Researchers flag link between vitamin K status and COVID-19 mortality risk

05 Jan 2021 --- A potential link between vitamin K levels and COVID-19 symptom severity and mortality has been flagged by a team of researchers from Bispebjerg Hospital, in Denmark.

Led by Professor Allan Linneberg, director of Center for Clinical Research and Prevention, the researchers investigated whether low vitamin K status could be a common characteristic of hospitalized COVID-19 patients.

Moreover, they looked into whether a low vitamin K status may predict mortality in those patients. Their preliminary results have been submitted as a preprint.

“We measured a well-accepted blood biomarker of vitamin K status that reflects the functional vitamin K status that is a result of the actions of all vitamin K homologues (K1 and K2s),” Linneberg tells NutritionInsight.

“All vitamin Ks are believed to have similar actions, although there is still a need for more knowledge about that.”

“We believe Vitamin K2 can be a powerful force for health and wellbeing and that only research, transparency and verification together, can truly engage this force,” Dominik Mattern, vice president of marketing at Kappa Bioscience, tells NutritionInsight.

“We aim to bring more value to the category, our customers, health professionals and end-consumers by investing into research, developing a better understanding of the roles played by vitamin K2, next to D3, in the body. Its benefits for bone and cardiovascular health are backed with substantial scientific evidence, yet other applications might emerge as discoveries are made.”

Vitamin K spotlight
The study has been highlighted by Kappa Bioscience, manufacturer of K2 MK-7, which has been previously linked to positive health outcomes. 

Kaplan-Meier graph of cumulative risk of death stratified by dp-ucMGP levels.

The company recently supported a US-based University Hospitals (UH)’s research on the implications of vitamin K2 deficiency in COVID-19 pathogenesis and severity.

Furthermore, a Kappa Bioscience-funded study review positioned vitamin K metabolism as the “potential missing link” between lung damage and thromboembolism – two of the most serious outcomes observed in COVID-19 patients.

Linneberg explains that regarding public health, the findings are of potential interest if the function of vitamin K becomes broader to include a potential preventive effect against specific infection going off the rails. 

“It could strengthen the recommendations for intake of vitamin K in future, but we need to know more. Vitamin K has lived its life in the shadow of vitamin D attracting all the attention in recent years. That could have been a mistake,” he highlights.

The combination of vitamin K and D has been dubbed as a “perfect pair” by previous studies. The research was compiled by Kappa Bioscience to educate food and supplement formulators on the relationship between the two vitamins. 

Building on previous vitamin K studies
Previous promising data on the matter was published by Dr. Rob Janssen, a researcher at Canisius Wilhelmina Hospital, in Nijmegen, the Netherlands. The data showed a significant correlation between serum K2 status and the severity of COVID-19, and sparked global scientific interest. 

In the new study, vitamin K2 status – measured as dephosphorylated-undercarboxylated matrix Gla protein (dp-ucMGP) – was analyzed in over 138 COVID-19 patients, and compared to a control group of 140 persons from the general population, matched for similar age distribution. 

Levels of dp-ucMGP were significantly higher among COVID-19 patients, compared to the control population. 

The study examined whether low vitamin K status is a common characteristic of hospitalized COVID-19 patients. Of the 138 patients monitored, 43 died within 90 days from admission. Mortality was significantly associated with high age, hypertension, cardiovascular disease, and increased levels of dp-ucMGP, the research found.

Analyzing the data
A Kaplan-Meier graph of cumulative risk of death stratified by dp-ucMGP levels was created. 

“Mortality among COVID-19 patients appears to be strongly dependent on vitamin K2 status. This suggests that vitamin K plays a role in the disease mechanisms,” the researchers note. 

“In a state of severe vitamin K deficiency, the intrahepatic vitamin K-dependent activation of prothrombotic proteins is prioritized on the expense of peripheral activation of vitamin K-dependent proteins, such as the antithrombotic protein S, and calcification-inhibitory MGP,” Linneberg states.

“In addition, this may increase calcification and subsequent degradation of elastic fibers in lung tissue, leading to more severe lung damage in COVID-19 patients,” he explains.

Because of their structural differences, vitamin K1 and K2 have different outcomes in the body. Vitamin K1 is preferentially absorbed in the liver, whereas K2 is left available for extrahepatic tissues, the researchers detail.

Prevention before vaccination
Linneberg says that in many countries it will take a long time before the vaccination target is met and even then, there will be large proportions of unvaccinated individuals in most populations. 

Moreover, unvaccinated individuals may contract the virus and become severely ill, he says. 

The virus may mutate and change immunogenicity and maybe even escape the effects of vaccinations. 

“The more we learn about the disease the better we will be at treating it. The knowledge gained could also be valuable for treatment of other similar diseases. We just don’t know yet.”

He also advises to consult with a doctor, if one is taking certain types of anticoagulant medication, before taking vitamin K supplements. 

“This is because vitamin K interacts with some drugs. Besides that, there are few known side effects of taking vitamin K supplements at low to moderate doses. Unfortunately, the evidence about intake of vitamin K is limited for most populations and many countries don’t have consensus of how much is necessary.”

Going forward the team will conduct more research on the health effects of vitamin K with a focus on its effects on cardiovascular disease, bone health and other metabolic effects. 

“We are also eager to go into more detail with COVID-19-related effects of vitamin K,” Linneberg summarizes. 

By Kristiana Lalou, with additional reporting by Katherine Durrell