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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• 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.

It's in the Peel - The Protective Hull of These 61 Super Fruits Can Ward Off Cancer: Prunes, Plums, Jujube, Kiwi, Pitaya, Apple, Banana, Lemon, Cherry, Kumquat, Pomelo,...

Peru Ground Cherries could be among the most potent fruity anti-cancer agents nature has to offer.

In all the hoopla around "anti-nutrients", people tend to forget that the majority of the hailed phenols, flavenoids etc. serve the very same purpose, they protect the fruit of certain plants. For a recent study from the School of Public Health and the Chinese Academy of Sciences in Guangzhou, as well as the Peking Univerity Fang Li et al. have now compiled an extensive list of fruits, their peels, pulp and seeds and the corresponding anti-proliferative activity, you may want to use as an anti-cancer shopping guide, when you are grocery shopping... and if you do so, don't peel them: the protective peel is where nature stores most of the stuff that kills cancer cells by having them suffocate in their own reactive oxygen species!

Keep in mind, while the fruits can kill cancer in the petri dish you would be asking too much if you expect to cure existing cancer by just eating one or to servings of the top items on the list below per day. In conjunction with the nutrition & exercise tips you receive on the SuppVersity every day, they may yet contribute their share to render you "cancer proof".

Table 1: Anti lung-, breast-, liver- and colon-cancer activity of 61 fruits,  or rather their pulp, their peel and their seeds; marked in green are all values that are larger than the mean + 60% of the standard devidation (Li. 2013)

I have been thinking for quite some time about the optimal way to present the data, to pick a TOP10 or to come up with a selection and then realized that I - if I were in your position - would like to take a look at the data myself.

Instead of telling you what I thought were the most remarkable results I did thus decide to simply confront you with the complete data marking every value that is at least 60% above the mean + one standard deviation in green and ordering the data by the mean protective effect against the three different cancer types (lung, breast, liver, colon cancer) the researchers have tested for.

If you just take a cursory look at the data, the most striking observation the scientists made is unquestionably, the overall potency of the fruit polyphenols. What you have to keep in mind though is that we are talking about in-vitro studies and direct exposure to dosages of 50.09–141.79 mg/mL, as they were necessary to actually kill breast cancer cells are probably something you will never achieve no matter how many Peru ground cherries you eat. With the latter being among the most potent fruity anti-cancer "meds" we have, it is obvious that the question we will still have to answer pertains to the effects of actually eating any of these items.

It appears out of question that it's not going to hurt you. It should also be obvious that eating a packed of cherries is not going to rid you of existing cancerous growth. On the other hand, there is already plenty of evidence that

• cherries (in this case tart cherries) administered in an extract form, can reduce the risk of colon cancer in rodent models (Kang. 2003)
• polyphenol-rich cloudy apples juices can protect against gastric diseases associated with cancer formation (Graziani. 2005)

etc. The picture that's emerging though is that the in-vivo effects of the above and other fruit polypenols are more or less locally, namely in the gut, where the individual cell is directly exposed to a high amount of the active ingredients in the respective fruit. To achieve maximal benefits and actually battle cancer in other parts of our body than the gut, it may thus be necessary to isolate the molecules, compound them and inject them locally in the the cancerous tissue...

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Bottom line: While consuming high amounts of these anti-cancer fruits will have a plethora of health benefits, which will eventually protect you from cancer in all parts of your body, using them as a druglike medicine in our "war against cancer" would warrant extraction and isolation procedures that allow us to apply them in high concentrations to certain parts of our bodies.

I would bet money that all of the "superfruits" in the list above, also help to avoid prostate cancer

Suggested read & podcast: Last weeks' special issue of the SuppVersity Science Round-Up on prostate cancer is certainly something you either have remembered, when you went through the items on the list. And yes, while the scientists did not test for it, you bet that all of the "superfruits" in the list will also be good for your prostate. And just in case you missed the last installment of the Science RoundUp, I'd highly recommend you briefly go back to the corresponding seconds to read and listen to all the details | learn more about prostate cancer...

Although I doubt that isolating the nutrients and developing corresponding delivery systems entails insurmountable technical difficulties (in fact corresponding nano-technology would probably be available, already; cf. Khandelia. 2013), I am pretty sure nobody is going to do this; after all, the compounds themselves would not only be non-patentable, because naturally sourced, they would also compromise the sales of conventional cancer drugs and are thus a red rag to any of the big players in the business public health has become.

References:

• Graziani G, D'Argenio G, Tuccillo C, Loguercio C, Ritieni A, Morisco F, Del Vecchio Blanco C, Fogliano V, Romano M. Apple polyphenol extracts prevent damage to human gastric epithelial cells in vitro and to rat gastric mucosa in vivo. Gut. 2005 Feb;54(2):193-200.
• Kang SY, Seeram NP, Nair MG, Bourquin LD. Tart cherry anthocyanins inhibit tumor development in Apc(Min) mice and reduce proliferation of human colon cancer cells. Cancer Lett. 2003 May 8;194(1):13-9.
• Khandelia R, Jaiswal A, Ghosh SS, Chattopadhyay A. Gold Nanoparticle-Protein Agglomerates as Versatile Nanocarriers for Drug Delivery. Small. 2013 Feb 27. 
• Li F, Li S, Li HB, Deng GF, Ling WH, Wu S, Xu XR, Chen F. Antiproliferative activity of peels, pulps and seeds of 61 fruits. Journal of Functional Foods. 20 May 2013.

Fruit Olympics: Study Analyses Antioxidant and Total Phenolic Content of 62 Fruits

Did you ever want to know how your favorite fruit would perform in the most prestigious disciplines of the "Fruit Olympics", i.e. antioxidant capacity and phenolic content? Yes? Well, I guess a group of researchers from China has just done you a favor...

Xu et al. (Xu. 2011) analysed the antioxidant capacity by Ferric-reducing antioxidant power (FRAP) assays and the free radical scavenging capacities by Trolox equivalent antioxidant capacity assays (TEAC) and found:

Seven fruits had the strongest antioxidant activities among 62 tested fruits [...] they were Chinese date, pomegranate, guava, sweetsop, persimmon, Chinese wampee and plum (sanhua). In addition, olive showed the strongest free radical scavenging ability, and cherry and pineapple also had high antioxidant capacities. Because of their high antioxidant activities, it could be speculated that these fruits will be beneficial for the diseases caused by oxidative stress.

An interesting observation is that the total antioxidant capacity measured by FRAP and the radical scavenging capacities directly assessed by Trolox show only a weak correlation of R² = 0.0337 (0<1; R = 1 would indicate 100% correlated), which would "suggest that the compounds capable of reducing oxidants could be different from those scavenging free radicals in these fruits". By removing the four fruits with the highest antioxidant capacity, however, the correlation increases to R²=0.7169, which makes me think that the lack of correlation might be explained by artifices of the measuring process at high antioxidant concentrations. It is nevertheless an interesting thought that, after all, the amount of antioxidants (measured by FRAP) would only partly explain the free-radical scavenging capability of a certain food.

Figure 1: The Chinese or red date (also known as Jujuba), an antioxidant powerhouse with an abundance of polyphenols (photo by Marco Schmidt, Wikipedia)

Next to antioxidants, the "perfomance" in terms of total phenolic content, constitutes the second most prestigious discipline of the "Fruit Olympics". Xu et al. used the Folin–Ciocalteu method, "which relie[s] on the transfer of electrons from phenolic compounds to the Folin–Ciocalteu reagent in alkaline medium, and is a simple and widely used method" and found that

[...] the total phenolic contents varied from 11.88 to 585.52mg GAE/100 g with the difference of 49-fold, and the mean value was 71.80 mg GAE/100 g for 62 fruits.Chinese date (585.52    +/-18.59 mg GAE/100 g) had the highest total phenolic content, followed by sweetsop (405.41 +/-16.70 mg GAE/100 g), guava (194.11+/-7.01 mg GAE/100 g), pomegranate (146.94+/-0.04 mg GAE/100 g), Chinese wampee (116.10+/-7.48 mg GAE/100 g), cherries (114.56+/-4.72 mg GAE/100 g), persimmon (112.09+/-4.60 mg GAE/100 g) and plum (sanhua) (102.43    2.83 mg GAE/100 g), but pear (honey) had the lowest total phenolic content (11.88    0.11 mg GAE/100 g) among the tested fruits.

Another result is that olive oil had the highest content of gallic acid (50.25 ± 4.87 mg/100g), followed by wax apple and Chinese date. The latter also had the highest content of cyanidin-3-O-galacoside (13.5 ± 0.11 mg/100g, while one of my personal favorites, the pomegranate, outperformed the competition in terms of  quercetin-3-glucoside (11.1 ± 0.60 mg/100g). If you are looking for hesperitin, a natural COX-2 inhibitor (anti-inflammatory), lemons should be your "fruit athlete" of choice.

Figure 2: Although he is not among the "top athletes", a recent study has shown that "an apple a day [in fact] keeps the doctor away" (photo by Firr2000)

In view of all this data, don't forget the motto of the original Olympic Games: "Its taking part that counts!" Or, in other word, get your daily serving of healthy fruits and if you cannot stand Chinese dates, or Jujuba's as they are commonly called, as well, eat something less exotic - remember: A recent study validated the old saying "an apple a day will keep the doctor away".