Dimethylglycine

Health Care Professional Information

Scientific Name
N,N-dimethylglycine
Common Name

N,N-Dimethylglycine, (dimethylamino)acetic acid, N-methylsarcosine

Clinical Summary

Dimethylglycine (DMG) is a derivative of the amino acid glycine. It is found naturally in plant and animal cells and in certain foods such as beans, cereal grains, and liver. DMG is produced in cells during the metabolism of choline (1) and is considered an antioxidant and enhancer of oxygenation at the cellular level (2). It has been found that choline and DMG are present at higher levels in fetal than in maternal plasma, suggesting that choline provides glycine via DMG for glutathione synthesis in fetal development (3). Plasma DMG levels have also been found to be lower in children with cystic fibrosis than in healthy children (4). DMG has purported use in enhancement of the immune system, stimulation of neurological functions, management of autism and epilepsy (1) (5) (6). Some studies have shown that DMG may help enhance both humoral and cell-mediated immune responses in humans and animals (2) (7), enhance oxygen utilization during hypoxia, reduce lactic acid build-up in the blood during stressful events, and the number of seizures (1). However, conflicting data suggest that DMG has no effect on either specific or nonspecific immunity (8). DMG was also found to have no effect on oxygen consumption (VO2) in children with SLSJ-COX deficiency (9). The use of DMG to treat seizures or autism also stays controversial as clinical trials have yielded mixed results (1) (10) (11). DMG is non-toxic (7) and no significant adverse effects have been reported. DMG should not be confused with trimethylglycine (TMG), also know as betaine, that is involved in the methylation of homocysteine to form methionine.

Food Sources

Beans, cereal grains, liver

Purported Uses
  • Athletic-performance enhancer
  • Immunostimulant
  • Autism
  • Epilepsy
  • Attention deficit-hyperactivity disorder
  • Chronic fatigue syndrome
Mechanism of Action

DMG supplementation has been used to enhance physical performance in animals perhaps via improved oxygen utilization and reduced lactic acid formation, but clinical studies are lacking. In humans it is thought to enhance humoral and cell-mediated immune responses (2). Purported uses for DMG include autism, attention deficit-hyperactivity disorder, epilepsy, chronic fatigue syndrome, and athletic performance enhancement; however, no mechanisms of action have been uncovered to elucidate such claims. A recent metabolic analysis of healthy subjects correlated high plasma cholesterol levels with low levels for some metabolites related to mitochondrial metabolism including dimethylglycine (12). DMG has been used as an ester to increase the solubility and bioavailability of a prodrug used in cancer research (13). However, DMG is not the active moiety and there is no evidence it has any antitumor effects.

Pharmacokinetics

Absorption: DMG is absorbed from the small intestine and transported to the liver by the portal circulation.
Metabolism/Excretion: DMG is metabolized in the liver into monomethylglycine or sarcosine via an oxidative demethylation by the enzyme dimethylglycine dehydrogenase.

Literature Summary and Critique

Kern JK, Miller VS, Cauller PL, et al. Effectiveness of N,N-dimethylglycine in autism and pervasive developmental disorder. J Child Neurol, 2001;16(3):169-73.
This double-blinded, placebo-controlled study evaluated the effectiveness of dimethylglycine on autistic children. Thirty-seven children between 3 and 11 years of age with autism and/or pervasive developmental disorder were randomly assigned to either placebo or dimethylglycine for four weeks. Both placebo and the dimethylglycine groups showed an overall improvement in all behavioral measures compared with baseline. However, the improvement seen in the dimethylglycine group was not statistically different from that observed in the placebo group.

Liet JM, et al. The effect of short-term dimethylglycine treatment on oxygen consumption in cytochrome oxidase deficiency: a double-blind randomized crossover clinical trial. J Pediatr. 2003 Jan;142(1):62-6.
This randomized, cross-over, double-blind clinical trial investigated the effect of DMG on oxygen consumption in children with Saguenay-Lac-Saint-Jean cytochrome oxidase (SJS-COX) deficiency. Five children with SJS-COX syndrome were treated with placebo or DMG for 3 days, and were then administered the alternate treatment after a 2 week washout period. Oxygen consumption (VO2) was measured by indirect calorimetry before and after each treatment. DMG was well-tolerated and resulted in markedly increased DMG blood levels compared with baseline measures. Mean VO2 was lower after administration of DMG or placebo, but neither effect was statistically significant. DMG also had no effect on blood lactate, pyruvate, bicarbonate, or pH levels. Subject VO2 levels (101-135 mL-min-1m-2) were determined to be lower than published norms (150-160 mL-min-1m-2). The authors concluded that treatment with DMG does not substantially change VO2 in children with SJS-COX deficiency.

Dosage (Inside MSKCC Only)
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References
  1. Kern JK, Miller VS, Cauller PL, et al. Effectiveness of N,N-dimethylglycine in autism and pervasive developmental disorder. J Child Neurol. 2001;16(3):169-73.
  2. Graber CD, Goust JM, Glassman AD, et al. Immunomodulating properties of dimethylglycine in humans. J Infect Dis. 1981;143(1):101-5.
  3. Friesen RW, Novak EM, Hasman D, Innis SM. Relationship of dimethylglycine, choline, and betaine with oxoproline in plasma of pregnant women and their newborn infants. J Nutr. 2007 Dec;137(12):2641-6.
  4. Innis SM, Davidson AG, Bay BN, Slack PJ, Hasman D. Plasma choline depletion is associated with decreased peripheral blood leukocyte acetylcholine in children with cystic fibrosis. Am J Clin Nutr. 2011 Mar;93(3):564-8.
  5. Dimethylglycine (DMG). http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/dim_0097.shtml. Accessed December 8, 2009.
  6. Hariganesh K, Pratibha J. Effect of dimethylglycine on gastric ulcers in rats. J Pharm Pharmacol. 2000;52(12):1519-22.
  7. Reap EA, Lawson, JW. Stimulation of the immune response by dimethylglycine, a nontoxic metabolite. J Lab Clin Med. 1990;115(4):481-6.
  8. Weiss RC. Immunologic responses in healthy random-source cats fed N,N-dimethylglycine-supplemented diets. Am J Vet Res. 1992;53(5):829-33.
  9. Liet JM, Pelletier V, Robinson BH, et al. The effect of short-term dimethylglycine treatment on oxygen consumption in cytochrome oxidase deficiency: a double-blind randomized crossover clinical trial. J Pediatr. 2003 Jan;142(1):62-6.
  10. Bolman WM, Richmond JA. A double-blind, placebo-controlled, crossover pilot trial of low dose dimethylglycine in patients with autistic disorder. J Autism Dev Disord. 1999;29(3):191-4.
  11. Herbert JD, Sharp IR, Gaudiano BA. Separating Fact from Fiction in the Etiology and Treatment of Autism: A Scientific Review of the Evidence. http://www.quackwatch.org/01QuackeryRelatedTopics/autism.html. Accessed December 8, 2009.
  12. Bernini P, Bertini I, Luchinat C, et al. The cardiovascular risk of healthy individuals studied by NMR metabonomics of plasma samples. J Proteome Res. Nov 4 2011;10(11):4983-4992.
  13. Jones-Bolin S, Zhao H, Hunter K, et al. The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice. Mol Cancer Ther. Jul 2006;5(7):1744-1753.

Consumer Information

How It Works

Bottom Line: Dimethylglycine has not been used to treat cancer in humans.

Dimethylglycine is an amino acid found naturally in plant and animal cells and in many foods such as beans, cereal grains, and liver. It is used to improve energy, boost the immune system and to manage seizures and autism. There are some positive reports of DMG efficacy on the immune system. However, none of these claims have been confirmed in clinical trials.

Purported Uses
  • Athletic-performance enhancer
    There is no scientific evidence to support this use.
  • Immunostimulant
    There is conflicting data about the efficacy of dimethylglycine in boosting the immune system.
  • Autism
    Previous studies produced mixed results. Large scale clinical trials are needed.
  • Epilepsy
    Single case reports describe decreased seizure frequency but larger studies have not documented any benefit.
  • Attention deficit-hyperactivity disorder
    There is no scientific evidence to support this use.
  • Chronic fatigue syndrome
    There is no scientific evidence to support this use.
Research Evidence

Immunostimulation
Dimethylglycine showed positive immunomodulating properties in humans and animals. However, in some studies DMG did not increase immunity. And long-term use may not be good for immune system.

Management of Autism
Some studies suggest that DMG can improve symptoms in autistic children. However, DMG is no more effective than a placebo.

Special Point

DMG should not be confused with trimethylglycine (TMG), also know as betaine. TMG is involved in the methylation of homocysteine to form methionine.

E-mail your questions and comments to aboutherbs@mskcc.org.