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Possible Interaction Between Cranberry Products and Widely Used Blood-Thinner Warfarin (COUMADIN)

Worst Pills, Best Pills Newsletter article April, 2009

A recent controlled study confirmed that people with certain genetic types were susceptible to increased blood-thinning effects of warfarin (COUMADIN) when used with cranberry juice.

This information adds to a growing collection of information on this topic. Over the past several years, several case reports have emerged in which cranberry juice has possibly increased the blood thinning effect of warfarin.

Although in many of these cases other factors may have contributed to the...

A recent controlled study confirmed that people with certain genetic types were susceptible to increased blood-thinning effects of warfarin (COUMADIN) when used with cranberry juice.

This information adds to a growing collection of information on this topic. Over the past several years, several case reports have emerged in which cranberry juice has possibly increased the blood thinning effect of warfarin.

Although in many of these cases other factors may have contributed to the increased blood-thinning effect of warfarin (such as low food intake, infectious diseases and lack of information on warfarin doses), in some cases, no factors other than cranberry juice were identified that could account for the increased warfarin response.

Does the type of cranberry juice matter?

The interaction between cranberry and warfarin is most likely due to certain chemicals in the cranberry juice that increase the effect of warfarin. Since cranberries are grown in different conditions from place to place and from year to year, it is likely that the concentration of substances in cranberries that interact with warfarin will vary depending on the specific product that is used.

Also, cranberry juice products may vary substantially regarding the actual amount of cranberry juice present, particularly if they are combined with other fruit juices. One should consider the possibility that cranberry in other forms may also interact with warfarin, such as cranberry sauce and dried cranberries. One case report of increased warfarin effect occurred in a man who ate large amounts of cranberry sauce every day during the week after Thanksgiving.

Do cranberry products interact with other drugs?

There is little evidence that cranberry affects drugs other than warfarin.

For instance, one study found that cranberry juice did not interact with cyclosporine, a drug often used following organ transplants. This suggests that cranberry juice does not affect the CYP3A4 enzyme, which is the enzyme that metabolizes roughly half of all drugs.

Cranberry juice also does not appear to affect the metabolism of drugs by the enzyme CYP2C9.

Can we be sure that cranberry products interact with warfarin?

Case studies alone, such as those cited above, are often not sufficient to conclusively link a side effect with a cause. Better evidence comes from planned studies that control for other factors that could possibly affect the outcome, such as the recent study mentioned above; but studies looking for evidence of an interaction between warfarin and cranberry juice consumption that controlled for other factors also do not provide unequivocal evidence of an interaction between cranberry juice and warfarin. Some studies found no interaction.

However, a recent well-controlled study in healthy subjects found a 30 percent increase in the blood-thinning (anticoagulant) response to warfarin following two weeks of cranberry juice consumption. The concentrations of warfarin in the blood were not affected, but the anticoagulant effect of warfarin was increased.

There are several possible reasons that the results of the studies of cranberry juice and warfarin were inconsistent.

First, the studies were done in different countries and used a variety of cranberry preparations. Some used cranberry concentrate as capsules, while others used cranberry juice.

Second, the studies used different doses of the cranberry preparation for variable periods of time.

Third, the number of subjects or patients in the studies varied; one study that found no evidence of interaction involved only seven subjects, which is a small number for a study such as this.

However, even though the interaction between cranberry juice and warfarin is not perfectly established, there is enough evidence of an interaction to suggest that people taking warfarin should avoid (or severely limit) their intake of cranberry juice.

What You Can Do

People taking warfarin should avoid (or severely limit) their intake of cranberry juice. These people should also take the same precautions with other forms of cranberry such as cranberry sauce and dried cranberries. The results of the study described above, when taken together with recent case reports, strongly suggest that patients who are co-administered cranberry and warfarin should be closely monitored, or, preferably, cranberry should be avoided in such patients. If cranberry juice is deemed necessary — say, to help prevent urinary tract infections — inform the physician monitoring your warfarin therapy so that he or she can test for increased warfarin effect if necessary.