TMG (Trimethylglycine)

Trimethylglycine (TMG), also known as betaine, is a naturally occurring compound found in beets, spinach, and quinoa. It serves as one of the body's most important methyl donors, participating in the conversion of homocysteine to methionine via betaine-homocysteine methyltransferase (BHMT). This reaction is critical for maintaining healthy homocysteine levels, supporting the methionine cycle, and ensuring adequate SAMe (S-adenosylmethionine) production. TMG has gained significant attention in the longevity community specifically because NAD+ precursors (NMN, NR) and NAD+ itself consume methyl groups during metabolism. When NAD+ is broken down by CD38 or used by PARPs, the resulting nicotinamide must be methylated (by NNMT) to nicotinamide N-methylnicotinamide for excretion.

This process depletes the body's methyl pool. Supplementing TMG alongside NAD+ protocols helps replenish methyl groups and prevent elevated homocysteine. Beyond its role as a methyl donor, TMG acts as an osmolyte (protecting cells from dehydration stress), supports liver health by reducing hepatic fat accumulation, and has ergogenic properties — improving power output and body composition in some studies.