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Dietary supplement

SAM-e Complete 400 mg Ingredients & Drug Interactions

by Nature Made

SAM-e Complete 400 mg label
See full label image
Tablet Or Pill Category: Other Combinations
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 SAM-e Complete 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 Complete 400 mg is a dietary supplement by Nature Made with 2 active ingredients. 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 Complete 400 mg by Nature Made

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

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HelloPharmacist Scorecard of SAM-e Complete 400 mg by Nature Made

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: SAM-e (S-adenosylmethionine), a compound your body makes naturally and uses in numerous cellular processes. The 400 mg tablet also includes several inactive ingredients — cellulose, starch, silica, and magnesium stearate among them — that help form 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: Helps support healthy mood and joint comfort.
  • We looked for evidence on: Depression, Osteoarthritis, Fibromyalgia, mood support, joint 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.

SAM-e is likely effective for osteoarthritis pain and stiffness. It's possibly effective for depression and a liver condition called cholestasis (poor bile flow).

For Alzheimer's disease and ADHD, the evidence we hold is insufficient to rate whether it works. If you're considering SAM-e for one of these uses, talk it over with your doctor about what the current evidence supports for your situation.

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.

When taken by mouth at typical doses, SAM-e is generally well tolerated, though some people report stomach upset — nausea, constipation, diarrhea, or dizziness — and higher doses bring more side effects. One important caution: SAM-e may trigger or worsen mania in people with bipolar disorder, so let your doctor know if you have that condition before starting.

The safety data for SAM-e in pregnancy is rated possibly safe, but overall, safety is not well established, so use it only under the guidance of a healthcare provider. Lactation safety information is not on file.

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 start SAM-e, check with your doctor or pharmacist if you take any serotonergic drug — that includes most antidepressants (SSRIs, SNRIs), certain pain relievers, migraine medications, and others that affect serotonin levels. Also confirm your status if you take levodopa for Parkinson's disease.

No interactions are documented for the ingredients we could not 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.

SAM-e may help with osteoarthritis and possibly depression, but it's not for everyone. If you take an antidepressant, pain reliever that affects serotonin, or levodopa for Parkinson's, you'll need to check with your doctor or pharmacist first.

Those with bipolar disorder should avoid it without medical supervision.

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

Brand Nature Made
Barcode (UPC) 031604011635
Net contents 60 Enteric Coated Tablet(s)
Market status On market
Date entered into DSLD Jul 25, 2018
DSLD ID 179365
Product type Other Combinations
Supplement form Tablet Or Pill
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten 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 SAM-e Complete 400 mg by Nature Made, 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
031604011635
IngredientAmount% DV
Protein1 Gram(s)--
SAM-e400 mg--

Other ingredients: S-Adenosylmethionine Tosylate Disulfate, Cellulose Gel, Methacrylic Acid Copolymer, Stearic Acid, Silicon Dioxide, Triethyl Citrate, Magnesium Stearate, Color added, Mannitol, Sodium Starch Glycolate

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 use: Start with 1 tablet per day. For easier swallowing, take with water before and during ingestion. The best time to take SAM-e is on an empty stomach at least 30 minutes before a meal. If benefits are not achieved within two weeks, you may require a higher level of supplementation. To determine the proper level of supplementation that works for you, gradually increase the number of tablets (maximum 1600mg/day) until benefits are achieved.

General Statements

SAM-e is a moisture sensitive product. That is why at Nature Made, we use foil blister packaging to ensure that each tablet of our SAM-e Complete is fresh and safe when you take it.

Helps support A health mood & joint comfort Clinically studied ingredient Restores a healthy mood in as little as 7-14 days

When your emotions are healthy & balanced, you feel like yourself. However, sometimes emotions can get out of balance, causing you to feel moody. This imbalance can be associated with low levels of SAM-e (S-adenosylmethionine), a naturally occurring molecule produced by the body. SAM-e levels can run low due to various factors such as diet and aging. Mood improvement Days Replenish your SAM-e levels and feel the difference in as little as 7-14 days when taken daily. Helps support joint comfort Nature Made SAM-e also helps support joint comfort, which may naturally deteriorate with physical activity and age. SAM-e provides a source of sulfur, which is a critical component of joint tissue. Nature Made St. John's Wort is the #1 Pharmacist Recommended Mood Health supplement followed by Nature Made SAM-e based on the U.S. News & World Report - Pharmacy Times Survey Complete because studies have shown that SAM-e helps support a healthy mood & joint comfort

Restores a healthy mood in as little as 7-14 days when taken daily

Precautions

Foil blister pack ensures safety and freshness. Do not use if temper evident printed foil seal over tablets is broken.

Store in a cool, dry place, out of reach of children.

Caution: People with bipolar (manic) depression or who are experiencing severe issues with mood, including thoughts of suicide, should not take this or any other product containing SAM-e except under a doctor's supervision.

If you are pregnant or nursing, or taking prescription medications, including antidepressants, consult your doctor before using this product.

Storage

Store in a cool, dry place, out of reach of children.

FDA Statement of Identity

Dietary Supplement

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.

General

List No: 1163 P202 Cat: A852 1A232 ITEM # 590598

Brand IP Statement(s)

SAM-e Complete tablets are made to Nature Made's guaranteed purity and potency standards.

From the #1 pharmacist recommended mood health supplement brand, Nature Made SAM-e helps support a healthy mood.

Formulation

This product is gluten free.

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

See for yourself

SAM-e Complete 400 mg by Nature Made label

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

SAM-e Complete 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 Complete 400 mg by Nature Made

These are the 2 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Tablet(s) Dosage formTablet Or Pill Amounts shown are per serving.

Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.

Protein

1 Gram(s) per serving

SAM-e

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...

SAM-e monograph & interactions

Other (inactive) ingredients: S-Adenosylmethionine Tosylate Disulfate, Cellulose Gel, Methacrylic Acid Copolymer, Stearic Acid, Silicon Dioxide, Triethyl Citrate, Magnesium Stearate, Color added, Mannitol, Sodium Starch Glycolate. These complete the product’s ingredient list but are not active constituents.

Interaction report

SAM-e Complete 400 mg by Nature Made Drug Interactions

Want to check YOUR meds against SAM-e Complete 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 Complete 400 mg interact with 189 drugs. Click any drug to see the details.

1 of the 2 ingredients in SAM-e Complete 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 Complete 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 Complete 400 mg, from the product label.

Nature Made

See all Nature Made products
Name
Nature Made Nutritional Products
City
Mission Hills
State
CA
ZipCode
91346-9606
Phone Number
1-800-276-2878
Web Address
www.NatureMade.com
Pharmacist Counseling Corner

SAM-e Complete 400 mg by Nature Made: Common Questions

Does SAM-e Complete 400 mg by Nature Made interact with any medications?
Yes. Based on its ingredients, SAM-e Complete 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 Complete 400 mg contains 2 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take SAM-e if I have bipolar disorder?
No — the safety data advises against it. SAM-e can trigger or worsen manic episodes in people with bipolar disorder. Talk with your doctor before considering it.
What's the most common side effect?
Gastrointestinal upset is most common: nausea, constipation, diarrhea, or stomach ache. Side effects are dose-dependent and more frequent at higher doses. If they occur, they're often mild and short-lived.
Is SAM-e safe during pregnancy?
The data rates it as possibly safe, but overall safety is not well established. Talk with your doctor about whether to use it during pregnancy — that's an individual decision based on your situation.
Will SAM-e help my depression?
SAM-e is rated possibly effective for depression, meaning some evidence supports it but it's not conclusive. Whether it's right for you depends on your specific situation and other medications — check with your doctor or pharmacist.
How does SAM-e work for osteoarthritis?
The exact mechanism isn't detailed in our data, but SAM-e is rated likely effective for osteoarthritis, meaning there's solid evidence it can help with pain and joint symptoms.

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

Not sure if SAM-e Complete 400 mg is safe with your meds?

Our pharmacists answer your medication & supplement questions — free.

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.

SAM-e Complete 400 mg label
Go deeper

The Full Monographs Behind SAM-e Complete 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 Complete 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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