Low vitamin K intake impairs cognition, neurogenesis and elevates neuroinflammation in C57BL/6 mice

Authors: ZHENG, TONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MARSCHALL, SHANNON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WEINBERG, JASPER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; FU, XUEYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; TARR, ANDREW - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Shukitt Hale, Barbara; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2025
Publication Date: 1/28/2025
Citation: Zheng, T., Marschall, S., Weinberg, J., Fu, X., Tarr, A., Shukitt Hale, B., Booth, S. 2025. Low vitamin K intake impairs cognition, neurogenesis and elevates neuroinflammation in C57BL/6 mice. Journal of Nutrition. https://doi.org/10.1016/j.tjnut.2025.01.023.
DOI: https://doi.org/10.1016/j.tjnut.2025.01.023

Interpretive Summary: Vitamin K (VK) has important roles in blood coagulation and bone formation, but recently has been shown to be important to brain function as well. Low dietary VK intake, which is common among older adults, is associated with age-related impairments in cognition. This study investigated the effects of low VK (LVK) intake on brain function and cognition in mice. Male and female 9-month old mice were fed a LVK diet or a control diet for 6 months. As expected, the predominant VK form in the brain was significantly lower in LVK animals compared to controls. Low VK intake also led to impairments in recognition memory, a lower number of new brain cells being generated, and increased inflammation in the brain. These results show that it is important to have sufficient dietary levels of vitamin K to protect brain function and cognition.

Technical 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. Objectives: To elucidate the cellular and molecular mechanisms underlying VK’s effects on cognition, we investigated the effects of low VK (LVK) intake on cognition in C57BL/6J mice. Methods: Male and female 9-month old C57BL6 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 also showed reduced recognition memory in the novel object test by spending less percent of time exploring the novel object compared to controls (47.45%± 4.17 vs. 58.08%±3.03, p=0.04). 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.