Preprints.org has published a new paper examining the link between outcomes in patients with COVID-19 and low vitamin K status compared to patients with better vitamin K status and healthy controls. The study also demonstrates a link to COVID-19 patients that had other conditions such as cardiovascular diseases, which are linked to low vitamin K status, including a breakdown of tissue fibers as measured by elastin, which is involved with pulmonary disease.
One key factor in this study is the measurement of vitamin K status determined by the amount of the “inactive” vitamin K-dependent protein, desphospho-uncarboxylated Matrix Gla Protein (dp-ucMGP). Dp-ucMGP is inversely related to vitamin K status. NattoPharma, the leading vitamin K2 company, has promoted research on the benefits of supplemental vitamin K2 activating vitamin K-dependent proteins, including MGP, and validating these benefits for cardiovascular and bone health for more than 16 years, resulting in 19 published human studies with MenaQ7® Vitamin K2. Vitamin K2 is the most bioactive form of vitamin K in the activation of MGP and vitamin K-dependent proteins.
Vitamin K2 supplementation promoting active MGP for cardiovascular health is validated, including in a 3-year study with healthy postmenopausal women. In this trial using NattoPharma’s MenaQ7® Vitamin K2, arterial flexibility was maintained or even improved. This has put forward the hypothesis that adequate vitamin K status in heart health may improve outcomes.
Researchers from Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands, Maastricht University Medical Center+ and Cardiovascular Research Institute Maastricht (CARIM), The Netherlands, conducted the study. NattoPharma has maintained a long-time relationship with Maastricht University conducting and participating in many studies on vitamin K2 as well as with other institutions.
“The study represents an amazing finding,” explains Prof. Leon Schurgers, Professor of Biochemistry of Vascular Calcification and Vice Chair of Biochemistry at the Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, and co-author of the study. “While we do not suggest vitamin K2 is a treatment for COVID-19, this study illustrates that a poor vitamin K status – deduced from high dp-ucMGP levels – is linked to poor prognosis. Thus, hypothesizing that improving vitamin K2 status is linked to better health outcomes including cardiovascular, and perhaps even lung health.”
COVID-19 is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-COV-2), and while most patients have mild symptoms, a significant number develops respiratory failure. COVID-19 may also progress beyond the lungs including coagulopathy, a condition in which the blood’s ability to coagulate (form clots) is impaired, and thromboembolism, an obstruction of a blood vessel by a blood clot that has become dislodged from another site in the circulation. Coagulation is an intricate balance between clot promoting and dissolving processes in which vitamin K plays a well-known role. Further, it has been previously suggested for chronic obstructive pulmonary disease (COPD) that accelerated use of vitamin K stores in the body may also be a potential reason for vitamin K deficiency in patients with severe COVID-19.
In this study, Vitamin K status was evaluated in 123 patients with COVID-19 and 184 controls. Results of the study found that dp-ucMGP were significantly higher in COVID-19 patients compared to controls, and dp-ucMGP levels were significantly higher in COVID-19 patients with unfavorable outcomes compared to those with less severe disease (good outcome) – all pointing towards a link between vitamin K deficiency and disease severity. Also, low dp-ucMGP levels were significantly correlated with desmosine levels, a measure of the breakdown of elastin, which is an important factor for pulmonary health.
Vitamin K status was assessed by measuring the “inactive status” of the vitamin K-dependent MGP, a recognized indicator related to vitamin K status, and the rate of elastin degradation was assessed by measuring desmosine, a recognized marker. In this study, a significant correlation between reduced vitamin K status and accelerated elastic fiber degradation was shown.
The researchers found that deficiency of vitamin K might be suspected to be associated with worse COVID-19 outcomes, given that patients with severe COVID-19 are more likely to have comorbidities such as type 2 diabetes, hypertension, and cardiovascular diseases, which are associated with reduced vitamin K status.
According to NattoPharma Chief Medical Officer Dr. Hogne Vik, “Supplementation of vitamin K increases the vitamin K status in the body as measured by the level of active vitamin K-dependent proteins, and vitamin K2 is clearly the best form of vitamin K due to its superior bioactivity. MGP is the most potent known inhibitor of vascular calcification to date. MGP is a K-dependent protein already present in the body, but it needs adequate vitamin K2 to be activated to perform its function. Our three-year clinical study of healthy postmenopausal women showed that 180mcg of MenaQ7 Vitamin K2 as MK-7 daily resulted in not only cessation, but remarkably regression in arterial stiffness (i.e., their arteries became more flexible) in the MenaQ7 group through MGP activation.”
According to the study, vitamin K-dependent MGP is generally accepted as an inhibitor of vascular calcification, and there are scientific leads suggesting that MGP also plays a role in the pathogenesis of lung fibrosis. MGP is crucial for the protection of elastic fibers against mineralization and fibrosis may be present in lungs of patients with severe COVID-19.
The study concludes that Vitamin K status was reduced in patients with COVID-19 and related to poor prognosis. Importantly, vitamin K levels were significantly lower in COVID-19 patients compared to healthy controls, as has been shown in patients with comorbidities. Also, low vitamin K status seems to be associated with accelerated elastin degradation. In conclusion, vitamin K status was reduced in COVID-19 patients compared to controls and was associated with disease severity.
While inspired by the results, the study authors remain cautious and eager for next steps: “It might be tempting to speculate that vitamin K administration has an improving effect on vitamin K status in severe COVID-19 patients; however, this has never been studied in this patient group. Additionally, whether improving vitamin K status would correlate with better prognosis in SARS-CoV-2-infected individuals has to be tested,” they write. “Preliminary evidence was provided suggesting a potential mechanistic link between reduced vitamin K status and accelerated tissue degradation. An intervention trial is now needed to assess whether vitamin K administration improves outcome in patients with COVID-19.”
1 Dofferhoff, A.S.; Piscaer, I.; Schurgers, L.J.; Walk, J.; van den Ouweland, J.M.; Hackeng, T.M.; Lux, P.; Maassen, C.; Karssemeijer, E.G.; Wouters, E.F.; Janssen, R. Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19. Preprints 2020, 2020040457 (doi: 10.20944/preprints202004.0457.v1).
2 Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost. 2015 May;113(5):1135-44. Doi: 10.1160/TH14-08-0675.
3 Cranenburg EC, Koos R, Schurgers LJ, Magdeleyns EJ, Schoonbrood TH, Landewe RB, Brandenburg VM, Bekers O, Vermeer C. Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species. Thromb Haemost. 2010;104(4):811-22. Doi: 10.1160/TH09-11-0786.
4 Cranenburg EC, Vermeer C, Koos R, Boumans ML, Hackeng TM, Bouwman FG, Kwaijtaal M, Brandenburg VM, Ketteler M, Schurgers LJ. The Circulating Inactive Form of Matrix Gla Protein (ucMGP) as a Biomarker for Cardiovascular Calcification. J Vasc Res 2008;45:427-436. Doi: 10:1159/000124863