Wheat germ extract

Health Care Professional Information

Common Name

Fermented wheat germ extract, MSC (Code Name)

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), antimetastatic (6), 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
Constituents

Wheat germ
Benzoquinone compounds
(5)

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). 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, and induce apoptosis through caspase-3-mediated PARP cleavage (7).

Contraindications
  • Pregnant and nursing women.
  • Patients with hormone-sensitive cancers, as it may have estrogen-receptor activity.
  • 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.
    (8) (18)
Adverse Reactions

Mild, infrequent: diarrhea, nausea, flatulence, soft stool, constipation, dizziness (15) (18)

Herb-Drug Interactions

WGE should be taken at least 2 hours before or after consuming vitamin C (18).

Literature Summary and Critique

Demidov LV, 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. 2008 Aug;23(4):477-82.
This study included 52 patients with malignant skin melanoma who underwent radical surgery for tumor removal and complete resection of the regional nodes involved. Patients were randomized to receive dacarbazine (DTIC)-based adjuvant chemotherapy alone or supplemented with fermented wheat germ extract (FWGE) for 1 year. At 7-year follow-up, researchers observed significant differences in progression-free survival (mean PFS, 55.8 mo vs control group, 29.9 mo; P= .0137) and overall survival (mean OS, 66.2 mo vs control group, 44.7 mo; P=.0298) with FWGE supplementation. Investigators determined FWGE may be a useful adjuvant therapy in high-risk patients for skin melanoma. Larger studies are warranted.

Garami M, et al. Fermented wheat germ extract reduces chemotherapy-induced febrile neutropenia in pediatric cancer patients. J Pediatr Hematol Oncol 2004; 26(10): 631-635.
In this pilot study, 22 pediatric patients with different malignant tumors were given either WGE 12 g/m2 daily during cancer treatments or cancer treatments only (n=11 each). Researchers found no recognizable disease progression during the follow-up period, but there were significant between-group differences in frequency of febrile neutropenic events. The overall white blood cell and lymphocyte counts during such events were close to normal values in the WGE group compared with those in the control group. Since this is a preliminary study, randomized controlled trials are warranted with larger sample sizes to verify these effects.

Jakab F, et al. A medical nutriment has supportive value in the treatment of colorectal cancer. Br J Cancer 2003; 89:465-469.
This study was done to determine if WGE supplementation was beneficial for patients with colorectal cancer. A total of 66 patients were given WGE 9g once daily in addition to anticancer treatments, and 104 patients received only anticancer treatments. Data analysis revealed that patients who took WGE had fewer disease progression-related events compared with the control group. There was also an improvement in OS of patients on WGE, but more trials are needed with equal numbers of patients in the experimental and control groups.

Dosage (Inside MSKCC Only)
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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. ASCO Meeting Abstracts. June 21, 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. Biropharma USA Inc. AWGE Side Effects. 2014; http://www.avemarwge.us/side_effects. Accessed February 19, 2014.

Consumer Information

How It Works

Bottom Line: 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.
Research Evidence

Cancer treatment:
In a small study of 22 children with different cancers, 11 were given WGE during cancer treatments and 11 received only cancer treatments (control group). Researchers found certain white blood cell counts were close to normal in the WGE group compared with the control group.

In a study that looked at whether WGE could benefit patients with colorectal cancer, 66 patients were given WGE daily along with cancer treatments, and 104 patients received only cancer treatments (control group). Results showed that WGE improved overall survival for those taking WGE compared with the control group.

Another study in 52 patients with malignant skin cancer also used either WGE with cancer treatments or cancer treatments alone. After long-term followup of 7 years, an improvement in survival was noted.

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, flatulence, soft stool, constipation, dizziness.
Wheat germ extract may have estrogen receptor activity. Patients with hormone-sensitive cancers should consult with a physician before using WGE.

Special Point

WGE should be taken at least 2 hours before or after consuming vitamin C.

E-mail your questions and comments to aboutherbs@mskcc.org.