DMG

• Metabolic Support
• Immune Function
• Antioxidant Protection
• Energy Production

• Athletic Performance
• Cardiovascular Support
• Cognitive Function
• Detoxification Support
• Stress Adaptation

Dimethylglycine (DMG) exerts its biological effects primarily through its role as a methyl donor and metabolic intermediate in one-carbon metabolism. As a naturally occurring substance in the body, DMG is produced during the metabolism of choline and betaine (trimethylglycine) and serves as an intermediate in the conversion of betaine to glycine. In methylation pathways, DMG donates methyl groups (CH3) for various biochemical reactions, including the synthesis of DNA, RNA, hormones, neurotransmitters, and phospholipids. This methylation activity supports cellular repair, gene expression regulation, and detoxification processes.

DMG contributes to the body’s antioxidant defense system by supporting the production of glutathione, a major endogenous antioxidant, through its conversion to glycine, which is a precursor for glutathione synthesis. It also enhances the activity of antioxidant enzymes like superoxide dismutase (SOD) and catalase, helping to neutralize free radicals and reduce oxidative stress. In energy metabolism, DMG facilitates the conversion of homocysteine to methionine, which is then used to produce S-adenosylmethionine (SAMe), a universal methyl donor that supports numerous metabolic processes. DMG may improve oxygen utilization at the cellular level, potentially enhancing aerobic metabolism and ATP production, particularly during physical exertion or hypoxic conditions.

This mechanism has been proposed to explain its reported benefits for athletic performance and cardiovascular function. For immune function, DMG appears to modulate both humoral and cell-mediated immune responses. It enhances antibody production, particularly immunoglobulin G (IgG), and may improve the responsiveness of B and T lymphocytes. DMG also supports the activity of natural killer (NK) cells and macrophages, contributing to the body’s defense against pathogens and abnormal cells.

In cardiovascular health, DMG may help reduce homocysteine levels, a risk factor for cardiovascular disease, through its role in the methylation cycle. It also supports endothelial function and may help maintain healthy blood pressure and circulation. For neurological function, DMG crosses the blood-brain barrier and contributes to the synthesis of neurotransmitters through methylation reactions. It may support cognitive function by enhancing neurotransmitter production and protecting neurons from oxidative damage.

DMG also plays a role in detoxification processes by supporting phase II liver detoxification, particularly through methylation reactions that help convert toxins into water-soluble compounds for elimination. Additionally, DMG may function as an adaptogen, helping the body respond to various stressors by supporting adrenal function and stress hormone regulation.

125-500 mg per day, typically divided into 2-3 doses

DMG is generally well-absorbed in the gastrointestinal tract. Oral bioavailability is estimated to be approximately 70-80%. DMG is water-soluble and rapidly absorbed, with peak plasma concentrations typically occurring within 1-2 hours after ingestion.

Sublingual administration may improve absorption by bypassing first-pass metabolism in the liver, Taking on an empty stomach may enhance absorption rate, though it can be taken with food if GI discomfort occurs, Liposomal delivery systems potentially improve cellular uptake, Divided doses throughout the day maintain more consistent blood levels, Combining with vitamin B6, B12, and folate may support the metabolic pathways in which DMG functions, Mineral-complexed forms (calcium DMG, magnesium DMG) may offer improved stability and absorption

DMG can be taken with or without food, though taking on an empty stomach may enhance absorption. For athletic performance, taking a dose 30-60 minutes before exercise may be beneficial. For general health support, dividing the daily dose into 2-3 servings may provide more consistent metabolic support. For cognitive benefits, some practitioners recommend taking a portion of the daily dose in the morning.

Consistent daily use is typically more effective than intermittent supplementation for most applications. Avoid taking high doses late in the day as some individuals report increased energy that may interfere with sleep.

• Mild gastrointestinal discomfort
• Nausea (rare)
• Headache (rare)
• Fatigue or increased energy (variable response)
• Insomnia (when taken late in the day)
• Mild allergic reactions (very rare)

• Pregnancy and breastfeeding (due to limited safety data)
• Known hypersensitivity to DMG or related compounds
• Severe liver or kidney disease (use with caution due to limited research)
• Bipolar disorder (theoretical concern due to potential effects on neurotransmitters)
• Cancers that may be sensitive to methyl donors (theoretical concern, consult oncologist)

• Medications metabolized by methylation pathways (theoretical interaction)
• Antifolate drugs (methotrexate, trimethoprim) – potential interaction with one-carbon metabolism
• Levodopa – theoretical concern about methylation affecting neurotransmitter balance
• Immunosuppressant medications (due to DMG’s potential immune-modulating effects)
• Chemotherapy drugs (consult oncologist before use)

No established upper limit from regulatory bodies. Clinical studies have used up to 1800 mg daily without serious adverse effects. Most practitioners recommend not exceeding 1000 mg daily without medical supervision. DMG is generally considered to have a wide safety margin as it is a naturally occurring metabolite in the body.

In the United States, DMG is regulated as a dietary supplement under the Dietary Supplement Health and Education Act (DSHEA) of 1994. The FDA does not approve DMG for the treatment, prevention, or cure of any disease. The FDA has previously taken action against products labeled as ‘vitamin B15’ or ‘pangamic acid,’ as these are not recognized as vitamins or essential nutrients. DMG itself, however, is legally marketed as a dietary supplement.

Eu: Not approved as a food supplement ingredient in some EU countries. Regulatory status varies by country within the European Union. The European Food Safety Authority (EFSA) has not approved any health claims for DMG.

Canada: Regulated as a Natural Health Product (NHP) by Health Canada. Some DMG products have received Natural Product Numbers (NPNs) allowing specific limited claims.

Australia: Regulated by the Therapeutic Goods Administration (TGA) as a complementary medicine. Limited approved indications.

Japan: Not commonly included in the Japanese supplement market. No approved health claims under Japan’s Foods with Function Claims system.

Uk: Classified as a food supplement. No approved health claims under UK regulations following Brexit.

Russia: Has a longer history of use in Russia, dating back to research on ‘pangamic acid.’ Regulatory status as a supplement or medicine varies.

medium

$0.30-$1.50 per day for typical doses (125-500 mg)

DMG represents a moderate-cost supplement with variable value depending on the intended use. For general metabolic support, the cost-to-benefit ratio is reasonable, with a month’s supply typically ranging from $10-45 depending on brand and dosage. Compared to other methyl donors like SAMe, DMG is significantly more affordable (SAMe can cost $1-4 per day), though some research suggests SAMe may have more robust clinical evidence for certain applications. For athletic performance, the value proposition is questionable given the limited scientific evidence for benefit, though many athletes report subjective improvements that may justify the cost for them personally.

For immune support, DMG offers moderate value, though other immune-supporting supplements like vitamin C, vitamin D, and zinc provide similar benefits at lower cost with stronger evidence. The cost-effectiveness increases when purchasing higher-potency products and taking lower doses, as many people report benefits from as little as 125 mg daily. Sublingual and liquid formulations tend to be more expensive than capsules or tablets but may offer improved absorption. DMG is more expensive than its precursor betaine (trimethylglycine), which provides similar methyl-donating benefits and may be a more cost-effective option for some users.

Overall, DMG represents a moderate-value supplement that may be worth trying for specific applications, particularly for those who have not responded well to other more established supplements.

Pure DMG powder: 2-3 years when properly stored; Tablets and capsules: typically 2-3 years; Liquid formulations: 1-2 years if preserved properly

Store in a cool, dry place away from direct sunlight. Airtight containers are recommended to prevent moisture absorption. DMG is hygroscopic and can absorb moisture from the air, which may cause degradation. Refrigeration is not necessary but may extend shelf life in very hot or humid climates. Liquid formulations should be tightly sealed after use and may benefit from refrigeration after opening.

Moisture (DMG is hygroscopic and can absorb water from the environment), Heat (accelerates degradation reactions), Light exposure (particularly UV light), Oxygen (oxidation can affect stability), pH extremes (highly acidic or alkaline environments can accelerate degradation), Microbial contamination (particularly in liquid formulations), Interactions with other ingredients in multi-component supplements

Synthesis Methods

Natural Sources

Quality Considerations

Dimethylglycine (DMG) has a relatively short but interesting history as a dietary supplement, marked by both scientific investigation and controversy. DMG first gained attention in the 1960s and 1970s when it was incorrectly identified as ‘vitamin B15’ or ‘pangamic acid,’ terms that have no recognized scientific validity. The confusion stemmed from research in the Soviet Union, where scientists were studying a complex mixture of substances that included DMG along with other compounds. This mixture was erroneously labeled as vitamin B15 or pangamic acid, though it did not meet the criteria for classification as a vitamin.

In the 1970s, DMG gained popularity in the United States, particularly among athletes seeking performance enhancement. This was largely based on reports from Soviet bloc countries claiming improved oxygen utilization and endurance in athletes using the substance. However, these claims were not substantiated by rigorous scientific studies. During this period, the FDA took action against products labeled as vitamin B15 or pangamic acid, stating that these were not recognized vitamins and had no established nutritional value.

Despite regulatory challenges, interest in DMG continued, particularly in alternative medicine circles. In the 1980s, research began to focus more specifically on DMG rather than the ill-defined pangamic acid. Studies in animals showed potential benefits for immune function, leading to its use in veterinary medicine, particularly for performance horses and dogs. By the 1990s, DMG had found a niche in the supplement market, with claims expanding to include benefits for autism, seizure disorders, and mitochondrial diseases, though clinical evidence for these applications remained limited.

The Dietary Supplement Health and Education Act (DSHEA) of 1994 allowed DMG to be marketed as a dietary supplement in the United States, though specific health claims remained restricted. In recent decades, DMG has maintained a modest presence in the supplement market, primarily marketed for immune support, energy enhancement, and athletic performance. It has also gained some popularity in veterinary applications, where it continues to be used for performance animals. Throughout its history, DMG has been the subject of scientific debate, with proponents citing its role in biochemical pathways and critics pointing to the limited clinical evidence for its efficacy.

Unlike many traditional botanical remedies with centuries of historical use, DMG’s history as a supplement spans only about 50-60 years, and its use has been largely driven by modern nutritional theories rather than traditional healing practices.

Nye C, Brice A. (2005) Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database of Systematic Reviews (included assessment of DMG studies), James SJ, et al. (2004) Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. American Journal of Clinical Nutrition (review including DMG metabolism)

Limited current clinical trials specifically examining DMG supplementation, Some ongoing research on one-carbon metabolism and methylation pathways that may provide indirect evidence about DMG’s role, Veterinary studies examining DMG’s effects on immune function and athletic performance in animals