Two-year randomized controlled trial of vitamin K-1 (phylloquinone) and vitamin D-3 plus calcium on the bone health of older women

Bolton-Smith, Caroline, McMurdo, Marion E. T., Paterson, Colin R., Mole, Patricia A., Harvey, Julia M., Fenton, Steven T., Prynne, Celia J., Mishra, Gita D. and Shearer, Martin J. (2007) Two-year randomized controlled trial of vitamin K-1 (phylloquinone) and vitamin D-3 plus calcium on the bone health of older women. Journal of Bone and Mineral Research, 22 4: 509-519. doi:10.1359/JBMR.070116

Author Bolton-Smith, Caroline
McMurdo, Marion E. T.
Paterson, Colin R.
Mole, Patricia A.
Harvey, Julia M.
Fenton, Steven T.
Prynne, Celia J.
Mishra, Gita D.
Shearer, Martin J.
Title Two-year randomized controlled trial of vitamin K-1 (phylloquinone) and vitamin D-3 plus calcium on the bone health of older women
Journal name Journal of Bone and Mineral Research   Check publisher's open access policy
ISSN 0884-0431
Publication date 2007-04-01
Year available 2007
Sub-type Article (original research)
DOI 10.1359/JBMR.070116
Open Access Status
Volume 22
Issue 4
Start page 509
End page 519
Total pages 11
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing, Inc.
Language eng
Formatted 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.
Keyword Vitamin K
Vitamin D
Bone Densitometry
Bone turnover markers
Undercarboxylated osteocalcin
Serum Undercarboxylated Osteocalcin
British Elderly People
Mineral Density
Postmenopausal Women
D Supplementation
Hip Fracture
Plasma Phylloquinone
National Sample
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID MC_U120063239
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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