Dimethylglycine

• How It Works

  Dimethylglycine has been used to improve immune function and to manage autism and seizures, but evidenced is mixed or lacking.

  Dimethylglycine (DMG) 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
    Limited studies have produced mixed results, and a recent systematic review did not find evidence of benefit with DMG for autism symptoms. 
  • Epilepsy
    Single case reports describe decreased seizure frequency, but larger studies have not documented any benefit.
  • Attention deficit-hyperactivity disorder (ADHD)
    There is no scientific evidence to support this use.
  • Chronic fatigue syndrome
    There is no scientific evidence to support this use.
• Scientific Name

  N,N-dimethylglycine

• 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⁾. Choline and DMG are present at higher levels in fetal versus maternal plasma ⁽³⁾. Plasma DMG levels have been found to be lower in children with cystic fibrosis than in healthy children ⁽⁴⁾.

  Animal studies on whether DMG can enhance immune response are mixed ^(5) (6).

  Studies in humans are also quite limited. A few studies suggest DMG may help enhance both humoral and cell-mediated immune responses ⁽²⁾, and enhance oxygen utilization during hypoxia, as well as reduce lactic acid build-up in the blood during stressful events and the number of seizures ⁽¹⁾. However, DMG had no effect on oxygen consumption in children with SLSJ-COX deficiency ⁽⁷⁾, and its use to treat seizures or autism stays controversial as limited clinical trials have yielded mixed results ^(1) (8). In addition, a systematic review of supplements found no effects with DMG for autism symptoms ⁽¹¹⁾.

  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
  • ADHD
  • Chronic fatigue syndrome
• Mechanism of Action

  Choline and DMG are present at higher levels in fetal versus maternal plasma, suggesting that choline provides glycine via DMG for glutathione synthesis in fetal development ⁽³⁾.

  Enhanced physical performance in animals with DMG supplementation may occur via improved oxygen utilization and reduced lactic acid formation. In humans, it is thought to enhance humoral and cell-mediated immune responses ⁽²⁾. No mechanisms have been uncovered to elucidate claims of DMG for autism, attention deficit-hyperactivity disorder, epilepsy, chronic fatigue syndrome, or athletic performance enhancement. A recent metabolic analysis of healthy subjects correlated high plasma cholesterol levels with low levels for some metabolites related to mitochondrial metabolism including dimethylglycine ⁽⁹⁾.

  DMG has been used as an ester to increase the solubility and bioavailability of a prodrug used in cancer research ⁽¹⁰⁾. However, DMG is not the active moiety and there is no evidence it has any antitumor effects.

• 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. Reap EA, Lawson, JW. Stimulation of the immune response by dimethylglycine, a nontoxic metabolite. J Lab Clin Med. 1990;115(4):481-6.

  6. Weiss RC. Immunologic responses in healthy random-source cats fed N,N-dimethylglycine-supplemented diets. Am J Vet Res. 1992;53(5):829-33.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Gogou M, Kolios G. The effect of dietary supplements on clinical aspects of autism spectrum disorder: A systematic review of the literature. Brain Dev. Sep 2017;39(8):656-664.