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Compound

SAMe (S-Adenosyl Methionine)

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SAMe (S-Adenosyl Methionine). Universal methyl donor with antidepressant and liver-supportive evidence.

How it works. Donates methyl groups for neurotransmitter and phospholipid synthesis.

What the research supports. 2 graded claims. Strongest: Comparable to imipramine in depression (moderate).

How much to take. Typical dose: 400–1600 mg AM, enteric coated.

Side effects and interactions. 1 medication interaction listed. Serious: Serotonin syndrome with SSRIs.

Stacking. Pairs well with Milk thistle (silymarin), NAC.

Common forms. Available as Capsule or softgel, Powder, Sublingual or buccal, Liposomal liquid.

Key studies. 9 studies cited. The strongest are listed with links to PubMed.

Community. Experiences from people who have tried SAMe (S-Adenosyl Methionine). Anecdotes are not medical advice.

SAMe (S-Adenosyl Methionine). Universal methyl donor with antidepressant and liver-supportive evidence.

Molecular structureC15H22N6O5S · 398.4 g/mol

What it is

Universal methyl donor with antidepressant and liver-supportive evidence.

Food sources

Endogenously produced or biosynthesized moleculeStandardized pharmaceutical- or food-grade supplementCombined with cofactors that improve absorption or activity

Goals

Depression SupportMood EnhancementLiver HealthJoint Pain

How it works

Donates methyl groups for neurotransmitter and phospholipid synthesis.

Pathways

  • Donates methyl groups for neurotransmitter
  • phospholipid synthesis

Effects

  • +Comparable to imipramine in depression supports
  • +intrahepatic cholestasis supports

What the research supports

Comparable to imipramine in depressionmoderate
Improves intrahepatic cholestasismoderate

Strong: consistent results across large trials or meta-analyses. Moderate: several trials, mostly positive. Limited: small or mixed studies. Preclinical: animal or cell research only.

Typical dose
400–1600 mg AM, enteric coated
TimingConsistent daily timing recommended; split larger doses if GI tolerance is a concern.
With foodEmpty stomach
Best formMost evidence is based on the capsule or softgel form.
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Side effects & interactions

Common side effects

  • Nausea
  • Insomnia

Serious

  • Serotonin syndrome with SSRIs

Medication interactions

SSRIs/MAOIssevere

Serotonin syndrome risk.

Check any supplement–medication combination with your pharmacist before starting.

Combines with

Pairs well

Common forms

  • Capsule or softgel
  • Powder
  • Sublingual or buccal
  • Liposomal liquid

Key studies

9 studies cited in total.

SAMe for depression: a meta-analysis ↗
Meta-analysis · Cochrane Database · 2016

Comparable to imipramine for moderate depression.

PubMed: SAMe (S-Adenosyl Methionine) — Comparable to imipramine in depression ↗
Systematic review · PubMed (NLM) · 2026

Opens current human and preclinical literature matching SAMe (S-Adenosyl Methionine) and "Comparable to imipramine in depression". Filter by RCT, meta-analysis, or year on the results page.

PubMed: SAMe (S-Adenosyl Methionine) — Improves intrahepatic cholestasis ↗
Systematic review · PubMed (NLM) · 2026

Opens current human and preclinical literature matching SAMe (S-Adenosyl Methionine) and "Improves intrahepatic cholestasis". Filter by RCT, meta-analysis, or year on the results page.

Discussion

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