Vitamin K1 intake is associated with higher bone mineral density and reduced bone resorption in early postmenopausal Scottish women: no evidence of gene-nutrient interaction with apolipoprotein E polymorphisms

Am J Clin Nutr. 2008 May;87(5):1513-20. doi: 10.1093/ajcn/87.5.1513.


Background: Polymorphisms in the apolipoprotein E (APOE) gene are associated with fracture risk, and a potential mechanism is through vitamin K transport.

Objective: We investigated the relation between dietary vitamin K(1) intake, APOE polymorphisms, and markers of bone health.

Design: We measured bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) in a cohort of Scottish women aged 49-54 y in 1990-1994 (baseline) and in 1997-2000 (visit 2). At visit 2, bone markers (urinary pyridinoline crosslinks and serum N-terminal propeptide of type 1 collagen) were measured, 3199 women completed a food-frequency questionnaire, and 2721 women were genotyped for APOE.

Results: Compared with quartile 3 (Q3) of energy-adjusted vitamin K(1) intake (mean: 116 microg/d), women in the lowest quartile (mean: 59 microg/d) had lower BMD (analysis of variance; FN, Q1: 0.831 +/- 0.122 g/cm(2); Q3: 0.850 +/- 0.126 g/cm(2); P < 0.001; LS, Q1: 1.000 +/- 0.170 g/cm(2); Q3: 1.020 +/- 0.172 g/cm(2); P = 0.009), remaining significant at the FN after adjustment for age, weight, height, menopausal status or use of hormone replacement therapy, socioeconomic status, and physical activity (P = 0.04). Vitamin K(1) intake was associated with reduced concentrations of pyridinoline crosslinks (Q1: 5.4 +/- 2.0 nmol/mmol; Q4: 5.1 +/- 1.9 nmol/mmol; P = 0.003). Carriers of the E2 allele had greater LS BMD at visit 2 and lost less BMD than did carriers of the E4 allele (E2: -0.50 +/- 1.22%/y; E4: -0.71 +/- 1.17%/y; P = 0.05). After adjustment for confounders, the P value for BMD loss (0.03 for LS and 0.04 for FN) did not reach the level of significance required for multiple testing (P = 0.012). No interaction was observed between dietary vitamin K and APOE on BMD.

Conclusions: Vitamin K(1) intake was associated with markers of bone health, but no interaction was observed with APOE alleles on BMD or markers of bone turnover.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon / methods
  • Amino Acids / urine
  • Analysis of Variance
  • Apolipoproteins E / genetics*
  • Bone Density / drug effects*
  • Bone Density / physiology
  • Bone Resorption
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / metabolism
  • Collagen Type I / urine
  • Diet
  • Exercise / physiology
  • Factor Analysis, Statistical
  • Female
  • Humans
  • Middle Aged
  • Peptides / urine
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Postmenopause
  • Scotland
  • Surveys and Questionnaires
  • Vitamin K 1 / administration & dosage*
  • Vitamin K Deficiency / physiopathology


  • Amino Acids
  • Apolipoproteins E
  • Collagen Type I
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • pyridinoline
  • Vitamin K 1