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

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]
Betaine and homocysteine · meta-analysis
Reliable homocysteine lowering.
Open on PubMed ↗
[2]
Betaine and exercise performance · review
Small strength/power signals.
Open on PubMed ↗
[3]
Betaine and blood lipids · RCT
High doses may raise LDL/total cholesterol.
Open on PubMed ↗

See all studies on PubMed ↗

Scoped PubMed search, not a curated bibliography: the individual PMIDs for this entry have not yet been verified one by one. For that reason it is not used to support a high grade and is awaiting review.

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.

Related molecules

NMNB Nicotinamide Riboside (NR)B

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