Lentinan

Some of the medicinal properties of Shiitake mushroom are attributed to a sugar molecule named lentinan.

Most studies on lentinan has been done on ancer prevention and cancer treatment.

In laboratory tests, lentinan does not kill cancer cells directly, but enhances a number of aspects of the immune system, which may aid in the slowing of tumor growth.

Lentinan also kills viruses and microbes directly in laboratory studies.

Most studies involving lentinan involve intravenous or intramuscular injections.

It is uncertain whether the ingestion of shiitake mushrooms provides similar effects.

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

Lentinan also kills viruses and microbes directly in laboratory studies.

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.

In addition to their primary structures, immunopotentiation activity of beta-D-glucans is linked to their molecular weight and triple helical conformation.

In vivo studies suggest that 1,3 beta glucan increases IL-4-producing cells, suggesting a stimulation of Th2-mediated immunity.

In addition to antitumor activity, lentinan also possesses immune-regulatory effects, antiviral activity, antimicrobial properties, and cholesterol-lowering effects.

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.

Lentinan also was shown to induce apoptosis in gastric cancer cells, and this effect was enhanced when combined with docetaxel and cisplatin.

In urothelial bladder cancer cell lines, increased concentrations of lentinan alone or combined with gemcitabine correlated with enhanced T24 cell apoptosis.

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.

In addition, lentinan can heal chromosome damage caused by anticancer treatments.

Medicinal properties

In some countries, parenteral lentinan is classified as an antineoplastic polysaccharide and is available for clinical use.

Lentinan is known as a biological response modifier (BRM) which is often taken as a synonym for an immunomodulator.

Its anti-tumour action is host mediated; lentinan is claimed to enhance cell-mediated immune responses in vitro and in vivo which probably plays a part in its anti-tumour activity.

The effect of lentinan on T cells has been thoroughly investigated.

Intraperitoneal lentinan administration resulted in complete tumour regression in 7 of 8 BDF1 mice inoculated with FBL-3 erythroleukemia cells.

When monoclonal antibodies (mAb) against both CD4 and CD8 were given before the lentinan treatment the tumour growth inhibition stopped.

Recent studies add to the evidence for this theory, patients with advanced cancer were demonstrated to have an imbalance between Th1 and Th2 responses, and thus impaired cell-mediated immunity.

Flow cytometry of peripheral blood samples found that intravenous administration of lentinan (2 mg, three times per week) cancelled the Th2-dominant condition in patients with digestive cancers.

It was also suggested that the proportions of Th1/Th2 cells may have been restored.

There have been several other studies supporting the theory that the anti-tumour activity is T-cell mediated including those that propose a different mechanism of action.

It has been suggested that there is correlation between the vascular dilation and haemorrhage (VDH) reaction and the anti-tumour effects of lentinan.

VDH was induced in mice by lentinan, but those receiving a combination of anti-CD4 and anti-CD8 mAb before lentinan treatment did not show a VDH response, and either mAb subset alone had no effect, showing that VDH is T cell dependent.

Across several strains of mice, those which showed a high VDH response after lentinan treatment, also showed high responses to bradykinnin.

The bradykinnin induced skin reaction was examined in B10D2 mice bearing S908D2 sarcoma treated with lentinan and fluorouracil either alone or in combination.

Separately the agents had no effect on tumour growth; their combination resulted in complete regression and augmented the skin reaction, whereas the former treatments had not.

The results support the theory and the assumed mechanism is induction of haemorrhagic necrosis in the tumour.

These results have also been found in reliable journals although they are not as recent as the T cell experiments.

In various cancer models, lentinan has also been shown to enhance activity of gemcitabine, paclitaxel, docetaxel and cisplatin, and monoclonal antibodies.

Addition of lentinan to standard cancer therapies, considered chemoimmunotherapy, resulted in improved survival in hepatocellular and gastric cancers, and improved quality of life in patients with esophageal carcinoma.

Improvements in quality of life were also seen with an oral formulation of lentinan in some cancer patients.

However, well-designed large-scale studies are needed to establish the role of lentinan as a useful adjunct to cancer treatment.

An early study found that intraperitoneal injections of an aqueous extract of shiitake, of which the active substance was lentinan, greatly inhibited (81%) the growth of tumours arising from sarcoma 180 ascites cells implanted in Swiss albino mice.

The findings have been supported in many trials since and although it is a dated article, they are often cited in new articles.

The study was also published in the highly reputable journal, Nature, which has an impact factor of 25.8, which lends much support to the findings.

Moreover lentinan has been shown to potentiate the effects of other drugs such as 5-fluorouracil (5-FU) and cis-diamminedichloroplatinum (II) (CDDP) in cancer treatment.In Japan, a purified lentinan has been approved for clinical use.

It has proven effective in prolonging the survival of cancer patients, particularly those with gastric and colorectal cancer.

Side Effects & Safety

Contraindications

Prior reactions to lentinan from shiitake mushroom ingestion.

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.

Case Reports

Chest tightness: Following parenteral injection of lentinan.

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.

Herb-Drug Reactions

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

References

  • https://www.mskcc.org/cancer-care/integrative-medicine/herbs/lentinan
  • Medicinal Mushrooms – An Exploration of Tradition, Healing & Culture. Christopher Hobbs, L. Ac. Botanica Press, imprint of Book Publishing Company, Summertown, TN, USA. 1986.
  • University of Texas Health Science Center at Houston. “Mushroom extract, AHCC, helpful in treating HPV.” ScienceDaily. ScienceDaily, 28 October 2014. www.sciencedaily.com/releases/2014/10/141028122424.htm.
  • Kupcova K., et.al. Antimicrobial, Cytotoxic, Anti-Inflammatory, and Antioxidant Activity of Culinary Processed Shiitake Medicinal Mushroom (Lentinus edodes, Agaricomycetes) and Its Major Sulfur Sensory-Active Compound-Lenthionine. Int J Med Mushrooms. 2018;20(2):165-175. doi: 10.1615/IntJMedMushrooms.2018025455.
  • Barry W. Ritz, PhD. Active Hexose Correlated Compound (AHCC) and Immune Outcomes in Humans: A Review. Fermented mushroom extract affects immune outcomes and immune cell populations
    Natural Medicine Journal, January 2011 Vol. 3 Issue 1.
  • https://www.mskcc.org/cancer-care/integrative-medicine/herbs/shiitake-mushroom
  • https://www.mycomedica.eu/shiitake.html
  • 4.11 The potential of fungi used in traditional Chinese Medicine: Shiitake (Lentinula edodes) by Dawn Soo, 2002. http://www.davidmoore.org.uk/Sec04_11.htm
  • https://www.indigo-herbs.co.uk/natural-health-guide/benefits/shiitake-mushroom
  • https://www.huffpost.com/entry/cancer-foods_b_1192207