Shiitake – Lentinula edodes

Chinese nameXiang Gu (Fragrant Mushroom)

L. edodes is an important ingredient in Asian cuisine and its annual production (2 million tonnes) is second only to the common button mushroom (Agaricus bisporus). As well as being delicious, it has an excellent nutritional profile with high levels of B vitamins and pro-vitamin D2 (ergosterol)1.
Lentinan, a highly purified polysaccharide from L. edodes, is licensed in Japan for the treatment of gastric cancer and L. edodes is also one of the main species from which the popular mushroom α-glucan extract AHCC (Active Hexose Correlated Compound – reported to be the second most widely used supplement by cancer patients in Japan, after Agaricus subrufescens2) is derived. L. edodes is also the source of LEM, a crude mycelial extract containing glycoproteins, nucleic acid derivatives, vitamin B compounds and ergosterol with proven immunomodulating properties.
Other bioactive compounds from L. edodes include eritadenine, which shows promise for lowering cholesterol levels, and Lentin, an anti-fungal protein, which also inhibits HIV-1 reverse transcriptase activity and proliferation of leukaemia cells3.

CANCER – Analysis of 5 clinical trials with a total of 650 participants shows that the addition of Lentinan at 2mg/week to standard chemotherapy offers a significant advantage over chemotherapy alone in terms of survival for patients with advanced gastric cancer, patients with lymph node metastasis having slightly better results than patients without4.
Additional trials confirm increased survival, reduced side effects from chemotherapy and improved quality of life in patients with colorectal, hepatocelluar, oesophagel, breast cancer and metastatic prostate cancer5,6. In a trial with 69 metastatic prostate cancer patients the 50% survival length of treated and control patients was 48 and 35 months respectively, while the five-year survival rate of treated patients was 43%against 29%in the control group7.
Although usually delivered by injection, Lentinan is also orally bioavailable although the clinical dosage is likely to be significantly higher8,9.
Clinical trials using AHCC, a polysaccharide extract from multiple mushroom species including L. edodes, have shown positive effects in a number of cancers including breast, prostate and liver with reduction in side-effects from conventional treatment and improvement in haematopoetic parameters and cancer markers at a dose of 3g/day10-16.

CHOLESTEROL CONTROL – Eritadenine has been shown to be a potent inhibitor of S-adenosylhomocysteine hydrolase and to accelerate excretion of ingested cholesterol and its metabolic decomposition. When added to the diet of rats (0.005%), eritadenine caused a 25% decrease in total cholesterol in one week1.
Early studies indicated that levels found in whole shiitake mushrooms were too small to have a significant effect but recent research has shown the presence of eritadenine at levels 10 times higher than originally thought, indicating therapeutic possibilities for shiitake, particularly in cases where patients have shown statin intolerance17,18. .
In clinical trials dried L. edodes (9g/day) decreased serum cholesterol 7-10% in patients suffering from hypercholesterolemia and 90g/day fresh L. edodes (equivalent to 9g/day dried mushroom) led to a decrease in total cholesterol of 9-12% and triglycerides of 6-7%1.

HEPATITIS B – Polysaccharide extracts from L. edodes have been shown to have broad anti-viral and hepatoprotective properties19. In a study of 40 patients with chronic hepatitis B, LEM at 6g/day for 4 months led to improved liver function and resulted in 17 patients becoming seronegative for Hbe antigen (HbeAg)20.

HIV – LEM increased the T-cell count in HIV patients with AIDS symptoms from 1250/mm3 to 2550/mm3 after 60 days1.

CANDIDAIn vitro studies show L. edodes to have consistently high levels of antimicrobial activity, including the highest anti-candidal action among several mushroom species.

Main Therapeutic Application – Cancer, cholesterol control, especially as an adjunct to statins.
Key Components – Polysaccharides and eritadenine.
Dose – 2-6g/day polysaccharide extract for immune support. 9g/day dried fruit body for cholesterol control.
Because eritadenine’s cholesterol-lowering action differs from that of prescription statins or natural sources of statins such as Pleurotus ostreatus or Monascus purpureus, it can usefully be combined with them in cholesterol control protocols.
Safety – Although there have been a number of reports of dermatitis (Shiitake Dermatitis) developing following consumption of L. edodes these have been related to consumption of the raw mushroom and no cases have been reported for the use of L. edodes in supplement form21-26.

1. Shiitake (Lentinus edodes). Wasser SP. In: Encyclopedia of Dietary Supplements. New York : Marcel Dekker, 2005. pp. 653–664.
2. Nationwide survey on complementary and alternative medicine in cancer patients in Japan. Hyodo I, Amano N, Eguchi K, Narabayashi M, Imanishi J, Hirai M, Nakano T, Takashima S. J Clin Oncol. 2005;23(12):2645–2654.
3. Lentin, a novel and potent antifungal protein from shitake mushroom with inhibitory effects on activity of human immuno-deficiency virus-1 reverse transcriptase and proliferation of leukaemia cells. Ngai PH, Ng TB. Life Sci. 2003;73(26):3363–3374.
4. Individual patient based meta-analysis of lentinan for unresectable/recurrent gastric cancer. Oba K, Kobayashi M, Matsui T, Kodera Y, Sakamoto J. Anticancer Res. 2009;29(7):2739–2745.
5. Effects of lentinan in advanced or recurrent cases of gastric, colorectal, and breast cancer. Taguchi T. Gan To Kagaku Ryoho. 1983;10(2 Pt 2):387–393.
6. Combination therapy with lentinan improves outcomes in patients with esophageal carcinoma. Wang JL, Bi Z, Zou JW, Gu XM. Mol Med Rep. 2012;5(3):745–748.
7. Effect of lentinan for advanced prostate carcinoma. Tari K, Satake I, Nakagomi K, Ozawa K, Oowada F, HigashiY, Negishi T, Yamada T, Saito H, Yoshida K. Hinyokika Kiyo. 1994;40(2):119–123.
8. Inhibition of human colon carcinoma development by lentinan from shiitake mushrooms (Lentinus edodes). Ng ML, Yap AT. J Altern Complement Med. 2002;8(5):581–589.
9. The medicinal benefits of Lentinan (β-1, 3-D glucan) from Lentinus edodes (Berk.) singer (Shiitake Mushroom) through oral administration. Yap AT, Ng MH. Int J Med Mushrooms. 2005;7(12):175–192.
10. Immunomodulatory and anticancer effects of active hemicellulose compound (AHCC). Ghoneum MH, Wimbley M, Salem FB, McKlain A, Atallah N, Gill G. Int J Immunotherapy. 1995;11(1):23–28.
11. Prognostic improvement of patients with advanced liver cancer after active hexose correlated compound (AHCC) treatment. Cowawintaweewat S, Manoromana S, Sriplung H, Khuhaprema T, Tongtawe P, Tapchaisri P, Chaicumpa W. Asian Pac J Allergy Immunol. 2006;24(1):33–45.
12. Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses. Gao Y, Zhang D, Sun B, Fujii H, Kosuna K, Yin Z. Cancer Immunol Immunother. 2006;55(10):1258–1266.
13. Dramatic prostate-specific antigen response with activated hemicellulose compound in metastatic castration-resistant prostate cancer. Turner J, Chaudhary U. Anticancer Drugs. 2009;20(3):215–216.
14. An evidence-based review of a Lentinula edodes mushroom extract as complementary therapy in the surgical oncology patient. Shah SK, Walker PA, Moore-Olufemi SD, Sundaresan A, Kulkarni AD, Andrassy RJ. JPEN J Parenter Enteral Nutr. 2011;35(4):449–458.
15. Effect of active hexose-correlated compound in women receiving adjuvant chemotherapy for breast cancer: a retrospective study. Hangai S, Iwase S, Kawaguchi T, Kogure Y, Miyaji T, Matsunaga T, Nagumo Y, Yamaguchi T. J Altern Complement Med. 2013;19(11):905–910.
16. Reduction of adverse effects by a mushroom product, active hexose correlated compound (AHCC) in patients with advanced cancer during chemotherapy – the significance of the levels of HHV-6 DNA in saliva as a surrogate biomarker during chemotherapy. Ito T, Urushima H, Sakaue M, Yukawa S, Honda H, Hirai K, Igura T, Hayashi N, Maeda K, Kitagawa T, Kondo K. Nutr Cancer. 2014;66(3):377–382.
17. Production of the bioactive compound eritadenine by submerged cultivation of shiitake (Lentinus edodes) mycelia. Enman J, Hodge D, Berglund KA, Rova U. J Agric Food Chem. 2008;56(8):2609–2612.
18. Quantification of the bioactive compound eritadenine in selected strains of shiitake mushroom (Lentinus edodes). Enman J, Rova U, Berglund KA. J Agric Food Chem. 2007;55(4):1177–1180.
19. Polysaccharide and extracts from Lentinula edodes: structural features and antiviral activity. Rincão VP, Yamamoto KA, Ricardo NM, Soares SA, Meirelles LD, Nozawa C, Linhares RE. Virol J. 2012;9:37.
20. Shiitake, Lentinus edodes: Functional properties for medicinal and food purposes. Mizuno T. Food Rev Int. 1995;11(1):109–128.
21. Shiitake dermatitis: flagellate dermatitis after eating mushrooms. Haas N, Vogt R, Sterry W. Hautarzt. 2001;52(2):132–135.
22. Systemic allergic contact dermatitis due to consumption of raw shiitake mushroom. Kopp T, Mastan P, Mothes N, Tzaneva S, Stingl G, Tanew A. Clin Exp Dermatol. 2009;34(8):e910–913.
23. Shiitake dermatitis now occurs in France. Hérault M, Waton J, Bursztejn AC, Schmutz JL, Barbaud A. Ann Dermatol Venereol. 2010;137(4):290–293.
24. Shiitake dermatitis: a report of 3 cases and review of the literature. Chu EY, Anand D, Dawn A, Elenitsas R, Adler DJ. Cutis. 2013;91(6):287–290.
25. Shiitake Dermatitis – Now Also in Poland. Baran W, Batycka-Baran A, Maj J, Szepietowski JC. Acta Derm Venereol. 2015;95(1):102–103.
26. Shiitake dermatitis: toxic or allergic reaction? Corazza M, Zauli S, Ricci M, Borghi A, Pedriali M, Mantovani L, Virgili A. J Eur Acad Dermatol Venereol. 2015;29(7):1449–1451.