OTTAWA, Ontario — An international team has found a surprising new benefit of consuming vitamin K — a nutrient in leafy greens. Not only is it important in blood clotting, but a new study reveals vitamin K prevents cell death.
According to Harvard’s School of Public Health, vitamin K comes in two forms. The main type is phylloquinone, which is found in green leafy vegetables like collard greens, kale, and spinach. The other type is menaquinones, which is found in some animal and fermented foods. It can also be produced by bacteria in the human body.
Researchers from Helmholtz Munich, Tohoku University, University of Ottawa, and Technical University of Dresden discovered the fully reduced form of vitamin K acts as an antioxidant that inhibits ferroptotic cell death. Researchers say ferroptosis “is a natural form of cell death in which cellular iron pays an important role and which is characterized by the oxidative destruction of cellular membranes.” Recently, ferroptosis has been found as a driver of Alzheimer’s and other degenerative diseases.
Scientists solve a 50-year-old mystery
Researchers also solved a puzzle that has stumped many for more than 50 years. They were able to identify ferroptosis suppressor protein-1 (FSP1) as the warfarin-insensitive enzyme that’s reducing vitamin K.
“Surprisingly, we identified that vitamin K, including phylloquinone (vitamin K1) and menaquinone-4 (vitamin K2), is able to efficiently rescue cells and tissues from undergoing ferroptosis,” says Dr. Eikan Mishima, the study’s first author, in a university release.
For the study, researchers examined a number of naturally occurring vitamins, as well as their derivatives. They were able to identify new molecules that showed how vitamin K suppresses ferroptosis.
In 2019, researchers identified the enzyme FSP1 as a novel and strong inhibitor of ferroptosis. They were able to show that FSP1 broke down the chemical compound coenzyme Q10 into a fully reduced form called hydroquinone, which suppressed ferroptosis. Now, researchers discovered that the fully reduced form of vitamin K is a strong lipophilic antioxidant and stops ferroptosis by trapping free radicals.
“The reduced forms of vitamin K and coenzyme Q10 are not very stable, so our finding that FSP1 can maintain them in their active (reduced) state is key to understanding how they are able to function to maintain cell viability,” notes study co-author Derek Pratt, the University Research Chair in Free Radical Chemistry at the University of Ottawa.
Vitamin K a ‘stepping stone’ for anti-aging treatments?
Researchers also identified that FSP1 is the enzyme that reduces vitamin K to vitamin K hydroquinone. Because of this, it drives a novel non-canonical vitamin K cycle.
The team’s research established a breakthrough in understanding the metabolism in vitamin K. They now understand the molecular mechanism of why vitamin K constitutes the antidote for overdosing of warfarin.
“Our results therefore link the two worlds of ferroptosis research and vitamin K biology. They will serve as the stepping stone of the development of novel therapeutic strategies for diseases where ferroptosis has been implicated,” explains Dr. Marcus Conrad, from the Institute of Metabolism and Cell Death at Helmholtz Munich. “Thus, new aspects of the role of vitamin K throughout the evolution of life are expected to be unveiled.”
The study is published in the journal Nature.
