2oz=$25 4 oz=$40 8oz=$65 1 pound =$89

Scientific Name(s): Coriolus versicolor, Polyporus versicolor, Trametes versicolor L. ex Fr. Quel. Common Name(s): Cloud mushroom, Kawaratake (Japan), Krestin, Polysaccharide peptide, Polysaccharide-K, PSK, PSP, Turkey tail, Turkey tail mushroom, Yun zhi (China)

Clinical Overview Use T. versicolor extract (ie, PSK) is approved as a pharmaceutical-grade medicine in Japan and has been used for more than 30 years as a treatment for cancer. In clinical trials, PSK has been used as an adjuvant to chemotherapy to manage gastric, colon, and colorectal cancer, whereas the extract PSP has been used for late-stage lung cancer and as a prebiotic. bination medicinal mushroom formulation of T. versicolor plus Ganoderma lucidum was observed to clear oral human papilloma virus (HPV) in patients with HPV-positive gingivitis. Dosing Cancer: As an adjuvant to chemotherapy, PSK 3 g/day orally for up to 7 years has been used in postsurgical colon, colorectal, and gastric cancer patients (may be given alternating with 4-week courses of chemotherapy). PSP 3.06 g/day for 1 month was administered to conventionally treated patients with stage III to IV non–small cell lung cancer (NSCLC). Prebiotic: PSP 1,080 mg (3 capsules) 3 times daily. Contraindications Contraindications have not been determined. Pregnancy/Lactation Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking. Interactions None well documented. Adverse Reactions Diarrhea, darkened stools, and darkened nail pigmentation have been reported. 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. Toxicology Research reveals little or no information regarding toxicity. Scientific Family Polyporaceae Botany T. versicolor (also known as Coriolus versicolor or Polyporus versicolor) is a mushroom in the Basidiomycotina division (Basidiomycetes) and monly known as "turkey tail." The turkey tail fungus is found throughout North America, Asia, and Europe. Its fruiting bodies overlap one another, forming a dense mass that grows on tree trunks, stumps, and fallen trees. The distinctive layers created by these bodies may be light to dark brown or gray. The polysaccharides of the fruiting bodies are sweet and mild in taste, and mercially marketed as a tea used in Asian and European traditional medicine.1, 2, 3 History T. versicolor has been consumed for centuries in Asia as part of a traditional diet and has been used medicinally.4 Folklore remedies of turkey tail include the treatment of lung and liver infections. In China, turkey tail has been used as a preventive and curative agent for liver infections and liver cancer. In Japan, it is considered a panacea for a variety of cancers. Overall, the mycelium and fruiting body of the mushroom are considered to have immune stimulatory and anticarcinogenic activities. Clinical research with PSK began around 1970 and has focused on its immunotherapeutic efficacy in stomach, colorectal, esophageal, nasopharyngeal, lung, and breast cancers. In Japan, it has been approved as a pharmaceutical-grade medicine for cancer treatment and used for more than 30 years with consistent clinical efficacy.1, 5, 6, 7 In Chinese medicine, C. versicolor is characterized as being slightly cold and enters the meridians of the liver, spleen, and lung. It is predominantly used to treat cirrhosis, chronic active hepatitis, rheumatoid arthritis, leukemia, and bronchitis.2 It has also been used for its analgesic, anti-inflammatory, antihyperlipidemic, and antiatherosclerotic effects.8 Chemistry Protein-bound polysaccharides, or PSPs, refers to the class pounds abundant in certain mushrooms. PSPs monly used in East Asia as a nutritional intervention and biological response modifier. PSP from T. versicolor is a potent immunomodulatory that stimulates proinflammatory cytokines (ie, interferon-gamma, interleukin 2 [IL-2]), natural killer cell activity, T-cell proliferation, and activation of plement system.9 At least 6 other polysaccharide fractions (all acidic heteropolysaccharides) have been isolated from the fruiting bodies of T. versicolor, with molecular weights ranging from 568 to 1,840 kDa, protein content of 3.9% to 8.5%, and various ratios of the monosaccharides mannose, rhamnose, glucuronic acid, glucose, and fructose; glucose was the predominant sugar (82.8% to 90.5%). More than 40% of the protein content of the crude mass was removed during purification. Bioactivity was associated with effects on molecular weight, protein content, and glucuronic acid amounts.(8) An extracellular polysaccharopeptide (ePSP) has also been prepared from fermented mycelia of the LH-1 strain of T. versicolor, which has a position than the intracellular PSP. ePSP prised mainly of polysaccharides and is 13.8% protein; its position is mostly glucose (82.27 mg/g), galactose (8.67 mg/g), mannose (8.18 mg/g), and xylose (0.87 mg/g).10 Evidence points to a lipid (primarily linoleic acid) or fatty acid ester in PSK, instead of the polysaccharopeptide, as the moiety responsible for activating Toll-like receptor 2 (TLR2). By facilitating phagocytosis of the polysaccharopeptide via macrophages and dendritic cells, the ponent appears to work synergistically with the protein-bound beta-glucan to generate immune response.7 Uses and Pharmacology 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.1, 4, 7, 11, 12, 13, 14

Antibiotic activity Antibiotic effects of C. versicolor has been described against S. aureus, S. enteritidis, and S. typhimurium.36, 37

Antifungal activity In vivo studies in mice suggest a protective effect of PSK against Candida infection, mainly through TNF-alpha activity.38

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.2, 3, 8

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.15 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.16

Clinical data A randomized, single-blind study (N=472) evaluated the ability of a medicinal bination 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 bination (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. pared with 5% in the control group (P<0.001).17

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).7

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).18, 19 Another clinical study of 579 patients followed for 5 years also supports use of PSK as an adjuvant immunochemotherapeutic agent following curative gastric resection.20, 21 Three meta-analyses of clinical trials in gastric cancer patients published through 2005 provide evidence of a benefit in survival with adjuvant use of pared with chemotherapy alone.22, 23, 24 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.25 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.26, 27 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 pared 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 pared 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.23 Two of the above trials were included in a 2006 meta-analysis that investigated adjuvant chemotherapy with PSK and oral fluorinated pared 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).28 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.42 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.29 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.30, 31, 32, 33 The Cochrane Collaboration is currently conducting a systematic review and meta-analysis of available data regarding medicinal mushroom use in colorectal cancer.34

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 pared 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 parable 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.12

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 pared 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 pared to the vehicle.10

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 pounds were 2-phenylacetaldehyde, ethyl 2-methylpropanoate, linalool, 2,3-butanedione, and methionil. Cytotoxicity and mutagenicity tests revealed no statistically significant events.4

Prebiotic activity Prebiotics are consumed orally, fermented in the gut, and change position 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 pared 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.35

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 pared 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 pared with controls, whereas the PSK adjuvant group exhibited a 14-fold increase in IL-2.39 Dosing

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.29, 40 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.29

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).35 Pregnancy / Lactation Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking. Interactions None well documented. Adverse Reactions Adverse effects observed include diarrhea, darkened stools, and darkened nail pigmentation. PSK is considered to be very well tolerated.1 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.29 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.29 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.41 Toxicology 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.4