Study hints at differences between vitamins K1 & K2 for heart health

By Stephen Daniells contact

- Last updated on GMT

© Getty Images / NatchaS
© Getty Images / NatchaS
The potential heart health benefits of vitamin K are not linked to the K1 form (phylloquinone) but may be due to vitamin K2 (menaquinones), according to pooled data from large European studies.

Researchers from the Netherlands, the UK, and France focused on desphospho‐uncarboxylated matrix Gla protein (dp-ucMGP), which is a biomarker of vitamin K status. Their analysis revealed that there was a causal relationship between lower dp-ucMGP levels and decreased coronary heart disease (CHD) risk, but no causal relationship between  phylloquinone and lower CHD risk.

“This inconsistent result may reflect the influence of menaquinones in the association with CHD,” ​they wrote in Clinical Nutrition.

“Menaquinones should be taken into account since menaquinones have a higher absorption and bioavailability than phylloquinone, and therefore may be more beneficial to human health,” ​they added.

Vitamin K facts

There are two main forms of vitamin K: phylloquinone, also known as phytonadione, (vitamin K1) which 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.

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.

The potential health benefits of the vitamin include cardiovascular​ and bone health​, with some data also supporting a role for prostate health​ and cognitive benefits​.

The wider benefits of vitamin K were also highlighted in a 2009 study by Joyce McCann, PhD, and Bruce Ames, PhD, from Children's Hospital Oakland Research Institute​.

Study details

Natto © Getty Images kuppa_rock
Natto is a rich source of vitamin K2 (MK-7). Image © Getty Images / kuppa_rock

For the new study, the European scientists used the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study, CARDIOGRAMplusC4D and the UK Biobank, which provided data on 103,097 CHD cases.

Using genetics to predict both vitamin K (phylloquinone) concentrations and dp-ucMGP, the researchers found that phylloquinone was not causally related to CHD risk, but “lower genetically predicted dp-ucMGP concentration was associated with a lower CHD risk with a RR of 0.96 […] for every 10 [microgram per liter] decrease in dp-ucMGP.” ​In other words, for every 10 microgram per liter decrease in dp-ucMGP, the relative risk of CHD decreased by 4%.

Since dp-ucMGP is linked to vitamin K status and vitamin K1 was not impacting CHD risk, the authors suggested that the potential heart health benefits of vitamin K may be linked to the K2 form (menaquinones).

“Decreased dp-ucMGP concentrations, representing long-term increased vitamin K intake, may be causally associated with a decreased CHD risk,” ​wrote the researchers. “Whether this association reflects the influence of menaquinones in the association with CHD or MGP as a causal factor leading to CHD needs to be further investigated.”

Vitamin K2 heart health benefits

The potential cardiovascular benefits of K2 have been reported by other researchers in the past, including in randomized clinical trials.

A 2015 paper published in Thrombosis and Haemostasis​ reported that 180 microgram per day of vitamin K2 for three years may inhibit age-related stiffening of the artery walls, and improve vascular elasticity.

Recently, a paper published in the Journal of the American Heart Association​ indicated that higher inactive dp-ucMGP was associated with a range of negative cardiovascular measures, such as higher pulse wave velocity (a measure of arterial stiffness) and central pulse pressure.

“A K2-specific recommended daily intake (RDI)”

Commenting on the new study’s findings, Eric Anderson, Sr VP of global marketing and business development at NattoPharma, a supplier of vitamin K2 to the supplements market, said: “While it is true that ‘improving K status’ will impact cardiovascular health, this paper helps to emphasize that all K vitamins are not the same. NattoPharma’s research has shown that vitamin K2 supplementation can halt and even regress progression of arterial stiffness, and that is accomplished through the activation of MGP.

“NattoPharma has been at the forefront of making the industry aware of the research around Vitamin K2 and K-dependent proteins. Our long-term mission is to elucidate Vitamin K2’s benefits beyond Vitamin K1, as this Clinical Nutrition paper has shown, with the ultimate goal of securing a K2-specific recommended daily intake (RDI).”  

Source: Clinical Nutrition
Published online ahead of print, doi: 10.1016/j.clnu.2019.04.024
“Circulating phylloquinone, inactive Matrix Gla protein and coronary heart disease risk: A two-sample Mendelian Randomization study”
Authors: S.R. Zwakenberg et al.

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