what is it with Cranberry juice and warfarin!

Anticoagulation clinic!! - a place to advice patients about diet, and monitoring treatment closely. Today..I had a patient ask me about Cranberry and products ..and taking them with warfarin. Well..I didnt know the right answer. She has an aunt diagnosed with cancer..and she would like to take cranberry for its antioxidant/anticancer property. So ..I delved into some evidence.....
What does FDA say -  In 2006, FDA issued warning about a potential interaction between the two in raising the INR. This was based on a UK health committee's warning about the same interaction. The warning came after 12 reports of a suspected interaction!! (Just 12 reports...without any base??)


What is the mechanism of interaction - Warfarin  is a racemic mixture of the R- and S-enantiomers, with the S-enantiomer having 2-5 times more anticoagulant activity.It was proposed that some Flavinoids in Cranberry products might inhibit cytochrome P450 (CYP) 2C9, the enzyme responsible for the hepatic elimination of S-warfarin. But many studies have shown  no effect on CYP2C9(J of Exp Pharm 2010), although some questionable effect on the less important enzyme, CYP3A4(Drug Met & Dis 2009)


What does evidence say -  The same year as FDA put up the warning...the first randomised trial on this was published( J of Amer Diet Asssoc,2006). Just with 7 patients...taking 250cc of Cranberry juice /day......no difference in INR was found during 3 months duration. Another study in Clin Pharm in 2009 showed no difference in INR among warfarin pts taking 240cc/day of cranberry juice Vs placebo for 2 weeks.
A recent review in Amer J of Medicine concluded that no interaction exists between warfain and Cranberry products consumed in moderation (around 250cc/day). We don't know about excessive consumption though.
So, thats pretty much it......... SAFE to tahe warfarin and Cranberry products (may be < 300 cc/day). Anticoagulants like Dabigatran are on the horizon...which might have less interaction...and would be the way forward.