Casey Adams10.01.08
After three decades, medicinal mushrooms have been the subject of focused research and steady market growth. Still, questions linger: How do they support such a wide range of health benefits? How do they so significantly bolster the immune system? Is the mycelium more potent than the fruiting body? Are extracts more effective than whole mushrooms? Is cold-water extraction better than hot water or ethanol extraction?
The size of the medicinal mushroom market is another mystery pervading the industry. Multiple supply channels, delivery systems and packaging challenge statistics. Offshore sellers compete with domestic growers and manufacturers. Medicinal mushrooms are sold in a myriad of venues. To complicate matters further, restaurants increasingly serve specialty/medicinal mushrooms, health practitioners are prescribing mushrooms for a variety of patients, and Health food markets, fairs, internet, and even drug store chains are stocking mushroom supplements.
It is sill possible, however, to extrapolate significant growth. Global production of edible and medicinal mushrooms shroomed from 1.2 million tons in 1981 to an estimated 7 million tons in 1999 and approximately 9.9 million tons in 2004. The U.S. market consumes only a fraction of this volume, however.
In the 2006 crop year, the U.S. produced a little more than 400,000 tons of Agaricus species (the largest mushroom genus). Sales of U.S.-produced Agaricus mushrooms in crop year 2006 were $915 million, up 8% from the previous crop year. Sales of imported mushrooms made an even bigger jump, reporting a 30% increase from the year before at $236 million for the first 10 months of 2007. Sales of specialty/medicinal mushrooms comprise only a fraction of total mushroom sales, with an estimated $40 million sold by U.S. growers for crop year 2006. Notably, organic U.S. specialty mushroom production grew to 8 million pounds from less than 2 million pounds produced a crop year earlier-a phenomenal 400% leap.
David Law, biologist and CEO of Gourmet Mushrooms, Inc. says that restaurants are increasingly ordering their organic specialty/medicinal mushrooms, illustrating a trend among an affluent, aging generation. "Their patrons are realizing that mushrooms have many health benefits," he said. Gourmet Mushrooms, a three-decade Sebastopol, CA-based certified organic mushroom grower, has experienced consistent annual growth. "If we produced all we could sell, we could double our sales every two years," Mr. Law estimates.
Some mushroom supplement manufacturers are reporting double-digit growth despite weakening supplement sales in other categories. Hank Cheatham, director at Quality of Life Labs, Purchase, NY, adds that this growth is expected to continue. "The population continues to age and people are becoming more aware of mushrooms' healthy immune response."
Sales of some species are on a steeper growth trend. Yori Takeda, COO at Torrance, CA-based Atlas North America estimates that its Agaricus blazei mushroom supplement and bulk sales have shot up 300% during the past four years.
Even with this kind of growth, it is apparent that medicinal mushroom use in North America seriously lags behind the rest of the world, particularly Asia. In the mid-1990s, medicinal mushroom sales in the U.S. accounted for less than 1% of worldwide sales. Even with the estimated 20-40% growth since then, U.S. sales still remain far behind Asia and the rest of the world.
Scientists have cataloged some 50,000 mushrooms, and identified less than 20,000 different mushroom species. Some estimate there may be more than 150,000 mushroom species within the Fungi kingdom, which likely encompasses more than 1.5 million total species. Biologists have described less than 5% of Fungi species.
While more than 600 mushroom species have revealed immune stimulation effects, much of the research has focused on a narrower range of less than 50 species. The more popular parallel their respective research. The more researched commercial medicinal mushrooms include maitake (Grifola frondosa), shiitake (Lentinula edodes), reishi (Ganoderma lucidum), turkey tail (Coriolus versicolor or Trametes versicolor), Agaricus blazei (Murrill), Cordyceps sinensis, lion's mane (Hericium erinaceus), and split-gill (Schizophyllum commune).
With so many mushrooms showing positive effects, raw material buyers and consumers have a lot to digest. Jeff Chilton, president of Nammex, Gibsons, British Columbia, Canada, discussed some of the current market leaders. "Reishi mushroom continues to be a best-seller for us. The volume of research that supports its effectiveness and use for immune system issues has given it a strong following among American health practitioners. Reishi works on many levels due to its unique combination of polysaccharides and triterpenes," he explained. "Other species gaining ground are shiitake, maitake and cordyceps, all of which are well researched. Cordyceps has truly taken the West by storm."
Mushroom expert and renowned herbalist Christopher Hobbs, LAc, AHG, confirms this hierarchy among research results. "The best species remain shiitake, turkey tail, split-gill, Wolfiporia [cocos], some Ganoderma spp., and cordyceps," he offered.
Differentiation comes by way of the need for alternatives. "Many come to us unhappy with their current healthcare options. They discover our Agaricus blazei immune support products after seeing the research and hearing about us. A. blazei appears to be getting more attention from the medical community in North America," commented Atlas' Mr. Takeda.
The challenge for medicinal mushroom suppliers continues to be education. There is no lack of research or traditional use, however. Mushrooms have enjoyed thousands of years of traditional treatments, and a growing body of controlled and peer-reviewed research has confirmed many of these.
In the 1960s and 1970s, Asian universities, hospitals and laboratories began reporting significant in vivo research results, with laboratories confirming cellular mechanisms. These revealed antimicrobial, cholesterol-lowering, anti-inflammatory, antioxidant, anti-mutagenic, anti-tumor, adaptogenic and immunostimulation effects.American researchers finally took notice when Dr. Tetsuro Ikekawa's groundbreaking epidemiological study showed significantly lower cancer rates among Japanese mushroom growers between 1972 and 1986.
European and American research-some by prestigious universities and medical centers-began adding to continuing Asian research. By the mid-1990s, thousands of controlled studies had documented medicinal mushrooms' range of health benefits. While most clinical research to date has been adjunctive to conventional therapies for ethical reasons, human studies have consistently confirmed animal and laboratory models. As of August 2008, there were 4087 mushroom studies and scientific papers filed with the U.S. National Library of Medicine.
Mr. Hobbs was one of the first American authors to catalog this plethora of mushroom research and history in his 1995 classic, Medicinal Mushrooms. His pioneering compilation introduced many consumers and practitioners to the history, characteristics, attributes and medicinal effects of mushrooms for the first time. During the next decade, several rigorous treatises on mushroom science brought increased familiarity. One of the more prolific mushroom authors to rise to prominence was Paul Stamets, who is now regarded as one of America's leading fungal experts. Mr. Stamets has published six books on the subject, each accompanied by dramatic natural photographs.
Mr. Stamets, also founder and director of Olympia, WA-based Fungi Perfecti, LLC, says recent mushroom research is showing unique antimicrobial effects. "We have strong activity of our mushroom extracts against bacteria such as E. coli, staphylococcus, and tuberculosis strains, and a wide variety of viruses from pox to flu viruses," he said. Some of this new evidence is based on testing carried out by the National Institute of Allergy and Infectious Diseases (NIAID) during the past few years. More than two million samples of various agents were submitted to NIAID. The samples Mr. Stamets submitted were among the few natural agents that illustrated true anti-pox activity, according to Dr. John Secrist III who oversaw the program.
Mark Kaylor, PhD, MH, a consultant for Maitake, Inc., East Rutherford, NJ, adds that, "One of the most intriguing areas of recent research is ongoing with the lion's mane mushroom and its use in Alzheimer's and senility. Initial animal studies showed that lion's mane stimulates nerve growth factor, a substance that has demonstrated benefit in Alzheimer's patients."
Quality of Life Labs' AHCC-Active Hexose Correlated Compound-is derived from shiitake mushroom sub-species. "Clinical studies show it enhances the immune system by increasing the activity of the white blood cells," said Mr. Cheatham. Recent research has revealed that two specific cytokines-interferon (IFN-y) and tumor necrosis factor (TNF-a)-increase after several weeks of AHCC intake. Mr. Cheatham points out that AHCC has also shown encouraging results for influenza prevention and recovery, and is currently being tested against West Nile Virus at Colorado State University.
Cancer research has by far attracted the most attention over the past three decades of mushroom research. Few natural products have been subjected to the kind of anticancer research rigor mushrooms have. Hundreds of studies have illustrated various anticarcinogenic effects, many of which have been confirmed by adjunctive human studies. Positive effects in breast cancer, lung cancer, prostate cancer, cervical cancer, bladder cancer and colon cancer have attracted the most attention.
Most of the popular medicinal mushroom species have shown anti-tumor effects. Of these, the jury is out in terms of which is more potent. Mr. Hobbs confirms this. "It's still not clear if one species is any better than another for certain kinds of cancer," he said. "When it comes to serious or chronic disease, I would want to rely on a species or several that have a lot of research and history of use behind them." Besides being prudent, this statement illustrates the luxury so much research on medicinal mushrooms has afforded proponents.
Most of the dramatic health effects of mushrooms have been attributed to their polysaccharides and polysaccharide-protein complexes. Lab research has isolated multiple polysaccharide types within each species. Twenty-nine unique polysaccharides have been isolated in maitake, for example. Mushroom polysaccharides are primarily glucans with different glycosidic linkages, including 1,3 and 1,6 beta-glucans, and 1,3 alpha-glucans. The complex branching and even helical nature of mushroom glucans appears to be significant. Schizophyllan polysaccharides with (1,3)-b-glucans with 1,3-b-d-linked glucose with 1,6-b-d-glucosyl side groups have been described as "stiff triple-stranded" helices in laboratory research, for example. Schizophyllan (SPG) is an active macrophage stimulator, increasing T cell (a type of white blood cell) and NK (natural killer) cell activity and inhibiting various infective agents.
Various immunostimulatory effects have also been attributed to polysaccharide-protein complexes such as PSK (krestin), PSP, lentinan and others. While many varieties contain different levels of the various beta-glucans, many researchers believe it is their unique protein sequencing that differentiates effects among species.
Medicinal mushrooms also contain a variety of nutrients such as protein. Shiitake can be as much as 17% protein, while oyster mushrooms can be 30% protein by weight.
Several also contain vitamin B complexes, in addition to a variety of macro-minerals and trace elements. For example, shiitake can contain as much as 126 mg of calcium and 247 mg of magnesium per serving. Reishi also contains magnesium, calcium, zinc, iron, copper and trace minerals. Many are good sources of selenium.
Maitake and several other mushrooms also contain ergosterols (provitamin D2), along with phosphatidylcholine and phosphatidylserine. The ergosterol content in Agaricus blazei has been identified as an anti-tumor agent in several studies.
Fungi Perfecti's Mr. Stamets released a paper in 2005, which reported that samples of shiitake, reishi and maitake each increased from less than 500 IU of D2 in indoor growing conditions to 46,000 IU, 2760 IU and 31,900 IU, respectively, following six to eight hours of sunlight exposure. Mr. Stamets believes "mushrooms are the best source of vitamin D2 of any land-based organism."
Various antioxidants have been isolated among popular mushroom varieties. Constituents such as ganoderic acid (G. lucidum), cordycepic acid (C. sinensis), linzhi (G. frondosa), agaric acid (several), sizofilan and sizofiran (S. commune), galactomannan (C. sinensis), and various triterpenoids (several) can actively reduce oxidative radicals and stimulate the immune system. "Some recent research has identified the oyster mushroom as containing lovastatin-like compounds," Mr. Chilton said. (Lovastatin is the main compound in cholesterol-lowering drugs.)
Mr. Stamets points out that mushrooms often contain suites of diverse constituents that are useful to the body. "For instance, reishi has more than 100 ethanol-soluble triterpenoids-many of which are useful as anti-inflammatory agents. Since there are so many benefits from these forms, we believe providing constellations of active constituents is better than one alone. The human body sorts out the compounds it most needs."
This issue brings up another point: mushrooms provide standardization complexity because of their multitude of constituents. Many are active conjunctively, and it is difficult to select a single one. For example, Cordyceps sinensis extracts are often standardized to 5-10% "cordycepic acid," which is actually mannitol, a common sugar found in nature. But, Mr. Stamets said, "Cordycepic acid is a useless marker for identifying cordyceps."
So are one-constituent markers in mushroom extracts even useful? Mr. Stamets believes this is difficult to prove according to current mushroom data, which is why he and other scientists are working toward establishing a "constellation of active ingredients" (AIs) for particular mushrooms. "What is needed, and what we are working on, is a list of AIs that will fingerprint the product as being authentic," he says. This of course creates a multilayered complexity, as extraction can upgrade some constituents while downgrading others," he explained. "Although one marker may be degenerated from its original form during heat treatment, for instance, this does not mean the product has been 'harmed,' as heat can increase bioavailability, especially for [other] constituents tightly bound up within the chitin-like exoskeleton of the fungal cell walls."
Mechanisms for immune stimulation are both mysterious and intriguing in mushroom research. Researchers have debated these along with constituent activity. One prominent theory proposes that beta-glucans stimulate the immune system by resembling molecules on bacterial cell walls. As macrophages come into contact with these bacterium "phantoms," immune cells are mobilized. Once inside macrophages, these complex polysaccharides are thought to stimulate cytokines active in tumor inhibition.
Differently branched beta-glucans have been observed stimulating immune cells as well. For example, certain beta-glucans from maitake will stimulate T cell production, while differently bonded-chain beta-glucans from Agaricus blazei stimulate NK cells yet few T cells.
Quality of Life Labs' Mr. Cheatham described this polysaccharide multiplicity. "AHCC specifically targets the body's first line of defense-the NK cells. AHCC may more than triple NK cell function, while also enhancing the function and count of other white blood cells including B, T, T-helper, lymphokine activated killer cells [LAK], macrophages; as well as the cytokine chemical messengers interferon gamma, interleukin-2, -12 and tumor necrosis factor [TNF]."
Mechanisms go beyond polysaccharides and branched polysaccharide-protein complexes. Gourmet Mushrooms' Mr. Law and Mr. Stamets of Fungi Perfecti discussed how mycelia survive for centuries by defending against the many microbes living in moist soils. "The particular enzyme and protein combination a mushroom species develops is specific to its own defense of the microorganisms in its immediate environment," Mr. Law said.
The mushroom's relationship with its environment may also explain why many mushroom species detoxify heavy metals. "The genetic information assembled by the mushroom species expresses particular proteins that drive the process of binding to certain heavy metals within the soil. When consumed, these metabolites become active within the body to assist in the chelating process," Mr. Law noted. Indeed, several mushroom varieties such as cordyceps, reishi, Agaricus blazei and maitake have been shown to be effective in reducing the effects of heavy metal and radiation poisoning.
Both Mr. Law and Mr. Stamets understand this mechanism within a larger context. "I believe both habitats and humans have immune systems, and since we share many of the same pathogens that afflict fungi, we can benefit from understanding roles of fungi in natural habitats, and use this knowledge to improve host defense of resistance in humans," Mr. Stamets commented.
Delivery systems for medicinal mushrooms range from liquids and powdered extracts to dried whole powders and teas. Parts used include the fruiting body (cap and stem) and the mycelia (colonizing rooting network).
Each delivery system has its proponents. As an acupuncturist and renowned herbalist, Mr. Hobbs naturally emphasizes full spectrum extracts and whole mushrooms. "A freeze-dried, enzymatically degraded fruiting body (or mycelium in some cases) extract is the best form, in my opinion. Or a dried tea might be okay if the heat doesn't reduce the effectiveness," he said. "I would avoid tincture products with alcohol for the most part, although these might extract some low molecular weight compounds that could have some beneficial effects. I still think it is generally better to eat the whole mushroom where the cell walls are broken down to make the glucans and other compounds available to interact with the immune system on the way through the GI tract."
Mr. Cheatham from Quality of Life Labs shared his perspectives on the advantages of products with a low molecular weight. "The major advantage Kinoko AHCC has over whole medicinal mushrooms is its low molecular weight of 5000 Daltons. Medicinal mushrooms typically have a molecular weight of more than 300,000 Daltons. The benefit of a lower molecular weight is greater bioavailability," he explained.
Mr. Stamets also urges consideration for a mushroom's growing region. "There is increasing concern about heavy metal contamination and pesticide residues such as Dursban, which is commonly seen from producers in heavily polluted, industrialized, deforested regions of the world," he said. "People want to be sure the mushrooms they purchase are organically grown and that the country of origin is clearly identified."
Gourmet Mushrooms, Inc. has gone to the extent of taming wild Cordyceps cultures by growing in controlled organic conditions. The company's Malcolm Clark, along with his Japanese associates, journeyed to 12,000 feet in Nepal to collect cordyceps cultures from their normal hosts-caterpillar larvae. Upon returning to Sebastopol, CA, the cultures were adapted to mycelia growing upon grain substrate, offering the market a vegan organic mycelia. Capillary electrophoresis testing of the domesticated mycelia has confirmed nucleoside matching with their wild cordyceps cousins.
There has been some debate regarding potency of mycelia (rooting system) versus mushroom fruiting bodies. Mr. Law contends that grain-substrate mycelia offer the distinct advantage of safety and consistency of the mushroom's complement of protein expression, enzymes and polysaccharides. "Mycelium can live up to 2000 years, and cover an expanse of terrain in the wild. Throughout this period, mycelia will develop immunity against a variety of pathogens, allowing them to express complex protein and enzyme combinations that also stimulate the human immune system." Mr. Law referred to an incredible ancient 2200-acre mycelia land mass in Oregon documented by Mr. Stamets.
Mr. Stamets adds that mycelia grown on grain substrates can also provide unique benefits. "The majority of starches within rice medium upon which the fungi are grown are enzymatically converted into other sugars useful for the immune system and for building beta-glucan-like structures."
Mr. Stamets and Mr. Law agree that mycelia provide constituents that the fruiting body may not and vice versa in some cases. "The mushrooms that form from mycelium are arrays of compacted mycelium and do not produce the extracellular, antimicrobial constituents, being laminated together. Within them are intracellular and structural components in their exoskeletons that are more useful for the erection of a sporulating fruitbody-the mushroom," said Mr. Stamets.
Standardized extraction of particular polysaccharides is still very useful. As Donna Noonan, vice president at Maitake Products, Inc points out, "Our flagship products [D-Fraction and SX-Fraction] are time-tested and well researched standardized extract products from the maitake mushroom."
Jeff Chilton agrees. He described Nammex' extraction process, which enhances polysaccharide availability. "It is a distinct therapeutic advantage to have a 100% pure, easily assimilated mushroom powder or extract."
While some question ethanol extraction, ethanol appears to extract certain antiviral elements more efficiently. "Hot water extracts of fruitbodies lack this [antimicrobial] activity, when compared side by side [with ethanol extractions]," said Mr. Stamets. "Moreover, the ethanol fractions pull out powerful antioxidants-ergothioneines-whereas the water fractions pull more of the soluble polysaccharides. Combining both of these groups provides a shield of resistance directly and indirectly."
So perhaps there is room for all of these delivery systems in mushroom therapy. Mr. Hobbs believes a variant approach to mushroom supplementation will both add benefit and prevent immune tolerance. "It is probably good to change the species every three to five months so the immune system doesn't get too complacent," he said. "I would think that using one species for three months, then switching to another for three months or so is the best way."
Mushroom choices and their uses can be dizzying, which is why many adopt combination therapy. And most experts believe combination therapy can be quite successful if approached carefully. "I don't tend to like more than a few species in a formula, and not the 'kitchen sink' formulas that have all the species," Mr. Hobbs cautioned.
Gourmet Mushrooms' Mr. Law feels combination therapy should contain one of each type of mushroom. "One gilled, one jelly and one polypore [mushroom] will offer a nice broad mix of constituents," he said.
Mushrooms are increasingly being blended with other agents too. "We have combined stabilized Agaricus blazei extracts with complementary antimicrobial agents such as bamboo leaf extract," said Atlas' Mr. Takeda.
Nammex' Mr. Chilton confirms a trend of combining mushrooms of different species among his customers. "Not only are we experiencing inquiries from new companies, but our established customers are now broadening their offerings with new species," he said.
While there exists a variety of new growth opportunities, most executives believe the market for medicinal mushrooms still has a long way to go before approaching maturity. Comparing the U.S. market with Asia, Mr. Chilton said, "This is a billion-dollar category in Asia, and it is just starting to get noticed here in North America."
For the future, Mr. Stamets believes that the mysteries of medicinal mushrooms may also provide a much broader range of healing mechanisms. "Tapping into the natural wisdom of these highly evolved organisms gives us new hope in solving many of the critical issues we face today, including: fighting disease, destroying toxic wastes, replacing chemical pesticides, creating ethanol from cellulose, and most important, constructing the fabric of life upon which soils are based," he commented. "By partnering with mushrooms, we are supporting a healthier future for our descendants."
About the author:
The size of the medicinal mushroom market is another mystery pervading the industry. Multiple supply channels, delivery systems and packaging challenge statistics. Offshore sellers compete with domestic growers and manufacturers. Medicinal mushrooms are sold in a myriad of venues. To complicate matters further, restaurants increasingly serve specialty/medicinal mushrooms, health practitioners are prescribing mushrooms for a variety of patients, and Health food markets, fairs, internet, and even drug store chains are stocking mushroom supplements.
It is sill possible, however, to extrapolate significant growth. Global production of edible and medicinal mushrooms shroomed from 1.2 million tons in 1981 to an estimated 7 million tons in 1999 and approximately 9.9 million tons in 2004. The U.S. market consumes only a fraction of this volume, however.
In the 2006 crop year, the U.S. produced a little more than 400,000 tons of Agaricus species (the largest mushroom genus). Sales of U.S.-produced Agaricus mushrooms in crop year 2006 were $915 million, up 8% from the previous crop year. Sales of imported mushrooms made an even bigger jump, reporting a 30% increase from the year before at $236 million for the first 10 months of 2007. Sales of specialty/medicinal mushrooms comprise only a fraction of total mushroom sales, with an estimated $40 million sold by U.S. growers for crop year 2006. Notably, organic U.S. specialty mushroom production grew to 8 million pounds from less than 2 million pounds produced a crop year earlier-a phenomenal 400% leap.
David Law, biologist and CEO of Gourmet Mushrooms, Inc. says that restaurants are increasingly ordering their organic specialty/medicinal mushrooms, illustrating a trend among an affluent, aging generation. "Their patrons are realizing that mushrooms have many health benefits," he said. Gourmet Mushrooms, a three-decade Sebastopol, CA-based certified organic mushroom grower, has experienced consistent annual growth. "If we produced all we could sell, we could double our sales every two years," Mr. Law estimates.
Some mushroom supplement manufacturers are reporting double-digit growth despite weakening supplement sales in other categories. Hank Cheatham, director at Quality of Life Labs, Purchase, NY, adds that this growth is expected to continue. "The population continues to age and people are becoming more aware of mushrooms' healthy immune response."
Sales of some species are on a steeper growth trend. Yori Takeda, COO at Torrance, CA-based Atlas North America estimates that its Agaricus blazei mushroom supplement and bulk sales have shot up 300% during the past four years.
Even with this kind of growth, it is apparent that medicinal mushroom use in North America seriously lags behind the rest of the world, particularly Asia. In the mid-1990s, medicinal mushroom sales in the U.S. accounted for less than 1% of worldwide sales. Even with the estimated 20-40% growth since then, U.S. sales still remain far behind Asia and the rest of the world.
An Array of Choices
Scientists have cataloged some 50,000 mushrooms, and identified less than 20,000 different mushroom species. Some estimate there may be more than 150,000 mushroom species within the Fungi kingdom, which likely encompasses more than 1.5 million total species. Biologists have described less than 5% of Fungi species.
While more than 600 mushroom species have revealed immune stimulation effects, much of the research has focused on a narrower range of less than 50 species. The more popular parallel their respective research. The more researched commercial medicinal mushrooms include maitake (Grifola frondosa), shiitake (Lentinula edodes), reishi (Ganoderma lucidum), turkey tail (Coriolus versicolor or Trametes versicolor), Agaricus blazei (Murrill), Cordyceps sinensis, lion's mane (Hericium erinaceus), and split-gill (Schizophyllum commune).
With so many mushrooms showing positive effects, raw material buyers and consumers have a lot to digest. Jeff Chilton, president of Nammex, Gibsons, British Columbia, Canada, discussed some of the current market leaders. "Reishi mushroom continues to be a best-seller for us. The volume of research that supports its effectiveness and use for immune system issues has given it a strong following among American health practitioners. Reishi works on many levels due to its unique combination of polysaccharides and triterpenes," he explained. "Other species gaining ground are shiitake, maitake and cordyceps, all of which are well researched. Cordyceps has truly taken the West by storm."
Mushroom expert and renowned herbalist Christopher Hobbs, LAc, AHG, confirms this hierarchy among research results. "The best species remain shiitake, turkey tail, split-gill, Wolfiporia [cocos], some Ganoderma spp., and cordyceps," he offered.
Differentiation comes by way of the need for alternatives. "Many come to us unhappy with their current healthcare options. They discover our Agaricus blazei immune support products after seeing the research and hearing about us. A. blazei appears to be getting more attention from the medical community in North America," commented Atlas' Mr. Takeda.
A Plethora of Research
The challenge for medicinal mushroom suppliers continues to be education. There is no lack of research or traditional use, however. Mushrooms have enjoyed thousands of years of traditional treatments, and a growing body of controlled and peer-reviewed research has confirmed many of these.
In the 1960s and 1970s, Asian universities, hospitals and laboratories began reporting significant in vivo research results, with laboratories confirming cellular mechanisms. These revealed antimicrobial, cholesterol-lowering, anti-inflammatory, antioxidant, anti-mutagenic, anti-tumor, adaptogenic and immunostimulation effects.American researchers finally took notice when Dr. Tetsuro Ikekawa's groundbreaking epidemiological study showed significantly lower cancer rates among Japanese mushroom growers between 1972 and 1986.
European and American research-some by prestigious universities and medical centers-began adding to continuing Asian research. By the mid-1990s, thousands of controlled studies had documented medicinal mushrooms' range of health benefits. While most clinical research to date has been adjunctive to conventional therapies for ethical reasons, human studies have consistently confirmed animal and laboratory models. As of August 2008, there were 4087 mushroom studies and scientific papers filed with the U.S. National Library of Medicine.
Mr. Hobbs was one of the first American authors to catalog this plethora of mushroom research and history in his 1995 classic, Medicinal Mushrooms. His pioneering compilation introduced many consumers and practitioners to the history, characteristics, attributes and medicinal effects of mushrooms for the first time. During the next decade, several rigorous treatises on mushroom science brought increased familiarity. One of the more prolific mushroom authors to rise to prominence was Paul Stamets, who is now regarded as one of America's leading fungal experts. Mr. Stamets has published six books on the subject, each accompanied by dramatic natural photographs.
Mr. Stamets, also founder and director of Olympia, WA-based Fungi Perfecti, LLC, says recent mushroom research is showing unique antimicrobial effects. "We have strong activity of our mushroom extracts against bacteria such as E. coli, staphylococcus, and tuberculosis strains, and a wide variety of viruses from pox to flu viruses," he said. Some of this new evidence is based on testing carried out by the National Institute of Allergy and Infectious Diseases (NIAID) during the past few years. More than two million samples of various agents were submitted to NIAID. The samples Mr. Stamets submitted were among the few natural agents that illustrated true anti-pox activity, according to Dr. John Secrist III who oversaw the program.
Mark Kaylor, PhD, MH, a consultant for Maitake, Inc., East Rutherford, NJ, adds that, "One of the most intriguing areas of recent research is ongoing with the lion's mane mushroom and its use in Alzheimer's and senility. Initial animal studies showed that lion's mane stimulates nerve growth factor, a substance that has demonstrated benefit in Alzheimer's patients."
Quality of Life Labs' AHCC-Active Hexose Correlated Compound-is derived from shiitake mushroom sub-species. "Clinical studies show it enhances the immune system by increasing the activity of the white blood cells," said Mr. Cheatham. Recent research has revealed that two specific cytokines-interferon (IFN-y) and tumor necrosis factor (TNF-a)-increase after several weeks of AHCC intake. Mr. Cheatham points out that AHCC has also shown encouraging results for influenza prevention and recovery, and is currently being tested against West Nile Virus at Colorado State University.
Cancer research has by far attracted the most attention over the past three decades of mushroom research. Few natural products have been subjected to the kind of anticancer research rigor mushrooms have. Hundreds of studies have illustrated various anticarcinogenic effects, many of which have been confirmed by adjunctive human studies. Positive effects in breast cancer, lung cancer, prostate cancer, cervical cancer, bladder cancer and colon cancer have attracted the most attention.
Most of the popular medicinal mushroom species have shown anti-tumor effects. Of these, the jury is out in terms of which is more potent. Mr. Hobbs confirms this. "It's still not clear if one species is any better than another for certain kinds of cancer," he said. "When it comes to serious or chronic disease, I would want to rely on a species or several that have a lot of research and history of use behind them." Besides being prudent, this statement illustrates the luxury so much research on medicinal mushrooms has afforded proponents.
A Multitude of Constituents
Most of the dramatic health effects of mushrooms have been attributed to their polysaccharides and polysaccharide-protein complexes. Lab research has isolated multiple polysaccharide types within each species. Twenty-nine unique polysaccharides have been isolated in maitake, for example. Mushroom polysaccharides are primarily glucans with different glycosidic linkages, including 1,3 and 1,6 beta-glucans, and 1,3 alpha-glucans. The complex branching and even helical nature of mushroom glucans appears to be significant. Schizophyllan polysaccharides with (1,3)-b-glucans with 1,3-b-d-linked glucose with 1,6-b-d-glucosyl side groups have been described as "stiff triple-stranded" helices in laboratory research, for example. Schizophyllan (SPG) is an active macrophage stimulator, increasing T cell (a type of white blood cell) and NK (natural killer) cell activity and inhibiting various infective agents.
Various immunostimulatory effects have also been attributed to polysaccharide-protein complexes such as PSK (krestin), PSP, lentinan and others. While many varieties contain different levels of the various beta-glucans, many researchers believe it is their unique protein sequencing that differentiates effects among species.
Medicinal mushrooms also contain a variety of nutrients such as protein. Shiitake can be as much as 17% protein, while oyster mushrooms can be 30% protein by weight.
Several also contain vitamin B complexes, in addition to a variety of macro-minerals and trace elements. For example, shiitake can contain as much as 126 mg of calcium and 247 mg of magnesium per serving. Reishi also contains magnesium, calcium, zinc, iron, copper and trace minerals. Many are good sources of selenium.
Maitake and several other mushrooms also contain ergosterols (provitamin D2), along with phosphatidylcholine and phosphatidylserine. The ergosterol content in Agaricus blazei has been identified as an anti-tumor agent in several studies.
Fungi Perfecti's Mr. Stamets released a paper in 2005, which reported that samples of shiitake, reishi and maitake each increased from less than 500 IU of D2 in indoor growing conditions to 46,000 IU, 2760 IU and 31,900 IU, respectively, following six to eight hours of sunlight exposure. Mr. Stamets believes "mushrooms are the best source of vitamin D2 of any land-based organism."
Various antioxidants have been isolated among popular mushroom varieties. Constituents such as ganoderic acid (G. lucidum), cordycepic acid (C. sinensis), linzhi (G. frondosa), agaric acid (several), sizofilan and sizofiran (S. commune), galactomannan (C. sinensis), and various triterpenoids (several) can actively reduce oxidative radicals and stimulate the immune system. "Some recent research has identified the oyster mushroom as containing lovastatin-like compounds," Mr. Chilton said. (Lovastatin is the main compound in cholesterol-lowering drugs.)
Mr. Stamets points out that mushrooms often contain suites of diverse constituents that are useful to the body. "For instance, reishi has more than 100 ethanol-soluble triterpenoids-many of which are useful as anti-inflammatory agents. Since there are so many benefits from these forms, we believe providing constellations of active constituents is better than one alone. The human body sorts out the compounds it most needs."
This issue brings up another point: mushrooms provide standardization complexity because of their multitude of constituents. Many are active conjunctively, and it is difficult to select a single one. For example, Cordyceps sinensis extracts are often standardized to 5-10% "cordycepic acid," which is actually mannitol, a common sugar found in nature. But, Mr. Stamets said, "Cordycepic acid is a useless marker for identifying cordyceps."
So are one-constituent markers in mushroom extracts even useful? Mr. Stamets believes this is difficult to prove according to current mushroom data, which is why he and other scientists are working toward establishing a "constellation of active ingredients" (AIs) for particular mushrooms. "What is needed, and what we are working on, is a list of AIs that will fingerprint the product as being authentic," he says. This of course creates a multilayered complexity, as extraction can upgrade some constituents while downgrading others," he explained. "Although one marker may be degenerated from its original form during heat treatment, for instance, this does not mean the product has been 'harmed,' as heat can increase bioavailability, especially for [other] constituents tightly bound up within the chitin-like exoskeleton of the fungal cell walls."
Mysterious Mechanisms
Mechanisms for immune stimulation are both mysterious and intriguing in mushroom research. Researchers have debated these along with constituent activity. One prominent theory proposes that beta-glucans stimulate the immune system by resembling molecules on bacterial cell walls. As macrophages come into contact with these bacterium "phantoms," immune cells are mobilized. Once inside macrophages, these complex polysaccharides are thought to stimulate cytokines active in tumor inhibition.
Differently branched beta-glucans have been observed stimulating immune cells as well. For example, certain beta-glucans from maitake will stimulate T cell production, while differently bonded-chain beta-glucans from Agaricus blazei stimulate NK cells yet few T cells.
Quality of Life Labs' Mr. Cheatham described this polysaccharide multiplicity. "AHCC specifically targets the body's first line of defense-the NK cells. AHCC may more than triple NK cell function, while also enhancing the function and count of other white blood cells including B, T, T-helper, lymphokine activated killer cells [LAK], macrophages; as well as the cytokine chemical messengers interferon gamma, interleukin-2, -12 and tumor necrosis factor [TNF]."
Mechanisms go beyond polysaccharides and branched polysaccharide-protein complexes. Gourmet Mushrooms' Mr. Law and Mr. Stamets of Fungi Perfecti discussed how mycelia survive for centuries by defending against the many microbes living in moist soils. "The particular enzyme and protein combination a mushroom species develops is specific to its own defense of the microorganisms in its immediate environment," Mr. Law said.
The mushroom's relationship with its environment may also explain why many mushroom species detoxify heavy metals. "The genetic information assembled by the mushroom species expresses particular proteins that drive the process of binding to certain heavy metals within the soil. When consumed, these metabolites become active within the body to assist in the chelating process," Mr. Law noted. Indeed, several mushroom varieties such as cordyceps, reishi, Agaricus blazei and maitake have been shown to be effective in reducing the effects of heavy metal and radiation poisoning.
Both Mr. Law and Mr. Stamets understand this mechanism within a larger context. "I believe both habitats and humans have immune systems, and since we share many of the same pathogens that afflict fungi, we can benefit from understanding roles of fungi in natural habitats, and use this knowledge to improve host defense of resistance in humans," Mr. Stamets commented.
Multiple Delivery Systems
Delivery systems for medicinal mushrooms range from liquids and powdered extracts to dried whole powders and teas. Parts used include the fruiting body (cap and stem) and the mycelia (colonizing rooting network).
Each delivery system has its proponents. As an acupuncturist and renowned herbalist, Mr. Hobbs naturally emphasizes full spectrum extracts and whole mushrooms. "A freeze-dried, enzymatically degraded fruiting body (or mycelium in some cases) extract is the best form, in my opinion. Or a dried tea might be okay if the heat doesn't reduce the effectiveness," he said. "I would avoid tincture products with alcohol for the most part, although these might extract some low molecular weight compounds that could have some beneficial effects. I still think it is generally better to eat the whole mushroom where the cell walls are broken down to make the glucans and other compounds available to interact with the immune system on the way through the GI tract."
Mr. Cheatham from Quality of Life Labs shared his perspectives on the advantages of products with a low molecular weight. "The major advantage Kinoko AHCC has over whole medicinal mushrooms is its low molecular weight of 5000 Daltons. Medicinal mushrooms typically have a molecular weight of more than 300,000 Daltons. The benefit of a lower molecular weight is greater bioavailability," he explained.
Mr. Stamets also urges consideration for a mushroom's growing region. "There is increasing concern about heavy metal contamination and pesticide residues such as Dursban, which is commonly seen from producers in heavily polluted, industrialized, deforested regions of the world," he said. "People want to be sure the mushrooms they purchase are organically grown and that the country of origin is clearly identified."
Gourmet Mushrooms, Inc. has gone to the extent of taming wild Cordyceps cultures by growing in controlled organic conditions. The company's Malcolm Clark, along with his Japanese associates, journeyed to 12,000 feet in Nepal to collect cordyceps cultures from their normal hosts-caterpillar larvae. Upon returning to Sebastopol, CA, the cultures were adapted to mycelia growing upon grain substrate, offering the market a vegan organic mycelia. Capillary electrophoresis testing of the domesticated mycelia has confirmed nucleoside matching with their wild cordyceps cousins.
There has been some debate regarding potency of mycelia (rooting system) versus mushroom fruiting bodies. Mr. Law contends that grain-substrate mycelia offer the distinct advantage of safety and consistency of the mushroom's complement of protein expression, enzymes and polysaccharides. "Mycelium can live up to 2000 years, and cover an expanse of terrain in the wild. Throughout this period, mycelia will develop immunity against a variety of pathogens, allowing them to express complex protein and enzyme combinations that also stimulate the human immune system." Mr. Law referred to an incredible ancient 2200-acre mycelia land mass in Oregon documented by Mr. Stamets.
Mr. Stamets adds that mycelia grown on grain substrates can also provide unique benefits. "The majority of starches within rice medium upon which the fungi are grown are enzymatically converted into other sugars useful for the immune system and for building beta-glucan-like structures."
Mr. Stamets and Mr. Law agree that mycelia provide constituents that the fruiting body may not and vice versa in some cases. "The mushrooms that form from mycelium are arrays of compacted mycelium and do not produce the extracellular, antimicrobial constituents, being laminated together. Within them are intracellular and structural components in their exoskeletons that are more useful for the erection of a sporulating fruitbody-the mushroom," said Mr. Stamets.
Standardized extraction of particular polysaccharides is still very useful. As Donna Noonan, vice president at Maitake Products, Inc points out, "Our flagship products [D-Fraction and SX-Fraction] are time-tested and well researched standardized extract products from the maitake mushroom."
Jeff Chilton agrees. He described Nammex' extraction process, which enhances polysaccharide availability. "It is a distinct therapeutic advantage to have a 100% pure, easily assimilated mushroom powder or extract."
While some question ethanol extraction, ethanol appears to extract certain antiviral elements more efficiently. "Hot water extracts of fruitbodies lack this [antimicrobial] activity, when compared side by side [with ethanol extractions]," said Mr. Stamets. "Moreover, the ethanol fractions pull out powerful antioxidants-ergothioneines-whereas the water fractions pull more of the soluble polysaccharides. Combining both of these groups provides a shield of resistance directly and indirectly."
So perhaps there is room for all of these delivery systems in mushroom therapy. Mr. Hobbs believes a variant approach to mushroom supplementation will both add benefit and prevent immune tolerance. "It is probably good to change the species every three to five months so the immune system doesn't get too complacent," he said. "I would think that using one species for three months, then switching to another for three months or so is the best way."
Managing Medicinal Mushroom Use
Mushroom choices and their uses can be dizzying, which is why many adopt combination therapy. And most experts believe combination therapy can be quite successful if approached carefully. "I don't tend to like more than a few species in a formula, and not the 'kitchen sink' formulas that have all the species," Mr. Hobbs cautioned.
Gourmet Mushrooms' Mr. Law feels combination therapy should contain one of each type of mushroom. "One gilled, one jelly and one polypore [mushroom] will offer a nice broad mix of constituents," he said.
Mushrooms are increasingly being blended with other agents too. "We have combined stabilized Agaricus blazei extracts with complementary antimicrobial agents such as bamboo leaf extract," said Atlas' Mr. Takeda.
Nammex' Mr. Chilton confirms a trend of combining mushrooms of different species among his customers. "Not only are we experiencing inquiries from new companies, but our established customers are now broadening their offerings with new species," he said.
While there exists a variety of new growth opportunities, most executives believe the market for medicinal mushrooms still has a long way to go before approaching maturity. Comparing the U.S. market with Asia, Mr. Chilton said, "This is a billion-dollar category in Asia, and it is just starting to get noticed here in North America."
For the future, Mr. Stamets believes that the mysteries of medicinal mushrooms may also provide a much broader range of healing mechanisms. "Tapping into the natural wisdom of these highly evolved organisms gives us new hope in solving many of the critical issues we face today, including: fighting disease, destroying toxic wastes, replacing chemical pesticides, creating ethanol from cellulose, and most important, constructing the fabric of life upon which soils are based," he commented. "By partnering with mushrooms, we are supporting a healthier future for our descendants."
