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 somatostatin 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.