Turkey tail mushroom

Last Updated: September 28, 2022

Turkey Tail Mushroom (Trametes versicolor) is a mushroom that is a source of a polysaccharide, known as polysaccharide K, that is established as a cancer adjunct therapy for the immune system.

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1.

Sources and Composition

1.1

Sources

Trametes versicolor, more commonly known as Turkey Tail Mushroom,

Historically, Turkey Tail polysaccharide (specifically PSK) have been used in Japan as anti-cancer adjuvants alongside other cancer therapies; first approved in 1977 as a prescription medication (in regards to isolated PSK) and in 1987 PSK itself accounted for more than 25% of total national expenditure for anticancer agents in Japan.[1]

1.2

Composition

The main bioactives in Turkey Tail are:

  • Polysaccharide K (PSK)[2][3]
  • Polysaccharide-peptide (PSP) from the water-soluble fragment[4][5]

2.

Neurology

2.1

Pain

PSP has been tested in rats to assess its interactions with pain (hot-plate test for tactile heat pain, acetic acid writhing test for chemical pain) and PSP appeared to have weak pain sensitizing effects relative to control.[6] This increase in pain sensitivity appears to have been related to pro-inflammatory effects of PSP, and was significantly inhibited by anti-inflammatories.[6]

3.

Inflammation and Immunology

3.1

Mononuclear Cells

PSK may stimulate proliferation of PBMCs while inducing accumulation of interleukins (particularly IL-1α) within the cell.[6] Increased IL-8 levels result after stimulation of PBMCs by PSK, and this has been found in persons following oral ingestion of 1g PSK (with spikes appearing in 42-44% of persons within 3 hours, assay could not detect less than 25pg/mL) to a fairly variable level of 30-125pg/mL (data extracted from graph).[7]

3.2

Natural Killer Cells

The polysaccharide PSK appears to be a TLR2 agonist, and can stimulate Natural Killer (NK) cells to produce IFN-γ and increase their cytotoxicity;[8] although it is contested as to whether this is direct or indirect NK cell activation (may be vicarious through Dendritic Cells).[9][10] Abolishment of the TLR2 receptor in mice abolishing NK cell activity induced by PSK.[8]

Interactions between tumors and Turkey Tail mushroom are partially dependent on NK cells, and mostly dependent on both NK cells and T-Cells.[7]

In women with breast cancer who had NK cell activity significantly reduced due to radiotherapy, a trend towards increasing NK cell activity was noted with 6g daily after 4 weeks but aside from not being present at 6 weeks nor being present with 9g ingestion this failed to be statistically significant.[11] This same trend existed for NK cell count.[11]

3.3

T-Cells

In vitro, incubation of 10-200ug/mL PSK appears to increase CD4+ and CD8+ T-cells and overall splenocyte proliferation.[8]

An increased level of cytotoxic T-cells against tumors has been noted in animals fed PSK (100mg/kg) after injection of tumor cells.[8]

Total levels of CD8 cytotoxic T-cells appear to increase after ingestion of 3-9g Turkey Tail over 6 weeks in women with breast cancer, but this was not statistically significant.[11]

3.4

B-Cells

Although increasing splenocyte proliferation, 10-200mcg/mL PSK appears to reduce the percentage of B-Cells in vitro from 46.8+/-0.6% to 22.4+/-1.9%[8] which may be related to the ability of PSK to suppress B-Cell growth via IL-15 secretion from T-Cells.[12]

A trend to increase CD19+ B-cells was noted in women given 6-9g Turkey Tail daily for 6 weeks.[11]

4.

Interactions with Cancer

4.1

Breast Cancer

Mechanistically, the polysaccharide PSK appears to activate PBMCs via the TLR2 receptor directly and PBMCs then activate Natural Killer (NK) cells to release IFN-γ and lyse breast cancer cells.[13] TLR2 activation appears to enhance NK cell activity (as well as TLR8,9),[14] and PSK has once been demonstrated to enhance breast cancer therapries that target HER2 (a protein that is seen as a breast cancer therapeutic target[15]); with this study noting augmentation of Trastuzumab (Herceptin™).[13]

In women with breast cancer (Stage I-III) consuming Turkey Tail mycelia powder at 3, 6, or 9g daily (two divided doses) over 6 months resulted in normalization of lymphocyte counts that were reduced by radiotherapy at only 6-9g daily (3g not being significantly different than placebo) with the measurement after 6 weeks exceeding pre-radiation levels.[11]

4.2

Leukemia

In promyelocytic leukemia cells (HL-60), incubation of various extracts of Turkey Tail resulted in both the ethanolic and water extracts suppressing cell viability in a concentration dependent manner with more efficacy in the water extract; with 7.5-10mcg/mL suppressing viability to lower than 25% of baseline.[5]

Proliferation also appears to have been reduced at 5-10mcg/mL water extract of Turkey Tail that was associated with a decrease of cells in S phase (41.2% to 11.3%) with concomitant increases in G1 and G2/M phases.[5]

In regards to cytokines, a suppression of IL-8 was noted in HL-60 cells.[5]

5.

Safety and Toxicicity

Up to 9g of Turkey Tail daily for 6 months in women with Breast Cancer has failed to note any significant side effects and was deemed well tolerated.[11]

References
3.^Sakagami H, Sugaya K, Utsumi A, Fujinaga S, Sato T, Takeda MStimulation by PSK of interleukin-1 production by human peripheral blood mononuclear cellsAnticancer Res.(1993 May-Jun)
4.^Zaidman BZ, Yassin M, Mahajna J, Wasser SPMedicinal mushroom modulators of molecular targets as cancer therapeuticsAppl Microbiol Biotechnol.(2005 Jun)
7.^Kato M, Hirose K, Hakozaki M, Ohno M, Saito Y, Izutani R, Noguchi J, Hori Y, Okumoto S, Kuroda D, et alInduction of gene expression for immunomodulating cytokines in peripheral blood mononuclear cells in response to orally administered PSK, an immunomodulating protein-bound polysaccharideCancer Immunol Immunother.(1995 Mar)
8.^Lu H, Yang Y, Gad E, Wenner CA, Chang A, Larson ER, Dang Y, Martzen M, Standish LJ, Disis MLPolysaccharide krestin is a novel TLR2 agonist that mediates inhibition of tumor growth via stimulation of CD8 T cells and NK cellsClin Cancer Res.(2011 Jan 1)
9.^Azuma M, Sawahata R, Akao Y, Ebihara T, Yamazaki S, Matsumoto M, Hashimoto M, Fukase K, Fujimoto Y, Seya TThe peptide sequence of diacyl lipopeptides determines dendritic cell TLR2-mediated NK activationPLoS One.(2010 Sep 2)
11.^Torkelson CJ, Sweet E, Martzen MR, Sasagawa M, Wenner CA, Gay J, Putiri A, Standish LJPhase 1 Clinical Trial of Trametes versicolor in Women with Breast CancerISRN Oncol.(2012)
13.^Lu H, Yang Y, Gad E, Inatsuka C, Wenner CA, Disis ML, Standish LJTLR2 agonist PSK activates human NK cells and enhances the antitumor effect of HER2-targeted monoclonal antibody therapyClin Cancer Res.(2011 Nov 1)
14.^Moreno M, Mol BM, von Mensdorff-Pouilly S, Verheijen RH, von Blomberg BM, van den Eertwegh AJ, Scheper RJ, Bontkes HJToll-like receptor agonists and invariant natural killer T-cells enhance antibody-dependent cell-mediated cytotoxicity (ADCC)Cancer Lett.(2008 Dec 8)