Scientific Research & Medicinal Fungi
By Dianna Smith
According to my supermarket purchase of Prevention Magazine, mushrooms are the latest superfood they recommend we incorporate into our diets in efforts to enhance our health and sense of well-being.1 Of course, many mycophiles have been way ahead of this movement and have been consuming what is commonly referred to as ‘medicinal’ fungi in the form of pills or tinctures for years already either to prophylactically prevent illness or with the expectation that they can enhance their immune systems to restore health if suffering from diabetes, heart diseases, cancers, Alzheimer’s or any other disorder.
Evidence suggests humans have enjoyed a close and long association with fungal organisms as fire starters, styptics, bandages, as food for making breads, cheeses, tofu, soy sauce, flavor enhancers, preservatives, as alcohol used to mark and cement ritual, social and political relationships, and as hallucinogens to facilitate connections to the spirit realm of unpredictable gods or ancestors. Today they are being fashioned into furniture, art, insulation, and packaging. They are being investigated and used for bioremediation of heavy metals, toxic wastes, radiation, and explosives.2 Fungi are employed in reforestation projects,3 numerous and varied industrial applications, as alternative fuels, as pesticides in farming,4 in food production and vitamin manufacture. We have discovered that fungi are chemical factories that also have the potential to provide us with new medicines as well as nutritious food.
Fungi and animals branched away from plants about a billion or so years ago, and from each other about a half billion or so years ago. Their common ancestor may have been a single-celled organism with sperm-like animal characteristics containing a nucleus and DNA. Since we share more of the same DNA with them than we do with plants, it is thought that at least some representatives of the fungi kingdom just might be a better fit for humans than plant-sourced drugs. In the effort to survive against competition and predation by bacteria, insects, animals, viruses and other microbes, fungi have evolved numerous enzymes and secondary metabolites to deal with these challenges. Our own immune systems also have evolved complex processes designed to defend themselves against sudden or slowly changing threats from evolving bacteria, viruses, fungi and the diseases associated with them. To the extent that many of our microbial enemies and friends are the same, there is the potential that their chemical compounds will be found to be useful in helping us survive similar assaults. Some fungi, those that enable us to prevail against bacterial infection, have already proven to be helpful to humans and other animals. Fungal medicines from yeast, of course, also have the unfortunate consequence of killing good as well as pathogenic bacteria. In this respect they are not unlike other plant or chemically-based medicines.
ANTIBIOTICS
Fungi in the form of many different kinds of antibiotics5 derived from penicillin have been a major source of change in the health of humans to treat microbial infections from the 1940s onward. Their use led to the decline in fatality of children with bacterial meningitis, strep throat, whooping cough and epidemics of tuberculosis and pneumonia, controlling deadly infections from war wounds and from dental procedures and serious surgeries. They have saved countless millions of lives. But, they are not recommended for prophylactic use. Overuse in domesticated animals intended for the food market, as well as in humans for viral infections, where they are ineffective, has led to the establishment of resistance to current antibiotics.6 Developing new approaches to kill harmful bacterial infections is a continuing challenge for researchers. Bacteria, like cancers, evolve quickly to avoid being destroyed by our treatments, our drugs, and our complicated immune system. In fact, evidence is emerging that at least some bacterial infections appear to be associated with stomach and intestinal cancers.7 Others cause the proliferation of cancer cells.8 If caught in the earliest stages, some antibiotics have even been found to cause the regression of certain tumors.9
STATINS
Lovastatin is derived from enzymes produced by the secondary metabolites of Aspergillus terreus fungi. It has been widely employed as a cholesterol-lowering drug for people at risk of developing cardiovascular disease. It prevents the liver from manufacturing cholesterol and is believed to reduce the number heart attacks, strokes and deaths in cardiac patients unable to derive benefits from following clinical practice guidelines through diet and life-style changes.10 There is also lovastatin in oyster mushrooms which in two different studies have been fed to rabbits and rats in powdered form. The formulation constituted 10% of the diet in rats and 5% in the rats. It was found to significantly reduce their levels of blood cholesterol, but it would be impractical for humans to consume equally large doses. Sales of statins are among the highest of all drugs in pharmaceutical history, but like all medicines, they can cause side effects, some of which are severe.11 Red yeast rice has been fermented by Monascus purpureus and has been used in Asia as a food colorant for Peking duck, a food preservative, a spice and an ingredient in rice wine.12 It has been found to contain monacolins, natural statins that lower cholesterol levels. There are numerous brands of red yeast rice manufactured and sold in the U.S. They purport to control cholesterol levels, but these are not in the least effective, since the FDA ruled that as nutritional supplements lacking uniform quality control, they cannot contain anything above trace amounts of monacolins.13 Nevertheless, manufacturers, sales outlets and some physicians who are proponents of using natural products continue to suggest that the red yeast supplements foster cardiac heath.14
CYCLOSPORIN
Cyclosporine is a ‘natural’ immunosuppressant drug made from another species of soil fungus, Tolypocladium inflatum, a stage in the life cycle of Cordyceps subsesdsilis that parasitizes beetle larvae. It serves patients undergoing transplant surgery by suppressing the immune system’s natural response of rejecting a foreign organism (which results in increased susceptibility to bacterial, fungal and viral pathogens). It is also used for some autoimmune diseases that don’t respond well to other medications such as rheumatoid arthritis, ulcerative colitis, Crohn’s Disease and psoriasis.15 However, it should not be taken with St. John’s wort, typically used for mild depression, since the herb is known to interfere with the action of the immunosuppressant,16 as well as HIV and anti-cancer drugs.17
CLAVICEPS spp.
Alkaloids from strains of Claviceps purpurea, an ergot alkaloid grain parasite have been used in the past by European mid-wives for heavy menstruation, to stimulate women’s contractions during and following child birth and also to induce abortions.18 There is evidence that the mycotoxin effected the people in many different cultures over the past five thousand years. In Medieval Europe during wet periods, stored grain used for baking bread was occasionally infected with the parasite and consumption caused many to hallucinate, compulsively dance, lose gangrenous limbs and often collapse in agonizing death. The alkaloid continues to infect domesticated farm animals. Today ergot alkaloids are used to treat migraines,19 and the symptoms of Parkinson’s. In the last century it has been employed to make Lysergic acid diethylamide (LSD) and currently is being studied for its capacity to reduce anxiety.20 A number of our most influential mycologists were among the first Americans to experience the profound effects of this drug and fungal psilocybin beginning in the 1960’s counter-culture movement.
ANTIFUNGAL MEDICINES
Other fungi have been found to work as antifungal agents (Micafungin) and are helpful in treating candidemia, abscesses and esophageal candidiasis.21 Micro-fungi continue to be investigated for their potential medicinal benefits.
PHARMACOLOGICAL PROPERTIES OF MEDICINAL MACRO-FUNGI
More recently, some researchers have begun to focus their attention on macro-fungi as possible sources of new medicines. This effort has been promoted especially in East Asian countries which historically looked to China to enhance their own healing traditions. In China, mushrooms and other substances, inorganic as well as organic, have been employed throughout history for their reputed dietary and health-enhancing attributes in everyday cuisine as well as their potential to stave off starvation. To provide basic health care to the rural population, the Chinese government sought to revive the medical practices of the urban educated elite from imperial times. As of the 1980’s, Chinese researchers were ordered to examine the medical literature of the past millennia to find evidence that the ingredients used were capable of preventing and curing diseases which modern scientific biomedicine continues to find challenging. It was expected that numerous useful medicines would be revealed that could be substituted for expensive ‘western’ pharmaceuticals. As cheaper and presumably better ‘natural’ medicines that withstood the test of time, they could also be marketed and sold throughout the world as safe and modestly-priced alternatives to ‘western’ medicine.
It is not surprising that of 540 fungi listed in three books published in China in the 1980’s and 1990’s, all have been assigned therapeutic properties based partly on reinterpretation of their uses in the past in accordance with modern medical concepts. They are considered among the most potent and comprehensively effective ‘super-medicines’ having the power to prevent and cure maladies ranging from colds and wrinkles to obesity, diabetes, heart diseases, cancers and Alzheimer’s. Of these 331 or 61% are said to have antitumor functions.22 Unlike medicinal micro-fungi or modern medicines, initial comments regarding their therapeutic properties appear to imply that there are no negative consequences of using them.
It has been estimated that there are at least 1,000 known macro-fungi with medicinal properties.23 What is in fungi that makes them ‘medicinal’? There are hundreds of polysaccharides and other bioactive compounds in different fungi that make up their chitin cells walls. (These are also used in the food industry as additives in sour cream, cheese spreads, frozen desserts and salad dressings). Beta-glucans are sugars that can be found in the cells walls of plants, bacteria and algae, as well as fungi (including lichens). Many glucans appear to be capable of triggering immune responses, and possibly antioxidant, antiviral and antibacterial activity responsible for accelerating the healing of wounds. In Asia, they are being used to boost the immune systems of patients with weakened body defenses. They are considered potentially useful for patients suffering from a wide-range of disorders including HIV/AIDS, chronic fatigue syndrome, asthma, multiple sclerosis, Lyme disease, lung infections, burns, canker sores, ulcerative colitis, yeast infections, irritable bowel syndrome, rheumatoid arthritis, ear infections, psoriasis, diabetes, physical and emotional stress, and liver problems. They are also used to lower cholesterol, reduce blood pressure, turn gray hair to its youthful original color, and to prevent wrinkles and aging.
In test tubes, petri dishes and in lab animals, some of these polysaccharides (plant as well as fungal) are capable of inducing macrophage activity and destroying tumor cells of specific cancers. Beta-glucans appear to have positive biological effects on tumors, diabetes and hepatitis by stimulating the immune system.24 But can they do this in human beings? How does the human immune system react to their presence? Is it always positive? What is the level of proof we should be willing to accept to begin taking fungal medicinals for prevention or potential cure of diseases?
According to Tero Isokauppila and Mark Hyman, authors of Healing Mushrooms: A Practical and Culinary Guide to Using Mushrooms for Whole Body Health (2017) a recent book on medicinal fungi:
“These compounds act as immunomodulators – with each different strain having specific positive effects on your health. For example, the maitake mushroom contains a polysaccharide that has been shown to lower blood pressure, stabilize blood sugar, and lower cholesterol, while the shitake mushroom has a polysaccharide that has proven to be more aggressive targeting HIV- infected cells than the most-used HIV-treatment pharmaceutical on the market and also effectively stimulates antibodies that counteract the effects of hepatitis B. All the polysaccharides found in the medicinal mushrooms we will discuss in this book activate the generation of cells that kill foreign pathogens.”25
IMMUNE SYSTEM
As you may have gathered from reading the above statement, arguments for utilizing medicinal fungi to prevent and cure disease focus on the immune system and the free-radical theory of aging. The human immune system comprises many biological cells and processes that protect the body mainly from microbial pathogens and tumors and repair damage. Except in the cases of autoimmune diseases,genetic immunodeficiency, or acquired immunodeficiency as a result of HIV/AIDS or immunosuppressant drugs used to prevent organ transplant rejection, it is generally able to distinguish intruders from normal ‘self’ tissues.
As a legitimate high-quality food, fungi aid us to become stronger, more energetic, and healthy thanks to the effects of their nutrients on our native immune systems. As food, some fungi may even help us fight pain associated with inflammation, such as arthritis and rheumatism. But are they ‘medicines’ capable of treating disorders like obesity, arterial sclerosis, heart disease, diabetes, cancers, or fungal diseases to which we are prone? Are there known benefits to humans eating processed dried fungi in pill or tincture form that cannot be met by regularly eating a meal made with a few fresh or dried mushrooms cooked along with other recognized healthy sources of nutrients? Are they unique in their ability to provide drugs or so-called nutraceuticals capable of preventing and curing diseases? There are many plants polysaccharides with biologically active chemical structures.26
Humans and fungi share roughly 30% of their DNA with each other. Drugs derived from fungi that are aimed at attacking fungal cells have a decent chance of also attacking human cells presumably because of their genetic similarity. The mortality rate of patients who do develop infections from Aspergillus, for example, is about 50%.27 Candidiasis, a common hospital fungal infection of the blood appears also to be a cause for concern as it may have a similar mortality rate.28 We are beginning to notice that different species of fungi also are part of the human microbiome, and while less numerous than resident helpful and pathologic bacteria species, they may have positive as well as negative effects on our health. In patients receiving immune-suppressive drugs, the diversity of the fungal and bacterial gut and bone- marrow biome is greatly reduced in some patients. It is believed there is a relationship between their diversity and the ability of transplant patients to live beyond three years. Populations of Saccharomyces boulardii, for example, increase when psyllium, the fiber in Metamucil, is taken. The entire gastrointestinal biome functions better when the fiber is present.29 Presumably, the fiber in cooked mushrooms is equally beneficial and perhaps a better choice.
The study of fungal polysaccharides has been intensely pursued especially in Asia and every year the research is becoming more sophisticated. Currently, at least some researchers are trying to identify what aspects of the immune system are reacting to particular polysaccharides. Many of the same generation of Asian scientists are just beginning to look at the polysaccharides in select herbs and are finding thatthese also are capable of improving innate immune responses and immunotherapy.30 I suspect that as more research is performed on the vegetables, fruits, eggs, nuts and other foods consumed by humans, we will begin to comprehend the importance of eating a varied diet to support the functioning of a healthy individual. In the west, our focus has been on defining the vitamins and minerals in foods, the aim being to prevent illness due to malnutrition. And every year we declare one or more foods as being miraculous healers. The next step is to concentrate their good qualities in a pill, so we don’t have to eat the real food! I suspect that we will eventually gain a greater appreciation of the capacity of all-natural unprocessed foods to sustain us and to avert some of the diseases we acquire from poor eating habits, lack of exercise, smoking and immoderate alcohol consumption.
CURRENT STATE OF RESULTS OF CLINICAL STUDIES ON MEDICINAL FUNGI
The most researched stars of mushroom nutraceuticals include species of Sparassis spp., Fomitopsis betulinus (Piptoporus betulinus), Flammulina velutipes, Pleurotus and various jelly fungi used in Asian cuisines for their reputed dietary-medicinal properties. The most potent natural and comprehensively effective ‘super-medicines’ being hailed as cures for maladies ranging from wrinkles and obesity to diabetes, heart disease, cancers and Alzheimer’s also includes Lentinula edodes, or Shitake mushrooms, Hericium spp., Ophiocordyceps spp., Grifola frondosa, Trametes versicolor, Inonotus obliquuis or chaga, and Ling zhi, Ganoderma lucidum. Let’s now take a look at the status of research currently available on some of the medicinal fungi believed to possess properties capable of healing us and preventing us from aging.
LION’S MANE: Hericium erinaceus
Hericium erinaceus is a commonly used and consumed mushroom in Asia, especially since it has been widely cultivated in recent years. Its potential to become a source of bio-active compounds to make drugs for dementia and Alzheimer’s is frequently mentioned in popular literature on medicinal mushrooms. One study suggests that erinicine A in Hericium erinaceus may work to decrease amyloid plaques in the cerebral cortex and hippocampus. At least it appears to have worked on the brains of 5- month-old mice.31 More studies are needed before we can conclude that consuming Hericium erinaceus will result in improved cognitive functioning of human patients with Alzheimer’s disease. Today it is being marketed as an alternative ‘smart drug’ that “enhances overall cognitive function”. It contains several Nerve Growth Factors (NGF),32 in which are proteins that are considered important for the generation, growth, and health of nerve cells. A company called ‘Braintropic’ seems to be the place to visit for information on nootropic ‘smart pills’. They claim on their website that the Hericium in their formulation is uniquely capable of promoting regrowth of brain nerve cells.33 These statements appear to be based on observations of a Japanese study consisting of two groups of 15 Japanese men and women between the ages of 50-80 demonstrating mild cognitive impairment. At the close of the trial, the group receiving four 250 mg tablets a day for 16 weeks of the dried Hericium demonstrated significant increases in mental function compared with the control group taking placebos. But the effects didn’t last. Four weeks after the end of the 16-week trial period, their cognitive function scores of the group taking the supplement significantly decreased.34 Other health benefits purportedly include: immune system support;35 neurological health support; antioxidant properties; digestive health support; liver support to reduce effects of alcohol consumption;36 allergy support; stress and anxiety support.37
Despite absence of solid evidence showing that something in Hericium erinaceus is capable of stalling or repairing brain damage due to Alzheimer’s disease in humans, this delicious fungus is understandably high on everyone’s list of must-have supplements.
SHIITAKE: Lentinus edodes
Shiitake is the world’s second most cultivated mushroom, and one of the most widely consumed. Shiitake mushroom is rich in Lentinan, a beta-glucan polysaccharide that is said to ‘boost the immune system’. Lentinan has been used in Japan as an adjuvant therapy for cancer since the 1980s38. It does not kill cancer cells, but in enhancing the weakened immune system, it may prolong the lives of patients with certain cancers when employed with chemotherapy. The Sloane-Kettering Cancer Center determined that more studies are needed.39 A more recent study using Lentinan in 36 patients with liver cancer showed that those who ingested the test material for 47 weeks survived just under 3 months longer (16.3 months) than those who took the supplement between 7 and 12 weeks (13.6 months).40 These mushrooms are also said to help prevent heart disease in mice by lowering cholesterol levels. They help treat infections such as hepatitis by producing interferon,41 a group of natural proteins that stops viruses from multiplying. Other benefits include immune system support42 in the case of 52 healthy men and women between the ages of 21 and 41 years who were given either 5 or 10 grams of shiitake a day for 4 weeks. The mushrooms are said to provide cardiovascular and blood pressure support, diabetes support; liver support; digestive health support; (and everyone’s favorite) – weight loss support.43 A study involving rats fed a high fat diet, showed a significant correlation between the reduction in adipose tissue body fat and consumption of high doses of Shiitake mushroom powder, compared with rats on medium or low shiitake mushroom diets over a six-week period. Researchers in Japan have determined that a relatively small percentage of the population experiences a toxic skin dermatitis lasting up to 10 days due to consumption of raw or inadequately cooked Shitake. The reaction is attributed to the lentinan polysaccharide.44 A recent trial performed with 52 men and women between the ages of 21 and 41 years of age demonstrated they all exhibited improved cell function of T and NK cells, improved gut immunity, an increase in tumor necrosis factor and a decrease in inflammation following daily consumption of shitake mushrooms over a four-week period.45
CHAGA: Inonotus obliquuis (Ach. Ex Pers.) Pilát (1942)
Chaga is believed to have widespread healing attributes. Although frequently referred to as a ‘fruiting body’, the blackish tumor-like growth on white and yellow birch trees called chaga is the sterile sclerotia of a white rot fungus that grows from white and yellow birch tree trunks. Inonotus obliquuis produces a short-lived resupinate fruiting body within the birch, which may be exposed for a short while once the dead tree falls. Its spores are spread by air currents and probably obligate insects as well.
In an effort to boost the mystique surrounding this fungal growth, it is sometimes claimed on medicinal fungi websites that sell chaga that it had been used in ancient China. It is the “King of Plants” or “King of Herbs” or “Herb of Immortality” (Bai Hua Rong/ Hua Jie Kong Jun) mentioned in the 2nd century AD classic the Ben Cao Jing, a no longer extant guide written for rulers and educated officials on living an ethical and healthy long-life in sync with cosmic seasonal patterns of change. Proponents of medicinal fungi are fond of claiming the book was written in 2800 BCE and that its contents were successfully
employed for many thousands of years.46 This claim, however, is historically inaccurate. Moreover, in pre- modern times, the Chinese did not use chaga to cure anything, let alone cancer. The fungus, in fact, was not mentioned in any of the classical medical texts prior to the late 20th century when studies on the sterile conk were first begun! China does not export native chaga. Chinese edible mushroom businesses need to import chaga from other parts of the world including Finland, Russia, Japan, and Canada for processing and domestic use. 47 It is marketed for export to westerners to cure every disease mentioned in any small, poorly conducted and inconclusive study, especially for cancer. Studies suggest, however, that there is nothing tumoricidal in the fungus. Positive outcomes in mice appear to be due to stimulation of the immune system.48
The first verifiable mention of ‘chaga’ stems from 16th century Russia. The word ‘comes from the language of the Komi-Permyak indigenous people who live to the west of the Ural Mountains in the Kama River Basin. It means simply ‘clinker’ referring to the sterile conk’s resemblance to coal slag and its probable use in fire-making. Chaga is distributed in the circumboreal regions of the northern temperate and sub-arctic areas at higher latitudes on several species of birch.49 In modern times, it has been used as a substitute for coffee or tea. In the Soviet Union of the 1960s and was touted as a traditional Russian folk cure for cancer, tuberculosis, heart, liver disorders, immunodeficiency virus, stomach ulcers as well as a diuretic presumably because the gall-like charcoal black masses of cracked cankerous tissue resembles a cancerous growth. The Russian government approved it for use as an anti-cancer agent in the 1950’s although evidence for its efficacy in humans appears to have been non-existent. In the late twentieth century, Inonotus obliquuis was featured as the cause of a miraculous cure and was made popular by its use in the 1967 novel, Cancer Ward by Alexander Solzhenitsyn.
Until recently, most studies on chaga have been conducted in Russia. It boasts an impressive list of medicinal properties. As the most powerful fungal source of antioxidants it confers the highest degree of protection against DNA degradation and against the damaging effects of free radicals. It is supposedly anti-parasitic, anti-inflammatory and immunomodulating. An in vitro study of chaga extracts from Finland, Russia and Thailand validated its high anti-microbial and high antioxidant activity. This white heart-rotter is also reported to have several additional therapeutic effects including being anti-malarial and having the ability to reduce high LDL cholesterol levels. It is said to also protect and ‘detoxify’ the liver, fight hepatitis, ulcers, diabetes, gastritis, and inflammatory diseases such as Shingles. It may be anti-viral against the Herpes simplex virus; in vitro studies done in Russia, suggest it may also have potential for HIV-1.50
A study done on 8 mice after being administered chaga extract for 14 days demonstrated that they were able to endure a forced swimming experiment twice as long as the 8 subjects in the control group (1 hour vs. 30 minutes) without toxic effects on the liver. Researchers concluded that chaga has potential as an anti-fatigue agent for sports competitors.51 As a result, it is currently used to treat chronic fatigue syndrome. It is also credited with knocking out the common cold; slowing the aging process and thus increasing longevity. Chaga extracts are believed to nourish the skin via its melanin compounds and it is now a popular cosmetic product. The substance is high in melanin (black color of the mycelium), sterols and secondary metabolites (triterpenes). Some claim that the rich source of melanin in chaga serves to “protect your skin and hair from sun damage.”52 One study suggests a water extract equivalent to dosage given to cancer patients in Japan can suppress cancer progression, reduce weight and maintain body temperature in tumor-bearing mice when taken daily.53 In vitro studies in petri dishes and in vivo studies on mice suggest chaga has potential against human brain cancer cells.54 Ergosterol peroxide in chaga has been found to inhibit the growth of colon cancer cell lines associated with colitis in mice.55 Chaga continues to be used in Russia to treat inoperable breast cancer, hip, gastric, pulmonary, stomach, skin, and colon cancers as well as Hodgkin’s lymphoma. To date, however, no repeatable clinical trials have been performed on humans.56
Chaga was sold for use in Japan, eastern Europe and Russia under the name ‘Befungin’. It has been used to treat stomach, lung and other cancers since then. While pharmacological investigation and clinical trials in Asian nations continues today, evidence for its efficacy for curing cancer is still lacking. Results of one study measuring the tumor-killing effects on cancer and normal cells in vitro and in vivo of endo- polysaccharides from chaga demonstrated these are not toxic, but they are also not cytotoxic to cancer cells. Mice who survived the daily dose of 30 mg a day for 60 days are believed to have done so due to stimulation of the immune system.57An oral solution of Befungin manufactured in Russia sells on Amazon. Oddly (or perhaps not), no claims are made for its cancer-killing properties, although the pharmaceutical company describes it as having: ….an abundance of Beta-D-Glucans which help balance the response of the body’s immune system.
This means that chaga helps boosts the immune system when necessary but slows it down when it’s overactive. This makes chaga a natural Biological Response Modifier (BRM). Chaga supports the integrity of blood vessels and provides soothing properties in times of irritation. This can be helpful for those suffering from pain and neuropathy. Due to its immune-boosting properties, chaga has long been used to support gastrointestinal health in Eastern culture. Studies also have shown that the betulinic acid found in chaga is able to break down LDL cholesterol–bad cholesterol–in the bloodstream.57 There is an often-repeated old anecdotal report stating that 75% of 50 Russian psoriasis patients were cured or saw improvement in their skin condition after 9 to 12 weeks of chaga treatment.58 It is frequently mentioned that it is being studied by the U.S. National Cancer Institute. To be clear, that doesn’t mean it has proven successful, only that it is being studied. But according to the Memorial Sloan-Kettering Cancer Center, “no clinical trials on humans have been conducted to access its safety or efficacy for disease prevention or for the treatment of liver diseases, cancer, cardiovascular diseases or diabetes.” However, many fungiphiles drink chaga regularly and claim it makes them feel healthier, more energetic and youthful. It is counter-indicated if a patient is taking blood thinners or from diabetic medications.59 Many commercial sources recommend we should take 1 gram a day of chaga or 2 grams if fighting an infection. However, the charred tumor-like growth is high in soluble and insoluble oxalates and high consumption over time may have toxic effects. The insoluble oxalates, which are found also in spinach, almonds and beet leaves, can interfere with the absorption of certain nutrients and are believed to have led to kidney damage in a 72-year-old Japanese female liver cancer patient who took 4-5 teaspoons of chaga daily over six-months.60 A recent study by Michael Beug, Chairman of the toxicology committee for the North American Mycological Association (www.namyco.org), notes that some people have reported adverse incidents as a result of consuming high levels of chaga.61 Caution is advised.
Its ‘efficacy’ in having the capacity to improve blood and digestion has variously been attributed to its Beta-D-glucans, and the triterpenoids betulin and betulinic acid, which are found primarily in the bark of white birch (22%). However, the amount of betulinic acid in a chaga conk is minimal (+ or – 3%) compared with what is in the bark. Also, its usefulness is hard to confirm because of its poor solubility in aqueous solutions.62 The dosage of between 30-80 pills each containing up to 500 mg a day of betulinic acid over a period of many weeks would be required to achieve any of the therapeutic effects observed in mice! It is likely that a preparation would just pass through the digestive system without leaving a trace.
A rumor spread by North American supplement sellers claimed that both Russian and Japanese chaga were contaminated due to radiation poisoning from the Chernobyl (1987) and the Fukushima (2011) nuclear disasters. However, since the major jet streams flow from west to east, it should not be surprising that radioactive fallout from those catastrophic events deposited significantly more radiation on our continent than on birch trees of Eurasia and Japan.63 If decimated, due to overharvesting, it will soon be an unreliable source of potential medicine. The Chinese are, however, working on cultivating the sclerotium and fruiting body of chaga and believe the spawn could be a significantly more potent source of ergosterol than the wild form.64 Teas and cold drinks made with chaga and a sweetener are delicious and possibly nutritious, but whether or not it is ‘medicinal’ is highly questionable given the current level of evidence available. I think it is significant that in eastern Europe and Siberian myths, the birch is honored as the tree of life and fertility. All parts of it from the juice to the leaves and bark are used medicinally. Might the reverence held for chaga have something to do with this fact.
MAITAKE: Grifola frondosa
(‘King of Mushrooms’, ‘Dancing Mushroom’, ‘Cloud Mushroom’, ‘Hen of the Woods’)
Grifola frondosa is an especially popular edible fungus in Japan and has been cultivated in the past two decades for food and medicinal use as a dietary supplement. The active compound is believed to be the protein bound polysaccharide beta 1,6-glucan. It may be able to effect macrophages, T cells and natural killer cells, interleukin-1 and superoxide anions. Claims have been made for Maitake’s beneficial use in preventing and slowing cancer,65 HIV infections,66 hepatitis B, diabetes and hypertension. It is also used in the treatment of obesity and hyperlipidemia. No studies support claims of reducing blood pressure, high cholesterol levels or for weight loss in humans. In Traditional Chinese Medicine (TCM) it is employed in the treatment of gastrointestinal ailments, anxiety and hemorrhoids. Early in vitro laboratory studies suggest that Maitake exhibited anticancer effects in petri dishes. In animals, it appears to slow the growth of some cancerous tumors as well as lower levels of blood sugar in rats. A small uncontrolled study conducted by Memorial Sloane-Kettering Cancer Center and completed by 2009 showed Grifola frondosa extract appeared to stimulate the immune systems of 34 post-menopausal breast cancer patients, who were already free of cancer. Two withdrew from the study: one due to nausea and swelling joints and the other due to rash and pruritus. No toxicity to the extract was observed. High and intermediate doses of the liquid extract increased some immunological parameters and depressed others. The study concluded, “Oral administration of a polysaccharide extract from Maitake mushroom is associated with both immunologically stimulatory and inhibitory measurable effects in peripheral blood. 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.”67 A more recent Phase II study with 18 patients measured the effect of Maitake extract on disorders in bone marrow stem cells and concluded that it may have immunomodulatory benefits.68 Further study is needed. A recent meta- analysis of previous studies concludes that evidence for direct anti-cancer effects of Maitake extracts is lacking, although it may elevate the functional capacity of monocytes, T and NK cells in cancer patients.69 It is not recommended for people taking blood pressure medications, as it can increase their effects. Since it can lower blood sugar, it is not recommended for use by diabetics.70 Patients taking warfarin should not consume Maitake. Other possible side effects include an increase in white blood cell count, indicating a possible allergic response.71
POLYPORUS UMBELLATUS (Pers.) Fries
The white rot fungus commonly known as the ‘Umbrella Polypore’ has been employed in traditional Chinese medicine for many ailments related to edema, scanty urine, urinary dysfunction, vaginal discharge, jaundice and diarrhea.72 It is also credited with having immune- enhancing properties, anti-oxidative activity, anticancer activity, anti-inflammatory activity, liver- protection activity and the capacity to promote hair growth. The main metabolite believed responsible for the diuretic effects is ergone derived from ergosterols found in the sclerotia produced from mycelium in a submerged culture of potato dextrose agar. A few other fungi tested also had high levels of ergone including Tricholoma matsutake and Ganoderma applanatum. Another study suggests fungal metabolites from Polyporus umbellatus appear to have been effective in inhibiting bladder cancer in rats.73
TURKEY TAIL: Trametes versicolor
Studies in vitro and in vivo suggest Trametes versicolor can boost immune cell production and energy in patients with Chronic Fatigue Syndrome. Trametes versicolor is currently being used as part of cancer suppression therapy in both China and Japan. Substances called PSP (polysaccharide peptide) and PSK (polysaccharide krestin) have been used in small human trials: they may have extended the survival rate of victims of gastric cancer over 3 year period by 40%, as well as colorectal and breast cancer by 9% over a five-year period, but not esophageal or cervical-uterine cancers.74 Turkey tail extracts may have anti-viral effects as it seems to reduce the frequency of Herpes simplex outbreaks; it is allegedly protective of the liver; it appears to ameliorate side effects of cancer radiation and chemotherapy when used as an adjunct therapy. It is believed to improve the immune system following treatment with standard radiation and/orchemotherapy.75 A study demonstrated that PSP seemed to protect healthy mice from the effects of a single whole body irradiation. On the other hand, mice with tumors had a lower incidence of tumor growth than those that recived PSP with or without radiation. The increase in immune activation seems to have led to larger tumors. In vitro and in vivo studies suggest PSP decreased the growth of lung tumor, but not of liver metastases. PSP has no cytotoxic effect on mouse lines of hepatoma, sarcoma, melanoma, breast cancer or placental choriocarcinoma.76
There is a very promising ongoing Trametes versicolor breast cancer study at Bastyr University in Washington state. It started around 2010 or so. The study’s estimated completion date for Phase III of the trial was listed as March 31, 2018.77 I am looking forward to learning what the published results are. A confirmed significant result regarding its ability to instruct the immune system to ‘evaporate’ any one type or more breast cancers would be a welcome life-changing discovery. It would also be wonderful if it is shown to function as an adjunct medicine that continued to lengthen and improve the lives of patients who have already completed radiation treatments and/or chemotherapy. To date, however, no further information is available in the form of a peer-reviewed journal article.78
OPHIOCORDYCEPS sinensis (Cordyceps sinensis)
Cordyceps sinensis, or ‘yartsa gunbu’ as the Tibetans call it, has been employed for at least 2,000 years as an ‘herb’ that gives a tired person energy to work without needing much food or sleep to keep them going. It may increase oxygen levels in blood cells. In China it is believed to restore energy of aging men and women, promote the ability of the elderly to engage in sex, improve sexual endurance, fertility and longevity. The wild form that grows from insect larvae found high up on the Tibetan Plateau and Himalayas from between roughly 10,000 to 16,500 feet above sea level, as well as in a few Chinese Nepalese, Bhutanese and Indian regions, is becoming increasingly rare and more costly than ever.79 The fungus has been found to contain heavy metals, including arsenic and as a result, sales have been regulated by the Chinese Food and Drug Administration beginning in 2016.80 It has been taken and valued for enhancing energy when needed, as well as feelings of youthfulness in aging men and couples, and is considered a special gift to be given to elderly recipients on their birthday. The fact that it transforms itself from a winter insect larva into a mysterious ‘magical’ plant emerging from the earth in summer no doubt was deemed as significant to users as its reported effects on the libido. In modern China it is used to treat fatigue, enhance mental clarity in the aging, for prostate health, erectile dysfunction, to replenish the kidneys, moisten the lungs, reduce night sweating, cardiovascular diseases, respiratory diseases like COPD,81 hypertension, hyperlipidemia, hyperglycemia, renal failure,82 cholesterol reduction and so on. It is also reported to have antioxidant properties. Currently a sterile strain called Paecilomyces hepialid is being cultivated in China and is widely used. Some studies suggest that the fungus has real potential for use to enhance endurance. One study done suggests that the fungus improved learning and memory in aging mice.83 Results from another study on three groups of mice showed that those given a daily dose of the oral extract over a period of three weeks prior to a swimming endurance test did either 30% or 73% better than the mice given a placebo. The group given the highest dose did best. Most older Chinese continue to use Cordyceps spp., in any form available for general libido and longevity concerns.84 Despite its far cheaper price and easy availability, Viagra has never taken hold in China, although it has been found outside China in capsules reputed to be Cordyceps sinensis. It just isn’t the same and is not considered as potent for dealing with some of the other reasons people take the Cordyceps medicines. The medicine first came to the world’s attention in 1992, the year the Chinese women’s track team won First Place at the Olympics. Many were suspicious that they owed their success to illegally using steroids, but the Chinese were delighted to credit Cordyceps sinensis for its role in their training.
Other researchers throughout the world, including in the U.S., are cultivating the mycelium of different species in the Cordyceps militaris complex. The energizing bioactive molecule is cordycepin. The fungus also contains glutamic acid, sterols, sugars, amino acids, vitamins and minerals. Cordycepin is a focus of current research on its various antibacterial, anticancer, antiviral and immune regulation bioactivities.85 A published study performed in China involving a mouse-derived breast cancer suggests that an enriched version of cordycepin containing 7 times the amount found in a single fruiting body of Cordyceps militaris has the ability to stimulate the native immune system, delay tumor growth by suppressing the Treg cell population, as well prolonging the survival rate of the mouse subjects.86 Further studies need to be done to learn if cordycepin-enriched Cordyceps militaris powder will be a useful therapy that could serve to eradicate radiotherapy and chemotherapy-resistant cancer cells in humans. In a double-blind study, roughly half of 167 kidney failure patients about to undergo renal transplant surgery had been given 3-6 grams daily for periods from days to a year prior to their operations. All the patients received standard immunosuppressive therapy (consisting of pulse therapy with methylprednisolone and cyclophosphamide followed later by mycophenolate mofetil and prednisone). Those in the group that received supplements of Cordyceps sinensis appeared to have had fewer instances of liver damage (from 18.35% down to 7.53%). However, survival rates between the two groups showed no difference. Several studies suggest that Cordyceps increases testosterone in rats. Cordycepin, however, does not appear to be the key ingredient in producing this effect.87 Another study done in China demonstrated that an extract of Cordyceps sinensis appeared to both increase mental acuity and promote sexual function in castrated rats suggesting it does indeed have ‘antiaging’ effects.88 We have no information yet on effective and optimal dosage requirements. No bad reactions have been reported except for mild gastric discomfort, nausea, diarrhea and dry mouth. No safety information is available on use when pregnant or in children.89 Another study just announced in Scientific Reports suggests that cordycepin from Cordyceps militaris seems to be effective in blocking inflammation, pain and disease progression experienced by osteoarthritis in mice and rats. It is hoped that further research on this treatment will ultimately be able to help the many people who currently suffer from this chronic age-related disease.90
REISHI: Ganoderma lucidum and relatives
Nowadays, many health products with Ganoderma as an ingredient are readily available, especially in East Asia, Europe and North America. They are taken for their perceived anti-cancer, anti-aging, anti- microbial and anti-viral functions, among many others. It is often hailed as ‘the king of herbs’ (a 21st century marketing slogan), and a panacea for many ailments. Researchers studying the medicinal properties of Ganoderma lucidum or Lingzhi, claim it has a long history of use in China. Mention is repeatedly made of its antiquity of use as referenced in the no longer extant medical treatise of the first or second century A.D., the Shen Nong Ben Cao Classic on Health. However, as explained in the 2019 McIlvainea article entitled “LINGZHI, Ganoderma ling zhi (Curtis) P. Karst (1881), the Chinese Mushroom of Immortality”, it is unlikely that any mushroom, much less a Ganoderma was the subject of the two- thousand-year-old text. The term ling-zhi historically referred to a large number of different substances believed to be Elixirs of Immortality. They did not refer specifically or only to species of fungi, much less any Ganoderma. Elixirs were not medicines as we think of them. In the first millennia and beyond, they consisted of various durable minerals and metals that could be liquified and fashioned into pills. They had magical properties which were believed to be able to transform humans into godlike spirits capable of walking on water, flying to the pole star, or dematerializing at will – provided the ingredients were ritually prepared and consumed by worthy adepts who observed a long list of taboos.
Ganoderma lucidum is credited with the following pharmacological activities: it is antimicrobial, antiviral, antitumor, anti-inflammatory, antiallergic, antiatherogenic, and immunomodulating.91 It also is considered useful in obesity treatment.92 The active medicinal compounds in Ganoderma include diverse secondary metabolites, including sterols, alkaloids and terpenoids. Which one or more of the numerous different compounds are responsible for the recorded effects on health continues to be elusive. Some claim it is the ganoderic acids and other say the polysaccharides.93 Although it is commonly implied in research articles that extracts of Ganoderma species have been used to treat numerous diseases over the past two thousand years, the fact is that it has only been used as a medicine within the past 30 years. Ganoderma lucidum (Ganoderma ling zhi, Ganoderma sechuanese, Ganoderma sinense, etc.) is used in Asian hospitals to treat HIV and AIDS. Asian laboratory studies suggest that it may stimulate certain cells of the immune system, but evidence is lacking on its ability to fight infections. The polypore is believed to prevent cardiovascular disease by lowering high blood pressure, high glucose levels and cholesterol pressure. Unfortunately, unbiased controlled animal or human trials employing placebos are lacking. One good quality recent randomized, double-blind and placebo-controlled study for cardiovascular risk of 84 patients with type 2 diabetes mellitus and metabolic syndrome was done over a 16-week period. The participants were divided into three groups, one received capsules of 3 grams a day of Ganoderma lucidum, another group received the same amount of Ganoderma lucidum with the addition of Cordyceps sinensis and the third group received the placebo. While there was no overall increased risk of adverse effects from either active treatment, there were also no statistically significant improvements or differences between the treated and the placebo groups.94
It is used to stimulate the immune system. Existing, if poorly-designed studies suggest that cancer patients are slightly more likely to respond positively to chemotherapy and radiation than those who do not take the Ganoderma lucidum extract. But it does not have a significant effect on killing cancer cells when used alone. Patients taking the Ganoderma lucidum have reported that they enjoyed a better quality of life than patients who were in the control group. No studies recorded whether or not patients who took the Ganoderma medicine lived longer than those who did not. It said to have extended the lifespan of mice.95
Ganoderma lucidum has also been used to reduce inflammation. It may have antihistamine effects. While there are some testimonial affirmations that taking a Ganoderma tincture may alleviate allergic symptoms, this feature has not been scientifically tested in humans.96 The polypore is also employed to increase strength and stamina, although no scientific evidence with humans supports this use. However, there is a study done on mice that is said to have ‘improved the anti-fatigue capacity without any effect on weight loss/gain’. Ganoderma lucidum has also been used to treat lower urinary tract symptoms: one study suggests that extracts may improve urinary flow in men with slight-to-moderate LUTS97. Larger, long- term studies are needed to see if it can improve LUTS in men who have more severe symptoms. It is said to protect rat brains from trauma-induced oxidative stress98. Extracts have led to an increase weight gain of birds infected with Eimeria tenella99. Late twentieth century purported benefits also include control of blood glucose levels, immune system immunomodulation, anti-bacterial properties, and protection of the liver100. It is also available without prescription on Amazon for making your teeth brilliant.
A study conducted with 18 healthy adults between ages of 22-52 years given a commercially available capsule containing 1.44 grams of dried Ganoderma lucidum over a four-week period determined there was no liver, renal or DNA toxicity.101 According to reviewers of studies involving the use of Ganoderma lucidum for cancer treatment, evidence suggests that it is generally well-tolerated by patients and may enhance the immune system of patients when also taken with chemotherapy and radiation. Except for a few minor reactions, one reference to toxicity with Ganoderma being used medicinally involved a case where it was found that the cancer patient was taking an adulterated commercially produced powder formulation over a period of a month that resulted in elevated liver enzymes. Another study by Canadian researchers suggested that toxicity was observed in peripheral blood monocular cells of healthy adults, healthy children and pediatric patients undergoing chemotherapy for cancers. They advise that Ganoderma lucidum extracts be used with caution as there appears to be potential for toxicity.102 It isnot recommended for those who are pregnant, take a blood thinner, or use an immunosuppressant. It may also make chemotherapy drugs less effective. When used alone, it does not demonstrate the same level of effectiveness as standard medical treatments. In classical Chinese medicine practitioners employed hot water to make a tea. Most proponents of using Ganoderma lucidum recommend combining preparations made by ethanol extraction with those of hot water extraction methods. Further studies using improved methods of measuring results are needed to know if using Ganoderma lucidum tinctures prolong the lives of patients.103
BUT WHICH IS THE ‘TRUE’ GANODERMA LUCIDUM & DOES IT MATTER?
The species concepts in the Ganoderma lucidum complex, however, lack consensus in morphology and taxonomy.104 There are as many as 219 species of Ganoderma in the world, at least 80 of which in commerce – all are morphologically similar (their spores are double-walled), but phylogenetically they form 6 monophyletic lineages not mirrored in their geographic distributions.105 Most species are tropical. Ganoderma ‘lucidum’ (Curtis) P. Karst. (1881) sensu stricto, grows on hardwoods in Europe. Although mycologists throughout the world have argued that Ganoderma lucidum is present in China, DNA analysis has recently confirmed that what has been called Ganoderma lucidum in China is not conspecific. Assuming there are benefits to consuming the Ganoderma employed in the Chinese medical texts, not knowing for certain which one was referred to limits further research on the medical usefulness of these different species. For example, the widely used medicinal species in biochemical and pharmaceutical studies has been assumed to be Ganoderma lucidum, but evidence has emerged that what everyone has been calling Ganoderma lucidum is, in fact, a different species.106 In 2012 it has been described and named as Ganoderma ling zhi by Y. Cao, et al.107
The fungus mentioned in a late sixteenth century Pharmacopeia seems to be a Chinese Ganoderma, but we do not know for certain which one it is. To complicate matters further, there are now known to be several species of shiny Ganoderma in China including Ganoderma ling zhi; G. mastoporum Wang et al. 2012; G. multipileum Wang et al. 2012; G. sichuanense Yao et al.2013; G. sichuanense Zhou et al 2015; G. foricatum Wang et al, 2014; G. lucidum Yang & Feng 2013; G. tropicum (Jungh.) Bres., G. sinense, G. flexipes Cao & Yuan (2013), G. hoehnelianum; G. leucocontextum Li et al. 2014; G. multipileum D. Hou, Ganoderma tsugae Murrill, and Ganoderma mutabile (closely related to Ganoderma applanatum).108 Do Chinese pharmacists always prepare their capsules using just Ganoderma lingzhi, or all of them? To confuse matters more, Chinese mycologists disagree on whether or not Ganoderma lingzhi and Ganoderma sichuanense are the same or different species based on morphological considerations. Zhou et al. (2015) argued that they are different based on their respective ecological environments. Richter et al. (2015) pointed out that according to the rules of nomenclature, the new taxon name for Ganoderma lingzhi should be the oldest valid name, Ganoderma sichuanense. Currently, Index Fungorum lists Ganoderma lingzhi as a later synonym of Ganoderma sichuanense.109 Meanwhile, most of the world’s research scientists continue to refer to ‘Lingzhi’ as Ganoderma lucidum!
A study conducted in China comparing 32 batches of commercially grown Ganoderma lucidum and 12 batches of Ganoderma sinense revealed that the two mushrooms are chemically different. The highly lauded triterpenes of Ganoderma lucidum were found to be completely absent from the native Chinese Ganoderma sinense.110 Ganoderma sinense is quite possibly the one referred to in the Ming Dynasty Pharmacopeias. Given that different species of Ganoderma have different collections of compounds, and the fact that we are not anywhere near certain which compounds might be helpful medicinally, why would anyone take any product for an extended period – or till the bottle is empty – without knowing whether or not there is fact-based evidence proving its universal effectiveness in either preventing or curing a plethora of illnesses? At any rate, it is reasonable to ask healthy mycophiles what they think they are getting from their Ganoderma tinctures. On the east coast of N.A., many who consume teas, tinctures and pills don’t differentiate between the locally available Ganoderma tsugae, the Hemlock Varnish Shelf, and Ganoderma lucidum, a species that grows on hardwoods in Europe, and that many mistakenly assume exists in North America. Everyone is blindly assuming all have the same medicinal properties that will improve us spiritually as well as physically. Unlike pharmaceutical drugs with defined amounts of medication reliably distributed in each pill, natural products of even the same species vary widely in the potency of their presumed beneficial ingredients. Incidentally, a study conducted last year called “Evaluation on quality consistency of Ganoderma lucidum dietary supplements collected in the United States” found that the vast majority of supplements sold in the U.S. do not have the purported medicinal compounds in them. Just 8 of 19 product samples contained the triterpenes of the reishi fungus. Only six of the 19 were free of starches from the combined mycelium and its rice or grain substrate. Just 5 of the 19 products were authentic. The remaining 14 contained no high molecular weight beta-glucans.111 Buyer be aware! In another recent study of U.S. 20 manufactured reishi products in the form of teas, tablets and pills and 17 grown-your-own kits, it was determined that 93% of the manufactured products and about half of the grow-your-own (GYO) kits contained the Ganoderma ling zhi native to China – 11 of which also contained additional material from non-native G. applanatum, G. austral, G. gibbosum, G. sessile and G. sinense. One GYO kit was the European Ganoderma lucidum.112 Knowledge of exactly which compounds in so-called medicinal mushrooms are proven effective still evades researchers.
FREE-RADICAL THEORY OF AGING & ROLE OF ANTIOXIDANTS
We are not completely defenseless against the activities of free-radicals. Antioxidants are believed to provide protection against nasty free-radicals, believed to be a causative factor in developing inflammation and the diseases most associated with aging: cancers, heart diseases, diabetes, dementia, macular degeneration, cataracts, Parkinson’s and Alzheimer’s. Antioxidants are said to consist of a wide variety of hundreds and perhaps thousands of different chemical substances. These include but are not limited to minute amounts of vitamin E, vitamin C, beta-carotene, lycopene, Selenium, flavonoids, the B vitamins,116 zinc, resveratrol, and omega-3 and omega-6 fatty acids. Food-borne antioxidants are also found in a plethora of vegetables, fruits, tea, coffee, extra virgin oil, fish, fungi and other sources of carotenoids and polyphenol. Some of the most highly touted medicinal marvels for these maladies include echinacea, green tea, ginseng, turmeric, SOD, cinnamon, saw palmetto, pomegranate juice, argan oil, kava kava, canola oil,117 coconut oil,118 gingko, moringa leaves, pomegranates, blueberries, ginseng, licorice root, juice detoxes, milk thistle, and of course, medicinal fungi. Every year new antioxidants are discovered and promoted suggesting they can turn back aging and free-radical damage. One of these according to Dr. Joseph Mercola who recently appeared on the Dr. Oz show is astaxanthin, “the number one supplement that you’ve never heard of that you should be taking.”119
We are told they serve to counter feared potentially toxic effects of immoderate food, drink and drug choices and to restore ‘balance’ to our weakened immune systems. Fungal medicinal supplements are also taken to charge up the innate immune system so that it is on always on high alert and ready to resist and if necessary, destroy any disorders that might threaten to interfere with the normal functioning of healthy humans. Life-extension proponents often argue that age itself is a disease that can be defied. By taking the right combination of natural herbal or fungal ingredients, they claim we should be able to prolong our active lives indefinitely.120
Robert Bowman, nutrition Professor Emeritus of Food Science at Penn State studying mushrooms for health recommends we eat mushrooms that have high amounts of the antioxidants ergothioneine and glutathione to ward off neurodegenerative diseases like Parkinson’s disease and Alzheimer’s. Apparently, mushrooms are the best source of getting these two antioxidants, and he advises replenishing them regularly.121 Glutathione is an antioxidant found in plants, animals (including humans), fungi, cyanobacteria and halobacteria (archaea). It is produced by the body and is an abundant tripeptide found in all cells. Low levels are associated with cancers, but high levels are thought to protect cancerous cells resistance to chemotherapeutic drugs.122 A Phase IIb study of glutathione’s effect on Parkinson’s disease demonstrated that the group of participants taking the placebo had more robust improvement than the two groups taking a 100 mg and 200 mg of intranasal glutathione. One of approximately 12 patients in the high dose group developed cardiomyopathy.123 Taking glutathione supplements, whether naturally or synthetically derived does not appear to be a good idea.
Ergothioneine is an amino acid derived from Claviceps purpurea. It is not synthesized in the body. It is absorbed with foods which contain this protein building chemical. It can be found in dietary sources such as kidney beans, black beans, oat bran, King Crab, meat and organs of animals that graze on ergothioneine containing grasses, and other foods. It can even be found in certain bacteria. Especially high levels are found in edible mushrooms. First discovered in 1909, in vitro studies spanning a period of toughly 70 years have been done on the substance, but we still do not know what functions it serves in the physiology of animals, including humans. It has been approved for use by the FDA as a nutrient supplement in soft drinks, cookies, cakes, candy, fruit drinks and coffee and tea at 5 mg per serving. A 5 mg 30-day supply of this “new generation antioxidant” sells for $94.124 It is also being marketed as a cream to prevent wrinkling and sun damage to the skin. There is an observational study performed at the National University of Singapore over a 6-year period involving 663 seniors over the age of 60 designed to measure the effect of eating the equivalent of over 300 grams or roughly a half a plate of cooked edible mushrooms a week on the cognitive functioning of the participants. The researchers determined 90 scored less than 1.5 standard deviations below the mean on score of participants (with similar ages and education levels) on intelligence tests had lower levels of ergothioneine in their bloodstreams, which was correlated with eating fewer mushrooms.
They concluded that these subjects experienced mild cognitive decline.125 Meanwhile many people are taking ergothioneine supplements to prevent or ward off Alzheimer’s as well as liver damage, cataracts, diabetes, and heart disease. The researchers and authors of this preliminary study plan on marketing a product containing this ingredient. While it is probably safe in the amounts found in foods, currently there is not enough information available to determine whether or not it is safe when taken as a supplement. According to www.webmd.com, we would be wise to avoid taking these supplements, especially if pregnant or breast- feeding.126
In the 1990s some studies appeared to show that people who ate little in the way of vegetables and fruits were at greater risk of acquiring chronic health conditions than people who ate a lot of them. Researchers began to conduct trials to gauge the impact of single and combinations of known antioxidants. These studies have produced disappointing results. It turns out that the majority of antioxidants either have no effect on a person’s susceptibility to disease or they have demonstrated that some antioxidants even promoted the growth of certain cancers.127
The free-radical and antioxidant explanations for initiating diseases associated with aging has become accepted dogma by nutritionists, vitamin and fungal supplement distributors in recent years, despite growing scientific evidence that suggests the situation is much more complicated than presumed.128 Yes, numerous studies show that toxic reactive oxygen species (ROS) and oxidative damage increase with age in model organisms such as yeast, nematodes, fruit flies, and mice. Oxidative damage is not the whole story representing the causes of aging. The “underlying reason the damage is generated, and cannot be fully cleared, is biological imperfectness.” There is no such thing as a perfect cell. Cellular respiration and damage is a consequence of life that increases with aging.129 There are undoubtedly many causes, including the activities of free radicals, but to postulate there is a single cause to aging that can be mitigated by counteracting their effects with antioxidant supplements is contraindicated by numerous scientific studies.130 Yet Today, antioxidants continue to be added to milk, energy drinks, cereals, fruit juices, sport bars and other processed foods and promoted as ‘super-foods’.
Fungal and herbal medicines currently fall into the category of ‘dietary supplements.’ Thanks to the lobbying efforts of vitamin companies looking out for their own business interests under the guise of protecting the public’s right to decide for themselves what is good for them, these are loosely regulated by the FDA. Makers of supplements do not have to prove their products are safe or effective. Retailers can say just about anything they want regarding the efficacy of their health products under the guise of providing educational heath information as long as they include a disclaimer: “These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.”131 This is often at the bottom of a website page or bottle in barely legible, tiny print. One result of the lack of laws designed to protect consumers rather than manufacturers is that in New York, Connecticut and Indiana tests of store brand supplements revealed that four out of five herbal supplements sold have been found to not have the ingredients listed on their labels.132
Medicinal fungi outlets are also selling products that are difficult if not impossible to compare in terms of the quality, quantity, age, purity, potency and presumed efficacy of the ingredients used. With natural products in general, the levels of various compounds and their therapeutic activity will vary, often greatly, depending on ecological conditions including the substrate, time of year the fungus is gathered, what pathogens it may be fighting against, where it was collected, and perhaps especially by how it is processed. Some marketers sell spores, others sell hot water or dual extraction tincture, or pills filled with either the mycelium or the fruiting bodies, or a combination of fungi after they have been dried and powdered. Does it matter if the fruiting bodies are immature or mature? Data is still out on the best substrates to employ when cultivating fungi for medicinal purposes. What, if anything, is added to products produced for treatment and distribution? What might be the differences in potency, if any, when growing it on coffee grinds, rice, barely, hay or wood? If this doesn’t bother you, cheaper sources of fungal medicinals can be found online at Amazon,133 which markets a full 20 pages of powders and tinctures from a large variety of companies situated throughout the planet providing immune boosting medicinal fungal products that promise to prevent and cure every disease imaginable. Prices are a little less than buying directly from a preferred U.S. cultivator-manufacturer. One must be cautious, though, when buying products from unknown sources. The quality of some Chinese medicinal fungal products compared to those made in the U.S. is often highly variable.134 For the most part, however, the highly lauded studies were performed just on non-human animals or a limited number of humans in a manner that is not randomized or controlled for the introduction of biases.
Many of us have been convinced that the antioxidants in fungi and other ‘super-foods’ are capable of boosting the immune system so that we won’t experience colds, allergic reactions, Alzheimer’s, heart diseases, cancers and so on. Yet hundreds of studies refute the validity of claims that these supplements can protect us from aging.135 Because we mistakenly believe that more nutrients will provide us added health insurance and protection, we can and do overload on antioxidants, and in doing so we may actually block oxidative protection against pathogens.136 Studies suggest that overloading on antioxidants actually decreases energy production in the mitochondria and thereby causes muscle weakness and fatigue. Moreover, antioxidants do not seem to work for all varieties of diseases in patients,137 and they may actually increase rather than decrease one’s chances of mortality. Antioxidants can also be used by cancer cells to prevent the immune system from destroying them.138
Another point often ignored by advocates of using fungi for their antioxidant capacity is that the body itself produces a plethora of antioxidants to counter the deleterious effects of free-radicals to prevent and repair cellular damage. But since not all antioxidants needed can be produced by the body, we are also dependent on food sources to supply the rest. However, only a tiny portion of the antioxidants in antioxidant-rich foods actually gets into our bloodstream. They are not likely to directly neutralize free radicals. Those that do enter the bloodstream, whether from mushrooms or pomegranates are due to their ‘nutrigenomic’ effects in stimulating the body’s innate antioxidant network and of genes that serve to control inflammation. This is why in 2012 the USDA decided to no longer display the ‘oxygen radical absorbance capacity” (ORAC) of foods listed in its database of nutrients. This change is because “mounting evidence that the values indicating antioxidant capacity have no relevance to the effects of specific bioactive compounds, including polyphenols, on human health.” Also, “The data for antioxidant capacity of foods generated in vitro (test-tube) methods cannot be extrapolated to in-vivo (human) effects and the clinical trials to test benefits of dietary antioxidants have produced mixed results.”198
The vast majority of studies on the medicinal effects of macro-fungi have not been performed in accordance with accepted scientific standards to eliminate biases of researchers or patients. To date, most assertions regarding the capacity of fungal compounds to prevent and cure diseases are based on results of studies limited to describing what happens to human tissue samples exposed to fungal extracts in a test tube or petri dish; on genetically engineered rodents; or on a very small number of patients. Few published studies employ randomized placebo-controlled double-blind trials. It is not surprising that they are often unrepeatable by researchers employing recommended standards of testing. These facts have not deterred believers from continuing to espouse their utility in mitigating a plethora of disease conditions based on suggestive, but often unproven and incomplete data. Fortunately, with a few known exceptions, most appear safe to consume within limits. As much as we all would love to find a magic tonic or pill to mitigate or even prevent the infirmities that often accompany aging, there is no getting away from the fact that we are not immortal. There should be little doubt, however, that edible fungi, along with other nutritious foods, are efficacious in helping us live healthy and productive lives.
REFERENCES
- Prevention Magazine, December 2017, p12.
- https://www.researchgate.net/publication/247480134_Bioremediation_of_Hazardous_Wastes – A_Review.
- Ilona Amos, “‘Magic’ mushrooms to boost Caledonian Forest restoration,” The Scotsman, April 20, 2018. https://www.scotsman.com/news/environment/magic-mushrooms-to-boost-caledonian-forest-restoration-1-4727383.
- Deodatus Balile, “Fungal pesticide saves crops from locusts,” Science and Development Network, 7/27/07. https://www.scidev.net/global/biotechnology/news/fungal-pesticide-saves-crops-from-locusts.html.
- “Antibiotics Guide”, August 23, 2016. https://www.drugs.com/article/antibiotics.html.
- Susan Brink, “New Medical Worry: Deadly Fungal Infection That Resists Treatment,” National Public Radio, Inc., January 24, 2017.
- Elie J. Diner, “The Enemy of My Enemy is My Friend – Microbial Solution to the Emperor of all Maladies,” Elio Schaechter’s Small Things Considered Blog, May 16, 2016. http://schaechter.asmblog.org/schaechter/2016/05/the-enemy-of-my-enemy-is-my-friend-a-microbial-solution-to-the-emperor-of-all-maladies.html.
- Tim Newman, “Antibiotics may increase the risk of bowel cancer,” Medical News Today, April 5, 2017. https://www.medicalnewstoday.com/articles/316734.php.
- Ernestina Marianna De Francesco, et al., “Vitamin C and Doxycycline: A synthetic lethal combination therapy targeting metabolic flexibility in cancer stem cells (CSCs),” Oncotarget, 2017. http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=18428&path%5b%5d=59195.
- Taylor F. et al., “Statins for the primary and secondary prevention of cardiovascular disease,” Cochrane Database of Systematic Reviews, January 31, 2013. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004816.pub5/abstract.
- “Cholesterol Drugs,” webmd.com.
- https://www.medicinenet.com/red_yeast_rice_and_cholesterol/article.htm#what_is_the_present_status_of_red_yeast_rice.
- Denis R. Benjamin, “Medicinal Mushrooms: The Story of Red Yeast Rice” Fungi Magazine, Vol. 6, No. 2: Summer 2013.
- Dr. Andrew Weil, “Red Yeast Rice for Cholesterol Control?” January 2009. https://www.drweil.com/health-wellness/body-mind-spirit/heart/red-rice-yeast-for-cholesterol-control/.
- https://medlineplus.gov/druginfo/meds/a601207.html.
- Steffen Bauer, et al., “Alterations in cyclosporine: A pharmacokinetics and metabolism during treatment with St. John’s wort in renal transplant patients,” British Journal of Clinical Pharmacology, February 2003; 55(2) 203-211.
- Simon Singh and Edzard Ernst, M.D., Trick or Treatment: The Undeniable Facts about Alternative Medicine, (N.Y.: Norton, 2008) 206.
- Thomas Miedaner and Hartwig H. Geiger, “Biology, Genetics, and Management of Ergot (Claviceps spp.) in Rye, Sorghum, and Pearl Millet,” To xins, March 7, 2015, 659-678, http://www.mdpi.com/2072-6651/7/3/659. Stephanie L. Arnold and Daniel G. Panaccione, “Biosynthesis of the Pharmaceutically Important Fungal Ergot Alkaloid Dihydrolysergic Acid Require a Specialized Alle of cloA, Applied and Environmental Microbiology, American Society of Microbiology, 83:e00805-17.
- M.J. Eadie, “Ergot of Rye – the first specific for migraine,” Journal of Clinical Neuroscience, January 11, 2004, 4-7. https://www.ncbi.nlm.nih.gov/pubmed/14642357; Ben Vasler, “Ergotamine,” Chemistry World, September 14, 2016, Article available at https://www.chemistryworld.com/podcasts/ergotamine/1017416.article; “Ergotamine,” Wikipedia https://en.wikipedia.org/wiki/Ergotamine.
- Karen Harris-Rees, “Taking a medical trip,” Chemistry World, August 28, 2007; Roland R. Griffiths, Ph.D., “Johns Hopkins Psilocybin Research Project: Studies of Mystical Experience, Adverse Effects, Meditation in Healthy Volunteers, and Palliative Effects in Cancer Patients – Implications for Spirituality and Therapeutics”. April 23, 2017. http://psychedelicscience.org/conference/clinical/johns-hopkins-psilocybin-research-project-studies-of-mystical-experience-adverse-effects-meditation-in-healthy-volunteers-and-palliative-effects-in-cancer-patients-implications-for-spirituality-and-therapeutics.
- “Micafungin,” Medscape, https://reference.medscape.com/drug/mycamine-micafungin-342585.
- Yu-Cheng Dai et al, “Species Diversity and Utilization of Medicinal Mushrooms and Fungi in China (Review),” International Journal of Medicinal Mushrooms, (11)3:287-302, 2009.
- S.P. Wasser, “Medicinal Mushroom Science: History, current status, future trends, and unsolved problems,” International Journal of Medicinal Mushrooms, 2010: 12: 1-16.
- X. Tan, et al., “Structure-activity relationship of plant polysaccharides,” Zhongguo Zhong Yao Za Zhi. 2017; 42:4104–4109. https://www.ncbi.nlm.nih.gov/pubmed/29271146.
- Tero Isokauppila and Mark Hyman, Healing Mushrooms: A Practical and Culinary Guide to Using Mushrooms for Whole Body Health, (N.Y.: Penguin), 2017, 20-21.
- X. Tan, et al., “Structure-activity Relationship of Plant Polysaccharides,” Zongguo Zong Yao Za Zhi, 2017 Nov.;42(21):4104-4109.
- Sarah Everts, “The fungus among us: Researchers race to study the human mycobiome and how it affects our health,” Chemical and Engineering News, Vol. 94, Issue 30, July 25, 2016, 24-27. See full version https://doi.org/10.1155/2017/3780572.
- Laura Beil, “I, Mold: Conquering the Rising Tide of Infection is Hindered by the Many Similarities Between Humans and Fungi, Science News, Vol. 177:11, May 22, 2010, 26.
- Theodoros Kelesidis and Charalobos Pothoulakis, “Efficacy and Safety of the probiotic Saccharomyces boulardii for the Prevention and Therapy of Gastrointestinal Disorders,” Therapeutic Advances in Gastroenterology, v.5(2) 2012 March. Online article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296087/.
- N. Zhu, et al., “Comparison of immunoregulatory effects of polysaccharides from three natural herbs and cellular uptake in dendric cells,” International Journal of Biological Macromolecules, 2016 (Dec.;93(Pt A):940-951; X. Lv, et al., “Comparative studies on the immunoregulatory effects of three polysaccharides using high content imaging system,” International Journal of Biological Macromolecules, 2016, May:86:28-42.; Hui Liao, et al., “Are the Therapeutic Effects of Huangqi (Astragalus membranaceus) on Diabetic Nephropathy Correlated with Its Regulation of Macrophage iNOS Activity?,” Journal of Immunological Research, 2017:3780572.
- Tsai-Teng Tzeng, “The Cyanthin Diterpenoid and Sesterterpene Constituents of Hericium erinaceuds Mycelium Ameliorate Alzheimer’s Disease-Related Pathologies in APP/PS1 Transgenic Mice,” International Journal of Molecular Science, 2018, 19(2),598.
- NGF is a substance in the brain that was first discovered in the 1940s.
- Braintropic, https://www.braintropic.com/nootropics/lions-mane-mushroom/.
- K. Mori, et al., “Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial,” Phytotherapy Research, March 23, 2009 (3): 367-372.
- X. Sheng, et al., “Immunomodulatory effects of Hericium erinaceus derived from polysaccharides are mediated by intestinal immunology,” Food Functionality, March 22, 2017 8(3): 1020-1027. https://www.ncbi.nlm.nih.gov/pubmed/28266682.
- F. Cul, et al., “Protective Effects of Extracellular and Intracellular Polysaccharides on Hepatoxicity by Hericium erinaceus SG-02,” Current Microbiology, September 2016, 71(3) 379-385.
- Mayumi Nagano, et al., “Reduction of depression and anxiety by 4 weeks Hericium erinaceus intak,” Biomedical Research, 2010. https://www.jstage.jst.go.jp/article/biomedres/31/4/31_4_231/_article/-char/ja/.
- Bryant Furlow, “Shiitake Mushroom, Lentinan, and Cancer,” Cancer Therapy Advisor, May 1, 2017. https://www.cancertherapyadvisor.com/home/tools/fact- sheets/shiitake-mushroom-lentinan-and-cancer/.
- Memorial Sloan-Kettering Cancer Center, https://www.mskcc.org/cancer-care/integrative-medicine/herbs/shiitake-mushroom.
- N. Isoda, et al., “Clinical efficacy of superfine dispersed lentinan (beta-1,3-glucan) in patients with hepatocellular carcinoma,” Journal of Hepto-Gastroenterology, March-April 2009; 56(90): 437-441.
- Y. Kabir, et. al., “Effect of Shitake (Lentinus edodes) and maitake (Griforla frondosa) mushrooms on blood pressure and plasma lipids of spontaneously hypertensive rats,” Japanese Journal of Nutritional Science and Vitaminology, October 1987, 33(5) 341-346.
- X. Dai, et al., “Consuming Lentinula edodes (Shiitake) Mushrooms Daily Improves Human Immunity: A Randomized Dietary Intervention in Healthy Young Adults,” Journal of the American College of Nutrition, April 2015; 34(6) 478-487.
- D. Handayani, et al., “Dietary Shiitake Mushroom (Lentinus edodes) Prevents Fat Deposition and Lowers Triglyceride in Rats Fed a High-Fat Diet,” Journal of Obesity, October 19, 2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199106/
- Michael Beug, “Shitake Dermatitis Alert,” North American Mycological Association. http://www.namyco.org/shiitake_dermatitis.php.
- X. Dai, et al.,” Consuming Lintinula edodes (Shiitake) Mushrooms Daily Improves Human Immunity: A Randomized Dietary Intervention in Healthy Young Adults,” Journal of American College of Nutrition, 2015; 34(6)478-487.
- https://www.cancerdefeated.com/the-chinese-single-this-out-as-the-king-of-plants/1246/.
- Min-Woong Lee, et al., “Introduction to Distribution and Ecology of Sterile Conks of Inonotus obliquuis,” Mycrobiology, December 2008, Vol. 36 (4): 199-202.
- Kim Yo, et al., “Anti-cancer effect and structural characterization of endo-polysaccharide from cultivated mycelia of Inonotus obliquus,” Life Science, 2006 May 30;79(1):72-80.
- Min-Woong Lee, et al., “Introduction to Distribution and Ecology of Sterile Conks of Inonotus obliquuis,” Mycrobiology, December 2008, Vol. 36 (4): 199-202.
- V.A. Shibnev, et al., “Antiviral activity of aqueous extracts of the birch fungus Inonotus obliquuis on the human immunodeficiency virus” Vapr. Viruloso 2015;60 (2):35-38 https://www.ncbi.nlm.nih.gov/pubmed/26182655.
- Z. Yue, et al., “Effect of Inonotus obliquuis Polysaccharides on physical fatigue in mice,” Journal of Traditional Chinese Medicine, August 2015, 35(4): 468-472. https://www.ncbi.nlm.nih.gov/pubmed/26427119.
- Youn MJ, Kim JK, Park SY, et al. Potential anticancer properties of the water extract of Inonotus[corrected] obliquus by induction of apoptosis in melanoma B16-F10 cells. Journal of Ethnopharmacology, Jan 21 2009;121(2):221-228.
- Satoru Arata, et al., “Continuous intake of the Chaga mushroom (Inonotus obliquuis) aqueous extract suppresses cancer progression and maintains body temperature in mice,” Heliyon, 2016 May; 2(5).
- X. Ning, et al., “Inhibitory effects of a polysaccharide extract from the Chaga medicinal mushroom, Inonotus obliquuis (higher Basidiomycetes), on the proliferation of human neurogliocytoma cells,” International Journal of Medicinal Mushrooms, 2014, 16 (1) 29-36; Z. Yue, et al.,” Journal of Traditional Chinese Medicine. Aug 2015;35(4):468-472.
- M. Kobori, et al., “Ergosterol peroxide from an edible mushroom suppresses inflammatory responses in RAW264.7 macrophages and growth of HT29 colon adenocarcinoma cells,” British Journal of Pharmacology, 2007 Jan; 15092): 209-219.
- “Chaga Mushroom,” Memorial Sloane Kettering Cancer Center, https://www.mskcc.org/cancer-care/integrative-medicine/herbs/chaga-mushroom.
- https://www.amazon.com/Befungin-Chaga-Mushroom-100ml-3-4/dp/B01HOUQ07A/ref=sr_1_1_a_it?ie=UTF8&qid=1518558812&sr=8-1&keywords=befungin.
- E.A. Dosychev, et al., “Treatment of psoriasis with chaga fungus preparations,” Vestnik Dermatologii I Venerologii, May 1973:79-83. Translation 2011 https://www.chagatrade.ru/images/psoriasis_chaga.pdf.
- https://www.mskcc.org/cancer-care/integrative-medicine/herbs/chaga-mushroom.
- Y. Kikcuchi, et al., “Chaga mushroom-induced oxalate nephropathy,” Clinical Nephrology, June 2014;81(6):440-444.
- Michael Beug, « Oxalates in Chaga – A Potential Health Threat”, McIlvainea, Vol. 28, 2019, https://www.namyco.org/mcilvainea.php.
- “Bioavailability of Betulinic Acid, a DIY anti-cancer supplement with an increasing popularity,” Supplemental Facts, new developments, deceptions & general background for consumers. http://supplement-facts.org/2012-5.php#.WoG-emaZOL4.
- Winiarek, et al., “Atmospheric dispersion of radionuclides from the Fukushima-Daichii nuclear power plant,” CEREA, 2013, updated 2014.
- J.H. Kang, et al., “Ergosterol peroxide from Chaga mushroom (Inonotus obliquuis) exhibits anti-cancer activity by down-regulation of the β-catenin pathway in colorectal cancer,” Journal of Ethnopharmacology, September 15, 2015, 173-303, https://www.ncbi.nlm.nih.gov/pubmed/26210065; C.C. Tsai, et al., “Inonotus obliquuis extract induces apoptosis in the human colorectal carcinoma’s HCT-116 cell line,” Journal of Biomedicine & Pharmacotherapy, December 2017 96:1119-1126; Y. Sun, et al., “In vitro antitumor activity and structure characterization of ethanol extracts from wild and cultivated Chaga medicinal mushroom, Inonotus obliquuis (Pers.: Fr.) Pilat (Aphyllophoromycetideae),” International Journal of Medicinal Mushrooms, 2011; 13 (2): 121-130.
- R. Soares, et al., “Maitake (D fraction) mushroom Extract induces apoptosis in breast cancer cells by BAK-1 gene activation,” Journal of Medicinal Foods, June 2011; 14(6):563-572; P. Rossi, et al., “B-glucans from Grifola frondosa and Ganoderma lucidum in breast cancer: an example of complementary and integrative medicine,” Oncotarget, May 15, 208; 9(37):24837-24856.
- N.B.A. Hirosaki, et al., “Effects of Maitake (Grifola frondosa) glucan in HIV-infected patients,” Mycoscience, 2009, 41:293-295.
- “Maitake,” Memorial Sloan Kettering Cancer Center. https://www.mskcc.org/cancer-care/integrative-medicine/herbs/maitake.
- K.M. Wesa, et al., “Maitake mushroom extract in myelodysplastic syndromes (MDS): A Phase II study,” Cancer Immunological Immunotherapy, February 2015; 64(2):237-247.
- Yuki Masuda, et al., “Antitumor activity of orally administered maitake a-glucan by stimulating antitumor immune response in murine tumor,” (2017) PLOS ONE Journal, 12(3): e0173621. Open access article: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173621.
- Moshe Frenkel, et al., “Integrating Dietary Supplements into Cancer Care,” Integrative Cancer Therapies, Feb. 25, 2013, https://journals.sagepub.com/doi/10.1177/1534735412473642.
- “Maitake,” Memorial Sloan Kettering Cancer Center. https://www.mskcc.org/cancer-care/integrative-medicine/herbs/maitake.
- Ying-Yong Zhao, “Traditional Uses, phytochemistry, pharmacology, pharmacokinetics and quality control of Polyporus umbellatus (Pers.) Fries: A Review,” Journal of Ethnopharmacology, Vol. 149, Issue 1 August 26, 2013, 35-48.
- G. Zhang, et al, “Inhibition of urinary bladder carcinogenesis by aqueous extract of sclerotia of Polyporus umbellatus and polyporus polysaccharide,” American Journal of Chinese Medicine, 2011:39(1):135-144.
- M. Torisu, et al., “Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer,” Cancer Immunological Immunotherapy, 1990: 31(5) 261-268.
- M. Nimoto, et al., “Postoperative adjuvant immune-chemotherapy with mitomycin C, futraful and PSK for gastric cancer,” Japanese Journal of Surgery, November 18, 1988 (6) 681-686.
- Liu WK, Ng TB, Sze SF, Tsui KW. Activation of peritoneal macrophages by polysaccharopeptide from the mushroom, Coriolus versicolor. Immunopharmacology (1993) 26(2):139–46.10.1016/0162-3109(93)90006-C; Wang HX, Ng TB, Liu WK, Ooi VE, Chang ST. Polysaccharide-peptide complexes from the cultured mycelia of the mushroom Coriolus versicolor and their culture medium activate mouse lymphocytes and macrophages. Int J Biochem Cell Biol (1996) 28(5):601–7.10.1016/1357-2725(95)00157-3; Mohammed H. Saleh, et al., “Immunomodulatory Properties of Coriolus versicolor: The Role of Polysaccaropeptide, Frontiers in Immunology, 2017;8: 1087. Open access: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592279/.
- Carolyn J. Torkelson, et al., “Phase I Clinical Trial of Trametes versicolor in Women with Breast Cancer,” International Scholarly Research Network: Oncology, Volume 2012, 251632.pdf; Paul Stamets, “Trametes versicolor (Turkey Tail Mushrooms) and the Treatment of Breast Cancer,” Global Advances in Health and Medicine. 2012; 1(15):18.
- https://www.clinicaltrials.gov/ct2/show/NCT01922921?term=PSK+breast+cancer+seattle&rank=1.
- Daniel Winkler, “Caterpillar Fungus (Cordyceps sinensis) Production and Sustainability on the Tibetan Plateau and the Himalayas,” Asian Medicine. 5(2): 291- 316.
- Alice Yan, “Arsenic in wild ‘organic’ Cordyceps sinensis products,” South China Morning Post, February 5, 2016. https://oriveda.wordpress.com/2017/07/12/arsenic-in-wild-organic-cordyceps-sinensis-products/.
- Lei Yang, et al, “Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive pulmonary disease,” Experimental and Therapeutic Medicine, Published online January 19, 2018. https://www.spandidos-publications.com/10.3892/etm.2018.5777.
- T. Hong, et al., “Cordyceps sinensis (a traditional Chinese medicine) for kidney transplant recipients,” Cochrane Database Systematic Review. October 12, 2015.
- D.B. Ji, et al., “Antiaging effect of Cordyceps sinensis extract,” Phytotherapeutic Research., 2009;23(1):116-122.
- Ashok Kumar Panda and Kailash Chandra Swain, “Traditional Uses and medicinal potential of Cordyceps sinensis of Sikkum,” Journal of Ayurveda Integrative Medicine, January-March 2011; 2 (1): 9-13. Full article available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121254/.
- Xiofeng Zhou, et al., “Separation of cordycepin from Cordyceps militaris fermentation supernatant using preparative HPLC and evaluation of its anti-bacterial activity as an NAD+-dependent DNA ligase inhibitor,” Experimental and Therapeutic Medicine, Published online July 20, 2016. https://www.spandidos-publications.com/10.3892/etm.2016.3536.
- Min-Ho Jeong, et al., “Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mice-derived breast cancer,” Oncology Reports August 6, 2013. www.spandidos-publications.com.
- S.F. Leu, et al., “The in vivo and in vitro stimulatory effects of cordycepin on mouse leydeg cell steroidogenesis,” Bioscience, Biotechnology and Biochemistry Journal, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21512251.
- D.B. Ji, et al., “The Antiaging effect of Cordyceps sinensis extract,” Phytotherapy Research, January 2009; 23 (1): 116-122.
- “Cordyceps,” https://examine.com/supplements/cordyceps/.
- Cornelia H. de Moor, et al, “The polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritis,” Scientific Reports 9, March 18, 2019, https://www.nature.com/articles/s41598-019-41140-1.
- Wang, P. Y., Zhu, X. L. & Lin, Z. B. Antitumor and Immunomodulatory Effects of Polysaccharides from Broken-Spore of Ganoderma lucidum. Frontiers of Pharmacology 3, 135 (2012); A. Berger, et al. Cholesterol-lowering properties of Ganoderma lucidum in vitro, ex vivo, and in hamsters and minipigs. Lipids in Health and Disease 3, 1 (2004). Zhan, L., Tang, J., Lin, S., Xu, Y. & Qin, C. “Prophylactic Use of Ganoderma lucidum Extract May Inhibit Mycobacterium Tuberculosis Replication in a New Mouse Model of Spontaneous Latent Tuberculosis Infection,” Frontiers in Microbiology 6, 1490 (2015).
- C. J. Chang, et al., “Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota,” Nature Communications 6, 7489 (2015).
- R. Akbar and W.K. Yam, “Interaction of ganodermic acid on HIV related target: molecular docking studies,” Bioinformation, December 21, 2011; U. Lindequist, et. al., “The pharmacological potential of mushrooms,” Evidence-Based Complementary and Alternative Medicine 2, 285–299 (2005; T. Akihisa, et al., “Anti-inflammatory and anti-tumor-promoting effects of triterpene acids and sterols from the fungus Ganoderma lucidum,” Chemical Biodiversity, 2007. 4:224– 231; Jun-Wei, et al., “Production of individual ganoderic acids and expression of biosynthetic genes in liquid statis and shaking cultures of Ganoderma lucidum,” Applied Microbiology and Biotechnology, January 2010, Vol. 85, Issue 4, 941-948.
- Nerida L. Klupp, et al., “A double-blind, randomized, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome,” Scientific Reports 6, Article #:29540 (2016). Article online at https://www.nature.com/articles/srep29540; Nerida L Klupp, et al, “Ganoderma lucidum mushroom for the treatment of cardiovascular risk factors,” Cochrane Database of Systematic Reviews, http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007259.pub2/full.
- N. Bhardwaj, et al., “Suppression of inflammatory and allergic responses by pharmacologically potent fungus, Ganoderma lucidum,” Recent Patents on Inflammation and Allergy Discovery, 2014;8(2):104-17. https://www.ncbi.nlm.nih.gov/pubmed/24948193.
- Y. Jiang, et al., “Development of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (Higher Basidiomycetes) polysaccharides injection formulation,” International Journal of Medicinal Mushrooms, 2014, 411-414.
- M. Noguchi, et al., “Randomized clinical trial of an ethanol extract of Ganoderma lucidum in men with lower urinary tract symptoms,” Asian Journal of Andrology, September 1, 2008, 10(5):777-785. https://www.ncbi.nlm.nih.gov/pubmed/18097505.
- “Changes in weight-gain, fecal oocyst count and packed cell volume of Eimeria tenella-infected broilers treated with a wild mushroom (Ganoderma lucidum) aqueous extract,” Journal of South African Veterinarian Association, June 2009, 97-102.
- O. Huseyin, et al., “Ganoderma lucidum Protects Rat Brain Tissue Against Trauma-induced Oxidative Stress”, Korean Journal of Neurotrauma. October 13, 2017, 78-79, https://www.ncbi.nlm.nih.gov/pubmed/29201838.
- S.P. Wasser, et al., “Reishi or Lingzhi (Ganoderma lucidum),” Encyclopedia of Dietary Supplements, 2005:680–90.
- Sissi Watchtel-Galor, et al., “Ganoderma lucidum (‘Lingzhi’), a Chinese medicinal mushroom: Biomarker responses in a controlled Human supplementation study,” British Journal of Nutrition, Volume 91, Issue 2, February 2004: 263-269.
- S.K. Gill and M.J. Rieder, “Toxicity of a Traditional Chinese medicine, Ganoderma lucidum, in children with cancer,” Canadian Journal of Clinical Pharmacology Summer 2008, 15(2)e275-285.
- X. Jin, et al., “Ganoderma lucidum,” Cochrane Database Systematic Review April 5, 2016, https://www.ncbi.nlm.nih.gov/pubmed/27045603.
- Yun Cao, et al., “Species clarification of the prize medicinal Ganoderma mushroom ‘Lingzhi’,” Fungal Diversity, September 2012, Volume 56, Issue 1: 49-62.
- L.W. Hou, et al., “Global diversity of the Ganoderma lucidum complex (Ganodermataceae, Polyporales) inferred from morphology and multi-locus phylogeny,” Phytochemistry, Volume 114, June 2015: 7-15.
- S.G. Hong and H.S. Jung, “Phylogenetic analysis of Ganoderma based on nearly complete mitochondrial small-subunit ribosomal DNA sequences,” (2004). Mycologia, 96 (4): 742–55. doi:10.2307/3762108. JSTOR 3762108.
- Y. Cao, et al., “Species clarification of the prize medicinal Ganoderma mushroom, Lingzhi”, Fungal Diversity, 56(1):49-62 (2012).
- Y. Cao and H.S. Yuan, “Ganoderma mutabile sp. nov. from southwestern China based on morphological and molecular data,” Mycological Progress, February 2013, Issue 1: 121-126.10.1007/s11557-012-0819-9.
- Anon Thawthong, et al., “Ganoderma sichuanense (Ganodermataceae, Polyporales) new to Thailand,” MycoKeys 22:27-43, June 2017.
- J. Da, et al., “Comparison of two official Chinese pharmacopoeia species of Ganoderma based on chemical research with multiple technologies and chemometrics analysis” Journal of Chromatography, January 27, 2012; 1222: 59-70.
- Ding-Tao Wu, et al., “Evaluation on Quality consistency of Ganoderma lucidum dietary supplements collected in the United States,” Scientific Reports, 2017. Full article online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552695/.
- Andrew L. Loyd, et al., “Identifying the “Mushroom of Immortality: Assessing the Ganoderma Species Composition in Commercial Products,” Frontiers in Microbiology, 2018: 9:1557. www.ncbi.nim.nih.gov.
- Denham Harmon, “Aging: a theory based on free radical and radiation chemistry,” Journal of Gerontology 11:298-300, 1956.
- Stephanie Liou, “About Free Radical Damage,” Stanford.edu/group/hopes/cgi-bin/hopes_test/about-free-radical-damage.
- “Free radical, antioxidants: Impact on Human Health,” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249911/.
- James Nam, “High Dose Vitamin B Supplements Should Not Be Taken for Lung Cancer Prevention,” by Cancer Therapy Adviser, August 23, 2017. https://www.cancertherapyadvisor.com/author/james-nam-pharmd/page/44/.
- Elisabetta Lauretti and Domenico Practico, “Effect of canola oil consumption on memory, synapse and neuropathology in the triple transgenic mouse model of Alzheimer’s disease,” Scientific Reports 7, 2017, Article #: 17134. https://www.nature.com/articles/s41598-017-17373-3.
- “The Coconut Oil Miracle: Where is the Evidence” by the Coconut Oil Research Center, www.coconutresearchcenter.org.
- “Is Dr. Oz Right? The Truth About the Latest Anti-Aging Antioxidant,” www.bodyecology/articles/anti-aging.php.
- http://www.lifeextension.com/Magazine/2017/4/Exclusive-Report-On-2016-Aging-Conferences/Page-01.
- Kastalia Medrano, “Why Mushrooms May Be the Best Food to Help Fight Aging,” Newsweek, 11/9/17.
- S. Sing, et al., “The central role of glutathione in the pathophysiology of human diseases,” Journal of Experimental Therapeutic Oncology, 2012, 9(4): 303-316.
- https://pubchem.ncbi.nlm.nih.gov/compound/L-Ergothioneine#section=Chemical-Vendors. J Allen, et al., “Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers,” Journal of Alternative and Complementary Medicine, September 17, 2011 (9): 827-833. https://www.ncbi.nlm.nih.gov/pubmed/21875351.
- https://us.supersmart.com/article.pl?id=0634&fromid=GGPLA&gclid=EAIaIQobChMIrsCXqrig4QIVDEwNCh3cFAMsEAQYASABEgIHyvD_BwE.
- https://www.sciencedaily.com/releases/2019/03/190312103702.htm.
- https://www.webmd.com/vitamins/ai/ingredientmono-1183/ergothioneine.
- “Antioxidants: Beyond the Hype,” The Nutrition Source, Harvard School of Public Health, hsph.harvard.edu.
- Hui Wang, et al., “NRF2 activation by antioxidant antidiabetic agents accelerates tumor metastasis,” Science Translational Medicine, Vol. 8, Issue 334, April 13, 2016; Jeremy Michael Van Raamsdonk and Siegfried Hekimi, “Superoxide dismutase is dispensable for normal animal lifespan,” Proceedings of the National Academy of Sciences U.S.A., April 10, 2012; 109(15):5785-5790.; E.R. Stadtman, “Protein Oxidation and Aging,” Science, 257:1220-1224, August 28: 1992.
- Vadim N. Gladyshev, “The Free Radical Theory of Aging Is Dead. Long Live the Damage Theory!” Antioxidants and Redox Signaling, Feb. 1, 2014: 20(4):727-731.
- Jerome Lapointe and Siegfried Hekimi, “When a Theory of Aging Ages Badly,” Cellular and Molecular Life Sciences, Jan: 67(1):1-8.
- See F.D.A. U.S. Food and Drug Administration guide on labeling: Chapter IV. Claims, https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/DietarySupplements/ucm070613.htm.
- Dan Mitchell, “Why the Supplement Industry Is So Powerful,” Time Magazine, March 11, 2015, http://time.com/3741142/gnc-vitamin-shoppe-supplements/
- Julia Belilluz, “Amazon is a giant purveyor of medicinal quackery,” September 2016. www.vox.com.
- Jianping Han, et al., “An authenticity survey of herbal medicines from markets in China using DNA barcoding,” Nature, Scientific Reports 6, Article number 18723 January 7, 2016; “Hepatoxicity due to a formulation of Ganoderma (LING ZHI)”, Journal of Hepatology, August 4, 2004. http://www.journal-of-hepatology.eu/article/S0168-8278(04)00258-2/fulltext
- G. Bjelakovic, et al., “Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis,” Journal of the American Medical Association. February 28, 2008; 299 (7): 765-66. https://www.ncbi.nlm.nih.gov/pubmed/17327526; “Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases,” Cochrane Database Systematic Review, March 14, 2012, https://www.ncbi.nlm.nih.gov/pubmed/22419320. Volkan I. Sayin, et al., “Antioxidants Accelerate Lung Cancer Progression in Mice,” Science Translational Medicine and Research, Volume 6, No, 221, January 29, 2014, 1-8.
- “Antioxidants and Cancer – Should I Take Them?,” Care Oncology, July 14, 2018, https://careoncology.com/antioxidants-and-cancer-should-i-take-them/.
- “Antioxidant supplements cannot be recommended for gastrointestinal cancer prevention,” Cochrane Report, 3/4/16 pp.1-4.
- Selenium. Linus Pauling Institute Micronutriment Information Center. https://lpi.oregonstate.edu/mic/minerals/selenium; A. Barbul and A. Ullyargol, “Use of arginine in multiple organ dysfunction syndrome and sepsis,” PubMed.gov. https://www.ncbi.nlm.nih.gov/pubmed/17713410; K. Akhilender Naidu, “Vitamin C in human health and disease is still a mystery? An overview,” Journal of Nutrition, August 21, 2003, 2:7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC201008/; “Vitamin E: Overview,” Mayo Clinic, October 18, 2017. https://www.mayoclinic.org/drugs-supplements-vitamin-e/art-20364144; S.K. Myung, et al, “Effects of antioxidant supplements on cancer prevention: meta-analysis of randomized controlled trials,” Annals of Oncology, Vol. 21, Issue 1, 1 January 2010, 166-179. https://academic.oup.com/annonc/article/21/1/166/145445.
- Randolph M. Howes, Antioxidants Linked to Deadly Unintended Consequences, 2012.; Randolph M. Howes. “The free radical fantasy: a panoply of paradoxes,” Annals of the New York Academy of Sciences. May 2006, Volume 1067:22-26: Katja E. Menger, et al., “Fasting, but Not Aging, Dramatically Alters Redox Status of Cysteine Residues on Proteins in Drosophila melanogaster,” Cell Reports, June 30, 2015; 11(12):1856-1165. https://www.cell.com/cell-reports/fulltext/S2211-1247(15)00569-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124715005690%3Fshowall%3Dtrue: Melinda Wennar Moyer,”Antioxidants May Make Cancer Worse,” Scientific American, Oct. 7, 2015; Hans-Klaus Goischke, “Vitamin D Supplementation as Add-on Therapy in Multiple Sclerosis – Balance Between Benefit and Risk?: A Commentary on Vitamin D Supplementation in Central Nervous System Demyelinating Disease – Enough Is Enough,” International Journal of Molecular Sciences, March 2019, 20(6), 1513.
- A. Hervera, et al., “Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons,” Nature Cell Biology, February 2018, 307-319.
- Society of Chemical Industry, “Button Mushrooms Contain Ads Much Antioxidants as Expensive Ones,” Science Daily (2008, February 12). www.sciencedaily.com/releases/2008/02/080206090452.htm.
- K.E. Menger, et al., “Fasting, but not aging, dramatically alters the redox status of cysteine residues on proteins in Drosophila melanogaster,” Cell Reports, 2015, May, Volume 11, Issue 12. Full text is online at https://www.cell.com/cell-reports/fulltext/S2211-1247(15)00569-0.
- Lien Ai Pham-Huy, et al., “Free Radicals, Antioxidants in Disease and Health,” International Journal of Biomedical Science, 2008, June: 4(2):89-96.
- D. Fusco, et al, “Effects of antioxidant supplementation on the aging process,” Clinical Interventions in Aging, 2007; 2(3):377-387; A. Bardia, et al, “Efficacy of antioxidant supplementation in reducing cancer incidence,” Mayo Clinic Proceedings 2008, Jan; 83(1):23-34.
NAMA Store >