Fermented Wheat Germ Extract

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This section does not replicate the other information on this topic but provides additional details or context most relevant to professionals.

Modes of action

Fermented wheat germ extract lowers VEGF and Cox-2 protein and mRNA levels.¹Imir NG, Aydemir E, Şimşek E. Mechanism of the anti-angiogenic effect of Avemar on tumor cells. Oncology Letters. 2018 Feb;15(2):2673-2678.

FWGE’s cytostatic and growth delay effects were linked to impaired glucose utilization which influenced the cell cycle, cellular ATP levels, and the NADH/NAD⁺ ratio. The growth delay effect in response to FWGE treatment led to induction of autophagy.²Otto C, Hahlbrock T et al. Antiproliferative and antimetabolic effects behind the anticancer property of fermented wheat germ extract. BMC Complementary and Alternative Medicine. 2016 Jun 1;16:160.

FWGE controls pancreas tumor propagation primarily by regulating glucose carbon redistribution between cell proliferation-related and cell differentiation-related macromolecules.³Boros LG, Lapis K et al. Wheat germ extract decreases glucose uptake and RNA ribose formation but increases fatty acid synthesis in MIA pancreatic adenocarcinoma cells. Pancreas. 2001 Aug;23(2):141-7. 

Preclinical evidence

Notable preclinical evidence is listed here; clinical evidence is in How can FWGE help you? What the research says ›

Improving treatment outcomes

FWGE enhanced the efficacy of several conventional treatments in preclinical studies.

Cancer as a whole

• FWGE showed an additive to synergistic drug interaction with 5-fluorouracil (5-FU) or dacarbazine (DTIC), reducing tumor size and metastasis in mouse models.⁴Mueller T, Voigt W. Fermented wheat germ extract—nutritional supplement or anticancer drug? Nutrition Journal. 2011 Sep 5;10:89; Mueller T, Jordan K, Voigt W. Promising cytotoxic activity profile of fermented wheat germ extract (Avemar®) in human cancer cell lines. Journal of Experimental & Clinical Cancer Research. 2011 Apr 16;30(1):42.
• FWGE showed antimetastatic effects in three metastasis models (3LL-HH, B16, and HCR-25). It also enhanced the antimetastatic effects and decreased the toxic side effects of 5-FU and DTIC in metastasis animal models.⁵Hidvégi M, Rásó E et al. MSC, a new benzoquinone-containing natural product with antimetastatic effect. Cancer Biotherapy & Radiopharmaceuticals. 1999 Aug;14(4):277-89. 
• FWGE alone or combined with vitamin C inhibited metastasis formation in tumor models compared to vitamin C alone.⁶Hidvégi M, Ráso E et al. Effect of Avemar and Avemar + vitamin C on tumor growth and metastasis in experimental animals. Anticancer Research. 1998 Jul-Aug;18(4A):2353-8. 

Breast cancer

• FWGE enhanced the efficacy of tamoxifen in promoting apoptosis and decreasing estrogen receptor activity in ER+ breast cancer cells⁷Marcsek 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 Biotherapy &  Radiopharmaceuticals. 2004 Dec;19(6):746-53.
• Combining FWGE with any of the endocrine treatments (tamoxifen, examestane, or anastrasol) enhanced the efficacy compared to endocrine monotherapy and showed greater effects (50% inhibition) when used alone than any of the other monotherapies.⁸Tejeda M, Gaál D, Szűcs I, Telekes A. Avemar inhibits the growth of mouse and human xenograft mammary carcinomas comparable to endocrine treatments. Journal of Clinical Oncology 2007 Jun;25(18_suppl): 21132.

Gastric cancer

• 2,6-Dimethoxy-1,4-benzoquinone (2,6-DMBQ), the major bioactive compound found in fermented wheat germ extract, significantly reduced cell growth and induced G1 phase cell cycle arrest and apoptosis in gastric cancer cells.⁹Zu X, Ma X et al. 2,6-DMBQ is a novel mTOR inhibitor that reduces gastric cancer growth in vitro and in vivo. Journal of Experimental and Clinical Cancer Research. 2020 Jun 9;39(1):107.

Leukemia

• FWGE inhibited Jurkat leukemia cell growth by more than 50% and induced apoptosis.¹⁰Comin-Anduix B, Boros LG 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. Journal of Biological Chemistry. 2002 Nov 29;277(48):46408-14. 
• FWGE inhibited the growth and attenuated the progression from G2-M to G0-G1 phase of the cell cycle in human HL-60 promyelocytic leukemia cells.¹¹Saiko P, Ozsvar-Kozma M et al. Avemar, a nontoxic fermented wheat germ extract, induces apoptosis and inhibits ribonucleotide reductase in human HL-60 promyelocytic leukemia cells. Cancer Letters. 2007 Jun 8;250(2):323-8.

Liver cancer

• FWGE enhanced the cytotoxicity of cisplatin in all tested hepatocellular carcinoma (HCC) cells and cytotoxicity of 5-Fu in a synergistic manner in HepJ5 cells.¹²Tai CJ, Wang WC et al. Fermented wheat germ extract induced cell death and enhanced cytotoxicity of Cisplatin and 5-Fluorouracil on human hepatocellular carcinoma cells. Evidence-Based Complementary and Alternative Medicine. 2013;2013:121725.

Lung cancer

• Fermented wheat germ protein showed cytotoxicity against non-small cell lung cancer cells and inhibited growth of A549 xenografts in mice.¹³Levis DJ, Meckler JF, O’Donnell RT, Tuscano JM. A fermented wheat germ extract contains protein components active against NSCLC xenografts in vivo. Current Issues in Molecular Biology. 2023 Aug 25;45(9):7087-7096.
• 2,6-DMBQ, the major bioactive compound found in fermented wheat germ extract, suppressed cell growth and migration in non-small cell lung cancer cells.¹⁴Xie X, Zu X, Laster K, Dong Z, Kim DJ. 2,6-DMBQ suppresses cell proliferation and migration via inhibiting mTOR/AKT and p38 MAPK signaling pathways in NSCLC cells. Journal of Pharmacological Sciences. 2021 Mar;145(3):279-288.

Lymphoma

• Fermented wheat germ proteins induced apoptosis in non-Hodgkin lymphoma cells and augmented immune effector mechanisms, as measured by NK cell killing activity, degranulation, and production of IFNγ.¹⁵Barisone GA, O’Donnell RT et al. A purified, fermented, extract of Triticum aestivum has lymphomacidal activity mediated via natural killer cell activation. PLoS One. 2018 Jan 5;13(1):e0190860.
• FWGE inhibited the growth of both sensitive and 5-FdUrd/Ara-C cross-resistant H9 human lymphoma cells.¹⁶Saiko P, Ozsvar-Kozma M 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. Oncology Reports. 2009 Mar;21(3):787-91.
• FWGE induced apoptosis of 20-40% in 24 hours in T and B tumor lymphocytic cell lines but not in healthy peripheral blood mononuclear cells.¹⁷Fajka-Boja R, Hidvégi M et al. Fermented wheat germ extract induces apoptosis and downregulation of major histocompatibility complex class I proteins in tumor T and B cell lines. International Journal of Oncology. 2002 Mar;20(3):563-70. 

Oral cancer

• High concentration of FWGE reduced the viability of oral tongue squamous cell carcinoma cells and enhanced the effects of cisplatin and 5-fluorouracil on viability.¹⁸Zhurakivska K, Risteli M et al. Effects of fermented wheat germ extract on oral cancer cells: an in vitro study. Nutrition and Cancer. 2022;74(6):2133-2141.
• FWGE inhibited viability and induced cell apoptosis in human oral squamous carcinoma SCC-4 cells and inhibited the migration and invasion of metastatic SCC-4 cells.¹⁹Yang MD, Chang WS et al. Inhibitory effects of AVEMAR on proliferation and metastasis of oral cancer cells. Nutrition and Cancer. 2016;68(3):473-80.

Ovarian cancer

• FWGE enhanced the cytotoxicity of cisplatin and docetaxel in human ovarian cancer cell lines.²⁰Judson PL, Al Sawah E et al. Characterizing the efficacy of fermented wheat germ extract against ovarian cancer and defining the genomic basis of its activity. International Journal of Gynecological Cancer. 2012 Jul;22(6):960-7; Wang CW, Wang CK et al. Preclinical evaluation on the tumor suppression efficiency and combination drug effects of fermented wheat germ extract in human ovarian carcinoma cells. Evidence-based Complementary and Alternative Medicine. 2015;2015:570785.

Optimizing your body terrain

Immune function

• FWGE was linked to an altered immune response ²¹Mueller T, Voigt W. Fermented wheat germ extract—nutritional supplement or anticancer drug? Nutrition Journal. 2011 Sep 5;10:89. and enhanced immune activity, resulting in death of tumor cells in animal studies ²²Mueller T, Voigt W. Fermented wheat germ extract—nutritional supplement or anticancer drug? Nutrition Journal. 2011 Sep 5;10:89; Telekes A, Hegedus M, Chae CH, Vékey K. Avemar (wheat germ extract) in cancer prevention and treatment. Nutrition and Cancer. 2009;61(6):891-9.
• FWGE showed activity toward restoring the immune function of blastic transformation of peripheral blood lymphocytes of mice.²³Hidvégi M, Rásó E, Tömösközi Farkas R, Lapis K, Szende B. Effect of MSC on the immune response of mice. Immunopharmacology. 1999 Apr;41(3):183-6.

Inflammation

• FWGE lowered the inflammatory response especially related to oxidative stress and lowered LPS-triggered partial disruption of epithelial integrity in porcine intestinal epithelial cells.²⁴Karancsi Z, Móritz AV et al. Beneficial effect of a fermented wheat germ extract in intestinal epithelial cells in case of lipopolysaccharide-evoked inflammation. Oxidative Medicine and Cellular Longevity. 2020 Aug 5;2020:1482482.
• FWGE synergized with lipopolysaccharide and PMA in the induction of the transcription of cytokine genes and release of inflammatory cytokines.²⁵Telekes A, Kiss-Tóth E et al. Synergistic effect of Avemar on proinflammatory cytokine production and Ras-mediated cell activation. Annals of the New York Academy of Sciences. 2005 Jun;1051:515-28.
• FWGE inhibited the activity of the inflammatory enzymes cyclooxygenase-1 and -2 in HT-29 human colon carcinoma cells.²⁶Illmer C, Madlener S et al. Immunologic and biochemical effects of the fermented wheat germ extract Avemar. Experimental Biology and Medicine (Maywood, NJ). 2005 Feb;230(2):144-9.

Metabolism

• FWGE was linked to increased normal function of mitochondria, restoring normal metabolism and cell death processes, without any general or liver-specific toxic effects with A250 (a highly purified fraction of FWGE) in cell studies ²⁷Bencze G, Bencze S et al. Mito-oncology agent: fermented extract suppresses the Warburg effect, restores oxidative mitochondrial activity, and inhibits in vivo tumor growth. Scientific Reports. 2020 Aug 25;10(1):14174.

Oxidative stress

• FWGE lowered a marker of oxidative stress (intracellular reactive oxygen species) in IPEC-J2 cells exposed to mycotoxins.²⁸Pomothy JM, Pászti-Gere E, Barna RF, Prokoly D, Jerzsele Á. The impact of fermented wheat germ extract on porcine epithelial cell line exposed to deoxynivalenol and T-2 mycotoxins. Oxidative Medicine and Cellular Longevity. 2020 Dec 8;2020:3854247.
• FWGE at low dose (0.1%) efficiently decreased cellular ROS production and the lipid peroxidation rate in primary hepatocyte cell cultures of rat origin with LPS-induced inflammatory response, although higher concentration of FWGE (1%) increased the rate of both ROS and malondialdehyde synthesis.²⁹Mackei M, Vörösházi J, Sebők C, Neogrády Z, Mátis G, Jerzsele Á. Fermented wheat germ extract as a redox modulator: alleviating endotoxin-triggered oxidative stress in primary cultured rat hepatocytes. Oxidative Medicine and Cellular Longevity. 2020 Dec 8;2020:3181202.
• FWGE lowered the level of intracellular ROS in LPS-treated porcine intestinal epithelial cells.³⁰Karancsi Z, Móritz AV et al. Beneficial effect of a fermented wheat germ extract in intestinal epithelial cells in case of lipopolysaccharide-evoked inflammation. Oxidative Medicine and Cellular Longevity. 2020 Aug 5;2020:1482482.
• FWGE induced oxidative stress that promoted cytotoxicity in human cancer cell lines.³¹Otto C, Hahlbrock T et al. Antiproliferative and antimetabolic effects behind the anticancer property of fermented wheat germ extract. BMC Complementary and Alternative Medicine. 2016 Jun 1;16:160.

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