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A scientific overview of pterostilbene, including a comparison with resveratrol, clinical indications, and regulatory information.

A scientific overview of pterostilbene, including a comparison with resveratrol, clinical indications, and regulatory information.

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    PteroPure Presentation PteroPure Presentation Presentation Transcript

    • ChromaDex’s pTeroPure Pterostilbene ®Jeremy Bartos, Ph.D.
    • Agenda 2• Introduction to pTeroPure pterostilbene ®• The science of pterostilbene• Other pTeroPure branded ingredients• Safety, dosing, regulatory, and other misc• Wrap up *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Company Overview: ChromaDex ® 3ChromaDex is a publicly traded, innovative natural products company thatprovides proprietary, science-based solutions and ingredients to the dietarysupplement, food and beverage, cosmetic and pharmaceutical industries.• Science-based company with a proven reputation for scientific leadership in high-growth natural products industry• Strong base business model experiencing high growth and providing for early access to high-potential proprietary products• First major proprietary product, pTeroPure® pterostilbene, is a potential blockbuster in multiple market channels *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • ChromaDex supplies research-grade natural compounds 4and performs analytical testing services supporting R&Dand QA for the following customer base:• Dietary Supplements• Food & Beverage• Cosmeceuticals• Pharmaceutical• Government• Universities & Research Institutions *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • 5 What is ?• Branded, proprietary ingredient sold by ChromaDex• Patents pending based on in-house applications and technology licensed from the USDA and UC-Irvine *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Recipient of the Frost & Sullivan 2010 Most 6Promising Ingredient of the Year Award *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • What is Pterostilbene? 7• Methylated resveratrol pterostilbene resveratrol• Phytoalexin (plant defense system); functions in the plant as an anti-fungal, anti-microbial• Naturally found in small berries (blueberries, huckleberries, grapes, etc.) *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene vs. Resveratrol 8 1Pterostilbene is: pterostilbene• More bio-available than resveratrol - Greatly improved oral absorption 1 3 - Greater metabolic stability resveratrol 2 *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene vs. Resveratrol: Bioavailability 9 % in blood after oral administration F= % in blood after direct IV administration From Kapetanovic et al.; Canc. Chemother. Pharmacol. 2010 Nov 30.Conclusion: pterostilbene taken orally (in capsules) is 70-90% bioavailable, compared to 20-30% of resveratrol *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene vs. Resveratrol 10 1Pterostilbene is:• More bio-available than resveratrol pterostilbene - Greatly improved oral absorption - Greater metabolic stability• Longer half-life in the body than resveratrol - resveratrol: ~14 minutes in blood (Asensi et al, Free Radic Biol Med, 33, 387, 2002) 3 1 - pterostilbene: ~ 105 minutes in blood (Remsberg et al, Phytother. Res. 22, 169, 2008) resveratrol 2 *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene vs. Resveratrol: half-life 11 From Kapetanovic et al.; Canc. Chemother. Pharmacol. 2010 Nov 30.Conclusion: pterostilbene lasts much longerin the blood than resveratrol *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene vs. Resveratrol 12 1Pterostilbene is:• More bio-available than resveratrol pterostilbene - Greatly improved oral absorption 1 3 - Greater metabolic stability• Longer half-life in the body than resveratrol - resveratrol: ~14 minutes in blood resveratrol (Asensi et al, Free Radic Biol Med, 33, 387, 2002) 2 - pterostilbene: ~ 105 minutes in blood (Remsberg et al, Phytother. Res. 22, 169, 2008)• More lipophilic than resveratrol - Higher potential for cellular uptake *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene vs. Resveratrol: cellular uptake 13 From Kapetanovic et al.; Canc. Chemother. Pharmacol. 2010 Nov 30. *p<0.01, from Nutakul et al, J. Agric. Food Chem. 59, 10964 (2011) Conclusion: Pterostilbene’s cellular uptake is superior to resveratrol in in vitro studies *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene vs. Resveratrol: Better Tissue Distribution 14 From Kapetanovic et al.; Canc. Chemother. Pharmacol. 2010 Nov 30.Conclusion: Resveratrol is cleared from the body faster and doesnot have the tissue distribution that pterostilbene does *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene and Resveratrol Synergism 15 LPO = H2O2-induced lipid peroxidation R Mikstacka, et al.; Plant Foods Hum Nutr. 65, 57 (2010) XConclusion: Pterostilbene and resveratrol act synergistically inprotecting human erythrocytes from damage due to oxidative stress *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Agenda 16• Introduction to pTeroPure pterostilbene ®• The science of pterostilbene• Other pTeroPure branded ingredients• Safety, dosing, regulatory, and other misc• Wrap up *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • pTeroPure Pterostilbene summary 17Potential Claims Features/Benefits Objections• Cholesterol • Compound structure • Synthetic• Oxidative Stress • - greater bioavailability • Cost/dose• Cognitive Function • - superior cellular uptake • No NDI• Blood Pressure • - lipophilic • Not water soluble• Blood Glucose • GRAS – safe • No human clinical data• NMSK • Human clinical data – efficacy and (yet)• Atherosclerosis clinical proof• Inflammation • Sustainable source• Neuroprotection • History in supplements back to 2008• Insulin increase • Patented claims• UV protection • High purity• Anxiolytic • Consistent material• Obesity• Skin whitening• Anti-oxidant• Anti-carcinogenic• Anti-microbial• Anti-fungal• Analgesic• Memory *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Cholesterol: in vitro 18 PPARα: involved in fatty acid and lipid catabolism; activation leads to decreased triglyceride and very low density lipoprotein (VLDL) synthesis PterostilbeneCiprofibrate (PPARαactivatingpharmaceutical)Resveratrol(reverse effect)Conclusion: Pterostilbene activates PPARα better than ciprofibrate *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Cholesterol: in vivo 19Conclusion: Pterostilbene raises the HDL (good) cholesterol andsignificantly lowers the LDL (bad) cholesterol in animal studies *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Cholesterol: Clinical Studies 20First Human Clinical study in collaboration with the University ofMississippiAnticipated completion by January 2012; data made public by July 2012• Primary Endpoint: Cholesterol• Secondary Endpoints: Blood Pressure and Oxidative Stress Markers• 4 Arms with 20 people per arm = 80 total participants - Placebo - 100mg pterostilbene/day - 250mg pterostilbene/day - 100mg pterostilbene + 200mg grape extract/day *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Cholesterol 21Docking of Pterostilbene in the PPARα Ligand-Binding DomainDocking of pterostilbene inside PPARα ligand binding domain. Pterostilbene has H-bond interactionswith the Tyr464, Ser280, and Phe351 amino acids that are involved in PPARα activation. Mizuno et al., Bioorg. Med. Chem. 16:3800-3808, (2008) Conclusion: With an excellent fit in the hydrophobic binding cavity, Pterostilbene is a “key” that “starts” PPARα *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • 22Cholesterol Summary• Among the stilbenes tested, only pterostilbene was a stimulant of PPARα activity in hepatic cells in vitro.• Plasma lipoprotein cholesterol and glucose lowering effects of pterostilbene in hypercholesterolemic hamsters are consistent with the in vivo lipid lowering actions previously reported for PPARα agonists (e.g., fenofibrate).• Pterostilbene had an excellent structural alignment for H-bond interactions with three key L-amino acids of the ligand binding domain involved in PPARα activation.• Pterostilbene is unique as a natural product PPARα agonist. *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene vs. Cholesterol Pharmaceuticals 23 *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene IP and Cholesterol Use 24 *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Blood Sugar Control 25 Conclusion: Pterostilbene lowers blood glucose levels in preliminary published animal studies *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Blood Sugar Control 26Insulin Production Conclusion: Pterostilbene raises insulin levels in published preliminary animal studies *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene vs. Diabetes Pharmaceuticals 27 *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Inflammation 28 Paul et al. Carcin. 31, 1272 (2010) The mucosa samples were randomly selected from each group, homogenized and assayed by ELISA for the different cytokines. n = 12 in control group; n = 6 in pterostilbene group **p<0.01, ***p<0.005.Conclusion: Pterostilbene lowered the production of inflammatorycytokines TNF-α, IL-1β and IL-4 in the colonic mucosa of rats andthus acts as an anti-inflammatory *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Inflammation: in vivo 29ControlPterostilbene The rat colon sections were incubated with the respective antibodies. Representative sections are Paul et al. Carcin. 31, 1272 (2010) shown. Control cells (no pterostilbene) had heavier brown staining. Conclusion: Pterostilbene was shown to reduce both iNOS and COX-2 expression in abnormal rat colon tissue and dose-dependently inhibited iNOS expression in abnormal human colon cell lines *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • 30 Inflammation: dose response Remsberg et al., Phytother. Res., 22, 169 (2008)Conclusion: Pterostilbene was shown to reduce PGE2 levels in thepresence and absence of a pro-inflammatory cytokine *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Vasodilation/eNOS: Resveratrol 31Conclusion: Resveratrol induces eNOS which should leadto vasodilation, does pterostilbene act in the same manner? *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Vasodilation/eNOS: Pterostilbene and Quercetin 32Conclusion: Pterostilbene induces nitric oxide synthase via eNOSpathway, especially in the presence of quercetin (synergistic). *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Vasodilation/eNOS: Pterostilbene and Quercetin 33 Ferrer et al, Neoplasia 7(1), 37-37 (2005)Conclusion: Pterostilbene and quercetin induce nitric oxidesynthase via eNOS pathway, which should lead to vasodilation. *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Anti-Oxidant: dose response 34Conclusion: Pterostilbene anti-oxidant potential is dose dependentand similar to that of resveratrol *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Anti-Oxidant: radical scavenging 35 DPPH Radical Scavenging Test 500 500 IC50 (ug/ml) 400 300 200 100 3.01 4.9 0 kojic acid resveratrol pterostilbeneConclusion: pterostilbene has a similar anti-oxidant potential asresveratrol *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Oxidative Stress Protection 36Measuring Oxidative Stress Conclusion: Muscarinic receptor subtype 1 transfected cells were the most sensitive to oxidative stress *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Oxidative Stress Protection 37Joseph et al., J. Agric. Food Chem. 56:10544-10551 (2008) Conclusion: Pterostilbene protects against oxidative stress in transfected COS-7 cell assay; Resveratrol does not *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Oxidative Stress Protection 38 Joseph et al., J. Agric. Food Chem. 56,10544 (2008) Conclusion: Pterostilbene protected against the decrease in dopamine release following oxidative stressor. *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Oxidative Stress Protection 39Cognitive Function/Neuroprotection Morris Water Maze Test 1st trial 2nd trial Description: The Morris Water Maze test involves placing the rodent in a pool of water where it must use external visual cues to remember the location of a hidden platform just below the water’s surface. Purpose: The MWM test measures spatial learning and memory. This is one of the most popular tasks in http://www.mcg.edu/Core/Labs/sabc/Morriswatermaze.htm behavioral neuroscience and is sensitive to both the amnestic and memory-enhancing effects of drugs. *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Oxidative Stress Protection 40Cognitive Function/Neuroprotection Conclusion: An increase in brain pterostilbene levels leads to a decrease in the distance traveled between two trials (memory improvement) *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Oxidative Stress Protection 41Cognitive Function/NeuroprotectionConclusion: an increase in brain pterostilbene levels leads to adecrease in the amount of time to get to the platform between twotrials (memory improvement) *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Oxidative Stress Protection 42IP *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Non-melanoma skin cancer (NMSC) 43• Most common cancer: 1 in 7 Americans - >1 million new cases each year - <1,000 deaths each year• Actinic keratosis (AKs) are pre-cancerous lesions that can give rise to non-melanoma skin cancer - >10 million Americans have AKs - Increased risk for other cancers• Celecoxib Trial: COX-2 inhibitor - NMSC slowed but not prevented - Is there more to NMSC progression than COX-2? *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • NMSC 44UDP-Glucuronosyltransferases (UGTs) UGTs prevent melanoma invasiveness • 12-Lipoxygenase (12-LOX) are not expressed in normal epithelia but often constitutively active in epithelial abnormalities • (12-LOX) converts Arachidonic Acid to 12-HETE • UGTs metabolize HETEs Conclusion: UGTs may prevent progression of AKs to skin cancer by metabolizing HETEs *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • NMSC 45UDP-Glucuronosyltransferases (UGTs) 3 different UGTs are expressed in melanocytes but are lost during melanoma progression • UV rays down-regulate UGT expression in vivo Conclusion: The down-regulation of UGTs by UV light may aid in the progression of NMSC *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • NMSC 46UDP-Glucuronosyltransferases (UGTs) • Loss of UGTs inversely correlates to lipoxygenase (12-LOX) over- expression • 12-LOX plays a direct role in skin carcinogenesis in mice - 12-HETE is elevated in NMSC in mice (>50x) Hypothesis: 12-HETE drives skin cancer progression, thus inhibiting de-regulation of arachidonic acid metabolites may prevent NMSC *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • NMSC 47Celecoxib • Clinical trial of 240 patients • Double-blind, placebo controlled randomized trial • Significant decrease in amount of new NMSC after 11 months • But no difference in the number of new AKs Conclusion: Celecoxib may slow down NMSC, but not prevent it because: • 12-LOX is not inhibited by Celecoxib • Inhibition of COX-2 leads to increased LOX activity Hypothesis: An agent that can maintain proper LOX and COX signaling could prevent NMSC *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • NMSC 48Pterostilbene Hypothesis • Pterostilbene up-regulates UGT expression • Pterostilbene down-regulates COX- 2 expression X Hypothesis: Pterostilbene may be able to regulate both sides of the arachidonic acid metabolites pathway, thereby preventing NMSC *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Agenda 49• Introduction to pTeroPure pterostilbene ®• The science of pterostilbene• Other pTeroPure branded ingredients• Safety, dosing, regulatory, and other misc• Wrap up *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • 50• 50:50 blend of pTeroPure pterostilbene and 99% curcumin• Animal health, sports nutrition markets Potential Claims Features/Benefits • Oxidative-stress • Pursuing provisional patents • Inflammation • Animal clinical study - Digestive • Both components are self-affirmed - Laminitis GRAS - Arthritis • Sustainable source • Cholesterol • Consistent material • Anti-carcinogenic • Blood glucose • Blood pressure/ circulation *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • 51• Animal Health: - One year exclusivity in equine market for Platinum Performance - Rest of animal health market open *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • 52• Because pTeroPure is lipophilic, a water soluble version is needed for beverage, premix markets• pTeroPure-WS is currently available in liquid form (25mg/ml of pTeroPure)• Potential for additional Glanbia collaboration on a solid version of pTeroPure-WS . *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Agenda 53• Introduction to pTeroPure pterostilbene ®• The science of pterostilbene• Other pTeroPure branded ingredients• Safety, dosing, regulatory, and other misc• Wrap up *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pharmacokinetics: Pterostilbene 54 *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene Safety 5528-day subchronic toxicity study in miceDoses/day (mg/kg of body weight): 30, 300, 3000- HED for a 154 pound person = 125 mg/day, 1.25 g/day, 12.5 g/day, respectively M.J. Ruiz et al.; J. Agric. Food Chem. 57, 3180 (2009) *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene Dosage 56Human dose translation from animal studies is based on body surface area (BSA) HED = human equivalent dose Reagan-Shaw et al.; FASEB J. 22(3):659-61 (2008) *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Pterostilbene Dosage 57Cholesterol paper (A.M. Rimando, et al.; J. Agric. Food Chem. 53, 3403; 2005) hamsters: 2.5 mg/kg = 0.337 mg/kg for humans = 24.6 mg for a 160 pound personDiabetes paper (L. Pari & M.A. Satheesh; Life Sci. 79, 641; 2006) rats: 10 - 40 mg/kg = 1.62 - 6.48 mg/kg for humans = 117.8 - 471.3 mg for a 160 pound personCognitive Function paper (J. Joseph et al.; J. Agric. Food Chem. 56, 10544; 2008) rats: 2.5 - 10 mg/kg = 0.41 - 1.62 mg/kg for humans = 29.8 - 117.8 mg for a 160 pound personRecommended dose: 50-150 mg per day *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Clinical Research Plan 58• Short term - Complete Ole Miss cholesterol study: 5/12 - Cognitive function clinical study (Tufts): Q2 2012 - Blood glucose clinical trial: Q3/Q4 2012 - Cosmeceutical studies: Q4 2012• Long term - Expanded multi-site cholesterol clinical study to bolster future qualified health claim (2013) - Phase IIa clinical study on the effect of pterostilbene on non- melanoma skin cancer (late 2012) - Obesity clinical study (2013) *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Regulatory Status 59U.S.• Self-affirmed GRAS (May 2011) - Submitting dossier to FDA for a letter of no objection early 2012 *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • pTeroPure Pterostilbene GRAS 60 GRAS self-affirmation for pTeroPure Pterostilbene in collaboration with AIBMR Completed May 2011 Letter of No Objection from FDA Anticipated by late 2012 *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Regulatory Status 61U.S.• Self-affirmed GRAS (May 2011) - Submitting dossier to FDA for a letter of no objection early 2012• DSHEA status - Not grandfathered in under DSHEA - Considered a dietary ingredient based on definition set forth in FD&C Act section 2011(ff)(1)(E) - GRAS - Found in food supply *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • NDI draft guidance 62From: Draft Guidance for Industry: Dietary Supplements: New Dietary Ingredient Notifications and Related IssuesBUTpTeroPure Pterostilbene meets the requirements of a “dietary ingredient” as set forth insection 201(ff)(1)(E) in that pTeroPure: 1) is self-affirmed as GRAS (safe) 2) is present in the food supply (Dodo Organics line of products)Therefore: pTeroPure does not need an NDI because it is alreadyconsidered a “dietary ingredient”. *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Regulatory Status 63Rest Of World• Currently only available in US markets - Awaiting completion of first human clinical trial: mid 2012 - Strategic plan under development to roll out to international markets: Q3 2012 *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Intellectual Property 64• WO 2010/010578 A2: “A key intermediate in the preparation of stilbenes” (manufacturing, world-wide exclusivity)• US 2006/0057231 A1: “Pterostilbene as a new agonist for the peroxisome proliferator-activator receptor alpha isoform” (cholesterol, world-wide exclusivity)• US 2009/0069444 A1: “Method to ameliorate oxidative stress and improve working memory via pterostilbene administration” (oxidative stress/cognitive function, world-wide exclusivity)• USSN 13/105,470: “Anxiolytic effect of pterostilbene” (anti-anxiety, world- wide exclusivity)• USSN 61/484,977: “Method for inducing UDP-Glucuronosyltransferase activity using pterostilbene” (provisional, co-inventors, world-wide-exclusivity) *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Current pTeroPure Pterostilbene 65 Products on the Market Direct to Physician *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Current pTeroPure Pterostilbene 66 Products on the Market Internet/Direct to Consumer *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. This document contains confidential information, and neither this document nor the information contained herein may be *These statements have not been evaluated by the Food and Drug Administration. disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation. This product is not intended to diagnose, treat, cure, or prevent any disease.
    • Current pTeroPure Pterostilbene 67 Products on the Market Retail *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. This document contains confidential information, and neither this document nor the information contained herein may be *These statements have not been evaluated by the Food and Drug Administration. disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation. This product is not intended to diagnose, treat, cure, or prevent any disease.
    • 68Available in GNC and Walgreens, with additional retail stores in 2012 *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Bibliography I 69• A.M. Rimando, et al.; J. Agric. Food Chem. 50, 3453 (2002)• M. Asensi, et al.; Free Radic Biol Med. 33(3), 387 (2002)• Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research: Estimating the safe starting dose in clinical trials for therapeutics in adult healthy volunteers, U.S. Food and Drug Administration, Rockville, Maryland (2002)• J. Joseph et al.; Free Rad. Biol. Med. 32:153-161, (2002)• Deplanque et al., J. Neurosci. 23:6264-6271 (2003)• A.M. Rimando, et al.; J. Agric. Food Chem. 53, 3403 (2005)• P. Ferrer, et al.; Neoplasia 7, 37 (2005)• L. Pari & M.A. Satheesh; Life Sci. 79, 641 (2006)• N. Suh et al.; Clin. Canc. Res. 13, 350 (2007)• M.H. Pan, et al.; J. Agric. Food Chem. 55, 7777 (2007)• J. Joseph et al.; J. Agric. Food Chem. 56, 10544 (2008)• Reagan-Shaw et al.; FASEB J. 22(3), 659 (2008)• C.M. Remsberg et al.; Phytother Res. 22, 169 (2008)• C.S. Mizuno et al.; Bioorg Med Chem. 16, 3800 (2008)• M.J. Ruiz et al.; J Agric Food Chem. 57, 3180 (2009) *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • Bibliography II 70• M. Pan et al; Evid. Based Complement Alternat. Med. 7, 1 (2009)• M.H. Pan et al; Carcin. 30, 1234 (2009)• J.G. Schneider et al.; J. Surg. Res. 161, 18 (2010)• R. Mikstacka et al.; Plant Foods Hum Nutr. 65, 57 (2010)• S. Paul et al.; Carcin. 31,1272 (2010) *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.
    • 71 Thank you! pTeroPure Pterostilbene Jeremy Bartos, PhDpTeroPure, a brand of ChromaDex, Inc. E: jeremyb@pteropure.com T: 949-600-9694 *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. This document contains confidential information, and neither this document nor the information contained herein may be disclosed, summarized, reproduced, disseminated or quoted or otherwise referenced in any manner, in whole or in part, without the express prior written consent of ChromaDex Corporation.