International Journal of Medicinal Mushrooms, Vol. 6, pp. 195–218 (2004)
© 2004 by Begell House, Inc. 195
Medicinal Value of Turkey Tail Fungus Trametes
versicolor (L.:Fr.) Pilát (Aphyllophoromycetideae).
A Literature Review*
Christopher R. Hobbs
Institute for Natural Products Research, Davis, California, USA
Address all correspondence to Christopher R. Hobbs, Institute for Natural Products Research, 644 Miller Drive, Davis, CA
95616, USA; firstname.lastname@example.org
ABSTRACT: Trametes (=Coriolus) versicolor (L.:Fr.) Pilát, is a small, ﬂ exible polypore fungus that is
an important part of the forest ecology as a recycler of dead and dying trees in forests throughout the
world. Of all the mushrooms used today for their medicinal qualities, more research has been performed
on this species than any other, including shiitake (Lentinus edodes), or reishi (Ganoderma lucidum). High-
molecular-weight fractions from the mycelium have been studied in human clinical trials, especially
polysaccharide Krestin (PSK), which is an approved drug paid for by national health care in Japan. PSK
is given orally (often 3 grams/day), along with several chemotherapy protocols. Numerous in vitro and in
vivo studies show enhancement of immune functions, antiviral eﬀ ects, and cholesterol-regulating eﬀ ects,
among others. New clinical trials demonstrate improved quality of life after surgery and in combina-
tion with chemotherapy, as well as extended 5- and 10-year survival rates, especially for patients with
colorectal and stomach cancers. Further studies are needed in order to clarify the most eﬀ ective forms
of the whole fruiting body extracts, mycelium extracts, and their high-molecular weight fractions, along
with the optimum dose. Safety issues, while not completely determined for long-term treatment, dur-
ing pregnancy, or in combination with pharmaceutical drugs, seem to be of low concern, with no noted
published side eﬀ ects or interactions with drugs reported.
KEY WORDS: Trametes versicolor, turkey tail fungus, polysaccharide Krestin, traditional Chinese
medicine, medicinal mushrooms, immunosuppressive acidic protein
CT: chemotherapy; CQ: carbazilquinone; DC: dendritic cells; 5′-DFUR: doxiﬂ uridine; ECG: electrocardiogram; FT:
FT-207, a furanyl analog of 5-ﬂ uorouracil; 5-FU: 5-ﬂ uorouracil; HLA: human leukocyte-associated antigens; HSPx:
heat shock protein; i.p.: intraperitoneal; IL-x: interleukin; IAP: immunosuppressive acidic protein; IFN: interferon;
iNOS: Inducible nitric oxide synthase; i.v.: ntravenale; LPO: lipoperoxide; M-CSF: macrophage colony-stimulating
factor; MMC: mitomycin-C; MMP-x: matrix metalloproteinase; MOLT-4: human lymphoblastic leukemia cell; MT-4:
membrane type-4; NO: nitric oxide; NSCLC: non-small cell lung cancer; OK: OK-432, chemotherapeutic agent; PG:
prostaglandin; PKC: protein kinase C; PLCC: postoperative long-term cancer chemotherapy; p.o.: oral method; PPD:
puriﬁ ed protein derivative; PMN: polymorphonuceocytes; PSK: polysaccharide krestin; PSP: polysaccharopeptide;
RT: radiotherapy; SOD: superoxidedismutase; SPCV: small polypeptide Trametes versicolor; STAT: signal transducer
and activator of transcription; TCM: traditional Chinese medicine; TGF-x: transforming growth factor; 1/ 2:
T-helper cels; TNF: tumor-necrosis factor; Tv: Trametes versicolor; WBC: white blood cells.
* An updated version of this monograph with additional material will be published in a forthcoming book by Christopher Hobbs,
Medicinal Mushrooms, ird Edition, New York: ieme Medical Publishers, Inc., ISBN: 1-58890-298-6. To reserve a copy upon
publication, call 800-782-3488, fax +1-212-947-1112, or visit www.thieme.com.
196 International Journal of Medicinal Mushrooms
C. R. HOBBS
Trametes (=Coriolus) versicolor (L.:Fr.) Pilát (turkey
tail; in Japan, T. versicolor is known as kawaratake,
which means “mushroom by the river bank”; in
China, the fungus is called yun-zhi (Yang et al.,
1993), meaning “cloud fungus.” It has been re-
nowned in Japan and China as medicine for thou-
sands of years. T. versicolor one of the most easily
identiﬁ able polypores and the most common wood
rotting species on dead hardwoods; this multicolored
mushroom is recognized throughout the world and
is thought to have had a long history of use. Native
to tropical, subtropical, and temporate zones, this
species is highly adaptive, growing on the widest
assortment of woods. Turkey tail is one of the
most potent and the best studied of all medicinal
mushrooms (Hobbs, 1995; Stamets, 2000). High-
molecular-weight fractions from the mycelium have
been studied in human clinical trials, especially PSK
(polysaccharide Krestin), which is an approved drug
paid for by national health care in Japan.
A patient with stomach cancer reported beneﬁ ts
from an herbal tea called Saru-no-koshikake, which
contained turkey tails as an ingredient (Mitomi et
PSK, the ﬁ rst polysaccharide fraction from turkey
tails, was ﬁ rst approved by the Japanese Ministry for
the treatment of cancer in 1977, and by 1987 it ac-
counted for 25.2% of the total national expenditure
for anticancer agents (Fukushima, 1989; Mizuno,
1999). Florists in Europe recently adopted this fun-
gus as one of the top species for commercial design
(Poppe and Heungens, 1991).
e lipid fraction from the carpophores of T.
versicolor amounts to 1.7% of the total weight and
contains the lanostane-type tetracyclic triterpenoid
ergosta-5,7,22,trien-3-ol (ergosterol) as the major
sterol (common in many other Polyporaceae), along
with smaller amounts of ergost-7-en-3-ol (fungis-
terol) (Yokoyama et al., 1975; Endo, 1981). ey also
contain β-sitosterol, stigmast-5-en-3-ol (Kim et al.,
1979), and hydroxymethylquinoline (Abraham and
Spasov, 1991). A sesquiterpene, coriolin, and de-
oxycoriolic acid have been isolated from the related
species, T. consors (Zhou and Yang, 1999).
e predominance of chemical, pharmacological,
and toxicological data is on two principal immu-
nologically active polysaccharide-protein complexes
with approximate molecular weights of 100 kDa
from T. versicolor, PSP (polysaccharopeptide), and
PSK (polysaccharide “Krestin”). Both complexes are
produced commercially by deep-layer cultivation of
the mycelium COV-1 and CM-101 strains. PSK
is composed of a complex of strand of β-glucans
(glucose polymers) bound to polypeptide chains
containing high amounts of aspartic and glutamic
acids, along with lower amounts of many other
amino acids (Tsukagoshi et al., 1984; Fungi Re-
search Institute, 1993). e carbohydrate glucan
backbones have main chains with β1→3 linkages
and varying degrees of branching at 4′ and 6′. ese
bond to polypeptides through O- or N-glycosidic
links. PSK powder is soluble in water, is practically
insoluble in ethanol, and contains 34–35% carbohy-
drate (ca. 92% glucan) and 28–35% protein (Ueno
et al., 1980). Zhang et al. (2001) determined the
approximate monosaccharide content to be -glu-
cose 1, -mannose 0.074, -galactose 0.067, and
ese compounds are variously called in the
literature glycoproteins, proteoglycans, or polysac-
charopeptides. ey may be most related to the
glycoproteins (Nelson and Cox, 2000). ese are
not yet fully characterized and may be related to the
integrins and other signaling molecules of plant and
animal cells. ese are information rich and have
many opportunities for hydrogen bonding and other
PSP, ﬁ rst isolated in 1983, is similar in composi-
tion to PSK, and includes small amounts of 1→
3, 1→4, and 1→6 linked galactose molecules, also
1→6 mannose and 1→4 arabinose linkages (Yang
and Zhou, 1993). e similarities and diﬀ erences
between PSP and PSK have been detailed by the
Fungi Research Institute (1993). Both PSP and PSK
Volume 6, Issue 3, 2004 197
MEDICINAL VALUE OF TURKEY TAIL FUNGUS TRAMETES VERSICOLOR
have been found to be immunomodulating and ef-
fective against tumor cells.
e high-molecular-weight glucans from PSP,
and PSK associated with the cell walls of many
species of fungi vary considerably in their degree of
branching, molecular weight, and amounts of other
sugars and amino acid residues. Some are α-glucans,
and some are true heteropolysaccharides (Ooi and
e glucans are also associated with other sugar
polymers such as mannose. For instance, when the
monosaccharides from Trametes versicolor were ana-
lyzed after being hydrolyzed, they found a propor-
tional composition of glucose 1.0, mannose 0.074,
galactose 0.067, and xylose 0.0178 (Zhang et al.,
2001). Tertiary structures may also play a role in the
immunomodulating eﬀ ects of various glucans. One
group showed the triple-helix conﬁ guration of some
native glucans is important for activity (Falch et al.,
2000), while other groups have found similar activ-
ity in all the β-glucans they tested, higher activity
in larger molecular weight glucans and in glucans
with increased β-1→6 crosslinking, at least in yeast
glucans (Sakagami et al., 1989; Okazaki et al., 1995;
Kulicke et al., 1997; Cleary et al., 1999).
e importance of intact tertiary structures, espe-
cially in ﬁ nished products, may be notable, because
solvents and heat during the processing of various
species may change or completely disrupt them.
What eﬀ ect this has on activity is not clear, and it
is not known what conﬁ gurations of these diﬀ erent
compounds lead to the highest immunomodulatory
responses, let alone the greatest clinical eﬃ cacy, in
humans. Traditional preparations of medicinal spe-
cies, used for thousands of years, might give some
support to the idea that a hot-water extraction (de-
coction) might preserve at least part of the activity.
Commercial preparations today are made from
hot water extracts, which are said to remove the
thermostable polysaccharopeptides, which are then
concentrated and puriﬁ ed (Cui and Chisti, 2003).
e amount of puriﬁ cation of a crude extract of
Trametes versicolor (Tv) will aﬀ ect its eﬀ ectiveness
as an immunomodulator and antitumor substance.
In one study, immuno suppressive acidic protein
(IAP) was induced in the serum of mice treated
with PSK and other crude extracts of Tv, but not in
the serum of mice treated with puriﬁ ed β-glucan
from Tv (Ebina, 2001).
Miyazaki et al. (1974) isolated an antitumor
polysaccharide that did not contain nitrogen and
called it coriolan. Several patents were taken out on
coriolan, but no further research has been published
in the international literature since 1986 (Sumio et
Many preliminary in vivo and in vitro studies
have shown that PSK has wide immunomodula-
tory eﬀ ects and a broad antineoplastic scope when
administered orally or by injection. At least one
group demonstrated probable absorption of ¹⁴C-
labeled PSK from the digestive tract into the blood
and subsequent migration to bone marrow, salivary
glands, brain, liver, spleen, pancreas, and tumor tis-
sue (Ikuzawa et al., 1988). ey report that about
70% was excreted in the expiratory air after 24 hours
and 15–20% in the urine after 72 hours. PSK had
diﬀ erent fates after absorption in mice, based on a
PSK antibody-indirect immunoﬂ uorescent staining
model (Endoh et al., 1988).
Although by far the greatest amount of research
has been performed on PSP and PSK, whole mush-
room extracts are widely produced for use as dietary
supplements and professional products for clinical
use by a wide range of practitioners. e aqueous ex-
tract of Tv is reported to contain PSP-like molecules
of various molecular weights. e larger molecules
are said to have the highest immunomodulatory ef-
fects. Hydroalcoholic extracts are likely to have less
activity, partly because the high-molecular weight
compounds are precipitated by alcohol and may not
go into solution.
Studies show PSP, PSK, and whole fruiting body
and mycelial extracts have a broad spectrum of
immunological eﬀ ects, some of which might be
triggered by contact with immune tissue in the
digestive tract. Mushroom cell wall components
198 International Journal of Medicinal Mushrooms
C. R. HOBBS
such as PSP are likely to interact with Langerham
cells in the mouth and have complex interactions
with dendritic cells in the Peyer’s patches in the
small intestine (Tomochika et al., 1989). rough
these interactions, many kinds of immune cells are
subsequently aﬀ ected. Tv extracts, in vitro and in
vivo, given p.o. or i.p. are known to stimulate ac-
tivity and proliferation of T cells, B lymphocytes,
monocytes and macrophages, bone marrow cells,
natural killer cells, and lymphocyte-activated killer
cells. Increased secretion of antibodies, increased
phagocytic functions of the reticuloendothial
system, and an inducer of the gene expression of
cytokines (IL-2, IL-6, interferons, and TNF) was
also seen (Tsukagoshi et al., 1984; Li et al., 1990;
Chu et al., 2002). ese eﬀ ects were associated with
stimulation of ex vivo tumor cytotoxic activity of
splenocytes and T-killer cells in mice. Tv extracts
often have a greater immunological eﬀ ect in animals
with depressed immunological function associated
with tumor implantation or chemotherapy than in
those with normal immune function. However, more
eﬀ ective therapeutic results are seen in animals and
in human trials when some intact immune function
is present (Nomoto et al., 1983).
Researchers (Wu et al., 1998) report that a pro-
tein-bound polysaccharide (PSP) derived from the
mycelium of Trametes versicolor has diﬀ erent immu-
nological eﬀ ects in normal mice, depending on their
age. In young mice (5 months old), PSP in the diet
produced no obvious immuno-enhancing eﬀ ects at
dietary concentrations of up to 1%. However, in old
mice (23 months), PSP as 1% of the diet produced
a signiﬁ cant, though modest immuno-enhancing
eﬀ ect (Wu et al., 1998).
For a review of the early pharmacological work
performed on PSP, see Yang et al. (1992).
Immunological Effects of Aqueous
Activation and increased proliferation of immune cells
• Promoted lymphocyte proliferation at concentra-
tions of 100–800 µg/mL in vitro (Li et al., 1990). Both
lymphocytes and macrophages were activated in
vitro after exposure to PSP, but no direct cytotoxicity
was noted against ﬁ broblasts, hepatoma, or chorio-
carcinoma cells (Wang et al., 1986).
Reticuloendothelial System Activation
• Phagocytic functions were enhanced (Mayer, 1980; Li
et al., 1990).
• PSK administered to mice without induced im muno-
deﬁ ciency stimulated increased production of NO in
PMNs, along with IFN-γ, but the increase was not
enough to induce tumor cell killing in vitro (Asai et
• In a study involving 27 patients with digestive can-
cers and nine healthy volunteers, PSK (3 g/day) was
reported to counteract the M2-dominant condition,
perhaps through improvement of the Th1/Th2 ratio.
A number of studies have shown that an imbalance in
Th1 and Th2 responses can relate directly to cell-me-
diated impairment in patients with advanced cancers
(Hazama and Oka, 2002).
• In colon-tumor-bearing mice, IFN-γ production was
increased nonstatistically and IL-4 signiﬁ cantly de-
creased when PSK was administered p.o. IL-12 was
increased when spleen cells were stimulated with
Con A with PSK in vitro. These results suggest the
ability of PSK to shift the Th1/Th2 balance toward
Th1 dominance in tumor-bearing mice (Wada et al.,
• IL-2 production and the delayed-type hypersensitivity
response from activated T-lymphocytes was restored
after suppression by cyclophosphamide. Interferon-α
and -γ induction by human peripheral leukocytes at
10–1000 µg/mL was seen (Li et al., 1990).
• Interferon and the gene expression of interleukin (IL)-
12 was increased in the spleen of tumor-bearing mice
inoculated with Candida albicans after an oral dose of
PSK (Ohmura et al., 2003). PSP enhanced IFN-α and IFN-
γ in human peripheral leukocytes 4 and 8 times higher,
respectively, than in control groups (Li et al., 1990).
Dendritic Cell Viability
• PSK reversed inhibition of functional maturation of
dendritic cells (DC) exposed to tumor-derived factors
in vitro. DC are important antigen-presenting cells
promoting tumor-inhibiting immune effects in animals
(Okuzawa et al., 2002).
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MEDICINAL VALUE OF TURKEY TAIL FUNGUS TRAMETES VERSICOLOR
• PSK could counteract dendritic cell cytokine-medi-
ated immunosuppresion in patients with advanced
cancers when given in combination with radiation or
chemotherapy (Kanazawa et al., 2003).
• Reduction in CD4-positive T cells seen in tumor-
bearing mice was prevented by PSK (Ohmura et al.,
Natural Killer Cell Activity, Viability
• PSK decreased expression of protein kinase C-α and
increased PKC-δ and PKC-ε levels, showing that PSK
and IL-2 stimulate NK cells through different effects
on PKC isoenzymes (Garcia-Lora et al., 2003).
• PSP reversed the suppression of natural killer cell func-
tion, as well as lymphocyte proliferation and white
blood cell production caused by cyclophosphamide
(Qian et al., 1997). PSP given orally ( 1.2 g/day) did not
offer protective effects against cyclophosphamide-
induced cytopenia in rats. PSP at 1.2 g/day did not
change neutrophil, lymphocyte, or platelet counts in
rats given i.v. cyclophosphamide (60 mg/kg) (Zhou et
• PSK (oral) restored antibody (IgG) production in mice
bearing Sarcoma 180, but not in nor mal mice (Hobbs,
• Prolongs survival time of irradiated mice (Zhu,
• Reversed the atrophy of the gut-associated lymphoid
tissue (GALT) in rats and increased the number of
Peyer’s patches and the number of thoracic duct
lymphocytes induced by total parenteral nutrition, a
condition that is known to happen in humans (Naka-
saki et al., 1997).
• After lethal infection of mice by Candida albicans,
i.p. administration of PSK doubled survival time. The
most effective dose was 250 mg/kg 24 hours before
infection. PSK induced gene expression of TNF-α and
increased leukocyte function after 6 hours to 1 day af-
ter inoculation. β-1-3-glucanase signiﬁ cantly reduced
the effectiveness of PSK (Ohmura et al., 2001).
• Increased granulocyte production in cyclo phos-
phamide-induced granulocytopenia in mice i.p.
(Mayer and Drews, 1980).
• PSK had a suppressive effect on the expression of heat
shock protein HSP47 and HSP60 but not HSP72/73 at
the mRNA level in human tumor strains. HSPs have
recently been suggested as an autoantigen in autoim-
mune diseases (Morino et al., 1997).
• An extracellular polysaccharide from Trametes
versicolor administered to mice (i.p. or p.o.) chal-
lenged with herpes or inﬂ uenza viruses caused se-
rum interferon induction and inhibited a decrease in
phagocytosis (Chen, 1986).
Effects of PSK on Prostaglandin
PSK stimulated PG-12 production from rat endo-
thelial cells, suppressing platelet aggregation (Taka-
hata et al., 1985).
Antitumor, Anticancer Effects
In many parts of the world, Tv extracts are used
as adjuvants in cancer therapy, both as prescription
items, for instance in Japan, or as dietary supple-
ments taken by patients along with conventional
treatment, with or without the knowledge of their
physicians. As health food supplements they are also
increasingly consumed with the idea that they might
help prevent or assist the body with cancer, aging,
viral infections (such as the common cold), and a
host of other ailments.
As a cancer-preventive agent used on a regular ba-
sis as a supplement, Tv extracts can possibly inhibit
carcinogenesis by reducing the eﬀ ects of some car-
cinogens, such as those occuring in tobacco smoke
or asbestos, on susceptible host cells.
e use of Tv extracts during conventional cancer
treatments, such as chemo- and radiation therapy,
have a rational basis because some research shows
that it might reduce the possibility of secondary
malignancies induced by radiotherapy and cytotoxic
chemotherapy. Tv extracts can also protect healthy
host cells during radiation and chemotherapy treat-
200 International Journal of Medicinal Mushrooms
C. R. HOBBS
ments by either directly or indirectly acting as an
antioxidant, reducing the eﬀ ects of oxidative stress.
e immunoprotective eﬀ ects of Tv extracts might
be particularly useful for immunocompromised pa-
tients such as the elderly or patients with HIV or
other infections who choose to undergo chemo- or
In vitro and in vivo studies show that Trametes
versicolor demonstrates anticancer, antitumor, anti-
carcinogenenic, and antiproliferative eﬀ ects. ese
eﬀ ects can be at least partly explained by a number
of speciﬁ c biological eﬀ ects, such as inhibition of
metalloproteinases and other enzymes related to
metastatic activity and their ability to suppress
cancer cell growth and increase the expression of
tumor cell surface antigens such as human leuko-
cyte-associated antigens (HLA), which can enhance
recognition and thus elimination of the cancer cell
by the host immune system (Iguchi et al., 2001).
e impaired antitumor CD4+ T-cell response in
gut-associated lyphoid tissue (GALT) of pathogen-
free mice was improved by an oral dose of PSK,
which suppressed the growth of colon 26 carcinoma
inoculated into the cecum, augmented the tumor-
neutralizing activity of mesenteric lymph node cells,
and decreased the levels of immunosuppressive fac-
tors such as transforming growth factor (TGF)-β
(Harada et al., 1997).
A 70% ethanolic extract of the fruit bodies re-
duced cell growth of hormone-responsive human
prostate cancer cells and downregulated the produc-
tion of PSA. It had less eﬀ ect on androgen-unre-
sponsive prostate cancer cells. e extract increased
levels of the signal transducer and activators STAT
1 and STAT 3 in one of these cell lines (Hsieh and
Antitumor, Anticancer Effects of Tv Extracts
Inhibition of Tumor Cells
Inhibition of DNA Synthesis
• PSK dose-dependently inhibited DNA synthesis in
MCF-7, a human breast cancer cell line. A PSK dose
of 200 µg/ml caused a 50% inhibition of DNA synthesis
(Aoyagi et al., 1997).
• DNA synthesis in human breast cell cancer line MCF-
7 was reduced in vitro (50% inhibition at 200 µg/ml)
and estrogen receptor (ER) expression on MCF-7 cells
was not changed by exposure to PSK. At high PSK
concentrations, ER expression decreased (Aoyagi et
Enhancement of Cytokine Production
• PSP activated human natural killer cells to increased
cytotoxicity against several different tumor cells lines,
which resembled the effects of IL-2 in the same sys-
tems. The highest activity was seen at 100 µg/ml. The
activation was inhibited when the concentration was
1000 µg/ml (Pedrinaci et al., 1999).
• PSK induced up-regulation of interferon-gamma
(IFN-gamma)-expression and down-regulation of
transforming growth factor-beta (TGF-beta)-expres-
sion, and augmented the manganese superoxide dis-
mutase (Mn-SOD) in tumor tissue from an implanted
cancer cell clone line (QR-32) in mice (Habelhah,
1998). Down regulation of TGF-beta and other inva-
sion-related factors such as uPA, MMP-2, and MMP-9
could suppress tumor cell invasiveness (Zhang et al.,
• PSP injected into nude mice alone along with C6 rat
glioma cells did not reduce tumor volumes, nor did
it enhance the tumor-suppressive effects of radiation,
but it did increase NK cell, lymphocyte, and granulo-
cyte counts in blood and spleen, counteracting some
of the immunosuppresive effects of radiation treat-
ment (Mao et al., 2001).
• PSP has been observed to enhance the transcription
of tumor necrosis factor gene in mouse peritoneal
macrophages, indicating an immunomodulatory effect
of PSP (Liu et al., 1993).
• PSK has shown antitumor activity in animals with ad-
enosarcoma, ﬁ brosarcoma, mastocytoma, plasmacy-
toma, melanoma, sarcoma, carcinoma, and mammary,
colon, and lung cancer (Tsukagoshi et al., 1984).
• PSP showed tumor-inhibiting activity in animals with
Sarcoma 180, P388 leukemia, monocytic leukemia,
Ehrlich ascitic tumor, histiocytic lymphoma, human
lung adenocarcinoma, and various cancers of the liver,
stomach, nose, and throat (Yang et al., 1993).
• In various in vitro and in vivo models, PSK could sup-
press pulmonary and rat hepatoma metastasis, human
prostate cancer, lyphatic metastasis of mouse leuke-
Volume 6, Issue 3, 2004 201
MEDICINAL VALUE OF TURKEY TAIL FUNGUS TRAMETES VERSICOLOR
mia, and mouse colon cancer, prolonging the survival
time in spontaneous metastasis models (Kobayashi et
• PSK eliminated both primary and metastatic tumors
in the double grafted tumor system in mice, and was
more effective in the model than lentinan or a fraction
from Agaricus brasiliensis (=A. blazei ss. Heinem.) for
eliminating both. PSK eliminated both primary and
metastatic tumors in a similar model by inducing a
sequential antitumor immune mechanism, while a
fraction from A. brasiliensis had a direct cytotoxic
effect on primary tumors only (Ebina, 2003a,b).
• Oral PSK could increase the number of Peyer’s
patches and led to an enhanced mitogenic lympho-
cyte response from gut-associated lymphatic tissue
in tumor-bearing mice (Matsunaga et al., 1987).
Tumor Cell Killing Effect
• PSK could up-regulate nitric oxide synthase gene
expression and production of nitric oxide in mouse
PMNs, but not enough to stimulate killing of tumor
cells in mice in vitro (Asai et al., 2000).
• Although the PSK and PSP inhibit proliferation of some
human cancer cell lines (Yang et al., 1992a; Iguchi et
al., 2001), not all cancers respond to Tv polysaccha-
ropeptides (Wang et al., 1986; Dong et al., 1997).
Inhibition of Carcinogenesis
• Oral administration of PSK as 10% and less of rat
feeds suppressed carcino gen-induced cancers of the
colon, esophagus, breast, and lung (Tsukagoshi et al.,
• Kobayashi et al. (1994) demonstrated that PSK
(polysaccharide Kureha) could ameliorate oxidative
stress in tumor-bearing rats. Administration of PSK (50
mg/kg, i.p.) 12 days after tumor development caused
superoxide release from red blood cells to rapidly
decrease. The authors also reported that in colon and
gastric cancer patients in whom oxidative stress was
found to be twice that of healthy individuals, PSK (3
g/day, p.o.) caused oxidative stress levels to fall to low
levels; however, after 7 days patients showed reduced
SOD levels and increasing lipoperoxide (LPO) levels.
Therefore, the authors suggest that PSK should only
be administered to cancer patients for a period not
exceeding 7 days, that treatment should begin 7 days
before chemotherapy, and that to prevent damage
produced by anticancer agents in the form of oxygen
free radicals, PSK should be administered in combina-
tion with these agents while monitoring superoxide
• In vitro studies reveal that PSP acts selectively on HL-
60 leukemic cells, arresting the cell in the G-phase of
the cell cycle and inducing apoptosis (Hsieh et al.,
• PSK dose dependently stimulated apoptosis in human
pancreatic cancer cell line NOR-P1 induced by 1 nM of
docetaxel through the NF-kappaB activation pathway
(Zhang et al., 2003).
• PSP was effective at inhibiting the proliferation of
breast cancer cells when they were incubated for 7
days. PSP increased p21 expression and decreased
cyclin D1 expression which was used to partly explain
the effect of PSP on apoptosis as measured by the
TUNEL assay (Chow et al., 2003).
• PSK/PSP has controlled various carcinomas in experi-
mental animals and humans (Ng, 1998). PSP is active
against Ehrlich ascites carcinoma, P388 leukemia, and
Sarcoma 180 (Yang et al., 1992a).
• A fraction further reﬁ ned from the total polysaccharide-
peptide crude powder of Tv inhibited the prolifera-
tion of a human hepatoma cell line, dose-dependently
(Dong et al., 1996).
• Other work (Dong et al., 1997) has not found antipro-
liferative effects of T. versicolor polysaccharopeptides
against HL-60 human leukemic cells.
• Dong et al. (1996) observed that T. versicolor polysac-
charopeptides dose-dependently inhibited the prolif-
eration of a human hepatoma cell line (HEPG2), but
not the normal human fetal hepatocytes.
• In nude mice, the progression of Sarcoma 180 was
measurably reduced by the administration of polysac-
charopeptides (Dong et al., 1996).
• Data obtained in vitro and in vivo suggest that PSP
can slow the progression of murine H238 tumors (Mao
et al., 1996).
• An intriguing feature of this compound is that injection
of PSK at one tumor site has been shown to inhibit
202 International Journal of Medicinal Mushrooms
C. R. HOBBS
tumor growth in other sites, thus helping to prevent
metastasis (Ebina and Kohya, 1987).
• Increased metastatic foci in mice subjected to ro-
tational stress before, during, and after tumor cell
implantation and the associated reduction in NK cell
activity was signiﬁ cantly reversed by early administra-
tion of PSK (Ishihara et al., 1999).
• Other in vitro tests showed that PSK inhibited pro-
liferation and invasion of human KATO-3 gastric and
Colo205 colonic cancer cell lines and enhancement
of HLA class-1 expression on tumor cells (Iguchi et al.,
• PSK could suppress tumor cell invasiveness by down-
regulating invasion factors TGF-β1, µPA, MMP-2, and
MMP-9 in two human tumor cell lines, pancreatic
cancer cell line (NOR-P1) and gastric cancer cell line
(MK-1P3). PSK did not affect viability, proliferation,
or adhesion of the cell lines (Zhang et al., 2000).
• PSK could inhibit the proliferation of human umbilical
vein endothelial cells at 10 µg/mL and basic ﬁ broblast
growth factor (bFGF)-induced angiogenesis in vivo,
suggesting that PSK binds to bFGF, interfering with
bFGF-induced endothelial cell prolifeation, which can
inhibit angiogenesis (Wada et al., 2002).
Tumoricidal Activity, Cytotoxicity
• Unlike the higher molecular weight (ca. 100k) PSP, a
small polypeptide (SPCV) isolated from Tv demon-
strated signiﬁ cant cytotoxic effects on human tumor
cell lines (IC50, 30 µ/mL), inhibiting growth of leukemia
cells at a signiﬁ cantly higher rate than PSP. SPCV also
increased WBC and IgG levels (Yang et al., 1992).
• Neither tumoricidal activity or cytotoxicity could be
seen when 5 tumor cell lines were cultured in a solu-
tion with 2.5 to 10 µg/mL PSP, however, PSP activated
the transcription of tumor necrosis factor gene from
cultured peritoneal macrophages in the same culture
(Liu et al., 1993).
• PSK signiﬁ cantly inhibited growth of, and demon-
strated a cytotoxic effect in 4 human cancer cell lines
from the colon, stomach, liver, and pancreas, inhibiting
DNA and RNA syntheses in a colon cancer cell line at
10 mg/mL (Takeda et al., 1997).
• PSK inhibited several mechanisms of cancer cell
metastasis. In vivo, it suppressed spontaneous lung
metastases of melanoma cells in mice. In vitro, PSK
inhibited chemotaxis of the tumor cells, reduced tu-
mor cell adhesion and haptotaxis to components of
the basement membrane (Matsunaga et al., 1996).
• PSK administration was able to delay the increase of
p53 expression after radiation stress in mouse embryo
cells, which coincided with an associated decrease in
mitosis and increase in apoptosis, perhaps contrib-
uting to an antiteratogenic effect (Kagohashi et al.,
Immunoprotective Effect During Radiation and Che-
• PSP could signiﬁ cantly augment radiation-induced
damage to C6 glioma cells in vitro, and tumor vol-
umes were consistently reduced, compared with
non-treated controls given only radiation treatment.
PSP given with radiation treatment did not increase
efﬁ cacy of the radiation, but NK cells, lymphocyte and
granulocyte counts in the blood and spleen were sig-
niﬁ cantly higher in PSP-treated animals, demonstrat-
ing its immunoprotective effect (Mao et al., 2001).
ANTIVIRAL, ANTIBACTERIAL, AND
In several in vitro experiments, PSK was found to
inhibit reverse transcriptase and binding of HIV
with lymphocytes (Hirose et al., 1987) and block the
cytopathic eﬀ ect of HIV through inhibition of giant
cell formation as well as HIV-speciﬁ c antigen ex-
pression in MT-4 and MOLT-4 cells (Tochikura et
al., 1987); and inhibit cell-to-cell infection of HIV-1
and HIV-2 and HTLV-I (Tochikura et al., 1989).
Both normal and T-cell-deﬁ cient athymic mice
were protected by PSK administration from murine
cytomegalovirus infection, but the treatment had
little eﬀ ect on NK- and T-cell-deﬁ cient mice. Both
NK-cell and T-cell activity were seen as necessary
for the mice to overcome cytomegalovirus infection
(Okada and Minamishima, 1987).
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MEDICINAL VALUE OF TURKEY TAIL FUNGUS TRAMETES VERSICOLOR
PSK was able to inactivate the infectivity of HSV-
type 1 (HSV-1) and HSV-type 2 (HSV-2) from
patients with herpes genitalis. HSV-1 and HSV-2
from the patients was inactivated by PSK, dose-
dependently after 30–60 minutes. PSK might be
clinically useful for inactivating HSV in peripheral
lesions (Monma et al., 1997).
When given i.p., Tv extracts could increase host
resistance to bacterial and fungal infections (Chu et
al., 2002). PSP had little to no antibacterial eﬀ ects
directly (Ng et al., 1996), but did have antibacterial
eﬀ ects through stimulation of host defense.
PSK has also demonstrated antiviral activity. It
may inhibit HIV infection by modifying the viral
receptor or by stopping HIV from binding with
lymphocytes (Tochikura et al., 1987). PSP could
inhibit the interactions between HIV-1 gp120 and
immobilized CD4 receptor in a series of in vitro
assays (Collins and Ng, 1997).
Another mechanism through which PSK is re-
ported to have general antiviral activity is through
the stimulation of interferon (IFN) production
(Ebina et al., 1987).
PSK had a pronounced protective eﬀ ect against
lethal infection with Candida albicans in mice.
e maximum eﬀ ect occurred when the PSK was
injected at 250 mg/kg i.p. 24 hours before inocula-
tion of 1 × 10⁶ C. albicans. A 30-day survival rate
increased by 60%, and mean survival time increased
by 209%. Both the β1→3 glucan and the protein
moiety were seen as necessary for maximum activity
(Ohmura et al., 2001).
e resistance and survival time of tumor-bear-
ing mice challenged with Candida albicans infection
was increased with oral administration of PSK. A
signiﬁ cant reduction of fungal counts was also noted
(Ohmura et al., 2003).
e action of PSK appears to be through NK cell
activation against lethal cytomegalovirus infection
(Ebihara and Minamishima, 1984).
Nitrogen-containing polysaccharides extracted
from Ttrametes versicolor mycelia increased antibac-
terial potency and prolonged antibacterial eﬀ ects
of anti biotics and can increase antibiotic sensitivity
in antibiotic-resistant bacteria (Kureha Chemical
Industry Co., 1978).
PSK could inhibit B-cell growth and activate T
and NK cells in Epstein-Barr virus (EBV)-infected
umbilical cord blood lymphocytes in the absence
of EBV-speciﬁ c immunological memory, exerting
enhanced cytotoxicity against EBV-infected B cells
(Liu et al., 2002).
PSK supported hepatic function (Ito and Hidaka,
1980b) and the possible preven tion of liver cancer
(Wang, 1989). Two polyoxygenated ergosterol de riv a-
tives showed cytotoxicity (in vitro) against hepatoma
cells (Valisolalao et al., 1983).
PSP given to rats for 7 days (300 mg/kg/day, i.p.)
reduced binding aﬃ nity of [14C]-paracetamol to
liver microsomes by 25%, and signiﬁ cantly reduced
serum glutamic-oxaloacetic transaminase levels, but
did not reverse depletion of glutathione after a toxic
dose of paracetamol (Yeung et al., 1994).
A glycoprotein obtained from the mycelia of Tram-
etes spp. showed activity (in animal and in vitro tests)
against experimental hypertension and thrombosis.
e protein inhibits blood platelet aggregation and
is analgesic, antipyretic, antihyperlipemic, antiar-
rhythmic, anti-inﬂ ammatory, and vasodilating. It
has also been shown to reverse conditions associ-
ated with nephron disorders, improve proteinuria
and proteinemia-associated conditions, and regulate
prostaglandin formation and degradation (Ikuzawa
et al., 1985).
PSK (i.p.) could induce peritoneal macrophage
colony-stimulating factor (M-CSF) gene expres-
sion, as well as protect macrophages from oxidative
injury, reducing their transformation to foam cells
in the process of atherogenesis, which was related
by researchers (Yuan et al., 1996) with its previously
demonstrated ability to prevent the progression of
atherosclerosis in hypercholesterolemic rabbits.
is could be partly due to its ability to enhance
superoxidedismutase (SOD) activity and improve
glutathione peroxidase activity through induction of
mRNA transcription (Pang et al., 2000a,b).
204 International Journal of Medicinal Mushrooms
C. R. HOBBS
Whole T. versicolor has been shown to lower se-
rum cholesterol in animals (Yagishita et al., 1977).
PSK can inhibit ox-LDL-induced macrophage
apoptosis and promote NO-induced macrophage
apoptosis; Raw264.7 macrophages can be induced
to express iNOS mRNA when stimulated with PSK,
IFN-γ, and LPS in vitro; PSK can enhance the ef-
fects of IFN-γ and LPS and suppress the inhibitory
eﬀ ects of ox-LDL. e prevention and treatment
eﬀ ects of PSK on atherosclerosis may be realized by
its induction of iNOS (Wang et al., 2001).
A powdered extract (from a 70% ethanolic tincture)
of Trametes versicolor was tested in rats by injection
in a Hippocratic screening of higher fungi and dem-
onstrated mild tranquilizing and diuretic activity
(Malone et al., 1967).
An analgesic eﬀ ect of PSP i.v. was noted in three
diﬀ erent pain models in rats in acute and chronic
inﬂ ammatory pain (Teng et al., 2002) and could be
mediated by IL-2 activation (Gong et al., 1998).
HUMAN CLINICAL STUDIES
Cancer Adjuvant Treatment
Although some of the studies are small and of uncer-
tain methodology according to recent international
standards, starting in the early 1970s, a suﬃ cient
number of human clinical trials, along with the
mass of preliminary in vitro and in vivo research
showing a broad sprectrum of immunomodulating,
antitumor, and anti-metastatic eﬀ ects, have been
performed to give PSP and especially PSK (and
perhaps by association Trametes versicolor water
extracts in general, which contain the fractions) an
air of credibility, especially as adjuvants in cancer
treatment protocols along with chemotherapy.
e Japanese government has approved these and
a few other mushroom extracts—for instance from
Lentinus edodes—as adjuvant drugs for the treat-
ment of specﬁ c cancers (resected gastric cancer and
colorectal cancers and for palliation of small cell lung
cancer) as long as it is administered in combina-
tion with chemotherapeutic agents (Sugiyama et al.,
2002). Much of the antitumor activity proposed for
PSK has been elucidated suﬃ ciently on a molecular
and genetic level, based on numerous in vitro, in
vivo, and human studies; yet many oncologists in Ja-
pan still lack conﬁ dence in its eﬃ cacy. ey are often
prescribed and paid for by national health care.
It has been suggested in the literature that, all
other things being equal, some patients respond
to PSP and PSK better than others. Some intact
immune function has been shown to be a positive
factor, and in one trial, HLA B40-positive antigen
status was associated with an increased survival in
breast cancer patients, as compared to B40-negative
status, when both groups were given PSK along with
conventional chemotherapy (Yokoe et al., 1997). In
another study, HLA-A2-antigen-positive status was
associated with a better response to postoperative
administration of PSK than to chemotherapy and
was said to be a predictor for PSK-responsive pa-
tients (Ogoshi et al., 1997).
In one study (Sugimachi et al., 1995), lympho-
cytes from 36 patients with gastric cancer and 26
with colorectal cancer were examined. e PSK-
reactive group, 52.8% for gastric cancer patients
and 50.0% for colorectal cancer, was deﬁ ned by a
1.3-fold increase in ³H-thymidine uptake in the
lymphocytes. e researchers that the proceedure
outlined in this study might help identify “respond-
ers,” increasing the eﬀ ectiveness of treatments with
Other questions—such as the most eﬀ ective dose
of PSK; the best type of extract or whole mushroom
powder; perhaps whether an extract of the whole
fruiting body is less, more, or as eﬀ ective than PSK
or PSP; and the frequency of administration—need
to be answered through further clinical trials.
In a 1992 study (Nio et al., 1992), 29 patients
with gastric cancer and 18 with colorectal cancer
were given 3.0 g of PSK before surgery, either daily
or every 2 days, or no PSK. e dose frequency made
no diﬀ erence in the outcomes, but in the patients
who received PSK for less than 14 days, the response
of the peripheral blood lymphocytes (PBLs) to PSK
and Con A was stronger than before the start of PSK
administration, and in addition, long-term admin-
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MEDICINAL VALUE OF TURKEY TAIL FUNGUS TRAMETES VERSICOLOR
istration of PSK resulted in reduced activity of the
suppressor cells in the regional node lymphocytes
PSK and PSP have been used both orally and in-
travenously as an immune adjuvant in clinical medi-
cine. PSK has been shown to be eﬀ ective against
many human cancers (Kidd, 2000) but seldom with
satisfactory results administered alone.
Cancer patients given 3 g of PSK per day have
shown increased interfer on production (Ebina et al.,
1987a). In cancer patients, PSK also antagonisti-
cally elevated the activity of phosphofructokinase
and showed antioxidant activity, work ing as a su-
peroxide and hydroxyl radical scavenger (Nakamura
et al., 1986).
Numerous clinical trials were performed in Japan on
thousands of patients with stomach cancer, mostly
after surgery to remove the cancerous tissue, over
the last 30 years, with either chemotherapy alone
or with PSK and chemotherapy.
An early controlled clinical trial was started in
July, 1974, comparing curative resection surgery
alone; surgery with chemotherapy; and surgery,
chemotherapy, and PSK in groups with 1412 total
patients from 12 medical institutes. Of 848 evaluable
patients, the 3-year survival rates were 79.2%, 77.0%,
and 85.2% with PSK (Imaizumi et al., 1984), but a
later analysis of the data showed less diﬀ erence. Ten-
year survival rates were 67.6%, 64.3%, and 63.9%,
which showed no signiﬁ cant diﬀ erence among the
groups (Imaizumi et al., 1990).
Most of the clinical trials summarized in Table 1
showed positive beneﬁ ts when PSK was added to a
long-term chemotherapeutic agent after immediate
treatment with chemotherapy. Survival rates after
2–7 years often increased by 10% up to 20%. Some
research showed that the best increase in survival
times was observed when PSK was alternated with
chemotherapy (Nakazato et al., 1994).
In a multicenter trial conducted from 1978 to
1981, 751 patients who underwent macroscopi-
cally curative resection for gastric cancer and who
took either mitomycin C or futraful (MMC+FT)
were compared for preoperative granulocyte and
lymphocyte count ratios (G/L). While in the cases
with a preoperative G/L ratio of <2.0 no signiﬁ cant
diﬀ erence in survival rates could be seen, in the pa-
tients with a G/L ratio of >2.0 the 5-year survival
rate of the PSK group (n = 182) was 68.7%, while
that of the non-PSK group (n = 182) was 55.4%
(p = 0.007) (Nakajima et al., 1989; Toge and Yama-
A meta-analysis published in December 1993 re-
ported on six clinical trials evaluating the 5-year sur-
vival rate of groups receiving either chemotherapy or
chemotherapy plus PSK for patients with advanced
gastric cancers. e authors determined that the 5-
year survival rate with chemotherapy plus PSK was
superior to those receiving the same chemothera-
peutic regime alone. e odds ratio was 0.75 (95%
conﬁ dence interval, 0.62–0.93, p < 0.01). Based on a
meta-analysis on three further trials starting in 1977,
PSK proved to be most eﬀ ective with patients with
T2 and T3 primary tumor subgroups (Sakamoto
and Nakazato, 1993).
In a 1994 multicenter randomized but unblinded
study involving 262 patients given either a standard
regime of chemotherapy or chemotherapy plus PSK
at 46 institutions, after curative resection for gastric
cancers, PSK improved the 5-year disease-free rate
in groups receiving either PSK plus chemotherapy
or chemotherapy alone (70.7 vs. 59.4%, p = 0.047),
and the 5-year survival (73.0 vs. 60.0%, p = 0.044)
(Nakazato et al., 1994). e PSK patients received
oral PSK (3.0 g/day) daily for 4 weeks alternating
with oral ﬂ uorouracil (150 mg/day) for 4 weeks, and
the standard treatment patients received alternat-
ing ﬂ uorouracil and 4 weeks of rest from treatment.
Both groups received 10 courses. Overall, a reduction
of about 20% in recurrence and death was seen in
the patients receiving long-term oral PSK.
In another study with 224 patients being treated
after curative resection for poorly-diﬀ erentiated
gastric cancer, 1-(2-tetrahydrofuryl)-5-ﬂ uorouracil
(tegafur) and uracil were given, along with PSK in
one group and uracil in another group for 1 year.
No diﬀ erences in terms of toxicity rate or outcomes
between the two groups was observed. Uracil at 12
mg/kg was the most eﬀ ective dose (Sugimachi et
206 International Journal of Medicinal Mushrooms
C. R. HOBBS
TABLE 1. Summary of Clinical Trials—PSK for Gastric Cancer After Curative Resection
times Outcomes Year
Kaibara et al. 66 — 2 yr MMC and PSK, 2-year survival was doubled over MMC alone. 1976
Fujimoto et al. 230 — 3 yr Survival rate increased in one subgroup with better intact immune response with PSK. 1979
Hattori et al. — — 3 yr Mitomycin-C (20 + 10) mg after gastrectomy and long-term PSK, FT-207, or (PSK+FT-207); group (P+F) showed
best results at 1 year in stage IV, at 2 yr in stage III, and at 3 yr in all stages.
Kano et al. — — 5 yr Mitomycin-C, FT-207, a furanyl analog of 5-ﬂ uorouracil, and PSK; survival rates for all stage III and IV patients
were 52.8 and 19.3% in PLCC group. Rates were 26.7 and 2.2% in control groups (p < 0.05); in curative cases of
stage IV, 5-year survival rate was 50.0% in PLCC group and 11.1% in controls.
Hirono et al. 435 — — PSK, FT-207 and Levamisole not effective on Borrmann 4-type cancer in 2 randomized controlled trials. 1984
Nakajima et al. 3630 412 3, 4 yr Most positive results in survival rates was combined therapy (FT + PSK) over single administration (FT) to rela-
tively early stage patients (30%, difference); PSK, MMC, FT combination (10%) and PSK, OK, MMC, FT (22%).
Kanabe et al. 58 — 2 yr Mitomycin-C + FT 207 + OK 432 + PSK (29 cases) and chemotherapy Mitomycin-C + FT 207 (29 cases); survival
rate of PSK group was higher than chemo group throughout observation period, statistical signiﬁ cance in some
periods; 50% survival rate was 10 mo in chemotherapy group and 18 mo in immunochemotherapy group.
Nakazato et al. 168 22 2 yr Carboquon (CQ) dose 2 mg/m2 once a wk, then PSK 2 g/m2 daily for 4 wk. Group A: CQ intermittently; Group
B: CQ PSK in alternate doses; Group C: controls. Survival rate of stage III stomach cancer patients in Group B
was higher than in Group A, the difference being statistically signiﬁ cant between 20 and 24 mo after surgery.
Ichihashi et al. — 16 7 yr Retrospective survival analysis on separate subgroups S1, S2, N1, and N2. CQ + PSK group was better than
CQ-alone group in survival rate for S1 + S2 (N1-2) group by 11.5%, and a statistically signiﬁ cant difference was
observed between the two groups (p = 0.089).
Niimoto et al. 579 97 5 yr On stratiﬁ cation, MMC + FT + PSK group showed the best survival rate in cases with positive lymph node
metastases, positive serosal invasion, and positive lymph node metastases plus serosal invasion, and in cases
of undifferentiated carcinoma by histological type and in those with a preoperative positive PPD reaction
(p < 0.01 or p < 0.05).
Nakazato et al. 262 46 3 yr Disease-free survival curves and overall survival curves of group with PSK were signiﬁ cantly (p = 0.018 and
p = 0.045) better than those receiving chemotherapy alone.
Maehara et al. 255 — 15 yr 15-year survival rate was 45.7% for patients in no-chemotherapy group and 56.9% for chemotherapy group;
most signiﬁ cant for patients with ps(–)n(+) (p < .05) and ps(+)n(–) (p < .05).
Kondo et al. 103 103 7 yr Patients with S1 + S2 (N1–2) disease survived signiﬁ cantly longer when treated with combination CQ and PSK. 1991
Sakamoto et al. 229 — 2 yr Disease-free survival improved with PSK when preoperative IAP was lower than 580 µ/mL. 1992
Nakazato et al. 262 46 5 yr Disease-free 70.7 vs. 59.4%; survival rate 73.0% vs. 60%. 1994
Osawa et al. 185 16 5, 10 yr 5- and 10-year survival rates were 9.8 and 3.1% (PSK without ﬂ uorouracil) and 11.1 and 11.1% (with ﬂ uoroura-
cil) (p = 0.062).
Chemotherapeutic agents included 1-(2-tetrahydrofuryl)-5-ﬂ uorouracil (Uracil), 1-(2-tetrahydrofuryl)-5-ﬂ uorouracil (Tegafur), Mitomycin C (MMC), 5-ﬂ uorouracil (5-FU), Levamisole, and
carbazilquinone (CQ), futraful (FT).
Abbreviations: prognostic serosal (ps) invasion [ps(–) or ps(+)] and lymph node metastasis [n(–) or N(+)] was examined.
Volume 6, Issue 3, 2004 207
MEDICINAL VALUE OF TURKEY TAIL FUNGUS TRAMETES VERSICOLOR
Non-small cell lung cancer (NSCLC) is a common
cause of cancer death, and patients often present at
Radiotherapy plus PSK was more eﬀ ective than
radiotherapy (RT) alone for increasing the 5-year
survival rate in 185 patients in studies performed
from 1976 to 1985. e rate in patients with stage
I or II disease with PSK was 39%, and without was
16%. With stage III disease, the survival rates were
16% and 5%. e diﬀ erence was statistically sig-
niﬁ cant (Hayakawa et al., 1993). e group looked
at the same patient population but with the 170
patients with squamous cell carcinoma. ey were
given PSK only when tumor shrinkage was deemed
satisfactory after RT. Compared with the responders
to RT that didn’t receive PSK, the 5-year survival
rates with patients with stage I–II or stage III dis-
ease was 39% and 26%, and with no PSK, 17% and
8%, which was statistically signiﬁ cant (Hayakawa
et al., 1997).
In a double-blind, placebo-controlled random-
ized study, 38 patients who had completed conven-
tional treatment for advanced NSCLC were given
either PSP or a placebo for 28 days. A signiﬁ cant
increase in blood leukocyte and neutrophil counts,
serum IgG and IgM, and body-mass index was
seen in the PSP patients, compared with those
receiving placebo. Signiﬁ cantly fewer PSP patients
were withdrawn because of disease progression than
their controls (5.9 and 23.5%, respectively; p = 0.04).
Patients receiving PSP did not report signiﬁ cant
adverse reactions (Tsang et al., 2003).
A number of positive new studies with PSK in
combination with various chemotherapeutic regimes
are encouraging. In a randomized controlled study
the survival of 124 patients in a PSK group plus
chemoterapy for 1 year after surgery was slightly
better than with chemotherapy alone (91.4% and
80.8%, which was not signiﬁ cant), but the 2-year
recurrence rate was lower in PSK groups (Takashima
et al., 1988).
In a randomized, controlled study with 462 cu-
ratively resected colorectal cancers, PSK was given
orally for over 3 years following mitomycin C (by
i.v. on the day of surgery and 1 day following) and
5-ﬂ uorouracil (5-FU) orally for 5 months. At the
time of reporting, the average study follow-up was
4 years. e increased disease-free survival curve of
the PSK group over the control group (who only
received the two drugs) was statistically signiﬁ cant
(Mitomi et al., 1992).
In a similar study, PSK was administered after
the same chemotherapeutic regime as the previous
study to 56 patients and a placebo to a group of
55 control patients. e rate of remissions and the
survival rate in the patients taking PSK was sig-
niﬁ cantly higher (p < 0.05) than the control group.
Enhanced immune functions, including enhanced
polymorphonuclear leukocyte activity, was said
to be a signiﬁ cant factor in explaining the results
(Torisu et al., 1990).
In a more recent study, the 3-year survival of 48
curatively resected patients diagnosed with colo-
rectal cancer (pTNM stages II and III) receiving
ﬂ uoropyrimidine plus 3 grams of PSK daily for an
average of 11 months was signiﬁ cantly better than
in 10 patients receiving chemotherapy alone (Kudo
et al., 2002).
PSK, along with cisplatin and UFT, was given to
10 patients with advanced colorectal cancer who had
distant metastasis in the liver or lung for 2 months.
Serum levels of sIL-2R and IL-10, previously shown
to be elevated in patients with advanced colorectal
cancer, were reduced (Shibata et al., 2002).
In 27 patients with digestive cancers and 9
healthy volunteers, an analysis of MHC class II+
monocytes and monocytes producing IL-10, MCP-
1, and IL-12 was performed before and after daily
oral doses of PSK (3 g/day for 7 days). MHC class
II+ monocytes declined with cancer progression,
and IL-10 and MCP-1-producing monocytes
were much higher in patients (M2-dominant sta-
tus) with advanced cancer than on healthy patients.
IL-10 and MCP-1-producing monocytes decreased
signiﬁ cantly after PSK. PSK administration might
be useful for counteracting the M2-dominant con-
dition common in patients with digestive cancers,
improving the balance between 1 and 2, which
208 International Journal of Medicinal Mushrooms
C. R. HOBBS
indicates impaired cellular immune status (Hazama
and Oka, 2002).
PSK plus 5′-DFUR chemotherapy for 1 year was
only slightly better at increasing overal survival in
a group of patients with stage II and III colorectal
cancer after surgery with a follow up time of 6.5
years (Koda et al., 2003), but in another random-
ized controlled study with 446 patients with pri-
mary colon cancer after surgery, 10 courses of oral
PSK (3 g/day) followed by oral 5-FU signiﬁ cantly
increased the survival from cancer deaths, but not
the 7-year overall survival rate from all causes (Ito
et al., 2004).
In 201 stage II or III colorectal cancer patients
with prior surgery, oral PSK plus tegafur/uracil for
2 years following mitomycin treatment, the 3-year
disease-free survival rate was 80.6%, compared with
68.7% in the control group receiving only chemo-
therapy. For stage III patients, the respective values
were 83.0% and 59.3%. PSK was more eﬀ ective for
preventing distant metastases, especially lung me-
tastases (Ohwada et al., 2003). After an extended
followup with the same patient group, the patients
receiving oral PSK (3 g/day) and chemotherapy daily
for 2 years had a 5-year disease-free survival rate of
73% (stage II, n = 123) and 58.8% (stage II, n = 68); the
recurrence rate was reduced by 43.6% and mortality
by 40.2% in the PSK group, and the 5-year survival
was 81.8% in the PSK group and 72.1% in the control
group. Notably, the disease-free and overall survival
in the PSK group in stage III patients was 60.0%
and 74.6%, compared with 32.1% and 46.4% in the
control group (Ohwada et al., 2004).
PSK, lentinan, or no mushroom extract with anti-
tumor drugs administered in a group of 58 patients
with hepatocellular carcinoma along with either
percutaneous ethanol injection or transcatheter arte-
rial emobolization made no signiﬁ cant diﬀ erence in
mean survival time, mortality rate, time to progres-
sion, or T4/T8 lymphocytes (Suto et al., 1994).
Type IV collagen serum levels were measured as a
marker for metastasis of hepatic and gastrointestinal
cancers and found to be signiﬁ cantly elevated in the
group receiving the chemotherapy alone, compared
with the group receiving chemotherapy plus PSK up
to 12 months after surgery. e 3-year survival rate
for patients with colorectal cancer stages II and III
receiving chemotherapy plus PSK was signiﬁ cantly
higher than in those receiving chemotherapy alone
(Kudo et al., 2002).
Nasopharyngeal, Esophageal Cancers
PSK was tested as an adjuvant immunotherapy in a
group of patients with carcinoma of the naso pharynx
(n = 21) and found to signiﬁ cantly increase (35 vs. 25
months) the median survival time over the control
group (n = 17) as well as the 5-year survival rate (28%
vs. 15%). All patients in both groups had previous
radiotherapy with or without chemotherapy (Go and
Chung, 1989). An earlier study of nasopharyngeal
carcinoma patients (n = 67) reported similar results
(Chung et al., 1987). e dose was 1 gram, 3 times
daily, for a minimum of 1 month. ree cases of
toxicity were noted.
Among 174 patients with esophageal cancer
that underwent esophagectomy, the group receiv-
ing radiotherapy (RT) and chemotherapy (CT) plus
PSK had better survival times than seen in a group
receiving RT and CT, but the outcome was not sta-
tistically signiﬁ cant (Ogoshi et al., 1995a). e results
were, RT, RT + PSK, RT + CT, and RT + CT + PSK
were 40.0%, 42.3%, 29.1%, and 37.2%, respectively.
However, when postoperative serum levels of α-1-
antichymotrypsin and sialic acid were abnormal, the
survivability beneﬁ t for patients receiving PSK was
statistically signiﬁ cant (Ogoshi et al., 1995b). e
authors indicate that levels of the preoperative mark-
ers α−1-antichymotrypsin and sialic acid could help
identify PSK responders.
PSP increased the rate of remission in esopha-
geal cancer patients to 72% when it was added to
chemotherapy, whereas those on chemotherapy
alone had a remission rate of 42%. PSP also raised
the 1-year survival rate for this type of cancer by
11%. e main immunologic pathways activated
by PSP to inhibit tumors are through helper T
cell, NK cell, and complement C3 (Yang et al.,
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MEDICINAL VALUE OF TURKEY TAIL FUNGUS TRAMETES VERSICOLOR
In a group of 34 patient volunteers with squamous
cell carcinoma of the uterine cervix, 21 received ei-
ther 3 or 6 grams PSK daily combined with radiation
therapy. e patients in the PSK groups had less
giant cell formation and an increased lethal damage
to tumor cells. PSK was most eﬀ ective in patients
whose tumors were radioresistant (Hayashi, 1988).
In combination with radiation in stage III
uterine cervical cancer patients, PSK (3-6 g/day)
prolonged the life span and appeared to have en-
hanced the sensitivity of the cancers to radiation
ther apy. One study performed at the Department
of Gynecology, National Cancer Center Hospital
in Tokyo (Kasamatsu, 1982), tested the inﬂ uence
of PSK on the survival rate with cervical cancer
patients. PSK was given orally in the dose of 3-6
grams a day in conjunction with radiation therapy.
After radiation, patients having no observed tumor
cells remaining was 36% with PSK and 11% with-
out. e 2-year survival rate was 94% with PSK and
74% without; the 3-year survival rate was 85% and
59%; the 5-year survival rate 64% and 41%. e rate
of cancer deaths within 5 years was 21% with PSK
and 52% without.
In a study that spanned 1980 through 1990, 227
patients with operable breast cancer, vascular inva-
sion in the tumor, and/or metastatic lymph nodes
were randomized into chemotherapy (CT), CT
plus Levamisole, or CT plus PSK. While the risk
ratio was lower in the PSK group, no statistical
diﬀ erence was seen in the disease-free survival or
overall survival between the three groups. However,
the survival curve of the PSK group tended to be
better than that receiving chemo alone (p = 0.0706)
(Lino et al., 1995).
In a group of 525 patients with stage II estrogen
receptor-positive breast cancer, the 5-year overall and
relapse-free survival rate did not signiﬁ cantly diﬀ er
between patients receiving a daily oral dose of 600 mg
ftorafur or a daily oral dose of 3 grams PSK, starting
2 weeks after surgery. However, the most eﬀ ective
treatment was tamoxifen plus ftorafur (94.2%), com-
pared with tamoxifen alone (86.9%) or tamoxifen
plus PSK (89.9%) (Morimoto et al., 1996).
Among 134 patients with operable breast cancer,
patients with vascular invasion in the tumor and/or
in metastatic lymph nodes were randomized into
two groups. One group received a chemotherapy
cocktail with PSK (3 g/day) and one with just che-
motherapy. Patients were typed as HLA-A, -B-, C
with a lymphocytotoxicity test. e 5- and 10-year
disease-free survival rate for patients with B40+
was 100% in both cases, but only 76% and 55% for
patients that were B40– (Yokoe et al., 1997).
PSK was given to a group of 73 patients with non-
lymphocytic leukemia in complete remission in a
randomized cooperative trial. After 6 months, PSK
had a borderline beneﬁ cial eﬀ ect on remission dura-
tion (p = 0.089) and duration of survival (p = 0.062).
No signiﬁ cant diﬀ erences in duration of remission
and survival between the groups was seen after 12,
18, and 24 months; however, in the patients who
did maintain complete remission for more than
270 days, PSK had a suggestive beneﬁ cial eﬀ ect
(p = 0.105) by prolonging the 50% remission rate
by 418 days (885 vs. 467 days).
A controlled double-blind phase II clinical trial of
PSP was conducted in 485 cancer patients (211
control patients) treated with the polysaccharide-
peptide (3 g/day for 3 0 days p.o.) in combination
with radio- and chemotherapies. e patients were
diagnosed with cancers of the esophagus, stomach,
and lung. PSP reduced side eﬀ ects from the con-
ventional therapies, with most signiﬁ cant beneﬁ ts
being reduced pain and improvement of poor ap-
petite, tiredness, weakness, and dryness of the mouth
and throat. e clinicians noted that in TCM, this
indicates an invigorating action on the heart and
spleen. Compared to control patients, body weight
in the PSP group was sig niﬁ cantly higher, and their
210 International Journal of Medicinal Mushrooms
C. R. HOBBS
T-cell ratio, NK-cell activity, and IL-2 levels were
also higher. To counteract the decreases in white
blood cell, hemoglobin, and platelet levels that ac-
company chemo- and radiotherapy, batyl alcohol is
often given at the same time. PSP in place of batyl
alcohol produced comparable results. Overall, PSP
was eﬀ ective for 82% but only 45% among those
also given batyl alcohol (p < 0.001) (Liu and Zhou,
Other uncontrolled clinical studies have reported a
signiﬁ cant decrease in cyclophosphamide-induced
chromosomal damage in children (Tsukagoshi et al.,
1984) and fewer sick days and increased immunity
in patients with recurrent genital herpes (3–5 g/day)
When an elderly patient with lier metastiasis from
gastric cancer was given CPT-11 (20 mg × 2/day ×
2/week) and PSK (3.0 g/day), the tumor was reduced
by greater than 50% after 13 weeks of treatment.
After 20 weeks the patient reported no adverse ef-
fects from the treatment. e researchers suggested
that low dose CPT-11 with PSK might produce
fewer side eﬀ ects than the chemotherapeutic agent
alone with signiﬁ cant tumor reduction (Takahashi
and Mai, 2001).
TOXICITY AND CONTRAINDICATIONS
Unlike many standard anticancer drugs, the PSK
in T. versicolor produces few, if any, side eﬀ ects on
the bone marrow or other organs, and it shows no
immunosuppressive action. In general, T. versicolor
has very low levels of toxicity and produces few or
no side eﬀ ects (Tsukagoshi et al., 1984). e oral
LD₅₀ of PSP is reported as 10.0 mg/kg. Negative
results were found on the Ames and chromosome
distortion tests ( Jong and Yang, 1999).
No toxicity or related changes in growth or de-
velopment was seen in rats and monkeys given PSP
for 180 days at up to 12 g/kg daily. ECG and blood
chemistry was normal, and no histopathological
changes were seen (Zhang et al., 1989). PSP did
not aﬀ ect mouse embryonic development, ovarian
steroidogenesis, ovulation, or midterm gestation in
mice (Ng and Chan, 1997).
Because of their demonstrated ability to coun-
teract the immunosuppressive activity of cyclophos-
phamide, PSP and PSK should be avoided during
immunosuppressive chemotherapy (Li et al., 1990;
Qian et al., 1997).
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