- How It Works
- Purported Uses
- Research Evidence
- Patient Warnings
- Side Effects
- Special Point
- Dosage (Inside MSKCC Only)
Scientific Name
Coriolus versicolor, Trametes versicolor, Polyporus versicolor, Polystictus versicolor
Common Name
PSK, PSP, VPS, Trametes versicolor, Turkey Tai, Yun Zhi, Kawaratake, Krestin
Brand Name
Krestin
Clinical Summary
Coriolus versicolor is a mushroom of the Basidiomycetes class. It was used initially in Traditional Chinese medicine as a tonic, but recent studies suggest that it has immunostimulant and anti-tumor properties. Polysaccharide-K (PSK), a proprietary product derived from Coriolus, was developed for cancer treatment in Japan. When used as an adjuvant, PSK appears to improve survival rates in patients with gastric (1) (2) and colorectal (3) (4) (5) cancers. Other Coriolus extracts, such as polysaccharide-peptide (PSP) and VPS, are available as dietary supplements. One clinical study demonstrated that when used in conjunction with chemotherapy, PSP may benefit patients with advanced non-small cell lung cancer (6). Other clinical studies using Coriolus extract alone or in combination with other botanicals also suggest positive immunomodulatory effects (7) (8). However, studies on breast cancer (9), hepatocellular carcinoma (10), and leukemia (11) produced mixed results. A hot water extract of Coriolus, VPS, was found to enhance development of large intestinal tumors in mice (12). Coriolus extracts are generally well tolerated but minor adverse effects have been reported.
Many over-the-counter Coriolus products are not standardized, making it difficult to compare potency between brands. It is also unclear if PSK, PSP and other Coriolus extracts have comparable effects.
Purported Uses
- Cancer prevention
- Cancer treatment
- Chemotherapy side effects
- Hepatitis
- Herpes
- Immunostimulation
- Infections
- Radiation therapy side effects
- Strength and stamina
Constituents
Proteoglycans: Polysaccharide-K (PSK), a beta-1,4-glucan (isolated from the CM-101 strain), polysaccharide-P (PSP), isolated from the COV-1 strain
Mechanism of Action
Coriolus versicolor is thought to be a biological response modifier. The proteoglycan constituents are responsible for its immunostimulant and anticancer activities. Many different mechanisms of action have been proposed. PSK has been found to induce cytokine expression in human peripheral blood mononuclear cells in vitro. In another studies, PSP, as well as Coriolus extract, selectively induced apoptosis of human promyelocytic leukemia HL-60 cells (13) (23). It also increased apoptotic cell death in cells that had been treated with camptothecin. In these cells, PSP reduced cellular proliferation, inhibited cell progression through both the S and G2 phases of DNA replication, reduced 3H - thymidine uptake, and prolonged DNA synthesis time (14). An additional in vitro study showed that a medicinal mushroom blend that included Coriolus Versicolor inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in the invasive human breast cancer cell line MDA-MB-231 (15). DNA-microarray analysis indicated that the mushroom extract inhibited the expression of cell cycle regulatory genes and suppressed metastatic behavior through the inhibition of cell adhesion, cell migration, and cell invasion . The inhibition of metastatic behavior was linked to the suppression of urokinase plasminogen activator (uPA) (15). PSP has also been shown to inhibit the interaction between HIV-1 gp120 and CD4 receptor, HIV-1 transcriptase activity, and glycohydrolase enzyme activity associated with viral glycosylation (16). Several animal studies report of synergism between PSK and biologic therapies, including a concanavalin A-bound L1210 vaccine and the IgG2a monoclonal antibody against human colon cancer cells (17). PSP induces cytokine production and T-cell proliferation and prevents immune suppression due to cyclophosphamide in animal models. Peritoneal macrophages isolated from mice that were fed PSP show increased production of reactive nitrogen intermediates, superoxide anions, and tumor necrosis factor (18). PSP also shows analgesic activity in mouse models (19). Non-small cell lung cancer patients have increased leukocyte and neutrophil counts, and increased serum IgG and IgM after consumption of PSP (6). Healthy volunteers as well as breast cancer patients who used a formula containing Coriolus and Salvia were found to have elevated counts of T-helper lymphocytes (CD4+), high ratio of CD4+/CD8+), and elevated absolute counts of B-lymphocytes (7) (8). TNF-alpha and IL-8 gene expression were also found to be significantly induced after PSK administration in healthy volunteers and gastric cancer patients, although individual response varied (20).
Pharmacokinetics
Absorption
Animal studies with radiolabeled PSK show that it is partially decomposed to small molecular products in the digestive tract. The full molecular spectrum of labeled PSK is absorbed within 24 hours following oral administration in mice. Peak plasma levels of low molecular weight substances occur at 0.5-1 h in rats and 1-2 h in rabbits, while molecules the size of PSK appear in serum after 4, 10, and 24 h.
Distribution
Radiolabeled PSK or its metabolites are detected in the digestive tract, bone marrow, salivary glands, thymus, adrenal gland, brain, liver, spleen, pancreas, and tumor tissue in sarcoma-bearing mice. Activity remains high longest in the liver and bone marrow.
Excretion
Approximately 70% of radiolabeled PSK is excreted in expired air, 20% in feces, 10% in urine, and 0.8% in bile. Approximately 86% is excreted within 24 h.
(4)
Adverse Reactions
Adverse reactions from Coriolus are rare. However, passage of dark colored stools (not originating from occult blood) (21), darkening of fingernails (22), and low-grade hematological and gastrointestinal toxicities have been reported when used in conjunction with chemotherapy agents (3). However, such effects may be caused by the chemo agents themselves.
Herb-Drug Interactions
None known
Herb Lab Interactions
None known
Literature Summary and Critique
Wong CK, et al. Immunomodulatory effects of Yun Zhi and Danshen capsules in health subjects—a randomized, double-blind, placebo-controlled, crossover study. Int Immunopharmacology 2004;4:201-211.
One hundred healthy subjects were given a combination of Yun Zhi (Coriolus versicolor, 50 mg/kg body weight) and Danshen (Salvia miltiorrhiza, 20mg/kg body weight) capsules or placebo for four months. After a 2-month washout period, subjects who received Coriolus and Salvia capsules were given placebo while those on placebo received Coriolus and Salvia capsules for another four months. Researchers used flow cytometry and cDNA expression arrays to assess immune functions and gene expression. Results indicated that oral consumption of Coriolus-Salvia capsules significantly increased the peripheral blood mononuclear cell (PBMC) gene expression of interleukin (IL-2) receptor, increased the percentage and absolute counts of T helper cell and ratio of Thelper/Tsuppressor cells, and also the production of interferon-gamma from PBMC. Since T helper cells participate in both cell mediated and humoral immunities, Coriolus-Salvia combination may be used to enhance immune function. Studies are being conducted in cancer patients to determine the immunomodulating potential of these agents.
One hundred healthy subjects were given a combination of Yun Zhi (Coriolus versicolor, 50 mg/kg body weight) and Danshen (Salvia miltiorrhiza, 20mg/kg body weight) capsules or placebo for four months. After a 2-month washout period, subjects who received Coriolus and Salvia capsules were given placebo while those on placebo received Coriolus and Salvia capsules for another four months. Researchers used flow cytometry and cDNA expression arrays to assess immune functions and gene expression. Results indicated that oral consumption of Coriolus-Salvia capsules significantly increased the peripheral blood mononuclear cell (PBMC) gene expression of interleukin (IL-2) receptor, increased the percentage and absolute counts of T helper cell and ratio of Thelper/Tsuppressor cells, and also the production of interferon-gamma from PBMC. Since T helper cells participate in both cell mediated and humoral immunities, Coriolus-Salvia combination may be used to enhance immune function. Studies are being conducted in cancer patients to determine the immunomodulating potential of these agents.
Nakazato H, et al. Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Lancet 1994;343:1122-6.
A randomized, controlled, multicenter evaluation of chemotherapy with or without PSK in 262 patients after curative gastrectomy. Chemotherapy consisted of intravenous mitomycin C on postoperative days 1 and 7 plus 150 mg/d oral fluorouracil. The PSK group received 3 g/d oral PSK for 4 weeks alternating with 4 weeks fluorouracil, while control patients received only fluorouracil alternated with 4 weeks without treatment. Ten courses were given to both groups. PSK patients experienced a greater 5-year disease-free rate (70.7% vs. 59.4%) and 5-year survival rate (73% vs 60%) than the control group. Because eligibility criteria included a positive PPD, this trial only represents the benefits of PSK in patients with a preserved immune response.
References
- Nakazato H, et al. Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Study Group of Immunochemotherapy with PSK for Gastric Cancer. Lancet 1994; 343(8906): 1122-6.
- Niimoto M, et al. Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years. Jpn J Surg 1988; 18(6): 681-6.
- Ohwada S, et al. Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study. Br J Cancer 2004; 90(5): 1003-10.
- Mitomi T, et al. Randomized, controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. The Cooperative Study Group of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and Rectum (Kanagawa). Dis Colon Rectum 1992; 35(2): 123-30.
- Torisu M, et al. Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer. Cancer Immunol Immunother 1990; 31(5): 261-8.
- Tsang KW, et al. Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer. Respir Med 2003; 97(6): 618-24.
- Wong CK, et al. Immunomodulatory effects of yun zhi and danshen capsules in health subjects—a randomized, double-blind, placebo-controlled, crossover study. Int Immunopharmacol 2004; 4(2): 201-11.
- Wong CK, et al. Immunomodulatory activities of Yunzhi and Danshen in post-treatment breast cancer patients. Am J Chin Med 2005; 33(3): 381-95.
- Iino Y, et al. Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Anticancer Res 1995; 15(6B): 2907-11.
- Suto T, et al. Clinical study of biological response modifiers as maintenance therapy for hepatocellular carcinoma. Cancer Chemother Pharmacol 1994; 33: S145-8.
- Ohno R, et al. A randomized trial of chemoimmunotherapy of acute nonlymphocytic leukemia in adults using a protein-bound polysaccharide preparation. Cancer Immunol Immunother 1984; 18(3): 149-54.
- Toth B, Coles M, Lynch J. Effects of VPS extract of Coriolus versicolor on cancer of the large interstine using a serial sacrifice technique. In Vivo 2006;20(3):341-6.
- Yang X, et al. The cell death process of the anticancer agent polysaccharide-peptide (PSP) in human promyelocytic leukemic HL-60 cells. Oncol Rep 2005; 13(6): 1201-10.
- Wan JMF, Sit WH, Yang X, Jiang P, Wong LY. Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells. Chinese Medicine. 2010;5:16.
- Jiang J, Sliva D. Novel medicinal mushroom blend suppresses growth and invasiveness of human breast cancer cells. Int J Oncol. 2010 Dec;37(6):1529-36.
- Collins RA, Ng TB. Polysaccharopeptide from Coriolus versicolor has Potential for Use Against Human Immunodeficiency Virus type I Infection. Pharmcology Letters 1997; 60(25): 387-387.
- Tsukagoshi S, et al. Krestin (PSK). Cancer Treat Rev 1984; 11(2): 131-55.
- Liu WK, et al. Activation of peritoneal macrophages by polysaccharopeptide from the mushroom, Coriolus versicolor. Immunopharmacology 1993; 26(2): 139-46.
- Ng TB, Chan WY. Polysaccharopeptide from the mushroom Coriolus versicolor possesses analgesic activity but does not produce adverse effects on female reproductive or embryonic development in mice. Gen Pharmacol 1997; 29(2): 269-73.
- Kato M, et al. Induction of gene expression for immunomodulating cytokines in peripheral blood mononuclear cells in response to orally administered PSK, an immunomodulating protein-bound polysaccharide. Cancer Immunol Immunother 1995; 40(3): 152-6.
- Shiu WCT, et al. A Clinical Study of PSP on Peripheral Blood Counts during Chemotherapy. Phytotherapy Research 1992; (6): 217-218.
- Kidd, PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev 2000 5(1): 4-27.
-
Lau CB, et al. Cytotoxic activities of Coriolus versicolor (Yunzhi) extract on human leukemia and lymphoma cells by induction of apoptosis. Life Sci 2004; 75(7): 797-808.
How It Works
Bottom Line: Coriolus versicolor extracts have been studied in cancer patients with some positive results. However, more studies are needed to verify such effects.
Coriolus versicolor is a mushroom that was used in traditional Chinese medicine as a tonic. PSK and PSP, polysaccharide compounds isolated from Coriolus, were shown to improve immune function in patients with certain cancers when used in conjuction with chemotherapy.
Purported Uses
- To prevent and treat cancer
When used in combination with certain chemotherapy regimens, PSK has been shown to benefit patients who have undergone surgical removal of stomach and colorectal cancers. Clinical trials in patients with breast cancer, leukemias, and liver cancer do not show beneficial results. - To reduce the side effects of chemotherapy
Animal studies suggest that PSK can prevent chemotherapy-induced immune suppression, but no clinical trials have been performed to confirm this effect in humans. - To stimulate the immune system
Studies in animals and human volunteers suggest that PSK might stimulate the immune system. Whether this stimulation results in improved fighting of disease has not been determined. - To treat infections
Coriolus’ effects against infections have not been studied in the laboratory or in clinical trials. - To reduce the side effects of radiation therapy
Studies in mice and rats suggest that PSK can prevent radiation therapy-induced immune suppression, but this is yet to be proven in clinical trials.
Research Evidence
Gastric Cancer:
Two randomized, controlled clinical trials have examined the effectiveness of PSK in patients who underwent curative surgery (full removal of the tumor) for gastric cancer.
Two randomized, controlled clinical trials have examined the effectiveness of PSK in patients who underwent curative surgery (full removal of the tumor) for gastric cancer.
In the first study, the patients received 3 grams of PSK alone, normal chemotherapy alone, or chemotherapy and PSK together for one year, starting two weeks after surgery. After five years, the group that took chemotherapy and PSK had the highest survival rates.
In the second study, half of the patients alternated four weeks receiving fluorouracil, four weeks taking 3 grams of PSK daily, while the other half alternated four weeks of fluorouracil with four weeks of no treatment. Ten courses were given altogether. After five years, the PSK plus chemotherapy group had higher survival rates. However, only patients with a preserved immune response were allowed to take part in this study, so the results might not apply to immune-suppressed patients.
Colon Cancer:
In randomized controlled study, patients received chemotherapy (5-FU) with or without 3 grams of PSK daily, starting after surgery. Chemotherapy was given for six months, while PSK was continued for three years. Those patients who had taken PSK had a higher average survival rate than those who had received chemotherapy alone.
Breast Cancer:
PSK was combined with chemotherapy to measure its effects in patients undergoing surgical removal of operable breast cancer. The patients randomly received combination chemotherapy (5-fluorouracil, cyclophosphamide, mitomycin C, and predonisolone) with or without 3 grams of PSK daily. Each treatment cycle lasted 28 days and was carried out at 6-month intervals for 5 years. Those patients who took PSK along with chemotherapy had a slightly longer average survival time, but the difference was not statistically significant. More clinical trials are needed, and should test PSK in combination with other chemotherapy regimens.
Patient Warnings
This product is regulated by the F.D.A. as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
Side Effects
- Passage of dark colored stools
- Darkening of fingernails
- Low-grade toxicities have been reported when used in conjunction with chemotherapy agents. However, such effects may be caused by the chemo agents themselves.
Special Point
PSK is approved for clinical use in Japan. Purified PSK, PSP extracts or raw Coriolus extract alone or in combination with other herbs were used in clinical studies. However, the clinical effects of these products have not been compared.
Dosage (Inside MSKCC Only)
This field is only visible to only Inside MSKCC users.
Aliases
PSK
Trametes versicolor
Yun Zhi
E-mail your questions and comments to aboutherbs@mskcc.org.
