Introduction

A concern among many Ovarian Cancer patients is what supplement should I take and is it safe to take?  In the vast sea of supplements and claims about their use with cancer treatments, it becomes difficult to identify which one may have the most benefit.   A shining beacon of hope may be available in the supplement known as "Maitake D-Fraction" which will not effect chemotherapy1, promotes immune system activation, and may have specific anticancer activity3.

Relatively unknown to Americans, Maitake (pronounced as my-tah-key) is one of several medicinal mushrooms, which include Reishi and Shiitake, that is native to Northeastern Japan but is now grown in America.  This mushroom was in such demand during the feudal era of Japan that it's weight was exchanged in silver due to it's taste and health benefits.  It was not until the the early 1980's, however, when the first research on the "D-Fraction" (which is made from the fruiting body mushroom) of the Maitake mushroom was conducted by the late Dr. Kanichi Mori, then the head of the Japanese Mushroom Institute.  His research, and countless other researchers after him, demonstrated immune and anticancer activity In Vitro and In Vivo in many documented labratory, animal, and human cases.

Out of all the cancer research conducted with Maitake D-Fraction, there have never been any done on Ovarian Cancer.  Despite this fact, several other cancers (such as breast and prostate) have had several studies performed with D-Fraction with impressive results, so it's plausible that there may be similar effects on Ovarian Cancer cells lines.



How Does Maitake D-Fraction Work?

Maitake D-Fraction's power comes from it's highly active Beta-Glucans (beta-1,3/1,6 glucan) which are a non-digestable Polysaccharide (long chain carboydrate).  These beta-glucans are what researchers believe give D-Fraction the ability to enhance the immune system via oral administration by activating Macrophages (by binding with the compliment receptor 3 and dectin-1 receptor4), T cells, B cells, and natural killer (NK) cells among others.  Researchers also believe this complexing branching of the beta-glucans helps D-fraction provide the tumor reduction seen in several animal studies3.



Maitake D-Fraction Anti-Cancer Effects

D-Fraction seems to have a unique way of working with the immune system that also helps to attack cancer.  While research still continues, the following is known about D-Fraction's anti-cancer effects:

  • Broad-Spectrum Cytokine Inducer (Cytotoxic):  Stimulates tumor inhibitors by activating macrophages which result in elevated production of cytotoxic T lymphocytes and many additional cytokines such as Interleukin-1ß, Inerferon alpha/beta (macrophages produce these to 'interfere' with growth of diseased cells), Interleukin-6 (cases T-cell activation, produces antibodies by stimulating B-cells), Interleukin-10 (down regulates inflammatory processes), Interleukin-12 (stimulates natural killer (NK) cells which are types of T- cells that attack cancerous or diseased cells).  This process helps tissues get free of tumor cells and inhibits cancer metastsisis5,6,7 .

  • Inhibits Metastasis:  The primary goal of most conventional treatment is to prevent the spread (metastasis) of cancer cells (which then form into tumors).  Maitake D-Fraction has been shown in an animal study to reduce metastasis down to only 10% if used daily (a 91.3% reduction in cancer progression was observed in a study using mice and MM-164 liver cancer).  The study showed 100% metastasis for the mice in the control group (which received no Maitake D-Fraction)8,11.

    Another study by the Department of Physiology at Tulane University School of Medicine (New Orleans, LA) showed that Beta-Glucan (of which Maitake D-Fraction has) "was most efficacious" in maintaining survival of mice with breast cancer.  They stated that mortality decreased from 100% to 20% when beta-glucan was administered intravenously.  They also discovered that the macrophages that received the beta-glucans "possessed significantly greater anti-tumor activity...than normal macrophages". 

  • Prevents Angiogenesis (Anti-Angiogenic):  For cancer to spread (metastasis), tumors must grow new blood vessels, known as angiogenesis, which help the tumor gain nutrients and oxygen.  Maitake D-Fraction has been observed in vivo to inhibit angiogenesis by stimulating tumor necrosis factor and in vitro to enhance the migration capability of human vascular endothelial cells.  Further Maitake D-Fraction enhanced VEGF and TNF-α production by the activated peritoneal macrophages. These results suggest that the anti-tumor activity of the D-Fraction is not only associated with the activation of the immuno-competent cells but also possibly related to the carcinoma angiogenesis induction9.
  • Apoptosis Inducer (Cancer Cell Death):  Apoptosis is known as "programmed cell death" or "cell suicide", something cancer cells lack which but normal cells do all the time.  Chemotherapy, in contrast, aims for necrosis or "random cell murder" which involves cell rupture and release of cytonic materials which randomly exert their adverse effects on other healthy cells.  In a study by the New York Medical College, Maitake D-Fraction was shown to induce apoptosis in PC-3 (prostate cancer) cells which are very aggressive androgen-independent human prostate cells in abnormal condition.
  • Anti-Inflammatory Action:  It's known that there is a molecular connection between inflammation and cancer. Although there is not enough research on this, a 2002 paper stated that the fatty acid compounds in the Maitake mushroom (thus why it's important to also take whole maitake capsules as described later in this article) is comparable to those of the drugs Vioxx and Celebrex14. 



Maitake D-Fraction in Cancer Treatment
A concern is always how a supplement interacts with chemotherapy and if it has any side-effects.  Thankfully, research shows Maitake D-Fraction to be generally safe overall, safe to take with chemotherapy, helps alleviate side-effects of chemo, and may even be Synergistic with certain chemotherapies. 
 

  • Can Be Taken Orally:  Due to the unique beta-glucan branching, Maitake D-Fraction can be taken orally whereas other medicinal mushrooms must be made into an intravenous version to be effective (such as Shiitake under the drug name 'Lentinan' in Japan2).  It's interesting to note that Maitake and Shiitake are in the same branch of medicinal mushrooms, have almost similar immune and anti-cancer effects, yet only Maitake can be taken orally.  When looking at existing research on Shiitake being used intravenously as Lentinan in humans, the anti-cancer effect can be seen.  Based on how Lentinan works intravenously and known that Maitake D-Fraction can be taken orally, it will be interesting to see the results of a completed, well designed, clinical trial of Maitake D-Fraction in humans (clinical trial IND# 54,589 is underway in this aspect, but recruitment of patients has been slow).
  • Does Not Interfere With Chemotherapy or Radiation:  Maitake D-fraction doesn't affect the activity of liver enzyme (Cytochrome P450) that breaks down drugs. This means taking Maitake D-fraction neither accelerates nor decelerates the metabolism of other drugs.  In addition the Memorial Sloan Kettering Cancer Center, a leading cancer research center, has a policy to discontinue any herbal supplements during chemotherapy and/or radiation, as little is known about how they work with such treatments. The Center exempts Maitake extract from this restriction and also uses it with chemotherapy and radiation treatments. They stated this in their speeches at medical conferences twice, and Maitake Products, Inc. received a personal email from Dr. Cassileth (Chief of Integrative Medicine Service) stating the same1.
  • Synergistic Effect with Chemotherapy:  Chemotherapy is designed to attack cancer cells directly (for instance Carboplatin will attack the RNA or DNA of rapidly dividing cells such as cancer to prevent them from dividing) whereas Maitake D-Fraction stimulates the immune-competent cells and potentiates their action against cancer cells.  In one study the chemotherapy drug Mitomycin C (MMC), which is only used in salvage ovarian cancer, was observed in a study with tumor-bearing mice.  D-Fraction alone demonstrated superior tumor growth inhibition to that of MMC (about 80% vs 45%).  When MMC and D-Fraction were given together, cutting each dose by half, tumor inhibition was enhanced (nearly 98%).  Researcher Hiroaki Nanba, Ph.D. suspects that this demonstrates a synergistic effect between MMC and Maitake (i.e., tumor cells are directly attacked by MMC while the immune system is activated by D-Fraction).  He further states that he has seen many advanced cancer patients recover from severe side-effects caused by chemotherapy by taking Maitake D-Fraction (orally) as an ajuvant10.
  • Amelioration of Chemotherapeutic Side-Effects (Quality of Life):  Chemotherapy is nasty, you know that.  Everything from nausea to hair loss comes as a result of it.  Maitake D-Fraction was shown to reduce these side-effects drastically such as lost appetite, vomiting, nausea, hair loss and white blood cell efficiency in 90 percent of patients; pain was reduced in 83 percent of patients3,8.
  • Safe to Use:  Perhaps the longest safety trial known is that of Maitake, as it has been used for hundreds of years in Asia.  To date, there has been no evidence to suggest any toxicity for either Maitake mushroom or the D-fraction both of which are generally recognized as safe.  In fact, D-Fraction has been exempted from the Phase I study for toxicity, by the FDA, and entered directly into the Phase II clinical study (IND# 54,589 for breast and prostate cancer).  I can almost guarantee that the chemotherapy you are on has never been exempted from a Phase I toxicity study.

    That being said, there are two groups who should be cautious about using D-Fraction:  Those with a history of an allergic reaction to mushrooms and those with autoimmune diseases (hyperactive immune systems).  Needless to say, you should always let your physician know if you are taking D-Fraction and have the manufacturers contact information (and the dosage you are taking) with you at all times for medical personnel (doctors always need to know your complete medical workup)3.

 


Does it Really Work?

  • Case reports from Japan involving 165 cancer patients with various cancers showed remarkable improvement.  In the case reports, patients had been using chemotherapy with only minimal benefits until Maitake D-Fraction was added to their regimen.  In several cases involving liver and lung cancer patients, they went from Stage III status to Stage I.  Symptomatic improvement or tumor regression was experienced in 73.3 percent of breast cancer patients, 66.6 percent of lung cancer patients, and 46.6 percent of liver cancer patients11.  It must be noted that there was no control group (in other words no group received a placebo or went without Maitake D-Fraction) in this study so no objective comparison can be made.
  • Animal Studies have shown remarkable effects with Maitake D-Fraction (as described earlier in this article), however no FDA clinical trials have been completed (although one has been ongoing for several years now, IND# 54,589) due to difficulty in selecting candidates due to previous FDA criteria which was very restrictive.  In addition In Vitro studies have also shown very promising effects of Maitake D-Fraction (such as the PC-3 prostate cancer cell study).
  • Beta Glucans from mushrooms are commonplace around the world, and specifically in Japan where they are turned into approved anti-cancer medication.  As described earlier, the Shiitake mushroom is used under the drug name 'Lentinan' where it is given intravenously to cancer patients in addition to (or as) first line chemotherapy.
  • A personal experience happened with my mother, who was stage IIIC ovarian cancer.  I first discussed using Maitake D-Fraction Grifron Pro (from Maitake Products, Inc.) with one of her Gynecologic Oncologists.  He stated, after reviewing some material I presented to him, that it couldn't do any harm and might do some good.  It was not until months later when she was able to get out of the hospital that she began taking it via her J-Tube (directly into the jejunum).  I administered roughly 20 to 25 drops (or often a 'full' dropper that came with the Grifron Pro Maitake D-Fraction) into 2oz of water and flushed it down the tube three times per day.  During this time she experienced her lowest CA-125 levels and progressed to one of her healthiest and active states while on an Phase II clinical trial.  Eventually she had her J-Tube removed and was unable to receive D-Fraction due to constant vomiting.  Her levels went quickly back up (while being on the same chemotherapy) and never went back to those low levels again despite using other chemotherapy treatments.  She was on no other supplements during this time (besides a multivitamin or vitamin C), and, In my opinion, D-Fraction was helping by observing at the CA-125 levels alone.



How to Take and What to Buy

Therapeutic amount of Maitake D-Fraction is 1.0mg per kilo of body weight3 per day (although one study suggests 6mg per kilo is warranted12).  To find your weight in kilos, multiply your weight in pounds times 0.45.  (i.e., 150lbs = 68 kilos which equals 68 drops of Grifron Pro® Maitake D-Fraction®).  Divide your dosage three times so it can be taken three times per day, between meals (do not take with meals for full effect).

Research shows that D-Fraction may be maximized if combined with vitamin C (more than 1000mg) and whole Maitake tablets (such as Grifron Maitake caplets).  Those who fear taking Vitamin C (or any antioxidant) will be assured that recent research shows those fears are unwarranted and have no impact on chemotherapy13.

The most reliable form of Maitake D-Fraction (and Maitake products) in the United States are from Maitake Products Inc. (www.maitake.com) under their 'Grifron Pro®' brand (professional strength which is more concentrated) who have been producing it in the United States since 1991.  They have scientists and administration that come straight from Japan (some are from the Japanese equivalent of the FDA), and they have been involved in and supported many laboratory and clinical studies of D-Fraction by the National Cancer Institute (NCI), Georgetwon University, Cancer Treatment Centers of American, New York Medical College, and many others.



Conclusion

Maitake D-Fraction is one of the first supplements I came across and was excited about during my mom's battle with cancer, and was the only one that I can personally say I saw have some effect.  In addition it's excellent safety record, potential anti-cancer activity, immune boosting activity, and lack of interfering with chemo makes it an almost "why not" in my opinion.  I do not suggest, however, that you do no take Maitake D-Fraction as an 'alternative' treatment, but as an adjunct treatment with your conventional chemotherapy under your doctor's supervision.  While some studies show that Maitake works just fine on it's own, it's use with some chemotherapy (remember not all were tried) shows a syngertic effect that may increase effectiveness and to use it without conventional treatment is simply risky.  As with any supplement I write about, I suggest you print out this article, and present it to your physician / oncologist on your next appointment for their review.



Disclaimer

The information provided on this site is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional or any information contained on or in any product label or packaging. You should not use the information on this site for diagnosis or treatment of any health problem or for prescription of any medication or other treatment. You should consult with a health-care professional before starting any diet, exercise or supplementation program, before taking any medication, or if you have or suspect you might have a health problem. You should not stop taking any medication without first consulting your physician.

These statements have not been evaluated by the FDA. The products (Maitake D-Fraction) described in this article are not intended to diagnose, treat, cure, or prevent any disease.

 

References


1 Email from Maitake Products, Inc. (Scientific Affairs Department) received on 6/5/2007
2 http://www.cancerguide.org/cit_lentinan.html
3 Maitake Products, Inc. Maitake D-Fraction® Product Brochure
4 Brown, G.D. & Gordon S. "Immune recognition.  A new receptor for beta-glucans." Nature, 20016;413(6851):36-37
5 Sakurai, T., et al.  "Effect of intraperitoneally administered beta-1,3-Dglucan, SSG, obtained from Sclerotinia sclerotiorum IFO 9395 on the functions of murine alveolar macrophages." Chem Pharm Bull (Tokyo), 1991;39:214-217
6 Hishida, I, et al. "Antitumor activity exhibited by orally administered extract from fruit body of Grifola frondosa (maitake)." Chem Pharm Bull, 1998;36:1819-1827
7 Adachi, K., et al. "Potentiation of host-mediated antitumor activity in mice by b-glucan obtained from Grifola frondosa (maitake)." Chem Pharm Bull, 1987;35:262-270
8 Maitake Magic:  http://www.amazon.com/Maitake-Magic-Sensuke-Konno/dp/1893910199
9 Matsui, K., et al. "Effects of maitake (Grifola frondosa) D-Fraction on the carcinoma angiogensis." Cancer Lett, 2001; 172(2):193-198  or http://www.cancerletters.info/article/S0304-3835(01)00652-8/abstract
10 http://orthomolecular.org/library/jom/1997/articles/1997-v12n01-p043.shtml11 Konno, S. "Maitake D-Fraction: Apoptosis inducer and immune enhancer." Alternative & Complementary Therapies, April 2001: 102-107
12 J Clin Oncol 26: 2008 (May 20 suppl; abstr 3024)  http://www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=55&abstractID=35636
13 "Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials."  Cancer Treat Rev. 2007 Aug;33(5):407-18. Epub 2007 Mar 23   http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17367938&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum14 Zhang, Yanjun, et al. "Cyclooxygenase Inhibitory and Antioxidant Compounds from the Mycelia of the Edible Mushroom Grifola frondosa." J. Agri. Food Chem. 50 (2002), pp.7581-7585