Vitamines K, bon pour le cerveau des seniors?

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Exploratory analysis of covariation of microbiota-derived vitamin K and cognition in older adults
Angela McCann The American Journal of Clinical Nutrition, Volume 110, Issue 6, December 2019, Pages 1404–1415,

Background
Vitamin K has multiple important physiological roles, including blood coagulation and beneficial effects on myelin integrity in the brain. Some intestinal microbes possess the genes to produce vitamin K in the form of menaquinone (MK). MK appears in higher concentration in tissues, such as the brain, particularly MK4, than the dietary form of phylloquinone (PK). Lower PK concentrations have been reported in patients with Alzheimer disease while higher serum PK concentrations have been positively associated with verbal episodic memory. Despite knowledge of the importance of vitamin K for various health parameters, few studies have measured MK concentration and biosynthesis by gut commensals.

Objective
The aim of the current study was to investigate the relation between genes involved in gut-microbiota derived MK, concentrations of MK isoforms, and cognitive function.

Methods
Shotgun metagenomic sequencing of the gut microbiome of 74 elderly individuals with different cognitive ability levels was performed. From this, gene counts for microbial MK biosynthesis were determined. Associations between clusters of individuals, grouped based on a similar presence and prevalence of MK biosynthesis genes, and cognitive ability were investigated. Fecal MK concentrations were quantified by HPLC to investigate correlations with subject clusters.

Results
Separation of subject groups defined by banded quantification of the genetic potential of their microbiome to biosynthesize MK was associated with significant differences in cognitive ability [assessed using the Mini-Mental State Examination (MMSE)]. Three MK isoforms were found to be positively associated with MMSE, along with the identification of key components of the MK pathway that drive this association. Although the causality and direction of these associations remain unknown, these findings justify further studies.

Conclusions
This study provides evidence that although total concentrations of MK did not covary with cognition, certain MK isoforms synthesized by the gut microbiome, particularly the longer chains, are positively associated with cognition.

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Vitamin K2 (Menaquinone-7) Reverses Age-Related Structural and Cognitive Deterioration in Naturally Aging Rats
by Hany A. Elkattawy Antioxidants 2022, 11(3), 514;

Aging is a naturally occurring process inevitably affecting each living human. The brain is adversely affected by aging with increased risks of developing various neurological disorders. Thus, it is essential to investigate practical approaches that can counteract the impact of aging on the brain.

Vitamin K2 (Vit. K2) is a naturally occurring vitamin with reported valuable therapeutic effects. The current study highlights the role of Vit. K2 administration in counteracting age-related changes in the brain using naturally aging rats. Three-month-old rats were assigned to two groups: an ageing control group receiving a drug vehicle and an ageing group orally gavaged with Vit. K2 (30 mg/kg, once daily 5 days per week). Treatment was continued for 17 months. Ten three-month-old rats were used as the adult control.

Vit. K2 improved functional performance, reduced social anxiety, depressive-like behavior, and enhanced memory performance with concomitant preservation of hippocampal and cerebral cortex tyrosine hydroxylase expression. Biochemically, Vit. K2 administration restored oxidative-anti-oxidative homeostasis in the brain. Vit. K2 modulated inflammatory signaling, as evidenced by suppression in the brain of NLRP3, caspase-1, Il-1β, TNFα, IL-6, and CD68 expression. Concomitantly, histopathological examination revealed consistent hippocampal and cerebral cortex improvement.

Thus, it can be inferred that Vit K2 can slow down age-related changes in the brain associated with modulation of NLRP3/caspase-1/Nrf-2 signaling.

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Traduction de l'étude

La vitamine K2 (ménaquinone-7) inverse la détérioration structurelle et cognitive liée à l'âge chez les rats naturellement vieillissants
par Hany A. Elkattawy Antioxydants 2022, 11(3), 514 ;

Le vieillissement est un processus naturel qui affecte inévitablement chaque être humain vivant. Le cerveau est affecté par le vieillissement avec des risques accrus de développer divers troubles neurologiques. Ainsi, il est essentiel d'étudier des approches pratiques qui peuvent contrecarrer l'impact du vieillissement sur le cerveau.

La vitamine K2 (Vit. K2) est une vitamine naturelle avec des effets thérapeutiques précieux rapportés. L'étude actuelle met en évidence le rôle de Vit. Administration de K2 pour contrecarrer les changements liés à l'âge dans le cerveau en utilisant des rats vieillissants naturellement. Des rats âgés de trois mois ont été répartis en deux groupes : un groupe témoin vieillissant recevant un véhicule de médicament et un groupe vieillissant gavé oralement avec de la Vit. K2 (30 mg/kg, une fois par jour 5 jours par semaine). Le traitement a été poursuivi pendant 17 mois. Dix rats âgés de trois mois ont été utilisés comme contrôle adulte.

Vit. K2 a amélioré les performances fonctionnelles, réduit l'anxiété sociale, le comportement de type dépressif et amélioré les performances de la mémoire avec la préservation concomitante de l'expression de la tyrosine hydroxylase de l'hippocampe et du cortex cérébral. Biochimiquement, Vit. L'administration de K2 a restauré l'homéostasie oxydative-antioxydante dans le cerveau. Vit. Signalisation inflammatoire modulée par K2, comme en témoigne la suppression dans le cerveau de l'expression de NLRP3, caspase-1, Il-1β, TNFα, IL-6 et CD68. Parallèlement, l'examen histopathologique a révélé une amélioration constante du cortex hippocampique et cérébral.

Ainsi, on peut en déduire que la Vit K2 peut ralentir les changements liés à l'âge dans le cerveau associés à la modulation de la signalisation NLRP3/caspase-1/Nrf-2.

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Association of Vitamin K Insufficiency With Cognitive Dysfunction in Community-Dwelling Older Adults
Kotaro Azuma Front Nutr. 2022 Jan 31;8:811831.

Vitamin K is a fat-soluble vitamin shown to be associated with several age-related diseases. Although a small number of epidemiological studies described the relationship between vitamin K status and cognitive impairment, vitamin K status was estimated by relatively special methods in previous reports. Here, we demonstrated the association of the concentration of undercarboxylated osteocalcin (ucOC) in serum, which is a biomarker for vitamin K insufficiency, with cognitive function in a cross-sectional study.

A total of 800 community-dwelling older adults (mean age = 75.9) were invited to geriatric health examination, including a Mini-Mental State Examination (MMSE) and a blood test. By using binary logistic regression analysis, the risk of cognitive impairment equivalent or below the mild cognitive impairment level for each tertile of ucOC was examined, with the lowest tertile as the reference.

We found a significant association of 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. As far as we know, this is the first report on the significant association of single ucOC measurement and cognitive impairment.

Our analysis also suggests that vitamin K insufficiency could be associated with selected categories of cognitive function. Since the single measurement of ucOC in serum is a simple and widely available method for vitamin K evaluation, it could be useful as a biomarker of neurodegenerative diseases affecting the cognitive functions.

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Vitamin K dietary intake is associated with cognitive function in an older adult Mediterranean population
Lucía Camacho-Barcia, Age and Ageing, Volume 51, Issue 2, February 2022,

Background
In the last years, evidence that dietary vitamin K could have a role in the cognitive domain has increased. However, data from large trials are limited. The objective of this study was to assess the association of 2 year changes in the dietary intake of vitamin K with cognitive function measured through neuropsychological performance tests.

Methods
In 5,533 participants of the multicentre PREDIMED-Plus study (48.1% women, age 65.1 ± 4.9 years with overweight/obesity and metabolic syndrome), we assessed the adjusted odds ratios of cognitive function decline according to 2 year changes in vitamin K intake. Participants answered a battery of cognitive function tests and Food Frequency Questionnaires (FFQs) in order to estimate the vitamin K dietary intake.

Results
After adjusting for potential cofounders, the highest tertile of change of dietary vitamin K intake (median [IQR]; 194.4 μg/d [120.9, 373.1]) was inversely associated with a Mini-Mental State Examination (MMSE) score ≤24 (OR [95% CI]; 0.53 [0.35, 0.79] P for trend = 0.002) compared with a decrease in the intake of vitamin K (median [IQR]; −97.8 μg/d [−292.8, −51.5]). A significant positive association between changes in dietary vitamin K intake and the semantic verbal fluency test scores (OR [95% CI]; 0.69 [0.51, 0.94] P for trend = 0.019) was found.

Conclusions
An increase of the intake of dietary vitamin K was associated with better cognitive function scores, independently of recognised risk factors for cognitive decline, in an older adult Mediterranean population with high cardiovascular risk.

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Traduction de l'étude

L'apport alimentaire en vitamine K est associé à la fonction cognitive dans une population méditerranéenne âgée
Lucía Camacho-Barcia, Âge et vieillissement, volume 51, numéro 2, février 2022,

Arrière-plan
Au cours des dernières années, les preuves que la vitamine K alimentaire pourrait jouer un rôle dans le domaine cognitif se sont multipliées. Cependant, les données des grands essais sont limitées. L'objectif de cette étude était d'évaluer l'association des changements de 2 ans dans l'apport alimentaire en vitamine K avec la fonction cognitive mesurée par des tests de performance neuropsychologiques.

Méthodes
Chez 5 533 participants à l'étude multicentrique PREDIMED-Plus (48,1 % de femmes, âgées de 65,1  ± 4,9 ans présentant un surpoids/obésité et un syndrome métabolique), nous avons évalué les rapports de cotes ajustés du déclin de la fonction cognitive en fonction des changements sur 2 ans de l'apport en vitamine K. Les participants ont répondu à une batterie de tests de fonctions cognitives et de questionnaires de fréquence alimentaire (FFQ) afin d'estimer l'apport alimentaire en vitamine K.

Résultats
Après ajustement pour les cofondateurs potentiels, le tertile le plus élevé de variation de l'apport alimentaire en vitamine K (médiane [IQR] ; 194,4 μg/j [120,9, 373,1]) était inversement associé à un score au Mini-Mental State Examination (MMSE) ≤ 24 (OR [IC95%] ; 0,53 [0,35, 0,79] P pour trend = 0,002) comparé à une diminution des apports en vitamine K (médiane [IQR] ; −97,8 μg/j [−292,8, −51,5]). Une association positive significative entre les modifications de l'apport alimentaire en vitamine K et les scores du test de fluidité verbale sémantique (OR [IC à 95 %] ; 0,69 [0,51, 0,94] P pour la tendance = 0,019) a été trouvée.

conclusion
Une augmentation de l'apport en vitamine K alimentaire a été associée à de meilleurs scores de fonction cognitive, indépendamment des facteurs de risque reconnus de déclin cognitif, dans une population méditerranéenne âgée à haut risque cardiovasculaire.

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Association of Dietary Vitamin K Intake With Cognition in the Elderly
Anni Wang Front. Nutr., 23 June 2022

Several previous studies discussed the association between vitamin K (VK) status and cognition. But the association between dietary VK consumption and cognitive performance in the elderly was not well understood. Therefore, we investigated the correlation between dietary VK intake and the cognition of the elderly. Our research used the data of the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. The dietary intake of VK was assessed by two 24-h dietary recalls. The cognitive function was measured in the survey of NHANES, including the Consortium to Establish a Registry for Alzheimer’s disease Word Learning subtest (CERAD W-L), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Logistic regression and restricted cubic spline models were applied to assess the relationship between dietary VK intake and cognition. Compared with the lowest dietary VK intake group, the multivariate-adjusted odds ratio (OR) [95% confidence interval (95% CI)] of low CERAD W-L score for the highest intake group was 0.39 (0.26–0.60), the multivariate-adjusted OR (95% CI) of low AFT score was 0.59 (0.38–0.92), and the multivariate-adjusted OR (95% CI) of low DSST score was 0.44 (0.29–0.65), respectively.

There was an L-shaped dose–response relationship between dietary VK intake and low CERAD W-L score. There was a linear dose–response relationship between dietary VK intake and low AFT score, and there was also a linear dose–response relationship for the low DSST score. In addition, we also found a negative association between VK from vegetables and the risk of low CERAD W-L scores.

Dietary VK intake and VK intake from vegetables were inversely related to the risk of low cognitive performance of the elderly.

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Vitamin K status and inflammation are associated with cognition in older Irish adults
A Kiely Nutr Neurosci. 2020 Aug;23(8):591-599.

Studies have shown associations between reduced vitamin K status and poor cognitive function. However, despite this apparent link, direct studies measuring cognitive function, vitamin K status and inflammation are lacking. In the current study, The ELDERMET cohort was investigated to identify associations between cognition, vitamin K status and inflammation. The primary aim of the ELDERMET study was to investigate the relationship between gut bacteria, diet, lifestyle and health in 500 older Irish adults. Significant differences in serum phylloquinone, dietary phylloquinone and inflammatory markers were found across varying levels of cognitive function, after controlling for sex, age, body mass index (BMI), triglycerides and blood pressure. In addition, significantly higher levels of dietary phylloquinone were found in those with better cognition compared to those with the poorest function. Higher levels of inflammatory were also associated with poor cognition. Furthermore, both dietary and serum phylloquinone were significant independent predictors of good cognitive function, after controlling for confounders.

This study highlights the importance of dietary vitamin K as a potentially protective cognitive factor; it also provides evidence for the correlation between cognition and inflammation. Strategies should be devised by which elderly populations can access rich dietary sources of phylloquinone to maintain cognition.

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Traduction de l'étude

Le statut en vitamine K et l'inflammation sont associés à la cognition chez les adultes irlandais âgés
Un Kiely Nutr Neurosci. 2020 août ;23(8):591-599.

Des études ont montré des associations entre un statut réduit en vitamine K et une mauvaise fonction cognitive. Cependant, malgré ce lien apparent, les études directes mesurant la fonction cognitive, le statut en vitamine K et l'inflammation font défaut. Dans la présente étude, la cohorte ELDERMET a été étudiée pour identifier les associations entre la cognition, le statut en vitamine K et l'inflammation. L'objectif principal de l'étude ELDERMET était d'étudier la relation entre les bactéries intestinales, l'alimentation, le mode de vie et la santé chez 500 adultes irlandais âgés. Des différences significatives dans la phylloquinone sérique, la phylloquinone alimentaire et les marqueurs inflammatoires ont été trouvées à différents niveaux de fonction cognitive, après contrôle du sexe, de l'âge, de l'indice de masse corporelle (IMC), des triglycérides et de la pression artérielle. De plus, des niveaux significativement plus élevés de phylloquinone alimentaire ont été trouvés chez les personnes ayant une meilleure cognition par rapport à celles dont la fonction est la plus faible. Des niveaux plus élevés d'inflammation étaient également associés à une mauvaise cognition. De plus, la phylloquinone alimentaire et sérique étaient des prédicteurs indépendants significatifs d'une bonne fonction cognitive, après contrôle des facteurs de confusion.

Cette étude met en évidence l'importance de la vitamine K alimentaire comme facteur cognitif potentiellement protecteur ; il fournit également des preuves de la corrélation entre la cognition et l'inflammation. Des stratégies devraient être élaborées par lesquelles les populations âgées peuvent accéder à des sources alimentaires riches en phylloquinone pour maintenir la cognition.