SX-fraction (called Grislin in Japan), a proprietary extract derived from Maitake Mushroom, has been patented in three countries.  Japan, the US and Canada, entitled, “A Glycoprotein with Anti-diabetic, Anti-hypertensive, Anti-obesity and Anti-hyperlipidemic effects.”  Its new patent against PCOS (Polycystic Ovary Syndrome) is now registered in the same three countries.

 PCOS is a leading cause of infertility, affecting 5-10 % of women of reproductive age and believed to be closely associated with insulin resistance or metabolic syndrome.  SX-fraction is known to help increase insulin sensitivity balancing out the endocrine system. As a consequence, PCOS patients taking SX-fraction report that they start ovulating periodically and even become pregnant naturally.  A number of such clinical cases have been reported already.  Also, PCOS patients often repeat miscarriage.  However, after taking SX-fraction, the risk for miscarriage is reduced.  Therefore, SX-fraction may be useful for those PCOS patients who have not achieved goals of conventional therapy.  It is also appreciated by patients as a safe and natural substance with no side effects or a risk for secondary disease.*

 SX-fraction is a proprietary Maitake extract originally developed for people with metabolic syndrome. Improvement of health markers including the body weight is often seen among the patients taking SX-fraction. This confirms the fact that controlling insulin resistance is one of the most essential factors of maintaining good health.  SX-fraction is not just a mushroom extract but also a substantial proprietary natural agent with accumulated scientific validation of several important health benefits. The registration of its patent in the three countries has strengthened its significance.

(*)   OHSS (Ovarian Hyperstimulation Syndrome) exhibits complications such as swollen ovaries, ascites or pleural effusion, a condition often caused by taking fertility drugs repeatedly.

Combination for Improved Weight Control with Medicinal Mushrooms and Other Compounds

 Ken Babal, C.N.

 Most of us know by now that there is no “magic pill” for weight-loss. Reducing body fat requires less food (calories in) along with an increase in energy expenditure (calories out). Nutritionists will disagree about the best proportions of protein, fat and carbohydrate, but there is a strong consensus that limiting high-glycemic foods and controlling blood sugar are critical factors and keys to successful weight management. This is because sharp blood sugar fluctuations lead to insulin resistance and increase the likelihood that calories will be stored as fat. There are, however, highly effective agents that support blood sugar levels, block absorption of starch, and improve fat metabolism, thereby enhancing a person’s weight-loss efforts.

Insulin Resistance and Metabolic Syndrome

Insulin resistance is a condition in which muscle cells become resistant to the effects of insulin, causing insulin and glucose levels to remain high. Insulin resistance develops over years of excessive intake of sugars and high-glycemic foods coupled with a sedentary lifestyle. Insulin resistance is recognized as a chief underlying cause of abdominal obesity, high blood pressure, high triglycerides and low HDLs. This cluster of conditions, which often appear together, is referred to as metabolic syndrome or syndrome X, and sets the stage for diabetes, heart disease and some types of cancers.

Abdominal obesity is an important feature of metabolic syndrome and an indicator of developing insulin resistance. Abdominal obesity is not overall obesity, but specifically the “spare tire” around the waist determined by waist measurement. A waist circumference of more than 39 inches for men and 34 inches for women indicates abdominal obesity and is a red flag for insulin resistance.

Most people who are overweight have insulin resistance. There’s a “chicken and egg” debate, though, as to which event happens first. Does being overweight cause insulin resistance or vice versa? One thing we know is insulin lowers blood sugar by facilitating its entry into cells to be burned for energy. Insulin, however, is also a fat storage hormone because it converts glucose ultimately into fat. Because the link between diabetes and obesity is so strong, the combination has been termed “diabesity.” It is likely that each contributes to the other; the more obese one is the more likely one is insulin resistant; and the more insulin resistant, the greater likelihood of obesity.

SX-Fraction from Maitake Mushroom

The anti-obesity activity of maitake mushroom has been studied in both animals and humans.¹ Results of tests with overweight rats indicate that after 18 weeks those fed maitake powder lost weight, whereas controls gained weight. In a human study, thirty patients were given twenty 500 mg. maitake tablets for a period of two months with no change in their regular diets. All of the patients lost weight (between 7 and 26 pounds) with an average loss of 11 to 13 pounds.

Maitake has been shown to contain immune stimulating compounds, which have been concentrated in the extract called D-Fraction. Further research was conducted to identify and isolate maitake’s insulin enhancing, anti-obesity fraction. The result was SX-Fraction, a glycoprotein so-named because it demonstrated a remarkable ability to improve features of syndrome X. In 2007, it was awarded a U.S. patent for anti-diabetic, anti-hypertensive, anti-obesity and anti-hyperlipidemic effects.² In 2001, a clinical study found that Type 2 diabetics taking SX-Fraction for two months were able to significantly reduce their fasting blood glucose, triglycerides, insulin and body weight.³

SX-Fraction is available as a stand-alone, but is also found synergistic effect when used with Phase2® bean extract, L-carnitine and Tremella mushroom.

 Synergistic Compounds

Phase2® (phaseolamin) is a standardized extract from white kidney bean (Phaseolus vulgaris) that inhibits alpha-amylase, an enzyme the body produces to break down starches into sugars. Phaseolamin reduces the rate of assimilation of starches such as potatoes, pasta, bread and rice. These high-glycemic carbs tend to cause rapid elevations in blood sugar. Also, the primary role of carbohydrate is to provide fuel for energy. However, if we are not physically active carbs are easily converted into body fat.

A randomized, double-blind, placebo-controlled study was performed with 60 overweight subjects who were divided into two groups.⁴ Phaseolamin or placebo was taken one tablet per day before a main meal rich in carbohydrates. After thirty days, subjects receiving phaseolamin had greater reduction of body weight, BMI, fat mass, adipose tissue thickness and waist/hip/thigh circumferences while maintaining lean body mass compared to subjects receiving the placebo.

L-Carnitine is a vitamin-like amino acid that aids fat metabolism because it helps the body utilize fat as a source of energy. Healthy bodies can manufacture it, but if it is in short supply fats accumulate in tissues. Specifically, L-carnitine serves to shuttle fatty acids across cell membranes and into the mitochondria where they are burned for energy. Its impact on fat metabolism is so efficient, many doctors prescribe it to reduce high triglycerides (a blood fat). There is evidence that some forms of obesity may be related to a genetic propensity to produce less L-carnitine. Animal studies have shown that, in conjunction with a slight reduction in calories, L-carnitine can significantly improve weight loss.

Tremella is a gelatinous mushroom composed of 70 percent fiber, which makes it useful for weight management, irregularity and managing cholesterol. Fiber is important to move food along the digestive tract. Another benefit is its ability to act like a sponge, absorbing fats and sugars and slowing their entry into the bloodstream.

Thus, SX-Fraction, a glycoprotein extract from Maitake mushroom is considered as one of an alternative method for improving insulin sensitivity and small or moderate weight loss.

References

1. Ohtsuru, M. “Anti-Obesity Activity Exhibited by Orally Administered Powder of Maitake (Grifola frondosa),” Anshin, 188-200, July 1992.
2. U.S. Patent No. 7,214,778 for “Glycoprotein with Anti-Diabetic, Anti-Hypertensive, Anti-Obesity and Anti-Hyperlipidemic Effects from (Grifola frondosa), and a Method for Preparing Same.” (2007)
3. Konno, S. et al “A possible hypoglycemic effect of maitake mushroom on type 2 diabetic patients.” Diabetic Med. 18, 2001.
4. Celleno, L et al “A Dietary Supplement Containing Standardized Phaseolus vulgaris Extract Influences Body Composition of Overweight Men and Women.” Int J Med Sci 2007,4; pp 45-52.

Medicinal Mushrooms  For OPTIMUM HEALTH AND LONGEVITY

 Ken Babal, C.N.

We all know that vitamin and mineral supplements can augment diets by providing essential nutrients that ward off disease. Likewise, botanicals can help us stay well, and can be used medicinally. There is yet a third category that ranks high for cultivating optimum health and resistance to disease. This is the mushroom category. Mushrooms are members of the fungal family, sometimes referred to as the third kingdom. Being neither plant nor animal, they possess highly unique characteristics that confer a wide array of health benefits.

In addition to essential nutrients, mushrooms contain many compounds with protective and therapeutic actions. Of particular interest is beta glucan, a complex carbohydrate, or polysaccharide that activates cellular immunity. Although we generally think of carbohydrates as providing energy, research reveals that some are involved in molecular recognition and cellular communication. Beta glucans are found in other foods, including oats and yeast. However, their chemical structures and effects are different from those of the beta glucans in mushrooms.

For thousands of years, mushrooms have been revered in China and Japan for their ability to maintain and improve health, preserve youth, and increase longevity. In many classic herbal formulations they are considered the main ingredient, or emperor. Today, there are hundreds of scientific studies validating the traditional usage of mushrooms. In numerous experiments and clinical trials, mushrooms have demonstrated antiallergenic, antibacterial, anti-inflammatory and antiviral actions, and an ability to sensitize cells to insulin.

There are a number of active ingredients in mushrooms that are obtained by alcohol extraction or methods other than simple hot water extraction.

The following are some examples of proven medicinal mushroom standardized extracts.

D-Fraction from Maitake  is perhaps the most famous of the mushroom extracts, having been the focus of much anticancer research. D-Fraction is a concentrated extract containing a protein-bound beta glucan, which has been shown to stimulate vital components of cellular immunity such as T cells, B cells, macrophages and natural killer (NK) cells.¹ Last year, a breakthrough study found that D-Fraction up-regulates twenty-two apoptosis genes, including the BAK-1 gene.² Researchers concluded that D-fraction has strong anti-cancer properties in breast cancer cells through BAK-1 gene expression. This is highly significant because it places D-fraction in a unique category apart from ordinary “immune boosters,” antioxidants and apoptosis-inducers.

Maitake is also the source of a unique glycoprotein called SX-Fraction, which has been shown to enhance insulin sensitivity. SX-Fraction is a completely different compound from D-Fraction, and was awarded a US patent in 2007 for anti-diabetic, anti-hypertensive, anti-obesity and anti-hyperlipidemic effects.³ Studies at Georgetown University found that SX-Fraction reduced levels of fasting blood glucose, blood pressure and body weight in genetically obese and diabetic rats. The extract also prevented hypertensive rats on a high sugar diet from developing insulin resistance. Furthermore, a clinical study found that Type 2 diabetics taking SX-Fraction for two months were able to significantly reduce their fasting blood glucose, triglycerides, insulin and body weight.⁴

Reishi is perhaps the most renowned of all medicinal mushrooms, and is prescribed as an anti-aging tonic. It is said to be a supreme “shen” (spiritual) tonic that invokes peacefulness and changes how we perceive life. Reishi is widely used in Asia to support cardiovascular functions and reduce LDL cholesterol. It has been found to be effective in preventing and treating arteriosclerosis, angina and shortness of breath associated with coronary heart disease.

Reishi contains steroid-like compounds (triterpenes) that inhibit inflammation and histamine, the chemical responsible for allergic symptoms. Medicinal triterpenes are fat-soluble and are concentrated by alcohol extraction.

Lion’s Mane is one of the edible mushrooms widely distributed in Japan and China.  Studies show that a class of compounds in Lion’s Mane, called hericenones, is able to regenerate neurons by stimulating production of Nerve Growth Factor.⁵ In addition, a fat-soluble fraction isolated from Lion’s Mane, called amyloban, is able to protect against neuronal cell death caused by toxic beta amyloid peptide, the main component of plaque that develops in the brains of Alzheimer’s disease patients.⁶

A study at a Chinese Pharmaceutical University compared Lion’s Mane extract with donepezil (Aricept), a common Alzheimer’s drug.⁷ Results showed that rats treated with the extract performed a water maze test equal to or better than those receiving the drug, depending on the dosage of the extract. Also, a double-blind, placebo-controlled study, demonstrated that Lion’s Mane is effective in patients diagnosed with mild cognitive impairment.⁸

And others mushrooms extracts are Agaricus, Cordyceps, Shiitake, Tremella, Meshima, Chaga, Coriolus and Poria. Agaricus enjoys superstar status in Japan. Its medicinal actions include counteracting or preventing tumors, fighting viruses, lowering cholesterol, regulating blood sugar levels and enhancing immunity. Cordyceps strengthens lung power and is a good choice for those who require energy for physical work or sports. It is considered one of the best sexual tonic. Shiitake is the most researched mushroom in the world, and is the source of two extensively studied derivatives used in Japan: lentinan and LEM. Tremella is a mushroom whose skin hydrating properties make it particularly useful as a beauty aid, both internally and externally. When compared to a form of hyaluronic acid, it demonstrated a stronger water holding capacity (500 hundred times its weight). Meshima mushroom has been attracting attention as being particularly protective of breast tissue. Researchers from Indiana University found that an extract of Meshima suppresses growth and invasive behavior of breast cancer cells.⁹ Chaga has received wide acclaim as a medicinal mushroom mentioned in the 1968 novel Cancer Ward. In Russian medicine, a tea made from Chaga is used as to treat ulcers and tuberculosis, and to counteract or prevent tumors. The immune-enhancing activities of Coriolus and its constituents have been extensively studied in Japan since the mid-1970s, with over 400 clinical studies conducted on it. It is the source of PSK (polysaccharide-K) (brand name Krestin), one of the all-time best-selling cancer drugs sold mainly in Europe and Japan. Poria is very popular in traditional Chinese formulations for tonifying the spleen and kidney and for clearing dampness.

References

1. Kodama, N. et al. “Effect of Maitake (Grifola frondosa) D-Fraction on the Activation of NK Cells in Cancer Patients,”  Journal of Medicinal Food 6 (4) 2003, pp. 371-377.

2. Soares, R. et al. “Maitake (D-Fraction) Mushroom Extract Induces Apoptosis in Breast Cancer Cells by BAK- 1 Gene Activation,” Journal of Medicinal Food XX(X) 2011, pp. 1-10.

3. US Patent No. 7,214,778 for “Glycoprotein with Anti-diabetic, Anti-hypertensive, Anti-obesity and Anti-hyperlipidemic Effects from Grifola Frondosa, and a Method for Preparing Same.” (2007)

4. Konno, S. et al “A possible hypoglycemic effect of maitake mushroom on type 2 diabetic patients.” Diabetic Med. 18, 2001.

5. Kawagishi, H and Zhuang, C. “Compounds for dementia from Hericium erinaceum.” Drugs of the Future, 2008, 33(2): 149-155.

6. Nagai, K. et al “Dilinoleoyl-phosphatidylethanolamine from Hericium erinaceum protects against ER stress-induced Neuro2a cell death via protein kinase C pathway.” J Nutr Biochem, 17 (2006) 525-530.

7. Kawagishi, H et al “Anti-dementia effects of a low polarity fraction extracted from Hericium erinaceum.” Abstracts of the 5^th  International Medicinal Mushroom Conference, p. 18-19, September 5^th – 8^th, 2009, Nantong, China.

8. Mori, K et al “Improving Effects of the Mushroom Yamabushitake (Hericium erinaceum) on Mild Cognitive Impairment: A Double-blind Placebo-controlled Clinical Trial.” Phytother Res, 23, 367-372 (2009).

9. Sliva D. et al “Phellinus Linteus Suppresses Growth, Angiogenesis, and Invasive Behavior of Breast Cancer Cells Through the Inhibition of AKT Signaling” British Journal of Cancer, 2008, pp. 1348-56.

 Harry G. Preuss; Bobby Echard,¹ Jia Fu,¹ Nicholas V. Perricone², Debasis Bagchi,³ Mark Kaylor⁴, and Cun Zhuang⁴

‘Department of Biochemistry, Georgetown University Medical Center, Washington, District of Columbia, USA.
²Michigan State University College of Human Medicine, East Lansing, Michigan, USA.
³Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, Texas, USA.
⁴Mushroom Wisdom, East Rutherford, New Jersey, USA.

ABSTRACT: We assessed whether SX-Fraction derived from maitake mushroom could play a beneficial role in the treatment of a laboratory model of type-1 diabetes by decreasing circulating glucose levels and lowering blood pressure (BP). We injected 50 mg/kg body weight (BW) streptozotocin (STZ) intraperitoneally (i.p.) into 48 male Sprague-Dawley rats (SD) to produce a laboratory model of type-1 diabetes. SD were divided into four groups of 12 SD. A control group ate straight pulverized rat chow. To three treatment groups, we added into the pulverized rat chow: gliclazide (10 mg/kg), pioglitazone (10-30 mg/kg), or maitake SX-Fraction (2.5 g/kg). In addition to measuring BW, circulating glucose level, and BP, the following procedures were also carried out: insulin challenge (insulin sensitivity), losartan challenge (renin—angiotensin system activity), Nw-nitro-L arginine-methyl ester hydrochloride (LNAME) challenge (nitric oxide [NO] system activity), and evaluation of serum angiotensin converting enzyme (ACE) activity. All treatments compared with control generally decreased circulating glucose levels, but only the maitake SX-Fraction consistently enhanced measured insulin sensitivity. We found that maitake SX-Fraction could significantly lower systolic blood pressure (SBP) in diabetic SD. In general, only SD receiving maitake SX, not the two drugs, showed decreased activity of the renin—angiotensin system and increased NO system activity compared with control under the conditions examined. Our results suggest that maitake SX-Fraction may be useful for treating perturbations in glucose-insulin me­tabolism and elevated BP in type-1 diabetes.

ABSTRACT

This study aimed to determine the effects of an extract from Maitake mushroom (“SX-fraction”, SX) on ovulation in patients with polycystic ovary syndrome (PCOS). Thirty patients were randomly assigned to either of the following two treatment arms for three months: the SX group (n = 15), which prescribed 207 mg/day of SX, and the control group (n = 15), which received 7.5 g/day of Shakuyaku-Kanzo-To (SKT; a Chinese herbal medicine). Ovulation was judged by the change of basal body temperature and ultrasonography. During the treatment period, 66.7% of the patients in the SX group ovulated compared with 30.8 % in the SKT group; however, the difference was not statistically significant (p = 0.0581). During the same period, ovulation was confirmed in 22 out of 45 menstrual cycles (48.9%) in the SX group, while for the SKT group ovulation was confirmed in 15.4% (P = 0.0011). Estradiol and the estradiol/testosterone ratio also showed a statistically significant increase (P = 0.032 and 0.038, respectively) when those compared before and after treatment with SX. The SX group was 14 times more likely than the SKT group to induce ovulation (95% CI: 1.093 – 196.45). These results summarized; 1) SX was effective in the treatment of PCOS and 2) The SX regimen improved the ovulation rate independent of insulin resistance. In conclusion, SX appears to promote aromatization of testosterone to estradiol in granulosa cells.

Harry G. Preuss^1~, Bobby Echard¹, Debasis Bagchi², Nicholas V. Perricone³

1. Georgetown University Medical Center, Department of Physiology, Washington, D.C. USA
2. University of Houston College of Pharmacy, Department of Pharmacological and Pharmaceutical Services, Houston, TX 77204, USA
3. Michigan State University College of Human Medicine, East Lansing, MI  USA

Abstract

Objective: We assessed the ability of two commercially-available fractions labeled SX and D derived from the edible maitake mushroom to overcome many age-associated metabolic perturbations such as progressive, age-related elevation of blood pressure, over activity of the renin-angiotensin system (RAS), decreased insulin sensitivity, and inflammation in an in vivo laboratory model.

Design and Method: We divided forty mature, female Sprague-Dawley rats (SD) into five groups of eight. SD ingested regular rat chow containing added sucrose (20% w/w). The groups received baseline diet alone (control) or baseline diet containing captopril, nia­cin-bound chromium, maitake fraction SX, or maitake fraction D. In addition to blood pressure readings, the following procedures were implemented: losartan and insulin chal­lenges, evaluation of serum ACE activity, glucose tolerance testing, blood chemistries, LNAME challenge, and measurement of various circulating cytokines.

Results: We found that implementation of all test conditions stopped the gradual elevation of systolic blood pressure (SBP) in the SD over the four months of study, even reversing some of the previous elevation that occurred over time. In general, the treatment groups showed decreased activity of the RAS estimated by less lowering of SBP after losartan challenge and decreased serum ACE activity and were more sensitive to exogenous insulin challenge. TNFa levels decreased in all four test groups suggesting a lessening of the inflammatory state.

Conclusions: We believe our data suggest that maitake mushroom fractions lessen age-related hypertension, at least in part, via effects on the RAS; enhance insulin sensitivity; and reduce some aspects of inflammation — actions that should lead to a longer, healthier life span.