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Hydra Head Six

Hydra Head Six The Six Headed Hydra must be slain. Like the mythical beast of yore, catabolic pathways relentlessly attack gruelingly earned muscle mass from many angles, particularly in dieting, post-cycle situations, and muscle wasting conditions. From the ancient myth of the divine hero Heracles to the modern reality of supplement science, HH6 is a revolutionary, industry defining natural, non-androgenic anti-catabolic. This isn’t putting a Band-Aid on a gash, only to watch it regenerate its destruction anew -- HH6 cauterizes with fire. This is not your grandpa’s tired old creatine, glutamine, or BCAA product. This is a brand new way of attacking -- a level of innovation that already makes it a living legend. The Six Heads – Six Pathways for Eliminating the Catabolic Threat The First Head The most tantalizing way to decrease catabolism and muscle loss is to directly increase anabolism. Vitamin C 2-phosphate (VC2P) does exactly that. You will see that name, again -- and for good reason. It’s badass. This is not the Vitamin C that was in the orange juice your mom made you for breakfast this morning. VC2P is a much more stable, long acting derivative of regular Vitamin C (1,2). More importantly, it is the only form of Vitamin C that can accmulate in muscle cells following oral supplementation (3). It has been shown to promote both skeletal muscle fiber hypertrophy and differentiation.(4) Ursolic acid is a triterpenoid found in numerous plants. It has long been demonstrated in the data to have a myriad of beneficial effects, but it normally has poor bioavailability. HH6 complexes it in a cyclodextrin for superior solubility, thus partitioning, thus bioavailability. It potentiates amino acid (leucine) induced muscle differentiation (5). Further, it has been shown to increase muscle mass, fiber size (both slow and fast twitch), as well as exercise capacity and grip strength (6). Lastly, Ursolic Acid produced an increase in serum irisin levels and muscle strength (38) -- a fact which may underlie the recomposition effects that users of high-dose ursolic acid products have noted. The Second Head Dieting is stress. With a sustained decrease in calories, the body thinks it is starving. This sets off a cascade of metabolic events designed to reduce calorie hungry muscle mass in order to decrease energy expenditure.One of these mechanisms is through increasing cortisol/glucocorticoid activity. Prolonged, excess activation of the glucocorticoid axis is profoundly catabolic. Our most trusted weapon, VC2P potently inhibits hydrocortisone induced cellular damage. (7, 8) Magnolol, a neolignan from magnolia, also blunts the glucocorticoid cascade via its GABA-A inhibitory activity.(9,10) The Third Head Catabolism is also made widely manifest through the runaway production of reactive oxygen species and inflammation. As with cortisol, it is a normal and necessary part of cellular processes, but like other people’s daughters on spring break, it is bad news when they run wild. VC2P is not only longer acting than Vitamin C, it is a more potent free radical scavenger (11). Magnolol attenuates inflammation and damage with its own antioxidant activity (12). Oenothera odorata is a perennial plant from South America. Oenothera odorata root extract suppresses expression of peroxide and superoxide dismutase, reducing muscle atrophy compared to control.(13) The Fourth Head Our next pathway is one that you might not typically tend to think of – blood flow. Dieting and weight loss cause vasoconstriction via alpha adrenergic receptor upregulation and increased activity signalling. This decreases the uptake of pro-anabolic nutrients to the muscle cell, as well as decreasing the clearance of catabolic byproducts of metabolism. Ligustrazine is a component of the widely popular Chinese herb, Chuanxiong, which has been found to possess vasorelaxant properties (14). It induces this vasodilation through an increase in nitric oxide and cGMP (15, 16, 17). This is the same mechanism as the boner pills, in case you were wondering. (And we know you were.) Magnolol comes to the aid in this fight from the opposite direction. It inhibits vascular contractions through a number of alternate cellular signaling pathways like Akt, eNOS, TRB3, and PPAR-gamma.(18, 19) The Fifth Head Malificent nutrient partitioning is yet another way your body gets you, proving its hatred of the strong and beautiful. Basically, nutrients and calories go preferentially to the formation, growth, and maintenance of adipose tissue instead of muscle. Quite obviously, we want to remedy and reverse this – and we are. Increasing the use of adipose tissue as fuel spares muscle mass, and it increases glucose uptake in muscle vs. fat. This increases protein synthesis while also increasing lipolysis, in a virtuous circle. VC2P positively impacts lipid metabolism by decreasing lipogenesis and increasing lipolysis (20). Magnolol stimulates glucose uptake in muscle cells by increasing GLUT4 at the cell surface (21). Further, it activates key protein synthetic elements of the insulin signaling pathway, including mTor and Akt, as well as lipid oxidation pathways like AMPK and PGC-1a. (21, 22) Ursolic acid acts as an insulin mimetic, increasing GLUT4, glucose uptake, as well as glycogen content of muscle (23). Even better, it increases brown fat in skeletal muscle, thus increasing thermogenesis, fatty acid oxidation, and energy expenditure.(24) Ligustrazine increases mitochondrial biogenesis, thus increasing fatty acid utilization. This not only increases fat burning (and may improve insulin related health issues), it spares glucose for use in muscle cells, to preserve energy and mass.(25) The Sixth Head Our final and most important tactic in our fight is to directly decrease catabolism itself. That is what this product is for, after all. When dieting, you have to work out less, or you are going to get crushed by overtraining and free radicals and inflammation looting and burning your muscle stores. This decrease in muscle fiber overload is essentially like a mini-version of being bed-ridden. The literature on denervation, hind-leg/tail suspension, immobility, and cold muscle tissue covers this aspect of metabolism, extensively. Ligustrazine postpones muscle atrophy indenervated muscle by reducing the expression of a number of catabolic enzymes (26). It has likewise been found to do so in tail suspension (simulating weightlessness), with a reduction in atrophy.(27) One of the most important mechanisms for muscle fiber damage and destruction is an imbalance of intracellular calcium ions. Ligustrazine protects against Ca2+ overload, protecting the muscle mitochondria and the cell (28, 29). This protection has been found to protect against protein degradation and muscle loss (31). Our trusted brother in arms, VCP2, releases ascorbate in the muscle cell to protect against this calcium ion excess (34). It also facilitates the action of IGF-1 on muscle cell formation in cold muscle tissue.(36) Ursolic acid produces hundreds of small changes in mRNA of muscle cell to combat muscle atrophy and weakness (30). This is mediated by a protein called ATF4, which is increased with glucose deprivation in the muscle cell (37). Magnolol suppresses catabolic proteins (including myostatin) and induces protein synthetic agents IGF-1 and Akt, mitigating inflammation and atrophy (32). Oenothera odorata root extract reduced or fully inhibited several catabolic indicators in denervated muscle, supporting maintenance of muscle mass, strength, and volume.(33) Flawless Victory You have done the work, continue to reap the rewards. HH6 is an absolutely essential instrument in your battle to crush your enemies, see them driven before you, and to hear the lamentations of their women. 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. References: 1) Biochem Biophys Res Commun. 1994 Feb 28;199(1):394-402. A long-lasting vitamin C derivative, ascorbic acid 2-phosphate, increases myogenin gene expression and promotes differentiation in L6 muscle cells. Mitsumoto Y, Liu Z, Klip A. 2) Wound Repair Regen. 2011 Sep-Oct;19(5):597-607. Selection of proangiogenic ascorbate derivatives and their exploitation in a novel drug-releasing system for wound healing. Stumpf U, Michaelis M, Klassert D, Cinatl J, Altrichter J, Windolf J, Hergenröther J, Scholz M. 3) Milchwissenschaften. 1999; 54, 123–126. Ascorbyl-2-plyphosphate as a source of ascorbic acid for dairy cattle. MacLeod DD, Zhang X, Kennelly JJ, Ozimek L. 4) J Tissue Eng Regen Med. 2015 Jun 1. doi: 10.1002/term.2030. Effects of heat stimulation and l-ascorbic acid 2-phosphate supplementation on myogenic differentiation of artificial skeletal muscle tissue constructs. Ikeda K(1), Ito A(2), Sato M(2), Kanno S(2), Kawabe Y(2), Kamihira M(1,)(2). 5) The combination of ursolic acid and leucine potentiates the differentiation of C2C12 murine myoblasts through the mTOR signaling pathway. Kim M(1), Sung B(1), Kang YJ(1), Kim DH(1), Lee Y(1), Hwang SY(1), Yoon JH(1), YooMA(2), Kim CM(3), Chung HY(1), Kim ND(1). 6)PLoS One. 2012;7(6):e39332. doi: 10.1371/journal.pone.0039332. Epub 2012 Jun 20. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease. Kunkel SD, Elmore CJ, Bongers KS, Ebert SM, Fox DK, Dyle MC, Bullard SA, Adams CM. 7) J OculPharmacol. 1993 Spring;9(1):59-68. Effect of ascorbic acid 2-0-alpha-glucoside on hydrocortisone-induced cataract formation in developing chick embryos: I. Comparison of the preventive effect of ascorbic acid derivatives. Nagata M(1), Tanioka H, Mibu H, Hikida M, Akiba M, Yamamoto I. 8) J OculPharmacol. 1994 Fall;10(3):537-42. Effect of ascorbic acid 2-O-alpha-glucoside on hydrocortisone-induced cataract formation in developing chick embryos: II. Influence on glutathione and lipid peroxide contents in the lens. Nagata M(1), Hikida M, Mibu H, Muto N, Yamamoto I. 9) Biochim Biophys Acta. 2014 Oct;1840(10):3017-21. doi: 10.1016/j.bbagen.2014.06.016. Moderate concentrations of 4-O-methylhonokiol potentiate GABAA receptor currents stronger than honokiol. BaurR, Schuehly W, Sigel E. 10)ScientificWorldJournal. 2006 Jan 17;6:1-11. Neuroregulation of the hypothalamus-pituitary-adrenal (HPA) axis in humans: effects of GABA-, mineralocorticoid-, and GH-Secretagogue-receptor modulation. Giordano R(1), Pellegrino M, Picu A, Bonelli L, Balbo M, Berardelli R, Lanfranco F, Ghigo E, Arvat E. 11)Biol Pharm Bull. 2006 Apr;29(4):766-71. Characterization of the radical-scavenging reaction of 2-O-substituted ascorbic acid derivatives, AA-2G, AA-2P, and AA-2S: a kinetic and stoichiometric study. TakebayashiJ(1), Tai A, Gohda E, Yamamoto I. 12) Phytomedicine. 2009 Oct;16(10):976-81. doi: 10.1016/j.phymed.2009.03.001. The protective efficacy of magnolol in hind limb ischemia-reperfusion injury. Chen HY(1), Hung YC, Lee EJ, Chen TY, Chuang IC, Wu TS. 13) Biosci Biotechnol Biochem. 2015;80(1):80-8. doi: 10.1080/09168451.2015.1075861. Anti-skeletal muscle atrophy effect of Oenothera odorata root extract via reactive oxygen species-dependent signaling pathways in cellular and mouse model. Lee YH(1), Kim WJ(1), Lee MH(1), Kim SY(1), Seo DH(2), Kim HS(2), Gelinsky M(3), Kim TJ(1). 14) Biol Pharm Bull. 2010;33(8):1360-3. Endothelium-independent vasorelaxation by Ligusticumwallichii in isolated rat aorta: comparison of a butanolic fraction and tetramethylpyrazine, the main active component of Ligusticum wallichii. Kim EY(1), Kim JH, Rhyu MR. 15) Life Sci. 2005 Aug 12;77(13):1416-24. Role of cGMP signals in tetramethylpyrazine induced relaxation of the isolated rat aortic strip. Tsai CC(1), Lai TY, Huang WC, Liu IM, Liou SS. 16) PLoS One. 2014 Feb 5;9(2):e88243. doi: 10.1371/journal.pone.0088243. eCollection 2014. Tetramethylpyrazine ameliorates high glucose-induced endothelial dysfunction by increasing mitochondrial biogenesis. Xu Q(1), Xia P(1), Li X(2), Wang W(1), Liu Z(3), Gao X(1). 17) Life Sci. 2005 Aug 12;77(13):1416-24. Role of cGMP signals in tetramethylpyrazine induced relaxation of the isolated rat aortic strip. Tsai CC(1), Lai TY, Huang WC, Liu IM, Liou SS. 18) ClinExpPharmacol Physiol. 2012 Jan;39(1):28-36. doi: 10.1111/j.1440-1681.2011.05629.x. Effects of magnolol on vascular contraction in rat aortic rings. Seok YM(1), Kim HY, Garmaa O, Cha BY, Woo JT, Kim IK. 19) PLoS One. 2015 Mar 20;10(3):e0120366. doi: 10.1371/journal.pone.0120366. eCollection 2015. Magnolol administration in normotensive young spontaneously hypertensive rats postpones the development of hypertension: role of increased PPAR gamma, reduced TRB3 and resultant alleviative vascular insulin resistance. Liang X(1), Xing W(2), He J(3), Fu F(2), Zhang W(4), Su F(4), Liu F(1), Ji L(1), Gao F(2), Su H(5), Sun X(3), Zhang H(1). 20) Fish Physiol Biochem. 2010 Sep;36(3):749-55. doi: 10.1007/s10695-009-9349-z. Epub 2009 Aug 15. Effect of dietary ascorbate on lipogenesis and lipolysis activities in black sea bream, Acanthopagrus schlegelii. Ji H(1), Om AD, Yoshimatsu T, Umino T, Nakagawa H, Sakamoto S. 21) Biofactors. 2012 Sep-Oct;38(5):372-7. doi: 10.1002/biof.1029. Epub 2012 Jun 7. Honokiol and magnolol stimulate glucose uptake by activating PI3K-dependent Akt in L6 myotubes. Choi SS(1), Cha BY, Lee YS, Yonezawa T, Teruya T, Nagai K, Woo JT. 22) 1. Ross FiziolZhIm I M Sechenova. 2014 Jun;100(6):649-69. . Astratenkova IV, Rogozkin VA. 23) Biochim Biophys Acta. 2015 Jan;1850(1):51-61. doi: 10.1016/j.bbagen.2014.10.001. Epub 2014 Oct 13. The mechanism of action of ursolic acid as insulin secretagogue and insulinomimetic is mediated by cross-talk between calcium and kinases to regulate glucose balance. Castro AJ, et al. 24)PLoS One. 2012;7(6):e39332. doi: 10.1371/journal.pone.0039332. Epub 2012 Jun 20. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease. Kunkel SD(1), Elmore CJ, Bongers KS, Ebert SM, Fox DK, Dyle MC, Bullard SA, Adams CM. 25) PLoS One. 2014 Feb 5;9(2):e88243. doi: 10.1371/journal.pone.0088243. eCollection 2014. Tetramethylpyrazine ameliorates high glucose-induced endothelial dysfunction by increasing mitochondrial biogenesis. Xu Q(1), Xia P(1), Li X(2), Wang W(1), Liu Z(3), Gao X(1). 26) ZhongguoXiu Fu Chong Jian Wai KeZaZhi. 2012 May;26(5):597-600. [Effect of Ligustrazine on expressions of FoXO3a, MAFbx, and MuRF1 in denervated skeletal muscle atrophy rats]. Wang H(1), Liang B, Peng C, Wang P. 27) Space Med MedEng (Beijing). 2005 Aug;18(4):262-6. [Effects of Ligustrazine and Radix Astragali on activities of myosin adenosine triphosphatase of soleus muscle and muscle atrophy in tail-suspended rats]. Gao YF, Fan XL, He ZX, Wu SD, Song XA. 28)ZhongguoZhong Yao ZaZhi. 2009 Nov;34(21):2808-12.[Studies on protection and mechanism of tetramethylpyrazine on myocardial injury of rats with DHF]. Zhang X(1), Liu W, Zhou J, Fan C. 29)ClinExpPharmacol Physiol. 2003 Oct;30(10):793-8. Effect of tetramethylpyrazine on potassium channels to lower calcium concentration in cultured aortic smooth muscle cells. Wong KL(1), Chan P, Huang WC, Yang TL, Liu IM, Lai TY, Tsai CC, Cheng JT. 30) J Biol Chem. 2015 Oct 16;290(42):25497-511. doi: 10.1074/jbc.M115.681445. Epub 2015 Sep 3. Identification and Small Molecule Inhibition of an Activating Transcription Factor 4 (ATF4)-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy. Ebert SM(1), Dyle MC(2), Bullard SA(3), Dierdorff JM(3), Murry DJ(4), Fox DK(2), BongersKS(2), Lira VA(5), Meyerholz DK(6), Talley JJ(7), Adams CM(8). 31) 40th COSPAR Scientific Assembly. Held 2-10 August 2014, in Moscow, Russia, Abstract F5.2-12-14. The Effects of Ligustrazine on the Ca2+ Concentration of Soleus and Gastrocnemius Muscle Fibers in Hindlimb Unloaded Rat. Gao, Yunfang; Goswami, Nandu; Du, Bei; Hu, Huanxin; Wu, Xue 32)PLoS One. 2015 Nov 24;10(11):e0143594. doi: 10.1371/journal.pone.0143594. eCollection 2015. Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1. Chen MC(1), Chen YL(2), Lee CF(3), Hung CH(4), Chou TC. 33)Evid Based Complement Alternat Med. 2015;2015:130513. doi: 10.1155/2015/130513. Epub 2015 Apr 7. Effect of Oenothera odorata Root Extract on Microgravity and Disuse-Induced Muscle Atrophy. Lee YH(1), Seo DH(2), Park JH(2), Kabayama K(3), Opitz J(4), Lee KH(5), Kim HS(2), Kim TJ(1). 34) Br J Pharmacol. 2006 Jan;147(2):131-9. Ca2+-mediated ascorbate release from coronary artery endothelial cells. Davis KA(1), Samson SE, Best K, Mallhi KK, Szewczyk M, Wilson JX, Kwan CY, Grover AK. 35) ClinExpPharmacol Physiol. 2003 Oct;30(10):793-8. Effect of tetramethylpyrazine on potassium channels to lower calcium concentration in cultured aortic smooth muscle cells. Wong KL1, Chan P, Huang WC, Yang TL, Liu IM, Lai TY, Tsai CC, Cheng JT. 36)Exp Cell Res. 2011 Feb 1;317(3):356-66. doi: 10.1016/j.yexcr.2010.11.001. Epub 2010 Nov 9. IGF-I and vitamin C promote myogenic differentiation of mouse and human skeletal muscle cells at low temperatures. Shima A(1), Pham J, Blanco E, Barton ER, Sweeney HL, Matsuda R. 37) FEBS J. 2015 Sep;282(18):3647-58. doi: 10.1111/febs.13369. Epub 2015 Aug 1. ATF4 mediates necrosis induced by glucose deprivation and apoptosis induced by 2-deoxyglucose in the same cells. León-Annicchiarico CL(1), Ramírez-Peinado S(1), Domínguez-Villanueva D(1), Gonsberg A(1), Lampidis TJ(2), Muñoz-Pinedo C(1). 38) Korean J Physiol Pharmacol. 2014 Oct;18(5):441-6. doi: 10.4196/kjpp.2014.18.5.441. Epub 2014 Oct 17. Ursolic Acid-induced elevation of serum irisin augments muscle strength during resistance training in men. Bang HS et al.
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