Vitamin K deficiency linked to reduced neurogenesis and cognitive decline in mouse model

A study on mice found that a low intake of vitamin K reduces its concentration in brain tissue and impairs cognitive functions related to learning and memory. The researchers also observed reduced production of new neurons in the hippocampus and elevated neural inflammation. The findings were published in The Journal of Nutrition.

Vitamin K is a fat-soluble vitamin essential for blood clotting. It activates proteins that enable blood to coagulate properly. Without adequate vitamin K, even minor injuries can result in excessive bleeding. Vitamin K also contributes to bone health by regulating calcium deposition and supporting bone mineralization.

There are two main forms of this vitamin: vitamin K1 (phylloquinone), found primarily in leafy green vegetables, and vitamin K2 (menaquinone), which includes several subtypes produced by gut bacteria and found in fermented foods and animal products. The predominant form of vitamin K in the brain is menaquinone-4, a subtype of vitamin K2. Adequate intake of vitamin K has also been linked to a lower risk of osteoporosis and cardiovascular disease.

Study author Tong Zheng and his colleagues noted that previous research found higher concentrations of menaquinone-4 in the brains of deceased individuals who had better cognitive function prior to death. Other studies have associated greater brain levels of menaquinone-4 with fewer symptoms of dementia. With this background, the researchers aimed to investigate how vitamin K deficiency might affect cognitive function in mice.

The study involved sixty 9-month-old C57BL/6 mice, a widely used inbred laboratory strain known for its genetic consistency and sensitivity to dietary and metabolic changes. These characteristics make it a suitable model for nutritional neuroscience research.

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The mice were randomly assigned to one of two groups. One group received a control diet containing the recommended amount of vitamin K1 (1 mg/kg), while the other group received a diet low in vitamin K (80 μg/kg). Both diets were based on a vitamin K-deficient basal mix and did not include menadione, a synthetic precursor of vitamin K that is sometimes used in animal feed but is not permitted in human diets due to safety concerns.

The mice were kept on these diets for six months. After this period, a subset of the animals underwent two behavioral tests: the Morris water maze (to assess spatial learning and memory) and the novel object recognition test (to measure recognition memory). Two weeks after the behavioral assessments, the mice were euthanized, and their brain tissues were analyzed for vitamin K content and markers of neurogenesis in the hippocampus.

The researchers reported that more mice died in the low vitamin K group than in the control group, particularly males, and some displayed signs of visual impairment. Behavioral testing revealed that mice fed the vitamin-K-deficient diet had poorer recognition memory and required more time to learn the spatial task in the water maze, indicating cognitive deficits.

Examination of the hippocampus showed that the low vitamin K group had significantly fewer proliferating cells and immature neurons compared to the control group, suggesting reduced neurogenesis. Additionally, these mice exhibited increased signs of neuroinflammation, including changes in microglial morphology, indicating a shift toward a more activated, inflammatory state. Brain tissue analysis confirmed that menaquinone-4 concentrations were significantly lower in the vitamin-K-deficient group.

“Our data indicate that low vitamin K intake reduced menaquinone-4 concentrations 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,” the study authors concluded.

The study sheds light on the effects vitamin K deficiency has on cognitive functioning and brain physiology. However, it should be noted that this was a study on mice, not on humans. While mice and humans share many physiological similarities, they are still very different species. Effects on humans might not be identical.

The paper “Low Vitamin K Intake Impairs Cognition, Neurogenesis, and Elevates Neuroinflammation in C57BL/6 Mice” was authored by Tong Zheng, Shannon Marschall, Jasper Weinberg, Xueyan Fu, Andrew Tarr, Barbara Shukitt-Hale, and Sarah L Booth.