SAMe
S-Adenosyl-L-Methionine is a naturally occurring compound involved in over 100 methylation reactions in the body. In the brain, SAMe is essential for neurotransmitter synthesis (dopamine, serotonin, norepinephrine) and myelin maintenance. Used as a prescription antidepressant in Europe and as a supplement in the US. Also supports liver function and joint health.
Dosage
Standard: 400-1600 mg daily on an empty stomach. Start at 200-400 mg and increase gradually. Take in the morning — can be activating. Enteric-coated tablets preferred for stability. Often combined with B vitamins (B12, folate) which are needed for SAMe recycling.
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Half-Life
1.5-2 hours
Administration
Oral (enteric-coated tablets). Take on empty stomach 30 minutes before food. Enteric coating protects from stomach acid degradation.
Shop SAMe
99%+ purity · third-party lab tested
Mechanism of Action
SAMe serves as the principal methyl donor in over 100 transmethylation reactions catalyzed by SAM-dependent methyltransferases. In the brain, it donates methyl groups to phosphatidylethanolamine N-methyltransferase (PEMT), converting PE to phosphatidylcholine and maintaining neuronal membrane fluidity critical for receptor function. It methylates DNA via DNMT enzymes, modulating gene expression epigenetically. SAMe is essential for catechol-O-methyltransferase (COMT) activity, which metabolizes dopamine and norepinephrine, and for phenylethanolamine N-methyltransferase (PNMT), which converts norepinephrine to epinephrine. It feeds the transsulfuration pathway, producing cysteine via cystathionine beta-synthase (CBS) and cystathionine gamma-lyase, ultimately supporting glutathione synthesis for antioxidant defense. SAMe also donates methyl groups for myelin basic protein methylation, essential for myelin sheath integrity and nerve conduction velocity.
Regulatory Status
Prescription antidepressant in Italy, Germany, and other European countries. Dietary supplement in the US. Available OTC in most countries.
Risks & Safety
Common
Nausea, diarrhea, anxiety, insomnia.
Serious
Can trigger manic episodes in bipolar disorder. Serotonin syndrome risk when combined with SSRIs or MAOIs.
Rare
Skin rash, increased homocysteine without B vitamin co-supplementation.
Compare SAMe With
Research Papers
9Published: October 27, 2024
AI Summary
S-adenosylmethionine (SAMe) is a natural compound implicated in the treatment of liver dysfunction. In this systematic review, our objective was to determine the efficacy, safety, and optimal dose of SAMe in liver diseases.
Published: September 30, 2021
AI Summary
Same-day protocols for craniotomy have been demonstrated to be feasible and safe. Its several benefits include decreased hospital costs, less nosocomial complications, fewer case cancellations, with a high degree of patient satisfaction.
Published: September 16, 2022
AI Summary
Consistent with the prediction, the analyses of the National Survey of Family Growth data showed that biological infertility, but not surgical infertility, was significantly associated with same-sex self-identified labels, behavior and sexual attraction in women.
Published: September 4, 2020
AI Summary
Major depressive disorder (MDD) is a recurrent illness with high rates of chronicity, treatment-resistance, and significant economic impact. This systematic review examines the evidence concerning the efficacy of SAMe as monotherapy or in combination with antidepressants.
Published: June 14, 2022
AI Summary
Published studies have reported many inconsistent results regarding the comparison of same-day discharge total joint arthroplasty (TJA) and inpatient TJA. More notably, many recent studies comparing same-day discharge TJA with fast-track TJA presented higher rates of complications for same-day disch
Published: September 17, 2024
AI Summary
Our aim was to determine the efficacy, safety, and optimal dose of SAMe in Central Nervous System (CNS) signs (e.g., mood, behavior). Overall, SAMe was effective in 24 of 36 studies, with adverse events mostly consisting of mild, transient gastrointestinal disturbances.
Published: January 3, 2024
AI Summary
S-adenosyl-L-methionine (SAMe), a natural substance, has antidepressant effects, but the exact effect remains unclear. This study examines the evidence concerning the efficacy of SAMe as a monotherapy or in combination with antidepressants.
Published: February 22, 2017
AI Summary
Findings from this review suggest a need for research that moves conceptually and methodologically beyond a focus on the individual to a focus on the dyad and the interpersonal, institutional, and cultural sources of minority stress that affect couple relationships.
Published: February 25, 2024
AI Summary
The SAMe-TT2R2 score identifies patients on vitamin K antagonists (VKAs) who are more likely to have poor time in therapeutic range (TTR); however, the association between SAMe-TT2R2 and clinical outcomes remains controversial.
Frequently Asked Questions
What is SAMe used for?
S-Adenosyl-L-Methionine is a naturally occurring compound involved in over 100 methylation reactions in the body. In the brain, SAMe is essential for neurotransmitter synthesis (dopamine, serotonin, norepinephrine) and myelin maintenance. Used as a prescription antidepressant in Europe and as a supplement in the US. Also supports liver function and joint health.
What are the side effects of SAMe?
Common: Nausea, diarrhea, anxiety, insomnia. Serious: Can trigger manic episodes in bipolar disorder. Serotonin syndrome risk when combined with SSRIs or MAOIs. Rare: Skin rash, increased homocysteine without B vitamin co-supplementation.
How is SAMe administered?
SAMe is administered via oral (enteric-coated tablets). take on empty stomach 30 minutes before food. enteric coating protects from stomach acid degradation..
What is the half-life of SAMe?
The half-life of SAMe is 1.5-2 hours.
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