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Dietary supplement

SAMe 400 mg Ingredients & Drug Interactions

by NOW

Tablet Or Pill Category: Non-nutrient/non-botanical
Most serious interaction: Moderate
The interaction bottom line Most serious interaction: Moderate

SAMe 400 mg is a dietary supplement by NOW 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 SAMe. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of SAMe 400 mg by NOW

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

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: SAMe (S-adenosyl methionine), a compound your body naturally makes that plays a role in several biochemical processes. The tablet also includes inactive ingredients like microcrystalline cellulose, stearic acid, and magnesium stearate, which are standard tablet fillers and binders.

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 biochemistry and joint health support.
  • We looked for evidence on: Depression, Fibromyalgia, Osteoarthritis, mood, cognitive function, cartilage health.
  • 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 helps joint pain and stiffness. For depression, the evidence is less certain—it's possibly effective, so some people do see a benefit, but it's not as well established as prescription antidepressants.

For other uses on the label, like cholestasis (liver bile-flow problems), the evidence is still preliminary, or in the case of Alzheimer disease and ADHD, there isn't enough reliable data to know if 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.

Short-term, SAMe is generally well tolerated in normal doses, but stomach upset is common—nausea, diarrhea, constipation, and headache are the most frequent complaints. These side effects tend to be worse at higher doses.

One important caution: if you have bipolar disorder, SAMe can trigger a manic episode, so it's not safe for you without a doctor's supervision. Overall, safety data is limited, especially long-term, so use it only under guidance from your 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.

Check your exact medications against this product if you take serotonergic drugs—antidepressants (SSRIs, SNRIs, tricyclics), migraine treatments, and certain pain or psychiatric medications. Also double-check if you're on levodopa for Parkinson disease.

No other interactions are documented for the ingredient we could check.

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 considering if you have osteoarthritis or want to explore it for depression alongside professional care. If you take any psychiatric medications, pain treatments, or Parkinson drugs, run them through our checker first.

Talk to your pharmacist or doctor before starting, especially if you have bipolar disorder or take any prescription medications.

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 Jul 24, 2025.

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 NOW
Barcode (UPC) 733739001399
Net contents 30 Tablet(s)
Market status On market
Date entered into DSLD Jul 24, 2025
DSLD ID 335305
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), Kosher, Gluten Free, Dairy Free
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 NOW, 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)
Servings per container
30
UPC/BARCODE
733739001399
IngredientAmount% DV
SAMe400 mg--

Other ingredients: Microcrystalline Cellulose, Stearic Acid, Pharmaceutical Glaze, Magnesium Stearate, Silicon Dioxide, Glycerin, Sodium Alginate, L-Arginine

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

Suggested Usage: Take 1 tablet 2 to 4 times daily, preferably on an empty stomach.

Formula

SAMe (S-adenosylmethionine), a compound native to the body, is a component of many biochemical reactions, including those that affect brain biochemistry and joint health. Numerous studies have indicated that SAMe can help to alleviate transient minor aches and pains resulting from overexertion or strain. In addition, because SAMe is also necessary for the synthesis of neurotransmitters, it plays an important role in mood support.

Stabilized SAMe, Smaller Tablet

Triangle K (Kosher)

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.

Precautions

Caution: For adults only.

Individuals with bipolar, depression, anxiety disorders or taking antidepressant medications should not take SAMe unless under professional medical supervision. Consult physician if pregnant/nursing, taking medication, or have a medical condition.

Keep out of reach of children.

Not manufactured with wheat, gluten, soy, milk, egg, fish, shellfish or sesame ingredients. Produced in a GMP facility that processes other ingredients containing these allergens.

Storage

Store in a cool, dry place after opening.

Formulation

Nervous system support No enteric coating needed Supports joint health

Amino acids

Made and quality tested in the USA with globally sourced ingredients.

Not manufactured with wheat, gluten, soy, milk, egg, fish, shellfish or sesame ingredients.

Natural color variation may occur in this product.

FDA Statement of Identity

A Dietary Supplement

General Statements

Family owned since 1968.

Seals/Symbols

GMP Quality Assured

Triangle K (Kosher)

See for yourself

SAMe 400 mg by NOW label

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

What’s inside

The Ingredients in SAMe 400 mg by NOW

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 Servings per container30 Amounts shown are per serving.

SAMe

Interacts with
189 drugs
400 mg per serving Form: S-Adenosyl-L-Methionine Disulfate Tosylate

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...

SAMe monograph & interactions

Other (inactive) ingredients: Microcrystalline Cellulose, Stearic Acid, Pharmaceutical Glaze, Magnesium Stearate, Silicon Dioxide, Glycerin, Sodium Alginate, L-Arginine. These complete the product’s ingredient list but are not active constituents.

Interaction report

SAMe 400 mg by NOW 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

SAMe 189

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.

SAMe2 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
The maker

Brand information

Manufacturer and brand details for SAMe 400 mg, from the product label.

NOW

See all NOW products
Name
NOW Foods
Street Address
395 S. Glen Ellyn Rd.
City
Bloomingdale
State
IL
ZipCode
60108
Web Address
nowfoods.com
Pharmacist Counseling Corner

SAMe 400 mg by NOW: Common Questions

Does SAMe 400 mg by NOW 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.
What does SAMe actually do in my body?
SAMe is a compound your body naturally makes that's involved in several chemical reactions—it helps with mood regulation, joint health, and liver function. This supplement tops up what your body already produces, but we don't fully understand all the ways it works yet.
Is SAMe safe to take long-term?
Short-term use is generally well tolerated, but long-term safety isn't well established. You should use it only under the guidance of a healthcare provider, and talk with them about how long you'll take it.
Can I take SAMe if I have bipolar disorder?
No—SAMe can trigger a manic episode in people with bipolar disorder, so it's not safe for you. Talk to your doctor or psychiatrist before considering any new supplement.
What side effects should I watch for?
The most common are stomach upset—nausea, diarrhea, constipation—plus headache, dizziness, and insomnia. Side effects are usually mild and more likely at higher doses, but if they're bothersome, mention it to your pharmacist.
Does SAMe actually work for joint pain?
For osteoarthritis, yes—there's solid evidence that SAMe helps reduce joint pain and stiffness. For depression, the evidence is less strong, but some people do see a benefit.

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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Ask a pharmacist

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
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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