Maitake

• How It Works

  Maitake demonstrated anticancer effects in laboratory studies. Research is underway to test its anticancer effects in humans.

  Maitake is a mushroom that traditionally has been used in Japan and China as part of the diet and to treat diabetes and hypertension. Like other medicinal mushrooms, it contains a complex sugar called beta-glucan. In laboratory and human studies, maitake extract was able to stimulate various cells and factors in the immune system. Studies in animals show that it slows the growth of certain tumors and lowers blood sugar levels. More studies are being conducted to determine if maitake has the same effects in humans.

• Purported Uses
  • To prevent and treat cancer
    Laboratory studies and small uncontrolled studies in humans show that maitake extracts slow the growth of tumors and stimulate certain immune cells.
  • To manage diabetes
    Maitake reduces blood glucose levels in rats.
  • To lower high cholesterol
    There are no data to back this claim.
  • To lower high blood pressure
    There are no studies to support this claim.
  • As an immune stimulant
    Maitake stimulates the activity of certain immune cells in laboratory studies and in mice. It has also been shown to stimulate immune function in a small group of cancer patients. Larger studies are needed.
  • To lose weight
    There are no data to back this claim.
• Do Not Take If
  • You are taking blood sugar-lowering medications: Maitake can increase their effects.
  • You are taking warfarin: Maitake may interact with warfarin resulting in an elevated international normalized ratio (INR).
• Side Effects

  An increased number of white blood cells which may indicate an allergic reaction.

• Scientific Name

  Grifola frondosa

• Clinical Summary

  Maitake is an edible mushroom consumed widely in Asia as food and used in traditional medicine to treat diabetes and hypertension. Its extracts are commercially available as dietary supplements marketed to “enhance immune function” and to treat HIV and cancer. Beta 1,6-glucan, a protein bound polysaccharide, has been identified as the active constituent. Maitake extracts exhibited hypoglycemic effects in a few studies ^(9) (12). Preliminary data also suggest that they may be useful in inducing ovulation in patients with polycystic ovary syndrome ⁽²²⁾.

  In other studies, maitake demonstrated antitumor effects ⁽¹⁶⁾, enhanced bone marrow colony formation, reduced doxorubicin toxicity ⁽¹¹⁾, and inhibited tumor metastasis in vitro ⁽¹³⁾. In a murine model, an orally administered extract promoted maturation of hematopoietic cells to functionally active myeloid cells and enhanced peripheral blood leukocyte recovery following chemotoxic bone marrow injury ⁽¹⁷⁾. A novel polysaccharide, MZF, was shown to induce dendritic cell maturation and enhanced antitumor response ⁽²⁰⁾; a Selenium-enriched polysaccharide enhanced the antitumor activity of 5-Fu ⁽³⁰⁾; and a combination of polysaccharides and vitamin C was reported to induce apoptosis and autophagy in human hepatoma cells ⁽³¹⁾. Maitake also enhanced interferon activity against bladder cancer cells ⁽¹⁸⁾ and alleviated inflammation associated with inflammatory bowel disease ⁽¹⁹⁾; and a maitake fraction showed anti-leishmanial effects ⁽³²⁾.

  In a small non-controlled study, tumor regression or significant improvements in symptoms were observed in half of the subjects who took maitake extract ⁽⁵⁾. In a trial of postmenopausal breast cancer patients, oral administration of a maitake extract was shown to have immunomodulatory effects ⁽¹⁴⁾; and to enhance neutrophil and monocyte function in patients with myelodysplastic syndrome  ⁽²⁵⁾. More studies are underway to evaluate maitake’s anticancer potential.

• Food Sources

  Maitake mushroom is an edible fungus. The whole mushroom can be fried or boiled.

• Purported Uses
  • Cancer prevention
  • Diabetes
  • High cholesterol
  • Hypertension
  • Immunostimulation
  • Weight loss
• Mechanism of Action

  Maitake is thought to exert its effects through its ability to activate various effector cells, such as macrophages, natural killer cells, and T cells, as well as interleukin-1 and superoxide anions ^{(2) (3) (4) (13)}. Studies also suggest possible hypoglycemic activity ⁽⁹⁾. The antidiabetic effect of alpha-glucan may be due to its effects on insulin receptors by increasing insulin sensitivity and ameliorating insulin resistance of peripheral target tissues ⁽¹²⁾.

  Maitake extract enhanced the growth and differentiation of mouse bone marrow cells treated with doxorubicin, a chemotherapeutic agent ⁽¹¹⁾. In addition, it may modulate antigen presentation as evidenced by protective effects against tumor implantation following transfer of dendritic cells from tumor-bearing mice that were treated with maitake ⁽¹⁵⁾.

  In other studies, maitake D fraction demonstrated antitumor activity by upregulating expression of a proapoptotic gene, BAK-1 ⁽²³⁾; and prevented breast carcinogenesis, blocked tumor invasiveness, reduced angiogenesis, and increased overall survival in a murine model ⁽²⁶⁾. In addition, maitake polysaccharides were found to induce apoptosis GFPs induced via the mitochondrial-dependent apoptotic pathway in human breast cancer cells ⁽²⁷⁾; the beta glucan GFPBW1 also showed antitumor effects that are thought in part due to activation of macrophages via the Dectin-1/Syk/NF-κB signaling pathway ⁽²⁴⁾; and an orally administered maitake alpha-glucan was found to activate dendritic cells and macrophages in Peyer’s patches, resulting in induction of systemic antitumor T-cell response ⁽²⁸⁾.

  Maitake also exerted antidepressant effects in mice, involving activation of the α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, which are important mediators for the treatment of depression ⁽²⁹⁾.

• Contraindications

  Maitake may not be appropriate for those taking hypoglycemic medications because it can have synergistic effects ⁽⁹⁾.

• Adverse Reactions

  Asymptomatic eosinophilia ⁽²⁵⁾.

• Herb-Drug Interactions

  Warfarin: Maitake may interact with warfarin resulting in an elevated international normalized ratio (INR) ⁽²¹⁾.
  Hypoglycemic medications: Maitake may increase their effects  ⁽⁹⁾.

• Herb Lab Interactions

  Maitake may lower blood glucose levels ⁽⁹⁾.

• References

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

  2. Adachi K, Nanba H, Kuroda H. Potentiation of host-mediated antitumor activity in mice by beta glucan obtained from Grifola frondosa (maitake). Chem Pharm Bull 1987;35:262-70.

  3. Kubo K, Aoki H. Nanba H. Anti-diabetic activity present in the fruit body of Grifola frondosa (Maitake). Biol Pharm Bull 1994;17:1106-10.

  4. Horio H, Ohtsuru M. Maitake (Grifola frondosa) improve glucose tolerance of experimental diabetic rats. J Nutr Sci Vitaminol 2001;47:57-63.

  5. Kodama N, Komuta K, Nanba H. Can Maitake MD-fraction aid cancer patients? Altern Med Rev 2002;7:236-9.

  6. Miura NN. Blood clearance of (1—>3)-beta-D-glucan in MRL lpr/lpr mice. FEMS Immunol Med Microbiol 1996;13:51-7.

  7. Ohno N, et al. Characterization of the antitumor glucan obtained from liquid-cultured Grifola frondosa. Chem Pharm Bull 1986;34:1709-1715.

  8. Nanba H, Kubo K. Maitake D-fraction: Healing and preventive potential for cancer. J Orthomolecular Med 1997;12:43-9.

  9. Konno S, et al. A possible hypoglycaemic effect of maitake mushroom on Type 2 diabetic patients. Diabet Med 2001 Dec;18(12):1010

  10. Yamada Y, et al. Antitumor effect of orally administered extracts from fruit body of Grifola frondosa (maitake). Chemotherapy 1990;38:790-6.

  11. Lin H, et al. Maitake beta-glucan MD-fraction enhances bone marrow colony formation and reduces doxorubicin toxicity in vitro. Int Immunopharmacol 2004 Jan;4(1):91-9.

  12. Hong L, Xun M, Wutong W. Anti-diabetic effect of an alpha-glucan from fruit body of maitake (Grifola frondosa) on KK-Ay mice. Pharm Pharmacol. 2007 Apr;59(4):575-82.

  13. 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 Jun;31(6):1104-8.

  14. Deng G, Lin H, Seidman A, et al. A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects. J Cancer Res Clin Oncol. 2009 Sep;135(9):1215-21

  15. Harada N, Kodama N, Nanba H. Relationship between dendritic cells and the D-fraction-induced Th-1 dominant response in BALB/c tumor-bearing mice. Cancer Lett. 2003;192(2):181-7.

  16. Shomori K, Yamamoto M, Arifuku I, Teramachi K, Ito H. Antitumor effects of a water-soluble extract from Maitake (Grifola frondosa) on human gastric cancer cell lines. Oncol Rep. 2009 Sep;22(3):615-20.

  17. Lin H, de Stanchina E, Zhou XK, et al. Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in peripheral blood from paclitaxel hematotoxicity. Cancer Immunol Immunother. 2010 Jun;59(6):885-97.

  18. 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 Apr;105(7):1011-5.

  19. Lee JS, Park SY, Thapa D, et al. Grifola frondosa water extract alleviates intestinal inflammation by suppressing TNF-alpha production and its signaling. Exp Mol Med. 2010 Feb 28;42(2):143-54.

  20. Masuda Y, Ito K, Konishi M, Nanba H. A polysaccharide extracted from Grifola frondosa enhances the anti-tumor activity of bone marrow-derived dendritic cell-based immunotherapy against murine colon cancer. Cancer Immunol Immunother. 2010 Oct;59(10):1531-41.

  21. Hanselin MR, Vande Griend JP, Linnebur SA. INR elevation with maitake extract in combination with warfarin. Ann Pharmacother. 2010 Jan;44(1):223-4.

  22. 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 Dec;16(12):1295-9.

  23. Soares R, Meireles M, Rocha A, et al. Maitake (D fraction) mushroom extract induces apoptosis in breast cancer cells by BAK-1 gene activation.J Med Food. 2011 Jun;14(6):563-72.

  24. Fang J, Wang Y, Lv X, et al. Structure of a β-glucan from Grifola frondosa and its antitumor effect by activating Dectin-1/Syk/NF-κB signaling. Glycoconj J. 2012 Aug;29(5-6):365-77.

  25. Wesa KM, Cunningham-Rundles S, Klimek VM, et al. Maitake mushroom extract in myelodysplastic syndromes (MDS): a phase II study. Cancer Immunol Immunother. (2015) 64:237–247 DOI 10.1007/s00262-014-1628-6

  26. Roldan-Deamicis A, Alonso E, Brie B, Braico DA, Balogh GA. Maitake Pro4X has anti-cancer activity and prevents oncogenesis in BALBc mice. Cancer Med. 2016 Sep;5(9):2427-41.

  27. Zhang Y, Sun D, Meng Q, Guo W, Chen Q, Zhang Y. Grifola frondosa polysaccharides induce breast cancer cell apoptosis via the mitochondrial-dependent apoptotic pathway. Int J Mol Med. 2017 Oct;40(4):1089-1095.

  28. Masuda Y, Nakayama Y, Tanaka A, Naito K, Konishi M. Antitumor activity of orally administered maitake α-glucan by stimulating antitumor immune response in murine tumor. PLoS One. 2017 Mar 9;12(3):e0173621.

  29. Bao H, Ran P, Sun L et al. Griflola frondosa (GF) produces significant antidepressant effects involving AMPA receptor activation in mice. Pharm Biol. 2017 Dec;55(1):299-305.

  30. Mao G, Li Q, Deng C, et al. The synergism and attenuation effect of Selenium (Se)-enriched Grifola frondosa (Se)-polysaccharide on 5-Fluorouracil (5-Fu) in Heps-bearing mice. Int J Biol Macromol. 2018 Feb;107(Pt B):2211-2216.

  31. Zhao F, Zhao J, Song L, Zhang YQ, Guo Z, Yang KH. The induction of apoptosis and autophagy in human hepatoma SMMC-7721 cells by combined treatment with vitamin C and polysaccharides extracted from Grifola frondosa. Apoptosis. 2017 Nov;22(11):1461-1472.

  32. Sultana SS, Ghosh J, Chakraborty S, et al. Selective in vitro inhibition of Leishmania donovani by a semi-purified fraction of wild mushroom Grifola frondosa. Exp Parasitol. 2018 Sep;192:73-84.