Circulating phylloquinone, inactive Matrix Gla protein and coronary heart disease risk: A two-sample Mendelian Randomization study (Zwakenberg SR et al.)
Results of a study that aimed to investigate the causal relationship between genetically predicted vitamin K concentrations and the risk of coronary heart disease (CHD) via a two-sample Mendelian Randomization technique have recently been published in Clinical Nutrition journal. The reason for such an approach lies in the ambiguity of multiple observational studies and small-scale intervention studies suggesting that high vitamin K intake is associated with improved markers for cardiovascular health, and in the fact that vitamin K is not a single vitamin – it is a family of vitamins comprised of vitamins K1 (phylloquinone) and K2 (menaquinone). Circulating phylloquinone solely represents phylloquinone (vitamin K1) intake, while dephosphorylated uncarboxylated Matrix Gla Protein (dp-ucMGP) represents both phylloquinone and menaquinone (vitamin K2) intake.
For the purpose of this study, the authors used data from three studies: European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case cohort study, CARDIOGRAMplusC4D and the UK Biobank, and altogether they examined 103,097 CHD cases. Genetically predicted vitamin K concentrations were measured using circulating phylloquinone and dephosphorylated uncarboxylated MGP (dp-ucMGP). Inverse-variance weighted (IVW) analysis was used to obtain Risk Ratios (RRs) for the causal relationship between phylloquinone and dp-ucMGP concentrations and CHD risk.
As a result of using the genetic score for circulating phylloquinone, the researchers found that circulating phylloquinone was not causally related to CHD risk (RR 1.00 (95%-CI: 0.98; 1.04)). Lower genetically predicted dp-ucMGP concentration was associated with a lower CHD risk with a RR of 0.96 (95%-CI: 0.93; 0.99) for every 10 μg/L decrease in dp-ucMGP. They concluded that, “This study did not confirm a causal relationship between circulating phylloquinone and lower CHD risk. However, lower dp-ucMGP levels may be causally related with a decreased CHD risk. This inconsistent result may reflect the influence of menaquinones in the association with CHD.”
“This paper is significant because it articulates the difference in health impact between vitamins K1 and K2, and highlights that vitamin K2 must be obtained for a cardiovascular benefit,” says Dr. Katarzyna Maresz, president of the International Science and Health Foundation. “Huge number of participants that have been involved in this study and also the method used, namely Mendelian randomization, speak in favour of the fact that while vitamin K2 supports heart health through impact on Matrix Gla Protein, vitamin K1 is not cardio-protective,” she adds.
Zwakenberg SR, Burgess S, Sluijs I, Weiderpass E, Beulens JWJ, van der Schouw YT (2019) Circulating phylloquinone, inactive Matrix Gla protein and coronary heart disease risk: A two-sample Mendelian Randomization study, Clinical Nutrition 2019 May 7, pii: S0261-5614(19)30200-6, doi: 10.1016/j.clnu.2019.04.024