How newly discovered vitamin K mechanism could have broad implications for treating diseases

Vitamin K has been widely used to reverse severe bleeding from overuse of the blood thinner warfarin. But how vitamin K is processed into a reduced, clotting-promoting form was unclear.

Now, an international team of scientists led by Germany’s Helmholtz Munich has identified the enzyme performing that task and along the way showed that vitamin K could suppress a type of cell death called ferroptosis, which is marked by oxidative disruptions to lipid that makes up cellular membranes.

The findings, published in Nature, could have broader implications, the researchers said. That’s because ferroptosis has been implicated in degenerative diseases like Alzheimer’s disease, acute organ injuries and treatment-resistant cancer.

Back in 2019, the current study’s senior author, Marcus Conrad, led a team to identify an enzyme they called ferroptosis suppressor protein 1 (FSP1) as a potent inhibitor of ferroptosis.

In the new study, Conrad and colleagues showed in mice that vitamin K could protect tissues from ferroptosis with a little help from FSP1.

In mouse models of ferroptosis in the liver or kidney, the researchers showed that vitamin K suppressed ferroptosis, reduced infiltration of inflammatory cells and therefore protected against tissue damage.

Turns out, FSP1 could help reduce vitamin K to a form called vitamin K hydroquinone, or VKH2, which acts as an antioxidant to trap harmful atoms, preventing them from destructing the lipids in cell membranes, the team found.

Warfarin busts blood clotting by inhibiting a clot-promoting pathway of VKH2. Because additional VKH2 is the reason why vitamin K supplementation can relieve warfarin poisoning, the researchers wondered if FSP1 is the enzyme that’s responsible for reducing vitamin K to VKH2 when the main pathway is blocked.

Indeed, mice with their FSP1 gene removed suffered from severe bleeding after warfarin overdose despite treatment with vitamin K, whereas animals with one F2P1 gene could be rescued by vitamin K.

Findings from the study could offer insights beyond the molecular mechanism of vitamin K as the antidote for warfarin overdose. They will “serve as the stepping stone for the development of novel therapeutic strategies for diseases where ferroptosis has been implicated,” Conrad said in a statement.

This isn’t the first case where vitamin supplements were found to have therapeutic potential. Recently, researchers from Indiana University School of Medicine found niacin, or vitamin B3, could activate the HCAR2 receptor in the brain, leading to reduced protein plaques and improved cognition in mice.

Because ferroptosis can cause ischemia-reperfusion injury, damage resulting from blood supply returning to tissue after ischemia, vitamin K could serve as a potent means to stave off the problem in people at high risk of ischemia, two researchers from Moffitt Cancer Center suggested in a commentary alongside the current study.