Pharmanex Workshop ReishiMax

Michael N. Chang, Ph.D. Chief Scientific Advisor Ph.D. in Organic Chemistry Post-doctoral Fellowship at MIT Over 20 years of pharmaceutical business experience 35 patents

Josh Zhu, M.D., Ph.D. Director of Clinical Affairs & Manager of Clinical Pharmacology Capital Institute of Medicine Ph.D. in Molecular and Cellular Physiology Member of six American medical societies

Reishi and Immunity: A Scientific Overview Presented by Michael N. Chang, Ph.D. Chief Scientific Advisor, Nu Skin Enterprises, Inc. This material is provided for scientific and educational purposes only and should not be distributed or used in conjunction with the sale or distribution of any dietary supplement product.

The Human Immune System ...…is a complicated network of cells, antibodies and proteins that serves following three main functions: 1. Removes waste and harmful material, to ensure the normal function of the body. 2. Defends against pathogens - bacteria, fungi and virus. 3. Kills and removes dead and altered cells.

The Human Immune System ......is delicately balanced by a very sophisticated feedback regulation and control system Prolonged immune deficiency can lead to infection, frequent sickness, lack of vigor and energy and impaired metabolism. On the other hand, chronic activation of immune system can also lead to certain autoimmune conditions such as arthritis, lupus, nephritis, allergy, etc.  

Immune Cells Recognize and Destroy: Pathogens and Altered Cells Chemical message alerts immune system that an invader is present Immune cell “swallows” foreign invader

Cell Surface Antigen How does it work? Pathogens, such as bacteria, fungus, virus, have carbohydrates protruding outside of its surface. Altered cells also have carbohydrate antigens protruding.

Reishi Mushroom Reishi (Ganoderma lucidum) mushroom is a fungus occurring as a shelf-like form on the sides of trees and stumps in densely wooded mountains with high humidity and low light. The Reishi mushroom is a fungus that occurs as a shelf-like form on the sides of trees and stumps. In nature it grows in densely wooded mountains with high humidity and low light. It is rarely found since it flourishes mainly on the dried trunks of dead plum pasonia trees. The spores of Reishi also have such tough outer husks that make germination next to impossible. This accounts for its rarity. The spores of Reishi have such tough outer husks that germination is next to impossible, which accounts for its rarity

Reishi Growing Process Zoom in of Reishi body 1 1. Reishi body 2. Basidiomycete produces sporidium 3. Mycelium 3 2 Growth of Basidiomycete

Types of Reishi There are 62 types of Reishi, of which six are most common: RED BLACK BLUE WHITE YELLOW PURPLE RED Reishi is preferred because it can produce the highest quality extract and has been subject to the most scientific evaluation There are 62 types of Reishi, of which six are most common: red, blue, yellow, black, white and purple. Pharmanex has chosen to use red Reishi in ReishiMax because it can produce the highest quality extract and has been subject to the most scientific evaluation.

Cultivation of Reishi In 1971, Yukio Naoi, a researcher of the Kyoto University in Japan, successfully developed the artificial cultivation of Reishi, which resulted in reproducible and consistent production of Reishi. A new cultivation method by Yukio Naoi from the University of Japan increased the availability of Reishi to everyone. This cultivation method resulted in the ability to cultivate Reishi in large quantities. The Reishi strain is transplanted to the cut of the original wood, so that the Reishi can absorb the nutrients of the wood The cultivation period takes between 120-200 days. This method makes it very similar to the natural habitat of wild Reishi with out the use of pesticides and heavy metals.

Compounds Identified in Reishi Mushrooms

Reishi Spores These highly active substances are the essence of Reishi They are the reproductive cells that are released at maturity However, Reishi spores are protected by an extremely hard shell which prevent us from optimally absorbing the actives Reishi spores contain the reproductive cells that are released at maturity. Unfortunately, the outer shells of the mushroom make it extremely hard to obtain these spores and prevent us from optimally absorbing the actives therein.

Traditional Use Reishi, also known as Lingzhi, is one of the most valued herbal products in Traditional Chinese Medicine (TCM) Reishi’s earliest herbal remedies were recorded between 206 B.C. - 8 A.D. In Taiwan, families often give Reishi to their aging grandparents Reishi is also known as Lingzhi. It is one of the earliest herbal remedies that has been recorded between the years of 206 B.C.-8A.D, and it is one of the most valued and potent herbal products used in Traditional Chinese Medicine. In China, Reishi is a Traditional Chinese Medicine herb of choice as a general tonic for promoting longevity, vitality and endurance, and general health preservation.

Clinical Research Approach for Reishi The polysaccharides of Reishi can regulate our immune system. It is generally recognized that certain polysaccharides cannot be absorbed by the human body. When our intestine senses the presence of certain polysaccharides, receptors within our body will create a series of signals which then stimulate the body to carry out biological actions that regulate the immune system.

Research Findings: Reishi Mushroom & Extracts Cell support Immune dysfunction-related diseases Liver protection Nervous system dysfunction Cardiovascular protection and blood sugar support

Pre-Clinical Studies Animal and in vitro studies have shown that Reishi extracts: Enhances activity of lymphocytes and natural killer (NK) cells Enhances activity of cytokines and macrophages Decreases histamine release from mast cells Wang SY, et al. International Journal of Cancer 1997;70(6):699-705. Lu Z, Lin ZB. 1994 International Symposium on Ganoderma Research, October 24-26, 1994, Beijing Medical University, Beijing , China, Program and Abstracts, p. 82.

Clinical Studies In clinical studies, Reishi extracts have been shown to: Increase levels of T-cell counts, CD4/CD8 ratio, cytokine IL-2, complement C3 and immunoglobulin G Lower levels of T-suppressor cell counts Improve vigor and appetite Shorten recovery time Kupin, V. (1992). The 4th International Symposium on Ganoderma lucidum, Hyatt Regency hotel, June 10, 1992, Seoul, Korea, Program and Abstracts, pp. 36-39. Yang QY, Wang, M. M. (1996). 1996 Taipei International Ganoderma Research Conference, Taipei International Convention Center (TICC), August 15-15, 1996, Abstracts, Special Lecture.

Clinical Application for Reishi Reishi stimulates the immune system’s ability to recognize pathogens and altered cells Reishi provides complementary therapy to promote health and longevity stimulates the formation of antibodies stimulates the ability of proliferation of immune cells modulates the function of T cells and NK cells

Optimal Immune System Support Presented by Josh Zhu, M.D., Ph.D. Director of Clinical and Pharmacology Affairs, Pharmanex, LLC This material is provided for scientific and educational purposes only and should not be distributed or used in conjunction with the sale or distribution of any dietary supplement product.

Scientifically Proven Health Benefits Supports healthy immune system functions* Stimulates proliferation of defensive immune cells in your body, including T Cells, B Cells & NK cells* ReishiMax follows the 6S process with standardization. ReishiMax is standardized to the highest level of actives found in any Reishi extract. The actives ingredients found in Reishi are triterpenes and polysaccharides. These two actives make Reishi a potent herb. ReishiMax is standardized to 6% triterpenes and 13.5% polysaccharides. Not only does Reishimax contain these active ingredients, but our product contains a 1% extract of 100% cracked spores! * 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.

Use of the best Reishi species: RED Reishi or Ganoderma lucidum Use of the best Reishi cultivation method: solid tree trunk, organic cultivation for 120-200 days Free of pesticides, free of heavy metals, and no unwanted microbial contamination

Use of Pharmanex’ proprietary manufacturing process to extract active components from Reishi

Reishi spores 100% Cracked spores Cracked Reishi Spores Reishi spores 100% Cracked spores — 3000X magnification under an electronic microscope

Proprietary Formula Contains 1% Reishi spores (100% cracked) Standardized to 6% Reishi triterpenes 13.5% Reishi polysaccharides

ReishiMax Pre-Clinical Studies A recent comparative study demonstrated enhanced immune functions by ReishiMax: Increased serum antibodies* Stimulated proliferation of immune cells* Modulation of the T cell functions* Enhanced the NK cell functions* According to the results of animal and in vitro studies, ReishiMax has been demonstrated to -stimulate the formation of antibodies -stimulate the ability of proliferation of immune cells and -modulate the function of T cells. These studies show that ReishiMax has the ability to enhance and help maintain a healthy immune system. * 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.

Humoral and Cell-Mediated Immune Humoral immune: Blocking and eliminating infectious agents via humoral molecules, such as Immunoglobulin G (IgG) Cell-mediated Immune: Blocking and eliminating infectious agents via immune cells, such as T cells and NK cells

ReishiMax enhances humoral immune functions* Placebo 0.585 1.170 ReishiMax GLP 2.925 0.585 (g/kg) Other Reishi +25% +27% +15% p=0.01 p<0.01 by ANOVA 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 Serum IgG (mg/ml) By Medical Institute at National Taiwan University * 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.

ReishiMax enhances cell-mediated immune functions* Placebo 0.585 1.170 ReishiMax GLP 2.925 0.585 (g/kg) Other Reishi 1000 2000 3000 4000 5000 Interleukin-2 (pg/ml) p<0.001 by ANOVA +405% +822% +799% p=0.12 By Medical Institute at National Taiwan University * 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.

Higher Amount of Actives min 10 20 30 40 50 mAU 100 200 Other Reishi product GA Ganoderol B Ganoderol acid DM-std ReishiMax

Recent Publications ReishiMax GLp contains unique polysaccharides that are responsible for immuno-modulating activities Conducted by Pharmanex SAB member Chi-Huey Wong at Academia Sinica in Taiwan Published: Wang YY, Wong CH, et al. Bioorganic & Medicinal Chemistry 2002;10:1057-1062. Three new active compounds (lanostanoids) identified in Reishi Conducted by Pharmanex Scientists - J. Chang, M. Chang, and others. Published: Ma J, Ye Q, et al. Journal of Natural Products 2002;65(1):72-75. According to the results of animal and in vitro studies, ReishiMax has been demonstrated to -stimulate the formation of antibodies -stimulate the ability of proliferation of immune cells and -modulate the function of T cells. These studies show that ReishiMax has the ability to enhance and help maintain a healthy immune system.

Higher Solubility ReishiMax Reishi A Reishi B 90% 71% 80% 70% 51% 60% 10% 20% 30% 40% 50% 60% 70% 80% ReishiMax Reishi A Reishi B By Pharmanex Research Center at Shanghai Medical University

Competitive Advantage 6S process Best natural Red Reishi species Organic cultivation Cracked spores Proprietary manufacturing technology Highest level of actives on the market Scientifically proven Pharmanex ReishiMax has a strong competitive advantage over other Reishi products. -Pharmanex ReishiMax contains the highest levels of actives on the market for a Reishi product -the Reishi mushroom is organically grown. The natural log cultivation method grows reishi without the use of pesticides, heavy metals or unwanted debris -Pharmanex ReishiMax uses the most scientifically studied strain of Reishi. Red Reishi -Only ReishiMax incorporates the “cracked spore” technology -As with all of our Pharmanex products, ReishiMax is produced under our strict 6S process to ensure quality ingredients, qualified manufacturers, and certified independent laboratory verification -A health food license was granted for ReishiMax by the Taiwan DOH in April 2002. It is only one of 23 licenses that have been issued for health foods by the DOH!

Recommended Usage Take twice daily with meals: 1 capsule each time for health maintenance 2 capsules each time for immune modulation Safe and well tolerated at the recommended dosage ReishiMax is safe and well tolerated at the recommended dosage. ReishiMax is recommended twice daily with meals. For normal health maintenance, one capsule should be taken twice daily. For immune modulation, two casules of ReishiMax should be taken twice daily with food.

Taken together, ReishiMax and Tegreen 97 provide a comprehensive cellular health maintenance program* * 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.

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