Agaricus

• How It Works

  Agaricus extract may benefit patients with certain cancers, but more studies are needed to confirm these observations.

  Agaricus blazei is an edible mushroom grown in Brazil and Japan. It is used to treat arteriosclerosis, hepatitis, hyperlipidemia, diabetes, dermatitis, and cancer. Laboratory studies and experiments done in mice have shown that agaricus can stimulate the immune system and has anticancer effects. Compounds present in agaricus may prevent the formation of blood vessels needed for tumor development.

• Purported Uses
  • Arteriosclerosis
    There are no clinical data to support this use.
  • Cancer treatment
    One study showed that oral agaricus extract improved quality of life in patients with gynecological cancers.
  • Chronic hepatitis
    Agaricus is used in traditional medicine to treat hepatitis. A small clinical study showed that agaricus helps improve liver function in patients with hepatitis B.
  • Diabetes
    There are limited laboratory data suggesting that agaricus mushroom has antidiabetic effects. One small clinical study showed that agaricus reduced blood glucose levels in healthy subjects.
  • Hyperlipidemia
    One small clinical study showed that agaricus reduced cholesterol level in healthy subjects.
  • Stimulant
    There are no clinical data to support this use.
• Do Not Take If
  • You are allergic to agaricus or other mushrooms.
  • You are taking drugs that are substrates of Cytochrome P450 3A4: Agaricus may increase the risk of side effects of these drugs.
• Side Effects
  • May cause liver damage in cancer patients.
  • Reports of lip swelling.
• Scientific Name

  Agaricus blazei Murrill

• Clinical Summary

  Agaricus blazei is an edible mushroom native to Brazil and is cultivated in Japan for medicinal uses. It has been used to treat arteriosclerosis, hepatitis, hyperlipidemia, diabetes, dermatitis, and cancer. Polysaccharides and antiangiogenic compounds present in agaricus may be responsible for its antitumor properties. Agaricus was also shown to have antidiabetic effects in vitro and in animal studies ^(8) (9).

  In humans, studies of agaricus extracts suggest benefits including improved insulin resistance in diabetic patients ^(10) (11), reduced weight, body fat, serum glucose, and cholesterol levels in healthy individuals ⁽¹²⁾, and improved quality of life in patients with ulcerative colitis ⁽³⁰⁾.

  Antitumor and immunomodulatory effects of agaricus have also been shown ^{(3) (4) (6) (21) (22)}. An agaricus extract enhanced doxorubicin-induced apoptosis against drug-resistant human hepatocellular carcinoma ⁽²⁴⁾. Oral agaricus extract improved natural killer cell activity and quality of life in gynecological cancer patients undergoing chemotherapy ⁽⁷⁾. Other preliminary data show that daily intake of agaricus powder improves quality of life among cancer patients in remission ⁽²⁶⁾. Although no survival improvements with agaricus extract supplementation were reported in multiple myeloma patients, immunomodulatory effects were observed ⁽²⁹⁾. Agaricus extract did not confer any benefits in elderly females ⁽²⁵⁾. Larger studies are needed to resolve the ambiguity.

  Whereas a small study reported that agaricus extract may improve liver function in patients with hepatitis B ⁽¹³⁾, liver damage and deaths ⁽¹⁴⁾ along with cheilitis ⁽¹⁵⁾ have been reported following consumption. Brefeldin A, a compound isolated from agaricus, was shown to have estrogenic activity, but did not stimulate growth of breast cancer cells ⁽²⁷⁾.

• Food Sources

  Agaricus is an edible fungus. It is available as freeze-dried mushrooms or as concentrated liquid extracts, teas, or capsules. The whole mushroom is often added to soups, sauces, or hot teas.

• Purported Uses
  • Arteriosclerosis
  • Cancer treatment
  • Diabetes
  • Hepatitis
  • Hyperlipidemia
  • Stimulant
• Mechanism of Action

  Agaricus extract was shown to exert estrogen-like activity and may help prevent atherosclerosis via dual roles in cell signaling, macrophage development suppression and endothelial cell recovery from vascular damage ⁽¹⁶⁾. Both aqueous and organic extracts of agaricus offered protection to cells exposed to methyl methanesulphonate, a mutagenic agent. The stimulus produced by linoleic acid on beta-DNA polymerase, an enzyme involved in repair mechanism following exposure of DNA to alkylating agents, is thought responsible for such an effect ⁽¹⁹⁾.

  Ergosterol, a major constituent of agaricus, was found to inhibit tumor growth in mice via direct inhibition of tumor-induced angiogenesis ⁽⁶⁾. Other studies demonstrated that polysaccharides present in agaricus extract caused activation of macrophages ⁽⁵⁾ or natural killer cells ⁽¹⁷⁾ and induced cytotoxic T-lymphocyte activity in tumor-bearing mice. Specifically, activation of natural killer cells was mediated through IL-12-induced IFN-gamma expression ⁽¹⁸⁾. Agaricus extract stimulates caspase 3 activation and reduces telomerase activity ⁽¹⁹⁾ possibly through regulation of Akt signaling ⁽²⁰⁾ thereby inducing apoptosis in cancer cell lines. Blazeispirol A, produced by agaricus fermentation, causes both caspase-dependent and -independent cell death in human Hep 3B cells ⁽²¹⁾. Agaritine, a hydrazine-containing constituent also exhibits antitumor activity toward U937 leukemic cells mediated through apoptosis ⁽²²⁾. In another study, polysaccharides isolated from agaricus were shown to induce apoptosis in HL-60 cells through a signaling cascade of mitochondrial caspase-3-dependent pathway ⁽²⁸⁾.

• Contraindications
  • An in vitro study suggests that agaricus extract has estrogen-like activity ⁽¹⁶⁾ and therefore should be used with caution. Patients with hormone-sensitive cancers should discuss its use with their physician.
  • Hypersensitivity to agaricus.
• Adverse Reactions
  • Consumption of agaricus has been associated with hepatic dysfunction in cancer patients ⁽¹⁴⁾.
  • Cheilitis has also been reported ⁽¹⁵⁾.
• Herb-Drug Interactions

  Cytochrome P450 substrates: Agaricus inhibits CYP3A4 and can affect the intracellular concentration of drugs metabolized by this enzyme ⁽²³⁾.

• Herb Lab Interactions
  • May lower blood glucose level ⁽⁸⁾.
  • May cause an elevation of liver enzymes ⁽¹⁴⁾.
• References

  1. Fujimiya Y, Suzuki Y, Oshiman K, et al. Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis. Cancer Immunol Immunother. May 1998;46(3):147-159.

  2. Itoh H, Ito H, Amano H, et al. Inhibitory action of a (1—>6)-beta-D-glucan-protein complex (F III-2-b) isolated from Agaricus blazei Murill (“himematsutake”) on Meth A fibrosarcoma-bearing mice and its antitumor mechanism. Jpn J Pharmacol. Oct 1994;66(2):265-271.

  3. Kimura Y, Kido T, Takaku T, et al. Isolation of an anti-angiogenic substance from Agaricus blazei Murill: its antitumor and antimetastatic actions. Cancer Sci. Sep 2004;95(9):758-764.

  4. Lee YL, Kim HJ, Lee MS, et al. Oral administration of Agaricus blazei (H1 strain) inhibited tumor growth in a sarcoma 180 inoculation model. Exp Anim. Oct 2003;52(5):371-375.

  5. Mizuno M, Morimoto M, Minato K, et al. Polysaccharides from Agaricus blazei stimulate lymphocyte T-cell subsets in mice. Biosci Biotechnol Biochem. Mar 1998;62(3):434-437.

  6. Takaku T, Kimura Y, Okuda H. Isolation of an antitumor compound from Agaricus blazei Murill and its mechanism of action. J Nutr. May 2001;131(5):1409-1413.

  7. Ahn WS, Kim DJ, Chae GT, et al. 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. Int J Gynecol Cancer. Jul-Aug 2004;14(4):589-594.

  8. Gray AM, Flatt PR. Insulin-releasing and insulin-like activity of Agaricus campestris (mushroom). J Endocrinol. May 1998;157(2):259-266.

  9. Swanston-Flatt SK, Day C, Flatt PR, et al. Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetes Res. Feb 1989;10(2):69-73.

  10. Kim YW, Kim KH, Choi HJ, et al. Anti-diabetic activity of beta-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei. Biotechnol Lett. Apr 2005;27(7):483-487.

  11. Hsu CH, Liao YL, Lin SC, et al. The mushroom Agaricus blazei Murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes: a randomized, double-blinded, and placebo-controlled clinical trial. J Altern Complement Med. Jan-Feb 2007;13(1):97-102.

  12. Liu Y, Fukuwatari Y, Okumura K, et al. Immunomodulating Activity of Agaricus brasiliensis KA21 in Mice and in Human Volunteers. Evid Based Complement Alternat Med. Jun 2008;5(2):205-219.

  13. Hsu CH, Hwang KC, Chiang YH, et al. The mushroom Agaricus blazei Murill extract normalizes liver function in patients with chronic hepatitis B. J Altern Complement Med. Apr 2008;14(3):299-301.

  14. Mukai H, Watanabe T, Ando M, et al. An alternative medicine, Agaricus blazei, may have induced severe hepatic dysfunction in cancer patients. Jpn J Clin Oncol. Dec 2006;36(12):808-810.

  15. Suehiro M, Katoh N, Kishimoto S. Cheilitis due to Agaricus blazei Murill mushroom extract. Contact Dermatitis. May 2007;56(5):293-294.

  16. Dong S, Furutani Y, Suto Y, et al. Estrogen-like activity and dual roles in cell signaling of an Agaricus blazei Murrill mycelia-dikaryon extract. Microbiol Res. Oct 17 2011.

  17. Takimoto H, Wakita D, Kawaguchi K, et al. Potentiation of cytotoxic activity in naive and tumor-bearing mice by oral administration of hot-water extracts from Agaricus brazei fruiting bodies. Biol Pharm Bull. Mar 2004;27(3):404-406.

  18. Yuminamochi E, Koike T, Takeda K, et al. Interleukin-12- and interferon-gamma-mediated natural killer cell activation by Agaricus blazei Murill. Immunology. Jun 2007;121(2):197-206.

  19. Gao L, Sun Y, Chen C, et al. Primary mechanism of apoptosis induction in a leukemia cell line by fraction FA-2-b-ss prepared from the mushroom Agaricus blazei Murill. Braz J Med Biol Res. Nov 2007;40(11):1545-1555.

  20. Jin CY, Moon DO, Choi YH, et al. Bcl-2 and caspase-3 are major regulators in Agaricus blazei-induced human leukemic U937 cell apoptosis through dephoshorylation of Akt. Biol Pharm Bull. Aug 2007;30(8):1432-1437.

  21. Su ZY, Tung YC, Hwang LS, et al. Blazeispirol A from Agaricus blazei fermentation product induces cell death in human hepatoma Hep 3B cells through caspase-dependent and caspase-independent pathways. J Agric Food Chem. May 11 2011;59(9):5109-5116.

  22. Akiyama H, Endo M, Matsui T, et al. Agaritine from Agaricus blazei Murrill induces apoptosis in the leukemic cell line U937. Biochim Biophysica Acta. May 2011;1810(5):519-525.

  23. Engdal S, Nilsen OG. In vitro inhibition of CYP3A4 by herbal remedies frequently used by cancer patients. Phytother Res. 2009 Jul;23(7):906-12.

  24. Lee JS, Hong EK. Agaricus blazei Murill enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells by NFκB-mediated increase of intracellular doxorubicin accumulation. Int J Oncol. 2011 Feb;38(2):401-8.

  25. Lima CU, Souza VC, Morita MC, Chiarello MD, Karnikowski MG. Agaricus blazei Murrill and inflammatory mediators in elderly women: a randomized clinical trial. Scand J Immunol. 2012 Mar;75(3):336-41.

  26. Ohno S, Sumiyoshi Y, Hashine K, Shirato A, Kyo S, Inoue M. Quality of life improvements among cancer patients in remission following the consumption of Agaricus blazei Murill mushroom extract. Complement Ther Med. 2013 Oct;21(5):460-7.

  27. Dong S, Furutani Y, Kimura S, et al. Brefeldin A is an estrogenic, Erk1/2-activating component in the extract of Agaricus blazei mycelia. J Agric Food Chem. 2013 Jan 9;61(1):128-36.

  28. Li X, Zhao X, Wang H, Han J, Liu L.A polysaccharide from the fruiting bodies of Agaricus blazei Murill induces caspase-dependent apoptosis in human leukemia HL-60 cells. Tumour Biol. 2014 Sep;35(9):8963-8.

  29. Tangen JM, Tierens A, Caers J, et al. Immunomodulatory Effects of the Agaricus blazei Murrill-Based Mushroom Extract AndoSan in Patients with Multiple Myeloma Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplantation: A Randomized, Double Blinded Clinical Study. Biomed Res Int. 2015;2015:718539.

  30. Therkelsen SP, Hetland G, Lyberg T, Lygren I, Johnson E. Effect of a Medicinal Agaricus blazei Murill-Based Mushroom Extract, AndoSan™, on Symptoms, Fatigue and Quality of Life in Patients with Ulcerative Colitis in a Randomized Single-Blinded Placebo Controlled Study. PLoS One. 2016 Mar 2;11(3):e0150191.