Dietary vitamin K influences intra-individual variability in anticoagulant response to warfarin.
The relationship between dietary intake of vitamin K, fat, plasma vitamin K concentrations and anticoagulation response to warfarin within individuals, as well as the contribution of dietary vitamin K to differences in warfarin dose requirements between individuals were investigated in 53 patients on warfarin therapy who had stably controlled anticoagulation. Each patient completed a dietary record of all foods consumed on a daily basis for 4 weeks. Each week a blood sample was taken for measurement of the international normalized ratio (INR), plasma vitamin K, triglycerides and warfarin enantiomer concentrations. The patients' genotype for CYP2C9 was also determined. Regression analysis of the data showed that, for each increase of 100 microg in the daily dietary intake of vitamin K averaged over 4 d, the INR was reduced by 0.2. There was no correlation between warfarin daily dose and average daily dietary vitamin K intake when calculated over 28 d. The regression model for warfarin dose showed that, while dietary vitamin K had no effect, CYP2C9 genotype (P = 2%) and age (P < 1%) significantly contributed to inter-patient variability in warfarin dose requirements. A consistent intake of vitamin K could reduce intrapatient variability in anticoagulation response and thus improve the safety of warfarin therapy.
Khan
T
T
Department of Clinical Pharmacology, School of Clinical and Laboratory Sciences, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK.
Wynne
H
H
Wood
P
P
Torrance
A
A
Hankey
C
C
Avery
P
P
Kesteven
P
P
Kamali
F
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D001778:Blood Coagulation Disorders / Q000097:blood / Q000188:drug therapy*; D001823:Body Composition; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D016896:Treatment Outcome; D014812:Vitamin K / Q000008:administration & dosage* / Q000097:blood; D014859:Warfarin / Q000627:therapeutic use*
D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin