38 replies to this topic

[thedevinroy]

• DMAE pyroglutamate: http://www.ncbi.nlm....pubmed/19756528
• Coffee contains pyroglutamate: http://www.ncbi.nlm....pubmed/16546340
• Activates glutamate binding sites to a lesser degree than glutamate or aspartate. High doses block Adrenal receptors: http://www.ncbi.nlm..../pubmed/1976055
• Massive doses have cholinergic effects in rats: http://www.ncbi.nlm..../pubmed/3448611
• Comparison of Nooglutyl & L-pyroglutamyl-D-alanine: http://www.ncbi.nlm..../pubmed/8704601
• L-pyroglutamyl-D-alanine restores LTP: http://www.ncbi.nlm..../pubmed/7609900
• Possibly Regulates Thyroidism: http://www.ncbi.nlm....pubmed/21330373

Though I have never studied this compound before, the last one struck me as particularly odd. It mentions the enzyme "Glutaminyl Cyclase" which is the enzyme in the body responsible for the transformation from glutamate to pyroglutamate. This "cyclic" action I thought was spontaneous, but now it seems to me as if the body of mammals purposefully creates pyroglutamate in peptides and proteins. The enzyme isn't a bad thing, but unregulated (like in dementia), the enzyme causes strange formations in amyloid deposits (Search on pubmed, comes up a lot: http://www.ncbi.nlm....m=pyroglutamate).

My conclusion is that this thing is more or less natural, and it has less toxicity than glutamate or aspartate. You'd get more brain damage from drinking diet soda than taking the supplement.

Edited by devinthayer, 14 November 2011 - 04:11 PM.

[chrono]

My conclusion is that this thing is more or less natural, and it has less toxicity than glutamate or aspartate. You'd get more brain damage from drinking diet soda than taking the supplement.

Natural doesn't mean that increasing it is a good idea, and taking a large dose of nothing but PGA is probably a lot different than ingesting something with smaller amounts (especially if you're doing it every day). Though honestly, there's lots of unhealthy things you can do and remain pretty much ok, diet soda is a good example I'm curious to see how much PGA coffee actually contains, but looks like we'd need the full text to see the data.

My line of thinking usually goes that I wouldn't risk taking something where toxicity becomes a problem at some unknown dosage unless it provides a compelling benefit, and my impression is that this stuff is weaker than most things we consider nootropic (even piracetam?). I guess its MOA might make it valuable in some instances, though combining it with other glutamatergics might not be a great idea.

Edited by chrono, 14 November 2011 - 07:34 PM.

[thedevinroy]

My conclusion is that this thing is more or less natural, and it has less toxicity than glutamate or aspartate. You'd get more brain damage from drinking diet soda than taking the supplement.

I'm not sure if that follows. Natural doesn't mean that increasing it is a good idea, and taking a large dose of nothing but PGA is probably a lot different than ingesting something with smaller amounts. Though honestly, there's lots of unhealthy things you can do and remain pretty much ok I'm curious to see how much PGA coffee actually contains, but looks like we'd need the full text to see the data.

Not sure if it follows either. My logic was that since it wasn't as excitotoxic as aspartate or glutamate, then it can't be that bad. But, yes, you do have a point. Everything causes cancer it seems... not saying it causes cancer, but I am saying that there are so many unknowns, that all this time is could be eating too much pig meat that causes pancreatic cancer... it could be eating crayons gives Alzheimer's. We just don't know a lot of things yet. Pyroglutamate could cause some disease down the line like pink fingernails and blue toes. Who knows...

But what I can say is that I'm not too worried about it. That's my opinion.

[chrono]

haha, certainly. I'm not that worried about it either. Unless we're on CR, our diets probably hurt us all more than something like this. And what you said did follow, I edited my post when I woke up a little more ^^

The link with amyloid is interesting, too. Hooking pGlu to the N-terminus of Aβ seems to make it a lot more sinister [1]. But the formation seems to be catalyzed by glutaminyl cyclase, and I couldn't find any evidence that it could occur simply in the presence of L-PGA.

Edited by chrono, 14 November 2011 - 08:14 PM.

[thedevinroy]

haha, certainly. I'm not that worried about it either. Unless we're on CR, our diets probably hurt us all more than something like this.

The link with amyloid is interesting, too. Hooking pGlu to the N-terminus of Aβ seems to make it a lot more sinister [1]. But the formation seems to be catalyzed by glutaminyl cyclase, and I couldn't find any evidence that it could occur simply in the presence of L-PGA.

Exactly what I concluded. EDIT: in my head.

Edited by devinthayer, 14 November 2011 - 08:09 PM.

[noos]

This person is a long term user of pyroglutamic acid with no problems
http://www.amazon.co...iews/B004CCUCUA


I am taking Mg pidolate which I think is a Mg salt of pyroglutamic acid and there is not report for problems
http://docs.google.c...ate_FALL_03.pdf

Edited by noos, 14 November 2011 - 11:24 PM.

[chrono]

This person is a long term user of pyroglutamic acid with no problems
http://www.amazon.co...iews/B004CCUCUA

The kind of problem we're speculating about in this thread would be the result of excitotoxicity and maybe other neurotoxic mechanisms. It is extremely unlikely that anyone would notice this unless it's severe, without removing their brain and examining it histologically/etc. For instance, aspartame is also excitotoxic (I believe it cleaves into aspartic acid, which Devin mentioned above, and methanol), and can cause severe MS-like problems in a small number of people; many more drink it without noticing anything, but that doesn't mean it isn't having a subtle negative impact on brain function and structure over time.

[thedevinroy]

This person is a long term user of pyroglutamic acid with no problems
http://www.amazon.co...iews/B004CCUCUA


I am taking Mg pidolate which I think is a Mg salt of pyroglutamic acid and there is not report for problems
http://docs.google.c...ate_FALL_03.pdf

Mg Pidolate sounds very interesting. The magnesium would prevent some excitotoxic effects from the pyroglutamate (pidolate haha sounds so funny). Yes, pidolate is pyroglutamate. Anyhow, the pidolate will probably still have the same nootropic effects minus the glutamate receptor activation. Does it increase NMDA density like Piracetam? With such a lower affinity, I wonder if the cell can detect it and ups its receptor densities.

If I were to give pyroglutamate a shot, it would be the Mg Pidolate salts. Any brands good?

[noos]

I take a pharmaceutical product.
The PDF I posted was from aor.ca
It seems they use another salt of MG now.
The person who uses pyr acid reviews Source Naturals´s. Looke if they have Mg Pidolate.

PS neither aor nor source naturals carry Mg pidolate

Edited by noos, 16 November 2011 - 01:59 AM.