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Agmatine Sulfate

  • Supports cognitive health
  • Helps to reduce stress and promote a healthy mood
  • May help with fitness performance and to support a healthy circulatory system 


Agmatine (also known as 4-(aminobutyl)guanidine) is a newly understood neurotransmitter that is produced from L-Arginine, through the L-Citrulline pathway. It is synthesized in the brain and stored in synaptic vessels, for use in receptor signalling pathways. Studies have suggested that this supplement has a wide range of potential benefits, including use in stress-reduction, promoting a healthy mood, support for cognition, learning, and memory, and for promoting a healthy brain and circulatory system.


This compound is found in several food sources and is a natural product of biochemical pathways in the human body. Consequently, it is considered to be generally safe for use. The recommended serving size for this supplement is 600 – 1200 mg, taken once to twice daily. Do not exceed the suggested serving size. Side effects may include nausea and diarrhoea and are more prominent at higher serving sizes. 


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Agmatine Reviews


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  • A potent natural biogenic compound derived from the amino acid, L-Arginine and often used for its improvements in cognitive health, fitness performance, and intra-workout energy.

  • Benefits may include stress-reduction, enhanced mood, promotion of cognitive health and memory, as well as support for a healthy circulatory system.

  • Standard serving size is 600 – 1200 mg, taken once to twice daily. It is not recommended to exceed the suggested serving recommendation.

  • Side effects may include nausea and diarrhoea, at larger serving sizes. 



Agmatine Sulphate (Clonidine-displacing substance, 4-(aminobutyl)guanidine, Decarboxylated arginine) is a naturally-occurring chemical compound that is derived from an amino acid called L-Arginine. It was first discovered by a German scientist in 1910, and research into its effects has been ongoing since then. It has been used in research for a number of different effects in the body, although the majority of research has been based on animal models and in vitro studies.

Research suggests that this supplement may be effective in reducing feelings of stress and improving mood. This supplement may help to support a healthy brain through its neuroprotective effects, while also supporting healthy memory and learning capacity. Studies have also indicated its potential to be used as a support supplement for a healthy cardiovascular system.[1]

This natural amino acid derivative has recently been discovered to act as a neurotransmitter, meaning that it helps to convey chemical messages in the brain – thus producing a variety of benefits, which we’ll explore below. It has been used in research for pain-relief (especially when used alongside better-known painkillers) and as a neuroprotective supplement. Some research has also focussed on this supplement’s potential to be used alongside pharmaceutical agents for mood and pain.

This supplement is found in several forms of fermented foods and is a byproduct of bacterial metabolism. Foods that contain this compound include wine, beer, sake, and instant coffee.[2] The common form of administration in studies up until now has been by use of injections, and there is some room for more research into the effects of this supplement when it is taken by in a powdered/oral form.

This supplement works through several mechanisms. It is an NMDA receptor antagonist, an alpha-2-adrenergic receptor activator, and a serotonin signal enhancer. It also helps to regulate nitric oxide production and may also block calcium and potassium channels.




Agmatine Effects / Benefits

1.     Agmatine for Stress 


This neurotransmitter is thought to play an important role in the body’s natural stress-reduction mechanisms. Animal studies have indicated that when mammals are subjected to a stressful environment, there is an increase in cerebral and plasma concentrations, leading researchers to label it as a natural stress-reducing supplement. An increase in this compound’s concentration is also observed in subjects with hypoxia (lack of oxygen).[3]

This compound influences a number of different receptors in the brain which have effects on stress reduction. For example, this supplement acts as an activator of imidazoline receptors.[4] By activating imidazoline receptors, it helps to increase endorphins (natural ‘feel-good’ chemicals in the brain),[5] which, in turn, help to reduce stress and to promote a positive mood.

Some studies have indicated that this amino acid derivative may help to increase the firing of neurons in the locus coeruleus – an area of the brain that is associated with the body’s response to stress and mood changes.[6] Research focussing on alcohol withdrawal and the associated feelings of stress has further pointed to Agmatine’s role as an anti-stress agent.[7]

Furthermore, research suggests that the supplement’s ability to increase imidazoline signalling may also help to increase the effects of many different types of compounds and supplements that are used to reduce pain. While this supplement itself appears to be only mildly capable of reducing feelings of pain, it seems to be more beneficial when taken alongside other supplements for pain.[8]


2.     Agmatine for Mood


This supplement appears to have the potential to support a healthy mood, through a number of interactions with neurotransmitter systems in the brain. However, researchers are still trying to find out exactly how this works. It seems to have a modulating effect on mood, with the potential to act as a ‘mood regulator’.

Some pharmaceutical agents for mood target the agmatinase enzyme, which is responsible for the break down of this neurotransmitter. Interestingly, some agents work to increase the activity of the enzyme, while others reduce its actions. However, both these actions seem to be beneficial for mood. For example, SSRIs increase concentrations of this compound,[9] while other agents for mood reduce these concentrations.[10] What this shows is that the Agmatine neurotransmitter is clearly involved in mood, but in a ‘bell-curve’ fashion – too great a concentration and too low a concentration are both detrimental to mood.


Some of this supplement’s positive effects on mood may also be related to its ability to target the brain’s NMDA receptors.[11] These receptors are important for a number of processes in the brain, including regulation of mood.Importantly, this compound also has effects on serotonin signalling. Serotonin has long been known to be involved in supporting a good mood, and many supplements for mood target serotonin receptors. The exact mechanism by which Agmatine influences these receptors is still being researched, but researchers have indicated that it has a positive effect on serotonin signalling, which is important for supporting a healthy mood.


3.     Agmatine for Cognition, Memory, and Learning


A number of studies have pointed to Agmatine’s ability to influence cognitive performance (possibly including memory and learning capacity). This supplement interacts with adrenergic receptors (including epinephrine and norepinephrine), as well as catecholamine receptors, both of which are important for efficient cognitive performance.


Even more, studies have shown that this compound is stored in the hippocampus (a part of the brain associated with learning)[12], and is released by the brain during memory formation and in the process of learning new tasks.[13] It is also found in different areas of the brain associated with the process of learning (like the stratum radiatum and both prefrontal and perirhinal cortices).[14]


This research has led scientists to make the claim that Agmatine is a neurotransmitter involved in the process of memory formation. Some research has indicated that large serving sizes of this supplement (above the recommended usage) may be detrimental to learning. However, when used correctly, this supplement has the potential to help support healthy memory and learning, especially with tasks involving the hippocampus[15] and the prefrontal cortex. [16]


4.     Agmatine for a Healthy Brain


Agmatine is often referred to as a neuromodulator – meaning that it helps to maintain a healthy level of neurotransmitters in the brain. This is especially relevant as it interacts with several important receptor systems like the NMDA receptors, adrenergic receptors, and the serotonin receptors, all of which are of vital importance in supporting a healthy brain.


Furthermore, some research suggests that it is useful in protecting the brain from stress (neuroprotective) – especially from high concentrations of glutamate and NMDA transmitters. These results have been confirmed in animal studies but are yet to be studied with human participants.[17] Several additional animal studies have also pointed to this supplement’s neuroprotective effects[18], providing further basis for the claim to support a healthy brain!


5.     Support for a Healthy Circulatory System


Recent studies have pointed to this supplement’s ability to help support a healthy circulatory system. This appears to be due to its ability to interact with nitric oxide. Nitric oxide is important for blood circulation and has a dilating effect on the blood vessels[19] – reducing blood pressure and allowing increased blood flow through the body. Similarly to its ability to support a healthy brain, Agmatine seems to have a modulating effect on nitric oxide – it can both increase production (causing vasodilation) and decrease it (causing vasoconstriction)[20], to help maintain and regulate healthy levels.


Importantly, this supplement does not convert directly into nitric oxide as is often (incorrectly) assumed. It is a metabolite of L-Arginine, which IS converted into nitric oxide (through the chemical pathway of L-Arginine à L-Citrulline).[21] Agmatine activates a receptor called the α2A receptor, which is responsible for triggering the synthesis of nitric oxide.[22]


6.      Possible Support for Physical Energy


Animal studies have indicated that blood glucose levels tend to drop after supplementation with this compound, as a result of its interactions with imidazoline receptors.[23] Researchers have suggested that this supplement triggers an increased deposit of glucose into skeletal muscle cells. This would explain the observed drop in blood glucose levels and may also be related to the increase in endorphins seen during supplementation.[24] More studies are needed to assess whether these effects remain true for oral Agmatine supplements taken by healthy humans.




Agmatine Sulphate Recommended Usage


The suggested serving size for this supplement is around 600 – 1200 mg, taken once to twice daily. Due to a low level of research with human participants, it is not recommended to exceed 2400 mg daily. LiftMode Agmatine Sulfate in sold in a semi-transparent, reclosable airtight plastic jar, with a tamper-proof band to ensure product quality and purity.


Animal studies have suggested that this supplement has a good distribution through the body, with detectable concentrations found in all the organs. This supplement appears to have a particularly short half-life in the blood (around 10 minutes) but a much longer half-life in the brain (over 12 hours).[25]


Agmatine Side Effects and Warnings


This supplement is considered to be safe for use within the recommended serving size. There is room for further research into its safety and efficacy with human participants taking oral supplements. One human study using a serving size of up to 2670 mg per day suggested that side effects were not common and included mild nausea and diarrhoea.[26]


Do not use this supplement if you are taking any other medication. Please speak to your doctor if you have any underlying medical conditions. There is insufficient information about safety for pregnant and breastfeeding women – please speak to your doctor first if you’d like to use this supplement. 




In summary, this supplement is a powerful biogenic compound and a derivative of the amino acid L-Arginine (not to be confused with L-Citrulline). This natural supplement shows some promising effects, although most studies have been based on animal models and in vitro research. There is room for further research into its effects in humans.


This top cognition supplement has several potential benefits, including stress-reduction, supporting a healthy mood, and promoting learning and memory. It may also have beneficial effects on the circulatory system through its interactions with nitric oxide while promoting a healthy brain and potentially acting as a neuroprotective supplement against stress.


The recommended serving size is between 600 – 2400 mg, daily. It is not recommended to exceed the suggested usage for this supplement. Side effects may include nausea and diarrhoea, which may be more prominent if exceeding the suggested serving size.    





[1]Agmatine”, PubChem Open Chemistry Database, US National Library of Medicine, available online: https://pubchem.ncbi.nlm.nih.gov/compound/agmatine/

[2]Agmatine” Examine.com, available online from https://examine.com/supplements/agmatine/ [Accessed 5 March 2018]

[3] Feng Y, Piletz JE, Leblanc MH. “Agmatine suppresses nitric oxide production and attenuates hypoxic-ischemic brain injury in neonatal rats.” Pediatr Res. 2002 Oct;52(4):606-11.

[4] Piletz JE, Chikkala DN, Ernsberger P. “Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors.” J Pharmacol Exp Ther. 1995 Feb;272(2):581-7

[5] Chang CH, Wu HT, Cheng KC, Lin HJ, Cheng JT. “Increase of beta-endorphin secretion by agmatine is induced by activation of imidazoline I(2A) receptors in adrenal gland of rats.” Neurosci Lett. 2010 Jan 14;468(3):297-9.

[6] Ruiz-Durántez E, Ruiz-Ortega JA, Pineda J, Ugedo L. “Effect of agmatine on locus coeruleus neuron activity: possible involvement of nitric oxide.” Br J Pharmacol. 2002 Mar;135(5):1152-8

[7] Taksande BG, Kotagale NR, Patel MR, Shelkar GP, Ugale RR, Chopde CT. “Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats.” Eur J Pharmacol. 2010 Jul 10;637(1-3):89-101.

[8]Kolesnikov Y, Jain S, Pasternak GW. “Modulation of opioid analgesia by agmatine..” Eur J Pharmacol. 1996 Jan 18;296(1):17-22

[9] Taksande BG1, Kotagale NR, Tripathi SJ, Ugale RR, Chopde CT. “Antidepressant like effect of selective serotonin reuptake inhibitors involve modulation of imidazoline receptors by agmatine.” Neuropharmacology. 2009 Sep;57(4):415-24

[10] Halaris A, Zhu H, Feng Y, Piletz JE. “Plasma agmatine and platelet imidazoline receptors in depression.” Ann N Y Acad Sci. 1999 Jun 21;881:445-51.

[11] Askalany AR, Yamakura T, Petrenko AB, Kohno T, Sakimura K, Baba H. “Effect of agmatine on heteromeric N-methyl-D-aspartate receptor channels.Neurosci Res. 2005 Aug;52(4):387-92.

[12] Reis DJ, Yang XC, Milner TA. “Agmatine containing axon terminals in rat hippocampus form synapses on pyramidal cells.” Neurosci Lett. 1998 Jul 10;250(3):185-8.

[13] Liu P, Collie ND, Chary S, Jing Y, Zhang H. “Spatial learning results in elevated agmatine levels in the rat brain.” Hippocampus. 2008;18(11):1094-8.

[14] Liu P, Jing Y, Collie ND, Chary S, Zhang H. “Memory-related changes in L-citrulline and agmatine in the rat brain.” Hippocampus. 2009 Jul;19(7):597-602.

[15] Gaffan D, Parker A. “Interaction of perirhinal cortex with the fornix-fimbria: memory for objects and "object-in-place" memory.” J Neurosci. 1996 Sep 15;16(18):5864-9.

[16] Zhou HC, Sun YY, Cai W, He XT, Yi F, Li BM, Zhang XH. “Activation of β2-adrenoceptor enhances synaptic potentiation and behavioral memory via cAMP-PKA signaling in the medial prefrontal cortex of rats.” Learn Mem. 2013 Apr 17;20(5):274-84.

[17] Li YF, Gong ZH, Cao JB, Wang HL, Luo ZP, Li J. “Antidepressant-like effect of agmatine and its possible mechanism.” Eur J Pharmacol. 2003 May 23;469(1-3):81-8.

[18] Wang CC Chio CC, Chang CH, Kuo JR, Chang CP “Beneficial effect of agmatine on brain apoptosis, astrogliosis, and edema after rat transient cerebral ischemia.” BMC Pharmacol. 2010 Sep 6;10:11

[19] Raghavan SA, Dikshit M. “Vascular regulation by the L-arginine metabolites, nitric oxide and agmatine.Pharmacol Res. 2004 May;49(5):397-414.

[20] González C, Regunathan S, Reis DJ, Estrada C. “Agmatine, an endogenous modulator of noradrenergic neurotransmission in the rat tail artery.” Br J Pharmacol. 1996 Oct;119(4):677-84.

[21] Liu P, Jing Y, Collie ND, Chary S, Zhang H. “Memory-related changes in L-citrulline and agmatine in the rat brain.Hippocampus. 2009 Jul;19(7):597-602

[22] Joshi MS, Ferguson TB Jr, Johnson FK, Johnson RA, Parthasarathy S, Lancaster JR Jr. “Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells.” Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):9982-7.

[23] Chang CH, Wu HT, Cheng KC, Lin HJ, Cheng JT. “Increase of beta-endorphin secretion by agmatine is induced by activation of imidazoline I(2A) receptors in adrenal gland of rats.Neurosci Lett. 2010 Jan 14;468(3):297-9

[24] Khan S, Evans AA, Hughes S, Smith ME. “Beta-endorphin decreases fatigue and increases glucose uptake independently in normal and dystrophic mice.” Muscle Nerve. 2005 Apr;31(4):481-6.

[25] Roberts JC, Grocholski BM, Kitto KF, Fairbanks CA. “Pharmacodynamic and pharmacokinetic studies of agmatine after spinal administration in the mouse.” J Pharmacol Exp Ther. 2005 Sep;314(3):1226-33.

[26] Keynan O, Mirovsky Y, Dekel S, Gilad VH, Gilad GM. “Safety and Efficacy of Dietary Agmatine Sulfate in Lumbar Disc-associated Radiculopathy. An Open-label, Dose-escalating Study Followed by a Randomized, Double-blind, Placebo-controlled Trial.” Pain Med. 2010 Mar;11(3):356-68.