Cranberry Increases Anticoagulant Effects

Cranberries (Vaccinium macrocarpon) are very popular worldwide as a food and beverage, as well as an herbal supplement for treatment of digestive disorders and urinary tract infections. In the scientific literature, there are a few reports of an interaction between cranberry and warfarin [9, 11]. In one case report, when cranberry was administered together with warfarin, there was an increase in the international normalized ratio (INR) and significant bleeding. There is also one report of a very serious interaction in which a patient taking approximately 2 cups of cranberry juice daily for 6 weeks purportedly died as a consequence of this interaction [11]. Increases in the INR (up to 28%) have been reported when cranberry is administered with warfarin. However, it is important to remember that the case studies have not been supported by controlled clinical trials. For example, Lilja et al. [16] investigated the effects of cranberry juice on simultaneous administration of R-S-warfarin, tizanidine, and midazolam as drug probes for the CYP liver isozymes CYP2C9, CYP1A2, and CYP3A4 in a randomized crossover study. Ten healthy volunteers were administered 200 mL of cranberry juice or water three times daily for 10 day. On day 5, they ingested 10 mg racemic R-S-warfarin, 1 mg tizanidine, and 0.5 mg midazolam, with juice or water, followed by monitoring of drug concentrations and thromboplastin time. The results show that for a one-time dose of these three drugs, cranberry juice did not increase the peak plasma concentration or area under concentration-time curve (AUC) of any of the drugs or their metabolites, but slightly decreased (7%) the AUC of S-warfarin. Thus, cranberry juice did not change the anticoagulant effect of warfarin. Daily ingestion of cranberry juice for 10 day did not inhibit the activities of any of the liver enzymes responsible for drug metabolism. The study concluded that a pharmacokinetic mechanism for the cranberry juice-warfarin interaction seems unlikely. However, the limitations of this study are that it does not take into account repeated daily drug administration, or the suggestion that many food-drug interactions may take 2-4 weeks to be observed.

Green Tea Reduces Anticoagulant Effects

Beverages and dietary supplements that contain green tea also contain vitamin K and may therefore reduce the effect of warfarin and other anticoagulants. Green tea leaves contain high levels of vitamin K; however, the vitamin K levels in brewed beverages is much lower, thus only large amounts (1500-3500 mL/day) are reported to decrease the INR [2, 9].

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