Drug & supplement interaction

Bitter Orange + Isocarboxazid

Isocarboxazid brand name: Marplan.

Major Interaction
Medically reviewed by · Updated October 2026
The bottom line Major

Bitter Orange has a major interaction with Isocarboxazid. Theoretically, taking MAOIs with synephrine-containing bitter orange preparations might increase the hypertensive effects of synephrine, potentially leading to hypertensive crisis.

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

Bitter Orange and Isocarboxazid

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

Major

MONOAMINE OXIDASE INHIBITORS (MAOIs)

Why this applies to Isocarboxazid

Isocarboxazid falls under MONOAMINE OXIDASE INHIBITORS (MAOIs) — the group Bitter Orange interacts with.

Theoretically, taking MAOIs with synephrine-containing bitter orange preparations might increase the hypertensive effects of synephrine, potentially leading to hypertensive crisis.
Bitter orange contains tyramine, octopamine, and synephrine, which are MAO substrates.
Severity Major Likelihood Probable Evidence D

Interaction 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..

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

This is one combination I'd be really cautious about. Isocarboxazid (Marplan) is an MAO inhibitor, which means it slows down the enzyme that normally breaks down stimulant-type compounds and pressure-raising substances in your body. Bitter orange supplements contain synephrine, along with tyramine and octopamine, and these are exactly the kinds of substances that enzyme would normally clear out.

When you block that breakdown with Marplan and then add bitter orange, those stimulants can pile up. In theory that can push your blood pressure dangerously high, sometimes called a hypertensive crisis, with a pounding headache, chest pain, or a racing heart. Honestly, this caution is the same reason people on MAOIs are told to watch high-tyramine foods. The evidence here is more theoretical than proven, but given how serious the worst case is, I wouldn't take the chance. Please check with your pharmacist or doctor before using any bitter orange product.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Pellati F, Benvenuti S, Melegari M, Firenzuoli F. Determination of adrenergic agonists from extracts and herbal products of Citrus aurantium L. var. amara by LC. J Pharm Biomed Anal 2002;29:1113-9. . PubMed
  2. Visentin V, Morin N, Fontana E, et al. Dual action of octopamine on glucose transport into adipocytes: inhibition via beta3-adrenoceptor activation and stimulation via oxidation by amine oxidases. J Pharmacol Exp Ther 2001;299:96-104.
  3. Suzuki O, Matsumoto T, Oya M, Katsumata Y. Oxidation of synephrine by type A and type B monoamine oxidase. Experientia 1979;35:1283-4. 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

Bitter Orange Also Interacts With Other Medications

Bitter Orange has 9 major, 878 moderate, 71 minor known drug interactions in our database — the Isocarboxazid one above is one of them. If you take anything else, check it against the full list below.

Major 9 Moderate 878 Minor 71 No known interaction 1,872 (incl. Isocarboxazid)
Taking anything else?

Check Another of Your Medications Against Bitter Orange

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

Everything else you take

See Every Supplement That Interacts With Isocarboxazid

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Isocarboxazid page lists 81 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Brewer's Yeast (major), Cowhage (major) and Fever Bark (major).

By severity: 14 major · 55 moderate · 12 minor.

From our pharmacist’s overview on the Isocarboxazid page

“Isocarboxazid (Marplan) is an MAOI antidepressant, and that drug class carries some of the sharpest supplement and food hazards in the pharmacy, so read this list closely rather than skimming it. Fourteen of the 81 entries rate major, and most of the danger runs through tyramine.”

Reviewed by 2 · Jul 18, 2026

Open the Isocarboxazid interaction page

One more smart check

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

We hold 1,000 real supplement products containing Bitter Orange, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bitter Orange. Your product may carry other ingredients that interact with Isocarboxazid too, on top of Bitter Orange — 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 Bitter Orange and Isocarboxazid 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 Bitter Orange
Top 25%

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

29 days ago today
Medication Isocarboxazid
Steady interest

#2,551 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 Bitter Orange

What is Bitter Orange?

Bitter Orange
  • Weight loss
  • Athletic performance and energy
  • Digestive upset
  • Appetite control
  • Aromatherapy for stress (neroli oil)

Bitter orange is a citrus fruit whose extracts contain synephrine, a mild stimulant often added to weight-loss and energy supplements. Evidence that it works for weight loss or performance is limited, and because it can raise heart rate and blood pressure, people with heart problems, high blood pressure, or who are pregnant should avoid it. Talk to your pharmacist or doctor before using it, especially if you take other stimulants.

Read the full Bitter Orange monograph & all interactions
Medication

About Isocarboxazid

What Is Isocarboxazid Used For?

Brand name: Marplan

Isocarboxazid, sold as Marplan tablets, is used to treat depression. In the studies, the people helped had symptoms matching major depressive disorder, and many also had anxiety, panic or phobic symptoms.

It is not usually the first antidepressant tried because of its potentially serious side effects. It is not approved for children or for bipolar depression.

See full Isocarboxazid drug information
Keep checking

Other Drugs & Bitter Orange

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

9Major
878Moderate
71Minor
1,871No known interaction
9 Major 878 Moderate 71 Minor 1,871 No interaction
Major

9 interactions

Moderate

878 interactions

Showing 60 of 878 moderate interactions — see all 878 on the Bitter Orange page.

Minor

71 interactions

Showing 60 of 71 minor interactions — see all 71 on the Bitter Orange page.

No interaction 1,871 drugs checked — show the list

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

Showing the 60 most looked-up of 1,871 medications checked with no known interaction — see the full Bitter Orange list.

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

Can you take Bitter Orange with Isocarboxazid?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Bitter Orange and Isocarboxazid interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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

Still Have a Question About Isocarboxazid and Bitter Orange?

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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.