FWGE stands for Fermented Wheat Germ Extract and is the generic term for standardized extract manufactured by the fermentation of wheat germ by bakers’s yeast, also referred to as “MSC” in some studies and by the trade name Avemar®, registered trademark of Ariza Korlátolt Felelősségű Társaság, Hungary.
Most recent publication:
Bencze, G., Bencze, S., Rivera, K.D. et al. Mito-oncology agent: fermented extract suppresses the Warburg effect, restores oxidative mitochondrial activity, and inhibits in vivo tumor growth. Sci Rep 10, 14174 (2020).
a) Demidov LV, Manziuk LV, Kharkevitch GY, Pirogova NA, Artamonova EV, Adjuvant fermented wheat germ extract (Avemar) nutraceutical improves survival of high-risk skin melanoma patients: a randomized, pilot, phase II clinical study with a 7-year follow-up, Cancer Biother Radiopharm. 2008 Aug;23(4):477-82.
OBJECTIVE: The fermented wheat germ extract (FWGE) nutraceutical (Avemar), manufactured under "good manufacturing practice" conditions and, fulfilling the self-affirmed "generally recognized as safe" status in the United States, has been approved as a "dietary food for special medical purposes for cancer patients" in Europe. In this paper, we report the adjuvant use of this nutraceutical in the treatment of high-risk skin melanoma patients. METHODS: In a randomized, pilot, phase II clinical trial, the efficacy of dacarbazine (DTIC)-based adjuvant chemotherapy on survival parameters of melanoma patients was compared to that of the same treatment supplemented with a 1-year long administration of FWGE. RESULTS: At the end of an additional 7-year-long follow-up period, log-rank analyses (Kaplan-Meier estimates) showed significant differences in both progression-free (PFS) and overall survival (OS) in favor of the FWGE group. Mean PFS: 55.8 months (FWGE group) versus 29.9 months (control group), p = 0.0137. Mean OS: 66.2 months (FWGE group) versus 44.7 months (control group), p = 0.0298. CONCLUSIONS: The inclusion of Avemar into the adjuvant protocols of high-risk skin melanoma patients is highly recommended.
b) Sukkar SG, Cella F, Rovera GM, Nichelatti M, Ragni G, Chiavenna G, Giannoni A, Ronzani G, Ferrari C. A multicentric prospective open trial on the quality of life and oxidative stress in patients affected by advanced head and neck cancer treated with a new benzoquinone-rich product derived from fermented wheat germ (Avemar), Mediterr J Nutr Metab (2008).
Abstract Background and aim: Anorexia/cachexia syndrome is frequently correlated with increased oxidative stress (OS). A fermented wheat-germ extract with a standardized benzoquinone content (brand name Avemar) has been shown to exert an intense antioxidant activity with no side effects. The aim of this study was to investigate the effects of Avemar in patients affected by head and neck cancer, correlating the variations with OS with the quality of life as assessed by the Spitzer’s index. Patients and methods: A cohort of 60 patients affected by head and neck tumours (stage IIIa, IIIb, IV) were enrolled in the study following an open-label protocol. The patients were assigned to two subgroups, A or B. Group A was treated with conventional oncological therapy alone, and group B was treated with Avemar in addition to standard therapy. After 2 months only 55 patients survived and could be evaluated (29 in the control group and 26 in the Avemar group). Each patient was checked for circulating concentrations of hydroperoxides using the FRAS III test. Results: The levels of OS significantly decreased after 2 months in the group receiving Avemar (group). The value of Spitzer’s index was significantly higher in group B, attesting to an improved quality of life. Conclusion Although the specific active substance in Avemar has not yet been identified, the reduction in free oxygen radicals induced by it is correlated with a clinically significant improvement in the quality of life in patients with advanced cancer.
c) Barabás J, Németh Z., Recommendation of the Hungarian Society for Face, Mandible and Oral Surgery in the indication of supportive therapy with Avemar, Orv Hetil. 2006 Sep 3;147(35):1709-11.
The Hungarian Association of Oral and Maxillofacial Surgeons (Magyar Arc-, Állcsont- és Szájsebészeti Társaság) has reviewed the research results related to Avemar and issued its opinion as follows: For patients suffering from head- and neck tumors - primarily malignant tumorous diseases of the oral cavity, the progression of the disease can be slowed significantly, the five-year survival rate increased considerably, the quality of life improved, and the oxidative stress on the patients reduced by the long-term application of the supplementary formula Avemar. The Association considers the supportive treatment with the formula Avemar as an important part of the complex therapeutic protocols applied in stages II, III and IV of malignant tumorous diseases of the oral cavity.
d) Egészségügyi Tudományos Tanács Elnöksége, Recommendation of the Health Sciences Council's Presidency regarding the legal prerequisites for the legal use of AVEMAR dietary supplement as a neoplastic agent, Orv Hetil. 2007 Jan 28;148(4):173.
e) Bálint G, Apáthy A, Gaál M, Telekes A, Resetár A, Blazsó G, Falkay G, Szende B,
Paksy A, Ehrenfeld M, Shoenfeld Y, Hidvégi M., Effect of Avemar--a fermented wheat germ extract--on rheumatoid arthritis. Preliminary data, Clin Exp Rheumatol. 2006 May-Jun;24(3):325-8.
OBJECTIVE: To investigate the effect of the fermented wheat germ extract (Avemar)in patients with severe rheumatoid arthritis (RA). METHODS: Fifteen female RA (Steinbrocker II-III) patients, who had unsuccessfully tried two different DMARD treatments, were enrolled in an open-label, 1-year long, pilot clinical study. DMARD and steroid therapies were recorded and continued. All patients received Avemar as additional therapy. For measurement of efficacy the Ritchie Index, the Health Assessment Questionnaire (HAQ) and the assessment of morning stiffness were applied. Patients were evaluated at baseline, 6 and 12 months. For statistical analyses the Wilcoxon test was used.RESULTS: At both 6 and 12 months, Ritchie index, HAQ and morning stiffness showed significant improvements compared with the baseline values. Dosages of steroids could be reduced in about half of the patients. No side effects of Avemar were observed.
CONCLUSION: Supplementation of standard therapies with a continuous administration of Avemar is beneficial for RA patients.
f) Farkas E., Fermented wheat germ extract in the supportive therapy of colorectal cancer, Orv Hetil. 2005 Sep 11;146(37):1925-31.
The role of the product in the treatment of colorectal cancer is reviewed in the light of experimental and clinical results to date. The fermented wheat germ extract (code name: MSC, trade name: Avemar) registered as a dietary food for special medical purposes for cancer patients to complement the active oncotherapy, exerted a growth inhibitory effect in HCR-25 human colon carcinoma xenograft, and had a synergistic effect with 5-FU in mouse C-38 colorectal carcinoma. The product is capable of chemoprevention of colon carcinoma in F-344 rats. One of the most significant underlying mechanism is a highly cancer cell specific induction of caspase-3 mediated cleavage of PARP. In the frame of supportive therapy, fermented wheat germ extract proved to be efficient in the treatment of colorectal cancer in humans. 30 patients following radical operation were treated with standard postoperative therapy, 12 of them were given fermented wheat germ extract as additive treatment: following a 9 month long administration, no new distant metastases were detected, in contrast to 4 out 18 treated with standard therapy alone. Out of 34 patients following radical surgery and treated with chemotherapy, 17 who were given fermented wheat germ extract, achieved an improved survival rate. In the frame of a controlled multicenter open label cohort study, 170 colorectal cancer patients received anticancer therapies (chemo/radiotherapy) completed with fermented wheat germ extract in 66 of them. Results (fermented wheat germ extract vs. control): new recurrences: 3.0% vs. 17.3% (p < 0.01); new metastases: 7.6% vs. 23.1% (p < 0.01); deaths: 12.1% vs. 31.7% (p < 0.01), progression-related events in total: 16.7% vs. 42.3% (p < 0.001). Survival analysis showed significant improvements in the fermented wheat germ extract group, regarding progression-free (p = 0.0184) and overall survival probabilities (p = 0.0278). Strong predictors of survival determined by Cox's proportional hazards were UICC stage and fermented wheat germ extract treatment. Mild gastrointestinal side effects were observed in 9 cases. Supportive application of fermented wheat germ extract in colorectal cancer is highly recommended.
g) Sukkar, S.G, Edoardo, R., Oxidative Stress and Nutritional Prevention in Autoimmune Rheumatic Diseases, Autoimmunity Reviews, 3:199-206; 2004.
Abstract Background and aim: Anorexia/cachexia syndrome is frequently correlated with increased oxidative stress (OS). A fermented wheat-germ extract with a standardized benzoquinone content (brand name Avemar) has been shown to exert an intense antioxidant activity with no side effects. The aim of this study was to investigate the effects of Avemar in patients affected by head and neck cancer, correlating the variations with OS with the quality of life as assessed by the Spitzer's index. Patients and methods A cohort of 60 patients affected by head and neck tumours (stage IIIa, IIIb, IV) were enrolled in the study following an open-label protocol. The patients were assigned to two subgroups, A or B. Group A was treated with conventional oncological therapy alone, and group B was treated with Avemar in addition to standard therapy. After 2 months only 55 patients survived and could be evaluated (29 in the control group and 26 in the Avemar group). Each patient was checked for circulating concentrations of hydroperoxides using the FRAS III test. Results The levels of OS significantly decreased after 2 months in the group receiving Avemar (group). The value of Spitzer's index was significantly higher in group B, attesting to an improved quality of life. Conclusion Although the specific active substance in Avemar has not yet been identified, the reduction in free oxygen radicals induced by it is correlated with a clinically significant improvement in the quality of life in patients with advanced cancer.
h) Garami M, Schuler D, Babosa M, Borgulya G, Hauser P, Müller J, Paksy A, Szabó E, Hidvégi M, Fekete G., Fermented wheat germ extract reduces chemotherapy-induced febrile neutropenia in pediatric cancer patients, J Pediatr Hematol Oncol. 2004 Oct;26(10):631-5.
PURPOSE: An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (Avemar) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC. METHODS: Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline). There were no significant differences in the average age of the patients, the length of treatment time (MSC) or follow-up, the number of patients with central venous catheters, the number of chemotherapy cycles, the frequency of preventive counterneutropenic interventions, or the type and dosage of antibiotic and antipyretic therapy used in the two groups. RESULTS: During the treatment (follow-up) period, there was no progression of the malignant disease, whereas at end-point the number and frequency of febrile neutropenic events significantly differed between the two groups: 30 febrile neutropenic episodes (24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon signed rank test, P < 0.05).
CONCLUSIONS: The continuous supplementation of anticancer therapies with the medical nutriment MSC helps to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers.
i) Jakab F, Shoenfeld Y, Balogh A, Nichelatti M, Hoffmann A, Kahán Z, Lapis K, Mayer A, Sápy P, Szentpétery F, Telekes A, Thurzó L, Vágvölgyi A, Hidvégi M., A medical nutriment has supportive value in the treatment of colorectal cancer, Br J Cancer. 2003 Aug 4;89 (3):465-9.
MSC (Avemar) is a medical nutriment of which preclinical and observational clinical studies suggested an antimetastatic activity with no toxicity. This open-label cohort trial has compared anticancer treatments plus MSC (9 g once daily) vs anticancer treatments alone in colorectal patients, enrolled from three oncosurgical centres; cohort allocation was on the basis of patients' choice. Sixty-six colorectal cancer patients received MSC supplement for more than 6 months and 104 patients served as controls (anticancer therapies alone): no statistical difference was noted in the time from diagnosis to the last visit between the two groups. End-point analysis revealed that progression-related events were significantly less frequent in the MSC group (new recurrences: 3.0 vs 17.3%, P<0.01; new metastases: 7.6 vs 23.1%, P<0.01; deaths: 12.1 vs 31.7%, P<0.01). Survival analysis showed significant improvements in the MSC group regarding progression-free (P=0.0184) and overall survivals (P=0.0278) probabilities. Survival predictors in Cox's proportional hazards were UICC stage and MSC treatment. Continuous supplementation of anticancer therapies with MSC for more than 6 months is beneficial to patients with colorectal cancer in terms of overall and progression-free survival.
j) Jakab F, Mayer A, Hoffmann A, Hidvégi M., First clinical data of a natural immunomodulator in colorectal cancer, Hepatogastroenterology. 2000 Mar-Apr; 47(32):393-5.
BACKGROUND/AIMS: MSC (trade-name AVEMAR) is a applicable complex of multiple, biologically active molecules obtained from fermented wheat-germ extract. Preclinical studies suggest potent anti-metastatic activity and it has a favorable toxicity profile. It has been aimed in a pilot-scale, phase II clinical study to document whether or not MSC as a support to surgery or plus chemotherapy adds any therapeutic benefit compared to the same combination without MSC in colorectal cancer. METHODOLOGY: From 1998 to June 1999, 18 control patients and 12 consecutive colorectal cancer patients respectively, were enrolled into this study. All patients underwent curative surgery. The control group (18 patients) received no other therapy or adjuvant chemotherapy alone. The MSC group (12 patients) received MSC alone or plus adjuvant chemotherapy. Until now, the median follow-up has been 9 months. RESULTS: Interim data of the study document that in the MSC group no new metastases, neither hepatic nor other, have occurred, so far. On the contrary, several new metastases have developed in the control group. CONCLUSIONS: Orally administered MSC is a potent candidate to be regarded as a supportive therapy to surgery or plus chemotherapy for colorectal cancer patients.
a) - Mueller T, Voigt W., Fermented wheat germ extract--nutritional supplement or anticancer drug?, Nutr J. 2011 Sep 5;10:89.
Background: Fermented wheat germ extract (FWGE) is a multisubstance composition and, besides others, contains 2-methoxy benzoquinone and 2, 6-dimethoxy benzoquinone which are likely to exert some of its biological effects. FWGE interferes with anaerobic glycolysis, pentose cycle and ribonucleotide reductase. It has significant antiproliferative effects and kills tumor cells by the induction of apoptosis via the caspase-poly [ADP-ribose] polymerase-pathway. FWGE interacts synergistically with a variety of different anticancer drugs and exerted antimetastatic properties in mouse models. In addition, FWGE modulates immune response by downregulation of MHC-I complex and the induction of TNF-a and various interleukins. Data in the F-344 rat model provide evidence for a colon cancer preventing effect of FWGE. Clinical data from a randomized phase II trial in melanoma patients indicate a significant benefit for patients treated with dacarbazine in combination with FWGE in terms of progression free survival (PFS) and overall survival (OS). Similarly, data from studies in colorectal cancer suggested a benefit of FWGE treatment. Besides extension of OS and PFS, FWGE improved the quality of life in several studies.
Conclusion: In conclusion, available data so far, justify the use of FWGE as a non-prescription medical nutriment for cancer patients. Further randomized, controlled and large scale clinical studies are mandatory, to further clarify the value of FWGE as a drug component of future chemotherapy regimens.
b) Heimbach JT, Sebestyen G, Semjen G, Kennepohl E., Safety studies regarding a standardized extract of fermented wheat germ, Int J Toxicol. 2007 May-Jun;26(3):253-9.
"Avemar pulvis" is a powder consisting of an aqueous extract of fermented wheat germ, with the drying aids maltodextrin and silicon dioxide, standardized to contain approximately 200 microg/g of the natural constituent 2,6-dimethoxy-p-benzoquinone. The results of toxicological and clinical studies of this product demonstrate its safety for its intended use as a dietary supplement ingredient in the United States. Avemar pulvis has been used in Hungary since 1998 and is approved in that country, as well as in the Czech Republic, Bulgaria, and Romania, as a "medical nutriment for cancer patients." Acute and subacute toxicity studies using rodents orally administered Avemar pulvis showed that dose levels (2000 to 3000 mg/kg body weight [bw]/day) exceeding the normal recommended oral dosage (8.5 g/day or 121 mg/kg bw/day for a 70-kg individual) by up to approximately 25-fold caused no adverse effects. The test substance showed no evidence of mutagenicity or genotoxicity in vitro or in vivo. Clinical studies using Avemar pulvis as a supplement to drug therapy in cancer patients at doses of 8.5 g/day not only showed no evidence of toxicity, but also showed a reduction in the side effects of chemotherapy. Overall, it was concluded that Avemar pulvis would not be expected to cause adverse effects under the conditions of its intended use as an ingredient in dietary supplements.
c) Johanning GL, Wang-Johanning F., Efficacy of a medical nutriment in the treatment of cancer, Altern Ther Health Med. 2007 Mar-Apr;13(2):56-63; quiz 64-5.
Natural products are being used as supplements by cancer patients, with or without the knowledge of their cancer treatment team. It is important to know which of these products show efficacy against diseases such as cancer, and which are ineffective. It is also essential to define the mechanism(s) of action of natural products, especially as relevant to cancer prevention or treatment. The purpose of this article is to review the use of one such natural product, a fermented wheat germ extract (Avemar), in the treatment regimen of cancer patients. Avemar has shown efficacy in both animal cancer models and human clinical trials with cancer patients, but more well-controlled trials in humans are necessary to assess the full potential of Avemar in cancer treatment. Avemar exerts its anticancer effect via an array of mechanisms, likely because there are many undefined components in this product that modulate numerous biological systems in cancer patients.
d) Boros LG, Nichelatti M, Shoenfeld Y., Fermented wheat germ extract (Avemar) in the treatment of cancer and autoimmune diseases, Ann N Y Acad Sci. 2005 Jun;1051:529-42.
Avemar, the product of industrial fermentation of wheat germ, possesses unique cancer-fighting characteristics. Taken orally, Avemar can inhibit metastatic tumor dissemination and proliferation during and after chemotherapy, surgery, or radiation. Benefits of Avemar treatment have been shown in various human cancers, in cultures of in vitro grown cancer cells, in the prevention of chemical carcinogenesis, and also in some autoimmune conditions. This document reviews the clinical and experimental results obtained with this extract so far. Special references are made for its safety, including its coadministration with anticancer drugs, as well as for its immunomodulatory activity, its molecular targets, and its use in cancer clinical trials.
e) Nichelatti, M. & Hidvégi, M., Experimental and clinical results with Avemar (a dried extract from fermented wheat germ) in animal cancer models and in cancer patients,Nogyógyászati Onkológia, 7:180-185; 2002.
In the late 1990's, reports were published about a biotech process by which a fermented wheat germ extract could be produced. The product, called Avemar, available as a water soluble granulate for oral consumption, has gained much attention from cancer researchers of several countries, like Israel, Hungary, the United States, England and Russia. Studies show biological activity of Avemar that may be useful for the treatment of neoplastic diseases, effects which can be well used in the treatment of certain immune disturbances and improvement in patient quality of life which can be independent from the previous ones. ANIMAL EXPERIMENTS: Avemar treatment resulted in a statistically significant decreases in metastases compared with controls, 71% with 3LL-HH tumor (Lewis lung carcinoma), 50% decrease with HCR-25 human colon carcinoma and 85% with B16 melanoma. When used in combination with chemotherapy, Avemar did not reduce cytotoxic effect on primary tumors, but dramatically enhanced antimetastatic effect. CHEMOPREVENTIVE EFFECTS: In F-344 rats colon carcinogenesis was induced by injections of azoxymethane (AOM), 83% of AOM only animals developed colon tumors, an average of 2.3 tumors each. In animals given Avemar prior and after AOM injections, 44.8% developed colon tumors, and average of 1.3 tumors each, reducing tumor development by 70%. CLINICAL STUDIES: NEW METASTASES AND PROGRESSION-FREE SURVIVAL IN CANCER PATIENTS: An early open-label phase II clinical trial with Avemar was conducted in colorectal cancer patients, involving 30 consecutive subjects undergoing curative surgery. Patients were divided into control cohort and Avemar cohort groups. Patients of the control group received adjuvant chemotherapy alone (if necessary), whereas patients of the Avemar group received adjuvant chemotherapy (if necessary) plus 9 grams of Avemar once or twice daily, depending on their body weight. The median follow-up of all patients was 9 months, with range 6-11 months. No patients treated with Avemar showed new metastases, while in the control group 4 patients (22%) did. Another multicenter trial to evaluate disease progression-free and overall survival enrolled 170 consecutive colorectal cancer subjects. End-point analysis observed progression-related events (relapsed tumors, new metastatic lesions, deaths) were significantly more abundant in the control cohort, The log-rank test showed significant differences in favor of the Avemar patients, in both the cumulative probabilities of disease progression-free survival (primary endpoint) and overall survivals. Among all analyzed covariates (age, sex, UICC staging, Avemar treatment, radiotherapy and chemotherapy), the only strong predictors of survival in the Cox proportional hazards model were UICC stage and Avemar treatment. The treatment with Avemar was generally safe (no serious adverse events were recorded.) The results showed highly significant data in favor of Avemar treatment: that this wheat extract, in combination with surgery plus standard radio/chemoptherapy, can significantly inhibit overall tumor progression including the formation of new metastases, and could prolong the survival of colorectal cancer patients.
f) M. Boros, L.G., Cascante, M., Lee, W-N.P., Metabolic Profiling of Cell Growth and Death in Cancer: Applications in Drug Discovery, Drug Discovery Today, 7(6):18-26; 2002.
Metabolic profiling using stable-isotope tracer technology enables the measurement of substrate redistribution within major metabolic pathways in living cells. This technique has been demonstrated that tranformed human cells exhibit profound metabolic shifts and that some and anti-cancer drugs produce their effects by forcing a reversion of these metabolic changes. By revealing tumor-specific metabolic shifts in tumor cells, metabolic profiling enables drug developers to identify the metabolic steps that control cell proliferation, thus aiding the identification of new anti-cancer targets and screening of lead compounds for anti-proliferative metabolic effects.
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