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Agmatine, miracle supplement or bust?

agmatine

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#1 jack black

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Posted 18 November 2018 - 12:31 AM


According to https://www.selfhack.../blog/agmatine/

agmatine should be a miracle supplement for us all (proven to work on rats or mice of course).

 

anyone reporting any benefits in humans? i started taking it in the last 3 days and all I feel so far is being more tired (for sure), and maybe, maybe less social anxiety?

 

 

1) Agmatine Reduces Pain

Agmatine reduced hypersensitivity to pain and reduced the size of spinal cord injury in rats [R, R].

Furthermore, agmatine reduced neuropathic pain by preventing nitric oxide synthase activation and blocking NMDA receptors in rats [R].

In 2 studies (dose-escalation study and DB-PCT) of 61 participants with a herniated lumbar disk, agmatine supplementation for 10 days reduced pain and improved quality of life [R].

2) Agmatine May Help with Depression and Anxiety

By increasing NRF2, agmatine prevented depressive behavior in rats by protecting brain cells from high levels of the stress hormone cortisol [R].

Agmatine increased adenylate cyclase in the prefrontal cortex of rats. Decreased levels of adenylate cyclase are associated with depression [R, R].

Additionally, blocking the NMDA receptor prevents calcium overloading and reverses the decrease of monoamines (such as norepinephrine, epinephrine, and dopamine) in rats. Depression may be associated with a decrease of monoamines in the brain [R, R].

In a small pilot study of 3 depressed patients, agmatine supplementation caused a complete disappearance in depressive symptoms in all patients, likely through NMDA receptor-blocking and not through serotonin pathways [R].

Agmatine also reduced anxiety in rats during swimming tests and navigating mazes [R].

3) Agmatine May Promote Muscle Growth

Agmatine stimulated the production of luteinizing hormone (LH) in rats. Increased levels of LH increase testosterone levels. By increasing testosterone levels, agmatine contributed to an optimal hormonal environment for muscle growth and enhanced athletic performance [R].

Agmatine increased insulin sensitivity and uptake of glucose into the muscles of mice. Increased insulin sensitivity results in more effective shuttling of glucose and amino acids into muscles for growth and repair [R, R].

Agmatine also increased appetite in rats. An increased appetite can lead to increased caloric consumption, which is necessary for increasing muscle mass [R, R].

4) Agmatine May Protect the Brain from Damage Due to Stroke

By inhibiting iNOS and nNOS and increasing eNOS, agmatine protected against brain damage from stroke in rats. Increasing eNOS protects the brain by dilating the blood vessels to increase blood flow. This prevents damage during times of lack of oxygen from reduced blood flow to the brain (ischemic stroke). Additionally, agmatine decreased iNOS and nNOS, 2 enzymes that contribute to brain damage from stroke [R].

5) Agmatine May Improve Recording of Spatial Memory

Agmatine is increased during spatial learning tasks and is stored in high levels in the hippocampus (a region of the brain associated with memory). Its role as a neurotransmitter is associated with memory formation [R, R, R].

Agmatine improved spatial memory consolidation, or the initial recording and storing of a memory, but had no effect on the retrieval of memories in rats [R].

Agmatine increased brain-derived neurotrophic factor (BDNF) in the brains of rats, a molecule which stimulates the production of new brain cells (neurogenesis) [R].

Agmatine increased adenylate cyclase activity in the prefrontal cortex of rats, a molecule associated with memory formation [R].

6) Agmatine May Suppress Tumor Growth

Agmatine prevented the growth of connective tissue tumors in mice by the decreasing the level of molecules thought to be involved in tumor growth called polyamines [R, R, R].

Agmatine also prevented the growth of intestinal tumor cells in a lab study by decreasing polyamine production [R].

7) Agmatine May Improve Weight Loss and Prevent Weight Gain

Agmatine reduced weight gain in rats [R].

Agmatine increased fat burning, decreased fat composition, and increased muscle mass in rats [R].

8) Agmatine May Improve Insulin Sensitivity and Reduce Blood Sugar

Agmatine improved insulin sensitivity in insulin-resistant rats by reducing mTOR and glucose transporter 2 (GLUT2) production in rats [R, R, R].

Agmatine reduced blood sugar levels in rats by increasing β-endorphin production by the adrenal glands. β-endorphins cause the uptake of glucose from the blood into skeletal muscle tissue [R, R, R].

9) Agmatine May Help with Alzheimer’s Disease

Insulin resistance can lead to the accumulation of plaque and neurofibrillary tangles in the brain, which are the hallmarks of Alzheimer’s disease. Agmatine prevented cognitive decline by rescuing insulin signaling and preventing the accumulation of plaques and neurofibrillary tangles in the brains of rats [R, R].

10) Agmatine May Protect Against Hardening of the Arteries

Agmatine reduced plaques (atherosclerotic lesions) that lead to hardening of the arteries by 40% and increased good (HDL) cholesterol levels in mice [R].

11) Agmatine May Increase Nerve Repair

Agmatine increased nerve regeneration in rats with facial nerve injuries. This may be due to agmatine’s inhibition of nNOS, which can inhibit the growth and repair of neurons [R].

12) Agmatine Protects Against Seizures

Glutamate and the NMDA receptor have been implicated in the initiation and spread of seizure activity. Agmatine prevents seizures in mice and rats by blocking NMDA receptors [R, R].

13) Agmatine May Protect Against Stress

Agmatine significantly reduced high body temperature from prolonged heat stress and fever in mice caused by bacterial toxins called lipopolysaccharides (LPS). Agmatine also increased the survival rate of mice exposed to LPS [R].

14) Agmatine May Reduce Inflammation

Agmatine reduced inflammation by suppressing the expression of iNOS after inflammatory stimulation in rats [R].

In rats, agmatine prevented decreased blood pressure and kidney function associated with septic shock due to its anti-inflammatory effects [R].

15) Agmatine May Help with Alcohol and Morphine Withdrawal

Agmatine prevented symptoms of alcohol withdrawal such as “wet dog shakes,” anxiety, and tremors in rats [R, R].

 


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#2 experimenting

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Posted 18 November 2018 - 12:40 AM

I'd imagine NMDA blocker is the issue. Might block anxiety but also blocks arousal and cognition- I'm not into these kinds of supps. It's probably what's causing you the fatigue.
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#3 MankindRising

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Posted 18 November 2018 - 11:01 AM

I have tried it several times in an attempt to improve my social functioning, mixed results at mixed doses and not as effective as I hoped it would (keep in mind I was using other stuff at the time so might have interfered with results).

That being said it is a very effective NO booster.


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#4 jack black

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Posted 18 November 2018 - 03:21 PM

 

That being said it is a very effective NO booster.

 

pardon my ignorance, what does it do for me?


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#5 Oakman

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Posted 18 November 2018 - 08:34 PM

pardon my ignorance, what does it do for me?

 

He's talking about this attribute...

 

"In the muscle building and sports performance realm, agmatine works to provide the following potential benefits: Improved muscle pumps via the inhibition of nitric oxide synthase (NOS). Better intra-workout energy. In the role of a nootropic, aiding with mental clarity (focus), stress management and mental health."

 

https://www.tigerfit...ate-supplements

 

I've been taking it off and on and haven't been able to pin down any particularly noticeable benefits, but that doesn't mean it isn't doing what it's purported to do. I've got a couple hundred grams, so I'll see what happens.


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#6 jack black

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Posted 19 November 2018 - 04:10 AM

I must be retarded, because I can't figure out what "muscle pumps" are.

I guess it's not a huge priority for me.


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#7 Galaxyshock

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Posted 19 November 2018 - 09:50 AM

Agmatine seems to do a lot of different things, but in my experience the neurological effects aren't that strong in practice. Guess it depends what you're looking for, the "silent effects" that you can't really feel may alone be worth it to supplement Agmatine.


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#8 MankindRising

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Posted 19 November 2018 - 10:18 AM

I'd imagine NMDA blocker is the issue. Might block anxiety but also blocks arousal and cognition- I'm not into these kinds of supps. It's probably what's causing you the fatigue.

 

Its also a calcium channel blocker (though not as potent obviously as lets say pregabalin) might be an overlooked factor in its effect on mood. If you look at some of the calcium channel blockers (yes that includes phenibut) they can even induce manic like symptoms in some.


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#9 John250

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Posted 19 November 2018 - 10:28 PM

It’s in most pre-workouts. I never noticed anything from it.
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#10 jack black

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Posted 20 November 2018 - 07:37 PM

I decided to give it the benefit of the doubt and use it for at least a couple of weeks.

now, I noticed 2 effects:

1. when I had a headache and took a dose of agmatine, the pain didn't go away, but became a bit duller and I was not as bothered by it as I'm usually (i hate headaches).

2. it complements my weekday AM stimulant stack when I take the powder in coffee (that hides well the bad taste), it gives me same anti-anxiety and pro-social effects without a big hit in energy levels.

I think I'll keep it with my stimulant stack but will not take it on the weekends or PM without the stimulants.


Edited by jack black, 20 November 2018 - 07:38 PM.


#11 TheFountain

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Posted 22 November 2018 - 10:27 PM

Can I ask the dosage you are taking daily? How many days a week?



#12 jack black

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Posted 23 November 2018 - 05:15 AM

I have been taking about 750 mg 1-2 times a day for a week now, but plan to stop it on weekends. after taking this for a few days, it does feel like a mild antidepressant, and I'm more talkative, definitely due to agmatine effect.. interesting, I seem to have more mild headaches, too, but this could be due to stress and diet indiscretion.


Edited by jack black, 23 November 2018 - 05:22 AM.

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#13 jack black

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Posted 23 November 2018 - 07:26 PM

update: I noticed that I lost almost 3 lbs in the week on it, not even trying (and considering holiday). this is significant, because I'm at the lowest weight I've been in the last year. If I break below that, this will be a big breakthrough. I do seem to be less hungry in PM and evening. Maybe those are insulin/blood sugar effects?


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#14 jack black

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Posted 03 December 2018 - 03:59 PM

update after over 2 weeks: my weight fluctuated slightly above the lowest for me this year, so no breakthrough in weight loss on agmatine, but not worse either. interestingly, while on agmatine, it was harder for me to resist junk food, so it's actually a positive I didn't gain a lot of weight. so, there must be some minor effects on insulin/glucose metabolism.

initially i felt anti-anxiety/anti-depressive effects, but could not feel them in the second week. It made motivation noticeable worse (must be pro 5HT effect).

when I stopped, I didn't feel worse, but it has a long half life of course.

so, in summary, i would recommend it only for it's anti-anxiety/anti-depressive effects, but with cycling, and not good for ADHD and people with urges for junk food.

I can't comment on any weight lifting or anti-pain effects.


Edited by jack black, 03 December 2018 - 04:03 PM.

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#15 MankindRising

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Posted 03 December 2018 - 08:44 PM

update after over 2 weeks: my weight fluctuated slightly above the lowest for me this year, so no breakthrough in weight loss on agmatine, but not worse either. interestingly, while on agmatine, it was harder for me to resist junk food, so it's actually a positive I didn't gain a lot of weight. so, there must be some minor effects on insulin/glucose metabolism.

initially i felt anti-anxiety/anti-depressive effects, but could not feel them in the second week. It made motivation noticeable worse (must be pro 5HT effect).

when I stopped, I didn't feel worse, but it has a long half life of course.

so, in summary, i would recommend it only for it's anti-anxiety/anti-depressive effects, but with cycling, and not good for ADHD and people with urges for junk food.

I can't comment on any weight lifting or anti-pain effects.

Ive tried it a couple times myself and played around with different dosages and it does seem to have acute anti-depressive/anti-anxiety effects indeed, but like you I also found the dosing/halflife of agmatine tricky and discontinued it.

This was also my plan for next time (I still got nearly 100grams left of the stuff) to make sure I got a suitable regimen.


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#16 jack black

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Posted 04 December 2018 - 03:57 PM

LOL, shortly after posting that yesterday, a wave of withdrawal from it hit me. Yesterday was my second day without it and the day started normally and I felt fine, went through interviewing 2 workers and that went with breeze with no social anxiety whatsoever, and suddenly on the 3rd person, I started anxious, stuttering. and losing train of thought and speech. It was like running on empty and crushing. I do a lot of interviewing at work lately and before, the more I talked, the more energetic I felt (dopamine release?). Yesterday it reverted to old days, where talking drained me emotionally. 

 

After that, the whole PM was dysphoric and hard to concentrate at work. Went to bad early and almost felt like having a flu, but no fever. Today, I took agmatine with coffee in AM and feel fine again. This reminds me a bit the dysphoric rebound after stopping low dose SSRI a while back.

interestingly libido was low those last 2 weeks, just like with SSRI. This is weird, as agmatine should not work through 5HT?


Edited by jack black, 04 December 2018 - 04:01 PM.


#17 MankindRising

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Posted 04 December 2018 - 04:35 PM

LOL, shortly after posting that yesterday, a wave of withdrawal from it hit me. Yesterday was my second day without it and the day started normally and I felt fine, went through interviewing 2 workers and that went with breeze with no social anxiety whatsoever, and suddenly on the 3rd person, I started anxious, stuttering. and losing train of thought and speech. It was like running on empty and crushing. I do a lot of interviewing at work lately and before, the more I talked, the more energetic I felt (dopamine release?). Yesterday it reverted to old days, where talking drained me emotionally. 

 

After that, the whole PM was dysphoric and hard to concentrate at work. Went to bad early and almost felt like having a flu, but no fever. Today, I took agmatine with coffee in AM and feel fine again. This reminds me a bit the dysphoric rebound after stopping low dose SSRI a while back.

interestingly libido was low those last 2 weeks, just like with SSRI. This is weird, as agmatine should not work through 5HT?

It does act on serotonin to a fair degree from what I understand mainly 5ht2a (been a while since Ive read the examine.com article on it). Agmatine is also an opioid potentiator so this might also screw with libido effects. Also nmda antagonism isnt too good for normal sexual function so to speak, nmda signalling is necesarry for gnrh release and such.


Edited by MankindRising, 04 December 2018 - 04:44 PM.

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#18 jack black

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Posted 04 December 2018 - 07:47 PM

I checked the examine.com and the mechanism in depression is very complex.

 

 

Agmatine has been found to work synergistically with numerous antidepressants such as bupropion (at 10-20mg/kg agmatine injections, dependent on imidazoline receptors[130]), imipramine (0.01-50mg/kg,[97] although a failure noted elsewhere[127]), SSRIs (5-10mg/kg agmatine injections, dependent on imidazoline receptors),[127] and oddly putrescine (a polyamine) is synergistic with agmatine on depressive symptoms (0.001mg/kg agmatine injection).[84]

The antidepressant effects are abolished by L-arginine,[97][97] yohimbine (α2A receptor blocker),[89][97][97] and GMP itself;[97] another study noted that potassium channel inhibitors (which appears to be the mechanism that agmatine works via) are inhibtied by PDE5 inhibitors such as Viagra.[213] Blocking either the 5-HT1A,[89] 5-HT1B,[86] 5-HT2A,[86][89] or 5-HT2C[86] serotonin receptors blocks the effects as does blocking the delta and mu subunits of opioid receptors (but not kappa)[214] and opening potassium channels appears to prevent the effects of agmatine.[215]

The effects are not affected by prazosin (an α1A receptor blocker),[97] serotonin depletion,[125] blocking the beta-adrenergic system (propanolol),[86][89] or 5-HT3 receptors.[89]

The inhibition of potassium channels may underlie synergism,[215] as the classical antidepressants mentioned earlier tend to have the ability to inhibit potassium channels[216][217][218][219] as does adenosine (endogenous neurotransmitter)[220] and folic acid[221] while opening potassium channels appears to be a pro-depressant effect.[222][223] It was mentioned earlier that blocking a variety of serotonin receptors inhibits synergism, and serotonin likely mediates potassium channels via its receptor.[224] Finally, despite agmatine not per se inhibiting potassium channels at up to 500µM[225] its antidepressant effects are abolished with potassium channel openers.[215]

 

yeah, it does look like there is some increased signaling through multiple 5HT receptors indeed.

the effect is so strong, that the first day of 750mg after 2 day holiday does feel like low dose SSRI or low dose nefadozone that I took in the past (that helped a lot with anxiety/depression) but made worse motivation and too many blond moments. Maybe I need to decrease the dose, looks like for depression, one needs about 400mg and under?

 



#19 John250

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Posted 04 December 2018 - 08:49 PM

I never noticed anything from Agmatine but then again I’ve only used it in pre workouts and generally they include arginine ad citrulline which hinder its effects. It seems to be very promising. Since it’s an NMDA I think I’ll take it later in the day or at night so it won’t dull my amphetamines during the day. It’s effects on calcium channeling and NMDA antagonistic properties make it a great candidate for reducing amphetamine neurotoxicity.

Edited by John250, 04 December 2018 - 08:57 PM.


#20 MankindRising

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Posted 04 December 2018 - 10:58 PM

I never noticed anything from Agmatine but then again I’ve only used it in pre workouts and generally they include arginine ad citrulline which hinder its effects. It seems to be very promising. Since it’s an NMDA I think I’ll take it later in the day or at night so it won’t dull my amphetamines during the day. It’s effects on calcium channeling and NMDA antagonistic properties make it a great candidate for reducing amphetamine neurotoxicity.

My n=1, but high dose agmatine (2-3gram) in the evening on empty stomach left me wide awake.



#21 CalmDown

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Posted 24 December 2018 - 03:32 PM

It's been long noted in prior threads on agmatine that its most effacious effect is the a2 receptor agonism that lowers cAMP in the PFC. Which helps with higher executive functions. cAMP closes channels which stops/reduces signaling. This is the mechanism by which guanfacine and clonidine work. Albeit agmatine to a lesser extent while having other MOAs too.
Yes, cAMP in other areas of the brain help with LTP, but in the PFC, excess cAMP is a bad thing. Either raise norepinephrine, dopamine, or agonize the a2 receptor are the only 3 effective ways to lower cAMP in the PFC.

But the negative of a2 agonism is lowered blood pressure, which is where some people will say it isn't working/makes them too tired.

I don't have the links here because I'm about to have breakfast with my mother and am a bit rushed, but I can produce them later or you can look for other posts here about agmatine and find them.
But I just ordered some the other day to go along with my current stack and am looking forward to it. Standard dose is 1gram on an empty stomach
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#22 jack black

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Posted 24 December 2018 - 03:39 PM

It's been long noted in prior threads on agmatine that its most effacious effect is the a2 receptor agonism that lowers cAMP in the PFC. Which helps with higher executive functions. cAMP closes channels which stops/reduces signaling. This is the mechanism by which guanfacine and clonidine work. Albeit agmatine to a lesser extent while having other MOAs too.
Yes, cAMP in other areas of the brain help with LTP, but in the PFC, excess cAMP is a bad thing. Either raise norepinephrine, dopamine, or agonize the a2 receptor are the only 3 effective ways to lower cAMP in the PFC.

But the negative of a2 agonism is lowered blood pressure, which is where some people will say it isn't working/makes them too tired.

I don't have the links here because I'm about to have breakfast with my mother and am a bit rushed, but I can produce them later or you can look for other posts here about agmatine and find them.
But I just ordered some the other day to go along with my current stack and am looking forward to it. Standard dose is 1gram on an empty stomach

 

good point, I did notice it helps me get things done a bit more on top of my ADHD stack.

but this is at the expense of more lazy and asshole in PM or weekends as effects wear out. on the other hand, I don't want to dose it too often or it will lose its effects.



#23 CalmDown

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Posted 24 December 2018 - 05:04 PM

good point, I did notice it helps me get things done a bit more on top of my ADHD stack.
but this is at the expense of more lazy and asshole in PM or weekends as effects wear out. on the other hand, I don't want to dose it too often or it will lose its effects.


Yeah that's what I'm pressed to find more anecdotal reports on. The half life is only 2 hours, but many people report its half life in the brain, or lingering effects last all day.

I'm also curious as to tolerance because of how short the half life is. With such a short half life you would expect tolerance to not be an issue. On top of the concept that other a2 agonist drugs that are prescribed don't have big issues with tolerance. (except oxymetazoline, which I think is more an issue of its a1 agonism)

Best I can do is more research and give my own experiences when I do get it.
I will say I got some oxymetazoline the other day as it has similar moa, but with the a1 agonism as well and in larger doses it did make me more clear headed subjectively after I had added quercetin which increases cAMP(using it for mast cell stabilization)
just might need to add something to increase blood pressure whether that be salt or whatever else

#24 jack black

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Posted 11 January 2019 - 06:19 PM

more followup: after taking this a bit longer it emerged this is the most valuable part of my stack.

 

this is why: i was gone for a vacation and stopped taking my stack for a week. Noticed lowered emotions and energy levels in the middle of the week. right after coming back I restarted the stack (but forgot about the agmatine part). I was still sluggish and barely functioning at work (ADHD-like) for a few days and suddenly remembered about agmatine. The day I took it I felt head clearing, negative emotions going away, and social anxiety melting away.  Motivation at work increased.

 

i'm thinking now I may need to discontinue everything, except for agmatine to test it further.



#25 MankindRising

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Posted 12 January 2019 - 11:09 AM

more followup: after taking this a bit longer it emerged this is the most valuable part of my stack.

 

this is why: i was gone for a vacation and stopped taking my stack for a week. Noticed lowered emotions and energy levels in the middle of the week. right after coming back I restarted the stack (but forgot about the agmatine part). I was still sluggish and barely functioning at work (ADHD-like) for a few days and suddenly remembered about agmatine. The day I took it I felt head clearing, negative emotions going away, and social anxiety melting away.  Motivation at work increased.

 

i'm thinking now I may need to discontinue everything, except for agmatine to test it further.

Hey bud,

 

Much have you been taking (under the assumption empty stomach)? Also agmatine moa is complex but it involves nmda regulation (potentiation but also antagonism, more of a regulatory effect it seems), 5ht2a potentiation (I reckon this is why it can help with emotions, psychedelics also hit this receptor).

Also glad to hear you are feeling better with it.

I recently tried SAM-E, first 2 days were very profound and meaningfull to me, but it seems messing with methionine/sam-e eventually results in the accumilation of SAH and induces hallucinations/fear of death in me and generally speaking immune activation but in a way that my body seems to absolutely not agree with me.



#26 jack black

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Posted 14 January 2019 - 03:15 PM

about 500mg in my AM coffee on empty stomach. This is the perfect combo, as I need that coffee to wake up, but agmatine takes the edge away.



#27 jack black

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Posted 19 January 2019 - 06:33 PM

i forgot to mention that the metabolic hopes of agmatine were unfulfilled. i'm not losing any more weight, but at least my weight had been stable and not increasing much despite less than ideal diet.



#28 jack black

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Posted 09 April 2019 - 10:20 PM

i decided to update this. I have been taking agmatine on weekdays since the end of november, almost 6 months. Except for 2 week long vacations that i didn't feel like taking powder with me traveling. both times, i felt on edge and tight and didn't enjoy the vacations as much as i could. yesterday i went back to work and felt miserable. i wondered why, because i thought i took my usual weekday/workday stack. turned out i omitted agmatine by mistake. today i took agmatine and it's a whole lot of better day: I'm positive, sure of myself, talkative (even to the poit of being silly), and social anxiety melted a lot. this turned out to be a miracle supplement for myself. working gently but surely. i'll slowly discontinue the other things in my stack, because they don't seem to be working without agmatine.

no significant weight loss since, but weight super stable now and i'm eating more healthy now (less urge for unhealthy food).


Edited by jack black, 09 April 2019 - 10:22 PM.


#29 Oakman

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Posted 10 April 2019 - 01:08 AM

Back in Nov I posted variable results for occasional Agmatine. Recently I started adding 500 mgs Agmatine, 700 mgs Beta Alanine to my pre-workout (for cycling). 

 

Currently, that's being added to the PeakATP, NMN, D-Ribose, NAC, and Taurine in some juice I take. Surprisingly, what I felt was a truly noticeable increase in endurance, power output, and recovery. It feels real, it may go away with use, but right now Agmatine w/Beta Alanine seems a great no harm, no foul combo addition for endurance exercise. I look for changes and trends in the health stats I record pre, during, and post exercise and they've been improving. Hopefully it stays that way.

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#30 Harkijn

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Posted 27 June 2019 - 06:50 AM

 

Back in Nov I posted variable results for occasional Agmatine. Recently I started adding 500 mgs Agmatine, 700 mgs Beta Alanine to my pre-workout (for cycling). 

 

Currently, that's being added to the PeakATP, NMN, D-Ribose, NAC, and Taurine in some juice I take. Surprisingly, what I felt was a truly noticeable increase in endurance, power output, and recovery. It feels real, it may go away with use, but right now Agmatine w/Beta Alanine seems a great no harm, no foul combo addition for endurance exercise. I look for changes and trends in the health stats I record pre, during, and post exercise and they've been improving. Hopefully it stays that way.

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Are you still taking Agmatine 500 mgs and seeing mild positive effects? Thanks for letting us know.



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