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Agmatine: Everything You Could Possibly Want To Know

Agmatine

We’ve seen a lot of supplements come and go over the years, but one that seems to be sticking around is Agmatine.  Unfortunately, most of the info out there on Agmatine is biased or, in some cases, just completely wrong.

So, we decided to do what we do best and throw together a post about Agmatine from a scientific perspective.  In this article, we’ll discuss everything you could possibly want to know about Agmatine.  We’ll answer questions like:

  • What Is Agmatine?
  • Why Do People Use It?
  • What Are The Benefits?
  • Is It Safe?
  • Are There Side Effects?

And much, much more.  So let’s quit wasting time and get right into it, shall we?

What Is Agmatine?

Agmatine, also known as 4-(aminobutyl)guanidine, is a metabolite of the amino acid Arginine (which you’ve probably heard of).

In case you’re wondering, the term metabolite just means something that is created as a result of or as a byproduct of metabolism.  Agmatine is created when Arginine goes through a process known as decarboxylation.

This is where the carboxylic acid group is removed from Arginine.

Agmatine is also found in fermented drinks like:

  • Beer
  • Wine
  • Coffee

Bacteria convert naturally occurring Arginine into Agmatine, but the amount that naturally occurs in foods (fermented foods mostly) tends to be pretty negligible.

This is definitely one instance where supplementation is required.  You simply can’t get enough Agmatine from your food to really matter…Unless of course you’re a raging alcoholic, but then it’s safe to say the negatives outweigh the positives.

While many people think of Agmatine as a “pump supplement”, due mostly the the fact that it comes from Arginine, it’s actually most active in the brain where it functions as a neurotransmitter.

It’s partially stored in neurons (brain cells) and is capable of interacting with imidazoline, adrenergic, and NDMA receptors.  But more on that later.

Why Do People Use Agmatine Supplements?

Agmatine is an extremely versatile compound with an ever-expanding list of potential benefits.  Mostly, people use it in the form of supplements to:

  • have better pumps during exercise
  • enhance exercise performance
  • improve brain function
  • reduce pain

Now, it’s important to understand that not all of these “benefits” are proven by science.  The popularity of Agmatine supplements may be on the rise, but research hasn’t caught up yet.

The truth is, many of the claims made by supplement companies are tenuous at best.  With regards to how Agmatine may impact exercise specifically, there are literally no studies.  Not even in rodents.

What Are The Potential And Proven Benefits Of Agmatine Supplementation?

In the following section, we’ll look at the research (or lack thereof) in support of the alleged benefits we listed above.

Agmatine For Better Pumps

Like Arginine, Agmatine is commonly purported to enhance blood flow, also known as “the pump”.  In vitro, it has been shown to increase Nitric Oxide in Endothelial cells.

It does this by activating the enzyme Endothelial Nitric Oxide Synthase (eNOS).  Contrary to popular belief, Agmatine does not convert into Nitric Oxide like Arginine.  They accomplish the same thing — increasing Nitric Oxide production — but in different ways.

Agmatine may increase Nitric Oxide production but there is no human evidence for this at all.  Right now, it’s just in vitro and rodent studies and, while they do appear promising, we still need to confirm the findings in actual humans.

What works in mice doesn’t always work in humans.  In fact, it often doesn’t.  We’ve seen tons of supplements get hyped beyond belief because some rodent research indicated it might be useful, only to find out they don’t really work in Humans.

  • L-Arginine
  • Garcinia Cambogia
  • Hoodia

The list goes on, but you get the idea.  For now, you should view the pump-enhancement aspect of Agmatine with some healthy skepticism…

The preliminary research on Agmatine suggests that it can boost Nitric Oxide which could potentially enhance “the pump” during workouts.  However, until we see some human studies, it’s best not to jump to conclusions.  For now, Agmatine MAY be effective.

Agmatine And Exercise Performance

Agmatine is often used in pre-workout supplements because it’s widely believed that it enhances exercise performance.  To be crystal clear…

There are no studies in which it has been looked at as a performance enhancer in human subjects.

That said, it has a few mechanisms by which it can potentially improve exercise performance.

One way is simply by increasing Nitric Oxide levels, like we discussed in the pump section above.  Another way — this is definitely the more intriguing way — is by triggering the secretion of Beta-Endorphin.

Beta-Endorphin is a chemical released by the brain in response to certain stressors such as exercise.  It blunts pain perception and improves mood, both of which may result in performance enhancement.

Unfortunately, without any human studies, we can’t really draw any solid conclusions about how Agmatine can impact exercise performance.  It may work, but that still leaves the question of dosing.

Agmatine may enhance exercise performance, either by increasing N.O. levels or by Beta-Endorphin release.  However, there are absolutely no human studies so we can’t really draw any solid conclusions about how Agmatine really impacts exercise.

Agmatine And Pain

Agmatine has been shown to agonize the NDMA subclass of Glutamate receptors which are known to regulate pain perception.  Naturally, some of the research on it has been specifically geared towards pain management.

In mice, it has been shown to reduce inflammatory and neuronal pain.  It is thought to work by reducing plasticity, which this type of pain is reliant upon.  Agmatine has also been shown to interact with opiod receptors in such as manner that it actually enhances the pain reduction seen with Opiods while reducing tolerance at the same time.

One human study found that supplementation, at 2.67 grams per day, reduced pain associated with Radiculopathy.  It’s probably worth mentioning, however, that this study was funded and conducted by organizations that stood to benefit from positive results.

Does that mean the study is meaninless?  No, because the preliminary evidence supports the notion that Agmatine can be useful for pain reuction.  Still, more studies are needed.

Agmatine appears to have some capacity for pain reduction, at least when it comes to inflammatory or neuronal pain.  It may not reduce ALL pain.

Agmatine And Addiction

Since Agmatine interacts with adrenergic receptors — specifically, alpha-2-adrenergic receptors — there has been some research in the area of addition.  Adrenergic receptors play a role in addiction and, by preventing up-regulation of these receptors, Agmatine may help combat addiction.

It has been shown to reduce symptoms of alcohol withdrawal in mice, but human studies are non-existent.  Studies have also looked at how it can impact Cocaine addiction, but only in mice.

These studies haven’t had particularly promising results, but there are also differences between mice and humans with regards to the addictive potential of Cocaine.  Unfortunately, there haven’t been any human studies.

Right now, it seems like Agmatine may be kind of useful for treating some forms of addiction, but there’s really not a lot of evidence either way.  All the studies have taken place in rats, not humans.  While we may share a lot in common with rodents, addiction is a very human development.

Without studies in humans, it’s impossible to say how it impacts addiction.  All we have is a mechanism of action by which it may help with addiction.

The studies in mice with regards to addiction can’t really be extrapolated to humans because of major differences in the way our brains form addictions.  Without human studies, it’s tough to say how Agmatine impacts addiction or addictive behavior.

Agmatine And Brain Function

Another benefit commonly attributed to Agmatine is cognitive enhancement.  This stems from the fact that it acts as a neurotransmitter and impacts multiple kinds of receptors that can ultimately change the way we think and feel.

In the brain, Agmatine levels naturally increase when neurons are activated, indicating some sort of relationship between Agmatine and cognitive function in general.

In mice, it’s been shown to improve memory and learning capability as well as combat amnesia, so there’s plenty of reason to suspect that it may enhance cognitive function in humans…

Unfortunately, there’s absolutely no human evidence to support this notion.  All we have is a bunch of rodent research which indicates Agmatine MAY be effective.  That’s not proof though.  It’s just cause for more research…human research, preferably.

What Can I Expect From Agmatine Supplementation?

Honestly, it’s hard to say.  The most compelling evidence for Agmatine indicates that it may be useful for enhancing Nitric Oxide production and may dull your pain perception to some extent.

Both of these effects would be beneficial for performance and, yes…THE PUMP!

It’s certainly possible that Agmatine will make you perform better during your workouts.  It’s just not proven.

For that reason, it’s probably better to just say “try it yourself and see”, rather than speculate about how it may help you.

Is It Safe?  Are There Any Side Effects!?

There’s no reason to suspect that Agmatine isn’t safe.  The LD50 is extremely high, at 980mg/kg in mice.

The LD50 is simply the amount of a given substance it takes to kill half a test population of animals (usually mice).  It’s used as a basic benchmark to gauge the toxicity of various substances.

Although human studies are lacking all around, there was one in which subjects took a little over 3.5 grams per day and there were no adverse effects reported.

Ultimately,  Agmatine appears to be safe at standard supplemental doses of 1-3g daily.  Since it does interact with certain receptors in the brain, it could potentially clash with certain medications.  That’s worth noting if you’re on psychoactive medication of any kind.

If that’s the case, talk to your doctor about it.

Choosing The Right Agmatine Supplement?

Although Agmatine is present in small amounts in some foods and beverages (particularly alcoholic beverages like beer and wine), you need to take an Agmatine supplement in order to actually derive any notable benefit.

Surely the cons outweigh the pros when it comes to getting your Agmatine through alcohol…

You’ll typically find Agmatine in supplements labeled Agmatine Sulfate.  There are no other commonly used forms of Agmatine, though technically there are an unlimited number of possible chemical combinations.

So, when it comes to picking the right Agmatine supplement, it’s not so much a matter of what form.  It’s more about who you’re buying it from.  Not all supplement companies are trustworthy and Agmatine can get pretty expensive.

In other words, cheap Agmatine supplements can be riddled with impurities, so you want to go with a brand you can actually trust.

The Bottom Line

The use of Agmatine is definitely on the rise and while there is a lot of preliminary research that’s actually pretty promising, this is one situation where science just hasn’t yet caught up with the hype.

Agmatine may very well be useful for things like enhancing exercise performance and improving cognitive function.  Unfortunately, until more human studies are conducted, we just don’t know that much about it.

If you want to give Agmatine a shot, go for it!  There’s certainly nothing wrong with the try it yourself approach and anecdotal evidence.  The issue occurs when supplement companies frame those potential benefits as proven benefits.  You can decide for yourself what you think about Agmatine…

Have any thoughts on Agmatine?  Comment below…

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