SAMe

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

Grade B — Moderate Evidenceamino acid derivativemethylation
400–1600 mgMorning on empty stomach, 30 min before food. Second dose midday.

S-Adenosyl-L-Methionine (SAMe) is a naturally occurring molecule that serves as the body's primary methyl donor, involved in over 100 methylation reactions. It has strong clinical evidence as an antidepressant — comparable in efficacy to tricyclic antidepressants in multiple trials — and also supports liver function and joint health. SAMe works by facilitating the synthesis of neurotransmitters including serotonin, dopamine, and norepinephrine.

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

😊Mood🧬Longevity
Last reviewed: 2026-03-12

Quick Facts

Evidence

Grade B

Studies

3

Interactions

3

Forms

1

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

Alternatives to Consider

These supplements target similar goals and may be worth considering alongside or instead of SAMe.

L-Carnitine

Grade B

Amino acid derivative critical for fatty acid transport into mitochondria. ALCAR crosses the blood-brain barrier for cognitive support. Good evidence for exercise performance and male fertility.

🧬 Longevity

Related Supplements

Vitamin D3

Grade A — Strong Evidence

Essential hormone precursor. Most people in northern latitudes are deficient. Strong evidence for immunity, bone health, and mood.

Omega-3 Fish Oil

Grade A — Strong Evidence

Essential fatty acids with strong evidence for cardiovascular and mental health. EPA-dominant for mood; triglyceride form for absorption.

NAC (N-Acetyl Cysteine)

Grade B — Moderate Evidence

Precursor to glutathione (master antioxidant). Strong evidence for respiratory health, liver support, and psychiatric conditions.

Curcumin

Grade B — Moderate Evidence

Potent anti-inflammatory from turmeric. Must enhance bioavailability with piperine or specialized formulations.

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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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