In the sports nutrition industry, it’s typically used as a “nitric oxide booster” and gives impressive muscular pumps when taken prior to weightlifting, but it doesn’t work in the way that most people think.
This document discusses this phenomenal supplement, and explains why it is an obvious inclusion in so many pre workout supplements, including none other than Myokem’s Nitramine.
Supplementing with agmatine (typically in the form of agmatine sulfate) can yield a metabolic cascade that provides these benefits:
- Improved nitric oxide levels (via the inhibition of its breakdown, as discussed below)
- Cognitive focus enhancement
- Cardioprotective action (great for the heart and cardiovascular system)
- Neuropathic pain relief
- Improvement in appetite
- Anti-aging benefits
- Links to mood improvement
- …it’s even useful when dealing with drug addiction and withdrawal!
Ultimately, this is one of those supplements that the sports nutrition and bodybuilding communities have known about for years, yet nobody else in the general public or in the rest of the health world has really figured out.
We’ll break down the most important benefits one by one, starting with the one that we care about most when taking Nitramine:
The Nitric Oxide Boost
While amino acids like L-arginine and L-citrulline get converted into nitric oxide, agmatine actually influences your NO levels by inhibiting the enzymes that break down nitric oxide, known as nitric-oxide synthase, or nNOS. It also boosts nitric oxide in other mechanisms discussed lower below.
From the study cited above:
It has been suggested that some of the pharmacological actions of agmatine… may be due to the inhibition of nNOS.
Remember that nNOS acronym (nitric oxide synthase), because we’re going to use it a lot in this document. You’ll be happy you’re inhibiting it with agmatine when all is said and done.
But it may not mix cooperatively with L-arginine!
While the above sounds great, you’d think that it’d work even better if you combined it with L-arginine, or possibly L-citrulline, known nitric oxide boosters. However, that’s not the case, as they might negate the above effects of agmatine, because L-arginine will combat it by reducing the inhibition of nNOS that you’d get from agmatine.[1,2]
So when formulating a pre workout supplement, a company is wise to choose the citrulline path, or the agmatine path, lest they like to waste money. Due to the low dosage required (which is good for a concentrated pre workout), as well as the plethora of other benefits above and below, Myokem decided on agmatine for Nitramine.
The NMDA Receptor: a secondary nNOS mechanismAgmatine directly inhibits nNOS, but its not done yet: further downstream in its reaction, it also inhibits it indirectly via its inhibition of the NMDA receptor.
NMDA receptors are devices for controlling memory functions and synaptic plasticity (see image to the right), which is the ability for your synapses to strengthen or weaken as needed. This comes up later when talking about the cognitive benefits, but it is also pertinent with our nitric oxide activity:
NMDA activation also causes an increase in nNOS. But with agmatine inhibiting the NMDA receptors, it ultimately decreases nNOS[4,5], which boosts the amount of time your nitric oxide pumps last.
That was a bit crazy, but if you’re still with us, that’s the thing you’ll start to realize about agmatine:
The cascade of events that occurs when you supplement it affects several biological systems, and nearly every one of them is beneficial for athletes!
In fact, we fail to see any disadvantages to it at this time, but we’re hesitant to ever say the words “always” or “never”.
Inducing nitric oxide synthesis via the α2A receptor
But we’re not done talking about nitric oxide yet. There’s yet another way that agmatine promotes more nitric oxide, and that’s by acting on the alpha-2 receptor. This promotes vasodilation, or the expansion of your veins (which leads to more bloodflow and nutrient delivery to the muscles… ie… bigger pumps). L-arginine and D-arginine also work in this manner, but agmatine is 100x stronger in this particular process.
One issue with this mechanism is that it is going to counteract some of the effects of yohimbine / rauwolscine, which inhibit alpha-2 receptors. With both of these ingredients in Nitramine, it’s unclear which one “wins” this little battle, but we can say with certainty that you definitely still feel the effects of the rauwolscine in Nitramine.
Thankfully, when it comes to pumps, this is just one of the several ways that agmatine can promote a nitric oxide boost, so if this method is diminished, the other methods mentioned above are not.
These three actions of agmatine lay a fantastic groundwork for a lot of future reactions involving NO that will provide several of the following benefits. The total synergy of this supplement is what makes it so impressive and unique.
Cognitive focus enhancement
In the brain, agmatine is naturally stored in the hippocampus. It is a “learning molecule”: when rats are going through water mazes, agmatine levels increase by significant levels in the synapses in the hippocampus.[9,10] the studies vary by significance – some show a 60% boost in agmatine levels, whereas a few other studies have reported as much as 500% increase!
Regardless, we are still learning a lot about the brain, but agmatine is clearly involved to a significant degree when forming memories.
But can supplementing with agmatine improve cognition, or is this just an internal process?
It seems that most of the research cited above shows the brain using its own agmatine to help memory formation, and we’d love to see more research that explores what happens when it is ingested as a supplement.
One study that may help show its benefits is one in which rats were taught to avoid certain tasks, and agmatine administration did in fact facilitate the proper memory formation.
The issue with the study above is that the rats were injected with agmatine, so we’d definitely like to see more human research. Fact is, however, that there is clearly something going on with memory, cognition, and agmatine in the brain.
This is just icing on the cake
Given that Nitramine is such a focus-based pre workout supplement, it’s not surprising to see this as the main choice of nitric oxide boosters in the product. However, the additional cognition effects that may come from taking agmatine are just icing on the cake, considering the heavyweight nootropics that are already in the product (citicoline, huperzine A, caffeine, and L-Theanine) are likely to be felt to a much greater degree.
We’ll keep this brief here, because it starts to get away from the most important benefits that athletes look for, and it starts to get into medical conditions where you should definitely see your doctor instead of self-medicate.
However, be aware of the effects:
Decreased blood pressureFirst off, due to the nitric oxide boosting and vasodilation effects mentioned above, this helps relax blood vessels. That, in turn, reduces blood pressure.
This is shown in a number of rat studies, in which agmatine injections did in fact lower their blood pressure.[13,14,15]
At this point, it shouldn’t be surprising to see that there are still other mechanisms (beyond the nitric oxide boost) that help to decrease blood pressure. One is its antihypertensive action on the imidazoline receptor, which agmatine also acts upon.
Due to the decrease in blood pressure, agmatine also indirectly helped to decrease bleeding, which improved survival rates in rats that had hemorrhages.
Muscular performance from improved glucose metabolism
Above, we mention the imidazoline receptor, which has blood pressure lowering qualities. Well, another secondary reaction of this receptor is to release extra endorphins into the bloodstream.
Theoretically, this may induce better muscle performance, because β-endorphins are linked to an increase in skeletal muscle glucose levels[18,19], which are then linked to performance gains.
At this point, we’re getting a bit far downstream in the process, but the point is that this ingredient is linked to just about everything good that we want in a pre workout supplement!
Also note that this has not yet been tested in the field, and would be difficult to determine because the increase in nitric oxide would also potentially boost performance.
An interesting human study using high dosages of agmatine sulfate (2.67g – over 5x more than what’s in a scoop of Nitramine) showed that agmatine provided mildly analgesic properties, and it was noted after only 14 days.
The research was done on subjects with inflammatory and neuropathic pain from lumbar spine issues.
What’s more interesting is that the benefits remained two months after the subjects stopped taking agmatine.
It’s been postulated that agmatine might be synergistic with other painkillers (prescription stuff that we won’t mention here). Needless to say, there is definitely more research required on this one, but most users on this site aren’t here for these reasons.
Some patients with various mood disorders have issues with their agmatine levels. The issue is that some patients have too much in their serum, but they are sometimes also breaking down too much.
Agmatine supplementation can possibly counter some minor issues, however. Mood-enhancing effects have been found in mammals when supplementing with agmatine, and at extremely reasonable levels: the human equivalent of 220-435mg for a 150lb male – less than the amount in a scoop of Nitramine!
What’s interesting is that the study above was done using a “tail suspension test”. Researchers hang the mice from its tail for 6 minutes, and determine how long it’s willing to fight before it gives up, or goes immobile. With agmatine, they take longer to give up.
What’s the significance here? It’s that when taking agmatine, the rats effectively performed more sets before giving up on their bleak situation. To the degree of antidepressant drugs that we can’t mention here!
So if you’re not “feeling it” lately, grab some Nitramine and dig in. Between all of the focus factors, stimulants, and the boost of confidence from agmatine, you’ll be on your feet and fighting for more reps in no time at all.
The study concludes that the mechanism is most likely via the aforementioned NMDA receptors and alpha-2 adrenoreceptors. Unfortunately, they discovered this due to yohimbine and L-arginine stopping these mood improvements of agmatine.
As always, if you any form of mood disorder, you should seek medical attention immediately and do not attempt to self-medicate. Not all mood/personality issues are agmatine-related.
What is the preferred dosage?
This varies from user to user. 500mg-1000mg (which is what you get in one to two scoops of Nitramine) is the standard pre-workout dosage. Anecdotally, some believe that even higher dosages should be used, but getting too high of doses makes the pumps counterproductive – things become too stiff and uncomfortable!
Meanwhile, the painkiller study referenced above used over 2.5g of agmatine sulfate per day, but that’s not our goal here.
Nitramine is a focus and performance-based pre workout – huge pumps are not its primary selling point. With that said, the pumps from the product are incredible, and they’re likely boosted by the large dosage of betaine, which is most notably a power boosting amino acid.
Since the product is geared towards both athletes, weight loss dieters, and bodybuilders, 500mg per scoop is a good start. You can always add more in bulk if you so desire, but you really shouldn’t need too much more.
Are there any side effects of agmatine?
When digging through all the research, there are no known side effects at the reasonable dosages mentioned above.
The largest human study to assess this was the lumbar spine painkiller research, where participants took between 1.335g to 2.67g to 3.56g per day (the doses were divided throughout the day). At the 3.56g/day level, gastrointestinal distress was recorded, but it eventually went away.
This leads us to believe that somewhere around 2.5g per day is the maximum “safe” spot.
In animal studies, lethal doses have been discovered in mice, rats, and rabbits, and they’re quite high: 300mg/kg in mice, 980mg/kg in rats, and 3200mg/kg in rabbits. This converts to literally pounds and pounds of it per day for humans, and is of course highly unrecommended.
Where to buy bulk agmatine
You can get 500mg in each scoop of Nitramine, and free samples are offered below. If you are interested in supplementing additional amounts, you can compare products and prices on PricePlow’s agmatine page.
Ultimately, this compound is beyond impressive for a number of reasons, and there’s a reason why it’s in so many pre workout supplements. Why the rest of the world hasn’t figured it out, however, is a different question.