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 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 3 2

1. Reishi body 2. Basidiomycete produces sporidium 3. Mycelium 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

Compound Polysaccharides Triterpenes Nucleosides Fatty Acids Amino Acids, Vitamins, Minerals Function

Improves immunity, reinforces liver function, and stimulates insulin secretion Nourishes the liver, anti-allergy, anti-inflammation, maintains cholesterol, and eases pain Inhibits plaque agglutination, prevents thrombus formation Inhibits histamine release Replenishes nutrients

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 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 4 th 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*

* 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

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*

* 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*

1.6

p<0.01 by ANOVA

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0.0

+25% +27% +15% Placebo 0.585

1.170

2.925

ReishiMax GLP 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.

+25% p=0.01 0.585

Other Reishi (g/kg)

ReishiMax enhances cell mediated immune functions*

5000

p<0.001 by ANOVA

4000

+822% +799%

3000 2000

+405%

1000 0

Placebo 0.585

1.170

ReishiMax GLP 2.925

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.

p=0.12 0.585

Other Reishi (g/kg)

mAU 200

Higher Amount of Actives

Other Reishi product GA

100 0 mAU 0 10

ReishiMax GA

20 30 40 50

Ganoderol acid DM-std Ganoderol B

100 50 0 0 10 20 30 40 50 min min

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.

90% 80% 70% 60% 50% 40% 30% 20% 10% 0%

Higher Solubility

90% 71% ReishiMax Reishi A 51% 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

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 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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