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nutrition performance PREWORKOUT THE ULTIMATE PERFORMANCE ENHANCER The eminent scientist and inventor Alexander Graham Bell once said, “Before anything else, preparation is the key to success.” Well, Advanced Molecular Labs (AML) and its CEO, Steve Blechman, absolutely agree. That is why they’ve created the most scientifically advanced pre-workout formula that will completely PREPARE you for your next workout by packing your muscle cells with energy, by increasing exercise endurance so you can push your body to the limit for longer periods of time, and by generating the perfect blend of neurotransmitters that improve your mood and motivation to get into the gym and start pounding the weights with the utmost intensity and resilience! AML Preworkout Supports Neurotransmitter Production, Intensifying Energy and Motivation One of the most important aspects of a pre-workout supplement is the ability to increase focus in the gym. So when you feel like going to sleep instead of the weight room, your pre-workout supplement should be able to get you moving. A primary contributor to pre-workout fatigue is a weary central nervous system (CNS) that requires more than just energy from food to get you going. Fortunately, AML has discovered a unique blend of compounds that conquers CNS fatigue by reestablishing the required levels of the correct neurotransmitters to restore focus and motivation needed for intense training. Increased Dopamine Increases Drive to Exercise Although there have been a number of mechanisms proposed that explain the apparent increase in CNS fatigue, the “central fatigue hypothesis” states that an increase in the ratio of serotonin to dopamine within the CNS is associated with feelings of tiredness and lack of motivation, accelerating the onset of fatigue during prolonged exercise, whereas a low serotonin to dopamine ratio favors improved performance through the maintenance of motivation and arousal.1 Since serotonin is a neurotransmitter that has been linked to fatigue because of its well-known influence on sleep and drowsiness, it was originally thought that the serotonin to dopamine ratio was increasing because of greater serotonin production within the brain. However, it turns out that the serotonin to dopamine ratio was increasing primarily because of the degradation of dopamine associated with neuronal activity within the CNS associated with exercise or other AML Preworkout is the ultimate pre-workout formula that will completely PREPARE you for your next workout by packing your muscle cells with energy, and by increasing exercise endurance so you can push your body to the limit for longer periods of time. 000 MD musculardevelopment.com September 2014 BY MICHAEL J. RUDOLPH, PH.D. SENIOR SCIENCE EDITOR stressful stimuli.2 This new insight makes sense based on dopamine’s well-defined influence on motivation, arousal and attention. Consequently, increasing dopamine levels should improve CNS function and overall exercise performance. AML Preworkout Is Loaded With the Most Potent Dopamine Enhancers neurochemical environment in the brain for even greater mental focus that bolsters performance in the gym. The Energetic Buzz From Caffeine Caffeine is widely consumed as an ergogenic aid to improve exercise performance. Several mechanisms have been proposed to explain caffeine’s performance-enhancing influence, including enhanced muscular contraction force, increased cellular energy production within muscle and stimulation of the central nervous system (CNS). While increased contractile forces and energy production within muscle from caffeine consumption preferentially influence highintensity weight training, caffeine’s ability to stimulate the CNS has a greater impact Since reduced dopamine levels within the CNS decreases motivation and performance while inducing fatigue3, novel ways to increase dopamine production before your workout should boost exercise performance. The consumption of the dopamine precursor tyrosine was recently shown to provide this benefit, where subjects performed an exercise test while consuming either a placebo or tyrosine in a double-blind manner, one hour before cycling to exhaustion in 86 degrees Fahrenheit.4 The results showed the tyrosineconsuming group exercised for 16 percent longer compared to the placebo group, while also showing no increase in rate of perceived exertion despite a longer exercise time. This confirms that tyrosine consumption influences the ability to tolerate prolonged exercise, conceivably by increasing dopamine levels. AML Preworkout combines tyrosine with folic acid, which may further increase dopamine by increasing tetrahydrobiopterin (BH4) levels. As a co-factor for tyrosine hydroxylase, BH4 facilitates the conversion of tyrosine to L-dopa, which is a precursor to dopamine. The tropical plant mucuna pruriens is also found in AML Preworkout. This ingredient is loaded with the dopamine precursor L-dopa5, which has been shown to effectively increase diminished dopamine levels in patients with Parkinson’s disease.6 Interestingly, an additional clinical trial also indicated that mucuna pruriens was just as effective as some pharmaceuticals in the treatment of Parkinson’s disease, illustrating potent ability of mucuna pruriens to boost dopamine levels in the brain.7 on the mental aspect of training. The ability of caffeine to stimulate the CNS is due, in part, to its capacity to inhibit the adenosine receptor in the brain, which triggers the release of dopamine and adrenaline.8 The surge of dopamine and adrenaline from caffeine consumption will amp-up your neurochemistry for greater concentration and intensity while training in the gym. Simultaneously Increase Dopamine and Adrenaline for an Extra Boost Piperine (Bioperine) Provides Additional Adrenaline Release Adrenaline is a hormone produced by the adrenal glands that is well known for supporting the “fight-or-flight” response that occurs when we get scared, or deal with different forms of stress. Adrenaline activates several biochemical pathways that increase glucose and fatty acid levels in the blood, which provides energy for the muscle cell. The remarkable ability of AML Preworkout to simultaneously increase adrenaline and dopamine provides an even more robust AML Preworkout generates the perfect blend of neurotransmitters that improve your mood and motivation to get into the gym and start pounding the weights with the utmost intensity and resilience! Another neurotransmitter-enhancing compound found in AML Preworkout is the compound piperine, which is naturally found in black pepper. Piperine has been reported to trigger adrenaline release by activating the TRPV receptor in the brain, which stimulates the sympathetic nervous system, resulting in adrenaline release.9 It also improves the gastrointestinal absorption and systematic utilization of nutrients in AML Preworkout. September 2014 musculardevelopment.com Improved Muscular Endurance Another important feature of a pre-workout supplement is the ability to improve muscular endurance for extended levels of intensity while you work out. AML Preworkout is loaded with the amino acid beta-alanine, which has many positive effects on health and exercise performance. Within muscle cells, beta-alanine functions as a key building block for carnosine, the primary buffer within muscle tissue that counters the negative impact of lactic acid on exercise capacity. Several independent studies have clearly illustrated the positive influence of beta-alanine on carnosine production in muscle. In these studies, a significant increase in muscle carnosine of approximately 40 to 50 percent was measured after beta-alanine ingestion over a four- to eight-week time frame.10,11 In addition to beta-alanine supporting carnosine synthesis, it has also been shown to reduce muscle acidosis. In one study, subjects consuming beta-alanine for four weeks showed a much slower rise in acidity during high-intensity exercise.12 Moreover, the muscle-buffering function associated with beta-alanine intake has also been shown to improve endurance, as illustrated in a study where subjects ingesting beta-alanine demonstrated major improvements while performing a medium-intensity, high-repetition squat workout, compared to a placebo group.13 Heightened Vasodilation for Enhanced Blood Flow and Stamina The signaling molecule nitric oxide (NO) enhances performance by increasing blood flow caused by improved vasodilation. NO induces vasodilation by activating several cellular signaling cascades that relax the smooth muscle within the arterial wall, causing the arteries to dilate or open up. The increased blood flow from vasodilation delivers more essential nutrients and oxygen to laboring muscles while simultaneously removing metabolic waste, which collectively enhances muscular performance. NO is biosynthesized from the amino acid arginine, meaning increased consumption of arginine ought to boost greater production of NO. However, arginine is poorly absorbed by the intestine14 and is quickly broken down by the liver15, significantly reducing its bioavailability and capacity to increase NO production. On the other hand, the amino acid citrulline, which is quickly converted in the body into arginine, is more effectively absorbed by the intestines and avoids breakdown by the liver.16 Consequently, taking AML Preworkout, which contains copious amounts of citrulline, MD 000 nutrition performance represents a fantastic way to vigorously increase endogenous arginine levels and drive NO production for considerably improved stamina.17 Additional NO Boosters In addition to the potent NO-booster citrulline, AML Preworkout also possesses watermelon, beetroot, and grape skin extracts, which are rich in compounds that have also been shown to powerfully stimulate NO production18-20 for an added influence on vasodilation and performance enhancement. Enhanced Circulation With Potassium and Magnesium Citrate Increased potassium and magnesium intake promotes vasodilation, leading to reduced blood pressure. Numerous studies have shown higher potassium intake reduces the risk of stroke and many other cardiovascular diseases, likely due to their capacity to increase vasodilation, which reduces blood pressure.21,22 Although it is not well understood how these two elements enhance vasodilation, the incorporation of these two elements into AML Preworkout fortifies its capacity to bolster cardiovascular performance for improved endurance. Furthermore, potassium and magnesium complex with citrate in AML Preworkout. Citrate has also been shown to improve exercise performance by buffering lactic acid buildup in the muscle, further upgrading performance.23 AML Preworkout Contains the NO-Generating Folic Acid Tetrahydrobiopterin (BH4) has many different roles in the body, with one function being a catalyst that accelerates NO production. In fact, BH4 deficiency significantly contributes to many different circulatory diseases due to insufficient NO-driven vasodilation.24 Consequently, oral BH4 ingestion should conceivably boost NO production. Yet, studies have demonstrated that BH4 intake failed to show any significant improvement in vasodilation due to poor bioavailability.25,26 However, the biosynthesis of BH4 in the body can also be enhanced by consuming folic acid, which functions as a co-factor for the enzyme dihydrofolate reductase, which synthesizes BH4. In fact, oral consumption of folic acid was shown to improve NO production as well as vasodilation.27 Eradicate Lactic Acid for Improved Endurance With AML Preworkout Exercise-induced muscle fatigue is due to many different factors, including the accumulation of certain metabolites within the muscle cell such as ammonia.28,29 000 MD During intense exercise, the conversion of adenosine triphosphate (ATP) into adenosine monophosphate (AMP) provides the necessary energy for muscular contraction, while also increasing AMP levels. The greater amount of AMP from muscular contraction results in higher ammonia levels because the body breaks down AMP into ammonia, which increases ammonia levels. The accumulation of ammonia inhibits the metabolism of pyruvate in the muscle cell30, reducing energy production while also increasing lactic acid production, which consequently has a negative influence on exercise performance. Citrulline reduces the accumulation of ammonia by triggering the urea cycle, the biochemical pathway that reduces ammonia AML Preworkout is loaded with an assortment of the most effective muscle-building compounds available. levels by converting it into urea. This, of course, subsequently reduces lactic acid accumulation as well. Furthermore, citrulline has been found to reduce lactic acid levels during high-intensity exercise and significantly improve exercise performance.31 AML’s Unique Performanceenhancing Blend Augments Muscular Power The final element absolutely required of a pre-workout supplement is the capacity to increase strength and power output. AML Preworkout is loaded with an assortment of the most effective muscle-building and performance-enhancing compounds available. The first strength-promoting compound in AML Preworkout is creatine monohydrate, which is the most studied form of creatine on the market. In addition, creatine monohydrate is also one of the most heavily used supplements32, primarily because its effectiveness at improving strength and size. Many studies over the years have clearly shown that short-term creatine monohydrate supplementation increases power output during intense exercise. Furthermore, creatine supplementation with heavy weight training has the potential to stimulate muscle hypertrophy.33 These unique capabilities stem from creatine’s ability to function as a primary energy storage molecule that rapidly reverses the depletion of muscle cell energy (ATP) during muscular contraction, ultimately recharging energy levels within the muscle cell, prolonging muscular contraction for superior workouts and muscle growth.34 Also, creatine monohydrate potently drives muscle growth utilizing several different cellular mechanisms, including the stimulation of muscle cell formation35, increased muscle protein synthesis36 and inhibition of the muscledepleting molecule myostatin.37 AML Preworkout Powers Your Muscles With ATP Although the oral intake of ATP likely results in its rapid breakdown within the digestive tract, precluding its function as an energy source for the body, studies have shown that long-term oral administration of ATP still produces gains in muscle size and strength.38,39 This effect likely comes from the extensive extracellular functions of ATP that are primarily mediated through the adenosine receptors. Adenosine receptors are embedded in the plasma membrane of the cell. ATP acts as a signaling molecule directly upon these receptors, where it controls numerous functions, including increased muscular contraction by boosting muscle-cell calcium levels and decreased pain reception. The ability of ATP to mitigate pain reception likely supports a higher training intensity with a lower pain perception, for an enhanced training effect. AML Preworkout Improves Fluid Balance in the Muscle for Greater Strength Gains Natural osmolytes like betaine, found in many different foods such as whole grains, spinach, and shellfish, act as osmoprotectants by maintaining cell volume and fluid balance during stressful situations such as dehydration. Because of this, betaine plays a key role in many aspects of human health, as studies have shown that diets high in betaine decrease the risk for certain diseases.40,41 In addition to its function as an osmolyte, betaine also supplies the methyl group required for production of the anabolic creatine molecule.42 Accordingly, it has been shown that betaine significantly increases anaerobic power in the bench press and squat. Interestingly, additional studies have also shown that betaine increased muscle protein synthesis and lean body mass, while also reducing abdominal fat.43,44 Pre-workout Leucine Consumption Is Detrimental to Muscle Growth Despite the fact that leucine consumption during and after resistance exercise promotes musculardevelopment.com September 2014 muscle growth45, the consumption of leucine before training seems to diminish muscular performance. One reason being that preworkout consumption of leucine mitigates the conversion of glycogen into glucose within the muscle cell, effectively diminishing energy availability for muscle function.46 Another issue with pre-workout leucine consumption involves the increased potential for insulin-signaling desensitization— especially if leucine is also being ingested, as it should be, during and after weight training. Studies have shown that insulin resistance can occur with increased amino acid consumption, especially the branched-chain amino acid leucine.47,48 Of course, insulin resistance from the additional pre-workout leucine would reduce insulin’s anabolic properties, meaning a decrease in muscle growth. The final negative impact of pre-workout leucine comes from leucine’s ability to competitively inhibit dopamine production by preventing the uptake of the dopamineprecursor tyrosine into the brain.49 This effect References: 1. Acworth I, Nicholass J, et al. Effect of sustained exercise on concentrations of plasma aromatic and branched-chain amino acids and brain amines. Biochem Biophys Res Commun 1986;137, 149-153. 2. Davis JM and Bailey SP. Possible mechanisms of central nervous system fatigue during exercise. Med Sci Sports Exerc 1997;29, 45-57. 3. Roelands B, Watson P, et al. A dopamine/noradrenaline reuptake inhibitor improves performance in the heat, but only at the maximum therapeutic dose. Scand J Med Sci Sports 2012;22, e93-98. 4. Tumiltay L, Davison G, et al. Oral tyrosine supplementation improves exercise capacity in the heat. Eur J Appl Physiol 2011;111, 2941-2950. 5. Alleman RJ Jr, Canale RE, et al. A blend of chlorophytum borivilianum and velvet bean increases serum growth hormone in exercise-trained men. Nutr Metab Insights 2011;4, 55-63. 6. Tharakan B, Dhanasekaran M, et al. Anti-Parkinson botanical Mucuna pruriens prevents levodopa induced plasmid and genomic DNA damage. Phytother Res 2007;21, 1124-1126. 7. Katzenschlager R, Evans A, et al. Mucuna pruriens in Parkinson’s disease: a double blind clinical and pharmacological study. J Neurol Neurosurg Psychiatry 2004;75, 1672-1677. 8. Zheng X, Takatsu S, et al. Acute intraperitoneal injection of caffeine improves endurance exercise performance in association with increasing brain dopamine release during exercise. Pharmacol Biochem Behav 2014;122, 136-143. 9. McNamara FN, Randall A and Gunthorpe MJ. Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1). Br J Pharmacol 2005;144, 781-790. 10. Harris RC, Tallon MJ, et al. The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids 2006;30, 279-289. 11. Stellingwerff T, Anwander H, et al. Effect of two betaalanine dosing protocols on muscle carnosine synthesis and washout. Amino Acids 2010;42, 2461-2472. 12. Baguet A, Koppo K, et al. Beta-alanine supplementation reduces acidosis but not oxygen uptake response during high-intensity cycling exercise. Eur J Appl Physiol 2010;108, 495-503. 13. Hoffman J, Ratamess NA, et al. Beta-alanine and the hormonal response to exercise. Int J Sports Med 2008;29, 952-958. 14. Grimble GK. Adverse gastrointestinal effects of arginine and related amino acids. J Nutr 2007;137, 1693S-1701S. 15. Heyland DK, Dhaliwal R, et al. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr 2003;27, 355-373. 16. Cynober L. Pharmacokinetics of arginine and related amino acids. J Nutr 2007;137, 1646S-1649S. would increase the rate of CNS fatigue and overall sluggishness, ultimately hindering exercise performance. As a result of the negative effects associated with pre-workout leucine intake, AML Preworkout is absolutely leucine-free. compounds that principally function as antioxidants (such as vitamins C, E and the amino acids N-acetylcysteine and taurine), allowing for the sufficient natural generation of ROS from training for better muscle growth and recovery. AML Preworkout Supports ROS Exposure for Greater Muscle Growth AND RECOVERY For more information on AML PREWORKOUT, visit www.advancedmolecularlabs.com Intense weightlifting or exercise puts stress on the muscle cell, producing muscle damage that requires a recovery process to regenerate muscle function and increase muscle size. There is emerging evidence to suggest that reactive oxygen species (ROS) produced during intense training assists the recovery process. Moreover, it’s been shown that consumption of the powerful antioxidant vitamin C, which chemically negates ROS function, can attenuate the recovery of damaged muscle50 implying that antioxidants, in general, mitigate muscle repair and hypertrophy. For that reason, AML Preworkout does not contain For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a Research Scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security. 17. Schwedhelm E, Maas R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol 2008;65, 51-59. 18. Resende AC, Emiliano AF, et al. Grape skin extract protects against programmed changes in the adult rat offspring caused by maternal high-fat diet during lactation. J Nutr Biochem 2014;24, 2119-2126. 19. Breese BC, McNarry MA. Beetroot juice supplementation speeds O2 uptake kinetics and improves exercise tolerance during severe-intensity exercise initiated from an elevated metabolic rate. Am J Physiol Regul Integr Comp Physiol 2013;305, R1441-1450. 20. Muggeridge DJ, Howe CC, et al. A single dose of beetroot juice enhances cycling performance in simulated altitude. Med Sci Sports Exerc 2013;46, 143-150. 21. Blanch N, Clifton PM, et al. Effect of high potassium diet on endothelial function. Nutr Metab Cardiovasc Dis 2014. 22. D’Elia L, Iannotta C, et al. Potassium-rich diet and risk of stroke: Updated meta-analysis. Nutr Metab Cardiovasc Dis 2014;24, 585-587. 23. Russell C, Papadopoulos E, et al. Acute versus chronic supplementation of sodium citrate on 200 m performance in adolescent swimmers. Journal of the International Society of Sports Nutrition 2014;2014, 11:26 11, 1028-1037. 24. Gaede P, Vedel P, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003;348, 383-393. 25. Moens AL, Kietadisorn R, et al. Targeting endothelial and myocardial dysfunction with tetrahydrobiopterin. J Mol Cell Cardiol 2011;51, 559-563. 26. Alkaitis MS and Crabtree MJ. Recoupling the cardiac nitric oxide synthases: tetrahydrobiopterin synthesis and recycling. Curr Heart Fail Rep 2012;9, 200-210. 27. Youn JY, Gao L and Cai H. The p47phox- and NADPH oxidase organiser 1 (NOXO1)-dependent activation of NADPH oxidase 1 (NOX1) mediates endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction in a streptozotocin-induced murine model of diabetes. Diabetologia 2012;55, 2069-2079. 28. Barnes RH, Labadan BA, et al. Effects of Exercise and Administration of Aspartic Acid on Blood Ammonia in the Rat. Am J Physiol 1964;207, 1242-1246. 29. Wilkerson JE, Batterton DL and Horvath SM. Ammonia production following maximal exercise: treadmill vs. bicycle testing. Eur J Appl Physiol Occup Physiol 1975;34, 169-172. 30. Lowenstein JM. Ammonia production in muscle and other tissues: the purine nucleotide cycle. Physiol Rev 1972;52, 382-414. 31. Takeda K, Machida M, et al. Effects of citrulline supplementation on fatigue and exercise performance in mice. J Nutr Sci Vitaminol (Tokyo) 2011;57, 246-250. 32. Buford TW, Kreider RB, et al. International Society of Sports Nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr 2007;4, 6. 33. Harris RC, Soderlund K and Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond) 1992;83, 367-374. 34. Bemben MG and Lamont HS. Creatine supplementation and exercise performance: recent findings. Sports Med 2005;35, 107-125. 35. Willoughby DS and Rosene JM. Effects of oral creatine and resistance training on myogenic regulatory factor expression. Med Sci Sports Exerc 2003;35, 923-929. 36. Willoughby DS and Rosene J. Effects of oral creatine and resistance training on myosin heavy chain expression. Med Sci Sports Exerc 2001;33, 1674-1681. 37. Volek JS, Duncan ND, et al. Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc 1999;31, 1147-1156. 38. Wilson JM, Joy JM, et al. Effects of oral adenosine5’-triphosphate supplementation on athletic performance, skeletal muscle hypertrophy and recovery in resistancetrained men. Nutr Metab (Lond) 2013;10, 57. 39. Jordan AN, Jurca R, et al. Effects of oral ATP supplementation on anaerobic power and muscular strength. Med Sci Sports Exerc 2004;36, 983-990. 40. Craig SA. Betaine in human nutrition. Am J Clin Nutr 2004;80, 539-549. 41. Konstantinova SV, Tell GS, et al. Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and women. J Nutr 2008;138, 914-920. 42. Byerrum RU, Sato CS and Ball CD. Utilization of Betaine as a Methyl Group Donor in Tobacco. Plant Physiol 1956;31, 374-377. 43. Brigotti M, Petronini PG, et al. Effects of osmolarity, ions and compatible osmolytes on cell-free protein synthesis. Biochem J 2003;369, 369-374. 44. Hoffman JR, Ratamess NA, et al. Effect of 15 days of betaine ingestion on concentric and eccentric force outputs during isokinetic exercise. J Strength Cond Res 2011;25, 22352241. 45. Pasiakos SM, McClung HL, et al. Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis. Am J Clin Nutr 2011;94, 809-818. 46. Blomstrand E, Eliasson J, et al. Branched-chain amino acids activate key enzymes in protein synthesis after physical exercise. J Nutr 2006;136, 269S-273S. 47. Tremblay F, Lavigne C, et al. Role of dietary proteins and amino acids in the pathogenesis of insulin resistance. Annu Rev Nutr 2007;27, 293-310. 48. Newgard CB, An J, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 2009;9, 311-326. 49. Choi S, Disilvio B, et al. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines. Amino Acids 2013. 50. Ristow M, Zarse K, et al. Antioxidants prevent healthpromoting effects of physical exercise in humans. Proc Natl Acad Sci USA 2009;106, 8665-8670. September 2014 musculardevelopment.com MD 000