Mushrooms and Immunity

January 7, 2018

Mushrooms have become increasingly important as immune modulating agents and dietary supplements. In fact, over the last ten years there have been several thousand journal articles written about medicinal mushrooms and several hundred specifically about mushrooms and cancer. Now, an entire medical journal is dedicated to their study – the International Journal of Medicinal Mushrooms.

Mushrooms Have Health Benefits

Mushrooms have long been valued as delicious and nutritional foods by many societies. In Asia, it has been recognized that certain edible and non-edible mushrooms can have profound health benefits. In fact, a limited number of highly purified compounds derived from certain medicinal mushrooms are now being used in Asia and the U.S.

To explore this resurgent interest in mushrooms, in May 2002, Cancer Research UK commissioned a comprehensive study entitled Medicinal mushrooms: their therapeutic properties and current medical usage with special emphasis on cancer treatments. The authors included: John E. Smith, BSc MSc PhD DSc FIBiol FRSE, Emeritus Professor of Applied Microbiology, University of Strathclyde, Chief Scientific Officer, MycoBiotech Ltd, Singapore; Neil J. Rowan, BSc MSc PhD MIBiol MIFST, Lecturer, Department of Bioscience, University of Strathclyde; and Richard Sullivan, BSc MD PhD, Head of Clinical Programmes, Cancer Research UK. Much of the information below comes from the Executive Summary of this report. The entire report is available here.

The practice of using fungi, especially mushrooms, in Chinese Traditional Medicine (TCM), dates back into antiquity and has been recorded in ancient Chinese manuscripts. Increased scientific and medical research in recent decades, especially in Japan, Korea and China and more recently U.S., is confirming efficacy and identifying the bioactive molecules (especially the polysaccharides) which contain demonstrable anti-cancer activities. Most appear to act as immune system enhancers though some can have direct cytotoxic effects on cancer cells. Only a small number of studies have progressed successfully to objective clinical assessment in trials.

Medicinal Mushrooms

The main medicinal mushrooms both edible and non-edible include: Ganoderma lucidum (Reishi or Ling Zhi), Lentinus (Lentinula) edodes (Shiitake), Phellinus linteus, Porio cocos, Auricularia auricula, Hericium erinaceus, Grifola frondosa (Maitake), Flammulina velutipes, Pleurotus ostreatus (Oyster mushroom), Trametes (Coriolus) versicolor, Tremella fuciformis, Schizophyllum commune and the nonmushroom Cordyceps sinensis (the caterpillar fungus). The anti-tumour polysaccharides isolated from mushrooms include: water-soluble β-D-glucans, β-D-glucans with heterosaccharide chains of xylose, mannose, galactose or uronic acid or β-D-glucan-protein complexes – proteoglycans. Some are orally bioavailable.

The main medically important polysaccharide compounds that have undergone clinical trials include Lentinan (Lentinus edodes), Schizophyllan (Schizophyllum commune), PSK and PSP (Trametes versicolor) and Grifron-D (Grifola frondosa).

Mushroom-derived glucan and polysaccharo-peptides can act as immunomodulators. The ability of these compounds to enhance or suppress immune responses can depend on a number of factors including dosage, route of administration, timing and frequency of administration, mechanism of action or the site of activity. Several mushroom compounds have been shown to enhance the host’s innate (non-specific) and acquired (specific) immune responses and activate many kinds of immune cells that are important for the maintenance of homeostasis, e.g. host cells (such as cytotoxic macrophages, monocytes, neutrophils, natural killer cells, dendritic cells) and chemical messengers (cytokines such as interleukins, interferon, colony stimulating factors) that trigger complement and acute phase responses.

There have been extensive in vivo studies demonstrating the anti-cancer activity of the glucan polysaccharides and polysaccharide-peptides in animal models. These studies strongly suggest an immunomodulating mode of action. However, in in vitro studies on various cancer cell lines, there is strong evidence for direct cytotoxic effects on the cancer cells for some, but not all, of the polysaccharides.

Many of the mushroom polysaccharides have proceeded through Phase I, II and III clinical trials mainly in Japan and China. Lentinan (L. edodes) has demonstrated strong anti-tumor activity in a wide range of animal models and with human clinical trials where it has proved successful in prolonging the survival especially those patients with gastric and colorectal cancer. Lentinan has been approved as a drug in Japan and is considered an important adjuvant treatment for several cancers. Schizophyllan (S. commune) has proved useful for recurrent and inoperable gastric cancer, as well as increasing survival times of patients with head and neck cancers.

Reishi

Lingzhi (Ganoderma Lucidum), widely known as Reishi, is one family of mushrooms that is known for delivering superior health benefits in China. In fact, Red Reishi was found to contain some of the highest concentrations of Polysaccharides and Triterpenes, both unique in their ability to fight against certain illnesses. Reishi is also known to boost the immune system and enhance overall metabolism and numerous research papers have been published on its health benefits, including: anti-tumor, immunotherapeutic, lowering blood pressure, lowering cholesterol and blood sugar, improving cardiovascular functions, enhancing respiratory system and lungs functions, and chemotherapy support.

In addition, there are several clinical trials with Grifron-D, GD (G. frondosa) on breast, prostate, lung, liver and gastric cancers underway in Japan and U.S. Results to date are promising. In in vitro studies GD appears to inactivate glyoxalase I, an enzyme believed to metabolise chemotherapeutic compounds used against cancer cells thus potentially enhancing their bioavailability.

PSK and PSP

Two compounds, PSK and PSP (derived from mycelial cultures of T. versicolor) have shown worthwhile anti-cancer properties when given with traditional chemotherapeutic agents with no increases in side-effects. PSK has successfully been used in Phase I, II and III clinical trials with cancers of the stomach, esophagus, nasopharynx, colon, rectum and lung, and with subsets of breast cancer. PSK gave protection against the immunosuppression that normally is associated with surgery and long-term chemotherapy. PSK continues to be used extensively in Japan as an adjunct to standard radio and chemotherapy.

A significant observation from these studies is the apparent ability of all of the above mushroom-derived polysaccharides when administered with radiotherapy and/or chemotherapy to significantly reduce the side-effects so often encountered by patients.

The safety of all medicinal mushrooms or their extracts cannot be guaranteed simply because they have been used for many centuries with apparent safety. However, several purified mushroom polysaccharides have been in clinical use in Japan, China and the U.S. for several years with no reports of any significant short-term or long-term adverse effects.

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