✓ No active regulatory warningsFDA MedWatch, EMA EudraVigilance, WHO VigiBase, WADA Prohibited List · 2026-05-29
⚠ Bipolar patient on SAMe without mood stabilizer — mania risk [2]
⚠ SAMe + SSRIs — serotonin syndrome risk [2]
⚠ SAMe for OA: comparable to NSAIDs but takes 4 weeks (vs 1 week for NSAIDs) [2]
⚠ Unstable compound — poor-quality products may contain degraded SAMe [3]
ℹ️ Not obtained from food. Not applicable — this is not obtained from food in meaningful amounts; supplementation is the practical route.
🔬 Lab interpreter
Recommended test
No routine monitoring for SAMe supplementation
No routine monitoring for SAMe supplementation
Reference range / target
N/A
N/A
Monitor mood (PHQ-9) for depression indication [2].
Full lab monitoring ↓⚕ For professionals — confirm ranges against your local laboratory.
Clinical verdict
SAMe is a triple-threat: depression (meta-analysis: comparable to TCAs), osteoarthritis (comparable to NSAIDs), and liver disease (glutathione precursor in hepatocytes). Prescription drug in Italy, Germany, Spain. Faster antidepressant onset than SSRIs (1–2 weeks). Can trigger mania in bipolar — avoid without mood stabilizer. Expensive and unstable — refrigerate, enteric-coat, buy from reputable sources [1] [2] [3].
1 How much do I need?
👤 Adults: Specific dosage data under clinical review
👴 Elderly: Specific dosage data under clinical review
🤰 Pregnancy: See guidance
IV SAMe used for ICP with apparent safety. Oral supplementation data limited. Consult physician [3].
👦 Pediatric: See guidance
No pediatric data. Not recommended [1].
🏃 Athletes: Standard dose
⚖️ Obesity: Standard dose
Fat-soluble compounds may require dose adjustment in obesity.
🩺 Renal: Consult specialist
Dose adjustment may be needed in renal impairment.
🌱 Vegan: Standard dose
How to take
🍽 Timing: Empty stomach (30 min before meals). BID dosing. Morning + early afternoon to avoid insomnia [2].
💊 With food: Empty stomach preferred (food reduces absorption) [2].
🚫 Avoid: Bipolar patients without mood stabilizer. Concurrent SSRIs/SNRIs/MAOIs without supervision [2].
2 Which form?
| Form | Bioavailability | Vegan | Cost |
|---|---|---|---|
| ['SAMe tosylate (1,4-butanedisulfonate)', 'preferred', 'The most stable and most studied salt form. Used in Ital trials. Enteric-coated to prevent gastric degradation [2].'] | Standard | Check label | |
| ['SAMe disulfate tosylate', '', 'Alternative salt form. Similar bioavailability [2].'] | Standard | Check label |
3 Common questions
Is SAMe as effective as antidepressants? ▼
Meta-analyses show SAMe comparable to tricyclic antidepressants and superior to placebo for depression [2]. It may work faster (1–2 weeks vs 4–6 for SSRIs). It is a prescription antidepressant in Italy, Germany, and Spain. Limitations: expensive, unstable, must be enteric-coated.
Why is SAMe so expensive? ▼
SAMe is chemically unstable, requiring refrigeration, enteric coating, and careful manufacturing. This makes it one of the most expensive supplements at therapeutic doses ($1–3/day) [3]. Cheaper products may have degraded SAMe with reduced potency.
Can SAMe trigger mania? ▼
Yes — SAMe can trigger mania or hypomania in patients with bipolar disorder, similar to any antidepressant [2]. It should NOT be used as monotherapy in bipolar depression without mood stabilizer coverage.
How does SAMe help joints AND depression? ▼
SAMe participates in >100 methylation reactions. In the brain, it methylates phospholipids and is involved in neurotransmitter synthesis (mood). In cartilage, it supports proteoglycan synthesis [1]. Same molecule, different tissue effects.
4 Clinical evidence
Strong
SAMe is the body's principal methyl donor — biochemically well-established in >100 methylation reactions [1]. Depression: meta-analysis of 8 RCTs showed SAMe superior to placebo and comparable to tricyclic antidepressants for major depression [2]. Liver disease: SAMe is the precursor to glutathione in hepatocytes; IV SAMe improves liver function markers in alcoholic liver disease and cholestasis [3]. HIGH
Moderate
Osteoarthritis: meta-analysis showed SAMe 1,200 mg/day comparable to NSAIDs for OA pain with fewer GI side effects, but slower onset (4 weeks vs 1 week for NSAIDs) [2]. Adjunctive to SSRIs for treatment-resistant depression: STAR*D ancillary study showed benefit [2]. Intrahepatic cholestasis of pregnancy: IV SAMe improved pruritus and liver enzymes in several trials [3]. MODERATE
Insufficient
5 Safety, toxicity & adverse events
Absolute contraindications
✕ Bipolar disorder — can precipitate mania or hypomania
Relative
⚠ Concurrent serotonergic drugs (SSRIs, SNRIs, MAOIs) — serotonin-syndrome risk
⚠ Parkinson's disease — may interact with treatment
⚠ Anxiety disorders — may worsen in some individuals
🚩 Red flags
● Bipolar patient becoming hypomanic on SAMe — discontinue; this is expected antidepressant-induced mania [2]
● Patient on SSRI + SAMe — serotonin syndrome risk [2]
● SAMe stored at room temperature for weeks — likely degraded; ineffective [3]
6 Interactions
Drug interactions
SSRIs/SNRIs/MAOIs/triptans Major
Mechanism: SAMe increases serotonin, dopamine, and norepinephrine synthesis. Additive serotonergic activity with other serotonergic drugs. [2]
Effect: Serotonin syndrome risk. [2]
Action: Avoid concurrent use without psychiatric supervision [2].
Levodopa Moderate
Mechanism: SAMe methylates levodopa to 3-O-methyldopa via COMT. [1]
Effect: Potentially reduced levodopa efficacy. [1]
Action: Monitor Parkinson symptoms [1].
Supplement synergies
Folate + B12 · 400–800 µg folate + 500–1,000 µg B12
Support SAMe recycling through the methylation cycle. SAMe → homocysteine → methionine (requires folate + B12 as cofactors) → SAMe [1].
Support SAMe recycling through the methylation cycle. SAMe → homocysteine → methionine (requires folate + B12 as cofactors) → SAMe [1].
Betaine (TMG) · 500–2,000 mg/day
Alternative methyl donor that supports homocysteine remethylation, complementing SAMe [1].
Alternative methyl donor that supports homocysteine remethylation, complementing SAMe [1].
7 Regulatory
United States (FDA): Dietary supplement. No drug approval [1].
Italy, Germany, Spain: Prescription drug for depression and liver disease [3].
European Union: Available as both pharmaceutical and supplement depending on country [3].
South Korea: Available as dietary supplement.
8 US supplement products
35
on-market products containing SAMe (NIH DSLD)
Brands carrying SAMe (28)
Click a brand to see its SAMe products.
9 Frequently paired with
10 References (3)
[1]National Institutes of Health, NCCIH. SAMe. Updated 2024. www.nccih.nih.gov REVIEW Accessed: 2026-05-29
[2]Sharma A, et al. S-Adenosylmethionine (SAMe) for neuropsychiatric disorders: a clinician-oriented review of research. J Clin Psychiatry. 2017;78(6):e656-e667. doi:10.4088/JCP.16r11113 REVIEW Accessed: 2026-05-29
[3]Guo T, et al. S-adenosyl-L-methionine for liver diseases: a review. World J Hepatol. 2015;7(21):2348-2353. doi:10.4254/wjh.v7.i21.2348 REVIEW Accessed: 2026-05-29
11 Related articles
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12 Cite this page
Vancouver: Pkhakadze G. SAMe — safety profile [Internet]. Tbilisi: PHIG; 2026 [cited 2026 Jun 01]. Available from: https://supplement.ge/ingredients/same/
APA 7th: Pkhakadze, G. (2026). SAMe — Safety profile. Public Health Institute of Georgia. https://supplement.ge/ingredients/same/
📋 Editorial information
Author: Prof. G. Pkhakadze, MD, MPH, PhD
Institution: Public Health Institute of Georgia (PHIG)
Affiliation: David Tvildiani Medical University (DTMU)
First published: January 2026
Last reviewed: 2026-05-29
Next review: December 2026
References: 3 cited sources
COI: SupplementIndex receives no funding from supplement manufacturers. All content independently authored by PHIG.
Process: Systematic literature review
📄 License & reuse
Published under Creative Commons Attribution 4.0 International (CC BY 4.0). You may share and adapt for any purpose with attribution.
Pkhakadze G. "SAMe — Safety Profile." SupplementIndex, PHIG, 2026. https://supplement.ge/ingredients/same/ CC BY 4.0.
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Educational and public health purposes. CC BY 4.0. Consult your healthcare provider before starting any supplement. Corrections: info@accreditation.ge. Publisher: PHIG