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Shiitake Mushroom

James Meschino DC, MS, ROHP

General Features
Shiitake Mushroom (Lentinus edodes) has been used in traditional Chinese medicine for thousands of years, as is the case with reishi and maitake mushrooms. All of these mushrooms contain specific polysaccharides (e.g., beta glucans) that are known to modulate immune system activity and provide other health-promoting effects. Recently, researchers have begun to test Shiitake Mushroom in clinical trials with humans to help validate its traditional use in Chinese medicine and confirm its biological activity suggested by experimental studies.1 Shiitake mushrooms grow on the trunks and stumps of trees. They are native to many parts of Asia, but are now cultivated throughout the world (including the United States) for medicinal use. The fruiting body is used medicinally.1,2

Principle Active Constituents
The primary active constituent is reported to be a polysaccharide called lentinan, which is contained in Shiitake Mushroom preparations, referred to as Lentinus Edodes Mycelium Extract (LEM). Thus, commercially available LEM is a rich source of polysaccharides and lignans from the shiitake mushroom.2 Lentinan is a beta-glucan polysaccharide isolated from shiitake mushrooms, which has been used as the principle agent in recent  human studies.3

Clinical Application and Mechanism of Action
Experimental evidence has shown that a purified fraction of LEM, rich in shiitake lignans, stimulates the immune system by activating macrophage cells and increasing the proliferation of bone marrow cells, and it inhibits the cytopathic effects of HIV-1 virus in vitro.4,5 LEM has also shown that it increases lymphokine-activated killer (LAK ) cell activity by 42-56.9% in vitro (when combined with interleukin 2), which may be of importance in the complementary support of cancer therapy.6

    1. AIDS (HIV – Infection)

M. Gordon et al, have administered lentinan or placebo to HIV patients using I.V. method, in three small phase I/II placebo-controlled trials. Overall, lentinan treatment produced an increase in the number of CD4 cells ( T-helper cells ) and, in some patients, neutrophil activity. In one of the studies lentinan was used in conjunction with didanosine, which proved to be effective in raising the CD4 count by 142/mm3 on average, over a twelve-month period. In contrast, there was a decrease in the CD4 count in those patients receiving the didanosine alone. There were no significant side effects in the lentinan treatment group in regards to anemia, leukopenia, pancreatitis or neuropathy. Based on these findings, these researchers recommend a larger, longer clinical trial of lentinan in combination with didanosine in HIV patients, free of opportune infection.7

  1. Cancer Treatment Support

Several trials studying cancer patients have investigated the effects of lentinan as a cancer treatment support intervention. Repeated injections of lentinan have been shown to have beneficial effects on the immune systems of cancer patients.8,9,10,11,12 Two trials reported that lentinan injections prolonged life in people with a variety of advanced cancers.13,14 Another trial found that intravenous lentinan increased five-year survival rates in prostate cancer patients compared with those not given lentinan.15 It is not known whether or not oral consumption of Shiitake Mushroom extract would yield the same benefits as the injectable method used in these studies.

  1. Genital Warts

Oral supplementation of lentinan has been shown to significantly reduce the recurrence rate of genital warts (condyloma acuminata). A preliminary trial involving a group of men and women with genital warts found that those who took 12.5 mg of lentinan per day for two months after laser surgery, had a recurrence rate of only 10.5% as compared to 47% in the group that did not receive the lentinan.16

Dosage and Standardized Grade
The most current evidence suggests that Shiitake Mushroom extract or lentinan products should be standardized to 3.2% KS-2 polysaccharides per dose.

Therapeutic applications typically have used 100-400 mg (standardized extract), three times per day, with food.1 Recommended intake of LEM is 1-3 grams, two to three times per day. Purified lentinan is considered a drug in Japan.2

Adverse Side Effects, Toxicity and Contraindications
Shiitake mushrooms have an excellent record of safety, but have been known to induce temporary diarrhea and abdominal bloating when used in high amounts. It is important to take this product with food.2

Drug-Nutrient Interactions

  1. Immunosuppressive Medications (e.g., cyclosporin): As shiitake mushrooms and its extracts (e.g., LEM) are known to stimulate the immune system, they are contraindicated in cases where patients are taking immunosuppressive drugs.4,5
  2. Didanosine: Shiitake Mushroom extract has been shown to enhance the efficacy of didanosine in HIV patients when administered intravenously, and thus should be considered for use in these cases.7
  • Dietary Supplement Information Bureau. Shiitake Mushroom. intramedicine.com. Dietary Supplement Education Alliance 2001
  • Healthnotes Inc. 2001. Shiitake Mushroom. puritan.com/healthnotes
  • Gordon M, Bihari B, Goosby E, Gorter R, Greco M, Guralnik M, et al. A placebo-controlled trial of the immune modulator, lentinan, in hIV-positive patients: a phase I/II trial. J Med 1998;29(5-6):305-30
  • Suzuki H, et al. Immunopotentiating Substances in Lentinus edodes Mycelial Extract(LEM)– Activation of Macrophage and Proliferation of Bone Marrow Cell. Nippon Shokakibyo Gakkai Zasshi. Jul1988;85(7):1430
  • Suzuki H, et al. Inhibition of the Infectivity and Cytopathic Effect of Human Immunodeficiency Virus by Water-soluble Lignin in an Extract of the Culture Medium of Lentinus edodes Mycelia (LEM). Biochem Biophys Res Commun. Apr1989;160(1):367-73
  • Li JF, et al. Study on the Enhancing Effect of Polyporus Polysaccharide, Mycobacterium Polysaccharide and Lentinan on Lymphokine-activated Killer Cell Activity in vitro. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih. Apr1996;16(4):224-26.
  • Gordon M, et al. A Placebo-controlled Trial of the Immune Modulator, Lentinan, In HIV-positive Patients: A Phase I/II Trial. J Med. 1998;29(5-6):305-30
  • Miyakoshi H, Aoki T, Mizukoshi M. Acting mechanism of lentinan in human—II. Enhancement of non-specific cell-mediated cytotoxicity as an interferon inducer. Int J Immunopharmacol 1984;6:373–9.
  • Arinaga S, Karimine N, Takamuku K, et al. Enhanced induction of lymphokine activated killer cell after lentinan administration in patients with gastric carcinoma. Int J Immunopharmacol 1992;14:535–9.
  • Matsuoka H, Yano K, Seo Y, et al. Usefulness of lymphocyte subset change as an indicator for predicting survival time and effectiveness of treatment with the immunopotentiator lentinan. Anticancer Res 1995;15:2291–6.
  • Miyakoshi H, Aoki T, Mizukoshi M. Acting mechanism of lentinan in human—II. Enhancement of non-specific cell-mediated cytotoxicity as an interferon inducer. Int J Immunopharmacol 1984;6:373–9.
  • Arinaga S, Karimine N, Takamuku K, et al. Enhanced induction of lymphokine activated killer cell after lentinan administration in patients with gastric carcinoma. Int J Immunopharmacol 1992;14:535–9.
  • Matsuoka H, Yano K, Seo Y, et al. Usefulness of lymphocyte subset change as an indicator for predicting survival time and effectiveness of treatment with the immunopotentiator lentinan. Anticancer Res 1995;15:2291–6.
  • Matsuoka H, Seo Y, Wakasugi H, et al. Lentinan potentiates immunity and prolongs the survival time of some patients. Anticancer Res 1997;17:2751–6.
  • Tari K, Satake I, Nakagomi K, et al. Effect of lentinan for advanced prostate carcinoma. Hinyokika Kiyo (Acta Urol Japon)
  • Guangwen Y, Jianbin Y, Dongqin L et al. Immunomodulatory and therapeutic effects of lentinan in treating condyloma acuminata. CJIM 1999;5:190-2
Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal vitamin and mineral supplements.  All other supplements or dose alterations may pose a threat to the developing fetus and there is generally insufficient evidence at this time to determine an absolute level of safety for most dietary supplements other than a prenatal supplement.  Any supplementation practices beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium and the treatment of preeclampsia.)References:  Pregnancy and Lactation
1.     Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.2.     Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and Company Inc. 1998.3.     The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.

4.     Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine. Institute of Applied Complementary Medicine Inc. 1997.

 

  1. Dietary Supplement Information Bureau. Shiitake Mushroom. intramedicine.com. Dietary Supplement Education Alliance 2001
  2. Healthnotes Inc. 2001. Shiitake Mushroom. puritan.com/healthnotes
  3. Gordon M, Bihari B, Goosby E, Gorter R, Greco M, Guralnik M, et al. A placebo-controlled trial of the immune modulator, lentinan, in hIV-positive patients: a phase I/II trial. J Med 1998;29(5-6):305-30
  4. Suzuki H, et al. Immunopotentiating Substances in Lentinus edodes Mycelial Extract(LEM)– Activation of Macrophage and Proliferation of Bone Marrow Cell. Nippon Shokakibyo Gakkai Zasshi. Jul1988;85(7):1430
  5. Suzuki H, et al. Inhibition of the Infectivity and Cytopathic Effect of Human Immunodeficiency Virus by Water-soluble Lignin in an Extract of the Culture Medium of Lentinus edodes Mycelia (LEM). Biochem Biophys Res Commun. Apr1989;160(1):367-73
  6. Li JF, et al. Study on the Enhancing Effect of Polyporus Polysaccharide, Mycobacterium Polysaccharide and Lentinan on Lymphokine-activated Killer Cell Activity in vitro. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih. Apr1996;16(4):224-26.
  7. Gordon M, et al. A Placebo-controlled Trial of the Immune Modulator, Lentinan, In HIV-positive Patients: A Phase I/II Trial. J Med. 1998;29(5-6):305-30
  8. Miyakoshi H, Aoki T, Mizukoshi M. Acting mechanism of lentinan in human—II. Enhancement of non-specific cell-mediated cytotoxicity as an interferon inducer. Int J Immunopharmacol 1984;6:373–9.
  9. Arinaga S, Karimine N, Takamuku K, et al. Enhanced induction of lymphokine activated killer cell after lentinan administration in patients with gastric carcinoma. Int J Immunopharmacol 1992;14:535–9.
  10. Matsuoka H, Yano K, Seo Y, et al. Usefulness of lymphocyte subset change as an indicator for predicting survival time and effectiveness of treatment with the immunopotentiator lentinan. Anticancer Res 1995;15:2291–6.
  11. Miyakoshi H, Aoki T, Mizukoshi M. Acting mechanism of lentinan in human—II. Enhancement of non-specific cell-mediated cytotoxicity as an interferon inducer. Int J Immunopharmacol 1984;6:373–9.
  12. Arinaga S, Karimine N, Takamuku K, et al. Enhanced induction of lymphokine activated killer cell after lentinan administration in patients with gastric carcinoma. Int J Immunopharmacol 1992;14:535–9.
  13. Matsuoka H, Yano K, Seo Y, et al. Usefulness of lymphocyte subset change as an indicator for predicting survival time and effectiveness of treatment with the immunopotentiator lentinan. Anticancer Res 1995;15:2291–6.
  14. Matsuoka H, Seo Y, Wakasugi H, et al. Lentinan potentiates immunity and prolongs the survival time of some patients. Anticancer Res 1997;17:2751–6.
  15. Tari K, Satake I, Nakagomi K, et al. Effect of lentinan for advanced prostate carcinoma. Hinyokika Kiyo (Acta Urol Japon)
  16. Guangwen Y, Jianbin Y, Dongqin L et al. Immunomodulatory and therapeutic effects of lentinan in treating condyloma acuminata. CJIM 1999;5:190-2
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