CENEGENICS MUSCLE FORMULA

CENEGENICS MUSCLE FORMULA Sarcopenia, Myostatin, and the Role of Fortetropin from Cenegenics Medical Institute... The Global Leader in a proactive medical approach to optimized health

THERE IS A SIGNIFICANT AMOUNT OF RESEARCH EXAMINING MUSCLE AND ITS IMPORTANCE IN OVERALL HEALTH. Everyone Recognizes That Muscle Is Important For Its Role In Movement And Physical Activity. Most Individuals Do Not Know It Also Has Important Metabolic Functions. Studies Show That Lean Muscle Mass Is A Key Marker For Overall Health And Longevity. There Are Several Ways To Improve Muscle Mass And Function. Diet, Exercise And Hormonal Factors All Play Important Roles In Maintaining And Increasing Muscle. WE NOW RECOGNIZE THAT MYOSTATIN ALSO PLAYS A ROLE. MYOSTATIN IS A PROTEIN IN OUR BODY THAT PREVENTS MUSCLE GROWTH. Myostatin Levels In The Body Increase As One Ages. Research Now Suggests That Inhibiting Myostatin Improves Muscle Mass And Function. It Has Also Been Found That Using Testosterone Increases Myostatin Levels In The Body. We Know Testosterone Increases Muscle Mass But It Also Increases Myostatin Levels. The Ability To Inhibit Myostatin In Individuals Using Testosterone May Improve Gain In Lean Muscle And Has The Potential To Reduce Testosterone Doses One Needs To Take. CENEGENICS NEW MUSCLE FORMULA IS A NATURAL MIXTURE OF PROTEINS, LIPIDS, PEPTIDES AND OTHER BIOACTIVE MOLECULES DERIVED FROM FERTILIZED CHICKEN EGG YOLK AND PROCESSED IN A WAY THAT RETAINS THE BIOLOGICAL ACTIVITY OF THESE INGREDIENTS. These Ingredients Are Known To Have Pro-Myogenic And Anti-Inflammatory Effects. They Bind To Myostatin And Prevent It From Inhibiting Muscle Growth. Clinical Data Demonstrates These Active Ingredients Reduce Serum Myostatin Levels In Human Subjects. This Is An Oral Supplement Taken Once A Day. There Are No Known Side Effects. Individuals With Egg Allergies Should Not Take This, As This Is An Egg-Based Product. CENEGENICS MUSCLE FORMULA IS AN IMPORTANT SUPPLEMENT TO A BALANCED APPROACH TO IMPROVE LEAN MUSCLE MASS AND HEALTH ALONG WITH DIET, EXERCISE AND HORMONES. Call Cenegenics Now. 480.454.2370 CENEGENICS MUSCLE FORMULA FAQS MUSCLE FORMULA HOW IT WORKS The Key Active Ingredient In The Cenegenics Muscle Formula Is Fortetropin, Which Functions As A Modulator And Antagonist Of Myostatin Production. Muscle Formula Contains A Complex Mixture Of Proteins, Lipids, Peptides And Other Bioactive Molecules Derived From Fertilized Chicken Egg Yolk Pasteurized Using A Proprietary Process That Retains The Biological Activity. Certain Moieties In This Mixture Impart Their Pro-Myogenic Activity Through Action On The Tgf-Β Signaling Pathway. SUPPLEMENT FACTS/INGREDIENTS LIST Is The Cenegenics Muscle Formula A Hormone Or Involved With Hormone Replacement Therapy (Hrt)? The Main Ingredient In The Cenegenics Muscle Formula Is Fortetropintm, A Natural Dietary Supplement Developed To Improve Muscle Strength And Quality. It Is Not A Hormone Or Involved With Hrt. Is This Product Animal Or Plant Derivative? This Product Is Derived From Fertilized Chicken Egg Yolk And Composed Of Proteins, Peptides And Lipids. Are There Any Drug And/Or Allergic Interactions? There Are No Known Drug Interactions But Individuals Who Are Allergic To Egg Or Egg-Based Product Should Avoid Muscle Formula. Who Can Take The Cenegenics Muscle Formula? All Adults Over The Age Of 18 Can Take It. Do Responses Differ In Men And Women? Myostatin Is Found In Both Men And Women And Its Suppression Appears Be Similar. We Have No Evidence That It Works Differently In Men And Women. Using Muscle Formula To Decrease Myostatin Levels Should Have Similar Impacts With Respect To Myostatin Action In Both Men And Women. What Is The Dose? Current Recommendation Is 20 Grams (One Pouch) Daily WHAT IS THE COST? $250 Per Box Of 30 Pouches Free Shipping $200 Per Box If 12 Or More Are Purchased At One Time HOW LONG DOES EACH BOX LAST? 30-Day Supply Per Box (If Taken Once Daily) WHAT IS THE SHELF LIFE? 24 Months What Is The Best Way To Take The Muscle Formula? It Can Be Eaten As A Dry Powder. You Can Also Prepare As A Drink My Mixing One Pouch In Approximately 6-8 Fluid Ounces Of Cold Water And Consuming Immediately. For Best Consistency Mix In A Blender For 20-30 Seconds. 2 Cenegenics Muscle Formula Call 480.454.2370 to order!

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Sarcopenia SARCOPENIA: The Problem Age-related loss of lean muscle mass, strength, and functionality Multifactorial disease process that may result from suboptimal hormone levels, inadequate dietary protein, nutritional imbalances, lack of exercise, oxidative stress, and inflammation Muscle quality loss 2.5% per year Muscle mass loss 0.5-1% per year CAUSES OF SARCOPENIA: Nutrition Decreased protein/amino acid intake Activity Physical, Inactivity, Immobility Endocrine Age-Related Decline in Hormone levels (testosterone,gh,igf-1) Inflammation Elevation of cytokines (IL-6, TNFalpha) CURRENT MANAGEMENT OF SARCOPENIA: 1. Exercise Resistance training 2. Nutrition Dietary intake of essential proteins 3. Therapeutics Growth Hormones, Testosterone 4. Natural Supplemental Support Myostatin inhibition TESTOSTERONE: Critical metabolic hormone in aging Beneficial effects on mood, energy levels and patients sense of well-being, sexual function, lean body mass and muscle strength, bone mineral density and cognition Declines with age TESTOSTERONE/MYOSTATIN (MOL CELL ENDOCRINOL. 2009;302(1):26 32): Found to increase myostatin level in human subjects In men treated with graded doses of testosterone, myostatin levels were significantly higher in both young and older men Changes in myostatin levels were significantly correlated with changes in total and free testosterone TARGET OPPORTUNITY MYOSTATIN INHIBITION: Myostatin inhibition appears to potentiate or augment the effects of testosterone resulting in improved lean muscle gains and retention Important component as part of testosterone therapy Used as a stand alone therapy for muscle health GENETIC FOUNDATION: The gene encoding myostatin was discovered in 1997 This gene was named myostatin for its ability to inhibit muscle differentiation and growth Myostatin (also known as growth differentiation factor 8, abbreviated GDF-8) is a protein that in humans is encoded by MSTN gene 4 Cenegenics Muscle Formula Call 480.454.2370 to order!

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Myogenesis OBSERVATIONS: Increase in myostatin as a consequence of obesity compromises skeletal muscle health and systemic metabolism in a high proportion of older persons. Inhibiting myostatin may provide an effective means to simultaneously improve their physical function and metabolic health Inhibition of myostatin in adult and older animals significantly increases muscle mass and confers benefits upon measures of performance and metabolism. MYOSTATIN INCREASES AS A RESULT OF AGING AND OBESITY (WHITE TA, LEBRASSEUR NK. GERONTOLOGY. 2014 JAN 17. DOI: 10.1159/000356740): An increase in serum myostatin as a result of aging and obesity compromises skeletal muscle health and metabolism in aging adults Inhibiting myostatin may provide an effective means to simultaneously improve their physical function and metabolic health Myostatin Inhibition Has a Positive Impact on Several Aspects of Health: REDUCTIONS IN SERUM MYOSTATIN ARE ASSOCIATED WITH: IMPROVEMENT IN AGE-RELATED REDUCTIONS IN: Muscle mass and fiber cross-sectional area Declines in bone mineral content and density Declines in cardiac ejection fraction REDUCED: Glucose and triglycerides Fat mass, macrophage infiltration and inflammation Ectopic lipid accumulation in the liver Aortic atheromatous lesions in mice genetically predisposed to atherosclerosis 6 Cenegenics Muscle Formula Call 480.454.2370 to order!

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FORTETROPIN: Unique suppressor of serum myostatin Myostatin inhibition maintains muscle health Decrease muscle loss Improves function and vitality Fortetropin Reduces Serum Myostatin in Humans Study Design: Double blind, randomized, placebo-controlled, parallel, single-dose Dose Administration: 10 grams of Fortetropin mixed with vanilla fat free/sugar free pudding for active arm; 10 grams of vanilla fat free/sugar free pudding alone for placebo arm. A single dose of Fortetropin resulted in substantial reduction in serum Myostatin concentration over a 24 hour period MUSCLE HEALTH MULTIFACTORIAL APPROACH: Diet / Supplements Exercise Hormonal Target each pathway in process Individual support for diet and exercise Therapeutics Myostatin inhibition Testosterone Growth Hormones ADDITIONAL OPTIONS: Supports muscle health in conjunction with testosterone Provides a testosterone-free alternative Individuals who choose not to undergo therapy High risk cardiac population Women 8 Cenegenics Muscle Formula Call 480.454.2370 to order!

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CURRENT RESEARCH: Effects of Fortetropin on blood chemistry in women Effects of Fortetropin on Lean Body Mass, Strength, and Power in Resistance Trained Males Effects of Fortetropin and Testosterone on lean muscle and fat mass in an animal model CENEGENICS RESEARCH: Opportunity for research and publishing Protocols to monitor multiple therapies Dexa Scans VO2 max Muscle function tests Customized system to deliver care and collect data FUTURE PRODUCT GROWTH: Female product line Specialized formulations in muscle health Partnership in scientific research and development MUSCLE FORMULA IS POWERED BY FORTETROPIN, A PROPRIETARY FORMULA AND THE WORLD S ONLY CLINICALLY PROVEN MODULATOR OF MYOSTATIN IN THE BODY. Sarcopenia, Myostatin, and the Role of Fortetropin SARCOPENIA, THE GRADUAL LOSS OF SKELETAL MUSCLE MASS, STRENGTH AND FUNCTION WITH ADVANCING AGE, REPRESENTS A SIGNIFICANT THREAT TO INDEPENDENCE AND QUALITY OF LIFE. There is significant interest in understanding the biology of sarcopenia and developing therapeutic interventions to prevent, slow or reverse its progression 1. Myostatin is a protein found in humans and which plays an important role in regulation of skeletal muscle development. This secreted growth factor, expressed mainly in skeletal muscle but also in adipose tissue, is a potent negative regulator of skeletal muscle mass. Mice in whom the gene for myostatin has been removed have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. Results in animal models have shown that inhibition of myostatin with injectable compounds increases muscle mass Reducing myostatin concentration in muscle appears to be a promising candidate for treatment of diseases such as muscle wasting, obesity, or diabetes 1. THUS, THERE HAS BEEN GREAT INTEREST IN MYOSTATIN AS A POTENTIAL MEDIATOR OF SARCOPENIA AS WELL AS MODULATION OF MYOSTATIN AS A THERAPEUTIC TARGET. Suppressing serum myostatin concentration through genetic disruption or congenital absence has been demonstrated to have many potential health benefits besides increasing muscle mass, reducing age-related sarcopenia, and stimulating muscle healing.2,3 Animal studies reported that lack of myostatin activity resulted in reduced weight gain4, fat cell size5, and hyperglycemia, increased energy expenditure and improved leptin sensitivity6 as well as suppression of proatherogenic dyslipidemia, and aortic atherogenesis.7 FORTETROPIN, IS A NUTRITIONAL SUPPLEMENT MANUFACTURED AND DISTRIBUTED BY MYOS THERAPEUTICS. This food based product is a powder made from egg yolks and contains egg yolk membranes and flavoring. FORTETROPIN appears to be an all-natural inhibitor of myostatin. As the first step in developing this product, further documentation of the ability of this product to modulate serum myostatin concentration has recently been completed. In 2005, Colker noted that standard store-bought fertilized chicken eggs reduced serum myostatin concentration when administered to healthy young men.9 A method was then developed to concentrate and sterilize the active fraction of egg yolks without inactivating the effect. Administration of 10 grams of this extract, was administered in a clinical trial of 10 healthy men; however this study had no control subjects.8 This study demonstrated a significant reduction in serum myostatin concentration at 12 hours postdose (12.6 pg/ml) compared to their baseline values (27.5 pg/ml) with concentrations back to baseline levels within 24 to 30 hours postdose. Post hoc analysis of this data shows it to be statistically significant. 10 Cenegenics Muscle Formula Call 480.454.2370 to order!

OF NOTE, IT HAS BEEN ESTABLISHED THAT IN MEN, SERUM MYSOSTATIN CONCENTRATION REMAINS STABLE OVER A 24 HOUR PERIOD, WITH NO DIURNAL VARIATION10. RECENT STUDIES HAVE SHOWN THAT MYOSTATIN LEVELS ARE HIGHER IN OLDER THAN YOUNG MEN AND THAT MYOSTATIN INCREASES IN MEN TREATED WITH GRADED DOSES OF TESTOSTERONE, PERHAPS AS A COMPENSATING MECHANISM. However, myostatin levels were not significantly associated with lean body mass in either young or older men attesting to the complex nature of muscle mass regulation.11 A RECENT TRIAL CONFIRMED THAT FORTETROPIN REDUCES SERUM MYOSTATIN CONCENTRATION. In this study conducted at a clinical research organization, serum myostatin concentration measured in men at baseline and every 6 hours over the 24 hours following demonstrated a mean reduction of 30% ( data on file, Myos Therapeutics). THE POTENTIAL OF THIS EGG YOLK EXTRACT TO MODULATE MYOSTATIN AND PERHAPS ASSIST IN MUSCLE ACCRETION IN THOSE WITH REDUCED MUSCLE MASS IS OF OBVIOUS VALUE. It could additionally add to muscle growth in those with normal muscle mass, and reduce the exercise effort required to maintain muscle mass if its role as a myostatin inhibitor is confirmed. References White TA, Lebrasseur NK. Myostatin and Sarcopenia: Opportunities and Challenges A Mini-Review..Gerontology. 2014 Jan 17. [Epub ahead of print] Siriett V, Platt L, Salerno MS, Ling N, Kambadur R, Sharma M. Prolonged absence of myostatin reduces sarcopenia. J Cell Physiol. 2006 Dec; 209(3): 866-73. McCroskery S, Thomas M, Platt L, Hennebry A, Nishimura T, McLeay L, Sharma M, Kambadur R. Improved muscle healing through enhanced regeneration and reduced fibrosis in myostatin-null mice. J Cell Sci. 2005 Aug 1;118(Pt 15):3531-41. Burgess K, Xu T, Brown R, Han B, Welle S. Effect of myostatin depletion on weight gain, hyperglycemia, and hepatic steatosis during five months of high-fat feeding in mice. PLoS One. 2011 Feb 24;6(2):e17090. Nakatani M, Kokubo M, Ohsawa Y, Sunada Y, Tsuchida K. Follistatin-derived peptide expression in muscle decreases adipose tissue mass and prevents hepatic steatosis. Am J Physiol Endocrinol Metab. 2011 Mar;300(3):E543-53. Epub 2011 Jan 4. Choi SJ, Yablonka-Reuveni Z, Kaiyala KJ, Ogimoto K, Schwartz MW, Wisse BE.Am J Physiol Endocrinol Increased energy expenditure and leptin sensitivity account for low fat mass in myostatin-deficient mice. Metab. 2011 Jun;300(6):E1031-7. Epub 2011 Mar 22. Tu P, Bhasin S, Hruz PW, Herbst KL, Castellani LW, Hua N, Hamilton JA, Guo W. Genetic disruption of myostatin reduces the development of proatherogenic dyslipidemia and atherogenic lesions in Ldlr null mice. 2009 Aug;58(8):1739-48. Epub 2009 Jun 9. Colker, C. Effect on serum myostatin levels of high grade handled fertile egg yolk AJCN 2009. 28:3, Abstract 29. Colker, C. Randomized blind comparison of follistatin in standard store-bought unfertilized chicken eggs versus standard store bought fertile eggs. JACN, 25: 5; Abstract 65; October 2006. Vamvini MT, Aronis KN, Chamberland JP, Mantzoros CS. Energy deprivation alters in a leptin- and cortisol-independent manner circulating levels of activin A and follistatin but not myostatin in healthy males. J Clin Endocrinol Metab. 2011 Nov;96(11):3416-23. Epub 2011 Aug 24. Lakshman KM, Bhasin S, Corcoran C, Collins-Racie LA, Tchistiakova L, Forlow SB, St Ledger K, Burczynski ME, Dorner AJ, Lavallie ER. Measurement of myostatin concentrations in human serum: Circulating concentrations in young and older men and effects of testosterone administration. Mol Cell Endocrinol. 2009 Apr 10;302(1):26-32. Epub 2009 Jan 21. White TA, Lebrasseur NK. Myostatin and Sarcopenia: Opportunities and Challenges A Mini-Review..Gerontology. 2014 Jan 17. [Epub ahead of print] Siriett V, Platt L, Salerno MS, Ling N, Kambadur R, Sharma M. Prolonged absence of myostatin reduces sarcopenia. J Cell Physiol. 2006 Dec; 209(3): 866-73. McCroskery S, Thomas M, Platt L, Hennebry A, Nishimura T, McLeay L, Sharma M, Kambadur R. Improved muscle healing through enhanced regeneration and reduced fibrosis in myostatin-null mice. J Cell Sci. 2005 Aug 1;118(Pt 15):3531-41. Burgess K, Xu T, Brown R, Han B, Welle S. Effect of myostatin depletion on weight gain, hyperglycemia, and hepatic steatosis during five months of high-fat feeding in mice. PLoS One. 2011 Feb 24;6(2):e17090. Nakatani M, Kokubo M, Ohsawa Y, Sunada Y, Tsuchida K. Follistatin-derived peptide expression in muscle decreases adipose tissue mass and prevents hepatic steatosis. Am J Physiol Endocrinol Metab. 2011 Mar;300(3):E543-53. Epub 2011 Jan 4. Choi SJ, Yablonka-Reuveni Z, Kaiyala KJ, Ogimoto K, Schwartz MW, Wisse BE.Am J Physiol Endocrinol Increased energy expenditure and leptin sensitivity account for low fat mass in myostatin-deficient mice. Metab. 2011 Jun;300(6):E1031-7. Epub 2011 Mar 22. Tu P, Bhasin S, Hruz PW, Herbst KL, Castellani LW, Hua N, Hamilton JA, Guo W. Genetic disruption of myostatin reduces the development of proatherogenic dyslipidemia and atherogenic lesions in Ldlr null mice. 2009 Aug;58(8):1739-48. Epub 2009 Jun 9. Colker, C. Effect on serum myostatin levels of high grade handled fertile egg yolk AJCN 2009. 28:3, Abstract 29. Colker, C. Randomized blind comparison of follistatin in standard store-bought unfertilized chicken eggs versus standard store bought fertile eggs. JACN, 25: 5; Abstract 65; October 2006. Vamvini MT, Aronis KN, Chamberland JP, Mantzoros CS. Energy deprivation alters in a leptin- and cortisol-independent manner circulating levels of activin A and follistatin but not myostatin in healthy males. J Clin Endocrinol Metab. 2011 Nov;96(11):3416-23. Epub 2011 Aug 24. Lakshman KM, Bhasin S, Corcoran C, Collins-Racie LA, Tchistiakova L, Forlow SB, St Ledger K, Burczynski ME, Dorner AJ, Lavallie ER. Measurement of myostatin concentrations in human serum: Circulating concentrations in young and older men and effects of testosterone administration. Mol Cell Endocrinol. 2009 Apr 10;302(1):26-32. Epub 2009 Jan 21. Cenegenics Muscle Formula Call 480.454.2370 to order! 11

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