Shiitake has long been favored by Asian people as a gourmet and medicinal mushroom. They eat shiitake stir-fried, in soup and in decoction . Today shiitake is found in markets throughout North America and Europe as well as Asia. It is the world’s 2nd most commonly cultivated mushroom. Shiitake’s popularity is ever increasing throughout Asia, North America, Europe and other parts of the world, partly because of its exotic flavor and partly because of its nutritional and various medicinal properties.
Nutritional Health Benefits
This delicate mushroom is also excellent in its nutritional value. It is a particularly good source of minerals and vitamins B1 (thiamin), B2 (riboflavin), B3 (niacin) and D. It also contains all the essential amino acids and dietary fiber1.
The caloric value of 100g of dried Shiitake is higher than 100g of raw potatoes (80kcal) or beef loin (224kcal), but lower than that of whole wheat or brown rice (328-350kcal). The protein content of dried shiitake is comparable to that of chicken, pork and beef but the fat count is much lower and the dietary fiber count is considerably higher than those meats (Table 1). Shiitake contains almost all the essential amino acids, with lysine and arginine being particularly abundant (Liu and Bau, 1980), and methionine and phenylalanine lesss abundant (Lasota and Sylwestrzak, 1989). In laboratory analysis it was found that amino acids, protein, glycogen, lipids, ascorbic acid, and total ash contents increased as the fruiting body developed (Fasidi and Kadiri, 1990). Based on these findings, it may be desirable to consume fully mature fruiting bodies for maximum nutritional value. The researchers generally found higher concentrations of nutrients in the cap than the stem of the fungus. Shiitake contains dietary fiber in the ratio of 6.7g per 100g of dried shiitake, which is a figure much higher than that for brown rice (0.2g), and sweet potatoes (0.9g). Dietary fiber prevents constipation, obesity, diabetes, hypertension, colon cancer and arteriosclerosis by lowering cholesterol level. In addition to dietary fiber, dried shiitake contains higher contents of potassium (K), iron (Fe), phosphorus (P) and vitamin B and D than most food sources. But it does not contain vitamins A and C (Table 1).
|Table 1. Constituents of dried/fresh shiitake grown on different logs and other food sources (per 100g edible portion)|
|Food Source||Energy (Kcal)||Moisture (%)||Protein (g)||Fat (g)||Ash (g)||Carbohydrates (mg)|
|Dried / pitch pine||261||11.6||17.3||1.7||4.8||57.9||6.7|
|Dried / alder||277||11.0||14.2||2.7||2.8||62.5||6.5|
|Dried / Mongolian oak||277||8.9||17.1||2.5||3.7||60.8||7.0|
|Dried / oak||272||10.6||18.1||3.1||4.5||57.0||6.7|
|Fresh / oak||27||90.8||2.0||0.3||0.8||5.4||0.7|
|Food source||Minerals (mg)||Vitamins (mg)|
|Dried / pitch pine||20||206||3.6||-**||–||0||0.66||1.61||7.7||0|
|Dried / alder||16||352||7.4||–||–||0||0.62||1.05||6.4||0|
|Dried / Mongolian oak||16||343||6.9||–||–||0||0.70||1.56||9.8||0|
|Dried / oak||19||268||3.3||25||2,140||0||0.48||1.57||19.0||0|
|Fresh / oak||6||28||0.6||5||180||0||0.08||0.23||4.0||Ø|
The high amount of ergosterol in fresh shiitake makes dried Shiitake an important vitamin D source because ergosterol converts to vitamin D2 in the presence of sunlight. Studies have shown that exposing shiitake to direct sunlight for 3 hours/day increases the vitamin D2 content up to 5 times. Sunlight exposure also increases the free amino acid content which is about 2,180mg/dl in the dry fruiting bodies, and it makes them sweeter and less bitter (Kiribuchi, 1991).
Eating Shiitake can prevent various vitamin B and D deficiencies including beri-beri2 (thiamin); cheilosis3, glossitis4, corneal vascularization5, Seborrheic dermatitis6, nerve tissue damage (riboflavin); abnormal growth in infants and children (niacin); and rickets7 (vitamin D). Vitamin D boosts calcium absorption and thus plays an important role in bone formation.
Medicinal Health Benefits
Asian people have enjoyed shiitake fruiting bodies for ages as a folk or traditional medicine. Modern medicine has come up with more purified, concentrated shiitake derivatives. Among them, “lentinan” and “LEM” are the most frequently studied compounds. In the following sections, major published laboratory and clinical work available on the anti-tumor/ anti-viral/ anti-bacterial/ hepatoprotective effects, as well as cardiovascular effects will be reviewed.
Major active compounds isolated from Lentinula edodes
EPS and EPS4
Most people who enjoy mushrooms, as well as health-care practitioners, seem to be quite interested in whether and what medicinal effects shiitake has in its whole, powder or extract form. Study results have shown that shiitake and its derivatives, especially lentinan and LEM, have strong anti-tumor/ anti-viral activities, when taken both orally and by injection, both in animals and in humans. These substances were found to work by enhancing various immune system functions rather than attacking the tumor cells or viruses themselves.
When powdered shiitake was fed to tumor-implanted mice as 10% of their normal diet, the growth of tumor8 was inhibited by 40% (Nanba et al., 1987). When shiitake content was increased to 30%, tumor growth was inhibited by nearly 78%. When shiitake-supplemented feed (20%) was given a week after and on the same day of tumor implantation, the tumor inhibition rates were 53.9% and 72.4%, respectively. In a 1969 study by Dr. Chihara, the growth of Sarcoma 180 was inhibited by 67-81%, when aqueous shiitake extracts were injected or powdered dried shiitake was fed.
Lentinan is a most frequently studied substance due to its strong anti-tumor effects. Dr. Chihara (1970) found that when doses of 0.5-1mg lentinan per kg of body weight were administered to laboratory mice, Sarcoma 180 regressed or disappeared in 80-100% of the subjects. This purified polysaccharide has been shown to be nontoxic and enhance the immune response, inhibiting the growth of tumors9 in animal studies.
Besides lentinan, various polysaccharides extracted from L. edodes showed antitumor and immunostimulating activities. Ikekawa et al. (1969) found that an intraperitoneal10 injection of the freeze-dried water extract of shiitake (200mg/kg/day, for 10 days) produced an 80.7% tumor inhibition rate. Fuji et al. (1978) isolated a polysaccharide containing an -mannan-peptide complex (KS-2) that strongly inhibited tumor growth when administered to mice both orally and intraperitoneally in doses between 1 and 100mg per kg of body weight.
Human clinical studies
Cancer patients suffer from severe side effects associated with cancer chemotherapy, as well as cancer. In clinical trials, when lentinan was administered to cancer patients during chemotherapy, tumor growth was inhibited, the effectiveness of chemotherapy was improved and patients’ life spans were prolonged. In Japan, lentinan is approved for use as a drug to prolong the lives of patients undergoing chemotherapy for stomach cancer.
Lentinan was shown to increase the survival time for 3 patients with inoperable gastric cancer (Mashiko et al., 1992; Shimizu et al., 1981), and of women with recurrent breast cancer who have undergone surgical therapy (Kosaka et al., 1985). In a randomized controlled trial, 275 patients with advanced or recurrent gastric cancer were given either one of two kinds of chemotherapy11 alone or with lentinan injections. Statistically, the best results were obtained when lentinan was administered prior to chemotherapy (Taguchi et al., 1981). In another group of 16 patients with advanced cancer, lentinan (4mg/week for 4 weeks) was injected into malignant peritoneal and/or pleural effusions12. Eighty percent of the lesions showed clinical responses, and performance status13 was improved in 7 patients. The survival time for patients who responded immunologically to the treatment was 129 days and 49 days for those who did not respond (Oka et al., 1992).
Researchers found lentinan produces its biological effects, including anti-tumor effects, anti-bacterial effects (tuberculosis) and anti-viral effects (HIV), not by attacking cancer cells, bacteria or viruses directly, but activating different immune responses in the host. Aoki et al. identified lentinan’s immunostimulating effects in animal and human systems in vitro14 and in vivo15. Since the immune mechanisms behind various types of cancer are so complex and that highly purified substances are not subject to all situations or individuals, shiitake’s immune system strengthening effects in animals and humans are briefly listed in Table 2.
|Table 2. Immune effects of lentinan in vitro and in vivo in animals and humans|
|Activity||Experimental Animal System||Human System|
|in vitro||in vivo||in vitro||in vivo|
|Inhibition of immunosuppressive substance production||–||++||–||++|
|Imnmunopotentiative substance production||–||++||–||++|
|C3 splitting activity||–||+||–||–|
|Production of colony-stimulating factor||+||–||–||–|
|Production of lymphocyte-activating factor (IL-1)||+||+||+||+|
|Inhibition of prostaglandin release||–||+||–||–|
|Natural killer cell activation||+||+||±~+||++|
|Activation of helper T-cells||–||+||+||++|
|Activation of killer T-cells||+||+||+||–|
|Activation of cytotoxic macrophages||–||+||–||+|
|Delayed-type hypersensitivity reaction||+||+~++||–||–|
HIV/AIDS still remains as one of the greatest challenges of the modern medicine. Strong anti-viral activities of lentinan and LEM have drawn great attention in the medical community. LEM seems to be the stronger of the two. The major viral diseases studied in associated with anti-viral effects of L. edodes are Hepatitis B and HIV.
Lentinan has shown anti-viral activity in mice against viruses and virus-induced tumors16. Lentinan could also stimulate non-specific resistance against respiratory viral infections in mice. Notable protection was induced by lentinan administered through the nose before lethal influenza virus infection which could be confirmed by a reduction of the lung virus titres17. Lentinan also conferred complete protection against an LD7518 challenge dose of virulent influenza virus, and significantly prolonged the survival time in mice after an LD100 challenge administered through a vein.
Human clinical studies
Lentinan was successful in treating an HIV-infected patient with low helper-T cell and low lymphocyte counts and low NK cell activity. A drip infusion of lentinan restored these immune cell counts to normal (Aoki, 1984a). Lentinan is particularly active at augmenting helper-T cell activity (Akiyama et al., 1981 ) and thus, assists HIV treatment.
LEM may also be useful in the treatment of AIDS. It has been shown to inhibit HIV infection of cultured human T-cells (Izuka, 1990), and it potentiates the effects of AZT (one of anti-HIV medications) against viral replication in vitro (Tochikura et al., 1987). The mechanism of its action is not known for certain, but the extract was found to activate macrophages and stimulate the production of interleukin-1.
In addition to lentinan and LEM, water-soluble lignins with anti-viral and immunomodulating effects have also been isolated from shiitake mycelium (Hanafusa et al., 1990). JLS, a new compound recently derived from the mycelium, showed the ability to block the release of infectious Herpes simplex virus type I in animals (Sarkar et al., 1993). Shiitake contains water-solubilized lignin derivatives, such as EPS and EPS4, which have shown immunological and anti-viral activities not only against Herpes simplex I and II, but also against equine encephalitis, polio virus, measles, mumps, and HIV (Suzuki et al., 1989, 1990; Sorimachi et al., 1990). In addition, an aqueous extract of the mycelium (known as JLS-18), consisting of 65- 75% lignin, 15-30% polysaccharide, and 10-20% protein, inhibited the Herpes virus both in vitro and in vivo (Koga et al., 1991).
Even for healthy folks, there are benefits in eating mushrooms. The Star, a Malaysian daily newspaper, reported on a pilot study by the National University of Singapore. The study showed that people who ate about 30g of shiitake mushrooms a day for four weeks were less susceptible to flu symptoms during the flu season in Singapore (The Star, October 30, 2000 ).
Active compounds isolated from shiitake have shown potent anti-bacterial activities. Among them, lentinan is the most frequently studied compound as a promising anti-bacterial agent.
Lentinan is also effective against tuberculosis infections in the lungs of mice (Kanai and Kondo, 1981). It increased host resistance to infection with the potentially lethal Listeria monocytogenes19 (Aoki, 1984b). Lentinan may afford protection against toxic stress from bacterial endotoxin20. For instance, when lentinan was administered to rabbits with endotoxin, its clearance was increased (Yokota et al., 1991).
Human clinical studies
For instance, in a study of 3 patients with pulmonary tuberculosis who had shed drug resistant M. tuberculosis21 bacteria for 10 years, after treatment with lentinan, the excretion of M. tuberculosis ceased (Usuda, 1981). These findings have been supported by several animal studies (Kanai and Kondo, 1981; Kanai et al., 1980).
Sugano et al. noted in their 1982 study that the injection of LEM slowed the growth of cancerous liver tumors in rats. Studies by Lin and Huang (1987) and Mizoguchi et al. (1987) also observed that polysaccharide fractions from shiitake demonstrated liverprotective action in animals.
Human clinical studies
In an unrandomized, uncontrolled clinical study by Dr. Amagase (1987), 40 patients with chronic hepatitis orally took 6g of LEM per day for 4 months. Hepatitis B symptoms were alleviated in all of the patients, and the virus was inactivated.
One unique amino acid, called eritadenine, is believed responsible for shiitake’s ability to reduce cholesterol and lipids in blood (Yamamura and Cochran, 1974).
In a 1996 study, Dr. Kaneda found that blood serum cholesterol in lab mice was lowered by injection of hot water extract of shiitake. When eritadenine (0.005%) was added to the diet of rats, total cholesterol level was lowered by 25% in as little as one week (Chibata et al., 1969). The cholesterol-lowering activity of eritadenine was more remarkable in rats on a high-fat diet than in those on a low-fat diet (Rokujo et al., 1969). Eritadenine was found to accelerate cholesterol metabolism and excretion. It is highly expected as a potential anti-high blood pressure agent.
Human clinical studies
In a 1974 study by Suzuki and Oshima, 10 young Japanese women showed a decrease in serum cholesterol of 7% after one week on dried shiitake (9g). Another group who ate 90g of fresh shiitake showed a 12% drop in serum cholesterol after 7 days. A further study in young women on fresh shiitake (90g) for a week included butter (60g) in addition to the shiitake. In a control group of 10 women, only the butter was added to the diet for one week. In this group serum cholesterol showed a 14% increase, whereas the group on the shiitake and the butter showed a 4% decrease. A separate study found that people in their sixties or older showed a 9% drop in cholesterol, whether they took dried or fresh shiitake.
Toxicity and side effects
L. edodes is non-poisonous and safe, though some people may experience minor side effects or allergic reactions. Most common cases are shiitake dermatitis or diarrhea. They are associated with consumption of half-cooked or raw shiitake. During 17 years researchers have observed numerous cases of shiitake-induced dermatitis (Nakamura and Kobayashi, 1985; Ueda et al., 1992). Nakamura (1992) reviewed the clinical manifestations, laboratory findings, and sources of shiitake dermatitis. It is known that people who work indoors in the cultivation of shiitake are prone to an immune reaction to spores called “mushroom worker’s lung.” Antibodies to shiitake spore antigens can be demonstrated in people who show symptoms. Protective masks can help, but not entirely eliminate, an eventual reaction to the spores after continued exposure (Van Loon, 1992).
A watery extract of the whole fruiting body is reported to lessen the effectiveness of the blood platelets in the process of coagulation, so people who bleed easily or who are taking blood thinners should use caution when chronically using shiitake or its water-soluble fractions (Yang and Jong, 1989).
In a phase I clinical trial of 50 patients with advanced cancer, 0.5-50mg/person/day lentinan was given by injection for 2 weeks. Minor side effects such as a slight increase in GOT and GPT liver enzymes22 and a feeling of mild oppression on the chest were caused at 5mg/day, but these disappeared after lentinan administration was stopped.
In a phase II trial, only 17 of 185 patients with advanced cancer had similar transitory side effects. Skin eruptions were noted in 7 cases, mild oppression on the chest, 6 cases, and mild liver dysfunction, 4 cases (Taguchi et al., 1982).
In a follow-up phase III trial by the same researchers, 15 out of 275 patients experienced nausea and vomiting (2), heaviness in the chest (4), heat sensations (2), and one case each of face flushing, a rise in blood pressure, and heaviness in the head (Taguchi et al., 1981b; Aoki, 1984b). Lentinan seems to be very safe when given to humans in the dosage range of 1- 5mg/day once or twice a week by intravenous injection (Taguchi et al., 1982).
Shiitake is used medicinally for diseases involving depressed immune function, including cancer, AIDS, environmental allergies, and frequent flu and colds. It also appears beneficial for soothing bronchial inflammation and regulating urine incontinence (Liu and Bau, 1980), as well as for reducing chronic high cholesterol. According to one prominent Japanese researcher, lentinan is an immunomodulating agent. For older persons, it serves as a general rejuvenating agent, no matter what the condition of their health. For young people, it presents a potent protection from overwork and exhaustion (Aoki, 1984b) or chronic fatigue syndrom. In Japan, lentinan is currently classified as a drug, whereas LEM is considered a food supplement.
As more clinical research on Shiitake and preparations isolated from shiitake is published, the effective range of application will be more broadened. But the highly purified compounds including lentinan and LEM are subject to a particular situation or individual. Addition of shiitake to a daily diet is highly recommended to maintain good nutrition, to boost the immune system and to prevent various diseases. Shiitake containing almost all essential amino acids will serve as an excellent protein supplement.
1 dietary fiber: coarse, indigestible plant matter, consisting primarily of polysaccharides, that when eaten stimulates intestinal peristalsis
2 beri-beri: disease involving swelling, tingling or burning sensation in the hands and feet, confusion, difficulty breathing (from fluid in the lungs),and uncontrolled eye
3 cheilosis: cracking at the corners of the mouth and inflammation of the mucous membranes in the mouth
4 glossitis: swollen and reddened tongue
5 corneal vascularization: reddening, burning, itching of the eyes and sensitivity to light
6 Seborrheic dermatitis: unusual dryness and greasy scaling of the skin
7 rickets: a childhood disorder involving softening and weakening of the bones
8 Sarcoma 180 and MM-46. They are murine tumors.
9 Sarcoma 180 (Maeda et al., 1974b; Togami et al., 1982), ascites hepatoma 134 (Moriyama et al., 1981), and Ehrlich carcinoma (Ying et al., 1987)
10 administered by entering the peritoneum. Peritoneum is the serous membrane that lines the walls of the abdominal cavity and folds inward to enclose the viscera.
11 mitomycin C with 5-fluorouracil or tegafur
12 peritoneal/pleural effusion: an abnormal accumulation of fluid in the peritoneal and pleural space. Pleuron is the thin serous membrane that envelops each lung and
folds back to make a lining for the chest cavity.
13 performance status: one of the indicators doctors use for assessing how a patient’s disease is progressing and how the disease affects the daily living abilities of the
patient and for determining appropriate treatment and prognosis
14 in vitro: in an artificial environment outside the living organism
15 in vivo: within a living organism
16 VSV (vesicular stomatitis virus)-encephalitis, Abelson (Chang, 1981), and adenovirus type 12 virus-induced tumors (Hamada, 1981)
17 titer: concentration of a substance in solution or the strength of such a substance determined by adding to it a standard reagent of known concentration in carefully measured
amounts until a reaction of definite and known proportion is completed
18 LD: lethal dose. LD 75 is the amount of drug it takes to kill 75% of the subject group.
19 Listeria monocytogenes: a disease-causing bacterium that is food borne and causes an illness called listeriosis
20 endotoxin: toxin produced by certain bacteria and released upon destruction of the bacterial cell
21 Mycobacterium tuberculosis: a bacterium causing tuberculosis in human
22 GOT: glutamine-oxaloacetic transaminase, GPT: glutamic-pyruvic transaminase. These liver enzymes are elevated for a variety of reasons. They are checked for suspected liver disease, also for suspected mononucleosis, or to monitor the effect of long term drug therapy on the liver.
- Akiyama, Y. et al. 1981. Immunological characteristics of anti-tumor polysaccharides lentinan and its analogues,as immune adjuvants. In: Aoki, T. et al., eds: Manipulation of Host Defense Mechanisms. Amsterdam, the Netherlands: Excerpta Medica. International Congress Series 576.
- Amagase, H. 1987. Treatment of hepatitis B patients with Lentinus edodes mycelium. In: Proceedings of the 12th International Congress of Gastroenterology. Lisbon. pp. 197.
- Aoki, T. 1984a. Antibodies to HTL and HTL in sera from two Japanese patients, one with possible pre-AIDS. Lancet 20: 936-937.
- Aoki, T. 1984b. Lentinan. In: Femchel, R.L. and M.A. Chirgis, eds: Immunology Studies: Immune Modulation Agents and Their Mechanisms 25: 62-77.
- Arinaga, S. et al. 1992. Enhanced production of interleukin-1 and tumor necrosis factor by peripherial monocytes after lentinan administration in patients with gastric carcinoma. International Journal of Immunopharmacology 14: 43-47.
- Chibata, I. et al. 1969. Lentinacin: A new hypocholesterolemic substance in Lentinus edodes. Expenentia 25: 1237-1238.
- Chihara, G. et al. 1969. Inhibition of mouse Sarcoma 180 by polysaccharides from Lentinus edodes (Berk.) Sing. Nature 222: 631-688.
- Chihara, G. et al. 1970. Fractionation and purification of the polysaccharides with marked antitumor activity, especially lentinan, from Lentinus edodes (Berk.) Sing. (an edible mushroom). Cancer Research 30: 2776-2781.
- Fujimoto, T. et al. 1992. Evaluation of basic procedures for adoptive immunotherapy for gastric cancer. Biotherapy 5: 153-163.
- Hahafusa, T. et al. 1990. Intestinal absorption and tissue distribution of immunoactive and antiviral water-soluble [14C] lignins in rats. Yakubutsu Dotai 5: 661-674.
- Izuka, H. 1997. Production of Lentinus edodes mycelia extract (LEM). Food Reviews International 13: 343-348.
- Izuka, C. 1990. Antiviral composition extracts from basidiomycetes. European Patent Application EP 464,311. In: CA, 116: 76351z.
- Kanai, K., and E. Kendo. 1981. Immunomodulating activity of lentinan as demonstrated by frequency limitation effect on post-chemotherapy relapse in experimental mouse tuberculosis, In: Aoki, T. et al., eds: Manipulation of Host Defense Mechanisms. Amsterdam, the Netherlans: Excerpta Medica. International Congress Series 576.
- Kiribuchi, T. 1991. Effective uses of fungi by UV irradiation. 3. Change of free amino acid composition in fungi by suli or ultraviolet light irradiation. Nippon Kasei Gakkaishl, 42,415-421. In: CA, 115: 130700g.
- Koga, J. et al. 1991. Antiviral fraction of aqueous Lentinula edodes extract. European Patent Application EP 437,346 (Cl. 012pa/02), JP Application 90/3,818. In: CA, 115: 134197w.
- Kosaka, A. et al. 1985. Synergistic effect of lentinan and surgical endocrine therapy on the growth of DMBA-induced mammary tumors of rats and of recurrent human breast cancer. Int Coplgr Ser Excerpta Medica, 690,138-150. In: CA, 104: 81628b.
- Lasota, W., and J. Sylwestrzak. 1989. Chemical composition of cultivated mushrooms. Part . Shiitake Lentinus edodes (Berk.) Sing. Bromatol Chem Toksykol. 22: 167-171. In: CA, 114,205741m.
- Lin Z. and Huang Y. 1987. Protective action of Lentinan against experimental liver injuries. J. Beijing Med. Univ. 19: 93-95.
- Liu, B. and Y.-S. Bau Y. 1980. Fungi Pharmacopoeia. CA: Oakland: Kinoko Press.
- Maeda, Y.Y. et al. 1974. Unique increase of serum protein components and action of antitumour polysaccharides, Nature 252-250.
- Mashiko, H. et al. 1992. A case of advanced gastric cancer with liver metastasis completely responding to a combined immunochemotherapy with UFT, mitomycin C and lentinan. Gan to Kagaku Ryoho 19: 715-718.
- Miyakoshi, H., and T. Aoki. 1984a. Acting mechanisms of’ lentinan in human: . Augmentation of DNA synthesis and immunoglobulin production of peripheral mononuclear cells. Journal of Immunopharmacology 6: 365-371.
- Miyakoshi, H., and T. Aoki. 1984b. Acting mechanisms of lentinan in human: . Enhancement of non-specific cell- mediated cytotoxicity as an interferoninducer. Journal of Inmunopharmacology 6: 373-379.
- Mizoguchi, Y. et al. 1987. Protection of liver cells against experimental damage by extract of cultured Lentinus edodes mycelia (LEM). Gastroenterol. Jpn. 22: 459-464.
- Nakamura, T. 1992. Shiitake (Lentinus edodes) dermatitis. Contact Dermatitis 27: 65-70.
- Nakamura, T., and A. Kobayashi. 1985. Toxicodermia caused by the edible mushroom shiitake (Lentinus edodes). Hautarzt 36: 591-593.
- Nanba, H. et al. 1987. Antitumor action of shitake (Lentinus edodes) fruit bodies orally administered to mice. Chemical & Pharmaceutical Bulletin 35: 2453- 2458.
- Oka, M. et al. 1992. Immunological analysis and clinical effects of intra-abdominal and intrapleural injection of lentinan for malignant ascites and pleural effusion. Biotherapy 5: 107-112.
- Rokujo, T. et al. 1969. Lentysine: a new hypolipemic agent from a mushroom. Life Science 9: 381-385.
- Sakamaki, S. et al. 1993. Individual diversity of IL-6 generation by human monocytes with lentinan administration. International Journal of Immunopharmacology 15: 751-756.
- Sarkar, S. et al. 1993. Antiviral effect of the extract of culture medium of Lentinus edodes mycelia on the replication of herpes simplex virus type . Antiviral Research 20: 293-303.
- Sendo, F. et al. 1981. Augmentation of natural cell-mediated cytotoxicity by administration of lentinan in mice. In: Aoki T. et al., eds: Manipulation of Host Defense Mechanisms. Amsterdam, the Netherlands: Excerpta Medica. International Congress Series 576.
- Shimizu, T. et al. 1981. A combination of regional chemotherapy and systemic immunotherapy for the treatment of inoperable gastric cancer. In: Aoki T. et al., eds: Manipulation of Host Defense Mechanisms. Amsterdam, the Netherlands: Excerpta Medica. International Congress Series 576.
- Sorimachi, K. et al. 1990. Antiviral activity of water-solubilized lignin derivatives in vitro. Agricultural and Biological Chemistry 54: 1337-1339. In: CA, 113: 52122n.
- Suzuki, H. et al. 1989. Inhibition of the infectivity and cytopathic effect of human immunodeflciency virus by water-soluble lignin in an extract of the culture medium of Lentinus edodes mycelia (LEM). Biochemical and Biophysical Research Communications 160: 367-373. In: CA, 110: 2051571.
- Taguchi, T. et al. 1981. Phase and studies of lentinan. In: Aoki, T. et al., eds: Manipulation of Host Defense Mechanisms. Amsterdam, the Netherlands: Excerpta Medica. International Congress Series 576.
- Taguchi, T. et al. 1982. Clinical trials on lentinan (polysaccharide). In: Yamainura, Y. et al., eds: Immunomodulation by Microbial Products and Related Synthetic Compounds. New York: Elsevier. pp.467-475.
- Takeshita, K. et al. 1993. Effect of lentinan on lymphocyte subsets of peripheral blood, lymph nodes, and tumor tissues in patients with gastric cancer. Surgery Today 23: 125-129.
- Tani, M. et al. 1992. In vitro generation of activated natural killer cells and cytotoxic macrophages with lentinan. European Journal of Clinical Pharmacology 42: 623-627.
- Tani, M. et al. 1993. Augmentation of lymphokine-activated killer cell activity by lentinan. Anticancer Research 13: 1773-1776.
- Tochikura, T.S. et al. 1987. Suppression of human immunedeflciency virus replication by 3-azido-3-deoxythymidine in various human haematopoetic cell lines in vitro: augmentation by the effect of lentinan. Japan Journal of Cancer Research (Gann) 78: 583.
- Ueda, A. et al. 1992. Allergic contact dermatitis in shiitake (Lentinus edodes ([Berk.] Sing.) growers. Contact Dermatitis 26: 228-233.
- Usuda, Y. et al. 1981. Drug-resistant pulmonary tuberculosis treated with lentinan. In: Aoki T. et al., eds: Manipulation of Host Defense Mechanisms. Amsterdam, the Netherlands: Excerpta Medica. International Congress Series 576. p. 50.
- Van Loon, P.C. 1992. Mushroom worker’s lung: detection of antibodies against Shiitake (Lentinus edodes) spore antigens in shiitake workers. Journal of Occupational Medicine 34: 1097-1101.
- Yamamura Y., and K.W. Cochran. 1974. Chronic hypocholesterolemic effect of Lentinus edodes in mice and absence of effect on scrapie. Mushroom Science (Part ): 489-493.
- Yang, Q.Y., and S.C. Jong. 1989. Medicinal mushrooms in China. In: Crabbe K. and O. Hilber, eds: Mushroom Science (Part I): Proceedings of the 12th International Congress on the Science and Cultivation of Edible Fungi. Braunschweig, Germany: Institut für Bodenbiologie, Bundesforschungsanstolt für Landwirtschaft. pp. 631-643.
- Yokota, M. et al. 1991. Endotoxemia is masked in fungal infection due to enhanced endotoxin clearance by beta-glucan. International Surgery 76: 255-260.