Mushrooms as Medicines?

© Peter Werner
Original publication: Mycena News, December 2004

Mushrooms have long been used in traditional medicines in many parts of the world and are particularly well-represented in pharmacopeias of Asian traditional medicines. Until recently, the importance of mushrooms and their extracts were dismissed out of hand by medical researchers, who saw few medicinal compounds of interest in basidiomycetes and no empirical basis for the claimed efficacy of mushrooms used in traditional herbal medicine. This began to change some 30 years ago as Japanese researchers began to examine the the use of mushroom extracts, especially those of polypores, in the treatment of cancer.

Research has focused on a group of fungal cell wall polysaccharides known as ß-(1-3)/(1-6)-glucans. Well known examples include lentinin from Lentinula edodes (shiitake) and grifolan from Grifola frondosa (maitake), but compounds of this type are found almost universally among fungi. While it was previously believed that longchain polysaccharides like this would be physiologically inert because the digestive system would simply break them down into simple sugars, recent studies have found that these compounds are highly active, even (in fact, especially) those in which the component molecules are quite large.

Many of these compounds have been found to be strongly immunopotentiating, that is, they stimulate the production and activity of immune cells such as T-cells, macrophages, natural killer cells, and the like. The reasons for this are unclear, but several types of ß-glucan receptors are found in immune-type cells. It is thought that these receptors aid the immune system in recognizing invasion by something that is 'not self', and hence help marshal an immune response. Stimulation of ß-glucan receptors may be particularly useful in the treatment of cancer, as cancer cells are simply mutations of the body's normal cells and aren't always recognized as 'not self' by the immune system.

So much for theory - how do these mushroom extracts work in practice? Immunopotentiating ß-glucans have shown significant anti-tumor activity in vitro and some mushroom extracts have been demonstrated to significantly lower the rate of mutagen-induced cancer in mice when compared to an untreated control. However, as with many such promising anticancer compounds, success in actual clinical trails was limited. The use of lentinin or crude extracts of shiitake in combination with more traditional chemotherapy has been extensively studied in Japan. Several studies demonstrated increased length of survival in patients with certain types of cancer (though these studies were not always well-controlled), however, with many other types of cancer it was completely ineffective.

A recent literature review by Andrea Borchers and others from UC Davis School of Medicine suggests several ways in which research on mushroom extracts might be improved. Different compounds have been studied in many different tumor types, making comparison of their efficacy difficult. It would be more useful if these compounds were all tested on a few tumor types and if the more effective compounds were then screened against a wide range of tumor types.

Also, it needs to be more clear what is actually being administered. In many studies and reviews, crude mushroom extracts and purified compounds were treated as equivalent, though this may not be the case. Mushrooms contain a host of compounds that act on the immune system in different ways. The synergistic or inhibitory action of these compounds in combination is a real possibility. Crude extracts and purified compounds should both be tested against the same tumor models to establish which is more effective. Additionally, in vitro studies of Agaricus brasiliensis have shown that mushroom strain type, fruiting body age, and extraction from fruiting bodies vs extraction from mycelium significantly affected the immune-regulating effect of these extracts.

What about regular consumption of certain mushrooms or mushroom extracts as a dietary supplement to prevent cancer? A number of mushrooms are increasingly being used as "nutriceuticals", notably Lentinula edodes, Ganoderma lucidum and G. oregonense, and Agaricus brasiliensis (sold as Agaricus blazei, though the latter name properly refers to a species found in the eastern US and not the cultivated species that originated in Brazil). There are some intriguing studies hinting that there might be something to this, notably a study demonstrating that a group of enoki farmers showed significantly lower cancer rates than the general population of the same area, and a study from Korea (an area with a high rate of gastric cancer) showing an inverse correlation between gastric cancer rate and mushroom consumption. However, these studies did not control for factors such as sex, socioeconomic status, family history, etc and were too general to demonstrate a cause-and-effect relationship.

There are, of course, many other useful compounds that one can get from mushrooms. Mushrooms live in a constant battle with bacteria and other fungi and have developed a host of antibiotics to defend themselves from attack from other organisms. Modern antibiotic treatment was first ushered in with the discovery of penicillin from the imperfect fungus Penicillium. However, basidiomycetes represent a great untapped reservoir of such compounds - when a group of researchers screened extracts of 204 species of basidiomycetes collected in Spain, 109 were found to have antimicrobial activity. Considering that many strains of pathogenic bacteria are becoming increasingly resistant to our present arsenal of antibiotics, the importance of developing novel antibiotics is clear.

After a hiatus of several decades, research into the therapeutic effects of hallucinogenic compounds is once again active. This includes research into uses of psilocybin, a promising use of which is the treatment of obsessive-compulsive disorder (OCD). There have been a number of anecdotal reports of individuals with severe OCD (such as handwashing 200+ times per day) being relieved of obsessive thoughts during the psilocybin experience. More importantly, this effect has been lasting, with reports of individuals going for two years after the experience without OCD symptoms before relapsing. Controlled study of OCD treatment with psilocybin is now being carried out at University of Arizona. Another active study of the therapeutic use of psilocybin includes a study at UCLA investigating whether psilocybin can provide relief of death anxiety in terminal cancer patients. There is also quite a bit of anecdotal information that psilocybin use has a therapeutic effect for chronic sufferers of cluster headaches (an extremely severe recurring type of headache said to be more painful than migraine headaches). Psilocybin is said to break the cycle of headache recurrence, with effects lasting anywhere from two weeks to a year. At present, however, there is no active study looking at this effect.

Understanding of the medicinal properties of mushrooms is another area where amateur mycologists can make some contribution. Is the cancer rate among people who regularly consume wild mushrooms higher or lower than the rest of the population? Such an epidemiological study would be well worth carrying out. Do we observe that certain mushrooms are consistently avoided by certain other organisms or are slower to decay than others? There may be more to that than meets the eye.