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Ultimate Guide to Agmatine: Benefits, Side Effects & Dosages
Agmatine, also known as (4-aminobutyl) guanidine, is a derivative of the amino acid l-arginine. Stored in neurons, this compound (also referred to as "super arginine") is known to assist with central nervous system function, primarily as a neuromodulator and neurotransmitter.
Research into agmatine reveals a potential to improve the symptoms related to neuropathic pain, and the ability to assist with the treatment of drug addiction. Agmatine also helps to govern nitric oxide (NO) synthesis, as well as working to properly regulate cellular energy by overseeing polyamine metabolic function. This makes agmatine sulfate a popular pump-inducing supplement choice.
In the muscle building and sports performance realm, agmatine works to provide the following potential benefits:
Agmatine is typically listed on supplement labels as agmatine sulfate. Dosages range between 250 mg to 1,000 mg per scoop, with intake recommendations hovering between 1 to 2 grams per day. It should be noted that these products are usually focused on pump inducement and the muscle building process, so daily dosage recommendations may vary slightly compared to nootropic recommendations for mental clarity, stress reduction, etc.
Here are some packaging directions from one popular agmatine sulfate product:
So to recap, when used as a muscle pump-inducer, 500 to 1,000 mgs of agmatine sulfate should be taken 20-30 minutes prior to training. An optional 500 to 1,000 mgs may also be taken during training. Agmatine can be taken at any convenient time on non-training days.
This section will look at the major potential benefits of agmatine supplementation.
Benefit - An increase in insulin response lends itself to a leaner, more muscular physique.
Benefit - Improved focus, better overall health and sense of well-being, and a more relaxed state.
Benefit - Potential for improved state of well-being and lower anxiety levels. This can also assist with maintaining the motivation to pursue better health and fitness.
Benefit - Agmatine can improve vasodilation, leading to improved nutrient delivery to muscle cells, and an increase in muscle protein synthesis rates which impact the muscle building process.
Agmatine has the potential to create an anti-hypertensive environment, assisting the body in maintaining a healthier blood pressure level. [23][24][25]
Benefit - A healthier blood pressure allows for improved nutrient delivery, improving overall health and lending itself to a more optimal muscle building/recovery process.
Benefit - Agmatine supplementation has the potential to reduce neuro-damage caused by a stroke.
Benefit - Hardgainers, or individuals who have a more difficult time gaining weight, may benefit from agmatine supplementation. They are likely to eat more, even when full.
Benefit - Bolstered testosterone production yields a myriad of health benefits, including the ability to impact muscle tissue growth and maintenance.
No. Agmatine is a derivative of l-arginine (a conditionally essential amino acid), but they do not share the exact same researched benefits. Though arginine is required by the body and supports many important functions, supplementing with arginine will not provide the same benefits as supplementing with agmatine.
Arginine has the ability to convert directly into nitric oxide, but agmatine does not. Despite this difference, agmatine still has the ability to positively impact muscle pumps via other physiological mechanisms.
2) Roberts JC, et al. Pharmacodynamic and pharmacokinetic studies of agmatine after spinal administration in the mouse. J Pharmacol Exp Ther. (2005)
3) Fairbanks CA, et al. Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury. Proc Natl Acad Sci U S A. (2000)
4) Su RB, Li J, Qin BY. A biphasic opioid function modulator: agmatine. Acta Pharmacol Sin. (2003)
5) Keynan O, et al. 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)
6) Chang CH, et al. Increase of beta-endorphin secretion by agmatine is induced by activation of imidazoline I(2A) receptors in adrenal gland of rats. Neurosci Lett. (2010)
7) Hwang SL, et al. Activation of imidazoline receptors in adrenal gland to lower plasma glucose in streptozotocin-induced diabetic rats. Diabetologia. (2005)
8) Khan S, et al. Beta-endorphin decreases fatigue and increases glucose uptake independently in normal and dystrophic mice. Muscle Nerve. (2005)
9) Cheng JT, et al. Plasma glucose-lowering effect of beta-endorphin in streptozotocin-induced diabetic rats. Horm Metab Res. (2002)
10) Curry DL, Bennett LL, Li CH. Stimulation of insulin secretion by beta-endorphins (1-27 & 1-31). Life Sci. (1987)
11) Aricioglu F, Regunathan S, Piletz JE. Is agmatine an endogenous factor against stress. Ann N Y Acad Sci. (2003)
12) Taksande BG, et al. Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats. Eur J Pharmacol. (2010)
13) Gong ZH, et al. Anxiolytic effect of agmatine in rats and mice. Eur J Pharmacol. (2006)
14) Cortisol: Why ?The Stress Hormone? Is Public Enemy No. 1 | Psychology Today. (n.d.). Retrieved from https://www.psychologytoday.com/blog/the-athletes-way/201301/cortisol-why-the-stress-hormone-is-public-enemy-no-1
15) Krass M, et al. Antidepressant-like effect of agmatine is not mediated by serotonin. Behav Brain Res. (2008)
16) Aricioglu F, Altunbas H. Is agmatine an endogenous anxiolytic/antidepressant agent. Ann N Y Acad Sci. (2003)
17) Li YF, et al. Antidepressant-like effect of agmatine and its possible mechanism. Eur J Pharmacol. (2003)
18) Kotagale NR, et al. Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test. Pharmacol Biochem Behav. (2013)
19) Zomkowski AD, et al. Agmatine produces antidepressant-like effects in two models of depression in mice. Neuroreport. (2002)
20) Joshi MS, et al. Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells. Proc Natl Acad Sci U S A. (2007)
21) Haulic? I, et al. Preliminary research on possible relationship of NO with agmatine at the vascular level. Rom J Physiol. (1999)
22) Biolo, G. An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein, Am. J. Physiol. 273 (Endocrinol. Metab. 36): El22-E129, 1997
23) Raasch W, et al. Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine-mediated blood pressure reaction. Br J Pharmacol. (2002)
24) Schäfer U, et al. Effects of agmatine on the cardiovascular system of spontaneously hypertensive rats. Ann N Y Acad Sci. (1999)
25) Sun MK, Regunathan S, Reis DJ. Cardiovascular responses to agmatine, a clonidine-displacing substance, in anesthetized rat. Clin Exp Hypertens. (1995)
26) Uzbay IT, et al. Effects of agmatine on ethanol withdrawal syndrome in rats. Behav Brain Res. (2000)
27) Taksande BG, et al. Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats. Eur J Pharmacol. (2010)
28) Wang CC, et al. Beneficial effect of agmatine on brain apoptosis, astrogliosis, and edema after rat transient cerebral ischemia. BMC Pharmacol. (2010)
29) Agmatine reduced the expressions of nitric oxide synthase and peroxynitrite formation in rat cerebral cortex after transient global cerebral ischemia
30) Kim JH, et al. Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia. J Cereb Blood Flow Metab. (2010)
31) Lee WT, et al. Neuroprotective effects of agmatine on oxygen-glucose deprived primary-cultured astrocytes and nuclear translocation of nuclear factor-kappa B. Brain Res. (2009)
32) Kim JH, et al. Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia-like injury. Exp Neurol. (2004)
33) Feng Y, Piletz JE, Leblanc MH. Agmatine suppresses nitric oxide production and attenuates hypoxic-ischemic brain injury in neonatal rats. Pediatr Res. (2002)
34) Prasad A, Prasad C. Agmatine enhances caloric intake and dietary carbohydrate preference in satiated rats. Physiol Behav. (1996)
35) Taksande BG, et al. Agmatine in the hypothalamic paraventricular nucleus stimulates feeding in rats: involvement of neuropeptide Y. Br J Pharmacol. (2011)
36) Steer H. The source of carbon dioxide for gastric acid production. Anat Rec (Hoboken). (2009)
37) Keynan O, et al. 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)
38) Kalra SP, et al. Agmatine, a novel hypothalamic amine, stimulates pituitary luteinizing hormone release in vivo and hypothalamic luteinizing hormone-releasing hormone release in vitro. Neurosci Lett. (1995)
Research into agmatine reveals a potential to improve the symptoms related to neuropathic pain, and the ability to assist with the treatment of drug addiction. Agmatine also helps to govern nitric oxide (NO) synthesis, as well as working to properly regulate cellular energy by overseeing polyamine metabolic function. This makes agmatine sulfate a popular pump-inducing supplement choice.
In the muscle building and sports performance realm, agmatine works to provide the following potential benefits:
- Improved muscle pumps via the inhibition of nitric oxide synthase (NOS).
- Better intra-workout energy.
- In the role of a nootropic, aiding with mental clarity (focus), stress management and mental health.
- Helps to promote healthy insulin sensitivity, promoting leanness and muscle building.
- Increases appetite even when full, making it easier for underweight individuals to gain weight and muscle.
"Agmatine...shows promise for alleviating neuropathic pain and drug addiction. Agmatine supplementation can also protect from strokes and benefit cognitive health." - Examine.com
Agmatine Recommended Dosages and Use
Taken daily, a reasonable and effective dosage of agmatine recommend for improvement of mental function would be between 1.6 and 6.4 mg per kilogram of bodyweight. [1] This would equate to:- 120 lbs - 87 to 349 mg per day
- 140 lbs - 102 to 407 mg per day
- 160 lbs - 116 to 465 mg per day
- 180 lbs - 131 to 523 mg per day
- 200 lbs - 145 to 581 mg per day
- 220 lbs - 160 to 640 mg per day
- 240 lbs - 175 to 698 mg per day
Agmatine is typically listed on supplement labels as agmatine sulfate. Dosages range between 250 mg to 1,000 mg per scoop, with intake recommendations hovering between 1 to 2 grams per day. It should be noted that these products are usually focused on pump inducement and the muscle building process, so daily dosage recommendations may vary slightly compared to nootropic recommendations for mental clarity, stress reduction, etc.
Here are some packaging directions from one popular agmatine sulfate product:
- Core Nutritionals Agmatine Sulfate - Take 1-3 scoops (500-1500 mg) per day with food. For best results, take 30-60 minutes before your workout.
So to recap, when used as a muscle pump-inducer, 500 to 1,000 mgs of agmatine sulfate should be taken 20-30 minutes prior to training. An optional 500 to 1,000 mgs may also be taken during training. Agmatine can be taken at any convenient time on non-training days.
A Deeper Look at Agmatine Benefits
It bears repeating agmatine provides a strong dual-pronged attack. Not only does it function as a nootropic, working to improve mental clarity, lower stress levels, and increase focus and well-being, but it also assists with muscle pumps and insulin regulation which can only aid the muscle building process.This section will look at the major potential benefits of agmatine supplementation.
Agmatine and Pain Reduction
Agmatine has the potential to provide short-term pain relief, but only in regards to thermal hyperalgesia. [2] Agmatine does appear to provide a dose-dependent reduction in inflammation and neuropathic pain. [3][4] Agmatine supplementation also shows a statistically significant potential to reduce perceived pain. [5]
Benefit - Potential for improved quality of training, better focus, and a reduction in perceived pain, including pain derived from inflammation.
Agmatine, Blood Glucose and Insulin
Agmatine has been shown to activate imidazoline receptors. This activation assists in the reduction of blood glucose levels, which in turn appears to be associated with increases in endorphin. [6][7] Endorphin is able to increase glucose uptake into muscle tissue, even during periods of inactivity. [8][9] Another study has shown that endorphin works to help the pancreas secrete insulin. [10]Benefit - An increase in insulin response lends itself to a leaner, more muscular physique.
Agmatine, Stress, Anxiety and Cortisol
It appears that agmatine supplementation may help combat the negative impact of stress. [11] The body increases production of agmatine during periods of increased stress, seemingly as a protection measure. Agmatine also plays a vital role in the brain's ability to cope with stress, working to reduce anxiety. [12][13] Lowering stress helps to regulate bodily cortisol levels, working to improve health in a myriad of ways. [14]Benefit - Improved focus, better overall health and sense of well-being, and a more relaxed state.
Agmatine and Depression
Agmatine appears to have antidepressant qualities. Moderate dosages, though slightly less potent that depression drugs such as Tofranil (imipramine), show a promising ability to improve mood and reduce anxiety. [15][16][17] Agmatine also shows the ability to compliment usage of anti-depression drugs such as Wellbutrin (bupropion). [18][19]Benefit - Potential for improved state of well-being and lower anxiety levels. This can also assist with maintaining the motivation to pursue better health and fitness.
Agmatine, Nitric Oxide Modulation & Muscle Pumps
Agmatine has been noted to play a role in positively regulating NOS (nitric oxide synthase), the enzyme behind the production of nitric oxide. [20][21] This increase in nitric oxide activity improves vasodilation, which improves muscle pumps. Muscle pumps not only increase nutrient delivery to muscle tissue, but also impact protein synthesis rates allowing for a potential increase in the rate of muscle tissue growth. [22]Benefit - Agmatine can improve vasodilation, leading to improved nutrient delivery to muscle cells, and an increase in muscle protein synthesis rates which impact the muscle building process.
"In summary, the results of our study demonstrate that net protein synthesis during amino acid administration can be doubled by previous performance of heavy resistance exercise. Moreover, the data suggest a link between the stimulation of protein synthesis after exercise and an acceleration in amino acid transport. The greater rate of transport after exercise may be due to the increase in blood flow." [22]
Agmatine and Blood Pressure
Agmatine has the potential to create an anti-hypertensive environment, assisting the body in maintaining a healthier blood pressure level. [23][24][25]
Agmatine and Blood PressureBenefit - A healthier blood pressure allows for improved nutrient delivery, improving overall health and lending itself to a more optimal muscle building/recovery process.
Agmatine and Strokes
Agmatine shows promise as a stroke-related neuroprotector when used during pretreatment. [28][29][30][31][32][33] Simply stated, individuals who feel they are at risk of a stroke may benefit from agmatine supplementation if/when a stroke does occur.Benefit - Agmatine supplementation has the potential to reduce neuro-damage caused by a stroke.
Agmatine and Improved Appetite
Agmatine has been show to improve appetite after reaching the point of satiety. [34] During some studies, food consumption was increased by rates upwards of 44 to 54% over a 24 hour period. [35] Agmatine works in an opposite manner compared to yohimbine, which has been shown to suppress the appetite.Benefit - Hardgainers, or individuals who have a more difficult time gaining weight, may benefit from agmatine supplementation. They are likely to eat more, even when full.
Agmatine and Luteinizing Hormone
Agmatine supplementation may lead to the increased secretion of luteinizing hormone, though this effect appears to be dose dependent. [38] Luteinizing hormone plays a vital role in male testosterone production.Benefit - Bolstered testosterone production yields a myriad of health benefits, including the ability to impact muscle tissue growth and maintenance.
Agmatine supplementation may lead to the increased secretion of luteinizing hormone. Luteinizing hormone plays a vital role in male testosterone production.
Agmatine Side Effects
The following side effects have been associated with agmatine supplementation.- Increased appetite. Increased appetite, even when full. This makes agmatine a better overall choice when bulking or trying to gain weight, and a supplement that could potentially increase appetite during fat loss diets.
- Minor potential for gastrointestinal discomfort. Though agmatine has been shown to bolster gastrointestinal health [36], a very small percentage of individuals may experience minor gastrointestinal discomfort and nausea when supplementing on a daily basis. [37] It should be noted these side effects were noted on individuals supplementing with 3.5 grams of agmatine per day, over the course of a 3 week period.
- Limited testing at high dosages. There is limited research studying agmatine dosages above 2,600 mg per day. Though all indications hint that agmatine is rather non-toxic, there is little reason to take dosages higher than this. Most scientifically-backed benefits are derived from dosages ranging between 500 to 2,600 mg per day.
- Lowering of blood pressure. Because agmatine can exert a widening of blood vessels, which is a desirable benefit for most individuals, the resulting potential for a minor blood pressure drop may be undesirable for persons who are currently being treated for low blood pressure (hypotension).
Agmatine Frequently Asked Questions
Is agmatine found in any common foods?
Because it is a bacterial byproduct, agmatine can be found in fermented foods such as wine, beer and even instant coffee. These concentrations are extremely minimal; significantly lower than the amounts found in agmatine supplements.
Is arginine the same as agmatine?
No. Agmatine is a derivative of l-arginine (a conditionally essential amino acid), but they do not share the exact same researched benefits. Though arginine is required by the body and supports many important functions, supplementing with arginine will not provide the same benefits as supplementing with agmatine.Arginine has the ability to convert directly into nitric oxide, but agmatine does not. Despite this difference, agmatine still has the ability to positively impact muscle pumps via other physiological mechanisms.
How much agmatine can you take per day?
While research reveals that agmatine is quite non-toxic, limited studies have been performed on humans using dosages above 2.6 grams per day. For this reason it's recommended that you avoid super-loading.Can agmatine help with alcohol withdrawal?
Agmatine supplementation appears to attenuate symptoms related to withdrawal from alcohol, including anxiety and shakes. [26][27]Are there any supplements agmatine shouldn't be combined with?
There is research indicating that l-arginine, l-citrulline, yohimbine, D-aspartic acid and creatine may hinder agmatine absorption or effectiveness. For this reason it's recommend that you avoid taking agmatine at the same time as these other supplements.Can you stack agmatine with any other supplements to increase benefits?
It may be beneficial to stack agmatine with a growth hormone supplement to provide improved ergogenic enhancement in the form of better recovery, performance or stamina. Agmatine can also be taken with carbohydrates to help provide a glycogen resynthesis boost.
References
1) https://examine.com/supplements/Agmatine/2) Roberts JC, et al. Pharmacodynamic and pharmacokinetic studies of agmatine after spinal administration in the mouse. J Pharmacol Exp Ther. (2005)
3) Fairbanks CA, et al. Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury. Proc Natl Acad Sci U S A. (2000)
4) Su RB, Li J, Qin BY. A biphasic opioid function modulator: agmatine. Acta Pharmacol Sin. (2003)
5) Keynan O, et al. 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)
6) Chang CH, et al. Increase of beta-endorphin secretion by agmatine is induced by activation of imidazoline I(2A) receptors in adrenal gland of rats. Neurosci Lett. (2010)
7) Hwang SL, et al. Activation of imidazoline receptors in adrenal gland to lower plasma glucose in streptozotocin-induced diabetic rats. Diabetologia. (2005)
8) Khan S, et al. Beta-endorphin decreases fatigue and increases glucose uptake independently in normal and dystrophic mice. Muscle Nerve. (2005)
9) Cheng JT, et al. Plasma glucose-lowering effect of beta-endorphin in streptozotocin-induced diabetic rats. Horm Metab Res. (2002)
10) Curry DL, Bennett LL, Li CH. Stimulation of insulin secretion by beta-endorphins (1-27 & 1-31). Life Sci. (1987)
11) Aricioglu F, Regunathan S, Piletz JE. Is agmatine an endogenous factor against stress. Ann N Y Acad Sci. (2003)
12) Taksande BG, et al. Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats. Eur J Pharmacol. (2010)
13) Gong ZH, et al. Anxiolytic effect of agmatine in rats and mice. Eur J Pharmacol. (2006)
14) Cortisol: Why ?The Stress Hormone? Is Public Enemy No. 1 | Psychology Today. (n.d.). Retrieved from https://www.psychologytoday.com/blog/the-athletes-way/201301/cortisol-why-the-stress-hormone-is-public-enemy-no-1
15) Krass M, et al. Antidepressant-like effect of agmatine is not mediated by serotonin. Behav Brain Res. (2008)
16) Aricioglu F, Altunbas H. Is agmatine an endogenous anxiolytic/antidepressant agent. Ann N Y Acad Sci. (2003)
17) Li YF, et al. Antidepressant-like effect of agmatine and its possible mechanism. Eur J Pharmacol. (2003)
18) Kotagale NR, et al. Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test. Pharmacol Biochem Behav. (2013)
19) Zomkowski AD, et al. Agmatine produces antidepressant-like effects in two models of depression in mice. Neuroreport. (2002)
20) Joshi MS, et al. Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells. Proc Natl Acad Sci U S A. (2007)
21) Haulic? I, et al. Preliminary research on possible relationship of NO with agmatine at the vascular level. Rom J Physiol. (1999)
22) Biolo, G. An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein, Am. J. Physiol. 273 (Endocrinol. Metab. 36): El22-E129, 1997
23) Raasch W, et al. Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine-mediated blood pressure reaction. Br J Pharmacol. (2002)
24) Schäfer U, et al. Effects of agmatine on the cardiovascular system of spontaneously hypertensive rats. Ann N Y Acad Sci. (1999)
25) Sun MK, Regunathan S, Reis DJ. Cardiovascular responses to agmatine, a clonidine-displacing substance, in anesthetized rat. Clin Exp Hypertens. (1995)
26) Uzbay IT, et al. Effects of agmatine on ethanol withdrawal syndrome in rats. Behav Brain Res. (2000)
27) Taksande BG, et al. Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats. Eur J Pharmacol. (2010)
28) Wang CC, et al. Beneficial effect of agmatine on brain apoptosis, astrogliosis, and edema after rat transient cerebral ischemia. BMC Pharmacol. (2010)
29) Agmatine reduced the expressions of nitric oxide synthase and peroxynitrite formation in rat cerebral cortex after transient global cerebral ischemia
30) Kim JH, et al. Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia. J Cereb Blood Flow Metab. (2010)
31) Lee WT, et al. Neuroprotective effects of agmatine on oxygen-glucose deprived primary-cultured astrocytes and nuclear translocation of nuclear factor-kappa B. Brain Res. (2009)
32) Kim JH, et al. Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia-like injury. Exp Neurol. (2004)
33) Feng Y, Piletz JE, Leblanc MH. Agmatine suppresses nitric oxide production and attenuates hypoxic-ischemic brain injury in neonatal rats. Pediatr Res. (2002)
34) Prasad A, Prasad C. Agmatine enhances caloric intake and dietary carbohydrate preference in satiated rats. Physiol Behav. (1996)
35) Taksande BG, et al. Agmatine in the hypothalamic paraventricular nucleus stimulates feeding in rats: involvement of neuropeptide Y. Br J Pharmacol. (2011)
36) Steer H. The source of carbon dioxide for gastric acid production. Anat Rec (Hoboken). (2009)
37) Keynan O, et al. 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)
38) Kalra SP, et al. Agmatine, a novel hypothalamic amine, stimulates pituitary luteinizing hormone release in vivo and hypothalamic luteinizing hormone-releasing hormone release in vitro. Neurosci Lett. (1995)