Methylglyoxal, a molecule also produce by human body, it is one of the substances with an anti cancer potential that stands out.
I am enthusiast about it because of the following facts:
- It has clear science behind supported by a large amount of academic research
- Its anti cancer potential has been already demonstrated in humans
- It can eradicate most cancer types
- Its anti cancer action was even indicated by a Nobel Prize winner in multiple publications in the prestigious magazine “Science”
- It is cheap
- Relatively easy accessible and can be administrated orally
- Low to no toxicity to normal cells
I will start this article with a number of major historical facts indicating the potential behind Methylglyoxal:
- At the begging of the last century …
Dr. William F. Koch (1885-1967) (appointed Professor of Physiology at the Detroit College of Medicine in 1914, and subsequently became Chairman of that Department) published a paper entitled “A NEW AND SUCCESSFUL TREATMENT AND DIAGNOSIS OF CANCER”. In this paper he was stating the following: “This substance when purified, taken up in water and immediately injected subcutaneously into a cancer patient, causes practically no local reaction; but instead, after about 24 hours, a very decided focal reaction takes place. Wherever the cancer tissue may be, its’ cells are killed, their ionic concentration increases, the osmotic pressure increases, they take up water, swell and disintegrate. The swelling causes pain and the absorbed, disintegrated products are oxidized causing fever.”“Those two things, focal pain and fever, constitute a reaction which lasts all the way from 6 to 48 hours, depending upon the amount of cancer tissue killed, and of course this depends upon the quantity of substance injected. Such a reaction occurs only in cancer cases and only in the presence of cancer tissue. After the cancer tissue has disappeared, no more reaction can be elicited, no matter how large an injection is given, an important diagnostic aid. The specificity of the substance for cancer is evidenced by the fact that while giving these injections in rapid succession (that is daily or every two days for a period of five weeks), a blood count will rise from 2,850,000 to 4,600,000 red cells and the haemeglobin from 37% to 82%. Thus the delicate red cells are not injured. At the same time a mass of cancer tissue, the size of a large cabbage, will entirely disappear, and all the signs and symptoms of the particular cancer will disappear with it, function return, and the patient become clinically cured.“Stomach, liver and rectal cancers clear up the quickest. Uterus cancer responds slightly more slowly. Squamous cell carcinoma responds about one-half as fast as stomach cancer.” (Ref.)With his therapy W Koch successfully treated various cancer types. Here are a few examples of successful cases http://www.williamfkoch.com/web/version2/drkoch.php?id=151.0&dispID=disp(2);%20disp(3). There is so much to say about what happen following the success of Prof. Dr. William F. Koch, and at this link you can read all in details, but on short, unfortunately for the general health, Dr. Koch was never given the research facilities and cooperation by the medical profession he had asked for and wanted.
Here are a few pieces of information that can give us a view on the drug used by Dr. Koch:
– Once, Dr. Koch stated about his anti cancer substance the following: “The compound is difficult to make and it deteriorates rapidly. If I published it and quacks or unscientific men started mixing it and treating cancer with it, the results would be disastrous, not only possibly to the patients, but to the ultimate success of the treatment. Improperly mixed or administered the compound would fail to do its work.” (Ref.)
– In another article this is what I found: It was an oxygen uptake product of some kind. The formula was O = C = C = O. According to the formula that Koch published it was a 10e-6 dilution, i.e. homeopathic formulation. He called this substance Glyoxylide (Ref.)
– And here is another piece of info on his formula: The theory that Koch had was one in which he equated the dilution of his product to enzymes in the blood
So, despite offers, he never made the formula for his medicine available to medical groups or drug companies, for fear they would change and pervert it.
The substance that Koch suggested he was using was O = C = C = O, and it was considered essentially nothing by FDA. Her is a quote “The formula was O = C = C = O, which means nothing, really” (Ref.) As a result, his drug was classified as a fraud by the FDA (Ref.).
quackwatch.com is stating the following about Koch’s glyoxylide: “Does Koch’s glyoxylide exist? The molecule glyoxylide has been a subject of investigation by chemists including H. Staudinger in 1913  to Berson in 1986 . Recently Sulzle  reviewed the literature and considered the theoretical possibilities for the existence of a compound like glyoxylide. He found that all efforts to prepare, isolate, or chemically identify this compound failed. His studies on the theoretical physical chemistry of glyoxylide showed that the substance described by Koch cannot exist in nature. This, along with Jenssen’s failure to find anything in Koch’s “medicine” , confirms the conclusion that the glyoxylide which Koch claims to have invented did not exist.” However …
… Nearly 100 years latter, during 2015, here is a headline from the scientific news: “Existence of elusive molecule confirmed after more than a century”. (Ref.) This shows how scientist at University of Arizona, USA, have discovered a small molecule with only four atoms that was “never been observed, neither as a substance nor as a transient species, despite a century-long history of attempts”. And guess what was the molecule discovered? That was exactly O = C = C = O (OCCO), the same that dr. Koch was suggesting he was using to treat cancer and FDA was saying that it doesn’t exist :). This simple molecule was so hard to find because it splits into two carbon monoxide (CO) fragments after half a nanosecond or so of existence. The discovery was made in Sanov’s lab, when his graduate students were experimenting with glyoxal – a chemical compound with the formula OCHCHO. (Ref.). So Koch’s OCCO precursor is actually glyoxal. OCCO is now called ethylenedione. The relation between Koch’s work and Glyoxal is also shortly discussed here.
This proves the fact that if you don’t see it doesn’t mean automatically that it doesn’t exist. It also means, quackwatch and FDA were wrong and need to update their statements on the above.
Therefore, Koch succeeded to find a way to synthesizing OCCO and keep it stable somehow until giving it to the patient or use substances that would trigger its production in the human body (Ref.), and with this cure cancer and other diseases. For more information on Koch’s story please see williamfkoch.com, a site maintained by the Koch family.
- In the middle of the last century …
Dr. Albert Szent-Gyorgyi was the Nobel Laureate in Medicine in 1937 for the isolation and discovery of Vitamin C. (Ref.) he also discovered Iso-Flavones and vitamin P. In his last 40 years, he researched the regulatory processes of cell growth, and thereby the regulation of cancer itself.
As early as 1958, Szent-Györgyi also worked on Methylglyoxal and together with his collaborators, in their pioneering work on the biological role of Methylglyoxal, had put forward strong evidences for the anti-cancer and tumor growth inhibitory effect of Methylglyoxal. For example, they showed that Methylglyoxal could completely inhibit the tumor development in mice. Here is the ‘Science’ paper published in 1968: Cancerostatic Action of Methylglyoxal.
Even earlier than that, in 1963, the prestigious magazine ‘Science’ published a remarkable article about his research. In it Dr. Szent-Gyorgyi identified two substances, one called Retine, which inhibited cancer growth (ascites tumors), and the other called Promine, which promoted cell growth and made cancer grow faster. (Ref.) He suggested that these were very small molecules that were highly potent in controlling cell division. His research using mice achieved shrinkage of tumors by increasing the ratio of Retine to Promine with daily injections of Retine. Other researchers obtained similar results and there were no harmful or toxic side effects.
In another article in Science he announced that they have succeeded to extract Retine from human urine. (Ref.) I find this interesting since urine therapy as an anticancer approach was/is a technique used by some. And here is another article referring to glyoxal offering a hopeful target in the search for cancerostatic substances (Ref.) and more on his view on methylglyoxal (Ref.) In 1967 he announced that his laboratory had isolated and manufactured Retine (retards cell growth) in the form of a Carbonyl compound called Methylglyoxal. (Ref.)
In an interview in Prevention magazine in 1972 conducted by Jane Kinderlehrer, he explained that he and “Dr. Egyud have found that retine (methylglyoxal) stops the growth of cancer cells without poisoning other cells. When retine is present in sufficient concentration, no cell division can occur while vital cellular processes go on unhindered. And what is a good bit of luck, and not my cleverness, the white-haired scientist pointed out, is that if a cancer cell cannot grow, it dies by itself.” According to the researchers, retine is normally produced by the body and, when it is, it prevents the growth of existing cancer cells. But the body can lose its ability to produce this substance… “Putting the retine back in the body, just as we put insulin back into a diabetics body, can stop the growth of cancer… ” (Ref.)
Dr. Szent-Gyorgyi acknowledged the work of Dr. William Koch on the same subject saying, “A decade ago, a very intuitive researcher, Dr. William F. Koch, came to the same conclusion about the possible importance of Carbonyls in regulation of cell division and carcinostasis.”
- At the end of the last century and beginning of our century …
About 50 years latter Prof. dr. Manju Ray, a very good Indian scientist in Molecular Enzymology and Cancer Biochemistry, build on Methyloglyoxal’s anti cancer effects. In a series of papers, she further demonstrated the potential of Methyloglyoxal. But she did not stop to the theory. Instead she trialed the drug on 19 patients with very advanced stages of cancer and resulted in an overall cure rate of 70 percent in cancer patients who were diagnosed as terminally ill, results presented in 2001.
In 2006 Prof. Dr. Manju Ray, presented a 5 year follow-up phase II study with methylglyoxal. It showed that of the 46 patients enrolled, 18 were in complete remission (so there were no tumors in clinical scans to see). The follow-up after 5 years of the patients took an average of 4 to 56 months. The results of the study showed that 18 (39%) patients achieved a complete remission, 18 (39%) patients had partial regression and / or stable disease, while 8 (17%) patients had progression of their disease.” After this, another successful clinical trial was conducted (see below).
With all these results in humans, Prof. Ray clearly underpinned the great anticancer effect of Methylglyoxal.
- Methylglyoxal can also enable or increase the effectiveness of DNA disrupting chemo therapy (Ref.).
- Ketogenic Diet seems to also increase intracellular Methylglyoxal (Ref.)
- Methylglyoxal can be also found in Manuka Honey in concentration of about 250mg/kg and it is believed to be responsible for the antibacterial and antiviral activity of the honey. (Ref.) Professor Thomas Henle of University of Dresden, Germany announced in 2008 that research “unambiguously demonstrates for the first time that Methylglyoxal is directly responsible for the antibacterial activity of Manuka honey.” http://www.manukaonline.com/mgo-Manuka-Honey-benefits.html
- However, note that while the amount of Methylglyoxal present in the honey (250mg/kg) may serve as a good preventive measure, for cancer treatment purpose this is too little. Given the Methylglyoxal dose that is proposed to cure cancer (see the Dose and Administration section below), we would need to eat kilograms of honey each day, which is not feasible. This is why, as it will be further discussed, other sources of Methylglyoxal are used in the clinical trails.
Other interesting articles to read:
In conclusion, the anticancer effect of methylglyoxal has been known for a long time. But relatively recent work has shown that it acts exclusively against malignant cellular mitochondrial complex I and GAPDH to elicit its anticancer effect. It has been used on humans and found that
- methylglyoxal is potentially safe for human consumption and able to destroy cancer cells in vivo
- a methylglyoxal-based anticancer formulation was administered orally to diverse groups of cancer patients in India
- In first group (14 months, January 2000-February 2001) 24 patients were recruited and complete remission was observed for 11 patients and partial remission for 5 patients.
- In the second group (60 months, October 2000-September 2005) 46 patients were recruited and complete remission was observed for 18 patients and partial remission for 18 patients.
- In the third group (42 months, May 2005-October 2008) of the 23 patients complete remission was observed for 11 patients and partial remission for 7 patients.
- The treatment was found to be especially effective for adenocarcinoma of urinary bladder, breast, uterus, esophageal and gastrointestinal tract cancer.
- Several vital biochemical, radiological and other parameters were tested in patients who received treatment for a long time to assess the possible long term toxicity of methylglyoxal treatment, if any, and the results implicated no toxicity as per the parameter studied.
- All the results showed great promise of methylglyoxal treatment and demands further improvisation the methylglyoxal based therapeutics. (Ref.)
- Due to its mechanims of action it could complement anticancer strategies involving Chemo, 3BP, DCA, Artemisinin, and any other pro oxidant drug.
Methylglyoxal as anti cancer treatment in Humans: Clinical trials
A methylglyoxal-based anticancer formulation was developed and a three-phase study of treating a total number of 86 cancer patients was carried out. The results appear to be promising. Most of the cancer patients benefited greatly and a significant number of patients became free of the disease. Contrary to the effect of existing anticancer drugs, this methylglyoxal-based formulation is devoid of any toxic effect and reasonably effective against a wide variety of cancers. (Ref.)
Here are the result from one of the study 46 patients:
Previous in vitro and in vivo studies had shown remarkable anticancer effect of methylglyoxal. A recent toxicological study with four different species of animals has shown that methylglyoxal is potentially safe for human consumption (Ghosh et al, 2006). We have developed an anticancer formulation with methylglyoxal as the principal ingredient. To test the efficacy of this formulation, 46 patients suffering from different types of malignancies in different stages of the disease were randomly chosen: brain –2, head and neck –2, gastrointestinal –11, lung –6, gynecological –6, breast –3, urological –4, hematological –2, prostate –2, gall bladder –1, pancreas –2, others –5. The effect of the formulation on overall survival, regression of the tumours and general well being of the patients were analyzed. The follow-up of the patients ranged from 4–56 months. The results of the study show that 18 (39%) patients had complete remission, 18 (39%) patients had partial regression and/or stable disease condition, whereas 8 (17%) patients had progressive disease. In addition to the measurable improvement of the majority of the patients there was remarkable improvement in the quality of life of nearly all the patients. There was no significant adverse side effect in almost all the patients. The significant antitumour effect of methylglyoxal against a wide variety of cancer suggests that all the different types of cancer may have common altered site(s). Our next task will be to further improve this treatment and to evaluate its efficacy with a large number of patients. http://www.cancer-therapy.org/pdf/CT%204B.pdf (if at any point this link doesn’t work please contact me – I have the PDF available).
Clearly, the results are great as they indicate 78% response rate, including 39% complete remission.
- a patient in the Netherlands keeping his cancer under control from 2001 to 2005 with MG. Doctors recognising the patient would not be there in 2005 without MG (Ref.)
Methylglyoxal (MG) is a highly reactive dicarbonyl compound and a potent glycating agent, mainly generated as a by-product of glycolysis through a spontaneous degradation of triosephosphates. In cancer, since the glycolytic pathways is highly active there is a lot of Methylglyoxal being produced. That is even more during the administration of DNA disrupting agents such as some of chemotheraphies (see next paragraph). Figure below shows how Methylglyoxal is produced inside the cell.
The cellular response to antitumour drugs that modified DNA or disrupt DNA metabolism is to activate processes of DNA repair, including poly(ADP-ribose) polymerase. This depletes cells of NAD+ such that glyceraldehyde-3-phosphate dehydrogenase activity is depleted and triosephosphates, glyceraldehyde-3-phosphate and dihydroxyacetonephosphate, increase. Methylglyoxal is formed mainly by triosephosphate degradation and since triosephosphates is increased strongly during the DNA repair, a consequent dramatic increase in methylglyoxal formation is expected. The increase of methylglyoxal will be negative for cancer cell potentiating for example the cytotoxic effect of the antitumour agents. As a result, to block methylglyoxal, the cancer cell will over express of Glo1 (Ref.)
Indeed, it has been shown that in mammalian cells, MG is detoxified by the glyoxalase system, an enzymatic pathway consisting of two enzymes called glyoxalase 1 (Glo-1) and glyoxalase 2 (Glo-2) and is based on reduced glutathione (GSH). It has been shown that Glo-1 expression and activity is increased in many human cancer types such as colon, prostate, melanoma, lung, and breast and that Glo-1 overexpression is correlated with cancer progression and drug resistance (Ref.).
Accumulation of Methylglyoxal in cancer cells are known to lead to the inhibition of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (Ref1, Ref2, Ref3), an essential enzyme acting in the glycolsisis pathway. GAPDH inhibition depletes ATP profoundly depriving the cancer cells of energy. Note that 3-bromopyruvate (3BP) is also inhibiting (GAPDH) (Ref1., Ref2.).
Next to GAPDH inhibition, Methylglyoxal induces mitochondria-dependent apoptosis http://www.ncbi.nlm.nih.gov/pubmed/22098242
One of the potential anticancer mechanisms of MG may be related to GABA A receptor. This is because MG seems to be an activator of GABA A receptor (Ref.). And GABA is known to show anti cancer activity via the GABA A receptor (Ref.1, Ref.2).
As a side note the activation of GABA A receptor triggers an influx of Cl- ions (Ref.).
Dose and Administration:
MG oral administration:
According to the clinical trial above (Ref.):
- 30mg methylglyoxal/kg of body weight/day
- this was divided in 4 administration/day (i.e. 7.5mg/kg/administration)
- each dose was followed by a tablet of chewable vitamin C containing 400 mg of sodium ascorbate
- Taking the drug on an empty stomach is NOT recommended
- Each patient also received orally a mixture of the B vitamins twice a day: B15mg, B6 2.5 mg, B12 5 mg and B5 7.5 mg. This mixture is usually a standard composition of vitamin B complex available
- The duration of treatment at the same or at a reduced dose was determined by evaluating the response and general condition of the patient
Now here is how to translate the above dose into what the chemical suppliers are selling:
- Sigma and others provide 40% MG concentration in water
- The density of MG is 1.17g/ml at 25C; this means that each ml of 40% MG contains 468mg MG
- Since the dose suggested for a day is 30mg/kg, a person of 50kg will need 1500mg MG/day
- Since each ml of 40% MG contains 468mg MG, the 50kg patient would need 3.2ml of 40% MG each day
- As a result 0.8ml of 40%MG has to be administrated 4x/day
- As suggested in the clinical trial, each of the 0.8ml will be administrated with 60ml water (i.e. in a small glass of water) after meal
Note: in addition to Vitamin B and Vitamin C suggested in the clinical trial I would also add Curcumin capsules (8g/day or lower if this is not possible) to inhibit glyoxalase 1 and possibly increase the effectiveness of MG treatment. Here is a patent that is suggesting the same https://www.google.com/patents/US8163796
15.05.2016: Update on formulation and dose: I was just informed by one of the readers in contact with dr. Ray that in case of very aggressive cancers she is now suggesting 40mg/kg/day dose. Here is a quote of the info I received: “40 mg/Kg/day. 5 ml of her formulations has to be taken with half a cup of water/fruit juice after meal/snack four times a day, followed by one 500 mg chew-able Vitamin C (2000 mg daily total), and two tablet Polybion after lunch and dinner.”
23.05.2016: Update on formulation, dose and administration following conversation with Prof. Manju Ray:
- Methylglyoxal (MG) used is available commercially as 40% aqueous solution
- We now use 40 mg/kg/day in four divided doses
- For example a person of 50 kg will need 2000 mg MG in four divided
- 40% methylglyoxal means 40 gm/100 ml (irrespective of density)
- Take 100 ml of 40% solution, add 300 ml of water (preferably distilled water)
- Total vol of diluted solution is 400 ml
- 400 ml contains 40000 mg,
- so a person of 50kg that needs 2000 mg/day will use 20ml of this diluted solution every day, in 4 devided doses, each of 5ml
- Mix 5 ml of diluted solution with 50-75 ml of water or fruit juice and give the patient to drink
- Such a dose should be given 4 times daily in 5-6 hrs intervals
- After each dose of methylglyoxal, 1 tab of chewable Vit C = 500 mg should be chewed (not swallow)
- tablet of Polybion after lunch and dinner is OK
- Curcumin is OK
- My addition: Creatine supplement is a must 30-60 min prior to MG administration (see below why)
Although in the clinical studies they did not used Creatine, following these statements, I would clearly make sure that (maybe 30-60 minutes) prior to each MG administration there is a Creatine supplement administer too.
Update on 21-June-2016:
MG IV administration:
Based on recent discussions with prof Manju Ray here is a dose that makes sense:
Koch formulations administration:
“A successful product if taken sublingually will be tasteless at first. Then within a few minutes a slightly astringent (cotton mouth) feeling will be experienced followed by a metallic taste. Many will go on to experience a transient warm flushed feeling several minutes later, and/or feelings of increased pep and mental alertness. Those subjects having allergic symptoms will usually experience relief within a few minutes. If one or more of the above occur, the product should be considered good. The product need not be injected, but can be administered sublingually or by aerosol.”http://bioredox.mysite.com/OCThtml/howmade.htm
Koch formulations are:
It is recommended to be given
- 1 Vial per day for 10 days- then –
- 1 Vial per week for 10 weeks- then –
- 1 Vial per month for the balance or until vials are gone. (Ref.)
Other sources are suggesting
- 1 Vial each day during 14 days
Regardless of the approach, the Vials are alternated, e.g. first day one vial Rhodizonsaure, second day one vial Carbonylgruppen, next day again one vial Rhodizonsaure and so on. (Ref.)
In acute conditions 1-3 times daily 1 ampoule (of 2ml) injected intramuscularly (im) or subcutaneously (sc). (Ref.) The vial can be administrated sublingual but is is preferred via injection, i.m. or s.c.
More about the therapy in German: http://www.windstosser-museum.info/museum/manuskript/aufklaerung/25.pdf (use google translator to translate)
Here is an e-mail I received from a friend from Cancer Compass (Jcancom) on a new formulation:
An even more recent patent that you sent me was using at most 0.5mg/kg/day methylglyoxal in a chitosan encapsulation. This would be even better. The instructions they give seem easy to do. I wonder whether this formulation could be bought somewhere? https://www.google.com/patents/WO2015049689A1?cl=en
Here are a few articles on the same MG-chitosan combination:
- Immunomodulation of macrophages by methylglyoxal conjugated with chitosan nanoparticles against Sarcoma-180 tumor in mice http://www.sciencedirect.com/science/article/pii/S0008874913001901
- Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect
I will soon have a look at the encapsulation of MG with chitosan since this is probably a much better route of administration, and chitosan is available and cheap. As soon as I have news on this I will update the page.
Synergy and Antagonism:
Creatine: New paper published in 2016 from dr. Roy, suggesting Creatine as supporting MG treatment: These data strongly suggest that creatine supplementation may gain importance as a safe and effective supplement in therapeutic intervention with the anti-cancer agent MG. http://www.ncbi.nlm.nih.gov/pubmed/27138627
Nrf2 I inhibitors: Besides GLO1, Nrf2 favour the survival of cancer cells by protecting them from excessive dicarbonyl and/or oxidative stress (Ref.) Nrf2 is often referred to as the main activator of cellular antioxidant response but it is also the main regulator of GLO1 and AKRs expression thus playing a central role in cell response to MG stress. Nrf2 inhibitors are discussed here (Ref.) and include Ascorbic Acid.
One of the potential anticancer mechanisms of MG may be related to GABA A receptor. This is because MG seems to be an activator of GABA A receptor (Ref.). And GABA is known to show anti cancer activity via the GABA A receptor (Ref.1, Ref.2). Therefore, combining MG treatment with GABA supplementation may increase the chance for a successful treatment. GABA is a commercially available supplement.
MG triggers GABA A receptor activation which in turn triggers an influx of Cl- ions (Ref.). Intracellular Cl- on the other hand is expected to reduce DCA’s anti cancer activity as it will reduce the efficiency of the DCA-induced GSTZ1 inactivation process (Ref.). As a result, I would not combine MG with DCA.
Update 10-March-2017: Metformin:
A great anti cancer drug, accessible and low/no side effects, but according to this article, unfortunately, Metformin may increase the Glo1 activity and as a result reduce MG effectiveness. Thus, Metformin should not be combined with MG: https://www.ncbi.nlm.nih.gov/pubmed/24710646
Based on an anecdotal report, a patient receiving MG got seven / eight weeks after he started with the methylglyoxal high fever, (41degrees). He stopped for one week MG and started again with no other issues. (Ref.)
Overall, the potential beneficial effects of methylglyoxal far outweigh its possible toxic role in vivo, and it should be utilized for the benefit of suffering humanity. (Ref.)
Although in the clinical studies they did not used Creatine, following these statements, I would clearly make sure that (maybe 30-60 minutes) prior to each MG administration there is a Creatine supplement administer too.
Methylglyoxal can be bought from Western or Chinese chemical suppliers under CAS number 78-98-8. It is usually found as 40% Methylglyoxal in water solution. Here is an example of a supplier: https://www.scbt.com/datasheet-250394-methylglyoxal-solution.html
MG Clinics and Hospitals:
The Indian hospital from enclosed reference (Ref.) was still running clinical trials in May 2016. Patients can access MG at the following address in India: Lokmanya Medical Research Centre, Chinchwad, Pune 411 033
It seems that a Mexican clinic at Providence Pacific Hospital administered methylglyoxal to humans at the begging of 2000 but I can not find more info on that.
Methylglyoxal, also called pyruvaldehyde or 2-oxo-propanal (CH3-CO-CH=O or C3H4O2) is the aldehyde form of pyruvic acid.
Update on 21-June-2016:
Prof Koch’s formulation:
Yesterday, I was informed by a friend from Cancer Compass (thank you Jet) that various sources of information indicate that Dr. Koch shared his homeopathic data and formulas with a Dr. Eric Reinstorff in Germany (now deceased). But that Dr. Dieter Reinstorff in Hamburg, Germany (Eric’s son) is still manufacturing, distributing it, and using Koch’s homeopathic reagents.
Indeed, here is an interview (from 2005, in German) with Dr. Reinstorff referring to his work with Prof. Koch. As a result, he started up a small pharma company („REIKO“ Pharma Vertriebsgesellschaft GmbH, „REIKO“ comes from Reinstorff-Koch) owning 3 different products based on Koch’s formulations: Carbonylgruppen, Rhodizonsäure, Parabenzochinon. The products seems to be manufactured by Adjupharm GmbH in Germany while being advertised at the following website http://wulf-rabe.de/molekulartherapie.php. The products are available at most German pharmacies without prescription:
- Rhodizonsäure (10 vials costs 22 euro)
- Parabenzochinon (10 vials costs 22 euro)
- Carbonylgruppen comp. (10 vials costs 20 euro)
In USA, it seems that the above vials are available too but 10 vials would cost 300$ http://www.arrowheadhealthworks.com/KochTMT.htm
A pharmaceutical composition and treatment method to reduce the proliferation of cancerous or tumor cells, in which the combined active agents are methylglyoxal, ascorbic acid, creatine and melatonin.
Oral formulation of methylglyoxal and its imino acid conjugates for human use https://www.google.com/patents/US20030087951
The invention relates to an oral formulation of methylglyoxal and/or its imino acid conjugates for human use and methods for preparing the compositions. Particularly, the invention relates to compositions comprising methylglyoxal and more particularly, imino acid conjugates of methylglyoxal. The present invention also relates to formulations of methylglyoxal and imino acid conjugates of methylglyoxal that can be used for the treatment and suppression of malignant diseases including but not limited to the cancers of Colon, Prostate, Pancreas, Lung, Oral cavity, Glioblastoma, and Leukemia.
Sustained release formulations containing methylglyoxal and their therapeutic applications https://www.google.com/patents/WO2015049689A1?cl=en
A novel nano drug composition for the treatment of cancer comprising 0.125-0.5 mg of methylglyoxal as conjugated to nanoparticles of chitosan, its derivatives, or other polymers; 25-100 mg of ascorbic acid; 75-300 mg of creatine; and 0.125-0.5mg of melatonin, wherein all constituents are meant for each kg of body weight.
Treatment of cancer by oxidation-reduction potentiation of cancerostatic dicarbonyls https://www.google.com/patents/US8163796
A novel treatment regimen is described for the control and elimination of cancer cell populations including cancer stem cells. The disclosed protocol consists of a pretreatment step followed by a treatment step. The pretreatment step sensitizes cancer cells to apoptosis by altering their intracellular oxidation-reduction state via reduced glutathione depletion. The treatment step involves the sequential administration of a cancerostatic dicarbonyl compound to induce apoptosis. The use of nanoparticle delivery systems further enhances both the pharmacokinetic and pharmacodynamic properties of the pretreatment compounds and the cancerostatic dicarbonyls. Since the pretreatment and treatment compounds are carefully selected and delivered, normal cells are not affected and side effects are kept to a minimum.
Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems – role in ageing and disease http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649415/
Glycation of proteins, nucleotides and basic phospholipids by glyoxal and methylglyoxal – physiological substrates of glyoxalase 1 – is potentially damaging to the proteome, genome and lipidome. Glyoxalase 1 suppresses glycation by these α-oxoaldehyde metabolites and thereby represents part of the enzymatic defence against glycation. Albert Szent-Gyorgyi pioneered and struggled to understand the physiological function of methylglyoxal and the glyoxalase system. We now appreciate glyoxalase 1 protects against dicarbonyl modifications of the proteome, genome and lipome. Latest research suggests there are functional modifications of this process – implying a role in cell signalling, ageing and disease.
Methylglyoxal enhances cisplatin-induced cytotoxicity by activating protein kinase Cdelta. http://www.ncbi.nlm.nih.gov/pubmed/11707430/
Importantly, co-treatment of cells with the reactive carbonyl MGO and cisplatin increased apoptosis by 90% over the expected additive effect of combined MGO and cisplatin treatment. This same synergism was also observed when ROS generation was examined. MGO and cisplatin increased PKCdelta activity by 4-fold
Effects of methylglyoxal and glyoxalase I inhibition on breast cancer cells proliferation, invasion, and apoptosis through modulation of MAPKs, MMP9, and Bcl-2. http://www.ncbi.nlm.nih.gov/pubmed/26618552
Collectively, these data indicate that MG or inhibition of GLOI induces anticancer effects in breast cancer cells and that these effects are potentiated by combination of the 2.
Triple negative tumors accumulate significantly less methylglyoxal specific adducts than other human breast cancer subtypes http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170620/
Interestingly, the activity of glyoxalase 1 (Glo-1), an enzyme that detoxifies MG, was significantly higher in triple negative than in other subtype lesions, suggesting that these aggressive tumors are able to develop an efficient response against dicarbonyl stress. Using breast cancer cell lines, we substantiated these clinical observations by showing that, in contrast to triple positive, triple negative cells induced Glo-1 expression and activity in response to MG treatment.
Inactivation of glyceraldehyde-3-phosphate dehydrogenase of human malignant cells by methylglyoxal. http://www.ncbi.nlm.nih.gov/pubmed/9450641
The effect of methylglyoxal on the activity of glyceraldehyde-3-phosphate dehydrogenase (GA3PD) of several normal human tissues and benign and malignant tumors has been tested. Methylglyoxal inactivated GA3PD of all the malignant cells (47 samples) and the degree of inactivation was in the range of 25-90%, but it had no inhibitory effect on this enzyme from several normal cells (24 samples) and benign tumors (13 samples). When the effect of methylglyoxal on other two dehydrogenases namely glucose 6-phosphate dehydrogenase (G6PD) and L-lactic dehydrogenase (LDH) of similar cells was tested as controls it has been observed that methylglyoxal has some inactivating effect on G6PD of all the normal, benign and malignant samples tested, whereas, LDH remained completely unaffected. These studies indicate that the inactivating effect of methylglyoxal on GA3PD specifically of the malignant cells may be a common feature of all the malignant cells, and this phenomenon can be used as a simple and rapid device for the detection of malignancy.
Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect. http://www.ncbi.nlm.nih.gov/pubmed/25999714
Fourier transform infrared spectroscopy revealed the presence of imine groups in Nano-MG due to conjugation of the amino group of chitosan and carbonyl group of MG with diameters of nanoparticles ranging from 50-100 nm. The zeta potential of Nano-MG was +21 mV and they contained approximately 100 μg of MG in 1 mL of solution. In vitro studies with Nano-MG showed higher cytotoxicity and enhanced rate of apoptosis in the HBL-100 cell line in comparison with bare MG, but no detrimental effect on normal mouse myoblast cell line C2C12 at the concerned doses. Studies with EAC cells also showed increased cell death of nearly 1.5 times. Nano-MG had similar cytotoxic effects on A549 cells. In vivo studies further demonstrated the efficacy of Nano-MG over bare MG and found them to be about 400 times more potent in EAC-bearing mice and nearly 80 times more effective in sarcoma-180-bearing mice. Administration of ascorbic acid and creatine during in vivo treatments augmented the anticancer effect of Nano-MG.
Glyceraldehyde-3-phosphate dehydrogenase: a promising target for molecular therapy in hepatocellular carcinoma. http://www.ncbi.nlm.nih.gov/pubmed/22964488
Hepatocellular carcinoma (HCC) is one of the most highly lethal malignancies ranking as the third leading-cause of cancer-related death worldwide. Although surgical resection and transplantation are effective curative therapies, very few patients qualify for such treatments due to the advanced stage of the disease at diagnosis. In this context, loco-regional therapies provide a viable therapeutic alternative with minimal systemic toxicity. However, as chemoresistance and tumor recurrence negatively impact the success of therapy resulting in poorer patient outcomes it is imperative to identify new molecular target(s) in cancer cells that could be effectively targeted by novel agents. Recent research has demonstrated that proliferation in HCC is associated with increased glucose metabolism. The glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a multifunctional protein primarily recognized for its role in glucose metabolism, has already been shown to affect the proliferative potential of cancer cells. In human HCC, the increased expression of GAPDH is invariably associated with enhanced glycolytic capacity facilitating tumor progression. Though it is not yet known whether GAPDH up-regulation contributes to tumorigenesis sensu stricto, emerging evidence points to the existence of a link between GAPDH up-regulation and the promotion of survival mechanisms in cancer cells as well as chemoresistance. The involvement of GAPDH in several hepatocarcinogenic mechanisms (e.g. viral hepatitis, metabolic alterations) and its sensitivity to a new class of prospective anticancer agents prompted us to review the current understanding of the therapeutic potential of targeting GAPDH in HCC.
Anti-Cancer Strategies of Methylglyoxal http://www.ijpr.in/Data/Archives/2015/july/2006201502.pdf
Methylglyoxal a simple carbonyl compound containing a reactive aldehyde and a ketonic group which stops the growth of cancer cells without poisoning normal cells. It is also called as Retine. These are very small molecules that are highly potent in controlling cell division. This compound inhibits the enzymes required for cancer cell and infected cell to grow by respiration and does not harm normal cells. As cancer cells require large amount of energy to multiply which was provided by ATP. Methylglyoxal inactivates the enzyme Glyceraldehyde-3-phosphate Dehydrogenase (GA3PD) needed for the ATP production in cancer cells and there by starves the cell to death and normal cells remain unaffected. As it is a carbonyl group, it inhibits the mitochondrial respiration followed by Glycolysis and Kreb’s cycle which play a major role in the production of ATP and supplies the energy to infected cell up to demand. It also play a role in binding of oxygen at cellular level and preventing the proteins to desaturate and inhibits the production of free radicals. Hence suitable energy and oxygen are unavailable to cancerous cell to grow, leading to death of the cell. It was believed that “If cancer cell cannot grow, it dies by itself”. It desaturate the proteins of malignant cell at cellular level by means of its ketoaldehyde group with an aminoacid of a protein causing the death of cell
The results clearly indicate that Nano-MG may constitute a promising tool in anticancer therapeutics in the near future.
Cancerostatic Action of Methylglyoxal http://science.sciencemag.org/content/160/3832/1140
Creatine supplementation with methylglyoxal: a potent therapy for cancer in experimental models. http://www.ncbi.nlm.nih.gov/pubmed/27138627
In conclusion, it may be stated that the anti-cancer effect of MG is enhanced by concomitant creatine supplementation, both in chemically transformed (by 3MC) muscle cells in vitro as well as in sarcoma animal model in vivo. These data strongly suggest that creatine supplementation may gain importance as a safe and effective supplement in therapeutic intervention with the anti-cancer agent MG.
Curcumin inhibits glyoxalase 1: a possible link to its anti-inflammatory and anti-tumor activity. http://www.ncbi.nlm.nih.gov/pubmed/18946510
The results described herein provide new insights into curcumin‘s biological activities as they indicate that inhibition of Glo1 by curcumin may result in non-tolerable levels of MGO and GSH, which, in turn, modulate various metabolic cellular pathways including depletion of cellular ATP and GSH content. This may account for curcumin‘s potency as an anti-inflammatory and anti-tumor agent. The findings support the use of curcumin as a potential therapeutic agent.
Curcumin inhibits advanced glycation end product-induced oxidative stress and inflammatory responses in endothelial cell damage via trapping methylglyoxal http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732849/
Methylglyoxal (MGO) inhibits proliferation and induces cell death of human glioblastoma multiforme T98G and U87MG cells. http://www.ncbi.nlm.nih.gov/pubmed/27133062
We have also revealed that MGO induces senescence of U87MG but not T98G cells, but further studies are necessary in order to clarify and check mechanism of action of methylglyoxal and it Is a positive phenomenon for the treatment of GBM.
A novel mechanism of methylglyoxal cytotoxicity in prostate cancer cells. http://www.ncbi.nlm.nih.gov/pubmed/23333621
The results suggest that this physiological compound merits investigation as a potential chemo-preventive/-therapeutic agent, in differently aggressive prostate cancers.
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