Reishi and Immunity: A Scientific Overview Presented by Michael N. Chang, Ph.D. Chief Scientific Advisor, Nu Skin Enterprises, Inc. 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.

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 cells that have been altered as a natural process of the cell rejuvenation function. … is delicately balanced by a very sophisticated feedback regulation and control system

Immune Cells Recognize and Destroy: Invading Organisms and Damaged 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. Cells that have been altered during the normal cell rejuvenation process also have carbohydrate antigens protruding.

Reishi Mushroom Reishi (Ganoderma lucidum) mushroom is a fungus occurring as a shelf-like form growing on trees and stumps in densely wooded mountainous areas with high moisture and low light. The spores of Reishi have tough outer shells that make it difficult to obtain the nutrients inside. The rarity of Reishi is partly attributed to the difficulty of germination.

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

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.

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

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

Clinical Research Approach for Reishi The polysaccharides of Reishi can support 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 support the immune system.

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

Pre-Clinical Studies Animal and in vitro studies have shown that Reishi extracts: Supports activity of lymphocytes and natural killer (NK) cells Supports activity of cytokines and macrophages Supports healthy, normal histamine release from mast cells Wang SY, et al. 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: Supports healthy levels of immune cells and antibodies Improve vigor and appetite 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.

Application for Reishi Reishi supports the immune system’s ability to recognize unwanted organisms and cells that may have been damaged as a normal effect of the cell rejuvenation function. Reishi supports optimal health supports the body’s formation of antibodies supports the body’s ability to proliferate immune cells modulates the function of Natural Killer (NK) cells

Optimal Immune System Support Presented by Jia-Shi Zhu, M.D., Ph.D. Director of Clinical and Pharmacology Affairs, Pharmanex, LLC

Scientifically Proven Health Benefits Supports healthy immune system functions* Stimulates proliferation of defensive immune cells in your body, including NK cells* * 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 supportive immune functions by ReishiMax: Supports the formation of antibodies* Supports proliferation of immune cells* Supports NK cell functions* * 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 supports 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 supports 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 immune supporting 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.

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 Health food license granted by Taiwan 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

Taken together, ReishiMax and Tegreen 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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