The Intelligent & Relentless Pursuit of Muscle™

Micro-PA™ Directly Activates and Amplifies Hypertrophy

01/24/14
Mdbaker1

Here's what you need to know...

•  Weight training produces muscle growth by activating mTOR, which is the master enzyme responsible for muscle cell protein synthesis resulting in hypertrophy.

•  Muscle cells use phosphatidic acid (PA) to activate and regulate mTOR.

•  Subjects supplementing with PA achieved 50% greater increase in muscle cross-sectional area and lean body mass, 40% greater increase in total strength (upper and lower body), and 60% greater loss in body fat than the training-only group (Wilson et al 2014, in press).

•  Micro-PA™ contains a highly specialized form of unsaturated phosphatidic acid (PA), with enhanced bioavailability, that powerfully activates and amplifies muscle cell protein synthesis.

Muscle. We spend countless hours pushing iron to pack more of it on our bodies. We center our diets around fueling and feeding it. And we're constantly looking for ways to make better and faster gains.

For most of us, lifting weights is not just a hobby or simply something we do, it's very much a part of our identity. In fact, we probably spend more time thinking about stimulating muscle growth than most of us would like to admit, and we're always searching for the latest hypertrophy news.

If that's you, I have some information that will more than light up your brain's synapses. Some of it's a little geeky and technical, but it's also very important and provides a clearer, more focused picture of what's involved in gaining muscle.


The New Science of Hypertrophy

While performing a set of reps under load, your body begins converting mechanical information into biochemical action. The term for this is mechanotransduction, and it's the basis for the most powerful stimulus of intracellular protein synthesis (aka hypertrophy).

Here's exactly how that works. During eccentric movement, an enzyme is dislodged from the Z-lines of muscle cells that hydrolyzes phosphatidylcholine into phosphatidic acid (PA). PA in turn binds to and activates a kinase enzyme, called mTOR, which is the "master regulator" of muscle cell protein synthesis and muscle size.

PA-activated mTOR directly affects immediate and long-term changes in muscle growth. Simply put, if you want to gain muscle, you have to activate mTOR. And the more PA available to activate mTOR, the greater the effect on intracellular protein synthesis and the greater the muscle mass gains.


The Next Step: Orally Bioavailable PA

One of the industry's most innovative materials manufacturers is a company called Chemi Nutra. Chemi Nutra and its president Scott Hagerman are devoted to producing novel compounds that have a real impact on enhancing human performance. They have a huge budget for research and development, including the funding of scientific studies.

So it really grabbed my attention when Tim Ziegenfuss and Jeff Stout (both PhDs) informed me that Chemi Nutra had produced an orally bioavailable form of PA that activates mTOR. And the company had compelling research to back it up. Dr. Stout, who's involved in the Chemi Nutra PA research, began sending me information about the studies, as well as his personal thoughts on PA.

Here's a summary of the research and Dr. Stout's personal observations:


PA Research Summary

•  Many studies have demonstrated that PA activates and amplifies the "master regulatory enzyme" responsible for immediate and long term changes in muscle growth (aka protein synthesis).

•  PA bathed in-vitro with myoblast (baby muscle cells) resulted in an 8-fold increase activation of mTOR.

•  Supplemented PA increases protein synthesis via two mechanisms:

Directly – by entering the muscle cell and binding to mTOR.

Indirectly – by converting to lyso-phosphatidic acid and attaching to the muscle cell membrane, which increases intracellular PA, and in turn activates mTOR.

•  PA is a phospholipid that contains two fatty acids and a phosphate group, and must be unsaturated to activate mTOR. If the fatty acids are saturated (like the PA found in eggs), then PA simply gets incorporated into the cell membrane.

•  Bioavailability of PA significantly rises in 30 minutes and stays elevated for 7 hours.

•  A study, involving resistance trained men undergoing a very intense exercise program, showed subjects supplementing with 750 mg PA per day achieved:

50% greater increase in muscle cross-sectional area and lean body mass.

40% greater increase in total strength (upper and lower body)

60% greater loss in body fat than the training-only group (Wilson et al 2014, in press).

• Another study, involving resistance trained men undergoing an 8-week exercise program, showed subjects taking 750 mg of PA per day gained significantly more lean body mass and strength than the training-only group (Hoffman et al. 2013):

PA Study Chart


Micro-PA™ Logs & Users Forum

Micro-PA Logs & Users Forum

We're currently working with John Meadows, Christian Thibaudeau, IFBB pros Mark Dugdale and Amit Sapir, as well as a handful of other top athletes, testing and refining training techniques to reap the most benefits from Micro-PA.™ You can imagine how difficult it is to add muscle to those already at the top of their game, but results are very impressive. Everything we're doing is being posted and discussed in the Micro-PA Logs & Users Forum . So, if you're Micro-PA user, or if just you're interested in seeing what the pros are saying and doing, check it out.

As a serious lifter, you already train hard. Now it's time to ramp up the results of your efforts. Micro-PA™ does more than simply give you the edge in the gym. It directly activates and amplifies hypertrophy. This is not a hobby. And Micro-PA™ is not for those who treat it like one.

Micro-PA™ Workout Protocol

Schedule Supplement Dosing Instructions
01:00   Pre-Workout Micro-PA™ 6 capsules
00:30   Pre-Workout Indigo-3G® 6 capsules
00:15   Pre-Workout Plazma™ 500 ml dose
Workout Plazma™ 3 or 4 doses (500 ml each). Consume in half-dose pulses, spread evenly over the duration of the workout.
00:00 – 01:00
Post-Workout
Mag-10® 2 doses (500 ml each). Consume both doses within one hour post-workout.

PA Science Q & A

by Jeffrey Stout, PhD, Jacob Wilson, PhD

"Building Muscle Without Lifting Weights?"

"I guess I just still don't understand where PA comes in. Isn't the lifting and Plazma, Mag-10 (etc) consumption activating hypertrophy? When I read the article, it almost seemed like it was saying you could take Micro-PA, and do nothing else, and hypertrophy would be activated. Surely that's not the case. Maybe I missed something, but I'm otherwise I'm confused."

Resistance training increases PA "within" skeletal muscle or within the intracellular environment. This occurs via activating an enzyme (phospholipase D) which lies within components of muscle that are sensitive to eccentric contractions. These components are called zlines and hold the contractile elements of a muscle fiber together. When stretched phospholipase D, which is bound to the zlines, senses mechanical trauma and reacts by producing phosphatidic acid or PA. PA then binds to and activates mTOR, the master switch regulating protein synthesis.

It turns out, however, that PA can also activate mTOR in a totally different pathway if delivered in the extracellular (outside the cell) environment (Winter et al). More specifically, extracellular PA triggers the ERK signaling pathway, which then activates mTOR via a completely separate mechanism than intracellular PA.

In fact, if you block ERK signaling when giving cells PA, protein synthesis does not increase. In contrast, if you block ERK signaling after resistance training protein synthesis still increases. For this reason you will maximize muscle growth if PA is increased both inside and outside the cell.

This explains why two studies to date have shown that resistance training combined with PA supplementation resulted in more lean body mass and hypertrophy than resistance training alone (Hoffman et al. 2012 and Joy et al. 2013).

Micro-PA™


References

1. Gundermann, D et al. Soy-derived Phosphatidic Acid, Lysophosphatidic Acid and Phosphatidylserine are Sufficient to Induce an Increase in mTOR Signaling. Poster presented at the 2013 annual ISSN conference, and manuscript now in review for submission to publication.

2. Hoffman, JR et al. Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men. Journal of the International Society of Sports Nutrition. 9:47 2012.

3. Joy, JM et al. Phosphatidic Acid Supplementation Increases Skeletal Muscle Hypertrophy and Strength. Poster presented at the 2013 annual ISSN conference, and manuscript now in review for submission to publication.

4. Joy, JM et al. The Effects of 8 Weeks of Phosphatidic Acid Supplementation on Cardiovascular, Kidney, and Liver Safety in Health Young Males. Poster presented at the 2013 annual ISSN conference.

5. Purpura M et al. Effect of Oral Administration of Soy-Derived Phosphatidic Acid on Concentrations of Phosphatidic Acid and lyso-Phosphatidic Acid Molecular Species In Human Plasma. Poster presented at the 2013 annual ISSN conference.

6. Adegoke, OA, Abdullahi, A, Tavajohi-Fini, P. mTORC1 and the regulation of skeletal muscle anabolism and mass. Applied Physiology, Nutrition, and Metabolism. Vol. 37, No. 3: 395-406, 2012.

7. Donati C, et al. New insights into the role of sphingosine 1-phosphate and lysophosphatidic acid in the regulation of skeletal muscle cell biology. Biochimica et Biophysica Acta, 2012, http://dx.doi.org/10.1016/j.bbalip.2012.06.013.

8. Foster, D et al. Phosphatidic acid and lipid-sensing by mTOR. Cell Press Articles In Press, Trends in Endocrinology and METABOLISM XX (2012) 1-7.

9. Harrington, LS, Findlay, GM, and Lamb, RF. Restraining PI3K: mTOR signaling goes back to the membrane. TRENDS in Biochem Sci 30(1): 35-42, 2005.

10. Hornberger, TA, Chu, WK, Mak, YW, Hsiung, JW, Huang, SA, and Chien, S. The role of phospholipase D and phosphatidic acid in the mechanical activation of mTOR signaling in skeletal muscle. PNAS 103(12): 4741-4746, 2006.

11. Hornberger, TA, Sukhija, KB, Chien, S. Regulation of mTOR by mechanically induced signaling events in skeletal muscle. Cell Cycle 5(13): 1391-1396, 2006.

12. Hulmi JJ et al. Resistance exercise with whey protein ingestion affects mTOR signaling pathway and myostatin in men. J Appl Physiol 106: 1720-1729, 2009.

13. Laplante M et al. An emerging Role of mTOR in Lipid Biosynthesis. Current Biology 19, R1046-R1052, Dec 1, 2009. Elsevier Ltd.

14. Lehman, N, Ledford, B, Di Fulvio, M, Frondorf, K, McPhail, LC, and Gomez-Cambronero, J. Phospholipase D2-derived phosphatidic acid binds to and activates ribosomal p70 S6 kinase independently of mTOR. FASEB J 21: 1075-1087, 2007.

15. O’Neil, TK, Duffy, LR, Frey, JW, and Hornberger, TA. The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions. J Physiol 581.14: 3691-3701, 2009.

16. Rasmussen, BB. Phosphatidic acid: a novel mechanical mechanism for how resistance exercise activates mTORC1 signaling. J Physiol 587.14: 3415-3416, 2009.

17. Sengupta, S, Peterson, TR, and Sabatini, DM. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Molecular Cell 40: 310-322, 2010.

18. Stipp D. A New Path To Longevity. Scientific American, January 2012.

19. Veverka, V, Crabbe, T, Bird, I, Lennie, G, Muskett, FW, Taylor, RJ, and Carr, MD. Structural characterization of the interaction of mTOR with phosphatidic acid and a novel class of inhibitor: Compelling evidence for a central role of the FRB domain in small molecule-mediated regulation of mTOR. Oncogene 27: 585-595, 2008.

20. Vissing K et al. Differentiated mTOR but not AMPK signaling after strength vs endurance exercise in training-accustomed individuals. Scand J Med Sci Sports, 2011, doi 10.1111/j.1600-0838.2011.01395.x.

21. Walker, DK, Dickinson, JM, Timmerman, KL, Drummond, MJ, Reidy, PT, Fry, CS, Gundermann, DM, and Rasmussen, BB. Exercise, amino acids, and aging in the control of human muscle protein synthesis. J Am Coll Sport Med 43(12): 2249-2258, 2011.

22. Winter, JN, Fox, TE, Kester, M, Jefferson, LS, and Kimball, SR. Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway. Am J Physiol Cell Physiol 299: C335-C344, 2010.

23. Xu, Y, Fang, Y, Chen, J, and Prestwich, GD. Activation of mTOR signaling by novel fluoromethylene phosphonate analogues of phosphatidic acid. Bio Med Chem Letter 14: 1461-1464, 2004.

24. Yamada, AK, Verlengia, R, Bueno, CR. Mechanotransduction pathways in skeletal muscle hypertrophy. Journal of Receptors and Signal Transduction 2011.

25. Zanchi, NE, and Lancha, AH Jr. Mechanical stimuli of skeletal muscle: Implications on mTOR/p70s6k and protein synthesis. Eur J Appl Physiol 102: 253-263, 2008.

26. Zhang C et al. Glycerolipid signals alter mTOR complex 2 (mTORC2) to diminish insulin signaling. PNAS Early Edition, www.pnas.org/content/early/2012/01/10/1110730109.full.pdf.

01/24/14