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Daily Low-dose Vitamin K Supplementation Stabilizes INRs

Alicia M. Reese, Pharm.D., M.S., BCPS*
Eugenia M Stansbury, RPh, CACP+
February, 2006

A recently published case series describes eight patients on chronic warfarin therapy whose widely fluctuating INRs stabilized after adding low-dose (100 mcg) oral vitamin K to their daily regimen.1 The number of INRs in the therapeutic range increased and the standard deviation of the INR measurements decreased.

Other studies have shown that greater dietary vitamin K intake is associated with INR stability, whereas poorer intake is associated with instability of anticoagulation.2,3 How much vitamin K intake is enough to affect an INR? Sconce and colleagues 3 calculated a mean daily dietary vitamin K intake of 29 ± 17 mcg in unstable patients versus 76 ± 40 mcg in stable patients. A case series of three patients showed that, in vitamin K depleted patients, as little as 25 mcg in a multivitamin tablet was enough to have significant impact.4 Schurgers and colleagues 5 found that vitamin K supplementation in young healthy volunteers taking acenocoumarol did not affect the INR until doses of 150-200 mcg daily were reached. These doses are greater than the adequate intake for adults of 90-120 mcg daily as recommended by the Institute of Medicine.6 However, this study may not be generalizable to typical anticoagulated patients because these healthy subjects avoided foods rich in vitamin K, had low INR targets of 2.0, and the effect of a given vitamin K dose was assessed after only one week.

Although the report by Reese and colleagues did not assess the impact of vitamin K supplementation on clinical outcomes, it is reasonable to suggest that reducing INR variability will diminish the patient's risk of thromboembolism or hemorrhage. Furthermore, this inexpensive strategy of low-dose vitamin K supplementation should prove cost-effective by decreasing the frequency of monitoring and reducing adverse events. A larger prospective investigation of this intervention would provide insight into the impact of vitamin K supplementation on clinical events as well as potential cost benefits.

References

  1. Reese AM, Farnett LE, Lyons RM, Patel B, Morgan LA, Bussey HI. Low-dose vitamin K to augment anticoagulation control. Pharmacotherapy 2005;25(12):1746-1751.

  2. 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;116:651-6.

  3. Sconce E, Khan T, Mason J, Noble F, Wynne H, Kamali F. Patients with unstable control have poorer dietary intake of vitamin K compared to patients with stable control of anticoagulation. Thromb Haemost 2005;93:872-875.

  4. Kurnik D, Lubetsky A, Loebstein R, Almog S, Halkin H. Multivitamin supplements may affect warfarin anticoagulation in susceptible patients. Ann Pharmacother 2003;37:1603-6.

  5. Schurgers LJ, Shearer MJ, Hamulyak K, Stocklin E, Vermeer C. Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects. Blood 2004;104:2682-2689.

  6. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes : Vitamins; 2001 [cited 2006 January 25]. Available from: http://www.iom.edu/Object.File/
    Master/7/296/webtablevitamins.pdf
    .

About our ClotCare Guest Editors

* Dr. Reese is assistant professor of clinical pharmacy at Philadelphia College of Pharmacy, University of the Sciences in Philadelphia.

+ Dr. Stansbury is a pharmacist specialist at Allenmore Anticoagulation Clinic in Tacoma, WA

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