Agmatine – A small Molecule with Big potential

Agmatine ? A few years ago, sometime around 2010-2011, a new substance appeared on the dietary supplement market that not much was known about, but about which manufacturers were making serious claims.

A few years later, this substance is gaining a foothold in the supplement market, being sold as a standalone product, and being included in a great deal of pre-workout products.

We are talking about the substance agmatine and in this material we will pay a little more attention to it.

What is Agmatine (Agmatine)?

There are various definitions behind agmatine. It can also be found under its molecular name 4-(aminobutyl)guanidine.

It is a well-known substance to our body as it occurs naturally in various parts of our body, even in some food products.

It is a biogenic amine, an organic compound that is most commonly produced by the decarboxylation of certain amino acids.

In the case of agmatine, it is produced by the decarboxylation of the amino acid L-Arginine.

Agmatine is also considered a neurotransmitter and neuromodulator, as it is stored in neurons and released upon their activation.

Studies in rats show that agmatine is most highly concentrated in the stomach, small intestine, thyroid gland, and some parts of the brain.

Agmatine is also found in some foods, those with the most noticeable concentrations being wine (white and red), beer, sake, instant coffee, local produce, and fish.

Before you run out to the store and buy many of the products in question, we should clarify that while these foods are the richest in agmatine, the concentration in them is too low to be of practical importance.

What role does it play and what is its mechanism of action?

This is where the main problem with agmatine comes in. As this molecule has only started to receive attention since 1994 and especially in the last few years, its importance for the human organism and its mechanisms of action are not well understood.

Research to date has been conducted mostly in animals (rats and mice) and in vitro. Human studies are few and far between.

However, several mechanisms of action stand out.

One is by blocking NMDA receptors and activating imidazoline receptors. It also affects serotonin receptors .

Agmatine has the ability to block NOS (nitric oxide synthase) enzymes, which regulates nitric oxide levels in the blood.

Proven and potential benefits

The above-mentioned mechanisms of action, as well as some others less well studied, make agmatine potentially important in various areas of the human body and human health.

Regulate and reduce blood pressure

Agmatine has the ability to bind to imidazoline receptors.

These receptors are of three types, each with distinctive tasks:

  • mediate the actions needed to reduce blood pressure
  • important for the action and binding of the enzyme monoamine oxidase (MAO)
  • regulate insulin secretion by pancreatic beta cells

That it is an agonist at these receptors makes it important in regulating and reducing blood pressure.

Agmatine’s ability to increase nitric oxide levels contributes to the dilation and relaxation of blood vessels, again aiding in the reduction of blood pressure and circulation.

At this stage, blood pressure reduction has been demonstrated by injecting agmatine into rats with high blood pressure

Reducing the sensation of pain

Agmatine also has a good analgesic effect in certain pain-inducing conditions.

Tests in neuropathic pain and pain due to inflammation in rats have shown that agmatine successfully reduces the sensation of pain. 13,14

One study on humans with lumbar disc radiculopathy was also conducted on the analgesic effect of agmatine. 15

The study conducted included two groups:

  • placebo group of 48 people
  • a group of 51 people who took 2,670 g of agmatine sulfate daily for 14 days.

Scores are determined according to the VAS scale, the McGill questionnaire and the Oswestry disability index.

Improvements were seen in both groups, but were significantly better in the group taking agmatine. Pain perception was improved by 26.7% and quality of life by 70.80% (compared with 6% and 20% in the placebo group, respectively).

The results were maintained 60 days after stopping agmatine.

Agmatine also has the ability to significantly increase the duration of action of various opiates used in medicine as analgesics, such as morphine and fentanyl, for example.

It also manages to reduce the tolerance that develops to various opiates with prolonged use.

Reduce stress, anxiety and depression

There is a direct relationship between brain and plasma agmatine levels during stressful situations.

There is a significant increase in agmatine levels, probably due to an increase in the activity of the enzyme arginine decarboxylase, the enzyme by which agmatine is derived from the amino acid arginine.

Reduction of stress and anxiety has been demonstrated in various stress tests on mice – elevated plus maze, social and involving light cues.

The efficacy of agmatine in these studies is comparable to the drugs imipramine and diazepam.

Comparable efficacy of antidepressant properties with imipramine has also been observed in rat tests.

Agmatine also acts synergistically with other antidepressants – bupronide and SSRIs.

In humans, there has been one very small study from 2013 involving only three individuals suffering from depression.

Upon taking 2-3 grams of agmatine orally, all three subjects experienced remission of depression.

Increasing appetite

Agmatine has the ability to activate alpha-2 adrenergic receptors. Their stimulation in turn increases levels of the hormone neuropeptide Y, one of the main appetite stimulating hormones.

This effect was observed in 2 studies on rats, with injection of agmatine into the hypothalamus increasing the amount of food ingested over the next 24 hours by 40-50%.

Lowering blood glucose levels

A study on diabetic rats shows the serious potential of agmatine to lower blood sugar levels.

According to those conducting the study, this occurs through the activation of imidazoline receptors and the secretion of beta-endorphin. 27

What is more interesting in this case is that, thanks to beta-endorphin, glucose is stored in muscle tissue rather than fat tissue.

Recommended dosage and method of intake

At this stage, the optimal dose has not yet been determined.

In one study, daily doses of between 1.3 and 3.6 grams were used to reduce pain sensation in humans.

Possible interactions and side effects

No side effects were observed at the doses studied up to 3.6 grams, with the exception of a few reports of stomach upset at the highest doses.

It is not known how safe doses above those studied are.

Concurrent intake of agmatine with:

  • Arginine or citrulline, due to blocking some of the beneficial neurological effects, such as reducing pain sensation or reducing tolerance to opiates;.
  • Yohimbine and rauwolscine (rauwolscine) because they have opposite effects;
  • D-aspartic acid (D-aspartic acid), due to decreased effectiveness;
  • Alcohol – concomitant intake may increase the risk of ulcer.

In conclusion

Agmatine is a small molecule with a big potential. Unfortunately, we will have to wait a while until more research is conducted, especially on humans.

At this stage, nothing is known for sure and even the information available needs further investigation.

Which brings us to the next question – is agmatine worth it as a dietary supplement?

Rather no. Don’t be fooled by manufacturers’ claims. They are based precisely on the aforementioned rat studies.

Yes, agmatine has serious potential, but for the moment its effectiveness in athletic and non-athletic humans is highly questionable.

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Sources used