Which dietary supplements most frequently interact with antithrombotic and cardiovascular drugs, and what evidence supports those interactions?
Executive summary
Several widely used supplements—omega‑3 (fish oil), garlic, ginkgo biloba, ginger, ginseng, curcumin/turmeric, nattokinase, red yeast rice, vitamin K and vitamin E—are the supplements most frequently implicated in interactions with antithrombotic and cardiovascular drugs, with evidence ranging from case reports and pharmacovigilance signals to small clinical trials and systematic reviews showing possible bleeding risk or altered drug levels [1] [2] [3]. The strongest, most consistent signal in the literature concerns interactions with warfarin and other vitamin‑K‑sensitive regimens, while data for direct oral anticoagulants (DOACs) and antiplatelet agents are sparser and often mechanistic or observational rather than definitive randomized outcomes [2] [4] [5].
1. Top offenders named in clinical reviews and databases
Major reviews and clinical databases repeatedly flag curcumin/turmeric, ginkgo biloba, garlic, ginger, ginseng, green tea, cranberry, St John’s wort, nattokinase, red yeast rice, vitamin K, and vitamin E as supplements that either potentiate bleeding or alter anticoagulant/antiplatelet drug exposure, with Natural Medicines and systematic reviews estimating that roughly 180 supplements may interact with warfarin and more than 120 may interact with aspirin or clopidogrel [2] [6] [1].
2. Mechanisms behind the interactions: pharmacodynamic and pharmacokinetic pathways
Interactions occur by direct antiplatelet/anticoagulant effects (for example garlic, ginkgo, ginger, curcumin, and nattokinase reduce platelet aggregation or promote fibrinolysis), by altering vitamin K–dependent clotting pathways (high‑vitamin‑K supplements or foods changing warfarin response), or by modifying drug metabolism and transport (St John’s wort induces CYP enzymes affecting many cardiovascular drugs) [1] [7] [8].
3. Warfarin: the best‑documented and highest‑risk context
Warfarin shows the largest, clearest literature on supplement interactions: systematic reviews and observational reports document supratherapeutic INRs and hemorrhagic events with turmeric/curcumin and multiple reports linking cranberry, cannabis, green tea, ginkgo and others to variable INR changes or bleeding, and databases estimate dozens to hundreds of potential warfarin interactions overall [1] [4] [6] [2].
4. Antiplatelet drugs and bleeding risk: mixed evidence and case reports
Aspirin and P2Y12 inhibitors (clopidogrel) can experience additive bleeding risk when combined with products that impair platelet function—ginkgo, garlic, ginger, and ginseng figure repeatedly in case reports and small pharmacodynamic studies showing reduced platelet aggregation even when routine coagulation assays are unchanged, though randomized trials proving higher clinical bleeding with these combinations are limited [7] [2] [9].
5. DOACs, statins and the uncertain role of supplements
For DOACs (apixaban, rivaroxaban, dabigatran) and many CYP3A4‑metabolized cardiovascular drugs, concern focuses on supplements that alter absorption or CYP/P‑glycoprotein activity—St John’s wort is a classic inducer, and various herbal teas or turmeric are reported by patients and observational work to potentially modify exposure, but robust randomized pharmacokinetic outcome data are scarce and often limited to small studies or case reports [5] [3].
6. Clinical guidance, prevalence and evidence gaps
Clinical guidance emerging from AHRQ and specialty reviews recommends routine questioning about supplement use because supplement-taking is common among cardiovascular patients yet randomized data on hard outcomes (mortality, thrombotic events, major bleeding) are generally lacking; low‑strength evidence supports some intermediate benefits (omega‑3, vitamin K, garlic) but harms are inconclusive and require individualized assessment [3] [10] [11].
7. Takeaway for clinicians and researchers
The literature paints a precautionary picture: multiple supplements have plausible mechanisms and descriptive reports linking them to altered antithrombotic drug effect—especially with warfarin—yet large randomized trials proving clinical harm or safety are sparse, so clinicians should actively elicit supplement use, monitor INR or drug levels when feasible, and weigh case reports and pharmacologic plausibility against the limited trial data while research prioritizes high‑quality interaction studies [2] [3] [4].