T Nation

Ursolic Acid

Anyone have any experience with this supplement? Appears to have some interesting health and muscle building capabilities. I copied and pasted some info below (lots of info actually). Go to bottom for shortened version.

The first and foremost study regarding Ursolic Acid is one that has garnered a lot of press lately. It was published in the very prestigious journal Cellular Metabolism, and the research was performed by scientists from the University of Iowa. They used techniques to identify genes that were turned on and off by two muscle catabolic stressors ? starvation and denervation (think of spinal cord injury).

They then turned to a huge database of gene (mRNA actually) expression signatures from 1300 candidate chemicals and after screening for which turned the right genes on (the anabolic ones) and turned the right genes off (the catabolic ones) they came to one that stood out ? Ursolic acid. The researchers then gave Ursolic acid to starved mice and to denervated mice and they found that it indeed powerfully act as an anti-catabolic. They lost much less muscle than control mice.

The cool part is they went on to see if it acted as an anabolic. That is, they wanted to see what it did to normal mice on a normal diet. They feed Ursolic acid to a group of mice for 5 weeks and then found that their muscles grew around 15% bigger than a control group of mice over the same period. The muscle fibers themselves appear markedly bigger under the microscope, so this was hypertrophy going on. The muscle was fully functional as well, which was demonstrated by measuring grip strength. The Ursolic mice had a significantly stronger grip (I guess the made the mice hang on a tiny chin up bar till they dropped or something).

Now you probably think that since the mice grew bigger muscles they probably weighed more than the control mice. Such was not the case. That is because there was almost a proportional decrease in fat mass in respect to the increase in muscle mass. Essentially, the body was using the fat to fuel the energy needed to build the muscle!! That is what is known as a recomposition effect and it is seen with agents such as clenbuterol. It is not really seen with anabolic steroids though, since although ?roids? are great for building muscle, they don?t really affect fat mass in such an obvious and direct manner.

The researchers finally looked at how Ursolic acid worked (I told you, this paper is extremely thorough and comprehensive). Examination of which genes got turned on and which got turned off (via examining mRNA expression signals) showed strong signals for 18 being turned on and 51 being turned off. Two of the most potent ones to be turned off were ones strongly associated with muscle atrophy - atrogin-1 and MuRF-1.

The most potent one to be turned on was the one that encodes IGF-1 in muscle. The local production of IGF-1 is perhaps the single most instrumental process in the muscle hypertrophy response as it initiates the key steps of satellite cell recruitment into new myonuclei and protein synthesis via the kinase Akt.

So that paper was great and it?s what really convinced me this stuff has huge potential to be the real deal (once we figure out how best to use it and what the best dose is ? and you guys are gonna help me with that). But there is other research on Ursolic acid that has been published showing some other really cool things. A 2008 study demonstrated that Ursolic acid possesses good aromatase inhibitory activity in-vitro, meaning that it can potentially help reduce estrogen production in the body and increase testosterone. It also has been shown to be anabolic on bone via stimulation of osteoblast formation.

Of particular interest to me, a 2010 paper published in Bioorganic and Medicinal Chemistry showed that Ursolic acid and some of its derivatives are potent and selective inhibitors of the tissue specific cortisol elevating enzyme 11b-HSD1. And finally, if you are a drinker than you might be interested to know that a 2006 paper from Life Sciences showed that Ursolic protects the liver from toxicity due to ethanol consumption. And then there are anti-cancer, anti-oxidant, anti-viral??.the list really goes on and on.

Have Scientists Finally Discovered a Bona-Fide Natural Anabolic?

Scientific journal articles are released all the time that purportedly show amazing things from natural compounds. I have to break the news to you - most of them are bull****. Research is full of poorly designed studies, poorly carried out studies, and even outright fraud. It?s not that hard to weed out the ones which have a good possibility of being legitimate and which ones probably aren?t worth much attention. You can look at the study design - does it thoroughly take all variables into account?

And what about the authors and the sponsors of the study ? might there be a possibility of conflict of interest that may make you question the integrity of the author?s motives? And where is it published? Is it published in a major journal that has a high impact factor (a figure used to gauge the quality of a journal that is measured by accounting for the number of times articles are cited in other publications)?

I bring to you in this month?s column an article(Cell Metab. 2011 Jun 8;13(6):627-38.) that I find to be one of the most exciting pieces of research in the area of muscle building and natural products that I have seen in a long time ? if ever. It comes from a journal called Cell Metabolism, which has a very impressive impact factor of 18.207.

The thoroughness of the study and the obvious non-biased nature of the findings definitely caught my eye. The study examines a natural compound called Ursolic Acid which is found in many plants and foods such as apple peels (where it apparently is particularly abundant). This research impressed me so much that I decided to rush the ingredient to market through my brand E-Pharm, and by the time you read this it should be on the shelf under the name Ursobolic (and surely other companies will be releasing their versions as well).

So I am going to attempt to discuss this article and translate the hard science into layman?s terms the best I can. I hope you find it as interesting and impressive as I do.

Ursolic Acid and Muscle Atrophy
Skeletal muscle is a dynamic tissue that can undergo rapid growth (hypertrophy) or rapid shrinkage (atrophy) depending on the physiological conditions present in an animal or human. Situations where atrophy can prevail include starvation, nerve injury (i.e. spinal cord), diseases such as AIDS or cancer, and organ failure (heart, liver, kidney etc). To the contrary, muscle growth prevails during developmental stages and in response to stimuli such as exercise and certain drugs.

These two phenomena ? hypertrophy and atrophy ? are driven by a multitude of genes which become expressed (or repressed) in response to any one of the aforementioned physiological triggers.
The scientists that performed the study I am discussing decided to exploit these genes in a screening study to investigate small molecules which may have effects on muscle wasting. They began by mapping mRNA expression signatures in muscle of people subjected to atrophy producing stress.

Basically what this means is they starved a group of people, took biopsies of their muscles, and examined which muscle genes got activated and which got repressed. They detected hundreds of changes in mRNA expression in response to the fasting, and while most of these have physiological roles that have yet to be determined some of them of them encode proteins with known functions in muscle metabolism such as

Catabolic mRNAs (increased) ? fat oxidation, protein synthesis inhibition, glutamine transport, ubiquitin mediated proteolysis
Anabolic mRNAs (decreased) - glycogen synthesis, polyamine synthesis, angiogenesis, mitochondrial biogenesis
Armed with this valuable data on muscle genes the researchers then turned to an interesting technique of screening bioactive molecules that uses a tool called ?connectivity maps?. These connectivity maps utilize a vast database on over 1300 small compounds and their effects on gene expression on cells under various conditions. The map uses algorithms that allow researchers to screen for compounds that affect any mRNA expression signatures of interest they may have.

In the case of the researchers in the study under discussion, the vast gene expression data initially collected was first reconciled with similar data on mouse muscle atrophy (the connectivity map utilizes mouse data), and then after the connectivity map magic was done two compounds stood out ? Metformin and Ursolic Acid.
At this point they decided it was time to ?prove the pudding? so to speak, so they administered metformin and ursolic acid to mice and then starved them for a day. They found that the control mice lost 9% of their muscle weight.

Administration of Metformin had no effect on this. Ursolic acid treatment however dramatically reduced the muscle loss so that a net loss of only 2% of muscle weight was observed (and I would imagine some of this is due to water loss).

Since the fasting model of muscle atrophy successfully singled out Ursolic Acid as a strongly preventative bioactive molecule the researchers decided to examine another the model of muscle denervation, which was represented by the induction of spinal cord injury on some unfortunate mice. The mRNA signatures from this model of atrophy had some overlap with those seen in the fasting model, however there were substantial differences.

And when the author?s queried the connectivity map they found once again that Ursolic Acid came out as a top candidate. Most interesting however was the fact that Ursolic Acid was the only compound identified by both the fasting and the muscle denervation search strategies.

At this point of course it was time to once again turn to in-vivo experimentation for some real world validation, and just as in the case of the fasting model they found Ursolic Acid passed the test. The sciatic nerves in the left hindlimb muscles of mice were dissected, and after a period of time these muscles were compared to the contralateral un-dissected right hindlimb muscles. Control mice exhibited a marked atrophy of the dissected muscle in relation to the un-dissected muscle, but when Ursolic Acid was administered this atrophy was greatly diminished.

Ursolic Acid and Muscle Hypertrophy
A compound that can prevent muscle loss in conditions of wasting is of enormous medical value and these researchers discovered one that has the ability to do so within the physiological environments of two somewhat disparate pathological conditions. Some readers of this magazine may find this very interesting but muscle building is obviously where their real fascination lies, and preventing muscle loss in catabolic states is quite a different animal that building more mass in healthy living creatures.

Lucky for us these researchers tested Ursolic Acid in intact healthy mice. They simply fed the mice the compound in varying concentrations and after a period of five weeks they sacrificed them and compared their dissected muscles to control mice. Indeed, Ursolic Acid clearly had anabolic effects. The muscles were bigger (up to around 15% bigger) as were the muscle fibers themselves - which represents hypertrophy. But not only were the muscles bigger - measurements of grip strength showed they were stronger as well. That wasn?t the only interesting thing though.

Ursolic Acid and Fat loss
You figured that if these mice ingesting ursolic acid got such bigger muscles they probably gained weight. Such was not the case. To investigate this further the researches repeated the experiment but this time they fed the Ursolic Acid for 7 weeks instead of 5 weeks. Examination of muscle showed similar anabolic effects to the first time but when they looked at fat tissue they noticed dramatic mass reductions.

In fact the reductions in fat mass were pretty much proportional to the gains in muscle mass. Such an inverse response of tissues is indication of a classical ?repartitioning effect?. No differences in food intake were seen between Ursolic Acid mice and control mice, and examination of adipocytes (fat cells) revealed a marked reduction in size. Additionally, plasma cholesterol and triglycerides were reduced in Ursolic Acid treated mice.

How Does Ursolic Acid Work?
Ursolic Acid causes muscles to grow in healthy animals and minimizes muscle wasting in compromised animals - but how? The researchers tackled this question by once again examining mRNA levels in muscle (basically looking at which genes got turned on and which got turned off). Out of more than 16,000 mRNAs analyzed they found strong signals for 18mRNAs being decreased and 51 mRNAs being increased.

Amongst the ones that were most potently decreased were two that are strongly associated with muscle atrophy ? atrogin-1 and MuRF-1. On the other hand, one of the most highly upregulated mRNAs was for the one that encodes Insulin Growth Factor-1 (IGF-1). Autocrine (locally) produced muscular IGF-1 as you may know is considered one of the key signals in muscle growth and regeneration. Ursolic Acid was also shown to enhance the downstream effects of IGF-1, demonstrated by measurements of increased levels of Akt phosphorylation.

Will Ursolic Acid Work For Bodybuilders?
This is the key question isn?t it? Unfortunately I don?t have a definitive answer at the time I am writing this article. The research on it (which actually goes beyond what I have presented here) is so impressive to me that I firmly believe the stuff has to do something. It?s just a matter of figuring out dose and figuring out what scenarios the compound will be most useful in. So keep an eye out for this stuff. You surely be hearing about it more in the future. I think this stuff could be the ?real deal?


Ursolic Acid is believed to:

Reduce fat storage and increase fat burning, through inhibition of pancreatic lipase and enhanced lipolysis in fat cells. [1]

Reduce the conversion of blood sugar to fat, through inhibition of fatty acid synthase. [2]

Increase energy reserves in muscles by enhancing glycogen storage. [3]

Reduce abdominal (visceral) fat through the inhibition of 11bHSD1. [4]

Be anti-carcinogenic through inhibition of the STAT3 activation pathway. [5]

Lower cholesterol through the activation of peroxisome proliferator-activated receptor (PPAR)-α. [6]

Reduce estrogen levels through aromatase inhibition. [7]

Strengthen bones by enhancing differentiation and mineralization of osteoblasts. [8]

Increase lean muscle mass through enhanced sensitivity to IGF-1 and insulin, and the inhibition of atrogin-1 and MuRF1. [9]


[1] Arch Pharm Res. 2009 Jul;32(7):983-7.
Anti-lipase and lipolytic activities of ursolic acid isolated from the roots of Actinidia arguta.

[2] Biochem Biophys Res Commun. 2010 Feb 12;392(3):386-90.
Evaluation of inhibition of fatty acid synthase by ursolic acid: positive cooperation mechanism.

[3] Issled. Mekh. Vliyaniya Bal’neol. Faktorov Regul. Sist. Org. (1976), 101-2.
Effect of ursolic acid on the energy and carbohydrate metabolism of muscles

[4] Bioorg Med Chem. 2010 Feb 15;18(4):1507-15.
11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches.

[5] Mol Cancer Res. 2007 Sep;5(9):943-55.
Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells.

[6] Bioorg Med Chem Lett. 2011 Oct 1;21(19):5876-80.
Ursolic acid is a PPAR-α agonist that regulates hepatic lipid metabolism.

[7] Eur J Med Chem. 2008 Sep;43(9):1865-77.
Evaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition.

[8] Pharmacol Res. 2008 Nov-Dec;58(5-6):290-6.
Anabolic activity of ursolic acid in bone: Stimulating osteoblast differentiation in vitro and inducing new bone formation in vivo.

[9] Cell Metabolism. Volume 13, Issue 6, 8 June 2011, Pages 627-638
mRNA Expression Signatures of Human Skeletal Muscle Atrophy Identify a Natural Compound that Increases Muscle Mass

Press articles:

Apple peel helps build muscle and control weight - Daily Mail

An apple a day keeps your body toned and slender - Telegraph

Can a compound in apple peel help build muscle? - Health News - NHS Choices

Ursolic acid: apple anabolic - Ergo-Log

I just received this product in the mail, I have read and heard the same claims as you have posted. So will see what happens during dieting down if I keep more lean muscle tissue.Thanks for posting this.

great news sprtsgirl, please keep us updated.

I’ve taken it on and off for quite some time now. Decent results as far as appearance goes. Not dramatic but I can see a fuller yet still lean appearance when taking it. As far as actual body comp and/or dropping fat at high calories I didn’t experience anything drastic, mild at best. I did notice that it works very well as an anti inflammatory for me anyway. All of my aches and pains disappear when I take it. Coincidentally just received 8 bottle in the mail.

Piques my curiosity a bit, definitely gonna follow along with anyone sharing experiences…


Any word on ursolic acid? Seems/seemed to have some solid science/hype. Anyone have success with it?

I was recently researching about berberine, and posted some stuff in another thread, and preliminarily, it looked good, but apparently it activates atrogin-1 – BUT Ursolic acid reduces it (atrogin-1)!

Kunkel et al. [29] found that acute ursolic acid treatment of fasted mice reduced Atrogin-1 and MuRF1 mRNA levels in association with reduced muscle atrophy. Similarly, chronic ursolic acid treatment of unstressed mice reduced Atrogin-1 and MuRF1 expression and induced muscle hypertrophy.

[quote]BulletproofTiger wrote:
Any word on ursolic acid? Seems/seemed to have some solid science/hype. Anyone have success with it?

I was recently researching about berberine, and posted some stuff in another thread, and preliminarily, it looked good, but apparently it activates atrogin-1 – BUT Ursolic acid reduces it (atrogin-1)!

Kunkel et al. [29] found that acute ursolic acid treatment of fasted mice reduced Atrogin-1 and MuRF1 mRNA levels in association with reduced muscle atrophy. Similarly, chronic ursolic acid treatment of unstressed mice reduced Atrogin-1 and MuRF1 expression and induced muscle hypertrophy.


The bioavailability when taken orally is horrible. I’ve tried both the oral version and the “spray on” version…spray on is way better supposedly, but only if you absorb topicals well. I am one who doesn’t, and so the topical didn’t do anything of appreciable results for me (i.e. when compared to what I’m already doing with I-3G, MAG-10, and Plazma).

My results however are not the say all be all whatsoever. There are some who have taken the oral version with fats and had decent results apparently. I’ve tried the oral version both with and without fats…not that much of a difference for me.

The topical version has good science behind it…the solubility issue was addressed but for a topical only. But again, it is effective IF you have skin that will absorb it well. My didn’t unfortunately.

I’m hoping the collective chemistry minds at Biotest will be able to resolve the oral bioavailability issue in the future.

Thanks for your feedback Buffd Samurai. Yeah, poor bioavailability. that’s what I read was the biggest issue with it. Fats could help. Perhaps bacon is the answer? when isn’t it though? I did see that there was a transdermal product out there too, which sounded promising. It might be something I would consider down the road. I didn’t realize that some respond better than others to transdermals, though that does make sense.

Maybe the suppository route would be the way to go? Anybody wanna be the guinea pig, or admit they’ve already tried this? Lol. I’m not sure if the chemistry would technically lend itself to this. would it??.. On that note, here’s a a funny study with awesome results: http://www.ncbi.nlm.nih.gov/pubmed/22696033