Lentinan

Scientific Name(s): Lentinula edodes (Berk.) Pegler. Family: Tricholomataceae

Common Name(s): Shiitake , snake butter , pasania fungus , forest mushroom , hua gu

Clinical Overview

Uses of Lentinan

Lentinan is proving to be a valuable component in cancer and infection treatments. It has also demonstrated cholesterol-lowering and immune-regulatory properties.

Lentinan Dosing

The isolated polysaccharide lentinan from shiitake culture has been used IV at doses of 2 to 10 mg on a weekly schedule as adjunctive therapy in HIV as well as cancer, primarily in Japan.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Lentinan Interactions

None well documented.

Lentinan Adverse Reactions

Lentinan is derived from the shiitake mushroom, which is edible and is not generally associated with side effects. Lentinan side effects are rarely reported.

Toxicology

Research reveals little or no information regarding toxicology with the use of this product.

Botany

Lentinan is a polysaccharide derived from the vegetative parts of the edible Japanese shiitake mushroom. It is the cell wall constituent extracted from the fruiting bodies or mycelium of L. edodes . The mushroom is synonymous with Cortinellus edodes (Berk.) S. Ito and Imai, Armillaria edodes (Berk.) Sacc. and Cortinellus shiitake (Takeda) Henn. 1 Lentinan is synonymous with Tricholomopsis edodes Sing. The light, amber fungi are found on fallen broad-leaf trees, such as chestnut, beech, or mulberry. They have decurrent, even or ragged gills, a stem, and are covered with delicate, white flocking. 2 Shiitake mushrooms are commonly sold in food markets in the Orient and are now widely available in the United States, Canada, and Europe.

History

Lentinan is a complex polysaccharide that possesses immuno-stimulating antitumor properties. Lentinan was isolated from edible shiitake mushrooms that have been used in traditional oriental cooking and herbal medicine. Shiitake has been renowned in Japan and China as both a food and medicine for thousands of years. It is now commonplace throughout the world. Extracts of these mushrooms are now being incorporated into over-the-counter dietary supplements designed to improve the status of the immune system.

Chemistry

Lentinan is found in very low concentrations in fresh shiitake mushrooms. In 1 study, 200 kg of fresh mushrooms yielded 31 g of lentinan (0.02%). Lentinan is a water-soluble, beta-1,3 glucan polysaccharide characterized by beta-1,6 branched glucan linkages. At least 5 additional polysaccharides have been isolated from L. edodes . 1 Lentinan is a high molecular weight polysaccharide in a triple helix structure, containing only glucose molecules with mostly (1-3)-β-D-Glucan linkages in the regularly branched main chain with two β (1,6)-D-glucopyranoside branchings for every five β-(1,3)-glucopyranoside linear linkages. 2

Lentinan Uses and Pharmacology

The antitumor activity of lentinan has been recognized for almost 30 years. Because a number of naturally occurring polysaccharides had previously been found to have antitumor activity, lentinan was considered for detailed evaluation. In addition to antitumor activity, lentinan also possesses immune-regulatory effects, antiviral activity, antimicrobial properties and cholesterol-lowering effects. The pharmacology available on lentinan is vast. The following is a brief outline of key aspects.

When administered by intraperitoneal (IP) injection to mice implanted with Sarcoma 180, lentinan showed striking antitumor activity. Ten daily doses as low as 1 mg/kg per dose resulted in tumor growth inhibition of 95% to 100%, depending on the strain of mouse tested. Although 1 other polysaccharide fraction from L. edodes inhibited tumor growth, most other fractions were devoid of activity. 1

In rats with a model of colon cancer, lentinan was found highly effective in extending their life span. When treated with 5 IP injections 2 days apart, (2 mg/kg), 11 of 20 rats were found to be tumor-free at autopsy on day 42 of the study. Furthermore, lentinan significantly increased the life span of carcinomatous rats. In the control group, 50% of the rats lived 42 days compared with 70 days in the treated group. Four of 10 treated rats were still alive on day 210 of the study, while all of the controls had died by day 70. 3

Another study has reported effective results for lentinan in metastasis inhibition. 4 In combination therapy with IL-2, lentinan exhibited a synergistic effect against induced fibrosarcoma in mice. 5 The same combination again in mice had similar results against lung metastases. 6

Therapeutic effects of lentinan in the GI tract have been noted. A case study reports reduced primary tumor size, in a 63-year-old patient treated with lentinan combination therapy. Metastasis disappeared, and only mild thrombocytopenia occurred as a side effect. 7 Lentinan used as an agent for postoperative adjuvant therapy was investigated in GI patients with stages II to IV cancer. Stage IV patients had higher lymphocyte counts than control patients, suggesting lentinan's immuno-potentiating efficacy in advanced GI cancer. 8 Another study reports life span prolongation in stomach cancer patients, using lentinan combination therapy. 9 Other successful chemotherapies using lentinan include: CDDP and 5-FU, 10 mitomycin and 5-FU, 3 cisplatin with radiation 11 and interleukin 2. 12 Another study involving gastric cancer describes how lentinan causes marked development of reticular fibers related to antitumor effect and enhanced interstitial response. 13 Intracavitary injection of lentinan is a useful treatment for malignant effusions in gastric carcinoma patients. 14 Resistance to lentinan chemoimmunotherapy is also reported. 15

Lentinan's effects in other cancers have also been reported. In prostatic cancer, lentinan 2 mg weekly in combination with Tegafur was evaluated. A 5-year average survival rate of treated patients was 43% compared with 29% in the control group. 16 Another report referred to the safety and efficacy of lentinan posttreatment with surgical therapy in 33 breast cancer patients. 17 Lentinan has also been evaluated in cervical cancer patients. 18 , 19 , 20

Survival rates using lentinan therapies have increased. One study reports 129 days vs 49 days in malignant ascites and pleural effusion patients given lentinan 4 mg/week for 4 weeks. 21 A 4-year follow-up survey of stomach cancer patients reports survival at 1, 2, and 3 years with few reported side effects. 9

Although not directly cytotoxic, beta-1,3 glucan has been shown to enhance natural protective immunity.

When administered IP to mice with implanted tumors, lentinan effectively increased the activity of cytotoxic peritoneal exudate cells. 22 Kurokawa, et al draws a similar conclusion when reporting direct action of lentinan on tumor cells in mice by scanning electron microscopy. Lentinan contributes to antitumor immunity enhancement, but not to direct killing activity against tumor cells. 23 Evidence suggests that lentinan preferentially acts on T-cells and may enhance T-helper cell function. Furthermore, lentinan augments natural killer cell activity and activates macrophages. 24 Lentinan also triggers production of interleukin 1 by a direct action on macrophages or indirectly by augmenting colony stimulating factor. 25 Many other studies are available where lentinan is found to improve immune function by stimulating T-cell/killer cell/monocyte production, 8 , 12 , 14 , 26 , 27 , 28 , 29 , 30 , 31 increasing natural cell-mediated cytotoxicity, 32 stimulating production of acute-phase transport proteins, 33 affecting lymphocyte and enzyme concentrations 34 and activating complement. 35

Research reveals no clinical data regarding the use of lentinan for immune system effects.

Lentinan has antiviral activity and has been found to protect against encephalitis caused by the intranasally infected vesicular stomatitis virus in mice. 36 Lentinan enhances AZT's effects when used in combination against HIV for in vitro studies. 37 Additional discussion of lentinan's mechanism against HIV is reported in an article by the same authors. 38

Research reveals no clinical data regarding the use of lentinan for antiviral effects.

Tsujinaka, et al report that rabbits with induced septic insult without lentinan treatment had low platelet counts, elevated bilirubin and creatinine. In lentinan-treated septic animals, platelet counts did not decrease, and elevation of plasma bilirubin and creatinine levels were less prominent. Findings suggest a modified septic process by administration of lentinan. 39 Host resistance against microbial infection by lentinan is reviewed in another report by Kaneko, et al. 40

Research reveals no clinical data regarding the use of lentinan for antimicrobial effects.

The compound lentinacin has been shown to reduce cholesterol levels in rats by 25% after 7 days of oral administration in a dose as low as 0.005% of feed intake. 41 Other compounds isolated from shiitake have also been shown to lower blood cholesterol and lipids as well. 42

Research reveals no clinical data regarding the use of lentinan for cholesterol-lowering effects.

Dosage

The isolated polysaccharide lentinan from shiitake culture has been used IV at doses of 2 to 10 mg on a weekly schedule as adjunctive therapy in HIV as well as cancer, primarily in Japan. 43

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

In a phase 1 study conducted in 50 patients with advanced cancer, minor side effects were observed in 3 patients; in a study of 185 patients, 17 experienced minor adverse reactions. 3

Toxicology

The shiitake mushroom is edible and has not been associated with toxicity. In animals, lentinan shows little toxicity. In mice, the LD-50 is greater than 1,500 mg/kg (IP). Animal studies have been remarkable for lack of significant toxicity. 1 Few toxic effects are mentioned in 2 reports of lentinan use. 44 , 45

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