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Flora Manufacturing November 21, 2005 Contents The Digestive System Enzyme Units TNO Research Flora Digestive Products Enzymes in Digestion Mouth Carbohydrates -amylase Stomach Proteins Pepsin Small Intestine Carbohydrates amylase, sucrase, lactase, maltase trypsin, chymotrypsin carboxypeptidase, etc. lipase Proteins Fats Endogenous to the human body Digestive System Supplementary digestive enzymes are most effective when they work in the stomach and small intestine, and so must work over a broad pH range. When digestion is more rapid and thorough, ingested material passes more quickly through the digestive tract. This addresses problems which arise when food sits in the stomach too long causing excess acid and indigestion. pH 1.0 - 3.0 pH 6.0 - 8.0 Most Common Problems Associated with Improper Digestion Constipation, gas, bloating, heartburn Intolerance and allergies Reduced function of the immune system Lack of energy What does a comprehensive digestive enzyme formula look like? Lipases; break down fat as is found in butter, cheese, and meat. Proteases;break down protein as is found in meats, nuts, and cheese. Carbohydrases - break down starches, polysaccharides, sugars, and fiber as are found in fruits, vegetables, grains, and snack foods. How Do You Recognize a Good Formula? •Activity Units and not Weight •Broad Range of Activity •Acid Stability •Fungal Enzymes Anecdotal Evidence: I feel better after taking enzymes I have reduced gas, bloating, constipation… I eat less if I take enzymes I feel I am absorbing more from my food Only qualitative data, no quantitative results Do Fungal Enzymes increase the digestibility and bioaccessibility of proteins and carbohydrates? TNO: Background TNO Nutrition and Food Research Independent research organization in the Netherlands Link between fundamental research and its application to food and drugs NEC – TNO collaboration TNO: What is TIM? in vitro Dynamic gastrointestinal model Simulate stomach, small intestine and large intestine conditions Sampling during digestion Specific protocol development and validation STOMACH DUODENUM JEJUNUM ILEUM Study Protocol Aim: To determine the efficacy of exogenous NEC enzymes on the digestibility of proteins and carbs Standard FDA-type test meal Proteins, carbohydrates and fat Mouth, stomach and small intestine conditions Protocol: cont’d Meal mixed with artificial saliva and water Stomach secretions: acid and pepsin Duodenum: bicarbonate and pancreatin Small intestine Protocol: cont’d Gastric emptying and intestinal passage mimicked for humans Temperature, peristalsis, pH, etc… controlled by computer Sampling spots: Jejunum and Ileum Small intestine: Semi-permeable membrane Conditions Tested 1. 2. 3. 4. Perfect digestion Perfect digestion with NEC enzymes Impaired digestion (30% of pancreatin) Impaired digestion with NEC enzymes Most of us fall in between these two extreme conditions Condition 1: Perfect Digestion Jejunal Glucose Bioaccessibility Perfect Digestion Perfect Digestion with NEC Enzymes Glucose Absorbed g/L 2 1.8 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 0-1 Hours 1-2 Hours 2-3 Hours 3-5 Hours Ileal Glucose Bioaccessibility Perfect Digestion Perfect Digestion with NEC Enzymes 1.6 Glucose Absorbed g/L 1.4 1.2 1 0.8 0.6 0.4 0.2 0 0-1 Hours 1-2 Hours 2-3 Hours 3-5 Hours Total Free Glucose Bioaccessibility Small Intestine (Perfect Digestion) 2 1.5 1 0.5 0 Jejunum Control with NEC Enzymes 2.5 Control 3 Control with NEC Enzymes 3.5 Control Glucose Absorbed g/L 4 Ileum Total Free Nitrogen Bioaccessibility Small Intestine (Perfect Digestion) 3.5 1 0.5 Control with NEC Enzymes 1.5 Control 2 Control with NEC Enzymes 2.5 Control Nitrogen mmol/L 3 0 Jejunum Ileum Condition 2: Impaired Digestion Jejunal Glucose Bioaccessibility Impaired Digestion Impaired Digestion with NEC Enzymes Glucose Absorbed g/L 2 1.8 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 0-1 Hours 1-2 Hours 2-3 Hours 3-5 Hours Ileal Glucose Bioaccessibility Impaired Digestion Impaired Digestion with NEC Enzymes Glucose Absorbed g/L 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0-1 Hours 1-2 Hours 2-3 Hours 3-5 Hours Total Free Glucose Bioaccessibility Small Intestine (Impaired Digestion) 3 2.5 2 1.5 1 0.5 0 Jejunum Control with NEC Enzymes 3.5 Control 4 Control with NEC Enzymes 4.5 Control Glucose Absorbed g/L 5 Ileum Total Free Nitrogen Bioaccessibility Small Intestine (Impaired Digestion) 1 0.5 0 Jejunum Control with NEC Enzymes 1.5 Control 2 Control with NEC Enzymes 2.5 Control Nitrogen mmol/L 3 Ileum Importance of study First quantitative evidence supporting the use of supplemental digestive enzymes NEC fungal enzymes do not need enteric coating NEC digestive enzymes improve the digestibility and bioaccessibility of proteins and carbs Proves efficacy of NEC digestive enzymes Flora: Digestive Enzyme Products Teenager’s Blend Enzyme Adult’s Blend Enzyme Advanced Adult Enzyme Anti-Inflammatory Enzyme Teenager’s Enzyme Blend Amylase……………………………..5000 DU Alpha-G……………………………...100 GalU Protease 4.5…………………………5000 HUT Glucoamylase………………………10 AGU Lipase AN……………………………250 FIP Malt Diastase………………………..250 DP Protease 6.0…………………………1500 HUT Invertase……………………………..250 SU Cellulase……………………………..100 CU Protease (A. niger)………………….399.3 BLGU Protease (A. oryzae)………………..230.5 BLGU Lactase……………………………….1000 ALU Teenager’s Enzyme Blend Aid digestion of proteins, carbs, sugars, fats and dairy Maximize absorption of nutrients Geared towards teens with active lifestyle Addresses intolerances and other discomfort caused by certain foods Adult’s Enzyme Blend Amylase…………………………………....5000 DU Protease 4.5……………………………….10000 HUT Lipase AN………………………………….1000 FIP Bromelain………………………………….500000 FCC PU Protease 6.0………………………………8000 HUT Protease 3.0………………………………15 SAPU Alpha-G……………………………………125 GALU Glucoamylase……………………………..8 AGU Peptidase…………………………………..2000 HUT Malt Diastase………………………………300 DP Invertase……………………………………150 SU Cellulase……………………………………275 CU Hemicellulase……………………………...758.8 HCU Phytase……………………………………..1.9 FTU Adult’s Enzyme Blend Support digestion for adults on restrictive diets Efficiently digest processed and nutrient dense meals Wide pH of proteolytic activity Help alleviate gas, bloating, constipation, heartburn Advanced Adult’s Enzyme Amylase…………………………………....5000 DU Protease 4.5……………………………….14000 HUT Protease 6.0……………………………….10000 HUT Alpha-G………………………………………….175 GALU Bromelain………………………………….500000 FCC PU Protease 3.0………………………………15 SAPU Glucoamylase……………………………..8 AGU Peptidase…………………………………..2000 HUT Lipase AN……………………………………….75 FIP Lipase RO……………………………………….250 FIP Malt Diastase………………………………300 DP Invertase……………………………………150 SU Protease (A. niger)……………………………..399.3 BLGU Protease (A. oryzae)…………………………...230.5 BLGU Lactase…………………………………………..1000 ALU Cellulase……………………………………275 CU Hemicellulase……………………………...758.8 HCU Phytase……………………………………..1.9 FTU Advanced Adult’s Enzyme Full spectrum digestive enzyme formula Help maximize absorption of nutrients Alleviate symptoms of gas, bloating, constipation, heartburn High proteolytic activity Anti-inflammatory Enzyme Protease AM………………………………….25 AP Bromelain……………………………………..750000 FCC PU Protease 6.0………………………………….10000 HUT Papain………………………………………...500000 FCC PU Peptidase……………………………………..2500 HUT Protease (A. melleus)……………………….14950 U Protease (A. oryzae)………………………...50 U Anti-inflammatory Enzyme Proteolytic enzymes designed to mediate inflammatory response Joints and soft tissue as well as intestinal inflammation Specifically breakdown certain cytokines Fibrinolytic activity