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Agmatine

Agmatine is a metabolite of L-Arginine. It shows promise for alleviating neuropathic pain and drug addiction and shows some potential in protecting against strokes and benefitting cognitive health.

Our evidence-based analysis on agmatine features 352 unique references to scientific papers.

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Summary of Agmatine

Primary information, health benefits, side effects, usage, and other important details

Agmatine is derived from L-arginine through decarboxylation (the removal of a carboxylic acid group). It is stored in neurons and is released during neuronal activation. Agmatine is considered to be a neurotransmitter and neuromodulator.

Preliminary research suggests agmatine has potential use in the treatment of neuropathic pain and drug addiction. It also protects the brain from toxins and strokes.

Though supplementing agmatine by itself can increase the perception of pain, it works synergistically with painkillers like morphine and fentanyl. Agmatine’s synergy with opioids allows it to reduce pain killer tolerance, the possibility of addiction, and pain itself.

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 certain serotonin receptors as well. Further research is needed to determine the full extent of agmatine’s mechanisms.

There is a lot of animal evidence to suggest agmatine is a highly promising research chemical. It is not a common supplement because there is a lack of human evidence for its effects. Several studies have been done on people, but the majority use agmatine injections, not oral ingestion. Research must establish that agmatine’s effects will work following oral ingestion in order for wide-scale supplementation to be considered.

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How to Take

Medical Disclaimer

Recommended dosage, active amounts, other details

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 109-435mg 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 benefits as were observed in animal studies.

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Human Effect Matrix

Unlocked for Examine Plus members

The Human Effect Matrix summarizes human studies to tell you what effects Agmatine has on your body, how much evidence there is, and how strong these effects are.

Full details are available to Examine Plus members.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-c Notable - See study
In the trial on lumbar disc-associated radiculopathy, the degree of pain alleviation was fairly notable relative to placebo and persisted for two months after supplementation was ceased. No reference drug comparisons, unfortunately
grade-d Strong - See study
One very preliminary study exists, but remission was achieved in all three subjects with 2-3g agmatine.
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Things to Note

Primary Function:

Also Known As

Clonidine-displacing substance, 4-(aminobutyl)guanidine, Decarboxylated arginine

Do Not Confuse With

L-Arginine (parent structure)

Goes Well With

  • Bupropion (pharmaceutical antidepressant; agmatine augments its efficacy)

  • Opioidergic pain killers (such as morphine)

  • Cannabinoids (such as marijuana) as agmatine enhances signalling through the cannabinoid (CB1) receptor

  • Alcohol withdrawal (appears to reduce symptoms)

  • Although at this moment in time agmatine appears to be pretty nontoxic, there is insufficient toxicology testing for superloading. It may be prudent to stick within the 2,670mg dosage that has been used in humans

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Click here to see all 352 references.