EU grant to drive more research into increasingly 'omnipotent' Vitamin K2

It’s fitting that a relatively new institution—Maastricht University—is helping to drive research into the evolving benefits of a ‘new’ vitamin, Vitamin K2. That research will be buoyed by a multi-center EU grant announced today.

The research, which in Maastricht is spearheaded by Prof. Leon Schurgers, PhD, is part of his longstanding work on blood clotting factors that has been supported by Norwegian K2 supplier Nattopharma.  That work led naturally to looking at how blood parameters affected heart health.  The overarching concern is that cardiovascular disease, even after all these years of research, education, dietary interventions and so forth, continues to be the number one cause of death globally. We all have to die of something, of course, but cardiovascular risk factors have proven to have remarkable staying power when it comes to lost years of healthy lifespan.

Horizon 2020 grant

The work of Dr Schurgers and others working on Vitamin K2 will get a significant boost via the prestigious grant announced this week. Nattopharma announced that its International Research network was awarded an ITN (International Training Networks) research grant from the European Commission’s Horizon 2020 research program.  Nattopharma’s research network is coordinated by Queen Mary University of London and includes, in addition to Maastricht, University College of Dublin, Ludwig-Maximilians Universität München, and Karolinska Institutet in Stockholm.  It also includes UK charity, the Medical Research Council (MRC) Technology.

Nattopharma has worked with Maastricht University since 2004 to elucidate the benefits of its branded form of menaquinone 7 called MenaQ7.  The company said this grant will provide training in innovative therapeutic strategies that include MenaQ7, integrating early detection and prevention, to yield novel approaches to the management of chronic vascular and metabolic diseases that affect the increasing aging population of Western societies.

The grant that Nattopharma is participating in is called “EVOLuTION” (European Vascular Interventions and Therapeutic Innovation Network), and the money will be utilized to provide training for 11 early stage researchers (ESRs) in the management of chronic diseases in the field of cardiovascular disease.  The highly competitive ITN grants are meant to stimulate public-private partnerships to boost scientific excellence and business innovation.

“The Horizon 2020 research grant is one of the most prestigious grants in Europe. The successful grant assignment and the opportunity to allocate highly qualified researchers to further work on vitamin K research is a great recognition of the vitamin K2 platform by this collaboration so far,” Schurgers said. “I have great expectations for potential new and exciting observations that will arise from our mutual efforts – identifying even more positive health benefits of menaquinone-7.”

“The assignment of this Horizon 2020 grant is an honor that further validates the importance of the work we have been doing with Maastricht University, and shines a light on the impact vitamin K2 can have on improving global health,” said NattoPharma chief medical officer Hogne Vik.

The current grant is an addition to a similar $2.8 million (2.9 million Euro) grant Nattopharma’s research network received from the Commission in 2015.

Research to drive better health outcomes

NutraIngredients-USA visited Dr Schurgers at his research facility in Maastricht where he said that after considering a course of study in traditional medicine he opted for biochemistry because he thought there could be greater benefits for human health. Medical doctors tend to work with what is, rather than what could be, he said.

“When I was a kid I was always the one who was asking ‘why?’ What I realized is that an MD is a highly skilled person but they tend to be very narrow minded and they are very conservative. I always thought a doctor was someone who should work to try to keep the patient healthy. I was drawn to this research when I realized you could bring it back to the consumer on a translational platform of medicine,” he said.

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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. Image © iStock/yumehana

Dr Schurgers’ career and the history of the university dovetail in many ways: His undergraduate and graduate degrees were undertaken at the university, wrapping up his PhD in 2008, after which he accepted an associate professor role in biochemistry.  Dr Schurgers wrapped up his PhD only about 30 years after the university’s founding in 1976 as a way to bring new activity and investment to the Limburg region, where Maastricht is located.  Coal mining, long a mainstay of the local economy, had ceased about 10 years earlier, bringing hardship and stagnation.

Maastricht is also associated with another relatively new project—Europe itself. The Maastricht Treaty, signed 25 years ago (February 7, 1992), created the European Union in its current form. One aspect of that, the ability of citizens of the EU to travel to member countries without having to go through time-consuming border controls, has been especially beneficial to Maastricht, as the city occupies a sliver of the Netherlands sandwiched between Belgium and Germany.  And it has helped to make the university of the most cosmopolitan of the Netherlands, with almost half of the student body coming from other countries.

Dr Schurgers’ work has been housed in the university’s department of biochemistry, which forms an essential part of Cardiovascular Research Institute Maastricht (CARIM), the largest research institute of the University of Maastricht. The work includes molecular biology, biochemistry, animal and human nutrition, pharmacology, and clinical studies in the fields of atherosclerosis. Schurgers leads the work on Vitamin K-specific research  and supervises technical engineers, post docs and PhD students. In recent years there has bee a big campaign here in the Netherlands and also within our university in that we want to support a health lifestyle.

“The campaign urges people to quit smoking, to lose weight, to eat healthily,” Dr Schurgers said. “Right now I think we are at a point where we can start changing people’s long-term health. There is a lot of knowledge for things like vitamin D and now were are starting to build up that same kind of knowledge about vitamin K2. We’ve already done two clinical trials on Vitamin K2 right here at the university,” he said.

“Vitamin K2 is found in fermented foods like cheese, sauerkraut and natto. Vitamin K1 is found in leafy green vegetables like spinach and is located in the chloroplast membranes where is supports electron transport during photosynthesis. Only about 10% of the Vitamin K1 in the diet is absorbed. Vitamin K2 is readily available and readily absorbed because it is not bound in the chloroplast membranes,” he added.

Dr Schurgers said another key difference is in the different pharmacokinetics of the two forms of the vitamin.  What K1 that does get absorbed from the diet is gone quickly.

“When you are talking about vitamins K1 and K2 in supplements, the story is different.  Then the absorption is more or less the same.  But K1 has a very short half life.  It’s out of your blood stream in three or four hours.  With MK7, the peak is at about four hours.  Most of it ends up in the liver and then is redistributed to the peripheral tissues,” Dr Schurgers said.

New research avenues in arterial plaques

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Leon Schurgers PhD in his lab in Maastricht. NutraIngredients-USA photo.

One of the specialties of Maastricht University has been work on blood circulation and coagulation research.  A search on the Pubmed database shows Dr Schurgers as a lead or co-author on more than 80 papers, many of which are connected with the various forms of Vitamin K and blood parameters. Vitamin K is one of the four important agents for proper blood clotting.

Now, with new equipment in the laboratory and with support from Nattopharma, he can delve into the most recent connection of Vitamin K2 and broader concepts of cardiovascular health.  Vitmain K2’s connection to the activity of osteocalcin, a Vitamin K-dependent protein associated with bone formation and used as a marker for healthy bone density. Schurgers has already done work on Vitamin K2 in bone health, and has speculated on the wider potential for what he called an 'omnipotent' vitamin. The formation of arterial plaques is a complicated and as yet imperfectly understood process. But the osteocalcin-energizing property of Vitamin K2 has led the the theory that adequate levels of the vitamin could both help maintain bone mass by facilitating bone tissue growth but could also nip in the bud the formation of arterial plaques (made up mostly of calcium with some cholesterol) by soaking up excess calcium in the blood.

Elucidating the proteins

Schurgers outlined as his future research goals a plan to elucidate the molecular mechanisms of Vitamin K-dependent proteins (VKDP) by which vascular calcification is initiated and propagated. In particular, Schurgers said he plans to look into the interaction of these proteins and the apoptosis of vascular smooth muscle cells, the place where the calcification of arteries begins. At the moment, Schurgers said, the knowledge about this interaction is crude and needs to become much more detailed and granular before therapeutic strategies and be advanced with confidence. In addition, his future work will be focused on VKDP-based probes suitable for non-invasive molecular imaging of vascular calcification.