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Turkey Tail Fungus

Background & General Info

Turkey tail fungus belongs to a more advanced Basidiomycetes class of fungi and is scientifically named as Trametes versicolor, Coriolus versicolor, or Polyporus versicolor. This small, flexible polypore fungus plays a vital ecological role as a recycler of dead and decaying trees in the forests, inhabiting tree trunks, dead hardwood logs, and decomposing stumps in several diverse climates, particularly in North America. ^[1] It forms flat and leathery brackets in overlapping or fusing clusters that can entirely cloak stumps and logs. ^[2]

From the almost 60 species belonging to the genus Trametes around the globe, few of which having been biologically evaluated for their medicinal properties, Trametes versicolor (L.:Fr.) Lloyd stands as the most celebrated of all. Turkey tail fungus, as this species is famously branded in western cultures, is also referred to in China as yun zhi, or “cloud-like mushroom,” and in Japan as Kawaratake, which means a “mushroom by the riverbank”. ^[3] The distinct color bands on turkey tail mushroom’s upper surface and the white pores underneath make it a species that is easy to spot; such color banding differs even within a strain depending on the macro- and micronutrients absorbed by the fungus from its host. ^[2]

Turkey Tail Fungus - Botany

Turkey tail mushroom, as its name apparently implies, resembles the shape and colors of a wild turkey’s tail. Its species name, versicolor, denotes the multiple variable colors the mushroom displays, ranging in cap coloration from white, to brown, to cinnamon, to reddish brown, sometimes with shades of blue, green, and orange. ^[4] The mushroom is described as zonate because of its sharply contrasting concentric zones of color and texture, with the cap surface being finely fuzzy or velvety and the fuzzy zones alternating with smoother zones. ^[2][4] Flexible when fresh, the cap is nearly 10 cm across and is only a few millimeters thick. The cap can be either circular, semicircular, bracket-shaped, or kidney-shaped and frequently fuses and overlaps with other caps. ^[2][4] The pore surface on the other hand is whitish to pale grayish, with four or more minute round pores in every millimeter on the underside of the brackets and with tubes up to 3 mm deep. ^[4] The white, linear mycelium gives off a light yellow metabolite on overcolonized spawn and fruiting substrates and creates a thick mat similar to those of most polypores. ^[2]

History & Traditional Use

Turkey tail fungus owns a long rich history of food and medicinal use in Asia, dating back hundreds of years, especially in China where this mushroom goes by the name “yun zhi” or cloud fungus. ^[5] It is not actually considered a tasty mushroom because of its paper-like and fibrous texture, but the medicinal values of its fruiting bodies exceedingly compensate for this. ^[2] The Compendium of Chinese Materia Medica, which was written during the Ming Dynasty, mentioned and recorded several conventional uses of more than 120 strains of yun zhi in traditional Chinese medicinal practice, such as being a toxin remover, strengthener, energy booster, and enhancer of liver and spleen function and the immune response, especially when the mushroom is dried, ground, and prepared into tea. ^[3]

In 1965, a chemical engineer in Japan observed a case of cancer remission after oral consumption of “yun zhi,” leading eventually to the discovery of immunomodulatory activities of Trametes versicolor polysaccharide peptides. ^[6] Subsequently, other anticancer proteoglycan constituents of turkey tail fungus were identified, such as the closely related Krestin and polysaccharide peptide, which was first isolated in China in 1983. ^[5] Krestin, better known as polysaccharide K, of turkey tail fungus was approved as a prescription drug for cancer treatment in 1977 by the Japanese Ministry of Health and Welfare and is currently extensively used in this country as a routine adjuvant immunotherapy for diverse cancer types, both during and after radiation and chemotherapy. ^[7][8][9] Of note is the fact that turkey tail fungus’ polysaccharide K is the first polysaccharide endorsed as an antitumor drug by the aforementioned regulatory agency in Japan. ^[9] By 1987, greatly purified extract of Trametes versicolor strain CM-101 has become widely commercially available, with polysaccharide K making up over 25% of total national expenditure for anticancer agents in Japan. ^[8]

Turkey Tail Fungus - Herbal Uses

Turkey tail mushroom extract has long been employed in Asia and lately in Western countries as a cancer remedy owing to its alleged immunity-potentiating effects. Several naturopathic physicians and integrative oncologists in the United States commonly prescribe whole freeze-dried turkey tail mushrooms as treatment for breast cancer. ^[10] This mushroom is highly regarded in traditional Chinese medicine for its broad range of biological activities, including anticancer, antioxidant, and antiviral properties. ^[9] Its efficiency to impede carcinogenesis attributable to its bioactive polysaccharide K and polysaccharide peptide content has been well acknowledged, especially in Japan. ^[9] In conventional medicine, Trametes versicolor is prescribed as treatment not only of cancers but also of chronic hepatitis, rheumatoid arthritis, and infections of the respiratory, urinary, and digestive tracts. ^[3]

Turkey Tail Fungus - Constituents / Active Components

A 2015 qualitative phytochemical screening of an ethanolic extract from the fruiting bodies of Trametes versicolor detected secondary metabolites such as triterpenes, steroids, flavonoids, alkaloids, and, in small amounts, cardenolides. ^[11] Analysis via gas chromatography–mass spectrometry by Kamiyama et al. (2013) of an acetone extract prepared by Soxhlet extraction from turkey tail fungus positively identified 76 compounds, which can be categorized as alkyl esters, acetals, lactones, alkyl acids, heterocyclic compounds, alkyl alcohols, alkyl aldehydes, ketones, and aromatic compounds. The table below illustrates the compounds detected in Trametes versicolor acetone extract. ^[9]

Turkey Tail Fungus - Medicinal / Scientific Research

Up to this date, among all medicinal mushrooms with anticancer value and documented health-promoting properties, turkey tail fungus has been the most methodically researched and biologically evaluated. It has drawn considerable interest from the scientific community, along with other mushroom species such as shiitake (Lentinus edodes) and reishi (Ganoderma lucidum). High-molecular-weight fractions from the mycelium of turkey tail mushrooms have been investigated by several human clinical trials, especially its polysaccharide K, which in Japan is an approved drug orally provided at a dose of 3 grams daily, in conjunction with many chemotherapy protocols. According to the results of quite a few in vitro and in vivo studies, the administration of turkey tail fungus leads to an augmentation of immune functions and antiviral, anticancer, and cholesterol-regulating effects, among others. Turkey tail fungus treatment has also been attested by recent clinical trials to enhance quality of life after surgery and, in tandem with chemotherapy, extend 5- and 10-year survival rates in individuals with colorectal and stomach cancers. ^[1] Additionally, numerous publications have concluded that the polysaccharide K in turkey tail fungus is an immune modulator that stimulates the gene expression of IL-8 in peripheral blood mononuclear cells after oral administration, elicits the proliferation of T cells, and enhances the function of CD4+ T cells in gut-associated lymphoid tissues. ^[8]

Antioxidant And DNA-Protective:

Findings of Szeto et al. (2013) suggested the direct antioxidant attribute of turkey tail fungus (termed “yun zhi” in their study) against oxidant challenge on the DNA of lymphocytes, with the active constituent of the mushroom appearing to be membrane permeable. In this in vitro study, a commercial extract of yun zhi, known to play as an immunomodulator, was dissolved in water and diluted in five concentrations (101–105 μg/L) with suitable buffers, and lymphocytes collected from three healthy individuals were incubated with the yun zhi extract for half an hour, followed by 5 minutes of oxidant challenge by 45 μM hydrogen peroxide. In both standard alkaline comet assay and lysed cell comet assay performed in parallel, U-shaped dose–response was observed. A genoprotective effect against oxidative damage was exhibited by yun zhi at a concentration of 104 μg/L, as demonstrated in the standard alkaline comet assay, with a 25% decrease in comet score. On the other hand, lymphocytes seemed to have been protected in the lysed cell comet assay. ^[12]

Kamiyama et al. (2013) verified the antioxidant and anti-inflammatory activities of different extracts acquired from the Trametes versicolor mushroom, although the Trametes versicolor acetone extract proved to display the highest antioxidant activity (50.9%) in comparison with methanol (33.9%), n-hexane (29.5%), and chloroform (15.2%) extracts at a concentration of 500 µg/mL. The Trametes versicolor acetone extract presented a dose-dependent anti-inflammatory or lipoxygenase-inhibitory activity by 76.4% at 500 µg/mL, 55.6% at 200 µg/mL, and 37.0% at 100 µg/mL, with hexadecanoic acid being this extract’s chief component (18.11 mg/kg) among a total of 76 compounds detected, followed by 5-hydroxy-2-pentanone (17.33 mg/kg), lactic acid (3.25 mg/kg), and acetic acid (3.21 mg/kg). Furfural (1.48 mg/kg), γ-butyrolactone (0.51 mg/kg), furfuryl alcohol (0.49 mg/kg), 2-methoxy-4-vinylphenol (0.49 mg/kg), 2,6-dimetoxy-4-vinylphenol (0.33 mg/kg), and benzaldehyde (0.15 mg/kg) had also been isolated from the extracts, which were all probable principles of antioxidant activity. ^[9]

Anticancer:

Immunoceuticals that display anticancer properties in vitro or in animal and human studies have been acquired from turkey tail fungi. When taken orally, these substances are interesting in that their immunotherapeutic efficacy comes along with nontoxicity and good tolerance. Two promising proteoglycans isolated from turkey tail mushroom are polysaccharide K (also known as Krestin) and polysaccharide peptide. Since 1970, several Japanese trials have demonstrated the extension of survival at 5 years or beyond as a result of intervention comprising polysaccharide K in patients diagnosed with stomach, colon–rectum, esophagus, nasopharynx, lung (non-small cell-type), and HLA B40-positive breast cancers. On the other hand, phase II and III trials in China had investigated polysaccharide peptide, which, in double-blind trials, significantly extended five-year survival in patients with esophageal cancer and appreciably enhanced the quality of life, conferred considerable pain relief, and improved the immune status in majority of study participants (70–97%) suffering from cancers of the stomach, esophagus, lung, ovary, and cervix. Both of these proteoglycans have been found to boost immune cell production, improve chemotherapy symptoms, and ameliorate tumor infiltration by dendritic and cytotoxic T-cells, which, when coupled with their overall high tolerability, verified benefits to survival and quality of life, and compatibility with chemotherapy and radiation therapy, make polysaccharide K and polysaccharide peptide potential candidates in cancer management regimens. ^[6]

Preclinical and clinical studies have evinced the significant immunologic and oncologic attributes of Trametes versicolor, especially the polysaccharide peptides that can be extracted from it, in different cancer patients diagnosed with lung, gastrointestinal, and breast cancers; as a matter of fact, there have been a number of peer-reviewed publications concerning turkey tail fungus and its anticancer activities, including 37 in vitro articles, 55 animal studies, 43 published human clinical studies, and 11 review articles on gastrointestinal, breast, and lung cancers. ^[5] The mechanism of action of Trametes versicolor has been scientifically proposed to entail an improvement in both innate and adaptive immune responses via Toll-like receptor 2 (TLR2) agonist activity. ^[8]

A 2003 double-blind placebo-controlled randomized trial reported that 28-day administration of polysaccharide peptides from turkey tail fungus appeared to result in slower deterioration in patients with advanced non-small cell lung cancer. In this study, 34 patients were randomized into groups receiving either polysaccharide peptide treatment or control. Patients treated with polysaccharide peptide for 28 days were observed to exhibit significant improvement in blood leukocyte and neutrophil counts, serum IgG and IgM, and body fat percentage, as compared with control (p < 0.05). Additionally, fewer patients from the experimental group withdrew due to disease progression than their control counterparts (5.9 and 23.5%, respectively; p = 0.04), and there was an absence of adverse events related to Trametes versicolor polysaccharide peptide administration. ^[13]

A 2015 systematic review on polysaccharide K derived from Trametes versicolor mushroom accumulated clinical and preclinical evidences on its effectiveness and safety as treatment for lung cancer and substantiated its ability to improve immune function, decrease tumor-related symptoms, and extend survival among lung cancer patients. This review and analysis of scientific data comprised six randomized controlled trials, five nonrandomized controlled trials, and seventeen preclinical studies, nine of the reports being publications in the Japanese language and with polysaccharide K having been safely administered after or together with standard radiation and chemotherapy. Fifteen preclinical studies confirmed the anticancer effects of polysaccharide K through mechanisms involving immunomodulation and potentiation of immune surveillance and direct tumor suppression in vivo, leading to decreased tumor growth and antimetastatic effects. An enhancement of different survival measures such as median survival and 1-, 2-, and 5-year survival was demonstrated by the nonrandomized controlled trials, whereas the randomized controlled trials in this review mentioned benefits and favorable impact of polysaccharide K on various endpoints, including immune parameters and hematological function, performance status and body weight, tumor-related symptoms such as fatigue and anorexia, and survival. ^[7]

When adjoined to standard adjuvant chemotherapy comprising intravenous mitomycin plus oral fluorouracil, the protein-bound polysaccharide K has been proven to confer additional benefits in patients who had underwent curative gastrectomy as treatment of gastric cancer. In 46 institutions located in central Japan, 262 patients were randomly divided in this trial into a group treated with standard treatment alone or another receiving standard treatment in combination with polysaccharide K and were followed up for 5 to 7 years. The study results indicated a significant improvement in 5-year disease-free rate (70.7% vs. 59.4% in standard treatment group, p = 0.047) and 5-year survival (73.0% vs. 60.0%, p = 0.044) from treatment with polysaccharide K, which was clinically well tolerated by patients. ^[14]

A noteworthy number of epidemiologic and clinical studies on the immune effects of conventional cancer treatment indicate how immune function contributes to the prevention of breast cancer. Employing oral preparations from turkey tail fungi and their polysaccharide constituents in immune therapy has been proposed to bear potential as an adjuvant cancer therapy and secondary prevention strategy, ^[5] enhancing the immune response of women with breast cancer after standard chemotherapy and radiotherapy. Evaluating immunostimulatory effect in vitro by using splenocytes acquired from neu transgenic mice and TLR2 knockout mice, Lu et al. (2011) demonstrated that Krestin is a selective agonist of TLR2, which influences the activation of dendritic cells and T cells by Krestin, and that its oral administration in neu transgenic mice leads to a marked suppression of breast cancer growth. At a concentration of 10–200 µg/mL, Krestin treatment that lasted for 48–96 hours dose-dependently and time-dependently induced the proliferation of splenocytes, elevated the percentages of CD4+ (p = 0.01) and CD8+ T cells (p=0.0015) among all splenocytes, decreased the percentage of B cells (p=0.0003), and induced the secretion of Th1 cytokines. The antitumor property of Krestin relies on both CD8+ T cells and NK cells, but not CD4+ T cells, as indicated by the selective depletion of specific cell populations, and is mediated by TLR2 since in this study Krestin failed to inhibit the tumor growth in TLR2 knockout mice. ^[8]

Antiviral:

Major constituents of turkey tail fungi possess antiviral activity, high solubility in water, heat stability, and low cytotoxicity, making these compounds excellent antiviral agents in vivo. As a biological response modifier, polysaccharide K from turkey tail fungi had been confirmed by an early study to exhibit antiviral activity against human immunodeficiency virus (HIV) in vitro. The study employed either a novel infection system using MT-4 cells carrying human T-cell lymphotropic virus type I or a coculture system utilizing MOLT-4 cells and virus-producing cells MOLT-4/HIVHTLV-IIIB that efficiently stimulate multinucleated giant cells. Findings from the study indicated that polysaccharide K almost entirely hindered cytopathic effects, including giant cell formation, and HIV-specific antigen expression in both MT-4 cells and MOLT-4 cells at a concentration of 0.4 and 0.8 mg/mL, respectively, and possibly specifically hampered the first stages of HIV infection through modification of the viral receptor. ^[15]The antiviral potential of polysaccharide peptide isolated from turkey tail mushroom against HIV type 1 infection has also been validated by Collins and Ng (1997) in a series of in vitro assays. In this study, polysaccharide peptide was found to inhibit the interaction between HIV-1 gp 120 and immobilized CD4 receptor (IC50 = 150 μg/mL). It also potently suppressed recombinant HIV-1 reverse transcriptase (IC50 = 6.25 μg/ml) and a glycohydrolase enzyme related to viral glycosylation. ^[16]

Antiprotozoan:

At concentrations below 100 μg/mL, ethyl acetate and ethanol extracts from the fresh fruiting bodies of turkey tail mushrooms had been demonstrated to show anti-leishmanial activity against promastigotes of Leishmania amazonensis, a causative agent of the widespread human cutaneous leishmaniasis, with IC50 values of 101.8 ± 4.2 μg/mL and 97.4 ± 2.0 μg/mL, respectively. Moreover, cytotoxicity of these extracts against peritoneal macrophages obtained from BALB/c mice was noted. ^[11]

Cholesterol-lowering:

The polysaccharide K derived from turkey tail mushrooms has been found to decrease the levels of low-density lipoprotein in hyperlipidemic patients. The study results of Hor et al. (2011) demonstrated the lipid-lowering ability of turkey tail fungus extract to decrease and prevent accumulation of very high levels of cholesterol in the bloodstream. In this study, hypercholesterolemia was chemically elicited in rat models by poloxamer 407 at a dose of 500mg/kg, whose intraperitoneal administration significantly increased the serum lipid levels, such as total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels in hypercholesterolemic rats compared with normal control rats. Upon administration of turkey tail fungus extract however, a noteworthy reduction in serum total cholesterol (p < 0.01) and triglyceride (p < 0.05) levels and a decrease in coronary risk index (CRI) were observed in P-407-treated rats. Hypercholesterolemia was also induced in rat models in this study through feeding of a high-cholesterol diet comprising (by weight) 2% cholesterol, 0.5% cholic acid, and 10% butter, which significantly elevated (p < 0.001) the serum total cholesterol and low-density lipoprotein cholesterol levels of rats after 14 days of feeding. Oral administration of turkey tail fungus extract to rats fed with high-cholesterol diet led to a marked dose-dependent reduction in serum levels of total cholesterol and low-density lipoprotein cholesterol, a significant elevation of high-density lipoprotein cholesterol levels, and a decrease in CRI ratio. ^[17]

Hepatoprotective:

High-molecular-weight fractions of Trametes versicolor had been shown in a 2000 study to possess hepatoprotective activity and to significantly suppress the growth of human hepatoma cells in vitro; in particular, these fractions from turkey tail fungus significantly restored the function of regenerated hepatocytes. At a concentration of 100 μg/mL, hot water extract, ethanol-soluble fraction, and ethanol-insoluble fraction acquired from the basidiocarps of this mushroom displayed growth inhibition of SK-Hep-1 hepatoma cells of rats, with IC50 values of 36.9, 64.2, and 37.1 μg/mL, respectively. With respect to DNA and RNA biosynthesis, which was assessed in the study via [3H]thymidine incorporation in primary culture of hepatocytes isolated from regenerated rat liver 1 day following partial hepatectomy, hot-water extract and ethanol-insoluble fraction of turkey tail fungus enhanced the biosynthesis of DNA by 1.5 and 1.4 times that of the control, respectively, and increased RNA biosynthesis by 1.5- and 1.8-fold of that of the control, respectively. The same fractions had also potentiated the biosynthesis of protein by 1.4 and 1.5 times, respectively. ^[18]

Turkey Tail Fungus - Contraindications, Interactions, And Safety

Safety issues related to the use of turkey tail fungus appear to be low, with very few published reports on adverse effects and severe drug interactions. The use of this mushroom for long-term treatment and during pregnancy has not also been completely determined, so pregnant or lactating women are advised to avoid use. ^[1] In the study of Nakazato, Koike, Saji, Ogawa, and Sakamoto (1994), a treatment regimen with polysaccharide K resulted in only mild side effects, such as nausea, leucopenia, and liver function impairment, and overall, the treatment was characterized with excellent tolerability and compliance. ^[14]

A 2012 phase I study evaluated the maximum tolerated dose of a turkey tail fungus preparation when administered on a daily basis in divided doses for 6 weeks following recent completion of radiotherapy. This two-center, dose escalation trial involved nine women who were divided equally into three cohorts receiving doses of 3, 6, or 9 grams each of turkey tail fungus preparation. Nine adverse events were reported in this study, of which seven were categorized as mild; one, moderate; and one, severe. The immunological findings also demonstrated increased lymphocyte counts at doses of 6 and 9 grams/day, elevated functional activity of natural killer cells at a dose of 6 grams/day, and dose-related increases in CD8+ T cells and CD19+ B cells, but not CD4+ T cells or CD16+56+ NK cells, suggesting the safety and good tolerability of up to 9 grams/day of turkey tail fungus preparation in women with breast cancer in the postprimary treatment setting, as well as its potential worth in improving immune status of immunocompromised breast cancer patients after standard primary oncologic treatment. ^[10]

Article researched and created by Dan Ablir for herbshealthhappiness.com.
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