Trimethylglycine: The Methylation Nutrient Most People Overlook
If you’re not familiar with TMG, you’re not alone. Trimethylglycine, also known as betaine, is a naturally occurring compound found in foods such as beets, spinach, and shellfish. Despite its abundance in nature, it is often lacking in modern diets. Functionally, TMG serves as one of the body's most important methyl donors—molecules that donate a methyl group (a small cluster of carbon and hydrogen) to facilitate numerous biochemical reactions.
Why does that matter? Because methylation affects nearly everything: energy production, liver detoxification, mood, cardiovascular health, and even DNA repair. When methylation is sluggish — whether from genetics, stress, or nutrient deficiency — people can feel it in ways that range from fatigue and irritability to poor focus, slow recovery, or unexplained lab abnormalities like high homocysteine.
What TMG Does in the Body
TMG’s primary role is donating methyl groups in a critical pathway called the methionine–homocysteine cycle. In this cycle, TMG helps convert homocysteine — a potentially toxic amino acid — back into methionine, which the body uses to create S-adenosylmethionine (SAMe). This universal methyl donor drives over 200 reactions throughout your body.
In simple terms:
TMG lowers homocysteine (supporting heart and brain health)
Recycles methionine and boosts SAMe (supporting mood, detoxification, and hormone metabolism)
Protects cells from oxidative and osmotic stress (especially in the liver and kidneys)
A 2021 review in Life Sciences by Rosas-Rodríguez and Valenzuela-Soto found that glycine betaine (TMG) helps regulate gene expression, stabilize proteins, and reduce inflammation and oxidative damage in the liver, kidneys, cardiovascular system, and brain [source]. In conditions such as fatty liver disease, neurodegenerative changes, and chronic cardiovascular stress, TMG’s role as a methyl donor and antioxidant provides measurable cellular protection.
Earlier research in the International Journal of Biochemistry & Cell Biology also demonstrated that glycine betaine supplementation directly lowers homocysteine levels in animal models, supporting its cardiovascular and methylation benefits [source].
Who May Benefit from TMG Supplementation
Many people benefit from TMG without realizing it’s what they need. You might consider supplementation if you:
Have a known MTHFR variant or poor methylation genetics
Show elevated homocysteine on bloodwork (>10 µmol/L)
Struggle with fatty liver or consume alcohol regularly
Experience brain fog, fatigue, or low motivation despite normal labs
Eat a low-choline or plant-based diet
Have high oxidative stress from chronic illness, poor sleep, or environmental exposure
Want to support detox pathways and liver resilience
As a physician, I often use TMG as part of a broader methylation support plan — alongside nutrients like methylated folate (5-MTHF), vitamin B12 (methylcobalamin), and vitamin B6 (P-5-P). Together, they create the balanced one-carbon metabolism your body depends on for optimal gene expression, neurotransmitter balance, and cellular repair.
How to Take TMG
Typical dosage: 500–2,000 mg daily, usually divided into one or two doses with meals.
Start low: Begin around 500 mg per day and increase gradually as tolerated.
Timing: Morning or mid-day with food works best.
Pairs well with: methylated B vitamins and magnesium glycinate.
Monitor: Homocysteine levels can be rechecked 6–8 weeks after starting supplementation.
Most people tolerate TMG extremely well. In sensitive individuals, it can be mildly stimulating (because it increases SAMe and dopamine production), so start small and observe how your body responds. If you’re on SSRIs, SAMe, or have bipolar tendencies, discuss it with your clinician first.
Functional Benefits You Might Notice
Patients often describe:
Improved mental clarity and focus
Better mood stability
Enhanced liver function and reduced bloating
Faster recovery from stress or workouts
More consistent energy throughout the day
The Science Behind Its Protective Role
TMG doesn’t just support methylation — it also helps protect organs from osmotic and oxidative stress. For example:
In the liver, TMG replenishes SAMe, reduces fat accumulation, and supports bile flow, which can help in both non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver strain.
In the kidneys, it acts as an osmolyte — stabilizing cells under high salt and urea stress.
In the brain, it maintains membrane integrity and assists in homocysteine detoxification, which may have neuroprotective benefits.
All of this makes TMG one of the simplest, most effective ways to support your body’s foundational biochemistry.
Where to Find Quality TMG
As with most supplements, quality matters. Many commercial brands use lower-grade forms or unnecessary fillers. Pharmaceutical-grade, clinician-sourced options ensure purity and consistent dosing.
I recommend:
Designs for Health Homocysteine Supreme — Balanced, high-quality blend of TMG (trimethylglycine), methylfolate (5-MTHF), methylcobalamin (B12), and pyridoxal-5-phosphate (B6). Excellent foundational option for most patients seeking to optimize methylation and lower homocysteine.
Thorne Methyl-Guard or Methyl-Guard Plus — Clean, third-party tested, and ideal for those with sensitivities or who prefer vegan capsules. The Plus version contains higher concentrations of methyl donors and riboflavin for patients with persistently elevated homocysteine.
Pure Encapsulations Homocysteine Factors — Flexible formula that allows dose titration for patients needing individualized support or higher B-vitamin and TMG levels.
You can find all of these professional-grade options in my Fullscript store — where I’ve curated methylation and liver-support products I trust for my patients: https://us.fullscript.com/welcome/tayloredmedical.
Final Thoughts
If you’ve been working on your nutrition, detoxification, or methylation and still feel “stuck,” TMG might be the missing link. It’s inexpensive, well-tolerated, and backed by solid research.
Supporting methylation with TMG is one of the simplest, most effective ways to enhance cellular health, balance homocysteine, and improve long-term resilience — especially when combined with other methylation cofactors.
Explore my methylation support collection on Fullscript: https://us.fullscript.com/plans/tayloredmedical-methylation-support.
(Always consult your clinician before starting any new supplement, especially if you’re pregnant, nursing, or taking prescription medications.)
References
Rosas-Rodríguez JA, Valenzuela-Soto EM. The glycine betaine role in neurodegenerative, cardiovascular, hepatic, and renal diseases: Insights into disease and dysfunction networks. Life Sci. 2021;284:119943. doi:10.1016/j.lfs.2021.119943
Slow S, Lever M, Lee MB, et al. Betaine analogs alter homocysteine metabolism in rats. Int J Biochem Cell Biol. 2003;35(11):287–296. doi:10.1016/j.biocel.2003.10.001
