Robert C. Atkins, M.D.

Robert Barnett, Author & Nutritionist
in Tonics, Harper Collins, New York

Harriet Beinfeld
co-author of Between Heaven and Earth: A Guide to Chinese Medicine, Ballatine Books, New York

John Boik
in Cancer & Natural Medicine: A Textbook of Basic Science and Clinical Research, Oregon Medical Press, Princeton, Minnesota

Morton Broffman, Ph.D.
in Townsend Letter for Doctors & Patients

Etienne Callebout, M.D.
in An Alternative Medicine Definitive Guide to Cancer,
Future Medicine Publishing, Inc., Tiburon, Californi

Goro Chihara, Ph.D.
Teikyo University, Nogawa, Japan

W. Lee Cowden, M.D.
Conservative Medical Institute, Richardson, Texas

Subhuti Dharmananda, Ph.D.
Chinese Herbal Therapies for Immune Disorders, Eastwind Books, San Francisco, California

W. John Diamond, M.D.
Medical Director, Triad Medical Center, Reno, Nevada

Patrick Donovan, N.D.
University Health Clinic, Seattle, Washington

James Duke, Ph.D.
Economic & Medical Botanist (ret.), USDA

Daniel Gagnon, Medical Herbalist
President of Herbs, Etc., Santa Fe, New Mexico

M. Ghoneum, Ph.D.
Drew University of Medicine and Science

Christopher Hobbs, Herbalist
in Medicinal Mushrooms,
Botanica Press, Santa Cruz, California

Tetsuro Ikekawa, Ph.D.
National Cancer Center, Tokyo, Japan

Jan Lelley, Ph.D.
author of Die Heilkraft de Pilze: Gesund durch Mykotherapie

Takashi Mizuno, Ph.D.,
Professor Emeritus, Shizuoka University, Japan

Michael Murray, N.D. & Joseph Pizzorno, N.D.
in The Encyclopedia of Natural Medicines, MacDonald & Co., Ltd., London

Hiroaki Nanba, Ph.D.
Kobe Pharmaceutical University, Japan

Robert C. Rountree, M.D.
Helios Health Center, Boulder, Colorado

Jesse Stoff, M.D.
Solstice Clinical Associates, Tucson, Arizona

Glen M. Swartwout, O.D.
Remission-Foundation, Hilo, Hawai’i

Jack Taylor, D.C.
Dr. Taylor's Wellness Center, Rolling Meadows, Illinois

Ron Teeguarden, Herbalist
in Chinese Tonic Herbs,
Japan Publications, Tokyo

Leslie Tierra, Herbalist
in The Herbs of Life,
Crossing Press, Freedom, California

Michael Tierra, Herbalist
in The Way of Herbs,
Simon & Schuster, New York

Susan Weed
in Breast Cancer, Breast Health,
Ashtree Press, Woodstock, New York

Andrew Weil, M.D.
in Spontaneous Healing, 8 Weeks to Optimum Health, Self Healing Newsletter

Terry Willard, Ph.D.
Director, Wild Rose College, Calgary, Alberta, Canada

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Lentinan; i.e., polysaccharides extracted from a kind of black mushroom shiitake, has been clinically applied as an antitumor and antimetastatic drug, and has been reported to prevent both chemical and viral carcinogenesis. It is known that lentinan affects the tumorous vascular system resulting in the induction of hemorrhagic necrosis which is dependent on T-cells in the tumor.

Repeated mucosal necrosis-regeneration sequence in chronic ulcerative colitis induced with 3% dextran sulfate sodium led to colorectal carcinogenesis in azoxymethane-pretreated mice. In the present study, the additive treatment with lentinan in the azoxymethane-dextran sulfate sodium treated mice enhanced the colorectal high-grade dysplasia, though not significantly, and the splenic weight. This may show the proliferation of pathogenic splenic T cells resulting in a change for the worse of ulcerative colitis, anemia induced with hemorrhage and colorectal carcinogenesis; i.e., high-grade dysplasia of the mucosa and/or invasive adenocarcinomas of the colorectum. The present results may recommend chemoimmunotherapy while using lentinan, but not immunotherapy using lentinan alone, is indicated for the management of cancer patients.

PMID: 10767375, UI: 20232147

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Heterokaryotic nuclear hybrids overcoming the natural barriers of incompatibility have been studied in basidiomycetes. To produce these nuclear hybrids between incompatible mushrooms, which have several potent pharmacological effects, nuclear transfer was performed between Lentinula edodes and Coriolus versicolor. Nuclei from serine auxotrophs of Lentinula edodes, LE207 (Ser-) were transferred into the protoplasts of arginine auxotrophs of Coriolus versicolor, CV17 (Arg-), using 30% polyethylene glycol 4000 in 10 mM CaCl2-glycine solution (pH 8.0).

Nuclear transfer progenies were selected by nutritional complementation on minimal media supplemented with 0.6 M sucrose. The progenies were classified based on colony morphology to L. edodes-like, C. versicolor-like and non-parental type. Most of the progenies grew slower than either parent. The number of nuclei per cell was similar but the DNA content varied between progenies. The isozyme patterns of nuclear hybrids resembled either of the parent profiles or showed a mixed profile.

PMID: 10728662, UI: 20191006

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The caries-inhibiting effect of the extract from shiitake (Lentinus edodes), the most popular edible mushroom in Japan, was studied both in vitro and in vivo. Shiitake extract showed an inhibitory effect on water-insoluble glucan formation from sucrose by crude glucosyltransferases of Streptococcus mutans JC-2 and Streptococcus sobrinus OMZ-176. The firmly adherent plaque in the artificial plaque formation test was strongly inhibited by shiitake extract. The reduction of firmly adherent plaque caused an increase in the incidence of non- and loosely adherent plaque and a decrease in total plaque formation. A significantly lower caries score was observed in specific pathogen-free rats infected with S. mutans JC-2 and fed with a cariogenic diet containing 0.25% shiitake extract as compared with controls fed the cariogenic diet without shiitake extract.

PMID: 10601791, UI: 20069269

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Lentinan is a beta 1-->3 glucan isolated from Lentinus edodes (Shiitake mushroom) which has immune modulating properties. We have conducted two phase I/II placebo-controlled trials on a total of 98 patients. In one study at the San Francisco General Hospital (SFGH), ten patients each were administered 2, 5, or 10 mg of lentinan or placebo i.v. once a week for eight weeks.

In the second study at the Community Research Initiative in New York (CRI), two groups of 20 patients each were administered 1 or 5 mg of lentinan i.v. twice a week for 12 weeks, and ten patients were administered placebo (vehicle containing mannitol plus dextran 40) i.v. twice a week. Entry criteria were an HIV positive test, CD4 levels of 200-500 cells, age 18-60 years, and without current opportunistic infections. This study confirms, in Caucasian subjects also, the good tolerability of lentinan observed in Japanese cancer patients. Side effects were mainly mild, especially when infusion was carried out over a 30-minute period. In the SFGH study, where administration was over a ten minute period, there were nine side effects severe enough to be reported to the FDA (one case each of anaphylactoid reaction, back pain, leg pain, depression, rigor, fever, chills, granulocytopenia and elevated liver enzymes) and there were four patients who discontinued therapy because of side effects. In the CRI study, where infusion was over a 30-minute period, there were no side effects reportable to the FDA and there were four dropouts due to side effects or personal preference. Most side effects resolved promptly after the discontinuation of medication, and all of them were relieved within 24 hours. Patients in the study have shown a trend toward increases in CD4 cells and in some patients neutrophil activity. Because of the small numbers, these values do not have statistical significance. Inasmuch as no side effects such as anemia, leukopenia, pancreatitis or neuropathy were seen, and in view of the positive effects of lentinan on certain surrogate markers (recognizing that these were small studies), we recommended a long-term clinical trial of lentinan in combination with didanosine (ddI) or zidovudine in HIV positive patients. Most patients in these trials did not have measurable p24 levels. In the CRI trials of ten patients with elevated p24 levels, eight on lentinan and two on placebo had decreased p24 levels. Of these decreases, those with lentinan and one with placebo were marked. These results were provocative and needed confirmation. Subsequent to this study, a trial of lentinan in combination with didanosine (ddI) showed a mean increase of 142 CD4 cells/mm3 over a twelve month period, in contrast to a decrease in CD4 cells in patients on ddI alone (Gordon et al. 1995).

Publication Types: Clinical trial, Clinical trial, phase i, Clinical trial, phase ii ,Randomized controlled trial

PMID: 10503166, UI: 99432784

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Three kinds of antibacterial substances were extracted by chloroform, ethylacetate or water from dried Shiitake mushrooms (Lentinus edodes). These substances possess efficient antibacterial activities against Streptococcus spp., Actinomyces spp., Lactobacillus spp., Prevotella spp., and Porphyromonas spp. of oral origin. In contrast, other general bacteria, such as Enterococcus spp., Staphylococcus spp., Escherichia spp., Bacillus spp., and Candida spp. were relatively resistant to these substances. Chloroform extracts had bactericidal activity against both growing and resting bacterial cells of S. mutans and P. intermedia, whereas the other two extracts showed bacteriostatic activity against both growing and resting bacterial cells of S. mutans and resting bacterial cell of P. intermedia. The antibacterial activity of chloroform extracts and ethylacetate extracts were relatively heat-stable. The water extract was heat-labile.

PMID: 10221419, UI: 99236608

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The aqueous extract of the shiitake mushroom was found to decrease IL-1 production and apoptosis in human neutrophils, as measured by ELISA and flow cytometry respectively. It was found to increase IL-1 production and apoptosis in the U937 monocytic cell line. The extract showed no significant effects on the superoxide production of both neutrophils and U937 cells, as measured by chemiluminescence. The extract was further separated into high and low molecular weight components, and it was found that the low molecular weight component retained the activity of the whole extract. This further suggests that the active substance is a novel compound distinct from lentinan, a well-studied high molecular weight anti-tumour agent found in shiitake.

PMID: 10190187, UI: 99206185

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Antibodies against beta-glucan, lentinan from "Shiitake" (Lentinus edodes), were raised in the rabbit by subcutaneous immunization. Our antibodies did not recognize the other polysaccharides such as amylose, dextran, laminarin and galactan. It was proved that lentinan contents in mushroom could be measured by ELISA with the anti-lentinan antisera. Its contents were 3.5 mg/g fresh weight in Lentinus edodes. However, lentinan was not contained in Agaricus brazei, Agaricus bisporus and Ramaria bitrytis.

PMID: 8843335, UI: 97000193

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A plant polysaccharide, Aloe gel extract, was reported to have an inhibitory effect on benzo[a]pyrene (B[a]P)-DNA adduct formation in vitro and in vivo. Hence, chemopreventive effects of plant polysaccharides [Aloe barbadensis Miller (APS): Lentinus edodes (LPS), Ganoderma lucidum (GPS) and Coriolus versicolor (CPS)] were compared using in vitro short-term screening methods associated with both initiation and promotion processes in carcinogenesis. In B[a]P-DNA adduct formation, APS (180 micrograms/ml) was the most effective in inhibition of B[a]P binding to DNA in mouse liver cells. Oxidative DNA damage (by 8-hydroxydeoxyguanosine) was significantly decreased by APS (180 micrograms/ml) and CPS (180 micrograms/ml). In induction of glutathione S-transferase activity, GPS was found to be the most effective among plant polysaccharides. In screening anti-tumor promoting effects, APS (180 micrograms/ml) significantly inhibited phorbol myristic acetate (PMA)-induced ornithine decarboxylase activity in Balb/3T3 cells. In addition, APS significantly inhibited PMA-induced tyrosine kinase activity in human leukemic cells. APS and CPS significantly inhibited superoxide anion formation. These results suggest that some plant polysaccharides produced both anti-genotoxic and anti-tumor promoting activities in in vitro models and, therefore, might be considered as potential agents for cancer chemoprevention.

PMID: 10426820, UI: 99355758

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In the last three decades, numerous polysaccharides and polysaccharide-protein complexes have been isolated from mushrooms and used as a source of therapeutic agents. The most promising biopharmacological activities of these biopolymers are their immunomodulation and anti-cancer effects. They are mainly present as glucans with different types of glycosidic linkages such as (1-->3), (1-->6)-beta-glucans and (1-->3)-alpha-glucans, and as true herteroglycans, while others mostly bind to protein residues as polysaccharide-protein complexes. Three antitumor mushroom polysaccharides, i.e. lentinan, schizophyllan and protein-bound polysaccharide (PSK, Krestin), isolated respectively, from Lentinus edodes, Schizophyllum commune and Coriolus versicolor, have become large market items in Japan. Lentinan and schizophyllan are pure beta-glucans, whereas PSK is a protein-bound beta-glucan. A polysaccharide peptide (PSP), isolated from a strain of Coriolus versicolor in China, has also been widely used as an anti-cancer and immunomodulatory agent. Although the mechanism of their antitumor action is still not completely clear, these polysaccharides and polysaccharide-protein complexes are suggested to enhance cell-mediated immune responses in vivo and in vitro and act as biological response modifiers. Potentiation of the host defense system may result in the activation of many kinds of immune cells that are vitally important for the maintenance of homeostasis. Polysaccharides or polysaccharide-protein complexes are considered as multi-cytokine inducers that are able to induce gene expression of various immunomodulatory cytokines and cytokine receptors. Some interesting studies focus on investigation of the relationship between their structure and antitumor activity, elucidation of their antitumor mechanism at the molecular level, and improvement of their various biological activities by chemical modifications.

Publication Type: Review, academic

PMID: 10702635, UI: 20169495

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This review highlights some of the recently isolated and identified substances of higher Basidiomycetes mushrooms origin that express promising antitumor, immune modulating, cardiovascular and hypercholesterolemia, antiviral, antibacterial, and antiparasitic effects. Medicinal mushrooms have a long history of use in folk medicine. In particular, mushrooms useful against cancers of the stomach, esophagus, lungs, etc. are known in China, Russia, Japan, Korea, as well as the U.S.A. and Canada. There are about 200 species of mushrooms that have been found to markedly inhibit the growth of different kinds of tumors. Searching for new antitumor and other medicinal substances from mushrooms and to study the medicinal value of these mushrooms have become a matter of great significance. However, most of the mushroom origin antitumor substances have not been clearly defined. Several antitumor polysaccharides such as hetero-beta-glucans and their protein complexes (e.g., xyloglucans and acidic beta-glucan-containing uronic acid), as well as dietary fibers, lectins, and terpenoids have been isolated from medicinal mushrooms. In Japan, Russia, China, and the U.S.A. several different polysaccharide antitumor agents have been developed from the fruiting body, mycelia, and culture medium of various medicinal mushrooms (Lentinus edodes, Ganoderma lucidum, Schizophyllum commune, Trametes versicolor, Inonotus obliquus, and Flammulina velutipes). Both cellular components and secondary metabolites of a large number of mushrooms have been shown to effect the immune system of the host and therefore could be used to treat a variety of disease states.

Publication Type: Review, academic

PMID: 9987601, UI: 99142074

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Lentinan (LNT), a beta-glucan derived from Lentinus edodes (Berk.) Sign., is known to work positively against cachexia in patients with malignant tumors. Because the cachectin/tumor necrosis factor (TNF) is supposed to be one of the factors that mediate cancer cachexia, we tested the effects of LNT on TNF-induced cachexia in rats. First, we analyzed in detail the cachectic actions of TNF (0.2 mg/kg/day, 5 days, IV) on food and water intake, body weight, and locomotor activity. The day after the first administration of TNF (acute phase), food and water intake, as well as body weight, of all rats decreased. However, over the next few days of treatment (chronic phase), the rats gradually developed a tolerance to the cachectic actions of TNF. Specifically, after the third administration, the rats treated with TNF had a higher amount of water intake than the control rats. This was mainly due to an increase in daytime water intake. We also analyzed the effects of LNT (0.1 or 1.0 mg/kg, twice/wk. IV) on TNF-induced cachexia, and compared the data with those from the rats treated with TNF alone. The higher dosage of LNT significantly suppressed TNF-induced daytime polydipsia and increased the amount of nighttime water intake, as well as the meal size of nighttime food intake. These results suggest that LNT partially normalizes TNF-induced cachexia in rats.

PMID: 9089759, UI: 97245000

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Antitumor mechanisms of orally administered shiitake fruit bodies.

Functional properties of edible mushrooms.

Evidence for involvement of beta-glucan-binding cell surface lectins in human natural killer cell function.

In vitro chemopreventive effects of plant polysaccharides (Aloe barbadensis miller, Lentinus edodes, Ganoderma lucidum and Coriolus versicolor).

Effects of Lentinus edodes, Grifola frondosa and Pleurotus ostreatus administration on cancer outbreak, and activities of macrophages and lymphocytes in mice treated with a carcinogen, N-butyl-N-butanolnitrosoamine.

Substrates available for colonic fermentation from oat, barley and wheat bread diets. A study in ileostomy subjects.

Immunomodulation and anti-cancer activity of polysaccharide-protein complexes.

Therapeutic intervention with complement and beta-glucan in cancer.

Effects of lentinan on abnormal ingestive behaviors induced by tumor necrosis factor.

Targeting of natural killer cells to mammary carcinoma via naturally occurring tumor cell-bound iC3b and beta-glucan-primed CR3 (CD11b/CD18).

Activation, binding, and processing of complement component 3 (C3) by Blastomyces dermatitidis.