Almond Mushroom (Royal / Sun Agaric) – Agaricus subrufescens

Japanese nameHimematsutake
Chinese nameJi Song Rong
Portuguese nameCogumela del Sol

Although commonly known as Agaricus blazei Murrill (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. Recent analysis however, indicates that this is the same mushroom first identified by Charles Horton Peck in 1893 and called A. subrufescens and that this name should therefore have precedence2,3.

Although one of the newest medicinal mushrooms, A. subrufescens is rapidly becoming one of the most popular. Reported in a recent survey as being taken by 31% of urological cancer patients in Japan4, with the fastest growing US sales of any medicinal mushroom5 and one of the three most popular medicinal mushrooms in Taiwan, this relative of the common button mushroom, A. bisporus, exhibits broad clinical activity6. 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 antitumour activity7-18. Interestingly there appears to be an increase in structural diversity of its polysaccharides with maturation of the fruiting body19. A. subrufescens also contains high levels of lipids, including linoleic acid, oleic acid, stearic acid and ergosterol20.

CANCERA. subrufescens 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 radiotherapy21.

In a rat cachexia model A. subrufescens extracts, as well as powdered fruiting body, significantly reduced tumour size and promoted gain in body weight with reduction in AST levels and increased glycaemia22, while an in vivo study using severely immunodeficient mice found A. subrufescens polysaccharides to directly inhibit the growth of prostate cancer cells via an apoptotic pathway and to suppress prostate tumour growth via anti-proliferative and anti-angiogenic mechanisms with the greatest activity found in the broth fraction (compounds extracted from the liquid growth medium in which the mycelium was grown) rather than the mushroom itself23. A 2008 study reported significant increases in the NK cell activity of human volunteers given A. subrufescens polysaccharide extract at a dose of 3g/day compared to placebo24,while Ahn reports increased NK-cell activity and reduced chemotherapy-related side effects (appetite loss, alopecia, emotional stability and general weakness) from A. subrufescens polysaccharide extract in one hundred cervical, ovarian, and endometrial cancer patients treated either with carboplatin plus VP16 (etoposide) or with carboplatin plus taxol25. In two small Chinese clinical studies, a dose of 20g A. subrufescens fruiting body, taken twice daily as a tea, was reported to improve haematopoietic parameters and treatment outcomes in patients receiving chemotherapy for acute non-lymphocytic leukaemia in one study and improvement in immune status, haematopoietic parameters and quality of life measures in late stage alimentary tract tumours in another26,27.

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. subrufescens in a number of mainly breast cancer patients but at unspecified dosage28-30.

Although most of the published research strongly supports the use of A. subrufescens in cancer therapy, two studies studies looking at the protective properties of A. subrufescens have been published with negative outcomes (in one A. subrufescens given at 5% of diet did not have a suppressive effect on colon carcinogenesis in rats exposed to dimethylhydrazine, in another an aqueous extract did not affect the development of liver cancer induced by diethylnitrosamine). In a third study A. subrufescens supplementation failed to produce significant change in TNF-α, IFN-γ or IL-10 levels in immunosuppressed mice and it appears that there may be significant variation in activity between different extracts, as well as between different strains31-35.

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 extract24.

ALLERGIES – As potent immune modulators mushroom polysaccharides can reduce the level of Th2-mediated allergic reactions and A. subrufescens is no exception with Andosan, a proprietary combination of polysaccharide extracts from A. subrufescens (82%), H. erinaceus (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 cells36,37.

HEPATOPROTECTIVE – There is evidence from a number of small clinical studies indicating possible application of A. subrufescens in the treatment of chronic hepatitis. In one study 1500mg of polysaccharide 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 4638. In another A. subrufescens extract reduced GTP in 80% of 20 patients with hepatitis C39. 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 spleen40. One in vivo study also indicates therapeutic potential of A. subrufescens polysaccharide extract for alcoholic liver injury with 100mg/kg body weight producing improvements in liver enzymes as well as liver histology and mitochondrial membrane potential41.

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 also supports the use of mycelial biomass or of mycelial biomass/polysaccharide extract combinations.
Safety – Although A. subrufescens (like the common button mushroom A. bisporus) contains agaritine, a hydrazine-derived mycotoxin and group 3 carcinogen, this rapidly oxidises on exposure to air and during cooking with multiple studies confirming the safety of A. subrufescens as a functional food42-45.
One animal study showed A. subrufescens to enhance local and systemic inflammation with possible implications for development of atherosclerosis although a randomized clinical trial in elderly women showed no changes in cytokine levels46,47. Another report suggested a possible connection between consumption of an A. subrufescens extract and three cases of hepatic dysfunction in cancer patients, although the authors state that several other causative factors cannot be completely ruled out48. Cheilitis due to an A. subrufescens extract has also been reported49.

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4. 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(9):685–690.
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6. 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.
7. 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):363–366.
8. Structural characterization of a water-soluble β-d-glucan from fruiting bodies of Agaricus blazei Murrill. Dong Q, Yao J, Yang XT, Fang JN. Carbohydr Res. 2007;337(15):1417–1421.
9. Antitumour beta-glucan from the cultured fruit body of Agaricus blazei. Ohno N, Furukawa M, Miura NN, Adachi Y, Motoi M, Yadomae T. Biol Pharm Bull. 2004;24(7):820–828.
10. 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(1A):113–118.
11. Immunostimulatory activities of a low molecular weight antitumoral polysaccharide isolated from Agaricus blazei Murill (LMPAB) in Sarcoma 180 ascitic tumor-bearing mice. Niu YC, Liu JC, Zhao XM, Su FQ, Cui HX. Pharmazie. 2009;64(7):472–476.
12. Isolation and characterization of polysaccharides from Agaricus blazei Murrill. Gonzaga MLC, Ricardo NMPS, Heatley F, Soares SA. Carbohydr Polym. 2005;60(1):43–49.
13. 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(4):259–265.
14. 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, Nakamura T. Carbohydr Res. 1989;186(2):267–273.
15. Oral administration of Agaricus brasiliensis. S. Wasser et al. (Agaricomycetideae) extract downregulates serum immunoglobulin E levels by enhancing Th1 response. Morimoto T, Takagi M, Mizuno M. Int J Med Mushrooms. 2008;10(1):15–24.
16. An extract based on the medicinal mushroom Agaricus blazei Murill stimulates monocyte-derived dendritic cells to cytokine and chemokine production in vitro. Førland DT, Johnson E, Tryggestad AM, Lyberg T, Hetland G. Cytokine. 2010;49(3):245–250.
17. 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 DT, Saetre L, Bernardshaw SV, Lyberg T, Hetland G. Scand J Immunol. 2009;69(3):242–250.
18. Peroral effect on tumor progression of soluble β-(1-6)-glucans prepared by acid treatment from Agaricus blazei Murill. Fujiyama Y, Yamomoto H, Noji M, Suzuki I. Int J Med Mushrooms. 2000;2(1):43-49.
19. Structural characterization of beta-glucans of Agaricus brasiliensis in different stages of fruiting body maturity and their use in nutraceutical products. Camelini CM, Maraschin M, de Mendonça MM, Zucco C, Ferreira AG, Tavares LA. Biotechnol Lett. 2005;27(17):1295–1299.
20. 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(5):1409–1413.
21. 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):527–538.
22. Effects of Agaricus brasiliensis mushroom in Walker-256 tumour-bearing rats. Jumes FM, Lugarini D, Pereira AL, de Oliveira A, Christoff Ade O, Linde GA, do Valle JS, Colauto NB, Acco A. Can J Physiol Pharmacol. 2010;88(1):21–27.
23. Inhibitory mechanisms of Agaricus blazei Murill on the growth of prostate cancer in vitro and in vivo. Yu CH, Kan SF, Shu CH, Lu TJ, Sun-Hwang L, Wang PS. J Nutr Biochem. 2009;20(10):753–764.
24. Immunomodulating activity of Agaricus brasiliensis KA21 in mice and in human volunteers. Liu Y, Fukuwatari Y, Okumura K, Takeda K, Ishibashi K, Furukawa M, Ohno N, Mori K, Gao M, Motoi M. Evid Based Complement Alternat Med. 2008;5(2):205–219.
25. 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 WS, Kim DJ, Chae GT, Lee JM, Bae SM, Sin JI, Kim YW, Namkoong SE, Lee IP. Int J Gynecol Cancer. 2004;14(4):589–594.
26. Clinical observation on treatment of acute non lymphocytic leukaemia with Agaricus blazei. Tian XH, Liu ZG, Wang J, Ito H, Shimura K, Wang JZ. J Lanzhou Med Coll. 1994;20(3):169–171.
27. Observation on treatment effect of Agaricus blazei against alimentary tract tumour. Wang J, Mao XM, Cheng RZ, Wang JZ, Ito H, Shimura K. Gansu Med J. 1994;13(1):5–6.
28. White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation. Grube BJ, Eng ET, Kao YC, Kwon A, Chen S. J Nutr. 2001;131(12):3288–3293.
29. Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus). Chen S, Oh SR, Phung S, Hur G, Ye JJ, Kwok SL, Shrode GE, Belury M, Adams LS, Williams D. Cancer Res. 2006;66(24):12026–12034.
30. Medicinal properties and clinical effects of culinary-medicinal mushroom Agaricus blazei Murrill (Agaricomycetideae) (Review). Mizuno T. Int J Med Mushrooms. 2002;4(4):299–312.
31. Agaricus blazei (Himematsutake) does not alter the development of rat diethylnitrosamine-initiated hepatic preneoplastic foci. Barbisan LF, Spinardi-Barbisan AL, Moreira EL, Salvadori DM, Ribeiro LR, da Eira AF, de Camargo JL. Cancer Sci. 2003;94(2):188–192.
32. Screening for in vitro and in vivo antitumor activities of the mushroom Agaricus blazei. Ziliotto L, Pinheiro F, Barbisan LF, Rodrigues MA. Nutr Cancer. 2009;61(2):245–250.
33. Aqueous extract of culinary-medicinal Royal Sun mushroom, Agaricus brasiliensis S. Wasser et al. (Agaricomycetideae) effects on immunodepression in mice. Fantuzzi E, Anastacio LR, Nicoli JR, de Paula SO, Esteves Arantes RM, da Matta SLP, Vanetti MCD. Int J Med Mushrooms. 2010;12(3):227–234.
34. Variation of the antimutagenicity effects of water extracts of Agaricus blazei Murrill in vitro. Guterrez ZR, Mantovani MS, EiraAF, Ribeiro LR, Jordão BQ. Toxicol In Vitro. 2004;18(3):301–309.
35. Effects of the medicinal mushroom Agaricus blazei Murill on immunity, infection and cancer. Hetland G, Johnson E, Lyberg T, Bernardshaw S, Tryggestad AM, Grinde B. Scand J Immunol. 2008;68(4):363–370.
36. Oral treatment with extract of Agaricus blazei Murill enhanced Th1 response through intestinal epithelial cells and suppressed OVA-sensitized allergy in mice. Bouike G, Nishitani Y, Shiomi H, Yoshida M, Azuma T, Hashimoto T, Kanazawa K, Mizuno M. Evid Based Complement Alternat Med. 2011;2011. pii: 532180.
37. An extract of the medicinal mushroom Agaricus blazei Murill can protect against allergy. Ellertsen LK, Hetland G. Clin Mol Allergy. 2009;7:6.
38. The mushroom Agaricus blazei Murill extract normalizes liver function in patients with chronic hepatitis B. Hsu CH, Hwang KC, Chiang YH, Chou P. J Altern Complement Med. 2008;14(3):299–301.
39. Clinical utility of ABCL (Agalicus Mushroom Extract) treatment for C-type hepatitis. Jpn Pharmacol Ther. 2002;30(2):103–107.
40. Observation on the treatment effect of Agaricus blazei to the liver function of chronic hepatitis patients. Wang LR, Feng QR, Xu XY, Ma HL, Wang JZ, Ito H, Shimura K. J Lanzhou Med Coll. 1994;20(1):24–26.
41. Effects of polysaccharide from fruiting bodies of Agaricus bisporus, Agaricus brasiliensis, and Phellinus linteus on alcoholic liver injury. Uyanoglu M, Canbek M, van Griensven LJ, Yamac M, Senturk H, Kartkaya K, Oglakcı A, Turgak O, Kanbak G. Int J Food Sci Nutr. 2014;65(4):482–488.
42. Medical mushrooms used for biochemical failure after radical treatment for prostate cancer: an open-label study. Yoshimura K, Kamoto T, Ogawa O, Matsui S, Tsuchiya N, Tada H, Murata K, Yoshimura K, Habuchi T, Fukushima M. Int J Urol. 2010;17(6):548–554.
43. Phase I clinical study of the dietary supplement, Agaricus blazei Murill, in cancer patients in remission. Ohno S, Sumiyoshi Y, Hashine K, Shirato A, Kyo S, Inoue M. Evid Based Complement Alternat Med. 2011;2011:192381.
44. Safety study of culinary-medicinal Royal Sun Agaricus, Agaricus brasiliensis S. Wasser et al. KA21 (higher Basidiomycetes) assessed by prokaryotic as well as eukaryotic systems. Motoi M, Ohno N. Int J Med Mushrooms. 2012;14(2):135–148.
45. Royal sun medicinal mushroom, Agaricus brasiliensis Ka21 (higher Basidiomycetes), as a functional food in humans. Yamanaka D, Liu Y, Motoi M, Ohno N. Int J Med Mushrooms. 2013;15(4):335–343.
46. Pro-inflammatory effects of the mushroom Agaricus blazei and its consequences on atherosclerosis development. Gonçalves JL, Roma EH, Gomes-Santos AC, Aguilar EC, Cisalpino D, Fernandes LR, Vieira AT, Oliveira DR, Cardoso VN, Teixeira MM, Alvarez-Leite JI. Eur J Nutr. 2012;51(8):927–937.
47. Agaricus blazei Murrill and inflammatory mediators in elderly women: a randomized clinical trial. Lima CU, Souza VC, Morita MC, Chiarello MD, Karnikowski MG. Scand J Immunol. 2012;75(3):336–341.
48. 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;36(12):808–810.
49. Cheilitis due to Agaricus blazei Murill mushroom extract. Suehiro M, Katoh N, Kishimoto S. Contact Dermatitis. 2007;56(5):293–294.