Drug & supplement interaction

Limonene + Siponimod

Siponimod brand name: Mayzent.

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

Limonene has a moderate interaction with Siponimod. There's preliminary evidence that limonene might be a substrate for cytochrome P450 2C9 (CYP2C9), as well causing its induction.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Limonene and Siponimod

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Why this applies to Siponimod

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

There's preliminary evidence that limonene might be a substrate for cytochrome P450 2C9 (CYP2C9), as well causing its induction. So far, this interaction has not been reported in humans. However, watch for a decrease in the levels of drugs metabolized by CYP2C9 in patients taking limonene. Some drugs metabolized by CYP2C9 include nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (Cataflam, Voltaren), ibuprofen (Motrin), meloxicam (Mobic), and piroxicam (Feldene); celecoxib (Celebrex); amitriptyline (Elavil); warfarin (Coumadin); glipizide (Glucotrol); losartan (Cozaar); and others.
Severity Moderate Likelihood Possible Evidence D

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 body relies on a liver enzyme called CYP2C9 to process this drug, and early lab work hints that concentrated limonene might speed that enzyme up. If that happened, your siponimod could be cleared faster than intended, leaving less of it in your system. In practical terms, that might mean weaker control of your MS, so symptoms like numbness, weakness, or vision changes could creep back in.

I want to be honest about the evidence here: this is only seen in test tube and animal studies, never confirmed in people, so the real-world risk is uncertain. Everyday citrus and food flavoring almost certainly won't matter. Still, before starting a concentrated limonene supplement, please run it by your pharmacist or neurologist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Crowell PL. Prevention and therapy of cancer by dietary monoterpenes. J Nutr 1999;129:775S-778S. PubMed
  2. Miyazawa M, Shindo M, Shimada T. Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metab Dispos 2002;30:602-7. 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

Limonene Also Interacts With Other Medications

Limonene has 228 moderate known drug interactions in our database — the Siponimod one above is one of them. If you take anything else, check it against the full list below.

Moderate 228 No known interaction 2,602 (incl. Siponimod)
Taking anything else?

Check Another of Your Medications Against Limonene

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

Everything else you take

See Every Supplement That Interacts With Siponimod

This page covers Limonene 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 Limonene as Part of a Dietary Supplement Product? Check It for Interactions

We hold 89 real supplement products containing Limonene, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Limonene. Your product may carry other ingredients that interact with Siponimod too, on top of Limonene — 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 Limonene 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 Limonene
Steady interest

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

29 days ago today
Medication Siponimod
Steady interest

#2,547 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 Limonene

What is Limonene?

  • Heartburn and acid reflux
  • Digestive upset
  • Stress and mood support
  • Antioxidant support
  • General wellness

Limonene is a natural compound found in the peel of citrus fruits like oranges and lemons, and it is used as a flavoring agent and dietary supplement. People take it for heartburn, digestion, and general wellness, but solid human evidence is limited. It is generally well tolerated in food amounts, but talk with your pharmacist or doctor before using concentrated supplements.

Read the full Limonene 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 & Limonene

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

0Major
228Moderate
0Minor
2,601No known interaction
228 Moderate 2,601 No interaction
Moderate

228 interactions

Showing 60 of 228 moderate interactions — see all 228 on the Limonene page.

No interaction 2,601 drugs checked — show the list

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

Showing the 60 most looked-up of 2,601 medications checked with no known interaction — see the full Limonene list.

See the full Limonene 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
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Pharmacist Counseling Corner

Taking Limonene and Siponimod Together: Common Questions

Can you take Limonene 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.
How serious is the Limonene 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 Limonene?

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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.