Drug & supplement interaction

Lime + Ramelteon

Ramelteon brand name: Rozerem.

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

Lime has a moderate interaction with Ramelteon. Animal research shows that phenolics in lime juice inhibit cytochrome P450 3A4.

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

Lime and Ramelteon

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Ramelteon

Ramelteon falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Lime interacts with.

Animal research shows that phenolics in lime juice inhibit cytochrome P450 3A4. This has been demonstrated in rats treated with sildenafil, a CYP3A4 substrate, and high doses of lime juice.
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 Ramelteon (Rozerem). Your body relies on an enzyme called CYP3A4 to break this sleep medicine down. Lab and animal studies suggest the plant compounds in lime juice can slow that enzyme a bit. If CYP3A4 works slower, more ramelteon could linger in your system, which might make its effects stronger. In real life that could mean feeling extra drowsy, groggy, or dizzy the next morning.

That said, the evidence here is weak, coming only from rats given large amounts of lime juice. A squeeze of lime in your water or on your food is very unlikely to cause trouble. I'd only be cautious with concentrated lime supplements. If you use those, check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bailey DG, Dresser GK, Bend JR. Bergamottin, lime juice, and red wine as inhibitors of cytochrome P450 3A4 activity: comparison with grapefruit juice. Clin Pharmacol Ther 2003;73:529-37. PubMed
  2. Ademosun AO, Mohammed A, Oboh G, Ajeigbe OF. Influence of lemon (Citrus limon) and lime (Citrus aurantifolia) juices on the erectogenic properties of sildenafil in rats with L-NAME-induced erectile dysfunction. J Food Biochem 2022;46(2):e14074.

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

Lime Also Interacts With Other Medications

Lime has 885 moderate known drug interactions in our database — the Ramelteon one above is one of them. If you take anything else, check it against the full list below.

Moderate 885 No known interaction 1,945 (incl. Ramelteon)
Taking anything else?

Check Another of Your Medications Against Lime

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

From our Q&A

Questions About Lime or Ramelteon

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Lime or Ramelteon, 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 Ramelteon

This page covers Lime only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ramelteon page lists 228 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 9 major · 173 moderate · 46 minor.

From our pharmacist’s overview on the Ramelteon page

“Ramelteon (Rozerem) is a prescription sleep aid, and its 228 interacting supplements call for real care, starting with the nine rated major. The frustrating part is that the things sleepless people typically reach for, kava, CBD, a glass of wine before bed, sit at the heart of the problem.”

Reviewed by 2 · Jul 18, 2026

Open the Ramelteon interaction page

One more smart check

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

We hold 322 real supplement products containing Lime, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Lime. Your product may carry other ingredients that interact with Ramelteon too, on top of Lime — 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 Lime and Ramelteon 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 Lime
Top 25%

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

29 days ago today
Medication Ramelteon
Top half

#1,232 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 Lime

What is Lime?

Lime
  • Source of vitamin C
  • Digestive upset
  • Skin care
  • Mood and aromatherapy
  • Flavoring and food preservation

Lime is a common citrus fruit and a good natural source of vitamin C and plant antioxidants. As a food it is generally safe and enjoyed by most people, but evidence that lime treats any specific health condition is limited. Use the essential oil with care, and check with your pharmacist or doctor before using concentrated lime products for health reasons.

Read the full Lime monograph & all interactions
Medication

About Ramelteon

What Is Ramelteon Used For?

Brand name: Rozerem

Ramelteon tablets — sold as the brand Rozerem and as generic ramelteon — are used to treat insomnia when the main problem is trouble falling asleep at the start of the night. It is not indicated for difficulty staying asleep.

Clinical studies supporting its effectiveness ran up to six months in both adults and elderly patients.

See full Ramelteon drug information
Keep checking

Other Drugs & Lime

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

0Major
885Moderate
0Minor
1,944No known interaction
885 Moderate 1,944 No interaction
Moderate

885 interactions

Showing 60 of 885 moderate interactions — see all 885 on the Lime page.

No interaction 1,944 drugs checked — show the list

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

Showing the 60 most looked-up of 1,944 medications checked with no known interaction — see the full Lime list.

See the full Lime interactions page
See every supplement checked against Ramelteon, 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
Lime monograph › Uses, safety, and every drug interaction in one place Ramelteon supplement interactions › Every supplement checked against Ramelteon, ranked by severity Ramelteon 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 Lime and Ramelteon Together: Common Questions

Can you take Lime with Ramelteon?
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 Lime and Ramelteon 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 Ramelteon and Lime?

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.