Association of Vitamin K Insufficiency With Cognitive Dysfunction in Community-Dwelling Older Adults (Azuma K et al.)

The Frontiers in Nutrition journal has recently reported on the findings of a Japanese cross-sectional epidemiological study whose authors demonstrated the association of the concentration of undercarboxylated osteocalcin (ucOC) in serum, which is a biomarker for vitamin K insufficiency, with cognitive impairment among seniors. Previous epidemiological studies revealed that vitamin K status is linked to aging-related diseases, like osteoporosis and osteoarthritis. However, new epidemiological studies also demonstrate the relationship between vitamin K status and cognitive decline.

With a growing elderly population, the prevalence of neurodegenerative disorders is continuously increasing. Vitamin K has been recognized to play a significant role in cognitive health during aging. Some mechanisms of action of vitamin K that can support brain function include the following: activation of vitamin K-dependent proteins, a modulatory role in brain function and sphingolipid metabolism, inhibition of inflammation, and oxidative injury.

For this study, the researchers enrolled a group of 800 community-dwelling older Japanese adults (mean age = 75.9). After conducting geriatric health examination, including a Mini-Mental State Examination (MMSE) and a blood test, they found a significant association between impaired cognitive function and concentration of ucOC in the highest tertile of ucOC, with the odds ratio of 1.65 (95% CI, 1.06 to 2.59, P = 0.028). When the analysis was repeated with each domain of MMSE, the highest tertile of ucOC was associated with impaired orientation, calculation, and language.

The authors emphasized the fact that the single measurement of ucOC in serum is a simple, relatively inexpensive, and widely available method for vitamin K evaluation, and therefore it could be useful as a biomarker of neurodegenerative diseases affecting the cognitive functions. In their opinion, these findings can be a clue to generating the hypothesis that vitamin K has important roles in specific areas of the brain responsible for several categories of functions.

The analysis presented in the Japanese study is in line with increasing evidence suggesting that vitamin K insufficiency could be associated with cognitive impairment and that dietary interventions have the potential to protect against cognitive decline during aging.

The PREDIMED-Plus trial, which has recently been described in the Age and Ageing journal, aimed to assess the association of two-year changes in the dietary intake of vitamin K with cognitive function measured through neuropsychological performance tests. To that end, the researchers assessed the adjusted odds ratios of cognitive function decline according to two-year changes in vitamin K intake in 5,533 participants of the multicenter PREDIMED-Plus study (48.1% women, age 65.1 ± 4.9 years with overweight/obesity and metabolic syndrome). Participants answered a battery of cognitive function tests and Food Frequency Questionnaires (FFQs) to estimate their vitamin K dietary intake.

The results showed that a higher increase in vitamin K dietary intake was associated with a better cognitive function assessed by the MMSE test in an adult high cardiovascular risk population followed for two years. A significant positive association between changes in dietary vitamin K intake and the semantic verbal fluency test scores was also found.

The authors arrived at a conclusion that ”[…] increased intake of dietary vitamin K is associated with better cognitive function scores, independently of traditional risk factors for cognitive decline, in an older adult Mediterranean population.”

“Mild cognitive impairment (MCI) is a result of impaired cognitive function beyond the normal decline observed during the aging process. The research indicates, on one hand, that up to a third of cases of MCI develop into dementia, and, on the other, that vitamin K2 might positively affect many factors which will influence the progress of MCI such as cardiovascular diseases, insulin resistance and glucose metabolism, inflammation, and oxidative stress,” explains Dr. Katarzyna Maresz, president of the International Science and Health Foundation. “There are a lot of studies that showed that a specific K2 as MK-7, MenaQ7, improves vitamin K status in kids and adults. These noteworthy papers clearly demonstrate the large potential of vitamin K2 supplementation to improve brain development in kids and support brain function in adults and seniors.

“Although MK-4 is the main form of vitamin K in the brain, it is important to mention that supplementation with MK-7 increases MK-4 content in the brain tissue according to in vivo research,” Dr. Maresz emphasizes.


  1. Azuma K, Osuka Y, Kojima N, Sasai H, Kim H, Inoue S. Association of Vitamin K Insufficiency With Cognitive Dysfunction in Community-Dwelling Older Adults. Front Nutr. 2022 Jan 31;8:811831. doi: 10.3389/fnut.2021.811831
  2. Camacho-Barcia L, García-Gavilán J, Martínez-González MÁ, Fernández-Aranda F, Galié S, Corella D, Cuenca-Royo A, Romaguera D, Vioque J, Alonso-Gómez ÁM, Wärnberg J, Martínez JA, Serra-Majem L, Estruch R, Bernal-López MR, Lapetra J, Pintó X, Tur JA, Garcia-Rios A, Bueno-Cavanillas A, Delgado-Rodríguez M, Matía-Martín P, Daimiel L, Martín-Sánchez V, Vidal J, Vázquez C, Ros E, Canela MR, Sorlí JV, de la Torre R, Konieczna J, Oncina-Cánovas A, Tojal-Sierra L, Pérez-López J, Abete I, Sánchez-Villegas A, Casas R, Muñoz-Garach A, Santos-Lozano JM, Bouzas C, Razquin C, Martínez-Lacruz R, Castañer O, Yañez AM, Valls-Enguix R, Belló-Mora MC, Basterra-Gortari J, Basora J, Salas-Salvadó J, Bulló M. Vitamin K dietary intake is associated with cognitive function in an older adult Mediterranean population. Age Ageing. 2022 Feb 2;51(2):afab246. doi: 10.1093/ageing/afab246
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