Drug & supplement interaction

Zizyphus + Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate brand name: Activella.

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

Zizyphus has a moderate interaction with Estradiol, Norethindrone Acetate. Theoretically, zizyphus might decrease the levels and clinical effects of drugs metabolized by CYP1A2.

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

Zizyphus and Estradiol, Norethindrone Acetate

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

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Why this applies to Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Zizyphus interacts with.

Theoretically, zizyphus might decrease the levels and clinical effects of drugs metabolized by CYP1A2.
Animal research shows that zizyphus induces CYP1A2 enzymes. However, this effect has not been reported in humans.
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

If you take Activella (estradiol with norethindrone) for menopause symptoms, here's the gist of this one. Your body partly clears the estrogen in this combo using a liver enzyme called CYP1A2. In animal studies, zizyphus appeared to speed up that enzyme. In theory, a faster cleanup could lower your estrogen levels a bit, which might make the medicine work less well, meaning more hot flashes, night sweats, or vaginal dryness sneaking back.

The big caveat: this has only been seen in lab and animal research, never confirmed in people, so it may not matter at all. Eating jujube fruit as food is very unlikely to cause trouble. Before adding a concentrated zizyphus supplement, just run it by your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Jing XY, Peng YR, Wang XM, Duan JA. Effects of Ziziphus jujuba fruit extracts on cytochrome P450 (CYP1A2) activity in rats. Chin J Nat Med. 2015 Aug;13(8):588-94. 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

Zizyphus Also Interacts With Other Medications

Zizyphus has 468 moderate known drug interactions in our database — the Estradiol, Norethindrone Acetate one above is one of them. If you take anything else, check it against the full list below.

Moderate 468 No known interaction 2,362 (incl. Estradiol, Norethindrone Acetate)
Taking anything else?

Check Another of Your Medications Against Zizyphus

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

Everything else you take

See Every Supplement That Interacts With Estradiol, Norethindrone Acetate

This page covers Zizyphus only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Estradiol, Norethindrone Acetate page lists 212 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate) and Adrafinil (moderate).

By severity: 3 major · 171 moderate · 38 minor.

From our pharmacist’s overview on the Estradiol, Norethindrone Acetate page

“Activella pairs estradiol with norethindrone as hormone therapy, and because the treatment depends on steady hormone levels in the blood, supplements that raise or lower those levels warrant real scrutiny. Three of the 212 interacting ingredients rate major, and all three hit that weak point: St.”

Reviewed by 2 · Jul 18, 2026

Open the Estradiol, Norethindrone Acetate interaction page

How much people look this up

Where Zizyphus and Estradiol, Norethindrone Acetate 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 Zizyphus
Steady interest

#1,230 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Estradiol, Norethindrone Acetate
Steady interest

#2,373 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 Zizyphus

What is Zizyphus?

Zizyphus
  • Sleep problems and insomnia
  • Anxiety and stress
  • Digestive support
  • General nutrition (vitamin C and fiber)
  • Constipation

Zizyphus (jujube) is an edible fruit and traditional remedy used mainly for sleep, anxiety, and digestion. The fruit is a nutritious food, but human evidence for its medicinal benefits is limited and mostly preliminary. If you want to try a supplement form, talk with your pharmacist or doctor first, especially if you are pregnant, breastfeeding, or taking other medicines.

Read the full Zizyphus monograph & all interactions
Keep checking

Other Drugs & Zizyphus

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

0Major
468Moderate
0Minor
2,361No known interaction
468 Moderate 2,361 No interaction
Moderate

468 interactions

Showing 60 of 468 moderate interactions — see all 468 on the Zizyphus page.

No interaction 2,361 drugs checked — show the list

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

Showing the 60 most looked-up of 2,361 medications checked with no known interaction — see the full Zizyphus list.

See the full Zizyphus interactions page
See every supplement checked against Estradiol, Norethindrone Acetate, 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
Zizyphus monograph › Uses, safety, and every drug interaction in one place Estradiol, Norethindrone Acetate supplement interactions › Every supplement checked against Estradiol, Norethindrone Acetate, 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 Zizyphus and Estradiol, Norethindrone Acetate Together: Common Questions

Can you take Zizyphus with Estradiol, Norethindrone Acetate?
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 Zizyphus and Estradiol, Norethindrone Acetate 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 Estradiol, Norethindrone Acetate and Zizyphus?

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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.