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Dietary supplement

SAMe S-Adenosyl-Methionine 400 mg Ingredients & Drug Interactions

by Life Extension

SAMe S-Adenosyl-Methionine 400 mg label
See full label image
Capsule Category: Non-nutrient/non-botanical
Most serious interaction: Moderate
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking SAMe S-Adenosyl-Methionine 400 mg against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.

Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy

The interaction bottom line Most serious interaction: Moderate

SAMe S-Adenosyl-Methionine 400 mg is a dietary supplement by Life Extension with 1 active ingredient. Its ingredients are commonly taken for depression, osteoarthritis joint pain, liver conditions.Based on those ingredients, 189 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are S-Adenosyl-Methionine. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against SAMe S-Adenosyl-Methionine 400 mg by Life Extension

Ask about any prescription or over-the-counter medication and we check it for interactions with SAMe S-Adenosyl-Methionine 400 mg by Life Extension — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of SAMe S-Adenosyl-Methionine 400 mg by Life Extension

Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Sep 10, 2026

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 1 of its 1 active ingredient.
  • No proprietary blends here — you can verify the dose of every single component.

This product contains one active ingredient: S-Adenosyl-Methionine, or SAMe, at 400 mg per capsule. SAMe is a compound your body makes naturally and uses in many cellular processes, including mood regulation and joint health.

The capsule also contains inactive ingredients like cellulose, mannitol, and silica—standard binders and fillers that help hold the capsule together.

Does it work?

Strong evidence
Evidence for Intended Use · database check
By FDA rules, dietary supplements can’t claim to treat, cure, or prevent disease — so labels speak in careful marketing language. We discern each product’s intended use from its name, label claims, and label statements, then grade the clinical evidence for that use. How these ratings are computed

This product doesn't appear to be marketed for a specific use, so we graded Same's overall clinical evidence instead.

Strong

Strong clinical evidence supports Same for:

Why this rating?
  • We looked at the product name, claims, and label statements and couldn't find a stated purpose to grade.
  • Since the label doesn't commit to one use, we graded the ingredient's overall clinical evidence instead.
  • On file: Osteoarthritis — rated "Likely Effective" (Natural Medicines).
  • On file: Cholestasis — rated "Possibly Effective" (Natural Medicines).
  • On file: Depression — rated "Possibly Effective" (Natural Medicines).

The evidence for SAMe varies by condition. It's likely effective for osteoarthritis, meaning there's solid research backing its use for joint pain and stiffness.

For depression and cholestasis (a liver condition), the evidence suggests it may help, but the research is less robust. For Alzheimer's disease and ADHD, we don't have enough reliable evidence yet to say whether it works.

The evidence, ingredient by ingredient Same

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

Adverse-effect, pregnancy, and general safety data are on file for most of these ingredients.

Why this rating?
  • We hold adverse-effect (side-effect) data for 1 of the 1 matched ingredient.
  • Pregnancy & breastfeeding safety ratings cover 1 of 1.
  • General safety write-ups exist for 1 of 1.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

SAMe is generally well tolerated at standard doses, though side effects become more common at higher doses. The most frequent ones are stomach-related: nausea, diarrhea, constipation, and dry mouth.

Some people also report dizziness, headache, insomnia, or nervousness. There's one important caution: SAMe can trigger mania in people with bipolar disorder, so if that's you, talk with your doctor or pharmacist before taking it.

Safety during breastfeeding isn't well established; for pregnancy, the data suggests it may be safe, but because the evidence is limited, you'll want to discuss it with your own healthcare provider.

Side effects, ingredient by ingredient Same

Meds to double-check

Moderate interaction found
Known Interaction Concern · database check
Moderate identified

The most serious documented interaction for these ingredients is Moderate. Check your medications for a personalized result.

Why this rating?
  • 1 of the 1 matched ingredient can interact with medications — Same.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: Parkinson's medications.
  • For scale: 189 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking SAMe, check with your doctor or pharmacist if you take any serotonergic drugs—antidepressants (SSRIs, SNRIs, tricyclics), certain pain or migraine medications (tramadol, triptans), or anti-anxiety drugs—because the combination raises your risk of serotonin syndrome. Also confirm you're not on levodopa for Parkinson's, since SAMe may make it less effective.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with strong clinical evidence behind its ingredients' uses. Moderate medication interactions have been identified, and safety information is well characterized.

SAMe is worth considering if you have osteoarthritis or mild depression and your medications don't conflict with it. If you have bipolar disorder or take serotonergic drugs or levodopa, you need to clear it with your doctor or pharmacist first.

Check your exact medication list against our tool before you start, and talk it over with your own healthcare provider to be sure it fits your situation.

Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI

Assessment coverage: 1 of 1 active ingredient matched to our full ingredient reviews (monographs). Based on the product label dated Apr 22, 2016.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about SAMe S-Adenosyl-Methionine 400 mg, straight from the product label.

Brand Life Extension
Barcode (UPC) 737870105558
Net contents 50 Enteric Coated Capsule(s)
Market status On market
Date entered into DSLD Apr 22, 2016
DSLD ID 59061
Product type Non-nutrient/non-botanical
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for SAMe S-Adenosyl-Methionine 400 mg by Life Extension, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
1 Enteric Coated Capsule(s)
Maximum serving Sizes:
1 Enteric Coated Capsule(s)
UPC/BARCODE
737870105558
IngredientAmount% DV
S-Adenosyl-Methionine400 mg--

Other ingredients: Cellulose, Mannitol, Hydroxypropyl Methylcellulose Phthalate, Citric Acid, Silica, Stearic Acid, Glyceryl Triacetate, Sodium Starch Glycolate, Croscarmellose Sodium, Titanium Dioxide, yellow Ochre

Tap any ingredient to jump to its full detail below.

Label statements
These statements are the manufacturer’s wording, reproduced from the product label — the label is saying it, not HelloPharmacist. We don’t verify or endorse them.
FDA Disclaimer Statement

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

FDA Statement of Identity

Dietary Supplement

General Statements

To report a serious adverse event or obtain product information, contact 1-866-280-2852.

Supports Healthy Bones, Joints, and Emotional Well-Being*

Suggested/Recommended/Usage/Directions

Read the entire label and follow the directions carefully prior to use. DIRECTIONS: Take one (1) tablet two to three times daily in divided doses, preferably on an empty stomach, or as recommended by a healthcare practitioner. Take with co-factors vitamins B12, B6, and folic acid.

Precautions

CAUTION: SAMe should not be taken by those diagnosed with bipolar disorder.

WARNINGS: ~ KEEP OUT OF REACH OF CHILDREN.

~ DO NOT EXCEED RECOMMENDED DOSE. ~ Do not purchase if outer seal is broken or damaged.

~ When using nutritional supplements, please consult with your physician if you are undergoing treatment for a medical condition or if you are pregnant or lactating.

Storage

Store tightly closed in a cool, dry place.

General

Q01055D

Is this label outdated? Report a formula or label change and our pharmacy team will review it.

See for yourself

SAMe S-Adenosyl-Methionine 400 mg by Life Extension label

The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.

SAMe S-Adenosyl-Methionine 400 mg label

Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.

View the full label (PDF)
What’s inside

The Ingredients in SAMe S-Adenosyl-Methionine 400 mg by Life Extension

This is the 1 active ingredient this product is made of. Select it to open its full monograph.

Serving size1 Enteric Coated Capsule(s) Dosage formCapsule Amounts shown are per serving.

S-Adenosyl-Methionine

Interacts with
189 drugs
400 mg per serving

SAM-e is a compound your body makes naturally that is sold as a supplement, most often for depression and osteoarthritis. Some research suggests it ma...

S-Adenosyl-Methionine monograph & interactions

Other (inactive) ingredients: Cellulose, Mannitol, Hydroxypropyl Methylcellulose Phthalate, Citric Acid, Silica, Stearic Acid, Glyceryl Triacetate, Sodium Starch Glycolate, Croscarmellose Sodium, Titanium Dioxide, Yellow Ochre. These complete the product’s ingredient list but are not active constituents.

Interaction report

SAMe S-Adenosyl-Methionine 400 mg by Life Extension Drug Interactions

Want to check YOUR meds against SAMe S-Adenosyl-Methionine 400 mg?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

 Go to the checker
189Drugs
189 Moderate

Ingredients driving the most interactions

S-Adenosyl-Methionine 189

Individual Drug Interactions

The ingredients in SAMe S-Adenosyl-Methionine 400 mg interact with 189 drugs. Click any drug to see the details.

1 of the 1 ingredient in SAMe S-Adenosyl-Methionine 400 mg interact with drugs. Each result below shows which ingredient is responsible. S-Adenosyl-Methionine

Each ingredient & the kinds of drugs it affects

For each ingredient in SAMe S-Adenosyl-Methionine 400 mg with known interactions, here are the types of medications it can affect. Open any type for the detail — or search your exact drug in the checker above.

S-Adenosyl-Methionine2 drug types · 189 drugs

Levodopa

SAMe might reduce the effectiveness of levodopa.
SAMe methylates levodopa, which might reduce its effectiveness for treating Parkinson disease.

Likelihood Possible Evidence D
Serotonergic Drugs

Taking SAMe with serotonergic drugs might increase the risk of serotonin syndrome and other serotonergic side effects.
SAMe has serotonergic effects. Theoretically, combining serotonergic drugs with SAMe might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders. In one case report, SAMe 100 mg intramuscularly was given daily with clomipramine (Anafranil) 25 mg per day. When the clomipramine dose was increased to 75 mg per day the patient experienced serotonin syndrome about 48-72 hours later, requiring hospitalization.

Likelihood Possible Evidence D
S-Adenosyl-Methionine full monograph & interactions
The maker

Brand information

Manufacturer and brand details for SAMe S-Adenosyl-Methionine 400 mg, from the product label.

Life Extension

See all Life Extension products
Name
Quality Supplements and Vitamins, Inc.
City
Ft. Lauderdale
State
Florida
ZipCode
33309
Phone Number
1-866-280-2852
Web Address
www.lef.org
Pharmacist Counseling Corner

SAMe S-Adenosyl-Methionine 400 mg by Life Extension: Common Questions

Does SAMe S-Adenosyl-Methionine 400 mg by Life Extension interact with any medications?
Yes. Based on its ingredients, SAMe S-Adenosyl-Methionine 400 mg has a known interaction with 189 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
SAMe S-Adenosyl-Methionine 400 mg contains a single active ingredient, and that one ingredient can interact with many different medications on its own. We check it against each medication and show the mechanism responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take SAMe if I'm pregnant?
The data we have suggests SAMe may be safe in pregnancy, but evidence is limited. Because safety isn't certain, talk with your doctor or pharmacist about whether it's right for you during pregnancy—they know your full medical picture and can give you personalized advice.
What's the most common side effect?
Stomach upset is most common—nausea, diarrhea, constipation, or dry mouth. These tend to be mild and happen more often at higher doses. Starting with the lowest recommended dose can help.
Does SAMe really work for depression?
The evidence suggests it may help with depression, but the research isn't as strong as it is for osteoarthritis. If you're considering it for mood, talk with your doctor or pharmacist about how it compares to other options for you.
Is SAMe safe if I have bipolar disorder?
No—SAMe can trigger mania in people with bipolar disorder. If that's you, avoid this product and talk with your doctor or pharmacist about safer alternatives.
What is SAMe, and why is it in this supplement?
SAMe is a compound your body naturally produces and uses for mood, joint health, and liver function. This supplement gives you an extra dose to support those areas, especially for osteoarthritis and depression.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Not sure if SAMe S-Adenosyl-Methionine 400 mg is safe with your meds?

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Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.

SAMe S-Adenosyl-Methionine 400 mg label
Go deeper

The Full Monographs Behind SAMe S-Adenosyl-Methionine 400 mg’s Ingredients

Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.

Herb & supplement monograph

Same

Interacts with 189 drugs

SAM-e is a compound your body makes naturally that is sold as a supplement, most often for depression and osteoarthritis. Some research suggests it may help with these conditions, but the qu...

Read the full Same monograph →
Sources

Sources & How We Checked

SAMe S-Adenosyl-Methionine 400 mg's label data comes from the NIH Dietary Supplement Label Database; the ingredient interaction data is from the Natural Medicines database, reviewed by our pharmacists.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

The 31 references behind this product’s interaction data

Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.

Same 31 references
  1. Perna AF, Castaldo P, Ingrosso D, et al. Homocysteine, a new cardiovascular risk factor, is also a powerful uremic toxin. J Nephrol 1999;12:230-40.
  2. Mato JM, Camara J, Fernandez de Paz J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 1999;30:1081-9. PubMed
  3. Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150:522. PubMed
  4. Bradley JD, Flusser D, Katz BP, et al. A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis. J Rheumatol 1994;21:905-11.
  5. Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. Psychiatry Res 1992;44:257-62. PubMed
  6. Kagan BL, Sultzer DL, Rosenlicht N, Gerner RH. Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 1990;147:591-5. PubMed
  7. Rosenbaum JF, Fava M, Falk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand 1990;81:432-6. PubMed
  8. Domljan Z, Vrhovac B, Durrigl T, Pucar I. A double-blind trial of ademetionine vs naproxen in activated gonarthrosis. Int J Clin Pharmacol Ther Toxicol 1989;27:329-33.
  9. Konig B. A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med 1987;83:89-94. PubMed
  10. Lipinski JF, Cohen BM, Frankenburg F, et al. Open trial of S-adenosylmethionine for treatment of depression. Am J Psychiatry 1984;141:448-50.
  11. Almasio P, Bortolini M, Pagliaro L, Coltorti M. Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis. Drugs 1990;40:111-23. PubMed
  12. Friedel HA, Goa KL, Benfield P. S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs 1989;38:389-416. PubMed
  13. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137-52. PubMed
  14. Frezza M, Centini G, Cammareri G, et al. S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial. Hepatogastroenterology 1990;37:122-5.
  15. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  16. Charlton CG, Crowell B Jr. Parkinson's disease-like effects of S-adenosyl-L-methionine: effects of L-dopa. Pharmacol Biochem Behav 1992;43:423-31..
  17. Goren JL, Stoll AL, Damico KE, et al. Bioavailability and lack of toxicity of S-adenosyl-L-methionine (SAMe) in humans. Pharmacotherapy 2004;24:1501-7. PubMed
  18. Arnold O, Saletu B, Anderer P, et al. Double-blind, placebo-controlled pharmacodynamic studies with a nutraceutical and a pharmaceutical dose of ademetionine (SAMe) in elderly subjects, utilizing EEG mapping and psychometry. Eur Neuropsychopharmacol 2005; PubMed
  19. Nelson JC. S-adenosyl methionine (SAMe) augmentation in major depressive disorder. (Editorial). Am J Psychiatry 2010;167:889-91.
  20. Kim J, Lee EY, Koh EM, et al. Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients. Clin Ther 2009; PubMed
  21. Manzillo G, Piccinino F, Surrenti C, et al. Multicentre double-blind placebo-controlled study of intravenous and oral S-adenosyl-L-methionine (SAMe) in cholestatic patients with liver disease. Drug Invest 1992;4 (Suppl 4):90-100. DOI
  22. Carrieri PB, Indaco A, Gentile S, et al. S-adenosylmethionine treatment of depressioin in patients with Parkinson's disease: a double-blind, crossover study versus placebo. Curr Ther Res 1990;48(1):154-60.
  23. Pancheri P, Scapicchio P, Delle Chiaie R. A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder. Int J Neuro PubMed
  24. Medici V., Virata M. C., Peerson J. M., Stabler S. P., French S. W., Gregory J. F. III, Albanese A., Bowlus C. L., Devaraj S., Panacek E. A., Richards J. R., Halsted C. H. S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, ra
  25. Chitiva, H., Audivert, F., and Alvarez, C. Suicide attempt by self-burning associated with ingestion of S-adenosylmethionine: a review of the literature and case report. J.Nerv.Ment.Dis. 2012;200(1):99-101. PubMed
  26. Carney, M. W., Edeh, J., Bottiglieri, T., Reynolds, E. M., and Toone, B. K. Affective illness and S-adenosyl methionine: a preliminary report. Clin Neuropharmacol. 1986;9(4):379-385. PubMed
  27. Miccoli, L., Porro, V., and Bertolino, A. Comparison between the antidepressant activity and of S- adenosylmethionine (SAMe) and that of some tricyclic drugs. Acta Neurol (Napoli) 1978;33 (3):243-255.
  28. Bacci, Ballerini F., Lopez, Anguera A., Alcaraz, P., and Hernandez, Reyes N. [SAMe in the management of postconcussional syndrome]. Medicina Clinica (Barc.) 1983;80(4):161-164.
  29. Muscettola G, Galzenati M, Balbi A. SAMe versus placebo: a double blind comparison in major depressive disorders. Advances in Biochemical Psychopharmacology 1982;32:151-6.
  30. Capretto C, Cremona C, and Canaparo L. A double-blind controlled study of S-adenosylmethionine (SAMe) v. ibuprofen in gonarthrosis, coxarthrosis and spondylarthrosis. Clin Trials J 1985;22(1):15-24.
  31. Ancarani E, Biondi B, Bolletta A, et al. Major depression complicating hemodialysis in patients with chronic renal failure: a multicenter, double-blind, controlled clinical trial of S-adenosyl-L-methionine versus placebo. Curr Ther Res 1993;54(6):680-6. DOI

See these in context on the Same monograph →

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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