As Impressive as the Mountain: Vitamin K2 Proves Valuable for Boosting Brain Health, Impeding Inflammation, and Managing Mood

First discovered in the 1930s, vitamin K’s name was derived from the German word “koagulation,” reflecting its ability to clot blood. But we now know that vitamin K does so much more than coagulate — especially one form of the nutrient, vitamin K2. One of the most important roles of vitamin K2 is inhibiting calcium from settling in areas it shouldn’t, like blood vessels and kidneys, where calcification is not a good thing. Instead, vitamin K2 helps shuttle calcium to where it needs to be: the bones and teeth.  

Now, researchers out of AlMaarefa University in Saudi Arabia show that vitamin K2 also supports brain health, cognition, and mood — in aged rats, at least. Published in the journal Antioxidants, El-Sherbiny and colleagues find that supplemental vitamin K2 fights back on age-related changes to the brain, including reduced mood problems, better memory and learning, and dampened neuroinflammation and oxidative stress. With this research, vitamin K2 may soon be added to the list of natural and effective compounds for supporting cognition in the aging brain.

Vitamin K2’s Peak Performance 

Vitamin K2 is a collection of compounds known as menaquinones, with the most vital forms being MK-4 and MK-7. MK-4 is found only in certain animal foods, while MK-7 is more abundant in fermented foods because bacteria synthesize it. While we can convert vitamin K1 into MK-4, efficient conversion is low and varies individually — therefore, we need dietary sources of vitamin K2. 

Although vitamin K1 is readily available in the food supply, as it’s found widely in leafy green vegetables, dietary vitamin K2 is a little harder to find. The top two vitamin K2-rich foods are liver and a traditional Japanese dish made of fermented soybeans called natto — both of which are not commonly consumed dishes in the American diet. Other lesser-containing vitamin K2 foods include egg yolks, grass-fed butter, dark meat chicken, and some hard cheeses like Jarlsberg, Swiss, and Münster. 

Natto, a vitamin K2-rich Japanese dish made of fermented soybeans

In the brain, vitamin K2 exhibits potent antioxidant properties, promotes a healthier inflammatory response, and reduces apoptosis, a type of controlled and programmed cell death — in this case, neurons. Vitamin K2 also plays a vital role in the creation and metabolism of sphingolipids, a type of fat highly concentrated in brain cell membranes. Sphingolipids participate in several critical cellular events, like the growth, maturation, and survival of neurons, which is why sphingolipid dysfunctions are linked to cognitive disorders. 

Benefitting Behavior, Managing Memory, and Mastering Mood

In this study, El-Sherbiny and colleagues tested the cognitive and behavioral effects of vitamin K2 in the form of MK-7. The research team supplemented 3-month-old rats with vitamin K2 five days per week for 17 months, until they reached 20 months (approximately 60 to 65 human years). In a test monitoring anxious symptoms, aged rats who received vitamin K2 exhibited more social and less anxious behavior than the untreated aged rats. The supplemented rats also displayed fewer depressive symptoms, as seen during a forced swim test in which more swimming in the water indicates healthier moods and motivation. 

Vitamin K2 also improved memory scores in a maze test, which measures exploratory behavior and willingness to investigate a novel environment. In this test, rats are placed at the bottom of a “T” shape and given a choice between entering the left or right arms. In the second, third, and future trials, the rats should show less tendency to enter the same area, indicating memory of the past visits and an inclination for novelty. This test relies on many brain regions, including the hippocampus — the area most responsible for maintaining memory and learning abilities. The K2-supplemented rats displayed a significantly greater percentage of “correct” (novel) choices than the untreated aged rats. 

As the authors state in their paper, “The current results confirmed the incidence of [anxious], depressive-like behaviors, and memory deterioration in the aged untreated rats. However, these behavioral changes were attenuated by [vitamin] K2 administration.”

Vitamin K2 Kicks Inflammation and Oxidative Stress to the Curb

The Saudi team also analyzed how vitamin K2 affected biomarkers and structural changes inside the brain. The aged control rats showed markedly elevated levels of oxidative stress in the hippocampus and low levels of two vital antioxidants. Conversely, vitamin K2 effectively restored this impaired antioxidant versus oxidant balance. 

Vitamin K2 also activated Nrf-2, a compound that promotes antioxidant defense to protect cells in the central nervous system. In the aged rats, vitamin K2 increased Nrf-2 activity in the hippocampus and cerebral cortex (the brain region responsible for our highest mental capabilities) by 23-fold and 6-fold, respectively. 

With Nrf-2 activation comes an inhibition of the “inflammasome,” a complex that triggers apoptosis and the release of more pro-inflammatory cytokines. Vitamin K2 significantly dampened these inflammasome contributors, while control rats’ markers kept climbing. Along these lines, hippocampal inflammation was significantly higher in control animals, while vitamin K2-treated rats suppressed inflammatory markers. 

Lastly, supplemental vitamin K2 reduced the buildup of degenerated neurons seen in the aged control rats and promoted the expression of tyrosine, an amino acid that helps preserve cognitive function. The aged control rats showed a reduction in brain levels of tyrosine hydroxylase — the enzyme responsible for converting tyrosine into dopamine, the primary neurotransmitter acting on our pleasure and reward centers. Altered dopamine signaling is a hallmark of the aging brain, profoundly impacting cognitive function. 

Reaching New Peaks with Vitamin K2

With the rates of memory loss and cognitive disorders continually rising alongside the population of older adults, it’s more vital than ever to uncover novel yet simple strategies to preserving cognition with age — and this research points to the brain-related benefits of vitamin K2. Although natto and liver aren’t foods at the top of most Americans’ grocery lists, supplemental vitamin K2 is relatively easy to find and may benefit both your bones and brain. These benefits can be enhanced even further when combined with vitamin D, as these two vitamins work synergistically. As a side note, people taking blood thinners and certain other medications need to avoid vitamin K supplements, as the vitamin significantly alters the effects of these drugs. 

As Mohamed El-Sherbiny, Ph.D., the study’s senior author, concludes, “Vitamin K2 demonstrated [a] very promising impact in hindering aging-related behavioral, functional, biochemical and histopathological changes in the senile aging brain. Vitamin K2 can be proposed to be a promising approach to attenuate age-related disorders and preserve cognitive functions in aging individuals.”

References: 

Elkattawy HA, Ghoneim FM, Eladl MA, et al. Antioxidants (Basel). 2022;11(3):514. Published 2022 Mar 8.