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Maitake

Scientific Name(s): Grifola frondosa (Dickson ex Fr.) S. F. Gray.
Common Name(s): Dancing mushroom, Hen of the woods, Huishu hua, King of mushrooms, Maitake, Monkey's bench, Ram’s head, Sheep’s head, Shelf fungus

Clinical Overview

Use

Maitake has been used for its antiviral action and to treat diabetes, high blood pressure, cholesterol, and obesity. Maitake has been studied to a limited extent for treating cancer; however, the information available is not sufficient to recommend it for this use.

Dosing

Disease-prevention doses of commercial preparations range from 12 to 25 mg of the extract and 200 to 250 mg or 500 to 2,500 mg of whole powder daily. A trial among HIV-positive patients used doses of 6 g/day whole powder or 20 mg purified extract with 4 g whole maitake powder.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy during pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Information is limited.

Toxicology

Information is limited.

Botany

The maitake mushroom is found in northeastern Japan but also grows and is cultivated in the United States and Europe.1, 2 It is a basidiomycetes fungus in the Polyporaceae family (synonym, Polyporus frondosus Dicks. ex Fries).3, 4 The maitake mushroom grows in clusters near the foot of oak trees and can reach 50 cm in base diameter. One bunch can weigh up to 45 kg (100 lbs). Maitake has a rippling, flowery appearance resembling dancing butterflies, hence one of its common names, dancing mushroom.1

History

In China and Japan, maitake mushrooms have been consumed for 3,000 years, valued most for their legendary properties. Maitake's scientific name, G. frondosa, is derived from an Italian mushroom name referring to the gryfon, a mythological half lion and half eagle beast. Many years ago in Japan, the maitake actually had monetary value and was worth its weight in silver. In the late 1980s, Japanese scientists identified the maitake as more potent than lentinan, shiitake, suehirotake, and kawaratake mushrooms, all of which are used in traditional Asian medicine for immune function enhancement.1

Chemistry

The polysaccharide beta-glucan is present in low quantities (0% to 0.2%)2 in most of the mushrooms in the Polyporaceae family (eg, reishi mushroom) and possesses antitumor activity.1 The D fraction of beta-glucan appears to be the most active and potent form of the polysaccharide, a protein-bound extract developed in Japan.5 An MD-fraction has now been described, as well, with purportedly superior activity.1, 6 Both structure-functional relationship7 and fractionation by anion exchange chromatography of beta-glucan8 have been reported.

Neutral, acidic, and water-soluble polysaccharides have been extracted from maitake, and their structure has been determined.2, 4, 9, 10 Two different glycan conformations have been obtained from the plant.11 The beta-1,3-glycan grifolan conformation has been elucidated using magnetic resonance spectroscopy.12

Ascorbic acid analog and glycoside studies have been reported.13 A lectin from maitake has been isolated and characterized.14, 15 In addition, a grifolisin enzyme and the enzyme phytase have been described3, 16 and lysophosphatidylethanolamine has been identified in studies examining apoptosis in neuronal cells.17

Structural characterization of maitake extract constituents18 and carbon-13 nuclear magnetic resonance analysis of the fruit body's constituents19 have been conducted.

Uses and Pharmacology

Immunostimulant/Anticancer

Immunostimulant activity is a characteristic of many medicinal mushrooms, including shiitake, suchirotake, or kawaratake, that are used clinically as anticancer drugs in Japan.1 Maitake's polysaccharide may be slightly different from the beta-glucans found in other fungi. The large molecular weight of the polysaccharide molecule and branch structure configurations may be important for its antitumor or immunostimulant effect.20, 21, 22 In 1998, the US Food and Drug Administration approved an Investigational New Drug Application for a phase 2 pilot study on the effect of maitake D-fraction on advanced breast and prostate cancers.1

Animal data

Maitake extract has been studied in mouse and in vitro studies involving Escherichia coli.23 It activates macrophages;24, 25 enhances cytokine, natural killer, and cytotoxic-T cell production;1, 24 has antigen-specific antibody response;5 and is an immunostimulant protecting against toxicity of chemotherapeutic agents.26, 27, 28

Maitake demonstrated antitumor activity in mouse experiments4, 29, 30, 31 while in other experiments it exhibited synergism with coadministered chemotherapeutic agents.4, 27 Other experiments failed to show direct antitumor action.27 Prevention of metastasis by maitake has been demonstrated in mice.32

Some pharmacokinetic parameters of beta-D-glucan have been evaluated in mice.33 Experiments have attempted to evaluate dose-dependent anti-tumor activity as well as route, timing, and other factors.34, 35, 36, 37

Clinical data

There are a limited number of well-designed clinical trials investigating maitake's effects in cancer therapy. Additional controlled studies are needed.

Clinical case studies of liver, lung, stomach, breast, brain, and prostate cancers involving the use of maitake have been reported.1 A phase 1/2 dose-escalation trial in 34 postmenopausal (natural or treatment-induced) breast cancer patients who were currently disease-free, reported the largest functional immunological increases (more than 50% above baseline) in granulocyte response as well as production of interleukin (IL)-10, IL-2, and tumor necrosis factor-alpha by various subsets of T cells. Additionally, the largest increase occurred with the intermediate of 5 doses (approximately 5 to 7 mg/kg/day). In contrast, about a 20% decrease was noted in interferon-gamma production at a high dose (10 mg/kg/day). These results highlight the relativity of an "optimal dose," which is dependent on the specific immunological parameter measured.49

In a study of 165 patients, results suggested that quality of life indicators had improved. Of these patients, 90% reported an improvement in cancer-treatment symptoms (eg, nausea, hair loss) and 83% reported pain reduction.38

Insulin resistance/Diabetes/Polycystic ovary syndrome

Animal data

When maitake powdered fruit body was administered orally to genetically diabetic mice, blood glucose reduction was observed compared with a control group.39 Maitake may control blood glucose levels by possible reduction of insulin resistance and enhancement of insulin sensitivity.1

Clinical data

Insulin resistance and hyperinsulinemia are prominent features of polycystic ovary syndrome (PCOS). A randomized, open-label comparator trial (n = 57) investigated the ability of monotherapy and combination therapy of a maitake extract formulation (standardized to at least 18% SX-fraction) and clomiphene citrate to induce ovulation in women with PCOS. Nonresponders in either monotherapy group were subsequently given Maitake plus clomiphene combination therapy. Although ovulation cycle rates were significantly higher with clomiphene monotherapy than maitake extract (69.9% vs 41.7%, respectively), 87% of monotherapy nonresponders ovulated with the combination therapy.50

Other uses

A few reports, mostly of animal experiments, on maitake's effects on diabetes, hypertension, cholesterol, and viruses are available.

Hypertension

Hypertensive rats given 5% maitake mushroom powder had a reduction in blood pressure.40, 41 Similar blood pressure-lowering activity was seen in another study performed in rats, in which maitake extract lowered blood pressure from 200 to 115 mm Hg in 4 hours.42 In an unpublished human trial, 11 patients with documented essential hypertension took 500 mg maitake mushroom tablets twice daily. A mean decrease in diastolic blood pressure of approximately 8 mm Hg and a mean decrease in systolic blood pressure of about 14 mm Hg were reported.43

Hypercholesterolemia

Maitake altered lipid metabolism by inhibiting the accumulation of liver lipids and the elevation of serum lipids in hyperlipidemic rats.44 Similar results were seen in rats fed a high-cholesterol diet.45 In another report, total cholesterol and very low density lipoprotein-cholesterol decreased in rats given powdered mushroom preparations.40

Obesity

At least 2 studies are available concerning maitake's antiobesity activity. After 18 weeks, overweight rats fed unheated maitake powder lost weight compared with controls.46 In an observational study, 30 patients lost between 3 and 12 kg (7 and 26 lbs) after administration of 20 to 500 mg tableted maitake powder per day for 2 months.47

Antiviral

In an in vitro study, the D-fraction of maitake exhibited an inhibitory action on the hepatitis B virus alone and a synergistic action with interferon alpha-2b.48

A human trial of poor methodology attempted to demonstrate a positive effect on CD4+ count and viral load. In 35 HIV-positive patients given maitake powder and DM-fraction extract over 12 months, 85% reported an increased sense of well-being. The effect of maitake on CD4+ count and viral load was minimal.6

Neurological

An in vitro experiment demonstrated that lysophosphatidylethanolamine, a chemical component of maitake, evoked a cascade mechanism that resulted in the induction of neuronal differentiation and the halting of neuronal apoptosis.17

Dosing

Commercial preparations commonly provide 3 to 25 mg of standardized D- or MD fraction plus 75 to 250 mg whole powder per capsule. Whole powder capsules generally contain 100 to 500 mg, and a liquid extract of 1 mg D-fraction extract per drop is available.

Disease-prevention doses of commercial preparations range from 12 to 25 mg of the extract and 200 to 250 mg or 500 to 2,500 mg of whole powder daily. A trial among HIV-positive patients used doses of 6 g/day whole powder or 20 mg purified extract with 4 g whole maitake powder.

A trial among HIV patients used daily doses of 6 g whole powder per day or 20 mg purified extract with 4 g whole maitake powder.6

However, there are limited clinical studies to substantiate the efficacy or safety of this dose.1

Pregnancy / Lactation

Information regarding safety and efficacy during pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Information is limited.

Because potential adverse reactions exist from mistaken mushroom identity, use caution when obtaining this particular natural product. (For more information, see the Mushroom Poisoning Decision Chart monograph).

Toxicology

In vitro studies indicate maitake beta-glucan had a suppressive, but not cytotoxic, effect on hematopoiesis at 200 mcg/mL, while maitake-derived grifon-D extract was cytotoxic to human prostate cells at doses of 480 mcg/mL or more.28

References

1. Mayell M. Maitake extracts and their therapeutic potential. Altern Med Rev. 2001;6:48-60.11207456
2. Dikeman CL, Bauer LL, Flickinger EA, Fahey GC Jr. Effects of stage of maturity and cooking on the chemical composition of select mushroom varieties. J Agric Food Chem. 2005;53:1130-1138.15713030
3. Suzuki N, Nishibori K, Oodaira Y, et al. Grifolisin, a member of the sedolisin family produced by the fungus Grifola frondosa. Phytochemistry. 2005;66:983-990.15896366
4. Nie X, Shi B, Ding Y, Tao W. Preparation of a chemically sulfated polysaccharide derived from Grifola frondosa and its potential biological activities. Int J Biol Macromol. 2006;39:228-233.16822541
5. Nanba H. Antitumor activity of orally administrated "D-fraction" from maitake mushroom (Grifola frondosa). J Naturopathic Med. 1993;1:10-15.
6. Nanba H. Effects of Maitake (Grifola frondosa) glucan in HIV-infected patients.Mycoscience. 2000;41:293-295.11138730
7. Iino K, Ohno N, Suzuki I, Sato K, Ohsawa S, Yadomae T. Structure-function relationship of antitumor beta-1,3-glucan obtained from matted mycelium of cultured Grifola frondosa. Chem Pharm Bull. 1985;33:4950-4956.3830423
8. Ohno N, Iino K, Oikawa S, Sato K, Ohsawa M, Yadomae T. Fractionation of acidic antitumor beta-glucan of Grifola frondosa by anion-exchange chromatography using urea solutions of low and high ionic strengths. Chem Pharm Bull. 1986;34:3328-3332.3791504
9. Ohno N, Iino K, Suzuki I. Neutral and acidic antitumor polysaccharides extracted from cultured fruit bodies of Grifola frondosa. Chem Pharm Bull. 1985;33:1181-1186.4040819
10. Nanba H, Hamaguchi A, Kuroda H. The chemical structure of an antitumor polysaccharide in fruit bodies of Grifola frondosa (maitake). Chem Pharm Bull. 1987;35:1162-1168.3607939
11. Ohno N, Adachi Y, Suzuki I, et al. Two different conformations of antitumor glucans obtained from Grifola frondosa. Chem Pharm Bull. 1986;34:2555-2560.3769071
12. Ohno N, Ohsawa M, Sato K, Oikawa S, Yadomae T. Conformation of grifolan in the fruit body of Grifola frondosa assessed by carbon-13 cross polarization-magic angle spinning nuclear magnetic resonance spectroscopy. Chem Pharm Bull. 1987;35:2585-2588.3664855
13. Okamura M. Distribution of ascorbic acid analogs and associated glycosides in mushrooms. J Nutr Sci Vitaminol. 1994;40:81-94.7931730
14. Kawagishi H, Nomura A, Mizuno T, Kimura A, Chiba S. Isolation and characterization of a lectin from Grifola frondosa fruiting bodies. Biochim Biophys Acta. 1990;1034:247-252.2364082
15. Nagata Y, Yamashita M, Honda H, et al. Characterization, occurrence, and molecular cloning of a lectin from Grifola frondosa: jacalin-related lectin of fungal origin. Biosci Biotechnol Biochem. 2005;69:2374-2380.16377896
16. Collopy PD, Royse DJ. Characterization of phytase activity from cultivated edible mushrooms and their production substrates. J Agric Food Chem. 2004;52:7518-7524.15675798
17. Nishina A, Kimura H, Sekiquchi A, Fukumoto RH, Nakajima S, Furukawa S. Lysophosphatidylethanolamine in Grifola frondosa as a neurotrophic activator via activation of MAPK. J Lipid Res. 2006;47:1434-1443.16614393
18. Ohno N, Iino K, Takeyama T, et al. Structural characterization and antitumor activity of the extracts from matted mycelium of cultured Grifola frondosa. Chem Pharm Bull. 1985;33:3395-3401.4085071
19. Ohno N, Iino K, Suzuki I, Sato K, Oikawa S, Yadomae T. Carbon-13 nuclear magnetic resonance spectral analysis of the fruit bodies of Grifola frondosa. Chem Pharm Bull. 1985;33:1557-1562.4042232
20. Adachi K, Ohno N, Ohsawa M, Sato K, Oikawa S, Yadomae T. Physiochemical properties and antitumor activities of chemically modified derivatives of antitumor glucan "grifolan LE" from Grifola frondosa. Chem Pharm Bull. 1989;37:1838-1843.
21. Adachi K, Ohno N, Ohsawa M, Yadomae T. Change of biological activities of (1----3)-beta-D-glucan from Grifola frondosa upon molecular weight reduction by heat treatment. Chem Pharm Bull. 1990;38:477-481.
22. Ohno N, Asada N, Adachi Y, Yadomae T. Enhancement of LPS triggered TNF-alpha (tumor necrosis factor-alpha) production by (1-->3)-beta-D-glucans in mice. Biol Pharm Bull. 1995;18:126-133.7735226
23. Jin ZC, Qian J. Inhibitory effects of fifty kinds of herbal drugs, vegetables and chemicals SOS response [in Chinese]. Zhonghua Yu Fang Yi Xue Za Zhi. 1994;28:147-150.7842869
24. Adachi Y, Okazaki M, Ohno N, Yadomae T. Enhancement of cytokine production by macrophages stimulated with (1-->3)-beta-D-glucan, grifolan (GRN), isolated from Grifola frondosa. Biol Pharm Bull. 1994;17:1554-1560.7537572
25. Ohno N, Egawa Y, Hashimoto T, Adachi Y, Yadomae T. Effect of beta-glucans on the nitric oxide synthesis by peritoneal macrophage in mice. Biol Pharm Bull. 1996;19:608-612.8860968
26. Wu MJ, Cheng TL, Lian TW, Wang L, Chiou SY. Immunomodulatory properties of Grifola frondosa in submerged culture. J Agric Food Chem. 2006;54:2906-2914.16608207
27. Kodama N, Murata Y, Asakawa A, et al. Maitake D-Fraction enhances antitumor effects and reduces immunosuppression by mitomycin-C in tumor-bearing mice. Nutrition. 2005;21:624-629.15850970
28. Lin H, Chcung 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;14:21-27.
29. Lin JT, Liu WH. o-Orsellinaldehyde from the submerged culture of the edible mushroom Grifola frondosa exhibits selective cytotoxic effect against Hep 3B cells through apoptosis. J Agric Food Chem. 2006;54:7564-7569.17002422
30. 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;35:262-270.
31. Suzuki I, Itani T, Ohno N, et al. Effect of a polysaccharide fraction from Grifola frondosa on immune response in mice. J Pharmacobiodyn. 1985;8:217-226.3891963
32. Nanba H. Activity of maitake D-fraction to inhibit carcinogenesis and metastasis. Ann N Y Acad Sci. 1995;768:243-245.8526356
33. Miura NN, Ohno N, Aketagawa J, Tamura H, Tanaka S, Yadomae T. Blood clearance of (1-->3)-beta-D-glucan in MRL lpr/lpr mice. FEMS Immunol Med Microbiol. 1996;13:51-57.8821398
34. Suzuki I, Itani T, Ohno N, et al. Antitumor activity of a polysaccharide fraction extracted from cultured fruiting bodies of Grifola frondosa. J Pharmacobiodyn. 1984;7:492-500.6491867
35. Hishida I, Nanba H, Kuroda H. Antitumor activity exhibited by orally administered extract from fruit body of Grifola frondosa (maitake). Chem Pharm Bull. 1988;36:1819-1827.3203420
36. Suzuki I, Takeyama T, Ohno N. Antitumor effect of polysaccharide grifolan NMF-5N on syngeneic tumor in mice. J Pharmacobiodyn. 1987;10:72-77.
37. Ohno N, Adachi Y, Suzuki I. Antitumor activity of a beta-1,3-glucan obtained from liquid cultured mycelium of Grifola frondosa. J Pharmacobiodyn. 1986;9:861-864.3820062
38. Nanba H. Townsend Lett Doct Patient. 1996;84-85.
39. Kubo K, Aoki H, Nanba H. Anti-diabetic activity present in the fruit body of Grifola frondosa (maitake): I. Biol Pharm Bull. 1994;17:1106-1110.7820117
40. Kabir Y, Yamaguchi M, Kimura S. Effect on shiitake (Lentius edodes) and maitake (Grifola frondosa) mushrooms on blood pressure and plasma lipids of spontaneously hypertensive rats. J Nutr Sci Vitaminol. 1987;33:341-346.3443885
41. Kabir Y, Kimura S. Dietary mushrooms reduce blood pressure in spontaneously hypertensive rats (SHR). J Nutr Sci Vitaminol. 1989;35:91-94.2738717
42. Adachi K, Nanba H, Otsuka M, Kuroda H. Blood pressure-lowering activity present in the fruit body of Grifola frondosa (maitake): I. Chem Pharm Bull. 1988;36:1000-1006.3409391
43. Gerson S. (Director of the Foundation for Holistic Medical Research in NYC). 1994 (unpublished).
44. Kubo K, Nanba H. The effect of maitake mushrooms on liver and serum lipids. Altern Ther Health Med. 1996;2:62-66.
45. Kubo K, Nanba H. Anti-hyperliposis effect of maitake fruit body (Grifola frondosa): I. Biol Pharm Bull. 1997;20:781-785.9255420
46. Ohtsuru M. Anti-obesity activity exhibited by orally administered powder of maitake mushrooms (Grifola frondosa) [in Japanese]. Anshin. 1992:198-200.
47. Yokota M. Observatory trial at anti-obesity activity of maitake mushrooms (Grifola frondosa) [in Japanese]. Anshin. 1992:202-204.
48. Gu CQ, Li JW, Chao FH. Inhibition of hepatitis B virus by D-fraction from Grifola frondosa: synergistic effect of combination with interferon-alpha in HepG2 2.2.15. Antiviral Res. 2006;72:162-165.16846649
49. 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;135(9):1215-1221.19253021
50. 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):1295-1299.21034160

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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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