Reishi Mushroom Extract and Immune Support

By James P. Meschino, DC, MS

Reishi mushroom (ganoderma lucidum) is called the "mushroom of immortality" in China, where it grows wild on decaying logs and tree stumps in the coastal provinces. It has been used in Oriental medicine for over 2,000 years.^1,2 In recent years, its active ingredients have been the subject of intensive research regarding their apparent ability to help prevent or treat certain types of cancer; liver disease; HIV infection; acute or recurrent herpetic infections; high blood pressure; chronic bronchitis; allergies and asthma; and to favorably modulate immune function.³ The fruiting body of the mushroom is used in medicines.⁴

Active Constituents

Reishi mushrooms contain a number of active agents known to modulate function of the immune system in humans.

The primary agents include:

1. Specific polysaccharides - which occur in the form of beta-D-glucans bound to amino acids. These agents possess immune-modulating and anti-cancer properties;³
2. Triterpene compounds - known as ganoderic acids, have been shown to lower blood pressure, reduce platelet stickiness and may decrease LDL-cholesterol;⁵
3. Sterols, coumarin and mannitol.5

Clinical Application and Mechanism of Action

Anti-Cancer Agent - Cancer studies in animals have shown a 50 percent tumor regression rate with reishi mushroom extract treatment (e.g., connective tissue cancer model in mice).⁶ It is used by some cancer surgeons in Japan to treat patients; significant anti-tumor and immunostimulation effects have been noted in many of these cases.⁷ Polysaccharides from reishi mushrooms and other types of folk-medicinal fungi are patented in Japan for use as immunomodulators in the treatment of cancer. They are combined with chemo and radiotherapy, and have demonstrated an ability to reduce side effects, increase the efficacy of treatments, and accelerate recovery.^8,9

Studies from China have shown that reishi mushroom extract potentiates the tumoricidal capacity of macrophages and T-cells.^10,11 Reishi mushroom extract is also known to have other immune-modulating effects and antioxidant properties.^12-16

Animal studies show that the polysaccharide fraction of reishi mushrooms can induce apoptosis (programmed cell death of cancer cells) in leukemic cells and induce cellular differentiation in 40-45 percent of those treated with reishi polysaccharides, demonstrating significant cancer treatment potential. These effects were primarily due to the increased secretion of anti-tumor cytokines (signaling agents) induced by reishi mushroom polysaccharides (namely TNF-alpha and IFN-gamma), and these two cytokines acted synergistically on the inhibition of leukemic cell growth.¹⁷ In a related experiment, the D-glucan polysaccharide fraction of reishi mushroom was shown to produce dramatic tumor regression in a mice sarcoma study. In many animals, complete tumor regression occurred in the group injected with beta-D glucan fractions within a five-week period. The study by Y. Sone, et al. reported tumor inhibition rates of 90 percent, and tumor regression in 75 percent of afflicted animals.¹⁸

Immune System Enhancement (bronchitis, asthma, allergies, herpetic conditions and HIV infection) - As noted above, reishi mushroom extract modulates many components of the immune system, which in part accounts for its apparent anti-tumor properties. Chronic bronchitis in the elderly has been shown to respond favorably to treatment, using a concentrated reishi mushroom product in a trial involving 2,000 cases in China. This study demonstrated a success rate of over 60 percent. After several months of treatment, there was a noted rise in levels of immunoglobulin A in the sputum.¹⁰ Immunoglobulin A is the main immunoglobulin found in the respiratory tract. A deficiency is common in allergies,¹⁹ systemic lupus and rheumatoid arthritis.²⁰ Reishi mushroom extract supplementation has been shown to help improve cases of asthma and allergies. Two constituents of reishi mushroom extract, oleic acid and cyclooctasulfur, were shown to inhibit the release of histamine, which is likely how it benefits asthmatic and allergic patients.^10,21,22

GLhw-02, a specific protein-bound polysaccharide component of reishi mushroom extract, has been shown to possess potent antiviral properties against the herpes simplex virus (types 1 and 2) under experimental conditions.²³ A small human trial demonstrated that reishi mushroom extract reduced pain "dramatically" in two patients with postherpetic neuralgia, and in two other patients with severe pain due to herpes zoster infection (shingles, caused by the herpes virus).²⁴

Under experimental conditions, various ganoderic acids in reishi mushroom extract have been shown to be active anti-HIV agents, showing an ability to reduce viral replication by 50 percent at conservative doses.²⁵ Combined with other Oriental herbs, reishi is being used the treatment of AIDS-related complex, AIDS, and in formulas to treat chronic fatigue syndrome.^26,27,28

Finally, studies on male mice reveal that reishi mushroom extract was effective in enhancing the recovery of cellular immunocompetence after gamma-ray irradiation. Reishi mushroom supplementation significantly increased white blood cell count (leukocytes) and other parameters of immune function in these animals,²⁹ similar to astragalus supplementation in patients treated with chemo or radiation therapy. The combination of astragalus and reishi mushroom extract thus represents an effective means of daily immune support and a therapeutic intervention for a large number of immune compromised states (e.g., chronic fatigue; chronic bronchitis; herpes I and II recurrent infections; postherpetic neuralgia; recurrent apthous ulcers or canker sores; the common cold; HIV infection; etc.), and for patients undergoing chemo or radiation therapy.

Cardiovascular Health (high blood pressure and reduced platelet aggregation) - Two human controlled studies revealed that reishi mushroom extract can reduce high blood pressure to a significant degree (systolic and diastolic), even in patients who had previously failed to respond to established anti-hypertensive medications.^30,31 Animal studies reveal that reishi mushroom extract reduces blood pressure through a central inhibition of sympathetic nerve activity, although it does not slow heart rate or induce a sedative effect, in general.³² Under experimental conditions, reishi mushroom extract had a mild-to-moderate effect on reducing platelet aggregation, which may further help to decrease risk of cardiovascular disease.³³ It also increased endurance, blood flow to the brain, and improved oxygenation of cells. As such, it aids energy production on a cellular level, which may improve cardiovascular health, and is used to boost memory and intellectual capacity in some cultures,³⁴ including success in a study of Alzheimer's patients.³⁵

Liver - Protective Effects (hepatoprotective properties) - Reishi is prescribed in China for the treatment of chronic and acute hepatitis.³⁶ Various ganoderic acids in reishi mushrooms have strong antihepatotoxic properties,³⁷ which under experimental conditions have been shown to protect liver cells from chemically-induced injury, including protection from the highly toxic and lethal carbon tetrachloride.^38,39

Dosage and Standardized Grade

1. Therapeutic Applications: Typically 250 mg, one to four times per day is used, if taken as a single agent (standardized to 10-12.5 percent polysaccharide content).⁴⁰


2. General Wellness (immune, cardiovascular, liver support, etc.): Consider 30-120 mg per day (standardized to 10-12.5 percent polysaccharide content).

Reishi mushroom extract should be taken with food or it may cause stomach upset and loose stools.⁴¹

Adverse Side-Effects and Toxicity

Side-effects are infrequent and include dizziness; dryness of the mouth, throat and nasal areas; stomach upset; and loose stools.⁴¹ Reishi mushrooms contain agents that may be allergens to some patients, although allergic reactions are rare.⁴² Note that there is no cross-sensitivity to the reishi mushroom if a person is allergic to the button, or commonly eaten white mushroom found in most grocery stores.³⁵ In general, reishi mushroom has been shown to be nontoxic in animal toxicity studies and in humans, even when used at high therapeutic doses.³

Drug-Nutrient Interactions

When used in high therapeutic doses, reishi mushroom extract has the potential to enhance the effects of the following types of medications, and thus requires proper patient monitoring:

1. antihypertensives;^43,44


2. hypoglycemics;⁴⁵ and


3. anticoagulants (e.g. warfarin, coumadin).⁴⁶

Summary

In Asia, herbal agents such as reishi mushroom extract and astragalus have been used to improve various parameters of immune function; treat a variety of immune-compromised states; increase the white blood cell count in patients recovering from drug toxicity, chemotherapy and radiation therapy; and provide effective complementary support for HIV and cancer patients.

Recent experimental studies and intervention trials have helped substantiate the longstanding traditional use of these natural agents and confirm their safety profile and lack of toxicity. As it is known that the human immune system becomes weaker and less efficient as we age, it seems reasonable that natural health practitioners would introduce measures to help their patients reduce or halt the age-related decline in immune system function; this appears to partially explain the rising cancer incidence that occurs as we age and our increased susceptibility to more virulent and life-threatening infections (e.g., pneumonia).

In this regard, antioxidant supplementation has shown a remarkable ability to forestall age-related changes to the immune system and to reverse many aspects of immune function in subjects showing some decreased immune capabilities. In concert with this intervention, the use of herbal compounds containing immune-modulating polysaccharides and other active constituents, such as reishi mushroom extract and astragalus, represent a potent means through which to further augment immune function. This can help patients prevent and treat a significant number of chronic degenerative diseases, and reverse certain aspects of the aging process, especially in regards to immune, cardiovascular and liver function.

References

1. Jong SC, et al. Medicinal benefits of the mushroom ganoderma. Adv Appl Microbiol 1992;37:101-34.
2. Herbs to the rescue. Nutrition News 11/30/92;V.XVI N.11;p.4.
3. Jones K. Reishi (ganoderma): Longevity herb of the Orient; Part 2. Townsend Letter for Doctors & Patients 11/20/92;N.112; p.1008-1012.
4. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Foods, Drugs, and Cosmetics, 2nd ed. New York: John Wiley & Sons, 1996, 255-60.
5. Hobbs C. Medicinal Mushrooms. Santa Cruz, CA., Botanica Press, 1995, 96-107.
6. Ikekawa T, et al. 1968. Antitumor action of some basidiomycetes, especially phellinus linteus. Japan J Can Res 59:155-157.
7. Morishige F. (lecture) 1988. In Becoming Healthy with Reishi, III. Kampo I-Yaku Shimbun, Toyo-Igaku Sha Co., Ltd., Tokyo;12-20. Trans.
8. Tsukagoshi S, et al. 1984. Krestin (PSK). Cancer Treat Rev 11 (2):131-135.
9. Teikoku Chemical Industry Co., Ltd. 1982. Mushroom glycoproteins as neoplasm inhibitors. Japanese Patent No. 82 75,926, May 12, 1982; in Chem Abstr 97:4431:1j.
10. Lingzhi. In Chang, H-M. and p. P-H. But, editors. 1986. Pharmacology and Applications of Chinese Materia Medica. Vol I. Singapore: World Scientific;642-653.
11. Nakashima S, et al. 1979. Effect of polysaccharrides from ganoderma applanatum on immune responses I: enhancing effect on the induction of delayed hypersensitivity in mice. Microbiol Immunol 23(6):501-513.
12. Li Shih-chen. 1933. Pen T-sao Kang Mu. Shang Wu Printer, Shanghai. Trans.
13. Liu B, Y-S Bau. 1980. Fungi pharmacopoeia (sinica). The Kinoko Company, Oakland, California;168-169.
14. Lin JM, et al. Radical scavanger and antihepatotoxic activity of ganoderma formosanum, ganoderma lucidum and ganoderma neo-japonicum. J Ethnopharmacol Jun 1995;47(1):33-41.
15. Wang SY, Hsu ML, Hsu HC, Tzeng CH, Lee SS, Shiao MS, Ho CK. The anti-tumor effect of ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Cancer 1997 Mar 17;70(6):699-705.
16. Lee JM, Kwon H, Jeong H, Lee JW, Lee SY, Baek SJ, Surh YJ. Inhibition of lipid peroxidation and oxidative DNA damage by ganoderma lucidum [in process citation]. Phytother Res 2001 May;15(3):245-9.
17. Wang SY. The anti-tumor effect of ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Cancer May 1997;70(6):699-705.
18. Sone Y, et al. Structures and antitumor activities of the polysaccharides isolated from fruiting body and the growing culture of mycelium of ganoderma lucidum. Agr Biol Bhem 1985;49:2641-53.
19. Tizard IR. 1984. Immunology: An Introduction. Saunders, Philadelphia:pp-94,323.
20. Hayward AR. 1988. Immune Deficiency Disease. In Allergic Diseases from Infancy to Adulthood. Bierman C. Warren and David s. Pearlman, editors. W.B. Saunders, 2nd edition, 1988:pp.34.
21. Tasaka T, et al. 1988. Anti-allergic constituents in the culture medium of ganoderma lucidum (I). Inhibitory effect of oleic acid on histamine release. Agents and Actions 23; (3/4):153-156.
22. Tasaka T, et al. 1988. Anti-allergic constituents in the culture medium of ganoderma lucidum (II). The Inhibitory effect of cyclooctasulphur on histamine release. Agents and Actions 23(3/4):157-160.
23. Lee SY, Eo SK, et al. Antiherpetic activities of various protein-bound polysaccarides isolated from ganoderma lucidum. J Ethnopharmacol Dec 1999;68(1-3):175-81.
24. Hijikata Y, et al. Effect of ganoderma lucidum on postherpetic neuralgia. Am J Chin Med 1998;26(3-4):375-81.
25. el-Mekkawy S, et al. Anti-HIV-1 and Anti-HIV-1-protease substances from ganoderma lucidum. Phytochemistry Nov 1998;49(6):1651-57.
26. Willard T, Jones K. 1990. Reishi Mushroom. Sylvan Press, Issaquah, Washington, 1990.
27. Cohen M. Paths to wholeness in HIV Infection: A Comprehensive approach. In AIDS, Immunity and Chinese Medicine. Proceedings of the Ninth Annual Symposium of the Oriental healing Arts Institute, Oct. 23, 1988, Long Beach, California. BC Enger and ER Long, editors. OHAI, Long Beach, California, 1989;92-102.
28. Personal communication: Dharmananda,PhD, Institute of Traditional medicine, Portland, Oregon, March, 1992.
29. Chen WC, Hau DM, Lee S. Effects of ganoderma lucidum and krestin on cellular immunoceompetnece in gamma-ray-irradiated mice. Am J Chin Med 1995;23(1):71-80
30. Kammatsuse K, Kajiware N, Hayashi K. Studies on ganaderma lucidum: I. Efficacy against hypertension and side-effect. Yakugaku Zasshi 1985;105:531-3.
31. Jin H, Zhang G, Cao X., et al. Treatment of hypertension by ling zhi combined with hyptensor and its effects on arterial, arteriolar and capillary pressure and microcirculation. In: Nimmi H, Xiu RJ, Sawada T, Zheng C. (eds). Microcirculatory Approach to Asian Traditional Medicine. New York: Eslevier Science 1996,131-8
32. Lee SY. Cardiovascular effects of mycelium extract of ganoderma lucidum; inhibition of sympathetic outflow as a mechanism of its hypotensive action. Chem Pharm Bull (Tokyo) May 1990;38(95):1359-64.
33. Su C. Potentiation of ganodermic acid S on prostaglandin E (1)-induced cyclic AMP elevation in human platelets. Thromb Res Jul 2000;99(2):135-45.
34. Jong SC, et al. Medicinal benefits of the mushroom ganodermal. Adv Appl Microbiol. 1992;37:101-34.
35. Sahley BJ. Reishi mushroom, healing herb of the future. MMRC Health Educator Reports 01/31/97;p.1-2.
36. Tamura T, et al. Fermentation product as food for patients with liver failure. In Chem Abstr 108(13):110853m.
37. Hirotani M, et al. 1986. Ganoderic acids T, S and R, new triterpenoids from the cultured mycelia of ganoderma lucidum. Chem Pharm Bull 134 95): 2282-2285.
38. Gong Z, Z-B Lin. 1981. The pharmacological study of lingzhi (ganoderma lucidum) and the research of therapeutical principle of "fuzheng guben" in traditional Chinese medicine. Pei-Ching I Hseuh Yuan Hseuh Paoi 13:6-10. Trans.
39. Lin J.-M, Lin C-C, et al. Radical scavenger and antihepatotoxic activity of ganoderma formosanum, ganoderma lucidum and gonoderma neo-japonicum. J Ethnopharm 47: 33-41, 1995
40. Hobbs, C. Medicinal Mushrooms. Santa Cruz, CA: Botanica Press, 1995, 96-107
41. McGuffin M, et al., ed. Botanical Safety Handbook. Boca Raton: CRC Press: 1997:pp.55.
42. Horner WE, et al. Basidiomycete allergens: Comparison of three ganoderma species. Allergy Feb 1993; 48(2):110-16.
43. Lee SY. Cardiovascular effects of mycelium extract of ganoderma lucidum: Inhibition of sympathetic outflow as a mechanism of its hypotensive action. Chem Pharm Bull (Tokyo) May 1990;38(50):1359-64.
44. Kanmatsuse K, et al. Studies on ganoderma lucidum. In efficacy against hypertension and side-effects. Yakugaku Zasshi Oct 1985;105(10):942-47.
45. Hikino H, et. al. Mechanisms of hypoglycemic activity of ganoderan B: A glycan of ganoderma lucidum fruit bodies. Planta Med Oct 1999;55(5):423-28.
46. Tao J, et al. Experimental and clinical studies on inhibitory effects of ganoderma lucidum on platelet aggregation. J Tongji Med Univ 1990;10(4):240-43.

James Meschino,DC,MS
Toronto, Ontario
Canada
www.renaisante.com

Please take time to listen to Dr. Meschino's interviews at www.chiroweb.com/audio/meschino. The subjects of the first three are: Combining Traditional, Complementary and Natural Interventions, Benefits of Melatonin, and Using Natural Remedies to Manage Women's Health Issues.

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