Supplement evidence

091 / 575Mood & stress

S-adenosyl-L-methionine (SAMe)

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The short answer

May improve depressive or osteoarthritis symptoms in some trials, but evidence quality and products vary.

Evidence and scope: Conditional or population-specific
This status does not grade the ingredient for every goal, outcome, or person.
Important limitation: Benefit depends on the population, formulation, baseline status, and objective; results should not be generalized.
Before deciding: Key concern: Avoid with antidepressants, serotonergic medicines, bipolar disorder, Parkinson medicines, pregnancy, and surgery.

01 / PRACTICAL GUIDE

Dose, absorption, and combinations

These are indication-specific reference or studied ranges—not a personalized prescription. Start with the objective, then check the form, label, medicines, and health conditions.

Reference range by objective

Mood symptoms800–1,600 mg/day in divided doses in trials

Reference or studied range—not a personalized prescription. The product label or a clinician may specify a different dose.

Dose source ↗

Joint symptoms600–1,200 mg/day in trials

Reference or studied range—not a personalized prescription. The product label or a clinician may specify a different dose.

Dose source ↗

More is not automatically better. A clinician or product label may specify a different amount.

Absorption / solubilityWater-soluble

Water-soluble or readily water-dispersible. This does not mean excess is always harmless.

How it is commonly taken

Often taken on an empty stomach; enteric coating improves stability.

Do not combine casually

Avoid with antidepressants, serotonergic medicines, bipolar disorder, Parkinson medicines, pregnancy, and surgery.

Dose and use source ↗

Dose and use links lead to primary or official source material. Search links are discovery tools, not proof that every returned paper applies.

02 / EVIDENCE

What the research says

We keep supportive, mixed, negative, safety, and contextual findings together. The headline never replaces the underlying papers.

1research papers in this ledger

23unique primary studies represented

2,183unique participants represented

These are audited counts for this JIVANA collection, not search-result totals. Participants are counted once when multiple papers use the same cohort; review papers are not added again to participant totals.

Open the research timelineResearch timeline

Entries are ordered by publication year. A study period appears only when the source reports it.

2024

Mixed or qualifiedPMID 38423354

Efficacy and acceptability of S-adenosyl-L-methionine for depression

Moderate-certainty evidence favored SAMe monotherapy over placebo, but heterogeneity was substantial. Adding SAMe to antidepressants was not superior to placebo add-on, and comparative efficacy versus antidepressants remained uncertain; this does not support self-treating depression or changing prescribed care.

Published: 2024n=2,183 participants23 primary studies represented

Study design and methods

Design: Systematic review and meta-analysis of 23 randomized trials
Population: 2,183 adults with depression
Intervention: SAMe alone, SAMe added to an antidepressant, or SAMe versus an antidepressant
Outcome: Depressive symptoms and all-cause dropout

Funding or conflict note: Two authors reported relationships with pharmaceutical companies; the other authors declared no conflicts.

Open research record ↗

Unscreened discovery appendix—not evidence16 candidate publicationsSearch run: Aug 21, 2026

Complete for the displayed PubMed query at the search timestamp—not for all databases or every possible synonym. Candidates can be irrelevant, duplicate the same study, or report negative findings. They are never summed as evidence or participants until screened.

03 / SOURCES

Start with the source material

Official evidence overviewPubMed bounded human-evidence search Live PubMed discovery searchNational Library of Medicine

The live search is for discovery only. Search-result counts change and are not included in the audited totals above.

Recent PubMed discovery recordsDirect links to the first 12 records returned by the reproducible search. These are discovery candidates—not reviewed summaries or a count of supportive findings.

04 / EXPERT CONTEXT

Expert context—not evidence

Expert positions are dated context—not scientific evidence. They never raise the evidence status or become consensus by repetition.

No direct, source-verified endorsement is currently recorded. Research authorship or discussion alone is not treated as endorsement.