Trimethylglycine, also known as TMG or betaine, is an essential compound produced naturally by the human body. It can also be taken as a TMG supplement and occurs in certain foods.

This compound has been studied for its wide range of potential benefits for health and longevity. Studies show that TMG may improve cardiovascular health, enhance athletic performance and recovery, protect against conditions like depression, and promote optimal insulin function and blood glucose control.

In this guide, we will explore the science behind trimethylglycine, including its benefits for health and wellness, along with ideal dosages, potential risks, and how to find a quality TMG supplement. However, please bear in mind that this guide should not replace the advice of a medical professional. Always speak with your doctor or physician before starting a new supplement.

What is TMG?

Trimethylglycine is a methyl group donor compound that is present in the metabolic cycle of methionine. In the human body, TMG can donate one of its methyl groups to the compound homocysteine, transforming it back into methionine. This mechanism keeps homocysteine levels in the body from becoming elevated, thereby lowering the risk for the development of heart disease. 

Furthermore, researchers believe that through this donation by a methyl group, TMG may assist in the production of S-adenosylmethionine, which protects the cells against oxidative stress and DNA damage. TMG is recommended for the treatment of homocystinuria – excessively high homocysteine levels in the body – which can be exacerbated by 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and defects, as well as cystathionine beta-synthase (CBS) deficiencies and cobalamin cofactor metabolism (CBL) dysfunction.

Patients with MTHFR polymorphisms may experience over-methylation or under-methylation. Over-methylation can lead to overproduction of dopamine, serotonin, and norepinephrine in the brain, which may lead to psychological challenges like poor memory, confusion, and reduced libido.

Undermethylation, on the other hand, may present in the forms of seasonal allergies, depression, poor pain tolerance, and lower levels of dopamine and serotonin in the brain. This condition can be caused by protein deficiencies, nutrient malabsorption, histamine overload, or genetic mutations, including MTHFR mutations. In cases of undermethylation, TMG is recommended as a treatment option, along with optimising methionine, Sam-e, and vitamin B12 levels to facilitate the process of methylation.

TMG Potential Health Benefits

TMG supplements are associated with a number of different health benefits backed by years of scientific research. Discover more about the most notable trimethylglycine benefits below.

Lowering Homocysteine Levels

There is research available to suggest that TMG supplements could decrease levels of homocysteine in the blood. This amino acid can increase the risk of cardiovascular disease in high concentrations. A review of five studies conducted in 2013 found that taking 4g of TMG per day for a period of six weeks could reduce blood homocysteine levels in healthy adult patients.

Another review revealed similar results, noting that patients who took 4g of TMG per day displayed reductions in their blood homocysteine levels without any negative impacts on other aspects of their cardiovascular health, such as cholesterol levels or blood pressure readings.

It’s important to note that some studies have linked TMG supplements with increases in both LDL and total cholesterol levels, which could increase heart disease risk. More research is needed on trimethylglycine cholesterol links to gain a better understanding of how TMG can influence heart health.

Reducing Depression

There is evidence to suggest that using trimethylglycine for depression can improve the efficacy of certain antidepressant medications. TMG has been shown to enhance the actions of S-adenosyl-methionine (SAMe), a substance often used to treat mild to moderate cases of depression. In a study of 64 people with depression, those who took TMG and SAMe for a year experienced larger improvements in their condition than the patients who took SAMe alone.

TMG may also help to improve the symptoms of anxiety and depression on its own. Research suggests that these two conditions might be linked with high levels of homocysteine. By reducing these homocysteine levels, TMG could reduce the severity of these mental health conditions.

Promoting Better Insulin Function

A number of studies have found that TMG supplementation can improve insulin resistance, a condition in which the body’s ability to regulate blood glucose levels is impaired. One study found that higher intake of betaine and choline was effective at reducing insulin resistance. While another trimethylglycine for liver research paper noted that TMG could reverse insulin resistance in human liver cells. 

Trimethylglycine liver disease research also shows promise for using TMG to prevent and treat liver disease. One review notes that betaine supplementation inhibits inflammation, improves insulin resistance, limits oxidative stress in the liver, and boosts autophagy to promote better liver health and function. Researchers suggest that TMG works on AMP-activated protein kinase (AMPK), liver X receptor α (LXRα), protein kinase B (Akt), cysteinyl aspartate specific proteinase-3 (Caspase-3), and other signalling pathways to improve cases of liver disease.

Supporting NAD Precursor Supplementation

Anyone supplementing with NAD+ supplements or NAD precursors like NR and NMN should be taking TMG as well. NAD+ supplements can reduce methyl groups in the body, as NAD+ requires methyl groups to be broken down and removed from the body via excretion processes. 

Taking a TMG supplement alongside NAD precursors ensures that the body has optimal levels of methyl groups available for other essential functions. 

Treating Methylation Deficits in Autism

Autism spectrum disorder (ASD) has been linked in studies to impaired methylation. This complex condition involves the nervous system and brain dysfunction and impairments in the endocrine, immune, detoxification, and digestive systems. One path of treatment involves using trimethylglycine autism to support dysfunctions in the methylation process. TMG supplements upregulate the betaine-homocysteine methyltransferase (BHMT) enzyme, which increases methionine independent of B12 and folate levels.

Improving Physical Performance

TMG supplements may enhance exercise performance. A scientific review found that supplementation improved body composition and performance in patients who did resistance and endurance exercises. 

While the exact mechanisms behind this benefit are still unclear, researchers believe that TMG can enhance protein production, limit fatigue, and boost creatine synthesis to provide its performance-enhancing effects. Moreover, other research papers found that TMG supplementation notably improves power and muscle strength.

Improving Sleep Quality

Trimethylglycine sleep research shows that TMG supplementation can improve S-adenosylmethionine (SAMe) production in the body. Preliminary research shows that increasing SAMe levels may be able to mitigate obstructive sleep apnea, thus contributing to better quality sleep overall. This leads to better health, longevity, and mood stabilisation.

More research is needed to assess the mechanisms by which TMG and SAMe increases can benefit patients’ sleep quality.

Sources and Forms of TMG

Trimethylglycine can be found both naturally in food sources and as standardised supplements. While food sources are often the best sources of bioavailable nutrients, supplementation can be a valuable tool for enhancing health and longevity. Particularly if you have impaired methylation or certain nutrient deficiencies.

When it comes to trimethylglycine in foods, there are many food sources that offer varying concentrations of natural TMG. It is found most abundantly in:

• Wheat bran (1,339mg per 100g serving)
• Wheat germ (1,241mg per 100g serving)
• Spinach (600mg per 100g serving)
• Quinoa (390mg per 100g serving)

Additional sources include wheat flour bread, seafood products like shrimp, and beets.

Usage and Recommended Dosage

While no official dosage recommendations are currently available for TMG supplementation, most products available to buy offer between 750mg and 3,000mg (3g) of TMG per suggested serving. A review published in 2018 notes that trimethylglycine is safe when used in doses of up to 15g per day.

Potential Trimethylglycine Side Effects and Interactions

While most people who take TMG supplements experience few to no side effects, some unwanted effects may occur during use. The most common side effects are digestive issues, including bloating, cramps, nausea and vomiting, indigestion, and diarrhoea. These effects are most likely to arise when taking high doses of TMG.

Although rare, TMG supplementation can cause significant increases in the concentrations of methionine in the blood. This can lead to a build-up of fluid around the brain and may pose danger, especially to children, seniors, and pregnant and breastfeeding women. TMG supplements are not recommended for these groups, as there is limited safety and long-term research available. Always speak with your doctor before starting a TMG supplement or if you experience any unwanted side effects.

Conclusion

Trimethylglycine is a naturally occurring compound that facilitates optimal methylation in the body while reducing high homocysteine levels which can negatively impact heart and liver health. TMG also plays an important role in providing additional methyl groups for people supplementing with NAD precursors, ensuring that their bodies have enough methyl groups to support methylation and protect their health.

Supplementing with TMG has been shown to be an effective way of improving trimethylglycine levels in the body, along with eating TMG-rich foods such as wheat products, spinach, beets, and seafood. If you are interested in starting a TMG supplement to support your health and improve your body’s methylation processes, be sure to speak to your doctor or a qualified healthcare provider to find the best solutions for your needs.