Nootropic Review of Agmatine Sulfate. Uses, Benefits, Effects, Mechanism of Action, Side Effects, Dosage, User Experiences, and FAQs.

1. Agmatine Sulfate
Overview – Bene ts and Effects – Mechanisms of Action – Dosage – Side Effects – User Experience – FAQs
Summary: Agmatine is an amino acid that offers a wide of cognitive boosting bene ts. It also has excellent
effects on reducing neuropathic pain, as well as drug addiction habits. It is neuroprotectant and can reduce
tolerance built to many medications like benzodiazepines, morphine, and other painkillers. It also synergizes
with SSRI’s & cannabis.
Content
1 Overview
1.1 What is Agmatine Sulfate?
2 Bene ts and Effects
2.1 What Are the Bene ts of Agmatine Sulfate?
2.1.1 Reduces Pain Sensitivity
2.1.2 Reduces Symptoms of Anxiety & Depression
2.1.2.1 Studies and Research
2.1.3 Neuroprotection and Longevity
2.1.3.1 A Study on Effects of Agmatine Sulfate on Nerve Injury:
2.1.4 Improves Weight Loss and Prevents Weight Gain
2.1.5 Supports Muscle Growth
2.1.6 Helps Erectile Dysfunction and Infertility
2.1.7 Help with Alzheimer’s Disease
2.1.8 Helps Alcohol & Morphine Withdrawal
3 Mechanisms of Action
3.1 How Does Agmatine Sulfate Work?
4 Dosage
4.1 How to Take Agmatine Sulfate?
5 Side Effects
5.1 What Are the Side Effects of Agmatine Sulfate?
6 User Experiences
6.1 Reddit Review

2. 7 Frequently Asked Questions
7.1 Further and Related Readings
Agmatine Sulfate Youtube Video TTS
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Overview
What is Agmatine Sulfate?
Agmatine is a form of amino acid that derives from L-Arginine. It has been shown to inhibit receptors for the
neurotransmitter acetylcholine, which plays a major role in memory and reasoning.
Agmatine supplement also regulates levels of Nitric Oxide by the affecting nitric oxide synthase enzyme. It
controls cellular energy levels by in uencing polyamine metabolism and function.
In some studies, it has been shown to enhance the effects of both morphine and fentanyl to increase pain
killing, reduce tolerance, and lower addiction, as well as working synergistically with marijuana.
It is also found naturally in every day foods, including beer, wine, coffee, and other fermented foods.

3. Because it is capable of targeting multiple receptors, agmatine may bene t a spectrum of complex diseases,
including diabetes, Alzheimer’s disease, opioid addiction, mood disorders, and even cancer. Furthermore,
agmatine may enhance cognitive function, stress resiliency, mood, and athletic performance. The highest
levels of agmatine are found in the gut, where it is produced by the microbes living there. It is also found in
dietary form, mainly in fermented foods, and in supplemental form like agmatine sulfate. Agmatine is also
produced in small amounts within the body by the mitochondria in the liver.
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Bene ts and E ects
What Are the Bene ts of Agmatine Sulfate?
1. Reduces Pain Sensitivity
2. Reduces Symptoms of Anxiety & Depression
3. Neuroprotection & Longevity
4. Improves Weight Loss & Prevents Weight Gain
5. Supports Muscle Growth
6. Helps Erectile Dysfunction & Infertility
7. Help with Alzheimer’s Disease
8. Helps Alcohol & Morphine Withdrawal
Supporting research:
Agmatine sulfate bene ts the body and mind in many different ways and depending on the method it is
taken. Some of the most notable agmatine bene ts are:
Reduces Pain Sensitivity
In research studies, Agmatine shows to be an effective way for pain relief. Especially in the case of thermal
hyperalgesia, a condition where the body is sensitive to changes in temperatures. The body becomes
hypersensitive to heat or cold.
Agmatine improves those pain sensations, which is a result of its pro-circulations effect.

4. In studies looking at pain reduction in neuropathic conditions or in ammatory pain, agmatine was not found
to produce a statistically signi cant effect. However, anecdotal, rst-hand reports show that it actually did
work for neuropathic conditions. So in this speci c situation, it seems to be subjective to each individual.
Reduces Symptoms of Anxiety & Depression
Agmatine exhibits antidepressant effects and promotes mood improvement as well as anxiety reduction and
relief. It helps the brain and body manage and overcome stress by reducing anxiety and promoting a sense of
well-being.
By increasing NRF2, agmatine prevents depressive behavior by protecting brain cells from high levels of
stress hormone cortisol. [R]
Agmatine increases adenylate cyclase in the prefrontal cortex, and decreases levels of adenylate cyclase
which associate with depression. [R, R].
Furthermore, it blocks the NMDA receptor, prevents calcium overloading, as well as reverses the decrease of
monoamines such as norepinephrine, epinephrine, and dopamine. Depression often associates with a
reduction of monoamines in the brain [R, R]
Studies and Research
A small pilot study on three patients suffering depression, Agmatine supplement caused a complete
disappearance of depression symptoms in all patients. It most likely did so through NMDA receptor-blocking
and not through serotonin pathways. [R]
Agmatine also reduced anxiety in rats when they were put in swimming and maze navigation tests. [R]
Neuroprotection and Longevity
Agmatine acts as an anti-oxidant and is continuously under more research for its anti-aging and longevity
potential. It has been found to exhibit neuroprotective effects against oxidative damage and injuries to the
Central Nervous System (CNS). It is also believed to limit the activity of glutamate receptors and thus, the
over-excitation of neurons within the brain.
Additionally, by inhibiting iNOS and nNOS and increasing eNOS, Agmatine protects against brain damage
from stroke. Increasing eNOS protects the brain by dilating the blood vessels to increase blood ow. This
prevents damage during times of lack of oxygen from reduced blood ow to the brain (also known as
ischemic stroke).
Agmatine decreases iNOS and nNOS, two enzymes that contribute to brain damage from stroke. [R]
A Study on E ects of Agmatine Sulfate on Nerve Injury:

5. OBJECTIVE:
Evaluate the effect of agmatine sulphate on facial nerve regeneration after facial nerve injury using
electron and light microscopy.
METHODS:
The study was performed on 30 male Wistar albino rats split into: a control group, a sham-treated group, a
study control group, an anastomosis group, and an anastomosis plus agmatine sulphate treatment group.
The mandibular branch of the facial nerve was dissected, and a piece was removed for histological and
electron microscopic examination.
RESULTS:
Regeneration was better in the anastomosis group than in the study control group. However, the best
regeneration ndings were seen in the agmatine sulphate treatment group. There was a signi cant
difference between the agmatine group and the others in terms of median axon numbers (p < 0.004) and
diameters (p < 0.004).
CONCLUSION:
Agmatine sulphate treatment with anastomosis in traumatic facial paralysis may enhance nerve
regeneration. PMID: 28122652
Improves Weight Loss and Prevents Weight Gain
Individuals who struggle to gain weight can bene t from Agmatine supplements. In some studies, subjects
increased food consumption rates by 44% to 54% in 24 hours.
Moreover, in the following studies, Agmatine shows an increase in fat burning, a decrease in fat composition,
and an increase in muscle mass [R], which also contributes to the next bene t of Agmatine:
Supports Muscle Growth
Agmatine stimulates the production of luteinizing hormone (LH). Increasing these hormone levels lead to an
increase in testosterone levels.
By increasing testosterone levels, Agmatine contributes to an optimal hormonal environment for muscle
growth, enhances athletic performance, and fastens recovery. [R]
Agmatine also increases insulin sensitivity and the uptake of glucose into the muscle. Increasing insulin
sensitivity results in more effective shuttling of amino acids as well as glucose into the tissues for growth
and repair. [R] [R]
Helps Erectile Dysfunction and Infertility

6. Studies show that L-arginine is involved in the process of cell replication, in addition to enhancing blood
circulation, so it can help improve both sperm production and motility.
Men dealing with cardiovascular issues due to low levels of NO in the blood are more prone to experience
erectile dysfunction and fertility problems because an erection requires a relaxation of smooth muscles,
which Nitric Oxide triggers.
Although it doesn’t apply to every person, a signi cant rate of male infertility cases (92%) is treatable with L-
arginine supplements in combination with dilators, antioxidants and/or anti-in ammatories. [R]
Research suggests that high-stress levels lower L-arginine levels in the sperm production pathway. Therefore,
men with chronic stress speci cally can bene t from Agmatine supplement.
According to Dr. Axe, a combination of L-arginine, L-glutamate and yohimbine hydrochloride is a common
way of treating erectile dysfunction. And it works better than L-arginine alone. [R]
“In fact,” he says, “many of the most frequently prescribed medications for ED work similarly to L-arginine: by
increasing nitric oxide production.”
Furthermore, there’s research suggesting treatment with N-Acetyl Cysteine (NAC) and L-arginine together can
help balance hormones naturally and restore normal sexual function in women with polycystic ovary
syndrome and estrogen imbalances.
Other studies suggest that L-arginine with herbs such as chasteberry, green tea extract, and antioxidant
supplements improve pregnancy rates in women struggling to conceive. [R]
Help with Alzheimer’s Disease
Insulin resistance could cause an increase of plaque and neuro brillary tangles in the brain, which are the
signs of Alzheimer’s disease. Agmatine prevents cognitive decline by rescuing insulin signaling and avoiding
potential accumulation of those tangles. [R]
Helps Alcohol & Morphine Withdrawal
Agmatine reduces and to an extent, prevents, symptoms of alcohol withdrawal such as “wet dog shakes,”
anxiety, ashes, and shakings. [R] [R]
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Mechanisms of Action
How Does Agmatine Sulfate Work?

7. 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 speci c
serotonin receptors as well. Further research is needed to determine the full extent of agmatine mechanisms.
[R]
Agmatine was found to exert modulatory actions directly and indirectly at multiple key molecular targets
underlying cellular control mechanisms of cardinal importance in health and disease. It is considered capable
of exerting its modulatory actions simultaneously at multiple targets. The following outline indicates the
categories of control mechanisms and identi es their molecular targets:
Agmatine Sulfate Skeletal Structure
Neurotransmitter receptors and receptor ionophores. Nicotinic, imidazoline I1 and I2, α2-adrenergic, glutamate
NMDAr, and serotonin 5-HT2A and 5HT-3 receptors. Ion channels. Including: ATP-sensitive K+ channels,
voltage-gated Ca2+ channels, and acid-sensing ion channels (ASICs).
Membrane transporters. Agmatine speci c-selective uptake sites, organic cation transporters (mostly OCT2
subtype), extraneuronal monoamine transporters (ENT), polyamine transporters, and mitochondrial agmatine
speci c-selective transport system. Nitric oxide (NO) synthesis modulation. Both differential inhibition and
activation of NO synthase (NOS) isoforms is reported.

8. Polyamine metabolism. Agmatine is a precursor for polyamine synthesis, competitive inhibitor of polyamine
transport, inducer of spermidine/spermine acetyltransferase (SSAT), and inducer of antizyme. Protein ADP-
ribosylation. Inhibition of protein arginine ADP-ribosylation. Matrix metalloproteinases (MMPs). Indirect down-
regulation of the enzymes MMP 2 and 9. Advanced glycation end product (AGE) formation. Direct blockade of
AGEs formation. NADPH oxidase. Activation of the enzyme leading to H2O2 production. Wikipedia
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Dosage
How to Take Agmatine Sulfate?
There is currently no standard dosage for agmatine sulfate because there haven’t been enough human
studies for determination. These numbers are rough estimates to give an idea of typical, experimental dosing:
1. For treatment of neuropathic pain: 1,000 to 2,500 mg of agmatine (daily)
2. For improving cognitive function: 200 to 500 mg of agmatine (daily)
3. For vasodilation and enhanced recovery: 500 to 1000 mg of agmatine (30 minutes pre-workout)
Note: Agmatine is not absorbed well when taken with dietary protein, because it uses the same transporters
as arginine
Quoting Examine:
“There are no standard dosages for agmatine because of 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 217-435 mg 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
bene ts as were observed in animal studies.”
“The generally accepted daily dosage range for Agmatine Sulfate is between 250 mg and 2.5 grams. Avoid
taking higher than necessary dosages to reduce the risk of side effects.”
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9. Side E ects
What Are the Side E ects of Agmatine Sulfate?
According to studies conducted so far, it appears that Agmatine Sulfate is safe even in relatively high doses.
While there have been few studies conducted thus far, they have not shown any side effects to be associated
with this supplement.
If you follow the recommended Agmatine sulfate dosage protocol and do not have any pre-existing
contraindications for use, the risk of serious adverse effects is very low. Minor side effects included nausea,
diarrhea, and vomiting in a small percentage of participants, which cleared up after a few days of
discontinuing use. [R]
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User Experiences
Reddit Review
“Not only does it have varied anti-addiction properties to Opioids, amphetamines, caffeine, nicotine & alcohol,
but it also seems to make other drugs, and medicines more potent in their effects. It also shares the properties
of Ketamine’s antidepressant effects, via the mTOR AMPA pathway. A small study found a robust
antidepressant effect; all patients reported remission of depression. Considering that, shutting down
Serotonin production via parachlorophenylalanine, did not reverse the antidepressant effects, shows how
punchy this substance is. It’s also a painkiller. I’d recommend this be added to everyone’s stack, provided they
aren’t too fond of Alcohol, as I noticed it de nitely seems to blunt the good feelings of certain drugs.” Reddit
user
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Frequently Asked Questions
What is Agmatine Sulfate?
Agmatine Sulfate is a biogenic amine that is derived from the amino acid L-Arginine. This happens by a
process called decarboxylation, which is better known as the removal of carboxylic acid group from the
amino acid.
Is Agmatine safe?
Yes. And here is a 5 year-long, daily high dosage of Agmatine in order to measure and proof its safety: Clinical
follow-up consists of periodic physical examinations and laboratory blood and urine analyses. All
measurements thus far remain within normal values and good general health status is sustained throughout

10. the study period, up to 5 years. This case study shows for the rst time that the recommended high dosage of
agmatine may be consumed for at least 5 years without evidence of any adverse effects. [R]
How long does Agmatine take to work?
Agmatine starts working as soon as it enters the bloodstream, which is typically 15 – 30 minutes after
consumption. Users can expect to experience an increase in muscle pumps, vascularity and muscular
endurance within this timeframe. [R]
How much Agmatine should I take?
The generally accepted daily dosage range for Agmatine Sulfate is between 250 mg and 2.5 grams. Avoid
taking higher than necessary dosages to reduce the risk of side effects.
Can you take Agmatine with creatine?
This is the reason creatine and protein work so well together, in a nutshell. Bodybuilders can cut out the
creatine middle man by supplementing with agmatine sulfate directly. … You take creatine to improve the
protein effects. You take nitric oxide to improve the creatine effects.
Further and Related Readings
1. Agmatine – Wikipedia
2. Agmatine – Scienti c Review – Examine
3. Nootropics FAQs
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