Shiitake (Lentinus edodes)
Other Names
Shiitake (Japanese), xiang gu (fragrant mushroom, Chinese), black forest mushroom.
Key Components
Lentinan, ertadenine, LEM.
Natural Habitat
Far East, Japan, Korea, and China.
Overview
Used in Japan and China as a food and medicine for thousands of years, shiitake mushroom has been extensively studied for its immune boosting, anti-cancer, cholesterol-lowering, and anti-microbial properties. Shiitake is among the most popular and most studied medicinal mushrooms1. Its nutritional profile includes essential amino acids, lipids, vitamins B, C, minerals, and substantial amounts of ergosterol, the provitamin D2. Three substances identified in shiitake mushroom have been widely studied for their medicinal benefits: lentinan, ertadenine, and the shiitake mycelium extract known as LEM.
Lentinan, extracted from the cell wall of shiitake mushrooms, has immune-modulating and anti-cancer effects that have been demonstrated in a number of clinical, animal, and invitro studies. A clinical study of patients with advanced stomach, colorectal, and breast cancer found administration of lentinan from shiitake combined with chemotherapeutic agents improved immune response and prolonged life span3. Patients with malignant ascites and pleural effusion receiving injections of lentinan had improved Natural Killer cell activity and extended survival time with no serious toxicities4. In a study of stomach cancer patients, four-year follow up found remarkable lifespan prolongation effects in patients taking lentinan5. One animal study found lentinan had a 94.4% inhibition rate against tumors, activating lymphocytes and raising blood levels of four key anti-tumor cytokines (interleukin-1α, interleukin-2, interferon-γ, and tumor necrosis factor)6. Mice fed with lentinan before the introduction of human colon-carcinoma cells had significant regression of tumor formation and reduction in tumor size compared to mice not pre-fed with the mushroom extract7. In groups of mice treated repeatedly with a carcinogen, 100% developed cancer compared to 50% given shiitake extract8. Lentinan is licensed in Japan as a treatment for gastric cancer9.
Lentinan is also powerful anti-fungal and anti-viral. Studies have found it inhibits the growth of a variety of fungal species, and it shows activity against HIV in vitro10,11.
Eritadenine is a cholesterol-lowering compound found in shiitake in potentially therapeutic quantities12. Eritadenine from shiitake significantly reduced blood cholesterol in lab rats13,14. Clinical trials among Japanese women have found consuming shiitake caused a serum cholesterol drop of 7-9% in as little as a week15.
LEM is a water soluble extract from shiitake studied for its immunopotentiating and anti-viral properties16. Administration of LEM resulted in a rise in immune regulators within 2-6 hours in animal studies17. LEM fractions also stimulate immune Natural Killer cells, macrophages, T-cells, and interleukins18. In a study on colorectal cancer in animals LEM suppressed liver metastatis and prolonged survival time19. A LEM fraction also inhibited HIV replication in vitro and promoted the proliferation of bone marrow cells20. Another study found it significantly blocked the release of infectious herpes simplex virus21.
Interest in shiitake’s antimicrobial properties has increased in recent years due to problems with widespread antibiotic resistance22. Shiitake extracts tested on 29 bacterial and 10 fungal pathogens showed extensive antimicrobial activity against 85% of the organisms, including 50% of yeast and mold species23. Another study found shiitake extract inhibitory against all bacteria and fungi organisms tested24.
1 Stamets, Paul, and C. Dusty Wu Yao. Mycomedicinals: An informational treatise on mushrooms. MycoMedia, 2002. 52.
2 Hobbs, Christopher. Medicinal mushrooms: an exploration of tradition, healing & culture. No. Ed. 2. Botanica Press, 1995. 125.
3 Taguchi, T. Effects of lentinan in advanced or recurrent cases of gastric, colorectal, and breast cancer. Gan to kagaku ryoho. Cancer & Chemotherapy 10.2 Pt 2 (1983): 387.
4 Oka, Masaaki, et al. Immunological analysis and clinical effects of intraabdominal and intrapleural injection of lentinan for malignant ascites and pleural effusion. Biotherapy 5.2 (1992): 107-112.
5 Taguchi, T. Clinical efficacy of lentinan on patients with stomach cancer: end point results of a four-year follow-up survey. Cancer Detection and Prevention. Supplement: Official Publication of the International Society for Preventive Oncology, Inc 1 (1987): 333.
6 Yap, Ann-Teck, and Mah-Lee Ng. The medicinal benefits of lentinan (β-1, 3-D glucan) from Lentinus edodes (Berk.) Singer (shiitake mushroom) through oral administration. International Journal of Medicinal Mushrooms 7.1&2 (2005).
7 Ng, Mah-Lee, and Ann-Teck Yap. Inhibition of human colon carcinoma development by lentinan from shiitake mushrooms (Lentinus edodes). The Journal of Alternative & Complementary Medicine 8.5 (2002): 581-589.
8 Kurashige, S., Y. Akuzawa, and F. Endo. 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. Immunopharmacology and Immunotoxicology 19.2 (1997): 175-183.
9 Powell, M., 2010. Medicinal Mushrooms: A Clinical Guide, Mycology Press, East Sussex U.K. 64.
10 Ngai, Patrick HK, and Tzi Bun Ng. Lentin, a novel and potent antifungal protein from shiitake mushroom with inhibitory effects on activity of human immunodeficiency virus-1 reverse transcriptase and proliferation of leukemia cells. Life Sciences 73.26 (2003): 3363-3374.
11 Ngai, Patrick HK, and Tzi Bun Ng. Lentin, a novel and potent antifungal protein from shiitake mushroom with inhibitory effects on activity of human immunodeficiency virus-1 reverse transcriptase and proliferation of leukemia cells. Life Sciences 73.26 (2003): 3363-3374.
12 Enman, Josefine, Ulrika Rova, and Kris A. Berglund. Quantification of the bioactive compound eritadenine in selected strains of shiitake mushroom (Lentinus edodes). Journal of Agricultural and Food Chemistry 55.4 (2007): 1177-1180.
13 Fukushima, Michihiro, et al. Cholesterol-lowering effects of maitake (Grifola frondosa) fiber, shiitake (Lentinus edodes) fiber, and enokitake (Flammulina velutipes) fiber in rats. Experimental Biology and Medicine 226.8 (2001): 758-765.
14 Stamets, Paul, and C. Dusty Wu Yao. Mycomedicinals: An informational treatise on mushrooms. MycoMedia, 2002. 52.
15 Hobbs, Christopher. Medicinal mushrooms: an exploration of tradition, healing & culture. No. Ed. 2. Botanica Press, 1995. 134.
16 Yamamoto, Yoshiki, et al. Immunopotentiating activity of the water-soluble lignin rich fraction prepared from LEM: The extract of the solid culture medium of Lentinus edodes mycelia. Bioscience, Biotechnology, and Biochemistry 61.11 (1997): 1909-1912.
17 Morinaga, Hideo, et al. An in vivo study of hepatic and splenic interleukin-lβ mRNA expression following oral PSK or LEM administration. Cancer Science 85.12 (1994): 1298-1303.
18 Yamamoto, Yoshiki, et al. Immunopotentiating activity of the water-soluble lignin rich fraction prepared from LEM: The extract of the solid culture medium of Lentinus edodes mycelia. Bioscience, Biotechnology, and Biochemistry 61.11 (1997): 1909-1912.
19 Morinaga, Hideo, et al. An in vivo study of hepatic and splenic interleukin-lβ mRNA expression following oral PSK or LEM administration. Cancer Science 85.12 (1994): 1298-1303.
20 Suzuki, Harumi, et al. Structural characterization of the immunoactive and antiviral water-solubilized lignin in an extract of the culture medium of Lentinus edodes mycelia (LEM). Agricultural and Biological Chemistry 54.2 (1990): 479-487.
21 Sarkar, S., et al. Antiviral effect of the extract of culture medium of Lentinus edodes mycelia on the replication of herpes simplex virus type 1. Antiviral Research 20.4 (1993): 293-303.
22 Hearst, Rachel, et al. An examination of antibacterial and antifungal properties of constituents of shiitake (Lentinula edodes) and oyster (Pleurotus ostreatus) mushrooms. Complementary Therapies in Clinical Practice 15.1 (2009): 5-7.
23 Hearst, Rachel, et al. An examination of antibacterial and antifungal properties of constituents of shiitake (Lentinula edodes) and oyster (Pleurotus ostreatus) mushrooms. Complementary Therapies in Clinical Practice 15.1 (2009): 5-7.
24 Rao J.R., Millar B.C., Moore J.E. Antimicrobial properties of shiitake mushrooms (Lentinula edodes) (2009). International Journal of Antimicrobial Agents, 33 (6). 591-592.
Research
1. Lentin, a novel and potent antifungal protein from shiitake mushroom with inhibitory effects on activity of human immunodeficiency virus-1 reverse transcriptase and proliferation of leukemia cells
Ngai, P.H., and Ng, T.B. Life Sciences. 2003. 73 (26), 3363-3374.
Researchers isolated a new protein in shiitake mushroom, lentin, and evaluated it for its benefits. When tested against several species of fungi, it suppressed growth, suggesting it is a potent antifungal agent. Testing also revealed that lentin suppressed multiplication of leukemia cells and suppressed the activity of HIV-1 reverse transcriptase (which is necessary for the replication of the HIV virus).
2. Effects of lentinan in advanced or recurrent cases of gastric, colorectal, and breast cancer
Taguchi, T. Gan To Kagaku Ryoho. 1983. 10, 387-393.
In this clinical study, researchers evaluated the effects of lentinan, a polysaccharide from Lentinus edodes (shiitake mushroom) on gastrointestinal cancers. Cancer patients were given lentinan in combination with either mitomycine or tegafur (chemotherapy agents). Control groups received one of the two chemotherapy drugs without lentinan. Patients who received lentinan from shiitake mushroom lived longer than patients given chemotherapy drugs alone. Another group of patients with stable cancer given lentinan also had significantly longer life spans than those not receiving lentinan.
3. The medicinal benefits of lentinan (beta-1, 3-D glucan) from Lentinus edodes (Berk.) Singer (shiitake mushroom) through oral administration
Yap, A.T., and Ng, M.L. International Journal of Medicinal Mushrooms. 2005. 7 (1-2), 175-192.
In this in vivo study involving mice, researchers examined the effects of lentinan from shiitake mushroom on cancer. They achieved a 94% tumor reduction rate in the mice through oral administration of lentinan. Their tests revealed that the lentinan stimulated activity of interleukin-1a, interleukin-2, interferon gamma, and tumor necrosis factor alpha. Additional studies demonstrated lentinan’s ability to suppress tumor growth in immune deficient mice. Researchers conclude that lentinan can help boost the immune system.
4. Inhibition of human colon carcinoma development by lentinan from shiitake mushrooms (Lentinus edodes)
Ng, M.L., and Yap, A.T. The Journal of Alternative and Complementary Medicine. 2002. 8 (5), 581-589.
Researchers looked at the effects of lentinan from shiitake mushroom on human cancer cells implanted in mice. One group of mice was given lentinan daily for a week before being inoculated with human cancer cells. A control group of mice was not. The mice given lentinan had less tumor formation and smaller size tumors compared to the mice who were not given lentinan. In a related experiment, a group of mice were fed lentinan daily for a week; lymphocytes from the mice were transplanted into another group of mice, who were subsequently inoculated with cancer cells. Compared to a control group, the mice given lymphocytes from lentinan-fed mice had smaller tumors.
5. Quantification of the bioactive compound eritadenine in selected strains of shiitake mushroom (Lentinus edodes)
Enman, J., et al. Journal of Agricultural and Food Chemistry. 2007. 55 (4), 1177-1180.
In this study, researchers evaluated four strains of shiitake mushroom for their eritadenine content. Eritadenine is a naturally occurring cholesterol-lowering compound. They isolated the compound using methanol and analyzed it with further tests. All four strains showed up to ten times the amount of the cholesterol-lowering compound than was previously identified in other strains of shiitake. Researchers conclude that shiitake mushroom may be an excellent source of eritadenine for treatment of high cholesterol.
6. An examination of antibacterial and antifungal properties of constituents of shiitake (Lentinula edodes) and oyster (Pleurotus ostreatus) mushrooms
Hearst, R., et al. Complementary Therapies in Clinical Practice. 2009. 15 (1), 5-7.
Researchers evaluated the antibacterial and antifungal effects of shiitake and oyster mushroom extracts. The extracts were tested for the activities against 39 microbial agents. Ciproflaxin, an antibiotic, was used as the positive control. Shiitake mushroom extract performed favorably in comparison to the Ciproflaxin and oyster mushroom; it was effective against 85% of the microbial agents. Researchers conclude that the extract from shiitake mushroom has potential as an antibacterial, antifungal treatment.
7. Antimicrobial properties of shiitake mushrooms (Lentinula edodes)
Rao, J.R., et al. International Journal of Antimicrobial Agents. 2009. 33 (6), 591-592.
Researchers analyzed shiitake mushroom to identify and isolate natural antimicrobial compounds. They identified new metabolites not previously known, and tested various derived extracts against a number of fungal and bacterial agents. All extracts displayed a significant measure of effectiveness against the microbial agents tested.
8. Cholesterol-lowering effects of maitake (Grifola frondosa) fiber, shiitake (Lentinus edodes) fiber, and enokitake (Flammulina velutipes) fiber in rats
Fukushima, M., et al. Experimental Biology and Medicine. 2001. 226 (8), 758-765.
In this in vivo study involving rats, researchers looked at the effects of fiber from three species of mushroom on cholesterol levels. The rats were divided into four diet groups. All received a cholesterol-free diet for four weeks, plus one of the following: cellulose powder, maitake fiber, shiitake fiber, or enokitake fiber. While the rats who received any of the three mushroom fibers excreted more cholesterol, only those who consumed the maitake and enokitake fiber exhibited lower total cholesterol levels.
9. 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
Kurashige, S., et al. Immunopharmacology and Immunotoxicology. 1997. 19 (2), 175-183.
In this in vivo study, researchers looked at the effects of three mushrooms on cancer in mice. The mice were divided into four groups, and a carcinogenic chemical was given to all of them to induce cancer. Three different types of mushrooms, including Lentinus edodes (shiitake), were each given to one group of mice. The fourth group of mice, the control group, received no mushroom. 53% of the mice given shiitake mushroom remained cancer free, as did 46% to 65% of the other mushroom-fed mice. 100% of the control mice developed cancer. Mice given the carcinogen alone had suppressed macrophage and NK cell activity. Mice given the mushrooms, including shiitake, had greater macrophage and NK cell activity. Lymphocytes from the mushroom-eating mice were more effective against cancer cells as well.
10. An in vivo study of hepatic and splenic interleukin-l-beta mRNA expression following oral PSK or LEM administration
Morinaga, H., et al. Cancer Science. 1994. 85 (12), 1298-1303.
In this in vivo study, researchers examined the effects of two mushroom-derived substances on immune function. The two substances used were polysaccharide K from Trametes versicolor and the mycelia of Lentinus edodes. Mice were given one of the two substances. Within hours, levels of interleukin beta increased in the liver and spleen. Researchers believe that the interleukin stimulates natural killer or macrophage cells in the liver and may help to suppress metastasized colon cancer cells that have spread to the liver.
11. Clinical efficacy of lentinan on patients with stomach cancer: end point results of a four-year follow-up survey
Taguchi, T., et al. Cancer Detection and Prevention (Supplement). 1987. 1: 333-349.
Researchers evaluated the effects of lentinan from shiitake mushroom on survival rates of patients with advanced or recurring stomach cancer. Patients were given either tegafur (a chemotherapy drug) or tegafur plus lentinan. Those who received the lentinan plus tegafur lived significantly longer than those who received only the tegafur. Side effects of the lentinan were minimal. Researchers conclude that lentinan may be a helpful adjunct therapeutic treatment with tegafur.
12. Anticarcinogenic actions of water-soluble and alcohol-insoluble fractions from culture medium of Lentinus edodes mycelia
Sugano, N., et al. Cancer Letters. 1982. 17 (2), 109-114.
Researchers looked at fractions of the mycelia of Lentinus edodes for their effects on cancer in rats. A water-soluble fraction inhibited the formation of liver cancer; rats given the fraction had approximately 50% of liver cancers compared to control rats. One alcohol fraction of Lentinus inhibited liver cell proliferation; cancer cell proliferation in that group of rats was half the rate compared to the control group. A second alcohol fraction of Lentinus increased survival rates of rats with liver cancer.
13. Immunopotentiating activity of the water-soluble lignin rich fraction prepared from LEM—the extract of the solid culture medium of Lentinus edodes mycelia
Yamamoto, Y., et al. Bioscience, Biotechnology, and Biochemistry. 1997. 61 (11), 1909-1912.
In this series of in vitro experiments, researchers isolated and prepared a lignin from Lentinus edodes (shiitake mushroom) and examined it for its immune boosting effects. The lignan was compared to an extract from the mycelia of the same mushroom, and was found to have far more antiviral activity. The lignan boosted the effects of NK cells and macrophages and stimulated T cell activity in vitro. In human leukocytes infected with a virus, the lignan stimulated the secretion of interleukin-6, an important immune system cytokine.
14. Antiviral effect of the extract of culture medium of Lentinus edodes mycelia on the replication of herpes simplex virus type 1
Sarkar, S., et al. Antiviral Research. 1993. 20 (4), 293-303.
In this in vitro experiment, researchers looked at the antiviral effects of an extract from the mycelia of Leninus edodes (shiitake mushroom). African green monkey kidney cells that were infected with herpes simplex virus type 1 were treated with the extract. The virus did not spread beyond the kidney cells. Further testing revealed that the extract from shiitake mushroom likely prevented the virus from replicating at a later stage in the replication cycle. The researchers theorize the extract interfered with the encapsulation process of the virus.
15. Structural characterization of the immunoactive and antiviral water-solubilized lignin in an extract of the culture medium of Lentinus edodes mycelia (LEM)
Suzuki, H., et al. Agricultural and Biological Chemistry. 1990. 54 (2), 479-487.
Researchers isolated and identified a compound derived from the mycelia of Lentinus edodes. The fraction under study was designated as EP3, and its structure was analyzed. It was identified as a water-solubilized lignan (a type of phytoestrogen found in plants). EP3 showed demonstrated immune boosting and antiviral effects. It stimulated macrophage activity in study rodents and multiplication of bone marrow cells. In addition, EP3 suppressed replication of HIV in vitro.
16. Antibacterial effect of the culture fluid of Lentinus edodes mycelium grown in submerged liquid culture
Hatvani, N. International Journal of Antimicrobial Agents. 2001. 17 (1), 71-74.
Researchers tested the fluid in which Lentinus edodes (shiitake mushroom) was cultured. The fluid was tested for its effectiveness against Candida albicans, a fungus, and several species of bacteria. Testing indicated it was effective against Streptococcus pyogenes, Staphylococcus aureus and Bacillus megaterium. Researchers believe the active compound to be lenthionine.
17. Individual patient based meta-analysis of lentinan for unresectable/recurrent gastric cancer
Oba, K., et al. Anticancer Research. 2009. 29 (7), 2739-2745.
In this study, researchers evaluated data from 650 advanced gastric cancer patients to determine the effects of lentinan (from shiitake mushroom) given with chemotherapy. Patient outcomes were compared between patients who received chemotherapy only and those who received chemotherapy plus lentinan. They found that patients who received lentinan had significantly longer survival rates. In addition, researchers discovered that lentinan seemed to be more effective for patients whose cancer had spread to the lymph nodes, versus those whose cancer metastasized but did not involve the lymph nodes.
18. Aqueous extracts of Lentinula edodes and Pleurotus sajor-caju exhibit high antioxidant capability and promising in vitro antitumor activity
Finimundy, T.C., et al. Nutrition Research. 2013. 33 (1), 76-84.
Researchers investigated two mushrooms species, Lentinula edodes and Pleurotus sajor-caju, for their antioxidant and anti-cancer effects. They produced extracts of each and treated two cell lines with them: human laryngeal cancer and cervical cancer. Lentinula edodes had more polyphenols and a greater antioxidant activity against one type of free radical. Both mushroom extracts suppressed cancer cell proliferation and stimulated apoptosis; the anti-cancer effects were dose dependent. Researchers conclude that extracts from both mushroom types show potential as anti-oxidant, anti-cancer agents.
19. Direct cytotoxicity of Lentinula edodes mycelia extract on human hepatocellular carcinoma cell line
Yukawa, H., et al. Biological and Pharmaceutical Bulletin. 2012. 35 (7), 1014-1021.
Researchers investigated the anti-cancer effects of a polysaccharide fraction of dried, powdered shiitake mushroom mycelia. Human liver cancer cells were treated in vitro with the fraction; the cells died quickly. Researchers observed typical structural changes to the cells as they underwent apoptosis (cell death). Their investigations revealed that the mechanism for action was caspase-3 and caspase-8 pathways; caspase-3 and 8 are proteins associated with apoptosis. Researchers also tested the fraction against normal rat liver cells and normal mouse skin cells; the fraction had little to no effect on them. Researchers believe the shiitake mushroom fraction may be helpful in treating liver cancers.
20. Antihyperlipidemic effect of dietary Lentinus edodes on plasma, feces and hepatic tissues in hypercholesterolemic rats
Yoon, K.N., et al. Mycobiology. 2011. 39 (2), 96-102.
In this in vivo study involving mice, researchers examined the effects of shiitake mushrooms on cholesterol. Researchers worked with rats with high cholesterol, and gave one group feed with 5% fruiting bodies of Lentinus edodes. Total cholesterol, triglycerides, and LDL cholesterol decreased, and other cholesterol ratios measured showed great improvement compared to control rats. The mushroom-fed rats also lost weight and excreted more total lipids and cholesterol. Researchers looked at the liver cells of the mushroom-fed rats and found them to be normal. Researchers conclude that shiitake mushroom may be helpful in lowering cholesterol.
