Monday, March 19, 2012

Ursolic Acid and The Narrow Line Between Anabolism and Myotoxicity: +25% Increased Protein Accretion in In-Vitro Study, But Cell Death With 2x "Effective" Dose

Image 1: "An apple a day keeps the doctor away!" And though the ursolic acid in its peel may be part of the underlying mechanism, this does not make it a "natural anabolic", but rather another item on the list of "healthy stuff from real food"
The number of purported natural anabolics increases year by year. Against the background that most of these products are nothing but supplemental nonstarters in shiny bottles and boxes with "non-FDA approved" promises of "unparalleled muscle growth" on them, the recent release of a broad range of ursolic acid supplements must already be considered a "highlight". With a peer-reviewed rodent studies backing its anti-catabolic, pro-anabolic properties (Kunkel. 2011), it appears as if ursolic acid could be more than another potent placebo. And if we put things into perspective, in the end its potential beneficial effects on skeletal muscle hypertrophy are rather negligible compared to its previously proposed role as a therapeutic compound in various conditions such as Alzheimer’s diseases (Wilkinson. 2011), cancer (Kim. 2000; De Angel. 2010; Pinon. 2011), and diabetes (Zhang. 2006; Jayaprakasam. 2006).

More ain't more, but toxic! And even less is probably more than you can get.

Only recently, Vandré Casagrande Figueiredo and Gustavo A. Nader were able to confirm the muscle building effects in an in-vitro study using C2C12 myoblasts which were incubated with different concentrations of ursolic acid for 72h (Figueiredo. 2012).
Figure 1: Protein content and cell viability after 72h incubation with different concentrations of ursolic acid (in µM); light bars p > 0.05, statistically non-significant (data calculated based on Figueiredo. 2012)
As you can see in figure 1, this treatment lead to dose-dependent increases in protein accretion in the muscle cells. These increases reached statistical signficance only in the 10µM group (their real-world significance is even more questionable, as we don't know if similar concentrations can even be achieved by oral administration of ursolic acid).

The profound loss of protein in the higher dose groups and the subsequent decrease in cell viability, on the other hand, are statistically highly significant. Their real world significance does yet appear to be even more questionable, after all, it is rarely possible to double the serum concentration of a given substance by just ingesting twice as much. At the dosages that are present in the currently available supplements myotoxicity, as it was observed in this in-vitro study, is thusly probably not a real concern.

No reason to be afraid, but no reason to expect grandiose results, either

Image 2: These muscles were not build on ursolic acid - that's for sure.
In other words, while the study at hand did help us to elucidate the underlying mechanism of previously reported benefits under mostly atrophic (=muscle loss) conditions, its overall real-world significance in view of the negative, but also in view of the positive effects appears to be more than limited. If you also take into consideration that the scientists were able to rule out that ursolic acid exerts hyperplastic (cell proliferation) effects on skeletal muscle tissue, that its "muscle building" effects (referring to the increased protein accretion observed in the study at hant) was highly dependent on the presence of additional growth factors in the culture medium and that ursolic acid did not increase the myocyte RNA levels, it remains questionable whether the ingestion of respective (most certainly underdosed) supplements will produce any significant improvements in training and diet induced skeletal muscle hypertrophy.

In the end, the new data stand in line with the observations of Kunkel et al. who identified an increase in skeletal muscle insulin sensitivity and subsequent upregulation of the IGF-1 induced growth response as the underlying cause of the atrophy-inhibiting effects or ursolic acid. What can be said for sure, however, is that the currently available OTC supplements are in no way "muscle builders". According to the currently available research, they should rather be filed under "health supplements", along with alpha lipoic acid and the like. Now, that does obviously not exclude that the health improvements - above all the improvements in insulin sensitivity could not help you build muscle - the label "natural anabolic" does yet still appear largely misplaced.