Reishi Mushroom

• How It Works

  Reishi mushroom has antioxidant properties and may enhance immune response.

  Reishi mushroom contains complex sugars known as beta-glucans. Lab studies suggest that these compounds may help stop the growth and spread of cancer cells. When animals were fed beta-glucans, some cells of their immune system became more active.

  Limited data from clinical studies suggest reishi can strengthen immune response in humans. In addition, reishi mushrooms contain sterols that can act as precursors to hormones in the body, along with substances called triterpenes that may have blood pressure-lowering and anti-allergy effects. Reishi mushrooms have also been shown to slow blood clotting.

  Reishi mushroom can cause toxicity in some immune cells. There are also a few documented cases of liver toxicity. More studies are needed to show that reishi is safe and effective for use with cancer treatment.

• Purported Uses
  • To treat fatigue
    No scientific evidence supports this use.
  • To lower high cholesterol
    In one small study, a reishi mushroom product increased HDL-cholesterol level in patients with borderline elevations of cholesterol.
  • To treat HIV and AIDS
    Laboratory studies suggest that reishi mushroom may stimulate certain cells of the immune system, but evidence is lacking on reishi’s ability fight infections.
  • To lower high blood pressure
    Laboratory studies suggest that reishi mushroom may lower blood pressure. Human studies are lacking.
  • To stimulate the immune system
    Laboratory studies suggest that reishi mushroom may stimulate some cells of the immune system. A small clinical trial showed that reishi can enhance immune response in advanced-stage cancer patients. More studies are needed.
  • To reduce inflammation
    Laboratory studies suggest that reishi mushroom may have antihistamine effects. This has not been tested in humans.
  • For increased strength and stamina
    No scientific evidence supports this use.
  • To treat lower urinary tract symptoms (LUTS)
    One study suggests that reishi extracts may improve urinary flow in men with slight-to-moderate LUTS. Larger, long-term studies are needed to see if it can improve LUTS in men who have more severe symptoms.
• Do Not Take If
  • You are taking warfarin or other blood thinners: Reishi may increase the risk of bleeding.
  • You are undergoing chemotherapy: In theory, reishi may make some chemotherapy drugs less effective.
  • You are taking immunosuppressants: Reishi can stimulate immune responses.
  • You are taking cytochrome P450 2E1, 1A2, and 3A substrate drugs: Lab studies suggest compounds in reishi may affect drug concentrations, although clinical relevance in not clear.
• Side Effects

  Nausea and insomnia have been reported in a few patients.

  Case Reports

  • Liver toxicity: In two cases with the use of powdered reishi mushroom, one of which resulted in death.
  • Chronic diarrhea: In a 49-year-old man with non-Hodgkin’s lymphoma following long-term use of a powdered reishi mushroom extract.
  • Treatment error: A long-term user of reishi mushrooms was mistakenly treated for a parasite that in lab specimens appears similar in structure to reishi mushroom.
• Scientific Name

  Ganoderma lucidum

• Clinical Summary

  Reishi mushroom is a fungus that holds an important place in the traditional medical systems of China, Japan, Korea and other Asian countries for its health-promoting effects. It is used as an immunostimulant by patients with HIV and cancer. The active constituents include both beta-glucan polysaccharides and triterpenes ^(46) (47).

  Extracts of reishi were shown to have immunomodulatory ^{(2) (4) (5)}, renoprotective ⁽⁹⁾, anti-inflammatory ⁽³⁶⁾, and hepatoprotective ⁽³⁷⁾ properties both in vitro and in vivo. Clinical studies indicate its benefits in improving lower urinary tract symptoms (LUTS) in men ^(10) (20), and in exerting mild antidiabetic effects and improving dyslipidemia ⁽²⁹⁾. However, randomized controlled trials do not support the use of reishi to address cardiovascular risk factors associated with type 2 diabetes ^(38) (43). A pilot study of reishi spore powder did not find it helpful in treating patients with Alzheimer’s disease (AD) ⁽¹⁾.

  Reishi has also been studied for its anticancer potential. In vitro and animal studies indicate that it has immunomodulatory ⁽⁴⁵⁾ and chemopreventive effects ^(21) (46), alleviates chemotherapy-induced nausea ⁽¹³⁾, enhances the efficacy of radiotherapy ⁽²²⁾, and increases sensitivity of ovarian cancer cells to cisplatin ⁽²⁷⁾. It may also help prevent cisplatin-induced nephrotoxicity ⁽²⁸⁾.

  In small clinical studies, reishi increased plasma antioxidant capacity ^(6) (7), and enhanced immune responses in cancer patients ^(8) (40). In another study, a water-soluble reishi extract appeared to suppress development of colorectal adenomas ⁽⁴¹⁾. Remission of hepatocellular carcinoma was reported in a few cases in a single study ⁽²³⁾. Another case series suggests a dietary supplement containing Reishi mushroom spores may have a negative effect on gastrointestinal cancer patients ⁽⁴²⁾. Currently, there is no evidence for the use of reishi in first-line cancer treatment or to prolong long-term cancer survival. However, it may have a role in stimulating host immunity and enhancing tumor response ⁽⁴⁴⁾.

  An in vitro study reported that reishi mushroom extract has toxic effects in leukocytes ⁽¹⁴⁾. There are also a few documented cases of hepatotoxicity ^(24) (25). More research is therefore needed to determine its safety and effectiveness as an adjunctive cancer treatment.

• Purported Uses
  • Fatigue
  • High cholesterol
  • HIV and AIDS
  • Hypertension
  • Immunostimulation
  • Inflammation
  • Strength and stamina
  • Viral infections
  • Lower urinary tract symptoms
• Mechanism of Action

  Beta glucans, polysaccharides present in reishi, have demonstrated antitumor and immunostimulating activities ^(18) (40). Its triterpene compounds may inhibit tumor invasion by reducing matrix metalloproteinase expression ⁽¹⁶⁾, and tumor metastases by limiting attachment to endothelial cells ⁽¹⁷⁾. Recent findings indicate that reishi induces natural killer (NK) cell cytotoxicity against various cancer cell lines via activation of the natural cytotoxic receptors (NKG2D/NCR) and mitogen-activated protein kinase (MAPK)-signaling pathways, which result in exocytosis of perforin and granulysin ⁽³¹⁾. Reishi polysaccharides were also shown to increase expression of the major histocompatibility (MHC) class I and costimulatory molecules on melanoma cells, resulting in enhanced antitumor cytotoxicity ⁽³²⁾. In ovarian cancer cells, reishi induced G2/M phase cell cycle arrest, activated caspase 3 to induce apotosis, increased p53, and inhibited Akt expression ⁽²⁷⁾.

• Adverse Reactions

  Nausea and insomnia have been reported ^(43) (44).

  Case reports

  • Hepatoxicity: Two cases with the use of powdered reishi mushroom, leading to death in one instance  ^(24) (25).
  • Pseudoparasitosis/Chronic diarrhea: In a 49-year-old man with non-Hodgkin’s lymphoma following prolonged consumption of powdered reishi mushroom extract ⁽²⁶⁾.
  • Pseudoparasitosis: Due to similarity in structure with Clonorchis sinensis ova, in a patient with a history of long-term ingestion of reishi mushrooms  ⁽³⁹⁾.
• Herb-Drug Interactions
  • Anticoagulants / Antiplatelets: Reishi may increase the risk of bleeding ⁽¹²⁾.
  • Immunosuppressants: Reishi can enhance immune response ⁽⁸⁾.
  • Chemotherapeutic agents: Reishi can increase plasma antioxidant capacity, and in theory may interact with chemotherapeutic agents that rely on free radicals ⁽⁶⁾.
  • Cytochrome P450 substrates: In vitro, reishi polysaccharides inhibited CYP2E1, CYP1A2, and CYP3A, and may affect the intracellular concentration of drugs metabolized by these enzymes ⁽¹⁵⁾. However, clinical relevance is not known.
• Herb Lab Interactions
  • Reishi extracts may prolong INR, PT, and APTT ⁽¹²⁾.
  • Reishi mushroom spore powder may elevate the level of glycoprotein CA72-4. High levels of CA72-4 have been reported in several malignancies including gastrointestinal, ovarian, endometrium, and lung cancers  ⁽³⁵⁾.
• References

  1. Wang GH, Wang LH, Wang C, et al. Spore powder of Ganoderma lucidum for the treatment of Alzheimer disease: A pilot study. Medicine (Baltimore). May 2018;97(19):e0636. doi: 10.1097/md.0000000000010636

  2. Chen HS, Tsai YF, Lin S, et al. Studies on the immuno-modulating and anti-tumor activities of Ganoderma lucidum (Reishi) polysaccharides. Bioorg Med Chem. Nov 1 2004;12(21):5595-5601.

  3. Gao Y, Zhou S, Wen J, et al. Mechanism of the antiulcerogenic effect of Ganoderma lucidum polysaccharides on indomethacin-induced lesions in the rat. Life Sci. Dec 27 2002;72(6):731-745.

  4. Hsu MJ, Lee SS, Lin WW. Polysaccharide purified from Ganoderma lucidum inhibits spontaneous and Fas-mediated apoptosis in human neutrophils through activation of the phosphatidylinositol 3 kinase/Akt signaling pathway. J Leukoc Biol. Jul 2002;72(1):207-216.

  5. Wang SY, Hsu ML, Hsu HC, et al. The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Cancer. Mar 17 1997;70(6):699-705.

  6. Wachtel-Galor S, Szeto YT, Tomlinson B, et al. Ganoderma lucidum (’Lingzhi’); acute and short-term biomarker response to supplementation. Int J Food Sci Nutr. Feb 2004;55(1):75-83.

  7. Wachtel-Galor S, Tomlinson B, Benzie IF. Ganoderma lucidum (“Lingzhi”), a Chinese medicinal mushroom: biomarker responses in a controlled human supplementation study. Br J Nutr. Feb 2004;91(2):263-269.

  8. Gao Y, Zhou S, Jiang W, et al. Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol Invest. Aug 2003;32(3):201-215.

  9. Shieh YH, Liu CF, Huang YK, et al. Evaluation of the hepatic and renal-protective effects of Ganoderma lucidum in mice. Am J Chin Med. 2001;29(3-4):501-7.

  10. Noguchi M, Kakuma T, Tomiyasu K, et al. Randomized clinical trial of an ethanol extract of Ganoderma lucidum in men with lower urinary tract symptoms. Asian J Androl. Sep 2008;10(5):777-785.

  11. Hobbs C. Medicinal Mushrooms. 3rd ed. Loveland (OR): Interweave Press; 1996.

  12. Tao J, Feng KY. Experimental and clinical studies on inhibitory effect of Ganoderma lucidum on platelet aggregation. J Tongji Med Univ. 1990;10(4):240-243.

  13. Wang CZ, Basila D, Aung HH, et al. Effects of Ganoderma lucidum extract on chemotherapy-induced nausea and vomiting in a rat model. Am J Chin Med. 2005;33(5):807-815.

  14. Gill SK, Rieder MJ. Toxicity of a traditional Chinese medicine, Ganoderma lucidum, in children with cancer. Can J Clin Pharmacol. Summer 2008;15(2):e275-285.

  15. Wang X, Zhao X, Li D, et al. Effects of Ganoderma lucidum polysaccharide on CYP2E1, CYP1A2 and CYP3A activities in BCG-immune hepatic injury in rats. Biol Pharm Bull. Sep 2007;30(9):1702-1706.

  16. Chen NH, Liu JW, Zhong JJ. Ganoderic Acid me inhibits tumor invasion through down-regulating matrix metalloproteinases 2/9 gene expression. J Pharmacol Sci. Oct 2008;108(2):212-216.

  17. Li YB, Wang R, Wu HL, et al. Serum amyloid A mediates the inhibitory effect of Ganoderma lucidum polysaccharides on tumor cell adhesion to endothelial cells. Oncol Rep. Sep 2008;20(3):549-556.

  18. Mao T, van De Water J, Keen CL, et al. Two mushrooms, Grifola frondosa and Ganoderma lucidum, can stimulate cytokine gene expression and proliferation in human T lymphocytes. Int J Immunother 1999;15(1):13-22.

  19. Chan WK, Cheung CC, Law HK, et al. Ganoderma lucidum polysaccharides can induce human monocytic leukemia cells into dendritic cells with immuno-stimulatory function. J Hematol Oncol. 2008;1(1):9.

  20. Noguchi M, Kakuma T, Tomiyasu K, et al. Effect of an extract of Ganoderma lucidum in men with lower urinary tract symptoms: a double-blind, placebo-controlled randomized and dose-ranging study. Asian J Androl. 2008 Jul;10(4):651-8.

  21. Weng CJ, Yen GC. The in vitro and in vivo experimental evidences disclose the chemopreventive effects of Ganoderma lucidum on cancer invasion and metastasis. Clin Exp Metastasis. 2010 May;27(5):361-9.

  22. Kim KC, Jun HJ, Kim JS, Kim IG. Enhancement of radiation response with combined Ganoderma lucidum and Duchesnea chrysantha extracts in human leukemia HL-60 cells. Int J Mol Med. 2008 Apr;21(4):489-98.

  23. Gordan JD, Chay WY, Kelley RK, et al. “And what other medications are you taking?”. J Clin Oncol. 2011 Apr 10;29(11):e288-91.

  24. Yuen MF, Ip P, Ng WK, Lai CL. Hepatotoxicity due to a formulation of Ganoderma lucidum (lingzhi). J Hepatol. 2004 Oct;41(4):686-7.

  25. Wanmuang H, Leopairut J, Kositchaiwat C, Wananukul W, Bunyaratvej S. Fatal fulminant hepatitis associated with Ganoderma lucidum (Lingzhi) mushroom powder. J Med Assoc Thai. 2007 Jan;90(1):179-81.

  26. Wanachiwanawin D, Piankijagum A, Chaiprasert A, et al. Ganoderma lucidum: a cause of pseudoparasitosis. Southeast Asian J Trop Med Public Health. 2006 Nov;37(6):1099-102.

  27. Zhao S, Ye G, Fu G, Cheng JX, Yang BB, Peng C. Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin. Int J Oncol. 2011 May;38(5):1319-27.

  28. Pillai TG, John M, Sara Thomas G. Prevention of cisplatin induced nephrotoxicity by terpenes isolated from Ganoderma lucidum occurring in Southern Parts of India. Exp Toxicol Pathol. 2011 Jan;63(1-2):157-60.

  29. Chu TT, Benzie IF, Lam CW, et al. Study of potential cardioprotective effects of Ganoderma lucidum (Lingzhi): results of a controlled human intervention trial. Br J Nutr. 2012 Apr;107(7):1017-27.

  30. Jin X, Ruiz Beguerie J, Sze DM, Chan GC . Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev. 2012 Jun 13;6:CD007731.

  31. Chang CJ, Chen YY, Lu CC, et al. Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin. Innate Immun. 2014 Apr;20(3):301-11.

  32. Sun LX, Lin ZB, Duan XS, et al. Enhanced MHC class I and costimulatory molecules on B16F10 cells by Ganoderma lucidum polysaccharides. J Drug Target.2012 Aug;20(7):582-92.

  33. Boh B, Berovic M, Zhang J, Zhi-Bin L. Ganoderma lucidum and its pharmaceutically active compounds. Biotechnol Annu Rev. 2007;13:265-301.

  34. Paterson RR. Ganoderma – a therapeutic fungal biofactory. Phytochemistry. 2006 Sep;67(18):1985-2001.

  35. Liang Y, He M, Fan X, et al. An abnormal elevation of serum CA72-4 by Ganoderma lucidum spore powder. Ann Clin Lab Sci. 2013 Summer;43(3):337-40.

  36. Joseph S, Sabulal B, George V, Antony KR, Janardhanan KK. Antitumor and anti-inflammatory activities of polysaccharides isolated from Ganoderma lucidum. Acta Pharm. 2011 Sep 1;61(3):335-42.

  37. Jin H, Jin F, Jin JX, et al. Protective effects of Ganoderma lucidum spore on cadmium hepatotoxicity in mice. Food Chem Toxicol. 2013 Feb;52:171-5.

  38. Klupp NL, Chang D, Hawke F, et al. Ganoderma lucidum mushroom for the treatment of cardiovascular risk factors. Cochrane Database Syst Rev. 2015;2:CD007259.

  39. Ko KK, Murthee KG, Koh TH, et al. Reishi (lingzhi) ingestion mistaken for persistent Clonorchis infection. Pathology. Oct 2014;46(6):576-578.

  40. Sun LX, Li WD, Lin ZB, et al. Protection against lung cancer patient plasma-induced lymphocyte suppression by Ganoderma lucidum polysaccharides. Cell Physiol Biochem. 2014;33(2):289-299.

  41. Oka S, Tanaka S, Yoshida S, et al. A water-soluble extract from culture medium of Ganoderma lucidum mycelia suppresses the development of colorectal adenomas. Hiroshima J Med Sci. Mar 2010;59(1):1-6.

  42. Yan B, Meng X, Shi J, et al. Ganoderma lucidum spore induced CA72-4 elevation in gastrointestinal cancer: a five-case report. Integr Cancer Ther. Mar 2014;13(2):161-166.

  43. Klupp NL, Kiat H, Bensoussan A, et al. A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome. Sci Rep. Aug 11 2016;6:29540.

  44. Jin X, Ruiz Beguerie J, Sze DM, et al. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev. Apr 05 2016;4:Cd007731.

  45. Wang C, Shi S, Chen Q, et al. Antitumor and Immunomodulatory Activities of Ganoderma lucidum Polysaccharides in Glioma-Bearing Rats. Integr Cancer Ther. Sep 2018;17(3):674-683.

  46. Wu K, Na K, Chen D, et al. Effects of non-steroidal anti-inflammatory drug-activated gene-1 on Ganoderma lucidum polysaccharides-induced apoptosis of human prostate cancer PC-3 cells. Int J Oncol. Dec 2018;53(6):2356-2368.

  47. Guggenheim AG, Wright KM, Zwickey HL. Immune Modulation From Five Major Mushrooms: Application to Integrative Oncology. Integr Med (Encinitas). Feb 2014;13(1):32-44.