60 replies to this topic

[NDM]

Devinthayer has zero credentials in biochemistry and I don't understand why people abandonned all interest in centro & dmae simply because of his speculations. Speculations =/= facts.

[golden1]

yaaaaa... kind of a bit hyped when it should be presented as much more of a theoretical problem..no?

[Crispy Cat]

with my extremely limited knowledge(i really dont understand most of what i have read and please correct me if im wrong) looking through pubmed and google search over the last few daysit seems there are alot of articles that say dmae stops the choline from crossing the blood brain barrier
which although it raises choline in the body if it cant cross into the brain its not going to act as a good acetylcholine precursor for use with other nootropics which is what most (certainly myself) mainly buy centro for!

im not sure on the MS side of it.. but its something that worries me as like Devinthayer my mother suffers with MS all be it the early stages.. yet as Brainfogged pointed out no true cause has been found by any doctor or scientist!
It would be interesting if someone can find an article linking diets high in natural sources of dmae and MS ( i know my mums diet is mainly chicken and vegetable based)

the other negatives are of little importance to me but the increased risk of MS and dmae's apparent problems of producing what i would class as useful choline has definitely made me rethink how much i will use , how often and how long without cycling off of it...
im coming to the conclusion that occasional low dose rather than daily high dose will limit the possible negatives and hopefully still provide some of the lipofuscin removal benefits

[golden1]

Yeah but it stops some choline from crossing the bbb or all. That's kind of my point, there are studies that say it inhibits these things but usually nothing gets inhibited completely(and usually high doses are given in these studies, It's hard to figure out the equivalent dose for a human given the info inthose studies.. for me at least..). Hence, my question of it being blown out of proportion.

[Crispy Cat]

I guess thats why the other sources of choline were recommended by Devinthayer to get around what could be a partial block.. either by providing so much that some has to get through or providing a different type/composition to the blocked one .. not sure how it would work
I was recommended to this thread after finding I was still getting headaches with pramiracetam even with 800mg of centro 2x a day and a couple of eggs for breakfast
the headaches would normally indicate low choline.. as with alot of other racetams and explain why I had some very good days followed by alot of headache days!
i was personally looking for other explanations at the time as I was thinking I would be getting alot of choline from centro however this "blocking" would explain those headaches and possibly indicate to it also blocking the egg choline or that 2 eggs only provide minimal amounts of choline (?)
(not a very scientific test but its how im looking at it)
so hopefully when I revisit pramiracetam ill do it with some alpha gpc and get better and more consistent results ...
well unless someone has something equally surprising to tell me about alpha gpc :D

[renfr]

I speculate long term effects of chronic use will result in multiple sclerosis. Multiple Sclerosis is a brain degenerative disease that I speculate is from overactive choline dehygrogenase or underactive argininosuccinate synthetase. Overmethylation results in fatigue. The reason is that it speeds up the NOS enzyme, making more NOS and citrulline. Ammonia builds up, CPS1 expression is suppressed, and consequently, the citric acid cycle is affected (less ornithine, less fumarate), causing citrullination of proteins and fatigue from acetic acid build up, creating N-Acetyl-Aspartate, which complicates the problem...

It's a long discussion, and I keep getting clues from Pubmed studies. Overmethylation plays a big role in Multiple Sclerosis, but it is much more complicated than that. I'll do a blog on it sometime.

So in other terms drugs such as bacopa or pramiracetam that increase NOS are harmful to your health?

[Climactic]

I speculate long term effects of chronic use will result in multiple sclerosis. Multiple Sclerosis is a brain degenerative disease that I speculate is from overactive choline dehygrogenase or underactive argininosuccinate synthetase. Overmethylation results in fatigue. The reason is that it speeds up the NOS enzyme, making more NOS and citrulline. Ammonia builds up, CPS1 expression is suppressed, and consequently, the citric acid cycle is affected (less ornithine, less fumarate), causing citrullination of proteins and fatigue from acetic acid build up, creating N-Acetyl-Aspartate, which complicates the problem...

It's a long discussion, and I keep getting clues from Pubmed studies. Overmethylation plays a big role in Multiple Sclerosis, but it is much more complicated than that. I'll do a blog on it sometime.

So in other terms drugs such as bacopa or pramiracetam that increase NOS are harmful to your health?

Isn't NOS effectively a vasodilator? Nitric oxide has so many biological roles. There may be other reasons for not using DMAE, but I am not convinced that NOS is one of them. Please explain further.

[polymathic]

Great thread devinthayer. Though I'm a little confused on one point. Why exact is DMAE stimulating? First post says:

" Choline dehydrogenase turns DMAE into DMG and choline into TMG. This is the stimulating effect from DMAE"

But I thought DMAE inhibited choline dehydrogenase (which would subsequently lower betaine/dmg). Are you staying the stimulating effect comes from lowering DMG/Betaine?

[renfr]

I've read some studies and reports and really I don't think DMAE can lead to neurodegeneration.
According to the reports, people feel exactly the same effects they would have from choline supplementation : enhanced concentration, enhanced memory, helps with weight loss, better skin, less need for sleep, etc...
If DMAE was really inhibiting choline, then it would have the same effects as an anticholinergic : impaired memory, dilated pupils, vertigo/nausea, sleepiness, etc...
As far as I tried I've never felt any of these effects, as to explain birth defects maybe it is because DMAE is stimulating acetylcholine nicotinic receptors (the same as of tobacco and nicotine that both cause birth defects).
The stimulating effect may be very well caused by nicotinic receptors activation too, they higher heart rate and gives a stimulant like effect.
DMAE could be working like sulbutiamine, through a compensatory mecanism receptors are upregulated and knowing the drug is fast acting, in a matter of hours, choline transport and choline kinase aren't inhibited anymore and accumulated choline can be metabolized for it to activate the receptors, which is rather more a good thing than a bad thing.
Anticholinergics work by blocking the receptors, DMAE works by inhibiting choline floods, this is extremely different as blocking the receptors totally inactivate cholinergic function and yes this can lead to MS, dementia, alzheimers on long term but choline metabolism and transport inhibition gives more benefits than blocking receptors.
If this really scares you, take some soy lecithin or choline source and stack that with some caffeine (caffeine inhibits acetylcholinesterase) or huperzine a.
We need more studies on this compound but from my point of view is not an evil molecule.

[renfr]

I took 450mg DMAE with my normal stack and all I can say is that my memory recall is excellent.
I had to learn some stuff and I could just read it once or twice and then repeat all what I read which is kinda great.
The stack I took this day :
- 450mg DMAE
- 400mg pyritinol
- 12g soy lecithin non GMO
- 50mg caffeine
- 250mg bacopa
- Vitamin B complex (lots of B1 which is very good for the brain)

If DMAE were that harmful, I would rather have experienced a loss in cognitive function and a loss in concentration and I had the exact contrary.
I think that DMAE shouldn't be avoided and looks like devinthayer was a bit too much fearmonger. Maybe long term this stuff can be harmful, but we need a real study on that but punctually it seems to be rather safe.

Edited by renfr, 06 December 2012 - 06:42 AM.

[SuperjackDid_]

DMAE can increase in apoptosis level .

[renfr]

DMAE can increase in apoptosis level .

I saw that study, but that latter was specifically focused on skin benefits which is a good thing for the skin as apoptosis also means cell regeneration, for new cells to grow, the old ones need to die.

[SuperjackDid_]

I've read some studies and reports and really I don't think DMAE can lead to neurodegeneration.
According to the reports, people feel exactly the same effects they would have from choline supplementation : enhanced concentration, enhanced memory, helps with weight loss, better skin, less need for sleep, etc...
If DMAE was really inhibiting choline, then it would have the same effects as an anticholinergic : impaired memory, dilated pupils, vertigo/nausea, sleepiness, etc...
As far as I tried I've never felt any of these effects, as to explain birth defects maybe it is because DMAE is stimulating acetylcholine nicotinic receptors (the same as of tobacco and nicotine that both cause birth defects).
The stimulating effect may be very well caused by nicotinic receptors activation too, they higher heart rate and gives a stimulant like effect.
DMAE could be working like sulbutiamine, through a compensatory mecanism receptors are upregulated and knowing the drug is fast acting, in a matter of hours, choline transport and choline kinase aren't inhibited anymore and accumulated choline can be metabolized for it to activate the receptors, which is rather more a good thing than a bad thing.
Anticholinergics work by blocking the receptors, DMAE works by inhibiting choline floods, this is extremely different as blocking the receptors totally inactivate cholinergic function and yes this can lead to MS, dementia, alzheimers on long term but choline metabolism and transport inhibition gives more benefits than blocking receptors.
If this really scares you, take some soy lecithin or choline source and stack that with some caffeine (caffeine inhibits acetylcholinesterase) or huperzine a.
We need more studies on this compound but from my point of view is not an evil molecule.

Thank for your post ,i fully agreed with you .

DMAE help me so much sometime ,but taking everyday seem give some depression symptom .

[Guacamolium]

When I think of DMAE, I think "why would I buy that cholinergic over Alpha-GPC, CDP-Choline, or Centrophenoxine?

Bottom barrel cholinergic right thurr.

[deeptrance]

Devinthayer has zero credentials in biochemistry and I don't understand why people abandonned all interest in centro & dmae simply because of his speculations. Speculations =/= facts.

He probably went too far with his speculation about DMAE causing MS, but the rest of what he wrote is based on scientific research published in peer-reviewed journals. For example, here is an excerpt from the 4th of 4 citations he included in his opening post:

"Our results with DMAE are consistent with previous reports that DMAE is a competitive inhibitor of choline uptake and transport and an inhibitor of choline kinase."

and...

"The potential teratogenic effects of DMAE are of special concern as it is currently sold as a nutrient supplement that claims to enhance acetylcholine-related functions such as memory and learning. A related molecule found in many commercial products, diethanolamine, has been shown to disrupt choline metabolism and cause tumor formation in mice."

I've been taking DMAE 1-2 x daily for at least 3 years, and this thread has led me to decide that I must stop. It doesn't even do anything noticeable for me any longer, but I was in the habit of taking it and it's very cheap to obtain in bulk so I mindlessly kept it in my stack.

Edited by deeptrance, 26 May 2013 - 08:28 PM.

[ta5]

I can't refute the concerns others have raised. But, this study from last year makes it sound pretty good:

Drug Metab Lett. 2012 Mar;6(1):54-9.
New insights on dimethylaminoethanol (DMAE) features as a free radical scavenger.
Malanga G, Aguiar MB, Martinez HD, Puntarulo S.
Fisicoquimica, Facultad de Farmacia y Bioquimica, Junin 956, 1113 Buenos Aires, Argentina.
Recently, a number of synthetic drugs used in a variety of therapeutic indications have been reported to have antiaging effects. Among them, Dimethylaminoethanol (DMAE), an anologue of dietylaminoethanol, is a precursor of choline, which in turn allows the brain to optimize the production of acetylcholine that is a primary neurotransmitter involved in learning and memory. The data presented here includes new information on the ability of the compound to scavenge specific free radicals, assessed by Electron Spectroscopic Resonance (EPR), to further analyze the role of DMAE as an antioxidant. DMAE ability to directly react with hydroxyl, ascorbyl and lipid radicals was tested employing in vitro assays, and related to the supplemented dose of the compound.
PMID: 22300295

The full study is available from the publisher's site.

[caruga]

The author of the OP proposes raising betaine levels as the reason for DMAE's effects, but DMAE inhibits betaine production?

I suspect DMAE might promote cholestasis/reduce bile turnover.

Edited by caruga, 20 March 2014 - 11:50 AM.

[mrnootropic]

I've read some studies and reports and really I don't think DMAE can lead to neurodegeneration.
According to the reports, people feel exactly the same effects they would have from choline supplementation : enhanced concentration, enhanced memory, helps with weight loss, better skin, less need for sleep, etc...
If this really scares you, take some soy lecithin or choline source and stack that with some caffeine (caffeine inhibits acetylcholinesterase) or huperzine a.
We need more studies on this compound but from my point of view is not an evil molecule.

 

 

If DMAE were that harmful, I would rather have experienced a loss in cognitive function and a loss in concentration and I had the exact contrary.
I think that DMAE shouldn't be avoided and looks like devinthayer was a bit too much fearmonger. Maybe long term this stuff can be harmful, but we need a real study on that but punctually it seems to be rather safe.

 

I agree with both of your posts and was thinking the exact same thing when i was reading through this thread.

The amount of people that said, OK IM GIVING UP DMAE NOW. is crazy .. 

One speculation led people to throwing DMAE in the bin, mainly brought on because of fear of getting MS, that i havent seen any research or studies on.. 

 

If you get positive results from a supplement, there is no use in giving it up, unless the negatives outweigh the positive, i dont see this as the case for DMAE, it seems like the Positives & the Benefits of DMAE outweighs the risks & the negatives. (In small doses).

 

 

However i don't agree with Mega dosing anything that hasn't been researched for long term effects.

Just take sensible doses and you will be fine.

Even devinthayer who started the thread said , low dose DMAE is fine. I dont get why people reacted like this, saying im going to bin my dmae or should i bin it . lol. 

Edited by Mr.Nootropic, 23 May 2014 - 02:40 PM.

[Omnivus]

I bought some DMAE from a vitamin shoppe, and for the life of me I couldn't remember why. I know I read something about it online but couldn't remember why I was told to get it. So right now it's sitting in my vitamin closet untouched. lol

[Adaptogen]

http://health.wikinu...dents/444mwb2w/

Dimethylaminoethanol extends lifespan and improves learning in rodents

 

Edited by Adaptogen, 11 June 2014 - 11:29 PM.

[xks201]

I would think it would deplete choline and cause adverse effects.

[jroseland]

Do all these downside apply to Centrophenoxine? Or is it a different animal? I'm not seeing nearly as many bad reports about Centro online...

[Moltic]

I speculate long term effects of chronic use will result in multiple sclerosis. Multiple Sclerosis is a brain degenerative disease that I speculate is from overactive choline dehygrogenase or underactive argininosuccinate synthetase. Overmethylation results in fatigue. The reason is that it speeds up the NOS enzyme, making more NOS and citrulline. Ammonia builds up, CPS1 expression is suppressed, and consequently, the citric acid cycle is affected (less ornithine, less fumarate), causing citrullination of proteins and fatigue from acetic acid build up, creating N-Acetyl-Aspartate, which complicates the problem...

It's a long discussion, and I keep getting clues from Pubmed studies. Overmethylation plays a big role in Multiple Sclerosis, but it is much more complicated than that. I'll do a blog on it sometime.

 

Hey Devin, if you think that long term use of DMAE will result in multiple sclerosis from overactive choline dehydrogenase, does that mean other choline supplements such as CDP choline or Alpha GPC will have the same effect?

[Baten]

I bought some DMAE from a vitamin shoppe, and for the life of me I couldn't remember why. I know I read something about it online but couldn't remember why I was told to get it. So right now it's sitting in my vitamin closet untouched. lol

 

This obviously proves that buying DMAE makes one forgetful. Absolutely avoid buying DMAE.

(just joking obviously)

[thedevinroy]

I speculate long term effects of chronic use will result in multiple sclerosis. Multiple Sclerosis is a brain degenerative disease that I speculate is from overactive choline dehygrogenase or underactive argininosuccinate synthetase. Overmethylation results in fatigue. The reason is that it speeds up the NOS enzyme, making more NOS and citrulline. Ammonia builds up, CPS1 expression is suppressed, and consequently, the citric acid cycle is affected (less ornithine, less fumarate), causing citrullination of proteins and fatigue from acetic acid build up, creating N-Acetyl-Aspartate, which complicates the problem...

It's a long discussion, and I keep getting clues from Pubmed studies. Overmethylation plays a big role in Multiple Sclerosis, but it is much more complicated than that. I'll do a blog on it sometime.

Hey Devin, if you think that long term use of DMAE will result in multiple sclerosis from overactive choline dehydrogenase, does that mean other choline supplements such as CDP choline or Alpha GPC will have the same effect?

Wow someone called me a fear monger. A bit harsh, yea?

All I was saying is that the downstream effects of too much methylation, enough to cause fatigue , actually is pretty toxic in the long term. DMAE is a powerful methyl donor, and we take it like it's candy. Sugar isn't bad for you just like DMAE isn't bad for you. Too much, and it has long term side effects, but too little and you're not at optimal performance and that also has long term side effects.

Balance is key. Maybe you need more methyl donors, not less, in order to be in that happy place of a balanced anti-oxidant to energy ratio. I believe most people do.

So yeah, it was a little fear mongery of me to say all those things.

However, I am not saying that DMAE is good for everyone. If it causes a little crash later on, fine, but if it causes fatigue and muscle soreness and twitching... You're doing it wrong.

[thedevinroy]

I speculate long term effects of chronic use will result in multiple sclerosis. Multiple Sclerosis is a brain degenerative disease that I speculate is from overactive choline dehygrogenase or underactive argininosuccinate synthetase. Overmethylation results in fatigue. The reason is that it speeds up the NOS enzyme, making more NOS and citrulline. Ammonia builds up, CPS1 expression is suppressed, and consequently, the citric acid cycle is affected (less ornithine, less fumarate), causing citrullination of proteins and fatigue from acetic acid build up, creating N-Acetyl-Aspartate, which complicates the problem...

It's a long discussion, and I keep getting clues from Pubmed studies. Overmethylation plays a big role in Multiple Sclerosis, but it is much more complicated than that. I'll do a blog on it sometime.

Hey Devin, if you think that long term use of DMAE will result in multiple sclerosis from overactive choline dehydrogenase, does that mean other choline supplements such as CDP choline or Alpha GPC will have the same effect?

Wow someone called me a fear monger. A bit harsh, yea?

All I was saying is that the downstream effects of too much methylation, enough to cause fatigue , actually is pretty toxic in the long term. DMAE is a powerful methyl donor, and we take it like it's candy. Sugar isn't bad for you just like DMAE isn't bad for you. Too much, and it has long term side effects, but too little and you're not at optimal performance and that also has long term side effects.

Balance is key. Maybe you need more methyl donors, not less, in order to be in that happy place of a balanced anti-oxidant to energy ratio. I believe most people do.

So yeah, it was a little fear mongery of me to say all those things.

However, I am not saying that DMAE is good for everyone. If it causes a little crash later on, fine, but if it causes fatigue and muscle soreness and twitching... You're doing it wrong.

I Re-read some of my old stuff, and damn was I on point. Myelination inhibition, not overmethylation was the reason I was up in arms. I was super clear about it too.

I realize this is super controversial and even got some flack thrown at me. Geez, Reddit.

There is time for an apology. I have not mentioned PeMT activity in adults. Embryos of mice don't have much of it, so thus, the birth defects. Examine.com does state that adults have more of this enzyme. I'm here to tell you why.

Your liver. For one. If DMAE is made into a phospholipid, it can be converted to phosphatidylcholine. This enzyme is also in the brain, so long as you don't have Alzheimer's. Is there anything to worry about? Always and never. It's still controversial.

DMAE increases brain choline but not acetylcholine synthesis. I find that odd, as do a lot of people experiencing cholinergic effects. In fact, it seems to reduce choline uptake.

It's mysterious to me until you factor in the added effect of its inhibition on choline kinase. Simply put, you get more free choline and ATP... and less phospho choline and ADP.

And so is it a wash?

I don't know. If your PeMT activity is high, go for it. But how would you know? There isn't much research out there on humans, DMAE, and myelinogenesis.

If choline is not acetylated, choline becomes TMG and DMAE becomes DMG... Also pretty stimulating. DMAE does not increase acetylation, but ALCAR does...

Edited by devinthayer, 29 June 2016 - 11:07 PM.

[Acausal]

Zombie thread revival, but I have some anecdotal contribution here. I took DMAE for about.....fifteen years or so? Almost daily. Apart from increasing the potential of getting muscle cramps from time to time, I haven't noticed any MS. This was from age 15-30, give or take, dosage varied but anywhere from 200mg to 700mg/day. I don't know that it was necessarily a good idea, really, but I don't think I suffered any ill effect. Still, one data point makes for a poor study, so YMMV of course

[jack black]

i took it for on and off (mostly on) for over a year. it has modest stimulating effects at the daily dose of 300-600mg. Nothing negative that I noticed, except for rebound tiredness after stopping.

supposedly i have increased risk for MS per 23andMe. so, i'll try to read on it some more.

[thedevinroy]

Thanks for your input. It's good to hear everyone's input on there long term use. It might decrease the risk for MS and other neurodegenerative disorders - all depends on its net effect of myelination and how the dose curve affects it. Is it linear or inverse U shaped?

From what I read on long term studies on humans, it seems to be promising in neurogensesis but fall short of expectations at the doses that provide symptomatic relief.

Premenopausal women seem to have more PEMT, according to a study referencing the one I posted about years ago. Seems estrogen has a PEMT promoting factor.

http://www.ncbi.nlm....ubmed/17456783/

Wonder if there is any cases of premenopausal healthy women not getting assumed effects from DMAE - if the PEMT enzyme can keep up, that would be a good indication of something interesting...

Edited by devinthayer, 27 July 2016 - 10:52 PM.