Potential negative interaction of Agmatine and other supps
- 01-07-2014, 10:46 AM
Potential negative interaction of Agmatine and other supps
I've been reading up on Agmatine as I'm currently taking it and looking to buy more.
I came across some interesting info about possible negative interactions of Agmatine with other substances and wanted know whether it's valid.
List of ingredients that may not combine well with Agmatine:
L-Arginine or L-Citrulline - for some neurological effects; cardiovascular interactions not well elucidated.
Yohimbine or Rauwolscine - Agmatine activates the α2A receptor that these inhibit.
D-Aspartic Acid - due to reducing signalling via the NMDA receptors.
Can anyone confirm whether these points are accurate?
I know that a lot of people combine Agmatine and Citrulline, for example. Don't remember ever reading about any problems.
- 01-07-2014, 11:21 AM
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01-07-2014, 12:10 PM
Yohimbine and Rauwolscine inhibit the a2A receptor, so this would negate agmatine activity there, BUT agmatine doesn't work solely through the a2A receptor and some studies suggest that it doesn't do anything there at all.
With DAA, again you have possible negating effects so I would simply say to take DAA and agmatine at separate times if this is a concern. In the past I have taken DAA in the morning and agmatine before I train in the evening.
01-07-2014, 12:37 PM
OP, where did you see this? Links?
MAN's Prometheus Rising (RIP) contained both agmatine and daa, and it's one of my favorite products of all time.
01-07-2014, 12:42 PM
01-07-2014, 12:44 PM
01-07-2014, 12:57 PM
01-07-2014, 01:06 PM
It should be just fine to take DAA and agmatine together. That author was speaking very generally when in reality NMDA receptor subtypes can be very diverse, so it's not always as easy as A+B=C. A lot of studies (if not most) are done in vitro with specific NMDA receptor subtypes and very specific agonists and antagonists.
Just wanted to clarify before I get accused of bashing anybody's product.
Last edited by Aleksandar37; 01-07-2014 at 01:08 PM. Reason: clarifying NMDA as NMDA receptor
01-07-2014, 01:55 PM
this guy starts a thread all freaked out on stacking, based on a "hypothetical" series of thoughts with no firm basis of conclusion, and said "study" does not even use oral agmatine at all in any part of the study -- it is all injected
(to the credit of the author however, at least he points this fact out and also mentions further study is needed on orally ingested ag)
so much misunderstanding, leading to so much misinformation....
there is such thing as too much info, in case you didn't know
01-07-2014, 02:01 PM
01-07-2014, 02:08 PM
so now is it my turn to say "no, he was freaked out" and we go back and forth on the matter?
wow man..that post was rather needless as much as it was fruitless
my exaggeration is pointed reference to mad misinformation from ppl who glance thru these threads and read the highlights, without any real understanding of the concept let alone substance of the discussion, and parrot misinformation ignorantly accordingly..and I never said this applied to OP, I simply made a referenced remark to a concern he had, which was not even based on oral ingestion of agmatine to begin with, yet he made reference to in support of these claims he based on his reading (which would lead to some saying he was indeed "freaked out")
continue on with your trying to shape things to your own personal viewpoint however, sir
let me know how that works out for you
01-07-2014, 02:21 PM
01-07-2014, 02:25 PM
what article are you looking at?
please note bottom boldened .. why read further when the summary makes no mention to support any hypothesis of idea that is being put forward here?Summary (All Essential Benefits/Effects/Facts & Information)
Agmatine is a biogenic amine that is derived from L-arginine via decarboxylation (removal of a carboxylic acid group), and appears to be stored in neurons and released upon neuronal activation. Due to this and other properties, agmatine is a seen as a neurotransmitter or at least a neuromodulator. It's most relevant and interesting potential uses (research, overall, is preliminary) include the treatment of neuropathic pain, drug addiction, and protecting the brain from toxins and stroke.
Agmatine is known as a pleiotropic molecule, and has a large amount of direct mechanisms. These include inhibition of NMDA receptors and possibly also nicotinic acetylcholine receptors, and activation of imidazoline receptors; there is possibly activation of α2-adrenergic receptors but this is not 100% clear (some studies suggest that there is no effect). Agmatine also directly inhibits NOS enzymes (aside from iNOS, at concentrations too high to be concerned with) and may also inactivate these enzymes (more biologically relevant), but despite this apparent inhibition of Nitric Oxide metabolism it appears to directly act as a mimetic and circumvent its own inhibition; the result is somewhat of a regulation of nitric oxide in instances where it is improperly elevated. Other direct mechanisms include inhibition of calcium channels (fairly potent, with an IC50 value of 1.2ÁM) and inhibition of serotonin receptor subset 5-HT3.
Other mechanisms which are not ascertained if they are direct or vicariously through one of the aforementioned ones include activation of PI3K/Akt (found in multiple cell lines) and adenyl cyclase activation (noted in the prefrontal cortex, it is unsure if this is from serotonin or adrenergic receptors). A release of opioids (β-endorphins) has also been confirmed to be secondary to imidazoline receptor activation in the adrenal glands, and Ryanidine receptors are activated (which release intracellular calcium) although it is not sure if this causes or is a result of the nitric oxide interactions.
Agmatine has a large number of roles and mechanisms in the body. The primary four roles (that seem to be most important) involve positively influencing imidazoline receptors and α2-adrenergic receptors while inhibiting NDMA receptors and NOS enzymes
In regards to pain, there are mixed effects (as agmatine appears to have a modulatory role) but overall it appears to be analgesic. While agmatine in isolation can augment the perception of pain (by enhancing the signalling through a receptor known as ASIC3 that mediates pain associated with acidity), it appears to release β-endorphin and synergistically enhance the actions of any opioids. Due to the inherent release of a weak opioid and synergism with opioids, agmatine is able to reduce pain and pharmaceutically is synergistic with both morphine and fentanyl (increasing pain killing, reducing tolerance, and reducing addiction).
The ability of heat to cause pain in rats is normally reduced by cannabinoid signalling (such as Marijuana), and agmatine also appears to provide synergistic pain relief with cannabinoids. Other potential synergisms between agmatine and marijuana are not yet investigated, but it appears that anything through the CB1 receptor is augmented under the influence of agmatine.
Agmatine has both pro-pain and anti-pain mechanisms (technically speaking), but it appears that due to being very synergistic with established anti-pain pathways that the overall effect of agmatine injections into research animals is one of pain relief. The pain relief is fairly notable as well
For strokes, there are repeated studies in rats using injections of agmatine (around 100mg/kg) that suggest potent protective effects that near normalization of symptoms after 3-4 days with minor protective effects noted within a few hours. It is thought that this is due to modulating nitric oxide metabolism, as the increase in iNOS seen during stroke (which normally produces too much nitric oxide and damages tissue) is attenuated while the acute suppression of eNOS (which is protective) is preserved. Nitric oxide and its oxidative metabolite known as peroxynitrate are also attenuated, and this is thought to result in less overall damage.
When cognition and brain edema are tested after a stroke, they appear to be significantly reduced and almost normalized relative to control rodents.
Although there is no human evidence at this moment in time, agmatine appears to have potent protective properties against strokes
Another claim of agmatine supplementation are the anti-addictive properties, which appear to exist in rats who become addicted to opioidergic drugs (morphine, fentanyl, and oxycodone) where agmatine injections during drug administration reduce addictive effects. There is also a potential mechanism for agmatine to reduce Nicotine dependence (which needs to be explored further) and currently the only failure has been on cocaine, which is known to be low on a rewards scale in rats; cocaine may require a human study.
Agmatine may also help with alcohol and opioid drug withdrawal by reducing symptoms thereof.
Agmatine is potentially anti-addictive, and awaits human studies to confirm what is seen in rodent models
Overall, agmatine is a highly promising research chemical that will likely be important in the future. It's usage as a common supplement is limited by a lack of human trials at this moment in time, and although there are a few studies using oral ingestion here and there (which confirm that it does appear to be absorbed) the vast majority of studies use injections of agmatine. Future research will need to re-establish all the current observations following oral ingestion (or at least, more pharmacokinetic studies should be conducted including tissue distribution so we can make educated guesses on oral doses).
01-07-2014, 02:39 PM
01-07-2014, 02:43 PM
you're more than welcome to continue your own oversight and expertise in that role, alex
take care, and best to you in 2014
*as a sidenote, and to no one in particular:
I swear some of you guys would be soooo much better off if you'd get your nose out of those books, stop worrying about the latest "study", or investigating the latest-greatest-miracle pill on the market, and just go EAT FOOD and go DO WORK, hit the damn weights
that is all
01-07-2014, 03:16 PM
01-07-2014, 03:23 PM
I wasn't even remotely "freaked out" and was fairly sure that none of these are even an issue.
I made no "reference in support of these claims". I was simply asking a question.
I'm also not sure how you were so certain that none of the information provided in that article was based on studies of orally administered Agmatine.
You only looked at one part. The were over 100 Agmatine studies referenced and some used Agmatine orally.
All we're doing, is trying to have a civilized discussion about supplements.
If taking Agmatine together with DAA affects the efficacy of one of the substances, why wouldn't we want to talk about it?
01-07-2014, 03:26 PM
01-07-2014, 03:29 PM
01-07-2014, 03:35 PM
had I known as much, I never would have bothered taking the man approach, giving you benefit of doubt to work things out in private discussion, and saved my time for better things
I won't sit here and relay what are private communications, like some ppl do
I also had no intention of sending you any PMs, as this does not involve you at all
but for your own clarification, I simply corrected him on his intentions to "stick up" for you because he thought I was picking on you (which I wasn't), and told him if OP had an issue with my post, he could tell me himself
it simply did not involve him, at all.. and I still am puzzled over his arrogance that he feels he needs to be protector of all things unjust
01-07-2014, 03:37 PM
01-07-2014, 03:48 PM
01-07-2014, 03:55 PM
01-07-2014, 03:57 PM
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01-07-2014, 04:00 PM
Alex does have a good point and studies do reference orally taken agmatine.
One thing I dislike is when we, as students, educators or professionals in our field are told to keep our noses out of books. Yet when we get something wrong, we are told we don't know enough (think doctors in other threads).
We are also here to protect people from potentially hurting themselves in the gym (think patella tracking during a squat or proper form- all of which are born from an in depth understanding of functional anatomy).
Or in the case of biochem, do you still use trib to boost test? Arginine to increase vasodilation? or has science, and the board members who study it, informed you for the better?
Some of us like keeping up with studies in order to improve the people around us. I implore you to find one world class athlete who does not have an exercise specialist who helped him get there or someone like cooper who hasnt changed/ isnt changing a company for the better.
That statement, i feel, is directed at anyone who studies and enjoys studying anything and because of which i take offense, particulary when i have both time to study and workout.
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