Vitamin K is one of the 13 essential vitamins. It comes in two naturally occurring forms, K1, and K2. Vitamin K2 has many related forms, which are produced by our cells, or by intestinal bacteria. The MK subtypes of vitamin K2 possess a similar function to K1, but exactly how their mechanisms differ from vitamin K1 are still incompletely understood.1MK-4 is the most prominent vitamin K subtype in the brain.2MK-4 makes up >98% of vitamin K in the brain and is widely distributed, however, the highest concentrations of Vitamin K are in the midbrain, pons, and medulla.
Vitamin K in the Central Nervous System
Vitamin K-dependent processes were discovered in the context of the critical role it plays in blood clotting pathways; however, the role it plays in brain health is beginning to be better understood. In particular, Vitamin K is a cofactor for gamma-glutamyl carboxylase, an enzyme that is involved in activating a variety of other proteins, including those responsible for blood clotting and sphingolipid synthesis. Sphingolipids are a class of lipid molecules present in neuron and glial cell membranes. Sphingolipids play crucial roles in cell structure and are involved in signaling processes that regulate cell proliferation, differentiation, and senescence.
Aside from sphingolipid-related proteins, vitamin K is also an essential co-factor for other neuro-relevant proteins such as Gas6, and Protein S. Gas6 has been is neuroprotective, and promotes cell survival in a variety of contexts – including nutrient deprivation, and amyloid-beta-induced apoptosis. Gas6 also seems to play a role in the myelination process. Myelin being the lipid sheaths that cover neurons and are critical for neural firing and signal propagation. Protein S is less well-understood in the brain but is involved in the coagulation process. Two studies have shown that Protein S deficient mice are more susceptible to neural damage, both from chemical agents and from hypoxic injury.
Vitamin K Studies in Humans
Double-blind, placebo-controlled studies of vitamin K intervention with cognitive outcomes are lacking. However, warfarin and some other clotting inhibitors are potent vitamin K antagonists, so these populations have been investigated for cognitive function. Additionally, correlational studies have been carried out – measuring the correlation between serum levels of vitamin K subtypes and cognitive tests.
One study of 320 healthy men and women between 60 and 75 years of age found that higher levels of vitamin K1 were associated with improved performance on tests of verbal episodic memory. Another study of 7133, cognitively normal individuals over 65 found that vitamin K antagonist treatment to be associated with worse performance on visual memory tests and verbal fluency tests. However, the population taking vitamin K antagonists did not have a faster rate of cognitive decline than the rest of the population or deficiencies on the mini-mental state examination. Another longitudinal study of 599 Dutch individuals aged 55-65 years old, found no association between serum vitamin K levels and cognitive decline.