Integrative Medicine

Wheat germ extract

Health Care Professional Information

Common Name

Fermented Wheat germ extract, MSC (Code Name)

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Brand Name

Avemar, Avé, AvéULTRA, AWGE, OncoMAR

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Clinical Summary

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. Results from in vitro studies show that WGE has anticancer (1) (2) (12) (14) (16), antimetastatic (3), and immunomodulatory (2) (4) effects. It may also play a role in reducing cardiovascular symptoms due to chronic hypertension, diabetes and obesity (15).

Further, WGE increased estrogen receptor (ER) activity in vitro. However, when used along with tamoxifen, an ER antagonist, it enhanced efficacy of tamoxifen in ER positive breast cancer cells (5). The antitumor effect of WGE is comparable to other endocrine treatments in animal models (11). WGE also increased production of tumor necrosis factor and cytokines that are responsible for tumor cell death (6). Data from pilot studies indicate a beneficial role for WGE in patients with colorectal cancer (7) and in reducing treatment associated febrile neutropenia in pediatric cancer patients (8). It also prolonged survival of patients with melanoma when used with chemotherapy (13). However, these effects must be confirmed by large scale, well-designed clinical trials.

Because it potentiates estrogen receptor activity, patients with hormonal sensitive cancers should use WGE with caution. Reported mild side effects include diarrhea, nausea, flatulence, soft stool, constipation, and dizziness.

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Purported Uses
  • Autoimmune diseases
  • Cancer treatment
  • Immunomodulation
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Constituents

Wheat germ

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Mechanism of Action

Although the exact mechanism of action is not clear, the benzoquinone compounds are thought to be the active components. WGE was shown to increase TNF and cytokine production in vitro by activating certain metabolic pathways (6) involved in tumor cell death. It also demonstrated cytotoxic effects on human lymphoma cells by inducing apoptosis (14). WGE regulates tumor cell proliferation by inhibiting glycolysis and pentose cycle enzymes and induces apoptosis through caspase-3-mediated poly (ADP ribose) polymerase cleavage (4).

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Contraindications
  • Pregnant and nursing women.
  • Patients with organ or tissue transplants.
  • Patients with bleeding gastric or duodenal ulcers, enteritis/colitis, 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 the day after procedure.
    (10)
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Adverse Reactions

Mild and infrequent side effects may include diarrhea, nausea, flatulence, soft stool, constipation, dizziness (10) (13).

Wheat germ extract may have estrogen receptor activity. Patients with hormonal-sensitive cancers should consult with a physician before using WGE.

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Herb-Drug Interactions

WGE should be taken at least two hours before or after consuming vitamin C.
(10)

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Literature Summary and Critique
Demidov LV, Manziuk LV, Kharkevitch GY, Pirogova NA, Artamonova EV. 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 one year. At the 7-year follow-up, researchers observed significant differences in disease progression (PFS) and overall survival (OS) rates, with patients in FWGE group faring better. The mean PFS was 55.8 months for the FWGE group versus 29.9 months in controls (p = 0.0137); mean OS was 66.2 months for the FWGE group versus 44.7 months in the control group (p = 0.0298).
Fermented wheat germ extract may be a useful adjuvant 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.
Twenty-two pediatric patients with different malignant tumors participated in this study. Eleven patients were given 12g/m2/day of WGE during cancer treatments and eleven patients received only cancer treatments. Researchers found that there was no recognizable progression of disease during the follow-up period. But there was a significant difference in the frequency of febrile neutropenic events between the two groups. The overall white blood cell and lymphocyte counts during such events were close to normal values in the WGE group compared to those in the control group. Since this is a pilot study, randomized controlled trials are warranted with larger sample size 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. Sixty-six 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 to the control group. There was also an improvement in overall survival of patients on WGE. But more trials are needed with equal number of patients in the experimental and control groups.

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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 2001; 22(10):1649-1652.
  2. Jakab F, Mayer A, Hoffmann A, Hidvegi M. First clinical data of a natural immunomodulator in colorectal cancer. Hepatogastroenterology 2000; 47(32):393-395.
  3. Hidvegi M, Raso E, Tomoskozi-Farkas R, Paku S, Lapis K, Szende B. Effect of Avemar and Avemar + vitamin C on tumor growth and metastasis in experimental animals. Anticancer Res 1998; 18(4A):2353-2358.
  4. 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 2002; 277(48):46408-46414.
  5. Marcsek 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 Biother Radiopharm 2004; 19(6):746-753.
  6. 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 2005; 1051:515-528.
  7. Jakab F, Shoenfeld Y, Balogh A et al. A medical nutriment has supportive value in the treatment of colorectal cancer. Br J Cancer 2003; 89(3):465-469.
  8. 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 2004; 26(10):631-635.
  9. Boros LG, Nichelatti M, Shoenfeld Y. Fermented Wheat Germ Extract (Avemar) in the Treatment of Cancer and Autoimmune Diseases. Ann N Y Acad Sci 2005; 1051:529-542.
  10. Avemar. http://www.avemar.com (Accessed October 4, 2010).
  11. Tejeda M, D. Gaál, I. Szûcs, et al. Avemar inhibits the growth of mouse and human xenograft mammary carcinomas comparable to endocrine treatments. ASCO Annual Meeting 2007. Abstract No: 21132.
  12. 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. 2007 Jun 8;250(2):323-8.
  13. 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. 2008 Aug;23(4):477-82.
  14. 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 2009;21(3):787-91.
  15. 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. 2009 Jul 21.
  16. 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. 2012 Jul;22(6):960-7.
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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 in some cancer patients.
Patients should consult their physicians before taking WGE.

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Purported Uses
  • Cancer Treatment
    WGE was shown to improve quality of life in cancer patients. More data are needed to establish its use.
  • Autoimmune Diseases
    Studies done in mice show that WGE is beneficial, but human data are lacking.
  • Immunostimulation
    Data from in vitro and observational studies indicate that WGE has immunomodulatory effects.
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Research Evidence

Cancer Treatment:
This study involved twenty-two children with different cancers. Eleven of them were given 12g/m2/day of WGE during cancer treatments whereas eleven others received only cancer treatments. Researchers found the overall white blood cell and lymphocyte counts were close to normal values in the WGE group compared to those in the control group.

This study was done to determine the benefits of WGE for patients with colorectal cancer. Sixty-six patients were given WGE (9g once daily) along with cancer treatments whereas 104 patients received only cancer treatments. Results showed WGE had improved overall survival compared to those in control group.

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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 problem
  • You have sensitivity to gluten
  • You are fructose intolerant
  • It is recommended to discontinue Avemar usage 2 days before barium X-ray contrast examinations and resume 2 days after the completion of the examination.
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Side Effects

Mild and infrequent side effects may include diarrhea, nausea, flatulence, soft stool, constipation, dizziness.
Wheat germ extract may have estrogen receptor activity. Patients with hormonal-sensitive cancers should consult with a physician before using WGE.

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Special Point

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

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Last updated: September 27, 2012
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