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AGMATINE

Agmatine Sulfate
Summary: Agmatine is an amino acid that o ers a wide of cognitive boosting bene ts. It also has excellent e ects 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.

Table of Contents

1 Introduction
1.1 What is Agmatine?
2 Bene ts & E ects
2.1 Reduces Pain Sensitivity
2.2 Reduces Symptoms of Anxiety & Depression
2.2.1 Studies & Research
2.3 Neuroprotection & Longevity
2.3.1 A Study on E ects of Agmatine Sulfate on Nerve Injury:
2.4 Improves Weight Loss & Prevents Weight Gain
2.5 Supports Muscle Growth
2.6 Helps Erectile Dysfunction & Infertility
2.7 Help’s with Alzheimer’s Disease
2.8 Helps Alcohol & Morphine Withdrawal
3 Mechanism of Action
4 Dosage
4.1 How To Take Agmatine?
5 Side E ects
6 User Experience
7 Frequently Asked Questions
8 Further External Readings

Introduction

What is Agmatine?
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 a ecting 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 e ects 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, co ee, and other fermented foods.

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 [R ] [R ].

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. [R ]Self Hacked

Bene ts & E ects

Agmatine bene ts the body and mind in many di erent 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 e ective 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 e ect.

In studies looking at pain reduction in neuropathic conditions or in ammatory pain, agmatine was not found to produce a statistically signi cant
e ect. 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 e ects 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 & Research
A small pilot study on three patients su ering 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 & 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 e ects 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:
OBJECTIVE:
Evaluate the e ect 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 di erence 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 & 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 e ective
shuttling of amino acids as well as glucose into the tissues for growth and repair. [R ] [R ]

Helps Erectile Dysfunction & Infertility

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’s 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 ]

Mechanism of Action
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:

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 di erential inhibition and activation of NO synthase (NOS) isoforms is reported.

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

Dosage

How To Take Agmatine?

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:

• For treatment of neuropathic pain: 1,000 to 2,500 mg of agmatine (daily)

• For improving cognitive function: 200 to 500 mg of agmatine (daily)

• 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

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 e ects.

Side E ects
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 e ects 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 e ects is very low.

Minor side e ects included nausea, diarrhea, and vomiting in a small percentage of participants, which cleared up after a few days of discontinuing
use. [R ]

User Experience
 Not only does it have varied anti-addiction properties to Opioids, amphetamines, ca eine, nicotine & alcohol, but it also seems to
make other drugs, and medicines more potent in their e ects. It also shares the properties of Ketamine’s antidepressant e ects, via
the mTOR AMPA pathway. A small study found a robust antidepressant e ect; all patients reported remission of depression.
Considering that, shutting down Serotonin production via parachlorophenylalanine, did not reverse the antidepressant e ects, 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

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 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 e ects. [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 e ects.

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 e ects. You take nitric oxide to improve the creatine e ects.

Further External Readings

Agmatine – Wikipedia

Agmatine – Scienti c Review – Examine

Last Updated on: February 3, 2019 by Nootropics Information