No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Vitamin K status and cognitive function in healthy older adults
... The current analytical sample is based on an embedded subsample of 461 participants who underwent 2 cognitive testing sessions over a 4-y period as part of the Nutrition and Cognition (NutCog) substudy of NuAge. This substudy included participants aged 70-86 y, with a Modified Mini-Mental State (3MS) (24) score of >85/100 at baseline in 2006-2008 (NutCog T1) (25). For the purpose of the current study, 36 participants were removed due to the presence of self-reported conditions that may impair cognition (i.e., dementia, Parkinson disease, epilepsy, history of stroke) (25), and 39 were removed due to missing data on fatty acid concentrations (Figure 1). ...
... This substudy included participants aged 70-86 y, with a Modified Mini-Mental State (3MS) (24) score of >85/100 at baseline in 2006-2008 (NutCog T1) (25). For the purpose of the current study, 36 participants were removed due to the presence of self-reported conditions that may impair cognition (i.e., dementia, Parkinson disease, epilepsy, history of stroke) (25), and 39 were removed due to missing data on fatty acid concentrations (Figure 1). Accordingly, the final analytical sample included 386 participants. ...
... Trained research assistants administered a neuropsychological test battery to all NutCog participants between 3 mo prior to blood sampling and 2 mo following blood sampling (25). Six tests were administered, including the RL/RI-16 Free and Cued Recall Task (RL/RI-16 FCRT) (28), the Rey Complex Figure Test (29), the Stroop Color and Word Test (30), the Adapted Brown-Peterson Test (31), the Choice Reaction Time Test (32), and the Digit Symbol-Coding subtest of the Adult Intelligence Scale-III (33). ...
Background
Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are suggested to play a role in the prevention of cognitive decline. The evidence may be inconsistent due to methodological issues including interrelations with other long-chain (14 or more carbons) fatty acids (LCFAs) and use of sex as a confounding factor rather than an effect modifier.
Objective
This study evaluated the association between serum n-3 PUFAs and performance across four cognitive domains, overall and by sex, while controlling for other LCFAs.
Methods
386 healthy older adults (77.4 ± 3.8 years; 53% females) from the Québec Longitudinal Study on Nutrition and Successful Aging underwent a cognitive evaluation and blood sampling. Verbal and non-verbal episodic memory, executive functioning, and processing speed were evaluated. Serum LCFA concentrations were measured by gas chromatography. LCFAs were grouped according to standard fatty acid classes and according to a factor analysis using principal component analysis (FA-PCA). Multivariate linear regression models were performed, including unadjusted and adjusted models for other LCFAs.
Results
Higher n-3 PUFA concentrations were associated with better non-verbal memory and processing speed in fully adjusted models not including other LCFAs (betas of 0.21 and 0.19, respectively). The magnitude of these associations varied when other LCFAs were entered in the model (betas of 0.27 and 0.32, respectively) or when FA-PCA factors were considered (betas of 0.27 and 0.21, respectively). Associations with verbal episodic memory were limited to higher concentrations of eicosapentaenoic acid whereas there was no association between n-3 PUFAs and executive functioning. Higher n-3 PUFAs were associated with better verbal and non-verbal episodic memory in females, and with better executive functioning and processing speed in males.
Conclusions
These results suggest that other LCFAs should be considered when evaluating the association between n-3 PUFAs and cognitive performance in healthy older adults. Sex differences across cognitive domains warrant further investigation.
... Several nutrients (6)(7)(8), foods (9,10), and overall diet quality (11)(12)(13) have been related to cognition. Yet, limited consideration was given to dairy products and their plausible direct and indirect (eg, via improved functions, such as vascular (14)) influence in modulating cognitive function. ...
... and low-fat dairy product consumption (Wilks' λ = 0.995, F = 2.66 (12, 15398), p = .001) as determinants of executive functions remained unchanged in the fully adjusted models, and for yogurt as a determinant of memory (Wilks' λ = 0.998, F = 2.20 (6,11636), p = .040). Also, as an example, total dairy intake frequency remained significantly associated with executive functions when replacing the diet quality score with fruits and vegetables intake, and whole grains (Wilks λ = 0.995, F = 2.46 (12,15578), p = .003). ...
... Indeed, we also observed positive and independent associations of total fermented dairy intake, that is, cheese and yogurt, with the executive function domain before adjustment for diet quality. Mechanisms of action through which fermented dairy products may improve cognition could involve bioactive peptides that may increase brain dopamine levels (46) and through their high content in vitamin K2 that may contribute to higher vitamin K status (47), related to better memory (6). ...
Background
Dairy products provide essential nutrients such as calcium, vitamins B12 and D, and include bioactive peptides and fermented products, which may be beneficial for cognition, especially in older adults. Yet, few studies of large contemporary cohorts have investigated this relationship using sensitive domain-specific cognitive tests.
Methods
In community-dwelling older adults of the Canadian Longitudinal Study on Aging (2011-2015), we examined cross-sectional associations between total and specific dairy product intake and performance in three cognitive domains (executive functions, memory, psychomotor speed). Cheese, milk, yogurt, regular-fat, low-fat and fermented dairy product intake frequencies were estimated using a food frequency questionnaire; participants were classified into quartiles. MANCOVA models were applied to estimate differences.
Results
In 7,945 participants (65-86 y, 49% women, 97% Caucasian), the mean dairy product intake was 1.9 (1.1) times/d. Total dairy product, cheese and low-fat dairy product intake were positively associated with the executive function domain and yogurt intake with the memory domain (all p<0.05), independently of important covariates including age, gender, education and diet quality. Intakes of total dairy product, cheese and low-fat dairy were associated with verbal fluency specifically (all p<0.05). Participants with a dairy product intake > 2.5 times/d had a higher score compared to those consuming less. No associations were found with psychomotor speed.
Conclusions
This large cohort study suggests a specific role for dairy components in executive function phonemic verbal fluency and memory. Dairy product intake, a modifiable factor, may be targeted in cognitive health-promoting interventions.
... In the last five years, clinical observational studies have started investigating the impact of vitamin K on cognitive functions [14][15][16]. An increase in the dietary vitamin K intake has been shown to improve cognitive performance in geriatric patients [14,15]. is is confirmed by the fact that a decrease in serum concentrations of vitamin K is associated with deterioration in verbal episodic memory [16]. ...
... In the last five years, clinical observational studies have started investigating the impact of vitamin K on cognitive functions [14][15][16]. An increase in the dietary vitamin K intake has been shown to improve cognitive performance in geriatric patients [14,15]. is is confirmed by the fact that a decrease in serum concentrations of vitamin K is associated with deterioration in verbal episodic memory [16]. A case control study conducted by our group on the relationship between vitamin K and the percentage of time in therapeutic range (TTR%) confirmed that subjects with low vitamin K1 plasmatic concentrations (below 0.060 μg/ L) were more likely to show signs of neurodegenerative diseases [17]. ...
... e role of vitamin K in coagulation processes has been extensively studied and characterised [29]. Recent studies have suggested that the vitamin may also play a key role in cognitive performance [13][14][15][16]. Studies on animal models have suggested that vitamin K may be involved in memory consolidation. ...
Objectives:
Recent studies have suggested that vitamin K may exert significant effects on the central nervous system. The present study investigates the relationship between vitamin K plasmatic levels and cognitive functions in elderly patients on oral anticoagulant therapy (OAT).
Design:
At the Thrombosis Centre of Haematology, "Sapienza" University of Rome, 85 patients on OAT, aged between 75 and 92, were randomly enrolled in the study. Patients were on OAT with vitamin K antagonists (VKAs). Vitamin K1 concentrations were determined using standardized High-Performance Liquid Chromatography (HPLC). Cognitive functions were assessed using the Milan Overall Dementia Assessment (MODA).
Results:
MODA scores are positively correlated to vitamin K1 concentration. Patients with vitamin K1 below 0.100 μg/L and between 0.100 and 0.400 μg/L and between 0.100 and 0.400 μg/L and between 0.100 and 0.400 p < 0.001). Even long-term OAT (>10 years) does not affect MODA scores. Education seems to exert a greater role on the cognitive status in comparison with aging.
Conclusions:
The study shows a positive association between vitamin K1 concentration and cognitive status in elderly patients (≥75 years) on OAT. The relationship between vitamin K1 concentration and MODA scores is described by a linear model. Cognitive status is not influenced by the duration of OAT but by the years of education.
... NutCog T1 cognitive assessments were conducted in 2006-2008, 2-3 months preceding or proceeding the closest annual NuAge evaluation (i.e., either NuAge T3 or T4); and NutCog T2 assessments were conducted at 2-year follow up from NutCog T1 in 2008-2010. Of the 461 NutCog participants, 36 were excluded due to the presence of self-reported conditions that may impair cognition (i.e., dementia, Parkinson disease, epilepsy, and history of stroke), and 39 were removed due to missing data on circulating CVRF biomarker concentrations (Presse et al., 2013;Duchaine et al., 2022). Accordingly, the analytic sample comprised 386 participants at NutCog T1, of which 321 participants were evaluated at NutCog T2 (16.8% attrition). ...
... Serum TC, HDL-C, and TG concentrations were analyzed by the Center hospitalier de l'Université de Montreal clinical biochemistry laboratory using COBAS C-311 platform and TRIGL, CHOL2 and HDLC3 kits (Roche Diagnostic Corp. Indianapolis, IN, United States; Presse et al., 2013). LDL-C was obtained using the Friedewald equation: ...
Introduction: Cardiovascular disease risk factors (CVRFs) contribute to the development of cognitive impairment and dementia.
Methods: This study examined the associations between circulating CVRF biomarkers and cognition in 386 cognitively healthy older adults (mean age = 78 ± 4 years, 53% females) selected from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). Memory, executive function, and processing speed were assessed at baseline and 2-year follow-up. CVRF biomarkers included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, glucose, insulin, high sensitivity C-reactive protein (hs-CRP), homocysteine, protein carbonyls, and cortisol. Linear mixed models were used to determine associations between individual CVRF biomarkers and cognition at both time points.
Results: HDL-C was most consistently associated with cognition with higher values related to better performance across several domains. Overall, stronger and more consistent relationships between CVRF biomarkers and cognition were observed in females relative to males.
Discussion: Findings suggest that increases in the majority of circulating CVRFs are not associated with worse cognition in cognitively healthy older adults.
... Compounds ZINC000085950180 and ZINC000085511995 are composed of two naphthoquinones each in their structures. High levels of vitamin K has been shown to improve cognitive function and its deficiency may be associated with an increased risk of cognitive decline and dementia in older adults [122,123]. ...
... Serotonin and tryptophan, which are beneficial in digestive regulation, sleep cycle and improved mood, also have the indole moiety [48,49,53,55]. Moreover, vitamin K, a naphthoquinone derivative, has been reported to improve cognitive function [122,123]. The identified chemical series are worthy of further experimental testing to ascertain their potency for extensive medicinal chemistry and biological characterization. ...
Altered RNA editing has been linked to several neurodevelopmental disorders, including autism spectrum disorder (ASD) and intellectual disability, in addition to depression, schizophrenia, some cancers, viral infections and autoimmune disorders. The human ADAR2 is a potential therapeutic target for managing these various disorders due to its crucial role in adenosine to inosine editing. This study applied consensus scoring to rank potential ADAR2 inhibitors after performing molecular docking with AutoDock Vina and Glide (Maestro), using a library of 35,161 compounds obtained from traditional Chinese medicine. A total of 47 compounds were predicted to be good binders of the human ADAR2 and had insignificant toxicity concerns. Molecular dynamics (MD) simulations, including the molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) procedure, also emphasized the binding of the shortlisted compounds. The potential compounds had plausible binding free energies ranging from −81.304 to −1068.26 kJ/mol from the MM/PBSA calculations. ZINC000085511995, a naphthoquinone had more negative binding free energy (−1068.26 kJ/mol) than inositol hexakisphosphate (IHP) [−873.873 kJ/mol], an agonist and a strong binder of ADAR2. The potential displacement of IHP by ZINC000085511995 in the IHP binding site of ADAR2 could be explored for possible deactivation of ADAR2. Bayesian-based biological activity prediction corroborates the neuropharmacological, antineoplastic and antiviral activity of the potential lead compounds. All the potential lead compounds, except ZINC000014612330 and ZINC000013462928, were predicted to be inhibitors of various deaminases. The potential lead compounds also had probability of activity (Pa) > 0.442 and probability of inactivity (Pi) < 0.116 values for treating acute neurologic disorders, except for ZINC000085996580 and ZINC000013462928. Pursuing these compounds for their anti-ADAR2 activities holds a promising future, especially against neurological disorders, some cancers and viral infections caused by RNA viruses. Molecular interaction, hydrogen bond and per-residue decomposition analyses predicted Arg400, Arg401, Lys519, Trp687, Glu689, and Lys690 as hot-spot residues in the ADAR2 IHP binding site. Most of the top compounds were observed to have naphthoquinone, indole, furanocoumarin or benzofuran moieties. Serotonin and tryptophan, which are beneficial in digestive regulation, improving sleep cycle and mood, are indole derivatives. These chemical series may have the potential to treat neurological disorders, prion diseases, some cancers, specific viral infections, metabolic disorders and eating disorders through the disruption of ADAR2 pathways. A total of nine potential lead compounds were shortlisted as plausible modulators of ADAR2.
... a group of people 65 and older. In specific, Presse et al. [91] presented the findings of a cross-sectional investigation on 320 old people from the NuAge study who were aged 70 to 85 and free of cognitive decline in 2013. The findings highlighted the significance of vitamin K in memory consolidation by demonstrating that recruited people with greater blood phylloquinone significantly improved verbal episodic memory whereas no link was identified with non-verbal episodic memory, speed of processing, or executive skills [91]. ...
... In specific, Presse et al. [91] presented the findings of a cross-sectional investigation on 320 old people from the NuAge study who were aged 70 to 85 and free of cognitive decline in 2013. The findings highlighted the significance of vitamin K in memory consolidation by demonstrating that recruited people with greater blood phylloquinone significantly improved verbal episodic memory whereas no link was identified with non-verbal episodic memory, speed of processing, or executive skills [91]. ...
Neurodegenerative disease refers to a group of disorders that predominantly damage the neurons in the brain. Despite significant progress in the knowledge of neurodegenerative diseases, there is currently no disease-modifying drug available. Vitamin K was first established for its involvement in blood clotting, but there is now compelling evidence indicating its role in the neurological system. In particular, the results of recent studies on the effects of vitamin K2 on preventing apoptosis, oxidative stress, and microglial activation in neuron cells through its role in electron transport are very promising against Alzheimer’s disease. In addition to its protective effect on cognitive functions, its inhibitory effects on inflammation and α-synuclein fibrillization in Parkinson’s disease, which has been revealed in recent years, are remarkable. Although there are many studies on the mechanism and possible treatment methods of neurodegenerative diseases, especially Parkinson’s and Alzheimer’s disease, studies on the relationship between vitamin K and neurodegenerative diseases are very limited, yet have promising findings. Vitamin K has also been proposed for therapeutic use in multiple sclerosis patients to lower the intensity or to slow down the progression of the disease. Accordingly, the aim of this study is to review the current evidence for the use of vitamin K supplementation in neurodegenerative diseases, in particular Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis.
... However, only the results published at the beginning of the 21st, proving the relationship between the senile diseases and vitamin K deficiency, fully revealed its importance. [2][3][4][5][6][7][8][9][10][11][12] Thus now this protector of our blood, bones, kidney and brain is deemed essential to human health. ...
... It is worth noting, however, that the results of studies with the participation of patients presented so far in the literature are very promising and encourage their continuation. For example, studies by Presse et al. [12,65] proved a relationship between the low K1 levels and Alzheimer's disease as well as memory impairment in the elderly. ...
Vitamin K is one of the many health-promoting substances whose impact on the human body has been underestimated until recently. However, recently published research results have changed this situation, prompting some researchers to consider it a new panacea for diseases of old age. The result is a significant increase in interest in the accurate analysis of vitamin K in various types of samples, ranging from food, through dietary supplements, to biological matrices and clinical trials, both observational and interventional. This review summarizes the current state of knowledge about the proven and speculated biological activity of vitamin K and its importance for the world’s aging societies, including the methods used for its isolation and analysis in various matrices types. Of all the analytical methods, the currently preferred methods of choice for the direct analysis of vitamin K are chromatographic methods, in particular liquid chromatography-tandem mass spectrometry. This technique, despite its sensitivity and selectivity, requires an appropriate stage of sample preparation. As there is still room for improvement in the efficiency of these methods, especially at the sample preparation stage, this review shows the directions that need to be taken to make these methods faster, more efficient and more environmentally friendly.
... An additional tube for vitamin K analysis was collected at all time points as an indicator of a healthy diet [70]. Vitamin K was assessed by high-performance liquid chromatography (HPLC) [71]. HbA1c and vitamin K were processed, stored, and analyzed locally. ...
... Green leafy and cruciferous vegetables are an important food source of vitamin K, and its levels in serum can provide information about dietary patterns [80]. Reduced vitamin K status has also been associated with poor cognitive function in older adults [71,81]. Although vegetable intake was a commonly altered component of diet, improvements in the DIET group also resulted from other aspects of diet such as increasing fatty fish consumption, or decreasing processed foods. ...
Background
Healthy diet and exercise are associated with reduced risk of dementia in older adults. The impact of diet and exercise interventions on brain health is less consistent, especially with dietary interventions which rely on varying approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counseling approach to improve hippocampal volume among older adults at-risk for dementia.
Methods
Participants with vascular risk factors and subjective cognitive decline or early mild cognitive impairment were cluster randomized in groups of 3–4 to the diet intervention (DIET) or control education (ED) group. All participants engaged in 1 h of supervised exercise per week and additional exercise at home. DIET involved 1 h per week of group-based dietary counseling comprising education, goal setting, and strategy training. ED involved 1 h per week of group-based brain health education classes. Our primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included changes in cognitive function, blood biomarkers, diet, and fitness. Recruitment challenges and early discontinuation of the trial due to COVID-19 necessitated a revised focus on feasibility and preliminary efficacy.
Results
Of 190 older adults contacted, 14 (7%) were eligible and enrolled, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and DIET/ED sessions on average. All 6-month assessments prior to COVID-19 were completed but disruptions to in-person testing resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the study. Preliminary findings did not identify any significant changes in hippocampal volume; however, substantial improvements in diet and HbA1c were observed with DIET compared to ED ( d = 1.75 and 1.07, respectively).
Conclusions
High adherence and retention rates were observed among participants and preliminary findings illustrate improvements in diet quality and HbA1c. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated.
Trial registration
ClinicalTrials.gov identifier: NCT03056508 .
... 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)(12)(13)(14)(15)(16)(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. ...
... The finding of the present study was in line with the previous epidemiological studies, showing that lower vitamin K intake is associated with cognitive impairment (11,12,14,16,17). Among those studies, Kiely and colleagues employed the %ucOC as one of the indicators to evaluate the vitamin K status by measuring both carboxylated OC and ucOC (16). ...
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.
... Another study found a low intake of VK1 in nine of 31 elderly individuals who had early AD [20]. A cross-sectional study of 320 subjects between 60 and 75 years of age determined that there is a positive association between high serum levels of VK1 and verbal episodic memory, but not non-verbal episodic memory or executive functions [21]. Two other studies in elderly individuals (mean ages of 82 and 83, respectively) found a positive association between dietary intake of VK1 and memory questionnaire scores [22,23]. ...
... [20]. A cross-sectional study of 320 subjects between 60 and 75 years of age determined that there is a positive association between high serum levels of VK1 and verbal episodic memory, but not non-verbal episodic memory or executive functions [21]. Two other studies in elderly individuals (mean ages of 82 and 83, respectively) found a positive association between dietary intake of VK1 and memory questionnaire scores [22,23]. ...
Recent studies have highlighted the importance of vitamin K2 (VK2) in human health. However, there have been no clinical studies investigating the role of VK2 in the prevention or treatment of Alzheimer’s disease (AD), a debilitating disease for which currently there is no cure. In reviewing basic science research and clinical studies that have connected VK2 to factors involved in AD pathogenesis, we have found a growing body of evidence demonstrating that VK2 has the potential to slow the progression of AD and contribute to its prevention. In our review, we consider the antiapoptotic and antioxidant effects of VK2 and its impact on neuroinflammation, mitochondrial dysfunction, cognition, cardiovascular health, and comorbidities in AD. We also examine the link between dysbiosis and VK2 in the context of the microbiome’s role in AD pathogenesis. Our review is the first to consider the physiological roles of VK2 in the context of AD, and, given the recent shift in AD research toward nonpharmacological interventions, our findings emphasize the timeliness and need for clinical studies involving VK2.
... A tube for Vitamin K analysis was collected at all time points. Vitamin K was assessed by high-performance liquid chromatography (HPLC) (Presse et al., 2013). HbA1c and Vitamin K were processed, stored, and analyzed locally. ...
... Green leafy and cruciferous vegetables are an important food source of vitamin K, and its levels in serum can provide information about dietary patterns . Reduced vitamin K status has also been associated with poor cognitive function in older adults (Presse et al., 2013;Kiely et al. 2020). We observed a small between-group effect on serum Vitamin K levels, however this appears to have been driven by a regression in Vitamin K levels toward the mean among the EX+ED group. ...
Background:
Healthy diet and exercise are associated with reduced risk of dementia in older adults. Evidence for the impact of clinical trials on brain health is less consistent, especially with dietary interventions which often rely on varying intervention approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counselling approach among older adults with vascular risk factors (VRFs) and early dementia risk.
Methods: Participants with VRF’s and SCD or early MCI were cluster randomized into the intervention (exercise + Baycrest Brain-healthy Eating Approach (EX+DIET)) or control group (exercise + brain health education (EX+ED)). Both groups participated in 1-hour of supervised exercise per week and were prescribed additional exercise at home. EX+DIET involved 1-hour per week of group-based dietary counselling comprising didactic education focused on brain healthy eating recommendations, goal setting and strategy training. Whereas, EX+ED involved 1-hour per week of group-based brain health education. The primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included fitness, diet, cognition, and blood biomarkers. Recruitment challenges and early discontinuation of the trial due to COVID-19 necessitated a revised focus on feasibility and preliminary efficacy.
Results: Of 190 older adults contacted, 14 (7%) were eligible and randomized, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and diet/education sessions on average. All 6-month follow-up assessments pre-COVID-19 were completed but disruptions to testing during the pandemic resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the intervention. Mean improvements in peak oxygen consumption were observed in both EX+DIET (d = .98) and EX+ED (d =1.15) groups. Substantial improvements in diet and HbA1c were observed in the EX+DIET group compared to EX+ED (d = 1.75 and 1.07, respectively).
Conclusions: High adherence and retention rates were observed among LEAD participants and preliminary findings illustrate improvements in cardiorespiratory fitness and diet quality. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated.
Trial Registration: ClinicalTrials.gov identifier: NCT03056508
... Also, there are differences in the daily intake of vitamin K1 in elderly patients with Alzheimer's disease in comparison to healthy controls [39,40]. Presse et al. (2013) stated that elderly people with intact cognition level had high concentration of serum vitamin K1 in association with increased recollection tests and verbal episodic memory [41]. ...
... Also, there are differences in the daily intake of vitamin K1 in elderly patients with Alzheimer's disease in comparison to healthy controls [39,40]. Presse et al. (2013) stated that elderly people with intact cognition level had high concentration of serum vitamin K1 in association with increased recollection tests and verbal episodic memory [41]. ...
Vitamin K is a fundamental enzymatic co-factor implicated in the carboxylation of several vitamin K dependent proteins involved in the pathogenesis of certain age – related diseases. Inflammation is realized as an important factor in such diseases. Vitamin K is recognized to play an anti-inflammatory behavior that is distinct of its action as an enzymatic co- factor by suppressing many signaling pathways mainly the nuclear factor κB (NF-κB) signal transduction pathway. As well as to play a role as an antioxidant versus the generation of reactive oxidative species (ROS). The purpose of this review is to focus on the protective function of vitamin K as an anti-inflammatory agent in these age- associated diseases. And the importance of vitamin K complement as a protective nutrient in aging.
... Vitamin K, while it is more commonly known for its important role in blood coagulation [46], also acts as an essential nutrient in the central nervous system (CNS) [47,48]. Previous evidence has also shown that higher serum phylloquinone status in elderly people has been associated with better performance in verbal episodic memory, and higher dietary intake of vitamin K was also linked with less severe subjective memory complaints among older adults [49,50]. On the other hand, being a kind of carotenoid, lutein comprises not only the ability to reduce the risk of some chronic health disorders, but is also believed to aid in cognitive function, and is associated with word recall ability among older adults [51,52]. ...
... It should be noticed that due to the special processing of Matcha green tea, it presents higher amounts of fat-soluble nutrients than regular green tea, especially vitamin K and lutein, both of which show a beneficial effect on cognitive function in either animal or epidemiological studies [49,51,84,85]. Notably, in our dietary analysis, we found that higher consumption of vitamin K in daily diet excluding test drinks was inversely correlated with an increase in the MoCA score, which suggested the role of supplementing deficient vitamin K for the amelioration of cognitive deficits. ...
Matcha Green Tea Powder contains a variety of active ingredients beneficial to health, such as tea catechins, lutein and vitamin K. It is also known that these ingredients confer benefits upon cognitive functions of elderly people. Therefore, we aimed to investigate the relationship between a daily supplementation of Matcha and the change in cognitive functions of community-dwelling elderly people. A randomized, double-blind, placebo-controlled 12-week trial was performed. Sixty-one participants were recruited and randomly assigned to receive test drink containing 3 g powder from fresh Matcha or placebo powder per day. Changes in cognitive function were assessed utilizing a psychometric test battery. Daily food intake was assessed by a Brief-type Self-administered Diet History Questionnaire (BDHQ). In the gender-specific analysis, a significant cognitive enhancement was observed in the Montreal Cognitive Assessment (MoCA) score in the active group of women. In dietary analysis, we found a significant inverse correlation between consumption of vitamin K in daily diet, excluding test drinks, and change in MoCA. The present study suggests that daily supplementation of Matcha Green Tea Powder has protective effects against cognitive decline in community-dwelling elderly women.
... Subjects were nonfasted and blood samples were taken by a trained nurse using a vacutainer. Blood samples were centrifuged, and after serum was extracted, samples were stored at −80 • C. Serum phylloquinone was assessed by reverse-phase HPLC with fluorescence detection as described by Presse et al. (37). The inflammatory cytokines TNF-α, IL-6, and IL-8 (risk factors for cognitive decline) were measured using validated, commercial, multispot microplates (Meso Scale Diagnostics). ...
... While it remains to be fully elucidated, long-chain MKs have been shown to have a longer half-life than shorter-chain isoforms and PK, suggesting plasma kinetics may extend the bioavailability of long-chain MK for extrahepatic tissue uptake (56). While previous studies have reported higher serum PK concentrations were positively associated with verbal episodic memory (as measured by the cognitive test battery) in an aging population (37), evidence from the current study does not support a significant association between serum PK concentrations and cognition (Table 4). While the MMSE (which assesses writing, short-term memory, orientation, and time) is an excellent first-level screening tool, its usage as the sole instrument is an important limitation of the current study as it is not designed to determine subtle differences in cognitive function as accurately as other tests, and it has relatively low sensitivity for mild symptoms. ...
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.
... Higher VK intake has been reported to be associated with better cognitive performance or lower risk of Alzheimer's disease in at least 4 different cohorts of older adults (15)(16)(17)(18). Another study demonstrated that cognitively intact older adults with higher plasma PK concentrations performed better on cognitive assessments related to consolidation processes of the memory trace (19). ...
... This begs the question: Why were circulating VK concentrations consistently related to better cognitive performance while brain MK-4 was not? Consistent with our findings, higher plasma PK concentrations were related to a better performance on cognitive assessments related to consolidation processes of the memory trace in nondemented older adults from the NuAge study (19). Circulating PK concentrations were comparable in these studies (1.35 ± 0.82 nmol/L in GCS and 1.45 ± 1.80 nmol/L in NuAge). ...
Background:
Vitamin K (VK) exists in the form of phylloquinone (PK) and menaquinones (MKs). Roles of VK on cognitive health in the elderly are emerging, but there is limited evidence on VK uptake and metabolism in human brain.
Objectives:
The primary objective of this study was to characterize VK distribution in brains of an elderly population with varied cognitive function. In addition, associations among circulating (a biomarker of VK intake) and cerebral VK concentrations and cognition were investigated.
Methods:
Serum or plasma (n = 27) and brain samples from the frontal cortex (FC; n = 46) and the temporal cortex (TC; n = 33) were acquired from 48 decedents (aged 98-107 y; 25 demented and 23 nondemented) enrolled in the Georgia Centenarian Study. Both circulating and brain VK concentrations were measured using HPLC with fluorescence detection. Cognitive assessment was performed within 1 y prior to mortality. Partial correlations between serum/plasma or cerebral VK concentrations and cognitive function were performed, adjusting for covariates and separating by dementia and antithrombotic use.
Results:
MK-4 was the predominant vitamer in both FC (mean ± SD = 4.92 ± 2.31 pmol/g, ≥89.15% ± 5.09% of total VK) and TC (4.60 ± 2.11 pmol/g, ≥89.71% ± 4.43% of total VK) regardless of cognitive status. Antithrombotic users had 34.0% and 53.9% lower MK-4 concentrations in FC (P < 0.05) and TC (P < 0.001), respectively. Circulating PK was not correlated with cerebral MK-4 or total VK concentrations. Circulating PK concentrations were significantly associated with a wide range of cognitive measures in nondemented centenarians (P < 0.05). In contrast, cerebral MK-4 concentrations were not associated with cognitive performance, either before or after exclusion of antithrombotic users.
Conclusions:
Circulating VK concentrations are not related to cerebral MK-4 concentrations in centenarians. Cerebral MK-4 concentrations are tightly regulated over a range of VK intakes and cognitive function. Circulating PK may reflect intake of VK-rich foods containing other dietary components beneficial to cognitive health. Further investigation of VK uptake and metabolism in the brain is warranted.
... In human studies, vitamin K status has been associated with cognitive functions. When investigated in cognitively intact elderly individuals, higher serum vitamin K (phylloquinone) concentrations were correlated with enhanced verbal episodic memory and recollection tests [29]. In a group of geriatric patients, those in the highest tertile of dietary phylloquinone intake reported better global cognition and behavioural rating [30]. ...
The TAM receptor ligand Gas6 is known for regulating inflammatory and immune pathways in various organs including the brain. Gas6 becomes fully functional through the post-translational modification of multiple glutamic acid residues into γ-carboxyglutamic in a vitamin K-dependent manner. However, the significance of this mechanism in the brain is not known. We report here the endogenous expression of multiple components of the vitamin K cycle within the mouse brain at various ages as well as in distinct brain glial cells. The brain expression of all genes was increased in the postnatal ages, mirroring their profiles in the liver. In microglia, the proinflammatory agent lipopolysaccharide caused the downregulation of all key vitamin K cycle genes. A secreted Gas6 protein was detected in the medium of both mouse cerebellar slices and brain glial cell cultures. Furthermore, the endogenous Gas6 γ-carboxylation level was abolished through incubation with the vitamin K antagonist warfarin and could be restored through co-incubation with vitamin K1. Finally, the γ-carboxylation level of the Gas6 protein within the brains of warfarin-treated rats was found to be significantly reduced ex vivo compared to the control brains. In conclusion, we demonstrated for the first time the existence of a functional vitamin K cycle within rodent brains, which regulates the functional modification of endogenous brain Gas6. These results indicate that vitamin K is an important nutrient for the brain. Furthermore, the measurement of vitamin K-dependent Gas6 functionality could be an indicator of homeostatic or disease mechanisms in the brain, such as in neurological disorders where Gas6/TAM signalling is impaired.
... Menaquinone (Vitamin K) is an important nutrient for the human host, with roles in bone, heart, blood, immune, and cognitive health [40][41][42], and absorption of microbially sourced vitamin K from the small intestine is vital for human health [43]. Both nitric oxide and menaquinone are known antioxidant molecules [44,45], and microbially modulated nitric oxide has roles in promoting better exercise performance in the mouth microbiome [46]. ...
ABSTRACT
Background: The complex relationship among sleep, exercise, and the gut microbiome presents a unique opportunity to improve health and wellness. Here, we conducted the first large-scale investigation into the influence of a novel elite athlete-derived probiotic, consisting of a multi-strain Lactobacillus consortium, on sleep quality, exercise recovery, and gut microbiome composition in both elite athletes (n=10) and the general population (n=257). Results: Our two-phase study design, which included an open-label study followed by a controlled longitudinal study in a professional soccer team, allowed us to identify key interactions between probiotics, the gut microbiome, and the host. In the placebo controlled study, we observed significant improvements in self-reported sleep quality by 69%, energy levels by 31%, and bowel movements by 37% after probiotic intervention relative to after placebo. These improvements were associated with a significant decrease in D-ROMS (a marker of oxidative stress) and a significantly higher free-testosterone/cortisol ratio. Multi-omics analyses revealed specific changes in microbiome composition and function, potentially providing mechanistic insights into these observed effects. Conclusion: This study provides novel insights into how a multi-strain Lactobacillus probiotic modulates sleep quality, exercise recovery, and gut microbiome composition in both the general population and elite athletes, and introduces potential mechanisms through which this probiotic could be influencing overall health. Our results emphasize the untapped potential of tailored probiotic interventions derived from extremely fit and healthy individuals in improving several aspects of health and performance directly in humans.
... The procedure of blood and urine sampling, processing, and storage in the NuAge study was described in detail elsewhere (25,31). In short, 50 mL of blood and 6 mL of urine were obtained from each participant after an overnight fast. ...
Background:
Vitamin B-12 deficiency can result in irreversible neurological damages. It is most prevalent among older adults (∼5-15%), mainly due to impaired absorption. Vitamin B-12 bioavailability varies between food sources, so their importance in preventing deficiency may also vary.
Objective:
Using the NuAge Database and Biobank, we examined the associations between vitamin B-12 intake - total and by specific food groups - and low vitamin B-12 status and deficiency in older adults.
Methods:
NuAge included 1753 adults aged 67-84 years followed 4 years. Analytic samples comprised 1230 to 1463 individuals. Dietary vitamin B-12 intake was assessed annually using three 24-hour dietary recalls. Vitamin B-12 status was assessed annually as low serum vitamin B-12 (<221 pmol/L), elevated urinary methylmalonic acid (MMA)/creatinine ratio (>2 µmol/mmol), and a combination of both (deficiency). Vitamin B-12 supplement users were excluded. Multilevel logistic regressions, adjusted for relevant confounders, were used.
Results:
Across all study years, 21.8-32.5% of participants had low serum vitamin B-12, 12.5-17.0% had elevated urine MMA/creatinine, and 10.1-12.7% had deficiency. Median [IQR] total vitamin B-12 intake was 3.19 [2.31-4.37] µg/day. Main sources were "dairy" and "meat, poultry and organ meats". The ORs (95%CI) in the fifth compared to first quintile of total vitamin B-12 intake for low serum vitamin B-12, elevated urine MMA/creatinine and vitamin B-12 deficiency respectively were 0.52 (0.37-0.75; p-trend < 0.0001), 0.63 (0.37-1.08; p-trend = 0.091), and 0.38 (0.18-0.79; p-trend = 0.006). Similarly, ORs (95%CI) in the fourth compared to first quartile of dairy-derived vitamin B-12 intake were 0.46 (0.32-0.66; p-trend < 0.0001), 0.51 (0.30-0.87; p-trend = 0.006), and 0.35 (0.17-0.73; p-trend = 0.003). No associations were observed with vitamin B-12 from "meat, poultry and organ meats".
Conclusion:
Higher dietary vitamin B-12 intake, especially from dairy, was associated with decreased risk of low vitamin B-12 status and deficiency in older adults. Food groups might contribute differently at reducing risk of deficiency in older populations.
... In Irish adults ≥64 y old (mean ± SD age: 78 ± 9 y), higher circulating phylloquinone was associated with higher Mini-Mental State Examination scores (21). In 67to 84-y-old individuals without apparent cognitive impairment, higher plasma phylloquinone was associated with better verbal episodic memory scores but not with nonverbal episodic memory, executive function, or processing speed (22). In 80-to 90-y-olds without cognitive impairment at baseline, higher plasma phylloquinone was associated with a slower rate of cognitive decline (based on the person-specific change in scores on 19 cognitive tests) (7). ...
Vitamin K is linked to cognitive function, but studies in individuals with chronic kidney disease (CKD), who are at risk for both vitamin K insufficiency and cognitive impairment, are lacking. The cross-sectional association of vitamin K status biomarkers with cognitive performance was evaluated in ≥ 55 year-old adults with CKD (n = 714, 49% female, 44% Black). A composite score of a cognitive performance test battery, calculated by averaging the z-scores of the individual tests, was the primary outcome. Vitamin K status was measured using plasma phylloquinone and dephospho-uncarboxylated matrix gla protein ((dp)ucMGP). Participants with low plasma (dp)ucMGP, reflecting higher vitamin K status, had better cognitive performance based on the composite outcome (p = 0.03), whereas it did not significantly differ according to plasma phylloquinone categories (p = 0.08). Neither biomarker was significantly associated with performance on individual tests (all p > 0.05). The importance of vitamin K to cognitive performance in adults with CKD remains to be clarified.
... Vitamin K is a fatsoluble vitamin, mainly found in green vegetables and several vegetable oils (Chouet et al., 2015). Higher vitamin K intake is related to better memory performance, cognition, and behavior in older adults (Camacho-Barcia et al., 2022;Chouet et al., 2015;Presse et al., 2013). Dietary Se intake was positively related to telomere length in middle-aged and older populations in America (Shu, Wu, Yang, Wang, & Li, 2020), and every 20 mg increase in Se intake was associated with a 0.42% longer telomere length. ...
Dietary intervention is a safe, broad-spectrum, and low-cost preventive strategy for slow aging. The Okinawan, Mediterranean, and Dietary approaches to stop hypertension (DASH) diets, as well as caloric restriction (CR) and intermittent fasting (IF), are classic and reliable dietary patterns that slow aging by regulating nutrient-sensing pathways, gut microbiota, metabolism, and immunity. Moreover, the proportion of the three macronutrients (carbohydrate, protein and fat) is also vital for slowing aging, but the debates about the appropriate proportion, especially the ratio of carbohydrates and proteins, remain unknown. Strict and lifelong adherence to these regimens is difficult, thereby promoting the emergence of various dietary supplements, including natural CR mimics, probiotics, natural senolytics, vitamins and essential minerals. Combinations of different dietary patterns and supplements with distinct pathways may have additive effects. Individuals’ aging speed and dietary response are highly variable, thus highlighting the need for precise anti-aging dietary intervention. Nutrigenomics plays an important role in personalized dietary strategies. Therefore, this review critically compares the anti-aging effects of various dietary patterns and supplements, analyzes their mechanisms and combined use, and proposes future research directions to achieve personalized dietary strategies for slowing aging.
... A protective association between circulating phylloquinone and various measures of cognitive function has been reported in several observational studies of older adults without cognitive impairment. 3,17 We found that higher plasma phylloquinone concentrations measured at the most recent clinic visit prior to death were associated with overall better cognitive function, but not with any post-mortem neuropathological outcome. ...
Higher vitamin K intakes have been associated with better cognitive function, suggestive of a vitamin K mechanistic effect or simply reflective of a healthy diet. To test the hypothesis that brain vitamin K is linked to cognitive decline and dementia, vitamin K concentrations were measured in four brain regions, and their associations with cognitive and neuropathological outcomes were estimated in 325 decedents of the Rush Memory and Aging Project. Menaquinone‐4 (MK4) was the main vitamin K form in the brain regions evaluated. Higher brain MK4 concentrations were associated with a 17% to 20% lower odds of dementia or mild cognitive impairment (MCI) (P‐value < .014), with a 14% to 16% lower odds of Braak stage ≥IV (P‐value < 0.045), with lower Alzheimer's disease global pathology scores and fewer neuronal neurofibrillary tangles (P‐value < 0.012). These findings provide new and compelling evidence implicating vitamin K in neuropathology underlying cognitive decline and dementia.
... In this regard, a direct correlation between low Vit. K dietary intake, or its serum concentration, and deteriorated cognitive and behavioral performances has been reported in a population 65 years and older [29]. Moreover, research findings confirmed Vit. ...
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.
... In this regard, a direct correlation between low Vit. K dietary intake, or its serum concentration, and deteriorated cognitive and behavioral performances has been reported in a population 65 years and older [29]. Moreover, research findings confirmed Vit. ...
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.
... A cross-sectional analysis, examining specifically vitamin K and cognitive function, has found that a higher dietary intake was associated with better cognition and behaviour among older adults [14], and with better verbal episodic memory performance [15]. ...
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.
... Приемът на витамин К може да подобри когнитивната функция при здрави възрастни. Едно такова проучване показа, че витамин К 1 е свързан с по-добра словесна епизодична памет (17). Използването на антагонисти на витамин К е свързано с почести когнитивни нарушения (3). ...
... 13,14 Six studies demonstrated, in a population of 65 years and older, a direct correlation between low vitamin K dietary intake or serum concentration and deteriorated cognitive and behavioral performances. [15][16][17][18][19][20] Moreover, research findings show that vitamin K2 can protect neural cells against Aβ toxicity. 21 Cui et al. 22 connected aortic stiffness with an increased risk of dementia in older adults. ...
... However, a later study reported different antioxidant profiles of vitamin A and E in Italian centenarians [163]. Furthermore, the roles of vitamins B, D, and K in aging adults were also reported [164][165][166][167][168]. For example, apolipoprotein E (APOE) ε4 is a genetic predisposing factor that modulates the effect of vitamin B-12 on cognitive function [164]. ...
Population aging has recently been an important issue as the number of elderly people is growing worldwide every year, and the extension of social security costs is financially costly. The increase in the number of elderly people with cognitive decline is a serious problem related to the aging of populations. Therefore, it is necessary to consider not only physical care but also cognitive patterns in the future care of older adults. Since food contains a variety of bioactive substances, dietary patterns may help improve age-related cognitive decline. However, the relationship between cognitive function and individual food components remains ambiguous as no clear efficacy or mechanism has been confirmed. Against this background, this review summarizes previous reports on the biological process of cognitive decline in the elderly and the relationship between individual compounds in foods and cognitive function, as well as the role of individual components of food in cognitive function, in the following order: lipids, carotenoids, vitamins, phenolic compounds, amino acids, peptides, and proteins. Based on the research presented in this review, a proper diet that preserves cognitive function has the potential to improve age-related cognitive decline, Alzheimer’s disease, and Parkinson’s disease. Hopefully, this review will help to trigger the development of new foods and technologies that improve aging and cognitive functions and extend the healthy life span.
... To summarise, macrophages extend the list of cells, including the bacteria, intestinal epithelium, kidneys, the brain, and the endothelium [30][31][32]36,37], that are able to synthesise MK-4. Macrophages displayed the ability to synthesise endogenous vitamin MK-4 from various exogenous sources of vitamins K that could originate from the diet or bacteria. ...
Vitamins K exert a range of activities that extend far beyond coagulation and include anti-inflammatory effects, but the mechanisms involved in anti-inflammatory action remain unclear. In the present study, we showed that various forms of exogenous vitamins—K1, K3, K2 (MK-4, MK-5, MK-6 and MK-7)—regulated a wide scope of inflammatory pathways in murine macrophages in vitro, including NOS-2, COX-2, cytokines and MMPs. Moreover, we demonstrated for the first time that macrophages are able to synthesise endogenous MK-4 on their own. Vitamins with shorter isoprenoid chains—K1, K3 and MK-5—exhibited stronger anti-inflammatory potential than vitamins with longer isoprenoid chains (MK-6 and MK-7) and simultaneously were preferably used as a substrate for MK-4 endogenous production. Most interesting, atorvastatin pretreatment inhibited endogenous MK-4 production but had no impact on the anti-inflammatory activity of vitamin K. In summary, our results demonstrate that macrophages are able to synthesise endogenous MK-4 using exogenous vitamin K, and statin inhibits this process. However, the anti-inflammatory effect of exogenous vitamin K was independent of endogenous MK-4 synthesis.
... VK-rich food intake containing other bioactive molecules may act in synergy to cognitive health [176]. In a cross-sectional study, which comprised 320 old participants aged 70 to 85 years and without cognitive impairment, higher serum levels of PK were significantly connected with better verbal episodic memory performances (p = 0.048), exposing better cognition during aging [177]. ...
As human life expectancy is rising, the incidence of age-associated diseases will also increase. Scientific evidence has revealed that healthy diets, including good fats, vitamins, minerals, or polyphenolics, could have antioxidant and anti-inflammatory activities, with antiaging effects. Recent studies demonstrated that vitamin K is a vital cofactor in activating several proteins, which act against age-related syndromes. Thus, vitamin K can carboxylate osteocalcin (a protein capable of transporting and fixing calcium in bone), activate matrix Gla protein (an inhibitor of vascular calcification and cardiovascular events) and carboxylate Gas6 protein (involved in brain physiology and a cognitive decline and neurodegenerative disease inhibitor). By improving insulin sensitivity, vitamin K lowers diabetes risk. It also exerts antiproliferative, proapoptotic, autophagic effects and has been associated with a reduced risk of cancer. Recent research shows that protein S, another vitamin K-dependent protein, can prevent the cytokine storm observed in COVID-19 cases. The reduced activation of protein S due to the pneumonia-induced vitamin K depletion was correlated with higher thrombogenicity and possibly fatal outcomes in COVID-19 patients. Our review aimed to present the latest scientific evidence about vitamin K and its role in preventing age-associated diseases and/or improving the effectiveness of medical treatments in mature adults ˃50 years old.
... The Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) is a 4-year prospective cohort study (Gaudreau et al., 2007). The present study is based on an embedded subsample of 350 participants of the NuAge Database and Biobank who underwent additional cognitive evaluations as part of the Nutrition and Cognition substudy (for sample selection see the work of Presse et al., 2013). Participants had a Modified Mini-Mental State Examination (3MS, Teng & Chui, 1987) score greater than 85 at baseline, complete dietary data, and were considered free of self-reported health conditions that could impair cognition. ...
Objectives
This study examined the effect of dietary patterns and engagement in cognitive stimulating lifestyle (CSL) behaviors on the trajectory of global cognition, executive function (EF), and verbal episodic memory (VEM).
Methods
Western and prudent dietary patterns were empirically derived using food frequency questionnaire responses from 350 community-dwelling older adults (mean age: 73.7 years) participating in the Quebec Longitudinal Study on Nutrition and Successful Aging. CSL was represented by a binary composite indicator based on education, occupational complexity, and social engagement. Global cognition, EF, and VEM were assessed prospectively.
Results
Primary effect models revealed an association between higher Western dietary pattern score and a greater rate of decline in global cognition and EF. Higher Western dietary pattern adherence was also associated with poorer baseline VEM. Primary effect models also revealed that CSL was independently associated with baseline global cognition and EF. Effect modification models suggested an interactive effect between Western dietary pattern and CLS on global cognition only. No associations were found for prudent dietary pattern score.
Discussion
Contributing to existing research supporting the negative impact of consuming an unhealthy diet on cognitive function, the current study suggests increased vulnerability among older adults who do not engage in a CSL. These findings can inform the development of lifestyle intervention programs that target brain health in later adulthood.
... [168][169][170] Serum phylloquinone deficiency has reported to decrease the performance of episodic memory in a group of healthy population. 171 Furthermore, diminished serum levels of phylloquinone have found in Alzheimer's disease patients when compared to cognitively healthy individuals. 172 In various cohort studies, low levels of phylloquinone lead to poor cognitive functions and in-turn linked with higher expressions of inflammation. ...
Background: Alzheimer’s disease is known as one of the fastest growing lethal diseases worldwide where we have limited and undesired ways for regulating its pathological progress. Now-a-days, nutritional compounds have been using to treat several brain disorders and one of them; vitamins were strongly reported to combat cognition and memory deterioration in neurodegenerative diseases including Alzheimer’s disease.
Objective: Here, the author tried to find the precise physiological roles, status, and worth of vitamins in the brain and how exactly these nutrients modulate progression of Alzheimer’s disease.
Results & Discussion: After a comprehensive and systematic literature review, the author reports that vitamins have various targets in Alzheimer’s disease pathogenesis by which they act to avert the neuronal dysfunction in the disease. Several Alzheimer’s disease associated neurological deficits have reported regulating by vitamin intake but the beneficial effects identified mostly in combinatorial and long-term studies.
Conclusion: In this way, the author suggests that it might be better to test vitamins with other components over single vitamin approach for a compatible and synergistic effect as well as using a combination of vitamin with other compounds can target multiple pathways. This strategy may help in deteriorating memory dysfunction and cognition impairment in Alzheimer’s disease pathophysiology.
... Dietary deficiency of vitamin K is uncommon. It is abundant in lettuce, spinach, cauliflower and cabbage, and it can also be produced by gut microflora (Presse et al., 2013). ...
... Vitamin K essential role is reported in the synthesis of sphingolipid and protein Gas6 in the peripheral and central nervous system (Ferland 2012). Vitamin K has an essential role in the pathogenesis of Alzheimer's disease as it improves the cognitive function by regulating the sulfotransferase activity, growth factors, and tyrosine kinase receptor activity in the brain (Presse et al. 2008;Ferland 2012;Presse 2013). Intake of vitamin K also suppresses growth and invasion of human hepatocellular carcinoma via protein kinase A activation, which results in moderate suppression of tumor recurrence (Yoshida et al. 2008). ...
Vitamins are either fat-soluble (vitamin A, D, E, and K) or water-soluble (vitamin B and C) and required in small amounts for maintaining the healthy growth and normal function of the human body. Vitamin deficiency is a major public health issue worldwide. More than two billion people have found vitamin deficient and are mostly belong to developing countries. Vitamin A deficiency is of severe health concern under the age of 5 years children in several South-East Asian and African countries. Similarly, vitamin D and vitamin B12 deficiencies are the other major growing health concern. The global community must prioritize their action to eradicate hunger as well as vitamin deficiency in low- and middle-income countries. Various vitamin supplementation, food fortification, biofortification, and health policy programs are needed to improve the scenario of vitamin deficiency. Nutrition policy should transit from a simple reductionist method to multifaceted solutions and also work in the synergy of the scientific community to improve the health quality of large population. This chapter is mainly focused on vitamin types and their roles in human health, the global scenario of vitamin deficiency, and a significant source of vitamins to eradicate their deficiency.
... Moreover, people with early AD tend to consume less leafy green vegetables and vitamin K [197], and APOE4 carriers especially have reduced circulating vitamin K levels [198]. Vitamin K consumption is positively correlated with improved cognition and behavior among adults [199,200]. The reverse has also been demonstrated, whereby rats were exposed to lifelong vitamin K deficiency, resulting in cognitive and behavioral deficits [201]. ...
Alzheimer’s disease (AD) incidence is increasing and with no disease modifying agents available, preventative measures through lifestyle factors are being investigated. Combined with the prevention of AD risk factors such as heart disease, diabetes, and with more recent evidence, microbiome dysfunction, there is a substantial foundation for diet as a modifiable risk factor and preventative measure for AD. Recent evidence suggests AD associated pathologies, such as oxidative stress and inflammation, can be modulated by the lipids, vitamins, and polyphenols obtained through nutritional intake. Furthermore, epidemiological and preclinical evidence has uncovered certain compounds within foods that may have beneficial effects in the prevention of AD, including omega-3 fatty acids, vitamin E, and resveratrol among others. However, clinical data examining specific compounds are often inconsistent and fail to replicate the preclinical data. On the other hand, dietary patterns such as the Mediterranean or MIND diet have shown promise in terms of clinical outcomes for patients, indicating a reductionist approach to diet is not as effective as a holistic dietary pattern. In this review, we summarize some of the biological mechanisms of key compounds in their relation to AD and how they fit into a dietary pattern that supports the role of diet as a risk reducing factor for AD.
... Despite biological plausibility, evidence is somewhat lacking. In identified studies, increasing vitamin K intake was associated with reduced BMD loss (121), vitamin K deficiency with increased risk of knee osteoarthritis (122) and cartilage damage (123), higher plasma concentrations of phylloquinone with improved physical performance, gait speed, and endurance (124), higher serum or dietary phylloquinone with better cognitive function (125,126), and higher dephospho-uncarboxylated matrix Gla protein concentration (considered a reliable marker of vitamin K status and utilization) with lower handgrip strength and calf circumference (127). These studies are not without limitations, including potential confounding by other components of vitamin K-rich foods, such as green leafy vegetables, not adjusted for in analyses. ...
Appropriate dietary choices in later life may reduce the risk of chronic diseases and rate of functional decline, however, there is little well-evidenced age-specific nutritional guidance in the UK for older adults, making it challenging to provide nutritional advice. Therefore, the aim of this critical review was to propose evidence-based nutritional recommendations for older adults (aged ≥65 y). Nutrients with important physiological functions in older adults were selected for inclusion in the recommendations. For these nutrients: 1) recommendations from the UK Scientific Advisory Committee for Nutrition (SACN) reports were reviewed and guidance retained if recent and age-specific, and 2) a literature search conducted where SACN guidance was not sufficient to set or confirm recommendations for older adults, searching Web of Science up to March 2020. Data extracted from a total of 190 selected publications provided evidence to support age-specific UK recommendations for protein (1.2 g·kg-1·d-1), calcium (1000 mg·d-1), folate (400 μg·d-1), vitamin B-12 (2.4 μg·d-1), and fluid (1.6 L·d-1 women, 2.0 L·d-1 men) for those ≥65 y. UK recommendations for carbohydrates, free sugars, dietary fiber, dietary fat and fatty acids, sodium, and alcohol for the general population are likely appropriate for older adults. Insufficient evidence was identified to confirm or change recommendations for all other selected nutrients. In general, significant gaps in current nutritional research among older adults existed, which should be addressed to support delivery of tailored nutritional guidance to this age group to promote healthy aging.
... This is in line with our knowledge that MK-4 is a result of K1 conversion, and that cerebral MK-4 originates from K1 intake [98]. In humans, a few studies have shown a relationship between low levels of K1 and Alzheimer's disease and impaired memory performance in older adults [99,100]. However, specific relationships between higher K1 or MK-4 levels and sphingolipid synthesis requires further elucidation. ...
Vitamin K health benefits have been recently widely shown to extend beyond blood homeostasis and implicated in chronic low-grade inflammatory diseases such as cardiovascular disease, osteoarthritis, dementia, cognitive impairment, mobility disability, and frailty. Novel and more efficient nutritional and therapeutic options are urgently needed to lower the burden and the associated health care costs of these age-related diseases. Naturally occurring vitamin K comprise the phylloquinone (vitamin K1), and a series of menaquinones broadly designated as vitamin K2 that differ in source, absorption rates, tissue distribution, bioavailability, and target activity. Although vitamin K1 and K2 sources are mainly dietary, consumer preference for diet supplements is growing, especially when derived from marine resources. The aim of this review is to update the reader regarding the specific contribution and effect of each K1 and K2 vitamers in human health, identify potential methods for its sustainable and cost-efficient production, and novel natural sources of vitamin K and formulations to improve absorption and bioavailability. This new information will contribute to foster the use of vitamin K as a health-promoting supplement, which meets the increasing consumer demand. Simultaneously, relevant information on the clinical context and direct health consequences of vitamin K deficiency focusing in aging and age-related diseases will be discussed.
... Vitamin K is also linked to the development of AD, and it is believed that its protection is related to the reduction of oxidative stress, because it can prevent cell death after activation of the lipoxygenase pathway. Vitamin D levels are also low in patients with AD, and when administered together with a famous AD drug, the memantine, it was more effective than when the drug was administered alone [85]. ...
Alzheimer’s disease (AD) is a neurodegenerative disease that is usually accompanied by aging, increasingly being the most common cause of dementia in the elderly. This disorder is characterized by the accumulation of beta amyloid plaques (Aβ) resulting from impaired amyloid precursor protein (APP) metabolism, together with the formation of neurofibrillary tangles and tau protein hyperphosphorylation. The exacerbated production of reactive oxygen species (ROS) triggers the process called oxidative stress, which increases neuronal cell abnormalities, most often followed by apoptosis, leading to cognitive dysfunction and dementia. In this context, the development of new therapies for the AD treatment is necessary. Antioxidants, for instance, are promising species for prevention and treatment because they are capable of disrupting the radical chain reaction, reducing the production of ROS. These species have also proven to be adjunctive to conventional treatments making them more effective. In this sense, several recently published works have focused their attention on oxidative stress and antioxidant species. Therefore, this review seeks to show the most relevant findings of these studies.
Besides its role in coagulation, vitamin K seems to be involved in various other mechanisms, including inflammation and age-related diseases, also at the level of gene expression. This work examined the roles of two vitamin K2 (menaquinones) vitamers, namely, menaquinone-4 (MK4) and reduced menaquinone-7 (MK7R), as gene modulator compounds, as well as their potential role in the epigenetic regulation of genes involved in amyloidogenesis and neuroinflammation. The SK-N-BE human neuroblastoma cells provided a “first-line” model for screening the neuroinflammatory and neurodegenerative molecular pathways. MK7R, being a new vitamin K form, was first tested in terms of solubilization, uptake and cell viability, together with MK4 as an endogenous control. We assessed the expression of key factors in amyloidogenesis and neuroinflammation, observing that the MK7R treatment was associated with the downregulation of neurodegeneration- (PSEN1 and BACE1) and neuroinflammation- (IL-1β and IL-6) associated genes, whereas genes retaining protective roles toward amiloidogenesis were upregulated (ADAM10 and ADAM17). By profiling the DNA methylation patterns of genes known to be epigenetically regulated, we observed a correlation between hypermethylation and the downregulation of PSEN1, IL-1β and IL-6. These results suggest a possible role of MK7R in the treatment of cognitive impairment, giving a possible base for further preclinical experiments in animal models of neurodegenerative disease.
Cognitive impairment and dementia are burgeoning public health concerns, especially given the increasing longevity of the global population. These conditions not only affect the quality of life of individuals and their families, but also pose significant economic burdens on healthcare systems. In this context, our comprehensive narrative review critically examines the role of nutritional supplements in mitigating cognitive decline. Amidst growing interest in non-pharmacological interventions for cognitive enhancement, this review delves into the efficacy of vitamins, minerals, antioxidants, and other dietary supplements. Through a systematic evaluation of randomized controlled trials, observational studies, and meta-analysis, this review focuses on outcomes such as memory enhancement, attention improvement, executive function support, and neuroprotection. The findings suggest a complex interplay between nutritional supplementation and cognitive health, with some supplements showing promising results and others displaying limited or context-dependent effectiveness. The review highlights the importance of dosage, bioavailability, and individual differences in response to supplementation. Additionally, it addresses safety concerns and potential interactions with conventional treatments. By providing a clear overview of current scientific knowledge, this review aims to guide healthcare professionals and researchers in making informed decisions about the use of nutritional supplements for cognitive health.
K vitamini yağda çözünen bir vitamin olup doğada filokinon (K1), menakinon (K2) ve sentetik analog olarak da menadion (K3) formunda kullanılmaktadır. Genellikle koagülasyon üzerine rolü olduğu bilinen K vitamininin günümüzde kardiyovasküler hastalıklar, osteoporoz, vasküler kalsifikasyon, kanser, diyabet ve glisemik kontrol ile de ilişkisi olduğu bildirilmektedir. Aynı zamanda metabolizmada K vitaminine bağımlı proteinlerin karboksilasyonundan da sorumlu olan vitaminin alınımı son zamanlarda daha çok dikkat çekmektedir. Yapılan çalışmalarda K vitamininin beyinde miyelinizasyonun yoğun olduğu bölgelerde Menakinon-4 (MK-4) formunda bulunduğu saptanmış olan K vitamini eksikliğinin bilişsel performans bozukluğunun patogenezinde rol alabileceği bildirilmiştir. K vitamininin bu etkisini Gas-6 ve protein S gibi moleküller aracılığıyla veya nöronları oksidatif stres hasarına karşı koruyarak gösterdiği düşünülmektedir. Bu derlemede K vitamininin bilişsel performans üzerine etkilerini incelemek amaçlanmaktadır.
Alzheimer’s disease (AD) is the most common type of dementia that affects millions of individuals worldwide. It is an irreversible neurodegenerative disorder that is characterized by memory loss, impaired learning and thinking, and difficulty in performing regular daily activities. Despite nearly two decades of collective efforts to develop novel medications that can prevent or halt the disease progression, we remain faced with only a few options with limited effectiveness. There has been a recent growth of interest in the role of nutrition in brain health as we begin to gain a better understanding of what and how nutrients affect hormonal and neural actions that not only can lead to typical cardiovascular or metabolic diseases but also an array of neurological and psychiatric disorders. Vitamins and minerals, also known as micronutrients, are elements that are indispensable for functions including nutrient metabolism, immune surveillance, cell development, neurotransmission, and antioxidant and anti-inflammatory properties. In this review, we provide an overview on some of the most common vitamins and minerals and discuss what current studies have revealed on the link between these essential micronutrients and cognitive performance or AD.
Patients with Cystic Fibrosis (CF) are at high risk of fat-soluble vitamin deficiencies, even with supplementation. The contribution of a suboptimal vitamin K status to respiratory and endocrine pathophysiology in CF has been inadequately characterized. Cross-sectional study in adult CF patients (≥ 18 years old) from the Montreal Cystic Fibrosis Cohort. Vitamin K1 (VK1) was measured with high performance liquid chromatography (HPLC), using fasted serum samples collected during an oral glucose tolerance test (OGTT: 2h with plasma glucose & insulin every 30 min) (n = 168). Patients were categorized according to VK1 status (suboptimal defined as <0.30 nmol/L). Suboptimal VK1 levels were observed in 66 % of patients. Patients with a suboptimal VK1 status have a higher risk of colonization with Pseudomonas aeruginosa (p=0.001), lower body mass index (BMI) (p=0.003) and were more likely to have exocrine pancreatic insufficiency (p=0.002). Using an established threshold for VK1, we did show significantly reduced OGTT-derived measures of insulin secretion in patients with a VK1 status below 0.30 nmol/L (1st and 2nd Phase AUCINS/GLU (p=0.002 and p=0.006), AUCINS (p=0.012) and AUCINS/GLU (p=0.004)). Subclinical vitamin K deficiency is more common than other fat-soluble vitamin deficiencies in patients with CF. We demonstrate an association between a suboptimal VK1 status and measures of insulin secretion. We highlight the potential associations of mild vitamin K deficiency with pseudomonal colonization and lower BMI, although these need to be validated in prospective studies.
O livro enfatiza fatores que regem a vida humana do início ao fim e que podem ser muito diferentes entre indivíduos e populações: 1) caracteres genéticos herdados diretamente de nossos pais e indiretamente de nossos ancestrais, os quais permanecem relativamente estáveis ao longo da vida; 2) fatores ambientais (alimentação, condição e estilo de vida) até certo ponto controláveis, sendo a alimentação o mais importante. A primeira parte do livro trata da definição e da conceituação do processo de envelhecimento e seus efeitos na saúde. Seguem-se a apresentação e a discussão de mecanismos que promovem degradação molecular e celular responsáveis por distúrbios metabólicos que podem resultar em doenças crônico-degenerativas. A maior parte do texto é dedicada à apresentação de alimentos e compostos bioativos que agem combatendo o envelhecimento precoce e retardando doenças da idade. Por fim, faz-se uma discussão sobre conceitos de dietas saudáveis com sugestões para pesquisas, visando melhorar o perfil alimentar do brasileiro.
Alzheimer hastalığı, merkezi sinir sisteminin çeşitli bölgelerinde nöron ve sinaps kayıpları nedeniyle ortaya çıkan, bilişsel işlevlerde azalma, öz bakım eksiklikleri, çeşitli nöropsikiyatrik ve davranışsal bozukluklar ile karakterize progresif bir nörodejeneratif hastalıktır. Çok faktörlü bir hastalık olan Alzheimer hastalığının etiyolojisinde oksidatif stres, anormal tau protein metabolizması, amiloid birikimi, enflamasyon, yaş, genetik faktörler, kafa travmaları, vasküler hasar, enfeksiyonlar, çevresel faktörler ve beslenme gibi birçok faktör rol oynamaktadır. İnsan hayatını önemli ölçüde etkileyen, henüz tam olarak tedavi edilemeyen Alzheimer hastalığına karşı profilaktik ve tedavi edici yaklaşımlar geliştirilmektedir. Alzheimer hastalığında sağlıklı beslenmenin önemi vurgulanarak hastalar ve yakınları bilgilendirilmeye çalışılmaktadır. Bu derlemede, tüm dünya için önemli bir sağlık sorunu haline gelen Alzheimer hastalığı ile ilişkili vitaminlerin hastalıktaki rolü ve önemi hakkında bilgiler sunulmuştur.
Micronutrients are nutrients required by organism throughout life in small quantities to orchestrate a range of physiological functions. They are composed by vitamins, minerals, and trace elements. Micronutrient deficiencies are common in older adults, even in highly developed industrial nations. They result from insufficient supply and/or increase in micronutrient requirements. Micronutrient deficiencies can accelerate the physiological ageing process and aggravate the decline of cell renewal processes, immune defence, eyesight and hearing, and cognition. It is thus crucial to ensure that older adults receive an optimal supply of vitamins, minerals, and trace elements. We reviewed here the needs, main effects, and current research directions of the micronutrients of interest among older adults. There is a constantly growing certainty that improving the micronutrient supply to older adults, whether via nutrient-dense culturally appropriate diets or via multivitamin-mineral supplements, may be helpful to prevent or at least contain diseases observed with ageing.
Historically discovered for its role in blood coagulation, vitamin K is emerging as a vitamin of wide-ranging physiological implications. Whether through the vitamin K–dependent protein family or specific K vitamers, vitamin K is now known to be involved in bone and cardiovascular metabolism, inflammation, and brain and endocrine function. This chapter discusses the most recent scientific literature relating to vitamin K and points to ongoing and future research efforts.
Nutritional deficiencies often precede the diagnosis of cystic fibrosis (CF) in infants, and occur at a stage where the rapidly developing brain is more vulnerable to insult.
We aim to compare fat-soluble nutrient status of newly diagnosed non-screened infants with CF to that of healthy infants, and explore the association with neurodevelopment evaluated by electroencephalography (EEG).
Our results show that CF infants had lower levels of all fat-soluble vitamins and docosahexaenoic acid (DHA) compared to controls. The auditory evoked potential responses were higher in CF compared to controls whereas the visual components did not differ between groups. DHA levels were correlated with auditory evoked potential responses. Although resting state frequency power was similar between groups, we observed a negative correlation between DHA levels and low frequencies. This study emphasizes the need for long-term neurodevelopmental follow-up of CF infants and pursuing intervention strategies in the future.
Assessment of long-term phylloquinone exposure is challenging in studies investigating vitamin K in health. Data are equivocal as to whether a single measurement of circulating phylloquinone would be adequate. The primary purpose of the present study was to validate the use of a single measurement of serum phylloquinone as a surrogate for long-term phylloquinone exposure in healthy older adults. Using data from the Québec Longitudinal Study on Nutrition and Successful Aging, the objectives were to: 1) determine the reproducibility of circulating phylloquinone over 2 y (n = 234); 2) calculate how a single measurement would rank or classify individuals and attenuate the regression coefficient between circulating phylloquinone and a health outcome; and 3) investigate the association of a single measurement of serum phylloquinone with long-term phylloquinone intakes assessed over the year prior to the blood draw (n = 228). The variance analysis based on 2 blood samples showed a fair to good reproducibility for serum phylloquinone (intra-class correlation = 0.49). The correlation coefficient between the ranking of individuals based on a single measurement of circulating phylloquinone and the "true" ranking would be 0.70. The multiple regression analysis showed that long-term phylloquinone intake was the strongest predictor of serum phylloquinone (t = 4.94; P < 0.001). The partial correlation coefficient (r = 0.32) was comparable with those reported in studies where blood sampling and diet recording were juxtaposed and/or multiple blood samples were used. The present study provides evidence that the use of a single measurement of circulating phylloquinone is adequate for assessing long-term phylloquinone exposure in healthy older adults.
PsyScope is an integrated environment for designing and running psychology experiments on Macintosh computers. The primary
goal of PsyScope is to give both psychology students and trained researchers a tool that allows them to design experiments
without the need for programming. PsyScope relies on the interactive graphic environment provided by Macintosh computers to
accomplish this goal. The standard components of a psychology experiment—groups, blocks, trials, and factors—are all represented
graphically, and experiments are constructed by working with these elements in interactive windows and dialogs. In this article,
we describe the overall organization of the program, provide an example of how a simple experiment can be constructed within
its graphic environment, and discuss some of its technical features (such as its underlying scripting language, timing characteristics,
etc.). PsyScope is available for noncommercial purposes free of charge and unsupported to the general research community.
Information about how to obtain the program and its documentation is provided.
The role of vitamin K in the nervous system has been somewhat neglected compared with other physiological systems despite the fact that this nutrient was identified some 40 y ago as essential for the synthesis of sphingolipids. Present in high concentrations in brain cell membranes, sphingolipids are now known to possess important cell signaling functions in addition to their structural role. In the past 20 y, additional support for vitamin K functions in the nervous system has come from the discovery and characterization of vitamin K-dependent proteins that are now known to play key roles in the central and peripheral nervous systems. Notably, protein Gas6 has been shown to be actively involved in cell survival, chemotaxis, mitogenesis, and cell growth of neurons and glial cells. Although limited in number, studies focusing on the relationship between vitamin K nutritional status and behavior and cognition have also become available, pointing to diet and certain drug treatments (i.e., warfarin derivatives) as potential modulators of the action of vitamin K in the nervous system. This review presents an overview of the research that first identified vitamin K as an important nutrient for the nervous system and summarizes recent findings that support this notion.
In a previous report, we showed vitamin K to preferentially accumulate in brain regions rich in white matter and to positively correlate with certain sphingolipids. In rodents, pharmacological vitamin K deficiency has resulted in behavioral perturbations. To gain insight on the role of vitamin K status on brain function, we investigated learning abilities (Morris water maze), motor activity (open field), and anxiety (elevated plus maze) in distinct groups of 6-, 12-, and 20-mo-old female Sprague-Dawley rats that had been fed diets containing low (L; ~80 μg/kg diet), adequate (A; ~500 μg/kg diet), or high (H; ~2000 μg/kg diet) levels of phylloquinone (μg/kg diet; n = 9-12/diet) since weaning. In 20-mo-old rats, sphingolipids (cerebroside, sulfatide, sphingomyelin, ceramide, and gangliosides), phylloquinone, and menaquinone-4 were also assessed in cerebellum, midbrain, pons medulla, striatum, and hippocampus. Lifetime consumption of a low-vitamin K diet resulted in cognitive deficits in the 20-mo-old rats, with those in the L group having longer latencies than those in the H group (P < 0.05); this was associated with higher concentrations of ceramides in the hippocampus (P < 0.05) and lower gangliosides in the pons medulla and midbrain (P < 0.05). The low-vitamin K diet did not affect cognition at 6 and 12 mo of age, nor did it affect motor activity or anxiety at any age. Although much remains to be elucidated about the mechanism of action of vitamin K in cognition, this report points to vitamin K as an important nutritional factor contributing to cognitive health during aging.
There is a growing interest in the role of vitamin K in health, especially in aging populations. Knowledge of inter- and intra-individual variability of dietary vitamin K intake could be useful to accurately assess usual intake and rank participants in epidemiological studies. Our objectives were to: 1) estimate the variance components of vitamin K intake; 2) investigate whether day of the week, season, and energy intake are factors related to intra-individual variance; and 3) calculate the requisite number of days to achieve desired degrees of accuracy for estimating individual vitamin K intake, ranking individuals and estimating regression coefficient. Vitamin K intake was assessed in 939 older adults (67-84 y) enrolled in the Québec Longitudinal Study on Nutrition and Successful Aging study using 2 sets of 3 nonconsecutive multiple-pass 24-h dietary recalls (24HR) collected 6 mo apart. Each set included 2 weekdays and one weekend day. Intra- to inter-individual variance ratios for vitamin K intake were 3.2 (95% CI = 2.6-3.9) overall, 2.6 (95% CI = 2.1-3.5) for men, and 3.7 (95% CI = 2.9-5.0) for women. Day of the week (weekdays) and season (May to October) were positively and significantly associated with vitamin K intake but explained a negligible part of intra-individual variation (<1%). Adjusting for energy intake explained <7% of variance and did not affect the variance ratio. Six to 13 24HR are required to properly rank individuals according to their usual vitamin K intake and limit attenuation of the regression coefficient. These results should be considered in studies planning to assess vitamin K intakes in older adults.
Cholesterol, omega-3 fatty acids, and triglycerides have been postulated to play roles in affecting cognition in Alzheimer's disease (AD), the elderly, and obesity. Animal, human epidemiological, and in vitro studies each suggest an important role for cholesterol in the regulation of amyloid-beta (Abeta) protein and the pathogenesis of AD. In contrast, well controlled studies have failed to show an effect of cholesterol lowering with statins on cognition, indicating that the cholesterol effect is spurious or indirect, possibly mediated through other lipids. Administration of diedocosahexanoic acid (DHA), a dietary omega-3 fatty acid derived primarily from fish and plants, improves cognition and reduces lipid peroxidation in animals, including in mouse models of AD. DHA also blocks Abeta-mediated tau phosphorylation. In humans, fish consumption or administration of DHA has been associated with cognitive improvement in many, but not all, studies. Both human and animal studies show that obesity is associated with cognitive impairments and that lowering triglycerides improves cognition. Administration of triglycerides to mice decreases learning and memory and impairs long-term potential. The effect of triglycerides may be mediated in part by inducing resistance to positive cognitive features of gastrointestinal hormones such as leptin. Overall, these studies strongly suggest that some lipids affect cognition in AD, the elderly, and obesity through a variety of mechanisms yet to be fully defined.
Oxidative mechanisms of injury are important in many neurological disorders. Developing oligodendrocytes (pre-OLs) are particularly sensitive to oxidative stress-mediated injury. We previously demonstrated a novel function of phylloquinone (vitamin K(1)) and menaquinone 4 (MK-4; a major form of vitamin K2) in protecting pre-OLs and immature neurons against glutathione depletion-induced oxidative damage (Li et al. [ 2003] J. Neurosci. 23:5816-5826). Here we report that vitamin K at nanomolar concentrations prevents arachidonic acid-induced oxidative injury to pre-OLs through blocking the activation of 12-lipoxygenase (12-LOX). Arachidonic acid metabolism is a potential source for reactive oxygen species (ROS) generation during ischemia and reperfusion. Exposure of pre-OLs to arachidonic acid resulted in oxidative cell death in a concentration-dependent manner. Administration of vitamin K (K(1) and MK-4) completely prevented the toxicity. Consistent with our previous findings, inhibitors of 12-LOX abolished ROS production and cell death, indicating that activation of 12-LOX is a key event in arachidonic acid-induced pre-OL death. Vitamin K(1) and MK-4 significantly blocked 12-LOX activation and prevented ROS accumulation in pre-OLs challenged with arachidonic acid. However, vitamin K itself did not directly inhibit 12-LOX enzymatic activity when assayed with purified 12-LOX in vitro. These results suggest that vitamin K, or likely its metabolites, acts upstream of activation of 12-LOX in pre-OLs. In summary, our data indicate that vitamin K prevents oxidative cell death by blocking activation of 12-LOX and ROS generation.
The modulation of phosphosphingolipid synthesis by vitamin K depletion has been observed in the vitamin K-dependent microorganism, Bacteriodes levii. When cultured briefly without the vitamin, a reduction occurred in the activity of the first enzyme of the sphingolipid pathway, 3-ketodihydrosphingosine synthase. In this report, 16-day-old mice were treated with the vitamin K antagonist, warfarin. Brain microsomes from these animals showed a 19% reduction in synthase activity. Mice treated with warfarin for 2 weeks showed a major reduction in sulfatide level (42%), with a lesser degree or no reduction in levels of gangliosides and cerebrosides. In further experiments, mice were treated with warfarin for 2 weeks and a group was then injected with vitamin K1 (aquamephyton) for 3 days. Enzyme activity returned to a normal level within 2-3 days. Sulfatide levels had increased 33% in the vitamin K-injected group and ganglioside levels also increased, where levels of cerebrosides and sphingomyelin declined. Sulfatide synthesis determined by [35S] sulfate incorporation, showed a 52% increase in incorporation following administration of vitamin K for 3 days. These results suggest a role for vitamin K in the biosynthesis of sulfatides and other sphingolipids in brain. This putative role could be by post-translational protein modification analogous to the role of vitamin K in other systems.
Dietary intakes of retinol equivalents, alpha-tocopherol equivalents, vitamin D and phylloquinone were estimated from three sets of 4-d weighed diet records and compared to three corresponding fasting plasma concentrations of retinol, 25-hydroxyvitamin D, alpha-tocopherol, and phylloquinone measured in 34 healthy adults over 20 wk. The magnitude of the correlation between dietary vitamin intake and its corresponding biochemical measure is in part determined by the reproducibility of each of the measures, so within-to-between subject variance ratios were calculated for both dietary intakes and plasma concentrations. Phylloquinone was the only fat-soluble vitamin with a significant correlation between dietary intake and fasting plasma concentration (r = 0.51, P = 0.004). This correlation improved with an increase in both the number of independent diet records and independent plasma measures. Of the dietary intake measures, all the fat-soluble vitamins had greater within than between subject variance, with the highest measured for phylloquinone (6.86:1). Of the plasma measures, only phylloquinone had a within-to-between subject variance ratio greater than one (5.36:1). Comparisons across age and sex for dietary intake and plasma concentrations differed in pattern among the fat-soluble vitamins.
Studies with animals support a role for vitamin K (VK) in the biosynthesis of sphingolipids, a class of complex lipids present in high concentrations in the brain. In mice and rats, VK deficiency decreases levels of brain sulfatides and causes behavioral alterations. In light of its heterogeneity and to better understand the role of VK in the brain, we characterized the distribution of the two main VK vitamers, phylloquinone (K1) and menaquinone-4 (MK-4), in nine distinct brain regions. Weaning female Sprague-Dawley rats (n=5/dietary group) were fed diets containing either low (L, 80 microg/kg diet), adequate (A, 500 microg/kg diet) or high (H, 2000 microg/kg diet) levels of K1 for 6 mo. The main form of VK in the brain was MK-4, and it was present in significantly higher concentrations in myelinated regions (the pons medulla and midbrain) than in nonmyelinated regions. Both regional K1 and MK-4 increased with K1 intake (P<0.05). Sphingolipid distribution varied across brain regions (P<0.001) but was not affected by K1 intake. In the L and A groups but not the H group, brain MK-4 concentration was positively correlated with the concentrations of sulfatides (L, r=0.518; A, r=0.479) and sphingomyelin (L, r=0.515; A, r=0.426), and negatively correlated with ganglioside concentration (L, r=-0.398); A, r=-0.353). Sphingolipids are involved in major cellular events such as cell proliferation, differentiation and survival. The strong associations reported here between brain MK-4 and sphingomyelin, sulfatides and gangliosides suggest that this vitamer may play an important role in the brain.
Vitamin K: Past, Present, Future Essential for normal blood coagulation, possible roles in bone, vascular, and tumor metabolism, and a nutrient critical to the health of the newborn infant -- these are just some of the many health-promoting aspects of Vitamin K. Vitamin K in Health and Disease navigates the exciting research venues that have opened in the past few years surrounding this micro nutrient, particularly its role in skeletal and cardiovascular health. It also provides the historical timeline of vitamin K research and discovery that began in the 1930s. Comprehensive in scope, this book offers complete coverage of the chemistry of Vitamin K; deficiency signs and nutritional assessment; metabolism and biochemistry; and pharmacology. It also presents up-to-date scientific studies on the nutritional, metabolic, and medical aspects along with a review of current dietary requirements and the difficulty involved in establishing an appropriate dietary reference intake for Vitamin K. Extensive References, More than 45 Illustrations, Numerous Tables Based on John Suttie’s 35 years of experience directing a broad vitamin K research program, this work discusses plasma and non-plasma Vitamin K-dependent proteins. It also includes helpful tables on food sources, population intake of Vitamin K, and the impact of diet on the circulating levels of the vitamin – highlighting the role of vitamin K in health and disease. Vitamin K in Health and Disease provides a foundation for future innovations in research and in determining the best ways to implement current knowledge.
Fasting plasma phylloquinone concentrations were determined by reverse-phase high-performance liquid chromatography in a population of young (n = 131) and elderly (n = 195) human subjects. The distribution of values was non-Gaussian but was converted to Gaussian form after a logarithmic transformation of the data. The normal range derived from the lognormal distribution was 0.29–2.64 nmol/L (geometric means = 0.87 nmol/L, median = 0.86 nmol/L). Young females had significantly decreased plasma phylloquinone concentrations when compared with the elderly females whereas concentrations in young males were slightly higher than those in elderly males. A regression model was constructed and revealed that plasma phylloquinone concentrations were positively correlated with plasma triglycerides and alpha-tocopherol. Although the elderly subjects (means = 1.05 nmol/L) had higher levels of phylloquinone than the young subjects (0.94 nmol/L), when the concentration of phylloquinone in plasma is expressed as nanomoles phylloquinone per millimole of triglyceride, the elderly subjects (0.62 x 10(-6) showed decreased levels for phylloquinone compared with the young subjects (0.82 x 10(-6) (p less than 0.001).
Guidelines for submitting commentsPolicy: Comments that contribute to the discussion of the article will be posted within approximately three business days. We do not accept anonymous comments. Please include your email address; the address will not be displayed in the posted comment. Cell Press Editors will screen the comments to ensure that they are relevant and appropriate but comments will not be edited. The ultimate decision on publication of an online comment is at the Editors' discretion. Formatting: Please include a title for the comment and your affiliation. Note that symbols (e.g. Greek letters) may not transmit properly in this form due to potential software compatibility issues. Please spell out the words in place of the symbols (e.g. replace “α” with “alpha”). Comments should be no more than 8,000 characters (including spaces ) in length. References may be included when necessary but should be kept to a minimum. Be careful if copying and pasting from a Word document. Smart quotes can cause problems in the form. If you experience difficulties, please convert to a plain text file and then copy and paste into the form.
Gas6 is the newest member of the family of vitamin K-dependent proteins that acts as a ligand for the Axl family of RTK with homology to neural cell adhesion molecules. Gas6-Axl interactions have been implicated in anti-apoptotic activity. Here we report the first identification of Gas6 in the rat brain synaptosomes from three brain regions: striatum, hippocampus and frontal cortex. Furthermore, we discovered age-related and area-specific declines in the levels of Gas6 in the synaptosomes. The age effects on Gas6 levels were observed in all brain areas. Frontal cortex demonstrated the most dramatic decrease in Gas6 with aging (over 84% decline in old animals, as compared with young) (p<0.001). Gas6 levels in synaptosomes derived from striatum and hippocampus of the old animals were over 55% lower than those of the young (p<0.01). Phospholipid analysis of synaptosomes showed that in the cortex, decreases in Gas6 levels may be explained by age-related decrease in membrane phosphatidylserine composition. The brain area-specific decreases in Gas6 may in turn affect the RTK-regulated cell cycle, resulting in changes in distinct neuronal population viability. Thus, our findings suggest for the first time a role for Gas6 in brain aging.
The brain is enriched with sphingolipids, which are important membrane constituents and major lipid signaling molecules that have a role in motor and cognitive behavior. Vitamin K has been implicated in brain sphingolipid metabolism for more than 30 years. The in vitro and in vivo studies to date suggest a role of vitamin K in the regulation of multiple enzymes involved in sphingolipid metabolism within the myelin-rich regions in the brain. However, the precise mechanisms of action are not well understood. Further, the physiological consequences of the observed effects of vitamin K on sphingolipid metabolism have not been systematically studied.
Gas6 (growth arrest specific gene-6) is a ligand for members of the Axl subfamily of receptor protein-tyrosine kinases. One of these receptors, Tyro-3, is widely expressed in the central nervous system. We have used biochemical and histological techniques, including in situ hybridization, to determine the expression patterns of Gas6 mRNA and protein during development. Gas6 is widely expressed in the rat central nervous system (CNS) beginning at late embryonic stages and its levels remain high in the adult. Gas6 is detected as a single 85 kDa protein, which is encoded by a single 2.5 kb mRNA species. At embryonic day 14 it is detected in the heart, blood vessels, testes, choroid plexus, and in the ventral spinal cord. In the adult, Gas6 is expressed in the cerebral cortex, (predominantly in layer V), the piriform cortex, and the hippocampus (areas CA1, CA3 and the dentate gyrus). It is also expressed in thalamic and hypothalamic structures, the midbrain, and in a subset of motor and trigeminal nuclei. In the cerebellum, it is expressed in Purkinje neurons and deep cerebellar nuclei. Protein S, a protein related to Gas6, is only detected at low levels in the CNS. The spatial and temporal profiles of Gas6 expression suggest that it could potentially serve as the physiologically relevant ligand for Tyro-3 in the postnatal rat nervous system.
To elucidate the role of intestinal bacteria in the conversion of phylloquinone into menaquinone-4 (MK-4) we investigated the tissue distribution of vitamin K in germ-free rats. The rats were made vitamin K deficient by feeding a vitamin K-free diet for 13 days. In a subsequent period of 6 days, phylloquinone and menadione were supplied via the drinking water in concentrations of 10 and 50 μmol l−1. Menadione supplementation led to high levels of tissue MK-4, particularly in extrahepatic tissues like pancreas, aorta, fat and brain. Liver and serum were low in MK-4. Phylloquinone supplementation resulted in higher phylloquinone levels in all tissues when compared with vitamin K-deficient values. The main target organs were liver, heart and fat. Remarkably, tissue MK-4 levels were also higher after the phylloquinone supplementation. The MK-4 tissue distribution pattern after phylloquinone intake was comparable with that found after menadione intake. Our results demonstrate that the conversion of phylloquinone into MK-4 in extrahepatic tissues may occur in the absence of an intestinal bacterial population and is tissue specific. A specific function for extrahepatic MK-4 or a reason for this biochemical conversion of phylloquinone into MK-4 remains unclear thus far.
Vitamin K (VK) has a protective effect on neural cells. Methylmercury is a neurotoxicant that directly induces neuronal death in vivo and in vitro. Therefore, in the present study, we hypothesized that VK inhibits the neurotoxicity of methylmercury. To prove our hypothesis in vitro, we investigated the protective effects of VKs (phylloquinone, vitamin K(1); menaquinone-4, vitamin K(2) ) on methylmercury-induced death in primary cultured neurons from the cerebella of rat pups. As expected, VKs inhibited the death of the primary cultured neurons. It has been reported that the mechanisms underlying methylmercury toxicity involve a decrement of intracellular glutathione (GSH). Actually, treatment with GSH and a GSH inducer, N-acetyl cysteine, inhibited methylmercury-induced neuronal death in the present study. Thus, we investigated whether VKs also have protective effects against GSH-depletion-induced cell death by employing two GSH reducers, L-buthionine sulfoximine (BSO) and diethyl maleate (DEM), in primary cultured neurons and human neuroblastoma IMR-32 cells. Treatment with VKs affected BSO- and DEM-induced cell death in both cultures. On the other hand, the intracellular GSH assay showed that VK(2), menaquinone-4, did not restore the reduced GSH amount induced by methylmercury or BSO treatments. These results indicate that VKs have the potential to protect neurons against the cytotoxicity of methylmercury and agents that deplete GSH, without increasing intracellular GSH levels. The protective effect of VKs may lead to the development of treatments for neural diseases involving GSH depletion.
Dysregulation of myelin sulfatides is a risk factor for cognitive decline with age. Vitamin K is present in high concentrations in the brain and has been implicated in the regulation of sulfatide metabolism. Our objective was to investigate the age-related interrelation between dietary vitamin K and sulfatides in myelin fractions isolated from the brain regions of Fischer 344 male rats fed one of two dietary forms of vitamin K: phylloquinone or its hydrogenated form, 2',3'-dihydrophylloquinone (dK), for 28 days. Both dietary forms of vitamin K were converted to menaquinone-4 (MK-4) in the brain. The efficiency of dietary dK conversion to MK-4 compared to dietary phylloquinone was lower in the striatum and cortex, and was similar to that in the hippocampus. There were significant positive correlations between sulfatides and MK-4 in the hippocampus (phylloquinone-supplemented diet, 12 and 24 months; dK-supplemented diet, 12 months) and cortex (phylloquinone-supplemented diet, 12 and 24 months). No significant correlations were observed in the striatum. Furthermore, sulfatides in the hippocampus were significantly positively correlated with MK-4 in serum. This is the first attempt to establish and characterize a novel animal model that exploits the inability of dietary dK to convert to brain MK-4 to study the dietary effects of vitamin K on brain sulfatide in brain regions controlling motor and cognitive functions. Our findings suggest that this animal model may be useful for investigation of the effect of the dietary vitamin K on sulfatide metabolism, myelin structure and behavior functions.
Compendio de pruebas neuropsicológicas en que se ofrece también la información necesaria para seleccionar el test adecuado, cómo aplicarlo, cómo preparar al cliente, cómo interpretar los resultados y cómo ponerlos por escrito, así como duración, costo y validación de cada uno de ellos.
Nearly twice as many participants are represented in the current literature than were available at the time of the last major meta-analytic neurocognitive examination of apolipoprotein E (ApoE) epsilon allele combinations [Small, B.J., Rosnick, C.B., Fratiglioni, L., Backman, L., 2004. Apolipoprotein E and cognitive performance: a meta-analysis. Psychol. Aging 19, 592-600]. The meta-analysis in the current study sought to specifically examine (1) small effects and (2) possible moderating variables associated with ApoE allele combinations that may have been undiscoverable in previous examinations of smaller data sets. A total of 77 studies, representing 40,942 cognitively healthy adults were identified for inclusion in the current meta-analysis (random effects design). Results were congruent with the previous meta-analytic findings indicating that carriers of ApoE allele 4 (ɛ4) perform significantly worse on measures of episodic memory, executive functioning, and overall global cognitive ability. In addition, the current analysis revealed a small effect suggesting that ApoE allele 4 adversely impacts perceptual speed. In contrast to earlier studies, the results also indicate that increases in age result in significantly larger differences between ApoE ɛ4 carriers and ApoE non-ɛ4 carriers on measures of episodic memory and global cognitive ability. ApoE ɛ4 exerts broad, but specific, adverse small effects on a range of neurocognitive functions in cognitively healthy adults.
An increasing body of evidence points to a role for vitamin K in brain physiology through its participation in sphingolipid metabolism and biological activation of the vitamin K-dependent protein Gas6. One hypothesis is that vitamin K may also play a role in the pathogenesis of Alzheimer's disease. A recent study found that patients with early-stage Alzheimer's disease consumed less vitamin K than did cognitively intact control subjects. To learn more about the dietary intakes and food sources of vitamin K in these patients, a detailed analysis was conducted. Dietary vitamin K intakes were assessed from 5 nonconsecutive days of food records collected from 31 community-dwelling patients with early-stage Alzheimer's disease and in 31 age- and sex-matched cognitively intact control subjects. Mean vitamin K intake on a person-day basis was 63+/-90 microg/day in patients and 139+/-233 microg/day in control subjects. Vitamin K intakes were significantly less in participants with Alzheimer's disease (P<0.0001), even after adjusting for energy intakes (P=0.0003). Vegetables, fats, and fruits contributed more than 70% of total vitamin K intake in both groups. The main source of vitamin K was green vegetables, which contributed 33% and 49% to total intakes in patients and control subjects, respectively. This lower consumption of green vegetables in participants with Alzheimer's disease explained their lower vitamin K intakes overall. Despite their limitations, results are in line with the most recent research in both vitamin K and Alzheimer's disease and suggest a need to consider vitamin K in future investigations on the role of diet in Alzheimer's disease.
Fasting plasma phylloquinone concentrations were determined by reverse-phase high-performance liquid chromatography in a population of young (n = 131) and elderly (n = 195) human subjects. The distribution of values was non-Gaussian but was converted to Gaussian form after a logarithmic transformation of the data. The normal range derived from the lognormal distribution was 0.29-2.64 nmol/L (geometric means = 0.87 nmol/L, median = 0.86 nmol/L). Young females had significantly decreased plasma phylloquinone concentrations when compared with the elderly females whereas concentrations in young males were slightly higher than those in elderly males. A regression model was constructed and revealed that plasma phylloquinone concentrations were positively correlated with plasma triglycerides and alpha-tocopherol. Although the elderly subjects (means = 1.05 nmol/L) had higher levels of phylloquinone than the young subjects (0.94 nmol/L), when the concentration of phylloquinone in plasma is expressed as nanomoles phylloquinone per millimole of triglyceride, the elderly subjects (0.62 x 10(-6) showed decreased levels for phylloquinone compared with the young subjects (0.82 x 10(-6) (p less than 0.001).
Anecdotal observations of the behavior of rats with a vitamin K-deficiency suggested that this deficiency was associated with hypoactivity, general malaise, and a lack of exploratory behavior. These observations were pursued by assessing locomotor activity in a circular photocell-monitored track, open-field activity, and radial-arm maze performance in rats rendered vitamin K-deficient by dietary depletion or by warfarin treatment. There was a significant reduction (approximately 25% at the median) in the locomotor activity of dietary vitamin K-deficient rats compared with rats fed a control diet. In the open-field, warfarin administration was associated with a significant shift from more exploratory behaviors to less exploratory behaviors. Consistent with these findings, radial-arm maze assessment showed a comparative reduction in locomotor activity in the dietary vitamin K-deficient rats with no alteration in performance, i.e., short-term memory. These animal behavioral studies suggest that sub-clinical and clinical vitamin K-deficiency may contribute to physical and psychiatric symptomatology.
Review of published cases of pregnancies in which coumarin derivatives or heparin were administered demonstrates that use of either class of anticoagulant carries substantial risks. Of 418 reported pregnancies in which coumarin derivatives were used, one-sixth resulted in abnormal liveborn infants, one-sixth in abortion or stillbirth and, at most, two-thirds in apparently normal infants. In addition to the expected hemorrhagic complications, fetal effects of coumarin derivative administration include a specific embryopathy and central nervous system abnormalities. All available cases (including unpublished ones) of warfarin embryopathy and central nervous system abnormalities following gestational exposure to coumarin derivatives are reviewed, various complications are tabulated, critical periods of teratogenesis are discussed and possible mechanisms proposed. The use of heparin during gestation does not result in a significantly better outcome of pregnancy. In 135 published cases, the infants in one-eighth were stillborn, in one-fifth premature (a third of whom died) and, again at most, in two-thirds apparently normal. Because of the substantial risks of both clases of anticoagulants, and the inherent risks of pregnancy complicated by the indications for anticoagulation, prevention of pregnancy is usually indicated. If pregnancy occurs, a relatively normal outcome can be anticipated in about two-thirds of the pregnancies regardless of the anticoagulant used. Heparin does not appear to be a clearly superior alternative to coumarin derivatives.
A new Geriatric Depression Scale (GDS) designed specifically for rating depression in the elderly was tested for reliability and validity and compared with the Hamilton Rating Scale for Depression (HRS-D) and the Zung Self-Rating Depression Scale (SDS). In constructing the GDS a 100-item questionnaire was administered to normal and severely depressed subjects. The 30 questions most highly correlated with the total scores were then selected and readministered to new groups of elderly subjects. These subjects were classified as normal, mildly depressed or severely depressed on the basis of Research Diagnostic Criteria (RDC) for depression. The GDS, HRS-D and SDS were all found to be internally consistent measures, and each of the scales was correlated with the subject's number of RDC symptoms. However, the GDS and the HRS-D were significantly better correlated with RDC symptoms than was the SDS. The authors suggest that the GDS represents a reliable and valid self-rating depression screening scale for elderly populations.
Vitamin K-dependent protein S is an anticoagulant plasma protein that functions as a co-factor to activated protein C in the degradation of coagulation factors Va and VIIIa. We investigated the tissue/cellular distribution of protein S synthesis by Northern blotting, in situ hybridization, and immunohistochemistry. Northern blotting together with in situ hybridization, using specific oligodeoxynucleotide probes, demonstrated protein S mRNA in liver, lung, testis, epididymis, ovary, uterus, and brain. In the reproductive system, protein S mRNA was present in the cytoplasm of Leydig cells, interstitial cells of the ovary, epithelial cells of the epididymis, and in the endometrium, including endometrial mucous glandular membrane in the myometrium. Bronchial epithelial cells and alveolar macrophages were positive in the respiratory system. In the central nervous system, pyramidal neurons in the cerebral cortex and in the hippocampal region, and dentate fascia neurons gave strongly positive signals. Immunohistochemistry with monoclonal antibodies yielded a staining pattern that correlated well with results of in situ hybridization. In conclusion, results from Northern blotting, in situ hybridization, and immunohistochemistry suggested that rabbit protein S is expressed in several extrahepatic tissues. The presence of protein S transcripts in these fully differentiated cells suggests a cell type-specific gene expression which may be related to local anticoagulation or to other as yet unknown protein S functions.
The present study was undertaken to determine whether there is selective tissue distribution of vitamin K in the rat and whether this distribution mirrors the distribution of tissue vitamin K metabolism. The effects of feeding a vitamin K-free diet followed by resupplementation with phylloquinone (K1) were studied. K1 was recovered in all tissues. In K1-supplemented rats, most tissues accumulated K1 relative to plasma K1 with the highest levels in liver, heart, bone, and cartilaginous tissue (sternum). Low K1 levels were found in the brain. In the K1-free rats, relatively high K1 levels were still found in heart, pancreas, bone and sternum. Surprisingly, menaquinone-4 (MK-4) was detected in all tissues, with low levels in plasma and liver, and much higher levels in pancreas, salivary gland and sternum. MK-4 levels exceeded K1 levels in brain, pancreas, salivary gland and sternum. Supplementation with K1, orally and by intravenous infusion, caused MK-4 levels to rise. Some accumulation of K1 and MK-4 in the mitochondrial fraction was found for kidney, pancreas and salivary gland. In the liver the higher menaquinones (MK-6-9) accumulated in the mitochondria. The results indicate that: (1) there is selective tissue distribution of K1 and MK-4, (2) dietary K1 is a source of MK-4. The results also suggest there may be an as yet unrecognized physiological function for vitamin K (MK-4).
Plasma concentrations of phylloquinone in 42 fasting hemodialysis patients showed a much wider range than in healthy adults. Phylloquinone concentrations were best predicted by the concentration ratio of beta-very-low-density-lipoprotein to low-density-lipoprotein cholesterol (r = 0.71), which is closely related to chylomicron-remnant clearance. Phylloquinone concentrations in plasma were related to apolipoprotein E genotype in the order E2 > E3 > E4. The percentage of carboxylated osteocalcin (HBC) was related to the plasma concentration of phylloquinone in patients with the apolipoprotein E genotype E3/3 (r = 0.52, P < 0.05), and in patients with the genotypes E2/3 and E2/2 (r = 0.23, P < 0.1). Overall, plasma triglyceride concentration was a better predictor for HBC than was the plasma concentration of phylloquinone. These results point to the overriding importance of chylomicrons for the transport of phylloquinone to liver and bone. Delivery to osteocalcin-producing osteoblasts seemed impaired in patients with the low receptor-affinity apolipoprotein variant E2, suggesting a major role of receptor-mediated chylomicron-remnant uptake in the transport of phylloquinone to bone.
To examine the relationship between dietary phylloquinone intake and vitamin K status of postmenopausal Caucasian women.
Cross-sectional study, in which dietary intake was estimated using weighed record techniques and vitamin K status was measured by a single plasma phylloquinone concentration and 24-h urinary gamma-carboxyglutamic acid (Gla) excretion.
The metabolic research unit at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
402 healthy postmenopausal Caucasian women who were participating in a randomized trial to determine the effect of calcium supplementation on bone loss. Of the original group, 362 had complete weighed diet records, 358 had corresponding plasma phylloquinone concentrations, and 346 had corresponding urinary Gla measurements.
There was a significant correlation (r = 0.13, P = 0.01) between total dietary intake of phylloquinone (geometric mean = 89 micrograms/day) and plasma phylloquinone levels (mean = 1.12 nmol/l). Dietary intake was neither correlated with urinary Gla excretion (mean = 4.0 mumol/mmol creatinine) nor did it vary by season. The ratio of intra- to interindividual variance in phylloquinone intake was 2.6, from which it was estimated that 5 days of independent recording is necessary to estimate true usual dietary intake, assuming a correlation of 0.8.
A weighed record has the potential to be a reliable method for estimating dietary intakes of vitamin K which relate to plasma phylloquinone levels used as an indicator of vitamin K status in postmenopausal Caucasian women.
Biochemical indexes for assessing vitamin K nutritional status were evaluated in 263 healthy subjects (127 males, 136 females) aged 18-85 y. The influences of aging (stratified by decade), menopause, and sex were examined. Total, carboxylated, and undercarboxylated osteocalcin concentrations were affected by sex and aging with increases in the sixth decade in women attributed to menopause. Aging effects in the women and sex differences were eliminated when undercarboxylated osteocalcin was expressed as a percentage of the total. Plasma phylloquinone and undercarboxylated prothrombin (PIVKA-II) concentrations varied little with aging with the exception of lower concentrations of phylloquinone in women in their third decade compared with other ages and higher concentrations of PIVKA-II in younger males compared with younger females. Urinary gamma-carboxyglutamic acid (Gla)-creatinine excretion ratios increased significantly with age in both males (r = 0.68, P < 0.001) and females (r = 0.63, P < 0.001) with values 20% higher in the females on average over the entire age span. The undercarboxylated osteocalcin concentration, shown previously to be responsive to depletion and repletion of phylloquinone, was compared with the other indexes to determine its reliability as an indicator of vitamin K nutritional status. This measure appears promising because it correlated with plasma PIVKA-II concentrations (r = 0.27, P < 0.001) and with plasma phylloquinone concentrations (r = -0.35, P < 0.001), whereas the agreement between plasma phylloquinone and PIVKA-II concentrations was not as strong (r = -0.15, P < 0.05).
Intra- and interindividual variation of phylloquinone (vitamin K1) concentrations was investigated by repeat analysis of serum from 28 hemodialysis patients with different apolipoprotein E genotypes. Phylloquinone concentrations ranged from 0.1 to 9.0 nM, with a mean of 1.08 nM (standard deviation 1.90 nM).
Most of the variation in serum phylloquinone concentrations was due to differences between patients; the ratio of intra-to interindividual variation was 0.17. Serum triglyceride concentrations and apoE genotype together accounted for 64% of interindividual variation; in contrast, only 6% of intraindividual variation could be attributed to differences in triglyceride concentrations.
The small residual variance implies that different phylloquinone consumption levels contributed relatively little to the variation of serum concentrations (<36% of interindividual variance). The results suggest that individual disposition is a more important determinant of serum phylloquinone concentrations than dietary phylloquinone intake.
To clarify the origin of organ menaquinone-4 (MK-4), the distributions of phylloquinone and MK-4 were investigated in rats fed diets containing phylloquinone, MK-4 or menadione (1.1, 2.2 and 31 mumol/kg diet, respectively, 6 rats per group). Warfarin (2 x 1 mg/kg subcutaneously) was given (3 rats per group) to study the effect of vitamin K cycle blockage. In rats fed phylloquinone the vitamin accumulated mainly in liver and heart. Additionally, the diet resulted in significantly higher organ MK-4 concentrations compared with the vitamin K-deficient controls. The epoxide of MK-4 also was significantly higher in some organs. The MK-4 diet increased MK-4 concentration primarily in the heart, liver and lung. Rats fed menadione had significantly higher MK-4 and MK-4 epoxide concentrations in all organs examined. The greatest accumulations were in nonhepatic organs, particularly the pancreas, salivary gland and brain. Generally, liver and plasma had low MK-4 concentrations. Warfarin treatment lowered significantly the MK-4 concentrations, whereas MK-4 epoxide accumulated. The study shows the following: 1) dietary phylloquinone is accumulated mainly in the heart and liver, 2) the MK-4 accumulation in nonhepatic organs is due to synthesis rather than uptake and 3) MK-4 rather than phylloquinone may be the functional vitamin in nonhepatic organs.
We measured the vitamin K status in postmortem human tissues (brain, heart, kidney, liver, lung, pancreas) to see if there is a tissue-specific distribution pattern. Phylloquinone (K1) was recovered in all tissues with relatively high levels in liver, heart and pancreas (medians, 10.6 (4.8), 9.3 (4.2), 28.4 (12.8) pmol(ng)/g wet weight tissue); low levels (< 2 pmol/g) were found in brain, kidney and lung. Menaquinone-4 (MK-4) was recovered from most of the tissues; its levels exceeded the K1 levels in brain and kidney (median, 2.8 ng/g) and equalled K1 in pancreas. Liver, heart and lung were low in MK-4. The higher menaquinones, MK-6-11, were recovered in the liver samples (n 6), traces of MK-6-9 were found in some of the heart and pancreas samples. The results show that in man there are tissue-specific, vitamin-K distribution patterns comparable to those in the rat. Furthermore, the accumulation of vitamin K in heart, brain and pancreas suggests a hitherto unrecognized physiological function of this vitamin.
The established role of vitamin K in nutrition is as a cofactor in the post-translational conversion of specific glutamyl to gamma-carboxyglutamyl (Gla) residues in a limited number of proteins. Administration of the vitamin K antagonist warfarin has previously been shown to decrease brain sulfatide concentrations and decrease brain galactocerebroside sulfotransferase (GST) activity in young mice. A dietary deficiency of vitamin K has now been shown to decrease (P < 0.01) brain sulfatide concentrations of 30-d-old mice significantly (by 21%). Male 21-d-old rats fed an excess of vitamin K for 7 or 14 d had 26 and 31% (P < 0.05) greater GST activity and 15 and 18% (P < 0.05) greater brain sulfatide concentrations, respectively, than controls fed a vitamin K-deficient diet. Male 21-d-old rats fed a diet containing 500 mg of phylloquinone/kg diet had an intermediate response and were vitamin K sufficient by normal criteria. The vitamin K response was observed when either phylloquinone or menaquinone-4 was fed as a source of the vitamin. These data suggest that in addition to its recognized role in Gla synthesis, vitamin K status is important in the maintenance of normal complex lipid sulfatide metabolism in young rats and mice.
This investigation of 68 hemodialysis patients (ages 33 to 91) analyzed the association of biochemical indicators of vitamin K nutriture and bone metabolism, and related both to past bone fracture history and prospective bone fracture risk. Phylloquinone concentrations were significantly lower in the 23 patients with previous fractures compared to those without (0.93 vs. 1.50 nmol/liter, P < 0.003) and a smaller percentage of their serum osteocalcin was carboxylated (48.8 vs. 53.6%, P < 0.03). The 41 patients who never had fractures had nearly three times higher phylloquinone concentrations than the nine patients with fractures during a four-year follow-up period (1.59 vs. 0.55 nmol/liter, P < 0.002) and more carboxylated serum osteocalcin (55.2 vs. 42.0%, P < 0.01). None of the patients with phylloquinone concentrations over 2.2 nmol/liter had elevated intact parathyroid hormone (iPTH) concentrations, and only patients with less than 1 nmol/liter phylloquinone had severe hyperparathyroidism (iPTH > 300 ng/liter). Our data thus indicate that suboptimal vitamin K nutriture in hemodialysis patients is associated both with increased bone fracture risk and with a high prevalence of hyperparathyroidism.
The high-performance liquid chromatography (HPLC) assays used for the determination of endogenous phylloquinone, phylloquinone 2,3-epoxide, menaquinones, and most recently 2',3'-dihydrophylloquinone have evolved from the postcolumn reduction and fluorimetric detection methodology. The analytical system utilized to reduce vitamin K compounds to their fluorescent hydroquinones consists of a postcolumn, dry chemical reactor containing zinc metal. Hydroquinones are produced by chemical reduction over zinc in the presence of zinc ions, which are provided by the mobile phase. This on-line reduction process forms the core of the chromatographic systems used for the determination of vitamin K. Although the column configuration, injector type, mobile-phase composition, and flow rates of analytical systems may vary, the online, postcolumn reduction is essentially the same. This chapter describes two assays based on postcolumn reduction, but with significant enhancements made in the sensitivity of analytical systems: (1) a simplified method for the determination of fasting plasma or serum concentrations of phylloquinone and (2) an assay for the simultaneous determination of endogenous phylloquinone and phylloquinone 2,3-epoxide in plasma or serum.
The purpose of this study was to characterize the absorption and transport of phylloquinone (vitamin K1) by plasma lipoproteins. Twenty-six healthy subjects (11 men and 15 women) aged 20-78 y received phylloquinone in the amount of either 1.43 or 50 microg/kg body wt orally with a fat-rich meal containing 1.0 g/kg body wt of fat, carbohydrate, and protein and 7.0 mg cholesterol/kg body wt. Blood was obtained at baseline (0 h) and 3, 6, 9, and 12 h after the meal for the measurement of plasma lipid and phylloquinone concentrations in plasma and lipoprotein subfractions. In both groups of subjects, triacylglycerol concentrations peaked after 3 h in plasma and in the triacylglycerol-rich lipoprotein fraction, composed of chylomicrons and VLDLs. Plasma phylloquinone concentrations peaked at 6 h. At baseline and during the postprandial phase, > 53% of plasma phylloquinone was carried by the triacylglycerol-rich lipoprotein fraction. In 9 of the 11 subjects supplemented with 50 microg phylloquinone/kg, plasma lipoproteins were isolated by sequential ultracentrifugation. In these subjects the fraction of plasma phylloquinone carried by LDLs and by HDLs increased progressively from 3% and 4% at 3 h to 14% and 11% at 12 h, respectively. Our data indicate that whereas triacylglycerol-rich lipoproteins are the major carriers of phylloquinone, LDL and HDL may carry small fractions of this vitamin.
Gas6 (growth arrest specific gene-6) is a ligand for members of the Axl subfamily of receptor protein-tyrosine kinases. One of these receptors, Tyro-3, is widely expressed in the central nervous system. We have used biochemical and histological techniques, including in situ hybridization, to determine the expression patterns of Gas6 mRNA and protein during development. Gas6 is widely expressed in the rat central nervous system (CNS) beginning at late embryonic stages and its levels remain high in the adult. Gas6 is detected as a single 85 kDa protein, which is encoded by a single 2.5 kb mRNA species. At embryonic day 14 it is detected in the heart, blood vessels, testes, choroid plexus, and in the ventral spinal cord. In the adult, Gas6 is expressed in the cerebral cortex, (predominantly in layer V), the piriform cortex, and the hippocampus (areas CA1, CA3 and the dentate gyrus). It is also expressed in thalamic and hypothalamic structures, the midbrain, and in a subset of motor and trigeminal nuclei. In the cerebellum, it is expressed in Purkinje neurons and deep cerebellar nuclei. Protein S, a protein related to Gas6, is only detected at low levels in the CNS. The spatial and temporal profiles of Gas6 expression suggest that it could potentially serve as the physiologically relevant ligand for Tyro-3 in the postnatal rat nervous system.
We assessed the validity of the Physical Activity Scale for the Elderly (PASE) in a sample of sedentary adults (56 men, 134 women, mean age +/- [SD] 66.5+/-5.3 years) who volunteered to participate in a randomized controlled trial on the effect of aerobic conditioning on psychological function. Construct validity was established by correlating PASE scores with physiologic and performance characteristics: peak oxygen uptake, resting heart rate and blood pressure, percent body fat, and balance. The mean PASE scores were higher in men than in women (men = 145.8+/-78.0; women = 123.9+/-66.3, P<0.05), and in those age 55-64 years compared with those age 65 years and over (55-64 = 144.2+/-75.8; 65 and over = 118.9+/-63.9, P<0.05). PASE scores were also significantly higher in those who did not report a chronic health condition (cardiovascular disease, hypertension, cancer, or recent surgery). PASE scores were significantly associated (P<0.05) with peak oxygen uptake (r = 0.20), systolic blood pressure (r = -0.18) and balance score (r = 0.20). No significant associations of PASE score and diastolic blood pressure, resting heart rate, or percent body fat were noted. These results provide additional evidence for the validity of the PASE as a measure of physical activity suitable for use in epidemiology studies on the association of physical activity, health, and physical function in older individuals.
Few epidemiological studies that rely on the food frequency questionnaire (FFQ) for dietary assessment have measured biomarkers of vitamin K intake to independently confirm associations between self-reported dietary vitamin K intake and disease risk. Associations were examined between two sensitive biomarkers of vitamin K status, plasma phylloquinone and serum percent undercarboxylated osteocalcin (%ucOC), and self-reported usual phylloquinone intake as estimated from a FFQ. The influence of other dietary and nondietary factors on plasma phylloquinone concentrations was also examined. Dietary phylloquinone intake was estimated using a FFQ in 369 men and 468 women of the Framingham Offspring Study. The prevalence of high %ucOC concentrations (>/= 20%), suggestive of a low vitamin K status, was 44% in men and 54% in women, respectively. After multivariate adjustment, the odds of a high %ucOC was 2.5 greater for women (odds ratio: 2.5; 95% confidence interval [CI]: 1.2-5.1) and almost three times greater for men (odds ratio: 2.8; 95% CI: 1.3-5.9) in the lowest dietary phylloquinone intake quintile category compared to the highest quintile category. Fasting triglyceride concentrations, smoking status and season were associated with plasma phylloquinone concentrations, independent of dietary phylloquinone intake. Phylloquinone and green vegetable intake was linearly associated with plasma phylloquinone, after adjustment for potential confounding factors. There were limitations in the use of the FFQ to predict plasma phylloquinone, evident in an observed plateau effect and required nondietary adjustment factors. Despite these caveats, these findings support the use of a FFQ for a relative assessment of vitamin K status in population-based studies.
The plasma transport of stable isotope-labeled phylloquinone at physiologic doses from food was studied. A single bolus of 100 g (396 +/- 28 microg phylloquinone) deuterium-labeled collard greens was fed with a breakfast containing 24 g fat to 5 men (26 to 71 years). Eleven blood samples were obtained over 216 hours. Phylloquinone concentrations in plasma and lipoprotein subfractions were measured using high-performance liquid chromatography (HPLC), and the ion abundances of deuterated and endogenous phylloquinone were determined using gas chromatography/mass spectrometry (GC/MS). Plasma total phylloquinone concentrations peaked at 6 to 9 hours (10.51 +/- 4.38 to 8.30 +/- 4.64 nmol/L) and returned to baseline by 24 hours (1.26 +/- 0.38 nmol/L). The triglyceride-rich lipoprotein (TRL) fraction was the major carrier of phylloquinone; low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions contained smaller amounts. Maximum enrichment of plasma and TRL phylloquinone with deuterium (88% and 89%, respectively) was reached at 6 hours, respectively; t(1/2) was 22.8 hours (n = 3). Deuterated-phylloquinone was not detectable in plasma or TRL fraction at 72 hours. These results suggest rapid uptake and transport of physiologic doses of phylloquinone.
A modified high-performance liquid chromatography (HPLC) method, based on Davidson and Sadowski [Meth. Enzymol. 282 (1997) 408], with fluorescence detection after zinc postcolumn reduction was developed and validated for the analysis of phylloquinone (vitamin K1) in plasma or serum samples. Compensation for procedural losses of vitamin K1 was made by the method of internal standardization using a proprietary vitamin K derivative. Increased sensitivity of detection by the use of a high-sensitivity Waters 440 fluorescence detector and optimized chromatography conditions increased the sensitivity to 4 fmol vitamin K1. The response was linear and free from interfering peaks and from baseline drift. It is therefore adequately sensitive for 0.25 ml or less of plasma sample. Long-term reproducibility of quality assurance (QA) samples was verified over a period of 4 months. The intraassay precision estimates of the QA samples within-run with mean vitamin K1 concentrations of 0.4, 1.4 and 3.4 nmol/l were 5.2% (n=6), 8.2% (n=6) and 3.0% (n=12), respectively, while interassay precision estimates between runs were 16% (n=22), 12% (n=21) and 8.1% (n=15), respectively. The assay accuracy was validated by comparing the results we obtained for 14 samples from the Vitamin K External Quality Assessment Scheme (KEQAS) with the consensus of the results from the other participating laboratories. Good agreement was obtained, with y=1.06x-0.09, R2=0.99. Validation also included linearity of response, absence of interference and confirmation of vitamin K1 peak purity.