Turkey Tail

Generic name: Coriolus Versicolor, Polyporus Versicolor, Trametes Versicolor L. Ex Fr. Quel.
Brand names: Cloud Mushroom, Kawaratake (Japan), Krestin, Polysaccharide Peptide, Polysaccharide-K, PSK, PSP, Turkey Tail, Turkey Tail Mushroom, Yun Zhi (China)

Usage of Turkey Tail

C. versicolor extracts possess cytotoxic activity against cancer cells and endothelial cells and have the ability to inhibit the expression of the protumorigenic factors associated with inflammation.(Jędrzejewski 2020) C. versicolor may stimulate the production of cytokines and serve as a Th2/IL-10-dependent immunomodulator, and thus has potential in supporting cancer therapies.(Awadasseid 2017) Overall, polysaccharides, proteins, and lipids in T. versicolor extracts appear to work synergistically to modulate an immune response at multiple levels. Extracellular stimulation of pattern recognition receptors (ie, TLR2) can enhance maturation of macrophages and dendritic cells, activate cytotoxic CD8+ T-cells and natural killer cells, and selectively induce the production of numerous cytokines (ie, IL-1alpha, IL-1beta, IL-2, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor [TNF]-alpha). Stimulation of intracellular pathogen sensors (ie, inflammasome) has also been documented and is a critical step in activating both innate and adaptive immunity. T. versicolor extracts have been used for decades in Japan as a cancer treatment and adjuvant to chemotherapy. Other studies have focused on the antimicrobial, antiviral, and antioxidant properties of PSK. Increasingly, T. versicolor, its extracts, and other bioactive botanicals are being explored as medicinal foods, food products, and additives.(Kidd 2000, Kuan 2013, Li 2012, Quayle 2015, Wang 2013, Yang 2014, Zhang 2015)

Antibiotic activity

Antibiotic effects of C. versicolor has been described against S. aureus, S. enteritidis, and S. typhimurium.(Matijašević 2016, Shi 2016) The immunomodulatory potential of polysaccharides from C. versicolor against intracellular bacteria Neisseria gonorrhoeae has also been demonstrated in mice.(Pramudya 2019)

Antifungal activity

In vivo studies in mice suggest a protective effect of PSK against Candida infection, mainly through TNF-alpha activity.(Ohmura 2001)

Antioxidant activity

During exhaustive exercise, malondialdehyde (MDA), the end product of lipid peroxidation, and other key biomarkers of oxidation (ie, glutathione peroxidase, superoxide dismutase) were reduced in the brain tissue of rats administered T. versicolor. The effect on MDA occurred in a dose-dependent manner, with the high-dose group experiencing a lower level of MDA.(Chen 2013, Oyetayo 2012, Sun 2014)

Antiviral activity

In vitro data

An in vitro study with PSP demonstrated antiviral activity against HIV-1. The mechanism of action is postulated to include PSK interfering with the binding of HIV-1 to its cellular target.(Collins 1997) In another study, the mycelial extract from T. versicolor exhibited the highest antiviral activity against influenza H1N1 virus among extracts from 10 total Basidiomycetes mycelia. Additionally, T. versicolor was one of 4 species that demonstrated inhibition of herpes simplex virus 2, showing the highest therapeutic index of all 10 species tested.(Krupodorova 2014)

Clinical data

A randomized, single-blind study (N=472) evaluated the ability of a medicinal mushroom combination of T. versicolor plus G. lucidum to treat oral HPV. Patients who presented with gingivitis were swabbed buccally for HPV detection; 61 cases (13%) were positive for HPV16 or HPV18. They were randomly assigned to 400 mg/day of either the T. versicolor mushroom combination (dried ground fruit body) or control (Laetiporus sulphureus). After 2 months of treatment, HPV was cleared in 87.8% of those receiving the T. versicolor/G. lucidum combination compared with 5% in the control group (P<0.001).(Donatini 2014)

A longitudinal retrospective observational study was performed to evaluate efficacy and safety of a C. versicolor-based vaginal gel (N=183). Women treated with the vaginal gel were compared with women not treated with the gel. Both groups were monitored for HPV infection by an HPV DNA test, Pap smear (cytology), and colposcopy at baseline and after 6 months. HPV positive women were enrolled (n=97 treated and n=86 controls), and after 6 months, the HPV DNA test became negative in 67% of treated individuals versus 37.2% of the control group (P<0.0001). Furthermore, 76.1% versus 40.8% registered a colposcopy improvement (P=0.0005) and 60.4% versus 40.8% showed a remission (P=0.05), for treated individuals versus controls, respectively. It was concluded that the use of a C. versicolor vaginal gel in high-risk HPV patients is safe and effective based on all the examined tests.(Criscuolo 2021) These results were supported by the PALOMA study in which the efficacy of a C. versicolor–based vaginal gel in women with HPV–dependent cervical lesions was investigated. The conclusion was that treatment with the above-mentioned gel has demonstrated better clinical benefit than the conventional watchful waiting approach.(Serrano 2021)

Cancer

Because of its immunomodulatory effects, PSK is approved as a prescription drug in Japan for use in cancer treatment. Its antitumor activity is a result of its ability to induce maturation of dendritic cells, activate cytotoxic CD8+ T-cells and natural killer cells, and elicit the production of proinflammatory cytokines (ie, TNF-alpha, IL-1beta, IL-12).(Quayle 2015) In addition, it has been shown that protein-bound polysaccharides from the fungus C. versicolor induce RIPK1/RIPK3/MLKL-mediated necroptosis in breast cancer and melanoma cells, providing novel insights into the molecular effects of protein-bound polysaccharides on cancer cells.(Pawlikowska 2020)

Clinical data

In a multicenter, randomized clinical trial of 262 gastric cancer patients in Japan, administration of PSK as adjuvant treatment with standard chemotherapy following curative gastrectomy improved 5-year disease-free rate (P=0.047) and 5-year survival rate (P=0.044).(Fukushima 1996, Nakazato 1994) Another clinical study of 579 patients followed for 5 years also supports use of PSK as an adjuvant immunochemotherapeutic agent following curative gastric resection.(Iguchi 2001, Niimoto 1988) Three meta-analyses of clinical trials in gastric cancer patients published through 2005 provide evidence of a benefit in survival with adjuvant use of PSK compared with chemotherapy alone.(Kim 2001, Oba 2007, Ogoshi 1983)

A retrospective study of 185 patients with stage I to III NSCLC supports the use of PSK as adjuvant treatment after radiotherapy. The differences in 5-year survival rates were statistically significant.(Hayakawa 1993)

In 2 randomized clinical trials, PSK was useful as maintenance therapy following curative surgical operations in patients with colorectal cancer. In both trials, survival rate was significantly increased (P<0.05), probably due to increased immune system response induced by PSK.(Mitomi 1992, Torisu 1990) In a third randomized controlled study (N=205) conducted in patients with stomach cancer, a significant improvement in 5-year disease-free survival rate was observed with PSK 3 g/day plus oral tegafur/uracil 300 mg/day (73%) compared with tegafur/uracil alone (58.8%) (P=0.016). Mean disease-free survival was 50.3 months versus 40 months, respectively (P=0.031). In a subgroup of patients with stage III cancer, a significant benefit in 5-year overall survival was seen with PSK compared with controls (74.6% vs 46.4%; P=0.003); this effect was not observed in other subgroups. Additionally, the PSK group experienced a significant reduction compared with controls in lung metastases (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09 to 0.77; P=0.02) but not in recurrence at any other location.(Ogoshi 1983) Two of the above trials were included in a 2006 meta-analysis that investigated adjuvant chemotherapy with PSK and oral fluorinated pyrimidines compared with chemotherapy alone in patients with curatively resected colorectal cancer. One additional randomized controlled trial met inclusion criteria, for a total of 1,094 patients; the follow-up duration for all 3 trials was a minimum of 5 years postsurgery, and heterogeneity was not significant among the trials. The 5-year overall survival and disease-free survival rates were 79% and 72.2%, respectively, for PSK immunotherapy versus 72.2% and 65.9% for chemotherapy alone. Combining the data yielded a significant effect of PSK on overall survival (OR, 0.71; 95% CI, 0.55 to 0.9; P=0.006) and disease-free survival (OR, 0.72; 95% CI, 0.58 to 0.9; P=0.003).(Sakamoto 2006) In contrast, no benefit was seen with administration of C. versicolor in median time to progression, quality of life, response rates, progression-free survival, or overall survival in a small randomized placebo-controlled study that enrolled 15 patients with advanced hepatocellular carcinoma who were unfit for standard therapy.(Chay 2017)

A meta-analysis of studies (2 randomized controlled trials and 5 controlled trials) investigating immunomodulatory dietary polysaccharides documented improved survival and immune function in gastric, colon, and colorectal cancer patients administered oral glucan extracts from T. versicolor. Doses of PSK ranged from 200 mg to 3 g (administered daily, or for 4 weeks alternating with courses of chemotherapy) for up to 7 years. PSP was given at 3.06 g/day for 1 month in a small, double-blind, randomized controlled trial to patients with stage III to IV NSCLC.(Ramberg 2010)

Several review articles exist regarding use of PSK as a cancer chemopreventative agent. The effect is postulated to include induction of immunomodulatory cytokines and cytokine receptors, as well as antioxidant activity.(Garcia-Lora 2001, Kobayashi 1993, Ooi 2000, Yang 1992)

A systematic review and meta-analysis of randomized controlled trials concluded that C. versicolor natural products might have potential benefits on the overall survival and quality of life in cancer patients.(Zhong 2019)

Colitis

In vivo, YZP (a protein isolated from the fruiting bodies of T. versicolor) reduced TNF-alpha and IL-1beta production in macrophages activated by lipopolysaccharide. In vivo, weight loss was less severe in mice receiving adoptive transfer of YZP B-cells compared with controls. Similarly, reduction in colon length (an indirect marker of colitis) was less severe with YZP, and histological features of colon segments from YZP mice were comparable with those of healthy mice. Additionally, upregulation of inflammatory cytokines and colonic gene expression of regulatory cytokine IL-10 was improved in mice receiving YZP B-cells. These data also support the proposition that the nonglycosylated protein YZP is an important contributor to the actions observed in other studies with polysaccharopeptides.(Kuan 2013)

CNS effects

Animal and in vitro data

C. versicolor polysaccharides can significantly reduce the pathological characteristics of cerebral ischemia-reperfusion injury in rats and inhibit the apoptosis of nerve cells around the lesions. The mechanism of its effectiveness is related to inhibiting the activation of the p38MAPK signaling pathway.(Li 2020)

In vitro experiments seem to support the use of nutritional mushroom treatment for Meniere Disease. C. versicolor is able to reduce neuroinflammation and autoneurodegeneration and provide neuroprotection.(Scuto 2020)

Diabetes mellitus

A diabetic rat model was used to investigate the effect of T. versicolor on hyperglycemia and bone attrition in rats with induced diabetes. Rats were divided into 3 groups: nondiabetic controls, diabetic administered vehicle, and diabetic administered a novel strain of T. versicolor (LH-1) and its fermented ePSP (0.1 g/kg of weight for 28 days). On days 20 and 26, mean postprandial blood glucose was significantly lower in the T. versicolor ePSP diabetic group (157 and 225 mg/dL) than the vehicle diabetic group (201 and 292 mg/dL) (P<0.001 for each). Similarly, bone microarchitecture improved significantly in the ePSP group compared with the vehicle group, and was similar to that of controls in 2 of the 4 assessments. Strength of the femur was also significantly increased in the ePSP group compared to the vehicle.(Chen 2015)

Food product

In response to increasing market demand for low- or nonalcoholic beverages, a nonalcoholic, cereal-based fermented beverage was developed and systematically evaluated for basic nutritionally relevant parameters, flavor, and safety. The fungal mycelia of T. versicolor were used to ferment wort. The final ethanol concentration was determined to be 0.39% (v/v), which is within the legal definition of "nonalcoholic" for US and European markets. In stark contrast to the original wort and most cereal beverages fermented with bacteria or yeasts, the aroma of the final beverage was perceived as fruity, fresh, sweet, and slightly floral. Key aroma compounds were 2-phenylacetaldehyde, ethyl 2-methylpropanoate, linalool, 2,3-butanedione, and methionil. Cytotoxicity and mutagenicity tests revealed no statistically significant events.(Zhang 2015)

Medicinal mushrooms such as C. versicolor are extremely attractive as nutraceuticals. A novel kombucha beverage using C. versicolor displayed complex polysaccharides, phenols, and flavonoids. The extract was not cytotoxic for peripheral blood mononuclear cells (PBMC) in vitro (up to 500 mcg/mL), while the immunomodulatory effects depended on the chemical compositions. The most prominent effect was on the reduction of Th2 cytokines and IL-10 in PBMC cultures. Based on these results, novel kombucha products could be recommended as functional beverages or as nutraceuticals with potentially beneficial immunomodulatory effects for people with allergies.(Sknepnek 2021)

Prebiotic activity

Prebiotics are consumed orally, fermented in the gut, and change the composition and/or activity of the gut microbiome, which improve the health and well-being of the individual.

Clinical data

In a small, open-label, randomized controlled trial conducted in healthy volunteers (N=24), effects on the human gut microbiome of the prebiotic PSP isolated from the mycelia of T. versicolor were compared and contrasted with amoxicillin. There was no intervention via fecal microbiome analysis. Volunteers were randomized to 1 of 4 groups: amoxicillin 250 mg 3 times daily on days 8 to 14; PSP 1,200 mg 3 times daily for 14 days; Saccharomyces boulardii 250 mg 3 times daily for 14 days; or no treatment. PSP induced distinct shifts in the microbiome species that were different from control microbiomes; however, the divergence from baseline was small. The largest shifts in microbiome species resulted from administration of amoxicillin and were most notable on day 14, but were still altered from baseline 42 days after the last dose of antibiotic. Most notable in the amoxicillin group was the increase in prevalence of Escherichia and Shigella.(Pallav 2014)

Vaccinations

Because TLR agonists facilitate T-cell responses (via macrophage and dendritic cell maturation), they have great potential to augment not only antitumor but also antiviral immune responses. The selectivity of PSK to activate TLR2 was the premise behind evaluating PSK as a vaccine adjuvant. In vitro, PSK stimulated dendritic cell maturation and the production of proinflammatory cytokines in a dose-dependent manner. Subsequently, in vivo mice experiments showed that administration of PSK as an adjuvant to ovalbumin (OVA) peptide p323 vaccine significantly increased dendritic cell counts (P<0.001), upregulated the expression of activation markers (P=0.003 to P<0.0001), and increased the percentages of proliferating OVA-specific T-cells (P<0.0001). Total dendritic cell counts in the PSK group were also significantly higher compared with placebo than in mice receiving granulocyte macrophage-colony stimulating factor (GM-CSF) as an adjuvant treatment (P<0.0001). Additionally, the GM-CSF adjuvant group experienced almost a 5-fold increase in IL-2 production compared with controls, whereas the PSK adjuvant group exhibited a 14-fold increase in IL-2.(Engel 2013)

Turkey Tail side effects

Adverse effects observed include diarrhea, darkened stools, and darkened nail pigmentation. PSK is considered to be very well tolerated.Kidd 2000 No clinically important adverse effects were observed for PSK 3 g/day when given up to 7 years as an adjunct to standard chemotherapy in patients with curatively resected colon cancer. Turkey tail glucan products (PSP or PSK) have been safely consumed at doses of 1 g or more per day for up to 10 years in cancer patients.Ramberg 2010

No evidence of toxicity with PSP was observed in safety studies conducted in rats and monkeys at doses equivalent to 200 times the human dose given for 6 months.Ramberg 2010 Likewise, murine oral safety studies for ePSP (LH-1) revealed no obvious signs of toxicity at doses up to 1,000 mg/kg/day for 28 days. At a dose of 1,000 mg/kg in male mice, decreased platelets were observed; reassessment after removal of 3 data outliers revealed no significant differences in numbers of platelets among dosing groups in male and female mice.Lai 2011

Before taking Turkey Tail

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

How to use Turkey Tail

Cancer

In clinical trials, PSK as an adjuvant to chemotherapy has been dosed at 200 mg for 3 to 5 years in patients with curatively resected colorectal cancer; 3 g/day for 2 years in postsurgical colorectal cancer patients; and 3 g/day for 4 weeks, alternating with ten 4-week courses of chemotherapy for up to 7 years in postsurgical colon and gastric cancer patients.Ohwada 2004, Ramberg 2010

PSP 3.06 g was administered for 1 month in conventionally treated patients with stage III to IV NSCLC in a double-blind, randomized, placebo-controlled trial.Ramberg 2010

Prebiotic

PSP 1,080 mg (3 capsules) orally 3 times daily (based on standard medication instructions of the approved category II drug product available in China).Pallav 2014

Warnings

Research reveals little or no information regarding toxicity with use of turkey tail. Cytotoxicity and mutagenicity studies of a T. versicolor fermented, cereal-based, nonalcoholic beverage yielded no statistically significant events.Zhang 2015

What other drugs will affect Turkey Tail

None well documented.

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