Sun Agaric

Agaricus brasiliensis (formerly Agaricus blazei)
(from Medicinal Mushrooms – A Clinical Guide by Martin Powell)

Japanese name – Himematsutake
Portuguese name – Cogumela del sol
English name – Royal/Sun Agaric

Commonly known as A.blazei Murril (ABM), after a mushroom discovered in 1945 by the mycologist William A. Murrill growing on the lawn of his friend R.W.Blaze in Florida, the mushroom used therapeutically can be traced to spores and samples sent to Japan from the Piedade region of Brazil by a farmer of Japanese descent in 1965. It is now believed that the two are in fact different species with the name Agaricus brasiliensis proposed for the Brazilian mushroom1. It has also been suggested that A.blazei is the same mushroom first identified by Charles Horton Peck in 1893 and called A.subrufescens2.

Although one of the newest medicinal mushrooms, A. blazei is rapidly becoming one of the most popular. Reported in a recent survey to be taken by 31% of urological cancer patients in Japan3, with the fastest growing US sales of any medicinal mushroom4 and one of the three most popular medicinal mushrooms in Taiwan, this relative of the common button mushroom, A. bisporus, exhibits broad clinical activity5.

Its polysaccharides include several immunologically active low molecular weight fractions, while an α-1,6 and α-1,4 glucan complex, several polysaccharide-protein complexes, a glucomannan with a main chain of beta 1,2 linked mannopyranosyle residues and a heteropolysaccharide composed mainly of glucose, arabinose and mannose all show anti-tumor activity6-17. Interestingly, there appears to be a increase in structural diversity of its polysaccharides with maturation of the fruiting body18.

A. blazei also contains high levels of lipids, including linoleic acid, oleic acid, steric acid and ergosterol19.

Cancer – A. blazei polysaccharide extracts show strong in-vitro and in-vivo activity against a range of cancer cell lines, including lung and ovarian cancer and in vivo studies show positive results for Ehrlich ascites cancer, Sarcoma 180, human ovarian cancer and mouse lung cancer cell lines, as well as synergistic benefits with chemotherapy and radiotherapy20.

In a cachexia model A. blazei extracts as well as powdered fruiting body significantly reduced tumor size and promoted gain in body weight with reduction in AST levels and increased glycemia in rats21, while an in-vivo study using severe combined immunodeficient mice found A. blazei polysaccharides to directly inhibit the growth of prostate cancer cells via an apoptotic pathway and to suppress prostate tumor growth via antiproliferative and antiangiogenic mechanisms with the greatest activity found in the broth fraction (compounds extracted from the liquid growth medium on which the mycellium was grown rather than the mushroom itself)22.

A 2008 study reported significant increases in the NK cell activity of human volunteers with A. blazei polysaccharide extract at a dose of 3g/day compared to placebo23, while Ahn reports increased NK-cell activity and reduced chemotherapy related side effects (appetite, alopecia, emotional stability, and general weakness) from A. brlazei polysaccharide extract in one hundred cervical, ovarian, and endometrial cancer patients treated either with carboplatin plus VP16 (etoposide) or with carboplatin plus taxol24.

In two small Chinese clinical studies a dose of 20g twice a day of A. blazei fruiting body, taken as a tea (hot water extract), was reported to improve hematopoietic parameters and treatment outcomes in patients receiving chemotherapy for acute non-lymphocytic Leukemia in one study and improvement in immune status, hematopoietic parameters and quality of life measures in late stage alimentary tract tumors in another25,26.

The closely related A. bisporus shows in-vitro anti-aromatase activity, with conjugated linoleic acid identified as the main active component, and Mizuno reports positive clinical results with A. blazei in a number of mainly breast cancer patients but at unspecified dosage27-29.

Although most of the published research strongly support the use of A. brasiliensis in cancer therapy two studies studies looking at the protective properties of A. blazei have been published with negative outcomes (in one A. brasiliensis given at 5% of diet did not have a suppressive effect on colon carcinogenesis in rats exposed to dimethylhydrazine and in another an aqueous extract did not affect the development of liver cancer induced by diethylnitrosamine) and it appears that there may be significant variation in activity between different extracts, as well as between different strains30-33.

Diabetes – To date little clinical data has been published, although a 2008 study reported decreases in cholesterol and glucose levels, together with increased natural killer cell activity, at a dose of 3g/day polysaccharide extract23.

Allergies – As potent immune modulators mushroom polysaccharides can reduce the level of Th2 mediated allergic reactions and A. blazei is no exception with Andosan, a proprietary combination of polysaccharide extracts from A. blazei (82%), H. erinaceous (15%) and G. frondosa (3%), causing a shift towards a Th1 cytokine profile with consequent reduced risk of allergies and in-vitro inhibition of histamine release from mast cells34.

Hepatoprotective – There is evidence from a number of small clinical studies indicating possible application of A. blazei in the treatment of chronic hepatitis. In one study 1500mg of extract produced significant reductions in liver enzymes in a small number of hepatitis B patients over a 12 month period (AST reduced from 246 to 61 and ALT from 151 to 46)35. In another A. blazei extract reduced GTP in 80% of 20 patients with hepatitis C36. Wang et al also reported wide-ranging benefits in patients with chronic Hepatitis B at a dose of 20g fruiting body twice a day over a 3 month period including reduction in abdominal distension, fatigue and hepatodynia, together with increased retraction of the liver and spleen37.

CLINICAL SUMMARY Main Therapeutic Application – Cancer

Key Component – Polysaccharides

Dose – 3g/day polysaccharide extract has been used in clinical trials but the high activity of the culture broth supports clinical use of the biomass or of biomass/polysaccharide combinations.

Caution – One report has suggested a possible connection between consumption of an A. blazei extract and hepatic dysfunction in cancer patients, although the authors state that several other causative factors cannot be completely ruled out38. Cheilitis due to an A. blazei extract has also been reported39.

1. Nutritional and chemical composition of culinary-medicinal Royal Sun Agaricus (the Himematsutake mushroom) Agaricus brasiliensis S. Wasser et al. (Agaricomycetideae). Menezes M.C, Eira A.F, Silva G.F, Martins O.A, Meira D.R, Caramori C.A. Int J Med Mushr. 2008;10(2):189-194
2. Agaricus subrufescens, a cultivated edible and medicinal mushroom, and its synonyms. Kerrigan R.W. Mycologia. 2005;97(1):12-24.
3. Use of complementary and alternative medicine by patients with urologic cancer: a prospective study at a single Japanese institution. Yoshinura W, Ueda N, Ichioka K, Matsui Y, Terai A, Arai Y. Support Care Cancer. 2005;13:685-90.
4. Uncloaking the mysteries of medicinal mushrooms: the U.S. medicinal mushroom market continues to grow and evolve rapidly but its size still pales in comparison to the rest of the world. Adams C. Nutraceuticals World. October 01, 2008.
5. The medicinal mushroom Agaricus blazei Murrill: Review of literature and Pharmaco-toxicological problems. Firenzuoli F, Gori L, Lombardo G. Evid Based Complement Alternat Med. 2008;5(1):3-15.
6. Characterization of chemical composition of Agaricus brasiliensis polysaccharides and its effect on myocardial SOD activity, MDA and caspase-3 level in ischemia-reperfusion rats. Zhang S, He B, Ge J, Zhai C, Liu X, Liu P. Int J Biol Macromol. 2010;46(3):363-6.
7. Structural characterization of a water-soluble β-d-glucan from fruiting bodies of Agaricus blazei Murrill. Dong Q, Yao J, Yang X.T and Fang J.N. Carbohyd. Res. 2007;337:1417–1421.
8. Antitumor beta-glucan from the cultured fruit body of Agaricus blazei. Ohno N, Furukawa N, and Miura N. Biol Pharm Bull. 2004;24:820–828.
9. Tumor-specific cytocidal and immunopotentiating effects of relatively low molecular weight products derived from the basidiomycete Agaricus blazei Murrill. Fujimiya Y, Suzuki Y, Katakura R, and Ebina T. Anticancer Res. 1999;19:113–118.
10. Immunostimulatory activities of a low molecular weight antitumoral polysaccharide isolated from Agaricus blazei Murill (LMPAB) in Sarcoma 180 ascitic tumor-bearing mice. Niu Y.C, Liu J.C, Zhao X.M, Su F.Q, Cui H.X. Pharmazie. 2009;64(7):472-6.
11. Isolation and characterization of polysaccharides from Agaricus blazei Murrill. Gonzaga M.L.C, Ricardo N.M.P.S, Heatley F, and Soares S.A. Carbohyd. Polym. 2005;60:43–49.
12. Antitumor effect of a peptide-glucan preparation extracted from Agaricus blazei in a double-grafted tumor system in mice. Ebina T, and Fujimiya Y. Biotherapy. 1998;11:259–265.
13. Fractionation and antitumor activity of the water-insoluble residue of Agaricus blazei fruiting bodies. Kawagishi H, Inagaki R, Kanao T, Mizuno T, Shimura K, Ito H, Hagiwar T, and NakamuraT. Carbohyd. Res. 1989;186:267–273.
14. Oral administration of Agaricus brasiliensis S. Wasser et al. (Agaricomycetideae) extract downregulates serum immunoglobulin E levels by enhancing Th1 response. Morimoto T, Michihiro T.M, Masashi M.M. Int J Med Mushr 2008;10(1):30
15. An extract based on the medicinal mushroom Agaricus blazei Murill stimulates monocyte-derived dendritic cells to cytokine and chemokine production in vitro. Førland D.T, Johnson E, Tryggestad A.M, Lyberg T, Hetland G. Cytokine. 2010 Mar;49(3):245-50
16. Effect of an extract based on the medicinal mushroom Agaricus blazei murill on release of cytokines, chemokines and leukocyte growth factors in human blood ex vivo and in vivo. Johnson E, Førland D.T, Saetre L, Bernardshaw S.V, Lyberg T, Hetland G, Scand J. Immunol. 2009;69(3):242-50.
17. Peroral effect on tumor progression of soluble beta 1-6 glucans prepared by acid treatment from Agaricus blazei Murr. Fujiyama Y, Yamomoto H, Noji M, Suzuki I. Int J Med Mush 2000;2:43-4912.
18. Structural characterization of beta-glucans of Agaricus brasiliensis in different stages of fruiting body maturity and their use in nutraceutical products. Camelini C.M, Maraschin M, de Mendonça M.M, Zucco C, Ferreira A.G, Tavares L.A. Biotechnol Lett. 2005;27(17):1295-9.
19. Isolation of an antitumor compound (Ergosterol) from Agaricus blazei Murill and its mechanism of action. Takaku T, Kimura Y, Okuda H.J. Nutr. 2001;131:1409–1413.
20. Suppressing effects of daily oral supplementation of beta-glucan extracted from Agaricus blazei Murill on spontaneous and peritoneal disseminated metastasis in mouse model. Kobayashi H, Yoshida R, Kanada Y, Fukuda Y, Yagyu T, Inagaki K, Kondo T, Kurita N, Suzuki M, Kanayama N, Terao T. J Cancer Res Clin Oncol. 2005;131(8):527-38.
21. Effects of Agaricus brasiliensis mushroom in Walker-256 tumor-bearing rats. Jumes F.M, Lugarini D, Pereira A.L, de Oliveira A, Christoff Ade O, Linde G.A, do Valle J.S, Colauto N.B, Acco A. Can J Physiol Pharmacol. 2010;88(1):21-7.
22. Inhibitory mechanisms of Agaricus blazei Murill on the growth of prostate cancer in vitro and in vivo. Yu C.H, Kan S.F, Shu C.H, Lu T.J, Sun-Hwang L, Wang P.S. J Nutr Biochem. 2009;20(10):753-64.
23. Immunomodulating activity of Agaricus brasiliensis KA21 in mice and in human volunteers. Liu Y, Fukuwatari Y, Okumura K, Takeda K, Ishibashi KI, Furukawa M, Ohno N, Mori K, Gao M, Motoi M. Evid Based Complement Alternat Med. 2008;5(2):205-219.
24. Natural killer cell activity and quality of life were improved by consumption of a mushroom extract, Agaricus blazei Murill Kyowa, in gynecological cancer patients undergoing chemotherapy. Ahn W.S, et al. Int J Gynecol Cancer 2004;14(4):589-594.
25. Clinical observation on treatment of acute non lymphocytic leukemia with Agaricus blazei. X. Tian, Z. Lun and H. Ito. J. Lanzhou Med. Coll. 20 (1994), pp. 169–171
26. Observation on treatment effect of Agaricus blazei against alimentary tract tumor. Wang J., Mou X.M. and Cheng R.Z. Gansu Med J. 1994;13:5–7
27. White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation. Grube B.J, Eng E.T, Kao Y.C, Kwon A, Chen S. J Nutr. 2001;131(12):3288-93.
28. Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus). Chen S, Oh S.R, Phung S, Hur G, Ye J.J, Kwok S.L, Shrode G.E, Belury M, Adams L.S, Williams D. Cancer Res. 2006;66(24):12026-34.
29. Medicinal properties and clinical effects of culinary-medicinal mushroom Agaricus blazei Murrill (Agaricomycetideae) (Review). Mizuno T. Int J Med Mushr 2002;4:299–312.
30. Agaricus blazei (Himematsutake) does not alter the development of rat diethylnitrosamine-initiated hepatic preneoplastic foci. Barbisan L.F, Spinardi-Barbisan A.L, Moreira E.L, Salvadori D.M, Ribeiro L.R, da Eira A.F, de Camargo J.L. Cancer Sci. 2003;94(2):188-92.
31. Screening for in vitro and in vivo antitumor activities of the mushroom Agaricus blazei. Ziliotto L, Pinheiro F, Barbisan L.F, Rodrigues M.A. Nutr Cancer. 2009;61(2):245-50
32. Variation of the antimutagenicity effects of water extracts of Agaricus blazei Murrill in vitro. Guterrez Z.R, Mantovani M.S, Eira A.F, Ribeiro L.R, Jordão B.Q. Toxicol In Vitro. 2004;18(3):301-9
33. Effects of the medicinal mushroom Agaricus blazei Murill on immunity, infection and cancer. Hetland G, Johnson E, Lyberg T, Bernardshaw S, Tryggestad A.M, Grinde B. Scand J Immunol. 2008;68(4):363-70
34. An extract of the medicinal mushroom Agaricus blazei Murill can protect against allergy. Ellertsen L.K, Hetland G. Clin Mol Allergy. 2009:5;7-6.
35. The mushroom Agaricus blazei Murill extract normalizes liver function in patients with chronic hepatitis B. Hsu C.H, Hwang K.C, Chiang Y.H, Chou P. J Altern Complement Med. 2008;14(3):299-301
36. Clinical utility of ABCL (Agaricus Mushroom Extract) treatment for C-type hepatitis. Jpn Pharmacol Ther. 2002;30:103-7
37. Observation on the treatment effect of Agaricus blazei to the liver function of chronic hepatitis patients. Wang L. and Ma H. J Lanzhou Med Coll. 2004;20:24–26
38. An alternative medicine, Agaricus blazei, may have induced severe hepatic dysfunction in cancer patients. Mukai H, Watanabe T, Ando M, Katsumata N. Jpn J Clin Oncol. 2006 Dec;36(12):808-10.
39. Cheilitis due to Agaricus blazei Murill mushroom extract. Suehiro M, Katoh N, Kishimoto S. Contact Dermatitis. May 2007;56(5):293-294

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