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Updates on Medicinal Mushrooms for Cancer

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Scientific study of medicinal mushrooms through the last five decades has proved its many beneficial outcomes in cancer and other diseases and has led to rapid development of manufacturing businesses dealing with commercial cultivation of mushrooms. Medicinal mushrooms have been approved adjuncts to standard cancer treatments in Japan and China for more than 30 years and have an extensive clinical history of safe use as single agents or combined with radiation therapy or chemotherapy. I recently reviewed the past couple years of scientific publications on the topic of medicinal mushrooms for cancer and would like to highlight some of the new information here. First I will offer some general comments on medicinal mushrooms and cancer and then discuss some individual mushrooms that are commonly used.

A Russian article published earlier this year appropriately applies a pragmatic perspective on the relative effectiveness of mycotherapy in oncology. The authors state: "Irreversible epigenomic changes in cancer cells and their replicative immortality when cancer-specific targets are absent should take away any illusions about a fundamental possibility of pharmacological blockage of the cancer process once oncogenesis begins….effects of both traditional and alternative medicines on cancer clonogenic units within a particular range can lead to prolonged remission….with this in mind, we carefully consider the various possibilities of mycotherapy in controlling cancer activity….the aforementioned range is limited to non-disseminated cancer and depends on the absence of large secondary tumor nodes and the inexhaustibility of immune depots after chemotherapeutic treatment. The main therapeutic effect of (mushrooms) is dectin-1-mediated immunity, including the reprogramming of dendritic cells, which significantly increases the period during which tumors generate immune tolerance. An inhibitory effect of (mushrooms) on mediators of proliferative signaling is less significant. Mycotherapy is only one of the tools that can be used to balance remission.1

Beta-glucans, the chief active compound in mushroom extracts and mycelia, are fraught with quality issues. Few standards exist, and many fraudulent products are in the marketplace, spiked with polysaccharides. Estimates are that over 90 % of β-glucan on the market is counterfeit and adulterated. Large-scale mycelial production in bioreactors, although cost-effective, may not produce high quality products. Cheap substrates used for growing mycelia such as agricultural waste may contain contaminants and allergens (soy, whey, wheat, corn, barley, egg).2

Although earlier epidemiologic studies of dietary mushroom consumption in Asian populations have been associated with lower cancer risk,3 a recent publication showed this not to apply in the U.S. This prospective cohort study included women and men free of cancer at baseline: 68,327 women (Nurses' Health Study, 1986-2012) and 44,664 men (Health Professionals Follow-up Study, 1986-2012). Mushroom consumption based on biennial validated food frequency questionnaire found that in 26 years of follow up, with 22,469 incident cancer cases 5 or more servings of mushrooms per week had no significant different site-specific cancer risk in U.S. women and men than those who ate no mushrooms.4 These discordant findings may be due to genetic and epigenetic variables in the different populations.

Trametes versicolor (formerly known as Coriolus versicolor) remains the most well-documented mushroom in clinical trials for its benefits in cancer. PSP, a polysaccharide extracted from Trametes, has previously been shown to enhance immune status in patients with cancer of the lung, cervix, ovary, stomach and esophagus when used as adjuvant to chemotherapy.5 A Chinese review of PSP published this year confirmed that it activates and enhances function and recognition ability of immune cells, strengthens phagocytosis of macrophages, increases expression of NF-α, IL-1β and IL-6, histamine, and prostaglandin E, stimulates the filtration of both dendritic cells and T-cells into tumors and ameliorates the adverse events associated with chemotherapy.6

Grifola frondosa (Maitake) was approved as an adjunctive drug for cancer in China in 2010. This year He et al. published a review of 108 studies on the mushroom, including investigations into its anti-tumor and immunomodulatory properties.7 Grifola frondosa polysaccharide (GFP) or D-fraction is the main biologically active ingredient. Except for GFP, the vast majority of other Grifola polysaccharide preparations are ineffectiver when taken orally. GFP mainly enhances immunity and improves the body’s ability to destroy tumor cells However, in the retrieved articles for this review, most of the studies were preclinical trials that were performed on cultured cells and in animal models. These findings should be confirmed by clinical trials on patients.

Two reviews have been published this year on Lentinula edodes (Shiitake) and its active component lentinan. In the first review, 9474 lentinan-associated treatment cases were evaluated and summarized from 135 independent studies in China from 2004-2016 on various cancers including lung, gastric, colorectal, ovarian, cervical, non-Hodgkin lymphoma, pancreatic, cardiac, nasopharyngeal, and duodenal, showing solid effects of improved quality of life and efficacy of chemotherapy and radiation therapy.The second paper reviewed clinical data presented in the past 12 years showing that lentinan is effective not only in improving quality of life, but also in promoting the efficacy of chemotherapy during lung cancer treatment. Overall response rate in treating lung cancer was increased from 43.3% of patients receiving chemotherapy alone to 56.9% of lentinan plus chemotherapy (p < 0.001).9

Inonotus obliquus (Chaga), despite its popularity, remains unproven in any human clinical trials.10 With only cell studies and mouse models of cancers, it cannot be recommended at this time. Chaga also contains extremely high concentration of oxalate, and a case report of oxalate nephropathy from Chaga mushroom powder (4-5 tsp daily) taken for six months for liver cancer suggests caution with prolonged use of this mushroom.11

Agaricus bisporus (white button mushroom) has shown some success in a preliminary study of men with biochemically recurrent prostate cancer.12 I have designed a follow up study with Nutritional Fundamentals for Health that has recently been funded. We are attemptingI to replicate these findings in a study with prostate cancer patients and to assess single nucleotide polymorphisms SNPs for responders and non-responders.

                                                      
References
  1. Zmitrovich IV et al. Int J Med Mushrooms. 2019;21(2):105-119 
  2. Berovic M. Adv Biochem Eng Biotechnol 2019;169:3-25. 
  3. Shin A, et al. Nutr Cancer. 2010;62(4):476-83. 
  4. Lee DH, et al. Cancer Prev Res (Phila). 2019 Aug;12(8):517-526. 
  5. Eliza WL et al. Reetn Pat Inflamm Allergy Drug Discov. 2012;6(1):78-87 
  6. Dou H et al. Prog Mol Biol Transl Sci. 2019;163:361-381 
  7. He Y et al. 2019;163:221-261 
  8. Zhang M et al. Prog Mol Biol Transl Sci. 2019;163:297-328. 
  9. Zhang Y et al. J Cancer Res Clin Oncol. 2018 Nov; 144(11):2177-2186. 
  10. Duru KC Phytother Res. 2019 Aug;33(8):1966-1980 
  11. Kikuchi Y et al. Clin Nephrol. 2014 Jun;81(6):440-4. 
  12. Twardowski, MD et al. Cancer. 2015 Sep 1;121(17):2942-50.