TMG (Trimethylglycine / Betaine)
A methyl donor derived from beets that supports the methylation cycle, reduces homocysteine, and helps maintain methyl group availability when supplementing NAD+ precursors like NMN or NR.
Reviewed & fact-checked by
Dr. Jane Smith, MD, PhDChief Medical Reviewer · Last updated: January 15, 2026
Medical Disclaimer: The information on this page is for educational and research purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
What Is TMG and Why Does It Matter for NMN Stacking?
Trimethylglycine (TMG), also known as betaine, is a naturally occurring compound found in beets, spinach, and whole grains. It carries three methyl groups, making it one of the most efficient methyl donors in human biochemistry.
The Methylation Connection to NMN
When NMN is converted to NAD+ in cells, a key enzymatic pathway involves NNMT (nicotinamide N-methyltransferase), which methylates nicotinamide as part of NAD+ catabolism. At higher NMN doses, this process can place significant demand on the body's methyl group pool.
TMG replenishes this pool by donating methyl groups through the betaine-homocysteine methyltransferase (BHMT) reaction, converting homocysteine back to methionine. This has two benefits: []
- Maintains methyl availability for ongoing NMN metabolism
- Lowers homocysteine, an independent cardiovascular risk marker
Homocysteine Lowering Evidence
Multiple RCTs have confirmed TMG's efficacy in reducing plasma homocysteine. A 2002 study in 42 patients with hyperhomocysteinemia demonstrated significant reductions with 6g/day TMG supplementation. []
Practical Notes
The characteristic "fishy" body odour at doses above 3g/day is caused by conversion to trimethylamine (TMA) by gut bacteria. This is dose-dependent and not harmful. Splitting doses (morning and evening) can reduce this effect.
Stacking Interactions
How TMG (Trimethylglycine / Betaine) interacts with other compounds
500mg–1000mg TMG per 500mg NMN is a widely used ratio. Stack together in the morning.
No significant interaction. Both can be taken simultaneously.
Safety Profile — Tier A
Well-tolerated — strong human evidence
Contraindications
- ●Hypermethylation conditions (consult physician)
- ●Kidney disease — monitor with healthcare provider
Side Effects
- ●Body odour (fishy smell) at doses above 3g — dose-dependent
- ●Nausea or gastrointestinal discomfort at high doses