Enokitake – Flammulina velutipes

Chinese nameJin Zhen Gu /Dong Gu
English nameVelvet Shank/Winter Mushroom/Golden Needle Mushroom

A common culinary mushroom, F. velutipes was the second earliest mushroom to be cultivated (cultivation started around 800 AD, after Auricularia auricula-judae -600 AD, and before Lentinula edodes -1000 AD). It shows considerable clinical promise, especially for cancer prevention protocols.
A study of 174,505 inhabitants of the Nagano area of Japan compared the cancer death rates among F. velutipes farmers with rates in the general population over a 15 year period (1972-86) and found that the F. velutipes farmers had a much lower death rate of 97.1 per 100,000, compared to 160.1 per 100,000 in the general population, with the suggestion that this was due to increased consumption of F. velutipes1.
Following on from the above a case-control study investigated the relationship between risk reduction of stomach cancer and intake of edible mushrooms in the same prefecture from 1998 to 2002. While the odds ratio (OR) of subjects who were eating hardly any mushrooms or mushrooms less than once a week was 1.00, consumption of F. velutipes more than three times a week produced a reduction to 0.66 (the OR of those taking L. edodes more than three times a week was 0.95)2.
As well as immunomodulatory polysaccharides3,5, F. velutipes is notable for its high protein content (31.2%), which includes a large number of protein-rich components with strong immunomodulatory and anti-cancer activity6-11.
F. velutipes extracts also demonstrate strong tyrosinase inhibition12.

F. velutipes extracts show exceptionally high anti-cancer activity in vitro. In one study of extracts from 38 mushrooms carried out by Bastyr University, F. velutipes had one of the highest levels of inhibitory activity against two oestrogen-dependent and one oestrogen-independent breast cancer cell lines13. In a separate study of aqueous extracts from 20 mushrooms and three mushroom polysaccharides, the aqueous extract from F. velutipes, together with that from Pleurotus ostreatus, showed the highest level of cytotoxic activity against androgen-independent prostate cancer cells14.
In vivo, EA6, a protein-bound polysaccharide isolated from the fruiting body of F. velutipes, augmented humoral immunity, cellular immunity, and IL-2 production in mice bearing Meth-A fibrosarcoma at 10mg/kg and administration after surgery markedly inhibited growth of the rechallenged Meth-Asolid tumour, while Proflamin (90%protein, 10% polysaccharide) isolated from the mycelium of F. velutipes abolished suppression of immunocompetence after cryosurgery at 10mg/kg/day15.
Another protein from F. velutipes, Fve, protected mice against liver cancer through activation of both innate and adaptive immune responses when administered orally at a dose of 10mg/kg16.
In clinical studies EEM, a combination of extracts from F. velutipes and Hypsizygus marmoreus, revealed superior results to MPA (methyl-acetoxy-progesterone) on the cachexia of advanced cancer patients with better clinical response, performance status (PS), and quality of life (QOL). EEM supplementation in combination with anti-cancer drugs improved the clinical response rate, PS, and QOL of advanced cancer patients compared to patients treated with anticancer drugs alone. EEM supplementation also reduced precancerous lesions on the oesophageal mucosa2.

ANTI-VIRAL – Co-administration of Fve, a protein from F. velutipes, with immunization against HPV-16 led to 60% of mice remaining tumour-free 167 days after challenge with tumour cells compared to 20% of those receiving immunization alone. The co-immunized mice showed enhanced production of HPV-16 E7 oncoprotein-specific antibodies as well as expansion of HPV-16 E7-specific interferon (IFN)-gamma-producing CD4(+) and CD8(+) T cells compared to mice immunized with HPV-16 E7 alone17.
Proteins from F. velutipes also show direct anti-viral activity, including ribosome inactivating activity and inhibition of HIV-1 reverse transcriptase, beta-glucosidase and beta-glucuronidase18.

FOOD ALLERGIES – Mice orally given five daily 200 μg doses of protein from F. velutipes before and after each of two intraperitoneal injections of ovalbumin significantly reduced symptoms of anaphylaxis and levels of plasma histamine on subsequent oral challenge with ovalbumin and demonstrated an impaired OVA-specific IgE response with a Th1-predominant cytokine profile19. Other research has demonstrated the ability of the F. velutipes protein Fve to enhance eosinophil apoptosis, with therapeutic implications for eosinophil-related allergic inflammation, and of an ethanol extract to suppress hypersensitive immune response20,21.

Main Therapeutic Application – Dietary supplementation in patients at risk of cancer or with chronic viral conditions.
Key Component – Proteins and polysaccharides.
Dose – F. velutipes fruiting body contains high levels of the therapeutically active proteins at a reasonable cost and is the preferred dosage form in most cases with 3-5g dried fruiting body equating to 30-50g fresh mushroom.
Safety – Flammutoxin, a protein found in F. velutipes that is cytolytic and cardiotoxic when injected has been shown to be non-toxic when absorbed orally22.

1. Beneficial effects of edible and medicinal mushrooms on health care. Ikekawa T. Int J Med Mushrooms. 2001;3(4):8–12.
2. Cancer risk reduction by intake of mushrooms and clinical studies on EEM. Ikekawa T. Int J Med Mushrooms. 2005;7(3):347.
3. Inhibitory activity of polysaccharide extracts from three kinds of edible fungi on proliferation of human hepatoma SMMC-7721 cell and mouse implanted S180 tumor. Jiang SM, Xiao ZM, Xu ZH. World J Gastroenterol. 1999;5(5):404–407.
4. Investigation of immunomodulating activity of the medicinal mushroom Flammulina velutipes (Curt.: Fr.) P. Karst. in vitro. Cytokine induction by fruiting body extract. Badalyan SM, Hambardzumyan LA. Int J Med Mushrooms. 2001;3(2-3):110–111.
5. Purification, characterization and immunomodulating properties of polysaccharides isolated from Flammulina velutipes mycelium. Yin HP, Wang Y, Wang YF, Chen T, Tang HL, Wang M. Am J Chin Med. 2010;38(1):191–204.
6. Effect of Flammulina velutipes polysaccharides on production of cytokines by murine immunocytes and serum levels of cytokines in tumour-bearing mice. Chang HL, Lei LS, Yu CL, Zhu ZG, Chen NN, Wu SG. Zhong Yao Cai. 2009;32(4):561–563.
7. FIP-fve stimulates interferon-gamma production via modulation of calcium release and PKC-alpha activation. Ou CC, Hsiao YM, Wu WJ, Tasy GJ, Ko JL, Lin MY. J Agric Food Chem. 2009;57(22):11008–11013.
8. Fungal immunomodulatory protein from Flammulina velutipes induces interferon-gamma production through p38 mitogen-activated protein kinase signaling pathway. Wang PH, Hsu CI, Tang SC, Huang YL, Lin JY, Ko JL. J Agric Food Chem. 2004;52(9):2721–2725.
9. Flammulin: a novel ribosome-inactivating protein from fruiting bodies of the winter mushroom Flammulina velutipes. Wang HX, Ng TB. Biochem Cell Biol. 2000;78(6):699–702.
10. High processing tolerances of immunomodulatory proteins in Enoki and Reishi mushrooms. Tong MH, Chien PJ, Chang HH, Tsai MJ, Sheu F. J Agric Food Chem. 2008;56(9):3160–3166.
11. Interruption of lung cancer cell migration and proliferation b fungal immunomodulatory protein FIP-fve from Flammulina velutipes. Chang YC, Hsiao YM, Wu MF, Ou CC, Lin YW, Lue KH, Ko JL. J Agric Food Chem. 2013;61(49):12044–12052.
12. Isolation of 1′,3′-dilinolenoyl’-2′-linoleoylglycerol with tyrosinase inhibitory activity from Flammulina velutipes. Jang SG, Jeon KS, Lee EH, Kong WS, Cho JY. J Microbiol Biotechnol. 2009;19(7):681–684.
13. In vitro effects on proliferation, apoptosis and colony inhibition in ER-dependent and ER-independent human breast cancer cells by selected mushroom species. Gu YH, Leonard J. Oncol Rep. 2006;15(2):417–423.
14. Cytotoxic effect of oyster mushroom Pleurotus ostreatus on human Androgen-independent prostate cancer PC-3 cells. Gu YH, Sivam G. J Med Food. 2006;9(2):196–204.
15. Immunomodulation and antitumour activity of a mushroom product, Proflamin, isolated from Flammulina velutipes (W. Curt.: Fr.) Singer (Agaricomycetideae). Maruyama H, Ikekawa T. Int J Med Mushrooms. 2007;9(2):109–122.
16. Oral administration of an Enoki mushroom protein FVE activates innate and adaptive immunity and induces anti-tumour activity against murine hepatocellular carcinoma. Chang HH, Hsieh KY, Yeh CH, Tu YP, Sheu F. Int Immunopharmacol. 2010;10(2):239–246.
17. Coadministration of the fungal immunomodulatory protein FIP-Fve and a tumour-associated antigen enhanced antitumour immunity. Ding Y, Seow SV, Huang CH, Liew LM, Lim YC, Kuo IC, Chua KY. Immunology. 2009;128(1Sup):881–894.
18. Isolation and characterization of velutin, a novel low-molecular weight ribosome-inactivating protein from winter mushroom (Flammulina velutipes) fruiting bodies. Wang H, Ng TB. Life Sci. 2001;68(18):2151–2158.
19. Oral administration of an edible-mushroom-derived protein inhibits the development of food-allergic reactions in mice. Hsieh KY, Hsu C, Lin JY, Tsai CC, Lin RH. Clin Exp Allergy. 2003;33(11):1595–1602.
20. Eosinophil apoptosis induced by fungal immunomodulatory peptide-fve via reducing IL-5α receptor. Hsieh CW, Lan JL, Meng Q, Cheng YW, Huang HM, Tsai JJ. J Formos Med Assoc. 2007;106(1):36–43.
21. Inhibitory effects of edible higher Basidiomycetes mushroom extracts on mouse type IV allergy. Sano M, Yoshino K, Matsuzawa T, Ikekawa T. Int J Med Mushrooms. 2002;4(1):37–41.
22. Spoerke DG, Rumack BH: Handbook of Mushroom Poisoning : Diagnosis and Treatment. CRC Press, 1994. p. 394.