Low Vitamin K Intake Impairs Cognition, Neurogenesis, and Elevates Neuroinflammation in C57BL/6 Mice

 Ask your competent? doctor how to eat healthy if on warfarin and can't consume Vitamin K foods.  You do want good cognition and no inflammation, right? That requires a diet protocol and I bet your incompetent doctor doesn't have one for you! 

When taking warfarin, it is crucial to avoid foods that can interact with the medication and affect its effectiveness. Here are some foods to avoid: 

Foods High in Vitamin K: Green leafy vegetables (e.g., spinach, kale, broccoli, collard greens)

• Liver
• Brussels sprouts
• Asparagus
• Cauliflower

Foods Containing Flavonoids: grapefruit juice, green tea, and cranberry juice. Other Foods: alcohol, black licorice, turmeric, avocado, and olive oil

Low Vitamin K Intake Impairs Cognition, Neurogenesis, and Elevates Neuroinflammation in C57BL/6 Mice

Tong Zheng

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https://doi.org/10.1016/j.tjnut.2025.01.023

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Abstract

Background

In addition to its important roles in blood coagulation and bone formation, vitamin K (VK) contributes to brain function. Low dietary VK intake, which is common among older adults, is associated with age-related cognitive impairment.

Objective

To elucidate the biological mechanisms underlying VK’s effects on cognition, we investigated the effects of low VK (LVK) intake on cognition in C57BL/6 mice.

Methods

Male and female 9-month old C57BL/6 mice (n=60) were fed a LVK diet or a control diet for 6 months. Behavioral tests were performed on a subset of animals (n=26) at 15 months and brain tissues were collected for follow-up analyses.

Results

Menaquinone-4 (MK4), the predominant VK form in the brain, was significantly lower in LVK animals compared to controls (15.6±13.3 vs 189±186 pmol/g, respectively, p<0.01). LVK animals showed reduced recognition memory in the novel object test by spending a lower percentage of time exploring the novel object compared to controls (47.45%± 4.17 vs. 58.08%±3.03, p=0.04). They also spent a significantly longer time learning the task of locating the platform in the Morris water maze test. Within the hippocampal dentate gyrus, LVK animals had a significantly lower number of proliferating cells, and fewer newly generated immature neurons compared to control animals. Additionally, more activated microglia cells were identified in the LVK animals.

Conclusion

Our data indicate that LVK intake reduced MK4 levels in brain tissues and impaired learning- and memory-related cognitive function. This impairment may be related to the observed reduced hippocampal neurogenesis and elevated neural inflammation.

Introduction

Within the next decade, it is estimated that there will be more Americans over the age of 65 years than under the age of 18 years [1], and many of these older adults will develop age-related cognitive impairments [2]. Modifiable factors, such as nutrition, have been implicated as important modulators for cognition [3], [4]. Growing evidence has shown that low vitamin K may have a role in age-related cognitive decline [5]. Green leafy vegetables are the main source of phylloquinone (PK), the primary form of dietary vitamin K [6], [7]. Concerningly, most adults do not consume the recommended quantity of these foods, leading to inadequate phylloquinone intake, especially among older adults in the U.S. [8]. Mostly known for its role in blood coagulation, phylloquinone is believed to also have important functions in the nervous system [9], [10]. Through recent and novel stable isotope experiments in rodent models, it has been shown that manipulation of dietary vitamin K causes rapid changes to the concentration of menaquinone-4 (MK4), which is the predominant form of vitamin K in the brain [11]. We also now know that all dietary forms of vitamin K convert to MK4 [12].

Observational data from the Rush Memory and Aging Project (MAP) demonstrated that higher postmortem brain levels of MK4 were associated with better cognitive function proximate to death. Further investigation of neuropathologically-defined outcomes also revealed that higher brain MK4 concentrations were associated with lower global dementia pathology, specifically fewer neurofibrillary tangles [13]. While these findings are encouraging, MK4 in the brain may simply be tracking healthy dietary patterns associated with higher vegetable intakes. Furthermore, the underlying biological mechanisms have yet to be elucidated. Thus, there is a critical need to establish the biological mechanism(s) underlying the cognition-protective effects of vitamin K in an animal model to overcome the limitations of observational data. Given that: 1) inflammation, which is closely associated with aging and neurodegeneration, impairs hippocampal neurogenesis; and 2) age-related cognitive decline is accompanied by reduced neurogenesis in the hippocampus, we propose that vitamin K’s protective effects on cognition and brain resilience may function through maintaining hippocampal neurogenesis and anti-inflammation.

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