title: Vitamin K for the primary prevention of cardiovascular disease.
abstract: BACKGROUND
  A deficiency in vitamin K has been associated with increased calcium deposition and coronary artery calcification, which may lead to cardiovascular disease.
  
  
  OBJECTIVE
  To determine the effectiveness of vitamin K supplementation as a single nutrient supplement for the primary prevention of cardiovascular disease.
  
  
  METHODS
  We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 8 of 12, 2014); MEDLINE (Ovid, 1946 to September week 2 2014); EMBASE Classic + EMBASE (Ovid, 1947 to September 18 2014); Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index, Science (CPCI-S) (both 1990 to 17 September 2014) on Web of Science (Thomson Reuters); Database of Abstracts of Reviews of Effects (DARE); Health Technology Assessment Database and Health Economics Evaluations Database (Issue 3 of 4, 2014). We searched trial registers and reference lists of reviews for further studies. We applied no language restrictions.
  
  
  METHODS
  We included randomised controlled trials of vitamin K supplementation as a single nutrient supplement, lasting at least three months, and involving healthy adults or adults at high risk of cardiovascular disease. The comparison group was no intervention or placebo. The outcomes of interest were cardiovascular disease clinical events and cardiovascular disease risk factors.
  
  
  METHODS
  Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias.
  
  
  RESULTS
  We included only one small trial (60 participants randomised) which overall was judged to be at low risk of bias. The study examined two doses of menaquinone (vitamin K2) over 3 months in healthy participants aged 40 to 65 years. The primary focus of the trial was to examine the effects of menaquinone (subtype MK7) on different matrix Gla proteins (MGP - vitamin K dependent proteins in the vessel wall) at different doses, but the authors also reported blood pressure and lipid levels. The trial did not report on our primary outcomes (cardiovascular disease clinical events) as it was small, short term and conducted in healthy participants.In terms of cardiovascular disease risk factors, no effects were seen for vitamin K2 on blood pressure or lipid levels, although the trial was small and findings are limited. The trial did not report any of our other secondary outcomes.
  
  
  CONCLUSIONS
  The very limited results of this review highlight the lack of evidence currently available to determine the effectiveness of vitamin K supplementation for the primary prevention of cardiovascular disease, and demonstrate the need for further high quality trials in this area.
authors.affiliation: Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, Warwickshire, UK, CV4 7AL.
authors.forename: Louise
authors.initials: L
authors.lastname: Hartley
authors.forename: Christine
authors.initials: C
authors.lastname: Clar
authors.forename: Obadah
authors.initials: O
authors.lastname: Ghannam
authors.forename: Nadine
authors.initials: N
authors.lastname: Flowers
authors.forename: Saverio
authors.initials: S
authors.lastname: Stranges
authors.forename: Karen
authors.initials: K
authors.lastname: Rees
mesh_terms: D000328:Adult; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged; D011322:Primary Prevention / Q000379:methods; D024482:Vitamin K 2 / Q000008:administration & dosage*
chemical_list: D000933:Antifibrinolytic Agents; D024482:Vitamin K 2