COLLAGEN PEPTIDES FOR HEALTHY JOINTS AND BONES

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1 COLLAGEN PEPTIDES FOR HEALTHY JOINTS AND BONES Collagen Peptides for a Healthy Lifestyle PRODUCED & MARKETED BY ROUSSELOT

2 ENSURING OPTIMUM JOINT AND BONE HEALTH FOR AN ACTIVE LIFESTYLE A healthy, active lifestyle is the goal of many modern consumers. Essential to achieving this are strong bones and joints. As the global population gets older, joint- and bone-related health concerns are becoming increasingly common. Physically active people, such as athletes, can also encounter joint discomfort and injury to connective tissue as a result of high-intensity exercise. In view of this, proactive consumers are looking for ways to maintain healthy joints and bones and are searching for products with added benefits to help maintain their active lifestyles. KEEPING ACTIVE Joint discomfort and restricted joint function affect almost 10% of men and 18% of women over the age of 60 1 seriously impacting their mobility currently, 80% of those affected suffer limitation in movement. 2 Joint related conditions can affect people across a broad age spectrum. People who regularly take part in high-intensity exercise, for example, place extreme pressure on their joints, often leading to joint discomfort. Extra strain is also put on joints by overweight individuals. Keeping bones healthy and strong are equally important, with one in three women and one in five men over the age of fifty experiencing a bone fracture. 2 Preserving healthy bones is vital to avoid unnecessary fractures and to maintain mobility while aging. Exercise combines with a healthy diet rich in calcium, vitamin D and protein is recommended to support bone health as we age. HEALTHY AND STRONG BONES Maintain bone mass density HEALTHY AND FLEXIBLE JOINTS Maintain cartilage and joint function

3 STAND OUT FROM THE CROWD As more consumers are seeking ways to stay active for longer, many are now looking beyond glucosamine and chondroitin sulfate products, to new active second generation joint health ingredients, such as collagen peptides. Rapidly gaining popularity, collagen peptides can be used alone or in combination with other ingredients, and are natural and safe, with no reported side effects. Additionally, based on the body s own connective tissue protein, Peptan collagen peptides resonate well with consumers, offering real value and proven benefits. Peptan is widely used in dietary supplements and can easily be integrated into functional food and beverage products. A large body of scientific evidence support the efficacy of collagen peptides (type 1) to support connective tissue and promote healthy joints. This evidence include in-vitro, in-vivo, and multiple placebo controlled clinical study Peptan has been extensively tested for its regenerative effect on cartilage tissue and demonstrated effect on reducing joint discomfort and stiffness in a double-blind, randomized, placebo-controlled study. 4 Peptan s ability to stimulate chondrocytes (joint cells) to produce more of the key joint matrix compounds, collagen and aggrecan, is shown in the below graph. 3 PEPTAN PROTECTING JOINTS Cartilage is made up of cellular building blocks (chondrocytes), which produce an extracellular matrix, consisting of collagen and proteoglycans (mainly aggrecan). Collagen fibers make up 70-95% of cartilage and are responsible for its structure and strength, while proteoglycans serve as lubricant to the joint. Healthy cartilage is maintained by a finely-balanced process that breaks down collagen and aggrecan and replaces them with a newly-formed matrix. If this balance is interrupted, enzymes can attack collagen and aggrecan leading to a loss of cartilage and joint function. To maintain healthy joints, it is essential to ensure this balance is protected and the necessary building blocks for collagen are available to support cartilage regeneration. Collagen peptides like Peptan are designed to support this process. Effect of Peptan B on aggrecan and type II collagen mrna expression after 8 days of treatment (qpcr). *: significant vs control p<0.05 Expression (arbitrary unit) Solvent control Aggrecan Peptan B 0,1 mg/ml Type II collagen * Peptan B 1 mg/ml PEPTAN COLLAGEN PEPTIDES DEMONSTRATED JOINT HEALTH BENEFITS A highly active process of cartilage formation can help to prevent excess matrix degradation and thus help maintain healthy joints. Collagen peptides such as Peptan have been proven to stimulate chrondrocytes to produce more collagen and aggrecan.

4 REDUCED JOINT DISCOMFORT AND IMPROVED MOBILITY In a double-blind, randomized, placebo-controlled clinical trial, 4 94 female participants aged suffering from knee joint pain or discomfort due to osteoarthritis were randomly assigned either 8 g of Peptan or a placebo per day for 6 months. Participants were assessed at the beginning of the trial, three months into the trial and at the end of the trial. These assessments were based on two established methods, a standardized questionnaire, the WOMAC score, to measure joint pain and joint function in daily life and the Lysholm score, to evaluate knee joint function when limping, walking, jumping and stair climbing. Participants who were given Peptan reported lowering WOMAC scores over time and recorded significantly lower pain scores at the end of the study. In comparison, no significant change was shown in the placebo group. Development of WOMAC scores (decreased score value = improvement) Placebo group Peptan group p<0.001 p< months 3 months 6 months Compared to the placebo group, participants who received Peptan also recorded significantly increased scores on the Lysholm system, demonstrating better knee movement. Development of Lysholm scores (increased score value = improvement) Placebo group Peptan group p<0.001 p< months 3 months 6 months Numerous clinical studies have shown similar effects. Recent scientific reviews on joint pain and joint mobility have concluded that collagen peptides are particularly beneficial to individuals with joint health issues in comparison to other nutraceutical ingredients, especially for reducing joint discomfort. 5,6,7 Multiple trials have also demonstrated that subjects with the greatest joint deterioration benefited the most from the effects of collagen peptides. 8,9 The effectiveness of collagen peptides has also been shown in athletes with activity-related joint pain in a 24-week study. At the end of the trial, an assessment of participants who consumed collagen peptides showed significantly reduced joint pain at rest, when walking, standing or carrying objects. 10

5 PEPTAN STRENGTHENING BONES Bones are in a constant state of flux. The maintenance of the bone matrix and minerals is dependent on a process called bone remodeling, or bone turnover, which replenishes the cells and matrix which form our bones. A B Bone turnover replaces approximately 15% of bone mass in healthy adults each year. Imbalanced rates of bone resorption and formation, leading to more bone loss than formation, 11 can lead to reduction in bone mass density over time. Representing around 90% of organic bone mass, collagen provides the structural framework on which calcium and other minerals are anchored. Collagen fibers also provide bone flexibility. Research has shown that a daily intake of 8-10 g/day of bioactive collagen peptides can assist in maintaining collagen levels and can help preserve bone health. 11,12 Osteoblasts Star-shaped cells Osteoblast cultures (bone cells) with addition of Peptan (A) or BSA protein (control) (B) Osteoclasts Round black cells PEPTAN COLLAGEN PEPTIDES DEMONSTRATED BONE HEALTH BENEFITS Peptan s beneficial effects on bone health have been documented in multiple in vitro and in vivo trials. 11,14,15 POSITIVE EFFECTS ON BONE FORMATION Peptan has been shown to preferentially stimulate the bone cells responsible for bone formation (osteoblasts) compared to cells involved in bone resorption (osteoclasts), triggering an increase in bone formation. These findings have been supported in various studies. 13,16,17,18

6 RESTORES BONE MINERAL DENSITY In a recent in vivo study at the Physiology and Ingestive Behavior Laboratory, INRA AgroParisTech, 15 ovariectomized (ovx) mice were used to mimic osteopenia in postmenopausal women and divided into two groups, with only one group fed a diet including Peptan over a 12-week period. A group of normal (non-ovariectomized) mice was also used as a control. The trial found that the group fed a diet with Peptan maintained the same bone mineral density (BMD) level as the non-ovariectomized mice over the test period. POSITIVE EFFECTS ON BONE STRENGTH In the same study the daily intake of Peptan over a 12-week period was investigated for the effect on bone size, bone strength and solidity. The results showed an increase in these parameterscompared to the ovariectomized (ovx) and control group. Increase in bone mineral density for Ovx mice fed Peptan for 12 weeks (g/cm 2 ) 0,025 0,020 0,015 0,010 Measure of BMD Increase in ultimate bone strength for Ovx mice fed Peptan for 12 weeks N Measure of bone strength 0,005 0 Control Ovx Ovx + Peptan Control Ovx Ovx + Peptan SCIENTIFIC REFERENCES 1 World Health Organisation (WHO), 2 International Osteoporosis Foundation (IOF), Rousselot in vitro study. Atlantic Bone Screen, France 4 Jiang, et al Peptan Collagen Peptides for Treatment of Knee Osteoarthritis: Agro Food Industry Hi Tech 25(2): Van Vijven J.P.J. et al., Symptomatic and chondroprotective treatment with collagen derivatives in osteoarthritis: a systematic review. Osteoarthritis and Cartilage, 20: Henrotin Y. et al., Nutraceuticals: do they represent a new era in the management of osteoarthritis? a narrative review from the lessons taken five products. Osteoarthritis and Cartilage, 19: Ragle R.L. et al., Nutraceuticals in the management of osteoarthritis: a critical review. Drugs & Aging, 29: Moskowitz, R., Role of collagen hydrolysate in bone and joint disease. Seminars in Arthritis and Rheumatism, 30: Benito-Ruiz P. et al., A randomized controlled trial on the efficacy and safety of a food ingredient, collagen hydrolysate, for improving joint comfort. International Journal of Food Sciences and Nutrition, 60: Clark, K.L. et al., Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Current Medical Research and Opinion, 24: Daneault, A. et al., Biological effect of hydrolyzed collagen on bone metabolism. Critical Reviews in Food Science and Nutrition, 10: Adams, M. et al., Postmenopausal osteoporosis: Treatment with calcitonin and a diet rich in collagen proteins. Casopis Lekaru Ceskych, 135: Daneault, A. et al, 2014, Hydrolyzed collagen contributes to osteoblast differentiation in vitro and subsequent bone health in vivo. Osteoarthritis and Cartilage 22: S Guillerminet, F. et al., Collagen peptides improve bone metabolism and biomechanical parameters in ovariectomized mice: an in vitro and in vivo study. Bone, 46: Guillerminet F. et al., Hydrolyzed collagen improves bone status and prevents bone loss in ovariectomized C3H/HeN mice. Osteoporosis International, 23: Mizuno, M. et al., Osteoblast-related gene expression of bone marrow cells during the osteoblastic differentiation induced by type I collagen. Journal of Biochemistry, 129: Andrianarivo, A.G. et al., Growth on type I collagen promotes expression of the osteoblastic phenotype in human osteosarcoma MG-63 cells. Journal of Cellular Physiology, 153: Lynch, M.P. et al., The influence of type I collagen on the development and maintenance of the osteoblast phenotype in primary and passaged rat calvarial osteoblasts: modification of expression of genes supporting cell growth, adhesion, and extracellular matrix mineralization. Experimental Cell Research, 216: Oesser, S. et al., Oral Administration of 14C Labelled Gelatine Hydroslysate Leads to an Accumulation of Radioactivity in Cartilage of Mice (C57/BL). Journal of Nutrition, 129: Sugihara, F., Quantification of hydroxyprolyl-glycine (Hyp-Gly) in human blood after ingestion of collagen hydrolysate. Journal of bioscience and bioengineering, 113 (2): Ichikawa, S. et al., Collagen-derived dipeptide, proline-hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts. Journal of dermatology, 37 (4): 330-8

7 PEPTAN COLLAGEN PEPTIDES INNOVATIVE INGREDIENTS FOR IMPROVED JOINT AND BONE HEALTH Collagen is the most abundant protein in the human body. It holds together all living tissue and provides the infrastructure of the musculoskeletal system, making it essential for mobility. Collagen peptides the hydrolyzed form of collagen are increasingly recognized as a highly effective solution for manufacturers targeting the bone and joint health market. They offer specific benefits that cannot be found in other protein sources, are derived from 100% natural sources, and are highly digestible and bioavailable. In fact, studies have shown that more than 90% of the peptides are digested and absorbed within 12 hours of oral ingestion, ensuring they are rapidly available in the connective tissue to stimulate endogenous collagen synthesis in bones and joints. 19,20,21 QUALITY FIRST Peptan is manufactured by Rousselot in its state-of-the-art certified plants in France and Brazil, meeting the highest international food and quality standards. Peptan are premium quality collagen peptides; 100% natural and safe, fully traceable and free from any preservatives or additives. Rousselot s Peptan collagen peptides can be easily and cost-effectively used in a range of dietary supplements and functional foods, beverages and nutraceuticals. HEALTHY STRONG BONES BOOST JOINT COMFORT SUPPORT CONNECTIVE TISSUE ADD VALUE TO YOUR PRODUCT WITH PEPTAN Deliver demonstrated joint and bone health benefits Meet growing demand for exciting nutraceuticals with added benefits for aging consumers, plus physically active or overweight individuals. SUPPORT LIGAMENTS AND TENDONS TO HELP REDUCE RISK OF INJURY ASK THE EXPERTS With application and expertise centers located around the world, Rousselot is continuously developing new product concepts and recipes to support our customers innovation focus. Our technical experts are available to provide local application advice to customers, anywhere in the world. Rousselot also offers local regulatory support and provides scientific evidence files to back up the efficacy of Peptan.

8 OUR SALES OFFICES AROUND THE WORLD EUROPE, MIDDLE EAST, AFRICA Northern, Central and Eastern Europe, UK and Ireland Rousselot B.V.B.A. Meulestedekaai Gent Belgium France, Southern Europe, Middle-East, Africa Rousselot S.A.S. 4 rue de l abreuvoir Courbevoie France Spain and Portugal Rousselot Gelatin S.L. Paratge Pont de Torrent, S/N Cervia de Ter (Girona) Spain Your Rousselot and Peptan sales contact information: SOUTH AMERICA AND CENTRAL AMERICA rousselot.brasil@rousselot.com Brazil Rousselot Gelatinas Do Brasil S.A. Rua Santo Agostinho, N 280 Distrito de Arcadas CEP Amparo - São Paulo Brasil South and Central America (except Brazil) Rousselot Argentina S.A. Avenida Gobernador Vergara Villa Tesei - Hurlingham (Provincia de Buenos Aires) Argentina NORTH AMERICA AND MEXICO gelatin.usa@rousselot.com Rousselot Inc South Rochester Street, Suite 250 Mukwonago, WI USA CHINA info@rousselotchina.com Rousselot China 25/A, No. 18 North Cao Xi Road Shanghai PO: China JAPAN AND SOUTH KOREA japan@rousselot.com Rousselot Japan K.K. Ishikin-nihonbashi Bldg, 6F Nihonbashihoncho, Chuo-Ku, Tokyo Japan SOUTH EAST ASIA sea@rousselot.com Taiwan, Hong Kong, Australia, New Zealand, India and Sri Lanka Rousselot (M) SDN. BHD. Block P3-21, Plaza Damas Jalan Sri Hartamas Kuala Lumpur Malaysia About Rousselot and Peptan: Rousselot and Peptan are both brands of Darling Ingredients Inc. Rousselot is the global leader of gelatin and collagen peptides. Rousselot s wide range of collagen peptides are marketed under the Peptan brand. We work in partnership with our customers all over the world, delivering innovative and advanced ingredient solutions manufactured through state of the art operations. We help our customers achieve their goals, enabling them to create world class pharmaceutical, food and nutritional products to inspire and excite today s demanding consumers. All rights reserved. No part of this brochure may be reproduced, distributed or translated in any form or by any means, or stored in a database or retrieval system, without the prior written permission of Rousselot. Rousselot alone retains the copyright to the entire content of this brochure and the intellectual property rights to all designations of our products stated in this brochure and intellectual property rights to the products themselves. Nothing in this brochure constitutes a license (explicit or implicit) of any of Rousselot s intellectual property rights. The duplication or use of product designations, images, graphics and texts is not permitted without Rousselot s explicit prior written consent. Rousselot makes no representation or warranty, whether expressed or implied, of the accuracy, reliability, or completeness of the information, nor does it assume any legal liability, whether direct or indirect, of any information. Use of this information shall be at your discretion and risk. Nothing herein relieves you from carrying out your own suitability determinations and tests and from your obligation to comply with all applicable laws and regulations and to observe all third party rights. This product is not intended to diagnose, treat, cure, or prevent any disease. You should always consult your medical provider when using the product together with medical treatments, diets or fitness programs. The uses and claims for Rousselot s products recommended in the brochure should be adapted to the current local regulatory environment. This statement has not been evaluated by the Food and Drug Administration. Rousselot SAS. RCS Nanterre (France) - Pictures: Rousselot,Shutterstock, istockphoto, CanStockPhoto - Design: wearewim.com V1.0 Rousselot Headquarters: Rousselot B.V. Kanaaldijk Noord NM Son The Netherlands Phone: +31 (0) Fax: +31 (0) peptan@rousselot.com peptan.com Collagen Peptides PRODUCED & MARKETED BY ROUSSELOT