Trimethylglycine
Amino Acid ·Exploratory record · not publication-reviewed ·Updated July 13, 2026
Trimethylglycine (TMG), also called betaine anhydrous, is a naturally occurring amino acid derivative that serves as a methyl donor in the body. It supports the remethylation of homocysteine back to methionine and is most commonly used to lower elevated homocysteine and to maintain methylation capacity, which can be taxed when supplementing NAD precursors such as nicotinamide riboside or niacinamide.
Exploratory record, not a reviewed medical publication.
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What the research says.
A quick, data-only summary. The full evidence, dosing, and sources are below.
Trimethylglycine is an amino acid most often used for lowers elevated plasma homocysteine, supports methylation capacity (same regeneration), may offset methyl group depletion from nad precursor supplementation. NutriStack rates the overall evidence as moderate. A typical adult dose is 500 mg to 6 g per day; 1 to 3 g daily is typical for homocysteine support, with up to 6 g daily used in clinical homocystinuria management, commonly taken as betaine anhydrous powder or capsules (avoid betaine hydrochloride, which is a different acid-supplying form). This profile indexes 9 sources.
- Gastrointestinal upset (nausea, diarrhea, bloating) at higher doses
- Fishy body odor at very high doses (from elevated trimethylamine)
- Possible increase in LDL and total cholesterol with high-dose supplementation
- Caution in individuals with kidney disease
- Caution in those with elevated cholesterol or cardiovascular risk due to potential LDL increase
The bottom line
Evidence rating moderate. Most-documented uses: lowers elevated plasma homocysteine, supports methylation capacity (same regeneration), may offset methyl group depletion from nad precursor supplementation. 9 sources indexed (1983–2014), with 0 interaction records on file.
How it works, mechanistically.
Core mechanism
TMG donates one of its three methyl groups to homocysteine via the enzyme betaine-homocysteine methyltransferase (BHMT), regenerating methionine and producing dimethylglycine as a byproduct. This pathway is independent of folate and vitamin B12, providing an alternative route to the methionine synthase pathway for clearing homocysteine, particularly in the liver and kidney. By replenishing methionine, TMG indirectly supports the production of S-adenosylmethionine (SAMe), the universal methyl donor used in DNA methylation, neurotransmitter synthesis, and phospholipid formation. TMG also functions as an organic osmolyte, stabilizing protein structure and cellular hydration under osmotic stress.8,6
Dosing & protocol.
TMG is water soluble and well absorbed orally. Taking it with food can reduce the chance of GI upset. It is often paired with B vitamins (folate, B6, B12) since these cofactors support the complementary folate-dependent homocysteine pathway.5,1
What it actually costs.
Real-world pricing across three quality tiers. Assumes Betaine anhydrous (TMG) powder.
TMG is inexpensive in bulk powder form; cost per effective dose is calculated around a typical 1000-1500 mg daily serving. Capsules and tested/certified premium brands cost more per gram than bulk powder. Betaine HCl products are priced for digestive dosing and are not directly comparable on a methyl-donor basis. Updated 2026-06-04.
Full safety detail.
Side effects
- Gastrointestinal upset (nausea, diarrhea, bloating) at higher doses
- Fishy body odor at very high doses (from elevated trimethylamine)
- Possible increase in LDL and total cholesterol with high-dose supplementation
Contraindications
- Caution in individuals with kidney disease
- Caution in those with elevated cholesterol or cardiovascular risk due to potential LDL increase
- Discuss with a clinician if combining with other methylation agents or if pregnant or breastfeeding
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Meta-analyses & systematic reviews
1- 1Effect of betaine supplementation on plasma homocysteine in healthy adults: a systematic review and meta-analysisMcRae MP · Journal of Chiropractic Medicine · 2013
Randomized controlled trials
5- 2Effect of betaine supplementation on power performance and fatigueHoffman JR et al. · Journal of the International Society of Sports Nutrition · 2009
Betaine supplementation was associated with modest improvements in muscular endurance and power output in trained subjects.
- 3Effect of homocysteine-lowering nutrients (betaine) on serum lipids: secondary analysis of supplementation trialsOlthof MR, van Vliet T, Verhoef P, Zock PL, Katan MB · PLoS Medicine · 2005
- 4Betaine supplementation lowers plasma homocysteine in healthy men and womenOlthof MR et al. · Journal of Nutrition · 2003
Daily betaine (6 g) reduced fasting plasma homocysteine concentrations in healthy adults compared with placebo.
- 5A dose-response relationship between plasma betaine and homocysteine lowering after betaine supplementationOlthof MR, van Vliet T, Boelsma E, Verhoef P · Journal of Nutrition · 2003
- 6Betaine in the treatment of homocystinuriaWilcken DEL et al. · New England Journal of Medicine · 1983
Betaine reduced plasma homocysteine in patients with homocystinuria by enhancing remethylation to methionine via the BHMT pathway.
Reviews & position papers
2- 7Effect of betaine supplementation on power performance and body composition: a review of resistance-exercise trialsCholewa JM, Guimaraes-Ferreira L, Zanchi NE · Amino Acids · 2014
- 8Betaine in human nutritionCraig SAS et al. · American Journal of Clinical Nutrition · 2004
Betaine donates a methyl group to homocysteine through BHMT, supporting methionine and SAMe regeneration and acting as an osmolyte.
Observational studies
1- 9Betaine in the treatment of homocystinuria due to cystathionine beta-synthase deficiencyWilcken DEL, Wilcken B, Dudman NPB, Tyrrell PA · New England Journal of Medicine · 1983
Common questions.
Quick answers about Trimethylglycine, drawn from the data on this page.
What is Trimethylglycine?
Trimethylglycine (TMG), also called betaine anhydrous, is a naturally occurring amino acid derivative that serves as a methyl donor in the body. It supports the remethylation of homocysteine back to methionine and is most commonly used to lower elevated homocysteine and to maintain methylation capacity, which can be taxed when supplementing NAD precursors such as nicotinamide riboside or niacinamide.
What is Trimethylglycine used for?
Commonly cited benefits of Trimethylglycine include: Lowers elevated plasma homocysteine; Supports methylation capacity (SAMe regeneration); May offset methyl group depletion from NAD precursor supplementation; Supports liver function and reduces hepatic fat accumulation; May modestly enhance physical performance and power output. NutriStack rates the overall evidence as moderate.
What is a typical dose of Trimethylglycine?
A typical adult dose of Trimethylglycine is 500 mg to 6 g per day; 1 to 3 g daily is typical for homocysteine support, with up to 6 g daily used in clinical homocystinuria management. The commonly recommended form is Betaine anhydrous powder or capsules (avoid betaine hydrochloride, which is a different acid-supplying form). These are general ranges, not personalized advice; confirm the right dose with a clinician.
What are the side effects of Trimethylglycine?
Reported side effects include gastrointestinal upset (nausea, diarrhea, bloating) at higher doses, fishy body odor at very high doses (from elevated trimethylamine), possible increase in ldl and total cholesterol with high-dose supplementation. This is educational information; check with a healthcare professional before use.
How strong is the evidence for Trimethylglycine?
NutriStack rates this as Moderate, meaning several aligned RCTs or one large RCT plus supporting reviews. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.
Use this with your stack
Trimethylglycine in NutriStack.
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