Potential Interaction Between Warfarin and High Dietary Protein Intake
Lori B. Hornsby, Pharm.D.; E. Kelly Hester, Pharm.D.; Amy R. Donaldson, Pharm.D.
Pharmacotherapy. 2008;28(04):536-539.
Abstract
A 55-year-old Caucasian man was receiving warfarin therapy after undergoing aortic valve replacement. His international normalized ratio (INR) was stabilized with warfarin 95 mg/week for 5 weeks. Commencement of a low-carbohydrate, high-protein diet resulted in a series of subtherapeutic INRs that led to a 16% increase in the dosage requirement to maintain therapeutic INRs. After the patient discontinued the diet, his INR increased, and several dosage reductions were required until his INR stabilized with his original dosage of 95 mg/week. Two additional case reports have described a possible interaction between warfarin and a high-protein diet. The potential for increased dietary protein intake to raise serum albumin levels and/or cytochrome P450 activity has been postulated as mechanisms for the resulting decrease in INRs. Given the available animal and human data that demonstrate alterations in drug metabolism in the presence of altered dietary protein intake, an increase in warfarin metabolism due to cytochrome P450 activation appears to be the most likely cause. In addition to the previously reported cases, this case indicates a potential interaction between warfarin and a high-protein diet. Because of the popularity of high-protein diets and because of the risks associated with inadequate or excessive warfarin anticoagulation, patients and health care providers should be aware of this interaction to ensure appropriate monitoring when warranted.
Introduction
Warfarin is well known for its interpatient variability and its low therapeutic index that requires close monitoring. Dietary considerations, such as vitamin K intake, contribute to fluctuations in international normalized ratios (INRs). However, little is known or reported about other dietary effects. With the rise in obesity and the continued cultural desire for weight loss, eating plans such as the Atkins diet and the South Beach diet, which focus on limiting or eliminating carbohydrate intake while allowing for increased protein intake, have been popular over the last decade.
To our knowledge, only two published cases have mentioned the possibility that a highprotein, low-carbohydrate diet may decrease the INR.[1] The cases described two possible mechanisms: one related to changes in total protein and albumin levels and one related to increased metabolism involving the cytochrome P450 (CYP) enzyme system.
Lori B. Hornsby, Pharm.D.; E. Kelly Hester, Pharm.D.; Amy R. Donaldson, Pharm.D.
Pharmacotherapy. 2008;28(04):536-539.
Abstract
A 55-year-old Caucasian man was receiving warfarin therapy after undergoing aortic valve replacement. His international normalized ratio (INR) was stabilized with warfarin 95 mg/week for 5 weeks. Commencement of a low-carbohydrate, high-protein diet resulted in a series of subtherapeutic INRs that led to a 16% increase in the dosage requirement to maintain therapeutic INRs. After the patient discontinued the diet, his INR increased, and several dosage reductions were required until his INR stabilized with his original dosage of 95 mg/week. Two additional case reports have described a possible interaction between warfarin and a high-protein diet. The potential for increased dietary protein intake to raise serum albumin levels and/or cytochrome P450 activity has been postulated as mechanisms for the resulting decrease in INRs. Given the available animal and human data that demonstrate alterations in drug metabolism in the presence of altered dietary protein intake, an increase in warfarin metabolism due to cytochrome P450 activation appears to be the most likely cause. In addition to the previously reported cases, this case indicates a potential interaction between warfarin and a high-protein diet. Because of the popularity of high-protein diets and because of the risks associated with inadequate or excessive warfarin anticoagulation, patients and health care providers should be aware of this interaction to ensure appropriate monitoring when warranted.
Introduction
Warfarin is well known for its interpatient variability and its low therapeutic index that requires close monitoring. Dietary considerations, such as vitamin K intake, contribute to fluctuations in international normalized ratios (INRs). However, little is known or reported about other dietary effects. With the rise in obesity and the continued cultural desire for weight loss, eating plans such as the Atkins diet and the South Beach diet, which focus on limiting or eliminating carbohydrate intake while allowing for increased protein intake, have been popular over the last decade.
To our knowledge, only two published cases have mentioned the possibility that a highprotein, low-carbohydrate diet may decrease the INR.[1] The cases described two possible mechanisms: one related to changes in total protein and albumin levels and one related to increased metabolism involving the cytochrome P450 (CYP) enzyme system.
