|Image 1: Can you really team up leucine (or HMB) and resveratrol to make tired mitochondria get a move on? NuSirt Sciences says "YES!" And in the dish and rodents it's actually already working.|
If you put Sirt1 & Sirt1 together, it suddenly makes sense!
In their latest study (and you bet a future product!) Bruckbauer et al. build on their previous research on the agonistic effects HMB, alpha-KIC or leucine have on skeletal muscle Sirt-1 activity (Bruckbauer. 2011) and rationalize that it seems legit to combine one Sirtuin portein promoter with another one in order to achieve an even more pronounced effect - makes sense, right? Resveratrol the proven AMPK-promoter and igniter of the longevity, gene transcription, cell survival and apoptosis regulating Sir2 proteins (=sirtuins) and leucine the mTOR promoting and, as of late, proven Sirt1 agonist, they could actually form a synergistic duo for fat oxidation, glucose management, the reduction of oxidative stress and inflammation and even longevity!
- resveratrol, leucine and HMB, alone, exerted only weak independent effects on Sirt1, Sirt 3 and AMPK
- resveratrol and leucine or HMB, combined, yielded Sirt1 and Sirt3 activity increases in the ~50% range (p < 0.05) and AMPK increases of +42% and +55% (p < 0.03); particularly noteworthy are the ~125-175% increases (p < 0.02) muscle cells (remember: Sirt3 is expressed in the mitochondria!)
- the ensuing increases in fatty acid oxidation in incubated muscle cells reached statistical significance in the presence of low (5 mM) glucose levels, only, when and 5 µM HMB or 0.5 mM leucine were co-incubated with 200 nM (~18%; p < 0.05), in the high glucose condition, however, all treatments broad about significant increases in fatty acid oxidation, of which those in the leucine- and HMB-resveratrol combination treatments were the most pronounced (118% and 91% stimulation, respectively; p < 0.005)
Outside of the box... ahh, I mean, ... the petri dish!
In view of the fact that 75% of the in-vitro high performers suck in the rodent model already and of those another 75% don't work in human trials you will be pleased to hear that NuScirt Sciences' resveratrol + leucine / HMB combination has already overcome the first of these hurdles: At least in DIO (diet-induced-obese) rodents who on a 6-week high fat diet regimen, the combination works.
What are the human equivalent doses, here? Since I know you would be asking I did the math for you and you will be pleasantly surprised (HED for 80kg humans)
- 12.5mg resv. = 9mg
- 225mg resv. = 136mg
- 2g HMB = 1.1-1.4g
- 10g HMB = 7.2g
- 24g leucine = 14.3g
- Supplementation with the respective human equivalent doses should yield the same astonishing results in humans as it did in the diet-induced obese mice.
- The protocol should have effects not just in morbidly obese diabetic human beings, but also in overweight and ideally even lean individuals.
- The supp must work if you don't put it into the chow, but pop it in separate doses (e.g. 3x/day) as a capsule or tablet.
Unfortunately, this is exactly why I don't believe that LeuResSirt, or whatever other stupid name the final product will be given, is going to work - I mean, come on, you can't tell me that there are not already people out there who get 15-20g of leucine everyday and pop resveratrol in 100x the necessary dose of 8-9mg everyday!? And did they turn into a beast, become fast-food resistant or lose fat magically? What? Yeah... that must be Phil Heath secret, right... how come I did not realize that before? ;-)
Bottom line: Regardless of the probably justified skepticism, I will still keep you posted on whether or not NuSirt knocks out another incredible (in the literal sense) human study like the one on NuFit (see "Testosterone - 12% Drop /W 75g Glucose? Fat Loss - Adzuki, Leucine + B6 or HiMaize & More"). So stay tuned, you all know that no supplement will ever more ergogenic than your daily dose of SuppVersity news!
- Bruckbauer A, Zemel MB. Effects of dairy consumption on SIRT1 and mitochondrial biogenesis in adipocytes and muscle cells. Nutr Metab (Lond). 2011 Dec 20;8:91.
- Bruckbauer A, Zemel MB, Thorpe T, Akula MR, Stuckey AC, Osborne D, Martin EB, Kennel S, Wall JS. Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice. Nutr Metab (Lond). 2012 Aug 22;9(1):77.