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EvoMuse

MyoSynergy

NEW MyoSynergy by EvoMuse Advanced Size & Strength Catalyst! NEW MyoSynergy by EvoMuse is a brand new, unique formula designed to potently trigger multiple pathways of muscle building at the cellular level. In addition, it will also aid in preventing muscle breakdown, boosting strength levels, and encouraging mitochondrial biogenesis. To better understand the inclusion of the specific ingredients in the formula, it is important to have a little bit of background on the ways the body upregulates muscle growth. We don't just grow or shrink unless we have the proper signals to do so. The primary growth signal, and the main anabolic focus of MyoSynergy, is the PI3K/AKT/mTOR pathway. Anabolic/Catabolic Signaling To trigger anabolism, the body primarily engages in the following sequence of events: Insulin Like Growth Factor 1 (IGF1) activates Phosphoinositide 3-Kinase (PI3K), which activates Protein Kinase B (Akt), which then activates the Mechanistic Target of Rapamycin (MTOR, also known as the mammalian Target of Rapamycin). Considered the master regulator of protein synthesis in muscle, MTOR is the key player in this cascade. IGF1 - PI3K - Akt - MTOR When this happens, we see the following take place (1,2): Protein Synthesis (muscle growth) Anti-catabolism (prevention of muscle breakdown) Myostatin inhibition (major governor on muscle growth) MuRF1 reduction (more on that below) Although it was previously thought that Myostatin generated a cellular signal to kickstart muscle breakdown, it has now been shown to instead block the above anabolic pathway (1,2). So inhibition of myostatin allows for accelerated anabolism. Catabolic Signaling is multifaceted and complex, but a couple of key players in the triggering of muscle protein degradation are MuRF1 and MAFbx (3–5). These can be activated by inflammatory cytokines like TGF-a and NF-kappaB, but are also susceptible to other mechanisms of activation (6). Now with this background out of the way, let's get into how MyoSynergy will favorably manipulate these pathways to greatly augment your ability to gain muscle! Astragalus Membranaceus 20:1 While Astragalus Membranaceus (AM) has numerous potential benefits, here we are focused on a few specific ones, namely IGF1 boosting, Myostatin inhibition, glucose and insulin signaling, and exercise performance. AM has been shown to upregulate IGF1 production, which, as noted above, kickstarts the entire anabolic cascade (7). Researchers later conducted a study to re-test this, and found that it did in fact increase IGF1 while also stimulating bone growth in rats, and suggested that AM "may be helpful in stimulating growth in children with short stature", which it is actually used for in traditional Korean medicine (8). In fully-grown adults, IGF1 is no longer responsible for bone growth, as it shifts its focus to other duties like muscle growth. So, sorry, MyoSynergy will not make you taller, you'll just have to distract people with your bigger muscles. As you recall from earlier, IGF1 activation is going to indirectly decrease Myostatin levels. In addition to that, another study showed that AM was able to reduce Myostatin more directly by inhibiting the NF-kappaB pathway (9). Aside from boosting IGF1 to enhance anabolism, AM also appears to have a pronounced effect on the way the body handles glucose and insulin. In one study, when researchers tried to fatten rats up and give them diabetes, AM was able to ameliorate "glucose toxicity", improve insulin sensitivity, and increase glucose uptake in the muscle cells (10). This boost in insulin sensitivity and increased muscle glycogen storage has been corroborated by other studies as well (9,11,12). Better skeletal muscle insulin sensitivity and more glucose uptake = bigger muscles. Nice. AM has also been shown to enhance exercise performance by reducing the accumulation of metabolic waste products (11). (-)Epicatechin (-)Epicatechin is an exciting ingredient with potential to stimulate muscle growth through multiple avenues. As we age, Myostatin increases while its inhibitors like follistatin and myogenin/MyoD (the latter two are responsible for regulating muscle cell differentiation) tend to decrease. This sets the stage for increased muscle loss. (-)Epicatechin has been shown to reverse this, decreasing Myostatin and improving the follistatin/myostatin ratio and increasing strength after only seven days of intake (13). As well, MyoStatin expression is one of the major limiting factors in muscle growth for people of all ages. Inhibition of MyoStatin by MyoSynergy should result in increased muscle growth rates for all users. (-)Epicatechin has also been shown in multiple studies to increase muscle capillarity and biogenesis of mitochondria, which persists even with cessation of use (14,15). More blood flow and mitochondria paves the road to enhanced hypertrophic capability and improved performance. In addition, (-)epicatechin has recently been shown to favorably regulate the function of specific proteins in control of muscular contraction (16). HICA HICA stands for Hydroxyicocaproic Acid, also known as Leucic Acid, and is a metabolite of the main MTOR activating amino acid L-Leucine. When you ingest Leucine, it goes down one of two metabolic pathways and either converts to KIC or HMB. If it gets converted to KIC, some of that gets converted to HICA. Now the problem with this traditional conversion cascade, is that KIC upregulates an enzyme called BCKDH, which then oxidizes BCAA's including Leucine, so it acts as a governor on the available Leucine pool in the bloodstream, eventually using it all up to halt MTOR activation. One of the main reasons people can get away with a lower protein intake on a ketogenic diet and still build muscle is because in ketosis, the body oxidizes (wastes) less Leucine, so each gram of protein is more anabolic. Now, this still needs to be shown in research, but theoretically HICA can sneak by the regulatory mechanisms that trigger BCKDH, therefore allowing more MTOR activation before the party gets shut down. A recent study published in the highly respected ISSN Journal looked at the effect of HICA supplementation for four weeks in male soccer players. The results showed an increase in lean body mass, 23% reduction in DOMS, and improved training alertness in the HICA group compared to placebo (17). A full daily dose of MyoSynergy exceeds the 1.5g of HICA used in this study. Another study performed on rats placed into casts analyzed the effect on both immobility induced atrophy and post removal protein synthesis. While the HICA didn’t prevent the atrophy, recovery was remarkably sped up to precasting rates in the HICA treated animals. Accelerated protein synthesis rates from HICA administration were indicated (35) ATP Previous research has led people to believe that adenosine triphosphate (ATP) is not orally bioavailable, thus dismissing its use as a sports supplement (18). While the research itself was not inherently incorrect, it turns out researchers were just measuring ATP at the wrong place (they should have been measuring venous portal blood). Since we now know more about the kinetics of oral ATP, it turns out the most effective time to ingest it is about 30 minutes pre-workout, so be sure to time one of your MyoSynergy doses accordingly. Before the more accurate testing methods were elucidated, a study was conducted that looked at the effect of ATP supplementation on strength training, and the results were a little surprising considering ATP's apparent lack of oral bioavailability. They found some interesting within group differences in the subject group taking a higher dose of ATP compared to the lower dose group, and concluded supplementation may provide some ergogenic benefits (19). Newer research from the prestigious exercise science researcher Jacob Wilson has demonstrated the ability of supplemental ATP to increase total body strength, vertical jump power, muscle thickness, and reduced muscle protein breakdown versus placebo after 12 weeks of resistance training (20). Broccoli Sprout Broccoli Sprout is a source of sulforaphane, which has numerous beneficial effects on general health, such as acting as a histone deacetylase inhibitor (21). It also acts as an antioxidant, and more specifically, modulates the redox environment in muscle cells to control exercise induced muscle damage (22,23). The main reason for inclusion of Broccoli Sprout, however, is the interaction with Myostatin. A recent study in the journal Epigenetics showed that sulforaphane significantly suppresses Myostatin, while also suppressing the negative feedback inhibitors of the Myostatin pathway (21). Forskolin Forskolin is well known to induce cyclic AMP production, which has several physiological effects. One of those effects is an increase in follistatin, which, as mentioned previously, counteracts the inhibitory effects of Myostatin on muscle growth (24,25). This cAMP activation has also been shown to directly activate MTOR by phosphorylating S6K1, mobilizing intracellular calcium stores and increasing ATP production (26). Forskolin has also been shown to enhance the PI3K/Akt pathway, triggering anabolism as well as angiogenesis (the creation of new blood vessels) (27,28). Cholecalciferol The final ingredient in MyoSynergy is Cholecalciferol, better known as Vitamin D3. Rates of Vitamin D deficiency continue to climb as people fear sun exposure and consume more nutrient devoid foods, a 2011 study showed that over 40% of the population was Vitamin D deficient, with certain ethnic groups being significantly higher (29). Aside from a multitude of health problems related to suboptimal Vitamin D status, it could also end up being a limiter of muscle growth, even at levels not considered to be an actual deficiency. A 2013 study looking at healthy, active subjects given supplemental Vitamin D3, showed that they increased peak isometric force and had decreased muscle damage biomarkers…and here's the kicker, they all had clinically sufficient Vitamin D status prior to supplementation (30). In a study looking at European Sea Bass, the researchers found the group with the highest supplemental Vitamin D3 dosage experienced muscle cell hyperplasia, showing a direct effect of cholecalciferol on muscle cell growth (31). Another 2013 study in human subjects found that supplemental cholecalciferol caused improvements in several tested parameters of muscle strength (32) In a group of people with low Vitamin D staus, supplemental cholecalciferol was shown to increase the concentration of the Vitamin D Receptors (VDR) by 30%, as well as actual muscle fiber size by 10% (33). Another study showed the same effect of cholecalciferol supplementation to increase VDR concentration, as well as decrease exercise induced muscle damage and inflammation by decreasing NF-kappaB (which could indirectly decrease Myostatin production) (34). In summary, MyoSynergy is designed to potently upregulate the body's main anabolic signals, inhibit catabolic pathways, and promote increases in strength and exercise performance. The specific combination and dosages of these novel ingredients should allow users to tap into a previously unattainable level of muscle growth. References: 1. Glass DJ. PI3 Kinase Regulation of Skeletal Muscle Hypertrophy and Atrophy. Curr Top Microbiol Immunol [Internet]. 2010 Jul [cited 2010 Jul 5]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/20593312 2. Glass DJ. Signaling pathways perturbing muscle mass. Curr Opin Clin Nutr Metab Care [Internet]. 2010 May [cited 2014 Mar 20];13(3):225–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20397318 3. Koyama S, Hata S, Witt CC, Ono Y, Lerche S, Ojima K, et al. Muscle RING-finger protein-1 (MuRF1) as a connector of muscle energy metabolism and protein synthesis. J Mol Biol [Internet]. 2008 Mar 7 [cited 2014 Mar 24];376(5):1224–36. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18222470 4. De Palma L, Marinelli M, Pavan M, Orazi A. Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy. Joint Bone Spine [Internet]. 2008 Jan [cited 2014 Mar 24];75(1):53–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17977773 5. Foletta VC, White LJ, Larsen AE, Léger B, Russell AP. The role and regulation of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy. Pflugers Arch [Internet]. 2011 Mar [cited 2014 Mar 23];461(3):325–35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21221630 6. Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol [Internet]. 2005 Oct [cited 2014 Mar 20];37(10):1974–84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16087388 7. Wu H, Zhou H. [Astragalus membranaceus promote expression of insulin-like growth factor 1 in rat model of olivo-cerebellar degeneration]. Zhongguo Zhong Yao Za Zhi [Internet]. 2007 Feb [cited 2014 Mar 24];32(3):242–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17432149 8. Kim M-Y, Kim JY, Lim D, Lee D, Kim Y, Chang GT, et al. Skeletal growth and IGF levels in rats after HT042 treatment. Phytother Res [Internet]. 2012 Dec [cited 2014 Mar 24];26(12):1771–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22388791 9. Liu M, Qin J, Hao Y, Luo J, Luo T, Wei L. Astragalus polysaccharide suppresses skeletal muscle myostatin expression in diabetes: involvement of ROS-ERK and NF-κB pathways. Oxid Med Cell Longev [Internet]. 2013 Jan [cited 2014 Mar 6];2013:782497. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract 10. Zou F, Mao X, Wang N, Liu J, Ou-Yang J. Astragalus polysaccharides alleviates glucose toxicity and restores glucose homeostasis in diabetic states via activation of AMPK. Acta Pharmacol Sin [Internet]. 2009 Dec [cited 2014 Mar 23];30(12):1607–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19960007 11. Yeh T-S, Chuang H-L, Huang W-C, Chen Y-M, Huang C-C, Hsu M-C. Astragalus membranaceus Improves Exercise Performance and Ameliorates Exercise-Induced Fatigue in Trained Mice. Molecules [Internet]. 2014 Jan [cited 2014 Mar 23];19(3):2793–807. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24595275 12. Liu M, Wu K, Mao X, Wu Y, Ouyang J. Astragalus polysaccharide improves insulin sensitivity in KKAy mice: regulation of PKB/GLUT4 signaling in skeletal muscle. J Ethnopharmacol [Internet]. 2010 Jan 8 [cited 2014 Mar 23];127(1):32–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19800959 13. Gutierrez-Salmean G, Ciaraldi TP, Nogueira L, Barboza J, Taub PR, Hogan MC, et al. Effects of (-)-epicatechin on molecular modulators of skeletal muscle growth and differentiation. J Nutr Biochem [Internet]. 2014 Jan [cited 2014 Mar 11];25(1):91–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24314870 14. Hüttemann M, Lee I, Perkins GA, Britton SL, Koch LG, Malek MH. (-)-Epicatechin is associated with increased angiogenic and mitochondrial signalling in the hindlimb of rats selectively bred for innate low running capacity. Clin Sci (Lond) [Internet]. 2013 Jun [cited 2013 Oct 7];124(11):663–74. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23252598 15. Taub PR, Ramirez-Sanchez I, Ciaraldi TP, Perkins G, Murphy AN, Naviaux R, et al. Alterations in skeletal muscle indicators of mitochondrial structure and biogenesis in patients with type 2 diabetes and heart failure: effects of epicatechin rich cocoa. Clin Transl Sci [Internet]. 2012 Feb [cited 2014 Feb 21];5(1):43–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22376256 16. Taub PR, Ramirez-Sanchez I, Ciaraldi TP, Gonzalez-Basurto S, Coral-Vazquez R, Perkins G, et al. Perturbations in skeletal muscle sarcomere structure in patients with heart failure and type 2 diabetes: restorative effects of (-)-epicatechin-rich cocoa. Clin Sci (Lond) [Internet]. 2013 Oct [cited 2014 Mar 11];125(8):383–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23642227 17. Mero AA, Ojala T, Hulmi JJ, Puurtinen R, Karila TA, Seppälä T. Effects of alfa-hydroxy-isocaproic acid on body composition, DOMS and performance in athletes. J Int Soc Sports Nutr [Internet]. 2010 Jan [cited 2014 Mar 6];7:1. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract 18. Coolen EJCM, Arts ICW, Bekers O, Vervaet C, Bast A, Dagnelie PC. Oral bioavailability of ATP after prolonged administration. Br J Nutr [Internet]. 2010 Dec [cited 2010 Dec 10];1–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21129239 19. Jordan AN, Jurca R, Abraham EH, Salikhova A, Mann JK, Morss GM, et al. Effects of oral ATP supplementation on anaerobic power and muscular strength. Med Sci Sports Exerc [Internet]. 2004 Jun;36(6):983–90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15179168 20. Wilson JM, Joy JM, Lowery RP, Roberts MD, Lockwood CM, Manninen AH, et al. Effects of oral adenosine-5’-triphosphate supplementation on athletic performance, skeletal muscle hypertrophy and recovery in resistance-trained men. Nutr Metab (Lond) [Internet]. 2013 Jan [cited 2014 Mar 23];10(1):57. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract 21. Fan H, Zhang R, Tesfaye D, Tholen E, Looft C, Hölker M, et al. Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells. Epigenetics [Internet]. 2012 Dec 1 [cited 2014 Mar 23];7(12):1379–90. Available from: http://www.pubmedcentral.nih.gov/art...rtype=abstract 22. Guerrero-Beltrán CE, Calderón-Oliver M, Pedraza-Chaverri J, Chirino YI. Protective effect of sulforaphane against oxidative stress: recent advances. Exp Toxicol Pathol [Internet]. 2012 Jul [cited 2014 Mar 19];64(5):503–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21129940 23. Malaguti M, Angeloni C, Garatachea N, Baldini M, Leoncini E, Collado PS, et al. Sulforaphane treatment protects skeletal muscle against damage induced by exhaustive exercise in rats. J Appl Physiol [Internet]. 2009 Oct [cited 2014 Mar 23];107(4):1028–36. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19713431 24. Winters SJ, Ghooray D, Fujii Y, Moore JP, Nevitt JR, Kakar SS. Transcriptional regulation of follistatin expression by GnRH in mouse gonadotroph cell lines: evidence for a role for cAMP signaling. Mol Cell Endocrinol [Internet]. 2007 Jun 15 [cited 2014 Mar 25];271(1-2):45–54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17482756 25. Wang Y, Ge W. Gonadotropin regulation of follistatin expression in the cultured ovarian follicle cells of zebrafish, Danio rerio. Gen Comp Endocrinol [Internet]. 2003 Dec [cited 2014 Mar 25];134(3):308–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14636638 26. Kwon G, Marshall CA, Pappan KL, Remedi MS, McDaniel ML. Signaling elements involved in the metabolic regulation of mTOR by nutrients, incretins, and growth factors in islets. Diabetes [Internet]. 2004 Dec [cited 2014 Mar 20];53 Suppl 3:S225–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15561916 27. Namkoong S, Kim C-K, Cho Y-L, Kim J-H, Lee H, Ha K-S, et al. Forskolin increases angiogenesis through the coordinated cross-talk of PKA-dependent VEGF expression and Epac-mediated PI3K/Akt/eNOS signaling. Cell Signal [Internet]. 2009 Jun [cited 2014 Mar 23];21(6):906–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19385062 28. Misra UK, Pizzo SV. Upregulation of AKT1 protein expression in forskolin-stimulated macrophage: evidence from ChIP analysis that CREB binds to and activates the AKT1 promoter. J Cell Biochem [Internet]. 2007 Mar 1 [cited 2014 Mar 23];100(4):1022–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17152074 29. Forrest KYZ, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res [Internet]. 2011 Jan [cited 2014 Mar 25];31(1):48–54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21310306 30. Barker T, Schneider ED, Dixon BM, Henriksen VT, Weaver LK. Supplemental vitamin D enhances the recovery in peak isometric force shortly after intense exercise. Nutr Metab (Lond) [Internet]. 2013 Jan [cited 2014 Mar 19];10(1):69. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24313936 31. Alami-Durante H, Cluzeaud M, Bazin D, Mazurais D, Zambonino-Infante JL. Dietary cholecalciferol regulates the recruitment and growth of skeletal muscle fibers and the expressions of myogenic regulatory factors and the myosin heavy chain in European sea bass larvae. J Nutr [Internet]. 2011 Dec [cited 2014 Mar 23];141(12):2146–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22013200 32. Diamond T, Wong YK, Golombick T. Effect of oral cholecalciferol 2,000 versus 5,000 IU on serum vitamin D, PTH, bone and muscle strength in patients with vitamin D deficiency. Osteoporos Int [Internet]. 2013 Mar [cited 2014 Mar 23];24(3):1101–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22422304 33. Ceglia L, Niramitmahapanya S, da Silva Morais M, Rivas DA, Harris SS, Bischoff-Ferrari H, et al. A randomized study on the effect of vitamin D3 supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women. J Clin Endocrinol Metab [Internet]. 2013 Dec [cited 2014 Mar 23];98(12):E1927–35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24108316 34. Choi M, Park H, Cho S, Lee M. Vitamin D3 supplementation modulates inflammatory responses from the muscle damage induced by high-intensity exercise in SD rats. Cytokine [Internet]. 2013 Jul [cited 2014 Mar 23];63(1):27–35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23669253 These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease. MyoSynergy Supplement Facts Serving Size: Capsules Servings per Container: 30 Amount Per Serving % Daily Value Epicatechin (90%) 100 mg ** Forskolin 55 mg ** Cholecalciferol 1,000 IU ** Astragalus Membranaceus 20:1 1 g ** HICA 2 g ** ATP 400 mg ** Broccoli Sprout 150 mg ** * Percent Daily Values are based on a 2000 calorie diet. ** Percent Daily Values not established. Other Ingredients: Rice Flour & Gelatin MyoSynergy Directions: Take 7 capsules about 1-1.5 hours before your workout. Warning: This product is intended to be consumed by healthy adults 21 years of age or older. This product should only be used under medical or dietetic supervision. This product is not intended as a sole source of nutrition and should be consumed in conjunction with an appropriate physical training or exercise program. This product is not suitable for children under 21 years of age or pregnant or nursing women. Do not exceed recommended serving. Keep out of reach of children. All statements on the website concerning all dietary supplements have not been verified by the Food & Drug Administration. These supplements are not intended to diagnose, treat, cure or prevent disease. All raws for Olympus Labs products are obtained overseas and then encapsulated, bottled, and packaged inside the USA. No raws for Olympus Labs products are produced inside the USA. Most of our raw material suppliers overseas hold GMP certification issued from local government authorities. Olympus Labs has conducted thorough due diligence on all of our raw material suppliers including proper background checks, R&D Certifications, and company registration documents.
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