Two-year randomized controlled trial of vitamin K1 (Phylloquinone) and vitamin D3 plus calcium on the bone health of older women

Abstract

Dietary supplementation with vitamin K1, with vitamin D 3 and calcium or their combination, was examined in healthy older women during a 2-year, double-blind, placebo-controlled trial. Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius. Introduction: The putative beneficial role of high dietary vitamin K1 (phylloquinone) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind, placebo-controlled trial in healthy Scottish women ≥60 years of age. Materials and Methods: Healthy, nonosteoporotic women (n = 244) were randomized to receive either (1) placebo, (2) 200 μg/day vitamin K1, (3) 10 μg (400 IU) vitamin D 3 plus 1000 mg calcium/day, or (4) combined vitamins K1 and D3 plus calcium. Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist, markers of bone turnover, and vitamin status. Supplementation effects were tested using multivariate general linear modeling, with full adjustment for baseline and potential confounding variables. Results: Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups. However, women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius. Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years, serum vitamin K1 increased by 157% (p < 0.001), the percentage of undercarboxylated osteocalcin (%GluOC) decreased by 51% (p < 0.001), serum 25-hydroxyvitamin D [25(OH)D] increased by 17% (p < 0.001), and PTH decreased by 11% (p = 0.049). Conclusions: These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K1 together with supplements of calcium plus moderate vitamin D3 to enhance BMC at the ultradistal radius, a site consisting of principally trabecular bone. The substantial increase in γ-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation. © 2007 American Society for Bone and Mineral Research.