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Nutrients Jun 2023Vitamin K and vitamin K-dependent proteins have been reported to be associated with a large spectrum of age-related diseases. While most of these associations have been... (Review)
Review
Vitamin K and vitamin K-dependent proteins have been reported to be associated with a large spectrum of age-related diseases. While most of these associations have been deduced from observational studies, solid evidence for the direct impact of vitamin K on cellular senescence remains to be proven. As vitamin K status reflects the complexity of interactions between dietary intake, gut microbiome activity and health, we will demonstrate the pivotal role of the diet-microbiome-health axis in human ageing and exemplify how vitamin K is implicated therein. We propose that food quality (i.e., food pattern) should be highlighted beyond the quantity of total vitamin K intake. Instead of focusing on a single nutrient, exploring a healthy diet containing vitamin K may be more strategic. As such, healthy eating patterns can be used to make dietary recommendations for the public. Emerging evidence suggests that dietary vitamin K is a modulator of the diet-microbiome-health axis, and this needs to be incorporated into the investigation of the impact of vitamin K on gut microbial composition and metabolic activities, along with host health outcomes. In addition, we highlight several critical caveats that need to be acknowledged regarding the interplay between diet, vitamin K, gut microbiome and host health that is pivotal for elucidating the role of vitamin K in ageing and responding to the urgent call of healthy eating concerning public health.
Topics: Humans; Gastrointestinal Microbiome; Vitamin K; Diet; Feeding Behavior; Aging
PubMed: 37375631
DOI: 10.3390/nu15122727 -
Molecular Cell Oct 2022The dietary factor vitamin K has been found to protect against ferroptosis, a form of cell death driven by lipid peroxidation. This reveals new dietary links to cancers...
The dietary factor vitamin K has been found to protect against ferroptosis, a form of cell death driven by lipid peroxidation. This reveals new dietary links to cancers and degenerative conditions and a key factor involved in warfarin poisoning.
Topics: Ferroptosis; Vitamin K; Warfarin; Lipid Peroxidation; Cell Death
PubMed: 36270246
DOI: 10.1016/j.molcel.2022.10.001 -
Nutrients Apr 2023Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting, however, that vitamin K (VK) may play an important role... (Review)
Review
Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting, however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic-related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in mice. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with those with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is, therefore, the intention of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and provide some historical context for recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon in the hope of raising awareness and encouraging continued VK-related investigations in this important and highly specialized sensory system.
Topics: Mice; Animals; Vitamin K; Vitamin K 1; Vitamins; Vitamin K Deficiency; Sense Organs; Vitamin K 2
PubMed: 37111170
DOI: 10.3390/nu15081948 -
Seminars in Arthritis and Rheumatism Aug 2022Osteoarthritis (OA) is a progressive disease for which there is no disease modifying therapy. Vitamin K levels and vitamin K antagonism have been associated with risk...
OBJECTIVE
Osteoarthritis (OA) is a progressive disease for which there is no disease modifying therapy. Vitamin K levels and vitamin K antagonism have been associated with risk and progression of OA which may have direct implications for clinical management, but these observational findings are susceptible to confounding. We aimed to estimate the causal association between vitamin K and OA risk using Mendelian randomisation (MR).
METHODS
We used data from the largest genome-wide association study (GWAS) of OA to date (up to 826,690 individuals) to estimate the effect of genetically predicted vitamin K level (instrumented using four variants derived from a GWAS of 2,138 individuals) on risk of all OA types, knee, hip, spine, hand OA, and total joint replacement. We employed the inverse-variance weighted method for the primary analysis and, in a series of sensitivity analyses, adjusted for sub-genome wide significant instruments and tested for potential bias from pleiotropy.
RESULTS
We showed that genetically predicted vitamin K levels were not causally associated with risk of OA overall (OR 0.98 per unit increase in log-transformed vitamin K1; 95%CI 0.96-1.01), knee (OR 0.98; 0.92-1.03), hip (OR 0.97; 0.88-1.07), spine (OR 0.97; 0.90-1.04), hand OA (OR 0.97; 0.91-1.04) or joint replacement (OR 0.96; 0.89-1.04). Results were similar across all sensitivity analyses.
CONCLUSION
We found little evidence of a causal association between genetically predicted vitamin K and OA risk. Larger genetic and interventional studies of vitamin K are required to confirm our findings.
Topics: Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Osteoarthritis; Polymorphism, Single Nucleotide; Vitamin K
PubMed: 35667331
DOI: 10.1016/j.semarthrit.2022.152030 -
Calcified Tissue International Feb 2023Vitamin K, a cofactor for the γ-glutamyl carboxylase enzyme, is required for the post-translational activation of osteocalcin and matrix Gla protein, which play a key... (Review)
Review
Vitamin K, a cofactor for the γ-glutamyl carboxylase enzyme, is required for the post-translational activation of osteocalcin and matrix Gla protein, which play a key role in bone and muscle homeostasis. In vivo and in vitro models for osteoporosis and sarcopenia suggest the vitamin K could exert a positive effect in both conditions. In bone, it increases osteoblastogenesis, whilst decreases osteoclast formation and function. In muscle, it is associated with increased satellite cell proliferation and migration and might play a role in energy metabolism. Observational trials suggest that high levels of vitamin K are associated with increased bone mineral density and reduced fracture risk. However, interventional studies for vitamin K supplementation yielded conflicting results. Clinical trials in sarcopenia suggest that vitamin K supplementation could improve muscle mass and function. One of the main limitations on the vitamin K studies are the technical challenges to measure its levels in serum. Thus, they are obtained from indirect sources like food questionnaires, or levels of undercarboxylated proteins, which can be affected by other environmental or biological processes. Although current research appoints to a beneficial effect of vitamin K in bone and muscle, further studies overcoming the current limitations are required in order to incorporate this supplementation in the clinical management of patients with osteosarcopenia.
Topics: Humans; Vitamin K; Bone Density; Sarcopenia; Bone and Bones; Osteocalcin; Muscles
PubMed: 35150288
DOI: 10.1007/s00223-022-00955-3 -
Journal of the American College of... Oct 2019
Topics: Anticoagulants; Atrial Fibrillation; Humans; Osteoporotic Fractures; Stroke; Vitamin K; Warfarin
PubMed: 31648708
DOI: 10.1016/j.jacc.2019.08.1026 -
Journal of Thrombosis and Haemostasis :... Sep 2022Vitamin K antagonists (VKAs), such as warfarin, are oral anticoagulants widely used to treat and prevent thromboembolic diseases. Therapeutic use of these drugs requires... (Review)
Review
Vitamin K antagonists (VKAs), such as warfarin, are oral anticoagulants widely used to treat and prevent thromboembolic diseases. Therapeutic use of these drugs requires frequent monitoring and dose adjustments, whereas overdose often causes severe bleeding. Addressing these drawbacks requires mechanistic understandings at cellular and structural levels. As the target of VKAs, vitamin K epoxide reductase (VKOR) generates the active, hydroquinone form of vitamin K, which in turn drives the γ-carboxylation of several coagulation factors required for their activity. Crystal structures revealed that VKAs inhibit VKOR via mimicking its catalytic process. At the active site, two strong hydrogen bonds that facilitate the catalysis also afford the binding specificity for VKAs. Binding of VKAs induces a global change from open to closed conformation. Similar conformational change is induced by substrate binding to promote an electron transfer process that reduces the VKOR active site. In the cellular environment, reducing partner proteins or small reducing molecules may afford electrons to maintain the VKOR activity. The catalysis and VKA inhibition require VKOR in different cellular redox states, explaining the complex kinetics behavior of VKAs. Recent studies also revealed the mechanisms underlying warfarin resistance, warfarin dose variation, and antidoting by vitamin K. These mechanistic understandings may lead to improved anticoagulation strategies targeting the vitamin K cycle.
Topics: Anticoagulants; Catalytic Domain; Fibrinolytic Agents; Humans; Vitamin K; Vitamin K 1; Vitamin K Epoxide Reductases; Warfarin
PubMed: 35748323
DOI: 10.1111/jth.15800 -
International Journal of Molecular... Aug 2021Vitamin K and Vitamin K-dependent proteins (VKDPs) are best known for their pivotal role in blood coagulation. Of the 14 VKPDs identified in humans to date, 6 play also... (Review)
Review
Vitamin K and Vitamin K-dependent proteins (VKDPs) are best known for their pivotal role in blood coagulation. Of the 14 VKPDs identified in humans to date, 6 play also important roles in skeletal biology and disease. Thus, osteocalcin, also termed bone Gla-protein, is the most abundant non-collagenous protein in bone. Matrix Gla protein and Ucma/GRP on the other hand are highly abundant in cartilage. Furthermore, periostin, protein S, and growth arrest specific 6 protein (GAS 6) are expressed in skeletal tissues. The roles for these VKDPs are diverse but include the control of calcification and turnover of bone and cartilage. Vitamin K plays an important role in osteoporosis and serum osteocalcin levels are recognized as a promising marker for osteoporosis. On the other hand, matrix Gla protein and Ucma/GRP are associated with osteoarthritis. This review focuses on the roles of these three VKDPs, osteocalcin, matrix Gla protein and Ucma/GRP, in skeletal development and disease but will also summarize the roles the other skeletal VKDPs (periostin, protein S and GAS6) in skeletal biology.
Topics: Animals; Bone Development; Humans; Osteocalcin; Osteoporosis; Vitamin K
PubMed: 34502245
DOI: 10.3390/ijms22179328 -
Methodist DeBakey Cardiovascular Journal 2024Pulmonary embolus (PE) carries a significant impending morbidity and mortality, especially in intermediate and high-risk patients, and the choice of initial... (Review)
Review
Pulmonary embolus (PE) carries a significant impending morbidity and mortality, especially in intermediate and high-risk patients, and the choice of initial anticoagulation that allows for therapeutic adjustment or manipulation is important. The preferred choice of anticoagulation management includes direct oral anticoagulants. Vitamin K antagonists and low-molecular-weight heparin are preferred in special populations or selected patients such as breastfeeding mothers, those with end-stage renal disease, or obese patients, among others. This article reviews the primary and longer-term considerations for anticoagulation management in patients with PE and highlights special patient populations and risk factor considerations.
Topics: Humans; Pulmonary Embolism; Anticoagulants; Risk Factors; Treatment Outcome; Blood Coagulation; Administration, Oral; Risk Assessment; Hemorrhage; Vitamin K; Clinical Decision-Making
PubMed: 38765210
DOI: 10.14797/mdcvj.1338 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Jan 2023Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including... (Review)
Review
Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including vaccination, drug therapy, and non-pharmaceutical intervention (NPI), dietary nutrition and mental health are also key factors in maintaining immune system health and combating emerging and sudden outbreaks of infections. As the main dietary nutrients, vitamins are active regulators of the immune response and exert a critical impact on the immunity of the human body. Vitamin deficiency causes increased levels of inflammation and decreased immunity, which usually starts in the oral tissues. Appropriate vitamin supplementation can help the body optimize immune function, enhance oral immunity, and reduce the negative impact of pathogen infection on the human body, which makes it a feasible, effective, and universally applicable anti-infection solution. This review focuses on the immunomodulatory effects of vitamin A, B, C, D, and E and proposes that an omics-based new systemic approach will lead to a breakthrough of the limitations in traditional single-factor single-pathway research and provide the direction for the basic and applied research of vitamin immune regulation and anti-infection in all aspects.
Topics: Humans; Vitamins; Vitamin A; Immune System; Vitamin K; Inflammation; Dietary Supplements
PubMed: 36647636
DOI: 10.12182/20230160107