1. Medicinal Mushrooms and Cancer
Michael Traub, ND, DHANP, FABNO
AANP Annual Conference
July 29, 2016
Who has a naturopathic practice that does not focus on oncology, but sees patients with cancer anyway?
What do you say or do for these patients that really makes a difference?
I did not deliberately become a naturopathic oncologist.
My mother was diagnosed with metastatic lung cancer and died 6 weeks later. I flew from Hawaii to be with her, to try to help, with a suitcase full of supplements and books and tapes and videos and she was interested in NONE of it. Finally I opened the Bible and read Psalms, and a peace came over her. It felt so good to finally do something that comforted her.
Cancer is something that affects ALL of us, both in our families and our practices.
As physicians, we do have a lot to offer
Mushrooms are used for cancer during surgery, chemotherapy and radiation therapy to support immune function, as well as following conventional treatments to prevent recurrence.
During the years that my practice evolved to focus primarily on naturopathic oncology, I have prescribed mushrooms as a fundamental part of almost any treatment plan for my cancer patients. However, I did so without much understanding of how they worked or how to choose them in a targeted fashion.

2. Integrative Medicine: A Clinician’s Journal 2014
My curiosity about the evidence basis for employing mycotherapy was kindled about a year ago when I read this review article written by Heather Zwickey and colleagues at the Helfgott Insititute of NCNM. Although interesting from an mechanistic perspective as can be seen by this next slide, it only wetted my appetite for a more pragmatic perspective.

3. Cordyceps, caterpillar mushroom Adenosine Cordycepin Nucleotide
Scientific Name
Common Name
Specific Constituent
Type of Constituent
Agaricus blazei
Agaricus
 β-D-glucan
Polysaccharide
Ganoderma lucidum
Reishi, lingzhi
Ganoderic acid
Danoderiol
Danderenic acid
Lucidenic acid
GLPS
Protein
Cordyceps sinensis
Cordyceps, caterpillar mushroom
Adenosine
Cordycepin
Nucleotide
Trametes versicolor
(formerly Coriolus)
Turkey tail
PSP
PSK
Polysaccharide peptide
Grifolia frondosa
Maitake
Grifolan
D-fraction
MD-fraction
Lentinula edodes
Shitake
Active Hexose Correlated Compound
(AHCC)
Adapted from Guggeheim, Wright, Zwickey 2014
Hence, I did extensive review of the literature, and I gave an introductory presentation this year at the AANP on the subject and included three more tables I created that organize the existing data on what mushrooms have efficacy in which cancers and which chemotherapeutic agents are enhanced by specific mushrooms. I’ll share these tables with you, which will simplify your decision-making when you prescribe mushrooms.
Paul Stamets, one of the most knowledgeable authorities on the science of fungi, also spoke at the AANP this year. If you have ever listened to Paul speak, whether in person or on you tube, you know he is an impassioned advocate for mushrooms in a variety of applications, and presents a convincing case for how fungi and humans have evolved in mutually beneficial ways.

4. Medicinal Mushrooms: Overview
Properties: immunostimulating, antimicrobial, anti-inflammatory, cardio-protective, anti-diabetic, hepato-protective and anti-cancer
Immunomodulating effects on Natural Killer cells, dendritic cells, T lymphocytes, macrophages and hematopoietic stem cells
Mushrooms have been used medicinally since at least 3000 BCE, primarily in Asia, although Hippocrates mentioned them in about 400 BC . Recent studies have confirmed that they have many medicinal properties:
And they have multiple effects on the immune system, modulating NK, DC, etc.
The antitumor effects of mushroom extracts have been attributed to the induction of apoptosis (programmed cell death) of cancer cells and the activation of NK cells and these other components of the immune system.

5. Medicinal Mushrooms and Cancer
Trametes versicolor (Coriolus)
Ganoderma lucidum (Reishi)
Grifolia frondosa (Maitake)
Lentinula edodes (Shitake)
Inonotus obliquus (Chaga)
Cordyceps sinensis
Hericeum erinaeus (Lion’s Mane)
Agaricus blazei, sylvaticus, bisporus (Button mushrooms)
Psilocybe cyanescens (Psilocybin)
There are hundreds of medicinal mushrooms. I have selected these as the most important to focus on in this presentation.
And in the time available, I will describe a few recent systematic reviews or clinical trials of each of these mushrooms

6. The fruiting body of a mushroom produces spores, releasing millions of them into the air, each spore containing half the genetic code necessary to form a new mushroom.

7. Another diagragm of the mushroom life cycle, with some added details about the sexual fusion of spores and the mating of mycelia

8. Mushrooms & Cancer Research has demonstrated potent:
Antineoplastic properties
Regulation of tumor genes
Decrease in tumor angiogenesis
Increase in malignant-cell phagocytosis
Chemo-sensitizing
Protection against chemo-induced bone marrow suppression
Tons of research that medicinal mushrooms have potent effects:
Studies have found beta-glucans in mushrooms are largely responsible for inducing tumor regression.

9. β-glucans
Mushroom polysaccharides are primarily responsible for the potent immunomodulating effects
Glucans can be extracted from cell walls of yeast, oat, barley, seaweeds, algae and bacteria, as well as fungi
Fungal polysaccharides include chitin, cellulose, β-glucans (eg lentinan, grifolan, krestin [PSK]) and α-glucans (eg glycogen), or polysaccharide-protein complexes
Specific receptors for glucans on immune cells
Vannucci L et al. Immunostimulatory properties and antitumor activities of glucans (Review). Int J Onc : , 2013
Mushroom polysaccharides are primarily responsible for the potent immunomodulating effects, and the β-glucans are the most studied within these polysaccharides and are principally obtained from the fruit body of various types of mushrooms.
Glucans can be extracted from cell walls of yeast, oat, barley, seaweeds, algae and bacteria, as well as fungi
They are found in fruit bodies, cultured mycelium and cultured broth from more than 700 species of Basidiomycetes mushrooms.
Fungal polysaccharides include chitin, cellulose, β-glucans (eg lentinan, grifolan, krestin [PSK]) and α-glucans (eg glycogen), or polysaccharide-protein complexes

10. Beta glucans can form large cylindrical molecules containing up to 250,000 glucose units
The length and branches of the β-glucan from various fungi are widely different.

11. β-D-glucan receptors on immune cell•
This figure shows the uptake and subsequent actions of β-glucan on immune cells.
β-glucans are captured by the macrophages via the Dectin-1 receptor with or without TLR-2/6. The large β-glucan molecules are then internalized and fragmented into smaller
sized β-glucan fragments within the macrophages. They are carried to the marrow and endothelial reticular system and subsequentlyreleased. These small β-glucan fragments are eventually taken up by the circulating granulocytes, monocytes or macrophages via the complement receptor (CR)-3. The immune response will then be turned on, one of the actions is thephagocytosis of the monoclonal antibody tagged tumor cells.
β-D-glucan binding to myeloid cell receptors also triggers, according to the bound receptor, a series of other signaling events that modulate innate and subsequently adaptive immune responses
• mainly through release of:
1) pro-inflammatory cytokines (IL-1α/β, IL-6, IL-8, IL-12, TNF-α)
2)cytotoxic molecules such as nitric oxide and hydrogen peroxide working also as inflammatory mediators

12. Immune Activation Induced by Beta-glucans
β-D-glucan binding to myeloid cell receptors also triggers, according to the bound receptor, a series of other signaling events that modulate innate and subsequently adaptive immune responses
• mainly through release of:
1) pro-inflammatory cytokines (IL-1α/β, IL-6, IL-8, IL-12, TNF-α)
2)cytotoxic molecules such as nitric oxide and hydrogen peroxide working also as inflammatory mediators
β-glucans can act on a variety of membrane receptors found on the immune
cells. It may act singly or in combine with other ligands. Various signaling pathway are activated and their respective simplified
downstream signaling molecules are shown. The reactors cells include monocytes, macrophages, dendritic cells, natural killer
cells and neutrophils. Their corresponding surface receptors are listed. The immunomodulatory functions induced by β-glucans
involve both innate and adaptive immune response. β-glucans also enhance phagocytosis and trigger acascade of cytokines release,
such as tumor necrosis factor(TNF)-α and various types of interleukins (ILs).

13. Specific effects of β-D-glucans on the immune system:
Increased number of circulating NK cells and increased NK cell activity
Increased antimicrobial activity of monocytes and neutrophils
Enhanced functional activity of macrophages (inducing NO production)
Stimulating proliferation of monocytes and macrophages
Stimulating production of pro-inflammatory molecules such as complement components, TNF-alfa, IL-2, IFN-gamma
Enhanced phagocytosis of neutrophils
Increased number of leukocytes
Induction of activation of NFkB-like nuclear transcription factor
β-D-glucans effect the immune system in a number of specific ways:
By increasing the number of NK cells and their activity
By increasing the antimicrobial actions of monocytes and neutrophils
By enhancing the activity of macrophages and inducing NO production
By stimulating proliferation of monocytes and macrophages
By stimulating production of complement components, TNF-alfa, IL-2 and IFN-gamma
By enhancing neutrophilic phagocytosis
By increasing the number of WBCs
And by activation of NFkB-like nuclear transcription factor

14. Limitations of Current Beta-glucans Research Chan GC, et al
Limitations of Current Beta-glucans Research Chan GC, et al. The effects of beta-glucan on human immune and cancer cells. J Hem Onc 2009, 2:25
No Beta-glucan standard with specific molecular weight and branches are available.
Most of the Beta-glucan publications used zymosan, which is a mixture of chitoxan, Beta-glucans and cell wall particles.
Most of the Beta-glucan containing herbal research are based on extracts rather than purified Beta-glucans
No well-characterized methods either qualitatively or quantitatively are currently available for assessing and comparing Beta-glucans from different sources
Lack of translational approach to apply knowledge of receptor and signal pathways of Beta-glucans to animal or clinical trials.
The exact immunological actions and signaling pathway induced by Beta-glucan are still unclear and have to be further defined.
The authors of this publication did a good job of acknowledging the current limitations in beta glucans research including:
No pure reference standard that can be used as a control
No well characterized qualitative or quantitative methods for assessing and comparing beta glucans

15. Dietary mushroom intake and cancer risk
Amsterdam street market

16. This epidemiological study evaluated the association between mushroom intake and the risk of breast cancer according to hormone receptor status among Korean women. Mushroom intake and breast cancer risk was examined among 358 breast cancer patients and 360 cancer-free controls.
Greater mushroom intake was related to lower risk of breast cancers among premenopausal women (for the highest vs. the lowest quartile intake). The association was stronger for premenopausal women with ER+/PR+ tumors (for the highest vs. the lowest quartile intake) than those with ER–/PR– tumors.
Higher mushroom intake was associated with lower risk of breast cancers among premenopausal women. The inverse association was more distinct among premenopausal women who were ER and PR positive.
The average intakes of mushrooms in cases and controls in our study were 5.1 g/day in cases and 9.7 g/day in controls.
The most commonly consumed mushrooms in this study were Pleurotaceae ostreatus (oyster mushroom), followed by Lentinus edodes (Shitake), Agaricus bisporus (button mushroom), and Flammulina velutipes (winter fungus). Agaricus bisporus (button mushrooms) also have aromatase inhibitor effects, and are recommended for women with ER+ breast cancer.

17. Case-control,retrospective study of 1,009 F in Southeast China to assess whether dietary intake of mushrooms as well as in combination with green tea reduces the risk of breast cancer.
Compared with non-consumers of mushrooms, those who had a daily intake of >10 g of fresh mushrooms and >4 g of dried mushrooms showed a statistically sig inverse association of breast cancer risk in both pre- and postmenopausal women :64% and 47% decreased risk of breast cancer respectively
The joint effects of dietary intakes of mushrooms and green tea conferred an additional decreased risk of breast cancer. Compared with the women who consumed neither dietary mushrooms nor green tea, the adjusted decreased risk of breast cancer was 89% in those who daily consumed 7 g/d of fresh mushrooms and 82% decreased risk in those who consumed 2 g/d of dried mushrooms, when combined with consuming tea made with1 g/d of dried green tea leaves

18. Here is the collated data from which these risk reductions from mushroom intake are derived

19. And here is the data on the combined effect of mushrooms and green tea in reducing breast cancer risk

20. Trametes (Coriolus) versicolor
Turkey tail
Trametes versicolor (various colors)
The common name Turkey Tail comes from the banding pattern on the fruiting bodies that resembles (in miniature, of course) the tail of a strutting turkey. The colors of the bands can be quite variable, depending on the genetics of the organism and its environment. Most of the bands are dark to light brown in color, alternating with light colored bands of white to tan, with still more bands of blue, orange, maroon, and other. The can be strikingly beautiful, and are among the most easily found fungi. The species has a widespread distribution, having been found in nearly every state in the United states and in most other countries.
Trametes contains polysaccharide Krestin (PSK) and polysaccharide peptide (PSP) – soluble in water, not ethanol – importance of using the proper extraction method
Trametes is the most extensively researched of all medicinal mushrooms with large scale clinical trials on PSK and PSP showing impressive results in a variety of cancers including gastric, oesophageal, lung, breast and colorectal1
PSK boosts NK cell production, improves side effects from chemo and RT, and enhances survival in cancers of the stomach, colon, uterus and lung in combin with conv tx
PSP enhances immune status in pts with cancer of the lung, cervix, ovary, stomach and esophagus when used as adjuvant to chemo

21. As shown in this systematic review and meta-analysis from 13 RPCDBT, A signif survival advantage was found with Trametes compared with conv tx alone.
Pts receiving Trametes had a 9% absolute reduction in 5 y mortality, resulting in 1 addnl pt alive for every 11 pts treated.
Pts with breast, cRC and gastric cancer who had been treated with chemotx showed the best results in combin with Trametes in 5 y survival

22. Trametes and Lung Cancer
Fritz H1, Kennedy DA2, Ishii M1, Fergusson D3, Fernandes R2, Cooley K2, Seely D4. Polysaccharide K and Coriolus versicolor extracts for lung cancer: a systematic review. Integr Cancer Ther May;14(3):201-11
28 studies included in analysis: 6 RCTs, 5 non-randomized CTs, 17 preclinical
15 of 17 preclinical studies supported anticancer effects for PSK through immunomodulation and potentiation of immune surveillance, and direct tumor inhibiting actions in vivo that resulted in reduced tumor growth and antimetastatic effects.
Nonrandomized controlled trials showed improvement of various survival measures including median survival and 1-, 2-, and 5-year survival.
Randomized controlled trials showed benefits on immune parameters and hematological function, performance status and body weight, fatigue and anorexia, and survival.
Overall most randomized controlled trials supported a positive impact for PSK on these endpoints
Dugald Seely and colleagues at the Ottawa Integrative Cancer Center published a systematic review of Trametes showing a positive impact on various survival measures in lung cancer in May of this year.

23. Torkelson from the Uminn Cancer Center and Standish and her colleagues at Bastyr Univ investigated the benefit of Trametes freeze dried mycelial powder in breast cancer pts in a Phase I, dose-escalation, clinical trial. They evaluated dosing safety and immune function following RT in 9 women with breast cancer following RT. Next slide

24. Findings from this study establish the safety of oral administration of a trametes versicolor preparation at 3, 6, 9 g doses
Higher oral doses of Tv at 6 and 9 grams/day were associated with faster recovery of lymphocytes and NK cell activity, as well as increased numbers of CD8 cytotoxicT cells and CD19 B cells.

25. There were sig decreases in abs lymphocyte counts and NK cell activity post-radiation therapy.
The change in absolute lymphocyte number did not change appreciably with the 3 gm dose of Trametes compared to the observational group, but did continue to sig increase over time with the 6 and and 9 gram doses
The NK cell activity change was most pronounced at weeks 2 and 4 with the 6 gm dose, and then decreased at 6 wks. This suggests that a better strategy might be to pulse dose the Trametes for optimal NK cell activity, such as 1 month on, 1 month off. This strategy has not been investigated to my knowledge.

26. Before we leave our friend Dr
Before we leave our friend Dr. Standish, there is another study her team at Bastyr conducted in collaboration with the UW showing that PSK not only activates NK cells but also enhanced the effect of trastuzumab (herceptin) in breast cancer cells and in transgenic mice, suggesting that Trametes may be a novel way to augment the anti-tumor effect of trastuzumab.

27. Study: RCT of PSK given at 3g qd x 2 years in conjunction with standard therapy in patients with stage II and III colorectal cancer.

28. 85.1% overall 5 y survival rate in the PSK treatment group compared to70.2% in the control group, a statistically significant difference.
PSK sig decreased the mean serum immunosuppressive acid protein (IAP) level and sig increased the mean population of NK cells compared to the controls

29. Cindy Wenner is a PhD at Bastyr where she currently is the co-director and project principal investigator of a NCCIM/NIH-funded Developmental Center for CAM Research (DCRC) grant examining the anti-tumor immunopotentiating effects of Trametes versicolor,
This study she published showed that PSK is a chemosensitizer, enhancing docotaxel-induced apoptosis, tumor suppression and augments anti-tumor immune responses in prostate cancer mice models

30. Meta-analysis of 3 large trials of PSK and CRC
All had surgery and chemo with and w/o PSK
Hot water extract of Trametes versicolor 3 gms/day
Increased survival and disease-free survival for treated patients (p=0.006)
Sakamoto J et al. Ca Immunol Immunother :
A meta-analysis of 3 large trials of PSK for CRC involving 578 patients, all of whom had surgery and chemotx, showed with a dose of 3 g/d there was sig increase in OS and DFS compared to controls.
While not enough evidence to support using Trametes alone for cancer tx, there are mountains of evidence showing its efficacy as an adjuvant therapy. Particularly in cases of breast cancer, gyn cancers, lung cancer, CRC, and gastric cancer, this mushroom should be a component of the tx plan, both during and after conv treatments.
A few unpublished case reports of Trametes a/w hepatotoxicity – unverified

31. Ganoderma lucidum Reishi
Represents a 2.5 billion $ industry in the US. (Bishop KS et al. From 2000years of Ganoderma lucidum to recent developments in nutraceuticals. Phytochemistry Jun;114:56-65.)

32. Cochrane review of RCTs using Ganoderma as cancer treatment in all types and stages of cancer was published in 2012, showing that it had a positive impact in QoL, as sig more subjects achieved an increase in performance status after taking Ganoderma compared to control groups (p< 0.01).
The meta-analysis results showed that patients who had been given Ganoderma with chemo/radiotherapy were 50% more likely to respond positively compared to chemo/radiotherapy alone (P = 0.02).
Ganoderma treatment alone did not demonstrate the same regression rate as that seen in combined therapy.
Ganoderma sig increased the percentage of CD3, CD4 and CD8 cells
WBCs amd NK-cell activity were marginally elevated.

33. Ganoderma and Advanced Cancer
30 advanced-stage cancer patients treated with 1800 mg Ganoderma extract, TID before meals for 12 weeks.
Immune parameters (cytokines, T cell subsets, mitotic response to phytohemagglutinin (PHA) and natural killer activity) were compared between baseline and after 12-week treatment
Significant increase in IL-2, IL-6, IFN-gamma, CD56+ cells
IL-1 and TNF-alpha significantly decreased
CD4:CD8 T cell ratios unchanged.
PHA significantly enhanced in most patients compared to baseline
Significant increase (P < 0.05) in mean NK activity compared to baselines (34.5 +/- 11.8% vs /- 8.3%)
Gao Y, et al. Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol Invest Aug;32(3):
In this 2003 publication, 30 advanced-stage cancer patients treated with 1800 mg Ganoderma extract, TID for 12 wk showed sig icr in NK activity compared to baseline

34. This review of the anticancer effects of Ganoderma published in 2005 includes a nice diagram (next slide) of the various stages of carcinogenesis that Ganoderma affects

35. Ganoderma can inhibit transformation, cell proliferation, angiogenesis, tumor growth, metastasis and cause cancer cell death in a variety of tumor types, as well as prolong survival and improve QOL

36. This study was a RCT of Ganoderma mycelia
This study was a RCT of Ganoderma mycelia. Patients with colorectal adenomas took 1.5g qd x 12 months
(N= 102 control vs. 96 Ganoderma
Number of adenomas at 12 months sig increased to 0.6 in the control group and decreased to in the Ganoderma group.
The total size of adenomas also increased in the control group and decreased sig in the Ganoderma group.

37. This was an open-label clinical trial in 47 patients with advanced colorectal caner who were given Ganoderma 5.4g /d x 12 weeks
compared to baseline, 41 of 47 patients had increased mitogenic reactivity, increased counts of CD3, CD4, CD8 and CD56 lymphocytes, and increased NK activity. However, none of these responses reached statistical significance.
In a population of patients with advanced cancer, these results are not surprising.

38. Ganoderma and Radioprotection
Mouse survival, hematology, levels of reduced glutathione in the liver, liver malondialdehyde and bone marrow chromosomal aberrations were assessed in mice exposed to a 4-Gy or 8-Gy radiation dose with or without B-glucan isolated from Ganoderma (500 μg/kg body wt ) (next slide)

39. Results showed a 66% reduction in mice death 30 days post-irradiation that were given B-glucan compared to 100% mortality when no radioprotective agent was used. When combined with the radioprotective drug amifostine, survival increased to 83%. Results also showed a significant decrease in bone marrow aberrations in mice pretreated with B-glucan.
The protection offered by amifostine at 300mg/kg body wt and by BG at 500 μg/kg body wt was comparable. However the effective dose of BG is much lower than that of amifostine

40. Grifolia frondosa Maitake
Grifolia grows in clusters at the base of trees, particularly oaks. It’s common name in English is ram’s head or sheep’s head.

41. Grifola frondosa (Maitake) King of Mushrooms
In Japan, the mushroom can grow to more than 100 lbs, earning this giant mushrooom the title “King of Mushrooms”

42. Grifolia frondosa for MDS
Stimulates hematopoietic progenitor cell differentiation, granulocyte colony-stimulating factor production, and recovery of peripheral blood leukocytes after bone marrow injury
In 18 patients with myelodysplastic syndrome, Grifolia enhanced in vitro neutrophil and monocyte function
Wesa KM et al. Maitake mushroom extract in myelodysplastic syndromes (MDS): a phase II study. Cancer Immunol Immunother Feb;64(2):237-47
Myelodysplastic syndromes are characterized by ineffective erythropoiesis with dysplastic bone marrow leading to peripheral cytopenia, risk of infection, and progression to acute myelogenous leukemia.
Grifolia frondosa beta-glucan stimulates hematopoetic progenitor cell differentiation, granulocyte colony-stimulating factor production, and recovery of peripheral blood leukocytes after bone marrow injury,
And in this study of 18 patients, neutrophil and monocyte function was enhanced, showing that Grifolia has potential in MDS.

43. phase I and II clinical trial
34 postmenopausal stage I, II or III breast cancer patients free of disease after initial treatment
Maitake liquid extract at .1, .5, 1.5, 3 and 5 mg/kg bid x 3 weeks
statistically significant association between maitake and immunologic function. The largest changes were seen with CD3+, CD4+, CD25+, CD56+ and NK cell (50% higher than base-line), both at a high dose of Maitake (10 mg/kg per day; 680mg qd in 150 pound individual)

44. Grifola in Prevention of Recurrent Bladder Cancer
313 bladder cancer patients after TURBT or partial cystectomy were followed for avg 7.6 yrs.
Recurrence rates for patients divided into 1 of 6 groups were:
Afterloading brachytherapy: 24%
Grifola: 34.9%
BCG: 35.1%
Mitomycin C: 41.7%
Thiotepa: 52.6%
Control: 64.7%
Yang D et al. Prevention of postoperative recurrence of bladder cancer: a clinical study. Zhonghua Wai Ke Za Zhi Aug;37(8):464-5
the insertion of the radioactive source after the placement of the applicator has been confirmed.

45. This in vivo study looked at the effect of MD-fraction from Maitake given at 8mg/kg/qd on cisplatin-induced myelosuppression in mice. Compared to control, the MD-fraction group had maintained total body weight and splenic weight.

46. Lentinula edodes Shiitake
Is a common edible mushroom native to East Asia which is cultivated and consumed in many Asian countries

47. A pilot study was published in 2011 of 7 cancer patients undergoing postoperative adjuvant or neoadjuvant Chemotherapy for breast cancer or gastrointestinal cancer. Next slide

48. They were given lentinula edodes mycelia extract 1800mg qd x 4 weeks and showed sig improvement in QoL, NK cell activity

49. AHCC – mycelium extract of Lentinula
Active hexose correlated compound (AHCC)]
Generic term to describe a plant polysaccharide extracted from a liquid culture of basidiomycetous mycelia of lentinula edodes
AHCC has immunostimulating activity, anticancer activity, cancer-preventive actions and can prevent side effects during cancer chemotherapy
Shigama K et al. Alleviating effect of active hexose correlated compound (AHCC) for anticancer drug-induced side effects in non-tumor-bearing mice. J Exp Ther Oncol 2009;8:43-51
Active hexose correlated compound (AHCC)
Generic term to describe a plant polysaccharide extracted from a liquid culture of basidiomycetous mycelia of lentinula edodes
AHCC has immunostimulating activity, anticancer activity, cancer-preventive actions and can prevent side effects during cancer chemotherapy

50. Prospective Consecutive Case Series of Hepatocellular Carcinoma
Background/Aims: We seek to determine whether AHCC can improve the prognosis of hepatocellular carcinoma (HCC) patients following surgical treatment.
Methods: A prospective cohort study was performed from February 1, 1992 to December 31, A total of 269 consecutive patients with histologically confirmed HCC were studied. All of the patients underwent resection of a liver tumor. Time to treatment failure (disease recurrence or death) and ten parameters related to liver function after surgery were examined.
Results: Of the 269 patients, 113 received AHCC orally after undergoing curative surgery (AHCC group). The AHCC group had a significantly longer no recurrence period (hazard ratio (HR), 0.639; 95% confidence interval (CI), 0.429–0.952; P=0.0277) and an increased overall survival rate (HR, 0.421; 95% CI, 0.253–0.701; P=0.0009) when compared to the control group by Cox's multivariate analysis.
Conclusions: This study suggests that AHCC intake can improve the prognosis of postoperative HCC patients.
Matsui K et al. Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study. J Hepatol 2002;37:78-86.
Matsui et al. compared 113 cases of HCC that were administered AHCC with 156 cases that were not administered AHCC after resection for liver cancer, and reported a significantly longer no recurrence period and overall survival rate in the group administered AHCC

51. A phase II study was published in 2010 of 74 patients with early prostate cancer treated with “expectant management” or what we now call active surveillance. The mean age of the patients was 73.5 years of age (range: 59–91 years of age).
They were given AHCC 4.5g qd x 6 months
Only 1 of 74 patients had PSA values decrease more then 50%. PSA was stable in all the other subjects. Anxiety statistically decreased at 6 months into the intervention. Adherence to treatment was very high.
Endpoint of PSA decrease of >50% is probably not appropriate for this intervention. An earlier study using the same endpoint had similar findings.

52. Inonotus obliquus (Chaga)
Parasitic on birch and other trees. The sterile conk is irregularly formed with appearance of burnt charcoal, due to the massive amounts of melanin. In Norwegian, the name is kreftkjuke' which literally translates as "cancer polypore", referring to the fungus' appearance or to its alleged medicinal properties. In Finnish, the name is pakurikääpä, combined from pahkura and kääpä translating as "wart polypore".

53. Inonotus obliquus (Chaga)
No published human trials
Cell studies:
Colorectal: Kang JH. July 2015, Lee HS. April 2015
Neurogliocytoma: Ning X. 2014
Breast and lung cancer: Nagaiyothi PC. 2014
Lung, colon, glioma: Lemieszek MK. 2011
Melanoma: Youn MJ. 2009
Hepatoma: Youn MJ. 2009
Mouse model
Sarcoma, lung, stomach, breast, cervical cancer. Chung MJ
There are no published human trials on Inonotus obliquus. Cell studies have shown anti-cancer effects for CRC, glioma, breast, lUng, Liver cancer and melanoma, and
In mouse models of sarcoma, lung, stomach, breast and cervical cancer

54. Inonotus obliquus (Chaga)
Contain extremely high oxalate concentration
Case report of oxalate nephropathy from Chaga mushroom powder (4 – 5 tsp/day) x 6 months for liver cancer
Kikuchi Y et al. Chaga mushroom-induced oxalate nephropathy. Clin Nephrol Jun;81(6):440-4.
Extremely high concentration of oxalates.
There is one published case report of oxalate nephropathy in a woman who took 4-5 tsp/d Chaga powder x 6 mo for liver cancer, suggesting that caution is advised in using high doses of this mushroom for more than a few months.
Renal biopsy specimens showed diffuse tubular atrophy and interstitial fibrosis. Oxalate crystals were detected in her tubular lumina and urinary sediment

55. Ophiocordyceps sinensis (Cordyceps)
Ophiocordyceps sinensis is not a mushroom but a fungus that parasitizes larvae of ghost moths and produces a fruiting body.
The fungus germinates in the living larva, kills and mummifies it, and then the stalk-like fruiting body emerges from the corpse.
It is known colloquially as caterpillar fungus,

56. Cordyceps has demonstrated prolonged survival in patients with hepatocellular carcinoma when included in combination with 12 other traditional chinese medicines.
101 patients with hepatocellular carcinoma were treated for a median of 13.4 months with adjunctive naturopathic therapy including Codyceps.
TT consists of extracts of Bezoar bovis, Talcum crystallinum (Kadinum), Rhei rhizoma, Hoelen, and Arecae semen.
B-T consists of extracts of Bezoar bovis, Kadinum, Rhei rhizoma, Phellodendri cortex, Arecae semen, and Mori folium.
OT consists of extracts of Bezoar bovis, Kadinum, Rhei rhizoma, Hoelen, Arecae semen, Mori folium, and Crassocephalum crepidioides.
HTT: a modification of TT containing Harpago
WBF. This is another traditional Chinese product containing extracts of Zizyphi fructus, Kadinum, Moutan cortex, Puerariae radix, Ginseng radix, Zingiberis rhizoma, Rhei rhizoma, Glycyrrhizae radix, Saposhnikoviae radix, and Trichosanthis radix.
Natural antioxidants (NAO).
UCR. This is derived from Guacatonga (Casearia sylvestris)
TIM. This is an extract of the bark of Tecoma ipe Mart
BG103. This is β-glucan extracted from the edible Agaricus blazei mushroom
BWS. This is derived from the seeds of loquat
BG105 is “Chaga,” an aqueous extract of an edible mushroom, Inonotus obliquus
Sandbath treatment
Lifestyle counseling

57. % of patients treated with Cordyceps surviving > 3 mo are shown on the blue line vs pts on the red line who were not treated with Cordyceps
There was sig correlation between number of natural agents administered and survival. Pts treated with 4 or more agents survived sig longer (40.2 mo) than pts treated with 3 or less agents (6.4 mo.). The greatest survival benefit was seen in pts treated with at least 4 agents that included Cordyceps.

58. Hericium erinaeus (Lion’s Mane)
Anti-cancer, immunostimulating, neuroregenerative, cardio-hepato-nephroprotective, antibiotic, etc.
Friedman M. J Agric Food Chem 2015 Aug 19;63(32):
Hericeum erinaeus is one of the more interesting-looking types of mushrooms. In place of the common mushroom cap is a large clump of spine-like structures a few mm loing
Widely consumed in Asian countries, not in the US
Also beneficial potentially in diabetes, fatigue, aging, hyperlipidemia, anxiety, depression, cognitive function.
As an aside, In 15 mushrooms tested for lovastatin content, he highest level was observed in Hericium erinaceus (FB) (14.38 μg/g) and Ganoderma lucidum (FB) (11.54 μg/g)
Cohen N, et al. Chemical composition and nutritional and medicinal value of fruit bodies and submerged cultured mycelia of culinary-medicinal higher Basidiomycetes mushrooms. Int J Med Mushrooms. 2014;16(3):

59. Hericium erinaceus (Lion’s Mane; Yamabushitake)
active against liver, colon and gastric cancer cells in vitro and tumor xenografts in mice in vivo
more effective and less toxic compared to 5-FU in all four in vivo tumor models.
Li G et al. Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers. J Ethnopharmacol Apr 28;153(2):521-30
Has demonstrated anti-cancer potential against human GI cancers in cell and mouse models.
In vivo, it has been found to be more effective that 5FU in all four GI tumor models tested

60. Hericium erinaceus - Neuroregeneration
Study of daily oral Hericium erinaceus in recovery following crush injury to the peroneal nerve in rats
Activities of H. erinaceus were compared to methylcobalamin, widely used in the treatment of peripheral nerve disorders.
Analysis of walking track indicated that return of hind limb function and normal toe spreading occurred earlier in treated groups than in MeB12 group.
Regeneration of axons and re-innervation of motor endplates/neuromuscular junction in extensor digitorum longus muscle of rats in treated groups developed better than in the control group.
imImunofluorescence studies showed that dorsal root ganglia neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt and MAPK signaling pathways compared to control group. Akt cascade plays a major role in mediating neurotrophin-promoted cell survival, while MAPK cascade is involved in mediating neurite outgrowth.
Wong KH1, Naidu M, David RP, Bakar R, Sabaratnam V. Neuroregenerative potential of lion's mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (higher Basidiomycetes), in the treatment of peripheral nerve injury (review). Int J Med Mushrooms. 2012;14(5):
Besides it is anti-cancer effects, Hericium erinaeus also exhibits more neuroregenerative activity than methylcobalamin in rats
This study looked at rats given H. erineus or MeB12 following experimentally-induced nerve injury in rats and found that the H. erineus group had enhanced nerve repair compared to the MeB12 group.
May be a reasonable choice for pts during or post-chemo for Chemotherapy-induced PN, esp in GI cancers   

61. Hericium erinaceus for mild cognitive impairment
Double-blind, parallel-group, placebo-controlled trial
50- to 80-year-old Japanese men and women with mild cognitive impairment
30 subjects were randomized into two 15-person groups, one of which was given Yamabushitake and the other placebo.
Yamabushitake group took four 250 mg tablets dry powder TID x 16 wk
At weeks 8, 12 and 16, the Yamabushitake group showed significantly increased scores on the cognitive function scale compared with the placebo group.
The Yamabushitake group's scores increased with the duration of intake, but at week 4 after the termination of the 16 weeks intake, the scores decreased significantly
Mori K, et al. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytother Res Mar;23(3):
50- to 80-year-old Japanese men and women with mild cognitive impairment
30 subjects were randomized into two 15-person groups, one of which was given Yamabushitake and the other placebo. The Yamabushitake group's cognitive function scores sig increased with the duration of intake compared to placebo, but at week 4 after the termination of the trial, the scores decreased significantly, suggesting that the effect is dependent on continued intake of the mushroom
This research group conducted another study, published in 2011, showing that Hericium erineaus prevented impairments of spatial short-term and visual recognition memory induced by β-amyloid, further indicating that this mushroom may be useful in the prevention of cognitive dysfunction. Mori K, Obara Y et al Biomed Res 32(1):67-72
The well-known herbalist David Hoffman was bit by a brown recluse spider last year – lost ability to give good talks and write – took Lion’s Mane and attributes his recovery to it

62. Hericium ramosum (H. coralloides) Comb Tooth
Oral administration of Hericium ramosum mycelia significantly increased concentrations of NGF in the hippocampus of intact mice.
Suruga K et al. Effects of Comb Tooth Cap Medicinal Mushroom, Hericium ramosum (Higher Basidiomycetes) Mycelia on DPPH Radical Scavenging Activity and Nerve Growth Factor Synthesis. Int J Med Mushrooms. 2015;17(4):331-8.
Another Hericium mushroom, Hericium ramosum, that looks more like coral or comb teeth, than a lion’s mane and was formerly known as Hericium coralloides, has also shown it can increase NGF.These results are the first concerning antioxidant activity and NGF synthesis from mycelia of this species.
Hericium coralloides would now be called "the mushroom formerly known as Hericium coralloides" if it were a pop star from the eighties who wore purple velvet, It is now known as Hericium americanum; it also hangs it spines from branches, but the spines are typically longer than 1 cm.

63. Agaricus blazei
Agaricus mushrooms contain agaratines – tyrosinase converts them into carcinogens – uncooked button mushrooms exposes us to some carcinogens – Koge T – Heat stability of
Eat mushrooms on pizza – cooked at high Temp – but not sautéed- heat not high enough
Toxicon – Isolation and characterization of a novel two component hemolysin
All mushrooms should be cooked to destroy toxins – makes them more digestible too

64. Ohno S et al. Phase I Clinical Study of the Dietary Supplement, Agaricus blazei Murill, in Cancer Patients in Remission.
Evid Based Complement Alternat Med. 2011;2011:192381
Cancer survivors took 1.8, 3.6, or 5.4 g ABM granulated powder (Kyowa Wellness Co., Ltd., Tokyo, Japan) per day orally for 6 months. Seventy-eight patients were assessed for safety of ABM (30/24/24 subjects at 1/2/3 packs per day, resp.). Adverse events were observed in 9 patients (12%). Most were digestive in nature such as nausea and diarrhea, and one patient developed a liver dysfunction-related food allergy. However, none of these adverse events occurred in a dose-dependent manner. This study shows that ABM does not cause problems in most patients within laboratory parameters at the dosages tested over 6 months. This trial supports previous evidence that the ABM product is generally safe, excluding possible allergic reaction.

65. Hepatoxicity of Agaricus blazei
An Alternative Medicine, Agaricus blazei, May Have Induced Severe Hepatic Dysfunction in Cancer Patients. Japan J Clinical Oncology :
Hisamochi A, Kage M, Arinaga T et al. Case Report: Drug-induced liver injury associated with Agaricus blazei Murill which is very similar to autoimmune hepatitis. Clinical Journal of Gastroenterology :
We report three cases of patients with advanced cancer who showed severe
hepatic damage, and two of whom died of fulminant hepatitis. All the
patients were taking Agaricus blazei extract, one of the most popular
complementary and alternative medicines among Japanese cancer patients. In
one patient, liver functions recovered gradually after she stopped taking
it, but she restarted taking it, which resulted in deterioration of the
liver function again. The other patients who were admitted for severe liver
damage had started taking it several days before admission. Although several
other factors cannot be completely ruled out as the causes of liver damage,
a strong causal relationship between the Agaricus blazei extract and liver
damage was suggested and, at least, taking the Agaricus blazei extract made
the clinical decision-making process much more complicated.
Comments by Dr. Sahelian: For the time being, limit your intake to
maximum 3 times a week and a full week off each month. It is not clear at
this time whether the problem was with the particular agaricus supplement
these patient were using, i.e, Himematsutake as it is called in Japan, or
whether the problem of liver harm applies to all brands. Was the
Himematsutake product these Japanese cancer patients were taking
contaminated with something else? It is also not clear whether the liver
problem is dose dependent. Sometimes patients with cancer will take a very
high amount of a supplement thinking more is better. It is also not clear
whether the liver damage occurred due to the fact that these patients may
have been on chemotherapy drugs which weakened their liver and immune
system.

66. On the other hand….
Agaricus blazei Murill (ABM) acts as an enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling via inhibition of NFκB activity
ABM, when combined with low doses of Dox, has the potential to provide more efficient therapeutic effects against drug-resistant human hepatocellular carcinoma.
Lee JS1, Hong EK. Agaricus blazei Murill enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells by NFκB-mediated increase of intracellular doxorubicin accumulation. Int J Oncol Feb;38(2):401-8.
On the other hand, Agaricus blazei Murill (ABM) acts as an enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling via inhibition of NFκB activity
ABM, when combined with low doses of Dox, has the potential to provide more efficient therapeutic effects against drug-resistant human hepatocellular carcinoma.

67. Study: RCT
Population: 100 cervical, ovarian and endometrial cancer patients tx with 3 cycles of carboplatin and etoposide or carboplatin and taxol
Intervention: Agaricus blazei Munill Kyowa (ABMK)
Results: Chemotherapy-associated side effects such as appetite, alopecia, emotional stability, and weakness were improved with Agaricus. No statistical difference in lymphokine-activated killer cells and monocyte activities.

68. Agaricus sylvaticus The Pinewood Mushroom
More than 300 species of Agaricus mushrooms – some are edible, some are poisonous
A sylvaticus stains reddish when cut

69. Study: randomized, double-blind, placebo controlled trial
46 patients between age 40 and 65 with stage II or III breast cancer receiving chemotherapy next slide

70.  Agaricus sylvaticus (2.1g bid x 6 months) improved nutritional status and reduced adverse drug reactions in bowel functions, nausea, vomiting, anorexia, and fever compared to placebo control group in patients with BC receiving chemotherapy.

71. quality of life measures were assessed
quality of life measures were assessed. After 6 months of tx, the agaricus intervention arm had significantly increased adhesion to physical activity, improved mood, reduced complaints of pain and alteration of sleep, had better appetites, reduced constipation, diarrhea, flatulence, nausea, and abdominal pain.

72. Research review of agaricus as adjuvant tx of breast cancer showed promising results in adjuvant tx of BC, a/w improvements in immunologic and hematologic parameters as well as QoL see next slide

73. 1.6g qid
10mg qd
Blazei tea 10 mg/d given to 5 stage IV BC pts resulted in increased number of NK cells
A bisporus decreased tumor cell prolif and tumor growth in mice in a 2006 publication by Chen

74. Agaricus bisporus White Button Mushrooms
we do not have adequate clinical trial data to prove that white button mushrooms are an adequate alternative to aromatase inhibitors, Yet for the estrogen receptor positive woman who is unable to tolerate standard aromatase inhibitor therapy, a diet high in mushrooms is a reasonable alternative. It is unlikely to hurt and might help and probably far better than doing nothing. Goal: 2 lbs of button mushrooms per month. Mostly cooked vs. raw – more digestible.

75. Aromatase Inhibition
Chen S, et al.Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus).
Cancer Res Dec 15;66(24):
White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation.
Grube BJ, Eng ET, Kao YC, Kwon A, Chen S.
J Nutr Dec;131(12):
Chen and his group at the City of Hope have conducted several trials demonstrating that A. bisporus mushrooms have aromatase inhibiting activity in breast cancer

76. Agaricus bisporus White Button Mushrooms
Jeong SC et al. Macrophage immunomodulating and antitumor activities of polysaccharides isolated from Agaricus bisporus white button mushrooms. J Med Food Jan;15(1):58-65
This finding was confirmed by Jeong and colleagues in this 2012 paper

77. 1+1 > 2 3 grams x 2 > 6?
Musroom combinations may exhibit synergistic effects

78. Synergy with Mushroom Combinations
Extract of Trametes and Ganoderma (I’m-Yunity-Too) combined is more active in inducing apoptosis of leukemia cells compared to Trametes (I’m-Yunity) alone, based on expression of caspase 3 and Bax
Ethanolic extracts of the combination were more anti-proliferative and induced apoptosis more, compared to aqueous extracts: more down-regulation of phosphorylation of Rb and increased poly(ADP-ribose) polymerase (PARP)
Hsieh TC, Wu JM. Regulation of cell cycle transition and induction of apoptosis in HL-60 leukemia cells by the combination of Coriolus versicolor and Ganoderma lucidum. Int J Mol Med (1):251-7.
The researchers conducting this study investigated similarities and differences between extracts prepared from I'm-Yunity (Trametes) and from a formulation denoted I'm-Yunity-Too combining I'm-Yunity and Ganoderma to see whether their combination might elicit an expanded efficacy and mechanism. The combination of Trametes and Ganoderma was more active in inducing cell death. Although hot water extraction is the common form of preparing these 2 mushrooms, this study found that Ethanolic extracts of the combination were more anti-proliferative compared to aqueous extracts: more down-regulation of phosphorylation of Rb and increased poly(ADP-ribose) polymerase (PARP)
Based on this study and the potential for synergism of mushroom combinations, I have begun prescribing Trametes and Ganoderma together, typically in doses of 3 g daily of each.

79. Maitake and Shiitake
Beta glucans of both were compared to either mushroom alone
Measures of phagocytosis, NK cell activity, IL-6, IL-12, IFN-gamma and CRP
Combination was strongest, followed by shiitake on its own
Vetvicka, V. and Vetvickova, J. Immune-enhancing effects of Maitake (Grifola frondosa) and Shiitake (Lentinula edodes) extracts. Annals of Translational Medicine Vol. 2, No. 2 (2014): 14.

80. Dosage
Most human trials found effectiveness with 6gm orally/day, taken either as 2 gm tid or 3 gm bid
Pioneering studies of IV injection of soluble or particulate glucan have documented significant regression of in vivo models of mammary cancer and melanoma in mice
Di Luzio et al.
If 2 ore more mushrooms are prescribed, I reduce the dose of each mushroom to achieve a daily dose of 6 gms

81. Fruiting body or mycelial extracts?
Simultaneous presence of different products may elicit multiple stimulatory activities and enhanced immunomodulatory effects. (Vannucci et al. 2013)
Some producers are using mycelial extracts rather than or in addition to fruiting body extracts
Most clinical research has focused on fruiting body extracts
More data is needed to determine if mycelial extracts or combined fruiting body and mycelial extracts are equivalent or superior to either alone.

82. Fruiting Body vs. Mycelial Extracts
active constituents in mushrooms principally beta-D-glucans, secondarily triterpenoids and ergosterol.
Starch is utilized as an indicator of adulteration.
Analytical methods that quantify active compounds demonstrate mushrooms fruiting bodies are high in beta-D-glucans and very low in starch.
Mycelium produced on cereal grains is low in beta-D-glucans and high in starch.
Ergosterol analysis shows the actual amount of fungal material in the products.
2014:1-27

83. Ergosterol
Ergosterol has antitumor and antioxidant properties, and is a precursor to vitamin D2
Exp Biol Med :
When exposed to sunlight (UVB), mushrooms as well as human skin convert ergosterol to ergocalciferol (provitamin D2).
DermatoEndocr ;1:

84. Triterpenoids
Mushrooms grown on natural substrates contain precursors that yield secondary metabolites such as triterpenoids whereas mycelium produced on cereal grains lack such precursors.
In addition to playing complementary role with beta-glucans in immune system activation, triterpenoid actions are hepatoprotective, lipid lowering, antioxidant, inhibition of histamine release and anti-inflammatory.
Triterpenoids are lipids, e.g. ganoderic acids, responsible for the bitter taste of reishi and this bitterness can be used as a quick method of determining the quality of a reishi product.
Int Immunopharm :

85. Beta-D-glucans
Beta-D-glucans are polysaccharide structural component of the cell walls of mushrooms, mycelium, yeast, certain bacteria, and cereal grains.
Unique structural differences of beta-D-glucans determine medicinal activity and explain why fungal beta-glucans are more active than cereal beta-glucans.
J Hem Onc :25

86. Beta-D-glucans
Beta-glucans activate or potentiate both innate and adaptive immune responses and have been described as “biological response modifiers” and “host defense” potentiators.
Beta-glucans increase the number and functional activity of macrophages, Natural Killer cells, and other subclasses of T-cells.
Beta-glucans are not degraded by digestive enzymes and pass intact into the small intestine where they activate specific beta-glucan receptor sites.
The immunological potentiation is not only anti-cancer but also increases protection against viral, bacterial, fungal and parasitic infections.
Exp Biol Med :
Int J Med Mushrooms :69-80

87. Beta glucans
Beta glucans and protein-bound beta glucans are responsible for the medicinal properties of mushrooms and mycelia.
Lentinan, a pure (1→3)beta- D-glucan [e], is extracted from shiitake mushroom Lentinus edodes .
PSK and PSP are protein-bound beta-glucans derived from the fermentation of Trametes mycelium.

88. Mushrooms have few quality control standards
The natural product market contains many fraudulent mushroom products, particularly spiked polysaccharides that manufacturers blend in.
DNA identification is not an accurate or appropriate method for finished products
Companies need to work with suppliers to test the raw liquid material to determine what the excipient/carrier content will be at the spray powder stage.
Unfortunately, excipient starches test the same as polysaccharides. Most of the industry does not realize this and purchases inferior raw materials.

89. Mushrooms for Specific Cancers
Indicated Mushrooms
Reference
Breast
Trametes, Ganoderma, Agaricus sylvaticus, Grifolia
Torkelson et al, 2012
Gonul et al, 2015
Colorectal
Trametes, Ganoderma,
Grifolia
Ohwada, et al, 2006
Gastric
Trametes
Eliza et al, 2012
GYN
Hepatocellular
Leukemia
Lymphoma
Ganoderma
Agaricus, Ganoderma,Len
Agaricus, Gano,Trametes
Cordyceps
Suprasert, et al, 2014
Li et al, 2015, Matsui2002
Hsieh et al, 2013
Lung
Prostate
Advanced cancer
Trametes, Gano, Cordyceps
Fritz, et al, 2015
Wenner et al, 2012
Gao, et al, 2003
Perhaps the most useful information I have to share with you today are the following 3 referenced tables I’ve compiled as a quick resource for what mushrooms to use with certain cancers and certain chemotherapeutic drugs, This first table is an expansion of one included in Dr Zwickey’s paper published last year in Integrative Medicine

90. Mushrooms and Specific Cancers
Reference
Ganoderma
Breast, colon, hepatocellular, leukemia (+Trametes), prostate, sarcoma
Hsieh TC and Wu JM, 2013
Chen et al, 2006
Gonul et al, 2015 Loganathan et al, 2014
Liu et al, 2009
Trametes
Breast, colon, gastric, prostate, leukemia (+Ganoderma)
Wenner et al, 2012
Eliza et al, 2012
Grifolia
Breast, colon
Deng et al, 2009
Masuda et al, 2010
Agaricus blazei
Hepatocellular, leukemia
Lee and Hong, 2011 (in vitro)
Li et al, 2014 (mice)
Cordyceps
Lentinula
Lung, lymphoma
Hepatocellular
Matsui et al, 2002
This is another way of looking at the evidence for the efficacy of specific mushrooms and certain cancers

91. Mushrooms and Chemotherapeutic Agents
Indicated Mushroom
References (mostly in vitro)
Trastuzumab
Trametes
Lu et al, 2011 (also in mice)
Cyclophosphamide
Ganoderma
Zhu et al, 2007
Cisplatin
Ganoderma, Cordyceps, Grifolia
Masuda et al, 2009
Yao et al, 2012
Docetaxel
Kinoshita et al, 2009 (human)
Wenner et al, 2012 (animal)
Doxorubicin
Agaricus
Lee and Hond, 2011
And this is the table on which mushrooms are indicated for specific cancer drugs
As Standish and colleagues have shown, PSK given with trastuzumab resulted in greatly increased cell-mediated cytotoxicity
In vitro and in vivo studies have also shown that β-D-glucans are effective enhancers of antitumor responses with other monoclonal antibody drugs
Cyclophosphamide-induced myelosuppression in mice treated with water-soluble Ganoderma extract x 7 days was reduced, with an increase in RBCs, WBCs, NK T cells, splenic Ganoderma was found to increase accumulation of cisplatin inside cancer cell line HepG2.
Cordyceps increased cytotoxicity of cisplatin in a NSCLC model
PSK increased efficacy of Docetaxel in the treatment of gastric carcinoma. Also confirmed in prostate cancer model.
Doxorubicin combined with Agaricus was accumulated at higher doses within hepatocellular carcinoma cells and increased apoptosis compared to doxorubicin alone In

92. Mushrooms and Vitamin D2
Mushrooms as well as human skin create vitamin D when exposed to sunlight
Mushrooms are rich in vit D precursor ergosterol, which UVB converts to ergocalciferols, aka provitamin D2
Keegan, RH, Lu Z, Bogusz JM, Williams JE, Holick MF, Photobiology of vitamin D in mushrooms and its bioavailability in humans Dermato-Endocrinology 5:1, 165–176;
Did you know that tasty mushrooms are one source for vitamin D, and that you can naturally multiply their levels by exposing them to sunlight?
We evolved living in more sunlight than today. We make our own vitamin D when sunlight hits our skin cells. Many people living in the northern hemisphere, however, suffer from lower levels of vitamin D during the fall, winter and spring. Fortunately, you can make your own supply of vitamin D-enriched mushrooms by simply exposing them to sunlight. You can sun dry or UV-zap store-bought or homegrown shiitake, maitake, button, and many other mushroom species.. The high vitamin D levels generated will last for more than a year. Surprisingly, even sliced and dried mushrooms—including wild ones picked the year before—will soar in vitamin D when placed outdoors under the sun. Now, the summer time, from June until September, is the best seasonal window for people in northern latitudes to make vitamin D enriched mushrooms!
See more at:
The commercially common sources of vitamin D are vitamin D3 (cholecalciferol) that comes from sheep’s wool (lanolin), pigskins, and some oily fish (mackerel, sardines, anchovies, herring, trout, and salmon). Mushrooms and animal skins create vitamin D when exposed to sunlight. Mushrooms are rich in the vitamin D precursor ergosterol, which ultraviolet B (between wavelengths of 290 nm to 315 nm) converts to ergocalciferols, also called provitamin D2. Mammalial epidermis has cholecalciferol, which ultraviolet light converts to D3.
Which is better, Vitamin D3 or D2? The New England Journal of Medicine published an exhaustive article comparing the metabolic pathways of vitamin D2 and vitamin D3 (Holick, 2007). Our enzymes convert both D vitamins into 25-hydroxyvitamin D, and then into the active form of 1,25-dihydroxyvitamin D in our kidneys. This form of vitamin D can bind to receptors in various tissues around the body for use. One advantage of vitamin D3 is its longevity after ingestion—staying in the bloodstream for weeks compared to days for vitamin D2. However, for people taking vitamin D supplements several times a week, there seems to be no significant advantage in taking one form or the other.
The most vitamin D was found in shiitake dried with gills up that were exposed to sunlight for two days, six hours per day. The vitamin D levels in these mushrooms soared from 100 IU/100 grams to nearly 46,000 IU/100 grams (see chart). Their stems, though, produced very little vitamin D, only about 900 IU. Notably, vitamin D levels dropped on the third day, probably due to over-exposure to UV.
Most interesting to me is that when we tested our mushrooms nearly a year after exposure, they preserved significant amounts of vitamin D2.
- See more at:

93. Here’s How to Do It
1) Obtain fresh organic shiitake, maitake, button, oyster, shimeji or other mushrooms.
2) On a sunny day in June, July or August, slice the fresh mushrooms. Place them evenly on a tray exposed directly to the sun from 10 am to 4 pm.
3) Before nightfall, cover the mushrooms with a layer of cardboard to block moisture from dewfall.
4) The next clear day repeat exposure to the sun from 10 am to 4 pm.
5) Remove the mushrooms and finish drying (if necessary in a food dehydrator until they are crispy).
6) When thoroughly dry, store in a glass jar or sealed container. Adding a tablespoon of uncooked rice as a moisture absorber will help keep the mushrooms dry. The mushrooms should be good for a year or more, depending upon conditions.
7) Take 10 grams daily per person, about a small handful. Rehydrate in water for one hour. The mushrooms will swell. Then cook as desired.
- See more at:

94. Psilocybe cyanescens: Magic mushrooms
Psychedelic medicine: a re-emerging therapeutic paradigm. CMAJ  Sept 8, 2015
Psychedelic medicine, once a controversial subject that led to the suppression of research on it for over 30 years, has recently re-emerged as a therapeutic paradigm, as described in an article in the Canadian Med Assn Jr last month.
Psilocybin is the active ingredient in magic mushrooms
There are about 40 Psilocybin containing mushroom species
Preliminary researhc has suggested that psilocybin may result in more conscious dying and with more tranquility

95. Study: double-blind placebo-controlled study led by UCLA psychiatrist Charles Grob
Population: 12 patients with advanced stage cancer and anxiety. Primary cancers included breast cancer in 4 subjects, colon cancer in 3, ovarian cancer in 2, peritoneal cancer in 1, salivary gland cancer in 1, and multiple myeloma in 1
4 had never had hallucinogen experience, 4 had experience greater then 30 years ago.
Intervention: 2 experiential sessions spaced several weeks apart of psilocybin 0.2mg/kg (13mg in 150 pound individual)
Outcome measures: Adverse events, State-Trait Anxiety Inventory, Beck Depression Inventory
Results: Consistent with previous research. no adverse psychological or physical effects from the treatment. All subjects tolerated the treatment sessions well, with no indication of severe anxiety or a “bad trip.” Common themes reported by subjects included examining how their illness had impacted their lives, relationships with family and close friends, and sense of ontological security. In addition, subjects reported powerful closeness to friends and family members and examined how they wished to address their limited life expectancy. In monthly follow-up discussions, subjects reflected on insights and new perspectives gained during their psilocybin treatment.

96. OB: oceanic boundlessness
AED: anxious ego dissolution
VR: visionary restructuraliztion
AA: auditory alterations
And RV: reduced vigilance
Positive mood, lowered anxiety, facilitated recollection and imagination

97. Psychopharmacologist Roland Griffiths
Though his initial studies focused on how psilocybin can help quell fear and anxiety in patients facing terminal illnesses, Roland’s vision is broader. He proposes that many of the world’s challenges, including the environmental crisis and hostilities within and between cultures, stem “from a lack of appreciation for the profound interconnectedness of all people and all things.” Interconnectedness is a “core feature” of the world’s ethical and moral systems as well as of the mystical or transcendent experiences induced by psilocybin under appropriate conditions, says Roland. He believes that “ultimately, systematic prospective study of mystical experiences and their consequences may be critical to the survival of our species and the healing of our planet.”
Asked to name the one person with whom he’d most like to work, Roland answered: “At the risk of sounding heretical to some present-day Buddhists, I would like to have collaborated with Siddhārtha Gautama (the historical Buddha). We are presently characterizing the acute and persisting effects of psilocybin in very experienced meditators. In my dream collaboration, the Buddha would have an experience with psilocybin. I would be fascinated to know if he thought such an experience was a help or a hindrance to understanding the nature of mind and to cultivating deep peace and compassion.”

98. In 2008,Roland Griffiths co-wrote a report in the Journal of Psychopharmacology comparing psilocybin with a placebo for people dealing with incurable diseases. Psilocybin resulted in "mystical experiences having substantial and sustained personal meaning and spiritual significance," according to the study, the first since 1972 to explore a hallucinogen's therapeutic value.
Griffths now has a clinical trial in process at Johns Hopkins looking specifically at psilocybin and cancer patients. He describes the experience of one of the participants,
Janeen Delany, who describes herself as an "old hippie" who's smoked plenty of marijuana. But she never really dabbled in hallucinogens -- until two years ago, at the age of 59.
A diagnosis of incurable leukemia had knocked the optimism out of the retired plant nurserywoman living in Phoenix. So she signed up for a clinical trial to test whether psilocybin -- the active ingredient in "magic mushrooms" -- could help with depression or anxiety following a grim diagnosis.
Delaney swallowed a blue capsule of psilocybin in a cozy office at Johns Hopkins University in Baltimore. She donned a blindfold, a blood pressure cuff and a headset playing classical music. With two researchers at her side, she embarked on a six-hour journey into altered consciousness that she calls "the single most life-changing experience I've ever had.”
The insights she gleaned during her encounter with psilocybin continue to shape her attitudes toward life and death.
Delany said her "trip" awakened a deep and reassuring sense of "knowing." She came to see the universe and everything in it as interconnected. As the music in her headphones reached a crescendo, she held her breath and realized it would OK -- no, really easy -- not to breathe anymore. She sensed there was nothing more she needed to know and therefore nothing she needed to fear about dying.
And that, paradoxically, has allowed her to live.
"When you take the veil of fear away from your life, you can see and experience everything in such a present way," she said. "I don't have to know what the future is. Every day is the day of days."

99. Another clinical trial underway here at New York University is assessing cancer-associated anxiety, as well as pain perception, depression, existential distress, QOL and mystical states of consciousness. The fact that these studies are being conducted at prominent medical centers underscores the legitimacy of this research topic.
one means by which psilocybin seems to work is to “substantially reduce cognitive activity in the brain’s ‘default mode network.’” This part of the brain is considered the “orchestra conductor,” the corporate executive”– a.k.a. the ego. If one inhibits the ‘default-mode’ power of the constructed ego, other areas of the brain have a chance to appear, connect, and create different kinds of meaning. One observation from the NYU team: “The fact that a drug given once can have such an effect for so long is an unprecedented finding.”

100. Research Challenges in Cancer Mycotherapy
Need for more well-designed randomized, placebo-controlled trials
Varying delivery methods and types of mushroom extracts used
Animal studies often use intra-peritoneal injection of purified mushroom extract making it difficult to translate dosage and form into human studies