Use of the Reishi mushroom for reliving migraine

Reishi Pure, Reishi PRO

Migraines are severe headaches, throbbing on one side of the head, sometimes on both sides of the head. The headaches are debilitating and affect the quality of life of those who suffer from it. In recent years there has been an increase in the number of adolescents who suffer from migraine. In recent years there has been an increase in cases of migraine especially among the ages group of 10 years to 30 years.

A research study published in the “International Journal of Pharmacy” in 2012 examined the effect of the Reishi mushroom (Ganoderma lucidium) on migraine symptoms.

Reishi is a traditional medicine for treating migraines in East and Central Asia. A study examined the effect of Reishi on the frequency and duration of migraines. It is well known that the use of conventional drugs for treating migraines, which are administered at a frequency of three times a week or more, increase the risk for side effects especially in children and adolescents.

Between March to May 2012, 220 questionnaires were collected from international clinic patients in Karachi. Of those, 66 patients were found to suffer from chronic migraine.

According to the questionnaires, the most common causes of migraine were: stress / tension 50.90%, sensitivity to light (photosensitivity) 48.18% and loud noise 45.5%.

The patients were taking Reishi for a period of a month to a year. Following the use of Reishi 62 patients (93.99%) reported pain relief and reduction in seizure frequency, 54 patients (83.18%) reported of having no side effects after taking Reishi. The side effects that were reported were sensitivity of the gastrointestinal tract; symptoms that are also typical to those who suffer from chronic migraine.

The Reishi mushroom has balancing effects on the nervous system; it allows the body to better handle stress and tension and allows for a more restful sleep. Among people with migraine that was associated with stress and tension, Reishi had demonstrated efficacy in reducing relapses occurred, while balancing the nervous system and improving its adaptability to daily stress.

The Cordyceps mushroom



Exotic mushroom which has unique healing properties. The mushroom is called “the Chinese Caterpillar mushroom” since it grows on larvae, adult insects or certain types of truffles (truffles Elaphomyces). This rare mushroom was kept secret for thousands of years in China, which in addition to its many virtues is difficult to locate in nature. The fresh mushrooms grow in rocky areas of the Himalayan, and only 20 years ago it was revealed to the world at large. Since 1980 the mushroom is being grown on substrates that do not contain insects. Furthermore, no differences were found in the composition or the medicinal properties of mushrooms that were grown in controlled conditions as compared to wild mushrooms (3).

Nowadays, 680 species of Cordyceps are known which are growing in six continents (1-2).

Traditional uses:

In traditional Chinese medicine the Cordyceps mushroom is used to create a balance in the body (homeostasis), for prevention and treatment of diseases of the respiratory system: asthma, cough, bronchitis and pneumonia, cold, flu, allergies and hay fever, kidney disease, strengthening the liver, heart and blood vessels diseases and decrease in sexual libido and as an aphrodisiac for both men and women.

Weakness, fatigue, is used for treating chronic pain, especially in the elderly.

Increases the ability of the body to handle infection, used as a supplement for people who receive cancer treatment (chemotherapy, surgery and radiation) (1).

The mushroom composition:


Compared to other mushrooms, the dry extract of Cordyceps contains the highest concentration of proteins. The dry extract contains 20-25% proteins and nucleic acids (nucleotides), where the protein contains 18 amino acids. Glutamic acid, arginine, aspartic acid, tryptophan and tyrosine can also be found in high concentrations (4).


Cordyceps contains a wide and unique range of nucleic acids. One of the most studied and unique nucleic acid produced by the Cordyceps mushroom is Cordycepin (3-deoxyadenosine). This nucleic acid integrates into the genetic material of human cells, and in this way prevents damage to the duplication of the genetic material (10).

Sugar-bound proteins of the Lectins type. The Lectins structure in the Cordyceps mushroom is unique and allows the body to recognize and treat damaged cells and even strengthen healthy or healing tissues.


The Cordyceps mushroom contains some essential steroidal structures: ergosterol (pro-vitamin D), phytosterols (1). Unique steroid component were discovered by a mushroom researcher named Chen.

H1-A sterol was found to be effective in cases of autoimmunity.

Additional ingredients:

Twenty eight saturated and unsaturated fatty acids, with blood lipids reduction activity and protection from cardiovascular disease (7).

Essential etheric fatty structures can also be found that react with the polyphenols of the mushroom which suppress excessive immune activity, especially autoimmune activity. Within these structures the Cyclosporine is a well known component which is used in medicine in order to prevent rejection of transplanted organs (14).

Vitamins: B2, B1, K, E, and B12. Minerals and trace elements (2,5).


Complex carbohydrates which are built from many simple mono-sugar molecules, and are interconnected by glycosides links. The Chitin found in the cell-wall of mushrooms is a polysaccharide (7).

The Cordyceps contains high concentration of polysaccharides that can compose up-to 8% of its total weight. Four types of β-D-Glycan (8), mannose, galactose and some glucose were isolated.

Reports on pharmacological findings for the following situations:

Immuno-modulator, anti-tumor, anti-oxidation, anti-inflammation, insecticide, anti-microbial, hypolipidemic, hypoglycemic, anti-aging, neuroprotective, renal protective (2).


  1. Bensky D, Clavey S, St ‥oger E. In: Chinese Herbal Medicine:Materia Medica, 3rd ed. Seattle: Eastland Press, 2004:770.
  2. Holliday J, Cleaver M. Medicinal value of the caterpillar fungi species of the genus Cordyceps (Fr.) Link (Ascomycetes). A review. Int J Med Mushrooms 2008; 10(3):219–234
  3. Mizuno T. Medicinal effects and utilization of Cordyceps (Fr.) Link (Ascomycetes) and Isaria Fr. (Mitosporic fungi) Chinese caterpillar fungi, “Tochukaso” (review). Int J Med Mushrooms

1999; 1:251–262.

  1. Holliday J, Cleaver P, Loomis-Powers M, et al. Analysis of quality and techniques for hybridization of medicinal fungus Cordyceps sinensis. Int J Med Mushrooms 2004; 6:147–160.
  2. Zhou X, Gong Z, Su Y, et al. Cordyceps fungi: Natural products, pharmacological functions and developmental products.J Pharm Pharmacol 2009; 61:279–291.
  3. KimSW, Hwang HJ, Xu CP, et al. Optimization of submerged culture process for the production of mycelial biomass and exo-polysaccharides by Cordyceps militaris C738. J Appl Microbiol 2003; 94:120–126.
  4. Chen SZ,ChuJZ.NMRand IR studies on the characterization of cordycepin and 2’deoxyadenosine [in Chinese]. Zhongguo Kang Sheng Su Za Zhi 1996; 21:9–12.
  5. Segelken R. Cyclosporin molds ‘sexual state’ found in New York forest Cornell students’ discovery could target additional sources of nature-based pharmaceuticals. Cornell University Science News, Sept 16, 2002.

Cholesterol Balance with Medicinal Mushrooms


Cholesterol is a fatty structure that is vital for many body functions. It participates in the  structure  of various hormones, especially hormones
related to the sexual and the reproductive systems, accumulates in lipid layers that engulf and protect organs and is an important part of the composition of bladder salts used for decomposition and digestion of food fats and more…

As a lipid structure found in the blood, cholesterol is very sensitive to oxidation damage that causes it to sediment in the walls of blood vessel, thus narrowing the blood vessels diameter which impairs normal blood flow up to full blockage and may even create blood clots 90% percent of our body cholesterol is produced by our own body and only 10% comes from dietary sources. Many factors affect the cholesterol production in the
liver. The cholesterol is carried in the blood by special proteins that are produced in the liver. The first is LDL that is also known as “ bad cholesterol” which carry the cholesterol from the liver through the blood vessels to the various body parts, while the second, HDL, “ good cholesterol” leaves the liver cholesterol free, and collect the excess cholesterol and transfer it back to the liver for metabolizing or secretion  from the body. It turns out that the proper levels HDL are very important if the cholesterol level is mildly higher than normal. However high HDL levels (in relations to other blood parameters) reduces the risks involved, especially the risk of Atherosclerosis in the blood vessel walls.

Many people think that high cholesterol levels are directly related to the amount of fat (especially saturated fats) that they consume in their diet. This is partially true because the main “activator” of cholesterol synthesis is the hormone insulin. When we consume carbohydrate rich foods especially empty and refined carbohydrates from white sugar, white bread, potatoes and sweetening syrups  sources (corn syrup), the insulin is secreted and the sugar is transformed into fat in the liver.

Modern drugs for reducing cholesterol levels decrease the total cholesterol and the LDL levels, but also the reduce levels of the good cholesterol (HDL). One of the side effects of these drugs is related to impairing the synthesis of the Q10 enzyme which is necessary for the body energy production. The deficiency in Q10 can cause muscle ache, especially leg muscle, and gum sensitivity and bleeding.

The “statins” family of drugs is composed from active ingredients that were originally isolated from medicinal mushrooms, and today they are synthesized chemically. Populations that historically consumed medicinal mushrooms regularly, hardly suffered from heart and blood vessel diseases that are the result of high blood lipid levels. Along the history, many healers gave medicinal mushrooms to people who suffered
from high levels of cholesterol and lipids in their blood. Today, when the  natural substances  is tested in clinical laboratories, the mushroom ability to reduce blood lipids, especially cholesterol, and elevating the good cholesterol levels (HDL) was proven.

The mushroom contains various ingredients that contribute to balancing the levels of the blood lipids by the following routes:

  1. Inhibiting cholesterol absorption from the intestine into the blood
  2. Increasing cholesterol secretion from the  liver  into the digestive system, and from there discharging it from the body while inhibiting its re-absorption.
  3. Suppressing the LDL cholesterol synthesis mechanism, without damaging the Q10 enzyme synthesis.
  4. Reduces the carbohydrate absorption from the intestine into the blood stream and by that reduces the insulin secretion that causes cholesterol synthesis.

The mushrooms that were scientifically proven to have cholesterol reducing effects are:

Pleurotus ostreatus A recent study published in 2010 in “Australian Journal of Medical Herbalism” tested the effect of Pleorotus on balancing the sugar and lipid levels in the blood of patients suffering from type 2 diabetes.

A double blind random study.

The study included 120 patients that were divided into 3 groups. Each group received conventional drug treatment for treating diabetes, an appropriate diet and physical activity. The patients filled questionnaires throughout the study. During the first months the patients did not receive any mushrooms for testing the effects of the regular treatment on the patients. Starting from the second month and during the following 3 months the groups indices were recorded weekly. Parameters checked were levels of glycated hemoglobin (HBa1c), blood sugar while fasting, lipid profile, blood pressure and life quality parameters.

After 3 months the mean results were:

Values at experiment start

Values at experiment end




Blood sugar






General cholesterol

Effect of oyster mushroom on glycemia, lipid profile and quality of life in type 2 diabetic patients: Australian Journal of Medical Herbalism 2010 22(2)

Miitake (Grifola frondosa)

In- vivo animal study examined the effect of the Miitake on the blood lipid profile. The Shiitake does not affect cholesterol synthesis in the
liver, but rather its absorption from the food in the intestine and its increased discharge from the body. Mice fed by Miitake received a cholesterol rich diet.
One group received the diet only and the other received a Miitake enriched diet.

The lipid blood level in mice that received a Miitake enriched diet was similar to this that received cholesterol rich diet with Miitake supplement. The mushroom caused increased discharge of the fat in the mice feces.
Anti-hyperliposis effect of maitake fruit body (Grifola frondosa) Biol Pharm Bull. 1997 Jul;20(7):781-5.

Cordyceps sinensis

By summarizing research results, the Cordyceps was found to reduce cholesterol and triglycerides levels, to increase HDL and to reduce LDL levels.

Zhu JS, Halpern GM, Jones K. The scientific rediscovery of a precious ancient Chinese herbal regimen: Cordyceps sinensis. Part II. J Altern Complement Med 1998; 4(4):429–457.


Breast Cancer


Many factors are correlated to higher  risk of  cancer. Not all the factors can be controlled or changed, for example age or cancer predisposition, but others most certainly can be controlled.  our mission to educate the public on the preventing measures that can be taken to reduce the risk of suffering from cancer and/or improving the chances of recovering from it. It has to be understood that when dealing with a disease that science has not fully deciphered as yet, all measures available to us must be taken.


1 – Diet – the food we consume affect our health, many of us do not put enough effort for changing their lifestyle and  diet . It is recommended for everyone, and particularly for those who were diagnosed with cancer, to check their eating habits. Some recommendations are to avoid industrial  foods, fried food, white sugar and its derivatives, salt and fat from living creatures. Since food can increase the risk for developing cancer, it can also assist in preventing and treating it. Educate yourself about anti-cancer diets, and also  meet a clinical nutritionist specializing in diets for cancer patients.

2 – exercise your  body and soul – Physical exercise is essential for the proper function of the body; perform regular exercise. It is recommended to do Yoga, Tai-Chi or another relaxing physical exercise. Integrative clinics for cancer patients that combine physical activity with chemotherapy show impressive results.

3 – Educate yourself about integrative treatments – Since no “magic” treatment for cancer exists as yet, it will do no harm to recruit additional help from other health systems. There are doctors out there who are more open in their approach for cancer treatment that will listen to your questions about complementary therapies on the eye level, and will help you to find the way to the right treatment for you. Remember, we are not
the product of a mass production line and each body is different, every soul is different.

4 – Know that there is a hope – many cancer patients recover from the disease, including those that science gave up on them, but they did not gave in, and they are alive and happy to these days… There is a hope.

5 – Avoid agents that facilitate the disease – contamination, radiation, chemical materials, physical inactivity and  un balanced diet are all cancer agents that can be changed; Make the change because you worth it.

Mycolivia Medicinal Mushrooms and cancer

The founders of “Mycolivia Medicinal mushrooms” established their company while treating their father that suffered from incurable cancer, and their grandmother that suffered on the same time from breast cancer. One of the brothers who is a medicinal chemistry graduate decided to find a cure for his father disease. After countless hours of studying the literature and consulting with professionals from both the conventional and alternative medicine fields, he realized that cancer treatment requires a conceptual change. He had read in many studies that medicinal mushrooms and their extracts can be used as an additional front for fighting cancer. The medicinal mushrooms have no side effects, they are safe to use and many studies confirm their ability to assist in fighting cancer and even improve the activity of conventional treatments. In fact, after a long study of the report of the UK Research Center that encourage the use of medicinal mushrooms for cancer treatment, and after finding out that the Japanese medical system (the equivalent of the government medical insurance) includes mushroom extracts in its treatment basket that is subsidized by the Japanese government, he decided to give both his father and grandmother mushroom extracts and also to concentrate on the study of medicinal mushrooms for the benefit of cancer patients and the general public. Three years later, Mycolivia Medicinal Mushrooms was founded – a company that specializes in growing, producing and developing food supplements from medicinal mushrooms only.

Medicinal mushrooms and polysaccharides

Medicinal mushrooms produce unique compounds that include various polysaccharide types that have a proven activity on the immune system. Various polysaccharides are used in cancer treatment that includes extracts of the Miitake, Shiitake and the Tremtes versicolor mushrooms.

Medicinal mushrooms – research and recommended reading material.

Medicinal mushrooms tested for treating cancer includes:



Trametes versicolor


Pleurotus austratus

Agaricus blazei

For additional information you search in Google the string “u.k cancer research medicinal mushrooms” and read the report of the England Cancer Institute.

Immune-enhancing effects of Maitake and Shiitake


Vaclav Vetvicka, Jana Vetvickova

University of Louisville, Department of Pathology, Louisville, KY, USA

All authors contributed equally.

Corresponding to: Dr. Vaclav Vetvicka. University of Louisville, Department of Pathology, 511 S. Floyd, Louisville, KY 40202, USA.

Background: The role of glucan in stimulation of immune reactions has been studied for several decades. In this report, we focused on the effects of orally administered glucan Maitake and Shiitake on immune reactions. Materials and methods: We measured phagocytosis, NK cell activity, and secretion of IL-6, IL-12, IFN-γ as well as C-reactive protein (CRP) after 14 days of oral application of tested glucans. For comparison, active hexose correlated compound (AHCC) was used in all reactions.

Results: We found significant stimulation of defense reaction. In all cases, the most active was the Maitake-Shiitake combination, with Maitake alone being the second strongest, followed by Shiitake on its own and AHCC.

Conclusions: Short-term oral application of natural immunomodulating glucans from Maitake and Shiitake mushrooms strongly stimulated both the cellular and humoral branch of immune reactions. These activities were significantly higher than those of AHCC.

Natural products have been used to help treat and/or prevent diseases throughout man’s history. Natural [1,3]-β-D-glucans isolated from yeast, grain and mushrooms are well-established biological response modifiers [for review see (1)]. Alpha-glucan-containing substances also have demonstrated an ability to enhance immune functions (2). Glucans are highly conserved carbohydrates and represent a group of chemically heterogeneous polysaccharides existing in various numbers of molecules of glucose bound together with several types and degrees of branching.

Research on the relationship between glucan and immune reactions began approximately 70 years ago with two starting points: one originated in Europe and the United States and the second in Japan. Based mainly on historical use of materials used for isolation of glucan, the Japanese groups focused on mushroom-derived glucans and the European and American groups studied glucans isolated from Saccharomyces cerevisiae.

Initial glucan research led to the discovery of glucan’s ability to stimulate the phagocytic system, enhance general defense mechanisms and promote resistance to tumors. During subsequent decades of research around the world, glucans were found to significantly stimulate defense reactions against infections and cancer [for review see (3,4)]. In addition, several additional important effects were later demonstrated, including reduction of stress (5), hypoglycemic effects, reduction of cholesterol level (6), and improvements of ulcerative colitis (7) Another advantage of using glucan as both specific and nonspecific activator of immune reactions is the fact that it has been shown to be effective in all species tested so far—from earthworms to humans (8).

Both Maitake and Shiitake glucans are among the most studied glucans (915). The Maitake mushroom extract used in our study is rich in β-glucans, while Shiitake whole mushroom powder is α-glucan rich. Active hexose correlated compound (AHCC) is a α-glucan-rich nutraceutical ingredient prepared by culturing Shiitake and other Basidiomycetes mushrooms. AHCC was originally developed for lowering blood pressure, but significant immunostimulating effects were found later (1618).

As some previously published studies have reported rather confusing results, we decided to evaluate the immunostimulating effects of Maitake mushroom extract, Shiitake whole mushroom powder, a blend of Maitake and Shiitake, as well as AHCC.


Female, 8-week-old BALB/c mice were purchased from the Jackson Laboratory (Bar Harbor, ME, USA). All animal work was done according to the University of Louisville IACUC protocol. Animals were sacrificed by CO2 asphyxiation.


Trypan blue, RPMI 1640 medium, sodium citrate, LPS, Limulus lysate texs E-Toxate, polymixin B and Wright stain were obtained from Sigma Chemical Co. (St. Louis, MO, USA). Fetal calf serum (FCS) was from Hyclone Laboratories (Logan, UT, USA).


MaitakeGold 404 (MTG404) extract is soluble glucan-rich extract isolated from Maitake fruit body (Grifola frondosa). The product, which is a glucan/protein complex, is derived by thermally extracting the fruit body of Maitake with water under pressure at 100 °C or more for 30 minutes to an hour. After that, alcohol is added to the extract at a final concentration of 20% to 60% by volume to remove floating material by filtration. The resulting extract is concentrated under heating to remove residual alcohol. The product is a hygroscopic powder in shades of brown which is soluble in water, alkaline solutions and dimethyl sulphoxide, with a molecular weight around 1,000 kD. MTG404 is produced by Yukiguni Maitake Co. (Niigata, Japan) and for this project was purchased from Tradeworks Group, Inc. (Brattleboro, Vermont, VT, USA).

The Shiitake mushroom used in this study is an alpha glucan-rich whole mushroom powder obtained from Gourmet Mushrooms, Inc. (Sebastopol, CA, USA). This mushroom is grown on brown rice, dried, and then ground into a fine powder.

AHCC (Amino-Up Chemical Company, Sapporo, Japan) is a proprietary, alpha glucan-rich nutraceutical ingredient prepared by culturing Shiitake and other Basidiomycetes mushrooms with rice bran and then subjecting the culture to an enzymatic reaction, followed by hot water extraction and freeze drying.

Oral treatment

Mice were treated orally twice/day for 14 days with either 61.5 μg/day MaitakeGold 404, 820 μg/day Shiitake, 820 μg Shiitake and 61.5 μg MaitakeGold 404, or 100 μg AHCC. PBS served as a negative control. The doses used in this study correspond to the recommended daily human-equivalent dose for each ingredient.


The technique employing phagocytosis of synthetic polymeric microspheres was described earlier (19,20). Briefly, peripheral blood cells were incubated with 0.05 mL of 2-hydroxyethyl methacrylate particles (HEMA; 5×108/mL). The test tubes were incubated at 37 °C for 60 min, with intermittent shaking. Smears were stained with Wright stain. The cells with three or more HEMA particles were considered positive. The same smears were also used for evaluation of cell types.

Evaluation of cytokine production

At the endpoints, blood was collected, serum prepared, filtered through 0.45 μm filters and tested for the presence of cytokines (IL-6, IL-12 and IFN-γ) using the Quantikine mouse IL-6, IL-12 or IFN-γ kit, respectively (R&D Systems, Minneapolis, MN, USA).

Evaluation of C-reactive protein (CRP) production

At the endpoints, blood was collected, serum prepared, filtered through 0.45 μm filters and tested for the presence of CRP using a CRP kit (Helica, Santa Anna, CA, USA).

NK cell assay

Spleen cells were isolated from the spleen of mice by standard methods. Cell suspension was generated by pressing minced spleen against the bottom of a petri dish containing PBS. After elimination of erythrocytes by 10-second incubation in distilled water, and five washes in cold PBS, the cells were resuspended in PBS and counted. The viability was determined by trypan blue exclusion. Only cells with viability better than 95% were used in subsequent experiments. Splenocytes (106/mL; 0.1 mL/well) 
in V-shaped 96-well microplates were washed three times with RPMI 1640 medium. After washing, 50 µL of target cell line YAC-1 (three different concentrations of target cells were used so the final effector-target ratio was 10:1, 50:1 and 100:1). After spinning the plates at 250 ×g for 5 min, the plates were incubated for 4 hr at 37 °C. The cytotoxic activity of cells was determined by the use of CytoTox 96 Non-Radioactive Cytotoxicity Assay from Promega (Promega, Madison, WI, USA) according to the manufacturer’s instructions. Briefly, 10 µL of lysis solution was added into appropriate control wells 45 min before the end of incubation. The next step was to spin the plates at 250 ×g for 5 min, followed by transferring 50 µL of supernatant into flat-bottomed, 96-well microplates. After 50 µL of reconstituted substrate was added into each well, plates were covered and incubated for 30 min at room temperature at dark. The optical density was determined by using a STL ELISA reader (Tecan U.S., Research Triangle Park, NC) at 492 nm. Specific cell-mediated cytotoxicity was calculated using the formula:


Student’s t-test was used to statistically analyze the data.

The effects of glucan on the phagocytic activity of professional phagocytes are well established. Therefore, a comparison of various glucans and/or their combinations should start with evaluation of how these compounds affect this reaction. We compared the activities of MaitakeGold 404, Shiitake, MTG404-Shiitake blend, and AHCC on phagocytosis of synthetic microspheres by peritoneal blood monocytes and neutrophils (Figure 1). With exception of AHCC and neutrophils, all tested samples significantly increased phagocytosis. The highest effects were observed in MaitakeGold 404-Shiitake combination.

Figure 1 Effect of 14 days of oral feeding on phagocytosis by mouse peripheral blood cells. *, represents significant differences between treated and control animals at P≤0.05 level.

Next, we focused on activation of NK cells. Human YAC-1 cells were incubated with mouse spleen cells isolated from animals stimulated by tested samples (Figure 2). Our data showed that MaitakeGold 404-Shiitake combination and MaitakeGold 404 alone activated NK cell toxicity in all tested E:T ratios. AHCC was active only in the highest E:T ratio.

Figure 2 Effects of 14 days of oral feeding on NK cell cytotoxicity. Different ratios of NK cells to target cells were tested for cytotoxicity. The data points shown are mean values from three experiments. *, the differences were significant at P≤0.05 level at all three effector to target cell ratios.

The effects on the cellular branch of immune reaction were followed by evaluation of possible activation of cytokine secretion. Serum obtained from mice fed with different samples was stored at –80 °C for no more than one week. The data summarized in Figure 3 showed that all samples significantly stimulated secretion of IL-6. The samples with the highest activity were MaitakeGold 404-Shiitake combination followed by MaitakeGold 404 alone. A different situation was found when we tested production of IL-12. Only MaitakeGold 404-Shiitake combination and Shiitake alone resulted in significantly elevated levels of IL-12 to spike to over twice the level of any other glucan and more than three times that of the PBS control (Figure 4). Effects on IFN-γ secretion were similar to those for IL-6 (Figure 5). CRP levels did not significantly change during the study (Figure 6).

Figure 3 Effect of 14 days of oral feeding on levels of IL-6. *, represents significant differences between treated and control animals at P≤0.05 level.

Figure 4 Effect of 14 days of oral feeding on levels of IL-12. *, represents significant differences between treated and control animals at P≤0.05 level.

Figure 5 Effect of 14 days of oral feeding on levels of IFN-γ. *, represents significant differences between treated and control animals at P≤0.05 level.

Figure 6 Effect of 14 days of oral feeding on levels of C-reactive protein (CRP).

More than forty years ago, β-glucans were first described as biological response modifiers that could stimulate tumor rejection in mice. As with many other natural immunostimulators, they were classified as “non-specific” because their molecular targets were unknown and their effects appeared to be pleiotropic. Nevertheless, extensive literature regarding the activity of β-glucans in animal tumor models exists (4). For the past 30 years, in Japan, several forms of mushroom-derived β-glucan have been used successfully in cancer patients (21).

Despite decades of extensive research, the knowledge of the relation between physicochemical characteristics (such as molecular weight, degree of branching, conformation or solubility) and immunological activities is still limited. Even less is known about the relationship between α-glucans and immune reactions. With the continuing discussion whether yeast-derived glucans are better than mushroom-derived glucans (or vice-versa), and a rather limited number of research studies directly comparing individual glucans, the quest for the biologically optimal glucan continues.

Individual commercially available glucans significantly differ in their biological activities and subsequently in price (22). Additional information can be found, but the number of glucans directly compared is still seriously limited (23,24). This investigation focused on the biological and immunological properties of two individual mushroom-derived glucan-rich polysaccharides, MaitakeGold 404 (β-glucan rich) and Shiitake (α-glucan rich), a combination of these two ingredients, and α-glucan rich AHCC.

Glucans were originally developed as stimulators of cellular immunity; therefore, phagocytosis is always the method of choice for characterization of effects on immune reactions. For our study, we used the 2-hydroxyethyl methacrylate microspheres. These particles have only a very light negative charge resulting in no nonspecific adherence to the cell membrane (25).

Using both phagocytosis and NK cell activity as a model in our study, the combination of MaitakeGold 404 glucan and Shiitake glucan consistently showed stronger activities than either mushroom ingredient alone or AHCC. When we compared these glucans directly, MaitakeGold 404 glucan was always more active, despite a significantly lower dose.

In addition to the direct activation of cells involved in immune reactions, the immunostimulating effects of natural molecules such as glucans are directly and/or indirectly caused by potentiation of synthesis and subsequent secretion of various cytokines. Individual glucans significantly differ in their effects upon cytokine synthesis (26,27). We previously showed significant effects of MaitakeGold 404 glucan on cytokine formation (28).

In the present study, we found that the MaitakeGold 404-Shiitake combination significantly enhanced production of all three tested cytokines, IL-6, IL-12 and IFN-γ. In all cases, the MaitakeGold 404 by itself was more active than the Shiitake alone. As cytokine production is extremely sensitive to the presence of LPS, contamination with LPS might mask the real effects of glucan. Therefore, we used LPS-free samples (depleted of any potential LPS by addition of 10 μg/mL of polymixin B) in parallel to normal samples. In each case, no significant difference in activity between normal and LPS-free sample was found (data not shown).

Our findings of levels of CRP showed no significant changes. These results correspond to the recently published study testing glucan effects on CRP levels in saliva of children with chronic respiratory problems (Richter 1).

Our current study clearly demonstrates that Maitake-derived glucan act via the same mechanisms as other highly active glucans to strongly stimulate immune defense reactions and, when combined with Shiitake glucan, the MaitakeGold 404-Shiitake blend is even more immunologically and biologically active than either glucan alone or AHCC

Disclosure: The authors declare no conflict of interest.

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