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Kathy Abascal, B.S., J.D., R.H. (AHG),
and Eric Yarnell, N.D., R.H. (AHG)
Abstract
Trametes versicolor or Coriolus versicolor (turkey tails) is a medic-
inal mushroom containing a number of protein-bound
polysaccharides that have shown strong potential in the
treatment of cancer. This discussion examines the use of Polysaccha-
ride Krestin (PSK), a proprietary polysaccharide extracted from T.
versicolor, in the treatment of gastric, colorectal, lung, breast, and
esophageal cancers. PSK has been approved in Japan for use as an
adjunct to surgery, chemotherapy, and radiation therapy for cancer,
and has shown significant benefits. This agent appears to act in part
by restoring the balance of dendritic and T-helper cells and cytokines
related to these cells’ function and maturation in cancer patients.
Introduction
The fan-shaped mushroom known as turkey tails (Trametes ver-
sicolor or Coriolus versicolor) can be found growing on logs
throughout the United States, Europe, and Asia. It has a distinc-
tive cap that is “zoned” into bands of brown, white, gray, or blue,
and grows in overlapping clusters. Turkey tails does not have a
culinary use, but it is said to make a pleasant, mushroom-fla-
vored chewing gum. And although it was recognized as a medic-
inal agent in the Chinese materia medica thousands of years
ago,1turkey tails is not a mushroom that has a central place in
traditional medicine, like Ganoderma lucidum (reishi), Cordyceps
sinensis (cordyceps), or Lentinula edodes (shiitake). Nonetheless, a
proteoglycan from turkey tails is today used in treating cancer in
Japan. Surprisingly, the potential benefits of turkey tails are
largely ignored by mainstream oncology in North America.
Polysaccharides
Mushroom proteoglycans consist of protein-bound polysaccha-
rides, and are recognized as having anticancer potential. This pre-
sentation reviews the use of a turkey tails proteoglycan,
(Polysaccharide Krestin), in treating cancer. PSK, sometimes
referred to by the brand name Krestin under which it is available
on a proprietary basis, has been used in Asia in treatment regi-
mens for cancer for over 30 years. This agent was reportedly dis-
covered when a Japanese engineer observed a neighbor with a
life-threatening cancer go into remission after taking turkey tails
mushrooms.
PSK is water-extracted from a particular strain of turkey tails
(CM-101) and is orally bioavailable.2It is nontoxic and has shown
a high degree of safety in chronic and subacute toxicity studies.
The only significant side effect of PSK observed in clinical practice
is reported to be an occasional darkening of the fingernails.2
In Japan, PSK is typically used as an adjunct to conventional
cancer treatments, and has only rarely been studied by itself in
treating cancer. However, a placebo-controlled, double-blind trial
involving 144 patients with stage III gastric cancer found that
PSK significantly extended disease-free survival, although it did
not strikingly extend overall survival.3The patients were given
PSK in a dose of 3 g daily for up to 2 months, 2 g daily for the
next 2–14 months, and 1 g daily from 14 to more than 80 months
after surgical resection, to the endpoints of disease recurrence or
distant metastasis. The study found that PSK increased immuno-
competence and appeared to require some degree of residual
immune function for positive effects.3
In a subsequent study of 111 patients with stages III and IV col-
orectal cancer, treated with the same protocol as in the study just
described, PSK improved 8-year survival to 40% versus 25%, and
disease-free survival to 25% versus 8% as compared to placebo.4
PSK as an Adjunctive Agent
Since the 1970s, numerous clinical trials have investigated PSK
as an adjunct to chemotherapy for cancer. These studies suggest
that PSK is most strongly indicated for cancers of the stomach,
esophagus, colon, rectum, and lung.
At least 10 studies have examined PSK as a component of
long-term chemotherapy for resected stomach cancer.2In all of
these studies PSK was administered orally at a dose of 3
g/day. In one of the earliest studies, a group of 66 patients
with stage IV stomach cancer were treated with mitomycin-C
178
DOI: 10.1089/act.2007.13410
A Turkey Tails Polysaccharide as
an Immunochemotherapy Agent
in Cancer
beginning on the day of surgery, followed by long-term
immunochemotherapy with a 5-fluorouracil (5-FU) derivative
plus PSK, with periodic administration of mitomycin-C. The 2-
year survival for this group was more than twice that of a simi-
lar group of patients treated with surgery and mitomycin-C
but without 5-FU or PSK.5
Subsequent studies using a similar regimen also had posi-
tive results. In a study of 110 patients with stomach cancer of
all stages, the postoperative combination of mitomycin-C with
long-term administration of tegafur (F-207) and PSK improved
3-year survival, and no deaths were reported for the first 2
years after surgery in a subset of patients with stage III dis-
ease.6
In 450 patients with advanced stomach cancer and invasive
metastasis, the combination of mitomycin-C given after resec-
tion, with long-term tegafur/PSK, doubled the rate of 5-year
survival over the chemotherapy regimen alone.7In two further
studies, of 579 patients with invasive metastasis and 53
patients with stage III stomach cancer, respectively, PSK again
increased the rate of 5-year survival.8,9 Other studies had simi-
lar findings for 5-year survival, and in one, PSK extended 15-
year survival.10–12
Current Status of PSK in Gastric Cancer
In Japan, PSK dosed at 3 g/day is approved as part of the stan-
dard treatment regimen for gastric cancer, and is covered by
insurance. Currently, the view is that the overall effect of PSK is
enhanced by alternating periods of its use with periods of
chemotherapy.13 Other studies of patients most helped by PSK
suggest that it is highly likely to increase long-term survival in
patients with limited dendritic-cell infiltration of gastric tumors
at the time of surgery.9
Colorectal Cancer
With establishment of the benefits of PSK as an adjunct to
chemotherapy for gastric cancer, investigations began of the
agent’s potential benefits in colorectal cancer. In a large multicen-
ter trial, 448 patients treated surgically for colon or rectal cancer
were randomized to receive either chemotherapy alone or PSK
plus chemotherapy. After the third year of treatment, PSK had
significantly improved both survival and the disease-free interval
in the colon-cancer group but not in the group with rectal
cancer.14
In a comparative study in which patients with untreated stage
II or III colorectal cancer underwent surgical resection and were
given a fluoropyrimidine after surgery, the 3-year disease-free
survival rate was 74.3% for PSK plus chemotherapy, as opposed
to 40.0% for chemotherapy alone.15 A marker of hepatic metasta-
sis in gastrointestinal (GI) cancers, type IV collagen, was present
at significantly lower levels in the blood of patients given PSK
plus chemotherapy than in the chemotherapy-only group for the
first 12 months after surgery.15
In a multicenter study of metastatic colon cancer with a 7-
year follow-up, PSK was given in alternating cycles with 5-FU
for 10 courses while a second cohort of patients received only 5-
FU.13 The mortality rate in the PSK-plus-5-FU-treated group
was 16.8%, versus 22.1% with 5-FU alone.13 While disease-free
survival was similar for the two study groups, 7-year survival
was significantly greater in the PSK group than in the
chemotherapy-only group, at 83.4% versus 78.5%. No toxic
effects of PSK were found in a meticulous review of the
patients’ medical records.
The 5-year follow-up of a randomized, controlled, 2-year
comparison of chemotherapy with tegafur plus 5-FU showed
a significant benefit from the addition of PSK in stage II and
III colorectal cancers.16 The mean disease-free survival in the
tegafur/5-FU/PSK group was 50.3 months, versus 40.0
months in the group given chemotherapy alone; 5-year dis-
ease-free survival was 73.0% in the former group versus
ALTERNATIVE & COMPLEMENTARY THERAPIES—AUGUST 2007 179
Trametes versicolor (turkey tails). Drawing ©2007 by Eric Yarnell, N.D.,
R.H. (AHG).
PSK and Metastasis
Metastasis is the ultimate cause of death in the vast majority of
patients who have cancer. Metastasis is a cascade of events beginning
with the escape of cancer cells from a primary tumor and ending in
the growth of these cells into new lesions at sites other than that of
the primary tumor. Intervention at any point in this cascade of events
is beneficial in combating cancer, and PSK shows potential at many
points in this process.
In a study in which mice were inoculated in both flanks with
fibrosarcoma cells, the injection of PSK into one of the resulting
tumors enhanced the activity of cytotoxic macrophages, causing this
metastatic tumor to shrink. Orally administered PSK also decreased
the number of metastatic nodules in this animal model of spontaneous
metastasis, and showed an ability to inhibit both the intravasation of
cancer cells from the primary tumor into the circulatory system and
the extravasation of tumor cells from the circulation to new sites of
tumor growth.a
aRef. 18.
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180 ALTERNATIVE & COMPLEMENTARY THERAPIES—AUGUST 2007
58.8% in the latter. The addition of PSK reduced disease
recurrence by 43.6% and mortality by 40.2%.16 PSK signifi-
cantly increased disease-free and overall survival in cases of
stage III disease (60.0% and 74.6%, versus 32.1% and 46.4%,
respectively).
A recent meta-analysis found that adding PSK to the treatment
of colorectal cancer (n = 1094) significantly improved overall and
disease-free survival as compared to chemotherapy alone.17
PSK and Other Cancers
Two studies have looked at PSK in esophageal cancer. One of
these was a retrospective, noncontrolled study of 133 patients to
whom PSK was given after surgery and radiation therapy. The
researchers concluded that PSK significantly improved 1- and
2-year survival.18 In a prospective,
randomized study of 158 patients,
PSK, again given after surgery and
radiation therapy, significantly
improved the 5-year survival rate
as compared with surgery and
radiation alone.19 This study found
that PSK improved survival in
patients with abnormally high lev-
els of alpha-1-antichymotrypsin,
sialic acid, or both.19
In a study of 34 patients with
nasopharyngeal cancer who had
undergone radiation and various forms of chemotherapy
before being randomized to receive PSK or placebo, the
patients given PSK had a 5-year survival rate of 28%, versus
15% for the placebo group.20 When given after radiation thera-
py in 2-week cycles to 185 patients with non–small-cell lung
cancer, PSK was associated with a 5-year survival of 27%, ver-
sus 7% for placebo. Patients with stage III disease fared better
than those with stage I or II disease.21
The benefit of PSK in breast cancer is more varied than that in
GI cancer. A retrospective analysis of breast cancer patients
treated for recurrent disease with surgery followed either by
mitomycin-C alone or by mitomycin-C plus PSK found that the
latter regimen significantly extended survival over surgery or
surgery plus mitomycin-C.22 A study of patients with vascularly
invasive breast cancer found strong trends toward extended 10-
year survival with PSK given together with chemotherapy after
surgery, as opposed to surgery and chemotherapy alone, and
also found extended disease-free intervals, but lacked statistical
evaluations.23,24 A retrospective analysis of PSK in breast cancer
showed that patients with HLA B40+ type breast cancers who
received PSK had a 100% survival at 10 years, even though the
use of PSK has not shown a clear benefit in breast cancer treat-
ment overall.24
A multicenter study of 67 patients in remission following ini-
tial chemotherapy for acute nonlymphocytic leukemia, who were
randomized to receive 2 years of maintenance chemotherapy
with or without PSK given for as long as 4.5 years, found a trend
toward benefit from the addition of PSK.25
How Turkey Tails Affects the Immune System
PSK is used to support and stimulate the immune system in
cancer and to offset the immunosuppressive effects of allopathic
cancer treatments. Research is being conducted to explain the
many ways in which PSK acts to produce these effects. One of
the most interesting areas of such investigation seeks to deter-
mine how PSK affects dendritic and T-helper cells and the cyto-
kines they secrete.
In the normal function of the immune system, antigen-present-
ing cells, such as dendritic cells, activate T-helper (Th) cells.3
Once activated, Th cells coordinate the response of other immune
cells. The balance between two types of Th cells—Th1 (Type 1)
and Th2 (Type 2) cells—is of great importance in cancer.
The substances secreted by Th1 and Th2 cells to maintain their
normal balance are known as
cytokines and chemokines. Immune
cells function through a complex
interplay of such substances. The
body uses the cytokine interleukin-12
(IL-12) as one of its tools to defend
against tumors. This cytokine helps
Th1 cells to proliferate, activate, and
mature. IL-12 also augments natural-
killer (NK) cell cytotoxicity against
tumor cells. However, when the
body is in a cancer-bearing state, IL-
12 production tends to be sup-
pressed, which decreases Th1 activity. Th2 dominance increases the
production of a different cytokine, IL-10, and when IL-10 is strongly
expressed, dendritic cells produce virtually no IL-12 and are unable
to induce the activation and maturation of Th cells.3
In healthy individuals, Th1 cells mobilize a defense against
cancer cells. But if they evade detection and grow, cancer cells
secrete substances that create a Th2 dominance, making the host
less able to challenge them.3Studies indicate that cancer signifi-
cantly reduces Th1/Th2 and dendritic cell type (DC1/DC2)
ratios, causing an inefficient immune response to the disease.6
Surgery causes a brief period of Th2 dominance that may give
residual tumor cells an opportunity to evade the immune
system.5Other causes of Th2 dominance include exposure to
heavy metals.4PSK, and some other plant polysaccharides, help
the body shift back to Th1 dominance, which leads to a more
effective response to cancer.
In a small study of patients with gastric and colorectal cancer,
treatment with PSK shifted the Th1/Th2 and DC1/DC2 bal-
ances to favor Th1 and DC1 dominance, respectively, signifi-
cantly decreasing IL-10 production.6Other studies confirm the
ability of PSK to promote Th1 dominance.7,8 In patients with
colorectal cancer, PSK decreased amounts of Th2 cytokines in
responders but not in nonresponding patients, and strongly
reduced IL-10 production in another study of patients with
advanced cancer.7,8
In patients with highly advanced cancer treated with PSK and
chemotherapy, the production of IL-10 and other Th1-suppress-
ing factors decreased significantly.9In vitro, PSK was found to
Adding PSK to the treatment of
colorectal cancer significantly improved
overall and disease-free survival as
compared to chemotherapy alone.
GJ 13_4_toc-223:GJ 13_2_toc-000 7/29/07 1:19 PM Page 180
increase the maturation of dendritic cells.26 This is noteworthy
because immune depression in malignancy is associated with a
failure of dendritic cell maturation.6In mice, PSK suppressed the
increase in Th2 cytokines caused by surgery and prevented liver
metastases of colon cancer cells injected into the spleen during
surgery.10 A study of rats found that preoperative administration
of PSK prevented a decrease in postoperative cellular immuni-
ty.11 Other studies found that PSK induced the Th1 cytokine IL-
12. Taken together, these studies explain how the effect of PSK on
the immune system improves the outcome of conventional can-
cer treatments that by themselves tend to depress the host
immune response.
Conclusion
There is strong evidence that, when used as an adjunct to
conventional cancer treatments, PSK can provide substantial
benefit by restoring immune function, alleviating symptoms,
and increasing survival. In view of this, it is confounding that
so little clinical research has been done in the United States on
PSK and similar proteoglycans.27 PSK is not even readily avail-
able in the United States, although products that manufactur-
ers claim are similar or identical to PSK are available under
other names, such as VPS (MushroomScience, Eugene, OR).28
Nor is information readily available on the quantity of PSK
contained in the intact turkey tails mushroom, making it diffi-
cult to calculate an effective dose of PSK with use of the whole
mushroom.
What is perhaps even more surprising is that so little basic
research has been done on turkey tails itself. Research on PSK
began with the observation that use of the whole turkey tails
mushroom brought complete remission in a case of advanced
cancer. However, other turkey tails’ polysaccharides also
show benefit in cancer (see box entitled PSP, Another Turkey
Tails Proteoglycan). Research on the use of PSK combined
with the turkey tails polysaccharide PSP, or on use of the
whole mushroom, is definitely warranted to determine
whether this may yield stronger beneficial effects than those
already observed.5In any case, there seems no doubt that
more practitioners should be advising patients on how PSK is
used in Japan to improve outcomes with conventional cancer
treatments.
References
1. Ho CY, Lau CBS, Kim CF, et al. Differential effect of Coriolus versicolor
(Yunzhi) extract on cytokine production by murine lymphocytes in vitro.
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2. Kidd PM. The use of mushroom glucans and proteoglycans in cancer
treatment. Altern Med Rev 2000;5:4–27.
3. Kondo M, Torisu M. Evaluation of an anticancer activity of a protein-
bound polysaccharide PS-K (Krestin). In: Torisu M, Yoshida T, eds. Basic
Mechanisms and Clinical Treatment of Tumor Metastasis. New York:
Academic Press, 1985.
4. Torisu M, Hayashi Y, Ishimitsu T, et al. Significant prolongation of dis-
ease-free period gained by oral polysaccharide K (PSK) administration after
curative surgical operation of colorectal cancer. Cancer Immunol
Immunother 1990;31:261–268.
5. Kaibara N, Soejima K, Nakamura T, et al. Clinical value of immuno-
chemotherapy with OK-432. Jpn J Surg 1976;6:54–59.
6. Hattori T, Niimoto M, Koh T, et al. PSK and FT-207 in gastric cancer
patients. Jpn J Surg 1979;9:110–117.
7. Kodama Y, Kano T, Tamada R, et al. Combined effect of prophylactic
lymphadenectomy and long-term combination chemotherapy for curatively
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8. Niimoto M, Hattori T, Tamada R, et al. Postoperative adjuvant immuno-
chemotherapy with mitomycin C, futraful and PSK for gastric cancer: An
analysis of data on 579 patients followed for five years. Jpn J Surg
1988;18:681–686.
9. Tsujitani S, Kakeji Y, Orita H, et al. Postoperative adjuvant immuno-
chemotherapy and infiltration of dendritic cells for patients with advanced
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10. Fujimoto S, Takahashi M, Minami T, et al. Clinical value of immuno-
chemotherapy with OK-432. Jpn J Surg 1979;3:190–196.
11. Mitomi T, Ogoshi K. Clinical study of PSK as an adjuvant immuno-
chemotherapeutic agent against gastric cancer. Jpn J Cancer Chemother
1986;13:2532–2537.
12. Nakazato H, Koike A, Saji S, et al. Efficacy of immunochemotherapy as
adjuvant treatment after curative resection of gastric cancer. Lancet
1994;343:1122–1126.
13. Ito K, Nakazato H, Koike A, et al. Long-term effect of 5-fluorouracil
enhanced by intermittent administration of polysaccharide K after curative
resection of colon cancer. Int J Colorectal Dis 2002;19:157–164.
14. Mitomi T, Tsuchiya S, Iijma N, et al. Randomized, controlled study on
adjuvant immunochemotherapy with PSK in curatively resected colorectal
cancer. Dis Colon Rectum 1992;35:123–130.
15. Kudo S, Tanaka J, Kashida H, et al. Effectiveness of immunochemotherapy
with PSK, a protein-bound polysaccharide, in colorectal cancer and changes
of tumor marker. Oncol Rep 2002;9:635–638.
16. Ohwada S, Ikeya T, Yokomori T, et al. Adjuvant immunochemotherapy
with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal
cancer: A randomized controlled study. Br J Cancer 2004;90:1003–1010.
17. Sakamoto J, Morita S, Oba K, et al. Efficacy of adjuvant immuno-
chemotherapy with polysaccharide K for patients with curatively resected
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als. Cancer Immunol Immunother 2006;55:404–411.
18. Okudaira Y, Sugimachi K, Inokuchi K, et al. Postoperative long-term
immunochemotherapy for esophageal cancer. Jpn J Surg 1982;12:249–256.
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ALTERNATIVE & COMPLEMENTARY THERAPIES—AUGUST 2007 181
PSP, Another Turkey Tails Proteoglycan
In China, the turkey tails proteoglycan, PSP, is used in treating
cancer.aIn patients with stomach, esophageal, and non–small-cell
lung cancers, PSP has been reported to ease symptoms of radiation
or chemotherapy and to enhance various immunologic functional
parameters.a
It appears that PSP primarily ameliorates fatigue, loss of appetite,
vomiting, dryness of the mouth, and other factors related to quality of
life, but there is less evidence of PSP having direct effect on overall
survival. However, one open-label, randomized trial in esophageal
cancer found that PSP significantly improved both 1- and 3-year
survival, and a subsequent study produced similar results.b
Unfortunately, no studies have been reported on whether a
combination of PSP and PSK might prove more useful than either
compound used alone.
aRef. 2.
bNg TB. A review of research on the protein-bound polysaccharide (Polysaccharopeptide,
PSP) from the mushroom Coriolus versicolor (Basidiomycetes: Polyporaceae). Gen Pharmacol
1998;30:1–4.
GJ 13_4_toc-223:GJ 13_2_toc-000 7/29/07 1:19 PM Page 181
20. Go P, Chung CH. Adjuvant PSK immunotherapy in patients with carci-
noma of the nasopharynx. J Int Med Res 1989;17:141–149.
21. Hayakawa K, Mitsuhashi N, Saito Y, et al. Effect of Krestin (PSK) as
adjuvant treatment on the prognosis after radical radiotherapy in patients
with non–small cell lung cancer. Anticancer Res 1993;13:1815–1820.
22. Sugimachi K, Inokuchi K, Matsuura H, et al. Hormone conditioned can-
cer chemotherapy for recurrent breast cancer prolongs survival. Jpn J Surg
1984;14:217–221.
23. Iino Y, Yokoe T, Maemura M, et al. Immunochemotherapies versus
chemotherapy as adjuvant treatment after curative resection of operable
breast cancer. Anticancer Res 1995;15:2907–2912.
24. Yokoe T, Iino Y, Takei H, et al. HLA antigen as predictive index for the
outcome of breast cancer patients with adjuvant immunochemotherapy
with PSK. Anticancer Res 1997;17:2815–2818.
25. Ohno R, Yamada K, Masaoka T, et al. A randomized trial of chemoim-
munotherapy of acute nonlymphocytic leukemia in adults using a protein-
bound polysaccharide preparation. Cancer Immunol Immunother
1984;18:149–154.
26. Okuzawa M, Shinohara H, Kobayashi T, et al. PSK, a protein-bound
polysaccharide, overcomes defective maturation of dendritic cells exposed
to tumor-derived factors in vitro. Int J Oncol 2002;20:1189–1195.
27. Borchers AT, Keen CL, Gershwin ME. Mushrooms, tumors, and immu-
nity: An update. Exp Biol Med 2004;229:393–406.
28. No author listed. MushroomScience. Online document at: www.
mushroomscience.com/ Accessed May 22, 2007.
Kathy Abascal, B.S., J.D., R.H. (AHG), is executive director of the Botan-
ical Medicine Academy, Vashon, Washington. Eric Yarnell, N.D., R.H.
(AHG), is president of the Botanical Medicine Academy, a specialty
board for using medicinal herbs, and is a faculty member at Bastyr Uni-
versity, Kenmore, Washington.
To order reprints of this article, e-mail Karen Ballen at: Kballen@liebert-
pub.com or call at (914) 740-2100.
182 ALTERNATIVE & COMPLEMENTARY THERAPIES—AUGUST 2007
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