Vitamin K2 Supplementation in Hospitalised COVID-19 Patients: A Randomised Controlled Trial

Margot P.J. Visser, Anton S.M. Dofferhoff, Jody M.W. van den Ouweland, Pim A. de Jong, Pieter Zanen, Henny van Daal, Eline B. Theeuwen, Cornelis Kramers, Rob Janssen, Jona Walk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: In observational studies, high levels of desphospho-uncarboxylated matrix gla protein (dp-ucMGP) that result from vitamin K deficiency were consistently associated with poor clinical outcomes during COVID-19. Vitamin K-activated matrix gla protein (MGP) is required to protect against elastic fibre degradation, and a deficiency may contribute to pathology. However, intervention trials assessing the effects of vitamin K supplementation in COVID-19 are lacking. Methods: This is a single-centre, phase 2, double-blind, randomised, placebo-controlled trial investigating the effects of vitamin K2 supplementation in 40 hospitalised COVID-19 patients requiring supplemental oxygen. Individuals were randomly assigned in a 1:1 ratio to receive 999 mcg of vitamin K2—menaquinone-7 (MK-7)—or a placebo daily until discharge or for a maximum of 14 days. Dp-ucMGP, the rate of elastic fibre degradation quantified by desmosine, and hepatic vitamin K status quantified by PIVKA-II were measured. Grade 3 and 4 adverse events were collected daily. As an exploratory objective, circulating vitamin K2 levels were measured. Results: Vitamin K2 was well tolerated and did not increase the number of adverse events. A linear mixed model analysis showed that dp-ucMGP and PIVKA-II decreased significantly in subjects that received supplementation compared to the controls (p = 0.008 and p = 0.0017, respectively), reflecting improved vitamin K status. The decrease in dp-ucMGP correlated with higher plasma MK-7 levels (p = 0.015). No significant effect on desmosine was found (p = 0.545). Conclusions: These results demonstrate that vitamin K2 supplementation during COVID-19 is safe and decreases dp-ucMGP. However, the current dose of vitamin K2 failed to show a protective effect against elastic fibre degradation.

Original languageEnglish
Article number3476
Number of pages14
JournalJournal of Clinical medicine
Volume13
Issue number12
DOIs
Publication statusPublished - Jun 2024

Keywords

  • COVID-19
  • desmosine
  • dp-ucMGP
  • matrix gla protein
  • menaquinone-7
  • vitamin K

Fingerprint

Dive into the research topics of 'Vitamin K2 Supplementation in Hospitalised COVID-19 Patients: A Randomised Controlled Trial'. Together they form a unique fingerprint.

Cite this