Succeed Cestaro Presentation 031209

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Business & Mgmt

Published on August 18, 2009

Author: steiner881

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Succeed Cestaro Presentation 031209

N-Oleoyl-Phosphatidyl-Ethanolamine (NOPE) + EGCG: Scientific & Clinical Support For Appetite Suppression & Weight Management 4463 White Bear Pkwy., Suite 105 White Bear Lake, MN 55110 © Chemi Nutra 2009

Succeed™ Next generation nutritional supplement compound for advanced appetite control and weight management. Proprietary composition of N-oleoyl-phosphatidyl-ethanolamine epigallocatechin gallate from standardized green tea extract. and EGCG NOPE

Next generation nutritional supplement compound for advanced appetite control and weight management.

Proprietary composition of

Proprietary Composition Of PhosphoLean™ NOPE+EGCG Gastro-protection of active constituents with release in the small intestine. Increased bioavailability. Increased intestinal levels of NOPE, thus of NOE. Markedly amplified activities of both components, enhancing the weight management property of Succeed™.

Gastro-protection of active constituents with release in the small intestine.

Increased bioavailability.

Increased intestinal levels of NOPE, thus of NOE.

Markedly amplified activities of both components, enhancing the weight management property of Succeed™.

Epigallocatechin Gallate (EGCG) Green Tea Extract activities: Antioxidant. Reduction of excess blood cholesterol. Improvement of insulin action. Helps to control weight homeostasis. Increases fat oxidation and thermogenesis. EGCG most active of green tea catechins: Enhances energetic metabolism. Increases catabolism of lipids and decreases accumulation of triglycerides. Decreases blood glucose. Positively affects cardiovascular system.

Green Tea Extract activities:

Antioxidant.

Reduction of excess blood cholesterol.

Improvement of insulin action.

Helps to control weight homeostasis.

Increases fat oxidation and thermogenesis.

EGCG most active of green tea catechins:

Enhances energetic metabolism.

Increases catabolism of lipids and decreases accumulation of triglycerides.

Decreases blood glucose.

Positively affects cardiovascular system.

N-Oleoyl-Phosphatidyl-Ethanolamine (NOPE) Natural occurring phospholipids in cellular membranes. Present in some foods: soy, eggs, milk, chocolate. Produced and metabolized in man. Precursor of N-oleoyl-ethanolamine (NOE).

Natural occurring phospholipids in cellular membranes.

Present in some foods: soy, eggs, milk, chocolate.

Produced and metabolized in man.

Precursor of N-oleoyl-ethanolamine (NOE).

N-Acyl-Ethanolamine N-acyl-ethanolamine or acyl-ethanolamides. Cell mediators synthesized on demand, starting from phospholipid precursors. ( N-Acyl-Phosphatidyl-Ethanolamine ): N-oleoyl-ethanolamine (NOE) N-palmitoyl-ethanolamine N-arachidoyl-ethanolamine (Anandamide)

N-acyl-ethanolamine or acyl-ethanolamides.

Cell mediators synthesized on demand, starting from phospholipid precursors. ( N-Acyl-Phosphatidyl-Ethanolamine ):

N-oleoyl-ethanolamine (NOE)

N-palmitoyl-ethanolamine

N-arachidoyl-ethanolamine (Anandamide)

N-Acyl-Ethanolamine & Appetite Control Lipid mediator involved in peripheral regulation of feeding. NOE Peripheral action. Anorectic action. Anandamide Central and peripheral action. Orexigenic action. NOE ANANDAMIDE

Lipid mediator involved in peripheral regulation of feeding.

NOE

Peripheral action.

Anorectic action.

Anandamide

Central and peripheral action.

Orexigenic action.

NAPE and NAE Intestinal Levels Starvation and re-feeding influence NAPE and NAE levels in the epithelium of intestinal mucosa. ( Duodenum )

Starvation and re-feeding influence NAPE and NAE levels in the epithelium of intestinal mucosa.

( Duodenum )

N-Acyl-Phosphatidyl-Ethanolamine (NAPE) Intestinal Levels Pmol / mmol P G. Peterson et al. Biochimica Biophysica Acta (2006) 1761:143 Measurements of individual N-Acyl species of NAPE in liquid extracts of tissue samples were carried out by GC-MS in the presence of deutero internal standards, after determination of lipid phosphorus (P) in each sample. Values are means ± SEM ( n =6). *P<0.05 when applying one way ANOVA followed by Tukey’s Post Hoc test. **P<0.01 when applying one way ANOVA followed by Tukey’s Post Hoc test. 1.4 + 0.09 1.3 + 0.09 1.5 + 0.21* 1.1 + 0.07 C20:4 NArPE 39 + 2.4 56 + 5.2 14 + 1.1** 43 + 6.7 C18:2 4.5 + 0.40 4.3 + 0.28 4.1 + 0.36 3.7 + 0.12 C18:1 n-7 8.2 + 0.45 11 + 11 3.4 + 0.19** 8.6 + 1.4 C18:1 n-9 NOPE 7.8 + 0.36 8.1 + 0.23 7.9 + 0.60 8.0 + 0.3 C18:0 20 + 0.97 20 + 0.70 15 + 1.1* 19 + 0.7 C16:0 Starved 24h and re-fed 4h Starved 24h and re-fed 1h Starved 24h Free- feeding ACYL GROUP N-Acyl composition of NAPE in rat intestine after starvation and re-feeding:

Mechanism Of Action N-Oleoyl-Ethanolamine (NOE) Activation of Intestinal Receptors: PPAR  GPR119 ANOREXIC EFFECT REDUCTION of FOOD INTAKE

Activation of Intestinal Receptors:

PPAR 

GPR119

PPAR  (Peroxisome Proliferator Activated Receptor) Nuclear receptors modulating genetic expression. Naturally occurring in intestine, liver, kidney, heart, muscles and adipocytes. Regulate differentiation of pre-adipocytes into adipocytes. Regulate lipolysis.

Nuclear receptors modulating genetic expression.

Naturally occurring in intestine, liver, kidney, heart, muscles and adipocytes.

Regulate differentiation of pre-adipocytes into adipocytes.

Regulate lipolysis.

GPR119 Protein G coupled membrane receptors. Mainly expressed in pancreas  cells and in gastro-intestinal tract. Metabolic results: Improved glucose handling. Slowed diabetes progression. Weight loss.

Protein G coupled membrane receptors.

Mainly expressed in pancreas  cells and in gastro-intestinal tract.

Metabolic results:

Improved glucose handling.

Slowed diabetes progression.

Weight loss.

Succeed™ Mechanism Of Action EGCG NOE EFFECTS Enhanced release of endothelium NO. Reduction of LDL oxidation. Improved vessel integrity. Improved insulin sensitivity. GPR119 activation. Improved glucose handling. Liver UCP2-UCP3 activation. Adipocyte PPAR  receptor activation. Increased lipidic catabolism. Boosts thermogenesis. Intestinal PPAR  receptor activation. Increased sense of satiety. Mechanism Mechanism

Succeed™ Animal Investigational Studies “ N-oleoyl-phosphatidylethanolamine reduced food intake and body weight of dietary rats ameliorating their antioxidant status.” B. Cestaro et al. Arc Sci Med 2005; 164: 101-107

“ N-oleoyl-phosphatidylethanolamine reduced food intake and body weight of dietary rats ameliorating their antioxidant status.”

Study Design 12 rats fed with standard diet (S-diet) 12 rats fed with caloric diet inducing obesity (OP-diet) 12 rats fed with OP-diet + NOPE-EGCG (OP-diet + Succeed™)

12 rats fed with standard diet (S-diet)

12 rats fed with caloric diet inducing obesity (OP-diet)

12 rats fed with OP-diet + NOPE-EGCG (OP-diet + Succeed™)

Results At 14 weeks, Group 3 (OP+NOPE diet) food intake was significantly lower than Group 2 (OP-diet). Weeks Food intake (g) Figure shows food intake in the treated groups.

At 14 weeks, Group 3 (OP+NOPE diet) food intake was significantly lower than Group 2 (OP-diet).

Results OP diet + Succeed TM Reduction of weight gain and total body fat. OP-diet+Succeed™ OP-diet S-diet 21.6 + 0.8 25.3 + 0.7 18.1 + 0.6 % Body fat 17.3 + 0.5 17.1 + 0.4 19.2 + 0.4 % Body proteins 57.1 + 0.6 53.4 + 0.5 58.6 + 0.6 % H 2 O 344.3 + 8.4 367.0 + 8.3 311.6 + 7.6 Final weight at 14 weeks 236.8 + 7.6 258.9 + 7.5 217.6 + 6.8 Weight at 10 weeks 106.06 + 0.9 106.65 + 1.1 106.1 + 1.0 Starting weight at 6 weeks GROUP 3 GROUP 2 GROUP 1

Results OP diet + Succeed TM Improvement of glucose, triglycerides and cholesterol plasma levels. OP-diet+Succeed™ OP-diet S-diet 1.04 + ±0.06 1.06 + 0.08 1.01 + 0.07 Cholesterol HDL 1.77 + 0.13 2.17 + 0.16 1.64 + 0.14 Total cholesterol 1.24 + ±0.12 1.78 + ±0.21 b 1.06 + 0.11 Triglycerides 9.65 + 0.59 10.59 + 0.55 9.89 + 0.48 Glucose GROUP 3 GROUP 2 GROUP 1

Results OP diet + Succeed TM Decrease of lipidic peroxidation (TBARS) and enhanced tissue antioxidant defense. OP-diet+Succeed™ OP-diet S-diet 140.81 + 7.98 128.42 + 9.15 154.67 + 10.36 Liver ATP (nmol/mg proteins) 30.74 + 2 26.17 + 1.47 35.98 + 2.83 Liver GSH (nmol/10 5 cells) 34.96 + 3.21 37.05 + 0.48 24.83 + 3.12 Liver TBARS (nmol/g tissue) 3.14 + 0.5 4.43 + 0.48 9.85 + 0.32 Plasma TBARS (nmol/ml) GROUP 3 GROUP 2 GROUP 1

Succeed™ Human Clinical Study “ Administration of a dietary supplement (N-oleoyl-phosphatidyl-ethanolamine and epigallocatechin-3-gallate formula) enhanced compliance with diet in healthy overweight subjects: a randomized controlled trial” M. Rondanelli et al. British Journal of Nutrition 2009; 101 :457-464

Study Design 138 Subjects (F=106 / M=32) GROUP 1 NOPE-EGCG complex N 71 (F=53 / M=18) GROUP 1 PLACEBO N 67 (F=53 / M=14) COMPLETED N 67 (F=50 / M=17) DROPPED OUT N 4 (F=3 / M=1) COMPLETED N 49 (F=39 / M=10) DROPPED OUT N 18 (F=14 / M=4)

Results COMPLETED DROP OUT SUBJECTS 94% 4 71 Succeed™ 73% 18 67 Placebo Succeed™ treated subjects complied with diet >94%, with a considerable difference with respect to placebo group. High drop out placebo group: Failure to follow the diet because of severe hunger. 94% 4 71 PhosphoLean™

Succeed™ treated subjects complied with diet >94%, with a considerable difference with respect to placebo group.

High drop out placebo group: Failure to follow the diet because of severe hunger.

Results Succeed™ positively affected mood: Enhanced sense of satiety / fullness . Enhanced capacity to pursue a low-calorie diet. Helped change eating habits. 1.42 -6.41 -4.21 Succeed™ 0.63 -1.24 -1.36 Placebo 1.42 -6.41 -4.21 Succeed™ HABER TEST BES BDI BDI = Beck Inventory Scale assesses depressive symptoms. BES = Binge Eating scale indicative of need for between meal eating. Haber Test = Sense of satiety during all treatment.

Succeed™ positively affected mood:

Enhanced sense of satiety / fullness .

Enhanced capacity to pursue a low-calorie diet.

Helped change eating habits.

Results Succeed™ significantly improved glucose metabolic parameters. -0.59 -18.50 Succeed™ -0.01 +2.58 Placebo -0.59 -18.50 Succeed™ HOMA INSULIN (pmol/L) HOMA = Homeostasis Model Assessment for insulin resistance assessment.

Succeed™ significantly improved glucose metabolic parameters.

Results Succeed™ improved anthropometric parameters. -2.34 -2.67 Placebo -3.45 -3.28 Succeed™ Waist Circumference (cm) Weight (kg) Anthropometric measurements: Body mass index (BMI). Waist-to-hip ratio. Waist circumference. Evaluation in clinical settings was used for rough estimation of abdominal fat volumes. Abdominal obesity is a Metabolic Syndrome health risk. -3.45 -3.28 Succeed™

Succeed™ improved anthropometric parameters.

Significantly helped committed people stay on their stressful low-calorie diets. Enhanced sense of satiety / appetite suppression. Decreased depressive symptoms. Decreased binge eating severity. Provided favorable changes in insulin resistance. Succeed™ Clinical Study Summary

Significantly helped committed people stay on their stressful low-calorie diets.

Enhanced sense of satiety / appetite suppression.

Decreased depressive symptoms.

Decreased binge eating severity.

Provided favorable changes in insulin resistance.

Succeed™ Supplement Facts Amount per serving (2 softgel capsules) Proprietary blend of N-oleoyl-phosphatidyl-ethanolamine (NOPE) and epigallocatechin gallate (EGCG) complex (PhosphoLean™) 690 mg *containing NOPE 170 mg* EGCG 120 mg* *Daily Value not established Ingredients: Soy oil, soy phospholipids enriched with N-oleoylphospatidylethanolamine (NOPE), gelatin, green tea extract, polyglyceryl oleate, glycerol, sorbitol, titanium dioxide, iron oxide, yellow # 13 and blue # 5

Amount per serving (2 softgel capsules)

Proprietary blend of N-oleoyl-phosphatidyl-ethanolamine (NOPE) and epigallocatechin gallate (EGCG) complex (PhosphoLean™) 690 mg *containing NOPE 170 mg* EGCG 120 mg* *Daily Value not established

Ingredients: Soy oil, soy phospholipids enriched with N-oleoylphospatidylethanolamine (NOPE), gelatin, green tea extract, polyglyceryl oleate, glycerol, sorbitol, titanium dioxide, iron oxide, yellow # 13 and blue # 5

A successful diet is one you can stay on.

Questions? Thank you! 4463 White Bear Pkwy., Suite 105 White Bear Lake, MN 55110 © Chemi Nutra 2009

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