Universal methyl donor
S-adenosylmethionine (SAMe)
Also searched as S-adenosylmethionine (SAMe).
Made from methionine and ATP, spent on DNA, histone, neurotransmitter and phospholipid methylation. The SAMe-to-sah ratio is the cell’s methylation capacity in one number.
In depth
S-adenosylmethionine — the body's universal methyl donor, upstream of neurotransmitter synthesis, DNA methylation and glutathione production. One molecule sitting at three separate crossroads.
What drives it
One-carbon metabolism increases it.
The cycle regenerates methionine, from which SAMe is made. Carried by the intermediary-metabolism and clinical reviews. doi 10.1016/j.molmet.2023.101755 · PMC9967593
Betaine methyl donor increases it.
Regenerating methionine feeds SAMe synthesis. Carried by the intermediary-metabolism, micronutrient and clinical reviews. doi 10.3390/nu18132141 · PMC9967593
NAD methylation leak reduces it.
NNMT consumes S-adenosylmethionine as the methyl donor for every nicotinamide it methylates. doi 10.1002/advs.202502727
What it drives
It increases DNA methylation.
The route from a vitamin to an epigenetic mark. SAMe is the substrate every methyltransferase draws on, including the DNA methyltransferases. Carried by the intermediary-metabolism and clinical reviews. doi 10.1016/j.molmet.2023.101755 · PMC9967593
It increases Mood.
SAMe supplies methyl groups for monoamine neurotransmitter synthesis and metabolism. Carried by the intermediary-metabolism and clinical reviews. doi 10.1016/j.molmet.2023.101755 · PMC9967593
It increases Rapid energy buffer.
Creatine synthesis is one of the largest single demands on the body's methyl groups - which is why dietary creatine spares SAMe for other methylation. Carried by the intermediary-metabolism reviews. doi 10.1016/j.molmet.2023.101755 · PMC9967593
It increases Dopamine clearance.
SAMe is the obligate methyl donor for COMT-catalyzed O-methylation of catecholamines. PMID 21095459
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.