Drug & supplement interaction

Berberine + Siponimod

Siponimod brand name: Mayzent.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Siponimod falls into 2 drug categories that Berberine can interact with; the most serious is rated moderate. Theoretically, berberine might increase serum levels of drugs metabolized by CYP2C9.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Berberine and Siponimod

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Berberine interacts with whole categories of medication. Siponimod falls into 2 of those categories, so it can interact with Berberine in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

1 of 2

Why this applies to Siponimod

Siponimod falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Berberine interacts with.

Theoretically, berberine might increase serum levels of drugs metabolized by CYP2C9.
Preliminary clinical research shows that berberine can inhibit CYP2C9. Theoretically, taking berberine with drugs metabolized by CYP2C9 might increase drug levels and increase the risk of adverse effects.
Severity Moderate Likelihood Possible Evidence B

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for Mayzent (siponimod): your liver leans heavily on an enzyme called CYP2C9 to clear it out of your system. Early research suggests berberine can slow that same enzyme down. If the enzyme works slower, siponimod can build up higher than expected, which may turn up its effects and side effects, things like a slower heart rate (especially when you first start it), headache, dizziness, higher blood pressure, or changes in liver tests.

I'll be honest, this is mostly theoretical and based on lower quality studies, so it may not cause trouble for everyone. But since siponimod already needs careful dosing based on your genetics, I wouldn't add berberine on your own. Please run it past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Siponimod also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, berberine might increase serum levels of drugs metabolized by CYP3A4.
In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4. Theoretically, use of berberine with drugs metabolized by CYP3A4 might increase drug levels and increase the risk of adverse effects.
Severity Moderate Likelihood Possible Evidence A

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the situation with these two together. Your body clears siponimod partly through a liver enzyme called CYP3A4. Berberine appears to slow that enzyme down a bit, so the worry is that siponimod could build up higher than expected in your system. Siponimod is not a prodrug, so more drug in your blood generally means stronger effects and a higher chance of side effects.

With siponimod, that could mean things like a slower heart rate, headaches, dizziness, raised blood pressure, or more risk of infection since it dampens the immune system. Right now this concern is mostly theoretical and based on lab and early research, so it may not cause real trouble for everyone. Still, before adding berberine, please run it by your pharmacist or neurologist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 2005;61:567-72. PubMed
  2. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  3. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
  4. Hermann, R. and von, Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012;78(13):1458-1477. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Berberine Also Interacts With Other Medications

Berberine has 1 major, 1,158 moderate known drug interactions in our database — the Siponimod one above is among them. If you take anything else, check it against the full list below.

Major 1 Moderate 1,158 No known interaction 1,671 (incl. Siponimod)
Taking anything else?

Check Another of Your Medications Against Berberine

Covers the 2,830 medications we’ve checked against Berberine. Pick one to open its full report.

From our Q&A

Questions About Berberine or Siponimod

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Berberine or Siponimod, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Siponimod

This page covers Berberine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Siponimod page lists 190 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate) and Active Hexose Correlated Compound (ahcc) (moderate).

By severity: 3 major · 147 moderate · 40 minor.

From our pharmacist’s overview on the Siponimod page

“Siponimod (Mayzent) treats secondary progressive multiple sclerosis, and because its blood level depends heavily on two liver enzymes, this is a supplement list to respect. Most of these entries can nudge siponimod levels up or down; the three rated major are grapefruit, which raises them, St.”

Reviewed by 2 · Jul 18, 2026

Open the Siponimod interaction page

One more smart check

Taking Berberine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 908 real supplement products containing Berberine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Berberine. Your product may carry other ingredients that interact with Siponimod too, on top of Berberine — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Berberine and Siponimod Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Berberine
Top 10%

#109 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Siponimod
Steady interest

#2,395 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Berberine

What is Berberine?

Berberine
  • Blood sugar control
  • High cholesterol
  • Heart and metabolic health
  • Digestive upset
  • Antimicrobial support
  • Weight management

Berberine is a yellow plant compound that has shown promise for lowering blood sugar and cholesterol in some studies, but the quality of research varies and it is not a replacement for prescribed medicine. It can cause stomach upset and should be avoided during pregnancy and breastfeeding. Always check with your pharmacist or doctor before starting it, especially if you take other medications.

Read the full Berberine monograph & all interactions
Medication

About Siponimod

What Is Siponimod Used For?

Brand name: Mayzent

Mayzent (siponimod) is approved for adults with relapsing forms of multiple sclerosis (MS). This includes three specific types: clinically isolated syndrome (a first episode of MS-like symptoms), relapsing-remitting MS (periods of attacks followed by recovery), and active secondary progressive MS (a phase where the disease gradually worsens but still has active relapses).

It is taken by mouth once daily and is intended as a long-term treatment to reduce relapses and slow disease progression.

See full Siponimod drug information
Keep checking

Other Drugs & Berberine

Browse every other medication we’ve checked against Berberine — both the ones with a known interaction and the ones without. Select any drug for the full detail.

1Major
1,158Moderate
0Minor
1,670No known interaction
1 Major 1,158 Moderate 1,670 No interaction
Major

1 interaction

Moderate

1,158 interactions

Showing 60 of 1,158 moderate interactions — see all 1,158 on the Berberine page.

No interaction 1,670 drugs checked — show the list

We also checked Berberine against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,670 medications checked with no known interaction — see the full Berberine list.

See the full Berberine interactions page
See every supplement checked against Siponimod, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

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

Keep exploring
Berberine monograph › Uses, safety, and every drug interaction in one place Siponimod supplement interactions › Every supplement checked against Siponimod, ranked by severity Siponimod drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Berberine and Siponimod Together: Common Questions

Can you take Berberine with Siponimod?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Berberine and Siponimod?
Siponimod belongs to more than one drug category, and Berberine interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Berberine and Siponimod interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

Still Have a Question About Siponimod and Berberine?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.