N-Oleoyl-Phosphatidyl-Ethanolamine (NOPE) + EGCG: Scientific & Clinical Support For Appetite Suppression & Weight

Management

4463 White Bear Pkwy., Suite 105White Bear Lake, MN 55110© Chemi Nutra 2009

Succeed™• Next generation nutritional supplement

compound for advanced appetite control and weight management.

• Proprietary composition ofN-oleoyl-phosphatidyl-ethanolamine

epigallocatechin gallate

from standardized green tea extract.

and EGCG

NOPE

Proprietary Composition Of PhosphoLean™ NOPE+EGCG

• Gastro-protection of activeconstituents with releasein the small intestine.

• Increased bioavailability.• Increased intestinal levels of NOPE,

thus of NOE.• Markedly amplified activities of

both components, enhancingthe weight managementproperty 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.

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).

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 &Appetite Control

Lipid mediator involved in peripheral regulation of feeding.

NOE• Peripheral action.• Anorectic action.Anandamide• Central and peripheral action.• Orexigenic action.

NOENOE ANANDAMIDEANANDAMIDE

NAPE and NAE Intestinal Levels

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

intestinal mucosa. (Duodenum)

N-Acyl-Phosphatidyl-Ethanolamine (NAPE) Intestinal Levels

N-Acyl composition of NAPE in rat intestine after starvation and re-feeding:ACYL GROUP

Free-feeding

Starved 24h

Starved 24h and re-fed 1h

Starved 24h and re-fed 4h

Pmol / mmol P

C16:0 19+0.7 15+1.1* 20+0.70 20+0.97

C18:0 8.0+0.3 7.9+0.60 8.1+0.23 7.8+0.36

NOPE C18:1 n-9 8.6+1.4 3.4+0.19** 11+11 8.2+0.45

C18:1 n-7 3.7+0.12 4.1+0.36 4.3+0.28 4.5+0.40

C18:2 43+6.7 14+1.1** 56+5.2 39+2.4

NArPE C20:4 1.1+0.07 1.5+0.21* 1.3+0.09 1.4+0.09

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.

G. Peterson et al. Biochimica Biophysica Acta (2006) 1761:143

Mechanism Of Action N-Oleoyl-Ethanolamine (NOE)

Activation of Intestinal Receptors:• PPAR • GPR119

ANOREXIC EFFECT

REDUCTION of FOOD INTAKE

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.

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.

Succeed™ Mechanism Of ActionEFFECTS NOE EGCG

Mechanism Mechanism

Increased sense of satiety.

Intestinal PPAR receptor activation.

Boosts thermogenesis.

Increased lipidic catabolism.

Adipocyte PPAR receptor activation.

Liver UCP2-UCP3 activation.

Improved glucose handling.

GPR119 activation. Improved insulin sensitivity.

Improved vessel integrity.

Enhanced release of endothelium NO.Reduction of LDL oxidation.

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

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™)

Results

At 14 weeks, Group 3 (OP+NOPE diet) food intake was significantly lower than Group 2 (OP-diet).10

15

20

25

30

35

40

6 8 10 12 14

Group 1: S-diet

Group 2: OP-diet

Group 3: OP+NOPE-diet

Weeks

Food

inta

ke (g

)

Figure shows food intake in the treated groups.

ResultsGROUP 1 GROUP 2 GROUP 3

S-diet OP-diet OP-diet+Succeed™

Starting weight at 6 weeks 106.1+1.0 106.65+1.1 106.06+0.9

Weight at 10 weeks 217.6+6.8 258.9+7.5 236.8+7.6

Final weight at 14 weeks 311.6+7.6 367.0+8.3 344.3+8.4

% H2O 58.6+0.6 53.4+0.5 57.1+0.6

% Body proteins 19.2+0.4 17.1+0.4 17.3+0.5

% Body fat 18.1+0.6 25.3+0.7 21.6+0.8

OP diet + Succeed TM

Reduction of weight gain and total body fat.

ResultsGROUP 1 GROUP 2 GROUP 3

S-diet OP-diet OP-diet+Succeed™

Glucose 9.89+0.48 10.59 +0.55 9.65 +0.59

Triglycerides 1.06 +0.11 1.78 +±0.21b 1.24 +±0.12

Total cholesterol 1.64 +0.14 2.17 +0.16 1.77 +0.13

Cholesterol HDL 1.01 +0.07 1.06 +0.08 1.04 +±0.06

OP diet + Succeed TM

Improvement of glucose, triglycerides and cholesterol plasma levels.

ResultsGROUP 1 GROUP 2 GROUP 3

S-diet OP-diet OP-diet+Succeed™

Plasma TBARS (nmol/ml) 9.85+0.32 4.43+0.48 3.14+0.5

Liver TBARS(nmol/g tissue) 24.83+3.12 37.05+0.48 34.96+3.21

Liver GSH(nmol/105 cells) 35.98+2.83 26.17+1.47 30.74+2

Liver ATP(nmol/mg proteins) 154.67+10.36 128.42+9.15 140.81+7.98

OP diet + Succeed TM

Decrease of lipidic peroxidation (TBARS) and enhanced tissue antioxidant defense.

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 1NOPE-EGCG complex

N 71(F=53 / M=18)

GROUP 1PLACEBO

N 67(F=53 / M=14)

COMPLETEDN 67

(F=50 / M=17)

DROPPED OUTN 4

(F=3 / M=1)

COMPLETEDN 49

(F=39 / M=10)

DROPPED OUTN 18

(F=14 / M=4)

ResultsCOMPLETEDDROP OUTSUBJECTS

94%471Succeed™

73%1867Placebo

• 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%471PhosphoLean™

1.42-6.41-4.21Succeed™

Results

• Succeed™ positively affected mood:– Enhanced sense of satiety / fullness . – Enhanced capacity to pursue a low-calorie diet.– Helped change eating habits.

0.63-1.24-1.36Placebo

1.42-6.41-4.21Succeed™

HABER TESTBESBDI

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.

-0.59-18.50Succeed™

Results

• Succeed™ significantly improved glucose metabolic parameters.

-0.01+2.58Placebo

-0.59-18.50Succeed™

HOMAINSULIN (pmol/L)

HOMA = Homeostasis Model Assessment for insulin resistance assessment.

Results

• Succeed™ improved anthropometric parameters.

-2.34-2.67Placebo

-3.45-3.28Succeed™

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.

-3.45-3.28Succeed™

• 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

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

A successful diet is one you can stay on.

Questions?

Thank you!

4463 White Bear Pkwy., Suite 105White Bear Lake, MN 55110© Chemi Nutra 2009