Cranberry Juice and Warfarin

[orangefoot]

I had a note printed on my INR result this week which says

***There may be an interaction between cranberry juice and warfarin. Until this is investigated we advise thatyou avoid or limit this drink*** (their asterisks)

I did a quick search and found that this was in the news in September, but I hadn't heard about it til now. Its not Vitamin K related but something to do with flavinoids and liver function, which leads to an increase in INR.

Hope everyone is well

[James]

http://bmj.bmjjournals.com/cgi/content/ful.../7429/1454?etoc

BMJ??2003;327:1454?(20?December), doi:10.1136/bmj.327.7429.1454

Possible interaction between warfarin and cranberry juice

Rafe Suvarna, senior medical assessor1, Munir Pirmohamed, professor of clinical pharmacology2, Leigh Henderson, senior scientific assessor1

1 Pharmacovigilance Risk Assessment Unit, Medicines and Healthcare Products Regulatory Agency, London SW8 5NQ, 2 Department of Pharmacology, University of Liverpool, Liverpool L69 3GE

Correspondence to: R Suvarna rafe.suvarna@mhra.gsi.gov.uk

After a chest infection (treated with cefalexin), a man in his 70s had a poor appetite for two weeks and ate next to nothing, taking only cranberry juice as well as his regular drugs (digoxin, phenytoin, and warfarin). Six weeks after starting cranberry juice he had been admitted to hospital with an INR (international normalised ratio) > 50. Before, his control of INR had been stable. He died of a gastrointestinal and pericardial haemorrhage. He had not taken any over the counter preparations or herbal medicines, and he had been taking his drugs correctly.

Credit: LIANE PAYNE

The Committee on Safety of Medicines has received seven other reports through the yellow card reporting scheme about a possible interaction between warfarin and cranberry juice leading to changes in INR or bleeding. In four cases, the increase in INR or bleeding after patients had drunk cranberry juice was less dramatic. In two cases, INR was generally unstable, and in another case INR decreased. Limited information is available about whether patients complied with their treatment in these cases.

Cranberry juice (Vaccinium macrocarpon) is popular and is also used to prevent cystitis.1 Interaction with warfarin is biologically plausible because cranberry juice contains antioxidants, including flavonoids, which are known to inhibit cytochrome P450 enzymes,2 and warfarin is predominantly metabolised by P450 CYP2C9.3 The constituents of different brands of cranberry juice may vary, and this might affect their potential for interacting with drugs. Whether the constituents of cranberry juice inhibit CYP2C9 and therefore the metabolism of warfarin or interact in another way needs further investigation. Until then, patients taking warfarin would be prudent to limit their intake of this drink.

------------------------------------------------------------------------

Funding: None.

Competing interests: None declared.

References

1. Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M, Uhari M. Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ 2001;322: 1571.[Abstract/Free Full?Text]

2. Hodek P, Trefil P, Stiborova M. Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem Biol Interact 2002;139: 1-21.[CrossRef][iSI][Medline]

3. Rettie AE, Korzekwa KR, Kunze KL, Lawrence RF, Eddy AC, Aoyama T, et al. Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Chem Res Toxicol 1992;5: 54-9.[iSI][Medline]

(Accepted November 13, 2003)

[James]

http://www.cranberryinstitute.org/news/PR/PR122303.htm

Statement on Warfarin Use and Cranberry Consumption

The Cranberry Institute recognizes concerns over the possible interaction between warfarin, a drug used for blood clot prevention, and cranberry juice consumption. In 2003, a report from the UK?s Committee on Safety of Medicines suggested that cranberry beverages might interact with warfarin medications, preventing their effectiveness. Acknowledging that this interaction is unproven and based upon only a few case reports, the Committee felt it important to notify the public due to the widespread usage of warfarin and consumption of cranberry products.

The Cranberry Institute takes this potential concern very seriously. The Cranberry Institute investigated the likelihood of a cranberry and warfarin interaction with experts in the fields of hematology, cardiology and pharmacology at centers of excellence in the United States and abroad. These experts informed us that, each of the cases can be explained by mechanisms other than interactions and to date, no interactions of cranberry with warfarin, or any other medication, have been found.

?In the cases cited in the UK, the reactions in those warfarin patients most likely were related to cranberry juice only by coincidence,? stated David Greenblatt, Ph.D., Chief of Clinical Pharmacology at Tufts University, Boston. ?There is no evidence to indicate that any component of cranberry juice has any effect on either the body?s clotting mechanisms themselves or warfarin?s metabolism and anti-clotting actions.?

Warfarin drugs are well documented as highly interactive with many other medical drugs and a multitude of foods and beverages. The Comprehensive Guide to Warfarin Therapy, jointly issued by the American Heart Association and the American College of Cardiology in April 2003, identifies a large variety of drugs and even herbal medicines as capable of modifying the body?s response to warfarin. It also warns that fluctuating levels of dietary vitamin K, (found commonly in green leafy vegetables and necessary for proper blood clotting), may affect the proper dosing of warfarin. Cranberries, like many other foods, are not a good source of Vitamin K.

Dr. Greenblatt also noted, ?Introducing any new food or beverage into the diet of a warfarin patient may alter the balance of vitamin K in the body, thereby affecting the body?s response to warfarin. Therefore, patients should not alter their diets without first consulting their physicians.?

Maintaining consistency of diet and other behaviors promotes warfarin?s effective use. Warfarin is a highly potent drug, and the diets of warfarin patients must be monitored and regulated meticulously. Therefore, the Cranberry Institute encourages patients concerned about potential warfarin interactions to consult their physicians before making any changes to their drug regimens or their diet.

To provide some context, scientific research points to a number of health benefits associated with cranberry consumption. Three well-controlled clinical studies, published in major medical journals, have shown that consumption of cranberry products on a regular basis significantly reduced bacteria in the urinary tract and reduced recurrence of urinary tract infections. Cranberries are also rich in antioxidants, which are increasingly associated with a variety of important health and wellness benefits, such as protection against heart disease and anti-aging. Cranberries offer a nutritious choice for the health conscious consumer. The public can enjoy cranberries in a variety of widely available forms, including fresh and frozen cranberries, cranberry juice, cranberry sauce, and sweetened, dried cranberries.

The Cranberry Institute intends to fully monitor emerging reports and support research on warfarin interactions and other issues relating to cranberry consumption, for the safety and health of consumers.

# # #

The Cranberry Institute is a not-for-profit organization dedicated to supporting research and increasing awareness about the health benefits of cranberry. Since 1951, the Institute has funded research that focuses on the health and medical benefits of cranberry in addition to topics related to agriculture and environmental stewardship.

For more information, contact:

Jere Downing, Executive Director

Cranberry Institute

3203-B Cranberry Highway

East Wareham, MA 02538

Phone: 1-800-295-4132

E-mail: cinews@earthlink.net