G3 Workshop North America Leadership Conference March 3, 2006 This material has been prepared by Pharmanex to be used in conjunction with general educational events and activities only. Alterations or modifications of this presentation without the express approval of Pharmanex is prohibited.

Mark R. Bartlett Ph.D. Sr. Director, Pharmanex New Product Development

Science & Tradition

MSNBC.com Spartan diet may slow aging NIH launches study to test practicality By Rob Stein The Washington Post As the rest of the nation has been supersizing, a small cadre of Americans such as Francesca Skelton have been radically downsizing their diets — not to slim down their physiques but to slow down the hands of time. Skelton is an adherent to the theory that "caloric restriction" can hold back the aging process by fundamentally altering basic metabolic functions in ways that protect the body from decaying as quickly. So for years, the District grandmother and others like her have been eating often radical diets carefully calibrated to slash calories they consume each day while still providing their bodies with the nutrients they need.

Green Tea and Longevity Green Tea Consumption (Cups/Day) Prospective, 11-year cohort study of 8,552 subjects in Yoshimi, Japan, From: H. Fujiki et al., Ann. N.Y.Acad.Sci., 928:274, 2001; used with author’s permission

Aging, Diet, Antioxidants… What we know about the aging process –DNA –Mitochondria What’s the connection between reduced calories and aging? Exogenous antioxidants vs endogenous antioxidants

Antioxidants Addresses the Root Cause of Aging: DNA Damage DNA (DeoxyriboNucleic Acid) is your genetic blueprint DNA enables healthy cell renewal into old age Aging Symptoms

Most Vulnerable to free radicals…

Free Radical Sources Environmental pollution (smog, ozone, NO 2 ) Radiation exposure: –sunlight (UV-light), X-rays, etc. Smoking: –10,000,000,000,000,000 free radicals/cigarette! Eating and Breathing: metabolism in your mitochondria

Mitochondria – The Energy Furnaces of the body Free Radicals SOD CAT

Starve Your Way to Health It works for mice and fruit flies, but can ultra-low-calorie diets extend the life of humans? By Jerry Adler and Anne Underwood Newsweek Jan. 19 issue - If the world is divided into people who live to eat and those who eat to live, perhaps there ought to be a third category for Brian Delaney. At 5 feet 11 inches and 139 pounds, Delaney, 40, is really, really thin. Thin, and hungry. He limits his calories to 1,800 a day, in part by eating just two meals, except when he has a dinner date, in which case that's the only meal he eats. After 10 years on this regimen—actually, he started out at 1,400 calories a day, less than half of what the average American male consumes—he still experiences "the same pit in my stomach" every afternoon, but now finds it "easier to deal with." Especially when he thinks of all the diseases he's avoiding. If Brian Delaney is right, he may well have the last laugh on the rest of humanity... sometime in the 22d century. MSNBC.com

Aging so far… DNA damage Cell membrane damage Uncontrolled free radical leakage from Mitochondria The most common link? Free Radicals

“… low levels of the antioxidant vitamins (vitamins A, E, and C) may increase risk for several chronic diseases. Most people do not consume an optimal amount of all vitamins by diet alone.” “It appears prudent for all adults to take vitamin supplements.” Journal of the American Medical Association Robert H. Fletcher, MD, MSc; Kathleen M. Fairfield, MD, DrPH, Harvard University Journal of the American Medical Association 2002; 287: Antioxidant Health Benefits

–R&D evaluated hundreds of fruits for… Extraordinary antioxidant power –Measurable (Scanner) –Protect cells, (DNA, Membranes) – Enhance internal antioxidant production 3 years ago… Pharmanex began Searching the World for Superfruits

Fruit Phytonutrients At least 1,000 phytochemicals identified with cell protective effects Very few (25) studied Fruits and vegetables – more than meets the eye We don’t eat enough fruits and vegetables

Families of Antioxidants Vitamin E: 8 natural forms

Families of Antioxidants Vitamin E: 8 natural forms Vitamin C:

Families of Antioxidants Vitamin E: 8 natural forms Vitamin C (Metallo-enzyme cofactors) –Selenium, Zinc, Manganese, Copper Enzyme Protein Zinc

Families of Antioxidants Vitamin E: 8 natural forms Vitamin C: 500 mg (Metallo-enzyme cofactors) –Selenium, Zinc, Manganese Flavonoids: –Catechins, –polyphenols etc

Families of Antioxidants Vitamin E: 8 natural forms Vitamin C (Metallo-enzyme cofactors) –Selenium, Zinc, Manganese Flavonoids: –Catechins, polyphenols etc Carotenoids: –Β-carotene, lutein, lycopene, α-carotene

Carotenoids uptake through the diet safe vitamin A sources (a- & b-carotene) antioxidants ( 1 O 2 quenchers) promote immune function (b-carotene) protect cellular DNA (lycopene) protect macular region of retina (lutein) Zeaxanthin Lutein

Your Antioxidant Network Vitamin E: 8 natural forms Vitamin C Metallo-enzymes (cofactors) –SOD, Catalase, Glutathione per. –Selenium, Zn, Mn, Cu Flavonoids: –Catechins, polyphenols etc Carotenoids: –Β-carotene, lutein, lycopene, α-carotene More than just One…

1.Provo R&D Center 2.Shanghai R&D Center 3.Beijing R&D Center Pharmanex Research Centers were involved…

–Almost all failed Selection criteria –All but Four (g+3) very special fruits years of searching

1.Gâc fruit (Chinese Bitter Cucumber) 2.Chinese Lycium (Wolfberry) 3.Cili fruit 4.Siberian Pineapple (Seabuckthorn) 3 Years of Searching and R&D 3 +1 Superfruits 3 Pharmanex Research Centers

Indigenous to Southern Asia Bangladesh, Burma, Cambodia, China, India, Japan, Laos, Malaysia, Philippines, Thailand, and Vietnam Traditionally used internally and externally* Topical: wound healing Internally: eye health, and to promote growth in children* Gâc - “ Fruit From Heaven ” *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.

Antioxidants in Gâc Pulp Extraordinarily rich in antioxidants, esp. lycopene, beta-carotene, vitamin E Unique fatty acids → Lipocarotenes™ Fruit flesh (mesocarp) Pulp (aril) Seeds

Gac Fruit Lycopene Content mcg/g wet weight Ishida et al., J Agric Food Chem 52:274, x more than tomatoes!

Gac Fruit Beta-Carotene Content mcg/g wet weight Ishida et al., J Agric Food Chem 52:274, x more than carrots!

Zeaxanthin in Chinese Lycium Fruit 40 x more than yellow corn! mcg/g wet weight

Vitamin C in Cili Fruit 60 x more than oranges! mg/100g wet weight

Antioxidant protection Vitamin C

Betacarotene Carotenoid protection

Lutein Betacarotene Carotenoid protection

Lutein Lycopene Betacarotene Carotenoid protection

Antioxidant protection Vitamin C Lutein Lycopene Betacarotene

Carotenoids and DNA damage (2006)

Carotenoids First line of defense antioxidants* Protect cell membranes* Protect DNA* Enhance communication in cell membranes* Found in a diet rich in fruits and vegetables Indicator of overall antioxidant health* *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.

Carotenoids Predict Antioxidant Status Recent paper published in the Journal of Nutrition –Carotenoids (blood) are indicator of total antioxidant status –Carotenoids interact with the antioxidant network –Vitamin E (blood) is not a good indicator of antioxidant status

Raman Spectroscopy Intense monochromatic light (one color only) interacts with molecules that have vibrational energy (e.g., carotenoids) and gets scattered at a higher wavelength (color). Sir C. V. Raman, Nobel Prize in Physics, 1930 Carotenoid molecules shift blue laser light color to green: from 473 nm to 510 nm

Pharmanex BioPhotonic Scanner Measures skin carotenoids –an indication of your personal antioxidant protection Easy & non-invasive Scientifically and clinically validated Gold standard Measure antioxidant effect of g3 in your own body!

Relative risk Servings tomato juice tomato fruits pizza tomato sauce from Giovanucci et al. J. of Natl. Canc. Inst. 87, 1767 (1995) Effect of tomato food products on prostate health risk Bioavailability

g 3 Increased Antioxidant Network Scores ~9,500 in 8 Weeks

0 2,000 4,000 6,000 8,000 10,000 Week 0Week 2Week 4Week 6Week 8 Antioxidant Score Tahitian NoniXanGo Noni & Xango vs. g3

Chinese Lycium (Wolfberry; Lycium chinense) 2000 years TCM history in China Longevity, wellness, vision Cellular rejuvenation:* protects DNA* –antioxidant (SOD, GPX) *Theses statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Other Ingredients Cili Fruit (Rosa roxburghii) Cardiovascular, antioxidant benefits:* –↓ oxLDL, increases SOD* Addresses symptoms of Aging*

g3 activates SOD and Catalase* –the body's catalytic antioxidant system –antioxidant protection inside the cell, where it is needed the most SOD: Superoxide Dismutase –most important antioxidant enzyme –requires copper, zinc & manganese (LifePak) Is Catalytically Active *Theses statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Vulnerable to Oxidation Vitamin C Lutein Lycopene Betacarotene

SOD CAT SOD Catalase Internal Antioxidants

You have the 3 most powerful tools of the entire nutritional supplement industry worldwide:  lifepak nano: The best multi-nutrient supplement.  : The best functional fruit juice.  BioPhotonic SCANNER: The best consumer test for antioxidant nutrition. The Measurable Difference

Key Business Takeaways G3™ supports your body’s antioxidant network* Lipocarotenes™ naturally increase absorption of antioxidants* SCS Certified ~ 9,500 increase in 8 weeks 6 times more powerful than Noni or Xango™* Proprietary and patent pending *Theses statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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