Medicinal mushrooms as a source of antitumor and
immunomodulating polysaccharides

By the term ‘mushrooms’, we generally mean the defi-nition of Chang and Miles (1992): ‘a macrofungus with a distinctive fruiting body which can be either hypogeous or epigeous, large enough to be seen with the naked eye and to be picked by hand’.

The number of mushrooms on Earth is esti-mated at 140,000, yet maybe only 10% (approximately 14,000 named species) are known. Mushrooms comprise a vast and yet largely untapped source of powerful new pharmaceutical products. In particular, and most impor-tantly for modern medicine, they represent an unlimited source of polysaccharides with antitumor and immuno-stimulating properties. Many, if not all, Basidiomycetes mushrooms contain biologically active polysaccharides in fruit bodies, cultured mycelium, culture broth. Data on mushroom polysaccharides have been collected from 651 species and 7 infraspecific taxa from 182 genera of higher Hetero- and Homobasidiomycetes. These poly-saccharides are of different chemical composition, with most belonging to the group of β-glucans; these have β-(1→3) linkages in the main chain of the glucan and additional β-(1→6) branch points that are needed for their antitumor action. High molecular weight glucans appear to be more effective than those of low molecular weight. Chemical modification is often carried out to im-prove the antitumor activity of polysaccharides and their clinical qualities (mostly water solubility).

Principal points of anti-tumor and immunomodulating effects of mushroom poly-saccharides. Most important among them are:

  • preven-tion of oncogenesis by oral consumption of mushrooms or their preparations;
  • direct antitumor activity against various allogeneic and syngeneic tumors;
  • immunopo-tentiation activity against tumors in combination with chemotherapy;
  • preventive effect on tumor metastasis.

A good example of preventive effect is given by Japa-nese research on their popular edible and medicinal mushroom, Hypsizygus marmoreus (Ikekawa 2001). Control mice were bred on an ordinary diet and treated mice with a diet containing 5% dried fruit body of H. marmoreus. All mice were i.p. injected with a strong carcinogen, methyl-cholanthrene, and carcinogenesis of the mice was investigated. At the end of the 76-week ob-servation, 21 of the 36 control mice developed tumors, but only 3 of 36 mice in the treated group had tumors. The authors concluded that the mechanism of cancer-inhibitory and cancer-preventing activities of edible mushrooms was due to immunopotentiation (Ikekawa 2001).
Researchers demonstrated that the cancer death rate of farmers whose main occupation was producing Flammulina velutipes (a well known medicinal mush-room in Japan) was remarkably lower than that of the general population in the Prefecture (Ikekawa 1995, 2001). Another similar observation in Brazil brought about extensive studies – and popularity – of Agaricus blazei (see below).

Mechanisms of antitumor and immunomodulating action by mushroom polysaccharides

Mushroom polysaccharides exert their antitumor action mostly via activation of the immune response of the host organism. These substances are regarded as biological response modifiers (BRMs; Wasser and Weis 1999). This basically means that:

  1. they cause no harm and place no additional stress on the body;
  2. they help the body to adapt to various environmental and biological stress-es; and
  3. they exert a nonspecific action on the body, supporting some or all of the major systems, including nervous, hormonal, and immune systems, as well as reg-ulatory functions (Brekhman 1980).

The immunomodulating action of mushroom polysaccharides is especially valuable as a prophylactic, a mild and non-invasive form of treatment, and in the prevention of metastatic tumors, etc.

Polysaccharides from mushrooms do not attack cancer cells directly, but produce their antitumor effects by activating different immune responses in the host. This has been verified in many experiments, such as the loss of the antitumor effect of polysaccharides in neonatal thymec-tomized mice or after administration of anti-lymphocyte serum (Ooi and Liu 1999). Such results suggest that the antitumor action of polysaccharides requires an intact T-cell component and that the activity is mediated through a thymus-dependent immune mechanism. Also, the antitumor activity of lentinan and other polysaccha-rides is inhibited by pretreatment with antimacrophage agents (such as carrageenan).

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 potentiate 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.  They can also be considered as multi-cytokine inducers able to induce gene expression of various immunomodulatory cytokines and cytokine receptors. Lymphocytes governing antibody production (β-cells) and cell-mediated cytotoxicity (T-cells) are also stimulated.

PREVENTION:

Cancer Research UK state ‘Human epidemiological studies in Japan and Brazil strongly suggest that regular consumption of certain medicinal mushrooms over prolonged periods of time significantly reduce the levels of cancer incidence’. And, ‘There is increasing evidence with experimental animals that regular feeding of powered medicinal mushrooms can have a cancer preventative effect, demonstrating both high anti tumour activity and restriction of tumour metastasis’.:Medicinal mushroom extracts can be used to improve quality of life by alleviating the side effects of radio and chemotherapy such as fatigue, reduced appetite, bone marrow suppression and the risk of opportunistic infection.

Cancer Research UK state, ‘These compounds have been shown to be safe when taken over long periods of treatment and significantly, these compounds appear to reduce the adverse effects of radiotherapy and chemotherapy. These results are in marked contrast to the well documented adverse side effects associated with most chemo therapeutic compounds and also to a lesser extent, certain immuno therapeutics that have been shown to be capable of causing fevers, chills, rash, oedema, arthralgia, hypotension, congestive heart failure or CNS toxicities’.Many compounds from medicinal mushrooms have been classified as anti-tumour agents by the US National Cancer Institute.

Why use a mushroom blend?

Researchers believe that to in order to maximise a response in the immune system, a mixture of mushroom polysaccharides is best. These polysaccharides increase the number and activity of killer T and NK (natural killer) lymphocytes. Combining medicinal mushroom species sends the immune system multiple stimuli to wake up the body's natural defences.

Why is it important mushrooms are organically grown?

Mushrooms can concentrate heavy metals, especially if they are grown near an industrialised area where pollutants from air and water can be taken up from the soil and passed directly into them.