- Maitake is an edible mushroom used for medicinal purposes.
- Various preparations and extracts are available and beta-glucans are the suggested key components.
- There is no evidence for direct anticancer effects but for effects on the host’s immune system.
- Maitake is well tolerated when used in medicinal doses but allergic reactions can occur.
Maitake is a mushroom indigenous to many Asian countries. Commercial preparations are available as preserved whole fruiting bodies, pulverized fruiting bodies and extracts from the mycelium. Like other species from this phylum, maitake contains polysaccharides (alpha-/beta-homo- and heteroglycans), proteins, nucleic and amino acids, minerals and trace elements, ergosterin, several vitamins and provitamins, phenols and flavonoids. The suggested key components are beta-glucans which are found in the cell walls of the fruiting bodies and mycelia.
There is limited evidence that extracts from maitake can increase the functional capacity of monocytes, T- and NK-cells in human cancer patients. There is no evidence from clinical trials that maitake extracts have direct anticancer effects.Maitake and its extracts are usually well tolerated; allergic reactions might, however, occur.
Assessed as up to date in January 2019 by Barbara Wider.
Assessed as up to date in February 2017 by Barbara Wider.
Summary first published in November 2011, authored by Markus Horneber.
Summary revised and updated in May 2015 by Markus Horneber.
Markus Horneber, CAM-Cancer Consortium. Maitake (Grifola frondosa) [online document]. February 8, 2017.
Grifola frondosa (Dicks.) Gray1.
The scientific name Grifola frondosa is derived from the griffin, the beast from Greek mythology with the head and wings of an eagle and the body of a lion, and frondosa, meaning leaflike.
History and providers
Maitake is growing wild in north eastern Japan and in temperate forests of Asia, Europe, and eastern North America. This mushroom has been consumed in Asia for hundreds of years and has an exceptional position in traditional Japanese herbology. Because of its valuable nutrients, maitake has also been cultivated in laboratories within the past two decades for use as a dietary supplement. Commercial maitake production worldwide may now be in excess of several ten-thousands tons with Japan being the main producer and consumer2,3. Commercial preparations are available as cultivated whole fruiting bodies, pulverized fruiting bodies or spora, extracts from mycelium cultures or fractions from certain compounds4.
As other species from this phylum, extracts from maitake contain polysaccharides (alpha-/beta-homo- and heteroglycans), proteins, nucleic and amino acids, minerals, organic selenium and other trace elements, ergosterin, vitamin C, E, B1, and B2, phenols and flavonoids5-9.
In the 1980s, Japanese pharmacists derived a polysaccharide compound from the fruit bodies, called D-fraction, with a molecular weight of about 106 Daltons which was patented in 1984 (cited in 2). Further purification of this fraction yielded the so-called MD-fraction, and was patented in the USA (cited in 2). Both fractions contain proteoglucans having beta-glucans as major and proteins as minor components.
The beta-glucans in maitake include 1,6 main chains with 1,3 or 1,6 side branches as well as 1,3 main chain with 1,6 side branching10-12. Recently heteropolysaccharides, called Z-fraction13 and GFPS1b14 were isolated from maitake mycelia, which in addition to glucose contain other sugars like arabinose, fucose, galactose and mannose connected with alpha- and beta-linkages. The majority of proteins found in maitake have a molecular weight range of 12–17 kDa, which is the typical range of proteins that regulate distinct membrane traffic pathways (FIPs).
In a phase I/II study with breast cancer patients, maitake liquid extract has been given orally at 0.1- 5 mg/kg twice daily11. Capsules or tablets available in stores or via the internet usually contain 200-400mg of extracts from mycelium cultures or 400-500mg pulverized fruiting bodies or spora. The manufacturers recommend doses of 1-2 capsules/tablets twice daily.
Claims of efficacy/alleged indications
Extracts from maitake are claimed to have various beneficial health effects, ranging from cancer treatment and prevention to activities against hepatitis B and human immunodeficiency virus infec¬tions. Other claimed benefits relate to the treatment of hyperlipidaemia, hypertension, diabetes, and obesity15,16.
Chen et al found evidence that maitake extracts induce ovulation in patients with polycystic ovary syndrome17.
In traditional Chinese medicine maitake is used to improve ailments of the upper gastrointestinal tract, calming nerves and treating haemorrhoids18,19.
Mechanisms of action
One of the hypothesized mode of action of extracts from maitake is an indirect one via activation of the host’s immunological defence mechanisms. The suggested key components for the immunological effects are the beta-glucans which are found in the cell walls of the fruiting bo-dies and mycelia of maitake20. Beta-glucans are naturally occurring polysaccharides, often linked to proteins and widely found in fungi, plants and several bacteria. Beta-glucans belong to a group of unique microbial structures, the pathogen associated molecular patterns (PAMPs) which can trigger immune responses via so-called pattern-recognition receptors, like Toll-like and C-type lectin receptors (CLR). Dectin-1, a member of CLR, is thought to be the main beta-glucan receptor and is expressed in humans on macrophages, most subsets of dendritic cells, subpopulations of T cells, B cells, mast cells, and eosinophils21-24.
There is evidence from in vitro and animal studies that maitake extracts are capable of
- inducing the proliferation and differentiation of human umbilical cord blood progenitor cells25 and cytokine release from various immune cells among them murine splenocytes and macrophages12,26,27,
- increasing phagocytosis of human polymorphonuclear neutrophils8,
- stimulating the production and secretion of G-CSF of human cord blood monocytes25,
- enhancing the recovery of mouse28, and human25 bone marrow cells from chemotherapy toxicity, and
- inhibiting metastasis29,
- inducing systemic antitumor immune response and to decreases immunosuppression30,31,
- increasing cytotoxic effects of e.g. Carmustine (BCNU) through enhanced inhibition of the glutathione-dependent detoxifying enzyme, glyoxalase I32
Prevalence of use
Prevalence data specifically for maitake are not available. One survey with cancer patients from Israel mentioned the use of “Chinese mushrooms” in a sample of 368 complementary medicine users to be around 4%33 and a nationwide survey in Japan reported that about 40% of cancer patients used indigenous Asian mushrooms or herbs34.
Several US companies have received the IND (investigational new drug) approval from the FDA for maitake fraction for Phase I/II clinical studies in cancer patients35.
Costs and expenditures
If capsules or tablets with extracts from mycelium cultures or pulverized fruiting bodies are used at doses recommended by the manufacturers, costs per day are about € 1 to 2.
If the polysaccharide fraction is applied at 1mg/kg as used in the phase I/II study, costs per day for a 70kg patient are about € 3 to 4.
Phase I/II clinical trial
A phase I/II dose escalation trial found dose-dependent effects of a liquid maitake extract on immu¬nologic parameters of disease-free breast cancer patients: increased cytokine production from monocytes and T-cells, and higher numbers of activated NK- and T-cells. The dose associated with the largest immunological effect varied for the different immunological parameters. The authors concluded that “cancer patients should be made aware of the fact that botanical agents produce more complex effects than assumed, and may depress as well as enhance immune function”11.
Another phase II trial investigated the effects of an oral maitake extract at 3 mg/kg twice daily for 12 weeks on immune functions in a small group (n=21) of patients with myelodysplastic syndromes (MDS). Maitake extract increased the capacity of neutrophils and monocytes to produce reactive oxygen species with or without stimulation by E. coli, phorbol ester, and N-formylmethionyl-leucyl-phenylalanine (measured by flow cytometry). The authors concluded that „Maitake has beneficial immunomodulatory potential in MDS“36.
Three case series published by the same group reported “immune-enhancing properties of maitake MD-fraction” and a “potential to decrease the size of lung, liver, and breast tumours”37-39. A critical comment on one of these case series, however, sounds a note of caution regarding the validity of the published results40.
Overall maitake mushroom can be regarded as safe, when consumed in food amounts. Dried maitake mushroom powder has been used safely in doses up to 2.25 grams daily for up to 28 weeks17. With enriched extracts being available, modern ‘users’ of maitake extracts could ingest much larger amounts of probably active ingredients which raises the likelihood of unexpected adverse effects from a traditionally “safe” mushroom. There is little reliable information to advise on the use during pregnancy and lactation.
Allergic reactions are possible. There is a report of hypersensitivity pneumonitis due to inhalation of maitake spore41. No dose-limiting toxicity was encountered in a recent dose escalation trial. Two patients in this trials experienced mild nausea, joint swelling, rash and pruritus which were possibly related to maitake extracts11. In a recent clinical trial, oral maitake extracts caused blood eosinophilia in several patients36. Konno et al. described mild hypoglycaemic effect of maitake extracts in diabetic patients42.
Known allergy to maitake mushrooms.
Maitake mushroom might lower blood glucose levels and might have additive effects when used with other herbs and supplements that also lower glucose levels. This might increase the risk of hypoglycaemia in some patients15.
There are reports of microbial contamination of dried mushroom43.
There is considerable variation in the content of polysaccharides in mushrooms depending on the production process and storage process44,45.
- CABI Bioscience Databases. CABI Bioscience Databases: Index Fungorum. 2011.
- Mayell M. Maitake extracts and their therapeutic potential. Altern Med Rev 2001; 6(1):48-60.
- Royse DJ. Specialty mushrooms; in: Janick J, (ed): Progress in new crops. Arlington,VA, ASHS Press, 1996, pp 464-475.
- Lindequist U, Rausch R, Fussel A, Hanssen HP. [Higher fungi in traditional and modern medicine]. Med Monatsschr Pharm 2010; 33(2):40-48.
- Wang C, Hou Y. Determination of Trace Elements in Three Mushroom Samples of Basidiomycetes from Shandong, China. Biol Trace Elem Res 2010; 142(3):843-847.
- Yeh JY, Hsieh LH, Wu KT, Tsai CF. Antioxidant properties and antioxidant compounds of various extracts from the edible basidiomycete grifola frondosa (maitake). Molecules 2011; 16(4):3197-3211.
- Naing A, Stephen SK, Frenkel M, Chandhasin C, Hong DS, Lei X, Falchook G, Wheler JJ, Fu S, Kurzrock R. Prevalence of complementary medicine use in a phase 1 clinical trials program: The MD Anderson Cancer Center Experience. Cancer 2011.
- Wu MJ, Cheng TL, Cheng SY, Lian TW, Wang L, Chiou SY. Immunomodulatory properties of Grifola frondosa in submerged culture. J Agric Food Chem 2006; 54(8):2906-2914.
- Jeurink PV, Noguera CL, Savelkoul HF, Wichers HJ. Immunomodulatory capacity of fungal proteins on the cytokine production of human peripheral blood mononuclear cells. Int Immunopharmacol 2008; 8(8):1124-1133.
- Tada R, Adachi Y, Ishibashi KI, Ohno N. An unambiguous structural elucidation of a 1,3-beta-d-glucan obtained from liquid-cultured Grifola frondosa by solution NMR experiments. Carbo-hydr Res 2008; 344(3):400-404.
- Deng G, Lin H, Seidman A, Fornier M, D'Andrea G, Wesa K, Yeung S, Cunningham-Rundles S, Vickers AJ, Cassileth B. A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects. J Cancer Res Clin On-col 2009; 135(9):1215-1221.
- Wang Y, Fang J, Ni X, Li J, Liu Q, Dong Q, Duan J, Ding K. Inducement of cytokine release by GFPBW2, a novel polysaccharide from fruit bodies of Grifola frondosa , through dectin-1 in macrophages. J Agric Food Chem 2013; 61(47):11400-11409.
- Masuda Y, Matsumoto A, Toida T, Oikawa T, Ito K, Nanba H. Characterization and antitumor effect of a novel polysaccharide from Grifola frondosa. J Agric Food Chem 2009; 57(21):10143-10149.
- Cui FJ, Tao WY, Xu ZH, Guo WJ, Xu HY, Ao ZH, Jin J, Wei YQ. Structural analysis of anti-tumor heteropolysaccharide GFPS1b from the cultured mycelia of Grifola frondosa GF9801. Bioresour Technol 2007; 98(2):395-401.
- Ulbricht C, Weissner W, Basch E, Giese N, Hammerness P, Rusie-Seamon E, Varghese M, Woods J. Maitake mushroom (Grifola frondosa): systematic review by the natural standard research collaboration. J Soc Integr Oncol 2009; 7(2):66-72.
- Preuss HG, Echard B, Bagchi D, Perricone NV, Zhuang C. Enhanced insulin-hypoglycemic activity in rats consuming a specific glycoprotein extracted from maitake mushroom. Mol Cell Bio-chem 2007; 306(1-2):105-113.
- Chen JT, Tominaga K, Sato Y, Anzai H, Matsuoka R. Maitake mushroom (Grifola frondosa) extract induces ovulation in patients with polycystic ovary syndrome: a possible monotherapy and a combination therapy after failure with first-line clomiphene citrate. J Altern Complement Med 2010; 16(12):1295-1299.
- Hobbs C. Medicinal Mushrooms - An exploration of Tradition, Healing & Culture. Summertown, Botanica Press, 2003.
- Chang ST, Miles PG. Mushrooms: Cultivation, Nutritional Value, Medicinal Effect, and Environ-mental Impact. ed 2, Boca Raton, CRC Press, 2004.
- Borchers AT, Stern JS, Hackman RM, Keen CL, Gershwin ME. Mushrooms, tumors, and immunity. Proc Soc Exp Biol Med 1999; 221(4):281-293.
- Harada T, Ohno N. Contribution of dectin-1 and granulocyte macrophage-colony stimulating factor (GM-CSF) to immunomodulating actions of beta-glucan. Int Immunopharmacol 2008; 8(4):556-566.
- Tsoni SV, Brown GD. beta-Glucans and dectin-1. Ann N Y Acad Sci 2008; 1143:45-60.
- Barreto-Bergter E, Figueiredo RT. Fungal glycans and the innate immune recognition. Front Cell Infect Microbiol 2014; 4:145.
- Goodridge HS, Wolf AJ, Underhill DM. Beta-glucan recognition by the innate immune system. Immunol Rev 2009; 230(1):38-50.
- Lin H, Cheung SW, Nesin M, Cassileth BR, Cunningham-Rundles S. Enhancement of umbilical cord blood cell hematopoiesis by maitake beta-glucan is mediated by granulocyte colony-stimulating factor production. Clin Vaccine Immunol 2007; 14(1):21-27.
- Kodama N, Mizuno S, Nanba H, Saito N. Potential antitumor activity of a low-molecular-weight protein fraction from Grifola frondosa through enhancement of cytokine production. J Med Food 2010; 13(1):20-30.
- Vetvicka V, Vetvickova J. Immune-enhancing effects of Maitake (Grifola frondosa) and Shiitake (Lentinula edodes) extracts. Ann Transl Med 2014; 2(2):14.
- Lin H, She YH, Cassileth BR, Sirotnak F, Cunningham RS. Maitake beta-glucan MD-fraction en-hances bone marrow colony formation and reduces doxorubicin toxicity in vitro. Int Im-munopharmacol 2004; 4(1):91-99.
- Masuda Y, Murata Y, Hayashi M, Nanba H. Inhibitory effect of MD-Fraction on tumor metastasis: involvement of NK cell activation and suppression of intercellular adhesion molecule (ICAM)-1 expression in lung vascular endothelial cells. Biol Pharm Bull 2008; 31(6):1104-1108.
- Masuda Y, Inoue H, Ohta H, Miyake A, Konishi M, Nanba H. Oral administration of soluble beta-glucans extracted from Grifola frondosa induces systemic antitumor immune response and decreases immunosuppression in tumor-bearing mice. Int J Cancer 2012.
- Louie B, Rajamahanty S, Won J, Choudhury M, Konno S. Synergistic potentiation of interferon activity with maitake mushroom d-fraction on bladder cancer cells. BJU Int 2010; 105(7):1011-1015.
- Finkelstein MP, Aynehchi S, Samadi AA, Drinis S, Choudhury MS, Tazaki H, Konno S. Chemosensitization of carmustine with maitake beta-glucan on androgen-independent prostatic cancer cells: involvement of glyoxalase I. J Altern Complement Med 2002; 8(5):573-580.
- Geva H, Bar-Sela G, Zhana D, Mashiach T, Robinson E. The use of complementary and alternative therapies by cancer patients in northern Israel. Isr Med Assoc J 2005; 7(4):243-247.
- Hyodo I, Amano N, Eguchi K, Narabayashi M, Imanishi J, Hirai M, Nakano T, Takashima S. Na-tionwide Survey on Complementary and Alternative Medicine in Cancer Patients in Japan. J Clin Oncol 2005; 23(12):2645-1654.
- Study of Grifola Frondosa (Maitake), Azacitidine, and Lenalidomide Available online. 2013.
- Wesa KM, Cunningham-Rundles S, Klimek VM, Vertosick E, Coleton MI, Yeung KS, Lin H, Nimer S, Cassileth BR. Maitake mushroom extract in myelodysplastic syndromes (MDS): a phase II study. Cancer Immunol Immunother 2015; 64(2):237-247.
- Kodama N, Komuta K, Nanba H. Effect of Maitake (Grifola frondosa) D-Fraction on the activation of NK cells in cancer patients. J Med Food 2003; 6(4):371-377.
- Kodama N, Komuta K, Nanba H. Can maitake MD-fraction aid cancer patients? Altern Med Rev 2002; 7(3):236-239.
- Kodama N, Komuta K, Sakai N, Nanba H. Effects of D-Fraction, a polysaccharide from Grifola frondosa on tumor growth involve activation of NK cells. Biol Pharm Bull 2002; 25(12):1647-1650.
- Black W. Several apparent errors surfaced on reading the article in the June 2002 issue of Alter-native Medicine Review by Kodama et al. entitled "Can maitake MD-fraction aid cancer patients"? Altern Med Rev 2002; 7(6):451-454.
- Tanaka H, Tsunematsu K, Nakamura N, Suzuki K, Tanaka N, Takeya I, Saikai T, Abe S. Successful treatment of hypersensitivity pneumonitis caused by Grifola frondosa (Maitake) mushroom using a HFA-BDP extra-fine aerosol. Intern Med 2004; 43(8):737-740.
- Konno S, Tortorelis DG, Fullerton SA, Samadi AA, Hettiarachchi J, Tazaki H. A possible hypoglycaemic effect of maitake mushroom on Type 2 diabetic patients. Diabet Med 2001; 18(12):1010.
- BfR. Caution when using dried mushrooms! Press releases of BfR 6. 28-2-2002.
- Brauer D, Kimmons T, Phillips M. Effects of management on the yield and high-molecular-weight polysaccharide content of shiitake (Lentinula edodes) mushrooms. J Agric Food Chem 2002; 50(19):5333-5337.
- Minato K, Mizuno M, Terai H, Tsuchida H. Autolysis of lentinan, an antitumor polysaccharide, during storage of Lentinus edodes, shiitake mushroom. J Agric Food Chem 1999; 47(4):1530-1532.