Ursolic Acid, Leucine or Placebo for mTOR, IGF-1, Irisin, Size & Strength Gains & Fat Loss? Plus: Tart Cherry Powder as Anti-Oxidant Immune Protector for Athletes

Weights are better than pills, but in some cases, they can also work synergistically.

A new month, a new exercise & supplementation research overview for the "SuppVersity Short News". In today's installment I am going to highlight the latest evidence for the beneficial anti-oxidant & immuno-protective effects of tart cherry powder in endurance athletes. I am going to discuss the disappointing results of a comparison between leucine and ursolic acid as mTOR-elevating, IGF-1 receptor modulators in the post-workout window. And I am going to contrast these findings to the results of a non-sponsored chronic resistance training + ursolic acid intervention from a group of Korean scientists.

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Obesity Research Upd. Nov. '14

Exercise Res. Upd. Nov '12(1)

Exercise Res. Upd. Nov '12(2)

Nutrition Res. Update Nov. '14

Weight Loss Tricks & More

Reductive Stress, Iron & the Military

• Tart cherry powder as anti-oxidant immuno-protector - Scientists from the Texas A&M University reported at the Eleventh International Society of Sports Nutrition (ISSN) Conference and Expo that the provision of tart cherries, not as whole fruits, but in 480 mg capsules that contained a freeze dried powder (one capsule daily), for 10 days leading up to a half-marathon, the 27 endurance trained or triathlete (21.8±3.9 yr, 15.0±6.0% body fat, 67.4±11.8 kg) men (n=18) and women (n=9) completed in less than one hour lead to a significant reduction of the immune response to exercise. In particular, the statistical analyses of the data revealed a...

  "[...] significant group x time quadratic effect [...] for WBC [white blood cell count] (p=0.034) [and] a trend toward a significant delta value based on group assignment for WBC (p=0.09)" (Goodenough. 2014).

  In spite of the fact that the mitigated immune response following exercise did, as Goodenough et al. point out "correlate with the decreased catabolic response indicated by BUN/Cr ratio and cortisol levels reported in a companion abstract", and notwithstanding the results of a similar study which found that
  

  "acute supplementation with powdered tart cherries over the 7 days leading up to, during, and 2 days after intense resistance exercise helps to minimize post-training perceptions of pain in the most biomechanically loaded regions of the quadriceps muscle group associated with the back squat compared to a placebo" (Levers. 2014),

  the overall benefits are probably negligible for normal trainees. For training junkies and professional athletes, though, the ameliorated stress and immune response, as well as a minor decrease in pain may yet be good reasons to give tart cherry supplements a try.
  

Homebrew blackberry "supplement" inhibits lipid oxidation.

In case you're not into tart cherries, a recent non-sponsored study that does not use a commercial supplement from the Islamic Azad University (Niloofari. 2014) shows that you can also boil 100g blackberries with some water for 10 minutes, then cool them and place them in a sealed containers in order consume 100ml of the black- berry "soup" daily. In said study the consumption of this extract lead to a significant reduction in the producton of lipid oxidation products in obese subjects during a standar- dized resistance training program. Accordingly, we can assume that this "homebrew" supplement will have similar protective effects on the cell membranes as the capped tart cherry extract from the perviously discussed study.

• Ursolic acid or leucine, what's more anabolic on paper? Yes, there is a good reason I underlined the words "on paper". Why? Well, the experiment David Church, Neil Schwarz, Mike Spillane, Sarah McKinley, Tom Andre and Darryn S Willoughby conducted may employ a randomized, cross-over design, but still investigated only the acute effects of 3g leucine (LEU), ursolic acid (UA) or placebo on IGF-1 (a serum regulator of MPS) and the Akt/mTOR pathway.
  
  The 9 apparently healthy, resistance-trained [regular, consistent resistance training (i.e. thrice weekly) for at least 1 year prior to the onset of the study] men between the ages of 18-30 who had volunteered to participate in this study consumed the supplements immediately afer a lower-body resistance exercise that involved 4 sets of 8-10 repetitions at 75-80% 1-RM on the angled leg press and knee extension exercises. A venous blood sample was obtained before, and 0.5, 2, and 6 hr post-exercise, whereas a vastus lateralis muscle biopsy was obtained before and 2 and 6 hr post-exercise. 
  

  

  Figure 1: the results of the ursolic acid vs. leucine comparison are not exactly exciting (Church. 2014).

  The analysis of these blood and muscle samples revealed that there were no differences  observed among the three "supplements" (one of them being the placebo) for serum IGF-1 (p > 0.05), the expression of IGF-receptors or the phosphorilation of Akt, and p70S6K (p > 0.05).
  
  The only significant difference the researchers observed was a significant increase in phosphorylated mTOR in response to the 3g of leucine compared to UA and PLC (p = 0.001).
   
• Ursolic acid: Different study different outcome - In the defense of ursolic acid it should yet be mentioned that Hyun Seok Bang et al. recently found that the chronic supplementation with 3x450mg/day of ursolic acid lead to concomittant increases in serum irisin and muscle strength, as well as impressive reductions in bod fat in twenty-four Korean men with over 3 years of resistance training experience.
  

  

  Figure 2: Changes in body composition (left) and IGF-1 & irisin levels (right) in response to 8 weeks of resistance training + placebo or resistance training + 3x450mg/day of ursolic acid (Bang. 2014).

  As you can see in Figure 2, significant increases in IGF-1 weren't observed in this study either. Accordingly, Church et al. may simply have been betting on the "wrong anabolic horse" and the chronic effects like the strength gain and fat loss Bang et al. observed in their trained subjects alluded them due to the nature of study, i.e. an acute vs. chronic exercise supplementation regimen.

BCAAs Don't Build Muscle, Study Says | Learn more

Bottom line: In view of the fact that the ursolic acid studies teach us not to judge a supplement by an acute / short-term study I refuse to make a commendation for or against tart cherries - no matter, whether they're fresh or powdered.

What I am willing to admit, though, is that the study by Bang et al. (2014) yielded pretty impressive results. Results that are not yet enough to fully convince me that all the hilarious claims you will find on ursolic acid supplements are true, but results that will have me keep an eye on future studies investigating the effect of chronic ursolic acid supplementation on body composition and physical performance | Comment on Facebook!

References:

• Bang, Hyun Seok, et al. "Ursolic Acid-Induced Elevation of Serum Irisin Augments Muscle Strength During Resistance Training in Men." The Korean Journal of Physiology & Pharmacology 18.5 (2014): 441-446.
• Church, David, et al. "A comparison of the effects of ursolic acid and l-leucine supplementation on IGF-1 receptor and AKT-mTOR signaling in response to resistance exercise in trained men." Journal of the International Society of Sports Nutrition 11.Suppl 1 (2014): P19.
• Goodenough, C., et al. "Powdered tart cherry supplementation mitigates the post-exercise immune response with reduction in total antioxidant status and serum triglyceride levels following an acute bout of intense endurance exercise." Journal of the International Society of Sports Nutrition 11.Suppl 1 (2014): P34. 
• Levers, K., et al. "Powdered tart cherry supplementation demonstrates benefit on markers of catabolism and muscle soreness following an acute bout of intense lower body resistance exercise." Journal of the International Society of Sports Nutrition 11.Suppl 1 (2014): P31. 
• Niloofari, A., Et Al. "Responses Of Oxidative Stress Indices To Resistance Exercise After Blackberry Extract Supplementation." IJBPAS 3.12 (2014): 2798-2810.

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.