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Dietary supplement

SAMe 400 mg Ingredients & Drug Interactions

by Natrol

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 9, 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 Natrol 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 Natrol

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

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HelloPharmacist Scorecard of SAMe 400 mg by Natrol

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 tablet also contains inactive ingredients — cellulose, cellulose gum, magnesium stearate, stearic acid, silica, and several others that help bind and preserve the tablet.

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: mood support, liver function and joint health.
  • We looked for evidence on: Depression, Osteoarthritis, Alcohol-related liver disease, Cirrhosis, Hepatitis C, Fibromyalgia — and 4 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 Cholestasis, Depression.
  • Also on file: Same is rated "Insufficient Reliable Evidence To Rate" for Alcohol-related liver disease, Cirrhosis, Fibromyalgia, Hepatitis C.

SAMe is likely effective for osteoarthritis, meaning the evidence supports its use for joint pain and stiffness. For depression, the evidence suggests it's possibly effective — some studies show benefit, but the data isn't as robust.

For liver disease (cholestasis), it's also possibly effective. 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 typical doses, though side effects become more common at higher doses. The most frequent reported side effects are nausea, diarrhea, constipation, headache, dizziness, insomnia, and dry mouth.

One important caution: SAMe may trigger mania in people with bipolar disorder, so if you have bipolar illness, talk with your doctor or pharmacist before taking it. Safety data during pregnancy is limited — it's rated possibly safe, but there isn't enough information to know for certain, so discuss it with your doctor or pharmacist if you're 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.

Before you take SAMe, check with your doctor or pharmacist if you take serotonergic drugs — antidepressants, anti-anxiety medications, certain pain relievers, or migraine treatments — because of the risk of serotonin syndrome. Also double-check if you take levodopa for Parkinson's disease, as SAMe may reduce how well it works.

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 depression and want a natural option, but you'll need to check it against any medications you take — especially antidepressants and Parkinson's drugs. If you have bipolar disorder or are pregnant or breastfeeding, talk with your doctor or pharmacist first before starting.

They can help you weigh the benefits and risks for 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 Jan 25, 2018.

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 Natrol
Barcode (UPC) 047469161415
Net contents 20 Enteric Coated Tablet(s)
Market status On market
Date entered into DSLD Jan 25, 2018
DSLD ID 78176
Product type Non-nutrient/non-botanical
Supplement form Tablet Or Pill
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Vegetarian, Adult (18 - 50 Years), 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 Natrol, 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:
2 Tablet(s)
Maximum serving Sizes:
2 Tablet(s)
Servings per container
10
UPC/BARCODE
047469161415
IngredientAmount% DV
S-Adenosyl-Methionine400 mg--

Other ingredients: Cellulose, Cellulose Gum, Methacrylate Polymer, Magnesium Stearate, Stearic Acid, Silica, Citric Acid, Ascorbic Acid, Triethyl Citrate, Colored with Riboflavin and Titanium Dioxide

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.
Brand IP Statement(s)

SAMe (S-Adenosyl-Methionine) is an amino acid that is produced by the body for positive mood. Diet, aging and other factors may lower SAMe levels. Fortunately Natrol SAMe helps support beneficial levels of SAMe in the body. SAMe is also beneficial for joint comfort and healthy liver function.

Suggested/Recommended/Usage/Directions

Directions: Take 2 tablets, one time daily, with a meal.

Formulation

No milk, egg, fish, crustacean shellfish, tree nuts, wheat, peanuts, soybeans, yeast, corn, glutens, artificial flavors, added sugar, starch or preservatives

100% vegetarian

General

ITEM: 16141 F: 3000008 B: 2007417-15064

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 400 mg per serving

General Statements

Helps support mood SAMe helps support healthy liver function Promotes joint health

FDA Statement of Identity

Dietary Supplement

Precautions

Consult your healthcare professional prior to use if you have or suspect a medical condition, or are taking prescription drugs or any prescription antidepressant. Do not use this product if you have bipolar disorder (manic depression) or are pregnant or lactating.

Keep out of reach of children.

Storage

Store in a cool, dry place.

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

See for yourself

SAMe 400 mg by Natrol 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 Natrol

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

Serving size2 Tablet(s) Dosage formTablet Or Pill Servings per container10 Amounts shown are per serving.

S-Adenosyl-Methionine

Interacts with
189 drugs
400 mg per serving Form: S-Adenosyl-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...

S-Adenosyl-Methionine monograph & interactions

Other (inactive) ingredients: Cellulose, Cellulose Gum, Methacrylate Polymer, Magnesium Stearate, Stearic Acid, Silica, Citric Acid, Ascorbic Acid, Triethyl Citrate, Colored with Riboflavin and Titanium Dioxide. These complete the product’s ingredient list but are not active constituents.

Interaction report

SAMe 400 mg by Natrol 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.

Natrol

See all Natrol products
Name
Natrol LLC
City
Chatsworth
State
CA
ZipCode
91311
Phone Number
1-800-262-8765
Web Address
www.natrol.com
Pharmacist Counseling Corner

SAMe 400 mg by Natrol: Common Questions

Does SAMe 400 mg by Natrol 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 joint pain?
SAMe is likely effective for osteoarthritis. Studies support its use for joint pain and stiffness, so it may be worth a try — but give it time, and let your doctor or pharmacist know you're taking it.
Can SAMe help with depression?
The evidence suggests SAMe is possibly effective for depression — some studies show it helps, but the proof isn't as strong as it is for osteoarthritis. It's an option to discuss with your doctor or pharmacist alongside other treatments.
What are the most common side effects?
At typical doses, SAMe is usually well tolerated. The most common side effects are nausea, diarrhea, constipation, headache, and insomnia — and they're more likely at higher doses. If you have stomach upset, try taking it with food or talk to your pharmacist about whether a lower dose would help.
Is SAMe safe if I have bipolar disorder?
SAMe may trigger mania in people with bipolar disorder, so it's not recommended without guidance from your doctor or pharmacist. If you have bipolar illness, definitely talk with them before taking it.
Can I take SAMe while pregnant?
SAMe is rated possibly safe in pregnancy, but there isn't enough reliable information to say for certain. Talk with your doctor or pharmacist if you're pregnant or breastfeeding — they can help you decide whether it's right for you.

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

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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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