TMG (Betaine / Trimethylglycine)
A direct methyl donor that lowers homocysteine, supports liver function, and provides a modest but real boost to strength and power output.
Strong for homocysteine reduction (FDA-approved as a drug for this in homocystinuria). Multiple RCTs support modest strength and power gains in resistance-trained subjects. Liver fat reduction in NAFLD shown in small trials. Homocysteine: 2–4 weeks. Performance: 6–8 weeks.
TMG (trimethylglycine, betaine) is a small molecule with three methyl groups it can hand off. It's the body's primary backup methyl donor when SAMe is running low — particularly important for converting homocysteine back to methionine in the liver. Strong methylation support has downstream effects on neurotransmitter synthesis, gene regulation, and detox. Athletes have taken interest because TMG modestly improves power output and lean body composition (~3–5% strength gains in some trials). It also spares choline by donating methyl groups in choline's place — relevant for anyone supplementing NMN/NR (which consume methyl groups).
- Form
- Anhydrous TMG (betaine anhydrous) — the standard form. Slightly sweet powder; mixes in water. Don't confuse with 'betaine HCl' which is a separate compound for stomach acid support.
- Dose
- 500–2,000 mg/day for general methylation / homocysteine support. 2,500 mg twice daily (5 g/day) for performance use — the dose used in the strength studies.
- Timing
- AM or pre-workout for performance. Anytime for methylation support. With or without food.
- Schedule
- Daily.
- Side effects
- Body / breath odor (rare, dose-dependent — like trimethylaminuria). Mild GI upset. Can raise LDL cholesterol modestly at high doses (5g+/day) in some — worth checking lipids if running long-term.
- Interactions
- Generally clean. Theoretical interaction with methotrexate.
- Contraindications
- Pre-existing high LDL cholesterol (relative — monitor). Trimethylaminuria (fish-odor syndrome).
- Lab markers
- Homocysteine — the most direct marker; target below 8 μmol/L. Lipid panel if running >2 g/day long-term.
- Food sources
- Beets and beet greens (where 'betaine' got its name), spinach, quinoa, wheat bran, whole grains, shellfish. Most people get 100–300 mg/day from diet — supplementing 1g+ is meaningfully more.
Pairs with
NMN, NR, or niacinamide — these methylate during clearance and burn through methyl donors; TMG offsets that drain. B12 + methylfolate + B6 (the homocysteine-clearing crew). Creatine (TMG is a precursor to creatine synthesis — synergistic for muscle).
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