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

Abstract

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.