Lentinan

• How It Works

  Lentinan may help extend the survival of patients with some cancers when used with chemotherapy.

  Lentinan is a type of sugar molecule called 1,3 beta glucan that comes from the shiitake mushroom. In laboratory tests, lentinan does not kill cancer cells directly. Instead, it enhances the immune system, which may aid in slowing the growth of tumors. Lentinan also kills viruses and microbes directly in laboratory studies.

• Purported Uses
  • To prevent and treat cancer
    Several clinical trials show that lentinan combined with chemotherapy extends survival in patients with stomach, prostate, colorectal, and liver cancers.
  • To lower cholesterol
    Laboratory studies support this use, but human data are lacking.
  • To stimulate the immune system
    Laboratory and a few human studies show that lentinan increases the activity of certain immune cells.
  • To treat infections
    Laboratory and a few human studies show that lentinan increases the activity of certain immune cells.
• Do Not Take If

  You’ve had skin rash reactions from eating shiitake mushrooms.

• Side Effects
  • Side effects with lentinan infusions are mainly mild, with more severe reactions (hypersentivity reaction, back pain, leg pain, depression, fever, chills, decreased white blood cell count, and elevated liver enzymes) related to short infusion times.

    Case Reports

  • A single case of chest tightness was reported following administration of lentinan.
  • Rash reactions from the ingestion of shiitake mushrooms that are related to lentinan content.
• Clinical Summary

  Lentinan, a polysaccharide, is derived from the mycelium of the shiitake mushroom body, and its active component is 1,3 beta glucan. In some countries, parenteral lentinan is classified as an antineoplastic polysaccharide and is available for clinical use. Only oral formulations and extracts, which are considered dietary supplements, are available for use in the United States.

  Although lentinan is a biological response modifier, it does not have a direct cytotoxic effect on tumor cells ⁽¹⁷⁾. In various cancer models, lentinan has also been shown to enhance activity of gemcitabine ⁽¹⁸⁾, paclitaxel ⁽¹⁹⁾, docetaxel and cisplatin ⁽²⁰⁾, and monoclonal antibodies ⁽²¹⁾. Addition of lentinan to standard cancer therapies, considered chemoimmunotherapy ⁽²²⁾, resulted in improved survival in hepatocellular ⁽¹⁾ and gastric ⁽¹¹⁾ cancers, and improved quality of life in patients with esophageal carcinoma ⁽¹⁵⁾.

  Improvements in quality of life were also seen with an oral formulation of lentinan in some cancer patients ^{(10) (14) (12) (13)}. However, well-designed large-scale studies are needed to establish the role of lentinan as a useful adjunct to cancer treatment.

• Purported Uses
  • Cancer prevention
  • Cancer treatment
  • High cholesterol
  • Immunostimulation
  • Infections
• Mechanism of Action

  Lentinan’s active polysaccharide, 1,3 beta glucan, is not cytotoxic but seems to enhance T-helper cell function and increase stimulation of interleukin, interferon, and normal killer cells ^(3) (4). In addition to their primary structures, immunopotentiation activity of beta-D-glucans is linked to their molecular weight and triple helical conformation, which varied greatly between batches and manufacturers ⁽²³⁾.

  In vivo studies suggest that 1,3 beta glucan increases IL-4-producing cells, suggesting a stimulation of Th2-mediated immunity ⁽⁵⁾. In addition to antitumor activity, lentinan also possesses immune-regulatory effects, antiviral activity, antimicrobial properties, and cholesterol-lowering effects ⁽⁶⁾.

  In murine bone marrow cells, lentinan enhanced repair of paclitaxel-induced DNA damage and protected against paclitaxel-induced apoptosis partly via modulation of cellular antioxidant levels ⁽²⁴⁾. Lentinan also was shown to induce apoptosis in gastric cancer cells, and this effect was enhanced when combined with docetaxel and cisplatin ⁽¹⁶⁾. In urothelial bladder cancer cell lines, increased concentrations of lentinan alone or combined with gemcitabine correlated with enhanced T24 cell apoptosis ⁽¹⁸⁾. Lentinan cotreatment with paclitaxel enhanced effects in a lung cancer cell line through ROS production and activation of NLRP3 inflammasome and ASK1/p38 MAPK signal pathway ⁽¹⁹⁾.

• Contraindications

  Prior reactions to lentinan from shiitake mushroom ingestion ^{(25) (26) (27)}.

• Adverse Reactions

  Side effects with lentinan infusions are mainly mild, with more severe reactions (anaphylactoid reaction, back pain, leg pain, depression, rigor, fever, chills, granulocytopenia and elevated liver enzymes) related to short infusion times ⁽⁹⁾.

  Case Reports

  Chest tightness: Following parenteral injection of lentinan ⁽⁷⁾.

  Shiitake dermatitis (rash): Patterns of whiplike, linear, erythematous wheals within 1 to 2 days after consumption of raw or even cooked shiitake mushrooms caused by toxic reactions to lentinan, which typically resolve within days to weeks of their appearance ^{(25) (26) (27)}.

• Herb-Drug Interactions

  Zidovudine (AZT): Lentinan may enhance activity when used along with AZT ⁽⁸⁾.

• References

  1. Yang P, Liang M, Zhang Y, et al. Clinical application of a combination therapy of lentinan, multi-electrode RFA and TACE in HCC. Adv Ther. Aug 2008;25(8):787-794.

  2. Hobbs C. Medicinal Mushrooms. 3rd ed. Loveland (CO): Interweave Press; 1996.

  3. Chihara G, Maeda Y, Hamuro J, et al.Inhibition of mouse sarcoma 180 by polysaccharides from Lentinus edodes (Berk.) sing. Nature. May 17 1969;222(5194):687-688.

  4. Hamuro J, Rollinghoff M, Wagner H. Induction of cytotoxic peritoneal exudate cells by T-cell immune adjuvants of the beta (1 leads to 3) glucan-type lentinan and its analogues. Immunology 1980;39:551.

  5. Dong SF, Chen JM, Zhang W, et al. Specific immune response to HBsAg is enhanced by beta-glucan oligosaccharide containing an alpha-(1—>3)-linked bond and biased towards M2/Th2. Int Immunopharmacol. Jun 2007;7(6):725-733.

  6. Reed F. Immunomodulating and antitumor activity of lentinan. Int J Immunopharm. 1982;4:264.

  7. Wada T, Nishide T, Hatayama K, et al. [A comparative clinical trial with tegafur plus lentinan treatment at two different doses in advanced cancer]. Gan To Kagaku Ryoho. Aug 1987;14(8):2509-2512.

  8. Tochikura TS, Nakashima H, Kaneko Y, et al. Suppression of human immunodeficiency virus replication by 3’-azido-3’-deoxythymidine in various human hematopoietic cell lines in vitro: augmentation of the effect by lentinan. Jpn J Cancer Res. Jun 1987;78(6):583-589.

  9. Gordon M, Guralnik M, Kaneko Y, et al. 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.

  10. Isoda N, Eguchi Y, Nukaya H, et al. Clinical efficacy of superfine dispersed lentinan (beta-1,3-glucan) in patients with hepatocellular carcinoma. Hepatogastroenterology. 2009 Mar-Apr;56(90):437-41.

  11. Oba K, Kobayashi M, Matsui T, Kodera Y, Sakamoto J. Individual patient based meta-analysis of lentinan for unresectable/recurrent gastric cancer. Anticancer Res. 2009 Jul;29(7):2739-45.

  12. Hazama S, Watanabe S, Ohashi M, et al. Efficacy of orally administered superfine dispersed lentinan (beta-1,3-glucan) for the treatment of advanced colorectal cancer. Anticancer Res. 2009 Jul;29(7):2611-7.

  13. Shimizu K, Watanabe S, Watanabe S, et al. Efficacy of oral administered superfine dispersed lentinan for advanced pancreatic cancer. Hepatogastroenterology. 2009 Jan-Feb;56(89):240-4.

  14. Yoshino S, Watanabe S, Imano M, et al. Improvement of QOL and prognosis by treatment of superfine dispersed lentinan in patients with advanced gastric cancer. Hepatogastroenterology. 2010 Jan-Feb;57(97):172-7.

  15. Wang JL, Bi Z, Zou JW, Gu XM. Combination therapy with lentinan improves outcomes in patients with esophageal carcinoma. Mol Med Report. 2012 Mar;5(3):745-8.

  16. Zhao L, Xiao Y, Xiao N. Effect of lentinan combined with docetaxel and cisplatin on the proliferation and apoptosis of BGC823 cells. Tumour Biol. 2013 Jun;34(3):1531-6.

  17. Sunagawa M, Isogai M, Harada T, et al. Giant Krukenberg tumor from a perforated gastric cancer that was successfully removed after multidisciplinary therapy: report of a case. Surg Today. Jan 2014;44(1):171-174.

  18. Sun M, Zhao W, Xie Q, et al. Lentinan reduces tumor progression by enhancing gemcitabine chemotherapy in urothelial bladder cancer. Surg Oncol. Mar 2015;24(1):28-34.

  19. Liu W, Gu J, Qi J, et al. Lentinan exerts synergistic apoptotic effects with paclitaxel in A549 cells via activating ROS-TXNIP-NLRP3 inflammasome. J Cell Mol Med. Aug 2015;19(8):1949-1955.

  20. Zhao L, Xiao Y, Xiao N. Effect of lentinan combined with docetaxel and cisplatin on the proliferation and apoptosis of BGC823 cells. Tumour Biol. Jun 2013;34(3):1531-1536.

  21. Allendorf DJ, Yan J, Ross GD, et al. C5a-mediated leukotriene B4-amplified neutrophil chemotaxis is essential in tumor immunotherapy facilitated by anti-tumor monoclonal antibody and beta-glucan. J Immunol. Jun 1 2005;174(11):7050-7056.

  22. Ina K, Kataoka T, Ando T. The use of lentinan for treating gastric cancer. Anticancer Agents Med Chem. Jun 2013;13(5):681-688.

  23. Chen YW, Hu DJ, Cheong KL, et al. Quality evaluation of lentinan injection produced in China. J Pharm Biomed Anal. May 5 2013;78-79:176-182.

  24. Attia SM, Harisa GI, Abd-Allah AR, et al. The influence of lentinan on the capacity of repair of DNA damage and apoptosis induced by paclitaxel in mouse bone marrow cells. J Biochem Mol Toxicol. Jul 2013;27(7):370-377.

  25. Mendonca CN, Silva PM, Avelleira JC, et al. Shiitake dermatitis. An Bras Dermatol. Mar-Apr 2015;90(2):276-278.

  26. Boels D, Landreau A, Bruneau C, et al. Shiitake dermatitis recorded by French Poison Control Centers – new case series with clinical observations. Clin Toxicol (Phila). Jul 2014;52(6):625-628.

  27. Chu EY, Anand D, Dawn A, et al. Shiitake dermatitis: a report of 3 cases and review of the literature. Cutis. Jun 2013;91(6):287-290.