D-Aspartic Acid - a research update
I've been reading a lot lately about D-Aspartic Acid (DAA) and its use as a supplement for the purpose of hormone manipulation. I've been doing more research on DAA and NMDA (N-methyl D-aspartate) receptor mediated hormone regulation and the more I read, the more excited I got about the possibilities associated with it. As far as performance enhancement supplements go, I believe this area of research has the greatest potential to bring us closer to steroid-like results without the negative side effects of steroids. This month, I'll go into a little more detail about exactly how DAA works at the molecular level and then introduce the reader to an exciting discovery I recently made that could dramatically enhance the effects of DAA supplements.
To refresh the reader's memory, DAA works by binding to and activating the NMDA receptor. NMDA receptors are found throughout the brain and are involved in various regulatory processes including memory storage and mood. As far as DAA supplements are concerned, the NMDA receptors in endocrine tissues such as the hypothalamus, pituitary gland and testes are of primary interest. When DAA is consumed, it is absorbed into the blood and preferentially taken up by the aforementioned endocrine tissue types. There it stimulates the NMDA receptors. In the hypothalamus, stimulation of the NMDA receptors leads to the production of the GnR hormone. GnRH stimulates the pituitary gland to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). LS and FSH are transported to the testes to initiate the process of steroidogenesis, which leads to the release of testosterone into the bloodstream.
The key here is therefore the NMDA receptor. The more this receptor is activated in the hypothalamus, the greater the release of GnRH and ultimately the greater the release of testosterone. The NMDA receptor is unique in that it requires activation by two ligands. In the hypothalamus, D-aspartic acid is the primary ligand for the NMDA receptor. The secondary ligand (or co-activator) is the amino acid glycine. Both DAA and glycine have specific binding sites on the NMDA receptor.
The administration of DAA leads to its uptake into the hypothalamus, where it stimulates the NMDA receptor. However, maximal stimulation also requires adequate amounts of the ligand that binds to the glycine binding site of the receptor. One might think that the consumption of glycine in the form of a supplement should ensure glycine co-activation. However, the scientific literature has shown that this method has limited efficacy.
The reason that glycine administration is not very effective in stimulating NMDA receptor activation is not clear, but one of the reasons is related to the fact that glycine is efficiently removed from synapses by the reuptake regulator glycine transporter 1 (GT1).
Interestingly, much of the scientific research published on the topic of stimulating NMDA receptor activity centers around the theory that NMDA receptor hypoactivity is a causative factor in schizophrenia. Over the years, scientists have investigated ways to stimulate NMDA activity for the purpose of treating schizophrenic patients. Targeting the GT1 protein has proven to be one of the most effective strategies. And one of the most effective ways to achieve this is through supplementation with a relatively simple amino acid.
Welcome to the world of Sarcosine
The simple amino acid I'm talking about is sarcosine. Sarcosine is also known as N-methyl glycine. Administering 2 grams of sarcosine per day has been shown to increase NMDA receptor activity quite effectively and this dosage appears to lead to an impressive reduction in both positive and negative symptoms in schizophrenic patients.
Of course, we are not concerned here with treating schizophrenia, but rather with maximizing stimulation of natural testosterone production. However, the mechanism in question is exactly the same for both purposes. By blocking the reuptake of glycine, one increases the concentration of glycine in the NMDA synapses of the neurons and thus increases NMDA nerve transmission. Some antidepressants or selective serotonin reuptake inhibitors (SSRIs) work in the same way, although the aim here is to increase transmission of the serotonergic or dopaminergic neurons and not the NMDA neurons.
Blocking glycine reuptake is not the only mechanism by which sarcosine stimulates DAA activity. Sarcosine can also bind to the glycine binding site of the NMDA receptor. It even binds there with a higher affinity than glycine. Knowing all this, one realizes that sarcosine has a quite dramatic effect on NMDA nerve transmission compared to glycine or other endogenous ligands for the glycine receptor such as D-serine.
The future
I will continue to explore new ways to investigate the amazing NMDA pathway for increasing hormone levels and enhancing performance. I trust that amino acid based supplements for the purpose of hormone manipulation are beyond the reach of regulatory intervention and therefore will not meet the same fate as prohormones and steroidal based estrogen blockers in the past.
Of course, I am not naïve enough to think that any effective testosterone booster or supplement for the purpose of performance enhancement will not incur the wrath of doping test organizations and misguided sports and fitness purists. However, when the day comes that people are tested for their amino acid levels and companies are visited by police officers with warrants for such products, then that will be the day the supplement industry should start to worry! But stranger things have happened - so you never know what's to come!