Low vitamin K status associated with COVID-19 mortality

Initial data published in Clinical Infectious Diseases, showing a significant correlation between serum K2 status and the severity of COVID-19, sparked scientific interest

A recent study, supported by Kappa Bioscience, has confirmed vitamin K status is lower in hospitalised patients with COVID-19, compared to healthy population control. The researchers also showed low vitamin K status to be predictive of higher mortality.

Initial data published in Clinical Infectious Diseases, showing a significant correlation between serum K2 status and the severity of COVID-19, sparked scientific interest.

A team from the Bispebjerg and Frederiksberg Hospital (Denmark), led by Professor Allan Linneberg, MD, PhD, Director of Center for Clinical Research and Prevention, then contacted Kappa Bioscience to explore possibilities for a collaboration. This led to the funding of two postdoctoral positions, with unrestricted grants for vitamin K-related research.

The team repeated previously performed research to investigate the hypothesis that low vitamin K status could be a common characteristic of hospitalised COVID-19 patients, and whether low vitamin K status may predict mortality in those patients. Their results were published this week in Nutrients.

Vitamin K2 status (measured as dephosphorylated-undercarboxylated matrix Gla protein – dp-ucMGP) was analysed in 138 COVID-19 patients and compared to a control group of 138 persons from the general population, matched for similar age distribution. Vitamin K2 status was significantly lower COVID-19 patients, compared to the control population.

43 of the hospitalised patients with COVID-19 died within 90 days from admission. Survival analysis showed low vitamin K2 status was associated with a higher mortality risk.

A Kaplan-Meier plot of the cumulated risk of death stratified by dp-ucMGP levels was created. Mortality among COVID-19 patients appears to be strongly associated with vitamin K2 status. “Although this association was partly explained by increasing co-morbidity with decreasing vitamin K status, these findings suggest that vitamin K could play a role in the disease mechanisms in COVID-19,” the authors said.

Professor Linneberg said: “It is hypothesised that 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. In addition, this may increase calcification and subsequent degradation of elastic fibres in lung tissue, leading to more severe lung damage in COVID-19 patients.”

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 research team highlighted the potential benefits of vitamin K2 supplementation: “As countries worldwide are experiencing second, or even third waves of the COVID-19 pandemic, there is an urgent need for measures to improve the outcome and long-term consequences of COVID-19. Supplementation with vitamin K2 represents an inexpensive and simple-to-use solution.”

“Our study shows that low vitamin K status predicts mortality in patients with COVID-19. Randomised, double-blind placebo-controlled clinical trials are now needed to document potential beneficial effects of vitamin K2 supplementation on the course of COVID-19,” Professor Linneberg said.

Kappa Bioscience, which participated in this study’s funding, announced earlier this year the initiation of the first clinical trial using its K2VITAL ingredient in COVID-19 patients. The trial aims to discover whether supplementation with vitamin K2 MK-7 could reduce pulmonary damage and coagulopathy in patients with severe COVID-19. Results are expected later this year.

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