Ursolic acid - Low dose works, high dose mytotoxic

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    Ursolic acid - Low dose works, high dose mytotoxic


    New study on UA that has jut been released

    Ursolic acid directly promotes protein accretion in myotubes but does not affect myoblast proliferation.

    Ursolic acid (UA) has been recently proposed as a potential candidate for the treatment of muscle wasting conditions because of its protein sparring/anabolic effects. Despite this finding, it is unknown whether this response is the consequence of a direct effect on the muscle fibre or if it is mediated by neural or other systemic factors. In the present study, we sought to determine if UA has direct effects in skeletal muscle cells, whether it can increase myoblast proliferation and whether UA can become myotoxic at higher doses. Our results demonstrate that UA directly promoted protein accretion in cultured myotubes but did not modulate myoblast proliferation. At higher doses, UA compromised cell viability in both myoblasts and myotubes. We conclude that the anabolic properties of UA seen in vivo and in vitro are likely a direct effect on the muscle cell, but at higher doses, the benefits decline in favour of a myotoxic outcome.
    Makes AppNuts Fat Free even more appealing and should serve as a caution for those who are mega dosing the other UA products.

    Remember folks, more isnt always better
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    How much UA are we talking as being to much?
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    What's the PMID?
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    Quote Originally Posted by JudoJosh View Post
    Remember folks, more isnt always better
    People really ignore this. If "three is good then six should be twice as good" mentality.
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    Quote Originally Posted by Rodja View Post
    What's the PMID?
    PMID: 22411156
    "The only good is knowledge and the only evil is ignorance." - Socrates
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    Quote Originally Posted by JudoJosh View Post
    PMID: 22411156
    Danke.
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    Quote Originally Posted by Rodja View Post
    Danke.

    haha
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    I was on to this in PA's forum too...a lot of people going against label and then complaining about results never made sense to me.
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    Does anyone have full access to the paper to understand how much they mean with lower and higher doses?
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    Quote Originally Posted by menphisdaemon View Post
    Does anyone have full access to the paper to understand how much they mean with lower and higher doses?
    ill try to find out. i know Fat Free is right in the middle dosage wise
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    Quote Originally Posted by R1balla View Post
    ill try to find out. i know Fat Free is right in the middle dosage wise
    Right in the middle dosage of what? what was the high and low dose used in the study anyone knows?
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    The study used several ursolic acid levels. It did not become myotoxic until > 10uM. With the current solubility issues surrounding ursolic acid its highly doubtful we are getting anywhere near those levels with oral ursolic acid.
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    You gotta take in a hell of a lot of UA to become toxic. But its effectiveness isnt directly correlated to concentration rather the environment it exists in. UA is much more effective when IGF levels are increased. This is a big part of why DHEA had been added to the mix.
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    im sick of this! everything now a days is bad for you
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    Quote Originally Posted by rochabp
    im sick of this! everything now a days is bad for you
    I agree!
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    I forgot were I read it but 1000mg a day should be Max for 8 weeks and min around 250mg a day I'll try to find out were I read it in a few still at work.
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    I read it on anabolics e-book edition. So I wonder what's doses this tests were done at
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    Quote Originally Posted by sepulvd View Post
    I read it on anabolics e-book edition. So I wonder what's doses this tests were done at
    This study was in vitro. You can only extrapolate what levels you might need to reach in serum to even get enough of an idea as to what real world dose this might translate. And that's not even considering the pharmacodynamics of oral ursolic acid.

    In other words this study has little real world application because of the limited pk/pd research on ursolic acid.

    It's not bad for you either, so I'm unsure why people are getting that impression. Throw the word "toxic" in any study and people **** their pants.
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    Quote Originally Posted by OrganicShadow View Post
    You gotta take in a hell of a lot of UA to become toxic. But its effectiveness isnt directly correlated to concentration rather the environment it exists in. UA is much more effective when IGF levels are increased. This is a big part of why DHEA had been added to the mix.
    Oral DHEA increases skeletal muscle igf-1? Do tell...
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    Quote Originally Posted by Royd The Noyd View Post
    The study used several ursolic acid levels. It did not become myotoxic until > 10uM. With the current solubility issues surrounding ursolic acid its highly doubtful we are getting anywhere near those levels with oral ursolic acid.
    agreed
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    Studies Ive found range in doses with test patients from 50mg-1600mg. All stating the potential effects of DHEA to increase serum IGF. From there, the environment of increased IGF will positively reinforce the action of UA to block cellular signals for muscular atrophy. While both IGF and UA are preventing degradation of mRNA proteins in skeletal muscles they lower serum triglycerides and adiposity.
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    Quote Originally Posted by OrganicShadow View Post
    Studies Ive found range in doses with test patients from 50mg-1600mg. All stating the potential effects of DHEA to increase serum IGF. From there, the environment of increased IGF will positively reinforce the action of UA to block cellular signals for muscular atrophy. While both IGF and UA are preventing degradation of mRNA proteins in skeletal muscles they lower serum triglycerides and adiposity.
    I believe that the serum igf increases from oral dhea supplementation in young men is negligible. Particularly because they already produce sufficient dhea. We see small igf serum increases in older men because they already have diminished dhea levels from aging (ex PMID 9008662). That's assuming serum IGF even correlates directly with skeletal muscle igf which is really what matters for a body composition enthusiast. Essentially you have a theory, which is fine by me since we as supplement companies have to use sound theory to create innovative products.
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    Quote Originally Posted by Royd The Noyd View Post
    I believe that the serum igf increases from oral dhea supplementation in young men is negligible. Particularly because they already produce sufficient dhea. We see small igf serum increases in older men because they already have diminished dhea levels from aging (ex PMID 9008662). That's assuming serum IGF even correlates directly with skeletal muscle igf which is really what matters for a body composition enthusiast. Essentially you have a theory, which is fine by me since we as supplement companies have to use sound theory to create innovative products.
    He has a hypothesis, not a theory.
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    Quote Originally Posted by Torobestia View Post
    He has a hypothesis, not a theory.
    Nope, its a theory.

    Hypothesis = educated guess
    Theory = explanation of why something is happening with evidence to support it.

    The claim made is DHEA will increase IGF levels (hypothesis). This evolves into a theory when they cite evidence indicating raised serum IGF levels by DHEA supplementation and then go on to hypothesize (or make an educated guess) that the serum IGF correlates with muscular IGF and that this increase on IGF will positively reinforce the action of UA to block cellular signals for muscular atrophy.


    So the theory is - IGF (as a result of DHEA supplementation) and UA will prevent the degradation of mRNA proteins in skeletal muscles they lower serum triglycerides and adiposity.

    Its a little more then just a guess which makes it a theory and not a hypothesis. But thanks for your contribution to the thread
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    Right. The theory is based on two seperate groups of research then bridged to a single conclusion.

    I state when I'm hypothesizing my own opinions. Never in the above did I say "I think"
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