A double-blind randomised controlled trial assessing the effect of menaquinone producing probiotics on vitamin K status

This double-blinded randomised controlled trial investigated whether menaquinones (MK) producing probiotics for 12 weeks improve vitamin K status, compared with placebo in 50-75 years old with at least one cardiovascular risk factor. Twenty participants were randomised to either MK-producing probiotics (n = 10) or placebo (n = 10). Plasma dephosphorylated-uncarboxylated matrix gla protein (dp-ucMGP) concentrations were the primary study outcome and determined at baseline, six and twelve weeks by a chemiluminescent InaKtif MGP assay, and analysed by linear mixed models. Secondary outcomes included serum MK-7 and phylloquinone and stool MK-4 to MK-10 and phylloquinone, assessed by linear regression. Three participants dropped out (two placebo, one intervention). Compliance was high; median 98% IQR 96-99 and 90% IQR 74-96 sachets used in intervention vs placebo arm. At 6 weeks, dp-ucMGP was significantly lower in the intervention group (-75.69 95%-CI -128.37; -22.92 pmol/l), but this difference diminished by 12 weeks (-38.63 95%-CI -94.49; 16.14 pmol/l) due to a reduction in the placebo group. Overall, the mean dp-ucMGP change over 12 weeks favoured the intervention (-59.89 95%-CI -110.7; -9.187 pmol/l). Statistically significant differences in secondary outcomes included higher serum MK-7, and faecal MK-6 and MK-7 concentrations in the probiotic vs placebo arm (e.g. 4.41 95%-CI 2.17; 6.65 μg/L for serum MK-7). No other secondary outcomes differed significantly. MK producing probiotics may enhance vitamin K status in older adults at elevated cardiovascular risk. Larger, longer-term studies are needed to assess functional outcomes. The Netherlands Trial Register: NTR7505, 27-09-2018.