Coop's Corner #2: L-Norvaline?

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    Post Coop's Corner #2: L-Norvaline?


    L-Norvaline has been advertised for several years as an arginase inhibitor, capable of preventing the degradation of arginine. This is thought to increase NO levels by virtue of increased arginine availability as a precursor to nitric oxide.

    Today we will look at what L-Norvaline will and will not do in healthy men.

    L-norvaline is a mixed arginase inhibitor, meaning that it degrades arginine not only in the liver (the site of urea production), but also various other locations including the GI lumen and endothelium of vasculature.

    To date, every study showing that norvaline was effective in improving vascular parameters was conducted in unhealthy populations: be it metabolic syndrome, hypertension, or diabetes. The common denominator in all these cases is vascular inflammation and subsequent endothelial dysfunction.

    Without getting too sciency, here are some passages worth reading:

    "In conditions of normally functioning endothelium, the balance between vasoconstriction and vasodilatation factors is supported. The basic vasodilatation agent in endothelium is NO. Infringement of the given balance leads to development of endothelial dysfunction. L-arginine serves as a source of NO in a cell. Inhibitors of arginase, suppressing activity of the given enzyme, promote NO biosynthesis increase, preventing the development of endothelial dysfunction. Application of L-norvaline promotes suppression of activity of arginase enzyme which allows for a raise in L-arginine stocks."

    Arginase Inhibitor in the Pharmacological Correction of Endothelial Dysfunction

    "Emerging evidence suggests that increased endothelial arginase activity decreases L-arginine availability for eNOS to produce NO under various pathological conditions [17]. The arginase inhibitor L-norvaline has been previously shown to improve endothelial NO release via inhibition of arginase [18]. Treatment of ApoE-/- mice with arginase inhibitors has been reported to improve endothelial function and reduce plaque formation [19]. It is however, not clear whether arginase is indeed involved in vascular inflammation responses, a crucial mechanism in atherogenesis. The present study further investigated whether arginase is involved in the modulation of endothelial inflammatory responses and whether this is dependent on NOS activity in endothelial cells. In cultured human endothelial cells, we demonstrate that the arginase inhibitor L-norvaline exerts anti-inflammatory effect at the same concentration ranges which exhibit arginase inhibitory activity [18]."

    Inhibition of S6K1 accounts partially for the anti-inflammatory effects of the arginase inhibitor L-norvaline


    What this is essentially saying is that people with endothelial dysfunction end up overexpressing arginase, which not only depletes the body of the arginine necessary for the NO/cGMP pathway, but it also seems to be involved in inflammation and atherogenesis. This is effectively an arginine deficiency. Norvaline ameliorates this deficiency by taking the activity of the arginase enzyme back to normal levels.

    Unfortunately, a similar effect would not be expected in healthy humans, wherein arginase expression is adequate and further reduction in endothelial arginase will prove worthless due to a lack of concomitant increases in eNOS expression. Furthermore, the anti-inflammatory effect of norvaline on the endothelium will be absent since healthy individuals should not have signs of atherosclerosis to begin with.

    In fact, supplementing with norvaline (at high doses) may be detrimental to health, as norvaline has demonstrated to reduce arginase expression in hepatocytes. Arginase is a key enzyme in ridding the body of nitrogenous waste. It catalyzes the last step of urea production. Urea is primarily how nitrogen is removed from the human body. If you inhibit hepatic arginase to a strong enough degree, there is potential for hyperammonemia due to negative feedback loops in the urea cycle, which often result in psychotic symptoms. Indeed, we see this with the rare care of congenital arginase deficiency.

    Lastly, norvaline may be able to inhibit arginase activity in the GI lumen. This is the sole potential utility that I see for norvaline in a healthy human. By inhibiting arginase activity in the lumen, it is possible that more ingested arginine will reach the plasma. Unfortunately, the same issue with eNOS expression holds true, and arginine has repeatedly failed to raise NO in healthy human subjects. Arginine may have other benefits, again seen primarily in cases of metabolic disorders.



    So the verdict on Norvaline?


    Low doses won't do anything, high doses may be detrimental to health, and medium doses co-ingested with arginine may increase arginine's bioavailability.

    The story changes completely if you have endothelial dysfunction.

    Stay tuned for round 3 next time I take a good stimulant dose
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    Another awesome thread. Awesome work Coop.
    http://anabolicminds.com/forum/workout-logs/231713-rob112-3-means.html
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    Thanks for the info man.
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    Thanks guys. These mini-articles will be exclusive to AM only (feel free to repost but I will only be posting them here). Only a major forum with ethics, such as this, will be empowered (with knowledge).

    These are all written fairly quickly and deviate from formal articles on multiple levels, but it should allow most people to understand what's going on without having to dig too much themselves. Due to the rapid nature of the writing process, I can do one every few days and look to have over a hundred by next year
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    I tried taking it around 7 or 8 years ago in bulk. It never did anything for me.
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    Quote Originally Posted by T-Bone View Post
    I tried taking it around 7 or 8 years ago in bulk. It never did anything for me.
    I'd strongly advise against the use of Norvaline in bulk. People seem to like to "up the dose," which can have toxic consequences as detailed above.

    In fact, since BBers consume high protein diets, the need for proper arginase function is tremendous
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    Quote Originally Posted by mr.cooper69 View Post
    Thanks guys. These mini-articles will be exclusive to AM only (feel free to repost but I will only be posting them here). Only a major forum with ethics, such as this, will be empowered (with knowledge).

    These are all written fairly quickly and deviate from formal articles on multiple levels, but it should allow most people to understand what's going on without having to dig too much themselves. Due to the rapid nature of the writing process, I can do one every few days and look to have over a hundred by next year
    I use to have an account on this one but I forgot my user name and email, it's been a long time. I have an account on other forums but I prefer this one as I just recently started posting in them again.
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    Quote Originally Posted by mr.cooper69 View Post
    I'd strongly advise against the use of Norvaline in bulk. People seem to like to "up the dose," which can have toxic consequences as detailed above.

    In fact, since BBers consume high protein diets, the need for proper arginase function is tremendous

    That was years ago, I've long since thrown it in the trash.
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    If you are looking to have 100 or so in the future, it would be nice to have a sub-forum specifically for the articles. Only you would have permission to post new threads, and members could only post replies.
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    Quote Originally Posted by domore View Post
    If you are looking to have 100 or so in the future, it would be nice to have a sub-forum specifically for the articles. Only you would have permission to post new threads, and members could only post replies.
    The thing is, I don't want this to be advanced discussion. I want this to be something all the regulars can understand. Am I succeeding in that so far?
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    Quote Originally Posted by mr.cooper69 View Post
    The thing is, I don't want this to be advanced discussion. I want this to be something all the regulars can understand. Am I succeeding in that so far?
    Almost, I have ADID though....
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    Quote Originally Posted by mr.cooper69 View Post
    The thing is, I don't want this to be advanced discussion. I want this to be something all the regulars can understand. Am I succeeding in that so far?
    I'd say so.
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    Quote Originally Posted by T-Bone View Post
    Almost, I have ADID though....
    Maybe I'll just add a "bottom line" at the end of each one. Though it pains me that most people will probably skip everything and go to that
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    There will always be those people. However, there will also be others that are eager to learn (especially considering you break it down into layman's terms). Regardless of what you end up deciding to do, you'll have readers. Guaranteed.
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    Quote Originally Posted by mr.cooper69 View Post

    The thing is, I don't want this to be advanced discussion. I want this to be something all the regulars can understand. Am I succeeding in that so far?
    Absolutely. It would be nice to reference past threads, instead of searching the mass quantity. I don't want them to get lost in the abyss.

    By explaining in layman's terms, you demonstrate commanding knowledge of the subject. It is easy to explain something among those in your field, but many seem to struggle explaining concepts to those outside of it. You definitely succeed at making it understandable.
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    I may be way off but I'll ask anyways...wasn't an older GDA product previously recommend as a prebed dosing to increase recovery and GH? I'm not looking for a "what is GH and why are we trying to boost it?" I'm merely asking to see if you came across anything supporting this GH theory is my memory serves me correctly.
    http://anabolicminds.com/forum/workout-logs/231713-rob112-3-means.html
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    Quote Originally Posted by rob112 View Post
    I may be way off but I'll ask anyways...wasn't an older GDA product previously recommend as a prebed dosing to increase recovery and GH? I'm not looking for a "what is GH and why are we trying to boost it?" I'm merely asking to see if you came across anything supporting this GH theory is my memory serves me correctly.
    The OG Slin sane wouldnt do this anyway because the main ingredient was a glucose blocker, not a GLUT4 translocator. I personally recommended it pre-bed because it enhanced my sleep quality, but I can't say there's any science to that
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    Quote Originally Posted by mr.cooper69 View Post

    The OG Slin sane wouldnt do this anyway because the main ingredient was a glucose blocker, not a GLUT4 translocator. I personally recommended it pre-bed because it enhanced my sleep quality, but I can't say there's any science to that
    Thank you sir.
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    These threads are great so far coop. Solid, detailed, factual, referenced info; followed by simple overall thoughts and overview. A little for everyone. Keep them coming for sure!
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    Great info Coop
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    Much appreciated coop


    Keep them coming brother.
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    Love it, norvaline... debunked :P
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    A really great job with these!
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    Quote Originally Posted by mr.cooper69 View Post
    The thing is, I don't want this to be advanced discussion. I want this to be something all the regulars can understand. Am I succeeding in that so far?
    Most definitely and you leave the door open for personal research to be followed up upon. Thank you Mr. Cooper for taking the time out to help shine light on topics that always seem gray. looking forward to the next installment
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    Loving these posts. Maybe add in what is considered low, medium, and high dosing, but otherwise solid content that is very nicely broken down.
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    Quote Originally Posted by bolt10 View Post
    Loving these posts. Maybe add in what is considered low, medium, and high dosing, but otherwise solid content that is very nicely broken down.
    indeed..i was thinking what a medium dose would be, and how much arginine could or would be added????
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    Good write-up Cooper! Thanks for the interesting info.
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    Quote Originally Posted by ELROCK View Post
    Good write-up Cooper! Thanks for the interesting info.
    lol am I barely speaking the English with you brotatos. Too not understanding how the phraseology is too flat or maybe language..how about for you to say.

    Cooper! Good write-up!!! "Man, this baby corners like it's on rails!",- Vivian aka Pretty Woman about the Lotus car.
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    Fantastic write ups Coop, loving your corner and in for more
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    I can hear the "we want more we want more" chant.
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    Quote Originally Posted by kissdadookie View Post
    I can hear the "we want more we want more" chant.
    Here ya go.

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    Quote Originally Posted by breezy11 View Post
    Yup, just found it this morning while shaking up my post workout protein and greens shake :P
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    Quote Originally Posted by mr.cooper69

    The thing is, I don't want this to be advanced discussion. I want this to be something all the regulars can understand. Am I succeeding in that so far?
    Yes - great write ups, some of the best stuff I've read in the many years I've been on AM- - you break it down in an easy to understand manner for us..Thx Coop
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    Sincere thanks to Coop. Your input is always appreciated.

    Like Tbone, I tried this stuff way back when it was all the rage. Didn't notice a thing and have never bothered with it again. Agmatine and nitrates are so much better than the days of AAKG and norvalline, it's not even funny.
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    Quote Originally Posted by bioman View Post
    Sincere thanks to Coop. Your input is always appreciated.

    Like Tbone, I tried this stuff way back when it was all the rage. Didn't notice a thing and have never bothered with it again. Agmatine and nitrates are so much better than the days of AAKG and norvalline, it's not even funny.
    Sadly AAKG and Norvalline seems to never want to go away :P
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    How much Norvaline is considered to much or a toxic dose?
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    Too many responses to read through, but what about combining norvaline and cit/mal?
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    Quote Originally Posted by 3clipseGT View Post
    How much Norvaline is considered to much or a toxic dose?
    There's insufficient data for me to make a judgment call, but I'd consider 200mg a low-medium dose

    Quote Originally Posted by FL3X MAGNUM View Post
    Too many responses to read through, but what about combining norvaline and cit/mal?
    There's no synergy so to speak
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    Quote Originally Posted by mr.cooper69 View Post

    There's insufficient data for me to make a judgment call, but I'd consider 200mg a low-medium dose
    So would you still drink purple wrathh? 100mg. Has me a little worried :/

    Edit: nm. Just read low wont do anything so I think it's ok? Haha
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    Quote Originally Posted by Afi140 View Post
    So would you still drink purple wrathh? 100mg. Has me a little worried :/

    Edit: nm. Just read low wont do anything so I think it's ok? Haha
    Totally fine
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