舞茸D-fraction对健康人群的安全性研究

声明 本文摘自 Alternative Maitake Products Inc Ridgefield Park NJ focusing on the treatment of various malignancies This biaoactive D fraction is the protein bound polysaccharide compound which is prepared by a standardized procedure developed by Maitake Products Inc Characteristically the D fraction is the acid insoluble alkali soluble and hot water extractable fraction consisting of either 1 6 linked glucan with 1 3 branches or 1 3 glucan branched with 1 6 glucosides The fraction has molecular weight of 1 106 daltons 3 Among the various maitake fractions prepared the D fraction was found to be most potent for enhancing the immune system via oral administration or injection demonstrating the highest reduction rate in cancer cell growth 1 This antitumor effect was associated with enhanced cytotoxic activity of macrophages1 and with the elevated interleukin 1 production in tumor bearing mice leading to the activation of cytotoxic T lymphocytes CTL 2 These findings are highly suggestive that the D fraction acts not only through direct activation of various immune effectors macrophages CTL natural killer cells etc targeting tumor cells but also through potentiation the activity or production of various lymphokines Thus such a potent immunostimulatory activity of D fraction may account primarily for its antitumor effect on cancer cells Recently an in vitro study of D fraction showed that it was capable of inducing apoptosis in prostate cancer cells 10 A separate study also demonstrated a chemosensitizing effect of D fraction in which the cytotoxic effect of the anticancer agent carmustine was significantly enhanced in combination with D fraction resulting in 90 percent cell viability reduction cell death 11These results suggest that the D fraction may be an alternative treatment modality for prostate cancer and may also work cooperatively with ongoing chemotherapy Although a number of animal and in vitro studies have confirmed that D fraction inhibits cancer proliferation not many human trials have yet been conducted However prior to such clinical trials the most important issue the safety of D fraction needs to be adequately addressed Some early animal and clinical studies showed that it was safe with no toxic or adverse effects 12 This was supported further by the fact that the U S Food and Drug Administration FDA had exempted D fraction from a phase study of toxicology and had also approved it for an investigational new drug IND application to conduct a phase pilot study on patients with advanced breast and prostate cancers 13 While these trials are underway we were interested in studying the actual effects of D fraction on healthy human subjects which had not yet been fully assessed and documented 划线部分翻译 先前的动物及临床研究中 该产品并未显示出毒副作用 美国食品及药 物管理局 FDA 免除了舞茸 D fraction 产品的一期毒性试验 批准直接用于晚期乳腺癌 和前列腺癌的二期临床试验 由此可见该产品安全可靠 Clinical Study on D fraction on Healthy Human Subjects Twenty eight 28 healthy subjects ages35 73 average age 50 including 14 males and 14 females participated in a randomized double blinded trial of D fraction for a month in Italy Various hematologic parameters such as complete blood count serum glucose total cholesterol and high density lipoprotein HDL bilirubin creatinin hepatic enzymes iron et cetera were evaluated before and after a month of D fraction intake Three Italian physicians Jano Paolo and Glauco were primarily in charge of this trial which was conducted in three separate public hospitals Twenty eight participants were randomized into three groups in the three hospitals Group consisted of 4 males and 5 females Group had 3 males and 6 females and Group had 7 males and 3 females Fifteen 15 participants were instructed to take 1 drop of D fraction per kg in body weight per day equally distributed at each meal 3 times per day in water For example a 60 kg person would ingest a total of 60 drops a day taking 20 drops at each meal Thirteen 13 participants received a placebo preparation and were told to follow the same instructions as the subjects in the D fraction group All participants were also instructed to continue their daily activities or routines such as working eating exercising having sex and so on Following the trial s completion statistical analysis of hematologic parameters was performed using factorial analysis of variance for repeated measures This analysis was performed by Francesca Gigli Berzolari Ph D Department of Scienze Sanitarie Applicate e Psicocomportamentali University of Pavia Italy The results of the statistical analysis are summarized in Table 1 First no participants had palpable ailments or adverse effects during the trial confirming the basic safety of D fraction in healthy subjects Second no essential and clear differences changes in 24 parameters tested was seen between the control and the D fraction groups after this 1 month trial However there were significant statistical differences P 0 05 in the measures for hemoglobin hematocrit and glutamic pyruvic transaminase alanine aminotransferase GPT ALT between the treatment and placeo group although those differences were actually very small Similarly the differences in red blood cells lymphocytes mean corpuscular hemoglobin mean corpuscular hemoglobin concentration and HDL were nearly statistically significant P 0 1 Thus these results suggest that these 8 parameters might be primarily affected or modulated with D fraction although the degree of such an influence would be minimal and hardly noticeable in healthy subjects It is also indicative of the possibility that some changes in 9 other parameters could be induced by D fraction with long term use In other words if people take D fraction or longer than 1 month the values for granulocytes eosinophil mean corpuscular value total cholesterol triglycerides creatinin alkaline phosphatase glutamic oxaloacetic transaminase aspartate aminotransferase GOT AST bilirubin and transferrin may subsequently be subject to some changes It should be reemphasized that even if this prediction was correct such changes would be considerably small but only significant statistically Overall 17of 24 parameters tested seemed to be somewhat affected by D fraction presumably providing some health benefits For example changes in the HDL and triglycide levels indicate that D fraction may improve lipid metabolism lowering the triglyceride concentration while elevating the HDL level there by preventing potential atherosclerosis or thrombosis and the morbid sequelae associated with vascular disease In addition lowering the creatinin concentration could indicate improved renal function while lowering the levels of bilirubin GPT ALT and GOT AST may indicate improved liver function with reduced hepatic cell damage injury These effects are still unproven what the present study confirmed is that D fraction is undoubtedly safe for normal patients in normal health and may even provide additional health benefits Conclusions Both in vivo and in vitro studies and limited clinical trials thus far support a potent immunostimulatory anticancer or antitumor as well as apoptosis inducing activity for D fraction which may have great potential for cancer treatment and prevention However information on the safety of D fraction or actual positive or negative effects of D fraction on healthy human subjects had yet been lacking or insufficient To the best of our knowledge this is the first study to assess the safety of D fraction in normal healthy subjects D fraction is indeed safe with negligible or few side effects It is also indicative that D fraction may help reduce the risk of cardiovascular disease and improve renal and liver function However larger randomized studies are still required to confirm these interesting findings further and delineate the clinical effectiveness and potential health benefits of D fraction Such studies are thus warranted Acknowledgments We thank Mr Paolo Clauser for his great support and assistance Our special gratitude goes to Mr Mike Shirota Maitake Products Inc for kindly providing Grifron Pro Maitake D Fraction used in the trial Reference 1 Hishida I Nanba H Kuroda H Antitumor activity exhibited by orally administered extract from fruit body of Grifola frondosa maitake Chem Pharm Bul l Tokyo 1988 36 1819 1827 2 Adachi K Nanba H Kuroda H Potentiation of host mediated antitumor activity in mice by glucan obtained from Grifola frondosa maitake Chem Pharm Bull Tokyo 1987 5 262 270 3 Mizuno T Zhuang C Maitake Grifola frondosa Pharmacological effects Food Rev Int 1995 11 135 149 4 Adachi K Aoki H Nanba H Otsuka M et al Blood pressure lowering activity present in the fruit body of Grifola frondosa Chem Pharm Bull Tokyo 1988 36 1000 1006 5 Kubo K Aoki H Nanba H Anti diabetic activity present in the fruit body of Grifola frondosa maitake Biol Pharm Bull 1994 17 1106 1110 6 Kubo K Nanba H The effect of maitake mushrooms on liver and serum lipids Altern Ther Health Med 1996 2 62 66 7 Nakai R Masui H Horio H et al Effect of maitake Grifola frondosa water extract on inhibition of adipocyte conversion of C3H10T1 2B2C1 cells J Nutr Sci Vitaminol Tokyo 1999 45 38