TMG (Trimethylglycine) — The Methyl Donor
TMG (betaine) is a methyl donor derived from beets that supports the methylation cycle, reduces homocysteine, and may protect against epigenetic aging. It is commonly paired with NMN to replenish methyl groups consumed in NAD+ synthesis.
Mechanism of Action
TMG donates methyl groups to homocysteine via betaine-homocysteine methyltransferase (BHMT), converting it to methionine. This reduces cardiovascular risk from elevated homocysteine and supports SAM (S-adenosylmethionine) production — the universal methyl donor for DNA methylation, neurotransmitter synthesis, and gene expression.
Human Trial Evidence
A 2005 Journal of Nutrition meta-analysis (Olthof & Verhoef) of 12 RCTs showed 6 g/day TMG reduced plasma homocysteine by 1.8 µmol/L. Multiple trials confirm dose-dependent homocysteine lowering at 1.5–6 g/day. TMG is widely used alongside NMN in longevity protocols to prevent methyl group depletion.
Dosing Protocol
500 mg–3 g/day. Sinclair protocol: 500 mg/day alongside NMN. Higher doses (3–6 g/day) for homocysteine lowering. Best taken with food. Split dosing (morning + evening) improves tolerability at higher doses.
Safety & Contraindications
Well-tolerated. At high doses (>6 g/day): fishy body odor (trimethylaminuria in susceptible individuals), GI upset. May increase LDL cholesterol at very high doses — monitor lipids. Generally safe for long-term use.