title: 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 K(1), 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.
  
  
  BACKGROUND
  The putative beneficial role of high dietary vitamin K(1) (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 > or =60 years of age.
  
  
  METHODS
  Healthy, nonosteoporotic women (n = 244) were randomized to receive either (1) placebo, (2) 200 microg/day vitamin K(1), (3) 10 microg (400 IU) vitamin D(3) plus 1000 mg calcium/day, or (4) combined vitamins K(1) and D(3) 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 K(1) 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 K(1) together with supplements of calcium plus moderate vitamin D(3) to enhance BMC at the ultradistal radius, a site consisting of principally trabecular bone. The substantial increase in gamma-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.
authors.affiliation: Nutrition Research Group, CVEU, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bolton-Smith
authors.forename: Marion E T
authors.initials: ME
authors.lastname: McMurdo
authors.forename: Colin R
authors.initials: CR
authors.lastname: Paterson
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Mole
authors.forename: Julia M
authors.initials: JM
authors.lastname: Harvey
authors.forename: Steven T
authors.initials: ST
authors.lastname: Fenton
authors.forename: Celia J
authors.initials: CJ
authors.lastname: Prynne
authors.forename: Gita D
authors.initials: GD
authors.lastname: Mishra
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Shearer
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D002112:Calcifediol / Q000097:blood; D002136:Calcium, Dietary / Q000008:administration & dosage*; D002762:Cholecalciferol / Q000008:administration & dosage*; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008875:Middle Aged; D015675:Osteocalcin / Q000737:chemistry / Q000378:metabolism; D010384:Pelvic Bones / Q000187:drug effects / Q000378:metabolism; D011884:Radius / Q000187:drug effects / Q000378:metabolism; D010837:Vitamin K 1 / Q000008:administration & dosage* / Q000097:blood
chemical_list: D002136:Calcium, Dietary; D015675:Osteocalcin; D002762:Cholecalciferol; D010837:Vitamin K 1; D002112:Calcifediol