Die Rolle von Heilpilzen in der Integrativen
                    Onkologie

Michael Jeitler; Christian S. Kessler

doi:10.1055/a-2537-2980

Zeitschrift für Phytotherapie, Table of Contents

Zeitschrift für Phytotherapie 2025; 46(02): 85-98
DOI: 10.1055/a-2537-2980

Forschung

Die Rolle von Heilpilzen in der Integrativen Onkologie

Ein narratives Review

Michael Jeitler

¹Institut für Sozialmedizin, Epidemiologie und Gesundheitsökonomie, Charité - Universitätsmedizin Berlin, korporatives Mitglied der Freien Universität Berlin und der Humboldt-Universität zu Berlin, Berlin, Deutschland

²Immanuel Krankenhaus Berlin, Abteilung für Innere und Integrative Medizin, Berlin, Deutschland

³Institut für Allgemeinmedizin & Interprofessionelle Versorgung, Universitätsklinikum Tübingen, Tübingen, Deutschland

⁴Robert Bosch Centrum für Integrative Medizin und Gesundheit, Bosch Health Campus, Stuttgart, Deutschland

,

Christian S. Kessler

¹Institut für Sozialmedizin, Epidemiologie und Gesundheitsökonomie, Charité - Universitätsmedizin Berlin, korporatives Mitglied der Freien Universität Berlin und der Humboldt-Universität zu Berlin, Berlin, Deutschland

⁵Charité Competence Center for Traditional and Integrative Medicine (CCCTIM), Charité - Universitätsmedizin Berlin, korporatives Mitglied der Freien Universität Berlin und der Humboldt-Universität zu Berlin, Berlin, Deutschland

› Author Affiliations

Abstract

Zusammenfassung

Hintergrund/Ziel Heilpilze haben eine lange Tradition in der (ost-) asiatischen Medizin und gewinnen zunehmend auch in der westlichen Medizin an Bedeutung. Eine wachsende Anzahl präklinischer Studien weist auf mögliche onkotherapeutische Eigenschaften hin. Dennoch ist die klinische Relevanz von Mykotherapeutika (jenseits von Antibiotika) bislang völlig unzureichend erforscht, sodass ihr potenzieller Nutzen für die medizinische Praxis weiterhin unklar ist. Dieser narrative Review soll einen Überblick über die klinische Evidenz, die Bedeutung und die potenzielle Rolle von Heilpilzen in der Komplementäronkologie geben.

Methoden Es wurden wissenschaftliche Datenbanken nach (randomisierten) kontrollierten klinischen Studien durchsucht, in denen Vollspektrumpräparate aus Heilpilzen bei Krebspatienten während und/oder nach einer konventionellen onkologischen Behandlung untersucht wurden. 9 Studien erfüllten die Einschlusskriterien (8 randomisierte kontrollierte Studien, 1 kontrollierte klinische Studie). Bei den untersuchten Heilpilzen handelte es sich um Agaricus sylvaticus (2 Studien), Agaricus blazei (2 Studien), Antrodia cinnamomea (1 Studie), Trametes versicolor (1 Studie) und Ganoderma lucidum (3 Studien); in allen Studien wurde mit Placebo verglichen. Die Präparate wurden oral verabreicht.

Ergebnisse Die Studienergebnisse deuten auf günstige Effekte von Heilpilzen hin, insbesondere bzgl. Lebensqualität und der Reduktion unerwünschter Wirkungen konventioneller Therapien. Zudem wurde über positive Auswirkungen auf die Antitumoraktivität und die Immunmodulation berichtet, z. B. eine erhöhte Aktivität natürlicher Killerzellen. Darüber hinaus lassen die Daten vermuten, dass Krebspatienten, die Mykotherapeutika erhalten, möglicherweise eine verlängerte Überlebenszeit aufweisen. Unerwünschte Ereignisse wurden nur in 3 Studien berichtet; hier traten v. a. gastrointestinale Reaktionen und ein Rückgang der Thrombozytenzahl auf. Die methodische Qualität der meisten inkludierten Studien war generell unzureichend.

Schlussfolgerung Heilpilze haben möglicherweise ein therapeutisches Potenzial für Krebspatienten während und nach konventionellen onkologischen Behandlungen, insbesondere hinsichtlich Lebensqualität, der Verringerung unerwünschter Wirkungen konventioneller Behandlungen und möglicherweise auch bezüglich anderer Surrogatparameter wie Immunfunktionen. Es besteht ein dringender Bedarf, die Sicherheit und mögliche Wechselwirkungen von Heilpilzen mit anderen arzneilichen Substanzen zu untersuchen. Qualitativ hochwertige klinische (und präklinische) Forschung ist erforderlich, um das Potenzial von Heilpilzen in der Krebstherapie zu klären.

Schlüsselwörter

Heilpilze - Mykotherapie - Integrative Onkologie - Komplementärmedizin - Naturheilkunde

Full Text

References

Literatur
1 Global Burden of Disease Cancer Collaboration. Fitzmaurice C, Allen C. et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol 2017; 3: 524-548
2 Urruticoechea A, Alemany R, Balart J. et al. Recent advances in cancer therapy: An overview. Current Pharmaceutical Design 2010; 16: 3-10
3 Miller KD, Nogueira L, Mariotto AB. et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin 2019; 69: 363-385
4 Haun MW, Estel S, Rucker G. et al. Early palliative care for adults with advanced cancer. Cochrane Database Syst Rev 2017; 6: CD011129
5 Astin JA. Why patients use alternative medicine: results of a national study. JAMA 1998; 279: 1548-1553
6 Ernst E, Cassileth BR. The prevalence of complementary/alternative medicine in cancer: a systematic review. Cancer 1998; 83: 777-782
7 Jeitler M, Ortiz M, Brinkhaus B. et al. Use and acceptance of traditional, complementary and integrative medicine in Germany – an online representative cross-sectional study. Front Med 2024; 11: 1372924
8 Grant SJ, Hunter J, Seely D. et al. Integrative oncology: International perspectives. Integr Cancer Ther 2019; 18: 1534735418823266
9 Wasser SP. Medicinal mushroom science: History, current status, future trends, and unsolved problems. Int J Med Mushrooms 2010; 12: 1-16
10 Wasser SP. Medicinal mushroom science: Current perspectives, advances, evidences, and challenges. Biomed J 2014; 37: 345-356
11 Geng X, Tian G, Zhang W. et al. A Tricholoma matsutake peptide with angiotensin converting enzyme inhibitory and antioxidative activities and antihypertensive effects in spontaneously hypertensive rats. Sci Rep 2016; 6: 24130
12 Shigesue K, Kodama N, Nanba H. Effects of maitake (Grifola frondosa) polysaccharide on collagen-induced arthritis in mice. Jpn J Pharmacol 2000; 84: 293-300
13 Gao W, Sun Y, Chen S. et al. Mushroom lectin enhanced immunogenicity of HBV DNA vaccine in C57BL/6 and HBsAg-transgenic mice. Vaccine 2013; 31: 2273-2280
14 Reis FS, Lima RT, Morales P. et al. Methanolic extract of Ganoderma lucidum induces autophagy of AGS human gastric tumor cells. Molecules 2015; 20: 17872-17882
15 Fan M-J, Lin Y-C, Shih H-D. et al. Crude extracts of Agaricus brasiliensis induce apoptosis in human oral cancer CAL 27 cells through a mitochondria-dependent pathway. In Vivo 2011; 25: 355-366
16 Zhang G-L, Wang Y-H, Ni W. et al. Hepatoprotective role of Ganoderma lucidum polysaccharide against BCG-induced immune liver injury in mice. World J Gastroenterol 2002; 8: 728-733
17 Kim HM, Kang JS, Kim JY. et al. Evaluation of antidiabetic activity of polysaccharide isolated from Phellinus linteus in non-obese diabetic mouse. Int Immunopharmacol 2010; 10: 72-78
18 Singdevsachan SK, Auroshree P, Mishra J. et al. Mushroom polysaccharides as potential prebiotics with their antitumor and immunomodulating properties: A review. Bioactive Carbohydrates and Dietary Fibre 2016; 7: 1-14
19 Wasser SP, Weis AL. Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective. Crit Rev Immunol 1999; 19: 65-96
20 Wasser SP. Medicinal Mushrooms in Human Clinical Studies. Part I. Anticancer, Oncoimmunological, and Immunomodulatory Activities: A Review. Int J Med Mushrooms 2017; 19: 279-317
21 Blagodatski A, Yatsunskaya M, Mikhailova V. et al. Medicinal mushrooms as an attractive new source of natural compounds for future cancer therapy. Oncotarget 2018; 9: 29259-29274
22 Joseph TP, Chanda W, Padhiar AA. et al. A Preclinical Evaluation of the Antitumor Activities of Edible and Medicinal Mushrooms: A Molecular Insight. Integr Cancer Ther 2018; 17: 200-209
23 Sakamoto J, Morita S, Oba K. et al. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials. Cancer Immunol Immunother 2006; 55: 404-411
24 Zhang Y, Zhang M, Jiang Y. et al. Lentinan as an immunotherapeutic for treating lung cancer: a review of 12 years clinical studies in China. J Cancer Res Clin Oncol 2018; 144: 2177-2186
25 Wasser SP. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol 2002; 60: 258-274
26 Rossi P, Difrancia R, Quagliariello V. et al. B-glucans from Grifola frondosa and Ganoderma lucidum in breast cancer: an example of complementary and integrative medicine. Oncotarget 2018; 9: 24837-24856
27 Torkelson CJ, Sweet E, Martzen MR. et al. Phase 1 clinical trial of Trametes versicolor in women with breast cancer. ISRN Oncol 2012; 2012: 251632
28 Ohno S, Sumiyoshi Y, Hashine K. et al. Quality of life improvements among cancer patients in remission following the consumption of Agaricus blazei Murill mushroom extract. Complement Ther Med 2013; 21: 460-467
29 Palomares MR, Rodriguez J, Phung S. et al. A dose-finding clinical trial of mushroom powder in postmenopausal breast cancer survivors for secondary breast cancer prevention. JCO 2011; 29: 1582-1582
30 Twardowski P, Kanaya N, Frankel P. et al. A phase I trial of mushroom powder in patients with biochemically recurrent prostate cancer: Roles of cytokines and myeloid-derived suppressor cells for Agaricus bisporus-induced prostate-specific antigen responses. Cancer 2015; 121: 2942-2950
31 Kodama N, Komuta K, Nanba H. Can maitake MD-fraction aid cancer patients?. Altern Med Rev 2002; 7: 236-239
32 Gao Y, Zhou S, Jiang W. et al. Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol Invest 2003; 32: 201-215
33 Suzuki N, Takimoto Y, Suzuki R. et al. Efficacy of oral administration of Lentinula eododes mycelia extract for breast cancer patients undergoing postoperative hormone therapy. Asian Pac J Cancer Prev 2013; 14: 3469-3472
34 Yoshimura K, Kamoto T, Ogawa O. et al. Medical mushrooms used for biochemical failure after radical treatment for prostate cancer: an open-label study. Int J Urol 2010; 17: 548-554
35 Valadares F, Garbi Novaes MRC, Canete R. Effect of Agaricus sylvaticus supplementation on nutritional status and adverse events of chemotherapy of breast cancer: a randomized, placebo-controlled, double-blind clinical trial. Indian J Pharmacol 2013; 45: 217-222
36 Costa Fortes R, Carvalho Garbi Novaes MR. The effects of Agaricus sylvaticus fungi dietary supplementation on the metabolism and blood pressure of patients with colorectal cancer during post surgical phase. Nutr Hosp 2011; 26: 176-186
37 Fortes RC, Recova VL, Melo AL. et al. Effects of dietary supplementation with medicinal fungus in fasting glycemia levels of patients with colorectal cancer: a randomized, double-blind, placebo-controlled clinical study. Nutr Hosp 2008; 23: 591-598
38 Costa Fortes R, Lacorte Recova V, Lima Melo A. et al. Life quality of postsurgical patients with colorectal cancer after supplemented diet with Agaricus sylvaticus fungus. Nutr Hosp 2010; 25: 586-596
39 Ahn W-S, Kim D-J, Chae G-T. et al. Natural killer cell activity and quality of life were improved by consumption of a mushroom extract, Agaricus blazei Murill Kyowa, in gynecological cancer patients undergoing chemotherapy. Int J Gynecol Cancer 2004; 14: 589-594
40 Tangen J-M, Tierens A, Caers J. et al. Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: a randomized, double blinded clinical study. Biomed Res Int 2015; 2015: 718539
41 Tsai M-Y, Hung Y-C, Chen Y-H. et al. A preliminary randomised controlled study of short-term Antrodia cinnamomea treatment combined with chemotherapy for patients with advanced cancer. BMC Complement Altern Med 2016; 16: 322
42 Chay WY, Tham CK, Toh HC. et al. Coriolus versicolor (Yunzhi) use as therapy in advanced hepatocellular carcinoma patients with poor liver function or who are unfit for standard therapy. J Altern Complement Med 2017; 23: 648-652
43 Oka S, Tanaka S, Yoshida S. et al. A water-soluble extract from culture medium of Ganoderma lucidum mycelia suppresses the development of colorectal adenomas. Hiroshima J Med Sci 2010; 59: 1-6
44 Zhao H, Zhang Q, Zhao L. et al. Spore Powder of Ganoderma lucidum Improves Cancer-Related Fatigue in Breast Cancer Patients Undergoing Endocrine Therapy: A Pilot Clinical Trial. Evid Based Complement Alternat Med 2012; 2012: 809614
45 Gao Y, Dai X, Chen G. et al. A Randomized, Placebo-Controlled, Multicenter Study of Ganoderma lucidum (W.Curt.:Fr.) Lloyd (Aphyllophoromycetideae) Polysaccharides (Ganopoly) in Patients with Advanced Lung Cancer. Int J Med Mushrooms 2003; 5: 14
46 Fortes RC, Novaes MRCG, Recova VL. et al. Immunological, hematological, and glycemia effects of dietary supplementation with Agaricus sylvaticus on patients’ colorectal cancer. Exp Biol Med (Maywood) 2009; 234: 53-62
47 Visser MR, Smets EM. Fatigue, depression and quality of life in cancer patients: how are they related?. Support Care Cancer 1998; 6: 101-108
48 Bottomley A. The cancer patient and quality of life. Oncologist 2002; 7: 120-125
49 Jin X, Ruiz Beguerie J, Sze D. et al. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev 2016; 4: CD007731
50 Hofer M, Pospisil M. Modulation of animal and human hematopoiesis by beta-glucans: a review. Molecules 2011; 16: 7969-7979
51 Sorimachi K, Akimoto K, Ikehara Y. et al. Secretion of TNF-alpha, IL-8 and nitric oxide by macrophages activated with Agaricus blazei Murill fractions in vitro. Cell Struct Funct 2001; 26: 103-108
52 Su Y-K, Shih P-H, Lee W-H. et al. Antrodia cinnamomea sensitizes radio-/chemo-therapy of cancer stem-like cells by modulating microRNA expression. J Ethnopharmacol 2017; 207: 47-56
53 Lin Y-S, Lin Y-Y, Yang Y-H. et al. Antrodia cinnamomea extract inhibits the proliferation of tamoxifen-resistant breast cancer cells through apoptosis and skp2/microRNAs pathway. BMC Complement Altern Med 2018; 18: 152
54 Martel J, Ojcius DM, Ko Y-F. et al. Phytochemicals as prebiotics and biological stress inducers. Trends Biochem Sci 2020; 45: 462-471
55 Kalaras MD, Richie JP, Calcagnotto A. et al. Mushrooms: A rich source of the antioxidants ergothioneine and glutathione. Food Chem 2017; 233: 429-433
56 De Silva DD, Rapior S, Fons F. et al. Medicinal mushrooms in supportive cancer therapies: an approach to anti-cancer effects and putative mechanisms of action. Fungal Diversity 2012; 55: 1-35
57 Aras A, Khalid S, Jabeen S. et al. Regulation of cancer cell signaling pathways by mushrooms and their bioactive molecules: Overview of the journey from benchtop to clinical trials. Food Chem Toxicol 2018; 119: 206-214
58 Ayeka PA. Potential of mushroom compounds as immunomodulators in cancer immunotherapy: A review. Evid Based Complement Alternat Med 2018; 2018: 7271509
59 Wasser SP. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms. Appl Microbiol Biotechnol 2011; 89: 1323-1332
60 Calabrese EJ. Cancer biology and hormesis: human tumor cell lines commonly display hormetic (biphasic) dose responses. Crit Rev Toxicol 2005; 35: 463-582
61 Friedman M. Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans. Foods 2016; 5: 80
62 Jayachandran M, Xiao J, Xu B. A Critical Review on Health Promoting Benefits of Edible Mushrooms through Gut Microbiota. Int J Mol Sci 2017; 18: 1934
63 Vivarelli S, Salemi R, Candido S. et al. Gut Microbiota and Cancer: From Pathogenesis to Therapy. Cancers (Basel) 2019; 11: 38
64 Boulangé CL, Neves AL, Chilloux J. et al. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med 2016; 8: 42
65 Harris ESJ, Cao S, Littlefield BA. et al. Heavy metal and pesticide content in commonly prescribed individual raw Chinese Herbal Medicines. Sci Total Environ 2011; 409: 4297-4305
66 Pilkington K, Wieland LS, Teng L. et al. Coriolus (Trametes) versicolor mushroom to reduce adverse effects from chemotherapy or radiotherapy in people with colorectal cancer. Cochrane Database Syst Rev 2022; 11: CD012053
67 Chen Q, Shu C, Laurence AD. et al. Effect of Huaier granule on recurrence after curative resection of HCC: a multicentre, randomised clinical trial. Gut 2018; 67: 2006-2016
68 Li J, Zou L, Chen W. et al. Dietary mushroom intake may reduce the risk of breast cancer: evidence from a meta-analysis of observational studies. PLoS One 2014; 9: e93437