Wheat germ extract

• How It Works

  Fermented wheat germ was shown to improve quality of life in cancer patients. More studies are needed.

  Fermented wheat germ extract (WGE) was developed by Mate Hidvegi, a Hungarian chemist, in the 1990s. It should not be confused with wheat germ oil. WGE is used as a dietary supplement by cancer patients in Hungary to improve quality of life. Laboratory studies show that WGE may have anticancer properties. Results from some clinical trials suggest WGE improves quality of life, but cancer patients should consult their physicians before taking WGE.

• Purported Uses
  • Cancer treatment
    WGE was shown to improve quality of life in cancer patients. More data are needed to establish its use.
  • Autoimmune disorders
    Animal studies show that WGE is beneficial, but human data are lacking.
  • Immunostimulation
    Data from test tube and observation studies show that WGE can regulate the immune system.
• Do Not Take If
  • You are pregnant or nursing.
  • You had an organ or tissue transplant.
  • You have bleeding, ulcers of the stomach and intestine, or severe absorption problems.
  • You have sensitivity to gluten.
  • You are fructose intolerant.
  • You are having barium X-ray contrast tests. Discontinue 2 days before and after test.
• Side Effects

  Mild and infrequent side effects include diarrhea, nausea, and vomiting.
  Wheat germ extract may have estrogen receptor activity. Patients with hormone-sensitive cancers should consult with a physician before using WGE.

• Brand Name

  Avemar, Avé, AvéULTRA, AWGE, OncoMAR

• Clinical Summary

  Fermented wheat germ extract (WGE) was developed in the 1990s by Hungarian chemist Mate Hidvegi. It should not be confused with wheat germ oil. WGE is used as a dietary supplement by cancer patients in Hungary to improve quality of life (QoL). Results from in vitro studies show that WGE has anticancer ^{(1) (2) (3) (4) (5) (18) (19)}, antimetastatic ^(6) (20), and immunomodulatory ^(2) (7) effects. Although it appears to increase estrogen receptor (ER) activity, WGE enhanced efficacy of tamoxifen, an ER antagonist, in ER+ breast cancer cells ⁽⁸⁾ as well as cisplatin in ovarian cancer cell lines ⁽⁵⁾. Animal models suggest WGE can reduce cardiovascular symptoms due to chronic hypertension, diabetes, and obesity ⁽⁹⁾, mitigate symptoms associated with lupus ⁽¹⁰⁾, and that its antitumor effect is comparable to other endocrine treatments ⁽¹¹⁾.

  Data from pilot studies indicate a beneficial role for WGE in patients with colorectal cancer ⁽¹²⁾ and in reducing treatment-associated febrile neutropenia in pediatric cancer patients ⁽¹³⁾. It also prolonged survival of patients with melanoma when used with chemotherapy ^(14) (15). However, these effects must be confirmed by large-scale, well-designed clinical trials. Because it potentiates estrogen receptor activity, patients with hormone-sensitive cancers should use WGE with caution.

• Purported Uses
  • Autoimmune disorders
  • Cancer treatment
  • Immunomodulation
• Mechanism of Action

  Benzoquinone compounds are thought to be the active components of WGE ⁽⁵⁾. In vitro, WGE attenuates cell cycle progression from G2-M to G0-G1 phase, reduces ribonucleotide reductase activity ^(3) (4), and stimulates immune function via increased natural killer (NK) cell activity and intercellular adhesion molecule 1 (ICAM-1) expression ^(16) (17). It also increases tumor necrosis factor (TNF) and cytokine production by activating metabolic pathways involved in tumor cell death ⁽¹⁴⁾. In other experiments, WGE demonstrated cytotoxic effects on human lymphoma cells by inducing apoptosis ⁽⁴⁾ and against ovarian cancer cells via poly(ADP-ribose) polymerase (PARP)-1 and PARP-12 expression ⁽⁵⁾. It was also shown to regulate tumor cell proliferation by inhibiting glycolysis and pentose cycle enzymes ⁽¹⁹⁾, and induce apoptosis through caspase-3-mediated PARP cleavage ⁽⁷⁾.

  Recent studies reported that WGE-treated human cancer cells had significantly lower levels of vascular endothelial growth factor (VEG) and Cox-2 mRNA and protein levels (both markers of angiogenesis) compared to untreated cells ⁽²¹⁾. WGE also demonstrated cytostatic and growth delay effects associated with impaired glucose utilization resulting in autophagy in human cancer cells ⁽²²⁾; and was found effective in inducing mobilization and homing of CD34(+) stem cells to the myocardial tissue, which may help stem cell-based regeneration of infarcted myocardium ⁽²³⁾.

• Contraindications
  • Pregnant and nursing women.
  • Patients with hormone-sensitive cancers, as it may have estrogen-receptor activity ⁽⁸⁾.
  • Patients with organ or tissue transplants.
  • Patients with bleeding gastric or duodenal ulcers, enteritis/colitis, or malabsorption syndrome.
  • Patients with sensitivity to gluten and those with fructose intolerance.
  • The manufacturer recommends discontinuing Avemar usage 2 days before barium X-ray contrast examinations and resume 2 days after procedure.
• Adverse Reactions

  Mild, infrequent: diarrhea, nausea/vomiting. ⁽¹⁵⁾

• References

  1. Zalatnai A, Lapis K, Szende B, et al. Wheat germ extract inhibits experimental colon carcinogenesis in F-344 rats. Carcinogenesis. Oct 2001;22(10):1649-1652.

  2. Jakab F, Mayer A, Hoffmann A, et al. First clinical data of a natural immunomodulator in colorectal cancer. Hepatogastroenterology. Mar-Apr 2000;47(32):393-395.

  3. Saiko P, Ozsvar-Kozma M, Madlener S, et al. Avemar, a nontoxic fermented wheat germ extract, induces apoptosis and inhibits ribonucleotide reductase in human HL-60 promyelocytic leukemia cells. Cancer Lett. Jun 8 2007;250(2):323-328.

  4. Saiko P, Ozsvar-Kozma M, Graser G, 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. Mar 2009;21(3):787-791.

  5. Judson PL, Al Sawah E, Marchion DC, 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. Jul 2012;22(6):960-967.

  6. Hidvegi M, Raso E, Tomoskozi-Farkas R, et al. Effect of Avemar and Avemar + vitamin C on tumor growth and metastasis in experimental animals. Anticancer Res. Jul-Aug 1998;18(4a):2353-2358.

  7. Comin-Anduix B, Boros LG, Marin S, 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. Nov 29 2002;277(48):46408-46414.

  8. Marcsek Z, Kocsis Z, Jakab M, et al. The efficacy of tamoxifen in estrogen receptor-positive breast cancer cells is enhanced by a medical nutriment. Cancer Biother Radiopharm. Dec 2004;19(6):746-753.

  9. Iyer A, Brown L. Fermented wheat germ extract (avemar) in the treatment of cardiac remodeling and metabolic symptoms in rats. Evid Based Complement Alternat Med. 2011;2011:508957.

  10. Ehrenfeld M, Blank M, Shoenfeld Y, et al. AVEMAR (a new benzoquinone-containing natural product) administration interferes with the Th2 response in experimental SLE and promotes amelioration of the disease. Lupus. 2001;10(9):622-627.

  11. Tejeda M, Gaal D, Szucs I, et al. Avemar inhibits the growth of mouse and human xenograft mammary carcinomas comparable to endocrine treatments. Journal of Clinical Oncology 25, no. 18_suppl (June 2007) 21132-21132. DOI: 10.1200/jco.2007.25.18_suppl.21132

  12. Jakab F, Shoenfeld Y, Balogh A, et al. A medical nutriment has supportive value in the treatment of colorectal cancer. Br J Cancer. Aug 4 2003;89(3):465-469.

  13. Garami M, Schuler D, Babosa M, et al. Fermented wheat germ extract reduces chemotherapy-induced febrile neutropenia in pediatric cancer patients. J Pediatr Hematol Oncol. Oct 2004;26(10):631-635.

  14. Telekes A, Kiss-Toth E, Nagy T, et al. Synergistic effect of Avemar on proinflammatory cytokine production and Ras-mediated cell activation. Ann N Y Acad Sci. Jun 2005;1051:515-528.

  15. Demidov LV, Manziuk LV, Kharkevitch GY, et al. 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. Aug 2008;23(4):477-482.

  16. Telekes A, Hegedus M, Chae CH, et al. Avemar (wheat germ extract) in cancer prevention and treatment. Nutr Cancer. 2009;61(6):891-899.

  17. Fajka-Boja R, Hidvegi M, Shoenfeld Y, et al. 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. Mar 2002;20(3):563-570.

  18. Shibuya N1, Inoue KI, Tanaka G. et al. Augmented Pentose Phosphate Pathway Plays Critical Roles in Colorectal Carcinomas. Oncology. 2015 Jan 14. [Epub ahead of print]

  19. Zhang JY, Xiao X, Dong Y, Wu J, Zhou XH. Antitumor Activities and Apoptosis-regulated Mechanisms of Fermented Wheat Germ Extract in the Transplantation Tumor Model of Human HT-29 Cells in Nude Mice. Biomed Environ Sci. 2015 Oct;28(10):718-27.

  20. Yang MD, Chang WS, Tsai CW, et al. Inhibitory Effects of AVEMAR on Proliferation and Metastasis of Oral Cancer Cells. Nutr Cancer. 2016;68(3):473-80.

  21. Imir NG, Aydemir E, Şimşek E. Mechanism of the anti-angiogenic effect of Avemar on tumor cells. Oncol Lett. 2018 Feb;15(2):2673-2678.

  22. Otto C, Hahlbrock T, Eich K, et al. Antiproliferative and antimetabolic effects behind the anticancer property of fermented wheat germ extract. BMC Complement Altern Med. 2016 Jun 1;16:160.

  23. Abdelmonem M, Kassem SH, Gabr H, Shaheen AA, Aboushousha T. Avemar and Echinacea extracts enhance mobilization and homing of CD34(+) stem cells in rats with acute myocardial infarction. Stem Cell Res Ther. 2015 Sep 14;6:172.