LONGECITY

DMAE causes birth defects.

DMAE is not metabolized into choline in the brain.

DMAE inhibits choline kinase.

DMAE inhibits choline transport.

DMAE inhibits transport and metabolism of choline into Phosphocholine, Phosphatidylcholine, and Sphingomyelin. The transporter that is inhibited is talked of more in this article.

Phosphatidylcholine and Sphingomyelin are used to make membranes and myelin in your cells and nerve sheathes. This is a very important process that if inhibited for a long period of time can cause unwanted aging and neurodegeneration.

DMAE is one step away from becoming betaine and also creates more betaine by raising choline levels (via inhibiting choline transport and metabolism, read above). Choline dehydrogenase turns DMAE into DMG and choline into TMG. This is the stimulating effect from DMAE. For more information on the methylation cycle, use this image.

The cure to your nootropic stack is with addition of Phosphatidylcholine when you MUST use DMAE. You may also use a combo of CDP-Choline, Uridine, and Fish Oil, which will help because CDP-Choline is created after the use of choline kinase.

Still, it would be better to supplement with straight TMG if you just want the stimulating effects. There are many other cholinergics that are not nearly as degenerative. For instance, CDP Choline or Alpha-GPC or even soy lecithin if you want to go oldschool.

Inhibition of choline transport and metabolism appears to be competitive.
Edited by devinthayer, 07 October 2011 - 09:05 PM.

I become very hyperactive when Im on DMAE. I think I have ADD but Im not diagnosed. I suffer from Hypersomnia and DSPS. I dont know why I get hyperactive and I haven't heard of anyone having the same reactions.

I dont think that DMAE is a useful drug in any case except for depression. When I take 50mg of DMAE for a couple of weeks my depression just disappears and even for a prolonged time. It also helps with my social- phobia. Also it can relieve muscle- soreness when starting working out.

I've evaluated DMAE on higher doses but the effects were just weird and distracting.

I've known about how DMAE interacts in the body. The birthdefect- report is a bit scary but luckily Im not a pregnant woman. So ill hold on to my DMAE bottle if I need it. Even though I think it´s a shitty drug.

What kind of longterm effects could happen from using DMAE do you think?

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.

Yes I know of MS, scary disease! Yes, not even doctors understand the real cause behind MS. I really hope that my DMAE use wont come back and take a huge chunk out off my ass.

You seem interested in this. Why is that? Is it for educational purposes?

My mother has MS. For a while she wasn't on any medicine, so I was looking for alternatives for her. She's on Interferon now, so that will help. If that medicine fails or she becomes allergic to it, I'll start my hunt again for alternative treatments. There seems to be a connection with overmethylation and signs of late onset citrullinemia. MS patients have citrulline damage, low urea acid, high N-Acetyl-Aspartate levels, increased expression of NOS, and high plasma DNA methylation... and the list goes on. Tabacco, not smoked, is preventative (nicotine is neuroprotective). Vinegar is a treatment. There are just some clear indications that the problem is more than just "overactive T Cells" or something.

Anyhow, that's off topic.

Multiple Sclerosis is not something you have to worry about unless you are using DMAE daily for years.

OT: Im sorry to hear about your mom. I hope that this article will be somewhat useful.



http://news.bbc.co.u...lth/7083323.stm

Well Im going to use DMAE sparingly! Thanks for the update. Some people use topical DMAE to get better skin but recent studies suggest that DMAE causes apoptosis in cells.

OT: Im sorry to hear about your mom. I hope that this article will be somewhat useful.



http://news.bbc.co.u...lth/7083323.stm

Well Im going to use DMAE sparingly! Thanks for the update. Some people use topical DMAE to get better skin but recent studies suggest that DMAE causes apoptosis in cells.

Thanks man. She takes extra Vitamin D now. Perhaps I should convince her to start taking ginkgo and astragulus root for the same reason. DMAE is an antioxidant with a nice tightening effect on the skin, but I tend to think Vitamins A, D, E, K would be better for the skin.

I wonder whether these observations about DMAE might also apply to centrophenoxine (meclofenoxate), as it’s an ester of DMAE and pCPA. Any thoughts?

Someone above said they get hyper/undepressed/etc from DMAE and I get the same effect from centrophenoxine so I would assume it is applicable. I felt like centrophenoxine was a pretty useless drug except for it's interesting mood effects(even such things as uncontrollable giggles lol), but only because it was an interesting state to be in a couple of times.. never took it regularly because it just didnt help with anything and taking it consecutively made me semi-depressed(negative thoughts, not overwhelming though) for a day or two after the effects wore off. I always thought the depression was from too much choline, but it could be other things as well seeing as its more than a simple precursor to choline.

Someone above said they get hyper/undepressed/etc from DMAE and I get the same effect from centrophenoxine so I would assume it is applicable. I felt like centrophenoxine was a pretty useless drug except for it's interesting mood effects(even such things as uncontrollable giggles lol), but only because it was an interesting state to be in a couple of times.. never took it regularly because it just didnt help with anything and taking it consecutively made me semi-depressed(negative thoughts, not overwhelming though) for a day or two after the effects wore off. I always thought the depression was from too much choline, but it could be other things as well seeing as its more than a simple precursor to choline.

Sounds like agitation from an accumulation of norepinephrine. Just a hunch. I would imagine centro is a methyl donor as well, and your report makes it seem so. Upon further research, I found it that it is converted in vivo to DMAE (page "v" in this report). Thus, any reported mood effects may in part be from DMAE, and not just the whole centrophenoxine molecule.

Centro also contains pCPA which may atrribute to some effects (same report: page 44):

In this report, the authors stated that several pharmacological properties of centrophenoxine may be attributed to the p-chlorophenoxyacetic acid (PCPA) moiety. Low doses of PCPA or centrophenoxine increased aggressiveness in mice, whereas high doses decreased aggressiveness. DMAE increased aggressiveness at high doses and decreased aggressiveness at low doses. The effects of centrophenoxine and PCPA were more similar to each other than with DMAE.

pCPA may be a wakefulness promoting enhancer: http://www.ncbi.nlm..../pubmed/7465937 which makes me think it affects histamine levels, thus increasing release of dopamine and norepinephrine. This may be attributing to a mood lift and possible agitation that you are experiencing. This could be from the other half of the molecule (a tropane and tricyclic natural pyschotropic), but the analogue containing pCPA (SAD 103) seemed to last longer.

The first report mentioned also explains on page 33:

In a study using DMAE p-chlorophenoxyacetic acid, Wood and Peloquin (1982) found that treatment of rats (dose and route not provided) resulted in increase levels of choline in the central nervous system of rats. These increased levels were accompanied by elevated steady state levels for acetylcholine within the hippocampus. DMAE was only about half as effective as DMAE p-chlorophenoxyacetate in increasing levels of choline in rat brains. The observed changes in choline levels were primarily extraneuronal.

Centrophenoxine (DMAE p-chlorophenoxyacetate) might actually be worse since it raises choline levels even higher than DMAE alone. This makes me wonder if it inhibits choline transport or metabolism more from a prolonged duration of action.
Edited by devinthayer, 17 October 2011 - 05:59 PM.

I have a still wrapped bottle of NOW True Focus http://www.nowfoods....cts/M010486.htm in my cupboard. It contains 60mg DMAE per serving, in light of this thread I am thinking of tossing it (I have pure Tyrosine and Dopa Mucuna but no Ginkgo or Taurine at hand) ?

60mg of DMAE won't kill you. In fact, it will be out of your system shortly, and it might provide some very positive short term benefits. The fact of the matter is that DMAE is harmless if you have enough Phosphatidylcholine from natural sources: eggs, lecithin, cauliflower, nuts, spinach, etc. Just make sure your dietary intake of choline is adequate (500mg of choline from natural sources). As long as you are not nursing, pregnant, or under the age of 16, I wouldn't worry about short term use of small amounts. DMAE is naturally found in fish, by the way.

Hmm, maybe I'll give it a shot. That True Focus does look interesting, for sure. Do I need Phosphatidylcholine or will CDP Choline or Alpha GPC do (I dont have any of the "cheap" choline sources handy)?

Hmm, maybe I'll give it a shot. That True Focus does look interesting, for sure. Do I need Phosphatidylcholine or will CDP Choline or Alpha GPC do (I dont have any of the "cheap" choline sources handy)?

Umm... sorry, you do need something with natural choline (PC) like from nuts, spinach, eggs, beef, etc. Wiki has a good list of choline sources. http://en.wikipedia....rces_of_choline Phospholipid synthesis is inhibited with DMAE, so it won't help just adding precursors.

This is horrible news to me. I've been having a profound anxiolytic response from taking 150mg of DMAE daily. What's the mechanism of action for it's antianxiety effects? Is CDP-Choline, Uridine, and Fish Oil a safe substitute that will have the same effects?
Edited by j03, 06 December 2011 - 11:40 PM.

im staying away from DMAE, seems it is more harmful than good. to make it good you need to stack it with stuff that it inhibits in order for it to give you the nootropic benefit.

This is horrible news to me. I've been having a profound anxiolytic response from taking 150mg of DMAE daily. What's the mechanism of action for it's antianxiety effects? Is CDP-Choline, Uridine, and Fish Oil a safe substitute that will have the same effects?

Actually, to have the same effects you would need TMG + Alpha GPC since DMAE raises both betaine and choline levels (start with 250mg TMG + 100mg Alpha GPC and adjust). Uridine and Fish Oil are completely different but would provide a beneficial synergy. If you continue to use DMAE, you will have to supplement your diet with Phosphatidylcholine.

This is horrible news to me. I've been having a profound anxiolytic response from taking 150mg of DMAE daily. What's the mechanism of action for it's antianxiety effects? Is CDP-Choline, Uridine, and Fish Oil a safe substitute that will have the same effects?

Actually, to have the same effects you would need TMG + Alpha GPC since DMAE raises both betaine and choline levels (start with 250mg TMG + 100mg Alpha GPC and adjust). Uridine and Fish Oil are completely different but would provide a beneficial synergy. If you continue to use DMAE, you will have to supplement your diet with Phosphatidylcholine.

I suggested CDP-Choline + Uridine + Fish Oil as a method to create phosphatidylcholine in vivo if you decide to use DMAE. Uridine actually does not play a part in preventing neurological decline from continued use, but it does have synergistic properties (on ACh and DA receptors).
Edited by devinthayer, 07 December 2011 - 10:48 PM.

My takeaway from your post is to NEVER use DMAE. In what cases would it be useful?

My takeaway from your post is to NEVER use DMAE. In what cases would it be useful?

if you have a stack that dont have the noots that Devin mention, then DMAE will just not make a difference or have a negative effect. i cannot add DMAE with my current stack since it most likely just reduce the cognitive effect.

My takeaway from your post is to NEVER use DMAE. In what cases would it be useful?

if you have a stack that dont have the noots that Devin mention, then DMAE will just not make a difference or have a negative effect. i cannot add DMAE with my current stack since it most likely just reduce the cognitive effect.

DMAE has temporary benefits because it increases levels of betaines and choline (which becomes TMG, a betaine). Betaines aid in methylation by recharging the SAMe cycle. Methylation is useful in treating lethargy and depression... too much is bad, too, but we won't go there. Choline is used to make the neurotransmitter, acetylcholine, used in the formation of memories and processing.

DMAE can be bad because it raises betaines and choline by inhibiting phospholipid synthesis, temprorarily slowing down things like myelinogenisis (which is the making of "insulation" around the "wires" of your nerves). Overtime this causes problems, but there would be no immediate problems... only benefits.

Sort of like smoking... it feels good and helps your cognition temporarily, but over time could cause problems.

My takeaway from your post is to NEVER use DMAE. In what cases would it be useful?

if you have a stack that dont have the noots that Devin mention, then DMAE will just not make a difference or have a negative effect. i cannot add DMAE with my current stack since it most likely just reduce the cognitive effect.

DMAE has temporary benefits because it increases levels of betaines and choline (which becomes TMG, a betaine). Betaines aid in methylation by recharging the SAMe cycle. Methylation is useful in treating lethargy and depression... too much is bad, too, but we won't go there. Choline is used to make the neurotransmitter, acetylcholine, used in the formation of memories and processing.

DMAE can be bad because it raises betaines and choline by inhibiting phospholipid synthesis, temprorarily slowing down things like myelinogenisis (which is the making of "insulation" around the "wires" of your nerves). Overtime this causes problems, but there would be no immediate problems... only benefits.

Sort of like smoking... it feels good and helps your cognition temporarily, but over time could cause problems.

but i need to stack it with the other stuff that you mention in order for it to be beneficial. i cant do that with my current stack. too much noots.

My takeaway from your post is to NEVER use DMAE. In what cases would it be useful?

if you have a stack that dont have the noots that Devin mention, then DMAE will just not make a difference or have a negative effect. i cannot add DMAE with my current stack since it most likely just reduce the cognitive effect.

DMAE has temporary benefits because it increases levels of betaines and choline (which becomes TMG, a betaine). Betaines aid in methylation by recharging the SAMe cycle. Methylation is useful in treating lethargy and depression... too much is bad, too, but we won't go there. Choline is used to make the neurotransmitter, acetylcholine, used in the formation of memories and processing.

DMAE can be bad because it raises betaines and choline by inhibiting phospholipid synthesis, temprorarily slowing down things like myelinogenisis (which is the making of "insulation" around the "wires" of your nerves). Overtime this causes problems, but there would be no immediate problems... only benefits.

Sort of like smoking... it feels good and helps your cognition temporarily, but over time could cause problems.

but i need to stack it with the other stuff that you mention in order for it to be beneficial. i cant do that with my current stack. too much noots.

Yep. You would need either CDP Choline + Fish Oil or Phosphatidylcholine to offset the damage.

A bottle of Lecithin is 10-12 bucks. Just take a tablespoon, plop it in some water, block your nose, and try not to gag. Works on cognition and morning vertigo. Lecithin is about 17% Phosphatidylcholine, so you need about 17.5 grams for a day's worth of choline (which is about a heaping tablespoon). At two heaping tablespoons a day (mid-day or afternoon; don't take at night), my hair follicles grew stronger or something, because a lot less hair came out in the comb. Lecithin is really good for the liver, too.

My takeaway from your post is to NEVER use DMAE. In what cases would it be useful?

if you have a stack that dont have the noots that Devin mention, then DMAE will just not make a difference or have a negative effect. i cannot add DMAE with my current stack since it most likely just reduce the cognitive effect.

DMAE has temporary benefits because it increases levels of betaines and choline (which becomes TMG, a betaine). Betaines aid in methylation by recharging the SAMe cycle. Methylation is useful in treating lethargy and depression... too much is bad, too, but we won't go there. Choline is used to make the neurotransmitter, acetylcholine, used in the formation of memories and processing.

DMAE can be bad because it raises betaines and choline by inhibiting phospholipid synthesis, temprorarily slowing down things like myelinogenisis (which is the making of "insulation" around the "wires" of your nerves). Overtime this causes problems, but there would be no immediate problems... only benefits.

Sort of like smoking... it feels good and helps your cognition temporarily, but over time could cause problems.

but i need to stack it with the other stuff that you mention in order for it to be beneficial. i cant do that with my current stack. too much noots.

Yep. You would need either CDP Choline + Fish Oil or Phosphatidylcholine to offset the damage.

A bottle of Lecithin is 10-12 bucks. Just take a tablespoon, plop it in some water, block your nose, and try not to gag. Works on cognition and morning vertigo. Lecithin is about 17% Phosphatidylcholine, so you need about 17.5 grams for a day's worth of choline (which is about a heaping tablespoon). At two heaping tablespoons a day (mid-day or afternoon; don't take at night), my hair follicles grew stronger or something, because a lot less hair came out in the comb. Lecithin is really good for the liver, too.

This is a lot of work to make just DMAE work. I will pass on this guy and go for something else.

Hey Devin, I have noticed that DMAE and TMG give me brain fog when I experimented with them in the past....does that mean there is too much methylation going on in my brain and therefore I need to take vinegar every day?

I take some DMAE when I have headaches, usually works wonders; using it for this purpose sparingly wouldn't be bad would it?
As a matter of fact it's one of my favorite supplements. Used to take centro now DMAE since it works about as good.
I would find it weird if it's widely sold as a supplement where it says to take it up to 3 times a day (200mg) if it's that destructive :<
Edited by Baten, 11 June 2012 - 09:43 AM.

Sort of like smoking... it feels good and helps your cognition temporarily, but over time could cause problems.

Guess this about wraps it up. Too bad, DMAE/Centrophenoxine was the only cholinergic substance I actually felt at all, and immediate at that.
Good thread, I would have kept on using it if I didn't read the information above. Makes you wonder that if you thoroughly research all of your supplements,
more examples of ones that do more harm than good would show up or not.
When I take DMAE my head clears up. No energy/irritation/aggression/anxiety/anxiolytic effects whatsoever besides clearing any and all brain fog.
Since it works so well I take it whenever I can use a clear, sharp mind. But well, if something is too good to be true I guess there's always a catch.
Edited by Baten, 14 June 2012 - 03:18 PM.

I realise this is an old thread now but im a little confused and dont understand the chemistry side so well..
I understand that Centrophenoxine is an "enhanced" DMAE but does this enhancement change the negative effects?
like Baten(s) post above i get very positive effects from centro and have a 1kg supply, ingesting 600-800mg twice a day!
will lecithin alone be ample protection against negative effects?
should i look at dropping dose and frequency?
your clarification and advice would be much appreciated!

Personally, I only take Centro occasionally for this reason. I think lipofuscin reduction by centro was also failed to reproduce in primates in one study, which makes me not put too much value on that property.

However, if you can get all your brain choline needs met by lecethin and CDP choline (or partially by Alpha GPC, which will help meet acetylcholine needs at least), daily centro might not do much harm. This requires taking quite a lot of them, though. And I'd skip the second daily dose; you don't need centro active during the night, and it lasts quite long naturally and disrupts sleep anyway. Having the stuff not active while you sleep at least provides some safety margin, if it still has some detrimental effect after alternate choline supplementation.

thanks Raza
i think ill be taking centro out of the stack maybe just keeping it for weekends..
when i start up my full regime again ill try replacing the daily centro with alpha gpc which also has given me nice effects previously..
not taking anything right now due to wanting to test another nootropics effects