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A water-soluble extract from culture medium of Ganoderma lucidum mycelia suppresses the development of colorectal adenomas

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A water-soluble extract from a cultured medium of Ganoderma lucidum mycelia (MAK) is one of the G. lucidum extracts that has been reported to show have exhibit cancer-preventive effects in the animal studies. To confirm cancer-preventive effects of MAK, we performed a no-treatment concurrent controlled trial on patients with colorectal adenomas. Patients who were determined to be carrying colorectal adenomas by colonoscopy were enrolled in this study. Patients in the MAK group took MAK (1.5 g/day) for 12 months. Follow-up colonoscopy was performed after 12 months, and the colonoscopists recorded the size, site and macroscopic type of all adenomas. Among 123 patients who enrolled in the MAK group, 96 eligible patients completed the trial. The 102 eligible patients in the no-treatment control group were selected randomly from our department's patients. The changes in the number of adenomas up to 12 months increased to 0.66 +/- 0.10 (mean +/- SE) in the control group, while decreasing in the MAK group to -0.42 +/- 0.10 (p < 0.01). The total size of adenomas increased to 1.73 +/- 0.28 mm in the control group and decreased to -1.40 +/- 0.64 mm in the MAK group (p < 0.01). The resultssuggest that MAK suppresses the development of colorectal adenomas - precancerous lesions of the large bowel.
... A large variety of cancer entities, studied sample sizes, outcomes, treatment durations and observation times were seen ( Table 1). The medicinal mushrooms investigated were Agaricus sylvaticus (two trials) (Fortes et al., 2008;Costa Fortes et al., 2010;Costa Fortes and Carvalho Garbi Novaes, 2011;Valadares et al., 2013), Agaricus blazei murill (two trials) (Ahn et al., 2004;Tangen et al., 2015), Antrodia cinnamomea (one trial) (Tsai et al., 2016), Coriolus versicolor (one trial) (Chay et al., 2017) and Ganoderma lucidum (three trials) (Gao et al., 2003a;Oka et al., 2010;Zhao et al., 2012). All mushrooms were administered orally. ...
... Oka et al. showed in a CT that a water-soluble extract from the culture medium of Ganoderma lucidum mycelia suppressed the development of colorectal adenoma (Oka et al., 2010). Follow-up colonoscopy was performed after 12 months, 96 patients completed the trial. ...
... Adverse events of treatment with medicinal mushrooms were poorly reported. Only in three trials there was an explicit reference to such events (Oka et al., 2010;Zhao et al., 2012;Tsai et al., 2016). No serious adverse events due to medical mushroom intake were reported. ...
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Medicinal mushrooms are widely used in East Asia for the treatment of various diseases, especially in complementary cancer care. While there is a growing interest in medicinal mushrooms in Western countries and an increasing number of pre-clinical studies indicate distinct anti-cancer and regenerative properties, little is known about their potential relevance for clinical practice. This review aims to provide an overview of the clinical evidence, significance and potential role of medicinal mushrooms in complementary cancer care. Scientific databases for (randomized) controlled clinical trials evaluating whole spectrum formulations of medicinal mushrooms (mushroom powder and mushroom extracts) in cancer patients during and/or after conventional oncological treatment were searched. Eight studies met our inclusion criteria (eight randomized controlled trials, one controlled clinical trial). The medicinal mushrooms investigated were Agaricus sylvaticus (two trials), Agaricus blazei murill (two trials), Antrodia cinnamomea (one trial), Coriolus versicolor (one trial) and Ganoderma lucidum (three trials); all were compared to placebo and administered orally. A variety of cancer entities, outcomes and treatment durations were observed. Study results suggested beneficial effects of medicinal mushrooms, particularly quality of life and reduction of adverse effects of conventional therapies. Also, positive effects on antitumor activity and immunomodulation were reported, e.g., an increased activity of natural killer cells. In addition, results might suggest a longer survival of cancer patients receiving mushroom preparations, although in most studies this was not significant when compared to placebo. Adverse events of treatment with medicinal mushrooms were poorly reported; gastrointestinal reactions and a decrease in platelet cell count occurred in some cases. The methodological quality of most studies was generally unsatisfying and most results were insufficiently reported in several respects. Medicinal mushrooms may have a therapeutic potential for cancer patients during and after conventional oncological care with regards to quality of life, reduction of adverse effects of conventional care and possibly other surrogate parameters like immune function. There is an urgent need to investigate the safety and possible interactions of medicinal mushrooms. High-quality clinical research is warranted in order to clarify the potential of medicinal mushrooms in cancer therapy.
... In parallel, we searched clinical trial databases to record clinical trial information and added some additional trials on Agaricus bisporus (one randomized phase II trial for prostate cancer, NCT04519879; one interventional clinical trial for breast cancer, NCT007090200), Coriolus versicolor (one randomized, parallel, double-blind, placebo-controlled trial for breast cancer, NCT00647075), Grifola frondosa (one randomized, interventional clinical trial for lung neoplasms and breast carcinoma, NCT02603016), and Trametes versicolor (one phase I clinical trial for breast cancer, NCT02568787) (Supplementary Materials, Table S3). Interestingly, four published reports on Agaricus blazei were based on one trial, but presented different results [16,18,29,30]. ...
... Decrease in both number and size of colorectal adenomas for the verum group. [29] Grifola frondosa Phase I/II, dose escalation trial, n = 34 ...
... Adverse events (AE) following treatment with mushrooms are generally not mentioned explicitly, except in a few trials [16,19,29]. This needs to be interpreted with caution, since some of the AE could be due to the underlying disease or concurrent treatment. ...
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Approximately 270 species of mushrooms have been reported as potentially useful for human health. However, few mushrooms have been studied for bioactive compounds that can be helpful in treating various diseases. Like other natural regimens, the mushroom treatment appears safe, as could be expected from their long culinary and medicinal use. This review aims to provide a critical discussion on clinical trial evidence for mushrooms to treat patients with diverse types of cancer. In addition, the review also highlights the identified bioactive compounds and corresponding mechanisms of action among the explored mushrooms. Furthermore, it also discusses mushrooms with anticancer properties, demonstrated either in vitro and/or in vivo models, which have never been tested in clinical studies. Several mushrooms have been tested in phase I or II clinical trials, mostly for treating breast cancer (18.6%), followed by colorectal (14%) and prostate cancer (11.6%). The majority of clinical studies were carried out with just 3 species: Lentinula edodes (22.2%), Coriolus versicolor, and Ganoderma lucidum (both 13.9%); followed by two other species: Agaricus bisporus and Grifola frondosa (both 11.1%). Most in vitro cell studies use breast cancer cell lines (43.9%), followed by lung (14%) and colorectal cancer cell lines (13.1%), while most in vivo animal studies are performed in mice tumor models (58.7%). Although 32 species of mushrooms at least show some promise for the treatment of cancer, only 11 species have been tested clinically thus far. Moreover, most clinical studies have investigated fewer numbers of patients, and have been limited to phase III or IV. Therefore, despite the promising preclinical and clinical data publication, more solid scientific efforts are required to clarify the therapeutic value of mushrooms in oncology.
... However, on the flip side, the adverse events (AE) following treatment with mushroom polysaccharides have not been that well documented. Few clinical trials have described the adverse effects of mushroom extracts [35,44,106]. Breast cancer patients undergoing onendocrine therapy along with G. lucidum recorded mild discomfort such as dizziness and dry mouth [35]. ...
... More frequent but less intense (grade 1 and 2) gastrointestinal symptoms (abdominal pain and diarrhea) were reported. Oka et al. [106] reported diarrhea, stomach discomfort and poor health in 6 out of 123 colorectal adenoma cases receiving G. lucidum. Such adverse effects or inabilities of mushroom polysaccharides have not been ideally worked out. ...
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Of the biologically active components, polysaccharides play a crucial role of high medical and pharmaceutical significance. Mushrooms have existed for a long time, dating back to the time of the Ancient Egypt and continue to be well explored globally and experimented with in research as well as in national and international cuisines. Mushroom polysaccharides have slowly become valuable sources of nutraceuticals which have been able to treat various diseases and disorders in humans. The application of mushroom polysaccharides for anticancer mycotherapy is what is being reviewed herein. The widespread health benefits of mushroom polysaccharides have been highlighted and the significant inputs of mushroom-based polysaccharides in anticancer clinical trials have been presented. The challenges and limitation of mushroom polysaccharides into this application and the gaps in the current application areas that could be the future direction have been discussed.
... 30 Not only may medicinal mushrooms offer benefits for people being actively treated for colon cancer, but they may also provide benefits to those interested in primary prevention of the disease. Oka et al. 31 enrolled subjects with colorectal adenomas detected on colonoscopy who received either no treatment or a water-soluble extract of G. lucidum at a dose of 1500 mg daily for 12 months. A total of 96 subjects took the mushroom extract, whereas 102 people served as no-treatment controls. ...
... In the control group, total size of adenomas increased to 1.73 -0.28 mm, whereas in the mushroom group it decreased to 2 1.40 -0.64 mm (P < 0.01). 31 ...
... Velikost ade nomů se vlivem Reishi zmenšila prů měrně o 1,4 mm, zatímco u skupiny bez léčby došlo naopak k nárůstu v průměru o 1,7 mm. Závěrem této studie proto bylo, že extrakt z Reishi může mimo jiné tlumit vývoj kolorektálních adenomů představu jících přednádorový stav ve střevech [33]. U 15 pacientů s gynekologickým kar cinomem byla zaznamenána vlivem léčby Reishi stabilizace onemocnění. ...
Article
Background: Mushrooms Reishi and Coriolus have been used for centuries in Asian countries to treat various diseases, mainly respiratory tract infections or pulmonary diseases, and more recently also cancers. Polysaccharides and triterpenes, which are found in these mushrooms, are their main bio-active components. Preclinical and clinical studies in humans presented their beneficial effects as immunomodulators; besides this, they possess a direct anticancer effect. In Asia, they are used after cancer treatment as single agents or in combination with chemotherapy or radiotherapy. Extracts from Coriolus have been approved for more than 30 years as an effective adjuvant addition to standard cancer treatment in Japan and China without obvious toxicity. Purpose: In this review, clinical studies with Reishi and Coriolus in cancer patients and their meta-analyses are briefly summarized. Conclusion: Both extracts from Reishi and Coriolus, if used in combination with standard therapy or as an adjuvant single agent, have shown benefits at immune function measures, tumor-related symptoms and performance status of cancer patients. Moreover, they have prolonged their disease-free interval and overall survival. They are well tolerated even in advanced cancer diseases and could be safely used continuously for long periods of time. Because of clinically approved efficacy and safety, they are applied mainly in some countries as a complementary therapy for various types of cancers.
... Back in 2010, Oka et al. [84], wishing to confirm the cancer-preventive action of the water-soluble extract of G. lucidum mycelia (MAK) in vivo, conducted a no-treatment concurrent controlled study with 123 patients with colorectal adenomas who were disposed to undergo colonoscopy. They were given 1.5 g/d MAK for 12 months, after which they underwent a colonoscopy to detect the size, location, and macroscopic type of adenomas, then the data were compared with the untreated control group. ...
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Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of selected medicinal mushrooms and their effects and mechanisms in in vitro and in vivo clinical studies are reported in this review. Besides, we analyzed the therapeutic use and pharmacological activities of mushrooms.
... In the randomized controlled human trials, it was emphasized that the group receiving G. lucidum supplementation had better disease stability and reduced viability of cancer cells. 64,66 In studies investigating G. lucidum spores and β-glucagon effects in rats, it has been reported that they inhibit inflammatory markers and tumor cells and increase survival of rats. 5,62,67,68 Different results can be obtained depending on the cell type in studies performed in cancer cells. ...
... Dans une autre étude, un meilleur taux de réponses a été obtenu chez les patients pour lesquels une association des composés polysaccharidiques de G. lucidum avait été réalisé avec la chimiothérapie / radiothérapie, comparé à ceux ayant eu recours uniquement à la chimiothérapie / radiothérapie (Jin et al., 2012). Une autre étude à quant à elle montré que l'utilisation des polysaccharides de G. lucidum inhibait la croissance des cellules d'adénome colorectal (Oka et al., 2010). (Yuen et al., 2004). ...
Thesis
Medicinal mushrooms have been used for several hundred years, mainly in Asian countries, for the treatment of various pathologies. More recently, they have been used in the treatment of cancer. As part of this thesis, we are particularly interested in the lingzhi mushroom (Ganoderma lucidum) also called immortality fungus, for its anticancer properties. We therefore reported on the mechanisms of action of both the total extracts of Ganoderma lucidum and the two main bioactive molecules groups, i.e., polysaccharides and triterpenes. Their efficiencies have been demonstrated through in vitro tests and clinical studies. Although these natural compounds have been shown to be effective as a standard therapy treatment in the treatment of cancer (used as monotherapy or in combination with radiotherapy or chemotherapy) in Japan and China for over 30 years, it is fundamental to mention that they can also have significant side effects requiring advices of uses for human health. RESUME : Les champignons médicinaux sont utilisés depuis plusieurs centaines d'années, principalement dans les pays asiatiques, pour le traitement de différentes pathologies. Plus récemment, ils ont été utilisés dans le traitement du cancer. Dans le cadre de cette thèse, nous nous sommes particulièrement intéressés au ganoderme luisant (Ganoderma lucidum) également appelé champignon de l’immortalité, pour ses propriétés anticancéreuses. Nous avons donc étudié les mécanismes d’action à la fois des extraits totaux de Ganoderma lucidum et des deux principaux groupes de molécules bioactives : les polysaccharides et les triterpènes. Leurs efficacités ont été mises en évidence au travers de tests in vitro et d’études cliniques. Bien que ces composés naturels aient prouvé leur efficacité en tant que traitement de support aux thérapeutiques standards dans le traitement du cancer (utilisations en monothérapie ou en association avec la radiothérapie ou la chimiothérapie) au Japon et en Chine depuis plus de 30 ans, il est fondamental de mentionner qu’ils peuvent également présenter des effets indésirables non négligeables nécessitant des conseils d’utilisations pour la santé humaine. MOTS-CLES : Cancer, Ganoderma lucidum, mécanismes d’action, polysaccharides, triterpènes
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The present study was designed to investigate the protective effect of a dietary water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi or Mannentake) mycelia (designated as MAK) on the induction and development of azoxymethane (AOM)-induced colon tumors in male F344/Du Crj rats. A total of 80 animals were divided into five groups at six weeks of age, groups 2, 3 and 4 being given weekly subcutaneous injections of AOM (15 mg/kg body weight) for the initial 3 weeks to induce colon tumors. Rats in group 1 and 5 were injected with the vehicle, 0.9% (w/v) saline, following the same schedule. Rats in groups 1, 2, 3, 4 and 5 were fed MF, MF, 1.25% MAK, 2.5% MAK and 2.5% MAK diets, respectively, starting 1 week before AOM treatment and throughout the six-month experimental period. There were no significant differences in number of ACF, total AC and AC per site among groups 2 to 4, but the tumor incidence was significantly lower, and tumor size was smaller in group 4 (AOM + 2.5% MAK) than in group 2 (AOM + MF). Additionally, beta-catenin positive tumor cell nuclei were significantly decreased in the MAK-fed rats (groups 3 and 4), which also demonstrated lowering of the PCNA labeling index and a shortened germinal region in the colon. The present results thus indicate that dietary MAK could act as a potent chemopreventive agent for colon carcinogenesis.
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A water-soluble extract from the culture medium of Ganoderma lucidum (Rei-shi) mycelia (MAK) has been shown to exert a potent chemopreventive effect. The present study was designed to investigate the effects of dietary MAK supplementation on the development of lung tumors initiated by N-nitrosobis (2-hydroxypropyl) amine (BHP) in male Slc:Wistar rats. A total of 77 animals, 6 weeks of age, were divided into 5 groups and given BHP (2,000 ppm) in their drinking water for 10 weeks. The normal controls were not supplied with BHP. After treatment with the carcinogen, the rats were fed a normal control MF solid diet, or the same diet containing MAK (1.25%, 2.5% or 5%) for 12 weeks. Macroscopically, all the doses of MAK reduced the number of nodules, and the effect of 5% MAK was found to be especially significant. Microscopically, an increase in the number of proliferating cell nuclear antigen (PCNA)-negative tumors and a decrease in the number of tumors strongly positive for PCNA were observed in the tissue sections from the rats that had received all the doses of MAK. The present results thus indicate that dietary supplementation with MAK inhibits the development of lung tumors, suggesting that MAK may be a potent chemopreventive agent against lung carcinogenesis.
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Ganoderma lucidum possesses significant antioxidant and anti-cancer properties. The effects of Lingzhi antioxidants on oxidative DNA damage and oxidative stress were investigated, in order to understand their roles in bladder chemoprevention. Antioxidant-enhanced extracts were tested, in terms of ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH.) inhibition, hydrogen peroxide (H(2)O(2)) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations, and cytotoxicity, using an in vitro pre-cancerous human uroepithelial cell (HUC-PC) tumorigenic model. Water-soluble extract (GLw) possesses relatively higher antioxidant capacities than the water-insoluble counterpart (GLe); however, under the challenge of carcinogenic 4-aminobiphenyl (ABP), GLw reduced the 8-OHdG concentration in HUC-PC culture, while GLe induced the formation of H(2)O(2) and 8-OHdG in a dose-dependent manner. The modern theory of antioxidant-oxidant balance seems to obey the theory of Yin-Yang in traditional Chinese medicine (TCM). Water-soluble and water-insoluble components of Ganoderma lucidum exhibited dual roles in oxidative DNA damage. Oxidative DNA damage may be an underlying mechanism of Lingzhi-induced apoptosis in bladder chemoprevention.