vitamin-k-semiquinone-radical and Alzheimer-Disease

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.

Topics: Alzheimer Disease; Humans; Multiple Sclerosis; Neurodegenerative Diseases; Parkinson Disease; Vitamin K

Alzheimer's disease (AD) is the most common cause of dementia in the elderly population, currently affecting 46 million people worldwide. Histopathologically, the disease is characterized by the occurrence of extracellular amyloid plaques composed of aggregated amyloid-β (Aβ) peptides and intracellular neurofibrillary tangles containing the microtubule-associated protein tau. Aβ peptides are derived from the sequential processing of the amyloid precursor protein (APP) by enzymes called secretases, which are strongly influenced by the lipid environment. Several vitamins have been reported to be reduced in the plasma/serum of AD-affected individuals indicating they have an impact on AD pathogenesis. In this review we focus on vitamin E and the other lipophilic vitamins A, D, and K, and summarize the current knowledge about their status in AD patients, their impact on cognitive functions and AD risk, as well as their influence on the molecular mechanisms of AD. The vitamins might affect the generation and clearance of Aβ both by direct effects and indirectly by altering the cellular lipid homeostasis. Additionally, vitamins A, D, E, and K are reported to influence further mechanisms discussed to be involved in AD pathogenesis, e.g., Aβ-aggregation, Aβ-induced neurotoxicity, oxidative stress, and inflammatory processes, as summarized in this article.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Humans; Lipid Metabolism; Vitamin A; Vitamin D; Vitamin E; Vitamin K

Hip fracture is among the most common causes of acute immobilization in elderly patients, and elderly patients with hip fracture are at high risk for a subsequent hip fracture. At baseline, both groups had high serum concentrations of ionized calcium, high urinary deoxypyridinoline (DPD) concentrations, suggesting immobilization-induced hypercalcemia. We previously showed deficiency of vitamins D and K(1) causes reduced bone mineral density (BMD) in female Alzheimer's disease (AD) patients. In a random and prospective study of AD patients, 100 patients received 45 mg menatetrenone, 1,000 IU ergocalciferol and 600 mg calcium daily for 2 years, and the remaining 100 (untreated group) did not. Treatment with MK-4 and vitamin D(2) with calcium supplements increases the BMD in elderly female patients with AD and leads to the prevention of nonvertebral fractures. The risk of hip fracture after stroke is 2 to 4 times as high as that in age-matched healthy controls. Hyperhomocysteinemia is a risk factor for both ischemic stroke and osteoporotic fractures in elderly persons. Randomized, controlled, double-blinded study of 628 consecutive elderly hemiplegic patients at least 1 year following first ischemic stroke. Patients were assigned to daily oral treatment with 5 mg of folate and 1,500 microg of mecobalamin or double placebos, and 559 completed the 2 year follow up. Plasma homocysteine levels in the decreased by 38% in the treatment group and increased by 31% in the placebo group. The number of the hip fractures per 1,000 patient-years was 10 and 43 for the treatment and placebo groups, respectively (p<0.001). In this Japanese population with a high baseline fracture risk, combined treatment with folate and vitamin B(12) is safe and effective in reducing the risk of a hip fracture in elderly stroke patients. Because of limited study power, the relative risk reduction may only be around 0.5.

Topics: Aged; Alzheimer Disease; Bone Density; Female; Hip Fractures; Homocysteine; Humans; Immobilization; Randomized Controlled Trials as Topic; Vitamin K

A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer disease (AD), who are prone to falls and have osteoporosis. We previously found that vitamin K deficiency and low 25-hydroxyvitamin D (25-OHD) with compensatory hyperparathyroidism cause reduced bone mineral density (BMD) in female patients with AD. This may modifiable by intervention with menatetrenone (vitamin K2) and risedronate sodium; we address the possibility that treatment with menatetrenone, risedronate and calcium may reduce the incidence of nonvertebral fractures in elderly patients with AD. A total of 231 elderly patients with AD were randomly assigned to daily treatment with 45 mg of menatetrenone or a placebo combined with once weekly risedronate sodium, and followed up for 12 months. At baseline, patients of both groups showed high undercarboxylated osteocalcin (ucOC) and low 25-OHD insufficiency with compensatory hyperparathyroidism. During the study period, BMD in the treatment group increased by 5.7% and increased by 2.1% in the control group. Nonvertebral fractures occurred in 15 patients (10 hip fractures) in the control group and 5 patients (2 hip fractures) in the treatment group. The relative risk in the treatment group compared with the control group was 0.31 (95% confidence interval, 0.12-0.81). Elderly AD patients with hypovitaminosis K and D are at increased risk for hip fracture. The study medications were well tolerated with relatively few adverse events and effective in reducing the risk of a fracture in elderly patients with AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Bone Density; Bone Density Conservation Agents; Etidronic Acid; Female; Hemostatics; Hip Fractures; Humans; Hyperparathyroidism; Male; Osteoporosis; Risedronic Acid; Vitamin D; Vitamin K; Vitamin K 2

Alzheimer's disease is characterized by the presence in the brain of amyloid plaques formed by the aberrant deposition of the amyloid-β peptide (Aβ). Since many vitamins are dysregulated in this disease, we explored whether these molecules contribute to the protein homeostasis system by modulating Aβ aggregation. By screening 18 fat-soluble and water-soluble vitamin metabolites, we found that retinoic acid and α-tocopherol, two metabolites of vitamin A and vitamin E, respectively, affect Aβ aggregation both in vitro and in a

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Caenorhabditis elegans; Protein Aggregates; Vitamin A; Vitamin E; Vitamin K; Vitamins

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the formation of amyloid plaques implicated in neuronal death. Genetics, age, and sex are the risk factors attributed to AD. Though omics studies have helped to identify pathways associated with AD, an integrated systems analysis with the available data could help to understand mechanisms, potential biomarkers, and therapeutic targets. Analysis of transcriptomic data sets from the GEO database, and proteomic and metabolomic data sets from literature was performed to identify deregulated pathways and commonality analysis identified overlapping pathways among the data sets. The deregulated pathways included those of neurotransmitter synapses, oxidative stress, inflammation, vitamins, complement, and coagulation pathways. Cell type analysis of GEO data sets showed microglia, endothelial, myeloid, and lymphoid cells are affected. Microglia are associated with inflammation and pruning of synapses with implications for memory and cognition. Analysis of the protein-cofactor network of B

Topics: Alzheimer Disease; Disease Progression; Humans; Multiomics; Neurodegenerative Diseases; Proteomics; Vitamin A; Vitamin K; Vitamins

Vitamin K antagonists (VKAs) are commonly used for their role in haemostasis by interfering with the vitamin K cycle. Since vitamin K also participates in brain physiology, this voxel-based morphometric study aimed to determine whether the duration of exposure to VKAs correlated with focal brain volume reduction in older adults.. In this exposed/unexposed (1: 2) study nested within the GAIT (Gait and Alzheimer Interactions Tracking) cohort, 18 participants exposed to VKA (mean age 75 ± 5 years; 33.3% female; mean exposure 2,122 ± 1,799 days) and 36 matched participants using no VKA (mean age 75 ± 5 years; 33.3% female) underwent MRI scanning of the brain. Cortical grey and white matter volumes were automatically segmented using statistical parametric mapping. Age, gender, educational level, history of atrial fibrillation, type of MRI, and total intracranial volume were included as covariables.. The duration of exposure to VKA correlated inversely across the whole brain with the subvolumes of two clusters in the grey matter (right frontal inferior operculum and right precuneus) and one cluster in the white matter (left middle frontal gyrus). In contrast, the grade of white matter hyperintensities did not differ according to the use of VKA.. We found focal atrophies in older adults exposed to VKA. These findings provide new insights elucidating the effects of VKAs on brain health and function in older adults.

Topics: Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Anticoagulants; Brain; Cohort Studies; Cross-Sectional Studies; Educational Status; Female; Gait Disorders, Neurologic; Gray Matter; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Sex Factors; Vitamin K; White Matter

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.

Topics: Aged; Aging; Alzheimer Disease; Case-Control Studies; Diet; Diet Records; Female; Food Analysis; Humans; Male; Nutritional Requirements; Nutritional Status; Vegetables; Vitamin K