Maitake D-fraction: a potent mushroom extract product against human malignancies

Townsend Letter for Doctors and Patients,  Dec, 2002  by Sensuke Konno

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The medicinal aspects of mushrooms have been known for centuries in the Orient, and the Chinese and Japanese people have long consumed a wide variety of mushrooms. However, Western people have neither known nor gained from the potential benefits of these mushrooms until recently. One reason for this disparity arises from misunderstanding or misconception about the nature and properties of mushrooms. Since mushrooms belong to the family of "fungi," many people have a general perception that mushrooms lack nutritional value while others have a less common but interesting thought that eating mushrooms may make one vulnerable to Candida or yeast infections. Neither view is now known to be valid, and to the contrary, mushrooms are rich in vitamins, minerals, amino acids, and fibers, but low in fat, cholesterol, and calorie content. (1) In addition, scientific and clinical research on mushrooms over the past 20 years has revealed a number of their medicinal properties that might provide remarkable health benefits. A particular focus of such research has been on "maitake" (Grifola frondosa), an edible, tasty mushroom, which literally means "dancing mushroom." It is a giant mushroom that often reaches 20 inches in diameter and may weigh up to 100 pounds. This mushroom has been available by cultivation since the mid-1980s, enabling scientists to study its medicinal properties and being widely available for public consumption. Many physiological benefits of maitake have been postulated, ranging from immunomodulatory and antitumor activities to treatment for hypertension, diabetes, hypercholesterolemia, obesity and hepatitis B infection. (2-10) Its antiviral activity against human immunodeficiency virus (HIV)/AIDS was also confirmed by the US National Cancer Institute in 1992. (11)

Maitake D-Fraction: Bioactive [Beta]-Glucan Extracted from Maitake

Most research on maitake mushroom has been performed using the bioactive extract product, namely "Maitake D-fraction," to assess its potential efficacy on various human malignancies. The main, active component of this unique D-fraction is the protein-bound polysaccharide, consisting of either [beta]-1,3 branches or [beta]-1,3 glucan branched with [beta]-1,6 glucosides. It is a hot water-extractable fraction with a molecular weight of~1 x 10 (6) dalton (2,12) and is prepared by a standardized procedure developed by Maitake Products, Inc. (Ridgefield Park, New Jersey). The D-fraction has demonstrated the most potent immune enhancement and antitumor activity regardless of the route of administration (oral or injection), resulting in the highest reduction rate in cancer proliferation. (13,14) For instance, D-fraction has been shown to have an antitumor effect on tumor-bearing mice,13 with the enhanced cytotoxic activity of macrophages and the elevated interleukin-1 production leading to the activation of cytotoxi c T-lymphocytes (CTL). (15) These findings are highly suggestive that D-fraction acts not only through direct activation of various immune effectors (macrophages, CTL, natural killer cells, etc.) targeting tumor cells, but also through potentiating the activity/production of various lymphokines.

Safety of D-Fraction

A critical and substantial question about Maitake D-fraction is its safety, which must be adequately addressed. D-fraction has been tested on mice, confirming its safety with no toxicity or adverse effects. (16) A non-randomized clinical study of D-fraction on 165 patients with various types of advanced cancers showed the significant improvements in their clinical status without any side/adverse effects. (16) In addition, side effects of patients receiving chemotherapy were ameliorated when D-fraction was given simultaneously Adverse symptoms such as nausea, hair loss and leukopenia were alleviated in 90% of patients, while a reduction in pain was reported in 83% of patients. (16) This finding suggests that D-fraction should be considered a valuable adjuvant in ongoing cancer chemotherapy.

Safety of D-fraction is further supported by the fact that the FDA has exempted D-fraction from a phase I study of toxicology. In 1998, the FDA granted Maitake Products, Inc. an Investigational New Drug (IND) Application to conduct a phase II pilot study using D-fraction on patients with advanced breast and prostate cancer. (17) These studies are currently underway at several institutions/hospitals, and other independent institutions are also planning to conduct similar trials.

D-Fraction: Potential Apoptosis Inducer

As mentioned above, the antitumor effect of D-fraction appears to be primarily attributable to its potent immunostimulatory activity; however, the exact mechanism has not yet been completely elucidated. In fact, the recent study on prostate cancer (CaP) cells, demonstrates that D-fraction is capable of inducing "apoptosis" (programmed cell death) in these CaP cells, (18) which may also account for another antitumor mechanism of D-fraction.

To explore a more effective and alternative modality for CaP treatment due to the poor efficacy of conventional therapies, we have conducted a study of D-fraction on human prostatic cancer PC-3 cells (the most aggressive and metastatic cancer cells) in vitro. (18) Such studies showed that D-fraction (480 [mu]g/ml) was capable of inducing severe (>95%) cell death in PC-3 cells within 24 h. In situ hybridization then confirmed that D-fraction-induced cell death had resulted most likely from apoptosis (Fig. 1). Thus, this finding suggests that D-fraction could be considered a potential apoptosis inducer. Whether vitamin C might potentiate such an apoptotic ability of D-fraction was also examined, because Vitamin C had been proposed to modulate the D-fraction bioactivity. (19) As little as 30 to 60 [mu]g/ml of D-fraction combined with 200 [mu]M of Vitamin C was found to be nearly as effective as 480 [mu]g/ml of D-fraction alone, resulting in >90% cell death in 24 h. Because a given concentration (200 [mu]M) of Vi tamin C alone had no effect on cells, it might have primarily served to potentiate the bioactivity of D-fraction. These results show that even the relatively low concentrations of D-fraction can be synergistically potentiated with Vitamin C to become highly cytotoxic to PC-3 cells, ultimately inducing apoptosis. This is also consistent with several clinical reports (unpublished) describing that D-fraction appeared to work cooperatively with Vitamin C in certain cancer patients.