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The Absence of an Interaction Between Warfarin and Cranberry Juice: A Randomized, Double-Blind Trial

From the Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts (Dr Ansell, Ms McDonough); and the Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts (Ms Zhao, Mr Harmatz, Dr Greenblatt).

The question of potentiation of warfarin anticoagulation by cranberry juice (CJ) is a topic of biomedical importance. Anecdotal reports of CJ-warfarin interaction are largely unconfirmed in controlled studies. Thirty patients on stable warfarin anticoagulation (international normalized ratio [INR], 1.7-3.3) were randomized to receive 240 mL of CJ or 240 mL of placebo beverage, matched for color and taste, once daily for 2 weeks. The INR values and plasma levels of R- and S-warfarin were measured during the 2-week period and a 1-week follow-up period. The CJ and placebo groups (n = 14 and 16, respectively) did not differ significantly in mean plasma R- and S-warfarin concentrations. Eight patients (4 on CJ, 4 on placebo) developed minimally elevated INR (range, 3.38-4.52) during the treatment period. Mean INR differed significantly (P < .02) only on treatment day 12; at all other time points, the groups did not differ. Cranberry juice has no effect on plasma S- or R-warfarin plasma levels, excluding a pharmacokinetic interaction. A small though statistically significant pharmacodynamic enhancement of INR by CJ at a single time point is unlikely to be clinically important and may be a random change. Enhanced warfarin anticoagulation attributed to CJ in anecdotal reports may represent a chance temporal association.

Key Words: Warfarin • anticoagulation • drug interactions • supplements

Address for reprints: Jack Ansell, MD, Lenox Hill Hospital, Department of Medicine, 6 Blackhall, 100 East 77th Street, New York, NY 10075; e-mail: jansell{at}lenoxhill.net.

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