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Dietary supplement

SAM-e 400 mg Ingredients & Drug Interactions

by GNC

SAM-e 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 23, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking SAM-e 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

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

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Check Your Meds Against SAM-e 400 mg by GNC

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

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HelloPharmacist Scorecard of SAM-e 400 mg by GNC

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 a single active ingredient: SAM-e (S-adenosylmethionine), supplied at 400 mg per tablet. SAM-e is a naturally occurring compound found in the body that plays a role in mood regulation and joint health.

The tablet also includes several inactive ingredients—microcrystalline cellulose, croscarmellose sodium, and others—that serve as binders and fillers to hold the tablet 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).

SAM-e is likely effective for osteoarthritis, making it a reasonable option if you're looking for joint support. For depression, the evidence rates it as possibly effective, meaning some evidence exists but it's not considered proven.

For cholestasis (a liver condition involving reduced bile flow), it's also rated possibly effective. The evidence is insufficient to rate its use for Alzheimer disease or ADHD, so we can't say whether it helps with those conditions based on the data we hold.

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.

SAM-e is generally well tolerated at standard doses, though some people report stomach upset—including nausea, diarrhea, constipation, and heartburn—especially at higher doses. Other side effects can include headache, dizziness, insomnia, and nervousness.

An important caution: SAM-e may trigger mania in people with bipolar disorder, so if you have that condition, talk with your doctor before taking it. Safety information is not well established overall, so use it only under the guidance of your healthcare provider.

We don't have reliable safety data for pregnancy and breastfeeding, so speak with your doctor or pharmacist about whether it's right for you if you're pregnant or nursing.

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 with your doctor or pharmacist before starting SAM-e if you take any serotonergic drugs—such as antidepressants (SSRIs, SNRIs, tricyclic antidepressants), certain pain relievers, or other serotonin-related medications—because the combination carries a Moderate risk of serotonin syndrome. Also confirm that levodopa for Parkinson disease won't be affected.

Use the medication search tool on this page to check your exact medications.

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.

SAM-e may help with osteoarthritis and possibly with depression, and many people tolerate it well. However, it can interact with antidepressants and other serotonergic medications—potentially raising the risk of serotonin syndrome—and it may weaken levodopa's effect in Parkinson disease.

Before you take this product, check with your doctor or pharmacist to make sure it won't interfere with your current medications, especially if you take any mood-related drugs or have bipolar disorder.

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 Oct 26, 2011.

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 SAM-e 400 mg, straight from the product label.

Brand GNC
Net contents 30 Tablet(s)
Market status On market
Date entered into DSLD Oct 26, 2011
DSLD ID 666
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 SAM-e 400 mg by GNC, 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:
2 Tablet(s)
Servings per container
30
IngredientAmount% DV
SAM-e400 mg--

Other ingredients: Microcrystalline Cellulose, Croscarmellose Sodium, Methacrylic Acid Co-Polymer, Silicon Dioxide, Colloidal, Magnesium Stearate, Triethyl Citrate, Stearic Acid, Citric Acid, Ascorbic Acid, Riboflavin

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

Formula

(s-adenosyl-methionine)

Precautions

CAUTION: Do not use if tamper-evident printed foil seal over tablets is broken.

KEEP OUT OF REACH OF CHILDREN.

WARNING: Do not use if pregnant or nursing. If you are taking prescription antidepressant medications, consult your physician before using this product, individuals with bipolar (manic) depression should not use this product unless under medical supervision.

Storage

Store in a cool, dry place.

General Statements

400 mg

A report published by the US Department of Health and Human Services suggest that SAM-e provides clinically significant health benefits for individuals seeking mood support (1600 mg daily), joint comfort and healthy liver function (1200 mg daily). SAM-e provides mood support, as well as, relief to joint discomfort, and these benefits are comparable to conventional therapies.

clinically proven benefits for mood and joint support and healthy liver function

ENTERIC COATED

For more information:

Made in the USA

SHOP NOW

General

CODE 130911 KHG

Suggested/Recommended/Usage/Directions

Directions For Adult Use Only: As a dietary supplement, take one tablet in the morning and one tablet in the afternoon for the first week. If after the first week the desired benefits are not achieved, then you may require a higher level of supplementation. Gradually increase the number of tablets up to four tablets in divided doses of two tablets (800 mg) throughout the day until benefits are achieved. Do not exceed four tablets daily.

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See for yourself

SAM-e 400 mg by GNC label

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

SAM-e 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 SAM-e 400 mg by GNC

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.

SAM-e

Interacts with
189 drugs
400 mg per serving Form: Disulfate Monotosylate

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...

SAM-e monograph & interactions

Other (inactive) ingredients: Microcrystalline Cellulose, Croscarmellose Sodium, Methacrylic Acid Co-Polymer, Silicon Dioxide, Colloidal, Magnesium Stearate, Triethyl Citrate, Stearic Acid, Citric Acid, Ascorbic Acid, Riboflavin. These complete the product’s ingredient list but are not active constituents.

Interaction report

SAM-e 400 mg by GNC Drug Interactions

Want to check YOUR meds against SAM-e 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

SAM-e 189

Individual Drug Interactions

The ingredients in SAM-e 400 mg interact with 189 drugs. Click any drug to see the details.

1 of the 1 ingredient in SAM-e 400 mg interact with drugs. Each result below shows which ingredient is responsible. SAM-e

Each ingredient & the kinds of drugs it affects

For each ingredient in SAM-e 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.

SAM-e2 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
SAM-e full monograph & interactions
The maker

Brand information

Manufacturer and brand details for SAM-e 400 mg, from the product label.

GNC

See all GNC products
Name
General Nutrition Corporation
City
Pittsburgh
State
PA
ZipCode
15222
Phone Number
1-888-462-2548
Web Address
gnc.com
Pharmacist Counseling Corner

SAM-e 400 mg by GNC: Common Questions

Does SAM-e 400 mg by GNC interact with any medications?
Yes. Based on its ingredients, SAM-e 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?
SAM-e 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.
Is SAM-e safe if I have bipolar disorder?
No. SAM-e may trigger mania in people with bipolar disorder, so you shouldn't take it without your doctor's approval. Talk with your healthcare provider first to see if it's appropriate for you.
What's the most common side effect?
The most common side effects are stomach-related: nausea, diarrhea, constipation, and heartburn. These tend to be more likely at higher doses, and most people who take standard doses tolerate it well.
Can I take SAM-e if I'm pregnant?
The data rates SAM-e as possibly safe in pregnancy, but we don't have enough reliable information to say for certain. Talk with your doctor or pharmacist about whether it's right for you while pregnant.
Does it really help with osteoarthritis?
Yes—the evidence rates SAM-e as likely effective for osteoarthritis. For depression, the evidence is weaker and rates it as possibly effective, so results may vary.
Are there any fillers in this?
Yes. The tablet includes several inactive ingredients like microcrystalline cellulose and croscarmellose sodium that help hold it together. If you have sensitivities to any of them, check the full ingredient list before you buy.

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

Not sure if SAM-e 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.

SAM-e 400 mg label
Go deeper

The Full Monographs Behind SAM-e 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

SAM-e 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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