Sustamine designed to enhance performance

Sustamine designed to enhance performance

Sustamine s Scientific Advantages The U.S. sports nutrition market is valued at $10 billion annually for drinks, shots, bars, gels, and supplements. 1 Sustamine is a unique, clinically tested ingredient that works on multiple levels to help provide the performance support that active consumers are looking for.* What is Sustamine? Sustamine is a unique dipeptide that combines the amino acids L-Glutamine and L-Alanine. Designed to assist with hydration, research suggests that Sustamine also supports the integrity of the gastrointestinal tract.* Sustamine has also been shown to stimulate the immune system and may support immune health.* How do dipeptides speed absorption and recovery? A dipeptide is a bonded chain of two amino acids, in this case, L-Glutamine and L-Alanine. Smaller than a complete protein, the dipeptide Sustamine is absorbed faster than individual amino acids. To get into cells, dipeptides and amino acids must wait for a transporter. A transporter can carry either a single amino acid or a dipeptide through the cell barrier at once. Through coupling for transport, dipeptides drastically reduce the time and energy needed for cellular recovery. How is Sustamine Produced? Sustamine is the result of a patented fermentation process that creates a highly stable product, and a dipeptide that is more bioavailable than L-Glutamine alone. Sustamine is allergen-free, vegetarian, tasteless, odorless, and the only GRAS L-Alanyl-L-Glutamine on the market. This makes Sustamine a great ingredient choice for beverages, bars and supplements formulated to support an active lifestyle. 1) Nutraingredients-USA Sports Nutrition Forum, Sept. 2016 Amino acids waiting for transport into cell Intestinal Cell Wall Intestinal Cell Dipeptides waiting for transport into cell Intestinal Cell Intestinal Cell Wall Dipeptides drastically reduce the time and energy needed to transport amino acids through cell barriers. Why a dipeptide? Dipeptides are absorbed more efficiently than protein Dipeptides do not require additional energy to break down bulky protein molecules Dipeptides increase amino acid transport into cells for faster recovery Dipeptides supply two amino acids for the energy costs of one Dipeptides might be more stable and effective than single amino acids Why combine L-Glutamine with L-Alanine? Sustamine's dipeptide form offers unique and even superior benefits over either amino acid alone* Improved bioavailability and absorption Sustamine is more bioavailable than L-Glutamine and may be more efficiently absorbed.* Exercise performance Sustamine may support exercise performance by enhancing electrolyte and water absorption in the intestines to assist hydration.* Improved hydration over water alone Research supports that rehydration with Sustamine appears to maintain visual reaction time to a greater extent than water alone at doses of >3 grams.* Increased L-Glutamine levels Sustamine significantly increases L-Glutamine blood levels over taking L-Glutamine alone and helps maintain L-Glutamine balance during rigorous exercise.* Increased product stability and quality Research indicates that combining L-Glutamine with another amino acid to form a substrate is more stable and less subject to degradation at high temperatures than L-Glutamine alone. This prolongs shelf life and enhances quality. Change in Time to Exhaustion (sec) Improvement of performance in endurance exercise during hydration stress. (Clinical Study) 200 150 50 0-50 - -150-200 Water only No fluid Sustamine w/water 0.05g/kg B.W. *p<0.05. vs No fluid When subjects ingested Sustamine during the rehydration period they obtained a significant benefit by increasing time to exhaustion. Hoffman JR et al. Journal of the International Society of Sports Nutrition 7:8, 2010 *

Sustamine s Marketing Advantages Sustamine is pure, soluble, stable, and taste-free Manufacturers and formulators will love the more practical benefits of Sustamine. Sustamine is proven to be % soluble, more stable than L-Glutamine alone, and taste-free. Pure. Sustamine is a pure, safe ingredient produced through a patented fermentation process. It is vegetarian, allergen-free, kosher, and contains no additives or preservatives. Soluble. Sustamine is freely soluble and transparent in water, so your functional beverage remains clear, not cloudy. And, Sustamine has been shown to remain soluble at the recommended dosage level for optimal results. Stable. Acid hydrolysis can degrade protein quality and deplete biological values. Sustamine is produced using fermentation, not acid hydrolysis, leading to increased end-product stability for longer shelf life. Though L-Glutamine is unstable in liquids, Sustamine is stable (even in liquids) and also in combination with other actives, such as vitamins or electrolytes. Taste-free. Most peptides have a strong, bitter taste that is difficult to mask. Sustamine is tasteless in water so the full flavor of your functional food or beverage comes through. Sustamine allows a wide array of product applications Sustamine is a unique ingredient that can be incorporated into a wide range of finished products designed to support sports performance, such as: Dietary supplements Energy/sport and electrolyte beverages Enhanced waters Fruit flavored and milk-based beverages Meal replacements Nutrition bars Yogurts Sustamine is backed by Kyowa Kyowa is an international health ingredient manufacturer and a world leader in the development, manufacturing, and marketing of nutraceuticals, pharmaceuticals, and food products. Kyowa provides the following marketing support for Sustamine: Co-branding program Trade education (manufacturers and healthcare professionals) Tradeshow events and lectures Consumer education Dedicated website Public relations Social media Sustamine claims The following claims are provided for informational purposes and should be reviewed by your legal counsel prior to use in marketing materials, including product labels. Rehydration with Sustamine appears to maintain visual reaction time to a greater extent than water at doses of >3 grams.* 5, 6, 7, 8, 9, 12 Preclinical research suggests Sustamine 5, 6, 7, 8, 9, 12 may support hydration.* Sustamine may support exercise 5, 6, 7, performance at doses of >3 grams.* 8, 9, 12 Sustamine helps maintain L-Glutamine balance during rigorous exercise at doses 5, 6, 7, 8, 9, 12 of >3 grams.* Sustamine may be more efficiently absorbed than L-Glutamine (free 4, 7, 12 glutamine).* Sustamine increases blood levels of L-Glutamine 224% greater than 4, 7, 12 L-Glutamine alone.* Sustamine is more bioavailable than L-Glutamine.* 4,7,12 Sustamine has superior absorption, stability and solubility compared to L-Glutamine.* 4,7,12 Sustamine helps to stimulate the immune 1, 2, 3 system.* 1, 2, 3 Sustamine supports immune health.* Sustamine supports the integrity of the 3, 10,11 gastrointestinal tract.* Sustamine supports maintenance of healthy intestine function.* 3,10,11 Sustamine promotes the integrity and optimal function of the intestinal barrier.* 3,10,11 *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.

Sustamine s Specifications References 1. Calder PC, Yagoob P. Glutamine and the immune system. Amino Acids. 1999:17(3):227-41. 2. Coeffier M, Marion R, Ducrotte P, Dechelotte P. Modulating effect of glutamine on IL-1 beta-induced cytokine production by human gut. Clin Nutr. 2003 Aug;22(4):407-13. 3. Furst P, Alteheld B, Stehle P. Why should a single nutrient glutamine improved outcome? The remarkable story of glutamine dipeptides. Clinical Nutrition Supplements. 2004;1:3-15. 4. Harris, R. L-glutamine absorption is enhanced after ingestion of L-alanylglutamine compared with the free amino acid or wheat protein. Nutrition Research. 2012, 32(4): p.272-277. 5. Hoffman, J.R., et al., Examination of the efficacy of acute L-alanyl-L-glutamine ingestion during hydration stress in endurance exercise. J Int Soc Sports Nutr, 2010. 7: p. 8. 6. Hoffman, JA. L-alanyl-L-glutamine ingestion maintains performance during a competitive basketball game.journal of the International Society of Sports Nutrition 2012, 9:4 7. Lima, A.A., et al., Effects of an alanyl-glutamine-based oral rehydration and nutrition therapy solution on electrolyte and water absorption in a rat model of secretory diarrhea induced by cholera toxin. Nutrition, 2002. 18(6): p. 458-62. 8. McCormack WP. Effects of L-alanyl-L-glutamine ingestion on one-hour run performance. Journal of American College of Nutrition, 2015. 22: p.1-9. 9. Rogero, M.M., et al., Effect of alanyl-glutamine supplementation on plasma and tissue glutamine concentrations in rats submitted to exhaustive exercise. Nutrition, 2006. 22(5): p. 564-71. 10. Scheppach W, et al. Effect of free glutamine and alanyl-glutamine dipeptide on mucosal proliferation of the human ileum and colon. Gastroenterology. 1994 Aug;107(2):429-34. 11. Snoeck V, et. al. The role of enterocytes in the intestinal barrier function and antigen uptake. Microbes Infect. 2005 Jun;7(7-8):997-4. 12. Thwaites DT, et al. H+/dipeptide absorption across the human intestinal epithelium is controlled indirectly via a functional Na/H exchanger. Gastreoenterology. 2002 May:122(5):1322-33. Description INCI Designation CAS No. Odorless, white crystalline powder Alanyl Glutamine 39537-23-0 Physical & Chemical Properties Empirical formula C8H15N3O4 Molecular weight 217.22 Chemical structure Specifications Appearance White, crystalline powder Identification Pass test State of solution Odorless and clear ph 5.0-6.0 Specific rotation(20 C) +9.0 - +11.0 Chloride (Cl) Not more than 0.020% Heavy metals (as Pb) Not more than 5 ppm Arsenic (AS2O3) Not more than 1 ppm Related substances Not more than 0.2% Loss on drying Not more than 0.5% Residue on ignition Not more than 0.10% Assay (dry basis) 98.0-102.0% Ammonium (NH4) Not more than 0.020% Sulfate (SO4) Not more than 0.020% Total plate count Not more than 1,000 CFU/g Fungi count Not more than CFU/g E. Coli Negative Manufacturing Process Sustamine is an ingredient manufactured in Japan, generated from glucose by using a patented fermentation process. The process enables the delivery of economically feasible peptides to the industry, and will also eliminate any risk of TSE contamination (Transmissible Spongiform Encephalopathy). Solubility Freely soluble in water Slightly soluble in alcohol (568.0 g/l at room temperature) Insoluble in fats and oils Transparent when dissolved in water Taste Slight acidic taste as a powder Tasteless when added to water Stability Liquid solution (2 g/l) stable at 122 C (test performed for 20 min.) Stable at ph1 (37 C, 4h) Good stability with other actives (vitamins etc.) Uses Sustamine is recommended for use in dietary supplements, energy, sport, and electrolyte beverages, enhanced waters, fruit flavored beverages, milk and non-milk based beverages and meal replacements, protein based beverages, nutritional bars and yogurts. Sustamine is self-affirmed GRAS. Safety Studies Acute oral toxicity Recommended Use Levels Oral use Storage Store at 15ºC to 30ºC in tight, light resistant containers Packaging Standard packing LD50 2,000 mg/kg 600-3000 mg/serving 5 kg, 20 kg

Sustamine Science Snapshot What is? Superior absorption is absorbed up to 224% better than standard L-Glutamine 1 A dipeptide consisting of two amino acids (L-Alanine and L-Glutamine) connected by a peptide bond designed for stability, and quick, efficient absorption.* L-Glutamine (mmol/l) 400 300 200 The mean change in the plasma concentration of Gln 224% AUC vs Gln A study comparing straight L-Glutamine vs. showed statistically significant increases in both peak and total plasma concentration levels, indicating superior absorption.* Time (hours) 0 1 2 3 4 5 6 Sports performance benefits 1. Improved time to exhaustion during high-intensity, one-hour treadmill run 2 700 600 500 400 300 200 Time to exhaustion (sec) * *: p<0.05, vs No Fluid * Rehydration with, at both high and low doses, significantly improved time to exhaustion compared to no hydration.* No Fluid Commercial sports drink 600 mg 2 g 2. Improved basketball skill performance 3 7 6 5 4 3 2 1-1 -2 Field Goal Shooting No Fluid Water #, & 2 g/l Average intake 3.1 ± 0.86g #: p<0.05, vs No Fluid &: p<0.05, vs Water 4 g/l Improved rehydration with helped field goal shooting as compared to no fluid or water alone.* 1. Harris, RC, et al., NBH: L-Glutamine absorption is enhanced after ingestion of L-Alanyl-Glutamine compared with the free amino acid or wheat protein. Nutr Res 2012, doi:10.1016/j.nutres.2013.02.003. 2. McCormack WP et. al. Effect of acute L-Alanyl-L-Glutamine and electrolyte ingestion on cognitive function and reaction time following endurance exercise. J Am Coll Nutr. (Published online June 22, 2015). 3. Hoffman, JR, et al., L-Alanyl-L-Glutamine ingestion maintains performance during a competitive basketball game. Jrnl Int Soc Sports Nutr 2012, doi:10.1186/1550-2783-9-4. 4. Publication in progress *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.

Sustamine Science Snapshot is a highly stable form of glutamine Glutamine in solution stability over time Room Temperature 40 C % ph3 ph7 ph9 80 60 40 20 Glutamine in solution is NOT stable and degrades over time. 0 1 2 3 0 1 2 3 0 1 2 3 in solution stability over time 4 5 C 20 C 40 C % ph3.1 ph6 ph9 80 60 40 20 is a very stable form of glutamine. 0 2 4 6 0 2 4 6 0 2 4 6 Why? Stable Soluble Taste-Free Vegetarian Ultra-Pure Science-supported The only GRAS L-Alanyl-L-Glutamine is the ONLY L-Alanyl-L-Glutamine backed by human clinical research. For more information about Sustamine contact: KYOWA HAKKO USA, INC. Customer Service: 800.596.9252 info@kyowa-usa.com 600 Third Ave. 19th Floor Tel: 212.319.5353 www.kyowa-usa.com New York, NY 16 Fax: 212.421.1283 www.sustamine.com Sustamine is a registered trademark of KYOWA HAKKO BIO CO., LTD. Copyright 2017 KYOWA HAKKO U.S.A., INC. All rights reserved. 4-17