501995
research-article2013
AOPXXX10.1177/1060028013501995The Annals of Pharmacotherapy
Letters
Quality Concerns of Over-the-Counter Vitamin K Supplements: Implications for Warfarin Therapy
Annals of Pharmacotherapy 47(10) 1372–1373 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028013501995 aop.sagepub.com
William R. Bartle, BScPhm, PharmD, FCSHP1, Nancy Presse, PhD, DtP2, and Guylaine Ferland, PhD2,3,4
TO THE EDITOR: Research has provided evidence that oral vitamin K supplementation of 100 to 150 µg/d could help stabilize international normalized ratios of patients with unstable warfarin therapy and poor vitamin K status.1 Such doses are not available as prescription drugs in Canada and the United States but are as over-the-counter vitamin K oral supplements. However, because they are not subjected to as stringent quality control standards as prescription drugs, physicians and pharmacists can be reluctant to recommend them. To provide some guidance in this matter, we assessed the quality (content accuracy and uniformity between tablets) of 4 over-the-counter supplements containing 100 to 120 µg of vitamin K per tablet. One prescription vitamin K supplement was used for comparison. The prescription supplement (supplement 1) contained 5 mg of phylloquinone (also referred to as phytonadione) per tablet, which is the plant form of vitamin K. Four over-the-counter supplements (supplements 2-5) were purchased in health food stores in the Toronto area (Ontario, Canada). Two labels indicated 100 µg of phylloquinone per tablet, one indicated 100 µg of menaquinone-7 (MK-7), and one indicated 120 µg of menaquinone-4 (MK-4). Menaquinones, also referred to as menatetrenone, are natural forms of vitamin K synthesized by bacteria (MK-7) or from phylloquinone in certain animal tissues (MK-4). Supplements were all single-ingredient products. Vitamin K content of 10 to 18 tablets from the same batch/bottle of each supplement were determined by high-performance liquid chromatography using postcolumn reduction with K1(25) [2-methyl-3-(3,7,11,15,19pentamethyl-2-eicosenyl)-1,4-naphthalenedione] (GLSynthesis Inc, Worcester, MA) as internal standard.2 For each supplement, arithmetic mean, standard deviation (SD), and percentage coefficient of variation (%CV; 100 × SD/mean) were computed. Supplements with mean vitamin K content between 85% and 115% and CV
research-article2013
AOPXXX10.1177/1060028013501995The Annals of Pharmacotherapy
Letters
Quality Concerns of Over-the-Counter Vitamin K Supplements: Implications for Warfarin Therapy
Annals of Pharmacotherapy 47(10) 1372–1373 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028013501995 aop.sagepub.com
William R. Bartle, BScPhm, PharmD, FCSHP1, Nancy Presse, PhD, DtP2, and Guylaine Ferland, PhD2,3,4
TO THE EDITOR: Research has provided evidence that oral vitamin K supplementation of 100 to 150 µg/d could help stabilize international normalized ratios of patients with unstable warfarin therapy and poor vitamin K status.1 Such doses are not available as prescription drugs in Canada and the United States but are as over-the-counter vitamin K oral supplements. However, because they are not subjected to as stringent quality control standards as prescription drugs, physicians and pharmacists can be reluctant to recommend them. To provide some guidance in this matter, we assessed the quality (content accuracy and uniformity between tablets) of 4 over-the-counter supplements containing 100 to 120 µg of vitamin K per tablet. One prescription vitamin K supplement was used for comparison. The prescription supplement (supplement 1) contained 5 mg of phylloquinone (also referred to as phytonadione) per tablet, which is the plant form of vitamin K. Four over-the-counter supplements (supplements 2-5) were purchased in health food stores in the Toronto area (Ontario, Canada). Two labels indicated 100 µg of phylloquinone per tablet, one indicated 100 µg of menaquinone-7 (MK-7), and one indicated 120 µg of menaquinone-4 (MK-4). Menaquinones, also referred to as menatetrenone, are natural forms of vitamin K synthesized by bacteria (MK-7) or from phylloquinone in certain animal tissues (MK-4). Supplements were all single-ingredient products. Vitamin K content of 10 to 18 tablets from the same batch/bottle of each supplement were determined by high-performance liquid chromatography using postcolumn reduction with K1(25) [2-methyl-3-(3,7,11,15,19pentamethyl-2-eicosenyl)-1,4-naphthalenedione] (GLSynthesis Inc, Worcester, MA) as internal standard.2 For each supplement, arithmetic mean, standard deviation (SD), and percentage coefficient of variation (%CV; 100 × SD/mean) were computed. Supplements with mean vitamin K content between 85% and 115% and CV
