the guggulsterone issue

korexite · 04-25-2005, 04:12 PM

First the study that it raises cholesterol and now this study.

Why are people still putting this in supplements?

Mol Pharmacol. 2005 Mar;67(3):948-54. Epub 2004 Dec 15. Related Articles, Links

The hypolipidemic natural product guggulsterone is a promiscuous steroid receptor ligand.

Burris TP, Montrose C, Houck KA, Osborne HE, Bocchinfuso WP, Yaden BC, Cheng CC, Zink RW, Barr RJ, Hepler CD, Krishnan V, Bullock HA, Burris LL, Galvin RJ, Bramlett K, Stayrook KR.

Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. burris@lilly.com

Guggulsterone (GS) is the active substance in guggulipid, an extract of the guggul tree, Commiphora mukul, used to treat a variety of disorders in humans, including dyslipidemia, obesity, and inflammation. The activity of GS has been suggested to be mediated by antagonism of the receptor for bile acids, the farnesoid X receptor (FXR). Here, we demonstrate that both stereoisomers of the plant sterol, (E)- and (Z)-GS, bind to the steroid receptors at a much higher affinity than to FXR. Both stereoisomers bind to the mineralocorticoid receptor (MR) with a Ki value of approximately 35 nM, which is greater than 100 times more potent than their affinity for FXR. Both (E)- and (Z)-GS also displayed high affinity for other steroid receptors, including the androgen (AR), glucocorticoid (GR), and progesterone receptors (PR) with Ki values ranging from 224 to 315 nM. In cell-based functional cotransfection assays, GSs behaved as antagonists of AR, GR, and MR, but as agonists of PR. Agonist activity was also demonstrated with estrogen receptor (ER) alpha; however, the potency was very low (EC50 > 5000 nM). In addition, GS displayed activity in functional assays in cell lines expressing endogenous AR, GR, ER, and PR. These data suggest that the variety of pharmacological effects exhibited by GS may be mediated by targeting several steroid receptors.

derekmac · 04-25-2005, 04:15 PM

Nice find. I think I saw this on Pubmed about a week ago.

korexite · 04-25-2005, 04:19 PM

Quote:

Originally Posted by derekmac

Nice find. I think I saw this on Pubmed about a week ago.

I would expect that something like this would be all over the net. I would never have seen it if someone had not specifically pointed it out to me on another forum. I have always been a bit leary since all the supposedly "good" studies are done by indians, who stand to profit from "good results" and that you could never get even the abstracts on those studies. First that cholesterol study, now this. Just makes one wonder a lot about what to trust on pubmed from third world research.

derekmac · 04-25-2005, 04:24 PM

Many of the abstracts and studies about guggul are also pretty old....I think I saw one that went back to 1983. Caveat Emptor, I guess.

korexite · 04-26-2005, 03:46 PM

well thanks for reading it. Other people dont seem to take kindly to my efforts to get comment and inform.

BringnIt · 04-26-2005, 03:49 PM

Aw, I didn't mean anything personally.

derekmac · 04-26-2005, 03:50 PM

Reminds me somewhat of the glutamine issue....there has yet to be a study showing the oral efficacy of glutamine in non burn patients, or people who have diseases, and yet glutamine is still highly touted, despite the science to the contrary.

People would do well to do a little research for themselves....knowledge is power.

korexite · 04-26-2005, 03:53 PM

Quote:

Originally Posted by derekmac

Reminds me somewhat of the glutamine issue....there has yet to be a study showing the oral efficacy of glutamine in non burn patients, or people who have diseases, and yet glutamine is still highly touted, despite the science to the contrary.

People would do well to do a little research for themselves....knowledge is power.

the thing is that here, unlike glutamine where you might not get a benefit, guggulsterones look to be harmful to both gains and even slightly to health if the LDL data is correct.

systemX · 04-26-2005, 11:29 PM

Quote:

Originally Posted by korexite

First the study that it raises cholesterol and now this study.

Why are people still putting this in supplements?

Mol Pharmacol. 2005 Mar;67(3):948-54. Epub 2004 Dec 15. Related Articles, Links

The hypolipidemic natural product guggulsterone is a promiscuous steroid receptor ligand.

Burris TP, Montrose C, Houck KA, Osborne HE, Bocchinfuso WP, Yaden BC, Cheng CC, Zink RW, Barr RJ, Hepler CD, Krishnan V, Bullock HA, Burris LL, Galvin RJ, Bramlett K, Stayrook KR.

Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. burris@lilly.com

Guggulsterone (GS) is the active substance in guggulipid, an extract of the guggul tree, Commiphora mukul, used to treat a variety of disorders in humans, including dyslipidemia, obesity, and inflammation. The activity of GS has been suggested to be mediated by antagonism of the receptor for bile acids, the farnesoid X receptor (FXR). Here, we demonstrate that both stereoisomers of the plant sterol, (E)- and (Z)-GS, bind to the steroid receptors at a much higher affinity than to FXR. Both stereoisomers bind to the mineralocorticoid receptor (MR) with a Ki value of approximately 35 nM, which is greater than 100 times more potent than their affinity for FXR. Both (E)- and (Z)-GS also displayed high affinity for other steroid receptors, including the androgen (AR), glucocorticoid (GR), and progesterone receptors (PR) with Ki values ranging from 224 to 315 nM. In cell-based functional cotransfection assays, GSs behaved as antagonists of AR, GR, and MR, but as agonists of PR. Agonist activity was also demonstrated with estrogen receptor (ER) alpha; however, the potency was very low (EC50 > 5000 nM). In addition, GS displayed activity in functional assays in cell lines expressing endogenous AR, GR, ER, and PR. These data suggest that the variety of pharmacological effects exhibited by GS may be mediated by targeting several steroid receptors.

Ummm... so in simple terms this means what???

korexite · 04-27-2005, 01:45 PM

Quote:

Originally Posted by systemX

Ummm... so in simple terms this means what???

basically that it blocks the androgen receptor (the receptor that makes testosterone and other steroids "work")

and that it activates the progesterone receptor, which I beleive is why people fell "hot", basically a menapausal "hotflash"

systemX · 04-27-2005, 10:16 PM

That sucks. Although I still think that everyone will one day get there wish and be able to take a pill that has no side effects and will allow you to drop to 8% bf overnight with no lean mass loss, without modifing their diet or having to work out. (I am a smart ass, I know)

Thanks for the info.
B)

Intense501 · 04-28-2005, 11:54 AM

So would these bonds to the steroid receptors be permanent? I'm not happy to hear this because I just ordered a bottle of Tight.

velikimajmun · 04-28-2005, 11:57 AM

Quote:

Originally Posted by Intense501

So would these bonds to the steroid receptors be permanent? I'm not happy to hear this because I just ordered a bottle of Tight.

no

Kraftydog · 04-29-2005, 12:24 AM

Quote:

Originally Posted by Intense501

So would these bonds to the steroid receptors be permanent? I'm not happy to hear this because I just ordered a bottle of Tight.

no, but it appears that they would likely impair androgen binding while you were taking the supplement. not a good thing

BringnIt · 04-29-2005, 12:42 AM

"That sucks. Although I still think that everyone will one day get there wish and be able to take a pill that has no side effects and will allow you to drop to 8% bf overnight with no lean mass loss, without modifing their diet or having to work out. (I am a smart ass, I know)"

Take DNP. I mean, aside from that death issue, no real side effects there...

Jox · 04-29-2005, 02:07 AM

Quote:

Originally Posted by derekmac

Reminds me somewhat of the glutamine issue....there has yet to be a study showing the oral efficacy of glutamine in non burn patients, or people who have diseases, and yet glutamine is still highly touted, despite the science to the contrary.

People would do well to do a little research for themselves....knowledge is power.

Then again 'science' says any more than 1g/lbs of bodyweight of protein is a waste, which goes against the wealth of user experience.

derekmac · 04-29-2005, 06:16 AM

Quote:

Originally Posted by Jox

Then again 'science' says any more than 1g/lbs of bodyweight of protein is a waste, which goes against the wealth of user experience.

The true worth of a supplement is scientific evidence, combined with anecdotal feedback. Where one is lacking, then there should be doubt.

Kraftydog · 05-01-2005, 08:09 PM

Quote:

Originally Posted by Jox

Then again 'science' says any more than 1g/lbs of bodyweight of protein is a waste, which goes against the wealth of user experience.

actually some sports studies have shown benefits to 1g+/lb

korexite · 05-03-2005, 09:03 PM

comments on the study?

Red3 · 05-04-2005, 10:04 AM

I just purchased Guggulbolic in a combo with Xenadrine NRG. Has anyone actually taken it on this site? Or just read studies? I want to know real results here.

derekmac · 05-04-2005, 04:33 PM

Guggulbolic

Kraftydog · 05-04-2005, 10:05 PM

Quote:

Originally Posted by Red3

I just purchased Guggulbolic in a combo with Xenadrine NRG. Has anyone actually taken it on this site? Or just read studies? I want to know real results here.

i have used guggulsteroes, pure Z&E and guggulbolic (original). They both occasionally made me feel hot, but did little, if anything for fat loss. Given the descriptions I have read and heard the effect was progesterone hot flash like.

krazykarl · 05-05-2005, 10:11 AM

Quote:

Originally Posted by korexite

the thing is that here, unlike glutamine where you might not get a benefit, guggulsterones look to be harmful to both gains and even slightly to health if the LDL data is correct.

Finished a bottle of a syntrax product with guggle a bit ago, and recently had bloodwork done. LDL was normal.

-krazy

CitadelArmyJAG · 05-05-2005, 10:30 AM

Quote:

Originally Posted by Kraftydog

no, but it appears that they would likely impair androgen binding while you were taking the supplement. not a good thing

I wasnt a big fan of tight... didnt feel like there was enough in it to get the job done.

pu12en12g · 05-05-2005, 11:07 AM

Great thread.

Hopefully Patrick Arnold will chime in.

thagman · 05-05-2005, 01:29 PM

bump

Kraftydog · 05-07-2005, 08:34 PM

Quote:

Originally Posted by thagman

bump

back up

korexite · 05-09-2005, 04:45 PM

Quote:

Originally Posted by Kraftydog

back up

thanks

nni · 05-10-2005, 08:14 AM

this might be a dumb question, but would this make the gugul better for women?

Kraftydog · 05-10-2005, 03:06 PM

Quote:

Originally Posted by nni

this might be a dumb question, but would this make the gugul better for women?

progesterone is not usually an issue for women, they typically have more than enough. Also its not clear what kind of activity its going to have at the PR. It might have benefits for menapausal women, but where androgen activity is not such a good thing, but I think on the whole, no.