TMG (Trimethylglycine)

TMG's primary mechanism is donation of methyl groups via BHMT (betaine-homocysteine methyltransferase), which transfers a methyl group from TMG to homocysteine, regenerating methionine and producing dimethylglycine (DMG) as a byproduct. This is one of two parallel pathways that recycle homocysteine (the other is folate/B12-dependent via methionine synthase). When the folate pathway is compromised (MTHFR variants, B12 deficiency), TMG provides an independent route to maintain methionine availability.,Methionine produced via this pathway is then converted to SAMe (S-adenosylmethionine), the universal methyl donor that participates in 200+ methylation reactions including DNA methylation, neurotransmitter synthesis (epinephrine from norepinephrine, melatonin from serotonin), phosphatidylcholine production, creatine biosynthesis, and detoxification of various xenobiotics. By supporting methionine recycling, TMG indirectly supports all SAMe-dependent processes.,TMG also functions as an osmolyte - it accumulates intracellularly during osmotic stress and protects cellular proteins and DNA from osmotic damage. This osmolyte function may underlie some of the ergogenic effects (cellular hydration during high-intensity exercise) and the liver-protective effects (hepatocytes use osmolytes during oxidative stress). Additionally, TMG has been shown to reduce hepatic fat accumulation in animal models of fatty liver disease and to modestly improve insulin sensitivity in some metabolic syndrome studies.

TMG's primary mechanism is donation of methyl groups via BHMT (betaine-homocysteine methyltransferase), which transfers a methyl group from TMG to homocysteine, regenerating methionine and producing dimethylglycine (DMG) as a byproduct. This is one of two parallel pathways that recycle homocysteine (the other is folate/B12-dependent via methionine synthase). When the folate pathway is compromised (MTHFR variants, B12 deficiency), TMG provides an independent route to maintain methionine availability.,Methionine produced via this pathway is then converted to SAMe (S-adenosylmethionine), the universal methyl donor that participates in 200+ methylation reactions including DNA methylation, neurotransmitter synthesis (epinephrine from norepinephrine, melatonin from serotonin), phosphatidylcholine production, creatine biosynthesis, and detoxification of various xenobiotics. By supporting methionine recycling, TMG indirectly supports all SAMe-dependent processes.,TMG also functions as an osmolyte - it accumulates intracellularly during osmotic stress and protects cellular proteins and DNA from osmotic damage. This osmolyte function may underlie some of the ergogenic effects (cellular hydration during high-intensity exercise) and the liver-protective effects (hepatocytes use osmolytes during oxidative stress). Additionally, TMG has been shown to reduce hepatic fat accumulation in animal models of fatty liver disease and to modestly improve insulin sensitivity in some metabolic syndrome studies.

What's safe to combine, and what belongs in a separate pin.

Storage. Store at room temperature (20-25C) in a cool, dry place. Anhydrous powder is hygroscopic - keep tightly sealed and dry. Capsules and tablets shelf-stable for 2+ years. Powder may clump with moisture exposure but remains potent.

Classified as a dietary supplement in the US (no FDA pre-approval). Pharmaceutical version (Cystadane) is FDA-approved for homocystinuria. EU permits TMG as a food supplement. Generally Recognized as Safe (GRAS) at typical supplement doses. Available widely over the counter.