Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. This double-blind 1:1 randomized control trial of vitamin K2 administration for type 2 diabetes mellitus revealed the potential role of vitamin K2 as a regulator of glycemic homeostasis, with potential for use as a TD2M intervention.

Evidence Rating Level: 2 (Good)

Type 2 diabetes mellitus (T2DM) remains a major public health issue, and in recent years, evidence has emerged associating gut microbiota dysbiosis to the disease. The literature has also demonstrated potential benefits of vitamin K2 on insulin sensitivity and glucose metabolism, as well as changes to microbiota composition when diets are insufficient in Vitamin K. This study sought to investigate vitamin K2 probiotic administration as a potential metabolic intervention that regulates blood glucose by acting on the gut microbiota. First, a double-blind 1:1 randomized controlled intervention of MK-7 (natural form of vitamin K2) for 6 months was conducted, with n = 30 in both experimental and control groups. After a 6-month intervention, circulating levels of vitamin K2 in the body were significantly increased in the experimental group (P < 0.001). Reductions of 13.4% in fasting serum glucose (Vkchange= −1.08±0.49 mmol/L, P = 0.048), 28.3% in insulin (Vkchange= −3.15±0.39 μU/mL, P = 0.005), and 7.4% in Hb1Ac levels (Vkchange= −0.57±0.23%, P = 0.019) were observed in the experimental group, with modest improvements in HOMA index and lipid parameters. Additionally, 16S rRNA sequencing and metabolomics analysis revealed increased beta diversity of microbial community composition in the experimental group compared to control group (P < 0.05). The ratio of Firmicutes and Bacteroidetes (F/B), an indicator of gut microbiota balance that is usually higher in those with T2DM, was significantly higher in the control group than the MK-7 groups (NC0=4.95±0.96, NC6=11.22±2.18, P = 0.012). Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae were relatively dominant families in the MK-7 treatment group compared to controls, whereas Enterobacteriaceae was a dominant family in the control group. A significant decrease in the total of branched-chain amino acids and histidine concentrations was observed (P <0.05), as well as an increase in secondary bile acids (SBAs) and short-chain fatty acids (SCFAs) associated with reductions in serum Hb1Ac, glucose, insulin and insulin resistance found in fecal samples for the MK-7 treated group. Finally, within 4 weeks of fecal microbiota transplantation (FMT) in mice, they displayed significantly improved glucose tolerance and insulin sensitivity, activated colon bile acid receptors, improved host immune-inflammatory responses, and increased GLP-1 concentrations. The above results evidence the potential role of vitamin K2 as an intervention for diabetes management.

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