DNC News

Graham Crackers, Avemar, and Cancer Treatment

April 30, 2007

Jacob Schor, ND

 

Subject: A product made of fermented wheat germ shows promise in treating cancer

 

Sylvester Graham (1794-1851)

Sylvester Graham (1794-1851)

 

A forgotten Fanatic:

Sylvester Graham is long forgotten. He was born in 1794 and, as an ordained Presbyterian minister, preached throughout his life on the benefits of vegetarianism, abstinence from alcohol and the value of whole wheat flour. If remembered for anything, he is famous for inventing Graham flour in 1829. He preached that the white bread of the time was unwholesome. Graham made his bread from pure unsifted and unbolted flour. He insisted that bread was dangerous to eat while still fresh. For reasons unclear to me, he argued that dry hard crusty loaves were preferable. He was also down on sex. He made and shipped his hard dry loaves to followers all over the country. Graham crackers are a leftover from his one time fame. His fanatical belief in the danger of white flour also remains in the public domain, even if we are not quite as fanatical as Graham was.

 

What is Germ?

Everyone knows that whole wheat bread is better for you than white bread. That's a given. Wheat grains are made of three components, the endosperm, the bran and the germ. The endosperm makes up the majority of the grain by weight, about 83%, and contains primarily starch and a little protein. This is the stuff that white flour is made from. It contains calories from the starch and protein but is relatively deficient in vitamins, minerals and other nutrients. The bran comes from the outer protective shell of the wheat kernel and makes up about 14% of the grain by weight. Bran is mostly indigestible fiber, though it does contain more nutrients than the white endosperm. The germ is the most nutritious part of the grain although it makes up only 2-3% of the grains weight. The germ is the actual plant embryo. It is rich in vitamins, minerals and other nutrients. Both bran and germ are removed from wheat during the milling process to make ‘white flour.' It is worth remembering these nutrition basics when talking about one of the new entries into the field of nutritional oncology. It is called Avemar

 

Avemar:

A product called Avemar made from fermented wheat germ extract was invented in the 1990s by a Hungarian scientist named Máté Hidvégi. To make Avemar, wheat germ is fermented with the yeast Saccharomyces cerevisiae for about 18 hours and the resultant product dried to a powder. This endproduct is standardized to contain 0.04% of methoxysubstituted benzoquinones which may be one of several active ingredients in Avemar.

 

Hidvégi isn't the first Hungarian to show interest in these benzoquinones for treating cancer. Albert Szent-Gyorgyi, who received a Nobel Prize for discovering ascorbic acid, was the first to propose their use as anticancer agents.

 

Safety:

It should come as no surprise to find that this product is safe. After all it's just fermented wheat germ. In animal studies, no adverse effect was seen when giving animal 2 grams per kilogram body weight per day. An equivalent dose for a 150 pound person would be 150 grams or about 5 ounces per day of the powder. Typical doses used in studies have been 9 to 18 grams a day. At these lower doses, human test subjects have reported only mild transient nausea, dizziness, constipation when using Avemar.

 

Mechanisms:

Quite a bit of work has been published which attempts to explain the mechanisms of action of Avemar. This is a complex substance and probably contains a number of active chemicals. It is assumed that the methoxy-substituted benzoquinones are at least part of the active principles. A number of different mechanisms have been identified by which Avemar acts against cancer. They include apoptosis induction via poly (ADP-ribose) polymerase, the immune system, major histocompatability comples (MHC) class 1, ribonucleotide reductase (RNR), cyclo-oxygenase (cox1 and cox-2) enzyme activity, intracellular adhesion molecule (ICAM) 1, tumor necrosis factor alpha (TNF-a) production, and transketolase (TK). If I write anymore about this, I'm sure to lose readers. [i]

 

Animal Research:

Numerous animal studies have demonstrated Avemar's benefit in cancer treatment. Scientists measure immune function by timing how long it takes an experimental animal to reject a skin graft from another animal. The faster the rejection, the better the immune system is working. Avemar increases immune function as measured by this skin graft test. [ii] Giving Avemar to test rats prevented them from developing colon cancer when given a cancer causing chemical. In the rats in the control group, 83% developed tumors while only 45% of the rats given Avemar did so. [iii] In a number of animal experiments giving vitamin C at the same time as the Avemar increased the effect at inhibiting metastasis. [iv]

 

Human Research:

At this point, we are still awaiting a definitive double blinded placebo controlled human trial. There are a number of open human trials and animal trials suggesting benefit.

 

In an article published in August 2003 in the British Journal of Cancer, Jakab Shoenfeld and his colleagues reported on an open trial of 66 patients with colorectal cancer. They received standard therapy plus 9 grams of Avemar a day. These patients were compared to 104 patients who received only standard treatment but no Avemar. The primary endpoint of the study was progression-free survival. Tumor progression was defined as an increase in size of tumor of at least 25% or the appearance of new lesions. Progression related events, including recurrent disease, metastasis, or death were more common in the control group than in those taking Avemar. In all, 42.3% of the control group had progression events while only 16.7% of the Avemar group did. This was an open trial, patients decided if they wanted to take this ‘experimental product.' They were not randomized. It seems that the sicker someone was at the start of the experiment, the more inspired they were to try something unusual. At the start of the trial 27% of the Avemar patients had stage IV disease while the control group only 4% were this advanced. [v]

 

Event Control Avemar p value
New Reccurences 17.3% 3.0% <0.01
New Metastases 23.1% 7.6%

<0.01

Deaths 31.7% 12.1% <0.01
Progression related events 42.3% 16.7% <0.001

[vi]

 

Another study from 2004, this one published in the Journal of Pediatric Hematological Oncology looking at the incidence of febrile neutropenia in children undergoing immunosuppressive chemotherapy. [vii] Avemar was given at the same time as chemotherapy in an open label matched-pair pilot trial. Control patients did not receive Avemar. Tumor staging was the same at the start of the study. The number and frequency of febrile illnesses was monitored and differed significantly between the two groups of patients. The Avemar patients had 30 febrile episodes in total in contrast to the control patients who had 46 episodes.

 

In another open-label, pilot trial but this one randomized clinical trial, Avemar was given along with chemotherapy to patients with stage III melanoma. Twenty-two patients were given Avemar in addition to the chemotherapy drugs DTIC. They were compared against twenty-four patients who only received the drugs. Again there was a significant difference in favor of the patients consuming Avemar in terms of progression-free survival. [viii]

Dosing: Avemar comes as powder in single serving packages that are stirred into water. The powder is flavored and sweetened. Human trials have used 9 grams of powder once or twice a day.

 

The question: Before any of you write to ask, I will confess that I do not know if you can make this at home.  Since Avemar is made by fermenting wheat germ with yeast, someone is bound to write me and ask, “Could I bake bread at home using loads of wheat germ and produce the same chemicals as in Avemar?” I don't know but it is an intriguing thought.

 

Further Information:

A nice review article on Avemar from the Annals of the New York Academy of Science is posted at:

http://www.avemar.hu/docs/43_Boros_et_al-NY.pdf

Links to full text of the human clinical trials can be found at:

http://www.avemarresearch.com/TOC.html

Research summary on Sloan-Kettering's website:

http://www.mskcc.org/mskcc/html/69418.cfm

___________________________________________

References:

[i] Integrative Medicine vol 6 no 2 April/May 2007

 

[ii] Immunopharmacology 1999 Apr;41(3):183-186

Hidvegi M, Raso E, Tomoskozi Farkas R, Lapis K, Szende B.

Birochem, Budapest , Hungary .

Effect of MSC on the immune response of mice

The supposed immunostimulatory actions of MSC, a new fermented wheat germ extract standardized to its benzoquinone composition (trade name: AVEMAR) were studied examining blastic transformation of peripheral blood lymphocytes of mice treated with MSC. It was found that MSC significantly increased the degree of blastic transformation caused by Concanavalin A. Using the B10LP to C57Bl skin graft system, MSC (0.03 and 3.0 g kg(-1) applied orally) acted in favour of restoring the immune function. On the other hand, 2,6-dimethoxy-p-benzoquinone (DMBQ), applied in equivalent doses (0.012 and 1.2 mg kg(-l)), did not shorten the rejection time of skin grafts. The immune restoring effect, as well as the blastic transformation enhancing potential of MSC may be exploited in various cases of decreased immune response.

 

[iii] Carcinogenesis. 2001 Oct;22(10):1649-52. Click here to read 

Wheat germ extract inhibits experimental colon carcinogenesis in F-344 rats.

•  Zalatnai A ,

•  Lapis K ,

•  Szende B ,

•  Raso E ,

•  Telekes A ,

•  Resetar A ,

•  Hidvegi M .

1st Institute of Pathology and Experimental Cancer Research, Semmelweis University , Budapest , Hungary . zalatnai@korb1.sote.hu

It has been demonstrated for the first time that a wheat germ extract prevents colonic cancer in laboratory animals. Four-week-old inbred male F-344 rats were used in the study. Colon carcinogenesis has been induced by azoxymethane (AOM). Ten rats served as untreated controls (group 1). For the treatment of the animals in group 2, AOM was dissolved in physiologic saline and the animals were given three subcutaneous injections 1 week apart, 15 mg/kg body weight (b/w) each. In two additional groups Avemar (MSC), a fermented wheat germ extract standardized to 2,6-dimethoxy-p-benzoquinone was administered as a tentative chemo-preventive agent. MSC was dissolved in water and was given by gavage at a dose of 3 g/kg b/w once a day. In group 3, animals started to receive MSC 2 weeks prior to the first injection of AOM daily and continuously thereafter until they were killed 32 weeks later. In group 4 the basal diet and MSC were administered only. At the end of the experiment all the rats were killed by exsanguination, the abdominal large vessels were cut under a light ether anesthesia and a complete autopsy was performed. Percentage of animals developing colon tumors and number of tumors per animals: group 1 - 0 and 0; group 2- 83.0 and 2.3; group 3 - 44.8 (P < 0.001) and 1.3 (P < 0.004), group 4 - 0 and 0. All the tumors were of neoplastic nature also histologically. The numbers of the aberrant crypt foci (ACF) per area (cm(2)) in group 2 were 4.85 while in group 3 the ACF numbers were 2.03 only (P < 0.0001).

PMID: 11577004 [PubMed - indexed for MEDLINE]

 

[iv] Anticancer Res. 1998 Jul-Aug;18(4A):2353-8.

Effect of Avemar and Avemar + vitamin C on tumor growth and metastasis in experimental animals.

•  Hidvegi M ,

•  Raso E ,

•  Tomoskozi-Farkas R ,

•  Paku S ,

•  Lapis K ,

•  Szende B .

Birochem Ltd., Budapest , Hungary . BIROCHEM@MAIL.DATANET.HU

Because of the observed immunostimulatory actions of a new fermented wheat germ extract--with standardized benzoquinone composition--we have investigated the eventual tumor growth- and metastasis-inhibiting effects of this preparation (Avemar) applied alone or in combination with vitamin C. Tumor models of different origin [a highly metastatic variant of the Lewis lung carcinoma (3LL-HH), B16 melanoma, a rat nephroblastoma (RWT-M) and a human colon carcinoma xenograft (HCR25)]--kept in artificially immunosuppressed mice were applied. The metastasis-inhibiting effects of the treatments have been studied both in the presence and in the absence (following surgical removal) of the transplanted primary tumors. Combined treatments with Avemar and vitamin C--administered synchronously--profoundly inhibited the metastasis formation in all the applied tumor models while, treatments with vitamin C alone did not exert such an inhibiting effect on the metastasizing process. The degree of the observed metastasis inhibition in certain models was significant, while in others--although it was meaningful--did not prove to be significant. It is noteworthy that treatment with Avemar alone in certain models exerted a more pronounced inhibiting effect on metastasis formation than the synchronous combined treatment with Avemar and vitamin C. Furthermore, if the time schedule of the combined treatment was changed (vitamin C--instead of being administered synchronously--was given one hour after the treatments with Avemar), the vitamin C rather decreased the metastasis inhibiting effect of Avemar. It should be mentioned however, that in the case of rat nephroblastoma, a different response was observed: while, in the case of synchronous combination significant inhibition of metastasis formation was observed, treatment with Avemar alone did not produce metastasis-inhibition. It is noteworthy that in this model the metastasis-inhibiting effect of the synchronous combination treatment proved to be even more pronounced if Avemar was administered in a 100 times smaller dose than its regularly applied dosage. Treatment with Avemar and vitamin C--administered in combination or separately--in the majority of experimental models (with the exception of rat nephroblastoma) did not inhibit the growth of the primary tumors. It is reasonable, therefore, to suppose that in the observed metastasis-inhibiting effect the eventual proliferation inhibiting effect of these remedies does not play an important role. According to the results of other experiments--carried out in our laboratory in parallel with those described here--Avemar proved to have a meaningful immunostimulatory effect. It might therefore be suggested that the observed metastasis-inhibiting effect of this preparation may be mainly due to its immunostimulatory properties. The possible therapeutic benefits of Avemar and Avemar plus vitamin C are also discussed.

 

[v] Br J Cancer. 2003 Aug 4;89(3):465-9.

A medical nutriment has supportive value in the treatment of colorectal cancer.

 

* Jakab F,

* Shoenfeld Y,

* Balogh A,

* Nichelatti M,

* Hoffmann A,

* Kahan Z,

* Lapis K,

* Mayer A,

* Sapy P,

* Szentpetery F,

* Telekes A,

* Thurzo L,

* Vagvolgyi A,

* Hidvegi M.

 

Department of Surgery and Vascular Surgery, Uzsoki Teaching Hospital of Budapest , Hungary .

 

MSC (Avemar) is a medical nutriment of which preclinical and observational clinical studies suggested an antimetastatic activity with no toxicity. This open-label cohort trial has compared anticancer treatments plus MSC (9 g once daily) vs anticancer treatments alone in colorectal patients, enrolled from three oncosurgical centres; cohort allocation was on the basis of patients' choice. Sixty-six colorectal cancer patients received MSC supplement for more than 6 months and 104 patients served as controls (anticancer therapies alone): no statistical difference was noted in the time from diagnosis to the last visit between the two groups. End-point analysis revealed that progression-related events were significantly less frequent in the MSC group (new recurrences: 3.0 vs 17.3%, P<0.01; new metastases: 7.6 vs 23.1%, P<0.01; deaths: 12.1 vs 31.7%, P<0.01). Survival analysis showed significant improvements in the MSC group regarding progression-free (P=0.0184) and overall survivals (P=0.0278) probabilities. Survival predictors in Cox's proportional hazards were UICC stage and MSC treatment. Continuous supplementation of anticancer therapies with MSC for more than 6 months is beneficial to patients with colorectal cancer in terms of overall and progression-free survival.

 

PMID: 12888813 [PubMed - indexed for MEDLINE]

 

[vi] Orv Hetil. 2005 Sep 11;146(37):1925-31.

[Fermented wheat germ extract in the supportive therapy of colorectal cancer]

[Article in Hungarian]

 

* Farkas E.

 

Biromedicina Elso Magyar Rakkutatasi Reszvenytarsasag, Budapest . elek.farkas@biromedicina.com

 

The role of the product in the treatment of colorectal cancer is reviewed in the light of experimental and clinical results to date. The fermented wheat germ extract (code name: MSC, trade name: Avemar) registered as a dietary food for special medical purposes for cancer patients to complement the active oncotherapy, exerted a growth inhibitory effect in HCR-25 human colon carcinoma xenograft, and had a synergistic effect with 5-FU in mouse C-38 colorectal carcinoma. The product is capable of chemoprevention of colon carcinoma in F-344 rats. One of the most significant underlying mechanism is a highly cancer cell specific induction of caspase-3 mediated cleavage of PARP. In the frame of supportive therapy, fermented wheat germ extract proved to be efficient in the treatment of colorectal cancer in humans. 30 patients following radical operation were treated with standard postoperative therapy, 12 of them were given fermented wheat germ extract as additive treatment: following a 9 month long administration, no new distant metastases were detected, in contrast to 4 out 18 treated with standard therapy alone. Out of 34 patients following radical surgery and treated with chemotherapy, 17 who were given fermented wheat germ extract, achieved an improved survival rate. In the frame of a controlled multicenter open label cohort study, 170 colorectal cancer patients received anticancer therapies (chemo/radiotherapy) completed with fermented wheat germ extract in 66 of them. Results (fermented wheat germ extract vs. control): new recurrences: 3.0% vs. 17.3% (p < 0.01); new metastases: 7.6% vs. 23.1% (p < 0.01); deaths: 12.1% vs. 31.7% (p < 0.01), progression-related events in total: 16.7% vs. 42.3% (p < 0.001). Survival analysis showed significant improvements in the fermented wheat germ extract group, regarding progression-free (p = 0.0184) and overall survival probabilities (p = 0.0278). Strong predictors of survival determined by Cox's proportional hazards were UICC stage and fermented wheat germ extract treatment. Mild gastrointestinal side effects were observed in 9 cases. Supportive application of fermented wheat germ extract in colorectal cancer is highly recommended.

 

PMID: 16255377 [PubMed - indexed for MEDLINE]

 

[vii] J Pediatr Hematol Oncol. 2004 Oct;26(10):631-5.

Fermented wheat germ extract reduces chemotherapy-induced febrile neutropenia in pediatric cancer patients.

 

* Garami M,

* Schuler D,

* Babosa M,

* Borgulya G,

* Hauser P,

* Muller J,

* Paksy A,

* Szabo E,

* Hidvegi M,

* Fekete G.

 

Second Department of Pediatrics, School of Medicine , Semmelweis University , Budapest , Hungary . miklos.garami@gyer2.sote.hu

 

PURPOSE: An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (Avemar) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC. METHODS: Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline). There were no significant differences in the average age of the patients, the length of treatment time (MSC) or follow-up, the number of patients with central venous catheters, the number of chemotherapy cycles, the frequency of preventive counterneutropenic interventions, or the type and dosage of antibiotic and antipyretic therapy used in the two groups. RESULTS: During the treatment (follow-up) period, there was no progression of the malignant disease, whereas at end-point the number and frequency of febrile neutropenic events significantly differed between the two groups: 30 febrile neutropenic episodes (24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon signed rank test, P < 0.05). CONCLUSIONS: The continuous supplementation of anticancer therapies with the medical nutriment MSC helps to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers.

 

PMID: 15454833 [PubMed - indexed for MEDLINE]

[viii] Demidov LV et al. Antimetastatic effect of MSC in high-risk melanoma patients 18 th UICC International Cancer Congress, Oslo , Norway 30 June-5 July, 2002. Int J Cancer2002;100(S13):408


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