Shiitake

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References

Amagase H. et al. L.E.M. May be Effective Against Treating Hepatitis B Cases. Abstr. 197 Gastroenterology World Congress, Lisbon, 1984.

Arinaga S. Enhanced induction of lymphokine-activated killer activity after lentinan administration in patients with gastric carcinoma. Int J Immunopharmacol 1992 14(4), 535-53

Arinaga S. Enhanced production of interleukin 1 and tumor necrosis factor by peripheral monocytes after lentinan administration in patients with gastric carcinoma. Int J Immunopharmacol 1992 14(1), 43-47.

Chang R. Functional properties of edible mushrooms. Nutr Rev. 1996 Nov;54(11 Pt 2):S91-S93. (Review)

Chang, S.-t., J. Buswell & S-w. Chiu (eds). Mushroom Biology and Mushroom Products. Proceedings of the First international Congress. Hong Kong: The Chinese University Press, 1993.

Gordon M, Guralnik M, Kaneko Y, Mimura T, Goodgame J, DeMarzo C, Pierce D, Baker M, Lang W. A phase II controlled study of a combination of the immune modulator, lentinan, with didanosine (ddI) in HIV patients with CD4 cells of 200-500/mm3. J Med 1995;26(5-6):193-207.
Abstract: This study was carried out to assess the safety and efficacy of a combination of lentinan, an immune modulator, and didanosine (ddI) in a controlled study in HIV positive patients with CD4 levels of 200-500 cells/mm3. Didanosine was administered to HIV patients at doses of 400 mg/day (po) for six weeks (bid), then 2 mg of lentinan i.v. was added per week for 24-80 weeks. A control group (20%) received ddI only. A total of 107 patients were enrolled at three sites, and 88 patients started the ddI/lentinan phase. The combination caused significant increases in CD4 levels up to 38 weeks, whereas ddI alone was significant at the 5% level at 14 weeks. Based on these data, lentinan qualifies as a participant in future multi-drug studies in HIV.

Gordon M, Bihari B, Goosby E, Gorter R, Greco M, Guralnik M, Mimura T, Rudinicki V, Wong R, Kaneko Y. A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial. J Med. 1998;29(5-6):305-330.
Abstract: 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).

Hanada K, Hashimoto I. Flagellate mushroom (Shiitake) dermatitis and photosensitivity. Dermatology. 1998;197(3):255-257.
Abstract: Flagellate skin lesions occur in some patients after eating the mushroom Lentinus edodes, and they are called shiitake dermatitis in Japan. We describe a 44-year-old man with such skin lesions on his trunk after eating L. edodes, who developed as well photosensitive skin lesions on exposed areas. Skin phototesting with UVB did not show a decreased minimum erythema dose; UVA irradiation provoked an erythematous lesion with nonspecific histological changes. Analysis of the case histories of 94 Japanese patients with shiitake dermatitis revealed that 44 (47%) also developed dermatitis on the skin exposed to sunlight. UVA photodermatitis has not been emphasized in previous reports. The relationship to bleomycin flagellate dermatitis is discussed.

Hirasawa M, Shouji N, Neta T, Fukushima K, Takada K.  Three kinds of antibacterial substances from Lentinus edodes (Berk.) Sing. (Shiitake, an edible mushroom). Int J Antimicrob Agents. 1999 Feb;11(2):151-157.
Abstract: 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.

Hitosugi M, Kitamura O, Takatsu A, Yoshino Y. Autopsy case of duodenal obstruction from impacted mushroom. J Gastroenterol. 1998 Aug;33(4):562-565. (Review)
Abstract: We report an autopsy case of duodenal bulb obstruction caused by a shiitake mushroom. A 74-year-old woman with depression was admitted to the hospital after suffering nausea and abdominal fullness for 3 days. Because the physical findings and laboratory data on admission revealed marked dehydration, lactated Ringer's solution was administered. Twelve hours later, the patient suddenly died. Autopsy showed an enlarged stomach filled with 850 ml of partially digested food. In the anal side of the pylorus, a 9-cm-diameter shiitake mushroom had become impacted, causing complete obstruction. We conclude that the patient suffered from duodenal bulb obstruction caused by the impacted mushroom and subsequently died of ileus. This case illustrates a rare cause of duodenal obstruction and emphasizes that ingested food can cause obstructive ileus and death.

Hobbs C. Medicinal Mushrooms. Santa Cruz, CA: Botanica Press, 1995, 125-128.

Jones K. Shiitake: The Healing Mushroom. Rochester, VT: Healing Arts Press, 1995.

Jong SC, Birmingham JM. Medicinal and therapeutic value of the shiitake mushroom. Adv Appl Microbiol. 1993;39:153-184. (Review)

Kabir Y, Yamaguchi M, Kimura S. Effect of shiitake (Lentinus edodes) and maitake (Grifola frondosa) mushrooms on blood pressure and plasma lipids of spontaneously hypertensive rats. J Nutr Sci Vitaminol (Tokyo). 1987 Oct;33(5):341-346.

Levy AM, Kita H, Phillips SF, Schkade PA, Dyer PD, Gleich GJ, Dubravec VA. Eosinophilia and gastrointestinal symptoms after ingestion of shiitake mushrooms. J Allergy Clin Immunol. 1998 May;101(5):613-620.
Abstract: BACKGROUND: Shiitake mushrooms are a dietary staple in Asia and are increasingly popular worldwide. A cholesterol-lowering study with shiitake showed that 17 of 49 participants withdrew because of rash or abdominal discomfort, and two had marked eosinophilia. One of these latter participants was subsequently challenged for 14 days with shiitake powder and again had eosinophilia. OBJECTIVE: We investigated whether ingestion of shiitake mushroom powder induces eosinophilia or symptoms. METHODS: We studied 10 normal persons. Each participant ingested 4 gm shiitake powder (open label) daily for 10 weeks (trial 1), and the protocol was repeated in these same subjects after 3 to 6 months (trial 2). Blood counts and serum samples were obtained biweekly (trial 1) or weekly along with stool specimens (trial 2). Eosinophil major basic protein and IL-5, IgE, and IgG antishiitake antibodies were measured in sera. Eosinophil-derived neurotoxin was measured in stool extracts. We defined responders as subjects having peak eosinophil counts four or more times their average baseline counts. RESULTS: Each trial had four responders, and trial 2 had one new and three repeat responders. Eosinophilia ranged from 400 to 3900/mm3. Responders had increased blood eosinophils, serum major basic protein, stool eosinophil-derived neurotoxin, and factors that enhanced eosinophil viability. Antishiitake IgE was not detected, and antishiitake IgG increased in two responders. Gastrointestinal symptoms coincided with eosinophilia in two subjects. Symptoms and eosinophilia resolved after discontinuing shiitake ingestion. CONCLUSIONS: Daily ingestion of shiitake mushroom powder in five of 10 healthy persons provoked blood eosinophilia, increased eosinophil granule proteins in serum and stool, and increased gastrointestinal symptoms. Shiitake ingestion suggests a model to study the eosinophil's role in the blood and gastrointestinal tract. Finally, our report raises concerns of possible adverse systemic reactions to this increasingly popular food.

Lin Y, et al. A double-blind treatment of 72 cases of chronic hepatitis with lentinan injection. News Drugs and Clin Remedies 1987;6:362-363. [Article in Chinese]

Lin MA, Wu ZB, Yang RF.  [Clinical observation on the effect of lentinan (776) in improving cellular immunofunction in leukemia patients]. Chung Hua Nei Ko Tsa Chih. 1985 Oct;24(10):592-5, 638. [Article in Chinese]

Murakami M, Kawabe K, Hosoi Y, Hojo S, Dobashi K, Iriuchijima T, Nakazawa T, Mori M. Decreased pulmonary perfusion in hypersensitivity pneumonitis caused by Shiitake mushroom spores. J Intern Med. 1997 Jan;241(1):85-88.
Abstract: Hypersensitivity pneumonitis is an occupational hazard of mushroom workers. We describe a patient with severe hypersensitivity pneumonitis caused by spores of the Shiitake mushroom (Lentinus edodes) who showed a marked decrease in pulmonary perfusion, as demonstrated by pulmonary scintigraphy. This patient was treated successfully with prednisolone. These results suggest that pulmonary vasculitis may be associated with patients with hypersensitivity pneumonitis, and that steroid therapy may be clinically useful in treatment.

Nakamura T. Shiitake (Lentinus edodes) dermatitis. Contact Dermatitis. 1992 Aug;27(2):65-70.
Abstract: Shiitake (Lentinus edodes) is a mushroom which is eaten in Chinese and Japanese meals and is nowadays the second most commonly produced edible mushroom in the world. Shiitake dermatitis was first described by Nakamura in 1977. This disease presents with very characteristic skin manifestations. From April 1974 to April 1991, I have observed 51 patients with shiitake dermatitis. The following description reviews the clinical manifestations, laboratory investigations and sources of shiitake dermatitis.

Nanba H, Kuroda H. Antitumor mechanisms of orally administered shiitake fruit bodies.
Chem Pharm Bull (Tokyo). 1987 Jun;35(6):2459-2464.

Nanba H, Mori K, Toyomasu T, Kuroda H. Antitumor action of shiitake (Lentinus edodes) fruit bodies orally administered to mice. Chem Pharm Bull (Tokyo). 1987 Jun;35(6):2453-2458.

Sastre J, Ibanez MD, Lopez M, Lehrer SB. Respiratory and immunological reactions among Shiitake (Lentinus edodes) mushroom workers. Clin Exp Allergy. 1990 Jan;20(1):13-19.

Sia GM, Candlish JK. Effects of shiitake (Lentinus edodes) extract on human neutrophils and the U937 monocytic cell line. Phytother Res. 1999 Mar;13(2):133-137.
Abstract: 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.

Taguchi I. Clinical efficacy of lentinan on patients with stomach cancer: End point results of a four-year follow-up survey. Cancer Detect Prevent Suppl 1987;1:333-349.
Abstract: End-point results of a 4-yr followup survey and a randomized control trial of lentinan (LNT) on patients with advanced or recurrent stomach cancer have been investigated in order to evaluate the clinical efficacy of LNT in combination with chemotherapeutic agent tegafur (FT). Eligible (68) patients in control groups were administered with FT consecutively at doses of 600 mg/day, and eligible (96) patients in the treated group were administered LNT in combination with FT. LNT was injected intravenously 2 mg weekly. Remarkable lifespan prolongation effects of LNT have been observed both at the end of the control trial and at the end of the followup survey (p less than 0.01) using Kaplan-Meier's method and the generalized Wilcoxian test. Remarkable survival at 1, 2 and 3 years has been observed in the treated group using lifetable analysis. Side effects of LNT have been transitional and not serious. Thus, LNT should be effective in combination with FT for patients with stomach cancer.

Taguchi T. [Lentinan]. Gan To Kagaku Ryoho. 1986 Oct;13(11):3294-3304. [Article in Japanese]

Taguchi T, Furue H, Kimura T, Kondo T, Hattori T, Itoh I, Ogawa N.  [Results of phase III study of lentinan]. Gan To Kagaku Ryoho. 1985 Feb;12(2):366-78. [Article in Japanese]
Abstract: A follow-up survey of survivals (Oct. 1 '80 to May 1, '84) in a randomized controlled study (Aug. '79 to Sept. 30' 80) of lentinan in combination administration with chemotherapeutic agents such as 5FU + mitomycin C or tegafur on patients with advanced or recurrent gastrointestinal cancer has shown that lentinan has been effective in such cases with regard to the following facts: 1) A life span prolongation effect at the end-point has been observed with statistical significance in lentinan treated patients as was found in the phase III study. 2) Using the life table analysis method, a higher rate of survival has been observed in the lentinan treated group, especially in combination with tegafur for gastric cancer, clearly showing such high survival rates as 12.97% (P less than 0.05) at two years after, and 9.51% (P less than 0.05) and 3.81%, at three and four years after respectively, and for colorectal cancer, 9.10% and 4.55% at two years and three years after, respectively.

Taguchi T. [Effects of lentinan in advanced or recurrent cases of gastric, colorectal, and breast cancer]. Gan To Kagaku Ryoho. 1983 Feb;10(2 Pt 2):387-393. [Article in Japanese]
Abstract: In order to evaluate clinical efficacy of Lentinan (LNT), a purified polysaccharide extracted from Lentinus edodes, randomized controlled studies with envelope method have been conducted on the patients with advanced or recurrent, stomach, colo-rectal and breast cancer. Administration condition of LNT for gastrointestinal cancer was designed as the following: LNT was administered intravenously at doses of 1 mg/person/day twice a week or 2 mg/person/day once a week in combination with mitomycine C + 5-FU (MF) or tegafur (FT). Control therapy was the administration of MF or FT alone. Survival curve drawn by Kaplan-Meier's method showed that life span prolongation effect of LNT was observed with statistical significance (P less than 0.05 or P less than 0.01) by use of generalized Wilcoxon's test. Moreover, improvement of host immune responses was observed in LNT treated group, and hematological survey showed that incidence rate of abnormal value was significantly low in LNT treated group. Thus, LNT should be effective for the patients with advanced or recurrent stomach or colo-rectal cancer in combination with chemotherapeutic agents such as MF or FT. Regarding advanced or recurrent breast cancer, study is underway. LNT has been administered as an agent for supportive therapy to the patients with complete response, partial response or stable diseases which were induced by prior surgery of oophorectomy. Again, life span prolongation effect of LNT has been observed with statistical significance (P less than 0.05). This result suggests that LNT would also be effective for the patients with advanced or recurrent breast cancer as an agent for supportive therapy.

Takehara M, Toyomasu T, Mori K, Nakata M. Isolation and antiviral activities of the double-stranded RNA from Lentinus edodes (Shiitake). Kobe J Med Sci. 1984 Aug;30(3-4):25-34.

Tan YH, Moore D. High concentrations of mannitol in the shiitake mushroom Lentinula edodes. Microbios. 1994;79(318):31-5.

Tarvainen K, Salonen JP, Kanerva L, Estlander T, Keskinen H, Rantanen T. Allergy and toxicodermia from shiitake mushrooms. J Am Acad Dermatol. 1991 Jan;24(1):64-66.
Abstract: Skin and respiratory symptoms developed within 2 months of exposure in a patient involved in the commercial production of shiitake mushrooms. A diagnosis of contact urticaria and allergic contact dermatitis from shiitake mushrooms was confirmed by prick and patch tests. The respiratory symptoms, their timing, the presence of precipitating IgG antibodies to shiitake spores and increased amounts of inflammatory cells and T lymphocytes in bronchoalveolar lavage indicated allergic alveolitis (mushroom worker's disease). A generalized exanthem developed in a second patient after eating raw shiitake mushrooms. Reactions to prick and patch tests with shiitake mushrooms were negative. The skin eruption in this patient corresponded to the previously reported shiitake-induced toxicodermia.

Threlkeld DS, ed. Anti-Infectives, Antiviral Agents, Didanosine. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Mar 1993, 406k-406t.

Threlkeld DS, ed. News, Keeping Up, December 1994, Lentinan. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Dec 1997, 805.

Wang GL, Lin ZB. [The immunomodulatory effect of lentinan]. Yao Hsueh Hsueh Pao. 1996;31(2):86-90. [Article in Chinese]
Abstract: Lentinan (LTN) was extracted from Lentinus edodes (Berk) Sing with molecular weight of 5 x 10(5). The effects of lentinan on cellular immune function were studied in vivo by measuring the cellular delayed type hypersensitivity (DTH) to dinitrofluorobenzene (DNFB) in cyclophosphamide (Cy)-comprised mice. The effect of lentinan on T lymphocyte proliferation to Con A on splenocytes and T lymphocyte subpopulations on thymocytes and on splenocytes from normal mice were also evaluated. Moreover, the effect of LTN on production of tumor necrosis factor (TNF) from murine peritoneal macrophage was also tested. LTN was administered at doses of 1, 5 and 10 mg.kg-1.d-1. The following results were observed: LTN administration(X6) augmented the T lymphocyts proliferation to Con A in normal mice; LTN restorated the DTH to DNFB impaired by single Cy(200 mg.kg-1 and 80 mg.kg-1, ip) after using LTN for 8 or 5 d; LTN administration (X6) either decreased the percentage of L3T4+ (Th), Lyt2+ (Ts) in thymocytes or increased the percentage of L3T4+, Lyt2+ in splenocytes; LTN(X6) administration elicited release of TNF from M phi in the presence of lipoplysaccharide (LPS). These results indicate that the immunomodulating effect of LTN may be relevant to change of T cell subpopulation and increase of TNF production.