Drug & supplement interaction

Yerba Mate + Mestranol, Norethynodrel

Mestranol, Norethynodrel brand name: Enovid-E.

Minor Interaction
The bottom line Minor

Mestranol, Norethynodrel falls into 3 drug categories that Yerba Mate can interact with; the most serious is rated minor. Theoretically, concomitant use of CYP1A2 inhibitors and yerba mate might increase levels and adverse effects of the caffeine in yerba mate.

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

Yerba Mate and Mestranol, Norethynodrel

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

Why Are There 3 Interactions?

Yerba Mate interacts with whole categories of medication. Mestranol, Norethynodrel falls into 3 of those categories, so it can interact with Yerba Mate in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS

1 of 3

Why this applies to Mestranol, Norethynodrel

Mestranol, Norethynodrel falls under CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS — the group Yerba Mate interacts with.

Theoretically, concomitant use of CYP1A2 inhibitors and yerba mate might increase levels and adverse effects of the caffeine in yerba mate.
Yerba mate contains caffeine. Caffeine is metabolized by CYP1A2. Theoretically, drugs that inhibit CYP1A2 may decrease the rate of caffeine clearance and increase caffeine levels.
Severity Minor 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 key thing to understand: this interaction works on the caffeine in your mate, not really on your birth control pill itself. The estrogen in Enovid-E (mestranol, along with the progestin norethynodrel) can gently slow down the liver enzyme called CYP1A2, which is the same enzyme your body uses to clear caffeine. So when that pathway is a little blocked, the caffeine from yerba mate may hang around longer than usual.

In real life, that could mean the mate hits you harder: more jitteriness, a racing heart, trouble sleeping, or feeling on edge. This is only a theoretical, minor concern based on how these drugs behave, not strong proof. If you notice caffeine bothering you more than usual, ease back on the mate and chat with your pharmacist or doctor.

References
  1. Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63. PubMed
  2. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Mestranol, Norethynodrel also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, yerba mate might increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that yerba mate extract inhibits CYP3A4 enzymes. Theoretically, taking yerba mate may increase levels and adverse effects of CYP3A4 substrates.
Severity Minor 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 your combination pill (the estrogen called mestranol plus the progestin norethynodrel). Your liver uses an enzyme known as CYP3A4 to help break these hormones down. In a lab dish, yerba mate appears to slow that enzyme a bit. The idea is that if it slows the breakdown, more hormone could linger in your body, which might nudge up estrogen-type side effects like nausea, breast tenderness, bloating, or headaches.

I want to be honest about how soft this is. This is theoretical and only based on test-tube work, not real people, and it's rated as a minor concern. A cup or two of mate is unlikely to cause trouble. If you drink it heavily or take concentrated extracts, just mention it to your pharmacist or doctor.

References
  1. Feltrin C, Farias IV, Sandjo LP, Reginatto FH, Simões CMO. Effects of Standardized Medicinal Plant Extracts on Drug Metabolism Mediated by CYP3A4 and CYP2D6 Enzymes. Chem Res Toxicol 2020;33(9):2408-2419. PubMed
Minor

CONTRACEPTIVE DRUGS

3 of 3

Mestranol, Norethynodrel also falls under CONTRACEPTIVE DRUGS.

Theoretically, contraceptive drugs might increase the levels and adverse effects of the caffeine contained in yerba mate.
Yerba mate contains caffeine. Contraceptive drugs decrease the rate of caffeine clearance by 40% to 65%.
Severity Minor 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 thing to know about this pair: it's really the caffeine in yerba mate that gets affected, not the birth control itself. Oral contraceptives like Enovid-E (the mestranol and norethynodrel combo) slow down how fast your body clears caffeine, by roughly 40% to 65%. So that same cup of mate may hang around longer and hit harder.

In plain terms, you might feel more jittery, notice a racing heart, trouble sleeping, or an upset stomach from caffeine you'd normally handle just fine. This is rated minor and is partly theoretical, so it's nothing to panic over. If you feel wired, simply easing back on mate usually does the trick. Check with your pharmacist if you're unsure.

References
  1. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
  2. Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 1985;28:425-8. 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

Yerba Mate Also Interacts With Other Medications

Yerba Mate has 8 major, 505 moderate, 572 minor known drug interactions in our database — the Mestranol, Norethynodrel one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Yerba Mate

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

Everything else you take

See Every Supplement That Interacts With Mestranol, Norethynodrel

This page covers Yerba Mate only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Mestranol, Norethynodrel page lists 188 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 · 140 moderate · 42 minor.

From our pharmacist’s overview on the Mestranol, Norethynodrel page

“The list for Mestranol and Norethynodrel (Enovid-E, a combined birth control pill) deserves genuine care, because several entries can quietly undo the pill itself. St.”

Reviewed by 2 · Jul 18, 2026

Open the Mestranol, Norethynodrel interaction page

One more smart check

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

We hold 68 real supplement products containing Yerba Mate, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Yerba Mate. Your product may carry other ingredients that interact with Mestranol, Norethynodrel too, on top of Yerba Mate — 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 Yerba Mate and Mestranol, Norethynodrel 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 Yerba Mate
Steady interest

#1,100 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Mestranol, Norethynodrel
Steady interest

#1,686 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 Yerba Mate

What is Yerba Mate?

Yerba Mate
  • Energy and alertness
  • Weight loss
  • Mental focus
  • Digestive support
  • Antioxidant support

Yerba mate is a caffeine-containing herbal beverage from South America that is widely enjoyed for its stimulating, coffee-like effects. While it is rich in antioxidants and is being studied for weight, blood sugar, and cholesterol, strong human evidence for most health claims is limited. Drinking very hot mate over many years has been linked to higher risk of certain cancers, so enjoy it warm and in moderation.

Read the full Yerba Mate monograph & all interactions
Keep checking

Other Drugs & Yerba Mate

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

8Major
505Moderate
572Minor
1,744No known interaction
Major

8 interactions

Moderate

505 interactions

Showing 60 of 505 moderate interactions — see all 505 on the Yerba Mate page.

Minor

572 interactions

Showing 60 of 572 minor interactions — see all 572 on the Yerba Mate page.

No interaction 1,744 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Yerba Mate and Mestranol, Norethynodrel Together: Common Questions

Can you take Yerba Mate with Mestranol, Norethynodrel?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Yerba Mate and Mestranol, Norethynodrel?
Mestranol, Norethynodrel belongs to more than one drug category, and Yerba Mate 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 Yerba Mate and Mestranol, Norethynodrel interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

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.