A Randomized, Double-Blind Trial of the Interaction between Cranberry Juice and Warfarin.

Therapeutic warfarin therapy is highly influenced by concomitant drug therapy or dietary factors by effecting warfarin metabolism or vitamin K status. Cranberry juice (CJ) was recently implicated to influence the INR in patients on warfarin based on a number of brief anecdotal or case reports. This study was designed to determine what influence, if any, daily cranberry juice consumption has on INR levels and plasma warfarin concentrations in patients stably anticoagulated with warfarin. Patients on warfarin for a variety of indications from a population of anticoagulation clinic patients were selected because of their past history of stable anticoagulation and willingness to participate in the study. Major inclusion criteria required a therapeutic INR range of 2.0 – 3.0, no hepatic or renal dysfunction, a stable INR (1.7 – 3.3) on at least 2 measurements within 8 weeks prior to study entry, and informed consent. The study consisted of a 2 week lead-in phase (with weekly INRs in range); a 2 week intervention phase (double-blind daily consumption of an 8 oz glass of cranberry juice or placebo); and a one week follow-up phase (35 day total). Any patient with an out of range INR during the intervention phase ceased the intervention but continued through follow-up. 30 patients were randomized, 14 to CJ and 16 to placebo. 28.6% (4/14) in the CJ group developed a minimally elevated INR and 7.1%(1/14) developed a low INR during the intervention phase. 25% (4/16) in the control group developed a minimally elevated INR during the intervention. There was no significant difference in the mean INRs from each group on each day of measurement except for day 11 of the intervention phase when the CJ group was significantly higher than the placebo group (p<0.02), although on day 15 (end of intervention) the mean INRs from both groups were identical. Plasma warfarin levels are currently pending and should be helpful in identifying any effect on warfarin clearance or warfarin plasma protein binding. A daily 8 oz glass of cranberry juice appears to have no consistent effect on the INR in patients on warfarin therapy compared to placebo.