DMG (N,N-Dimethylglycine)

What it is

Dimethylglycine is the amino acid glycine with two additional methyl groups. It is the little sister of betaine, which carries three methyl groups and is known as TMG. DMG is formed continuously in the body: the liver uses betaine to turn homocysteine back into methionine, and what remains is DMG. An enzyme in the mitochondria, dimethylglycine dehydrogenase, breaks it down further to sarcosine and finally to glycine.

How important this breakdown is can be seen from a rare inherited disorder. In 2001, a defect in precisely this enzyme was found in a 38-year-old man with lifelong muscle fatigue and a fish-like body odor; his DMG level was greatly elevated. DMG is therefore not a foreign agent but a normal intermediate whose amount the body regulates.

As a dietary supplement, DMG has an eventful history. In the 1950s, Russian studies in athletes reported better oxygen utilization and less fatigue. In the West, so-called pangamic acid then came onto the market as vitamin B15. It was never a vitamin; the preparations were often mixtures of calcium gluconate and DMG, and in 1978 the US drug authority FDA found that the evidence was lacking. DMG remained as a stand-alone product and has been sold as a dietary supplement since 1974.

How it is supposed to work

The classic explanation is that DMG improves oxygen utilization in tissue and scavenges free radicals. In the test tube and in mice, the sodium salt does indeed act as an antioxidant. Newer animal experiments also show that DMG binds to the glycine binding site of the NMDA receptor in the brain and has antidepressant-like effects in mice. Hopes for mood, concentration and behavior are derived from this.

Regarding the immune system, rabbits given DMG showed more than fourfold higher antibody titers after a flu vaccination. In humans, oxygen consumption has so far only been measured in 5 children with a mitochondrial disease: it did not change. The chain of action from the capsule to better oxygen turnover has therefore not been shown in humans.

What users are looking for

DMG is taken mainly by endurance athletes, by people who want to strengthen their immune system, and by parents of autistic children, in whose community DMG has been recommended for decades. User reports describe more energy, better speech or calmer behavior. In the largest autism study, some children did appear to respond, but on average the DMG group did not differ from placebo, and both groups improved. Such reports should be taken seriously, but they are hard to separate from the placebo effect.

What the studies show

The autism study

37 children aged 3 to 11 with autism or a related developmental disorder received DMG or placebo for 4 weeks, double-blind. Both groups improved on the behavioral scales, no more under DMG than under placebo. A smaller crossover study with 8 participants also found no difference, but used a low dose.

The epilepsy study

19 people with difficult-to-treat epilepsy and on average two to three seizures per day received DMG or placebo for 28 days, initially 300 mg, then 600 mg per day. Seizure frequency did not change. No toxic effects were observed.

The MS study

30 patients with progressive multiple sclerosis took 125 mg DMG per day or placebo for 12 months, allocated in a ratio of 2 to 1. Disability, fatigue, cognitive performance and gait developed in the same way in both groups. It is the longest controlled DMG study we found, but it is small.

Where the data stop

The main promises have not been confirmed in humans. For athletic performance there is only one controlled study with 16 track and field athletes who took pangamic acid, a mixture containing DMG, for three weeks: running time, heart rate and lactate did not differ from placebo. A review summarizes that studies with 100 to 200 mg daily in healthy people found no clear benefits for endurance. In children with a mitochondrial disease, DMG did not change oxygen consumption. All these studies were small, with 5 to 37 participants, and mostly lasted only a few weeks. A large, modern study on performance or the immune system is lacking; the positive immune finding from 1981 stands alone.

One open question concerns the heart. In two large cohorts with 4,150 and 3,733 heart patients, people with the highest endogenous DMG levels had a higher risk of heart attack, with a hazard ratio of 1.95, and higher mortality. This is an observation about the body’s own metabolism, not a statement about capsules, and no one has studied whether DMG taken as a supplement changes anything about it.

Status, approval and legal

In the EU Novel Food Catalogue, a legally non-binding orientation aid, DMG has no entry; it is not authorized as a novel food, and we found no evidence of its use as a food in the EU before 1997. That is why we list DMG among the experimental substances. It is nevertheless offered as a dietary supplement by German mail-order pharmacies, and there are no alerts in the European Rapid Alert System. DMG is not a medicine, not prescription-only and not banned. As a sodium salt, it is authorized in the EU as a feed additive for broiler chickens. DMG is not on the WADA 2026 doping list.

Safety

Where studies report on tolerability, DMG was well tolerated, in the longest over 12 months with a side effect profile similar to placebo. An early concern that DMG could be genotoxic together with nitrite has not been confirmed; in the test, the nitrite itself was responsible. Theoretically interesting is that DMG slows an enzyme that breaks down homocysteine. Whether intake raises homocysteine levels has never been measured. Systematic long-term data, data on pregnancy, breastfeeding and interactions with medicines are lacking, and there are no maximum amounts from EFSA, BfR or DGE. Anyone treating a child with autism or epilepsy should use DMG only in consultation with the treating physicians and never in place of an effective therapy.

Sources

• Graber et al., J Infect Dis 1981 – DMG and immune response in humans
• Kern et al., J Child Neurol 2001 – DMG in autism
• Bolman and Richmond, J Autism Dev Disord 1999 – crossover pilot study in autism
• Gascon et al., Epilepsia 1989 – DMG in epilepsy
• Wolfsegger et al., Neurol Res Pract 2021 – DMG in progressive MS
• Gray and Titlow, Med Sci Sports Exerc 1982 – pangamic acid and treadmill performance
• Liet et al., J Pediatr 2003 – DMG and oxygen consumption in COX deficiency
• McGregor et al., Kidney Int 2001 – DMG, BHMT and homocysteine
• Svingen et al., Arterioscler Thromb Vasc Biol 2013 – plasma DMG and risk of heart attack
• Hoorn, Mutat Res 1989 – DMG and mutagenicity under nitrosation conditions