TMG (Betaine)
TMG · trimethylglycine · betaine · betaine anhydrous
A methyl donor used to lower homocysteine and often paired with NMN/NR.
TypeSupplement / dietary
The grade answers: What does the human evidence support for: Methylation & homocysteine support?
Grade
C
Limited
The grade rates evidence quality — it is not advice to take or buy.
- Class
- Methyl donor
- Primary use
- Methylation & homocysteine support
- Evidence strength
- medium
- Last reviewed
- 2026-07-01
Bottom line
Reliably lowers homocysteine and has some sports-performance data — but whether that translates to longevity, or is even needed alongside NAD boosters, is unproven.
What the evidence says
Betaine (trimethylglycine) is a well-established methyl donor: it dependably lowers blood homocysteine, and there is reasonable evidence for small strength/power benefits in athletes. Its popularity in longevity stacks comes from a theory that NAD⁺ precursors like NMN consume methyl groups, so TMG 'replaces' them — a plausible idea that hasn't actually been shown to matter for outcomes in humans. High-dose betaine can also raise LDL/total cholesterol. Grade C: proven biochemical effect (homocysteine), unproven longevity payoff, with a lipid caveat.
Key studies
- [1]
- [2]
- [3]
Mechanism
Donates methyl groups to convert homocysteine back to methionine (an alternative to the folate/B12 pathway), supporting methylation reactions throughout the body.
Safety
Generally well tolerated; GI upset at higher doses. Notably, high-dose betaine has raised total and LDL cholesterol in some trials — relevant given the cardiovascular framing. Not a purely 'free' addition.
Dosage context
Homocysteine/performance trials use ~1.5–6 g/day; longevity-stack use is often ~500–1000 mg to 'offset' NAD-precursor methylation — a dose based on theory, not outcome data.
Examples of application
- Taken ~500–1000 mg to 'offset' NAD-precursor methylation (a theory).
- Or ~1.5–6 g/day where homocysteine lowering is the goal.
- Watched for a possible LDL rise at higher doses.
From the field
TMG is sold as the automatic partner to NMN. The homocysteine effect is real; the 'you must take it with your NAD booster' claim is theory, and the LDL signal is the part that gets left out. Grade C.