Leading Research Institution, Sloan-Kettering, Gives Agaricus Positive Review

Recently the Sloan-Kettering research institution rated Agaricus blazei. The institution has a page for Agaricus blazei designed for advice for health care professionals as well as consumers. To view the page visit this web address: http://www.mskcc.org/mskcc/html/69112.cfm According to the consumer page, Agaricus is noted for being potentially beneficial for cancer, diabetes, and cholesterol.

The page gives conflicting advice about Agaricus and the liver. The page points out an extremely small case study of 3 people in which Agaricus may have caused liver problems. Another small case study of 4 people showed Agaricus was beneficial for normalizing liver function. (Normalizing liver function study: http://www.ncbi.nlm.nih.gov/pubmed/18370584
Case study showing possible Agaricus liver problems: http://www.ncbi.nlm.nih.gov/pubmed/17105737)

Given the fact that Agaricus is consumed by a half million people, (See introduction of this paper for more info: http://jn.nutrition.org/cgi/content/full/131/5/1409) any potential toxicities/liver problems would have already been brought to the public's attention.

Research Shows Agaricus blazei Beneficial for Blood Sugar Control

Research has demonstrated that Agaricus blazei may be beneficial for supporting healthy blood sugar levels. An experiment with rats, conducted in 2005 showed that the mushroom improved the animal's insulin response. In 2007, a human study, which was randomized, doubled blinded, and placebo controlled, noted that the mushroom improved insulin response possibly by way of boosting adiponectin levels. In 2009, a human study which was also randomized, doubled blinded, and placebo controlled, noted that the
mushroom lowered blood sugar levels in all 56 subjects being researched.

References:
Kim YW, Kim KH, Choi HJ, Lee DS (April 2005). "Anti-diabetic activity of beta-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei". Biotechnol. Lett. 27 (7): 483–7. doi:10.1007/s10529-005-2225-8. PMID 15928854.

http://www.ncbi.nlm.nih.gov/pubmed/15928854

Hsu CH, Liao YL, Lin SC, Hwang KC, Chou P. (January-February 2007), "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. 13 (1): 97-102, PMID 17309383

http://www.ncbi.nlm.nih.gov/pubmed/17309383

Fortes RC, Novaes MR, Recôva VL, Melo AL. (January 2009), "Immunological, hematological, and glycemia effects of dietary supplementation with Agaricus sylvaticus on patients' colorectal cancer.", Exp Biol Med (Maywood). 234 (1): 53-62, doi:10.3181/0806-RM-193, PMID 18997106

http://www.ncbi.nlm.nih.gov/pubmed/18997106

Agaricus blazei vs. Viruses

Research has indicated Agaricus blazei (ABM) has an antagonistic relationship with viruses. In vitro research has indicated Agaricus blazei directly inhibits certain viruses such as the Poliovirus(1) and the Western equine encephalitis virus(2). Like other mushrooms, Agaricus blazei probably has an inhibitory effect on a much larger variety of viruses, although this has yet to be tested.

Two interesting in vivo experiments noted that Agaricus blazei could improve the efficiency of vaccination. The two experiments, which were conducted on mice, showed that ABM improved the ability of the Hepatitis B vaccine(3) as well as the vaccine for the foot-and-mouth disease virus(4). Researchers noted that mice treated with ABM produced a higher amount of antibody production specific to the vaccine. Researchers also noted that mice treated with ABM produced a higher number of T cells, important white blood cells of the immune system.

Reference:
1. Faccin LC, Benati F, Rincão VP, Mantovani MS (Jul 2007), "Antiviral activity of aqueous and ethanol extracts and of an isolated polysaccharide from Agaricus brasiliensis against poliovirus type 1.", Lett Appl Microbiol. 45 (1): 24-8, PMID 17594456
2. Sorimachi K, Ikehara Y, Maezato G (Jul 2001), "Inhibition by Agaricus blazei Murill fractions of cytopathic effect induced by western equine encephalitis (WEE) virus on VERO cells in vitro.", Biosci Biotechnol Biochem. 65 (7): 1645-7, PMID 11515550
3. Chen L, Shao HJ, Su YB (March 2004), "Coimmunization of Agaricus blazei Murill extract with hepatitis B virus core protein through DNA vaccine enhances cellular and humoral immune responses", Int Immunopharmacol 4 (3): 403–409, doi:10.1016/j.intimp.2003.12.015, PMID 15037217
4. Chen L, Shao H (15 January 2006), "Extract from Agaricus blazei Murill can enhance immune responses elicited by DNA vaccine against foot-and-mouth disease", Veterinary Immunology and Immunopathology 109 (1-2): 177–182, doi:10.1016/j.vetimm.2005.08.028, PMID 16213597

ABM as a cellular health Promotor

Agaricus blazei (ABM) has demonstrated a variety of ways it promotes cellular health. In vitro research has shown that ABM can induce apoptosis (shut down) unhealthy cells of the blood(1), ovaries(2), and fibrous connective tissue(3). In vitro research demonstrated ABM prevented the development of unhealthy cells of the liver(4).

Further in vitro research revealed that ABM had a protective effect on cells exposed to radiation(5) as well as cells exposed to the toxic chemical methyl methanesulphonate(6). In vitro research also demonstrated that healthy cells exposed to ABM were not damaged or adversly affected by ABM(7)(8)(9).

Reference:
1.Gao L, Sun Y, Chen C, Xi Y, Wang J, Wang Z (November 2007), "Primary mechanism of apoptosis induction in a leukemia cell line by fraction FA-2-b-β prepared from the mushroom Agaricus blazei Murill", Braz J Med Biol Res 40 (11): 1545–1555, doi:10.1590/S0100-879X2006005000181, PMID 17934651
2.Kobayashi H, Yoshida R, Kanada Y, Fukuda Y, Yagyu T, Inagaki K, Kondo T, Kurita N, Suzuki M, Kanayama N, Terao T (August 2005), "Suppressing effects of daily oral supplementation of beta-glucan extracted from Agaricus blazei Murill on spontaneous and peritoneal disseminated metastasis in mouse model", J Cancer Res Clin Oncol (Berlin; Heidelberg: Springer) 131 (8): 527–538, doi:10.1007/s00432-005-0672-1, PMID 15883813
3.Fujimiya Y, Suzuki Y, Oshiman K, Kobori H, Moriguchi K, Nakashima H, Matumoto Y, Takahara S, Ebina T, Katakura R (May 1998), "Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricusblazei Murill, mediated via natural killer cell activation and apoptosis.", Cancer Immunol Immunother (Springer Verlag) 46 (3): 147–159, doi:10.1007/s002620050473, PMID 9625538
4.Sorimachi K, Akimoto K, Koge T (February 2008), "Inhibitory effect of Agaricus blazei Murill components on abnormal collagen fiber formation in human hepatocarcinoma cells", Biosci Biotechnol Biochem 72 (2): 621–623, doi:10.1271/bbb.70700, PMID 18256462
5.Kubo N, Myojin Y, Shimamoto F, Kashimoto N, Kyo E, Kamiya K, Watanabe H (March 2005), "Protective effects of a water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi) mycelia and Agaricus blazei murill against X-irradiation in B6C3F1 mice: Increased small intestinal crypt survival and prolongation of average time to animal death", Int J Mol Med (Athens: D.A. Spandidos) 15 (3): 401–406, OCLC 39728400, PMID 15702228
6.Luiz RC, Jordão BQ, da Eira AF, Ribeiro LR, Mantovani MS (25 July 2003), "Mechanism of anticlastogenicity of Agaricus blazei Murill mushroom organic extracts in wild type CHO (K(1)) and repair deficient (xrs5) cells by chromosome aberration and sister chromatid exchange assays", Mutat Res (Amsterdam: Elsevier) 528 (1–2): 75–79, OCLC 1590350, PMID 12873725
7.Lee IP, Kang BH, Roh JK, Kim JR (January 2008), "Lack of carcinogenicity of lyophilized Agaricus blazei Murill in a F344 rat two year bioassay.", Food Chem Toxicol (New York: Pergamon) 46 (1): 87–95, doi:10.1016/j.fct.2007.07.001, PMID 17707568
8.Martins de Oliveira J, Jordão BQ, Ribeiro LR, Ferreira da Eira A, Mantovani MS (December 2002), "Anti-genotoxic effect of aqueous extracts of sun mushroom (Agaricus blazei Murill lineage 99/26) in mammalian cells in vitro", Food Chem Toxicol (New York: Pergamon) 40 (12): 1775–1780, doi:10.1016/S0278-6915(02)00156-4, PMID 12419691
9.Bellini MF, Giacomini NL, Eira AF, Ribeiro LR, Mantovani MS (August 2003), "Anticlastogenic effect of aqueous extracts of Agaricus blazei on CHO-k1 cells, studying different developmental phases of the mushroom", Toxicol in Vitro (Oxford; New York: Pergamon) 17 (4): 465–9, doi:10.1016/S0887-2333(03)00043-2, OCLC 13144158, PMID 12849730

Interleukin-12 fuels Natural Killer Cells and the Immune Response

Agaricus blazei (ABM) has demonstrated its ability to induce interluekin-12 in both in vitro as well as in vivo research.

In vitro research demonstrated ABM caused in increase in interleukin-12 production in human peripheral mononuclear cells (PBMC), monocytes, and macrophages.

In vivo research demonstrated ABM's effect on interleukin-12 in mice. Mice given ABM were noted to have increased activity of Natural Killer cells when compared to mice without ABM. Knowing Natural Killer cells are stimulated by interleukin-12, ABM was administered to mice which due to a genetic mutation, are unable to produce interleukin-12. These mice did not experience an increase in Natural Killer cell activity. This result strongly suggests that ABM increases Natural Killer cell activity by stimulating the production of interluekin-12.

Interleukin-12 has many jobs in the immune system. Some of its roles are presented below.

1. IL-12 increases activity of Natural Killer cells and T lymphocytes.
2. IL-12 stimulates production of interferon-gamma (IFN-γ) and tumor necrosis
factor-alpha (TNF-α), two important cytokines (signalling molecules) of the immune system.
3. Possible protection from food allergies due to research which has revealed a lack of IL-12 is associated with severe food allergys in animal models.


References:
Kasai H, He LM, Kawamura M, Yang PT, Deng XW, Munkanta M, Yamashita A, Terunuma H, Hirama M, Horiuchi I, Natori T, Koga T, Amano Y, Yamaguchi N, Ito M (2004), "IL-12 production induced by Agaricus blazei fraction H (ABH) involves toll-like receptor(TLR).",
Evid Based Complement Alternat Med 1 (3): 259–267, doi:10.1093/ecam/neh043, PMID 15841259

Yuminamochi E, Koike T, Takeda K, Horiuchi I, Okumura K (2007), "Interleukin-12- and interferon-gamma-mediated
natural killer cell activation by Agaricus blazei Murill", Immunology 121 (2): 197–206, doi:10.1111/j.1365-2567.2006.02558.x, PMID 17346284

Temblay JN, Bertelli E, Arques JL, Regoli M, Nicoletti C. Production of IL-12 by Peyer patch-dendritic cells is critical for the resistance to food allergy, J Allergy Clin Immunol. 2007 Sep;120(3):659-65. Epub 2007 Jun 28.
http://news.bbc.co.uk/2/hi/health/6254576.stm

TNF-α, a powerful tool of the Immune System

TNF-α (Tumor Necrosis Factor Alpha) is a chemical which is used by many immune system cells. A list of a few of its biological functions is presented below.

1. TNF-α is known to stimulate unhealthy cells of the body to shut down, an essential cellular process of the human body known as apoptosis.

2. Another role of TNF-α is to disrupt and inhibit the process of viruses and bacterial infections.

3. TNF-α also directs the processes of many different types of immune system cells. For example, TNF-α serves as a powerful attractant to signal neutrophils (the most common white blood cell of the immune system in the human body) to move to a specific location. TNF-α also increases the phagocytotic process of macrophages (the main process in which macrophages rid the body of pathogens and unhealthy cells).

Agaricus blazei (ABM) has demonstrated ability to induce TNF-α in both in vitro studies as well as in vivo studies. In vitro research has demonstrated ABM could increase TNF-α in two varieties of cell types, human monocytes and human umbilical vein endothelial cells.

In vivo research demonstrated ABM enhanced TNF-α in an animal model. In the particular experiment mice were infected with a lethal strain of the bacteria S. pneumoniae. Half of the mice received ABM prior to infection while the rest of the mice did not.
Scientists confirmed mice given ABM experienced an increase in
TNF-α (relative to mice not given ABM) by way of monitoring gene expression and gene products using microarrays and immunoassays. In addition, mice which received ABM had a higher rate of survival and lower rates of the lethal S. pneumoniae infection. Scientists concluded that since ABM had no antibiotic effect on S. pneumoniae, the increased resistance to S. pneumoniae was due to an upregulation of the immune system.


References:
Bernardshaw S, Hetland G, Ellertsen LK, Tryggestad AM, Johnson E (December 2005), "An extract of the medicinal mushroom Agaricus blazei Murill differentially stimulates production of pro-inflammatory cytokines in human monocytes and human vein endothelial cells in vitro", Inflammation 29 (4-6): 147–153, doi:10.1007/s10753-006-9010-2, PMID 17091395

Bernardshaw S, Johnson E, Hetland G (October 2005), "An extract of the mushroom Agaricus blazei Murill administered orally protects against systemic Streptococcus pneumoniae infection in mice", Scand J Immunol 62 (4): 393–398, doi:10.1111/j.1365-3083.2005.01667.x, PMID 16253127

Clinical Trial with Agaricus blazei Published

In 2009 a randomized, placebo-controlled, clinical trial documenting 6 months of Agaricus blazei consumption was published. The study revealed that consumption of the mushroom enhanced people's immune response. At the end of the study, subjects given Agaricus blazei increased their neutrophil levels (neutrophils are a type of white blood cell essential for the immune response).
http://www.atlasworldusa.com/

Economic Downturn Leaves Many Without Health Care Insurance

According to many news articles across the nation, people are having difficulty covering health care costs. Some find themselves unable to afford health care, while many others have lost health care coverage after losing work. To compensate, some people have resorted to healthier eating habits and consumption of health products.

The difference between natural health products and prescription drugs may not be as different than people might imagine. Examples abound in clinical drugs which have been isolated from nature. Examples of clinical drugs isolated from mushrooms also exist.

Penicillin, derived from Penicillium.
Lovastatin, derived from Aspergillus terreus.

Agaricus blazei could one day join the ranks of these mushrooms. According to a review published by UC Davis, in 2008, "Research on the large number of bioactive beta-glucans is urgently needed. Similar efforts should be undertaken to clarify the mechanisms of absorption and extent of bioavailability of other mushroom compounds, such as alpha-glucans and certain immunomodulatory proteins."

Agaricus blazei may enter the spotlight in the future, as it contains high concentrations of beta-glucans, alpha-glucans, and immunomodulatory proteins.

Reference:
Borchers AT, Krishnamurthy A, Keen CL, Meyers FJ, Gershwin ME (2008). "The Immunobiology of Mushrooms". Exp Biol Med 233 (3): 259–76. doi:10.3181/0708-MR-227. PMID 18296732.

Future Mushroom Research Shifts focus from the Immune System to Hormone Regulation

After the vast number of published studies demonstrating Agaricus blazei can stimulate a variety of important immune cells and their signaling molecules (cytokines), scientists have decided to look beyond the immune system to explain the health benefits offered by certain mushrooms.

Currently, there are human studies being conducted at the City of Hope Research Hospital in Duarte, California. There scientists are studying a “cousin” of Agaricus blazei, known as Agaricus bisporus, a mushroom in the genus Agaricus. Prior enzymatic assays done at City of Hope on isolated cells, have shown that Agaricus bisporus as well as Agaricus blazei inhibited the activity of enzymes aromatase and 5- alpha-reductase, enzymes responsible for the production of estrogen and dihydrotestosterone, respectively. Scientists have deemed this finding very intriguing and worth further study, due to the fact that elevated levels of estrogen and dihydrotestosterone have been strongly associated with various serious health conditions.

Reference:
Chen S, Oh SR, Phung S, Hur G, Ye JJ, Kwok SL, Shrode GE, Belury M, Adams LS, Williams D (December 2006). "Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus)". Cancer Res. 66 (24): 12026–34. doi:10.1158/0008-5472.CAN-06-2206. PMID 17178902

Mushroom Study Provides Dramatic Results

This month, a large case-control study examining the eating habits of 2,018 women, was published by researchers at the University of Western Australia. The study linked consumption of mushrooms with significant health protecting properties. Besides this important finding, researchers noticed a powerful synergistic effect between consumption of mushrooms and green tea, which was linked with dramatic health protecting benefits.

Researchers in the study pointed out that there was no difference in health benefits between fresh and dried mushroom consumption and according to the study, as little as one mushroom daily could offer a significant benefit. Researchers also noted that in addition to having a protective effect on subjects, mushrooms also seem to cut the malignancy of health conditions when they did appear. A positive correlation was also established between the amount of mushroom consumption and protective health benefits offered.

Another mushroom study might be published soon when scientists at the City of Hope Research Center in California finish investigating whether taking a mushroom extract twice a day for a month will offer benefits to patients with serious health issues. The study is focusing on the Agaricus bisporus mushroom, (a mushroom closely related to Agaricus blazei a mushroom which actually has lower levels of the biologically active compounds found in the Agaricus blazei mushroom.

Reference:
Zhang M, Huang J, Xie X. Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women. Int J Cancer 2009; 124(6); 1404-1408.

Interferon – γ, Trumpet Call of the Immune System

When the body first notices that its cells have been infected by bacteria, a virus, or are not functioning properly, natural killer cells (a type of immune cell) are the first to respond. Although, natural killer are efficient at eliminating these types of problematic cells, they often require the help of a more diverse group of specialized immune cells. The way in which natural killer cells recruit other immune cells, is by releasing a signaling molecule known as interferon–γ, or simply IFN-γ. When IFN- γ is released, it acts as an attractant to a large variety of immune cells which can better deal with the situation.
In 2007 a study published in the journal Immunology, demonstrated that oral administration of Agaricus blazei extract could increase IFN-γ production in both live mice and isolated mice tissue.

Some of the Roles of IFN-γ

1. Highlights malfunctioning cells with markers (class 1 MHC molecules that carry antigens) so the immune system can more readily identify and destroy them.
2. Increases antigen presentation to macrophage (increases macrophage’s ability to target newley encountered bacteria and viruses).
3. Increases macrophage’s ability to destory pathogens/unhealthy cells (via increasing lysomal activity).
4. Promotes natural killer cell activity.
5. Acts as a recruiter for other immune cells such as macrophage and cytotoxic T cells.

Reference:
Yuminamochi E, Koike T, Takeda K, Horiuchi I, Okumura K. Interleukin-12- and interferon-gamma-mediated natural killer cell activation by Agaricus blazei Murill. Immunology 2007;121:197-206.