SCIENCE ALERT: Vitamin K insufficiency associated with cognitive dysfunction in older adults (Front. Nutr)

Editor's Note

Vitamin K is a fat-soluble vitamin that exists in two forms, vitamin K1 (phylloquinone) and K2 (menaquinone), which are found in vegetables and in bacteria and fermented foods respectively. Several mechanisms of action have been reported, and epidemiological studies reveal that vitamin K status is associated with aging-related diseases, including osteoporosis and osteoarthritis. There are also some epidemiological studies on the relationship between vitamin K status and cognitive impairment; in these studies, vitamin K status was estimated by food-frequency questionnaires, measurement of dephosphorylated uncarboxylated MGP (dp-ucMGP), or direct measurement of vitamin K concentration by High Performance Liquid Chromatography (HPLC), all of which require relatively specialized methods which may limit translation of these findings into clinical settings.

Osteocalcin (OC) is a protein used as a biomarker for vitamin K insufficiency; concentration of undercarboxylated form of OC (ucOC) in serum is reported to be positively correlated with risk and is used as the indicator of vitamin K treatment for osteoporosis in several countries including Japan. The measurement of ucOC is commercially available in relatively low cost compared with other methods. The authors here report a cross-sectional study in which the association of ucOC concentration with cognitive function is examined. A total of 800 people (mean age = 75.9) were recruited into a follow-up study of the baseline examinations previously conducted.

The study demonstrates the association of vitamin K insufficiency, as evaluated by serum ucOC, with cognitive impairment in the community-dwelling older adult population. The researchers report that this is the first study focused on the significant association of single ucOC measurement and cognitive impairment and suggest that vitamin K insufficiency could be associated with selected categories of cognitive function. Although validation in independent studies will be required, these findings support the hypothesis that vitamin K has important roles in specific areas of brain responsible for several categories of functions and should promote future studies of vitamin K on a higher brain function including basic studies and clinical intervention studies.

January 2022

Frontiers in Nutrition

DOI: h ttps://doi.org/10.3389/fnut.2021.811831

Association of Vitamin K Insufficiency With Cognitive Dysfunction in Community-Dwelling Older Adults

Introduction

Vitamin K is a fat-soluble vitamin originally discovered as an essential factor in blood coagulation. Naturally existing vitamin K compounds are classified into two forms, namely vitamin K1 (phylloquinone) and K2 (menaquinone). Vitamin K1 is abundant in vegetables (1), while vitamin K2 is generated by bacteria and is contained in fermented foods (2, 3). For example, Japanese fermented soybeans (called “natto”) contain high concentrations of vitamin K2 (2). It is also known that the intestinal microbiome is another important source of vitamin K2 production (4).

Functions of vitamin K can be explained by facilitating γ-carboxylation of some proteins, including coagulation factors, osteocalcin (OC), and matrix Gla protein (MGP), which are catalyzed by γ-glutamyl carboxylase (GGCX) (5). To date, other modes of vitamin K actions have been discovered, such as regulation of transcription by activating steroid and xenobiotic receptor (SXR) (6), physical association with 17β-Hydroxysteroid dehydrogenase type 4 (17β-HSD4) (7), and covalent modification of Bcl-2 antagonist killer 1 (Bak) (8).

Of note, several epidemiological studies revealed that vitamin K status is associated with aging-related diseases, including osteoporosis (9) and osteoarthritis (10). Meanwhile, there is a small number of epidemiological studies on the relationship between vitamin K status and cognitive impairment (11–17). In these epidemiological studies, vitamin K status was estimated by food-frequency questionnaires, measurement of dephosphorylated uncarboxylated MGP (dp-ucMGP), or direct measurement of vitamin K concentration by High Performance Liquid Chromatography (HPLC), which will require relatively special methods and/or facilities and may limit translation of these findings into clinical settings.

Osteocalcin (OC) is a protein produced and carboxylated by GGCX in the presence of vitamin K in osteoblastic cells. The concentration of undercarboxylated form of OC (ucOC) in serum is reported to be positively correlated with a fracture risk (18). Furthermore, a high ucOC concentration is used as a biomarker for vitamin K insufficiency for the bone tissue, and as the indicator of vitamin K treatment for osteoporosis in several countries including Japan. The measurement of ucOC is commercially available in relatively low cost compared with other methods, estimating vitamin K sufficiency. Here, we report a cross-sectional study in which the association of ucOC concentration with cognitive function is examined.