Vitamin D and K status linked to reduced mortality risk, say researchers

By Nikki Hancocks

- Last updated on GMT

getty | ekaterina79
getty | ekaterina79

Related tags Research Vitamin k Vitamin d Cardiovascular disease

Combined low vitamin D and K status are associated with increased all-cause mortality risk and possibly with cardiovascular events, according to a newly published cohort study.

Vitamin K - found naturally in green leafy vegetables, fermented dairy products, and egg yolks -  is required for activation of certain proteins which inhibit calcification in the vascular system, therefore reducing risk of coronary heart disease and mortality​. 

The role of combined vitamin D and K status has mostly been investigated in studies on subclinical outcomes or in specific disease populations. In the general population, simultaneous low vitamin D and K status has previously been shown to be associated with arterial stiffness​ - thickening and stiffening of the artery wall and is related to high blood pressure or hypertension.

The current prospective study, published in the European Journal of Nutrition​, explores the association of vitamin D and K concentrations with all-cause mortality, cardiovascular mortality and cardiovascular events in the general population.

The team of researchers from the Netherlands conclude that combined low vitamin D and K status are associated with increased all-cause mortality risk and possibly with cardiovascular mortality and cardiovascular events, when compared with adequate vitamin D and K status.

Trygve Bergeland, VP Science & Product Development at Kappa Bioscience, developer of the vitamin D3+K2 supplement brand K2VITAL, says: "To our knowledge, this is the first study to investigate the association of combined vitamin D and K status with mortality outcomes in the general population.

“Interestingly, this research shows that the association of combined low vitamin D and K status with mortality was greater than one vitamin insufficiency alone, and amplified the risks.”


A sample of 4,742 middle-aged participants (53% female) were enrolled and followed for 14 years (median). Vitamin D and K status, respectively measured as 25-hydroxy vitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), were assessed through blood samples.

Mortality data were obtained from the municipal register, and the cause of death was obtained by linkage of the death certificates to the primary cause of death. Data on non-fatal cardiovascular events were derived from hospital discharge diagnoses.

Participants completed questionnaires to determine detailed information on demographic, health-related behaviors, diagnosis of cardiovascular and renal disease, family history, ethnicity, attained education, medication use, and frequency of sports

The reported results show that combined low vitamin D and K status was present in 20% of the cohort and was associated with a greater risk of all-cause mortality compared to normal vitamin D and K status, or low status of just one of the vitamins. For cardiovascular mortality and cardiovascular events, they observed similar trends although not statistically significant.

The report states: "Combined low vitamin D and K status was associated with a higher risk of all-cause mortality after follow-up with an incidence of 22% vs 7% for the combined high vitamin D and K status group: HR 1.44 (1.11–1.87), P-interaction < 0.001. After adjusting for potential confounders, the risk estimate became slightly stronger: 1.46 (1.12–1.90).

"The risks for only low vitamin D or low vitamin K status were: 1.13 (0.87–1.46) and 1.09 (0.81–1.48), respectively. The synergy index was 2.09."

Of course, this is an observational study and so the cause and effect cannot be confirmed.

Why co-supplement

Bergeland adds: "Proper nutrition is undeniably recognised as a crucial factor for good health. Vitamin D supplementation is common and certainly benefits bone health, with positive effects demonstrated on bone density and fracture prevention. Yet D needs to be balanced with K for proper cardiovascular health.

"Alone, it can increase calcium uptakes in the intestines but not activate Matrix Gla Protein (MGP), which is responsible for inhibiting calcification in the vascular system.

"In fact, important effects of vitamin D for bone and cardiovascular health are indirect: D stimulates the synthesis of vitamin K-dependent proteins, osteocalcin and MGP. These proteins require sufficient amounts of vitamin K to be active. With both vitamins commonly lacking in our diets, co-supplementation is advised."


Source: European Journal of Nutrition

van Ballegooijen, A. J., et al

"Combined low vitamin D and K status amplifies mortality risk: a prospective study"

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