Maitake (Grifola frondosa)

By the CAM Cancer Collaboration | 11. Sep 2020

Abstract and key points
What is it?
Does it work?
Is it safe?
References
Photo:Mostphotos.com

                  Photo: Mostphotos

Description

Maitake is a mushroom indigenous to many Asian countries. Commercial preparations are available as preserved whole fruiting bodies, pulverized fruiting bodies and extracts from the mycelium. Like other species from this phylum, maitake contains polysaccharides (alpha-/beta-homo- and heteroglycans), proteins, nucleic and amino acids, minerals and trace elements, ergosterin, several vitamins and provitamins, phenols and flavonoids. The suggested key components are beta-glucans which are found in the cell walls of the fruiting bodies and mycelia.

Efficacy

There is limited evidence that extracts from maitake can increase the functional capacity of monocytes, T- and NK-cells in human cancer patients. There is no evidence from clinical trials that maitake extracts have direct anticancer effects.

Safety

Maitake and its extracts are usually well tolerated; allergic reactions might, however, occur.

Citation

Horneber M, CAM Cancer Collaboration. Maitake (Grifola frondosa) [online document], Sep 11, 2020.

Document history

Latest update: September 2020

Next update due: September 2023

Scientific Name

Grifola frondosa (Dicks.) Gray1.

The scientific name Grifola frondosa is derived from the griffin, the beast from Greek mythology with the head and wings of an eagle and the body of a lion, and frondosa, meaning leaflike.

History and providers

Maitake is growing wild in north eastern Japan and in temperate forests of Asia, Europe, and eastern North America. This mushroom has been consumed in Asia for hundreds of years and has an exceptional position in traditional Japanese herbology. Because of its valuable nutrients, maitake has also been cultivated in laboratories within the past two decades for use as a dietary supplement. Commercial maitake production worldwide may now be in excess of several ten-thousands tons with Japan being the main producer and consumer2,3. Commercial preparations are available as cultivated whole fruiting bodies, pulverized fruiting bodies or spora, extracts from mycelium cultures or fractions from certain compounds4.

Ingredients

As other species from this phylum, extracts from maitake contain polysaccharides (alpha-/beta-homo- and heteroglycans), proteins, nucleic and amino acids, minerals, organic selenium and other trace elements, ergosterin, vitamin C, E, B1, and B2, phenols and flavonoids5-9.

In the 1980s, Japanese pharmacists derived a polysaccharide compound from the fruit bodies, called D-fraction, with a molecular weight of about 106 Daltons which was patented in 1984 (cited in 2). Further purification of this fraction yielded the so-called MD-fraction, and was patented in the USA (cited in 2). Both fractions contain proteoglucans having beta-glucans as major and proteins as minor components.

The beta-glucans in maitake include 1,6 main chains with 1,3 or 1,6 side branches as well as 1,3 main chain with 1,6 side branching10-12. Recently heteropolysaccharides, called Z-fraction13 and GFPS1b14 were isolated from maitake mycelia, which in addition to glucose contain other sugars like arabinose, fucose, galactose and mannose connected with alpha- and beta-linkages. The majority of proteins found in maitake have a molecular weight range of 12–17 kDa, which is the typical range of proteins that regulate distinct membrane traffic pathways (FIPs).

Dosage/administration

In a phase I/II study with breast cancer patients, maitake liquid extract has been given orally at 0.1- 5 mg/kg twice daily11. Capsules or tablets available in stores or via the internet usually contain 200-400mg of extracts from mycelium cultures or 400-500mg pulverized fruiting bodies or spora. The manufacturers recommend doses of 1-2 capsules/tablets twice daily.

Claims of efficacy/alleged indications

Extracts from maitake are claimed to have various beneficial health effects, ranging from cancer treatment and prevention to activities against hepatitis B and human immunodeficiency virus infec¬tions. Other claimed benefits relate to the treatment of hyperlipidaemia, hypertension, diabetes, and obesity15,16.

Chen et al found evidence that maitake extracts induce ovulation in patients with polycystic ovary syndrome17.

In traditional Chinese medicine maitake is used to improve ailments of the upper gastrointestinal tract, calming nerves and treating haemorrhoids18,19.

Mechanisms of action

One of the hypothesized mode of action of extracts from maitake is an indirect one via activation of the host’s immunological defence mechanisms. The suggested key components for the immunological effects are the beta-glucans which are found in the cell walls of the fruiting bo-dies and mycelia of maitake20. Beta-glucans are naturally occurring polysaccharides, often linked to proteins and widely found in fungi, plants and several bacteria. Beta-glucans belong to a group of unique microbial structures, the pathogen associated molecular patterns (PAMPs) which can trigger immune responses via so-called pattern-recognition receptors, like Toll-like and C-type lectin receptors (CLR). Dectin-1, a member of CLR, is thought to be the main beta-glucan receptor and is expressed in humans on macrophages, most subsets of dendritic cells, subpopulations of T cells, B cells, mast cells, and eosinophils21-24.

There is evidence from in vitro and animal studies that maitake extracts are capable of

  • inducing the proliferation and differentiation of human umbilical cord blood progenitor cells25 and cytokine release from various immune cells among them murine splenocytes and macrophages12,26,27,
  • increasing phagocytosis of human polymorphonuclear neutrophils8,
  • stimulating the production and secretion of G-CSF of human cord blood monocytes25,
  • enhancing the recovery of mouse28, and human25 bone marrow cells from chemotherapy toxicity, and
  • inhibiting metastasis29,
  • inducing systemic antitumor immune response and to decreases immunosuppression30,31,
  • increasing cytotoxic effects of e.g. Carmustine (BCNU) through enhanced  inhibition of the glutathione-dependent detoxifying enzyme, glyoxalase I32

Prevalence of use

Prevalence data specifically for maitake are not available. One survey with cancer patients from Israel mentioned the use of “Chinese mushrooms” in a sample of 368 complementary medicine users to be around 4%33 and a nationwide survey in Japan reported that about 40% of cancer patients used indigenous Asian mushrooms or herbs34.

Legal issues

Several US companies have received the IND (investigational new drug) approval from the FDA for maitake fraction for Phase I/II clinical studies in cancer patients35.

Phase I/II clinical trial

A phase I/II dose escalation trial found dose-dependent effects of a liquid maitake extract on immu¬nologic parameters of disease-free breast cancer patients: increased cytokine production from monocytes and T-cells, and higher numbers of activated NK- and T-cells. The dose associated with the largest immunological effect varied for the different immunological parameters. The authors concluded that “cancer patients should be made aware of the fact that botanical agents produce more complex effects than assumed, and may depress as well as enhance immune function”11.

Another phase II trial investigated the effects of an oral maitake extract at 3 mg/kg twice daily for 12 weeks on immune functions in a small group (n=21) of patients with myelodysplastic syndromes (MDS). Maitake extract increased the capacity of neutrophils and monocytes to produce reactive oxygen species with or without stimulation by E. coli, phorbol ester, and N-formylmethionyl-leucyl-phenylalanine (measured by flow cytometry). The authors concluded that „Maitake has beneficial immunomodulatory potential in MDS“36.

Case series

Three case series published by the same group reported “immune-enhancing properties of maitake MD-fraction” and a “potential to decrease the size of lung, liver, and breast tumours”37-39. A critical comment on one of these case series, however, sounds a note of caution regarding the validity of the published results40.

Overall maitake mushroom can be regarded as safe, when consumed in food amounts. Dried maitake mushroom powder has been used safely in doses up to 2.25 grams daily for up to 28 weeks17. With enriched extracts being available, modern ‘users’ of maitake extracts could ingest much larger amounts of probably active ingredients which raises the likelihood of unexpected adverse effects from a traditionally “safe” mushroom. There is little reliable information to advise on the use during pregnancy and lactation.

Adverse reactions

Allergic reactions are possible. There is a report of hypersensitivity pneumonitis due to inhalation of maitake spore41. No dose-limiting toxicity was encountered in a recent dose escalation trial. Two patients in this trials experienced mild nausea, joint swelling, rash and pruritus which were possibly related to maitake extracts11. In a recent clinical trial, oral maitake extracts caused blood eosinophilia in several patients36. Konno et al. described mild hypoglycaemic effect of maitake extracts in diabetic patients42.

Contraindication

Known allergy to maitake mushrooms.

Interactions

Maitake mushroom might lower blood glucose levels and might have additive effects when used with other herbs and supplements that also lower glucose levels. This might increase the risk of hypoglycaemia in some patients15.

Precautions/warnings

There are reports of microbial contamination of dried mushroom43.

Quality Issues

There is considerable variation in the content of polysaccharides in mushrooms depending on the production process and storage process44,45.

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