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evidence · mechanism · dose
Supplements/Compound

SAMe (S-Adenosyl Methionine)

Universal methyl donor with antidepressant and liver-supportive evidence.

Depression SupportMood EnhancementLiver HealthJoint Pain

Overview

Universal methyl donor with antidepressant and liver-supportive evidence.

Natural sources
    Common forms

      Mechanism of action

      Donates methyl groups for neurotransmitter and phospholipid synthesis.

      Pathways

        Effects on the body

        Organ system effects

        Evidence-based benefits

        Comparable to imipramine in depression

        Moderate evidence

        Improves intrahepatic cholestasis

        Moderate evidence

        Potential side effects

        Common
        • · Nausea
        • · Insomnia
        Rare
        • · Mania (bipolar)
        Serious
        • · Serotonin syndrome with SSRIs

        Drug interactions

        SSRIs/MAOIs
        Serotonin syndrome risk.
        severe

        Supplement interactions

        Pairs well with

        None listed.

        Avoid combining with

        No specific avoidances listed.

        Dosing & bioavailability

        Typical dose
        400–1600 mg AM, enteric coated
        With food?
        Empty stomach

        Where to buy

        Affiliate-style search links to reputable retailers. We don't endorse specific brands — verify third-party testing (USP, NSF, Informed Sport) before purchase.

        Compound
        SAMe (S-Aden…
        Amazon
        Wide selection · fast shipping
        Compound
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        iHerb
        Global delivery · curated brands
        Compound
        SAMe (S-Aden…
        Thorne
        Practitioner-grade · NSF tested

        Scientific evidence (9)

        Meta-analysisCochrane Database · 2016

        SAMe for depression: a meta-analysis

        Galizia I, et al.

        Cochrane review of SAMe in MDD.

        Key findings

        Comparable to imipramine for moderate depression.

        Open study
        Systematic reviewPubMed (NLM) · 1970

        PubMed: SAMe (S-Adenosyl Methionine) — Comparable to imipramine in depression

        Live PubMed search

        Live results for "SAMe (S-Adenosyl Methionine) Comparable to imipramine in depression" across the PubMed/MEDLINE peer-reviewed index.

        Key findings

        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.

        Open study
        Systematic reviewPubMed (NLM) · 1970

        PubMed: SAMe (S-Adenosyl Methionine) — Improves intrahepatic cholestasis

        Live PubMed search

        Live results for "SAMe (S-Adenosyl Methionine) Improves intrahepatic cholestasis" across the PubMed/MEDLINE peer-reviewed index.

        Key findings

        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.

        Open study
        Systematic reviewPubMed (NLM) · 1970

        PubMed: SAMe (S-Adenosyl Methionine) — randomized controlled trial

        Live PubMed search

        Live results for "SAMe (S-Adenosyl Methionine) randomized controlled trial" across the PubMed/MEDLINE peer-reviewed index.

        Key findings

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

        Open study
        Systematic reviewPubMed (NLM) · 1970

        PubMed: SAMe (S-Adenosyl Methionine) — meta-analysis

        Live PubMed search

        Live results for "SAMe (S-Adenosyl Methionine) meta-analysis" across the PubMed/MEDLINE peer-reviewed index.

        Key findings

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

        Open study
        Systematic reviewPubMed (NLM) · 1970

        PubMed: SAMe (S-Adenosyl Methionine) — pharmacokinetics

        Live PubMed search

        Live results for "SAMe (S-Adenosyl Methionine) pharmacokinetics" across the PubMed/MEDLINE peer-reviewed index.

        Key findings

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

        Open study
        Systematic reviewPubMed (NLM) · 1970

        PubMed: SAMe (S-Adenosyl Methionine) — safety adverse events

        Live PubMed search

        Live results for "SAMe (S-Adenosyl Methionine) safety adverse events" across the PubMed/MEDLINE peer-reviewed index.

        Key findings

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

        Open study
        Systematic reviewPubMed (NLM) · 1970

        PubMed: SAMe (S-Adenosyl Methionine) — dose response

        Live PubMed search

        Live results for "SAMe (S-Adenosyl Methionine) dose response" across the PubMed/MEDLINE peer-reviewed index.

        Key findings

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

        Open study
        Systematic reviewGoogle Scholar · 1970

        Google Scholar: SAMe (S-Adenosyl Methionine) — clinical evidence

        Live Scholar search

        Cross-database citation index for SAMe (S-Adenosyl Methionine) as it relates to "clinical evidence".

        Key findings

        Includes preprints, theses, and journal articles. Useful for tracking citation counts and follow-on work.

        Open study
        Educational use only. This profile is not medical advice. Consult a qualified healthcare professional before starting any supplement, especially if you take prescription medication or have a chronic condition.