Kappa Bioscience-supported study confirms correlation between low vitamin K status and more severe COVID-19

Oslo, 17 June 2021

A new study, supported by Kappa Bioscience, confirms that vitamin K status is lower in hospitalized patients with COVID-19, compared to healthy population control. Researchers also show low vitamin K status to be predictive of higher mortality.

Initial promising data published in Clinical Infectious Diseases, showing a significant correlation between serum K2 status and the severity of COVID-19, sparked scientific interest globally.¹

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.

They repeated previously performed research to investigate the hypothesis that low vitamin K status could be a common characteristic of hospitalized COVID-19 patients, and whether low vitamin K status may predict mortality in those patients. Their results were published this week in Nutrients.²

Vitamin K2 status (measured as dephosphorylated-undercarboxylated matrix Gla protein – dp-ucMGP) was analyzed 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 hospitalized patients with COVID-19 died within 90 days from admission. Survival analysis showed that 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 dependent on 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 note.

“It is hypothesized 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.”, Professor Linneberg 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 research team highlights a possible benefit 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. Randomized, 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 adds.

Kappa Bioscience, global leader for pure, all-trans vitamin K2 MK-7 ingredients, who participated in this study’s funding, announced earlier this year the initiation of the first-ever clinical trial using their K2VITAL® ingredient in COVID-19 patients. The interventional 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.³

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1. Dofferhoff, A. S., Piscaer, I., Schurgers, L. J., Visser, M. P., van den Ouweland, J. M., de Jong, P. A., ... & Janssen, R. (2020). Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of Severe Coronavirus Disease 2019. Clinical Infectious Diseases.

2. Linneberg, A.; Kampmann, F.B.; Israelsen, S.B.; Andersen, L.R.; Jørgensen, H.L.; Sandholt, H.; Jørgensen, N.R.; Thysen, S.M.; Benfield, T. The Association of Low Vitamin K Status with Mortality in a Cohort of 138 Hospitalized Patients with COVID-19. Nutrients, 2021, 13, 1985. https://doi.org/10.3390/nu13061985

3. https://www.clinicaltrials.gov/ct2/show/NCT04770740