SAM‑e
Natural methyl donor for mood support and joints, backed by human RCT data.
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Pharmacology
Contents
WHAT IS SAM-E?
Detailed overview
SAM-e (S-adenosylmethionine, ademetionine) is the body's primary methyl donor, formed from methionine and ATP, and a cofactor for hundreds of transmethylation reactions including the synthesis of monoamine neurotransmitters (serotonin, dopamine, norepinephrine). In randomized controlled trials SAM-e improved major depression symptoms both on its own and as an SSRI add-on in antidepressant non-responders, while in knee osteoarthritis its pain relief was comparable to nonsteroidal anti-inflammatory drugs. It is sold as a dietary supplement in the United States but is a prescription medicine (ademetionine) in several European countries for depression, joint complaints and intrahepatic cholestasis. Because of its activating effect it is usually dosed in the morning on an empty stomach.
Mechanism
Primary methyl donor (transmethylation)
Half-life
Short, roughly 2 hours in circulation
Legal status
Dietary supplement (US); prescription (EU)
Receptor profile
- Methylation cycle (transmethylation)Strong
- Monoamine neurotransmitters (serotonin, dopamine, norepinephrine)Moderate
- Cartilage and jointsModerate
Safety
Side effects, stop signs, contraindications
Side effects · 6
- Nausea, stomach upset, diarrhea, especially early in a course or at higher doses
- Insomnia or restless sleep if taken in the late afternoon or evening (activating effect)
- Headache
- Anxiety, restlessness or irritability in sensitive individuals
- May trigger mania or hypomania in bipolar disorder (mood switch)
- Dry mouth, sweating or mild palpitations may occur
Contraindications · 4
- Bipolar disorder: avoid without medical supervision due to the risk of triggering mania/hypomania
- Increased serotonin syndrome risk with serotonergic drugs (SSRIs, SNRIs, MAOIs, triptans); only under medical supervision
- Pregnancy and breastfeeding: although used in Europe for cholestasis of pregnancy, self-use only on medical advice
- Levodopa therapy in Parkinson's disease: SAM-e may theoretically methylate and inactivate levodopa
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial
Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M
Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: An 8-week double-blind, randomized, controlled trial
Sarris J, Byrne GJ, Bousman C, et al.
Oral Administration of S-Adenosylmethionine (SAMe) and Lactobacillus Plantarum HEAL9 Improves the Mild-To-Moderate Symptoms of Depression: A Randomized, Double-Blind, Placebo-Controlled Study
Ślifirski G, Król M, Turło J, et al.
S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research
Sharma A, Gerbarg P, Bottiglieri T, et al.
Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients
Kim J, Lee EY, Koh EM, et al.
Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review
Zhang Y, Li F, Wang H, et al.
FAQ
FAQ
Natural methyl donor for mood support and joints, backed by human RCT data.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.