PMID 36033779 Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials Meta-analysis · Front Public Health, 2022 Vitamin K2 improved lumbar-spine bone density and lowered uc-OC in postmenopausal women, but a fracture reduction was significant only after removing a heterogeneous study (meta-analysisA statistical synthesis combining results of multiple studies into one conclusion.).
Key summary
A meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of 16 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s and 6,425 postmenopausal women. Lumbar-spine BMD improved significantly (P=0.006), and undercarboxylated osteocalcin (uc-OC) and the uc-OC/cOC ratio fell. Fracture incidence showed no significant difference across 6 RCTs (RR=0.96, P=0.65) but became significant after excluding one heterogeneous study (RR=0.43, P=0.01). Adverse reactions did not differ from control.
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INTRODUCTION: Vitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone strength. However, some studies have been inconsistent on whether vitamin K2 (VK2) can maintain or improve bone mineral density (BMD) and reduce the incidence of fractures in postmenopausal women. Therefore, the main objective of this meta-analysis was to determine the effect of VK2 as a nutritional supplement on BMD and fracture incidence in postmenopausal women. METHODS: We searched PubMed, EMBASE, and Cochrane Library databases (published before March 17, 2022) and then extracted and pooled data from all randomized controlled trials (RCTs) that met the inclusion criteria. RESULTS: Sixteen RCTs with a total of 6,425 subjects were included in this meta-analysis. The overall effect test of 10 studies showed a significant improvement in lumbar spine BMD (BMD LS) (P = 0.006) with VK2. The subgroup analysis of VK2 combination therapy showed that BMD LS was significantly maintained and improved with the administration of VK2 (P = 0.03). The overall effect test of the six RCTs showed no significant difference in fracture incidence between the two groups (RR=0.96, P=0.65). However, after excluding one heterogeneous study, the overall effect test showed a significant reduction in fracture incidence with VK2 (RR = 0.43, P = 0.01). In addition, this meta-analysis showed that VK2 reduced serum undercarboxylated osteocalcin (uc-OC) levels and the ratio of uc-OC to cOC in both subgroups of VK2 combined intervention and alone. However, for carboxylated osteocalcin (cOC), both subgroup analysis and overall effect test showed no significant effect of VK2 on it. And the pooled analysis of adverse reactions showed no significant difference between the VK2 and control groups (RR = 1.03, 95%CI 0.87 to 1.21, P = 0.76). CONCLUSIONS: The results of this meta-analysis seem to indicate that VK2 supplementation has a positive effect on the maintenance and improvement of BMD LS in postmenopausal women, and it can also reduce the fracture incidence, serum uc-OC levels and the ratio of uc-OC to cOC. In conclusion, VK2 can indirectly promote bone mineralization and increase bone strength. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 35711002 Efficacy and safety of vitamin K2 for postmenopausal women with osteoporosis at a long-term follow-up: meta-analysis and systematic review Meta-analysis · J Bone Miner Metab, 2022 At long-term follow-up vitamin K2 raised lumbar and forearm bone density and lowered uc-OC, though the evidence stems largely from Japanese trials (meta-analysisA statistical synthesis combining results of multiple studies into one conclusion.).
Key summary
A long-term-follow-up meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of 9 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s and 6,853 postmenopausal women with osteoporosis. Percentage change in lumbar BMD (WMD 2.17) and forearm BMD (WMD 1.57) improved significantly, uc-OC fell, and osteocalcin rose. Minor adverse-reaction rates were somewhat higher in the K2 group (RR=1.33), but there were no serious adverse events. The authors note the evidence rests largely on Japanese practice.
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INTRODUCTION: Vitamin K2 supplementation has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, but further proof for the effectiveness of this practice is still needed. OBJECTIVE: To investigate whether vitamin K2 supplementation plays a role in maintaining bone mineral density (BMD) and reducing the incidence of fractures for postmenopausal women with osteoporosis at a long-term follow-up. MATERIALS AND METHODS: We searched systematically throughout the databases of PubMed, Cochrane library, and EMBASE from the dates of their inception to November 16 2021 in this meta-analysis and systematic review, using keywords vitamin K2 and osteoporosis. RESULTS: Nine RCTs with 6853 participants met the inclusion criteria. Vitamin K2 was associated with a significantly increased percentage change of lumbar BMD and forearm BMD (WMD 2.17, 95% CI [1.59-2.76] and WMD 1.57, 95% CI [1.15-1.99]). There were significant differences in undercarboxylated osteocalcin (uc-OC) reduction (WMD -0.96, 95% CI [-0.70 to 0.21]) and osteocalcin (OC) increment (WMD 26.52, 95% CI [17.06-35.98]). Adverse reaction analysis showed that there seemed to be higher adverse reaction rates in the vitamin K2 group (RR = 1.33, 95% CI [1.11-1.59]), but no serious adverse events related to vitamin K2 supplementation. CONCLUSION: This meta-analysis and systematic review seemed to support the hypothesis that vitamin K2 plays an important role in the maintenance and improvement of BMD, and it decreases uc-OC and increases OC significantly at a long-term follow-up. Vitamin K2 supplementation is beneficial and safe in the treatment of osteoporosis for postmenopausal women. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 25516361 Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials Meta-analysis · Osteoporos Int, 2015 Vertebral bone density improved in women with osteoporosis but not in those without it, and a fracture reduction was significant only in sensitivity analysis (meta-analysisA statistical synthesis combining results of multiple studies into one conclusion.).
Key summary
A meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of 19 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s and 6,759 participants. Vertebral BMD improved significantly in the subgroup of postmenopausal women with osteoporosis, but there was no significant BMD change in the subgroup without osteoporosis. For fractures, the pooled 7-study estimate was not significant (RR=0.63, P=0.08) and reached significance only in a sensitivity analysis excluding the heterogeneous study (RR=0.50, P=0.0005). The authors note the Japanese effect was not confirmed in Western countries.
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To identify the role of vitamin K2 for the prevention and treatment of osteoporosis in postmenopausal women, we conducted this meta-analysis of 19 randomized controlled trials. Our results showed that vitamin K2 might play a role in maintaining the bone mineral density and in reducing the incidence of fractures for postmenopausal women with osteoporosis. INTRODUCTION: Vitamin K2 has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, which was not confirmed in western countries. Thus, we conduct this meta-analysis to verify the hypothesis that vitamin K2 plays a role in the prevention and treatment of osteoporosis for postmenopausal women. METHODS: We searched the Cochrane Library, Pub Med, EMBASE, and ISI web of knowledge (until December 1, 2013) and reference lists of eligible articles. A meta-analysis of all-including randomized controlled trials was then performed. RESULTS: Nineteen randomized controlled trials encompassing 6759 participants have met the inclusion criteria. Subgroup analysis of postmenopausal women with osteoporosis revealed a significant improvement of vertebral BMD for both medium-term and long-term results favoring vitamin K2 group (p < 0.00001 and p = 0.0005). However, no significant difference in BMD changes was revealed for the non-osteoporosis subgroup analysis. As for the incidence of fractures, pooled analysis of the seven related studies demonstrated no significant difference in the incidence of fractures favoring vitamin K2 (RR = 0.63, p = 0.08). However, sensitivity analysis by rejecting the study inducing heterogeneity demonstrated a significant difference in the incidence of fractures favoring vitamin K2 (RR = 0.50, p = 0.0005). Significant differences were found in undercarboxylated osteocalcin reduction and osteocalcin increment. The result of adverse reaction analysis showed that vitamin K2 group seemed to have a higher adverse reaction rate (RR = 1.22, p = 0.06). CONCLUSIONS: This meta-analysis seemed to support the hypothesis that vitamin K2 plays kind of a role in the maintenance and improvement of vertebral BMD and the prevention of fractures in postmenopausal women with osteoporosis. The reduction of undercarboxylated osteocalcin and increment of osteocalcin may have some relation to the process of bone mineralization. However, the effect of vitamin K2 for postmenopausal women without osteoporosis had not been identified. Further high-quality RCTs with large sample size are needed to confirm the role of vitamin K2 in osteoporosis for postmenopausal women. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 25694037 Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial RCT · Thromb Haemost, 2015 MK-7 180 µg/day for 3 years improved arterial-stiffness indices in healthy postmenopausal women and cut dp-ucMGP by 50% (RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.).
Key summary
A 3-year double-blind randomized trial in 244 healthy postmenopausal women (120 MK-7, 124 placeboAn inert dummy treatment used as the comparison baseline.). MK-7 180 µg/day significantly lowered carotid-femoral pulse-wave velocity (cfPWV) and the stiffness index, with larger local improvements in women whose baseline stiffness was high. dp-ucMGP fell 50% versus placebo. These are surrogate-marker improvements; cardiovascular-event outcomes were not assessed.
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Observational data suggest a link between menaquinone (MK, vitamin K2) intake and cardiovascular (CV) health. However, MK intervention trials with vascular endpoints are lacking. We investigated long-term effects of MK-7 (180 µg MenaQ7/day) supplementation on arterial stiffness in a double-blind, placebo-controlled trial. Healthy postmenopausal women (n=244) received either placebo (n=124) or MK-7 (n=120) for three years. Indices of local carotid stiffness (intima-media thickness IMT, Diameter end-diastole and Distension) were measured by echotracking. Regional aortic stiffness (carotid-femoral and carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured using mechanotransducers. Circulating desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM), E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of acute phase markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index βsignificantly decreased in the total group, whereas distension, compliance, distensibility, Young's Modulus, and the local carotid PWV (cPWV) improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 35465686 Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial RCT · Circulation, 2022 Two years of MK-7 720 µg/day plus vitamin D did not slow aortic-valve or coronary-artery calcification progression - only dp-ucMGP fell (RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.).
Key summary
A 24-month double-blind multicenter randomized trial in 365 older men with an aortic-valve calcium score above 300 AU. MK-7 720 µg/day plus vitamin D 25 µg made no significant difference to valve-calcification progression (mean difference 17 AU, P=0.64), and aortic and coronary calcification progression also did not differ from placeboAn inert dummy treatment used as the comparison baseline.. Death and cardiovascular events did not differ either. In contrast, dp-ucMGP fell significantly - the surrogate marker improved while the imaging outcome did not.
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BACKGROUND: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis. METHODS: In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 µg MK-7 plus 25 µg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events. RESULTS: From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225-326 AU) and 292 AU (95% CI, 246-338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, -86 to 53 AU; P=0.64). The mean change in aortic valve area was 0.02 cm2 (95% CI, -0.09 to 0.12 cm2; P=0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, -0.11 to 0.02 m/s; P=0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; P=0.99), all-cause death (1 versus 4 patients; P=0.37), or cardiovascular events (10 versus 10 patients; P=0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (-212 pmol/L versus 45 pmol/L; P<0.001). CONCLUSIONS: In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03243890. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 39671130 Should We Recommend Vitamin K2 Supplement to Prevent Coronary Artery Calcification for Patients Receiving Statins and/or Warfarin? Review · Cardiovasc Drugs Ther, 2025 Warfarin acts on the same pathway (VKORC1) that regenerates vitamin K1 and K2, and clinical evidence for a benefit of K2 supplementation is still lacking (review).
Key summary
A review on whether K2 supplementation should be recommended to statinA common lipid-lowering drug that reduces LDL cholesterol./warfarin users because of coronary calcification. Warfarin inhibits VKORC1, blocking regeneration of the reduced forms of vitamin K1 and K2. The authors note that animal models show K2 slowing calcification, but clinical evidence in patients is lacking.
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Several reports suggest that in animal models, as well as in the clinical setting, long-term warfarin use increases coronary artery calcifications. The same has been reported for statins prescribed for patients at risk or with established atherosclerosis. Coronary calcifications are considered a risk marker for further cardiovascular events. However, numerous clinical trials have established that statins reduce the risk for cardiovascular events. Warfarin also has been shown to reduce the risk of cardiovascular events, including re-infarction. It has been suggested that the increase in coronary calcification can be viewed as a marker of stabilization of the coronary plaque in such patients. Warfarin inhibits the activation of Vitamin K epoxide reductase complex 1 (VKORC1), which blocks the regeneration of reduced vitamin K1 and K2. Vitamin K1 is predominantly localized to the liver, serving to carboxylate clotting factors. Vitamin K2 travels through systemic circulation, with significant and wide-ranging effects. Several studies using animal models of atherosclerosis have shown that vitamin K2 supplement can attenuate the progression of atherosclerosis, as well as coronary calcification. Clinical studies supporting this effect in patients are lacking. Yet, there is an increase in the use of over-the-counter vitamin K2 supplements, and several manuscripts recommended its use in patients receiving long-term warfarin to attenuate coronary calcification. However, it is unclear if this occurs in patients with atherosclerosis receiving warfarin or statins and if attenuating coronary calcification has beneficial or detrimental effects on cardiovascular outcomes. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
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