SAMe

Also known as: S-adenosylmethionine, SAM-e, ademetionine, AdoMet

Grade B — Moderate Evidenceamino acid derivativemethylation

Recommended Dosage

4001600 mg

Morning on empty stomach, 30 min before food. Second dose midday.

Key methyl donor involved in neurotransmitter synthesis. Cochrane-level evidence for depression, comparable to TCAs.

Last reviewed: 2026-03-09

Evidence Rating: Grade B — Moderate Evidence

Some RCTs with positive results, or strong observational evidence. More research may refine our understanding.

Interaction Warnings

SSRIs/SNRIs/MAOIsHigh Risk

Risk of serotonin syndrome — do NOT combine without physician oversight

TramadolHigh Risk

Serotonin syndrome risk

LevodopaModerate

May interfere with Parkinson's medication; avoid

⚠️ Important Notes

  • CONTRAINDICATED in bipolar disorder — may trigger mania
  • Enteric-coated for best stability
  • Store refrigerated; temperature-sensitive

Clinical Evidence (3 studies)

SAMe as adjunct to SSRIs for treatment-resistant depression

Papakostas GI (2009) — J Clin Psychiatry

Improved response rates in treatment-resistant depression

View on PubMed

SAMe for depression, liver, and osteoarthritis

Mischoulon D & Fava M (2002) — Am J Clin Nutr

Comprehensive evidence summary

View on PubMed

SAMe vs antidepressants: meta-analysis

Bressa GM (1994) — Acta Neurol Scand

Comparable to tricyclic antidepressants

View on PubMed

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⚕️ Important Disclaimer

This information is for educational purposes only. It is not medical advice. Always consult a healthcare provider before starting any supplement regimen, especially if you take medications or have health conditions.

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