Vitamin K and fractures: China meta-analysis shows ‘significant’ dose-response relationship
Published in the journal Medicine, researchers from Jinan, China, conducted a meta-analysis on five studies that looked at the association between dietary vitamin K – specifically vitamin K1 – and the risk of fractures.
“Results from this meta-analysis indicate that intake of dietary vitamin K is significantly associated with reduced risk of fractures,” they concluded.
Collating evidence
The researchers said the meta-analysis provided “additional evidence” to the “controversial” discussion around dietary vitamin K and risk of fractures.
“Our meta-analysis including a large number of participants and fracture cases may enhance the statistical power and solve the inconsistency of the studies on the relationship between dietary vitamin K intake and risk of fractures,” they wrote.
"To our knowledge, the present study is the first meta-analysis of the association between dietary vitamin K intake and risk of fractures. Our meta-analysis including 80,982 total subjects and 1,114 fracture cases showed that there was a significant inverse association between dietary vitamin K intake and risk of fractures.”
Pooled relative risks (RRs) showed risk of fracture among those with a dietary vitamin K intake to be 0.78 or somewhere between 0.56-0.99 using a 95% confidence interval (CI).
Specifically, they said findings showed a “significant dose-response relationship”.
For example, subjects with the highest dietary vitamin K intake were found to have a 22% reduction in the risk of fractures when compared to the lowest intake and an increase of 50 micrograms (μg) of dietary vitamin K per day was associated with a 3% decreased risk of total fractures.
Selecting and pooling research
The researchers systematically searched literature published in PubMed and EMBASE between January 1966 and July 11, 2016, using medical subject headings or free text words like ‘vitamin K’, ‘phylloquinone’ or ‘menaquinone’ to identify relevant studies.
Four cohort studies and one nested case-control study were selected for analysis from an initial 891 potential studies based on a series of selection criteria: prospective cohort study or nested case-control study; the exposure of interest was dietary vitamin K intake; the outcome was fracture; and the studies reported
relative risks (RRs) and 95% confidence intervals (CIs) for continuous variable of vitamin K intake or at least three quantitative categories of vitamin K intake.
The quality of each study was also assessed using the 9-star Newcastle-Ottawa Scale.
The studies finally selected were published between 1999 and 2012 and conducted in the United States, Denmark, Norway and China. Three studies included men and women and two just included women, all over the age of 30.
Dietary intake of vitamin K in the majority of studies (four out of five) was assessed with a food-frequency questionnaire, the other study used a 4-day or 7-day food record.
Statistical weakness?
Whilst the researchers had overall confidence in the strength of their meta-analysis, they acknowledged some limitations typically associated with such a model.
“As a meta-analysis, the residual confounding factors are always of concern in the included studies, and the possibility that other risk factors may impact the observed association between dietary vitamin K intake and risk of fractures. However, most of the studies were adjusted for a wide range of potential confounding factors, including age, BMI, BMD, physical activity, vitamin D and calcium intake, smoking and alcohol consumption,” they said.
Potential misclassification of intake also had to be considered, they said, but this simply prompted a focus on comparing the highest categories with the lowest categories in a bid to reduce this bias through a wider range.
To strengthen findings, the researchers said work had to go beyond meta-analysis and include additional “well-designed prospective cohort studies and clinical trials” to look into the specific benefits of dietary vitamin K.
Source: Medicine
Doi: 10.1097/MD.0000000000006725
“Vitamin K intake and the risk of fractures – a meta-analysis”
Authors: G. Hao, et al.
