Review paper makes strong case for unique activities of Vitamin K2

By Hank Schultz contact

- Last updated on GMT

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A new paper published in an international journal definitively makes the case that Vitamin K2 has different functions in the body beyond that of Vitamin K1, and that the two should not be grouped under the same heading for dietary purposes.

The paper was published in February in the International Journal of Molecular Sciences​.  It was written by a team led by Leon Schurgers, PhD, of the University of Maastricht in the Netherlands, who was done much of the scientific work on Vitamin K2, as well as experts from NattoPharma, the Norwegian supplier who helped fund the research as well as researchers from institutions in Germany and Poland.

The review paper, titled Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease​, is the first to take a detailed look into how the two substances are related, and how they function differently in the body.

“There have been a number of papers in the past that have looked at vitamin K,”​ said Eric Anderson, senior vice president of global sales and marketing for NattoPharma and one of the paper’s authors.

“This paper is different in that it looks at the body of evidence that has been complied over really the past 10 years that is making industry and people involved in health care more cognizant that Vitamin K2 is doing things in the body that Vitamin K1 is not,”​ Anderson told NutraIngredients-USA.

Slight differences in form give rise to different activities

First to forms: All forms of this vitamin are based on a 2-methyl-1,4-naphthoquinone ring structure called menadione.  They differ in their side chains.

Vitamin K1, or phylloquinone is found in green leafy vegetables such as spinach and some other plant sources like some nuts and fruits.  The principle activity of this form of the vitamin is to activate the blood’s clotting factors. This vitamin form actively interferes with the action of the most common blood thinning medication, Coumadin, also known as Warfarin, which is why patients using this drug must carefully watch their intake of foods containing this substance.

Vitamin K2, or menaquinone, is found in several different forms which are delineated in the length of their side chains.  Vitamin K2 is found in fermented foods such as natural hard aged cheeses and the Japanese specialty natto, a fermented soybean product that is little consumed outside of Japan.

“Menaquinones contain an unsaturated aliphatic side chain with a variable number of prenyl units. The number of prenyl units indicates the respective type of menaquinone. Vitamin K2 can be divided into subtypes, namely, short-chain (i.e., menaquinone-4; MK-4) and long-chain (i.e., MK-7, MK-8, and MK-9),”​ the paper states.

MK-7 is the best absorbed form of vitamin K2, which is why it has been the focus of commercial development by NattoPharma and other companies. Subsequent research on this form has shown that it plays important roles in bone health, by helping to mobilize calcium into and out of the bones. And it has been shown to have an important function in keeping excess calcium out of the arteries, where it forms an important portion of arterial plaques.

Time for a new RDI specific to Vitamin K2?

Prof. Schurgers said that the information contained in the present paper and another that will publish later this year show that it’s time that international health authorities start to recognize that the various forms of Vitamin K are different enough that it is not a one size fits all recommendation for dietary purposes.

“When exploring the non-coagulation, extrahepatic activities of vitamin K, it is clear that K2 in its various forms is the highlight of such activity. Therefore, although history and nomenclature have classed K1 and K2 into the same category, these molecules can have a very different action in the body,”​ he said. “Major health organizations, such as WHO, European Food Safety Authority (EFSA) and Food and Drug Administration (FDA) have established RDI for vitamin K, which is solely based on the dose of K1 to retain an appropriate blood clotting function. Differences between K1 and K2 merit recognition among national and international regulatory organizations, and remain open to research.” 

The review paper is the result of the INTRICARE (grant agreement No 722609) and EVOluTION (grant agreement No 675111) grants funded by the European Union within the Horizon 2020 Marie Skłodowska-Curie research and innovation program, awarded to NattoPharma’s International Research Network to train a total of 26 Early Stage Researchers (ESRs) focusing on harnessing endogenous mechanisms for health and the effect of vitamin K to hold or regress microcalcification and subsequent cardiovascular disease. 

Source:International Journal of Molecular Sciences
Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease
2019​, 20​(4), 896; doi:10.3390/ijms20040896
Authors: Halder M, Petsophonsakul P, Akbulut CA, Pavlic A, Bohan F, Anderson E, Maresz K, Kramann R, Schurgers L.

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