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Dietary supplement

SAMe 400 mg Ingredients & Drug Interactions

by Life Extension

SAMe 400 mg label
See full label image
Tablet Or Pill 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 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 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 400 mg by Life Extension

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

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HelloPharmacist Scorecard of SAMe 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 (SAMe), a compound your body makes naturally and uses in many chemical reactions, including those involved in mood, joint health, and liver function. The remaining ingredients are inactive—cellulose, mannitol, silica, and others—that serve as fillers, binders, and capsule materials to hold the tablet together and help it dissolve.

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
Strong

Clinical evidence supports at least one of this product's ingredients for its stated purpose.

Why this rating?
  • The label markets this product for: brain health and mood support.
  • We looked for evidence on: Depression, Fibromyalgia, Osteoarthritis, cognitive function, joint health, mood — and 1 related terms.
  • The strongest evidence on file: Same is rated "Likely Effective" for Osteoarthritis (Natural Medicines).
  • Also on file: Same is rated "Possibly Effective" for Depression.
  • Also on file: Same is rated "Insufficient Reliable Evidence To Rate" for Fibromyalgia.

SAMe is likely effective for osteoarthritis, meaning there's solid evidence it may help reduce joint pain and stiffness. For depression, the evidence is less certain—it's rated possibly effective, so some people may benefit, but more research is needed.

For other uses like cholestasis (a liver condition affecting bile flow) and Alzheimer disease, the evidence is either limited or not yet established. There isn't enough reliable data to know whether SAMe helps with ADHD.

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 typical doses, but side effects do happen—most commonly stomach upset (nausea, diarrhea, constipation), headache, dizziness, dry mouth, and nervousness. Higher doses bring more side effects.

One important caution: SAMe may trigger mania in people with bipolar disorder, so if you have that diagnosis, talk with your doctor before starting it. Safety in pregnancy and lactation hasn't been fully established; there isn't enough data to know either way, so discuss this with your doctor or pharmacist if you're pregnant, planning to become pregnant, or breastfeeding.

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.

Double-check any serotonergic medication before taking SAMe—that includes SSRIs, SNRIs, tricyclic antidepressants, and other drugs that raise serotonin. Also confirm that you're not on levodopa for Parkinson disease, since SAMe may reduce how well it works.

Your doctor or pharmacist can run your exact medications through the interaction checker on this page.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with clinical evidence supporting its stated purpose. Moderate medication interactions have been identified, and safety information is well characterized.

SAMe may be worth trying if you have osteoarthritis or are dealing with depression and want to explore it alongside or instead of other options. If you take any antidepressant, anti-anxiety medication, or levodopa for Parkinson disease, check with your doctor or pharmacist first—the interactions are real.

People with bipolar disorder should avoid it without medical guidance. Talk it over with your own healthcare provider before starting.

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 Aug 23, 2020.

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 400 mg, straight from the product label.

Brand Life Extension
Barcode (UPC) 737870217466
Net contents 60 Enteric Coated Tablet(s)
Market status On market
Date entered into DSLD Aug 23, 2020
DSLD ID 232766
Product type Non-nutrient/non-botanical
Supplement form Tablet Or Pill
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 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 Tablet(s)
Maximum serving Sizes:
1 Tablet(s)
UPC/BARCODE
737870217466
IngredientAmount% DV
S-Adenosyl-Methionine400 mg--

Other ingredients: Cellulose, Methacrylic Acid Copolymer, Mannitol, Citric Acid, Titanium Dioxide, Stearic Acid, Silica, Hydroxypropyl Methylcellulose, Glyceryl Triacetate, Sodium Starch Glycolate, Croscarmellose Sodium, 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.
Suggested/Recommended/Usage/Directions

Directions: Take one (1) tablet one 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 foil 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.

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

Storage

Store in a cool dry place.

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.

Formula

SAMe has multiple mechanisms of action that are used throughout the body Brain and Mood SAMe boosts brain cell methylation and facilitates youthful DNA enzymatic actions. These enzymatic actions are required for the healthy conversion of neurotransmitters such as norepinephrine, dopamine, and serotonin and may account for SAMe’s mood-elevating properties. SAMe also helps maintain acetylcholine levels which are necessary for cognitive function. Liver and Detox In order to perform its detoxification role, the liver continually performs large numbers of complex enzymatic reactions. SAMe facilitates healthy methylation enzymatic processes and boosts hepatic levels of glutathione, a critical antioxidant. Joint SAMe may help to ease inflammation and can support healthy joint mobility and function without side effects.

S-Adenosyl-Methionine

Formulation

Supports joints and emotional well-being

Non GMO LE Certified

Seals/Symbols

Non GMO LE Certified

FDA Statement of Identity

Dietary Supplement

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

See for yourself

SAMe 400 mg by Life Extension label

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

SAMe 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 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 Tablet(s) Dosage formTablet Or Pill 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, Methacrylic Acid Copolymer, Mannitol, Citric Acid, Titanium Dioxide, Stearic Acid, Silica, Hydroxypropyl Methylcellulose, Glyceryl Triacetate, Sodium Starch Glycolate, Croscarmellose Sodium, Yellow Ochre. These complete the product’s ingredient list but are not active constituents.

Interaction report

SAMe 400 mg by Life Extension Drug Interactions

Want to check YOUR meds against SAMe 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 400 mg interact with 189 drugs. Click any drug to see the details.

1 of the 1 ingredient in SAMe 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 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 400 mg, from the product label.

Life Extension

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

SAMe 400 mg by Life Extension: Common Questions

Does SAMe 400 mg by Life Extension interact with any medications?
Yes. Based on its ingredients, SAMe 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 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.
Will SAMe help my osteoarthritis?
There's solid evidence that SAMe may help with osteoarthritis pain and stiffness, so it's worth discussing with your doctor if you're interested in trying it. Results vary from person to person.
Can I take SAMe if I'm on an antidepressant?
Not without checking first. SAMe itself has serotonergic effects, and combining it with antidepressants raises the risk of serotonin syndrome—a serious condition with symptoms like agitation, confusion, and rapid heart rate. Talk with your doctor or pharmacist before adding this to your medications.
What are the most common side effects?
Stomach upset is the most common—nausea, diarrhea, constipation, and dry mouth top the list. You may also notice headache, dizziness, or nervousness. Higher doses bring more frequent side effects.
Is SAMe safe during pregnancy?
There isn't enough reliable data to say one way or the other. The rating is 'possibly safe,' but that means we don't have enough evidence to be confident. Talk with your doctor or pharmacist for personalized advice if you're pregnant or planning to become pregnant.
I have bipolar disorder—can I take SAMe?
SAMe may trigger mania in people with bipolar disorder, so you should not take it without guidance from your doctor. Discuss this with them before starting.
Does SAMe help with depression?
The evidence is 'possibly effective,' meaning some people may benefit, but it's not as well proven as it is for osteoarthritis. If you're interested in trying it for depression, talk with your doctor about whether it's right for you and how it fits with other treatments.

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

Not sure if SAMe 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 400 mg label
Go deeper

The Full Monographs Behind SAMe 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 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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