Mushrooms & Health: Reviewing the Latest Data

Paul Anderson NMD

The use of mushrooms, mushroom extracts and mushroom combinations in the care of human health is thousands of years old. There are few agents in the record of human history that can rival the duration, impact or reputation of mushrooms in medicine.

In some ways, one may believe that the use of mushrooms in healthcare is so well understood that research would have stopped being done long ago. This is the case, for the most part, in regard to research on many modern pharmaceutical agents (unless a researcher wishes to try a new indication with an old drug). A very brief search of the data shows many papers published in peer-reviewed medical literature, with some as current as two months ago. In this review, I have chosen four papers published in 2016 and one—which I believe is of note—from the bygone days of 2014. As one who is involved in research using many “old” agents (and some new), I find that when communicating with a patient regarding the utility of an agent in their healthcare, some mention of active and positive research on that agent increases their desire to use it and follow the therapeutic plan I have set out. This review is intended to briefly provide that information for medicinal mushrooms.

While there are plethora of mushrooms and mushroom fractions used in medicine, I am focusing this paper on those reported on in the five publications mentioned and cited in the references.

Crohn’s Disease

Therkelsen et al1 discussed the effect of the medicinal Agaricus blazei Murill-based mushroom extract on the symptoms, fatigue and quality of life in patients with Crohn’s disease in a paper published this summer. The results show significant improvement on symptoms, for both genders, in the mushroom treated group. The patients did not report any adverse effects of the mushrooms. The authors conclude that “Crohn’s patients with mild to moderate symptoms may have beneficiary effects of [the mushroom therapy] as a safe supplement in addition to conventional medication.” The effects of the mushroom in the GI tract, as well as systemically, are likely behind the benefits noted. These mushrooms (as many do) exhibit immunomodulatory effects which are so crucial to the care of people with autoimmunity. That the inflammatory bowel diseases have both a direct gut effect and a systemic effect (as we see, for example, with curcumin) is of great therapeutic benefit.

Malnutrition and Cachexia

Llauradó et al 2  studied oral administration of an aqueous extract from the oyster mushroom Pleurotus ostreatus that enhances the immunonutritional recovery of malnourished mice. I know that mouse studies are not preferred over human studies. But gaining the mechanistic information one can from an animal study in a condition such as malnourishment can “fast track” the trial of a natural agent in humans with the same or similar condition.

As one who struggles with the treatment of patients with cachexia (mostly secondary to cancer but not always), any agent that can potentially turn the biology of these suffering patients around is needed clinically. In cachexia, we know that a multi-agent approach is always required and that the more “at the core” of the cachexia biology the agent works, the more beneficial an addition to the therapy plan it is. The authors make some very promising discoveries in this respect which—when compared to the biological “faults” created by cachexia—make this agent worth a trial in cachexic and underweight patients:

“Oral treatment with CW-P normalized haemoglobin levels, liver arginase and gut mucosal weight. CW-P increased total liver proteins and DNA and protein contents in gut mucosa. Pleurotus extract provided benefits in terms of macrophages activation as well as in haemopoiesis, as judged by the recovery of bone marrow cells and leukocyte counts. Moreover, CW-P stimulated humoral immunity (T-dependent and T non-dependent antibodies responses) compared to non-supplemented mice. CW-P extract from the oyster mushroom can be used to develop specific food or nutritional supplement formulations with potential clinical applications in the immunotherapy.”

With the caveat that malnutrition and cachexia must be treated in a well-rounded manner, it seems to me that the availability of a potentially strong synergist to nutritional therapies in an aqueous form may be potentially lifesaving to these patients.

Ganoderma (Reishi) and Cancer

Jin et al 3 reviewed the role of Ganoderma lucidum (Reishi mushroom) in cancer treatment. As a preface, such reviews need to have their conclusions considered in the context of the “primary question” or the endpoint the review was focused on. This is important, as I have seen such reviews say “there is no scientific data to support…” and such a review was cited, only to find out that the review was answering a totally different question than the “no data” person was speaking of. With this in mind, the review was seeking to answer this question: “Should reishi be used as a first-line therapy in cancer?” This is a pretty tall order for anything to fill (let alone a mushroom), as the therapy of “cancer” is actually many entities and there are many variations related to stage, grade and patient immunity that can affect any therapeutic outcome. That said, the authors conclusions are summarized here:
The review did not find sufficient evidence to justify the use of G. lucidum as a first-line treatment for cancer.

It remains uncertain whether G. lucidum helps prolong long-term cancer survival.

However, G. lucidum could be administered as an alternative adjunct to conventional treatment in consideration of its potential of enhancing tumour response and stimulating host immunity.

1.   lucidum was generally well tolerated by most participants with only a scattered number of minor adverse events. No major toxicity was observed across the studies.

Future studies should put emphasis on the improvement in methodological quality while further clinical research on the effect of G. lucidum on long-term cancer survival is needed.
It is no surprise that Reishi didn’t have the data to take first place in the therapy of “cancer”—very few agents could claim that. It is also no surprise that it had excellent safety, enhanced host response and tumor immunity and was, by the reviewers, recommended for consideration as an adjunct in the care of a person with cancer.

Mechanisms of Immunological Benefit

Chang et al4 (the eldest paper reviewed, from way back in 2014) looked at Ganoderma lucidum stimulating NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin. Their conclusion was that Ganoderma, in their research, showed a cellular and molecular mechanism to account for the reported anticancer effects of G. lucidum extracts in humans. Of note, this was also an aqueous extract.

This mechanism actually has crossover from oncology effects to infectious disease as well. Perforin and granulysin are two cytolytic molecules that natural killer cells use to kill (hence the name of the cell type) any cell without “self” surface receptors. This includes things such as cancer cells, virally infected cells, bacteria and others.  Enhancement of natural killer cell function is well established in the basic immunology sciences as enhancing “surveillance” immunity and lowering infections and oncogenesis.

The Form of an Extract Does Matter
Lu et al5 in their paper published this summer, “Immunomodulatory properties of medicinal mushrooms: differential effects of water and ethanol extracts on NK cell-mediated cytotoxicity,” make an excellent point regarding the form of a mushroom extract and its effect on the mechanism and actual immunologic effect of the agent.

Through the same mechanisms mentioned above4, these researchers showed that aqueous extracts (note: most papers reviewed above used this form) allow these natural killer cell benefits and alcohol extracts block it. From the conclusions: “Water extracts enhance NK cell cytotoxic activity against cancer cells, whereas ethanol extracts inhibit cytotoxicity.” This difference in extraction processes is well known in herbal medicine and generally in botanical medicines and herbalism, the “method” of extraction is highly respected as to clinical outcome. This paper, and the fact that the majority of the studies presented today used aqueous extracts, enhances the notion that such extracts are likely superior to alcohol extracts in the case of immune responses of mushroom-based agents.

Implications for Practice

Medicinal mushrooms have a great pool of data supporting their use in modern times. They are also some of the most treasured agents in healthcare in the thousands of years of recorded history we have. My common thought is that if an agent has “stood the test of time” (and we know it to be effective), the science will not only prove that out, but also repeatedly support and elucidate more and more mechanisms explaining the clinically noted outcomes.