Which herbal supplements increase bleeding risk when taken with warfarin or DOACs?
Executive summary
Herbal and dietary supplements frequently increase bleeding risk when taken with warfarin: systematic reviews report potentiation with dozens of herbs (45 of 78 items in one review) and up to 84% of listed herbs increasing warfarin effect in another review [1] [2]. For DOACs the evidence is thinner but case reports and reviews show serious bleeding with combinations such as dabigatran plus herbal mixtures including ginger or cinnamon and warn that herbs can alter DOAC levels via CYP/P‑gp pathways [3] [4] [5].
1. Why clinicians and patients should treat “natural” as potent
Reviews of herb–warfarin interactions show many herbs potentiate anticoagulation and have been linked to minor (gum bleeding, purpura) and major (intracranial hemorrhage) events; one systematic review found potentiation with 45 herbs/foods and 20 agents associated with bleeding events including fatal outcomes [1] [6]. Another synthesis identified 114 herbal medicines reported to interact with warfarin and concluded 84% could increase bleeding risk [2]. These are not theoretical musings: case reports and longitudinal studies document clinically meaningful increases in INR and bleeding [7] [8].
2. Which herbs have the strongest or most-consistent signals
Published guidance and reviews repeatedly flag garlic, ginger, ginkgo, ginseng, danshen (Salvia miltiorrhiza), dong quai, chamomile, and papaya/papain as agents that may increase bleeding risk with warfarin [8] [1] [9]. Reviews categorize these interactions as pharmacodynamic (antiplatelet effects) or pharmacokinetic (CYP enzyme/P‑glycoprotein modulation) and note some agents contain coumarin-like compounds that directly potentiate vitamin‑K antagonists [10] [11].
3. DOACs: weaker evidence but dangerous case reports exist
DOACs were initially thought to have fewer food/herb interactions, but recent reviews and observational reports show herbs can affect DOAC exposure via CYP3A4 and P‑gp and that fatal bleeding has occurred when herbs were combined with DOACs — notably a reported fatality linked to dabigatran plus ginger and cinnamon in a case series [4] [3] [5]. High‑quality, large clinical trials are largely lacking; most alerts are from pharmacokinetic reasoning, case reports, and small studies [12] [13].
4. Mechanisms: two routes to more bleeding
Herb–anticoagulant interactions operate by (a) pharmacodynamic synergy — herbs with antiplatelet or fibrinolytic effects (ginger, garlic, ginkgo, fish‑oil/omega‑3s, etc.) add to anticoagulant bleeding risk; and (b) pharmacokinetic modulation — herbs that inhibit or induce CYP enzymes or P‑glycoprotein change plasma levels of warfarin (CYP2C9) or DOACs (CYP3A4/P‑gp), causing over‑ or under‑anticoagulation [10] [14] [4].
5. What the major clinical reviews and authorities recommend
National guidance urges patients on warfarin to report all supplements because many are untested and can increase bleeding risk; NHS specifically warns against St John’s wort and other unsupervised herb use with warfarin [15]. Reviews recommend extra monitoring (INR for warfarin), avoiding certain supplements before surgery, and cautious counseling because the evidence base varies and product content is inconsistent [6] [16] [12].
6. Limits of the evidence and competing views
Large randomized trials of most herb–anticoagulant combos do not exist. Many papers rely on case reports, small trials, heterogeneous herbal products, or in vitro enzyme studies; some individual studies find no interaction for specific agents (e.g., mixed data for ginger) while aggregated reviews find a net signal toward increased bleeding [7] [10] [6]. For DOACs, authoritative reviews note theoretical CYP/P‑gp interactions but acknowledge “no direct evidence” in many cases, even as case reports show catastrophic outcomes [17] [3].
7. Practical takeaway — what patients and clinicians should do now
Ask every patient about supplement use, discontinue or tightly supervise supplements with known or suspected interactions (garlic, ginger, ginkgo, ginseng, danshen, dong quai, chamomile, papaya/papain, high‑dose vitamin E and some fish‑oil preparations have been implicated), and increase monitoring (INR for warfarin; clinical vigilance and possible drug‑level checks or consultation for DOACs) if supplements are started or stopped [8] [1] [5]. Where evidence is weak but potential harm is high, err on the side of avoidance until safety is established [6] [12].
Limitations: available sources are dominated by reviews, case reports and observational studies; rigorous RCT data on many specific herb–DOAC combinations are not found in the cited material [12] [4].