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I have inserted a separate page for DMG, the banished vitamin B15. As far as I am concerned, DMG is the most remarkable  vitamin supporting the immune and neurological systems.  This article has also a link in my Get Angry section, and you will find out why if you read it.  DMG is an inexpensive anti-cancer vitamin that has been around for more than half a century, and is now being developed into a pharmadrug.   Since I wrote this article, there is more research and more writers and consumers are becoming aware of the value of DMG, which is great, as much suffering can be reduced by using this nutrient.
 

DMG - Is it  a Panacea?                          
By Elena N. Marcus  
July, 2005
 

           There is probably no other nutritional supplement that claims as many health benefits as DMG ((N,N-dimethylgycline)), and none more controversial. It is claimed that it benefits the energy processes, cardiovascular functions, glucose and oxygen utilization, and the immune response.  Supporters contend there are thousands of scientific studies proving it helpful in diabetes, alcoholism, autism,  skin conditions, liver toxicity, high blood pressure, schizophrenia, senility, chemical poisoning, blood homocysteine levels, allergies, and arthritis.  According to Elson Haas M.D., DMG “may be useful” in headache, angina, musculoskeletal chest pain, shortness of breath, insomnia, general stress, high cholesterol, high blood pressure, atherosclerosis. In Europe, according to Haas, it is being recognized as an antioxidant and a circulation booster. From personal communication, DMG eye drops, which are sold over the counter,  are used in Russia for cataracts and neurological conditions.  “More studies regarding all claims …must be done…” writes Haas at the end of his own enumeration [1]. The safety of DMG is unquestionable, as the equivalent of 500 gm/ per kg [sic!] in humans has shown no negative effects. [2] On the other hand, researchers in Russia have used just 100  mg per person, per day, to obtain positive therapeutic effects in heart disease and neurological conditions.  

Since money for double-blind studies on pure nutritional supplements is hard to come by, and apparently the studies which were done were not all published in mainstream journals, health consumers have to do their own risk management, by weighing the claimed benefits versus the claimed toxicity, in light of the evidence (sparse  as is), the history, and the cost.

The DMG indeed is an intermediary metabolite in several body systems. It is found in small quantities in some foods such as brown rice, brewer’s yeast, pumpkin and sunflower seeds, and liver. According to Haas, it was first extracted in 1951 by father and son Ernst Krebs Jr. and Sr. from apricot pits.  Most of the DMG in the body however is derived  from internal synthesis from betaine and choline.  Betaine, which is trimethylglycine (TMG),  is also sold as a food supplement. Studies show that TMG  lowers homocysteine levels,  high homocysteine being a dangerous marker for cardiovascular disease.  The TMG was found however to increase blood lipid levels [3]. On the other hand a group of Indian researchers found that  DMG  lowers both homocysteine and blood lipids [4]

Pure DMG (N,N-dimethylgycline), “when labeled as single ingredient compound for food use only” (as allowed by the FDA) is being sold in the United States as a nutritional supplement.  The only claim that can be made about it is that it reduces lactic acid in the blood, which in itself is no small matter, as lactic acid is a toxic substance.  Strenuous exercise increases lactic acid production, however, there are medical conditions in which lactic acid is high as well, due to metabolic defects. The FDA cannot ban DMG but it has a specific policy against DMG compounds, especially a DMG ester called pangamic acid.   It recommends legal action against “all pangamic acid products with accompanying labeling containing disease claims (including products containing dimethyl glycine mixed with other compounds such as calcium gluconate)…” Importation of such products is also prohibited.   Although, at one time pangamic acid apparently contained a compound which was toxic, instead of DMG, the FDA policy is not limited to such mishaps.  In 1992 the FDA  confiscated $3,775-worth of calcium pangamate ( pangamic acid) tablets from a distributor in Pennsylvania  on the following charge: “Adulterated – The product contains the food additive, N,N-dimethylglycine, which is unsafe because there is no regulation in effect prescribing the conditions under which the additive may be safely used” [5]. In spite of the fact that such compounds had long been recognized as harmless even by the most hardened health claim detractors, the FDA has been revising this policy regularly since first instituted in 1976. The 1970’s witnessed the most dramatic clash between the corporate medicine (with the FDA at its side) and naturopathic physicians supported by consumers, when Ernst T. Krebs Jr. and his followers -- against the wrath of established cancer institutions -- claimed that laetrile, a thiocyanate-yielding  compound which he isolated also from apricot pits, had anti-cancer properties.  Krebs  -- who had written about the therapeutic and cancer-preventive value of thiocyanate-yielding plants such as broccoli (which he called ‘nitrilosides’)  since the 1950’s-- claimed that both thiocyanate and dimethylglycine were vitamins (B 17 and B15 respectively).  Krebs credibility is vindicated as thiocyanate has been recognized as one of broccoli’s anti-cancer compounds since the early 1980s.

DMG a Nontoxic Outstanding Immune Booster

The DMG record seems to vindicate Krebs again.  Although not a vitamin yet, it appears to be a potent immune booster. In a study published in January 1981 in the Journal of Infectious Diseases C.D. Graber and his colleagues report that in a double blind-study with 20 human volunteers, DMG was found to cause a fourfold increase in the antibody response to pneumococcal vaccine.  From the entire study, the researchers concluded that “DMG enhances both humoral and cell-mediated responses in humans” [6].

A few years later, in 1990, E.A. Reap and J. W. Lawson from the Department of Microbiology, Clemson University, SC, have also proven the high immune response to DMG in rabbits. They found that DMG conferred a threefold to tenfold increase in immune markers in response to various antigens, without noted toxicity [7].

For every favorable DMG study, there are several studies demonstrating its worthlessness.  A study in 1982 for example showed that DMG didn’t improve treadmill performance in 16 male track athletes. Another studies disclaimed previous studies of athletic performance enhancement in horses[8].
 

Compound of DMG Attacks Tumor Cells

More recently, in a study published in December 2004, a group of researchers from the University of Belgrad  describes a new potentially chemotherapeutic compound containing dimethylglycine which was found to attack cancer tumor cells in rats without damaging normal cells [9].
 

A DMG Ester: an Ideal Antitumor Agent

In December 2001, a press release in Paris announced the collaboration agreement between Sonofi-Synthelabo (Paris Stock Exchange: Sicovam code 1205) and Cephalon (Nasdaq:CEPH) to develop and market angiogenesis inhibitors.  Angiogenesis is the part of the metastatic process by which new blood vessels are created, usually at the site of a tumor, allowing cancer genes to spread.  The agreements consists in the French laboratory creating the drugs, using Cephalon’s patented technology, in exchange for “co-promotion” in marketing rights in the United States, Canada and Mexico, and exclusive rights in Europe and the rest of the world, except Japan.  For CEP-7055, the first drug to be developed, Cephalon was to get approximately 32 million dollars.

According to the study authors, the mysterious CEP-7055 is a dimethylglycine ester. Accidentally, pangamic acid the DMG vehicle banned by FDA which has been researched and used for decades is also a dimethylglycine ester.

According to a study published in December 2003 by  D.E. Gingrich and his colleagues  CEP-7055 was a “dimethylglycine ester prodrug clinical candidate.”  The CEP-7055, of which name is not based on its chemical composition but on its owning company, is presented as “a novel, orally active …inhibitor…with potent antiangiogenetic activity and antitumor efficacy in preclinical models”  [10].

 
In another animal study published by the same authors from the Department of Oncology, Cephalon, Inc. West Chester,  Pennsylvania, (Note: it’s a ‘department’ but it’s not a university) CEP-7055 is a “fully synthethic orally active N,N –dimethylglycine ester of CEP-5214,” both this compounds being found very potent anti-cancer factors all in absence of “apparent cytotoxicity.” A single doze of CEP-7055 or CEP-5214 resulted in inhibition of angiogenesis (vascularization that permits metastasis). Chronic administration of CEP-7055 resulted in inhibition between 50 and 90 percent in the growth of a variety of tumors in mice, including melanomas, glioblastoma, lung carcinoma, pancreatic carcinoma, colon carcinoma, breast carcinoma and angiosarcoma. CEP-7055 appears an ideal anti-tumor agent as it engenders both apoptosis (cell death) and inhibition of blood vessel expansion[11].
 
Considering the long-standing claims regarding dimethylglycine and its anticancer properties, it is likely that the active compound in this DMG ester is nothing else but DMG. 

 
A prodrug is a drug expecting means of delivery, that is a method of making its therapeutic value available to the body. While a nutritional supplement cannot be patented in itself, a method that makes it easier to absorb can.  Pure DMG is chemically unstable (light, humidity, and heat destroy it), however it can be compounded with calcium gluconate to form pangamic acid as it was done in Ernst T. Kreb’s times.  As such, it was apparently tested around the world in numerous diseases, such as cardiovascular disease, diabetes, neurological and immune disorders, as well as cataracts.   Pure DMG however, in a more expensive individual, airtight wrapping, doesn’t need to be in a stailizing compound, as it can by-pass the digestive system and be easily absorbed when taken sublingually. Taken this way, it quickly enters its metabolic action in 15 minutes, according to an Italian study. Another way of delivering DMG  is through betaine (TMG), as DMG is one of its metabolite. Once in the liver, TMG delivers one of its methyl group and becomes DMG.  The TMG is being studied in relation with its capacity to lower homocysteine levels and in the process, giving out a methyl group and turning itself into DMG.   Homocysteine, a generator of free radicals and a marker for cardiovascular disease risk, can be lowered in healthy individuals with folic acid. Betaine does lower the level to a lesser extent, however, it may raise cholesterol and blood lipids which is not a good deal.  The DMG is not known to raise cholesterol, in the contrary, it apparently lowers blood lipids [4].

 

References:

 

1. Elson Haas M.D.. Staying Healthy with Nutrition, Celestial Arts, Berkeley, 1992.

 
2. Braverman, Pfeiffer, The Healing Nutrients Within, Keats, 1987:251.


3. Schwahn BC, Hafner D, Hohlfeld T, Balkenhol N. Laryea MD, Wendel U. Pharmacokinetics of oral betaine in healthy subjects and patients with homocystinuria, Br J Clin Pharmacol. 2003 Jan:55(1):6-13. [PubMed].


4. Gopalan Kutty N, Ananthalakshmi J. Comparison of the hypoglycaemic effects

of dimethyglycine and glibenclamide in normal and diabetic rats

 Xxxiii Annual Conference Of The Indian Pharmacological Society, Gandhinagar, December 28-30, 2000

Indian Journal of Pharmacology 2001; 33: 296-308


5. http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074396.htmThis is a current link with the FDA position on Pangamic Acid (and DMG as Vitamin B15). June 6, 2010


6. Graber CED, Goust JM, Glassman AD, Kendall R, Loadholt CB. Immunomodulating properties of dimethylglycine in humans, J Infect Dis 1981 Jan; 1143(1):101-5. [PubMed]


7. Reap EA, Lawson JW, Stimulation of the immune response by dimethylgycine, a nontoxic metabolite, J. Lab Clin Med. 1990 Apr:115(4):481-6.[PubMed]


8. Gray ME, Titlow LW. The effect of pangamic acid on maximal treadmill performance. Med Sci Sports Exerc. 1982;14(6):424-7.

 
9. Djinovic V, Momcilovic M, Grguric-Sipka S, Trajkovic V, Mostarica Stojkovic M, Miljkovic D, Sabo T. Novel ruthenium complex k2[Ru(dmgly)C14].2H20 is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes. J Inorg Biochem, 2004, Dec;98(12):2168-73. [PubMed].


10. Ruggeri B, Singh J, Gingrich D, Angeles T, Albom M, Yang S, Chang H, Robinson C, Hunter K, Dobrzanski P, Jones-Bolin S, Pritchard S, Aimone L, Klein-Szanto A, Herbert JM, Bono F, Schaeffer P, Casellas P, Bourie B, Pili R, Isaacs J, Ator M, Hudkins R, Vaught J, Mallamo J, Dionne C. CEP-7055: a novel, orally active pan inhibitor of vascular endotheliall growth factor receptor tyrosine kinases with potent antiangiogenic activity and antitumor efficacy in preclinical models. Cancer Res. 2003, Sep 15;63(18):5978-91.

 
11. Gingrich et al.  A new class of potent vascular endothelial growth factor receptor tyrosine kinase inhibitors…J Med Chem 2003 Dec. 4; 469(25):5375-88.

 
 
©    2005
 
Copyright: Elena N. Marcus  
 
Comprehensive information on DMG:
www.dmgdoctor.com/