Bulbine Natalensis + Ethinyl Estradiol, Ethynodiol Diacetate
Ethinyl Estradiol, Ethynodiol Diacetate brand names: Demulen 1/35, Zovia 1/35, Demulen Compack, Demulen 1/50, Zovia 1/50, and others.
Ethinyl Estradiol, Ethynodiol Diacetate falls into 3 drug categories that Bulbine Natalensis can interact with; the most serious is rated moderate. Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP1A2 substrates.
Read the full interaction reportBulbine Natalensis and Ethinyl Estradiol, Ethynodiol Diacetate
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Bulbine Natalensis interacts with whole categories of medication. Ethinyl Estradiol, Ethynodiol Diacetate falls into 3 of those categories, so it can interact with Bulbine Natalensis in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
1 of 3Why this applies to Ethinyl Estradiol, Ethynodiol Diacetate
Ethinyl Estradiol, Ethynodiol Diacetate falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Bulbine Natalensis interacts with.
In vitro research shows that Bulbine natalensis stem extract slightly induces CYP1A2 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP1A2 substrates; however, this has not been studied in humans.
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.
This combo pairs your birth control pill (which contains the estrogen ethinyl estradiol) with Bulbine natalensis. In lab dishes, this plant gently sped up an enzyme called CYP1A2 that helps your body break down estrogen. The worry here is mostly theoretical, but if it nudged that enzyme to work faster, your body could clear the estrogen a little quicker, which in turn could lower how well the pill protects you. In real life that can show up as breakthrough spotting or, in the worst case, reduced contraceptive reliability.
Important to know: this is based only on test-tube research, not people, so we honestly don't know if it matters in humans. Since an unplanned pregnancy is a big deal, please check with your pharmacist or doctor before adding this supplement.
- Husain I, Manda V, Alhusban M, et al. Modulation of CYP3A4 and CYP2C9 activity by Bulbine natalensis and its constituents: An assessment of HDI risk of B. natalensis containing supplements. Phytomedicine 2021;81:153416. PubMed
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 3Ethinyl Estradiol, Ethynodiol Diacetate also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro research shows that Bulbine natalensis stem extract induces CYP3A4 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP3A4 substrates, but this has not been studied in humans.
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.
Here's the gist for your birth control pill (the Demulen/Zovia/Kelnor family). The hormones in it, especially the ethinyl estradiol, are broken down in your body by an enzyme called CYP3A4. Lab and test-tube research hints that Bulbine natalensis may rev that enzyme up. If that happened in real life, your body could clear the hormones a little faster, which can lower their levels.
Why does that matter? With this kind of pill, weaker hormone levels can mean breakthrough bleeding or spotting and, more importantly, less reliable pregnancy protection. I want to stress this is only a theory from lab studies and hasn't been tested in people, so we don't know if it truly matters. Still, since an unplanned pregnancy is a big deal, please check with your pharmacist or doctor before combining them.
- Husain I, Dale OR, Manda V, et al. Bulbine natalensis (currently Bulbine latifolia) and select bulbine knipholones modulate the activity of AhR, CYP1A2, CYP2B6, and P-gp. Planta Med 2022;88(12):975-984. PubMed
P-GLYCOPROTEIN SUBSTRATES
3 of 3Ethinyl Estradiol, Ethynodiol Diacetate also falls under P-GLYCOPROTEIN SUBSTRATES.
In vitro research shows that Bulbine natalensis stem extract induces p-glycoprotein mRNA expression; however, effects on transporter expression were not evaluated.
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.
Here's the situation with your birth control pill (ethinyl estradiol with ethynodiol diacetate) and Bulbine natalensis. This combination pill is partly handled by a transporter in your body called p-glycoprotein, which acts like a gatekeeper moving drugs around and out. In lab dish studies, Bulbine appeared to ramp up this transporter, which could theoretically push more of your pill's hormones out and lower their levels in your blood.
If that happened, the real concern would be a weaker contraceptive effect, meaning a higher chance of breakthrough bleeding or even an unintended pregnancy. I want to be honest though: this is purely a theoretical, test-tube finding with no human data, and Bulbine itself raises liver and kidney safety questions. Please check with your pharmacist or doctor before combining them.
- Husain I, Manda V, Alhusban M, et al. Modulation of CYP3A4 and CYP2C9 activity by Bulbine natalensis and its constituents: An assessment of HDI risk of B. natalensis containing supplements. Phytomedicine 2021;81:153416. PubMed
What These Ratings Mean
Every interaction above is graded three ways — here’s the key to each label.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Bulbine Natalensis Also Interacts With Other Medications
Bulbine Natalensis has 919 moderate known drug interactions in our database — the Ethinyl Estradiol, Ethynodiol Diacetate one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Bulbine Natalensis
We haven’t checked that one against Bulbine Natalensis yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Bulbine Natalensis. Pick one to open its full report.
See Every Supplement That Interacts With Ethinyl Estradiol, Ethynodiol Diacetate
This page covers Bulbine Natalensis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl Estradiol, Ethynodiol Diacetate 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, Ethynodiol Diacetate page
“The stakes here are pregnancy prevention, so I read this list with genuine seriousness. Ethinyl estradiol with ethynodiol diacetate (Zovia, Demulen, Kelnor) is a combined birth control pill, and the interactions that concern me most are the ones that can quietly weaken it.”
Reviewed by 2 · Jul 18, 2026
Open the Ethinyl Estradiol, Ethynodiol Diacetate interaction page
Taking Bulbine Natalensis as Part of a Dietary Supplement Product? Check It for Interactions
We hold 51 real supplement products containing Bulbine Natalensis, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bulbine Natalensis. Your product may carry other ingredients that interact with Ethinyl Estradiol, Ethynodiol Diacetate too, on top of Bulbine Natalensis — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Bulbine Natalensis and Ethinyl Estradiol, Ethynodiol Diacetate 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.
#583 of 1,452 supplements looked up here in the last 7 days
#851 of 2,830 medications looked up here in the last 7 days
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.
About Bulbine Natalensis
What is Bulbine Natalensis?
- Boosting testosterone
- Improving libido
- Muscle building and athletic performance
- General male vitality
Bulbine natalensis is a South African plant marketed mainly as a testosterone-boosting and libido supplement, but the human evidence is essentially absent and most claims come from animal studies. Animal research has also raised concerns about possible liver and kidney harm at higher doses, so caution is warranted. Talk to your pharmacist or doctor before trying it.
Other Drugs & Bulbine Natalensis
Browse every other medication we’ve checked against Bulbine Natalensis — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
919 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Ibuprofen ›
- Aspirin ›
- Hydrocortisone ›
- Naproxen ›
- Doxycycline ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Tetracycline ›
- Lidocaine ›
- Ranitidine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Glyburide ›
- Methyltestosterone ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Oxybutynin ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Triamcinolone ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Indomethacin ›
- Miconazole ›
- Morphine Sulfate ›
- Trimipramine ›
- Acetaminophen ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Ivabradine ›
- Ivermectin ›
- Ketoprofen ›
- Lofepramine ›
Showing 60 of 919 moderate interactions — see all 919 on the Bulbine Natalensis page.
No interaction 1,910 drugs checked — show the list
We also checked Bulbine Natalensis against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Methylphenidate ›
- Rosuvastatin ›
- Metoprolol ›
- Levothyroxine, Liothyronine ›
- Tirzepatide ›
- Isotretinoin ›
- Metformin ›
- Docusate ›
- Semaglutide ›
- Amphetamine ›
- Lisdexamfetamine ›
- Methamphetamine ›
- Lisinopril ›
- Sumatriptan ›
- Amoxicillin ›
- Valacyclovir ›
- Hydroxyurea ›
- Bupropion ›
- Methotrexate ›
- Azithromycin ›
- Pregabalin ›
- Gabapentin ›
- Lamotrigine ›
- Dextroamphetamine ›
- Acyclovir ›
- Duloxetine ›
- Methylene Blue ›
- Ciprofloxacin ›
- Candesartan Cilexetil ›
- Amoxicillin, Clavulanate Potassium ›
- Insulin Degludec, Liraglutide ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Bisoprolol ›
- Aminophylline, Amobarbital, Ephedrine ›
- Amphetamine Aspartate, Amphetamine Sulfate, Dextroamphetamine Saccharate, Dextroamphetamine Sulfate ›
- Atenolol, Chlorthalidone ›
- Enalapril Maleate ›
- Bismuth Subcarbonate, Calcium Carbonate, Opium ›
- Ezetimibe ›
- Bendroflumethiazide, Rauwolfia Serpentina ›
- Cephalexin ›
- Ephedrine, Phenobarbital, Theophylline ›
- Canagliflozin, Metformin ›
- Insulin Aspart, Insulin Degludec ›
- Levetiracetam ›
- Candesartan Cilexetil, Hydrochlorothiazide ›
- Daunorubicin, Cytarabine ›
- Atenolol ›
- Levodopa ›
- Isoniazid, Pyrazinamide, Rifampin ›
- Saxagliptin, Metformin Xr ›
- Carbidopa, Levodopa ›
- Hydrocortisone, Clioquinol, Pramoxine ›
- Sodium Bicarbonate (otc Drug) ›
- Atropine Methyl Nitrate, Digestive Enzymes ›
- Cyclopentolate ›
- Efgartigimod Alfa-fcab ›
- Cytomegalovirus Immune Globulin ›
- Ceftolozane Sulfate, Tazobactam Sodium ›
Showing the 60 most looked-up of 1,910 medications checked with no known interaction — see the full Bulbine Natalensis list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Ethinyl Estradiol, Ethynodiol Diacetate Is Linked to Lower Levels of 7 Nutrients
Natural Medicines records Ethinyl Estradiol, Ethynodiol Diacetate as a medicine that can lower these. This is not an interaction with Bulbine Natalensis — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Ethinyl Estradiol, Ethynodiol Diacetate nutrient depletion report ›
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Bulbine Natalensis and Ethinyl Estradiol, Ethynodiol Diacetate Together: Common Questions
Can you take Bulbine Natalensis with Ethinyl Estradiol, Ethynodiol Diacetate?
Why are there 3 interactions listed for Bulbine Natalensis and Ethinyl Estradiol, Ethynodiol Diacetate?
How serious is the Bulbine Natalensis and Ethinyl Estradiol, Ethynodiol Diacetate interaction?
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.