Vitamin K2 Deficiency Shown to be Unnecessarily Prevalent (Riphage et al.)

Matrix Gla Protein (MGP) is a strong vitamin K-dependent inhibitor of soft tissue calcification. Researchers assessed the prevalence of functional vitamin K insufficiency, as derived from plasma desphospho-uncarboxylated MGP (dp-ucMGP), and investigated whether plasma dp-ucMGP is associated with all-cause and cardiovascular mortality in a large general population-based cohort in a study recently published in Nutrients.

The prospective general population-based Prevention of Renal and Vascular End-Stage Disease (PREVEND) study included 4275 subjects (aged 53 ± 12 years, 46.0% male). The prevalence of functional vitamin K insufficiency (i.e., dp-ucMGP > 500 pmol/L) was 31% in the total study population. This prevalence was significantly higher among elderly and subjects with comorbidities like hypertension, type 2 diabetes, chronic kidney disease, and cardiovascular disease (~50%), and this prevalence increased even further as the number of comorbidities increased.

After 10 years of follow-up, researchers found significant associations of low vitamin K status  with all-cause and cardiovascular mortality – 279 subjects had died, with 74 deaths attributable to cardiovascular causes. The researchers specified a cut-off value for dp-ucMGP to identify subjects at risk for mortality. The optimal cut-off value was 414 pmol/L for all-cause mortality and 557 pmol/L for cardiovascular mortality.

The researchers concluded that this study provides insights into the prevalence of functional vitamin K insufficiency and its clinical implications in a large general population-based cohort. It was demonstrated that functional vitamin K insufficiency is common in the general population and occurs even more frequently among the elderly and subjects with hypertension, type 2 diabetes, CKD, and CVD.

The researchers wrote that they “found that plasma dp-ucMGP was curvilinearly associated with an increased risk for all-cause and cardiovascular mortality. Importantly, a low vitamin K status is not only a clinically relevant risk factor for adverse health outcomes, but may also be a modifiable risk factor. Given the availability of vitamin K supplements, vitamin K insufficiency seems an attractive target for preventive intervention.”

Furthermore, Dr. Katarzyna Maresz, president of the International Science and Health Foundation, shared it was important to note the authors mentioned that “current recommendations on intake of vitamin K are exclusively based on vitamin K1, which is the major dietary form of vitamin K in most Western countries, and its function in coagulation. However, these recommended intake values do not reflect vitamin K2 and may be suboptimal for the extra-hepatic functions of vitamin K. In addition, several studies have suggested that vitamin K2 may be more effective in activating extra-hepatic vitamin K-dependent proteins than vitamin K1.”

Dr. Maresz adds, “At least 5 epidemiological studies have shown the Vitamin K2 – not K1 – is cardio-protective, and the most beneficial form are long-chain menaquinones, such as MK-7 and MK-9. Recently published paper, which evaluated the intake of Vitamin K1 and K2 in 168 countries showed that smoking is as bad for your head at a Vitamin K2 deficiency.”


Riphagen J et al. Prevalence and Effects of Functional Vitamin K Insufficiency: The PREVEND Study. Nutrients 2017, 9, 1334; doi:10.3390/nu9121334.


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