Warfarin Institute of America
DEDICATED TO YOUR HEALTH SINCE 2000
Kieu Tu Pham
Pharm D. Candidate
University of Colorado Health Sciences Center
School of Pharmacy
According to the Natural Medicines Comprehensive Database, the use of grape seed while on warfarin can possibly increase warfarin’s effect and the risk of bleeding due to the amount of tocopherol (one of the forms of vitamin E) found in grape seed oil.1 The amount of tocopherol present in grapes is relatively tiny. In 1 cup of American green or red seeded grapes (154gm), there are 0.3 mg of alpha-tocopherol and 0.11 mg of gamma-tocopherol present.2 Similarly, there are 0.29 mg of alpha-tocopherol and 0.11 mg of gamma-tocopherol are found in 1 cup of American green or red seedless grapes (160gm).2 One Unit is equivalent to 1 mg of dl -alpha tocopherol acetate or 0.6 mg d -alpha tocopherol.3 Based on documented reports of the potential interaction between warfarin and vitamin E, it takes a large dose of vitamin E (usually greater than 400 IU) to see the increase in INR and bleeding risk.4 The mechanism underlying this interaction is unknown; however, it is hypothesized that vitamin E interferes with the vitamin K-depending clotting factors and thus may prolong the prothrombin time (the number of seconds that takes the blood to clot) and increase the risk of bleeding.4
I have recently managed a patient’s warfarin therapy where INR seemed to change significantly when a large amount of grapes were added to her diet. This patient’s INR had been relatively stable for almost two years. At her last visit to our clinic, her INR went from 2.9 to 6.6. This INR value was checked twice. She did not seem to have any compliance issue and was doing well on a weekly dose of 9.5mg/week since November of 2005. During the interview, the patient denied any signs of bleeding, any changes in activity or medications, nor any changes in her health status. However, she later reported having eaten a large amount of green and red grapes daily for the past several weeks. She was then asked to hold two doses of warfarin and cut back on grape intake. Two days later, her INR went down to 4.1, and she was instructed to resume her weekly dose of 9.5 mg/week and come back in 1 week for another INR test. Editor's Note: Unfortunately Dr. Phan finished the experiential rotation and could not provide follow-up on this patient.
The case that I shared here and the information found on grape seed do not suggest any definite cause and effect relationship between grapes and warfarin. Without well-designed clinical trials, it is difficult to prove that eating excessive grapes or grape seed while on warfarin can cause a clinically significant interaction. Thus, the best advice for now is to eat a moderate amount of grapes and stay away from using grape seed supplement. Those managing warfarin therapy could question people about this if there is an unexplained rise in the INR.
References:
1. Natural Medicines Comprehensive Database: Jellin JM (Ed): Natural Medicines Comprehensive Database. Therapeutic Research Faculty, Stockton, California (Accessed on 3/27/06).
2. Calorie-Count Web Page. www.Calorie-Count.com. AeroDiet.com, Stamford, CT. (Accessed on 3/27/06).
3. Drugs Information Online Web Page. www.drugs.com. MicromedexTM and MultumTM, Greenwood Village, Colorado (Accessed on 3/30/06).
4. DRUG-REAX® System: Klasco RK (Ed): DRUG-REAX® System. Thomson Micromedex, Greenwood Village, Colorado (Accessed on 3/27/06).
© 2006 Kieu Tu Pham Used by permission
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Last updated March 30, 2006
