Supplement
Supports mitochondrial and cellular cofactor systems tied to energy and repair.[1478,1911,2170, etc.]
Superscript reference numbers link to the Sources bibliography.
Composite Rating
Blends evidence depth, community direction, safety friction, and completeness.
Evidence Intensity
100/100
High depth from human/RCT/meta counts
Community Direction
0
Mixed / Neutral • confidence Minimal
Safety Friction
100/100
High signal from adverse/interaction markers
Data Completeness
100%
Studies 15 • mentions 2 • links 25
Not medical advice. This product is for educational and informational purposes only. It does not diagnose, treat, cure, or prevent any disease and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider with any questions regarding a medical condition.
FDA disclaimer: These statements have not been evaluated by the Food and Drug Administration. Dietary supplements are not intended to diagnose, treat, cure, or prevent any disease. Results may vary. Not intended for use by pregnant or nursing women, individuals under 18, or those with known medical conditions without physician consultation.
If you are experiencing a medical emergency, call 911 or your local emergency number immediately.
Goal alignment: Energy, Longevity, Metabolic Health, Performance.[619,762,996, etc.]
Dose guide: Follow product label and start with the lowest effective daily serving..[619,762,996, etc.]
Category
Cofactor
Evidence Tier
HIGH
Daily Guide
Follow product label and start with the lowest effective daily serving.
Dosing Guide
Follow product label and start with the lowest effective daily serving.[1478,]
Clinical Depth
Humans: 404 • RCTs: 38 • Meta: 6
Cohort / Real-World
Cohort signals: 0
Safety Markers
Adverse signals: 448 • Interactions: 876
Freshness, trend, and study timeline for this item
Status
Trend
↑ Growing evidence base
Depth
922 total studies · 3 recent
Timeline
Animal-only studies
3,159
In vitro / tissue
1,490
Total indexed
922
Interaction signals
876
Safety adverse signals
448
Human studies
404
Weighted direction score: 0 (Mixed / Neutral)
High when >=2 human meta-analyses, or >=5 human RCTs with substantial human literature volume.
Animal-only studies
3,159
In vitro / tissue
1,490
Total indexed
922
Interaction signals
876
Safety adverse signals
448
Human studies
404
Randomized trials
38
Meta-analyses
6
Distribution of evidence by study design strength
Evidence Strength: High
Composite of study volume, RCTs, and meta-analyses
PMID 40014460 • 2025 Mar
Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis.
Neuropsychopharmacol Rep
Open PubMedPMID 36970898 • 2023
Effects of S-Adenosylmethionine on Cognition in Animals and Humans: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
J Alzheimers Dis
Open PubMedPMID 12019049 • 2002 May
Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis.
J Fam Pract
Open PubMedBenefit reports: 1
Adverse reports: 1
No-effect reports: 0
Mixed reports: 0
Unclear reports: 0
Signal confidence: 0.00
Benefits
Adverse
No Effect
Insufficient empirical signal for a directional adjustment.
Reddit evidence: 0 mentions (confidence 0.00).
Amazon signal: 0 products scanned (confidence 0.00).
GNC signal: 0 products scanned (confidence 0.00) [BLOCKED].
PerimeterX / captcha block encountered.
aggregate • unclear
Aggregate community signal: 2 directional mentions (benefit 1, adverse 1, no-effect 0, mixed 0).
Open mentionamazon
Amazon search for Sam-e
Rating: n/a | Reviews: n/a
Open productEvidence Sources
PUBMED • Humans + preclinical triage
Counts aggregated from automated literature sweep and tiering rules.
Outcome: Tier HIGH; humans 404, RCTs 38, meta-analyses 6.[1478,1911,2170, etc.]
Open sourcePUBMED • 2025 • Human evidence curation set
PMID 40014460 from Neuropsychopharmacol Rep.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,, etc.]
PMID 25774783 • 2015
S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysis.
PLoS One
Open PubMedPMID 31977026 • 2020 Aug 1
Influence of nutrients involved in one-carbon metabolism on DNA methylation in adults-a systematic review and meta-analysis.
Nutr Rev
Open PubMedPMID 27113121 • 2016 Jun 1
Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses.
Am J Psychiatry
Open PubMedPMID 36411659 • 2022 Dec
Efficacy of a food supplement based on S-adenosyl methionine and probiotic strains in subjects with subthreshold depression and mild-to-moderate depression: A monocentric, randomized, cross-over, double-blind, placebo-controlled clinical trial.
Biomed Pharmacother
Open PubMedPMID 40668877 • 2025 Jul 29
Metabolic Signature of Arsenic Exposure and Metabolism: The Folic Acid and Creatine Trial.
Environ Sci Technol
Open PubMedPMID 19422296 • 2009 May
Dietary supplement S-adenosyl-L-methionine (AdoMet) effects on plasma homocysteine levels in healthy human subjects: a double-blind, placebo-controlled, randomized clinical trial.
J Altern Complement Med
Open PubMedPMID 32589828 • 2020 Jun 25
Oral Administration of S-Adenosylmethionine (SAMe) and Lactobacillus Plantarum HEAL9 Improves the Mild-To-Moderate Symptoms of Depression: A Randomized, Double-Blind, Placebo-Controlled Study.
Prim Care Companion CNS Disord
Open PubMedPMID 30115553 • 2018 Oct
Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: An 8-week double-blind, randomized, controlled trial<sup/>.
Eur Neuropsychopharmacol
Open PubMedPMID 23392989 • 2013 Nov
S-adenosylmethionine and S-adenosylhomocysteine in plasma and cerebrospinal fluid in Rett syndrome and the effect of folinic acid supplementation.
J Inherit Metab Dis
Open PubMedPMID 32879489 • 2020 Sep
Cancer SLC43A2 alters T cell methionine metabolism and histone methylation.
Nature
Open PubMedPMID 37771507 • 2023
Are epigenetic mechanisms and nutrition effective in male and female infertility?
J Nutr Sci
Open PubMedPMID 39729999 • 2025 Feb 4
Disrupted methionine cycle triggers muscle atrophy in cancer cachexia through epigenetic regulation of REDD1.
Cell Metab
Open PubMedSearch fetch failed: Failed to fetch after retries: https://old.reddit.com/search.json?raw_json=1&sort=relevance&t=year&limit=12&q=%22s-adenosylmethionine%22%20(supplement%20OR%20dosage%20OR%20stack%20OR%20side%20effects%20OR%20review)%20(subreddit%3ASupplements%20OR%20subreddit%3ANootropics%20OR%20subreddit%3ABiohackers%20OR%20subreddit%3Alongevity%20OR%20subreddit%3ANutrition%20OR%20subreddit%3AHubermanLab%20OR%20subreddit%3ASleep%20OR%20subreddit%3AFitness%20OR%20subreddit%3Aketoscience%20OR%20subreddit%3AStackAdvice)
Fallback search failed: Failed to fetch after retries: https://old.reddit.com/search.json?raw_json=1&sort=comments&t=all&limit=16&q=%22s-adenosylmethionine%22%20(supplement%20OR%20capsule%20OR%20powder%20OR%20experience%20OR%20results%20OR%20side%20effects)
Broad search failed: Failed to fetch after retries: https://old.reddit.com/search.json?raw_json=1&sort=new&t=all&limit=16&q=s-adenosylmethionine
Use adverse/interactions PubMed signal counts for screening; perform clinician review before high-dose or multi-drug stack use.
Community Sources
PUBMED • 2023 • Human evidence curation set
PMID 36970898 from J Alzheimers Dis.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2002 • Human evidence curation set
PMID 12019049 from J Fam Pract.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2015 • Human evidence curation set
PMID 25774783 from PLoS One.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2020 • Human evidence curation set
PMID 31977026 from Nutr Rev.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2016 • Human evidence curation set
PMID 27113121 from Am J Psychiatry.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2022 • Human evidence curation set
PMID 36411659 from Biomed Pharmacother.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2025 • Human evidence curation set
PMID 40668877 from Environ Sci Technol.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2009 • Human evidence curation set
PMID 19422296 from J Altern Complement Med.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2020 • Human evidence curation set
PMID 32589828 from Prim Care Companion CNS Disord.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2018 • Human evidence curation set
PMID 30115553 from Eur Neuropsychopharmacol.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2013 • Human evidence curation set
PMID 23392989 from J Inherit Metab Dis.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2020 • Human evidence curation set
PMID 32879489 from Nature.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2023 • Human evidence curation set
PMID 37771507 from J Nutr Sci.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open sourcePUBMED • 2025 • Human evidence curation set
PMID 39729999 from Cell Metab.
Outcome: See linked PubMed abstract for methods and outcomes.[1478,1911,2170, etc.]
Open source