Agmatine is one of the most fascinating, and beneficial, substances.
It’s a metabolite of the amino acid arginine and is created and stored in many organs, including the brain. Therefore it’s been proposed to be a neurotransmitter, as it is co-released with other neurotransmitters and acts like a neurotransmitter itself.
Agmatine is amazing for the brain, exercise performance, energy metabolism and just general health.
It can be useful against learned helplessness, anxiety, depression, low motivation, hyperglycemia and much more that I’ll be discussing in this article (R).
The benefits seem almost innumberable.
Let’s start with the brain
Agmatine for brain health
Let me give you a few good reasons why agmatine is so great for the brain. Agmatine:
#1 Is very potent neuroprotective and can help prevent the neurological death of dopaminergic neurons.
One of the reasons people start to feel depressed and low in motivation is due to elevated oxidative stress which is killing the dopaminergic neurons. Agmatine protects these neurons against damage and death.
#2 Prevents the disruption of the blood brain barrier thus protecting the brain against toxins.
#3 Can increase allopregnanolone, which is a potent anti-depressant and anxiolytic hormone, by activating peroxisomal proliferator-activated receptor-α (PPARα), and its coactivator PGC1α.
#4 Protects against GSK-3β-induced signaling disruption in the hippocampus. GSK-3β is the enzyme that inhibits the formation of glycogen. This enzyme is elevated in the brains of depressed people and inhibiting it has an anti-depressant effect.
#5 Reduces fearfulness and the acquisition and/or consolidation of contextual fear stimuli (R).
#6 Prevents the dysregulation of serotonin and dopamine due to stress (R). This helps to keep mood stable during periods of stress and makes you more stress-resilient.
#7 Reduces the levels of acetylcholinesterase (the enzyme that breaks acetylcholine down) and oxidative stress markers and significantly increases the BDNF level in stressed mice (R). It effectively prevents inflammation-induced depression (R).
#8 Prevents the rise in cortisol due to stress, which makes it an effective adaptogen. It also protects the brain against excess cortisol itself (R).
#9 Acts as a 5-HT1A/B agonist (R). This is a biggy because 5-HT1A agonists lower dorsal raphe (DR) nucleus serotonin, but not median raphe (MR) nucleus serotonin. MR serotonin is elevated in people with depression and there are very few known natural 5-HT1B agonists (R). Only 5-HT1B/D agonists lower MR serotonin and agmatine appears to be an effective 5-HT1B agonist, which should help lower MR serotonin.
#10 Is an NMDA antagonist, which has anti-depressant properties.
#11 Can even potentiate the antidepressant-like effects of subthreshold doses of lithium (R). So it seems that agmatine and lithium would work nicely together for depression and/or bipolar.
#12 Is an inhibitor of neural and inducible nitric oxide synthase (nNOS and iNOS). This property makes agmatine very effective against neurological pain, anxiety, depression and neurological damage and death (R).
#13 Is effective against cerebral edema, which is swelling of the brain (R).
#14 Protects against tardive dyskinesia, due to its neuroprotective properties to the dopaminergic system (R). Tardive dyskinesia is involuntary muscle twitches. As a side note, serotonin is also involved in head twitching.
#15 Suppresses harmful reactive oxygen species (ROS) and oxidative stress.
#16 Promotes neurogenesis and remyelination (R).
#17 Reduces glial scars (R).
#18 Reduces hypoxic brain tissue damage (R).
#19 Suppressed the accumulation of Aβ and phosphorylated-tau, which may contribute
to reduce the cognitive decline in the mouse brain (R).
#20 Could be used as treatment for amnesia (R).
#21 Reduces ethanol-induced anxiolysis, opioid withdrawal anxiety, and depression in mammals. Agmatine has greater potential to reduce morphine dependency than other
imidazoline-1-specific ligands such as moxonidine and rilmenidine.
Most of the beneficial anti-depressant, anti-convulsant, anti-OCD and memory retrieval
effects of agmatine are due to the activation of the α2-adrenoreceptors and the imidazoline binding sites in addition to NMDA and nitric oxide antagonism (R, R).
Agmatine in the body
Agmatine is not only spectacular for the brain, but it’s also great for the body. As mentioned above, agmatine is also stored in organs, so we can expect benefits overall in the body.
Just to name a few. Agmatine:
#1 Lowers intestinal inflammation (R), which means it could be useful for irritable bowel syndrome (IBS).
#2 Lowers high blood sugar and increases insulin secretion in response to glucose (R).
#2 Improves energy metabolism by activating peroxisomal proliferator-activated receptor-α
(PPARα), and its coactivator PGC1α as well as increasing the expression of PPARγ and genes regulating to thermogenesis, gluconeogenesis, and carnitine (Car) biosynthesis and transport.
I quote from the study (R):
“The changes in gene expression were coupled with improved tissue and systemic levels of Car and short chain AcylCar, increased βoxidation and diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, increased hepatic ureagenesis and gluconeogenesis but decreased glycolysis.”
This is very important because excess glycolysis is elevated in cancer and the growth of tumors. Lowering glycolysis lowers available fuel for the tumors and also prevents the Warburg effect. Agmatine effectively lowers the lactate to pyruvate ratio (R). This brings us to our next point.
#3 Selectively suppresses growth in cells with high proliferative kinetics, such as transformed cells, through depletion of intracellular polyamine levels (R). The exogenous agmatine is also
reported to be an anti-proliferative agent which reduces the biosynthesis and increases the degradation of the cell growth and proliferative polyamines such as putrescine, spermidine
and spermine in different cancer cell lines (R). Agmatine can be converted to polyamines and polyamines have the potential to worsen cancer. But instead of fueling cancer growth, agmatine has the potential to inhibit it.
#4 Is mitochondrial protective and can prevent mitochondrial damage which can ensure energy production even in suboptimal conditions.
#5 Acts as an adaptogen and lowers cortisol secretion in response to stress (R).
#6 Causes the release of luteinizing hormone releasing hormone (LHRH) from the hypothalamus, which could have a beneficial effect on testosterone levels (R).
#7 Lowers blood pressure, irrespective of nitric oxide (R)
#8 Increases pain threshold and reduces neuropathic pain.
#9 Lowers water retention by increasing the excretion of salt (R).
#10 Reduces collagen scar formation and enhances functional recovery (R).
#11 Inhibits advanced glycation end products (AGE) formation (R). This means that agmatine can lower Hb1Ac levels.
#12 Increases urea. Some might think this is bad, but urea is actually anti-inflammatory and anti-viral.
#13 Increases cAMP, which in turn can stimulate the testes to pump out more testosterone.
#14 Lowers free fatty acid, which improves insulin sensitivity as excess free fatty acids in the presence of glucose causes insulin resistance (R).
My experience with agmatine
I’ve been using agmatine for 2 weeks now at doses of 500mg each morning.
- Able to focus for longer
- Feel calmer and more stress-resilient
- Feeling more creative
- Experiencing better mood and euphoria
- Tired earlier before bed, which is a bonus
- Experiencing an uptick in libido
- Experiencing whiter eyeballs
- Having more stable energy during the day
There are more but those are the big ones for now.
A few more testimonies on agmatine
So it’s probably been 2.5 weeks, where I’ve taken Agmatine spread out at least 5-6 times and I’ve have never felt better for a LOOONG time.
My sociability is improving dramatically, where I went from a pretty isolated individual, blaming my parents, the world for all of the mishaps that have happened to me.
That is gone.
I am enjoying music now, taking up my prior interests (music was a former interest), forgiven and moved on for a lot of pain that people have caused me.
All in all, it is extremely therapeutic and I highly recommend it to everyone.
The antidepressant effects persist even after use, and each time I take it, the stronger the effect post-use . I feel less stressed, my sleep is improving, sex is becoming way more enjoyable than it used to be.
Even if my mood dips due to stress, it usually does not dip that low and goes back to baseline much faster than prior Agmatine use.
The effect is so extreme, that I have no words for it to be honest. I’ve tried Ayahuasca, NSI-189 which was what I considered to be the most potent substances that I’ve tried before trying Agmatine.
This beats it, by far, and it really has to do with a simple understanding of what happens in anxiety & depression, which in essence is an atrophy of various of parts of the brain. Agmatine regrows these dead cells and restores our ability to be rational and thus prevent anxiety.u/snaxks1
I started taking agmatine for its supposed kratom boosting effects which seem to be minimal. But I only use it one day per week to save money, and only in one 750mg dose at that. (The norm is 2-3 doses of that size daily). At first I thought it did absolutely nothing & was a total waste of money, so I threw it in the drawer & forgot about it.
But with continued use, something very interesting I’ve noticed is that–the day AFTER taking Agmatine–I have a ton of energy & endurance compared to my normal lethargic self. Almost a manic (for me) energy. It’s great! I even enjoy SHOPPING, which is my absolute least fave thing in the world. So now I take it the night before I have to go somewhere or do something labor intensive & it works like a charm. Mind you, I’ve suffered from chronic fatigue for decades. Not sure if it’s CFS or something depression-related, but it’s nothing for me to sleep 13 hours & still need a nap…even with a stimulant. So this increased energy is huge.u/Survector_Nectar
As always, thanks so much for reading my article. Let me know in the comments below if you have any questions. And if you found this article to be insightful and helpful please like and share so this information can help others as well.
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