SAMe (S-Adenosylmethionine)

One of the better-evidenced supplements for depression and osteoarthritis. Enteric-coated tablets required for stability.

A rough internal score reflecting quantity, quality, and consistency of human evidence. Not a clinical recommendation.

Multiple meta-analyses confirm efficacy comparable to tricyclic antidepressants for depression and NSAIDs for osteoarthritis pain. Also well-studied for liver disease (cholestasis). AHRQ evidence review is favorable.

• Evidence-based for depression treatment
• Reduces osteoarthritis pain comparable to NSAIDs
• Supports liver methylation and detoxification
• Methyl donor for epigenetic processes

400–1600 mg daily for depression. 600–1200 mg daily for osteoarthritis. Start low and titrate up.

• GI discomfort and nausea
• Anxiety and insomnia
• Mania risk in bipolar disorder

Can trigger mania in bipolar disorder. Serotonin syndrome risk with SSRIs/SNRIs. Not for use with MAOIs.

Expensive and unstable. Enteric-coated, refrigerated tablets recommended. Must avoid butanedisulfonate salt if possible; tosylate form is better studied.

• Mood72
• Pain60
• Longevity40