Vitamin K deficiency pegged as “potential missing link” in COVID-19 pathogenesis

08 Oct 2020 --- A new Kappa Bioscience-funded study review has positioned vitamin K metabolism as the “potential missing link” between lung damage and thromboembolism – two of the most serious outcomes observed in COVID-19 patients.

The research team proposed that pneumonia-induced vitamin K depletion leads to a decrease in activated Matrix Gla protein (MGP) and protein S, aggravating pulmonary damage and coagulopathy, respectively.

“This kind of discovery is extremely important. We intend to take responsibility in increasing general understanding around the importance of vitamin K. We contacted the scientific team and offered to support further research,” Tryvge Bergeland, vice president of science at Kappa Bioscience tells NutritionInsight.

Lead co-author Dr. Rob Janssen from the Department of Pulmonary Health at the Canisius Wilhelmina Hospital in Nijmegen, The Netherlands, tells NutritionInsight that he and his colleagues were “very surprised” to find severely reduced vitamin K status in COVID-19 patients.

“When I first brought plasma samples of our COVID-19 patients to [the School for Cardiovascular Disease] CARIM in Maastricht, I would have expected that vitamin K levels were reduced, but the severity of the deficiency surprised me.” 

“It is important to perform high quality intervention studies to assess the role of vitamin K in treating and preventing severe COVID-19,” says Dr. Janssen.“Furthermore, I found it surprising that activation of factor II by vitamin K in the liver – stimulator of clotting – was hardly affected, whereas activation of MGP in lungs and blood vessels was severely compromised. There is a specific deficiency in COVID-19 patients outside the liver, whereas vitamin K status in the liver is hardly compromised,” he flags.

Pairing vitamin D with K
The study findings of severe vitamin K deficiency in COVID-19 patients may also impact the vitamin D sector, says Dr. Janssen.

Many experts have called for vitamin D supplementation to be added to help fight against COVID-19. However, this new study review points to “conflicting” research results.

The review found that vitamin D administration in a state of vitamin K deficiency may endanger pulmonary and vascular health. Its supplementation has been associated with premature mortality in vitamin K-insufficient stable kidney transplant recipients. 

“Unfortunately, it is not generally appreciated that vitamin D may exacerbate vitamin K deficiency,” notes Dr. Janssen. “Particularly in COVID-19 patients who are already vitamin K deficient, high-dose vitamin D supplementation may further deplete vitamin K stores.”

“It may therefore be prudent to first supplement vitamin K in invariably vitamin K-insufficient COVID-19-hospitalized patients and to start vitamin D supplementation in those who are vitamin D-deficient only when extrahepatic vitamin K status has been restored,” the review reads. 

Dr. Janssen, therefore, advises individuals who do not use vitamin K supplements as anticoagulant medications and are using vitamin D supplementation to combine vitamin D with K. Bergeland notes: “This study raises the important point that co-supplementation with vitamin K2 along vitamin D might be more beneficial.”

Industry has been catching on the trend of pairing the two vitamins. US-based Arthur Andrew Medical has unveiled KD Ultra, a dietary supplement combining vitamin D3 with the “most absorbable” full spectrum blend of vitamin K2. 

Infographic adapted by Kappa Bioscience.Kappa Bioscience, manufacturer of K2 MK-7, highlighted in previous research how D3 and K2 function more effectively in the presence of the other. 

Future research prospects
Whereas vitamin D status assessment is generally available, vitamin K status assessment is rarely performed. Moreover, there are very few laboratories that have an assay to quantify vitamin K status. Bergeland further adds that vitamin K1 deficiency is extremely rare and vitamin K2 deficiency, even if common, does not result in immediate symptoms.

These are some of the main reasons that have led to the role of vitamin K in fighting COVID-19 going “largely unexplored.”

“Medical doctors and researchers associate vitamin K only as an activator of clot-promoting factors in the liver. They usually don’t realize that vitamin K also activates other proteins, such as MGP in lungs that protect against lung damage and protein S in the blood vessel walls that protect against thrombosis,” Dr. Janssen explains.

He also stresses that reported false claims that vitamin K increases thrombosis risk are bound to prevent the widespread use of the vitamin.

The study authors consequently identify a need for further experimental evidence to link vitamin K deficiency with the pathology of COVID-19. They also hope to determine whether vitamin K supplementation has a place in treatment protocols. 

Notably, in April, better vitamin K status in patients with COVID-19 was linked to improved health outcomes, compared to patients with poor vitamin K status.

At the moment, Kappa Bioscience is now initiating scientific collaborations in Europe and the US to generate more data and increase our understanding on this “extremely important topic,” concludes Bergeland.

By Anni Schleicher

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