10 Supplements That Interact With the Most Prescription Drugs

St. John's Wort interacts with about every drug class in your medicine cabinet — and that's the easy one. If you take a prescription, scan this list first. These are the ten supplements with the longest interaction tables in our database.

1. St. John's Wort — Warfarin, SSRIs, MAOIs, oral contraceptives, chemotherapy. The poster child for "natural ≠ inert."
2. Berberine — Statins, metformin, BP meds, diabetes drugs, antifungals.
3. Magnesium — Thyroid hormone, PPIs, antibiotics, benzos, sleep meds.
4. Omega-3 (high dose) — Bleeding risk on top of warfarin, DOACs, and antiplatelets.
5. Ginkgo biloba — Antiplatelet, anticoagulant, and seizure-threshold concerns.
6. 5-HTP — SSRIs, MAOIs, triptans — serotonin syndrome risk.
7. Saffron — Antidepressants, blood thinners, blood-pressure meds.
8. Melatonin — Seizure meds, sedatives, benzos. Effects amplify, not just stack.
9. Vitamin K2 — Warfarin antagonism. Even MK-7 doses can drop INR meaningfully.
10. Calcium / Iron / Zinc — Chelate fluoroquinolones, tetracyclines, levothyroxine, bisphosphonates. Separate doses by 2–4 hours.

Bottom line

Tell your pharmacist about every supplement you take. The interactions above show up in real-world clinical case reports, not in theoretical tables — and they keep showing up because most patients don't think herbs count as drugs.

See the full interactions matrix with affected drug classes on Discover →