Fermented wheat germ extract | Cam-Cancer

Fermented wheat germ extract

Abstract and key points
  • Fermented wheat germ extract (FWGE) is produced from wheat germs of the genus Triticum vulgaris.
  • The active ingredient in FWGE is not yet known.
  • It has been claimed that orally used FWGE offers beneficial effects for cancer patients during chemo- and/or radiotherapy.
  • The evidence from clinical trials to support claims of efficacy is weak.
  • The oral intake of FWGE seems to cause no harm.

Fermented wheat germ extract (FWGE) is industrially produced and in clinical use. The production of FWGE involves fermenting wheat germs of the genus Triticum vulgaris by adding baker’s yeast (Saccharomyces cerevisiae). The medically active substances of FWGE are not yet known.

It has been proposed that 2,6-dimethoxy-p-benzoquinone and 2-methoxy benzoquinone found in wheat germ might act antiproliferative because of its high redox potential. FWGE is believed to increase efficacy of chemo- and radiotherapy, to reduce its side effects and to improve quality of life.

Although eight controlled clinical trials consistently reported positive results, the evidence for the claimed benefits is very weak, due to high risk of bias in trials published to this date. No placebo-controlled trials have been carried out.There is no toxicity known by the intake of FWGE. Side effects are rare and mild.

Document history

Assessed as up to date in January 2019 by Barbara Wider.
Assessed as up to date in February 2017 by Barbara Wider.
Assessed as up to date in April 2016 by Barbara Wider.
Assessed as up to date in January 2015 by Barbara Wider.
Assessed as up to date in August 2013 by Barbara Wider.
Fully revised and updated in June 2012 by Alexander Kalisch and Markus Horneber.
Summary first published in February 2011, authored by Alexander Kalisch and Markus Horneber.

Citation

Alexander Kalisch, Markus Horneber, CAM-Cancer Consortium. Fermented wheat germ extract [online document]. February 8, 2017.

What is it?

Description

Wheat germ is the embryo portion of the wheat kernel. It is a concentrated source of vitamins, minerals, and protein, and is sustained by the larger, starch storage region of the kernel—the endosperm. During the production of wheat flour, the wheat germ is usually removed. In whole wheat products, however, the wheat germ is either not removed or added again after processing. Fermented wheat germ extract (FWGE) is industrially produced and in clinical use.

Scientific names/brand names

FWGE involves fermenting wheat germs of the genus Triticum vulgaris by adding baker's yeast (Saccharomyces cerevisiae). FWGE is produced as an over-the-counter drug in more than ten countries and sold under the names Avemar, Avemar pulvis, Ave Ultra, MSC and Avé.

Ingredients

The production of FWGE involves fermenting (i.e. transforming sugar into ethanol by microorganisms) wheat germs of the genus Triticum vulgaris by adding baker`s yeast (Saccharomyces cerevisiae), adding filtered air and controlling the pH-level and temperature. The process takes about 18 hours. The dried product which is available on the market contains 63.2% FWGE and as technological addatives 35% maltodextrin and 1.8% kolloidal silicondioxid1,2,6. Dimethoxy-p-benzoquinone is used to standardize and robustify the production process and amounts up to 0.4 mg/g are found in the final product. 2-Methoxy benzoquinone can also be detected in the final product2.

Application and dosage

FWGE is dissolved in water and applied orally. The author’s of clinical trials used dosages of FWGE ranging from 8.5 g once to 9 g twice daily3-6. In a study of children the authors administred 12 g/m2/day4. A dose of 8.5 g/day contains 1.7 mg of 2,6-dimethoxy-p-benzoquinone which is equivalent to the consumption of 700 g of whole wheat bread7. According to the U.S. Department of Agriculture, individuals who are on a diet primarily based on whole wheat products have a daily intake of about 15 g wheat germ8-10.

History and providers

The idea of using FWGE for medical purposes was introduced by Hungarian Nobel laureate for medicine Dr. Albert Szent-Györgyi. He proposed the conjecture, that the benzoquinone found in wheat germ might act antiproliferative because of its high redox potential11. Later, a way of industrially producing FWGE was invented and patented by Hungarian biochemist Mate Hidvegi.

Mechanism of action/alleged indications/claims of efficacy

No single substance has been found that could explain the claimed antimetastatic, apoptotic and immune modulatory effect of FWGE. While Szent-Györgyi attributed the main effect to benzoquinones, it seems now most unlikely that these are the main active ingredients2,11.

n vitro studies and animal studies (partly unpublished) suggest different mechanisms of action. Explanations of the effectiveness of FWGE include, i) impeding the repair mechanisms of chemotherapy-induced damage in the DNA (inactivation of poly (ADP-ribose) polymerase)12, ii) improving the tumor defence of the body (impeding major histocompatibility complex class 1 expression13, increasing intercellular adhesion molecule 1 expression14 or iii) impeding the growth of malignant cells by changing the metabolism (change in pentose phosphate pathway)12,13. Apoptosis induced by FWGE12,15 and additive/synergistic effects of FWGE with 5-FU, Oxaliplatin and Irinotecan on different human cell cultures were observed in several in vitro studies16. FWGE is used as a supplement to chemo- and radiotherapy in the treatment of solid, malignant tumors, as it is believed to improve both the success of treatment, as well as patients` quality of life3-6,17. Furthermore, there are claims that FWGE can be used in chemotherapy to reduce the risk of neutropenic fever18.

Prevalence of use

The exact prevalence of use of FWGE is not known.

Legal issues

FWGE is available as a nutrient supplement in many countries.

Cost and expenditure

Daily dosage costs up to € 4 at current prices.

Does it work?

Eight controlled clinical trials in adults were carried out with patients diagnosed with head and neck cancer, malignant melanoma, and colorectal carcinoma and in children with diverse malignancies3 4 5 6 17 18 19; they are described in Table 1. All trials reported benefits of FWGE treatment: two studies found longer overall and progression-free survival times4,5, two studies identified reduced relapse rates3,5, three trials showed improved quality of life6,17,19 and another study found reduced incidence of febrile neutropenia18. However, the evidence that treatment with FWGE confers benefits to cancer patients is very weak, as all study data were at high risk of bias: only one study was a randomized clinical trial and all studies were open labelled, had small sample sizes, and poor reporting quality. All trials used the same patented FWGE from one manufacturer.

Is it safe?

Studies in animals showed neither toxicity nor mutagenic potential of FWGE8.

Adverse events

The American Food and Drug Administration (FDA) considers FWGE to be safe13. Side effects of FWGE include diarrhoea, nausea and vomiting, flatulence and constipation5.

Contraindications

There are no known contraindications.

Interactions

In vitro experiments and animal studies showed no pharmacological interactions with agents used for chemotherapy20.

Warnings

There are no known warnings.

References
  1. Pfeifer B. Avemar. Onkologie integrativ. München: Elsevier, Urban and Fischer; 2006: 226-29.
  2. Hidvegi, M., Farkas R, Lapis K, and Raso E. Immunmodulatory and metastasis inhibiting fermented vegetal material, United States Patent, Patent No. 6355474B1. 2002.
  3. Barabas J, Nemeth Z. [Recommendation of the Hungarian Society for Face, Mandible and Oral Surgery in the indication of supportive therapy with Avemar]. Orv Hetil. 2006;147:1709-11.
  4. 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;23:477-82.
  5. Jakab F, Shoenfeld Y, Balogh A, Nichelatti M, Hoffmann A, Kahan Z et al. A medical nutriment has supportive value in the treatment of colorectal cancer. Br J Cancer. 2003;89:465-69.
  6. Sukkar SG, Cella F, Rovera GM, Nichelatti M, Ragni G, Chiavenna G et al. A multicentric prospective open trial on the quality of life and oxidative stress in patients affected by advanced head and neck cancer treated with a new benzoquinone-rich product derived from fermented wheat germ (Avemar). Mediterr J Nutr Metab. 2008;1:37–42.
  7. Posner, ES. The technology of wheat germ separation in flour mills. Assoc Operative Millers Bull Suppl 1,2. 1985. Ref Type: Abstract
  8. Heimbach JT, Sebestyen G, Semjen G, Kennepohl E. Safety studies regarding a standardized extract of fermented wheat germ. Int J Toxicol. 2007;26:253-59.
  9. Tömösközi-Farkas R, Daood HG. Modification of chromatographic method for the determination of benzoquinones in cereal products. Chromatographia. 2004;60:227-30.
  10. U.S.Department of Agriculture, Economic Research Service USDA ERS. U.S. per capita foodconsumption accessed 8 February 2017.
  11. Johanning GL, Wang-Johanning F. Efficacy of a medical nutriment in the treatment of cancer. Altern Ther Health Med. 2007;13:56-63.
  12. Comin-Anduix B, Boros LG, Marin S, Boren J, Callol-Massot C, Centelles JJ 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;277:46408-14.
  13. 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;1051:529-42.
  14. Telekes A, Kiss-Toth E, Nagy T, Qwarnstrom EE, Kusz E, Polgar T et al. Synergistic effect of Avemar on proinflammatory cytokine production and Ras-mediated cell activation. Ann N Y Acad Sci. 2005;1051:515-28.
  15. Lee sn, Park H, and Lee KE. Ctyotoxic activities of fermented wheat germ extract on human gastric carcinoma cells by induction of apoptosis. Journal of Clinical Oncology. ASCO Annual Meeting Proceedings 23(16S), 4254. 2005.
  16. Mueller T, Jordan K, Voigt W. Promising cytotoxic activity profile of fermented wheat germ extract (Avemar(R)) in human cancer cell lines. J Exp Clin Cancer Res. 2011;30:42.
  17. Patel S. Fermented wheat germ extract: a dietary supplement with anticancer efficacy. Nutr Ther Metab 2014;32(2):61-67.
  18. Garami M, Schuler D, Babosa M, Borgulya G, Hauser P, Muller J et al. Fermented wheat germ extract reduces chemotherapy-induced febrile neutropenia in pediatric cancer patients. J Pediatr Hematol Oncol. 2004;26:631-35.
  19. Hidvegi, M, Moldvay J, and Lapis K. Fermented wheat germ extract improves quality of life in lung cancer patients. (In Hungarian.) (Medicus Anonymus/Pulmono 11: 13-14). 2003.
  20. Szende B, Marcsek Z, Kocsis Z, Tompa A. Effect of simultaneous administration of Avemar and cytostatic drugs on viability of cell cultures, growth of experimental tumors, and survival tumor-bearing mice. Cancer Biother Radiopharm. 2004;19:343-49.

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