UNASSIGNED: Extent and progression of coronary artery calcification (CAC) are strong predictors of myocardial infarction and mortality.
UNASSIGNED: This study aims to investigate if vitamin K2 and D supplementation can reduce CAC progression.
UNASSIGNED: A total of 389 participants were randomized to supplementation with vitamin K2 (720 μg/day) and D (25 μg/day) vs placebo in a multicenter double-blinded randomized controlled trial. The primary endpoint (progression of aortic valve calcification) has been reported. This study reports CAC progression in participants with no ischemic heart disease. CT scans were performed at baseline, 12, and 24 months. ΔCAC and coronary plaque volume were evaluated in the entire group and in 2 subgroups. A safety endpoint was the composite of myocardial infarction, coronary revascularization, and all-cause mortality.
UNASSIGNED: In total, 304 participants (male, mean age 71 years) were identified. The intervention and placebo group both increased in mean CAC scores from baseline to 24-month follow-up (Δ203 vs Δ254 AU, P = 0.089). In patients with CAC scores ≥400 AU, CAC progression was lower by intervention (Δ288 vs Δ380 AU, P = 0.047). Plaque analyses showed no significant difference in progression of noncalcified plaque volume (Δ-6 vs Δ46 mm3, P = 0.172). Safety events were fewer in participants receiving supplementation (1.9% vs 6.7%, P = 0.048).
UNASSIGNED: Patients with no prior ischemic heart disease randomized to vitamin K2 and D supplementation had no significant reduction in mean CAC progression over a 2-year follow-up compared to placebo. Although the primary endpoint is neutral, differential responses to supplementation in those with CAC scores ≥400 AU and in safety endpoints are hypothesis-generating for future studies.

Vitamins are essential organic compounds that vary widely in chemical structure and are vital in small quantities for numerous biochemical and biological functions. They are critical for metabolism, growth, development and maintaining overall health. Vitamins are categorised into two groups: hydrophilic and lipophilic. Vitamin K (VK), a lipophilic vitamin, occurs naturally in two primary forms: phylloquinone (VK1), found in green leafy vegetables and algae, and Menaquinones (VK2), present in certain fermented and animal foods and widely formulated in VK supplements. This review explores the possible factors contributing to VK deficiency, including dietary influences, and discusses the pharmacological and therapeutic potential of supplementary VK2, examining recent global clinical studies on its role in treating diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, cardiovascular disease, chronic kidney disease, diabetes, neurodegenerative disorders and cancers. The analysis includes a review of published articles from multiple databases, including Scopus, PubMed, Google Scholar, ISI Web of Science and CNKI, focusing on human studies. The findings indicate that VK2 is a versatile vitamin essential for human health and that a broadly positive correlation exists between VK2 supplementation and improved health outcomes. However, clinical data are somewhat inconsistent, highlighting the need for further detailed research into VK2\'s metabolic processes, biomarker validation, dose-response relationships, bioavailability and safety. Establishing a Recommended Daily Intake for VK2 could significantly enhance global health.

Vitamin K2 (VK2) is an effective compound for anti-ferroptosis and anti-osteoporosis, and Semen sojae praeparatum (Dandouchi in Chinese) is the main source of VK2. Chondrocyte ferroptosis and extracellular matrix (ECM) degradation playing a role in the pathogenesis of osteoarthritis (OA). Glutathione peroxidase 4 (GPX4) is the intersection of two mechanisms in regulating OA progression. But no studies have elucidated the therapeutic effects and mechanisms of VK2 on OA. This study utilized an in vivo rat OA model created via anterior cruciate ligament transection (ACLT) and an in vitro chondrocyte oxidative damage model induced by TBHP to investigate the protective effects and mechanisms of action of VK2 in OA. Knee joint pain in mice was evaluated using the Von Frey test. Micro-CT and Safranin O-Fast Green staining were employed to observe the extent of damage to the tibial cartilage and subchondral bone, while immunohistochemistry and PCR were used to examine GPX4 levels in joint cartilage. The effects of VK2 on rat chondrocyte viability were assessed using CCK-8 and flow cytometry assays, and chondrocyte morphology was observed with toluidine blue and alcian blue staining. The impact of VK2 on intracellular ferroptosis-related markers was observed using fluorescent staining and flow cytometry. Protein expression changes were detected by immunofluorescence and Western blot analysis. Furthermore, specific protein inhibitors were applied to confirm the dual-regulatory effects of VK2 on GPX4. VK2 can increase bone mass and cartilage thickness in the subchondral bone of the tibia, and reduce pain and the OARSI score induced by OA. Immunohistochemistry results indicate that VK2 exerts its anti-OA effects by regulating GPX4 to delay ECM degradation. VK2 can inhibit the activation of the MAPK/NFκB signaling pathway caused by reduced expression of intracellular GPX4, thereby decreasing ECM degradation. Additionally, VK2 can reverse the inhibitory effect of RSL3 on GPX4, increase intracellular GSH content and the GSH/GSSG ratio, reduce MDA content, and rescue chondrocyte ferroptosis. The protective mechanism of VK2 may involve its dual-target regulation of GPX4, reducing chondrocyte ferroptosis and inhibiting the MAPK/NFκB signaling pathway to decelerate the degradation of the chondrocyte extracellular matrix.

OBJECTIVE: The present study aimed to investigate the histomorphometric and immunohistochemical impacts of vitamin K2 on guided bone regeneration (GBR) in calvarial critical-size defects (CSDs) in diabetic rats.
METHODS: A total of 30 rats were used in this study, comprising 12 non-diabetic (control) rats and 18 with streptozotocin-nicotinamide-induced experimental Diabetes mellitus (DM). In all rats, two calvarial CSDs were created: one defect was left empty (E), the other was treated with bovine-derived bone graft and collagen-based resorbable membrane (GM). Study groups were as follows: control rats administered saline (n = 6, C-E and C-GM groups) or vitamin K2 (n = 6, CK-E and CK-GM groups) and diabetic rats administered saline (n = 6, DM-E and DM-GM groups) or vitamin K2 (n = 6, DMK-E and DMK-GM groups). After 4 weeks of saline or vitamin K2 administration, the rats were euthanized. Bone defect healing and new bone formation were assessed histomorphometrically, and osteocalcin and osteopontin levels were examined immunohistochemically.
RESULTS: Percentage of new bone formation was greater in CK-GM vs. CK-E and in DMK-GM vs. DMK-E [d = 3.86 (95% CI = 16.38-28.61), d = 1.86, (95% CI = 10.74-38.58), respectively, p < .05]. Bone defect healing scores were higher in CK-GM vs. CK-E and in DMK-GM vs. DMK-E [d = 2.69 (95% CI = -2.12 to -0.87), d = 3.28 (95% CI = 0.98-1.91), respectively, p < .05]. Osteocalcin expression levels were elevated in CK-GM vs. CK-E, in DMK-GM vs. DMK-E [d = 1.19 (95% CI = 0.08-1.41), d = 1.10 (95% CI = 0.02-1.22), respectively p < .05]. Vitamin K2 enhanced osteocalcin expression levels in DMK-E vs. DM-E [d = 2.78, (95% CI = 0.56-1.53), p < .05] and in DMK-GM vs. DM-GM [d = 2.43, (95% CI = 0.65-2.10), p < .05]. Osteopontin expression was enhanced in defects treated with GM vs. E defects [C-GM vs. C-E, d = 1.56 (95% CI = 0.38-2.01); CK-GM vs. CK-E, d = 1.91 (95% CI = 0.49-1.72); DM-GM vs. DM-E, d = 2.34 (95% CI = -1.12 to -0.50); DMK-GM vs. DMK-E, d = 2.00 (95% CI = 0.58-1.91), p < .05].
CONCLUSIONS: The research findings suggest that administering vitamin K2 in GBR for rats with DM favorably impacts bone healing in CSDs, presenting an adjunctive strategy for bone regeneration.

The available evidence on vitamin K status in cystic fibrosis (CF) is scarce, lacking data on vitamin K2 (menaquinones-MK). Therefore, we assessed vitamin K1, MK-4 and MK-7 concentrations (LC-MS/MS) in 63 pancreatic insufficient and modulator naïve CF patients, and compared to 61 healthy subjects (HS). Vitamin K1 levels did not differ between studied groups. MK-4 concentrations were higher (median <1st-3rd quartile>: 0.778 <0.589-1.086> vs. 0.349 <0.256-0.469>, p < 0.0001) and MK-7 levels lower (0.150 <0.094-0.259> vs. 0.231 <0.191-0.315>, p = 0.0007) in CF patients than in HS. MK-7 concentrations were higher in CF patients receiving K1 and MK-7 supplementation than in those receiving vitamin K1 alone or no supplementation. Moreover, vitamin K1 concentrations depended on the supplementation regime. Based on multivariate logistic regression analysis, we have found that MK-7 supplementation dose has been the only predictive factor for MK-7 levels. In conclusion, vitamin K1 levels in CF are low if not currently supplemented. MK-4 concentrations in CF patients supplemented with large doses of vitamin K1 are higher than in HS. MK-7 levels in CF subjects not receiving MK-7 supplementation, with no regard to vitamin K1 supplementation, are low. There do not seem to be any good clinical predictive factors for vitamin K status.

This review explores the likely clinical impact of Pregnane X Receptor (PXR) activation by vitamin K on human health. PXR, initially recognized as a master regulator of xenobiotic metabolism in liver, emerges as a key regulator influencing intestinal homeostasis, inflammation, oxidative stress, and autophagy. The activation of PXR by vitamin K highlights its role as a potent endogenous and local agonist with diverse clinical implications. Recent research suggests that the vitamin K-mediated activation of PXR highlights this vitamin\'s potential in addressing pathophysiological conditions by promoting hepatic detoxification, fortifying gut barrier integrity, and controlling pro-inflammatory and apoptotic pathways. PXR activation by vitamin K provides an intricate association with cancer cell survival, particularly in colorectal and liver cancers, to provide new insights into potential novel therapeutic strategies. Understanding the clinical implications of PXR activation by vitamin K bridges molecular mechanisms with health outcomes, further offering personalized therapeutic approaches for complex diseases.

Vitamin K2 (MK-7) has been shown to cause significant changes in different physiological processes and diseases, but its role in acute lung injury (ALI) is unclear. Therefore, in this study, we aimed to evaluate the protective effects of VK2 against LPS-induced ALI in mice. The male C57BL/6J mice were randomly divided into six groups (n = 7): the control group, LPS group, negative control group (LPS + Oil), positive control group (LPS + DEX), LPS + VK2 (L) group (VK2, 1.5 mg/kg), and LPS + VK2 (H) group (VK2, 15 mg/kg). Hematoxylin-eosin (HE) staining of lung tissue was performed. Antioxidant superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, and the Ca2+ level in the lung tissue were measured. The effects of VK2 on inflammation, apoptosis, tight junction (TJ) injury, mitochondrial dysfunction, and autophagy were quantitatively assessed using Western blot analysis. Compared with the LPS group, VK2 improved histopathological changes; alleviated inflammation, apoptosis, and TJ injury; increased antioxidant enzyme activity; reduced Ca2+ overload; regulated mitochondrial function; and inhibited lung autophagy. These results indicate that VK2 could improve tight junction protein loss, inflammation, and cell apoptosis in LPS-induced ALI by inhibiting the mitochondrial dysfunction and excessive autophagy, indicating that VK2 plays a beneficial role in ALI and might be a potential therapeutic strategy.

Natto is a traditional Japanese fermented product consisting of cooked soybeans fermented with Bacillus subtilis var. natto. We assessed three different B. subtilis strains and investigated their impact on product quality aspects, such as microbial quality, textural quality (poly-γ-glutamate strand formation), free amino acids (FAA), and volatile organic compounds (VOCs), but also the vitamin K1, K2 and B1 content, and presence of nattokinase. Using Bayesian contrast analysis, we conclude that the quality attributes were influenced by both the substrate and strain used, without significant differences in bacterial growth between strain or substrate. Overall, all the tested European legumes, except for brown beans, are adequate substrates to produce natto, with comparable or higher qualities compared to the traditional soy. Out of all the tested legumes, red lentils were the most optimal fermentation substrate. They were fermented most consistently, with high concentrations of vitamin K2, VOCs, FAA.

OBJECTIVE: The objective of this study was to evaluate the antimicrobial potential of nanocomposites containing vitamin K2, hydroxyapatite nanoparticles (nHAP), and chitosan (Chito)-coated dental implants against clinically relevant microbial strains.
METHODS: Four test compounds were prepared: vitamin K2 + nHAP, K2 + Chito + nHAP, vitamin K2, and vitamin K2 + Chito. Agar well diffusion test was conducted to assess the antimicrobial activity of these compounds against Staphylococcus aureus (S. aureus), Streptococcus mutans (S. mutans), Enterococcus faecalis (E. faecalis), and Candida albicans (C. albicans). Results: The vitamin K2 + nHAP nanocomposite exhibited antimicrobial activity against all tested microorganisms, with E. faecalis showing the highest sensitivity (25 mm zone of inhibition at 100 µL concentration). The K2 + Chito + nHAP nanocomposite demonstrated potent antimicrobial activity with C. albicans displaying the highest sensitivity (28 mm zone of inhibition at 100 µL concentration). Pure vitamin K2 showed limited antimicrobial activity, vitamin K2 combined with chitosan exhibited significant susceptibility to C. albicans, resulting in a substantial inhibition zone of 24 mm diameter at a concentration of 100 µL.
CONCLUSIONS: The synergistic effects of vitamin K2 with nHAP and chitosan highlight the potential of these nanocomposites for biomedical applications. These findings contribute to the development of effective nanocomposites to address antimicrobial resistance and improve infection control in various biomedical fields.

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.