Fermented wheat germ extract
Encyclopedia
Fermented wheat germ extract (FWGE), also called fermented wheat germ powder (FWGP), is a concentrated extract of wheat germ derived from the germ (endosperm
, or seed) of the wheat
plant. FWGE, which was invented in the early '90s in Hungary, differs from ordinary wheat germ in that it is fermented with baker's yeast
to concentrate biologically-active benzoquinones
.
FWGE is available commercially and is sold under the trade name Avemar. In the U.S., the product is classified as a dietary supplement
and is marketed as Ave by American BioSciences, Inc. (Blauvelt, NY). Avemar is manufactured in Hungary, by Biropharma Ltd. (a division of Biromedicina Corp.), where it is approved as a dietary food for cancer patients.
. Szent-Gyorgyi suggested that certain natural compounds called quinones, specifically methoxy-sustituted benzoquinones, naturally present in wheat germ, could help regulate cell metabolism. Fermenting wheat germ with baker’s yeast concentrated the most effective metabolism-regulating quinones such as 2,6-DMBQ, Szent-Gyorgyi noted, so they could be taken as a supplement without the need to consume impractically large amounts of wheat germ.
In the 1990s, Hungarian chemist Mate Hidvegi
along with Rita Tömösközi-Farkas, Károly Lapis, Erzsébet Rásó, and Béla Szende, developed and patented an industrial fermentation process for large-scale production of FWGE extract.
, animals, and human clinical trials. The inventors who hold the patent on the process for manufacturing FWGE (Mate Hidvegi, Rita Tömösközi-Farkas, Károly Lapis, Erzsébet Rásó, and Béla Szende) authored the majority of published research on the product to date.
, non-randomized
, open-label
clinical trial investigated the effects of FWGE on colorectal cancer. The FWGE treatment group included 66 patients who were already under treatment with standard care (i.e., chemotherapy and/or radiation) and elected to receive FWGE for 6 months in addition. The control group consisted of 104 patients who elected to receive standard care alone without FWGE. The rate of progression-related events was significantly lower in the FWGE group versus the control group (3.0% vs 17.3%, respectively), as was the incidence of new metastases (7.6% vs 23.1%) and mortality (12.1% vs 31.7%). Significant improvements in progression-free and overall survival probability were also noted in the FWGE group. However, the authors reported that, because the subjects were not randomly allocated to treatment, there were significant differences in the characteristics of the two groups at baseline (prior to FWGE therapy); namely, the control group was significantly older (66.1 vs. 61.7 years), had a greater proportion of patients who were receiving radiotherapy (53.8% vs. 27.3%) and a much shorter time interval from diagnosis to study entry (1.1 months vs. 11.2 months). In an open-label, non-randomized, non-blinded pilot trial in pediatric cancer patients with various solid cancers, the incidence of chemotherapy-related febrile neutropenia
was lower in patients treated with FWGE (30 episodes, 24.8%) than in control patients (46 episodes, 43.4%).
types in vitro (i.e., HT-29 human colon carcinoma cells, estrogen-positive breast cancer cells, T-cell and B-cell tumor lymphocytic cells, and Jurkat cells). In HT-29 human colon carcinoma cells, FWGE inhibited cell growth at a half-maximal concentration (IC50
) of 118 μg/mL after incubation for 7 days, and triggered cellular apoptosis (in 22% of cells) and necrosis
(in 28% of cells) at a concentration of 3200 μg/ml after 24-hour incubation. In estrogen-positive breast cancer cells, combined incubation with FWGE (625 μg/mL) and tamoxifen
(1 nM) resulted in a greater degree of cellular apoptosis than incubation with tamoxifen alone. in MIA pancreatic adenocarcinoma
cells, FWGE displayed inhibitory effects on glucose
consumption and RNA
ribose
formation, and led to increased synthesis of palmitate. FWGE was shown to stimulate the release of inflammatory cytokines in lipopolysaccharide
-stimulated macrophages, inhibit the survival of activated myeloid
cells, and increase the activity of stress kinases resulting in the activation of AP-1
transcription factor in HeLa
cells.
Endosperm
Endosperm is the tissue produced inside the seeds of most flowering plants around the time of fertilization. It surrounds the embryo and provides nutrition in the form of starch, though it can also contain oils and protein. This makes endosperm an important source of nutrition in human diet...
, or seed) of the wheat
Wheat
Wheat is a cereal grain, originally from the Levant region of the Near East, but now cultivated worldwide. In 2007 world production of wheat was 607 million tons, making it the third most-produced cereal after maize and rice...
plant. FWGE, which was invented in the early '90s in Hungary, differs from ordinary wheat germ in that it is fermented with baker's yeast
Baker's yeast
Baker's yeast is the common name for the strains of yeast commonly used as a leavening agent in baking bread and bakery products, where it converts the fermentable sugars present in the dough into carbon dioxide and ethanol...
to concentrate biologically-active benzoquinones
Benzoquinones
Benzoquinone is a quinone with a single benzene ring, of which there are only two:* 1,4-Benzoquinone, most commonly...
.
FWGE is available commercially and is sold under the trade name Avemar. In the U.S., the product is classified as a dietary supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
and is marketed as Ave by American BioSciences, Inc. (Blauvelt, NY). Avemar is manufactured in Hungary, by Biropharma Ltd. (a division of Biromedicina Corp.), where it is approved as a dietary food for cancer patients.
History of Development of FWGE
The process for manufacturing FWGE through fermenation with baker's yeast was first developed by Hungarian biochemist Albert Szent-GyorgyiAlbert Szent-Györgyi
Albert Szent-Györgyi de Nagyrápolt was a Hungarian physiologist who won the Nobel Prize in Physiology or Medicine in 1937. He is credited with discovering vitamin C and the components and reactions of the citric acid cycle...
. Szent-Gyorgyi suggested that certain natural compounds called quinones, specifically methoxy-sustituted benzoquinones, naturally present in wheat germ, could help regulate cell metabolism. Fermenting wheat germ with baker’s yeast concentrated the most effective metabolism-regulating quinones such as 2,6-DMBQ, Szent-Gyorgyi noted, so they could be taken as a supplement without the need to consume impractically large amounts of wheat germ.
In the 1990s, Hungarian chemist Mate Hidvegi
Máté Hidvégi
Mate Hidvegi is a Hungarian biochemist and co-inventor of Avemar, a fermented wheat germ extract based nutraceutical.-Life :...
along with Rita Tömösközi-Farkas, Károly Lapis, Erzsébet Rásó, and Béla Szende, developed and patented an industrial fermentation process for large-scale production of FWGE extract.
Research
FWGE has been the subject of research investigations involving isolated cells in vitroIn vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
, animals, and human clinical trials. The inventors who hold the patent on the process for manufacturing FWGE (Mate Hidvegi, Rita Tömösközi-Farkas, Károly Lapis, Erzsébet Rásó, and Béla Szende) authored the majority of published research on the product to date.
Human clinical trials
A non-blindedDouble-blind
A blind or blinded experiment is a scientific experiment where some of the people involved are prevented from knowing certain information that might lead to conscious or subconscious bias on their part, invalidating the results....
, non-randomized
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
, open-label
Open-label trial
An open-label trial or open trial is a type of clinical trial in which both the researchers and participants know which treatment is being administered....
clinical trial investigated the effects of FWGE on colorectal cancer. The FWGE treatment group included 66 patients who were already under treatment with standard care (i.e., chemotherapy and/or radiation) and elected to receive FWGE for 6 months in addition. The control group consisted of 104 patients who elected to receive standard care alone without FWGE. The rate of progression-related events was significantly lower in the FWGE group versus the control group (3.0% vs 17.3%, respectively), as was the incidence of new metastases (7.6% vs 23.1%) and mortality (12.1% vs 31.7%). Significant improvements in progression-free and overall survival probability were also noted in the FWGE group. However, the authors reported that, because the subjects were not randomly allocated to treatment, there were significant differences in the characteristics of the two groups at baseline (prior to FWGE therapy); namely, the control group was significantly older (66.1 vs. 61.7 years), had a greater proportion of patients who were receiving radiotherapy (53.8% vs. 27.3%) and a much shorter time interval from diagnosis to study entry (1.1 months vs. 11.2 months). In an open-label, non-randomized, non-blinded pilot trial in pediatric cancer patients with various solid cancers, the incidence of chemotherapy-related febrile neutropenia
Febrile neutropenia
Febrile neutropenia is the development of fever, often with other signs of infection, in a patient with neutropenia, an abnormally low number of neutrophil granulocytes in the blood. The term neutropenic sepsis is also applied, although it tends to be reserved for patients who are less well...
was lower in patients treated with FWGE (30 episodes, 24.8%) than in control patients (46 episodes, 43.4%).
Animal studies
In animals with transplanted human lung cancer, FWGE added to chemotherapy increased survival markedly. In rats exposed to a substance known to cause colon cancer (AOM), giving the rats FWGE reduced by 46% the number of animals developing colon cancer and reduced the size and number of tumors in those rats that did develop colon cancer. In mice with a variety of cancer types (highly metastatic lung cancer; melanoma, and human colon cancer), FWGE administered with vitamin C reduced metastasis (spread) of the cancers. Toxicity studies with FWGE showed no toxicity at levels several times above the amounts recommended for use.In vitro cell studies
FWGE was shown to have apoptotic effects in a variety of cultured cellCell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
types in vitro (i.e., HT-29 human colon carcinoma cells, estrogen-positive breast cancer cells, T-cell and B-cell tumor lymphocytic cells, and Jurkat cells). In HT-29 human colon carcinoma cells, FWGE inhibited cell growth at a half-maximal concentration (IC50
IC50
The half maximal inhibitory concentration is a measure of the effectiveness of a compound in inhibiting biological or biochemical function. This quantitative measure indicates how much of a particular drug or other substance is needed to inhibit a given biological process by half...
) of 118 μg/mL after incubation for 7 days, and triggered cellular apoptosis (in 22% of cells) and necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
(in 28% of cells) at a concentration of 3200 μg/ml after 24-hour incubation. In estrogen-positive breast cancer cells, combined incubation with FWGE (625 μg/mL) and tamoxifen
Tamoxifen
Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...
(1 nM) resulted in a greater degree of cellular apoptosis than incubation with tamoxifen alone. in MIA pancreatic adenocarcinoma
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...
cells, FWGE displayed inhibitory effects on glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
consumption and RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
ribose
Ribose
Ribose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....
formation, and led to increased synthesis of palmitate. FWGE was shown to stimulate the release of inflammatory cytokines in lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...
-stimulated macrophages, inhibit the survival of activated myeloid
Myeloid
The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...
cells, and increase the activity of stress kinases resulting in the activation of AP-1
AP-1
AP1 or AP-1 can refer to:* AP-1 * Autopista AP-1, a Spanish motorway* Caproni AP.1, a 1934 Italian attack aircraft monoplane* USS Henderson...
transcription factor in HeLa
HeLa
A HeLa cell is a cell type in an immortal cell line used in scientific research. It is the oldest and most commonly used human cell line. The line was derived from cervical cancer cells taken on February 8, 1951 from Henrietta Lacks, a patient who eventually died of her cancer on October 4, 1951...
cells.
Precautions
FWGE should not be taken by children or by women who are pregnant or breast feeding. It should not be taken by those who have undertaken organ or tissue transplants, or those who suffer from bleeding erosions or bleeding ulcers of the gastrointestinal tract, enteritis, colitis, or malabsorption syndrome. Patients taking prescription medicine should consult with their doctor before use.External links
- Avemar Research Homepage
- Summary info on fermented wheat germ as cancer-treatment botanical/nutritional complement, by Memorial Sloan-Kettering Cancer Center's Website