Coriolus – Trametes versicolor

Japanese nameKawaratake
Chinese nameYun Zhi
English nameTurkey Tail

T. versicolor is the most extensively researched of all medicinal mushrooms with large scale clinical trials on the extracts PSK (‘Krestin’) and PSP showing impressive results in a variety of cancers including gastric, oesophageal, lung, breast and colorectal1-8. PSK and PSP are both polysaccharide-protein complexes that are soluble in water but insoluble in ethanol9. PSK contains 34-35% polysaccharide (~92% glucan) and 28-35% protein10.
PSK has been shown to boost immune cell production, ameliorate chemotherapy and radiotherapy side effects, enhance immune status and tumour infiltration by dendritic and cytotoxic cells and significantly extend survival in cancers of the stomach, colon-rectum, oesophagus, nasopharynx, uterus and lung (non-small cell types), and in an HLA B40-positive breast cancer subset in combination with conventional treatment1. In addition to its immune related effects, PSK has shown an ability to enhance superoxide dismutase and glutathione peroxidase activity11,12.
PSP has been shown to significantly enhance immune status in 70-97% of patients with cancers of the stomach, oesophagus, lung, ovary and cervix8. Although most clinical trials have been conducted with the above proteoglycan extracts, there is also evidence of immunomodulatory action for T. versicolor mycelial biomass, with improvements of immune status in patients with chronic fatigue syndrome and enhanced clearance of low grade squamous intraepithelial lesions (LSIL) from the cervix.

CANCER – The use of T. versicolor extracts in cancer treatment is supported by a significant number of clinical trials8,13,14.

STOMACH CANCER – Multiple clinical trials of PSK given alongside surgery and chemotherapy at 3-6g/day significantly extended survival times in stomach cancer at all stages. Even in patients with advanced stomach cancer with metastasis PSK doubled 2-year and 5-year survival and extended 15-year survival15-20.

COLORECTAL – In different clinical trials PSK extended 5-year and 8-year survival after surgery and chemotherapy and after surgery, chemotherapy and radiotherapy21-23.

LUNG CANCER (NSCLC) STAGES I-III – PSK extended 5-year survival 2-4x for all cancer stages with stage III cancer patients taking PSK having a better prognosis than stage II patients without PSK24.

OESOPHAGEAL – PSK extended 5-year survival after surgery, radiotherapy and chemotherapy while in double-blind trials PSP significantly extended 5-year survival in oesophageal cancer as well as improving quality of life, providing substantial pain relief and enhancing immune status in 70-97% of patients with cancers of the stomach, oesophagus, lung, ovary and cervix at a dose of 3g/day25.

NASOPHARYNGEAL – PSK extended 5-year survival after radiotherapy and chemotherapy (28% vs, 15%)26.

BREAST CANCER – Evidence from clinical trials (given alongside chemotherapy) is mixed. In one trial PSK was shown to extend survival in patients with oestrogen receptor negative, nonmetastasised, stage II cancer but no benefit was shown in another. In a third trial significant benefit was seen in patients positive for HLA B40 with 100% survival after 10 years27-29.

CERVICAL/UTERINE CANCER – In combination with radiotherapy PSK (3-6g/day) given to patients with stage III uterine and cervical cancer enhanced survival and increased sensitivity of the cancers to radiotherapy30. In another trial cervical cancer patients given the same dose together with radiotherapy showed clearance of cancer cells in 36% of patients versus 11% of controls and improved 5-year survival from 48% to 79%9. In a recent study using T. versicolor biomass, supplementation with 3g/day produced a 72.5%regression rate in LSIL lesions, compared to 47.5% without supplementation, and also increased the clearance of high risk HPV strains from 8.5% to 91.5%31-33.

HIV – In several in vitro experiments PSK was found to exhibit anti-HIV activity through multiple routes34-35:
• Inhibition of HIV reverse transcriptase
• Inhibition of viral binding to lymphocytes
• Inhibition of cell-to-cell infection of HIV-1 and HIV-2
Use of T. versicolor supplementation (3.0g/day T. versicolor biomass) has been reported to improve HIV patients’ immune status and produce improvement in HIV related Kaposi’s sarcoma36,37.

HERPES – Clinically T. versicolor supplementation is seen to reduce the frequency of Herpes simplex virus (HSV) outbreaks and it has also been shown to inactivate HSV in a dose-dependent manner38.

CHRONIC FATIGUE SYNDROME (ME)T. versicolor biomass has shown promise in the treatment of Chronic Fatigue Syndrome with immune system activation and increased NK cell activity reported in patients at 1.5g/day (3.0/day for the first 2 weeks) over a 2 month period39.

HEPATOPROTECTIVET. versicolor polysaccharide extracts demonstrate hepatoprotective properties40,41.

CLINICAL SUMMARY
Main Therapeutic Application – Cancer.
Key Component – Polysaccharides.
Dose – Commercial polysaccharide extracts are commonly prescribed at 3g/day and for long term use may be given in cycles of two weeks on, two weeks off. Dosage for crude polysaccharide extracts is typically 3-6g/day for cancer and 1-2g/day for immune support. For chronic immune deficient conditions the biomass also shows promise at 3g/day.

REFERENCES
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2. Anticancer effects and mechanisms of polysaccharide-K (PSK): Implications of cancer immunotherapy. Fisher M, Yang LX. Anticancer Res. 2002;22(3):1737–1754.
3. A review of research on the protein-bound polysaccharide (polysaccharopeptide, PSP) from the mushroom Coriolus versicolor (Basidiomycetes: Polyporaceae). Ng TB. Gen Pharmacol. 1998;30(1):1–4.
4. Polysaccharopeptides of Coriolus versicolor: physiological activity, uses, and production. Cui J, Chisti Y. Biotechnol Adv. 2003;21(2):109–122.
5. Effects of PSK on T and dendritic cells differentiation in gastric or colorectal cancer patients. Kanazawa M, Yoshihara K, Abe H, Iwadate M, Watanabe K, Suzuki S, Endoh Y, Takita K, Sekikawa K, Takenoshita S, Ogata T, Ohto H. Anticancer Res. 2005;25(1B):443–449.
6. The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis. Jiménez-Medina E, Berruguilla E, Romero I, Algarra I, Collado A, Garrido F, Garcia-Lora A. BMC Cancer. 2008;8:78.
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10. Method of producing nitrogen-containing polysaccharides. Ueno S, Yoshikumi C, Hirose F, Omura Y, Wada T, Fujii T, Takahashi E. 1980. US Patent 4,202,969
11. Polysaccharide Krestin enhances manganese superoxide dismutase activity and mRNA expression in mouse peritoneal macrophages. Pang ZJ, Chen Y, Zhou M. Am J Chin Med. 2000;28(3-4):331–341.
12. Effect of polysaccharide krestin on glutathione peroxidase gene expression in mouse peritoneal macrophages. Pang ZJ, Chen Y, Zhou M, Wan J. Br J Biomed Sci. 2000;57(2):130–136.
13. Efficacy of Yun Zhi (Coriolus versicolor) on survival in cancer patients: systematic review and meta-analysis. Eliza WL, Fai CK, Chung LP. Recent Pat Inflamm Allergy Drug Discov. 2012;6(1):78–87.
14. PSP in clinical cancer therapy – a review. In: Yang Q (Ed.): Advanced Research in PSP. Hong Kong : Hong Kong Association for Health Care Ltd, 1999:68–75.
15. Postoperative long-term chemotherapy for advanced gastric cancer. Kaibara N, Soejima K, Nakamura T, Inokuchi K. Jpn J Surg. 1976;6(2):54–59.
16. Combined effect of prophylactic lymphadenectomy and long-term combination chemotherapy for curatively resected carcinoma of the stomach. Kodama Y, Kano T, Tamada R, Kumashiro R, Okamura T, Inokuchi K. Jpn J Surg. 1982;12(4):244–248.
17. Clinical study of PSK as an adjuvant immunochemotherapeutic agent against gastric cancer. Mitomi T, Ogoshi K. Gan To Kagaku Ryoho. 1986;13(8):2532–2537.
18. Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years. Niimoto M, Hattori T, Tamada R, Sugimachi K, Inokuchi K, Ogawa N. Jpn J Surg. 1988;18(6):681–686.
19. Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Nakazato H, Koike A, Saji S, Ogawa N, Sakamoto J. Lancet. 1994;343(8906):1122–1126.
20. Immunotherapy as adjuvant treatment after curative resection of gastric cancer. Kondo M. Lancet. 1994;344(8917):274.
21. Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer. Torisu M, Hayashi Y, Ishimitsu T, Fujimura T, Iwasaki K, Katano M, Yamamoto H, Kimura Y, Takesue M, Kondo M & Nomoto K. Cancer Immunol Immunother. 1990;31(5):261–268.
22. Randomized, controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. Mitomi T, Tsuchiya S, Iijima N, Aso K, Suzuki K, Nishiyama K, Amano T, Takahashi T, Murayama N, Oka H, Oya K, Noto T, Ogawa N. Dis Colon Rectum. 1992;35(2):123–130.
23. Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study. Ohwada S, Ikeya T, Yokomori T, Kusaba T, Roppongi T, Takahashi T, Nakamura S, Kakinuma S, Iwazaki S, Ishikawa H, Kawate S, Nakajima T, Morishita Y. Br J Cancer. 2004;90(5):1003–1010.
24. Effect of Krestin (PSK) as adjuvant treatment on the prognosis after radiotherapy in patients with non-small cell lung cancer. Hayakawa K, Mitsuhashi N, Saito Y, Takahashi M, Katano S, Shiojima K, Furuta M, Niibe H. Anticancer Res. 1993;13(5C):1815–1820.
25. Postoperative long-term immunochemotherapy for esophageal carcinoma. Okudaira Y, Sugimachi K, Inokuchi K, Kai H, Kuwano H, Matsuura H. Jpn J Surg. 1982;12(4):249–256.
26. Adjuvant PSK immunotherapy in patients with carcinoma of the nasopharynx. Go P, Chung CH. J Int Med Res. 1989;17(2):141–149.
27. Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. Toi M, Hattori T, Akagi M, Inokuchi K, Orita K, Sugimachi K, Dohi K, Nomura Y, Monden Y, Hamada Y. Cancer. 1992;70(10):2475–2483.
28. Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Iino Y, Yokoe T, Maemura M, Horiguchi J, Takei H, Ohwada S, Morishita Y. Anticancer Res. 1995;15(6B):2907–2912.
29. HLA antigen as predictive index for the outcome of breast cancer patients with adjuvant immunochemotherapy with PSK. Yokoe T, Iino Y, Takei H, Horiguchi J, Koibuchi Y, Maemura M, Ohwada S, Morishita Y. Anticancer Res. 1997;17(4A):2815–2818.
30. Enhancing effect of irradiation on carcinoma of the uterine cervix by administering the protein-bound polysaccharide kureha (PSK)–quantitative nuclear DNA analysis following irradiation. Hayashi Y. Nihon Sanka Fujinka Gakkai Zasshi. 1988;40(2):179–186.
31. Coriolus versicolor – innovation in prevention of oncogynecological diseases, especially HPV. Bogdanova J. Akush Ginekol (Sofia). 2008;47(Suppl3):51–53.
32. Coriolus versicolor supplementation in HPV patients. [Poster]. Couto JS, da Silva DP. 20th European Congress of Obstetrics and Gynaecology, 2008.
33. Coriolus – Assessment of the effect on patients infected with low and high-risk types of HPV. Borisov S. Clin J Mycol. 2012;3(2):2–3.
34. A biological response modifier, PSK, inhibits reverse transcriptase in vitro. Hirose K, Hakozaki M, Kakuchi J, Matsunaga K, Yoshikumi C, Takahashi M, Tochikura TS, Yamamoto N. Biochem Biophys Res Commun. 1987;149(2):562–567.
35. Polysaccharopeptide from the turkey tail fungus Trametes versicolor (L.:Fr.) Pilát inhibits Human Immunodeficiency Virus type 1 reverse Transciptase and Protease. Ng TB, Wang HX, Wan DCC. Int J Med Mushrooms. 2006;8(1):39–43.
36. The clinical use of Coriolus versicolor supplementation in HIV+ patients and the impact on CD4 count and viral load. [Poster]. Pfeiffer M. Presented at the III International Symposium on Mushroom Nutrition in Milan on Saturday, March 10th, 2001.
37. The effectiveness of Coriolus versicolor supplementation in the treatment of Kaposi sarcoma in HIV+Patients. [Poster]. Tindall J, Clegg E. Presented at the 10th International Congress of Mucosal Immunology in Amsterdam, June 28th–July 1st, 1999.
38. In vitro inactivation of herpes simplex virus by a biological response modifier, PSK. Monma Y, Kawana T, Shimizu F. Antiviral Res. 1997;35(3):131–138.
39. Coriolus. Munroe JA. J Integr Med. 2004;8:101–108.
40. Effects of a hot-water extract of Trametes versicolor on the recovery of rat liver function. Kim BK, Park SE, Kim SY, Hyun JW, Kim HW, Shim MJ. Int J Med Mushrooms. 2000;2(1):35–42.
41. Pharmacological studies on certain mushrooms from China. Ooi VEC. Int J Med Mushrooms. 2001;3(4):341–354.