Vitamin K supplementation to prevent cardiovascular disease

Background

Cardiovascular disease (CVD) refers to a group of conditions affecting the heart and blood vessels. CVD is a global burden and varies between regions, and this variation has been linked in part to dietary factors. Such factors are important because they can be modified to help with CVD prevention and management.This review assessed the effectiveness of vitamin K supplementation as a single supplement at reducing cardiovascular death, all-cause death, non-fatal endpoints (such as heart attacks, strokes and angina) and CVD risk factors in healthy adults and adults at high risk of CVD.

Study characteristics

We searched scientific databases for randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments) looking at the effects of vitamin K supplementation in healthy adults or those at high risk of developing CVD. We did not include people who already had CVD (e.g. heart attacks and strokes). The evidence is current to September 2014.

Key results

Only one small trial met our inclusion criteria. It included 60 participants aged 40 to 65 years. This study looked at the effects of vitamin K2 supplements on CVD risk factors (blood pressure and lipid levels) over three months in healthy participants. No differences in these risk factors were seen between the comparison groups, but this was a small study and the findings are limited. The trial did not look at fatal and non-fatal cardiovascular endpoints as it was small and short term.

The evidence is currently extremely limited and further high-quality trials are needed so that the effectiveness of vitamin K supplementation for CVD prevention can be determined.

Quality of the evidence

The only trial identified for this review was judged to be at low risk of bias (so there was less chance of arriving at the wrong conclusions because of favouritism by the participants or researchers). However the evidence is limited to one small trial and no firm conclusions can be reached at this time.

Authors' 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.

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Background: 

A deficiency in vitamin K has been associated with increased calcium deposition and coronary artery calcification, which may lead to cardiovascular disease.

Objectives: 

To determine the effectiveness of vitamin K supplementation as a single nutrient supplement for the primary prevention of cardiovascular disease.

Search strategy: 

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.

Selection criteria: 

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.

Data collection and analysis: 

Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias.

Main 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.

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