Vitamin K Properties in Stroke and Alzheimer's Disease: A Janus Bifrons in Protection and Prevention

Abstract

Vitamin K is essential for many physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Vitamin K vitamers are represented by lipophilic compounds with similar chemical structure (i.e., phylloquinone (vitamin K1) and menaquinone (vitamin K2)). Vitamin K deficiency can affect coagulation and vascular calcification, increasing the risk of hemorrhages, atherosclerosis, cerebrovascular diseases, and neurodegeneration. Recently, several studies have hypothesized a possible dual role of vitamin K vitamers in benefiting both vascular and cerebral health, e.g., by sphingolipids biosynthesis or ferroptosis inhibition. The aim of this narrative review is to deepen the understanding of biological activities of vitamin K and its possible dual protective/preventive actions in neurovascular and degenerative conditions, e.g., stroke and dementia. Given the difficulties related to hemorrhagic risk entailed in the prevention of strokes, the function of vitamin K antagonists is also investigated. Finally, we track the development of a clinical concept for a future preventive strategy and innovative use of vitamin K as a supplement to counteract neurovascular and pathological processes, focusing in particular on stroke and dementia.

Keywords: Alzheimer’s disease; amyloid B; biological activity; coagulation; neurodegeneration; stroke; vascular calcification; vitamin K.

Figure 1

Chemical structure of Vit K vitamers: phylloquinone or Vit K1 (A) and menaquinone-n (MKn) and Vit K2 (B) with menaquinone-3 3D structure (Bond color scheme: gray, carbon-carbon bonds; white, carbon-hydrogen; red, carbon-oxygen) (C) (National Center for Biotechnology Information (2025). PubChem Compound Summary for CID 5280483). (D) Carboxylation catalysis of Matrix Gla Protein. Integral membrane protein gamma-glutamyl carboxylase (GGCX) uses oxygen, carbon dioxide, and the reduced form of Vit K as cofactors to catalyze the subtraction of the gamma-hydrogen of glutamate residues and the addition of a carboxyl group. Chemical energy for the carboxylation is extracted from the oxidation of Vit K to Vit K epoxide [34]. (This image was created with BioRender.com (https://www.biorender.com/ accessed on 10 January 2025).

Figure 2

Vit K vitamer food sources and effects on the cerebrovascular system. Dietary sources of menaquinone and phylloquinone are meat and dairy products and vegetables, respectively. Menaquinone can also be synthesized internally by certain genera of intestinal bacteria in the microbiota. Vit K vitamers influence cerebrovascular health through promotion of vascular health, preventing vascular calcification, thrombosis, and atherosclerosis. Reduction in these conditions results in decreased risk of stroke and thus protection of brain function and health. (This image was created with BioRender.com (https://www.biorender.com/ accessed on 10 January 2025).