Description
Fermented wheat germ extract (FWGE) is industrially produced by fermenting wheat germs of the genus Triticum vulgaris with the addition of baker’s yeast (Saccharomyces cerevisiae). The medicinally active substances of FWGE are not yet known.
FWGE has been marketed as a dietary supplement for cancer patients. In the context of cancer, FWGE is believed to increase efficacy of chemo- and radiotherapy, to reduce their adverse effects and to improve quality of life.
Efficacy
Although six controlled trials consistently reported positive results, the evidence for the claimed benefits is very weak, due to high risk of bias in trials published. No placebo-controlled trials have been carried out.
The main results of the published studies report that patients using FWGE showed:
- Overall and progression-free survival times: Evidence from one RCTs (n=58) and an uncontrolled trial (n=176) suggest intake of FWGE leads to longer overall and progression-free survival times.
- Relapse rates: Two non-randomized CTs (n=45, n=176) found FWGE reduces relapse rates.
- Quality of life: Evidence from two small non-randomized CTs (n=16, n=60) suggest FWGE improves quality of life.
- Febrile neutropenia: One small non-randomized CT (n=22) suggests intake of FWGE reduces incidence of febrile neutropenia.
Safety
There is no known toxicity from ingestion of FWGE. Adverse events are rare and mild.
Description
FWGE involves fermenting wheat germs of the genus Triticum vulgaris by adding baker's yeast (Saccharomyces cerevisiae). Wheat germ is the embryo portion of the wheat kernel. It is a concentrated source of vitamins, minerals, and protein, and is sustained by the larger, starch storage region of the kernel. During the production of wheat flour, the wheat germ is usually removed. In whole wheat products, however, the wheat germ is either not removed or added again after processing. Fermented wheat germ extract (FWGE) is industrially produced and in clinical use.
The idea of using FWGE for medical purposes was introduced by Hungarian Nobel laureate for medicine Dr Albert Szent-Györgyi. He proposed the conjecture, that the benzoquinone found in wheat germ might act antiproliferative because of its high redox potential (Johanning 2007). Subsequently, a way of industrially producing FWGE was invented and patented by Hungarian biochemist Mate Hidvegi.
FWGE is produced as an over-the-counter product in more than ten countries and marketed under the names Avemar, Avemar pulvis, Ave Ultra, MSC and Avé.
Ingredients and quality issues
The production of FWGE involves fermenting (i.e. transforming sugar into ethanol by microorganisms) wheat germs of the genus Triticum vulgaris by adding baker`s yeast (Saccharomyces cerevisiae), adding filtered air and controlling the pH-level and temperature. The process takes about 18 hours. The dried product which is available on the market contains 63.2% FWGE and as technological additives 35% maltodextrin and 1.8% kolloidal silicondioxid (Hidvegi 2002, Pfeifer 2006, Sukkar 2008). Dimethoxy-p-benzoquinone is used to standardize the production process and amounts up to 0.4 mg/g are found in the final product. 2-Methoxy benzoquinone can also be detected in the final product (Hidvegi 2002).
Alleged indications
According to the manufacturer, “AVEMAR helps to support the immune system, quality of life, mental clarity, and cellular health”. (Avemar 2024)
In the context of cancer, FWGE has been marketed as a supplement to chemo- and radiotherapy in the treatment of solid malignant tumors, as it is believed to improve both the success of treatment, as well as patients` quality of life (Barabas 2006, Demidov 2008, Hidvegi 2003, Jakab 2003, Sukkar 2008, Patel 2014). Furthermore, there are claims that FWGE can be used in chemotherapy to reduce the risk of neutropenic fever (Garami 2004).
Application and dosage
FWGE is dissolved in water and applied orally. The authors of clinical trials used dosages of FWGE ranging from 8.5 g once to 9 g twice daily (Barabas 2006, Demidov 2008, Jakab 2003, Sukkar 2008). In a study of children, the authors administered 12 g/m2/day (Garami 2004). A dose of 8.5 g/day contains 1.7 mg of 2,6-dimethoxy-p-benzoquinone which is equivalent to the consumption of 700 g of whole wheat bread (Posner 1985).
Mechanism of action
No single substance has been found that could explain the claimed antimetastatic, apoptotic and immune modulatory effect of FWGE. While Szent-Györgyi attributed the main effect to benzoquinones, it seems now most unlikely that these are the main active ingredients (Hidvegi 2002, Johanning 2007).
In vitro studies and animal studies suggest different mechanisms of action. (Zhurakivska 2018; Yeend 2012) Explanations of the effectiveness of FWGE include:
- Impeding the repair mechanisms of chemotherapy-induced damage in the DNA (inactivation of poly (ADP-ribose) polymerase) (Comin-Anduix 2002, Judson 2012).
- Improving the tumor defense of the body (impeding major histocompatibility complex class 1 expression (Boros 2005), increasing intercellular adhesion molecule 1 expression (Telekes 2005, Fajka-Boja 2002).
- Impeding the growth of malignant cells by changing the metabolism (change in pentose phosphate pathway) (Comin-Anduix 2002, Boros 2005).
- Exerting anti-angiogenic effects by inhibiting VEGF and Cox-2 gene expression (Imir 2018).
- Exhibiting cytostatic and growth delay effects associated with impaired glucose utilization which lead to autophagy (Otto 2016).
- Apoptosis induced by FWGE (Comin-Anduix 2002, Marcsek 2004, Lee 2005, Saiko 2009, Judson 2012) and additive/synergistic effects of FWGE with 5-FU, Oxaliplatin and Irinotecan on different human cell cultures were observed in several in vitro studies (Mueller 2011).
Studies in animals showed neither toxicity nor mutagenic potential of FWGE (Heimbach 2007).
Legal issues
FWGE products are available as nutritional supplements in many countries.
Five controlled clinical trials have been carried out. Four in adult patients diagnosed with head and neck cancer, malignant melanoma, prostate cancer, and colorectal carcinoma (Barabas 2006, Demidov 2008, Jakab 2003, Sukkar 2008) and one in children with diverse malignancies (Garami 2004). These trials are described in Table 1.
Description of included studies
Despite encouraging results from the studies reported here, the evidence that treatment with FWGE confers benefits to cancer patients is very limited, as all study data were at high risk of bias: only one study was a randomized clinical trial (RCT), and all studies were open label, most had small sample sizes, and poor reporting quality. All trials used the same patented FWGE from one manufacturer.
Overall and progression-free survival times
Three studies reported benefits of FWGE treatment on survival and tumour progression. (Demidov 2008, Jakab 2003, Barabas 2006). In an RCT, overall and progression-free survival was evaluated in 58 patients with malignant melanoma. The results showed that after seven years of follow-up, overall and progression-free survival improved in the group that received FWGE (Demidov 2008).
In a non-randomized controlled trial of 176 patients undergoing oncological therapy, patients receiving FWGE had higher overall and progression-free survival rates, with metastases occurring less frequently in the group receiving FWGE (Jakab 2003).
A non-randomized study of 45 patients diagnosed with head and neck cancer found significantly fewer local recurrences and progression events in the group receiving FWGE (Barabas 2006).
Quality of life
One non-randomized controlled study (n=60) reported significantly better quality of life in head and neck cancer patients taking FWGE (Sukkar 2008).
Febrile neutropenia
A non-randomized controlled trial found a reduced incidence of febrile neutropenia among 22 children with various tumours being treated with chemotherapy and FWGE (Garami 2004).
Adverse events
The American Food and Drug Administration (FDA) considers FWGE to be safe (Boros 2005). Side effects of FWGE include diarrhoea, nausea and vomiting, flatulence and constipation (Jakab 2003, Demidov 2008).
Contraindications
There are no known scientifically documented contraindications, however the manufacturers of Avemar state that it should not be taken during pregnancy and breastfeeding.
It is also not recommended for patients undergoing organ or tissue transplantation, in case of bleeding erosions or ulcers of the gastrointestinal tract, malabsorption syndrome, gluten sensitivity (celiac disease) (Avemar 2014).
Interactions
In vitro experiments and animal studies showed no pharmacological interactions with agents used for chemotherapy (Szende 2004). Studies conducted in animals indicate that FWGE can stimulate immune function and therefore affect the effects of immunosuppressants (Hidvegi 2003; Gidali 2000; NMD 2023).
Manufacturers recommend the treatment be temporarily discontinued for two days before any procedure that involves the administration of contrast to the intestinal tract (Avemar 2014).
Warnings
There are no known warnings.
Avemar. Avemar products. Avemar tablet - 150 pcs (semi-monthly dose). Accessed January 25, 2024.
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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;1051:529-42.
Comin-Anduix B, Boros LG, Marin S, Boren J, Callol-Massot C, Centelles JJ et al. Fermented wheat germ extract inhibits glycolysis/pentose cycle enzymes and induces apoptosis through poly(ADP-ribose) polymerase activation in Jurkat T-cell leukemia tumor cells. J Biol Chem. 2002;277:46408-14.
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;23:477-82.
Fajka-Boja, R.; Hidvegi, M.; Shoenfeld, Y.; Ion, G.; Demydenko, D.; Tomoskozi-Farkas, R.; Vizler, C.; Telekes, A.; Resetar, A.; Monostori, E. Fermented wheat germ extract induces apoptosis and downregulation of major histocompatibility complex class i proteins in tumor t and b cell lines. Int. J. Oncol. 2002, 20, 563–570.
Garami M, Schuler D, Babosa M, Borgulya G, Hauser P, Muller J et al. Fermented wheat germ extract reduces chemotherapy-induced febrile neutropenia in pediatric cancer patients. J Pediatr Hematol Oncol. 2004;26:631-35.
Gidali J, Hidvégi M, Fehér I, et al. The effect of Avemar treatment on the regeneration of leukocytes, thrombocytes and reticulocytes in sublethally irradiated or cyclophosphamide treated mice. First Congress of the Hungarian Society of Clinical Oncology, Budapest, Hungary, November 10-11, 2000.
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Hidvegi, M, Moldvay J, and Lapis K. Fermented wheat germ extract improves quality of life in lung cancer patients. (In Hungarian.) (Medicus Anonymus/Pulmono 11: 13-14). 2003.
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Jakab F, Shoenfeld Y, Balogh A, Nichelatti M, Hoffmann A, Kahan Z et al. A medical nutriment has supportive value in the treatment of colorectal cancer. Br J Cancer. 2003;89:465-69.
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Judson PL, Al Sawah E, Marchion DC, Xiong Y, Bicaku E, Bou Zgheib N, et al.. Characterizing the efficacy of fermented wheat germ extract against ovarian cancer and defining the genomic basis of its activity. Int. J. Gynecol. Cancer 2012, 22, 960–967.
Lee sn, Park H, and Lee KE. Ctyotoxic activities of fermented wheat germ extract on human gastric carcinoma cells by induction of apoptosis. Journal of Clinical Oncology. ASCO Annual Meeting Proceedings 23(16S), 4254. 2005.
Marcsek Z, Kocsis Z, Jakab M, Szende B, Tompa A. The efficacy of tamoxifen in estrogen receptor-positive breast cancer cells is enhanced by a medical nutriment. Cancer Biother. Radiopharm. 2004, 19, 746–753.
Mueller T, Jordan K, Voigt W. Promising cytotoxic activity profile of fermented wheat germ extract (Avemar(R)) in human cancer cell lines. J Exp Clin Cancer Res. 2011;30:42.
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Otto C, Hahlbrock T, Eich K, Karaaslan F, Jurgens C, Germer CT, et al. Antiproliferative and antimetabolic effects behind the anticancer property of fermented wheat germ extract. BMC Complement. Altern. Med. 2016, 16, 160.
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Saiko P, Ozsvar-Kozma M, Graser G, Lackner A, Grusch, M, Madlener S, et al. Avemar, a nontoxic fermented wheat germ extract, attenuates the growth of sensitive and 5-FdUrd/Ara-c cross-resistant H9 human lymphoma cells through induction of apoptosis. Oncol. Rep. 2009, 21, 787–791.
Sukkar SG, Cella F, Rovera GM, Nichelatti M, Ragni G, Chiavenna G et al. 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;1:37–42.
Szende B, Marcsek Z, Kocsis Z, Tompa A. Effect of simultaneous administration of Avemar and cytostatic drugs on viability of cell cultures, growth of experimental tumors, and survival tumor-bearing mice. Cancer Biother Radiopharm. 2004;19:343-49.
Telekes A, Kiss-Toth E, Nagy T, Qwarnstrom EE, Kusz E, Polgar T et al. Synergistic effect of Avemar on proinflammatory cytokine production and Ras-mediated cell activation. Ann N Y Acad Sci. 2005;1051:515-28.
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Weitzen R, Epstein N, Oberman B, Shevetz R, Hidvegi M, Berger R. Fermented wheat germ extract (FWGE) as a treatment additive for castration-resistant prostate cancer: A pilot clinical trial. Nutrition and Cancer. 2022 Apr 21;74(4):1338-46.
Yeend T, Robinson K, Lockwood C, McArthur A. The effectiveness of fermented wheat germ extract as an adjunct therapy in the treatment of cancer: A systematic review. JBI Libr Syst Rev. 2012;10(42 Suppl):1-12.
Zhurakivska K, Troiano G, Caponio VCA, Dioguardi M, Arena C, Lo Muzio L. The Effects of Adjuvant Fermented Wheat Germ Extract on Cancer Cell Lines: A Systematic Review. Nutrients. 2018 Oct 19;10(10):1546.
Citation
CAM Cancer Consortium. Fermented wheat germ extract, March 2025.
Document history
Updated in January 2024 and January 2025 by Dana Mora and Barbara Wider. Assessed as up to date in January 2019, February 2017, April 2016, January 2015 and August 2013 by Barbara Wider. Revised and updated in June 2012 by Alexander Kalisch and Markus Horneber. Summary first published in February 2011, authored by Alexander Kalisch and Markus Horneber.
