title: A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation.
abstract: BACKGROUND
  Dietary vitamin K is usually inadequate to maximize serum osteocalcin gamma-carboxylation. Phylloquinone supplementation increases osteocalcin gamma-carboxylation; however, the amount required to maximize carboxylation is not known.
  
  
  OBJECTIVE
  This study assessed the ability of various doses of phylloquinone (vitamin K(1)) to facilitate osteocalcin gamma-carboxylation.
  
  
  METHODS
  Healthy adults aged 19-36 y participated in 2 substudies. In an initial dose-finding study (substudy A), 6 women and 4 men received a placebo daily for 1 wk and then phylloquinone daily for 3 wk: 500, 1000, and 2000 micro g during weeks 2, 3, and 4, respectively. Osteocalcin and undercarboxylated osteocalcin were measured at baseline and after each week of supplementation. Subsequently, to further delineate the gamma-carboxylation response of osteocalcin to various doses of vitamin K, 58 women and 42 men were randomly assigned to receive placebo or phylloquinone supplementation (250, 375, 500, and 1000 micro g/d) for 2 wk (substudy B). The percentage of undercarboxylated osteocalcin (%ucOC) was measured at baseline and weeks 1 and 2.
  
  
  RESULTS
  In substudy A, %ucOC decreased with phylloquinone supplementation (P < 0.0001); a greater reduction was observed with 1000 and 2000 micro g than with 500 micro g (P < 0.05). In substudy B, %ucOC decreased in all supplemented groups by week 1 (P for the trend < 0.0001), which was sustained through week 2. Phylloquinone supplementation decreased %ucOC dose-dependently; %ucOC was significantly different between the 250- micro g and the placebo groups and between the 1000- and 500- micro g groups but not between the 250-, 375-, and 500- micro g groups.
  
  
  CONCLUSIONS
  A daily phylloquinone intake of approximately 1000 micro g is required to maximally gamma-carboxylate circulating osteocalcin.
authors.affiliation: Institute on Aging, Department of Medicine, University of Wisconsin, Madison, USA. nbinkley@facstaff.wisc.edu
authors.forename: Neil C
authors.initials: NC
authors.lastname: Binkley
authors.forename: Diane C
authors.initials: DC
authors.lastname: Krueger
authors.forename: Tisha N
authors.initials: TN
authors.lastname: Kawahara
authors.forename: Jean A
authors.initials: JA
authors.lastname: Engelke
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Chappell
authors.forename: John W
authors.initials: JW
authors.lastname: Suttie
mesh_terms: D000328:Adult; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D015675:Osteocalcin / Q000378:metabolism*; D010837:Vitamin K 1 / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D015675:Osteocalcin; D010837:Vitamin K 1