Agmatine and Nitric Oxide

Agmatine is a great nitric oxide supplementThis article is about the influence of Agmatine on Nitric Oxide in the body.  As I started learning about nitric oxide and the nutrients involved in its generation, I noticed that there seemed to be several distinct quantum leaps in the development of nitric oxide supplements.  The first generation seemed to be oriented around L-arginine, the second around L-citrulline.  The third major focus seems to be agmatine.  No doubt, agmatine supplements have been around for several years, but it is only recently that they seem to have come into the mainstream of nitric oxide supplement formulas.   Interestingly, much of the early research on agmatine I could find seemed to indicate that it was a nitric oxide (NO) inhibitor.  As I dug a little deeper, I learned that agmatine both inhibits and stimulates NOS activity.  How could this contradiction exist?  I was determined to find out more and what I found was startling:  Because of the way in which agmatine works, it may be the best, so far, of all of the nitric oxide supplements on the market!

NOS Generates Nitric Oxide

As you have read in previous posts, there are three main enzymes, called nitric oxide synthase, that produce nitric oxide in the body.  These enzymes all take arginine and break it apart to produce citrulline and NO.  First there is NOS1 or neuronal nitric oxide synthase (nNOS), which produces nitric oxide in the brain to use primarily for signalling across the neurons.  Second, there is NOS2 or inducible nitric oxide synthase (iNOS), which the body uses to produce nitric oxide at a staggering rate as part of the immune system.  Nitric oxide in high concentrations is lethal to bacteria.  And third, is NOS3 or endothelial nitric oxide synthase (eNOS) which is produced in the lining of the blood vessels.  Nitric oxide here signals the blood vessels to relax and dilate, allowing more blood, oxygen and nutrients to the tissues and organs and allowing waste to be removed from our cells more efficiently.  Many of the incredible benefits people have noticed from nitric oxide such as wound healing, lower blood pressure, better sexual performance, muscle growth, weight loss, etc.  come from the activity of eNOS.

Science has learned that nitric oxide is great in the blood vessels but too much can have detrimental effects.  For instance, too much nitric oxide can lower blood pressure too much in recovering heart attack victims.  Also, too much nitric oxide in the brain can actually inhibit the repair of neurons.  The NO molecule kind of gets in the way of the repair work.   Naturally, your body has mechanisms to deal with too much of this powerful stuff where it is not wanted or needed.  One of them is Agmatine.


Agmatine is formed in the brain by the decarboxylation of arginine.  That means that the body breaks off the carboxyl group on the arginine molecule.   There are lots of important decarboxylation reactions in the body including histidine to histamine and 5-HTP to serotonin.  Besides being stored in the brain, agmatine is also stored in selected neurons throughout the body.

As I mentioned before, nitric oxide is an incredibly beneficial molecule, however iNOS activity increases nitric oxide in the immune cells, and if the body isn’t fighting infection, this excess nitric oxide can lead to chronic inflammation.  nNOS increases nitric oxide in the neuronal tissue, where an excess of the molecule can actually inhibit growth and repair.  This is obviously not wanted, especially in stroke patients.  Numerous studies have shown that agmatine will actually inhibit the activity of those to NOS enzymes so that they don’t over produce nitric oxide in places we don’t necessarily want it.  Here is a recent study discussing the effect.

The most amazing thing in that study, in my opinion, is that while agmatine inhibited iNOS and nNOS activity, it STIMULATED eNOS activity, protecting and even expanding the blood vessels in the brains of the study subjects.

“These observations prompted us to think that overproduction of NO from eNOS protects brain tissue by maintaining regional cerebral blood flow; however, NO production from either nNOs or iNOS leads to neurotoxicity. Thereafter, agmatine may reduce cerebral ischemia injury by inhibiting the detrimental effects of both iNOS and nNOS.”

This is huge!

Of course the big question is, does supplementing with agmatine actually increase agmatine in the body?  Studies seem to indicate that there is a pathway for gastrointestinal uptake of agmatine, at least in rats.  If the reviews on nutritional supplement sites are to be believed, there is strong anecdotal evidence that agmatine supplementation works for humans too.  It has been reported to increase blood flow and the pump one feels when doing resistance exercises.

There Is Even More To Agmatine

It is also reported to be an effective pain fighter and may be a driver of lutenizing hormone (LH) which your body needs to produce its most anabolic hormone, testosterone.  Furthermore, besides the neuro-protective benefits of agmatine, it also appears to act as a modulator of mental stress.

So for incredible pumps, improved blood flow, targeted increases in nitric oxide, increases in testosterone, creating an anabolic environment in which to grow stronger and increase endurance,  and a general feeling of well being, agmatine may be just what you are looking for.  Now you can see why I think that agmatine might be the best nitric oxide booster on the market.

Agmatine is a main ingredient in both Hemavol and Jack3d Micro.   Check out my reviews of these products here.  You can find these products and others agmatine nitric oxide supplements at, Vitamin Shoppe, and