Maitake – The Facts And The Controversy

All content © 2016 ORIVeDA • All rights reserved.
Nothing is allowed to be reproduced without permission.


During the 1990s Maitake was the first medicinal mushroom that became really popular in the West. It is one of the most promising medicinal mushrooms in terms of therapeutic potential.

This is in particular an achievement of the Japanese Prof. Dr. Hiroaki Nanba, who dedicated over 30 years of his life to Maitake-research.


Article Index


Biology of Maitake

Cultivation

Therapeutic Properties

Professor Hiroaki Nanba, Ph.D.

The technical properties of the D- and the MD-fraction

Commercial Maitake supplements

Controversy

Oriveda Grifolan® vs. MaitakeGold 404®

References


Biology of Maitake


Maitake is the more common -Japanese- name for Grifola frondosa, a wood-degrading mushroom that grows on dead or dying trees in the temperate regions of
many countries. In Anglo-Saxon countries it is also known as ‘Hen of the Woods’ (because it looks like a hen sitting on her nest – at least if you have a vivid imagination). In Japanese, ‘Mai’ means dance and ‘Take’ means mushroom, thus ‘Dancing Mushroom’.

It produces large fruiting bodies (usually ± 10 kgs, but in Japan specimens weighing up to 45 kgs (!) have been reported – hence its name ‘King of Mushrooms’) and is one of the most popular edible mushrooms collected in the fall in United States, with a taste that is similar to eggplant in flavor.

In feudal times in Japan the local lords offered Maitake mushrooms to the Shogun, and locals were paid the mushrooms weight in silver. Not bad if you found a 40 kgs specimen (a very rare find, though…)! Even in recent times Maitake hunters have been known to guard the location of their Maitake grounds carefully, sometimes revealing secret spots (where it may fruit for many years in a row) only in a will.

The basic nutritional composition of Maitake.

The basic nutritional composition of Maitake.
On the right the properties of a 10:1 ‘extract’ (only water has been extracted – not an actual extract)


Like many mushrooms, Maitake’s optimal growing conditions exist within a small bandwidth when it comes to temperature, moisture, humidity, and other environmental factors. It was first discovered and reported from Europe (England, Norway, Denmark and Finland) but is also commonly found in Eastern Canada and the Eastern, Midwestern, and South-Eastern United States, but rarely in the Pacific Northwest. Some parts of Northeastern Japan and the temperate hardwood regions of China have optimal conditions, but the combination of extensive foraging and development have limited its availability in the wild.


Cultivation


Until about 1980 Maitake was only available from the wild. The first cultivation techniques for Maitake were developed in 1979-1981, so it can be considered a relatively new cultivated mushroom when compared with the 1400-year cultivation history for Auricularia auricula (Jew’s Ear), the 1000-year history for Lentinula edodes (Shiitake) and the 400-year history for Agaricus bisporus (the common white button mushroom).

Typically its mycelium (the ‘roots’ of the mushroom) is inoculated into plastic bags filled with supplemented sterilized sawdust or other wood-containing wastes. The mycelium is allowed to grow through the bag, a process that can take up to a couple of months or more. At that time the sawdust has become annealed together to produce an artificial log.

Cultivating Maitake on wood-containing substrate is important – grains and rice (very cheap, and common in the US, usually) will not produce a high quality product.

When the mycelium begins to run out of food, an opening is made in the bag (in this case the top), and fresh air is allowed to enter. This fresh air, with its increased concentration of oxygen and decreased concentration of carbon dioxide, is a signal to the mycelium that it should form its fruiting body. It is a pretty efficient process, once the grower learns the right conditions for growth and fruiting.

Commercial production of Maitake began in 1981 in Japan. Until the late 90s, Japan was the major producer of Maitake accounting for 98% of worldwide production. Only 325 tons were produced in 1981. By 1997, world production of Maitake reached 331,000 tons. Currently China is the worlds biggest producer of cultivated Maitake.


Therapeutic Properties


Maitake is popular among consumers, not only because of its excellent flavor, but also because of its medicinal properties. In the last 30 years, over 70% of scientific articles on Maitake have dealt with one or more aspects of its medicinal properties.

Approximately 2000 years ago, Maitake (known as ‘Zhu Ling’ in Chinese) was used in a Chinese medicine called “Keisho”. Keisho was supposed to be improving the health of the spleen and stomach, calming nerves and treating hemorrhoids.

The Shen Nong Ben Cao Jing (the worlds oldest Materia Medica – published around 2000 years ago) describes the use of Zhu Ling as follows: “It is sweet and balanced. It mainly treats malaria, resolves toxins, gu toxins, gu influx, and ill matters and disinhibits the water passageways (= diuretic use). Protracted taking may make the body light and slow aging.“

In more recent animal experiments and human clinical trials, Maitake was found to have promising anti-tumor and anti-viral properties. Other therapeutic uses of this mushroom include blood pressure regulation, control of diabetes, normalizing cholesterol levels, treatment of chronic fatigue syndrome (CFS), and anti-HIV activitMore than

Over 20 bioactive beta-glucans (polysaccharides) have been isolated and purified from Maitake since 1980. Each of these bioactives has a basic structure of either a (1>6)(1>3)Beta-D-glucan or vice versa; and a heteroglycan or heteroglycan-protein complex (proteoglycan) as the major component.
Bioactive polysaccharides (mainly beta-glucans) are found in all medicinal mushrooms. Beta-glucans are increasingly being recognized for their non-specific immunomodulatory effects. These so-called natural ‘biological response modifiers (BRM)’ can be potent anti-viral and anti-tumor agents, not by killing viruses or cancer cells directly but because of their ability to activate the immune system. They do not kill pathogens, but help the body to kill pathogens, a much more efficient and natural process, which does not disturb the chemical balance of the body by subjecting it to ‘chemical leverage’ as used by most pharmaceuticals.

Augmenting what Japanese cancer researchers have termed ‘intrinsic host defense mechanisms’ is particularly promising because it is a property generally lacking in conventional anticancer drugs. Immunologists have discovered that receptors on the surface of innate immune cells called dectin-1 and complement receptor 3 (CR3 or CD11b/CD18) are responsible for binding to beta-glucans, allowing the immune cells to recognize them.

Research has shown Maitake also has a hypoglycemic (lowering blood sugar) effect, and therefore may be beneficial for the management of diabetes. The reason Maitake lowers blood sugar is due to the fact the mushroom contains a natural alpha glucosidase inhibitor. Alpha-glucosidase inhibitors are saccharides that act as competitive inhibitors of enzymes needed to digest carbohydrates.

Since cancer cells appear to have a preference for glucose, lowering blood sugar levels in cancer patients might produce beneficial effects for the patient. Clinical studies in cancer patients with Metformin, a common anti-diabetic drug, show similar beneficial effects.

Several beta-glucans isolated from Maitake have been patented in Japan as potential anti-tumor, anti-cancer and immuno-modulating agents. Scientists have been focussing on how these glucans stimulate the immune system. They appear to enhance the cytolytic and interleukin-1 (IL-1) and IL-2 productivity of macrophages or T-cells and to potentiate the delayed-type hypersensitivity response associated with tumor growth suppression. However, the relationship between these beta-glucans and the therapeutic effects is not yet fully elucidated and research is still on-going.

Summary of the main therapeutic properties (based on small scale human trials, animal tests):

  • Normalizing the immune function. Maitake is known in SE-Asia as the King of Immunity. The purified beta-glucan/proteoglycan high molecular weight fractions in particular have promising anti-cancer and anti-viral properties, achieved by stimulating the production of cytokines, macrophages, NK-cells and cytotoxic T-cells. It stimulates the production of IL-1, IL-2 and others.
  • Anticancer adjuvant. In combination with regular therapy (chemo, radiation) Maitake can lessen the side effects of these treatments and improves the quality of life.
    maitake as an adjuvant to chemo therapy
  • Anti-HIV. The high molecular weight fractions show an enhancing effect on helper T-cells (CD4+), the target cells of HIV. Viral load decreased.
  • Positive effect on Chronic Fatigue Syndrome (CFS)
  • Positive effect on persistent vaginal Candida albicans proliferation and uterine fibroids
  • Helps with diabetes; increases insulin sensitivity and lowers blood sugar (in particular Maitake fractions with a lower molecular weight)
  • Lowers blood pressure and helps to prevent an increase of blood pressure.
  • Helps to normalize the balance between good and bad cholesterol (HDL and LDL). Also shows a liver-protecting effect.
  • For sensitive people the blood pressure lowering effect can occur as an unwanted side effect when taking therapeutic doses. Despite this, Maitake is considered very safe, even at doses of 1600 mg/kg/day no negative effects were found.

Professor Hiroaki Nanba, Ph.D.



This article would not be complete without mentioning the Japanese professor Hiroaki Nanba. He is a professor in the Department of Microbial Chemistry at Kobe Pharmaceutical University in Kobe, Japan. He has a Ph.D. in Biochemistry and Immunology from Kyoto University, and is an award-winning researcher on the benefits and activities of medicinal mushrooms, his main focus during the last 3 decades being the study of Maitake constituents and their therapeutic effects.

In the early 1980s he was studying various medicinal mushrooms, especially Shiitake. During these years of research he found that some of the beta-glucans in Maitake have a unique structure (not only the common (1>3)(1>6) beta-glucans but also (1>6)(1>3) beta-glucans are found in Maitake) and he came to the conclusion that these were most likely the most powerful to have been studied to date, much more promising than Lentinan, a beta-glucan complex isolated from Shiitake.

The isolated Maitake beta-glucan fractions demonstrated more pronounced anti-tumor activity in lab and animal tests than other mushroom extracts that had been studied to date (being the early 80s that meant PSK, Lentinan and Schizophyllan). Maitake also demonstrated the most promise as an orally effective immuno-modulator. This made it potentially much easier to use compared to, for example, the well-known Lentinan which only showed good results when injected.

The core of most of his research was isolating/purifying the bioactive beta-glucans by optimizing the existing extraction processes and then testing the resulting extracts in both test tubes and animal models.

It was already known that the beta-glucans found in medicinal mushrooms were most likely responsible for the majority of their therapeutic effects. The problem was always how to efficiently isolate as pure as possible beta-glucan fractions in order to study them. Crude hot water extracts and non-extracted mushroom powders are until today still dominating the market of mushroom-based supplements. Without exception these products have limited to zero therapeutic potential.

In 1984 Nanba purified 6 beta-glucan fractions (A – F) from the fruiting body of Maitake, each one more pure than the previous one. One of these fractions clearly stood out, therapeutically speaking; being the fourth stage it was labeled ‘D-fraction’. The E-fraction (a further purified version of the D-fraction) also showed very strong anti-tumor activity, but only when injected. The D-fraction extraction / purification protocol was patented in Japan (1984 – JP5921-000901). The D-fraction is a proteoglycan complex (beta-glucans bonded with proteins) with a high molecular weight (± 1000 kD) and a glucan / protein ratio of ± 7 : 3. (2.33).

In 1997 Nanba found a way to optimize the D-fraction extraction protocol even more without losing the important oral administration factor (which was a problem with his E- and F-fraction) and his funding party (Yukiguni, Japan) patented the new procedure; this more pure variation of the D-fraction is known as the MD-fraction.

The MD-fraction is a major improvement over the D-fraction: this research paper has compared both products (as used in commercial supplements) and their effects on a large range of immune functions. The research clearly showed better effects for the MD-fraction, but also found standardisation problems, due to dilution (also see below).

maitake-cultivation

Chinese greenhouse with premium quality Maitake


The technical properties of the D- and the MD-fraction:

Highly purified proteoglycan extract from Maitake consisting mainly of beta-glucans with both (1>6) and (1>3) branching (the first type is unique for Maitake and not found in any other mushroom), a high molecular weight (± 1000 kD); bonded to proteins in a ratio of 2.33:1 up to 99:1, depending on the quality of the source material and the processing. Being a proteoglycan complex they resemble the PSK and PSP fractions that have been isolated from Coriolus versicolor. Animal tests and several human trials showed that these extracts have promising anti-tumor and anti-viral effects.

Looking at the time and resources-consuming extraction/purification process as described in the research and the patents for Maitake D- and MD-fraction, it is obvious for everybody with a basic understanding of chemistry that this will be a very expensive product and that the production process is probably too complex for large scale industrial production.

1 kg of dried Maitake powder provides 4 – 6 grams of pure MD-fraction (according to the patent). That means ± a 200 : 1 ratio; 200 kgs of dried Maitake (equals ± 1800 kgs fresh Maitake) are needed to produce 1 kg of extract! Even if you can cultivate, dry and powder Maitake for $10 p/kg (you can’t), you already spend $2000 on the raw materials. The most expensive phase (the processing) has yet to start.

ORIVeDA’s Chinese supplier did produce their own version of the MD-fraction, using a slightly modified version of the patented extraction/fractionating process. The purity was 92 – 98 %. Despite this positive result they decided not to pursue this project any further: the cost price of the final product would be around $ 4500 per gram(!) which makes it commercially useless.

Taking this into account and knowing that Japanese and American products will even have much higher production costs it is obvious that the extracts as described in the research are nowhere for sale in their optimal form.

This has consequences on the recommended dosage – for Maitake the dosage recommendation is often based on the existing research, but if the actual product is a diluted version of the researched product one needs to compensate for the dilution if therapeutic results are needed. More background on dosing can be found here.


Commercial Maitake supplements


Maitake (like almost all medicinal mushrooms) was unknown in the West until the 1990s. The US-based Maitake Products, Inc. (MPI) has popularized Maitake in the 90s, using very effective science-based marketing. They are known as Mushroom Wisdom, Inc. since 2010, and are still one of the two global market leaders in terms of sales. Their products are supposed to be based on the D-fraction research of Prof. Nanba, they even trademarked the phrase ‘D-Fraction’ for marketing purposes in 1995.

The other one is the Tradeworks Group, the worldwide distributor of Prof. Nanba’s MD-fraction. The MD-fraction is marketed and sold under the brandname MaitakeGold 404®, since 2002.

When the Tradeworks Group launched the MaitakeGold 404® / MD-fraction product in 2002 they were sued by Maitake Products, Inc. : “Tradeworks […] advertised their products as the extract used in clinical studies on D-fraction (a beta glucan). “Our D-Fraction has been the base for almost all science of maitake mushroom for the last 12 to 15 years,” said Mike Shirota, president and chief executive of Maitake Products”.

The Tradeworks Group hit back with a countersuit a few months later, stating that Maitake Products (MPI) misrepresented its D-fraction product in its trademark filing. “MPI represented that it ‘coined the term D-fraction,’ despite knowing and indeed acknowledging in the complaint that Dr. Hiroaki Nanba defined the D-fraction maitake extract, in published scientific articles, before MPI even existed”, the Tradeworks statement read.

Tradeworks added it believes MPI […] altered [research] articles to support its claims for their Maitake D-Fraction product.”


Controversy


So there is controversy. Let’s list the facts:

  • – In 1984 Prof. Nanba patented the production process of what later became known as the D-fraction. The actual term ‘D-fraction’ was introduced by Prof. Nanba in the 1980s in his research papers.
  • – In 1991 two Wall-Street businessmen started Maitake Products, Inc. (MPI)
  • – In 1995 they trademarked the phrase ‘D-fraction’ and introduced Grifron-Pro Maitake D-Fraction®, a liquid product consisting of “900mg pure Maitake D-fraction extract in a 1 fluid oz. bottle (sic)
  • – In 1997 Professor Nanba optimized the fractionation process of the D-fraction; the result was patented and became known as the MD-fraction.
  • – In 1998 MPI ’s flagship product, Grifron-Pro Maitake D-Fraction® was given an Investigational New Drug (IND) status by the U.S. FDA in order to conduct a Phase II pilot study on the treatment of advanced breast and prostate cancer. Oddly enough, there is no information available at all about the outcome of this pilot study, and the product in question has been renamed a few years later. When asked about the trial’s outcome, the company said this was ‘proprietary information’ only available to ‘qualified persons’.
  • – In 2002 the Tradeworks Group, acting as a representative of Yukiguni, the worlds biggest producer of Maitake at the time (and funding Prof. Nanba ’s research) lauched their MaitakeGold404® product, using science-based marketing similar to MPI’s approach.
  • – Late 2002 MPI sued the Tradeworks Group stating “Tradeworks […] advertised their products as the extract used in clinical studies on D-fraction (a beta glucan). “Our D-Fraction has been the base for almost all science of maitake mushroom for the last 12 to 15 years(Mike Shirota, CEO of MPI)
  • – Early 2003 the Tradeworks Group countersued MPI stating “MPI represented that it ‘coined the term D-fraction,’ despite knowing and indeed acknowledging in the complaint that Dr. Hiroaki Nanba defined the D-fraction maitake extract, in published scientific articles, before MPI even existed”, adding that “MPI […] altered [research] articles to support its claims for their Maitake D-Fraction product
  • – It is indeed unclear, not to say ‘questionable’ whether the product(s) MPI sell actually contain purified ‘D-fraction’ as described in Nanba’s publications.The specifications of their alleged D-Fraction-containing supplementsall state ‘Maitake PD-Fraction® Standardized to contain 30% proteoglucan;’, where ‘PD-Fraction’ stands for ‘Pre-D-fraction’. What ‘Pre-D’ actually is, is not further explained: is it A-, B- or C-fraction ? Or something else? Based on their own description, it is not pure D-fraction.
    When asked for a Certificate of Analysis the company states this is ‘proprietary information’. A direct question: “Is your D-fraction identical to prof. Hiroaki Nanba’s D-fraction as described in [….]” remains unanswered, even after repeated attempts.

Oriveda Grifolan® vs. MaitakeGold 404®


Independent research showed that MaitakeGold 404® (MTG) is more potent than Maitake D-fraction® Pro 4X in terms of immunological effects. Therefore we decided to compare ORIVeDA Grifolan® to MTG only (being the most potent product), using the product details and specifications available.

sup-facts-mtg

Supplement facts label of a typical private label product, containing 15% MaitakeGold 404® extract, mixed with a blend of non-extracted mycelium of other mushrooms


MaitakeGold 404® is used in many private label products. These are usually encapsulated / tabletted blends of non-extracted mushroom powder with 5 – 15 % of the actual MTG extract.
In our opinion none of these are really useful products, therapeutically speaking; the amount of active ingredients is too low.


There are also liquid based products containing pure MaitakeGold 404®. These products are composition-wise all identical, only the brandname (and the price) differs. The properties are as follows: 1 fl oz (30 ml) containing ± 1000 mg of MTG, with some vitamin C added (vitamin C has a synergistic effect in combination with Maitake extract and it also improves the bioavailability).


Supplement facts label of a liquid product, containing 100% MaitakeGold 404®


The optimal dose of pure MTG as described in dedicated research is 5 – 7 mg per kg bodyweight/day. As an example, a 60 kg (132 lbs) person should take 300 – 420mg per day, and an 80 kg (176 lbs) person should take 400 – 560 mg of pure MTG per day if the therapeutic goal is a significant immuno-therapeutic effect.

Taking this into account, one has to consume ± twelve bottles per month to get 400mg MTG daily. One bottle is ± $ 40.

MaitakeGold 404® guarantees only ≥ 20% beta-glucan (revealed in correspondence with their potential B2B customers, not on their labels) and nothing else. They do not specify proteoglycans or a glucan/protein ratio, which would help to establish a fingerprint identifying the authentic product.

One specific research paper noticed that MTG has standardisation issues because it does not contain pure MD-fraction but is probably diluted. The dilution used was held responsible for anamolous results during tests.

ORIVeDA Grifolan® is a powdered extract consisting of 91% fractionated Maitake extract, and 9% organic Rose Hip extract (with ≥ 20% natural vitamin C). The glucan / protein ratio is 2.06 : 1, similar to Nanba’s D-fraction patent specification. The authorized independent Certificate of Analysis showing these specifications can be found here.

Per serving (one serving = 1.1 gram) you get ≥ 300mg fractionated high molecular weight beta-glucan (≥ 30%) and ≥ 22mg natural vitamin C. More information about this product can be found here.

The lab-verified data can easily be compared against the specifications of other Maitake extracts. This comparison (see above) and the unquestionable high level of purity warrant the statement that Oriveda Grifolan® can be considered to be significantly more potent than the current market leaders’ Maitake products, therapeutically speaking.

Apart from that, the value for money is clearly the best in the world. How to determine this (and how to avoid other pitfalls you can encounter when looking for a good mushroom supplement) you can check this objective article.


All content © 2016 ORIVeDA • All rights reserved.
Nothing is allowed to be reproduced without permission.


References


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