Agmatine – More than a Pump Supplement

[aaronuconn]

Agmatine – More than a Pump Supplement

Agmatine is a metabolite of L-Arginine that is derived via decarboxylation, which is essentially the removal of a carboxyl group. This neurotransmitter has become immensely popular in the sports supplement world as an ingredient included in pre-workouts. In many ways, Agmatine succeeds where Arginine fails. Through it’s ability to inhibit nitric oxide synthase, users of the ergogen will notice increase muscle pumps. We commonly see it dosed pre-workout only at 500 – 1000mg. That’s all good and fun, but Agmatine’s potential goes way beyond a pre-workout supplement for the bros. Although human data is limited, this ingredient has shown potential to aid in fat loss, nutrient partitioning, b-endorphin release, pain reduction, appetite and anti-depressive effects.

Effects

Fat Loss

You rarely hear Agmatine being touted as a fat loss supplement, however it very well may have a widespread impact on metabolic systems. In a 2014 study looking at the metabolic influence of Agmatine, researchers found that rats that were given 55-75
mg/kg/day of Agmatine in their drinking water experienced increase levels of cAMP (commonly elevated with forskolin as many know), activation of PPAR (lipid metabolism), increased fat oxidation and enhanced mitochondrial function. A group of rats that were fed a high fat diet experienced a ~15% reduction in body weight with Agmatine. These changes weren’t due to a change in diet, therefore Agmatine played a major role in influencing body weight. [1]

Selective Nutrient Partitioning

Many supplements are being touted as a nutrient paritioner. Nutrient partitioning is the idea that you can increase muscle tissue insulin sensitivity and "drive" nutrients into these cells vs. adipose tissue. By enhancing glucose uptake to muscles, we would assume we would see increased muscle mass and minimized fat gain. This is ideal for any goal, whether it is a hypocaloric or hypercaloric diet. Where nearly all of these supplements fail is that they are increasing glucose uptake to muscle AND adipose tissue. We want selective glucose uptake to muscle cells. Agmatine to the rescue?

B-endorphin release may assist in an increase in glucose uptake within skeletal muscle. Agmatine, via its potential effects on enhancing beta-endorphin secretion, may act as a selective nutrient partitioner. [2]

A lot of Agmatine’s effects are secondary to activation of the imidazoline receptors. One of these secondary effects is lowering blood glucose, thus why some may recommend Agmatine as a GDA. Because of this, some people enjoy Agmatine pre-bed. Not only are their potential anxiolytic effects, but also the potential for lower blood glucose levels pre-bed, which would cause inhibition of hypothalamic ****tostatin release which in turn causes a better release of growth hormone pulses throughout the night. At the end of the day, increasing endogenous production of HgH via natural methods will most likely not yield positive body composition effects - not directly anyways.

Pain Perception

We finally have human data! A randomized, double-blind, placebo-controlled trial found that 1.3g to 3.56g of Agmatine daily was effective for “alleviating pain and improving quality of life in lumbar disc-associated radiculopathy”. [3] This, coupled with what we learned previously about Agmatine’s effect on B-endorphin release, show that Agmatine may have potential for pain relief. Note that its effects on pain relief are not well documented or that the effects are short lived. This could be due to the short serum half-life of 10 minutes. CNS half-life appears to be around 12 hours, however. [4]

Appetite

Neuropeptide Y is a neuropeptide that stimulates hunger. Neuropeptide Y and Alpha 2 adrenergic receptors have a relationship where if a2-adrenergic receptors are activated, neuropeptide Y increases. Agmatine has been shown to be a2-adrenergic receptor agonist and thus may cause an appetite increase. In a study conducted in 1996, it was found that Agmatine enhanced caloric intake in satiated rats but not hungry ones. [5] So in conclusion, if rats were full, Agmatine would allow them to consume more. It wasn’t making hungry rats hungrier.

Depression/Anxiety

A small pilot study showed 2-3g of Agmatine/day was able to induce remission of depression. That’s a powerful statement, so let’s delve into the details a bit. The three subjects were individuals who suffered from Major Depresssive Disorder, which was clinically assessed. Along with the 2-3g of Agmatine, they concomitantly ingested parachlorophenylalanine. Parachlorophenylalanine is used in humans and animals to study the effects of serotonin depletion. No other pharmaceutical drugs were ingested. The subjects reported remission of depression, which was not reversed by coningesting parachlorophenylalanine. This also suggests that Agmatine anti-depressive effects are not related to serotonin.

Dosing

There are many ways people have enjoyed dosing Agmatine. You of course have your pre-workout dosage, which typically ranges from 500mg - 1000mg. Some exceed this, but I've never found it necessary.

Prior to carbohydrate meals is another option. 500mg prior to carb-rich meals.

The most I've used in a day is 2g - never felt any need to exceed this. 1g before a carb heavy meal and 1g preworkout is something I've done before.

Some also like 500mg pre-bed.



[1] http://www.jbc.org/content/early/201...44726.full.pdf
[2] http://www.ncbi.nlm.nih.gov/pubmed/19913596
[3] http://www.ncbi.nlm.nih.gov/pubmed/20447305
[4] http://www.ncbi.nlm.nih.gov/pubmed/15933157
[5] http://www.ncbi.nlm.nih.gov/pubmed/8884952
[6] http://www.ncbi.nlm.nih.gov/pubmed/25287313

[Deadliftin]

Great write up!

One of my favorite ingredients!

[eatyourspinach]

Nice write up, a few things I've always found peculiar about examine's write up that maybe you can shed some light on firstly

"Agmatine's oxidative inactivation of the nitric oxide synthase enzyme (seen in this study with nNOS with a Ki of 29µM) is due to increasing the activity of the NADPH oxidase subunit[116] which arginine is known to hinder for nNOS[117][118] yet appears to increase activity for iNOS and eNOS.[346][117] In this sense, arginine is antagonistic to the effects of agmatine towards nNOS (a possible reason why supplemental arginine inhibits many neurological effects) but does not affect eNOS in the same manner.

It is not sure whether pairing either of these two agents with arginine will enhance systemic nitric oxide production (via eNOS; the mechanism underlying most of the blood pressure effects) or be antagonistic; both are plausible, with the former being due to increased nitric oxide production from eNOS and the latter due to quicker inactivation of the enzyme."

and in regards to Yohimbine/rauwolscine

"agmatine activates the α2A receptor that these inhibit"

[AJP1]

Nice literature. Thanks for the right up. Any negative effects observed?

[kbayne]

Nice literature. Thanks for the right up. Any negative effects observed?

Can cause GI distress in some if dosed too high.

[AMeyer9]

Can cause GI distress in some if dosed too high.

That's what I was thinking when it mentioned using 2-3g a day for depression.

[XCriticalBenchX]

Solid post bro, we need more of these straight and to the point, reference posts.

Mike

[ISurfNudeBrah]

Good stuff.

[Represente]

Good write up man. Agmatine is one of favorite raw ingredients to use. I typically use 750mg-1g a day tho.

[aaronuconn]

Nice write up, a few things I've always found peculiar about examine's write up that maybe you can shed some light on firstly

"Agmatine's oxidative inactivation of the nitric oxide synthase enzyme (seen in this study with nNOS with a Ki of 29µM) is due to increasing the activity of the NADPH oxidase subunit[116] which arginine is known to hinder for nNOS[117][118] yet appears to increase activity for iNOS and eNOS.[346][117] In this sense, arginine is antagonistic to the effects of agmatine towards nNOS (a possible reason why supplemental arginine inhibits many neurological effects) but does not affect eNOS in the same manner.

It is not sure whether pairing either of these two agents with arginine will enhance systemic nitric oxide production (via eNOS; the mechanism underlying most of the blood pressure effects) or be antagonistic; both are plausible, with the former being due to increased nitric oxide production from eNOS and the latter due to quicker inactivation of the enzyme."

and in regards to Yohimbine/rauwolscine

"agmatine activates the α2A receptor that these inhibit"

As far as I know, Agmatine is a weak alpha-2 agonist and it's short lived half life make it fine to dose together with yohimbine.

I'm not too sure on the first part of your question

[TheFugitive]

Agmatine stacks well with other pumping agents. I'm a fan

[eatyourspinach]

Agmatine stacks well with other pumping agents. I'm a fan

This is why I am curious, since it is supposed to hinder nNOS which apparently would affect vasodilation http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345541/

[poison]

Im not a fan, personally. It doesnt help performance or pumps nearly as well as other ingredients, and there are stronger gda's. I should try it for pain: i do have a herniated disc that flares up from time to time.

[kbayne]

Im not a fan, personally. It doesnt help performance or pumps nearly as well as other ingredients, and there are stronger gda's. I should try it for pain: i do have a herniated disc that flares up from time to time.

What other GDAs have the ability to be selective to muscle tissue, besides very high dosed TUDCA?

[Deadliftin]

Im not a fan, personally. It doesnt help performance or pumps nearly as well as other ingredients, and there are stronger gda's. I should try it for pain: i do have a herniated disc that flares up from time to time.

What do you prefer for GDA effects? I'm not saying Agmatine is best, just curious what else you like...

[AMeyer9]

This is why I am curious, since it is supposed to hinder nNOS which apparently would affect vasodilation http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345541/

Bruh, you may as well be talking to him in Russian

[TheFugitive]

This is why I am curious, since it is supposed to hinder nNOS which apparently would affect vasodilation http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345541/

It really comes down to the user, what have you noticed with agmatine? I feel it works best when combined with nitrates and or GMS

[TheFugitive]

http://www.ncbi.nlm.nih.gov/pubmed/15028568

[eatyourspinach]

It really comes down to the user, what have you noticed with agmatine? I feel it works best when combined with nitrates and or GMS

Never took it by itself so I couldn't tell you anything specifically attributed to it.

[poison]

What other GDAs have the ability to be selective to muscle tissue, besides very high dosed TUDCA?

A hard work out?

[aaronuconn]

This is why I am curious, since it is supposed to hinder nNOS which apparently would affect vasodilation http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345541/

Agmatine will inhibit nNOS and iNOS, however it's going to stimulate eNOS activity, which is very important when it comes to vasodilation. eNOS is what leads to the generation of NO in vascular endothelium

[kbayne]

A hard work out?

In regards to other ingredients, since you specifically said, there are stronger GDAs available.

[aaronuconn]

In regards to other ingredients, since you specifically said, there are stronger GDAs available.

It would be interesting to see how some ingredients with touted GDA effects measure up via blood glucose monitoring

[kbayne]

It would be interesting to see how some ingredients with touted GDA effects measure up via blood glucose monitoring

Agreed. I believe a few individuals have gone through and tested some ingredients and their effects on blood glucose pre, during, and post meals. I'd have to dig it up though.

[fahdalsheheata]

For me, not single thing is felt using agmatine

[poison]

In regards to other ingredients, since you specifically said, there are stronger GDAs available.

Berberine, hell, even narala. Agmatine adds literally zero subjective difference. Yes, I know what studies say, I just don't think it pans out in real life.

[ISurfNudeBrah]

Berberine, hell, even narala. Agmatine adds literally zero subjective difference. Yes, I know what studies say, I just don't think it pans out in real life.

What? Subjective... like you "feeling" your blood glucose is lower than normal?

I thought we were discussing objective GDA results here, like monitoring serum glucose levels when utilizing said ingredients. I would be very interested in seeing that data kbayne.

[urg862]

Great write up! I definitely like agmatine for pumps and its nutrient partitioning effects. I also liked how you included the potential impact on aiding fat loss as I have used a fat burning aid that included agmatine in its profile.

[poison]

What? Subjective... like you "feeling" your blood glucose is lower than normal?

I thought we were discussing objective GDA results here, like monitoring serum glucose levels when utilizing said ingredients. I would be very interested in seeing that data kbayne.

When man blueprint came out, I had high hopes, given jrods propensity for releasing cutting edge ****. I felt nothing and saw nothing beyond what 300mg narala would do, and ive taken agmatine alone, narala alone, multiple other gda's. Its negligible in effect, imo. Andbthatvwould explain why blueprint bombed.

[ISurfNudeBrah]

When man blueprint came out, I had high hopes, given jrods propensity for releasing cutting edge ****. I felt nothing and saw nothing beyond what 300mg narala would do, and ive taken agmatine alone, narala alone, multiple other gda's. Its negligible in effect, imo. Andbthatvwould explain why blueprint bombed.

I've personally only used slinsane before, but it seems to give me the ability to eat an ungodly amount of food (entire pizza), without getting a distended stomach/bloated feel. That's really it from what I remember.

I'd love to see actual data of serum glucose levels with these ingredients, as I'm not sure they are efficacious enough to make you go hypoglycemic to where you would actually "feel" it.