Ganoderma has been used as folk medicine since ancient times and
it is a popular health food frequently promoted as a cancer cure. It is
now well established from in vitro and animal studies that the polysaccharide
fraction of Ganoderma is largely responsible for its antitumor efficacy.
Although there is yet no controlled clinical trials in humans for Ganoderma
against cancer to date, the indications for its supplemental use can be
indirectly supported with clinical trial data from comparable fungal polysaccharides
because of a common final pathway of action mediated via the beta-glucan
receptor. Based on such indirect data, indications for Ganoderma use in
cancer include supplementation a) to reduce side-effects during chemotherapy
or radiotherapy, b) to prolonging survival and minimize metastasis, c)
to improve quality of life, and d) to prevent occurrence or recurrence.
In sum, although the cure of any cancer with Ganoderma alone is unlikely,
it is probably beneficial under defined circumstances in most cases of
Ganoderma has been recognized traditionally and scientifically as potentially useful in the treatment of cancer, but there is a notable discrepancy with the public's frequent impression that Ganoderma may be a cure for cancer and the lack of clinical trials demonstrating such efficacy. We intend to summarize the extent of available theoretical, experimental and clinical data for the use of Ganoderma supplementation in cancer and outline its indications, especially in the context of clinical results from bioactively similar polysaccharide derived biological response modifiers (BRM's) from other fungi (Mizuno 1996).
EXPERIMENTAL EVIDENCE OF GANODERMA'S POTENTIAL IN CANCER TREATMENT
Ikekawa et al. (1968) first reported on the efficacy of soluble extracts from Ganoderma in inhibiting transplanted sarcoma 180 in mice. This host-dependent antitumor activity has been subsequently confirmed to be from the polysaccharide fractions of Ganoderma (Sasaki et al., 1971). Multiple similar studies subsequently confirms this observation and antitumor efficacy of Ganoderma has been demonstrated from various species, at different stages of growth and using different solvents for extraction and different routes of administration. Antitumor activity has been demonstrated in vitro as well as in syngeneic tumor systems in animals. However, no human trials of Ganoderma against cancer in peer reviewed journals nor any controlled clinical trials in humans have yet been conducted or published.
From a theoretical point of view, it is important to note
that other fungal polysaccharides of comparable structure and function
as those found in Ganoderma have undergone rigorous clinical trials, including
Lentinan, Sizofilan, PSK (Krestin), and PSP. Since it is now increasingly
clear that immunostimulatory bioactivity from most beta-glucan based compounds
function via a similar beta-glucan receptor (Czop 1985), it has been possible
to hypothesize that Ganoderma polysaccharides should function similarly
(Chang, 1996). Clinical effects of various glucan based BRM's should therefore
be comparable. Results from Lentinan, Sizofilan, PSK and PSP human trials
demonstrated the efficacy of these glucan BRM's in prolonging survival
in recurrent or advanced gastric and colon cancer, lung cancer and gynecologic
cancers. Data from such bioactively comparable compounds all suggest improved
quality of life or survival for cancer patients may be possible with Ganoderma
INDICATIONS AND EVIDENCE SUPPORTING THE USE OF
GANODERMA SUPPLEMENTATION IN CANCER
Whilst some efficacy of Ganoderma in cancer is undoubted, it remains important to specify the various indications and cite the evidence to support its use. This can be discussed under four different circumstances:
B. As a supplement for cancer patients to enhance survival and reduce likelihood of metastasis. While only anecdotal data exists that Ganoderma supplementation may enhance survival of cancer patients, this survival advantage has been demonstrated for a number of comparable glucan BRM'S. Specifically, Lentinan use in advantage at 1, 2, 3 and 4 years in a randomized control trial (Taguchi 1987). Sizofilan given together with chemotherapy enhanced survival of cervical cancers irrespective of stage in a prospective randomized controlled trial (Inoue et al. 1993), significantly enhanced survival (P < .01) in lung cancer patients (Honma 1982) and improved five year survival of head and neck cancer from 73.4 to 86.7% was noted in another small study (Kimura et al. 1994). More appropriate for comparison to Ganoderma is perhaps and PSK or PSP, which are orally administered. Mitomi et al. (1994) found significantly improved survival and disease-free survival (P=0.013) in resected colorectal cancer given PSK supplementation over three years when compared to control in a multi-center randomized controlled trial. In an animal model, Ganoderma has been demonstrated to effectively prevent metastasis (Lee 1984), and these results are comparable to those of Lentinan (Suga 1994). Other glucan BRM's have been demonstrated to effectively prevent or suppress pulmonary metastasis of methylcholanthrene-induced sarcomas, human prostate cancer DU145M, and lymphatic metastasis of mouse leukemia P388 (Kobayashi et al. 1995). The recommended dose should be five to ten grams or more of fruiting body or equivalent per day, with a linear enhancement in efficacy expected up to 30 grams per day (Chang 1994).
C. As a supplement for cancer patients to improve quality of life. Again, only anecdotal information exists for Ganoderma in this situation but other oral glucan derivatives such as PSP has been found to be useful in improving quality of life in cancer patients (Yao 1993). Significantly, Ganoderma supplementation was noted to decrease pain in cancer patients (Kupin 1994). The recommended dose would be five to ten grams of fruiting body or equivalent per day (Chang 1994).
D. As a supplement for the prevention of occurrence or
recurrence of cancer. Since immune stimulation, especially Natural Killer
(NK) and Cytotoxic Lymphocyte (CTL) activation may be effective in the
immune prevention of cancer by enhanced immune surveillance (Lotzova 1985),
and Ganoderma has been demonstrated to enhance NK and CTL activity when
administered orally (Won et al. 1989), it is thus a candidate for prevention
of the occurrence or recurrence of cancer. Stavinoha et al. demonstrated
the efficacy of Ganoderma in the preventing the progression of microadenomatous
growths in animals (Stavinoha 1993), and the efficacy of other glucan BRM's
in primary and secondary cancer prevention have been similarly demonstrated
in vitro, in vivo and in clinical trials.
Although Ganoderma and its derivatives are not pharmaceuticals
and have not undergone rigorous clinical trials to be tested against cancer,
there is abundant in vitro, animal and indirect clinical evidence to support
its supplemental use in cancer. Standardization in bioactive polysaccharide
content and dosages will be necessary to assure its rational use, and clinical
trials in select cancers with defined endpoints will confirm its efficacy.
|Raymond Y. Chang
M.D., FACP. President, Institute of East-West Medicine, New York.
Born on lst, Dec., 1957 in Hong Kong
Education : 9/76 to 6/79 Brown University. Graduated B. A. (bio) magna cum laude 1980 6/79 to 5/83 Brown University Program in Medicine Providence. Graduated M.D Class of 1983
6/83 to 6/86 Medical Internship and Residency Yale University School of Medicine
7/86 to 7/87 Kaiser Foundation Fellow in General Internal Medicine, Cornell Medical College-NewYork Hospital
Academic Appointment ; Faculty Positions
7/87 to 1/97 Director, Urgent Care Center, Memorial Hospital, New York
9/95 to present Course Director, Complementary Medicine, Cornell Medical College
1/95 to present Associate Professor of Medicine, Cornell Medical College, New York
Publications and Presentations
- Chang, R. The use of CD4 count to predict hospitalisation in HIV emergencies. In ; Proceedings from the Xth International Conference on AIDS, 1994 August 7-12, Yokohama, Japan. 1994 : PB0080
- Chang, R. Limitations and Potential Applications of Ganoderma and Related Fungal Polyglycans in Clinical Onology (Presentation), at the First International Conference on Mushroom Biology and Mushroom Products. Hong Kong 1993 : 0-6-1 (96). -- Chang, R. Ganoderma Polysaccharides immunologic actions and modes of action. In ; Proceedings from 2nd International Ganoderma Conference, Beijing, China, 1994 . Chang, R. The Central Role of the 8-Glucan Receptor in Orchestrating Anti-tumor, Immunomodulatory, and other Medical Effects of Ganoderma Polysaccharides. In ; Reishi, Mizuno T. and Kim B. K. (eds.). 11 Yang, Seoul, 1996
- Chang. R. Limitations and prospects of current clinical Ganoderma Research. 1996 Taipei International Ganoderma Research Conference, Taipei, 1996
Chang, R. (1994). Effective dose of ganoderma in humans. In Proc. Contributed Symposium 59A,B. 5th Intl. Mycol. Congr., Buchanan PK, Hseu RS and Moncalvo JM (eds), Taipei, p. 101-13.
Chang, R. (1996). The Central Importance of the 7 -glucan receptor as the basis of immunologic bioactivy of ganoderma polysaccharides. In Reishi, Mizuno T, Kim BK (eds), II Yang Press, Seoul, p. 177-9.
Chang, R. (1996). Potential application of ganoderma polysaccharides in the immunosurveillance and chemoprevention of cancer. In Mushroom Biology and Mushroom Products, Proceedings of the 2nd International Conference, Royse DJ (ed), Penn State U. Press, University Park, p. 153-9.
Czop, J.K., & Austen, K.F. (1985). A 7 -Glucan inhabitable receptor on human monocytes, Immunol. 134, 2588-593
Honma, H., Oshima, S., Watanabe, S. et al. (1982). Clinical efficacy of schizophyllan (SPG) in treatment of lung cancers. A Randomized controlled study. Haigan 22: 499-512.
Ikekawa, T., Nakanishi, M, Uehara, N., et al. (1968) Antitumor action of some basidiomycetes, especially Phellinus linteus. Gann. 59: 155-157.
Inoue, M., Tanaka, Y., Sugita, N., et al. (1993) Improvement of long-term prognosis in patients with ovarian cancers by adjuvant sizofilan immunotherapy: a prospective randomized controlled study. Biotherapy. 6(l):13-8.
Jia, YF., Zhou, XB., Memg, H., and Zhang, LX. Effects of Ling Zhi on hemopoietic system in mice - immunopharmacological study (11). In The research on ganoderma (part I). Zhu S. and Mori M. (eds). Shanghai Med. U. Press, Shanghai, p.284-288.
Kimura, Y., Tojima, H., Fukase, S., Takeda, K. (1994) Clinical evaluation of sizofilan as assistant immunotherapy in treatment of head and neck cancer. Acta Oto-Laryngologica - Suppl. 511:92-5.
Kobayashi, H., Matsunaga, K., Oguchi, Y. (1995) Antimetastatic effects of PSK (Krestin), a protein-bound polysaccharide obtained from basidiomycetes: an overview. Cancer Epidemiology, Biomarkers & Prevention. 4(3):275-81.
Kupin, V. (1994) A new biological response modifier - ganoderma lucidum - and its application in oncology. In Proceedings from the 6th international symposium on ganoderma lucidum. Seoul, II Yang, p.36-37.
Lee, SS., Chen, FD., Chang, SC., et al. (1984). In vivo anti-tumor effects of crude extracts from the myeelium of ganoderma lucidum. J. of Chinese Oncology Society 5(3): 22-28.
Mitomi, T., Tsuchiya, S., lijima, N., et al. (1992). Randomized controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. Diseases of the Colon & Rectum. 35(2):123-30.
Miyamoto, T., Abe, T., Hasunuma, K. (1985). Japan Kokai Tokkyo Koho JP60, 199,810 [85,199.8101 (Cl. A61K7/06). Appl. 84/5,977. 24 Mar 1984.
Mizuno, T. (1996). A development of antitumor polysaccharides from mushroom fungi.
FFI Journal, 167:69-85. Shi, JH. (1993). PSP for the protection of the tumorous patients during chemotherapy. In 1993 PSP Intl. Symposium, Yang QY and Kwok CY (eds.), Fudan U. Press, Shanghai, p.2712.
Stavinoha, W. (1993). Short term dietary supplementation with ganoderma lucidum slows development and growth of microadenomatous lesions in the colon of rats treated with the carcinogen 1,2 dimethylhydrazine. Presented at the 5th international symposium on ganoderma lucidum, Seoul, Korea on June 17, 1993.
Suga, T., Shiio, T., Maeda, YY., Chihara, G. (1994). Antitumor activity of lentinan in murine syngeneic and autochthonous hosts and its suppressive effect on 3methylcholanthrene induced carcinogenesis. Cancer Res. 44:5132-7
Taguchi, T. (1987). Clinical efficacy of lentinan on patients with stomach cancer: end point results of a four-year follow-up survey. Cancer Detection & Prevention. Suppl. 1:333-49.
Won, SJ., Lee, SS., Ke, YH., Lin, MT. (1989) Enhancement of splenic NK cytotoxic activity by extracts of ganoderma lucidum mycelium in mice. J Biomed Lab Sci 2:201-213.
Yang, QY and Wang, MM. (1995). The effect of ganoderma lucidum extract against fatigue and endurance in the absence of oxygen. In Proc. Contributed. Symposium. 59A,B. 5th Intl. Mycol. Cong., Buchanan, PK., Hseu, RS and Moncalvo JM., (eds), Taipei, p.101-113.
Yao, PY., Gao, ZM., Fang, ST and Ke, L.(1993). Evaluation of the subsidiary effects of taking PSP orally on the chemotherapy of stomach cancer. In 1993 PSP Intl. Symposium, Yang QY and Kwok CY (eds), Fudan U. Press, Shanghai, p.269-70.