Category Archives: Nutraceuticals

MAITAKE MUSHROOM: Powerful immune support



Maitake mushroom is an edible mushroom from the species, Grifola frondosa. It is consumed widely in Asia as food and has a long history of use in traditional Asian medicine for numerous health-promoting purposes. Most Basidiomycetes mushrooms contain biologically active polysaccharides in their fruit bodies, culture mycelia, or culture broth.

Mushroom polysaccharides exert their antitumor action by activation of the host immune response. Beta 1,6-glucan, a protein-bound polysaccharide, has been identified as the active ingredient. The mushroom β-glucans, resembling bacterial cell walls, complex with complement on macrophages and activate an immune response, leading to release of various cytokines that are active in tumor inhibition. An intact T-cell immune system is essential for the antitumor activity of medicinal mushrooms.

The Maitake D-fraction, a bioactive extract, is a protein-bound polysaccharide (proteoglucan) that has been most widely studied as an adjunct to conventional radiation and chemotherapy. Interest in the West in the investigation of medicinal mushrooms as potential anticancer agents was piqued by epidemiological studies from Japan and Brazil suggesting that long-term exposure to local medicinal mushroom species was associated with lower cancer mortality rates.

Mechanism of Action in Cancer Care and Clinical Trials

Maitake mushrooms and the Maitake D-fraction prepared from them contain a type of polysaccharide (a large molecule formed by multiple sugar molecules linked together), called beta glucan (sometimes called beta glycan). Beta glucan is found in several mushrooms, yeasts, and other foods. A polysaccharide is a large and complex molecule made up of smaller sugar molecules. Beta glucan is believed to stimulate the immune system and activate certain cells and proteins that attack cancer, including macrophages, cytotoxic T-cells (Tc), natural killer cells, interleukin-1 and -2 and lymphokines. The end result is an increased defense against infections, AIDS, and cancer.

Maitake D-fraction in particular seem to have a specific antitumor action, potentially slowing the growth of tumors in the colon, lungs, stomach, liver, prostate, brain, breast and other organs. (It should be noted that any research references to the D-fraction also apply to the MD-fraction, as they are the same beta 1,6/ 1,3 glucan derived from Grifola frondosa.) Centers in the United States have begun to treat cancer patients with the D- and MD-fractions. For example, in February 1998, the U.S. Food and Drug Administration approved an Investigational New Drug Application (IND 54,589) for researchers to conduct a Phase II pilot study on the D-fraction’s potential effects on advanced breast and prostate cancers.

Maitake researchers have identified several ways Maitake can counter cancer:

1) By protecting healthy cells from becoming cancerous
2) By helping to prevent cancer metastasis
3) By slowing or stopping the growth of tumors

Studies have confirmed all three of these potential benefits. Preliminary but unpublished clinical data from a non-controlled study also suggest a fourth potential benefit: Maitake may work in conjunction with chemotherapy to lessen its side effects, such as hair loss, pain, and nausea, and to boost its positive effects.

The presumed mechanism of action of the Maitake mushroom has been assumed to be that of a biologic response modifier, providing T-cell dependent immune enhancement and activation that enhanced antitumor effect. Moreover, Maitake has also been to shown to effectively inhibit angiogenesis by blocking VEGF signaling. Most of the research on Maitake D-fraction has been done in Japan using an injectable form of the extract. A 1997 study published in the Annals of the New York Academy of Science found that Maitake D-fraction was able to enhance the immune system and inhibit the spread of tumors in mice implanted with breast cancer. In a 1995 report published in the same journal, researchers concluded that Maitake D-fraction was able to activate the immune systems of mice that had been injected with liver cancer cells. The extract seemed to prevent the spread of tumors to the liver and prevent the development of cancer in normal cells.

When Maitake D-fraction was given to patients receiving chemotherapy for a number of different cancers, response rates reportedly increased from 12% to 28%. Various chemotherapy side effects were also said to be ameliorated in patients receiving Maitake D-fraction. In the absence of toxicities, it is felt to be a useful adjuvant to chemotherapy. A recent study suggests a direct antitumor effect of Maitake D-fraction with induction of apoptosis observed in breast cancer cell lines. A trial of Maitake extract as treatment for breast cancer is also in progress.

Safety and Side Effects

The Maitake mushroom is edible and generally regarded as safe. There are no reported side effects of the mushroom extracts or the Maitake D-fraction. As Maitake may lower blood sugar, it should be used with caution in patients with diabetes on hypoglycemic agents with careful monitoring of glucose levels while a stable dose is being established. Patients with lymphoproliferative disorders should avoid taking this.

About the Author

Jonathan C. Cheng, M.D., Ph.D. is a board-certified radiation oncologist, who serves on the scientific board of advisors for ONCUCARE. He specializes in integrative oncology, which uses complementary therapies in concert with medical treatment to enhance its efficacy, improve symptom control, alleviate patient distress and reduce suffering.

References

  1. Cunningham-Rundles S, Lin H, Cassileth B. Are Botanical Glucans Effective in Enhancing Tumoricidal Cell Activity?American Society for Nutrition. J. Nutr. 2005. 135: 2919S.

  2. Deng G, Lin H, Seidman A, et al. A phase I/II trial of polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects. J Cancer Res Clin Oncol. 2009;135:1215-1221.

  3. Frenkel M, Abrams DI, Ladas EJ, Deng G, Hardy M, Capodice JL, Winegardner MF, Gubili JK, Yeung KS, Kussmann H, Block KI. Integrating dietary supplements into cancer care. Integr Cancer Ther. 2013 Sep;12(5):369-84. Epub 2013 Feb 25.

  4. Griessmayr PC, Gauthier M, Barber LG, Cotter SM. Mushroom-derived maitake PET fraction as single agent for the treatment of lymphoma in dogs. J Vet Intern Med. 2007;21:1409-1412.

  5. Hong F, Yan J, Baran JT, et al. Mechanism by which orally administered beta-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. J Immunol. 2004;173:797-806.

  6. Ko YT, Lin YL. 1,3-beta-glucan quantification by a fluorescence microassay and analysis of its distribution in foods. J Agric Food Chem. 2004; 252:3313-3318.

  7. Kodama N, Komuta K, Nanba H. Can maitake MD-fraction aid cancer patients? Altern Med Rev. 2002; 7:451.

  8. Kodama N, Komuta K, Nanba H. Effect of Maitake (Grifola frondosa) D-Fraction on the activation of NK cells in cancer patients. J Med Food. 2003 Winter; 6(4):371-7.

  9. Kodama N, Murata Y, Asakawa A, et al. Maitake D-Fraction enhances antitumor effects and reduces immunosuppression by mitomycin-C in tumor-bearing mice. Nutrition.2005; 21:624-629.

  10. Konno S. Potential growth inhibitory effect of maitake D-fraction on canine cancer cells. Vet Ther. 2004; 5:263-271.

  11. Konno S. Synergistic potentiation of D-fraction with vitamin C as possible alternative approach for cancer therapy. Int J Gen Med. 2009;2:91-108.

  12. Soares R, Meireles M, Rocha A, et al. Maitake (D fraction) mushroom extract induces apoptosis in breast cancer cells by BAK-1 gene activation. J Med Food. 2011;14: 563-572.

  13. Lee JS, Park BC, Ko YJ, Choi MK, Choi HG, Yong CS, Lee JS, Kim JA. Grifola frondosa (maitake mushroom) water extract inhibits vascular endothelial growth factor-induced angiogenesis through inhibition of reactive oxygen species and extracellular signal-regulated kinase phosphorylation. J Med Food. 2008 Dec;11(4):643-51.

  14. Memorial Sloan-Kettering Cancer Institute. Maitake. Accessed at: http://www.mskcc.org/cancer-care/herb/maitake

  15. Mayell M. Maitake extracts and their therapeutic potential. Altern Med Rev. 2001 Feb;6(1):48-60. Review.

  16. Nanba H, Kubo K. Effect of maitake D-fraction on cancer prevention. Ann NY Acad Sci. 1997;833:204-207.

  17. Nanba H. Activity of maitake D-fraction to inhibit carcinogenesis and metastasis. Ann NY Acad Sci. 1995; 768:243-245.

  18. National Institutes of Health. Available at: www.clinicaltrials.gov. Accessed August 11, 2005.

  19. Natural Standard. Maitake mushroom (Professional Monograph). http://www.naturalstandard.com.

  20. PDR Health. Maitake. Accessed at: http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101810.shtml

  21. Sullivan R, Smith JE, Rowan NJ. Medicinal mushrooms and cancer therapy: translating a traditional practice into western medicine. Perspect Biol Med. 2006;49:159-170.

  22. Talpur NA, Echard BW, Fan AY, Antihypertensive and metabolic effects of whole Maitake mushroom powder and its fractions in two rat strains. Mol Cell Biochem. 2002;237129-237136.

  23. Tanaka H, Tsunematsu K, Nakamura N, et al. Successful treatment of hypersensitivity pneumonitis caused by Grifola frondosa (Maitake) mushroom using a HFA-BDP extra-fine aerosol. Intern Med. 2004;43:737-740.

  24. US National Institutes of Health. Beta-glucan and monoclonal antibody 3F8 in treating patients with metastatic neuroblastoma. Accessed at: http://www.clinicaltrials.gov/ct2/show/NCT00492167 on September 8, 2008.

  25. US National Institutes of Health. Beta-glucan and rituximab in treating young patients with relapsed or progressive lymphoma or leukemia, or lymphoproliferative disorder related to donor stem cell transplantation. Accessed at: http://www.clinicaltrials.gov/ct2/show/NCT00087009 on September 8, 2008.

  26. Wasser SP. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol. 2002;60:258-274.

    By Dr Jonathan Cheng

CURCUMIN: Nature’s anti-inflammatory wonder

Curcumin is the major component of the Indian spice turmeric (Curcuma longa).  It has been used for thousands of years in the Orient as a healing agent for variety of illnesses. The ancient texts of Ayurveda (the science of long life) and traditional Chinese medicine describe the use of turmeric for the prevention and cure of several health problems and to improve general well-being.

It has attracted enormous interest because of its anti-inflammatory and chemopreventive activities. Epidemiological evidence indicates that the incidence of certain cancers is less in people who consume Curcumin than in those who do not. Basic science research and clinical studies demonstrated that Curcumin is a potent anti-inflammatory agent with strong therapeutic potential against a variety of cancers.

Mechanism of Action in Cancer

Curcumin has been shown to prevent a large number of cancers in animal studies. Laboratory data indicate that Curcumin can inhibit initiation, promotion, invasion, angiogenesis, and metastasis of tumors. Curcumin has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and downregulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4), and inflammation (NF-κB, TNF-α, interleukin [IL]-6, IL-1, COX-2, and 5-LOX).

In patients with colorectal cancer, oral Curcumin administered during the pre-surgery waiting period improved cachexia and the general health of patients. In a phase II trial of oral Curcumin in patients with advanced pancreatic cancer, no treatment-related toxic effects were observed and clinically relevant biological activity was seen in two patients despite limited absorption. More recently, a study from Zheijiang Provincial People’s Hospital in Zheijiang, China indicates that Curcumin is capable of inducing apoptosis (cell death) within triple negative breast cancer cells. Triple negative breast cancer (TNBC) is a type of cancer that generally defies conventional therapy.

Curcumin also acts as a potent chemosensitizer and radiosensitizer for tumors in some cases. Curcumin has also been shown to protect normal organs such as liver, kidney, oral mucosa, and heart from chemotherapy- and radiotherapy-induced toxicity. In fact, the consumption of Curcumin during radiotherapy reduced the severity of radiation dermatitis in breast cancer patients. The activity of Curcumin reported against leukemia and lymphoma, gastrointestinal cancers, familial polyposis, pancreatic cancer, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets.

Clinical trials are under way to investigate Curcumin as a way to prevent cancer in people with precancerous conditions, as a cancer treatment, and as a remedy for signs and symptoms caused by cancer treatments.

Safety and Side Effects

Curcumin has been used for centuries as a spice and food additive with minimal adverse effects, and the FDA is considering it as a GRAS (Generally Recognized as Safe) supplement. Curcumin may cause an upset stomach, especially in high doses or if given over a long period of time. Patients with gallbladder problems should be cautioned about the use of Curcumin due to the fact that Curcumin is capable of contracting the gallbladder and might exacerbate gallbladder disease. Historically, Curcumin has been considered safe when used as a spice in foods during pregnancy and breastfeeding. However, Curcumin has been found to cause uterine stimulation and to stimulate menstrual flow, and caution is therefore warranted during pregnancy. Animal studies have not found Curcumin taken by mouth to cause abnormal fetal development.

References

  1. Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer Lett. 2008;267:133-164.

  2. Bayet-Robert M, Kwiatkowski F, Leheurteur M, et al. Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol Ther. Jan 2010;9(1):8-14.

  3. Belcaro G, Hosoi M, Pellegrini L, Appendino G, Ippolito E, Ricci A, Ledda A, Dugall M, Cesarone MR, Maione C, Ciammaichella G, Genovesi D, Togni S. A Controlled Study of a Lecithinized Delivery System of Curcumin (Meriva®) to Alleviate the Adverse Effects of Cancer Treatment. Phytother Res. 2013 Jun 15.

  4. Cruz-Correa M, Shoskes DA, Sanchez P, et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2006;4:1035-1038.

  5. Dhillon N, Aggarwal BB, Newman RA, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. Jul 15 2008;14(14):4491-4499.

  6. Frenkel M, Abrams DI, Ladas EJ, Deng G, Hardy M, Capodice JL, Winegardner MF, Gubili JK, Yeung KS, Kussmann H, Block KI. Integrating dietary supplements into cancer care. Integr Cancer Ther. 2013 Sep;12(5):369-84. Epub 2013 Feb 25.

  7. Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 2010;62:919-930.

  8. Gupta SC, Kim JH, Kannappan R, Reuter S, Dougherty PM, Aggarwal BB. Role of nuclear factor-{kappa}B-mediated inflammatory pathways in cancer-related symptoms and their regulation by nutritional agents. Exp Biol Med (Maywood). 2011;236:658-671.

  9. Hanai H, Iida T, Takeuchi K, Watanabe F. Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2006;4:1502-1506.

10. He ZY, Shi CB, Wen H, et al. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest. Mar 2011;29(3):208-213.

11. Karin M, Greten FR. NF-kappaB: linking inflammation and

immunity to cancer development and progression. Nat Rev Immunol. 2005;5:749-759.

12. Kaur C, Kapoor HC. Anti-oxidant activity and total phenolic content of some Asian vegetables. Int J Food Sci Technol. 2002;37:153-161.

13. Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 2008;269:199-225.

14. Ryan JL, Heckler CE, Ling M, Katz A, Williams JP, Pentland AP, Morrow GR. Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res. 2013 Jul;180(1):34-43.

15. Shishodia S, Chaturvedi MM, Aggarwal BB. Role of curcumin in cancer therapy. Curr Probl Cancer. 2007 Jul-Aug;31(4):243-305. Review.

16. Sun XD, Liu XE, Huang DS. Curcumin induces apoptosis of triple-negative breast cancer cells by inhibition of EGFR expression. Mol Med Rep. 2012 Dec;6(6):1267-70.

17. Thamlikitkul V, Bunyapraphatsara N, Dechatiwongse T. Randomized double blind study of Curcuma domestica Val. for dyspepsia. J Med Assoc Thai. 1989;72:613-620.

18. Vadhan Raj S, Weber D, Giralt S, et al. Curcumin downregulates NF-KB and related genes in patients with multiple myeloma: results of a phase1/2 study [abstract]. Paper presented at: 49th American Society of of Hematology Meeting; December 8-11, 2007; Atlanta, GA

By: Dr Jonathan Cheng

Jonathan C. Cheng, M.D., Ph.D. is a board-certified radiation oncologist, who serves on the scientific board of advisors for ONCUCARE. He specializes in integrative oncology, which uses complementary therapies in concert with medical treatment to enhance its efficacy, improve symptom control, alleviate patient distress and reduce suffering.

 

One Disease- Cellular Disease

The conventional medical model lists hundreds of diseases and thousands of remedies for treating these diseases or their symptoms. More than 40 percent of Americans take at least one prescription drug and one-in-six takes at least three. There are currently over 600 approved cancer drugs. In no time at all, this palliative approach will have you taking a pill for cholesterol, a beta blocker for the heart, calcium for your bones, and so forth. In most cases these remedies are prescribed for alleviating or controlling the symptom(s), as in the case with blood pressure medication or insulin for diabetes. Meanwhile, the initial causes of the disease are rarely addressed. Often, practitioners of the alternative medicine model will do the same. They prescribe enzymes for poor digestion, antioxidants for low immunity, etc. I call this approach of treating the symptom, “fighting the battle and losing the war.” What then is this war that we must win?

ONE DISEASE, CELLULAR DISEASE

In a “purist” holistic health perspective, disease (non-health) is demystified. Let’s be realistic. Disease and its symptoms reside first at the cellular level. Let’s even be scientific. We are made up of hundreds of trillions of living intelligent cells which in turn make up our organs, bones, tissues, blood and brain. In this model, unhealthy cells lead to unhealthy organs, unhealthy organs lead to deficient metabolic activities, and this in turn leads to symptoms, which we name disease. It is safe to say that once you are diagnosed with a disease, the problem is usually systemic and bigger than just the symptoms. Usually, the causes that lead to disease are manifested in every cell of your body for some time before symptoms arise. We don’t catch diseases, we make them. In the holistic view, disease occurs at the cellular level.

Let me describe cellular disease in four points:

1) Once symptoms begin to manifest, most cells may be toxic and deficient in nutrients and energy. They are likely less efficient in conducting their myriad of metabolic activities including repair, detoxification, growth, and regeneration.
2) At the next level, due to cellular inefficiencies, the organs are now less efficient in conducting their own metabolic role(s). For example, with hypoglycemia, the pancreas is sluggish in regulating the blood sugar with insulin.
3) Realize now that the brain organs: hypothalamus, pituitary (master) gland, and the pineal gland, collectively known as the governing level responsible for overseeing all metabolism, are also affected by this cellular disease. They are rendered less efficient in controlling critically important metabolisms like that of blood sugar, pH (acidity/alkalinity), and even each beat of the heart.
4) Aggravating the problem, after years and often decades of metabolic inefficiencies (improper pH, blood sugar, temperature, fats, etc.), the cells, the organs, and the endocrine glands have become misprogrammed to tolerate these negative behaviors. The body now thinks it is in a “healthy” state of health. For example, when the hypothalamus becomes lazy in regulating the misbehaving pancreas, we have a chronic condition known as diabetes.

At this stage, metabolism is dysfunctional or operates poorly. Problems occur with the Krebs/ATP cycle, assimilation, absorption, elimination, protein synthesis, and the osmosis of oxygen and water (hypoxia and dehydration). There is chronic acidity and resulting acidosis. Not only do you have incorrect pH levels, but inefficient flushing of cellular debris causes you to accumulate acid ash inside and between your cells. These conditions lead to infestations of bacteria and parasites (fungus, yeast and Candida), to “bad” fats (high cholesterol) and lack of viscosity, and to the crystallization of fats and other unassimilated debris into plaque and arthritis. Your food / nutrient digestion and elimination have become deficient and you have lost your healing energy. The problem is now a vicious cycle.

ONE HEALTH, CELLULAR HEALTH

How do you restore cellular health? The holistic approach to cellular health is to first realize that the doctor is the body itself. Each cell is geared to self heal. The doctor is within, not without. After all, this body built itself from one tiny cell and managed quite well without an “external doctor” for decades, defending itself from millions of viral attacks, free radical damage, and constant pollution from food and the air. Holistic health is gained at the cellular level. This view is supportive of “the doctor within,” rather then employing an intervener. I call this approach “winning the war, not just the battle.”

Let me describe how to regain cellular health in five points:

1) First, do no harm: Begin by limiting the causes of cellular toxicity and burden. These include abuse of food, protein and sugar, dead, toxic and depleted food and beverages, and pollutants and toxins of all kinds including mental and emotional negativity. All substances including food, light, and even people, carry energy that can raise or lower your own energy level. Choose wisely; ask yourself before you eat or drink “Is this conducive to health or disease?”
2) Nourish your cells: Eat a high energy diet of fresh organic colorful fruits and vegetables with little meat and fish. Look for the “energy” in foods which we derive from natural minerals, trace elements, carbohydrates and chlorophyll contained in fresh and organic fruits and vegetables.

3) Increase cellular efficiency: Beyond avoiding harm and eating good foods, other factors are critical to health. Cellular oxygenation and detoxification can be vastly increased and achieved with movement and aeration. Let me suggest a few means to achieve movement and aeration:

a. Fasting is as important as eating. I call it “getting out of the way.” Fasting has been used as an element of health since the beginning of time. When a cat is sick, it stops eating until it gets better. During the fasting phase of the night, our liver is given a chance to perform a myriad of biochemical processes. Give yourself a chance by introducing safe and short fasts in your life daily, weekly, monthly and annually.

b. We humans must exercise in order for our cell to not rust. The value of exercise has been proven. Enough has been said, so just do it. Move your body, arouse your lymphatic systems and increase your pulse and your temperature moderately. This kills viruses, removes toxins, and balances fats in each cell of your body. Shake every cell in your body with daily exercise like walking, running, qi-gong, yoga, etc.

c. In natural medicine, we say that 50% of toxicity is caused by our emotions and our state of mind. Maintain your spiritual and emotional balance with exercises, yoga, qi-gong, tai chi, prayer, etc.

4) Reprogram the governing organs: With degenerative and chronic conditions, the dietary and lifestyle changes recommended above may not be sufficient to reprogram the governing organs of the brain. To regain the health of your brain organs, you must do more daily. I propose a diet rich in nutrients that are known to be deficient in the brain as well as foods rich in minerals and trace elements, green, blue and red pigments and carotenoids, chlorophylls, fatty acids omega 3, 6, 9, and gamma and alpha lipoic acids, which are “the good fats that heal.” You should also exercise more and engage in energy balancing activities.

5) Introduce Bio-Algae Concentrates (BAC) into your life: At this point, I suggest a shortcut to brain health. As an additional aid in restoring cellular health and as a magnificent brain food, I recommend BAC. It is an extremely efficient food and the best food complement on earth because it is a blend of microalgae with extraordinary nutritional values.