Vitamin K levels could help predict COVID-19 mortality, Kappa Bioscience-backed study finds

16 Jun 2021 --- A new Kappa Bioscience-backed study has found low vitamin K status to be predictive of higher mortality for COVID-19. The latest findings suggest that vitamin K could play a role in the disease mechanisms, with vitamin K2 proposed as a potential supplement to help improve outcomes of the disease.

The study also confirmed the results of a previous study that vitamin K status is lower in hospitalized patients with COVID-19 compared to healthy controls.

“I was stunned by the marked differences in levels of the biomarker of vitamin K status between COVID-19 patients and healthy controls, and between those COVID-19 patients that unfortunately died and those who survived,” the study’s lead author, Professor Allan Linneberg, tells NutritionInsight.

While more research is still needed, Kappa Bioscience says these preliminary results highlight vitamin K2’s potential as an inexpensive measure for reducing mortality in COVID-19 patients.

“There is an urgent need for measures to improve the outcome and long-term consequences of COVID-19,” the company states. “Supplementation with vitamin K2 represents an inexpensive and simple-to-use solution. However, intervention studies are needed.”

Kaplan-Meier plot of 30-days cumulated risk of dying, stratified by levels of vitamin K status. Lower dp-uc-MGP levels reflect higher vitamin K status.A stratified predictor of mortality 
The study was conducted at the Center for Clinical Research and Prevention at the Bispebjerg and Frederiksberg Hospital, Denmark, where Linneberg is the director. 

Researchers used a Kaplan-Meier plot of the cumulated risk of death stratified by vitamin K status. They concluded that mortality among COVID-19 patients appears to be strongly dependent on vitamin K status.

Vitamin K status was measured as dephosphorylated-undercarboxylated matrix Gla protein (dp-ucMGP). It was analyzed in 138 COVID-19 patients and compared to a control group of 138 people from the general population, matched for similar age distribution. 

Vitamin K status was significantly lower in COVID-19 patients compared to the control population. Forty-three of the hospitalized patients with COVID-19 died within 90 days of admission. Survival analysis showed that low vitamin K status was associated with higher mortality risk.

The mechanism of action
Linneberg submits the current theory behind the link between COVID-19 death outcomes and vitamin K status: “It is hypothesized that in a state of severe vitamin K deficiency, the supply of vitamin K will be prioritized for the liver to regulate blood clotting.”

“Only then, will the rest of our K supply be distributed to the rest of the body to activate other vitamin K-dependent proteins. These play key roles in regulating blood clotting, calcium metabolism, inflammation and more.”

As a result, this may increase calcification and subsequent degradation of elastic fibers in lung tissue, leading to more severe lung damage in COVID-19 patients, he details. 

Because of their structural differences, vitamin K1 and K2 have different outcomes in the body. Vitamin K1 is preferentially absorbed in the liver, whereas K2 is left available for extrahepatic tissues. 

Previous studies have indicated that vitamin K status plays a role in vascular calcification and that a low status of the vitamin is correlated with arterial stiffness. This suggests that a higher status of the vitamin could lead to more tissue flexibility and elasticity. 

A randomized intervention study is still needed to see if a lack of vitamin K causes poor outcomes in COVID-19 patients.Correlation or causation? 
The study does present some limitations that cannot be ruled out, according to Linneberg. 

“It is a possibility that severely ill patients consume more vitamin K in tissues and that starts a vicious circle.” 

Another limitation is that it also is not possible to rule out that low vitamin K status is a marker of comorbidity, meaning that there are other diseases that predispose to both COVID-19 mortality and low vitamin K status. 

More research needed
While the evidence is mounting that vitamin K can play an important role in improving outcomes, Linneberg stresses that there is currently not enough research on the potential role of vitamin K in COVID-19 to change guidelines for treatment or prevention.

“We need more research before we can advise whether we should treat patients with vitamin K and which patients should be targeted.”

Proper dosage also raises questions. “A lot more is to be learned when it comes to vitamin K. To deliver proof-of-concept evidence, a randomized intervention study is needed to see if it is actually a lack of vitamin K that causes poor outcomes in COVID-19 patients.”

A promising vitamin
Vitamin K2 has gained increased attention over the past few years. In 2020, 14 research papers about vitamin K status and associations to different health conditions and diseases were published, notes Dr. Trygve Bergeland, vice president science at KappaBioscience. 

He also observes there is also an increasing focus on studying a low vitamin K and vitamin D status together. 

“The Hoorn Study and the PREVEND study, published in 2020 concluded that the combined low vitamin D and K status was associated with increased all-cause mortality risk and possibly with cardiovascular mortality and cardiovascular events compared with adequate vitamin D and K status,” he highlights.

Vitamin K2 is underway to be tested in the largest dosage to date with kidney patients on dialysis. The NattoPharma-led study is testing the 1 mg dose to demonstrate product safety, among other health benefits. 

By Missy Green