Shiitake Mushroom

• How It Works

  Only a few studies have evaluated shiitake mushroom extract, with mixed results. Lentinan, a polysaccharide extracted from shiitake, may help extend the survival of patients with some cancers when used with chemotherapy, but additional studies are needed.

  Some of the medicinal properties of shiitake mushroom are attributed to a sugar molecule named lentinan, on which extensive research has been done. In laboratory tests, lentinan does not kill cancer cells directly, but enhances a number of aspects of the immune system, which may aid in the slowing of tumor growth. Lentinan also kills viruses and microbes directly in laboratory studies. Most studies involving lentinan involve intravenous or intramuscular injections. It is uncertain whether the ingestion of shiitake mushrooms provides similar effects. One clinical trial has shown shiitake extract alone is not an effective treatment for prostate cancer. More studies are needed.

• Purported Uses
  • To prevent and treat cancer
    A shiitake extract was found to be ineffective for the treatment of prostate cancer. However, an oral formulation of lentinan was shown to be effective in extending survival in patients with stomach, colorectal, pancreatic, and liver cancers. Larger studies are needed to confirm this effect.
  • To lower high cholesterol
    Compounds in shiitake have cholesterol-lowering effects in lab studies, but there is no proof from clinical trials of their ability to also lower cholesterol in people.
  • To stimulate the immune system
    Lentinan stimulates the activity of certain immune cells in lab studies and in people. However, it is unclear if lentinan or shiitake are effective in treating diseases such as AIDS and cancer.
  • To treat infections
    Although lab studies suggest antiviral and antibacterial properties, there is no scientific evidence to support this use in humans.
• Side Effects
  • Skin inflammation
  • Increased skin sensitivity to sunlight
  • Abnormally high level of certain white blood cells
  • Upset stomach
  • Pneumonia caused by hypersensitivity to spores
  • Small bowel obstruction from eating a whole shiitake mushroom
• Special Point
  • Shiitake mushrooms are a common part of the diet in many cultures. It is unknown what dose of lentinan is absorbed through the gastrointestinal tract when shiitake mushrooms are consumed.
• Scientific Name

  Lentinula edodes

• Clinical Summary

  Shiitake mushroom, native to East Asia, is cultivated worldwide for its purported health benefits. The fresh and dried forms of the mushroom are commonly used in East Asian cooking. It is also valued as an anticancer agent.

  Lentinan (1,3 beta-D-glucan), a polysaccharide isolated from shiitake is thought to be responsible for the mushroom’s beneficial effects. Although it has been shown to have anticancer effects ^{(1) (34) (35) (36)}, lentinan is considered a biological response modifier, rather than having a direct cytotoxic effect on tumor cells ⁽³⁷⁾. Studies conducted with shiitake extracts in vitro and in animal models reveal immunostimulatory ⁽⁴⁾, antiviral ⁽³¹⁾, hepatoprotective ^(5) (38), antihypercholemic ⁽³⁹⁾, antiproliferative ⁽⁴⁾, cytotoxic ⁽²¹⁾, antimutagenic ⁽⁶⁾, and anticaries ⁽⁷⁾ properties. Latcripin-13 domain isolated from shiitake was shown to exhibit antitumor activity in lung cancer cells ⁽⁴⁰⁾.

  In a randomized dietary intervention in young adults, eating shiitake mushrooms for 4 weeks altered immune function ⁽⁴¹⁾. An orally administered shiitake mycelial extract decreased the incidence of chemotherapy-associated adverse effects in a small study of patients with advanced gastrointestinal cancer ⁽²²⁾, and in combination with immunotherapy, improved QOL in cancer patients ⁽⁴⁸⁾. But a polysaccharide/oligosaccharide complex from shiitake extract failed to show effectiveness in the treatment of prostate cancer ⁽⁸⁾. More well-designed studies are needed to establish shiitake as a useful adjunct to cancer treatment.

• Food Sources

  Fresh or dried whole mushroom

• Purported Uses
  • Cancer prevention
  • Cancer treatment
  • High cholesterol
  • Immunostimulation
  • Infections
• Mechanism of Action

  Shiitake mushroom supplementation enhanced gut immunity by upregulating interleukin (IL)-23 secretion in a murine model of acute dextran sodium sulfate-colitis ⁽²⁹⁾. Shiitake extracts and the polysaccharide lentinan exerted antiviral effects, by acting on initial replication processes of poliovirus type 1 (PV-1) and bovine herpes virus type 1 (BoHV-1) ⁽³¹⁾. Another polysaccharide isolated from shiitake exhibited antibacterial effects in mice by increasing T-helper (Th1) cell immunity, resulting in activation of macrophage-mediated immune response ⁽³²⁾. The isolated protein lentin exhibited antifungal properties, inhibited proliferation of leukemic cells, and suppressed activity of human immunodeficiency virus-1 (HIV-1) reverse transcriptase ⁽³⁾. Shiitake consumption in adults altered immune function via increased proliferation of gamma delta-T and NK-T cells, increased secretory immunoglobulin A in saliva, increased IL-1alpha, IL-4, IL-10, and tumor necrosis factor (TNF)-α levels, and decreased macrophage inflammatory protein-1alpha/chemokine C-C ligand 3 (MIP-1alpha/CCL3) levels ⁽⁴¹⁾. A low-molecular-weight lignin from shiitake inhibits hepatitis C virus by binding to viral apolipoprotein E (apoE) before interacting with cell surface heparan sulfate ⁽³⁸⁾.

  Eritadenine from shiitake may exert antihypercholemic effects and regulate lipid metabolism by inhibiting S-adenosyl homocysteine hydrolase activity, and both eritadenine and shiitake mushroom supplementation upregulated CYP7A1 mRNA expression which was decreased in hypercholesterolemic mice ⁽³⁹⁾. High doses of shiitake mushroom prevented obesity in rats by increasing plasma triacylglycerol accumulation in the liver ⁽³⁰⁾.

  Dried shiitake extract caused apoptosis in human hepatocellular carcinoma (HepG2) cells by mediating caspase-3 and -8 pathways  ⁽²¹⁾. Inhibition of lung cancer cells by the Latcripin-13 domain isolated from shiitake was shown to be due to apoptotic induction ⁽⁴⁰⁾. Anticancer effects of the polysaccharide lentinan (1,3 beta-D-glucan) may be due to its ability to suppress cytochrome P450 1A enzymes that are known to metabolize procarcinogens to active forms ⁽²⁾. Polysaccharides SLNT1 and JLNT1 isolated from the mushroom also demonstrated antitumor effects by increasing serum IL-2 levels and TNF-α production, and by inducing apoptosis in tumor cells in mice ⁽³³⁾.

• Adverse Reactions

  Case Reports

  Hypersensitivity pneumonitis: In a lung cancer patient following exposure to shiitake spores ⁽¹⁰⁾, and in a 37-year-old man following inhalation of shiitake mushroom spores ⁽²³⁾.

  Dermatitis, photosensitivity, eosinophilia, and gastrointestinal upset: Following prolonged consumption of shiitake powder ^(11) (12).

  Shiitake dermatitis, flagellate erythema: Patterns of whiplike, linear, erythematous wheals after consumption of raw or even cooked shiitake mushrooms which has been associated with toxic reactions to the constituent lentinan ^{(24) (25) (26) (27) (42) (43) (44) (45) (46) (47) (49)}.

  Intermittent dermatitis over a 16-year period: Linked to consumption of shiitake mushrooms in a 45-year-old male ⁽¹⁹⁾.

  Esophageal symptoms: Linked to a food allergy in a 37-year-old man following consumption of shiitake mushroom ⁽²⁰⁾.

  Small bowel obstruction: Caused by ingestion of a whole shiitake mushroom, resulting in necrosis and mucosal damage in the small intestine ⁽²⁸⁾.

• Herb Lab Interactions

  Chronic consumption of shiitake may increase eosinophil count ⁽¹²⁾.

• References

  1. Ng ML, Yap AT. Inhibition of human colon carcinoma development by lentinan from shiitake mushrooms (Lentinus edodes). J Altern Complement Med 2002;8(5):581-589.

  2. Okamoto T, Kodoi R, Nonaka Y, et al. Lentinan from shiitake mushroom (Lentinus edodes) suppresses expression of cytochrome P450 1A subfamily in the mouse liver. Biofactors. 2004;21(1-4):407-409.

  3. Ngai PH, Ng TB. Lentin, a novel and potent antifungal protein from shitake mushroom with inhibitory effects on activity of human immunodeficiency virus-1 reverse transcriptase and proliferation of leukemia cells. Life Sci. Nov 14 2003;73(26):3363-3374.

  4. Israilides C, Kletsas D, Arapoglou D, et al. In vitro cytostatic and immunomodulatory properties of the medicinal mushroom Lentinula edodes. Phytomedicine 2008.

  5. Akamatsu S, Watanabe A, Tamesada M, et al. Hepatoprotective effect of extracts from Lentinus edodes mycelia on dimethylnitrosamine-induced liver injury. Biol Pharm Bull. 2004;27(12):1957-1960.

  6. de Lima PL, Delmanto RD, Sugui MM, et al. Letinula edodes (Berk.) Pegler (Shiitake) modulates genotoxic and mutagenic effects induced by alkylating agents in vivo. Mutat Res. 2001;496(1-2):23-32.

  7. Shouji N, Takada K, Fukushima K, Hirasawa M. Anticaries effect of a component from shiitake (an edible mushroom). Caries Res 2000;34(1):94-98.

  8. deVere White RW, Hackman RM, Soares SE, Beckett LA, Sun B. Effects of a mushroom mycelium extract on the treatment of prostate cancer. Urology 2002;60(4):640-644.

  9. Gordon M, Bihari B, Goosby E, 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):305-330.

  10. Suzuki K, Tanaka H, Sugawara H, et al. Chronic hypersensitivity pneumonitis induced by Shiitake mushroom spores associated with lung cancer. Intern Med 2001;40(11):1132-1135.

  11. Hanada K, Hashimoto I. Flagellate mushroom (Shiitake) dermatitis and photosensitivity. Dermatology. 1998;197(3):255-257.

  12. Levy AM, Kita H, Phillips SF, et al. Eosinophilia and gastrointestinal symptoms after ingestion of shiitake mushrooms. J Allergy Clin Immunol 1998;101(5):613-620.

  13. Hobbs C. Medicinal Mushrooms, 3^rd ed. Loveland (CO): Interweave Press; 1996.

  14. Sia GM, Candish JK. Effects of shiitake (Lentinus edodes) extract on human neutrophils and the U937 monocytic cell line. Phytother Res 1999;13(2):133-7.

  15. Isoda N, Eguchi Y, Nukaya H, et al. Clinical efficacy of superfine dispersed lentinan (beta-1,3-glucan) in patients with hepatocellular carcinoma. Hepatogastroenterology. 2009 Mar-Apr;56(90):437-41.

  16. Oba K, Kobayashi M, Matsui T, Kodera Y, Sakamoto J. Individual patient based meta-analysis of lentinan for unresectable/recurrent gastric cancer. Anticancer Res. 2009 Jul;29(7):2739-45.

  17. Hazama S, Watanabe S, Ohashi M, et al. Efficacy of orally administered superfine dispersed lentinan (beta-1,3-glucan) for the treatment of advanced colorectal cancer. Anticancer Res. 2009 Jul;29(7):2611-7.

  18. Shimizu K, Watanabe S, Watanabe S, et al. Efficacy of oral administered superfine dispersed lentinan for advanced pancreatic cancer. Hepatogastroenterology. 2009 Jan-Feb;56(89):240-4.

  19. Garg S, Cockayne SE. Shiitake dermatitis diagnosed after 16 years! Arch Dermatol. 2008 Sep;144(9):1241-2.

  20. Goikoetxea MJ, Fernández-Benítez M, Sanz ML. Food allergy to Shiitake (Lentinus edodes) manifested as oesophageal symptoms in a patient with probable eosinophilic oesophagitis. Allergol Immunopathol (Madr). 2009 Nov-Dec;37(6):333-4.

  21. Yukawa H, Ishikawa S, Kawanishi T, Tamesada M, Tomi H. Direct cytotoxicity of Lentinula edodes mycelia extract on human hepatocellular carcinoma cell line. Biol Pharm Bull. 2012;35(7):1014-21.

  22. Okuno K, Uno K. Efficacy of orally administered Lentinula edodes mycelia extract for advanced gastrointestinal cancer patients undergoing cancer chemotherapy: a pilot study. Asian Pac J Cancer Prev. 2011;12(7):1671-4.

  23. Ampere A, Delhaes L, Soots J, Bart F, Wallaert B. Hypersensitivity pneumonitis induced by Shiitake mushroom spores. Med Mycol. 2012 Aug;50(6):654-7.

  24. Chu EY, Anand D, Dawn A, Elenitsas R, Adler DJ. Shiitake dermatitis: a report of 3 cases and review of the literature. Cutis. 2013 Jun;91(6):287-90.

  25. Adriano AR, Acosta ML, Azulay DR, et al. Shiitake dermatitis: the first case reported in Brazil. An Bras Dermatol. 2013 May-Jun;88(3):417-9.

  26. Hamer S, Rabindranathnambi R. A wide-spread flagellate dermatitis. BMJ Case Rep. 2013 Jan 3;2013.

  27. Wang AS, Barr KL, Jagdeo J. Shiitake mushroom-induced flagellate erythema: A striking case and review of the literature. Dermatol Online J. 2013 Apr 15;19(4):5.

  28. Kusumoto M, Koganemaru M, Nakayama G, Iwamoto R. Dietary small bowel obstruction. BMJ Case Rep. 2013 Jan 25;2013.

  29. Chandra LC, Traoré D, French C, et al. White button, portabella, and shiitake mushroom supplementation up-regulates interleukin-23 secretion in acute dextran sodium sulfate colitis C57BL/6 mice and murine macrophage J.744.1 cell line. Nutr Res. 2013 May;33(5):388-96.

  30. Handayani D, Meyer BJ, Chen J, et al. A high-dose shiitake mushroom increases hepatic accumulation of triacylglycerol in rats fed a high-fat diet: underlying mechanism. Nutrients. 2014 Feb 12;6(2):650-62.

  31. Rincão VP, Yamamoto KA, Ricardo NM, et al. Polysaccharide and extracts from Lentinula edodes: structural features and antiviral activity. Virol J. 2012 Feb 15;9:37.

  32. Kim SP, Park SO, Lee SJ, Nam SH, Friedman M. A Polysaccharide isolated from the liquid culture of Lentinus edodes (shiitake) mushroom mycelia containing black rice bran protects mice against salmonellosis through upregulation of the Th1 immune reaction. J Agric Food Chem. 2014 Mar 19;62(11):2384-91.

  33. Wang KP, Zhang QL, Liu Y, Wang J, Cheng Y, Zhang Y. Structure and inducing tumor cell apoptosis activity of polysaccharides isolated from Lentinus edodes. J Agric Food Chem. 2013 Oct 16;61(41):9849-58.

  34. Isoda N, Eguchi Y, Nukaya H, et al. Clinical efficacy of superfine dispersed lentinan (beta-1,3-glucan) in patients with hepatocellular carcinoma. Hepatogastroenterology. Mar-Apr 2009;56(90):437-441.

  35. Oba K, Kobayashi M, Matsui T, et al. Individual patient based meta-analysis of lentinan for unresectable/recurrent gastric cancer. Anticancer Res. Jul 2009;29(7):2739-2745.

  36. Shimizu K, Watanabe S, Watanabe S, et al. Efficacy of oral administered superfine dispersed lentinan for advanced pancreatic cancer. Hepatogastroenterology. Jan-Feb 2009;56(89):240-244.

  37. Sunagawa M, Isogai M, Harada T, et al. Giant Krukenberg tumor from a perforated gastric cancer that was successfully removed after multidisciplinary therapy: report of a case. Surg Today. Jan 2014;44(1):171-174.

  38. Matsuhisa K, Yamane S, Okamoto T, et al. Anti-HCV effect of Lentinula edodes mycelia solid culture extracts and low-molecular-weight lignin. Biochem Biophys Res Commun. Jun 19 2015;462(1):52-57.

  39. Yang H, Hwang I, Kim S, et al. Lentinus edodes promotes fat removal in hypercholesterolemic mice. Exp Ther Med. Dec 2013;6(6):1409-1413.

  40. Wang J, Zhong M, Liu B, et al. Expression and functional analysis of novel molecule – Latcripin-13 domain from Lentinula edodes C91-3 produced in prokaryotic expression system. Gene. Jan 25 2015;555(2):469-475.

  41. Dai X, Stanilka JM, Rowe CA, et al. Consuming Lentinula edodes (Shiitake) Mushrooms Daily Improves Human Immunity: A Randomized Dietary Intervention in Healthy Young Adults. J Am Coll Nutr. Apr 11 2015:1-10.

  42. Mendonca CN, Silva PM, Avelleira JC, et al. Shiitake dermatitis. An Bras Dermatol. Mar-Apr 2015;90(2):276-278.

  43. Boels D, Landreau A, Bruneau C, et al. Shiitake dermatitis recorded by French Poison Control Centers – new case series with clinical observations. Clin Toxicol (Phila). Jul 2014;52(6):625-628.

  44. Corazza M, Zauli S, Ricci M, et al. Shiitake dermatitis: toxic or allergic reaction? J Eur Acad Dermatol Venereol. Jul 2015;29(7):1449-1451.

  45. Hiernickel C, Metz S, Elsner P. Shiitake dermatitis: an impressive case report. J Dtsch Dermatol Ges. May 2015;13(5):455-456.

  46. Hamer SE, Kulkarni K, Cohen SN. Shiitake dermatitis with oral ulceration and pustules. Clin Exp Dermatol. Apr 2015;40(3):332-333.

  47. Ade R, Sukut C, Wiser HJ, et al. Shiitake dermatitis demonstrating Koebner phenomenon. Int J Dermatol. May 2015;54(5):e179-181.

  48. Tanigawa K, Itoh Y, Kobayashi Y. Improvement of QOL and Immunological Function With Lentinula Edodes Mycelia in Patients Undergoing Cancer Immunotherapy: An Open Pilot Study. Altern Ther Health Med. 2016 Jul;22(4):36-42.

  49. Luber AJ, Ackerman LS. Flagellate shiitake mushroom dermatitis. Dermatol Online J. 2015 Aug 15;21(8). pii: 13030/qt7rm57553.