IngredientsDimethylglycine (DMG) is a derivative of the amino acid glycine with the structural formula (CH3)2NCH2COOH. Its systematic IUPAC name is N,N-dimethylglycine, and it is also known under the following names and designations:
When DMG was first discovered, it was referred to as Vitamin B16, but unlike true B vitamins, deficiency of DMG in the diet does not lead to any ill-effects and it is synthesized by the human body in the citric acid cycle, meaning it does not meet the definition of a vitamin.
DMG is found naturally in plant and animal cells and in certain foods such as beans, cereal grains, brown rice, pumpkin seeds, and liver. DMG can also form by dropping one of the methyl groups from trimethylglycine (TMG) or as a byproduct during choline metabolism; it occurs naturally in plants and some foods, including cereal grains, pumpkin seeds, brown rice, and beans.
While DMG occurs naturally as a metabolite in plant and animal sources, including precursors like betaine derived from beet molasses, commercial extraction from these natural materials is limited, with synthesis dominating production for purity and cost efficiency.
DMG is an abbreviation for dimethylglycine, an amino acid with the chemical formula (CH3)2NCH2COOH; it is derived from glycine, which is one of the 20 amino acids commonly used to synthesize proteins in humans. DMG is produced by many biochemical processes in the human body such as the citric acid cycle, also known as the Krebs cycle; it is also a byproduct of choline metabolism.
DMG is commercially available as a dietary supplement in several physical forms. Dimethylglycine comes as a capsule which can be taken orally once daily or as advised by a physician between food. It is also sold as tablets (including sublingual tablets), loose powder, and liquid preparations. Some formulations use the hydrochloride salt form (DMG HCl; N,N-dimethylglycine hydrochloride) for improved stability and solubility. One established industrial synthesis approach is the Eschweiler–Clarke reaction, in which glycine reacts with aqueous formaldehyde and formic acid to yield DMG. A common alternative method involves the condensation of chloroacetic acid with dimethylamine, followed by hydrolysis to form the product.
Dimethylglycine (DMG) was first described in 1943. It gained attention in the 1950s–1960s through studies conducted in the Soviet Union claiming improved oxygen use, reduced fatigue, and enhanced physical performance, leading to its widespread use among Russian athletes and cosmonauts.
During this period, DMG was often incorrectly marketed as vitamin B15 or pangamic acid, in which it was sometimes included. DMG entered the U.S. supplement market in 1974, and similar performance claims appeared in American reports in 1975.
DMG's use in health and maintenance goes back to the 1960s, where the Soviet Union came up with the idea that there was a "vitamin B15" and called it calcium pangamate; research over the years gave evidence that the biological activity ascribed to this substance was, in fact, due to DMG.
DMG gained prominence in the 1960s and 1970s for its perceived benefits in supporting both physical and mental well-being. Early research and anecdotal reports highlighted its role in enhancing stamina, reducing fatigue, and improving stress adaptation.
In the latter half of the 20th century, DMG became popular in the United States as a dietary supplement, with proponents claiming benefits for cardiovascular health, cognitive function, and even as a supportive remedy for children with developmental disorders.
Scientists have been aware of DMG's potential benefits for over a half-century, and it was first put to use as an addition to equine diets for racehorses in the 1970s and 1980s. Its use as an ergogenic aid for horses preceded significant exploration in human athletes.
After DMG's use became widespread in the 1970s in the United States as "vitamin B15," the FDA took action against its marketing under that designation. N,N-Dimethylglycine (DMG) has been marketed as a nutritional supplement since 1974 and has seen wide use in both human and animal health fields. Under the Dietary Supplement Health and Education Act (DSHEA) of 1994, DMG was permissible to sell as a dietary supplement ingredient.
DMG is an active amino acid and intermediate metabolite in the one-carbon choline cycle; its primary function is to contribute methyl groups for methylation reactions and provide other essential building blocks. Specifically, betaine yields N,N-dimethylglycine after transferring one methyl group to homocysteine. Scientifically, DMG functions as an intermediary in the metabolism of choline to glycine, contributing to the methylation cycle, which is essential for cellular function and energy production.
Once formed, DMG is rapidly oxidized in mitochondria by dimethylglycine dehydrogenase (DMGDH) to produce sarcosine, linking DMG metabolism directly to the folate-dependent one-carbon cycle. In mammalian liver cells, dimethylglycine and sarcosine, produced by choline oxidation, donate their methylene group to THF (tetrahydrofolate), through a process catalyzed by dimethylglycine dehydrogenase (DMGDH) and sarcosine dehydrogenase (SARDH), respectively.
THF is used as the acceptor of the incipient methyl group during the DMGDH reaction, thereby preventing the release of cell-toxic formaldehyde during catalysis; in the course of this reaction, N-5,10-methylene tetrahydrofolate is formed, which plays an important role in one-carbon metabolism. Regeneration of oxidized FAD is achieved by electron transfer to the human electron-transferring flavoprotein (hETF), which in turn transfers the electrons to the membrane-anchored ETF-ubiquinone oxidoreductase (ETF-QO) for further utilization in the mitochondrial respiratory chain.
DMG acts as an indirect methyl donor and functions as an efficient "methionine pump" by converting excess homocysteine molecules to methionine. Methionine is subsequently used to produce S-adenosylmethionine (SAMe), the body's principal methyl-group donor. Mechanistically, DMG participates in one-carbon metabolism, supporting amino acid and nucleotide synthesis and cellular methylation reactions.
In addition to generating methyl groups, dimethylglycine generates two-carbon molecules such as sarcosine, glycine, serine, and the ethanolamines, all of which are beneficial to the cell. For example, glycine functions as an important inhibitory neurotransmitter of the central nervous system; it is used to produce phosphocreatine, a high-energy phosphate molecule used in muscle tissue and in the tissue of the central nervous system.
Dimethylglycine generates two-carbon molecules such as sarcosine, glycine, serine, and ethanolamines, all of which are beneficial to the cell. Glycine functions as an important inhibitory neurotransmitter of the central nervous system and is used to produce phosphocreatine, a high-energy phosphate molecule used in muscle tissue and the tissue of the central nervous system.
DMG, a tertiary amino acid, has had wide acceptance as a nonfuel nutrient; presumably it enhances oxygen utilization by tissue and complexes free radicals. The compound's relationship with the NMDA (N-methyl-D-aspartate) glutamate receptor has also been a subject of investigation, given its structural similarity to glycine, a known NMDA receptor co-agonist. Research has revealed that DMG also possesses antidepressant properties, aiding in the reduction of ketamine-induced psychotomimetics (a finding derived from preclinical/animal work).
Variants in genes that encode methylation enzymes (e.g., MTHFR, BHMT) and in dimethylglycine dehydrogenase (DMGDH) can alter one-carbon flux. Rare DMGDH deficiency leads to elevated DMG in blood and urine and can be clinically benign or variably symptomatic. Common variants may subtly influence biomarker levels without creating a disease.
Homocysteine metabolism is linked to betaine-homocysteine methyltransferase (BHMT), a zinc metalloenzyme that converts glycine betaine (GB) to N,N-dimethylglycine (DMG); DMG is a known feedback inhibitor of BHMT. This feedback relationship is physiologically significant: elevated DMG can inhibit its own upstream generating enzyme, potentially affecting homocysteine clearance in settings of impaired renal function.
DMG has been investigated or proposed for roles in the following body systems and health areas, though the level of clinical evidence varies considerably across them:
There are some positive reports of DMG efficacy on the immune system; however, none of these claims have been confirmed in clinical trials. There is conflicting data about the efficacy of dimethylglycine in boosting the immune system.
Human evidence: In humans, only one small double-blind trial from 1981 showed increased antibody responses and higher leukocyte inhibition factor activity after DMG intake, suggesting enhanced immunity (Graber et al.). This study, published in the Journal of Infectious Diseases (Graber CD, Goust JM, Glassman AD, et al., 1981;143:101–5), remains the primary human trial demonstrating an immunomodulatory signal.
Animal evidence: The immunomodulating capacities of DMG were examined in a rabbit model in which female New Zealand white rabbits were immunized with either killed influenza virus or Salmonella typhi vaccine; experimental animals were force-fed 20 mg/kg body weight of DMG daily beginning 14 days prior to the first inoculation. Hemagglutination inhibition assays showed a more than fourfold increase in mean antibody titer to influenza antigen in the DMG-treated animals (p = 0.0006) after the first inoculation. This animal study (Reap EA, Lawson JW, J Lab Clin Med. 1990;115:481–6) provided important preclinical support for an immunostimulant role, but has not been replicated in adequately powered human trials.
Evidence strength: The immune evidence base is preliminary and inadequate. The human data rests essentially on a single small study; the more robust findings come from animal models (rabbit, cat) which cannot be directly extrapolated to humans without further controlled trials.
Limited studies have produced mixed results, and a recent systematic review did not find evidence of benefit with DMG for autism symptoms.
Key clinical trials:
There has been some interest in DMG's ability to improve the behaviour of children with autism; however, there do not appear to have been any large-scale multi-centre studies that conclusively provide evidence to support its use.
A separate metabolomics study (Kano et al., 2021, J Autism Dev Disord.) investigated plasma DMG in the context of oxytocin treatment for ASD. Among 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in subjects administered oxytocin compared with those given placebo at a medium effect size (FDR-corrected P = 0.043, d = 0.74, N = 83). Subgroup analyses of participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (PFDR = 0.004, d = 1.13, N = 60). This study found an association between endogenous DMG levels and the time-course efficacy of oxytocin on autistic social deficits, but did not directly test DMG supplementation.
Evidence strength: Insufficient. Human RCTs are small, of short duration, and have consistently failed to demonstrate statistically significant benefit over placebo. No large, adequately powered multicenter trial has been conducted.
Single case reports describe decreased seizure frequency, but larger studies have not documented any benefit.
Key clinical trial — Gascon et al. (1989): Nineteen institutionalized patients with frequent seizures (group average two to three per day; seizure types: generalized, akinetic/myoclonic) were treated randomly with either placebo or N,N-dimethylglycine (DMG) for 28 days. Dosage was 300 mg/day for the first 14 days and then 600 mg/day. Plasma levels were measured at baseline, days 2, 5, 8, 15, 22, 30, and 1 and 2 weeks after the study ended. No differences in seizure frequency were noted between placebo and DMG or between baseline and test conditions. No toxicity was noted. (Published in Epilepsia 1989;30:90–3.)
Early clinical research shows that taking dimethylglycine daily for 4 weeks does not improve generalized or akinetic/myoclonic seizures in patients with epilepsy. Earlier case reports and a 1982 letter by Roach & Carlin in the New England Journal of Medicine had raised initial interest, but subsequent controlled work did not confirm benefit. Animal studies (Freed WJ, Pharmacol Biochem Behav. 1985;22:641–3) demonstrated that DMG and related N-methylated glycine derivatives could prevent strychnine-induced seizures in rodents.
Evidence strength: Negative in controlled trials. The controlled clinical trial showed no benefit. Positive signals are limited to case reports and animal models.
There is no scientific evidence to support DMG as an athletic-performance enhancer in humans. Early clinical research shows that taking dimethylglycine daily for 3 weeks does not improve the performance of athletes.
Interest in DMG as an ergogenic aid originated with the Soviet research tradition and with anecdotal reports. When horses were supplemented with DMG at the rate of 1.6 mg/kg, they had lower blood lactate concentrations during strenuous exercise as compared to when unsupplemented. However, translation to human physiology proved more difficult. Multiple small human trials (reviewed in Tonda ME, Hart LL, Ann Pharmacother. 1992;26:935–7) examined DMG alongside L-carnitine and did not find significant performance advantages.
Enhanced physical performance in animals with DMG supplementation may occur via improved oxygen utilization and reduced lactic acid formation. No mechanisms have been uncovered to elucidate claims of DMG for autism, ADHD, epilepsy, chronic fatigue syndrome, or athletic performance enhancement.
Evidence strength: Negative to absent in humans. Preclinical (equine and laboratory animal) evidence suggests plausible mechanisms, but controlled human trials have not confirmed ergogenic effects.
A pilot study reported the results over a one-year double-blind, placebo-controlled trial of DMG in 30 randomized patients with progressive multiple sclerosis. No treatment effects were found between the placebo group and the DMG group for disability, fatigue, cognitive, or gait parameters. This trial (Wolfsegger T, Böck K, Schimetta W, et al., Neurol Res Pract. 2021;3:29) is the most recent and most methodologically rigorous human trial of DMG for a neurological indication. In this small long-term trial of patients with progressive multiple sclerosis, oral DMG also did not improve fatigue, cognition, gait performance, or disability status.
Evidence strength: Single negative pilot RCT. The sample size (30 patients) limits generalizability, but the direction of evidence is uniformly null.
An important, scientifically distinct area of investigation concerns elevated endogenous DMG plasma levels as a biomarker of cardiovascular risk, rather than therapeutic supplementation. In patients with recent acute coronary syndrome, higher baseline DMG was associated with increased risk of acute myocardial infarction, heart failure, and death over approximately 2.5 years (Lever et al., 2012). Similarly, in a large cohort with stable angina pectoris, DMG correlated with traditional coronary artery disease risk factors and independently predicted incident myocardial infarction during approximately 4.6 years of follow-up (Svingen et al., 2013, Arteriosclerosis, Thrombosis, and Vascular Biology).
This finding appears counterintuitive given DMG's proposed role as a metabolic intermediary that may promote homocysteine clearance. However, DMG accumulates in chronic renal failure (CRF) and independently predicts plasma total homocysteine concentrations, suggesting that reduced betaine-homocysteine methyltransferase (BHMT) activity is important in the pathogenesis of hyperhomocysteinemia in CRF. In other words, elevated plasma DMG may be a marker of impaired methylation capacity and accumulation rather than a cause of disease. Overall, DMG reflects interconnected pathways such as methylation, mitochondrial function, and cardiometabolic regulation, making it a valuable indicator of metabolic stress and early dysregulation.
A recent metabolic analysis of healthy subjects correlated high plasma cholesterol levels with low levels for some metabolites related to mitochondrial metabolism including dimethylglycine.
Evidence strength: Observational/epidemiological. Multiple prospective cohort studies demonstrate a consistent association between elevated plasma DMG and adverse cardiovascular outcomes. These are correlational findings; they do not establish that supplementing with DMG causes harm, but they call into serious question the safety assumption of therapeutic DMG elevation in individuals with pre-existing cardiometabolic disease.
A small randomized, double-blind trial investigated whether DMG supplementation could lower homocysteine in pre-dialysis chronic renal failure patients. As a result of the role of DMG in homocysteine metabolism, investigators examined whether increasing DMG levels through supplementation could have beneficial or adverse side effects in CRF, a clinical group with known elevated homocysteine. The trial (McGregor et al., Clin Chim Acta. 2004) found that DMG supplementation did not reduce homocysteine in this population.
A rat study (PubMed PMID 34059172) illustrated the complexity: when supplemented with DMG, plasma homocysteine concentration was significantly decreased in rats fed a folate-sufficient diet but significantly increased in rats fed a folate-deficient diet. This bidirectional effect depending on folate status underscores the complexity of DMG's role in one-carbon metabolism and the importance of nutritional context.
DMG should not be confused with trimethylglycine (betaine), which is involved in the methylation of homocysteine to form methionine. Although they are metabolically related, betaine has considerably stronger evidence for homocysteine-lowering in humans.
Dimethylglycine has been suggested for use as an athletic performance enhancer, immunostimulant, and a treatment for autism, epilepsy, or mitochondrial disease. There is no evidence that dimethylglycine is effective for treating mitochondrial disease. A specific double-blind randomized crossover clinical trial (Liet JM, et al., J Pediatr. 2003;142:62–6) examined short-term DMG treatment on oxygen consumption in cytochrome oxidase deficiency and did not demonstrate a meaningful effect. Although athletes taking DMG had a 23.6% increase over placebo control in the length of exercise time before exhaustion in one study, the results of this study could not be verified in adults and children.
Observations regarding DMG and cancer are preliminary and based on metabolomics and epidemiology rather than interventional studies. DMG is elevated in several tumor-related settings; urinary DMG was significantly increased in hepatocellular carcinoma in a West African cohort and correlated with clinical stage, suggesting potential utility for surveillance. Higher DMG has also been detected in esophageal tumor margins and in fecal samples of colorectal cancer patients. These divergent findings may reflect differences in population characteristics, disease stage, or sample types. No clinical trial has tested DMG supplementation in cancer prevention or treatment.
The following dosages are drawn exclusively from information reported in cited research or clinical references:
There isn't enough reliable information to know what an appropriate dose of dimethylglycine might be for humans for any specific indication, as no dose-finding study has established an optimal human dose. Commercial and practitioner sources have suggested doses ranging from 125 mg to 600 mg per day in divided doses, with short-term use possibly safe for up to 28 days, but these figures are not derived from formally established dose-response studies in humans.
When taken by mouth, dimethylglycine is possibly safe when used short-term, for up to 28 days. The safety of long-term use is unknown. In the epilepsy trial described above, no toxicity was noted at doses of 300–600 mg/day over 28 days.
DMG and the chemically related amino acids glycine, sarcosine, and betaine were tested in Salmonella typhimurium strain TA100 after treatment with sodium nitrite under acidic conditions using a modified Ames Salmonella/microsome assay; from subsequent testing of the individual components, investigators concluded that non-consumed nitrite was responsible for the mutagenic responses observed, and not the amines themselves. DMG cannot be considered mutagenic under the test conditions employed. (Hoorn AJ, Mutat Res. 1989;222:343–50.)
The epidemiological finding that elevated endogenous plasma DMG predicts cardiovascular events is scientifically notable. While these are observational data and do not directly prove that exogenous supplementation elevates cardiovascular risk, the consistent association across multiple independent cohort studies (Lever et al., 2012; Svingen et al., 2013) warrants attention, particularly in individuals with coronary artery disease, renal impairment, or existing metabolic dysregulation. Proposed mechanisms involve DMG's role as a BHMT feedback inhibitor, potentially impairing betaine-mediated homocysteine remethylation when DMG accumulates. DMG is a known feedback inhibitor of BHMT; researchers postulated that DMG might accumulate in CRF and contribute to hyperhomocysteinemia by inhibiting BHMT activity.
As demonstrated in the rat model noted above, when supplemented with DMG, plasma homocysteine concentration was significantly decreased in rats fed a folate-sufficient diet but significantly increased in rats fed a folate-deficient diet. This suggests that the safety and metabolic impact of DMG supplementation on one-carbon flux may be contingent upon adequate folate availability, adding complexity to its use in populations with poor nutritional status.
There isn't enough reliable information to know if dimethylglycine is safe to use when pregnant or breast-feeding; erring on the side of caution and avoiding use is the recommended approach.
Variants in genes that encode methylation enzymes (e.g., MTHFR, BHMT) and in dimethylglycine dehydrogenase (DMGDH) can alter one-carbon flux; rare DMGDH deficiency leads to elevated DMG in blood and urine and can be clinically benign or variably symptomatic. Individuals with such variants may have atypical responses to DMG supplementation, as their baseline catabolism of DMG is already impaired.
DMG metabolism is shaped by nutrition, liver and kidney function, and genetics, suggesting that individuals with compromised organ function may have substantially altered DMG handling. Given that DMG accumulates in chronic renal failure and correlates with hyperhomocysteinemia, supplementation in patients with impaired kidney function is a particular area of theoretical concern.
No formally characterized pharmacokinetic drug-drug interactions have been established for DMG in adequately powered human studies. Its involvement in methylation pathways theoretically positions it as a potential modifier of drugs or pathways dependent on SAMe, folate, or homocysteine; however, no specific interactions are documented in the available clinical literature reviewed here.
Health conditions that Dimethylglycine may help support.
Dimethylglycine (DMG) is the immediate metabolic product formed when betaine (TMG) donates a methyl group to homocysteine via BHMT, remethylating it to methionine. DMG itself can serve as a methyl donor in subsequent one-carbon metabolism reactions and is used in supplements to support methylation. Its direct role in lowering homocysteine is secondary to betaine's, acting primarily as a methyl carrier in the BHMT pathway.
Dimethylglycine (DMG) is the immediate metabolic product of betaine after methyl donation via BHMT, and it continues to provide methyl groups to the folate cycle via dimethylglycine dehydrogenase. Supplementation with DMG provides methyl donors to the one-carbon cycle and has been used clinically since the 1970s. It is tracked as a biomarker of BHMT methylation pathway activity.
Body systems that Dimethylglycine may help support.
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