I've also seen conflicting posts in the past....but do believe it to be safe to use both DAA/Agmatine together...and have done so....here's an article pulled from our website...
Clearing Up The Misconceptions About D-Aspartic Acid
Recently, there has been a lot of discussion online about D-Aspartic Acid and it’s effects on the NMDA receptor. And the big question is, “is D-Aspartic Acid potentially neuro-toxic?” I’m going to get a little technical here, and you science buffs will LOVE this section. But even if you don’t have a science background, I promise this will all make sense to you, and is well worth the read.
The short answer to the above question is “No.” At Serious Nutrition Solutions our customers’ health is our number one priority, and we strongly believe that D-Aspartic Acid is not neuro-toxic, otherwise we would not be selling it. That is why the following section is SO important to anyone with questions or concerns about the issue.
So let’s talk first about the NMDA receptor. The NMDA receptor is an ionotropic receptor that allows for the transfer of electrical signals between neurons in the brain and in the spinal column. Here’s how it works. For electrical signals to pass, the NMDA receptor must be open. And to remain open, both Glutamate and Glycine must be present to bind to the NMDA receptor. Once Glutamate and Glycine have bound to an NMDA receptor, that receptor is referred to as being “Activated.” Pretty straight forward, right? Ok, listen to this because there are two additional requirements.
Now, the NMDA receptors aren’t easily activated. In fact, it’s quite tough. The NMDA receptor is blocked by magnesium (Mg2+) so it needs to have sufficient depolarization first. Even if you have Aspartic acid present (or Glutamate), you still need Glycine to be there as well. So you need a few things at once to activate the NMDA receptors. And most importantly, the key thing is you need the depolarization of say an AMPA receptor nearby before ANY of the binding even matters.
So let’s dig a little further into the NMDA receptor. It’s quite fascinating. NMDA receptors have different sub-units, such as the NR2B and the NR2A sub-unit, and the effects of the sub-units differ upon activation. If you have no idea what an NR2B or NR2A sub-unit is, don’t worry!
The basic message I want you to understand is this. D-Aspartic Acid is highly unlikely to elicit toxicity. That’s because toxicity is most likely elicited from the NR2B sub-unit, which is exceedingly difficult to activate. The NR2A sub-unit is believed to have a higher affinity than the NR2B sub-unit when it comes to L/D-Aspartate.
But if by some rare anomaly in the multiverse D-Aspartic Acid could elicit neuro-toxicity, keep reading to discover how one would go about addressing this incredibly unlikely issue.
Antagonize Me
Ok, real quick. Let me briefly fill you in on NMDA antagonists – chemicals that deactivate the NMDA receptor. NMDAR antagonists fall into four categories, and this is important to understand for those “rare anomaly” situations:
1) Competitive antagonists, which bind to and block the binding site of the neurotransmitter Glutamate;
2) Glycine antagonists, which bind to and block the Glycine site;
3) Non-competitive antagonists, which inhibit NMDARs by binding to allosteric sites; and
4) Uncompetitive antagonists, which block the ion channel by binding to a site within it.
Solutions to Those Rare Anomalies
Does D-Aspartic Acid elicit neuro-toxicity? Again, we strongly believe that it does not, as evidenced by our willingness to indulge in this discussion and debunk the misinformation floating around online.
Huperzine A
Huperzine A has been shown to have significant enhancement in memory in normal individuals based on the Wechsler scales. This makes it a fantastic compliment to any D-Aspartic Acid cycle, as it is an uncompetitive antagonist to the NMDA receptor. Huperzine A has been observed to have no effect on the glutamate binding sites, no effects on the NMDA glycine regulatory site, and no effect on the NMDA polyamine site. So what does this mean?
Well, these are the things we really worry about when we talk about D-Aspartic Acid, NMDA receptors, and toxicity. For you science guys, Huperzine A most likely diminishes excitatory amino acid toxicity by blocking the NMDA ion channel and subsequent Ca2+ mobilization at or near the PCP and MK-801 ligand sites. For you non-science guys, Huperzine is potentially an effective solution to that rare anomaly.
And, if that rare anomaly in the multiverse ever did occur where there is over excitation of the NMDA receptor (say due to D-Aspartic Acid eliciting neuro-toxicity, which again is highly unlikely), Huperzine A would help “buffer” the over excitation down to “normal” levels, thus preventing damage due to the over excitation (or even preventing the over excitation in the first place).
Thus, should you still not believe that D-Aspartic Acid is neuro-friendly, Huperzine A combined with D-Aspartic Acid is strongly believed to help you with the potential neuro-toxicity concerns discussed online.
Agmatine
Like Huperzine A, Agmatine is also believed to be able to prevent the highly unlikely event of D-Aspartic Acid induced neuro-toxicity. In short, Agmatine is believed to do so by preventing over-excitation of NMDA receptors and reversing the levels of activation.
The important thing to distinguish here is that exogenous application of Agmatine and D-Aspartic acid work on different mechanisms for the NMDA receptor, so regardless of one being an antagonist and the other an agonist, they do not overlap. Exogenous D-aspartic acid application utilizes the R-type VGCCs and none of the others, while exogenous Agmatine is said to use the L-type VGCCs and shows no signs of inhibition of the R-type VGCCs. Exogenous application of Agmatine will enhance its regulatory role in the body so that in higher levels of NMDA receptor activation, it will inhibit the receptor from higher glutamate release (so over-excitation leading to potential neuro-toxicity) by inhibiting the receptor.
Reduce XT™
Another concern that has arisen online is D-Aspartic Acid’s effects on estrogen. While D-Aspartic Acid “might” elevate estrogen, fear not. Estrogen, despite all of its misconceptions, can actually HELP you build muscle. The important thing to note is an improved ratio of testosterone to estrogen in the body is ideal. Even if your estrogen levels increase slightly, as long as the testosterone to estrogen ratio has increased, the stage is set for powerful muscle building and strength enhancing results.
However, for those concerned about estrogen, SNS is releasing a brand new version of Reduce XT. This powerful anti-estrogen formula is designed to naturally control estrogen while supporting optimal testosterone production.