Data from the prospective general population-based Prevention of Renal and Vascular End-Stage Disease (PREVEND) study identified that functional vitamin K insufficiency was present in almost one in three of subjects.
Insufficiency rates were even higher (around 50%) in the elderly and subjects with other conditions like high blood pressure, type-2 diabetes, chronic kidney disease (CKD), and CV disease, found the research team from Groningen University.
Writing in Nutrients, the researchers established J-shaped risk curves linking the vitamin K biomarker (blood levels of desphospho-uncarboxylated Matrix Gla Protein (dp-ucMGP)) to all-cause and CV mortality. Risks for the respective outcomes started to rise substantially at 414 picomoles/ litre (pmol/l) and 557 pmol/l.
“We demonstrated that the prevalence of functional vitamin K insufficiency, as derived from plasma dp-ucMGP, was ~30% in the total study population,” wrote first author Dr. Ineke Riphagen
“Among the elderly and subjects with hypertension, type 2 diabetes, CKD, and CVD, prevalence was significantly higher (i.e. ~50%), and this prevalence increased even further as the number of comorbidities increased.
“Furthermore, we found J-shaped associations of plasma dp-ucMGP concentrations with all-cause and cardiovascular mortality,” Riphagen added.
Functional insufficiency was defined as a blood level of dp-ucMGP of >500 pmol/l. The figure was based on the shape of these risk curves.
Significance of vitamin K insufficiency
Vascular calcification is recognised as commonplace in patients with diabetes, high blood pressure and CKD, and as a significant risk factor for CV mortality.
Vitamin K (specifically the MK-7 form of vitamin K2) is a critical co-factor for converting inactive uc-MGP into its active form, which inhibits calcification of arteries and other soft tissues, the researchers explained.
The recognition of functional vitamin K insufficiency in relation to calcification and resultant CV disease has been held back by a lack of distinction by many Western health authorities between vitamin K1 and K2, suggest the researchers. Thus, at public health level, insufficient recognition may be given to the increasing body of evidence for bone and heart health benefits of K2.
Additionally, recommended vitamin K intake is often based purely on K1 and therefore may be sub-optimal for other functions such as bone health and prevention of calcification, they explain.
In the UK, NHS Choices makes no distinction between the two forms of vitamin K (let alone K2 subtypes), but describes blood clotting as the vitamin’s primary function. (Coagulation properties are widely recognised to be derived from the K1 form).
Indeed, lack of distinction between the K1 and K2 forms was a limitation within this study, acknowledged the researchers.
“Data regarding vitamin K intake or plasma vitamin K concentrations were not available in this study population, and therefore we could not distinguish between the two forms of vitamin K. However, plasma dp-ucMGP was found to be a sensitive marker for changes in vascular vitamin K status,” they said.
Association or causation?
The main objectives of this investigation were to identify the prevalence of vitamin K deficiency in a general population cohort, and to identify association between insufficiency of the vitamin with all-cause and CV mortality.
As the study is observational, poor vitamin K status (defined by dp-ucMGP level) cannot be concluded to cause CV mortality.
Nevertheless, recent intervention trials using vitamin K2 MK-7 have shown effectiveness in reversing kidney, heart and arterial calcification.
Additionally, results from a recent study that used Mendelian randomisation suggested that “the association of dp-ucMGP with coronary events and non-cancer mortality is causal.”
Vitamin K supplementation?
The recognition of such a high occurrence of vitamin K insufficiency in a general population cohort is important, suggest the researchers.
In conclusion, they propose that supplementation might be an important strategy to improve CV health.
“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.”
Volume 9, issue 12, 1334, doi: 10.3390/nu9121334
“Prevalence and Effects of Functional Vitamin K Insufficiency: The PREVEND Study”
Authors: Ineke J. Riphagen, Stephan J.L. Bakker