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All Studies   All Outcomes    Recent:   

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

Visser et al., Journal of Clinical Medicine, doi:10.3390/jcm13123476, KOVIT, NCT04770740
Jun 2024  
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Mortality -200% Improvement Relative Risk ICU admission -200% Hospitalization time 17% Vitamin K  KOVIT  LATE TREATMENT  DB RCT Is late treatment with vitamin K beneficial for COVID-19? Double-blind RCT 40 patients in Netherlands Shorter hospitalization with vitamin K (not stat. sig., p=0.52) Visser et al., J. Clinical Medicine, Jun 2024 Favorsvitamin K Favorscontrol 0 0.5 1 1.5 2+
RCT 40 hospitalized COVID-19 patients showing vitamin K2 supplementation was well-tolerated and reduced dp-ucMGP levels, reflecting improved vitamin K status, but did not affect desmosine, a marker of elastic fiber degradation. The study was not powered to assess effects on clinical outcomes. Authors suggest that the dose may have been insufficient to fully correct the vitamin K deficiency seen in COVID-19, and that higher doses might be required to achieve potential protective effects against inflammation or lung damage.
risk of death, 200.0% higher, RR 3.00, p = 1.00, treatment 1 of 20 (5.0%), control 0 of 20 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).
risk of ICU admission, 200.0% higher, RR 3.00, p = 0.60, treatment 3 of 20 (15.0%), control 1 of 20 (5.0%).
hospitalization time, 16.7% lower, relative time 0.83, p = 0.52, treatment median 5.0 IQR 6.0 n=20, control median 6.0 IQR 7.0 n=20.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Visser et al., 14 Jun 2024, Double Blind Randomized Controlled Trial, placebo-controlled, Netherlands, peer-reviewed, 10 authors, trial NCT04770740 (history) (KOVIT).
This PaperVitamin KAll
Vitamin K2 Supplementation in Hospitalised COVID-19 Patients: A Randomised Controlled Trial
Margot P J Visser, Anton S M Dofferhoff, Jody M W Va Den Ouwelan, Pim A De Jong, Piet Zanen, Henny Van Daal, Eline B Theeuwen, Cornelis Kramers, Rob Janssen, Jona Walk
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.
Institutional Review Board Statement: The study was approved by the ethical review board CMO Arnhem-Nijmegen on the 15th of February 2021 (NL74583.091.20). The local review committee of the Canisius-Wilhelmina Hospital approved the protocol (CWZ-nr. 107-2021). This trial is registered at, identifier NCT04770740. Informed Consent Statement: Informed consent was obtained from all 40 participants involved in the study. Conflicts of Interest: R.J. discloses the application of a patent on vitamin K in COVID-19 that is held by Emphysema Solutions Bv of which R.J. and J.W. are owners. M.P.J.V., J.W., R.J. and A.S.M.D. had a scientific collaboration with Kappa Bioscience A.S., which is a manufacturer of vitamin K2 (MK-7). R.J. and J.M.W.O. are owners of H.D., P.A.J., P.Z., E.B.T. and C.K. declare no competing interests. Abbreviations COVID-19: Coronavirus Disease 2019; dp-uc, desphospho-uncarboxylated; MGP, matrix gla protein; SARS-CoV, severe acute respiratory syndrome coronavirus; MK-7, menaquinone-7; PIVKA-II, protein induced by vitamin K absence or antagonist-II; PCR, Polymerase Chain Reaction; LMWH, low-molecular-weight heparin; eCRF, electronic Case Report Form; SMC, Safety Monitoring Committee; IL-6, interleukin-6; CT, Computed Tomography; LC-MS/MS, liquid chromatography with tandem mass spectrometry; ITT, intention to treat; AIC, Akaike's Information Criterion; BMI, Body Mass Index; ICU, Intensive Care Unit.
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Late treatment
is less effective
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