PMID: 

Nutr J. 2011 Sep 5 ;10:89. Epub 2011 Sep 5. PMID: 21892933

Abstract Title: 

Fermented wheat germ extract–nutritional supplement or anticancer drug?

Abstract: 

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-α 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.

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PMID: 

Ann N Y Acad Sci. 2005 Jun ;1051:529-42. PMID: 16126993

Abstract Title: 

Fermented wheat germ extract (Avemar) in the treatment of cancer and autoimmune diseases.

Abstract: 

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.

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PMID: 

Nutrients. 2017 Jul 10 ;9(7). Epub 2017 Jul 10. PMID: 28698513

Abstract Title: 

Anti-Inflammatory Activity of Citric Acid-Treated Wheat Germ Extract in Lipopolysaccharide-Stimulated Macrophages.

Abstract: 

Until recently, fermentation was the only processing used to improve the functionality of wheat germ. The release of 2,6-dimethoxy-1,4-benzoquinone (DMBQ) from hydroquinone glycosides during the fermentation process is considered a marker of quality control. Here, we treated wheat germ extract with citric acid (CWG) to release DMBQ and examined the anti-inflammatory activity of this extract using a lipopolysaccharide-activated macrophage model. Treatment of wheat germ with citric acid resulted in detectable release of DMBQ but reduced total phenolic and total flavonoid contents compared with untreated wheat germ extract (UWG). CWG inhibited secretion of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-12 and the synthesis of cyclooxygenase-2, while UWG only decreased IL-12 production. CWG and UWG induced high levels of anti-inflammatory IL-10 and heme oxygenase-1. CWG specifically inhibited phosphorylation of NF-κB p65 and p38 kinase at 15 min after LPS stimulation. Our study showed that citric acid treatment enhanced the anti-inflammatory activity of wheat germ extract.

PMID: 

J Microbiol Biotechnol. 2010 Aug ;20(8):1204-9. PMID: 20798583

Abstract Title: 

Antimicrobial activities of 1,4-benzoquinones and wheat germ extract.

Abstract: 

We evaluated the antibacterial activities of selected edible Korean plant seeds against the food-borne pathogens Staphylococcus aureus KCTC1927, Escherichia coli KCTC2593, Salmonella typhimurium KCTC2054, and Bacillus cereus KCTC1014. While screening for antibacterial agents, we discovered that wheat germ extract contains 2,6-dimethoxy-1,4-benzoquinone (DMBQ) and is highly inhibitory to S. aureus and B. cereus. This is the first report of the antibacterial activity of wheat germ extract. We also investigated the antibacterial activities of the 1,4- benzoquinone standards 1,4-benzoquinone (BQ), hydroquinone (HQ), methoxybenzoquinone (MBQ), and 2,6-dimethoxy- 1,4-benzoquinone (DMBQ). DMBQ and BQ were the most highly inhibitory to S. aureus and S. typhimurium, followed by MBQ and HQ. MICs for DMBQ and BQ ranged between 8 and 64 microgram/ml against the four foodborne pathogens tested. DMBQ and BQ showed significant antibacterial activity; the most sensitive organism was S. aureus with an MIC of 8 microgram/ml. BQ exhibited good activity against S. typhimurium (32 microgram/ml) and B. cereus (32 microgram/ml). The results suggest that wheat germ extract has potential for the development of natural antimicrobials and food preservatives for controlling foodborne pathogens.

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The following excerpt is from Dr. Cowan’s book Vaccines, Autoimmunity, and the Changing Nature of Childhood Illness (Chelsea Green Publishing, September 2018) and is reprinted with permission from the publisher

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PMID: 

Oncotarget. 2017 Oct 31 ;8(53):91209-91222. Epub 2017 Aug 24. PMID: 29207637

Abstract Title: 

Wheat germ agglutinin-induced paraptosis-like cell death and protective autophagy is mediated by autophagy-linked FYVE inhibition.

Abstract: 

Wheat germ agglutinin (WGA) is a lectin that specifically binds cell surface glycoproteins and disrupts nuclear pore complex function through its interaction with POM121. Our data indicate WGA induces paraptosis-like cell death without caspase activation. We observed the main features of paraptosis, including cytoplasmic vacuolation, endoplasmic reticulum dilation and increased ER stress, and the unfolded protein response in WGA-treated cervical carcinoma cells. Conversion of microtubule-associated protein I light chain 3 (LC3-I) into LC3-II and punctuate formation suggestive of autophagy were observed in WGA-treated cells. WGA-induced autophagy antagonized paraptosis in HeLa and CaSKi cells, which expressed autophagy-linked FYVE (Alfy) protein, but not in SiHa cells that did not express Alfy. Alfy knockdown in HeLa cells induced paraptosis-like cell death. These data indicate that WGA-induced cell death occurs through paraptosis and that autophagy may exert a protective effect. WGA treatment and Alfy inhibition could be an effective therapeutic strategy for apoptosis-resistant cervical cancer cells.

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PMID: 

Int J Biol Macromol. 2018 Oct 15 ;118(Pt A):1267-1275. Epub 2018 Jul 4. PMID: 29981325

Abstract Title: 

Dietary supplementation with purified wheat germ glycoprotein improve immunostimulatory activity in cyclophosphamide induced Balb/c mice.

Abstract: 

Wheat germ has been reported to possess critical biological activities. However, the molecular mechanisms are not fully illuminated. In this work, the immunostimulating activity of a newly purified wheat germ glycoprotein (WGPII) was investigated in immunosuppressed Balb/c mice. Subsequently, WGPII increased the indices of spleen and thymus. Histopathological analysis indicated the protective function of WGPII against cyclophosphamide (CTX) induced immunosuppression. It also showed that WGPII could strengthen macrophage phagocytosis capacity, and NK cell activity. Following, flow cytometry was used to investigate spleen T lymphocyte subpopulations, real-time polymerase chain reaction (RT-PCR) was used to investigate spleen secreted cytokines, and western blot was used to analysis the receptor protein and protein kinase. These results indicated that WGPII could enhance CD4+ and CD8+ splenic T lymphocytes, inflammatory cytokines (IL-β, IL-6, IL-12, TNF-α mRNA), receptor protein (TLR2, TLR4) and protein kinase (IRAK4, TRAF6, TAK1, p38-MAPK, pho-p38-MAPK, NF-κB p65, and nucleu-NF-κB p65) production. This study suggests that WGPII, used as a dietary supplement, could be considered a good candidate to improve immune functions.

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The following excerpt is from Dr. Cowan’s book Human Heart, Cosmic Heart: A Doctor’s Quest to Understand, Treat, and Prevent Cardiovascular Disease (Chelsea Green Publishing, November 2016) and is reprinted with permission from the publisher

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PMID: 

Nutrients. 2018 Oct 19 ;10(10). Epub 2018 Oct 19. PMID: 30347664

Abstract Title: 

The Effects of Adjuvant Fermented Wheat Germ Extract on Cancer Cell Lines: A Systematic Review.

Abstract: 

Fermented wheat germ extract (FWGE; trade name AVEMAR) is a natural compound derived from industrial fermentation of wheat germ. Its potential anticancer properties has emerged from recent studies. The aim of this systematic review is to summarize the data available in the scientific literature concerning the in vitro activity of FWGE on malignant cells. A systematic review of English articles in electronic databases has been performed. The primary outcomes of the review regarded types of cancer cell lines subjected to the investigation and the main results concerning cell viability, proliferation, and apoptosis observed within the studies. Sixteen articles were included in the final qualitative analysis. Various types of cancer cells treated with FWGE have been analyzed, showing mainly cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of apoptosis. FWGE can be a promising drug component in cancer treatment; however, further in vitro and in vivo studies are necessary to prove its effectiveness and safety in humans.

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