Vitamin K and Warfarin: Misunderstood Interaction

Nutritional Medicine A Textbook by Alan R. Gaby, MD

This article consists of excerpts from Nutritional Medicine (Fritz Perlberg Publishing), a comprehensive textbook by Alan Gaby, MD. This new, landmark book is a thorough and practical compendium on the use of dietary change, nutritional supplements, and other natural products for the prevention and treatment of more than 400 health conditions.

Written for busy practitioners who need reliable but clinically-relevant information to guide patient care, Nutritional Medicine combines literature reviews, case reports, thorough background material and Dr. Gaby’s lifetime of clinical experience in applying nutritional approaches to manage complex disorders and to promote health and wellbeing.

In addition to thorough reviews of nutritional interventions for nearly all of the common chronic disorders, the book also includes 61 chapters on specific vitamins, minerals, amino acids, and other compounds, reviewing in detail the biochemical effects, clinical indications, interactions, preparations, dosage and administration.

Nutritional Medicine contains 1,374 pages and more than 15,000 references. It is priced at $295. For further information, visit www.doctorgaby.com or call 603-225-01354. The following excerpts give a sense of the scope of material in the book, and the clinically-focused way in which it is presented.

Vitamin K and Warfarin: Misunderstood Interaction

Warfarin works by inhibiting the vitamin K-dependent activation of coagulation factors II, VII, IX, and X. Because this inhibition is competitive in nature, the effect of warfarin is influenced by dietary vitamin K intake. Increasing vitamin K intake inhibits the action of warfarin, whereas decreasing vitamin K intake has the opposite effect. For this reason, patients taking warfarin should keep their dietary intake of vitamin K consistent. 1

Studies have shown that supplementation with 100-150 µg/day of vitamin K1 results in fewer fluctuations of the International Normalized Ratio (INR) outside the normal range, thereby reducing risk of thrombotic events resulting from under-treatment, and risk of hemorrhagic events resulting from over-treatment. Vitamin K supplementation probably improves the stability of anticoagulation by decreasing the relative change in total vitamin K intake associated with variations in dietary vitamin K.

Seventy warfarin-treated patients with fluctuating INRs were randomly assigned to receive, in double-blind fashion, 150 µg/day of supplemental vitamin K1 or placebo for 6 months. The percentage of time patients were within the target INR range increased to a significantly greater extent in the vitamin K group (from 59% at baseline to 87%) than in the placebo group (from 63% at baseline to 78%; p < 0.01 for the difference in the change between groups). More patients achieved stable control of anticoagulation in the vitamin K group than in the placebo group (54% vs. 21%; p value not stated). 2

Eight patients (aged 45-79 years) receiving warfarin, whose INRs had been fluctuating for reasons that were not clear, were given 100 µg/day of supplemental vitamin K1 for 8-72 weeks. After vitamin K supplementation, INR fluctuations decreased in nearly all patients. A significant decrease was seen in the INR standard deviation (p < 0.05), and more INRs were within 0.2 units of the target range (57% vs. 32% prior to supplementation). 3

Despite this evidence, many practitioners advise patients taking warfarin to restrict dietary vitamin K intake. That advice is inappropriate for 2 reasons. First, as noted above, lower vitamin K intake results in greater fluctuations of INR values. Second, restricting vitamin K intake requires the avoidance of leafy green vegetables, which decreases the quality of the diet.

1. Franco V, Polanczyk CA, Clausell N, Rohde LE. Role of dietary vitamin K intake in chronic oral anticoagulation: prospective evidence from observational and randomized protocols. Am J Med 2004;116:651-656.
2. Sconce E, Avery P, Wynne H, Kamali F. Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood 2007;109:2419-2423.
3. Reese AM, Farnett LE, Lyons RM, et al. Low-dose vitamin K to augment anticoagulation control. Pharmacotherapy 2005; 25:1746-1751.

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