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Agmatine is a natural compound that’s derived from the amino acid L-Arginine and provides an incredible number of benefits to both athletes and non-athletes alike.
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.
Agmatine is a metabolite of L-Arginine. It shows promise for alleviating neuropathic pain and drug addiction. Agmatine supplementation can also protect from strokes and benefit cognitive health.
Agmatine is derived from L-Arginine through decarboxylation (the removal of a carboxylic acid group). It is stored in neurons and is released during neuronal activation. Agmatine is considered to be a neurotransmitter and neuromodulator.
Preliminary research suggests Agmatine has potential use in the treatment of neuropathic pain and drug addiction. It also protects the brain from toxins and strokes.
Though supplementing Agmatine by itself can increase the perception of pain, it works synergistically with painkillers like morphine and fentanyl. Agmatine’s synergy with opioids allows it to reduce pain killer tolerance, the possibility of addiction, and pain itself.
Agmatine has several mechanisms. It can inhibit N-methyl-D-aspartate (NMDA) and nicotinic acetylcholine receptors, as well as activate imidazoline receptors. Agmatine can also inhibit nitric oxide synthase enzymes, which allows it to regulate elevated levels of nitric oxide. Agmatine can inhibit calcium channels and certain serotonin receptors as well. Further research is needed to determine the full extent of Agmatine’s mechanisms.
There is a lot of animal evidence to suggest Agmatine is a highly promising research chemical. It is not a common supplement because there is a lack of human evidence for its effects. Several studies have been done on people, but the majority use Agmatine injections, not oral ingestion. Research must establish that Agmatine’s effects will work following oral ingestion in order for wide-scale supplementation to be considered.
The primary method of action for Agmatine Sulfate is by crossing the blood-brain barrier, entering into the central nervous system, and then binding to NMDA Glutamate receptors.
Since this is the chief neurotransmitter involved in synaptic plasticity and memory function, this may be responsible for a number of the associated cognitive benefits of this supplement.
Agmatine Sulfate also has some analgesic activities, releasing a number of opioid and endorphin chemicals, seeming to have some sort of synergistic effect on many of these chemicals.
It is also capable of enhancing the effects of both morphine and fentanyl to increase pain killing, reduce tolerance, and lower addiction. It appears to work especially synergistically with Marijuana.
Supplementing with 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
* Overcoming 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 some of the most important benefits starting with the one that we care about most when taking Nitramine:
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. 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.
What we know so far is that the brain is 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.
DECREASED BLOOD PRESSURE
First 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. 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.
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, 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!
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 anti-depressant drugs (Re-Uptake Inhibitors)!
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.
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 around 2.5 g is the 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.
There are no standard dosages for Agmatine due to the lack of human evidence for its effects. However, a single human study used 1,300-2,670mg of Agmatine, daily for the treatment of neuropathic pain. The estimated human dose for improving cognition is 1.6-6.4mg/kg of Agmatine, taken orally. This is based off of the 10-40mg/kg dosage range for rats, and is equivalent to 217-435mg for a 150lb person.
Supplementation should not exceed 6.4mg/kg of bodyweight. Studies on agmatine use a daily dosing protocol.
Agmatine is not absorbed well when taken with dietary protein, because it uses the same transporters as Arginine. Further research is needed to determine if oral Agmatine supplementation provides the same benefits as were observed in animal studies.
To learn more about Agmatine Sulfate: