Drug & supplement interaction

Red Clover + Ethinyl estradiol, Levonogestrel

Ethinyl estradiol, Levonogestrel brand name: Lybrel.

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

Ethinyl estradiol, Levonogestrel falls into 3 drug categories that Red Clover can interact with; the most serious is rated moderate. Theoretically, concomitant use of large amounts of red clover might interfere with estrogen therapy.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Red Clover and Ethinyl estradiol, Levonogestrel

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Red Clover interacts with whole categories of medication. Ethinyl estradiol, Levonogestrel falls into 3 of those categories, so it can interact with Red Clover in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ESTROGENS

1 of 3

Why this applies to Ethinyl estradiol, Levonogestrel

Ethinyl estradiol, Levonogestrel falls under ESTROGENS — the group Red Clover interacts with.

Theoretically, concomitant use of large amounts of red clover might interfere with estrogen therapy.
Red clover contains phytoestrogens which might have estrogenic activity in some people. Theoretically, red clover might compete for estrogen receptors and interfere with estrogen-containing drug therapy.
Severity Moderate 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

Lybrel is a combination birth control pill (ethinyl estradiol plus levonorgestrel) that you take to prevent pregnancy and steady your hormone levels. Red clover carries plant estrogens called isoflavones, which can attach weakly to the same estrogen receptors your pill works on. In theory, large supplement-strength amounts of red clover might nudge in on those receptors and slightly blunt how your pill behaves. I want to be clear though: this concern is theoretical, based on how the compounds look on paper, not on real-world failures.

The practical worry would be a small drop in your pill's reliability. Occasional food amounts aren't the issue; concentrated capsules are where I'd pause. Before adding red clover, please check with your pharmacist or doctor rather than changing anything on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr 1997;17:353-81. PubMed
  2. Wuttke W, Jarry H, Seidlova-Wuttke D. Plant-derived alternative treatments for the aging male: facts and myths. Aging Male 2010;13(2):75-81. PubMed
  3. Villaseca P. Non-estrogen conventional and phytochemical treatments for vasomotor symptoms: what needs to be known for practice. Climacteric 2012;15(2):115-124. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 3

Ethinyl estradiol, Levonogestrel also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.
In vitro evidence shows that red clover inhibits CYP1A2. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of caffeine, a CYP1A2 probe substrate.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

If you're taking Lybrel (a continuous birth control pill with ethinyl estradiol and levonorgestrel) and thinking about red clover, here's the honest picture. In a test tube, red clover's isoflavones can slow down an enzyme called CYP1A2, which plays a small role in clearing certain medicines. The theory is that this could let drug levels creep up a little. For your pill, that might mean a touch more of the usual estrogen-related effects like nausea, breast tenderness, or bloating.

But the real-world evidence is reassuring. A small human study showed standardized red clover did not actually change how the body handled a CYP1A2 test substance. So this interaction is mostly theoretical and rated as minor and unlikely. I still suggest a quick chat with your pharmacist, since red clover acts like a weak plant estrogen and isn't right for everyone.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Ethinyl estradiol, Levonogestrel also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, red clover might increase levels of drugs metabolized by CYP3A4; however, a small clinical study found no effect.
In vitro evidence shows that red clover might inhibit CYP3A4 isoenzymes. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of alprazolam, a CYP3A4 probe substrate.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

Your birth control pill, Lybrel, contains ethinyl estradiol and levonorgestrel, and both are cleared by a liver enzyme called CYP3A4. In a test tube, red clover looked like it might slow that enzyme a little, which in theory could let your pill's hormone levels creep up. If that happened, you might notice more of the usual estrogen-related effects like breast tenderness, nausea, bloating, or breakthrough spotting.

Here's the reassuring part: when researchers actually tested red clover in people, it did not change how the body handled a similar CYP3A4 medication. So this is mostly a theoretical concern, rated minor and unlikely. Still, since your pill matters for preventing pregnancy, it's worth a quick chat with your pharmacist or doctor before adding red clover.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  3. Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. 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

Red Clover Also Interacts With Other Medications

Red Clover has 43 moderate, 823 minor known drug interactions in our database — the Ethinyl estradiol, Levonogestrel one above is among them. If you take anything else, check it against the full list below.

Moderate 43 Minor 823 No known interaction 1,964 (incl. Ethinyl estradiol, Levonogestrel)
Taking anything else?

Check Another of Your Medications Against Red Clover

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

Everything else you take

See Every Supplement That Interacts With Ethinyl estradiol, Levonogestrel

This page covers Red Clover only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl estradiol, Levonogestrel page lists 239 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 195 moderate · 38 minor.

From our pharmacist’s overview on the Ethinyl estradiol, Levonogestrel page

“A daily birth control pill like Lybrel (ethinyl estradiol with levonorgestrel) only works when enough hormone stays in the bloodstream, and that is exactly what several supplements on this page can undermine. This list deserves genuine care, starting with the six major-rated entries.”

Reviewed by 2 · Jul 18, 2026

Open the Ethinyl estradiol, Levonogestrel interaction page

One more smart check

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

We hold 1,480 real supplement products containing Red Clover, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Red Clover. Your product may carry other ingredients that interact with Ethinyl estradiol, Levonogestrel too, on top of Red Clover — 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 Red Clover and Ethinyl estradiol, Levonogestrel 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 Red Clover
Top 25%

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

29 days ago today
Medication Ethinyl estradiol, Levonogestrel
Top 10%

#148 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 Red Clover

What is Red Clover?

Red Clover
  • Menopause symptoms (hot flashes)
  • High cholesterol
  • Bone health/osteoporosis
  • Skin and hair concerns
  • Women's health

Red clover is a plant rich in isoflavones (plant compounds with weak estrogen-like activity) that is most often used for menopause symptoms like hot flashes. The evidence is mixed and generally weak, with some studies showing modest benefit and others showing none. Because of its hormone-like effects, it's not for everyone—talk with your pharmacist or doctor before trying it, especially if you have a hormone-sensitive condition.

Read the full Red Clover monograph & all interactions
Keep checking

Other Drugs & Red Clover

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

0Major
43Moderate
823Minor
1,963No known interaction
43 Moderate 823 Minor 1,963 No interaction
Moderate

43 interactions

Minor

823 interactions

Showing 60 of 823 minor interactions — see all 823 on the Red Clover page.

No interaction 1,963 drugs checked — show the list

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

Showing the 60 most looked-up of 1,963 medications checked with no known interaction — see the full Red Clover list.

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

Can you take Red Clover with Ethinyl estradiol, Levonogestrel?
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 3 interactions listed for Red Clover and Ethinyl estradiol, Levonogestrel?
Ethinyl estradiol, Levonogestrel belongs to more than one drug category, and Red Clover 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 Red Clover and Ethinyl estradiol, Levonogestrel 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

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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.