Wheat germ extract

Purported Benefits, Side Effects & More
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Wheat germ extract

Purported Benefits, Side Effects & More
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Wheat germ extract

Common Names

  • Fermented wheat germ extract
  • MSC (Code Name)

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For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

Fermented wheat germ may improve quality of life in cancer patients, but data is limited and 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 has been used as a dietary supplement by cancer patients in Hungary to improve quality of life. However, studies in humans are quite limited, and cancer patients should consult their physicians before taking WGE.

What are the potential uses and benefits?
  • Cancer
    Limited data suggest WGE may improve quality of life in cancer patients, but larger well-designed studies are needed to establish its use.
  • Autoimmune disorders
    Animal studies suggest WGE is beneficial, but human data are lacking.
  • Immunostimulation
    Lab and observational studies suggest WGE can regulate the immune system.
What are the side effects?

Mild, infrequent: 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.

What else do I need to know?

Do Not Take if:

  • You are pregnant or nursing.
  • You had an organ or tissue transplant.
  • You have bleeding, stomach or intestinal ulcers, 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.
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For Healthcare Professionals

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 has been used as a dietary supplement by cancer patients in Hungary to improve quality of life.

In vitro studies suggest WGE may have 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 may reduce cardiovascular symptoms due to chronic hypertension, diabetes, and obesity (9), mitigate lupus symptoms (10), and have antitumor effects comparable to endocrine treatments (11).

Studies in humans are quite limited. A randomized trial of spermidine (extracted from wheat germ) failed to find improvements in memory in older adults with cognitive decline (24). Other studies suggest benefits of WGE in patients with colorectal cancer (12) , to slow progression of castration-resistant prostate cancer (25) and to reduce treatment-associated febrile neutropenia in pediatric cancer patients (13). When used along with chemotherapy, WGE may prolong survival of melanoma patients (15), but larger studies are needed to confirm these findings.

Because it potentiates estrogen receptor activity, patients with hormone-sensitive cancers should use WGE with caution (8).

Purported Uses and Benefits
  • Autoimmune disorders
  • Cancer
  • Immunomodulation
Mechanism of Action

Benzoquinone compounds are thought to be 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 NK cell activity and intercellular adhesion molecule 1 (ICAM-1) expression (16) (17). It also increases 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 also regulated tumor cell proliferation by inhibiting glycolysis and pentose cycle enzymes (19), and induced apoptosis through caspase-3-mediated PARP cleavage (7).

Compared to untreated cells, WGE-treated cancer cells had lower levels of VEGF, Cox-2 mRNA, and protein levels, markers of angiogenesis (21). WGE also contributed to impaired glucose utilization resulting in autophagy (22), and induced mobilization and homing of CD34(+) stem cells to the myocardial tissue, which may help stem cell-based regeneration of infarcted myocardium (23).

Contraindications

As evidence on safety is lacking and effects to the immune system are unclear, this product should be avoided in

  • 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.

In addition, the manufacturer recommends discontinuing Avemar 2 days before barium X-ray contrast examinations and resume 2 days after procedure.

Adverse Reactions

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

Dosage (OneMSK Only)
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. J Clin Oncol 25, no. 18_suppl (June 2007) 21132-21132.
  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;88(5):309-19.
  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.
  24. Schwarz C, Benson GS, Horn N, et al. Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial.  JAMA Netw Open. 2022 May 2;5(5):e2213875.
  25. 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.  Nutr Cancer. 2022;74(4):1338-1346. 
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