SAMe (S-Adenosyl-L-Methionine)
Also known as: S-adenosyl-L-methionine, S-adenosylmethionine, ademetionine, SAM-e, SAMe tosylate disulfate, SAMe 1,4-butanedisulfonate
SAMe is the body's principal methyl donor, made from methionine and ATP, and participates in neurotransmitter synthesis, phospholipid methylation, and cartilage proteoglycan production. As a supplement it is used for mood support and joint comfort. A 2024 meta-analysis of 23 trials found SAMe monotherapy superior to placebo for depressive symptoms with good acceptability, and older trials in knee and hip discomfort showed small effects. It is unstable and hygroscopic, so it is sold as a stabilized salt in enteric-coated, blister-packed tablets.
Research summary
Donates methyl groups for monoamine neurotransmitter synthesis and membrane phospholipid methylation; supports glutathione synthesis via transsulfuration.
Dosage
Daily amounts, of compound.
| Lowest studied | Typical range | Highest studied | Upper limit |
|---|---|---|---|
| 400 mg | 400–1,600 mg | — | — |
400–1,600 mg of SAMe ion daily, usually 400 mg once or twice daily to start, taken on an empty stomach in the morning. Doses refer to the SAMe ion; the stabilized salts (tosylate disulfate or 1,4-butanedisulfonate) are roughly 40–50% SAMe by weight, so verify the ion content on the supplier CoA. Mood trials commonly ran 6–12 weeks; joint trials often took several weeks for effect.
Standardization: stabilized SAMe salt assayed as SAMe ion (≥ 80% S,S-isomer)
Source material: yeast fermentation, stabilized as tosylate disulfate or butanedisulfonate salt
As supplied: Assumes a salt that is 50% SAMe ion (2 mg raw material per 1 mg SAMe). Tosylate disulfate grades are closer to 40%, requiring 2.5 mg per mg.
Format suitability
- Capsule
- Powder
- Tablet
- Softgel
- Gummy
- Liquid
Extremely hygroscopic and acid-labile; enteric-coated tablets in blister packs are the standard format. Capsules require moisture-protective packaging and stabilized grades. Not suited to powders, gummies, or liquids.
Formulation notes
Serotonergic: interacts with antidepressants (SSRIs, MAOIs), tramadol, dextromethorphan, and St. John's Wort. Can trigger mania in bipolar disorder. Often paired with B12 and folate.
- Notable drug interactions
Sources
Related ingredients
Curcumin Extract (95% Curcuminoids)
BotanicalA concentrated turmeric rhizome extract standardized to 95% curcuminoids, the form used in most joint and inflammation research.
Typical: 500–1,500 mg
N-Acetyl-Cysteine (NAC)
Amino acidAn acetylated form of the amino acid cysteine that is the rate-limiting precursor for glutathione, the body's principal intracellular antioxidant.
Typical: 600–1,800 mg
Curcumin Solid Lipid Particle (Longvida)
BotanicalA branded curcumin formulation in which curcumin is embedded in solid lipid particles to protect it from degradation in the gut and support delivery of free curcumin into circulation.
Typical: 400–800 mg
Curcumin with Turmeric Essential Oils (BCM-95)
BotanicalA branded turmeric extract that recombines curcuminoids with turmeric essential oil (turmerones) rather than using a synthetic carrier.
Typical: 500–1,000 mg
Vitamin D3 (Cholecalciferol)
VitaminThe form of vitamin D the body makes from sunlight and the most effective supplemental form for raising blood levels.
Typical: 1,000–2,000 IU