TMG
Trimethylglycine (TMG), also called betaine, is a naturally occurring derivative of glycine found in foods such as beets, spinach, whole grains and seafood. The body can also produce it by oxidizing choline. TMG has two major biological roles: it acts as an organic osmolyte that helps cells maintain water balance and protein function, and it donates methyl groups in one-carbon metabolism.
Methyl donation and homocysteine. In the liver and kidneys, betaine-homocysteine methyltransferase (BHMT) transfers a methyl group from TMG to homocysteine, regenerating methionine and producing dimethylglycine. This pathway complements the folate- and vitamin-B12-dependent remethylation pathway. Because of this, supplemental TMG can lower elevated homocysteine in many people.
SAM and methylation capacity. Methionine is converted to S-adenosylmethionine (SAM), the principal methyl donor used for DNA, protein, neurotransmitter and phospholipid methylation. By supporting remethylation of homocysteine, TMG can influence the SAM-to-SAH balance and therefore cellular methylation capacity. This does not mean that more methyl donors always produce better epigenetic outcomes; methylation is highly tissue- and gene-specific.
Liver metabolism. TMG is closely linked to hepatic lipid handling. Choline and betaine contribute to phosphatidylcholine synthesis and export of triglycerides from the liver. Experimental studies show protection against fatty-liver accumulation under some dietary conditions, and human studies have examined betaine in metabolic-associated fatty liver disease. Results are mixed, so TMG should not be treated as an established therapy for fatty liver.
Osmoregulation. TMG can accumulate inside cells without disrupting enzyme function, helping stabilize proteins and membranes under osmotic stress. This property is important in the kidney medulla and has been studied in liver, muscle and other tissues under stress conditions.
Exercise and body composition. Sports-nutrition studies have tested TMG for strength, power and body composition, often at doses around a few grams per day. Some trials report small improvements in power output or lean-mass-related measures, while others find little difference from placebo. The evidence is not as consistent as for creatine.
Cardiovascular considerations. Lowering homocysteine is biochemically plausible as a cardiovascular benefit, but reducing a risk marker does not automatically translate into fewer clinical events. Some studies also report increases in total or LDL cholesterol with higher-dose betaine supplementation, which complicates a simple cardiovascular-benefit narrative.
Longevity research. TMG intersects with one-carbon metabolism, mitochondrial function, osmotic stress resistance and liver health, all relevant to aging biology. Animal and cellular studies suggest protective effects in selected models, but there is no robust evidence that TMG supplementation extends human lifespan. Its geroscience interest is mechanistic rather than clinically proven.
Dietary context. Foods rich in betaine often come packaged with other beneficial nutrients, particularly whole grains, vegetables and seafood. Circulating betaine levels also depend on choline intake, genetics, kidney function and one-carbon metabolism, so individual response to supplementation varies.
Safety. TMG is generally well tolerated at commonly studied doses. Gastrointestinal discomfort and a characteristic body odor can occur at higher intakes. Because TMG can alter homocysteine and lipid markers, laboratory monitoring may be useful when high-dose supplementation is used for a specific metabolic purpose.
Overall, trimethylglycine is a physiologically important methyl donor and osmolyte with clear effects on homocysteine metabolism. Its roles in liver biology and cellular stress are credible, but broader claims about anti-aging, cardiovascular prevention or lifespan extension are substantially less established.