Vitamin K deficiency link to worse COVID-19 outcomes: researchers eager for next steps
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 has recently been published by The Preprints.org. 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.
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 desphospho-uncarboxylated matrix Gla-protein levels (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, in subjects with COVID-19, dp-ucMGP levels were significantly and positively correlated with desmosine levels, a measure of the breakdown of elastin, which is an important factor for pulmonary health.
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. While inspired by the results of the study, its 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,” they reported. “Vitamin K status was reduced in COVID-19 patients compared to controls and was associated with disease severity. 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,” they concluded.
“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. Matrix Gla protein (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. A three-year clinical study of healthy postmenopausal women showed that 180mcg of MenaQ7 Vitamin K2 as MK-7 daily resulted in not only cessation,2 but remarkably regression in arterial stiffness (i.e., their arteries became more flexible) in the MenaQ7 group through MGP activation,” says Dr. Katarzyna Maresz, president of the International Science and Health Foundation. “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, thus showing a significant correlation between reduced vitamin K status and accelerated elastic fiber degradation. It has to be tested now whether improving vitamin K status would correspond with better prognosis in SARS-CoV-2-infected individuals,” she emphasizes.
- Dofferhoff AS, Piscaer I, Schurgers LJ, Walk J, van den Ouweland JM, Hackeng TM, Lux P, Maassen C, Karssemeijer EG, Wouters EF, 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).
- 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.