TMG (Trimethylglycine)
Also known as: Trimethylglycine, Betaine, Betaine Anhydrous, Glycine Betaine
Lower numbers = closer to natural. Higher numbers = more enhanced.
Why this rating?
TMG (betaine) is glycine carrying three methyl groups, a dietary methyl donor found in beets and whole grains. It is used to lower homocysteine, support methylation, and (in the gym context) as a modest ergogenic and as methyl-donor "insurance" alongside NAD precursors. It is not a hormone or anabolic and does not directly build muscle. Rated 1 as a basic health/methylation supplement with, at most, a small ergogenic effect.
Overview
Trimethylglycine (betaine) is a naturally occurring methyl donor. It plays two roles that make it popular: it lowers homocysteine (via the BHMT remethylation pathway) supporting cardiovascular/methylation health, and it acts as an osmolyte with a modest ergogenic reputation for power and strength. In the longevity world it is the default "methyl support" paired with NAD+ precursors, though, honestly, that specific need is strongest with high-dose niacin rather than NMN/NR.
Purpose & Use Cases
Homocysteine Lowering
Reliably reduces plasma homocysteine, especially at higher doses (~4-6g/day), relevant to cardiovascular and methylation health.
Methyl-Donor Support
Regenerates SAM, buffering the methylation demand created when nicotinamide (from NAD turnover) or high-dose niacin is cleared by NNMT, the rationale for pairing it with NAD precursors.
Ergogenic (Betaine Angle)
As betaine anhydrous (~2.5g/day) it has modest evidence for improved power/strength and body composition, smaller and less consistent than creatine, so treat it as a secondary aid.
Benefits
- Lowers homocysteine (dose-dependent)
- Supports methylation / regenerates SAM
- Methyl-donor "insurance" for NAD precursors and niacin
- Modest ergogenic (power/strength) as betaine
- Cheap, non-hormonal, well tolerated
Good to Know
When is the methyl-donor support actually needed? (be honest)
The mechanism is textbook, NAD turnover and especially high-dose nicotinic acid (niacin) spend methyl groups when nicotinamide is cleared by NNMT, and TMG replenishes them. But the need is dose- and form-dependent: it is well-supported for high-dose NIACIN (which reliably raises homocysteine), and largely THEORETICAL for NMN/NR at normal supplement doses. A 1g/day NR RCT found no change in homocysteine or methylation. TMG is cheap, safe, and independently lowers homocysteine, so it is reasonable insurance, just not biochemically mandatory alongside NMN/NR.
TMG and betaine are the same thing
Trimethylglycine, betaine, betaine anhydrous, and glycine betaine are all the same molecule, glycine with three methyl groups. The "longevity methyl donor" and the "betaine ergogenic" are the identical compound viewed through two lenses.
The betaine ergogenic angle is real but modest
As betaine anhydrous (~2.5g/day) it has some evidence for improved power, strength, and body composition, likely via its osmolyte/cell-hydration role. The effect is smaller and less consistent than creatine. Treat it as a secondary aid, not a core performance supplement.
More is not automatically better (lipid caveat)
The doses that most strongly lower homocysteine (~6g/day) have raised LDL and triglycerides in controlled trials, potentially undoing the cardiovascular benefit. For general methyl support or ergogenic use, moderate doses (~1-3g/day) are the sensible default.
Dosage Guidelines
| Experience Level | Dosage Range |
|---|---|
| Beginner | 500 – 1000 mg/day |
| Intermediate | 1000 – 2500 mg/day |
| Advanced | 2500 – 6000 mg/day |
For methyl-support alongside NAD precursors, 500-1,000mg/day is typical. For the ergogenic (betaine) effect the studied dose is ~2.5g/day. Reliable homocysteine lowering needs ~4-6g/day, but note that at 6g/day trials have shown rises in LDL cholesterol and triglycerides, so more is not automatically better. Split higher doses; take with food.
No formal PK half-life is established. TMG is dosed once or twice daily, with its effect tracked by serum betaine and homocysteine rather than a plasma half-life.
Side Effects
GI Upset
uncommonNausea, diarrhea, or cramping, mainly at higher (multi-gram) doses.
Take with food; split the dose; lower it.
Body Odor ("Fishy" Smell)
rareHigh doses can raise trimethylamine, occasionally causing a fishy body odor.
Reduce dose; usually only at high intakes.
Raised LDL / Triglycerides
uncommonHigh-dose betaine (~6g/day) has been shown to increase LDL cholesterol and triglycerides in trials, potentially offsetting the cardiovascular benefit of homocysteine lowering.
Keep doses moderate (typically <=3g/day) unless a clinician is monitoring lipids; check a lipid panel if using high doses.
General Mitigation Strategies
Well tolerated at typical doses. The notable, non-obvious caution is the lipid effect at high (6g/day) intakes. The same doses that most strongly lower homocysteine can raise LDL/triglycerides, so keep doses moderate unless lipids are being monitored. Take with food to limit GI effects.
Post Cycle Therapy (PCT)
Not hormonal. No PCT required.
How It Works
TMG donates a methyl group to homocysteine via betaine-homocysteine methyltransferase (BHMT), regenerating methionine and thence S-adenosylmethionine (SAM), the body's universal methyl donor. This both lowers homocysteine and replenishes methylation capacity. Separately, betaine is an organic osmolyte that helps cells maintain hydration and volume under stress, the leading (if debated) explanation for its ergogenic effects on power output.
Fundamentals
Reference on the practices relevant to TMG (Trimethylglycine): how they are done and where they go wrong. Not a recommendation to use it.
Legal Status
Dietary supplement (USA); also an FDA-approved drug (Cystadane) for homocystinuria.
Legal status varies by country and changes over time. This is a general summary, not legal advice.
WADA Status
TMG/betaine is not on the WADA Prohibited List. It is a naturally occurring dietary methyl donor (also an approved drug for homocystinuria). No anabolic or stimulant action.