Heart Disease Linked to Vitamin K Deficiency

January 12th, 2018

Awake Goy

At-risk groups for deficiency are those subject to decreased production of K2 by normal intestinal microbiota, as seen in broad spectrum antibiotic use. Taking broad-spectrum antibiotics can reduce vitamin K production in the gut by nearly 74% in people compared with those not taking these antibiotics. Diets low in vitamin K also decrease the body’s vitamin K concentration.

What is Vitamin K?

If you’ve read about vitamins A, B, C, D, and E, you might feel like we’ve missed a few vitamins as we jump over to vitamin K. It’s important to know that vitamin K makes a variety of unique contributions to our health, and our knowledge about these contributions has been expanding in new and unexpected ways.

There are three basic types of vitamin K. Their common names are K1, K2, and K3. K1 is required for green plants to conduct the process of photosynthesis. Phylloquinone, also known as phytonadione, (vitamin K1) is found in green leafy vegetables such as lettuce, broccoli and spinach, and makes up about 90% of the vitamin K in a typical Western diet; and menaquinones (vitamins K2), which make up about 10% of Western vitamin K consumption and can be synthesized in the gut by microflora. The K2 form of vitamin K is made from K1 and K3 by bacteria and other microorganisms. It can also be made in the human body through a conversion process involving K1 and K3.

In plant foods, you won’t find much preformed K2, unless those plant foods have been fermented or otherwise transformed by bacteria or other microorganisms. Certain microorganisms can convert K1 into K2.

Menaquinones (MK-n: with the n determined by the number of prenyl side chains) can also be found in the diet; MK-4 can be found in animal meat, MK-7, MK-8, and MK-9 are found in fermented food products like cheese, and natto is a rich source of MK-7.

Vitamin K is an essential nutrient necessary for responding to injuries — it regulates normal blood clotting. In addition, by assisting the transport of calcium throughout the body, Vitamin K is also helpful for bone health: it may reduce bone loss, and decrease risk of bone fractures. Vitamin K2 is known as a procoagulant and may also be useful for atherosclerosis and heart disease.

Functional Vitamin K Insufficiency

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 cardiovascular disease (CVD), 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 cardiovascular 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 cardiovascular 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 cardiovascular 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 cardiovascular mortality.

As the study is observational, poor vitamin K status (defined by dp-ucMGP level) cannot be concluded to cause cardiovascular 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 cardiovascular 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.”

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