amen, what a great thread. I really really strongly feel that all this focus on acetylcholine and acetylcholine esterase inhibitors is quite dangerous.

Paradox nr. 1: Phosphatidylcholine is all good, but that does not apply to acetylcholine

I believe that most people are better off by making sure they get enough phosphatidylcholine as a brain building block. Same with DHA and uridine. So, eating things like soy, lecithin and eggs is just ggreat. This will allow for the structure of the brain to be rebuilt. Which is valuable. But then to kjump ship and make the stretch conclusion that the more acetylcholine as a neurotransmitter the better, well that is just nuts. To some extent, the neurotransmitter game is a zero sum one. You increase one and the others go down. Why would we want to lower dopamine and serotonin for example?

Paradox 2: Acetylcholine is way overhyped

People want to feel better. Then they fall into all these acetylcholine boosters and esterase inhibtors. I know I did. Luckily, I came across alpha GPC fairly early on and it gave me the nastiest deepest depression and really bad nause quite fast. I was really confused. Wasn't acetylcholine supposed to be the greatest thing around? This made me pay attention. I quickly found out that while I can take carnitine tartrate in vast amounts with no ill effects, acetyl carnitine fairly easily gives me bad anxiety. Not really deep depression but just bad anxiety. It too boosts acetylcholine as a neurotransmitter. Imagine the irony if indeed, as the above extracts suggest, acetylcholine esterase is what slows down alzheimers? So all this folks may be inducing quicker alzheimers. Have fun.

Paradox 3. People don't need better memory or more intelligence, they need more drive and better mood

I am a classical example of a person who is, if anything, too smart. It is easier to be happy and driven, if you are dumb. Just to give you an idea, I was a top5 student in a fairly large nation in high school. I really really do not need to get smarter. But lord knows I could use more drive, less anxiety and more happiness. Boosting acetylcholine and inhibiting its esterase is not the way to go to achieve. Quite the opposite. I have recently found out that DMAE actually gives me more drive, maybe exactly because it acts as a false acetylcholine precursors and reduces its amount. I love it. I have also noticed that CDP choline is OK. It really is lightyears away from alpha GPC choline. Converts to uridine and stuff. And is a breakdown product of acetylcholine, only gets recycled back if needed. Let's face it, most of us on this forum are too smart to begin with. That's the problem, i.e. acetylcholine dominance. Maybe the racetams help some of us as they deplete aceylcholine? Would make sense. Most of us would likely benefit far more from uridine, sulbutiamine, CDP choline, tyrosine, N-acetyltyrosine, inositol and forskolin. All of these boost dopamine or sensitive its receptors or increase their amounts. I believe that us on this forum are very often either acetylcholine dominant to begin with making our dopaminergic systems subpoptimal OR have messed up our dopaminergic systems by porn, alcohol, caffeine, drugs or maybe by excess focus on acetylcholine boosters and esterase inhibitors. Wake up folks.

And, finally, I have recently done a lot of research on folate, MTHFR, NADH, niacin and above all tetrahydrobiopterin. My friends, here's where about 50% of us have issues according to studies. And those of use that do, have really suboptimal dopaminergic systems to begin with. Which paradoxically may make us smarter, given the zero sum game between the neurotransmitters. Google with those terms and dopamine. There's your answer, not in acetylcholine.

[mrnootropic]

And, finally, I have recently done a lot of research on folate, MTHFR, NADH, niacin and above all tetrahydrobiopterin. My friends, here's where about 50% of us have issues according to studies. And those of use that do, have really suboptimal dopaminergic systems to begin with. Which paradoxically may make us smarter, given the zero sum game between the neurotransmitters. Google with those terms and dopamine. There's your answer, not in acetylcholine.

Hmm, very interesting.
Great post!!

I somewhat agree, i guess if you are interested in boosting your acetyl choline levels it would be wise to have a good balance between your other neurotransmitters, which could mean you should also boost the levels of your other neurotransmitters.

Or try to balance them without raising the levels of them (if possible), but i agree, most have suboptimal dopaminergic systems.

Edited by Mr.Nootropic, 03 September 2013 - 10:45 AM.

[Alexwkt]

Ukko,

I agree with a lot of what you said, I do very very well on PC, but the quantities are becoming so large there has to be other ways to solve this problem at a lower level.

I tried 100mcg of Huperzine A yesterday and it knocked me all over the place, but this could be many things like not the Huperzine at all as I have many complex problems going on and this could just be a coincidence as I am ill most days, MTHFR should be ignored in mercury toxic people as virtually all will exhibit all the signs of issues with it but actually the underlying cause is mercury and once that is going the MTHFR issues go away for most, it is ok to prop yourself up on B's in the meantime but you will not fix the underlying cause until the mercury is gone, been there done it for years with all the different B12's (all four of them), sublinguals, injections, tablets, all the different forms of folic acid as well and all the different forms of B6, all give me temporary fixes but nothing lasting at all.

Certainly not looking to get smarter I am looking to get better e.g. well and able to function, looks like I am back to large amounts of PC as this is the only thing that seems to work well for me.

I guess there is a big distinction between healthy people trying these things and people that have significant chemical imbalances, unfortunately for me I am in the later group looking for the missing pieces in my health puzzle.

[Endymion]

Amen, what a great thread. I really really strongly feel that all this focus on acetylcholine and acetylcholine esterase inhibitors is quite dangerous.

Paradox nr. 1: Phosphatidylcholine is all good, but that does not apply to acetylcholine

I believe that most people are better off by making sure they get enough phosphatidylcholine as a brain building block. Same with DHA and uridine. So, eating things like soy, lecithin and eggs is just ggreat. This will allow for the structure of the brain to be rebuilt. Which is valuable. But then to kjump ship and make the stretch conclusion that the more acetylcholine as a neurotransmitter the better, well that is just nuts. To some extent, the neurotransmitter game is a zero sum one. You increase one and the others go down. Why would we want to lower dopamine and serotonin for example?

Paradox 2: Acetylcholine is way overhyped

People want to feel better. Then they fall into all these acetylcholine boosters and esterase inhibtors. I know I did. Luckily, I came across alpha GPC fairly early on and it gave me the nastiest deepest depression and really bad nause quite fast. I was really confused. Wasn't acetylcholine supposed to be the greatest thing around? This made me pay attention. I quickly found out that while I can take carnitine tartrate in vast amounts with no ill effects, acetyl carnitine fairly easily gives me bad anxiety. Not really deep depression but just bad anxiety. It too boosts acetylcholine as a neurotransmitter. Imagine the irony if indeed, as the above extracts suggest, acetylcholine esterase is what slows down alzheimers? So all this folks may be inducing quicker alzheimers. Have fun.

Paradox 3. People don't need better memory or more intelligence, they need more drive and better mood

I am a classical example of a person who is, if anything, too smart. It is easier to be happy and driven, if you are dumb. Just to give you an idea, I was a top5 student in a fairly large nation in high school. I really really do not need to get smarter. But lord knows I could use more drive, less anxiety and more happiness. Boosting acetylcholine and inhibiting its esterase is not the way to go to achieve. Quite the opposite. I have recently found out that DMAE actually gives me more drive, maybe exactly because it acts as a false acetylcholine precursors and reduces its amount. I love it. I have also noticed that CDP choline is OK. It really is lightyears away from alpha GPC choline. Converts to uridine and stuff. And is a breakdown product of acetylcholine, only gets recycled back if needed. Let's face it, most of us on this forum are too smart to begin with. That's the problem, i.e. acetylcholine dominance. Maybe the racetams help some of us as they deplete aceylcholine? Would make sense. Most of us would likely benefit far more from uridine, sulbutiamine, CDP choline, tyrosine, N-acetyltyrosine, inositol and forskolin. All of these boost dopamine or sensitive its receptors or increase their amounts. I believe that us on this forum are very often either acetylcholine dominant to begin with making our dopaminergic systems subpoptimal OR have messed up our dopaminergic systems by porn, alcohol, caffeine, drugs or maybe by excess focus on acetylcholine boosters and esterase inhibitors. Wake up folks.

And, finally, I have recently done a lot of research on folate, MTHFR, NADH, niacin and above all tetrahydrobiopterin. My friends, here's where about 50% of us have issues according to studies. And those of use that do, have really suboptimal dopaminergic systems to begin with. Which paradoxically may make us smarter, given the zero sum game between the neurotransmitters. Google with those terms and dopamine. There's your answer, not in acetylcholine.

Nice post. I agree with a lot of what you say, Ukko, although I think it's a mistake to make blanket statements about the effects of individual neurotransmitters. Importantly, I think there's a lot of variation between individuals. Given our current paucity of knowledge, I think we should be mostly empirical in our approach to nootropics. Does it help me in achieving the specific goals I want to use it for - for example, increased focus, potentially at the expense of creativity; or increased memory at the expense of some other element of cognition/mood? If you're happy with some trade off, then I don't see why one shouldn't use it. If it doesn't work for you then end of story.

Fears about the long-term effects of any nootropic are certainly worth considering and I appreciate people bringing those concerns to our attention. The acetylcholinesterase theory is intriguing. I'd like to see some studies showing that AChE inhibition contributes to AD before I'll accept it though. You'd think it might be possible to induce AD in mice by dosing them with AChEIs. See reversible's post as I think this was dealt with already.

Edited by Endymion, 11 September 2013 - 11:33 AM.

[xks201]

I can't handle huperzine or aricept either. Even the smallest doses will put me on my ass for like 2 days.

[Ukko]

I can't handle huperzine or aricept either. Even the smallest doses will put me on my ass for like 2 days.

Yeah, you are likely acetylcholine dominant. Brainy, smart. Deep and reflective. Low drive and risk of long term mild depression. Did I get it right?

[xks201]

Yep. I wouldn't say low drive though. Maybe a tendency to procrastinate?

[Endymion]

Forer and Dunning-Kruger effects notwithstanding, I'd say I also fit that description (along with the majority of people on this forum, I imagine), and yet huperzine has a positive effect on me. I think human neurobiology is more complicated than that.

[Alexwkt]

I can't handle huperzine or aricept either. Even the smallest doses will put me on my ass for like 2 days.

that is what it did to me, a complete head spin for two days, won't be touching that stuff again.

back to large amounts of PC which works wonders on me.

atb

alex

[unregistered_user]

I can't handle huperzine or aricept either. Even the smallest doses will put me on my ass for like 2 days.

that is what it did to me, a complete head spin for two days, won't be touching that stuff again.

back to large amounts of PC which works wonders on me.

atb

alex

PC? What is that?

[Alexwkt]

pc = phosphatidylcholine

I take it as a supplement (many grams per day) and as soy lethicin products used

http://www.iherb.com...lbs-907-g/23289 2-3 tablespoons per day.

https://www.bodybio....product357.aspx 2 per day (expensive but the best quality)

http://www.iherb.com...0-Softgels/2649 10 per day (not as good quality as the one above but it allows me to take a lot more)

that combo above cleared my brain fog within a few days, as with everything always start low, I know people that have had trouble with it.

atb

alex

[Ukko]

Yeah, I react amazingly well to PC as well. A high dose gives me noticeable intelligence boost, reduces anxiety and so on. I can literally feel my brain light up so to speak. CDP choline does not seem to do much, but gives me no serious side effects either. Alpha GPS makes me an immediate depressed person with anxiety. Won't even tough AChE blockers.

[Alexwkt]

Ukko,

Same results here, my brain almost races when I have PC (but in a good way, not like caffeine), I get depth of thought deeper than without it, I can problem solve better (I am a software developer by trade), my brain reacts very well to the stuff that it needs and reacts very badly to the stuff that is no good, Huperzine A gave me a two day crushing headache not to be repeated..

As my doctor said, "take as much PC as you can afford" very very true for me.


ATB

Alex

[Ukko]

Ukko,

Same results here, my brain almost races when I have PC (but in a good way, not like caffeine), I get depth of thought deeper than without it, I can problem solve better (I am a software developer by trade), my brain reacts very well to the stuff that it needs and reacts very badly to the stuff that is no good, Huperzine A gave me a two day crushing headache not to be repeated..

As my doctor said, "take as much PC as you can afford" very very true for me.


ATB

Alex

That totally resonates with me. I fear people underestimate PC and lecithin. After all, the structure of the brain needs PC/lecithin, PS/lecithin, DHA/fish oil and to a lesser extent uridine. And to the extent acetylcholine is needed...it can, as I understand it, be scavenged from PC. Chemical weapons i.e. nerve gas, venoms, poisons and pesticides tend to be irreversible AChE inhibitors. Yet everyone is all GABA GABA about using reversible AChE inhibitors. That may be a second broad source of disappointment and confusion beyond PC and lecithin not being respected.

[dannyo]

Amen, what a great thread. I really really strongly feel that all this focus on acetylcholine and acetylcholine esterase inhibitors is quite dangerous.

Paradox nr. 1: Phosphatidylcholine is all good, but that does not apply to acetylcholine

I believe that most people are better off by making sure they get enough phosphatidylcholine as a brain building block. Same with DHA and uridine. So, eating things like soy, lecithin and eggs is just ggreat. This will allow for the structure of the brain to be rebuilt. Which is valuable. But then to kjump ship and make the stretch conclusion that the more acetylcholine as a neurotransmitter the better, well that is just nuts. To some extent, the neurotransmitter game is a zero sum one. You increase one and the others go down. Why would we want to lower dopamine and serotonin for example?

Paradox 2: Acetylcholine is way overhyped

People want to feel better. Then they fall into all these acetylcholine boosters and esterase inhibtors. I know I did. Luckily, I came across alpha GPC fairly early on and it gave me the nastiest deepest depression and really bad nause quite fast. I was really confused. Wasn't acetylcholine supposed to be the greatest thing around? This made me pay attention. I quickly found out that while I can take carnitine tartrate in vast amounts with no ill effects, acetyl carnitine fairly easily gives me bad anxiety. Not really deep depression but just bad anxiety. It too boosts acetylcholine as a neurotransmitter. Imagine the irony if indeed, as the above extracts suggest, acetylcholine esterase is what slows down alzheimers? So all this folks may be inducing quicker alzheimers. Have fun.

Paradox 3. People don't need better memory or more intelligence, they need more drive and better mood

I am a classical example of a person who is, if anything, too smart. It is easier to be happy and driven, if you are dumb. Just to give you an idea, I was a top5 student in a fairly large nation in high school. I really really do not need to get smarter. But lord knows I could use more drive, less anxiety and more happiness. Boosting acetylcholine and inhibiting its esterase is not the way to go to achieve. Quite the opposite. I have recently found out that DMAE actually gives me more drive, maybe exactly because it acts as a false acetylcholine precursors and reduces its amount. I love it. I have also noticed that CDP choline is OK. It really is lightyears away from alpha GPC choline. Converts to uridine and stuff. And is a breakdown product of acetylcholine, only gets recycled back if needed. Let's face it, most of us on this forum are too smart to begin with. That's the problem, i.e. acetylcholine dominance. Maybe the racetams help some of us as they deplete aceylcholine? Would make sense. Most of us would likely benefit far more from uridine, sulbutiamine, CDP choline, tyrosine, N-acetyltyrosine, inositol and forskolin. All of these boost dopamine or sensitive its receptors or increase their amounts. I believe that us on this forum are very often either acetylcholine dominant to begin with making our dopaminergic systems subpoptimal OR have messed up our dopaminergic systems by porn, alcohol, caffeine, drugs or maybe by excess focus on acetylcholine boosters and esterase inhibitors. Wake up folks.

And, finally, I have recently done a lot of research on folate, MTHFR, NADH, niacin and above all tetrahydrobiopterin. My friends, here's where about 50% of us have issues according to studies. And those of use that do, have really suboptimal dopaminergic systems to begin with. Which paradoxically may make us smarter, given the zero sum game between the neurotransmitters. Google with those terms and dopamine. There's your answer, not in acetylcholine.

Good point I kind of agree with you.

[unregistered_user]

What source of PC do you guys recommend?

[Ukko]

What source of PC do you guys recommend?

Lots of lecithin, like several table spoons, with something like yoghurt. Also gives you phosphatidylserine and funky insulin sensitizers like d-chiro-inositol. Cheap, healthy, delicious.

[unregistered_user]

Thanks! Are there just straight PC sources? What is everyone else taking? Is lecithin really the best?

[Ukko]

Thanks! Are there just straight PC sources? What is everyone else taking? Is lecithin really the best?

There are. And they are either lecithin pills or lecithin concentrate pills. http://www.amazon.co...m/dp/B00068UANS

[Alexwkt]

Thanks! Are there just straight PC sources? What is everyone else taking? Is lecithin really the best?

my doctor says this is the best quality

https://www.bodybio....product356.aspx

I use that and cheaper versions and lecithin (lots a couple of heaped tablespoons with un-denaturated whey protein and BCAA twice a day)

important to take some near bedtime as this is the time when the brain does most of the repair work PC is needed to fix the cell membranes, good quality omega's are important too, fresh linseed oil is next on my list to introduce.

http://highbarnoils.co.uk

atb

alex

[Ukko]

Oh boy, made a mistake. Bought a pre-training supplement called Hemavol. Had some. Felt so shit, so instantly depressed that I had to check its ingredients. Yes, the usual suspect: alpha GPC. Felt so bad it was almost amusing, to my wife. Here's another story from a poor bloke who overdosed alpha GPC: http://forum.bulletp...-hell-and-back/

[Alexwkt]

Its worth mentioning that I felt the same when taking SSRI's (antidepressants) a few years back when all the doctors did not know what was wrong with me as taking Huperzine A, I guess the rule of thumb is try a very little bit of anything new, many many months of SSRI's produced the same results, things did not improve over time, my guess is the same would happen with Huperzine A in my case.

[reversible]

I thought I might mention that taking large doses of choline or assorted other acetylcholine precursors carries dangers of its own.  Increased risk of lethal prostate cancer, for example.  See the linked study (by Richman et al. at Harvard school of public health, published in 2012 in the American Journal of Clinical Nutrition), the full text of which is freely available.

 

Men in the highest quartile of total dietary choline intake (ca. 550 mg) had a 70% higher likelihood of developing *lethal prostate cancer than those in the lowest quartile, with the most important plausible confounding factors being carefully controlled for. Validated dietary questionnaires were used to determine which forms of choline individual subjects consumed, and guess what?  The form of choline most strongly associated with the risk of developing *lethal prostate cancer was everyone's favorite, alpha-GPC!  (the association with free choline was also significant). Now, how about choking 1.2 g of the stuff down every day for years? 

 

If it's hard to think about why choline would have this effect, bear in mind that cancer cells proliferate rapidly, and thus need synthesis of cellular membranes (requiring choline) also to be rapid.  But before you say - "oh, this should only be a problem once someone already has cancer," let me point out that in this study, post-cancer-diagnosis dietary choline intake did not significantly correlate with increased risk of lethal cancer - only dietary exposure to choline prior to diagnosis did.  

 

Cancer isn't the sort of thing that just shows up one day out of nowhere.  We all have precancerous cells in our body all of the time, and it is left to the immune system and the body's corrective machinery (e.g., p53, "the guardian of the genome") to sort all of this out before tumorigenesis gets underway.  To avoid developing cancer, we need the correction process (cytostasis, DNA repair, killing of irreparable cells) to be faster than proliferation of aberrant cells.  In view of that, it should be easy to appreciate why dumping supraphysiological quantities of nutrients into the body that healthy cells don't really need but cancer cells do might be a bad idea.

 

As for me?  I'd rather take a hundred-odd micrograms of an exquisitely selective xenobiotic molecule.  Especially since it actually seems to be effective.

 

http://www.ncbi.nlm....les/PMC3441112/

[Alexwkt]

Reversible,

 

Thanks for the post, very interesting reading, certainly food for thought, I got the results back from genetic tests recently and it showed that I have lots of ++'s for a number of genes that are related to choline, what was more interesting was all the other compounds I have issues with they are widespread tweaking my supplements based on this report has produced very good results and has allowed me to lower my choline in take to small amounts (I take Alpha GPC just before exams only now 1-2gm).

 

PC I still take about 1gm per day I get fogged without it after about a week off it, so I will continue with that. One thing that all these studies do it test on the normal population, I would love to say I am normal but I am clearly not when it comes to chemical imbalances I wonder what the results would be if they tested people like me that have issues with PEMT genes, the biggest win recently is with upping my methyl donors, even though I am COMT++ and should avoid them I have enough genes messed up the other way that this is more than cancelling out the COMT++ issues.

 

Man this is complex stuff, no wonder most doctors swerve this area.

 

thanks again, I will have another read of your post later.

 

atb

 

alex

 

[reversible]

For what it's worth, there didn't seem to be a statistically significant association of PC intake with lethal prostate cancer risk in this study.  

 

I've been tweaking my own supplement use markedly downward over the last month or so after encountering some pretty hair-raising studies on NAC (which I'd been using with some success to mitigate bipolar depression).  Unfortunately I can't say how much of my present brainfog might be related to supplement-withdrawal since I've concomitantly thrown an anticonvulsant (lamotrigine) into the daily handful of pills (I know, I know, not very scientific -.but I hear it's jesus juice for type II bipolar disorder).  

 

 

[Alexwkt]

Reversible,

 

What issues are you finding with NAC, if it is tolerated it is normally very good to take in large quantities as long as your vitamin C ratio to NAC is 3/1 which mine is e.g. 12gm of vitamin C to 4gm of NAC per day.

 

I have a friend who has got rid of Bipolar (not sure what type) his was related to mercury in the brain, over 3 years of ALA chelation his done the trick for him along with a bunch of other interventions.

 

atb

 

alex