{
  "handle": "menaquinone-7",
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  "studies": [
    {
      "pmid": "36033779",
      "title": "Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials.",
      "journal": "Frontiers in public health",
      "year": "2022",
      "firstAuthor": "Ma ML",
      "authorCount": 10,
      "publicationTypes": "Meta-Analysis, Systematic Review, Research Support, Non-U.S. Gov't, Journal Article",
      "doi": "10.3389/fpubh.2022.979649",
      "url": "https://pubmed.ncbi.nlm.nih.gov/36033779/",
      "abstract": "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 reaction"
    },
    {
      "pmid": "32219282",
      "title": "The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials.",
      "journal": "Food & function",
      "year": "2020",
      "firstAuthor": "Kuang X",
      "authorCount": 6,
      "publicationTypes": "Journal Article, Meta-Analysis, Systematic Review",
      "doi": "10.1039/c9fo03063h",
      "url": "https://pubmed.ncbi.nlm.nih.gov/32219282/",
      "abstract": "BACKGROUND: Previous studies did not draw a consistent conclusion about the effects of vitamin K combined with vitamin D on human skeletal quality. METHOD AND FINDINGS: A comprehensive search on Web of Science, PubMed, Embase and the Cochrane Library (from 1950 to February 2020) and bibliographies of relevant articles was undertaken, with the meta-analysis of eight randomized controlled trials (RCTs) including a total of 971 subjects. Vitamin K combined with vitamin D significantly increased the total bone mineral density (BMD): the pooled effect size was 0.316 [95% CI (confidence interval), 0.031 to 0.601]. A significant decrease in undercarboxylated osteocalcin (-0.945, -1.113 to -0.778) can be observed with the combination of vitamin K and D. Simultaneously, subgroup analysis showed that K2 or vitamin K (not specified) supplement was less than 500 mug d-1, which when combined with vitamin D can significantly increase the total BMD compared with the control group fed a normal diet or the group with no treatment (0.479, 0.101 to 0.858 and 0.570, 0.196 to 0.945). CONCLUSIONS: The combination of vitamin K and D can significantly increase the total BMD and significantly decrease undercarboxylated osteocalcin, and a more favorable effect is expected when vitamin K2 is used."
    },
    {
      "pmid": "33753537",
      "title": "Safety and Efficacy of Vitamin K Antagonists versus Rivaroxaban in Hemodialysis Patients with Atrial Fibrillation: A Multicenter Randomized Controlled Trial.",
      "journal": "Journal of the American Society of Nephrology : JASN",
      "year": "2021",
      "firstAuthor": "De Vriese AS",
      "authorCount": 5,
      "publicationTypes": "Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial",
      "doi": "10.1681/ASN.2020111566",
      "url": "https://pubmed.ncbi.nlm.nih.gov/33753537/",
      "abstract": "BACKGROUND: In patients with normal renal function or early stage CKD, the risk-benefit profile of direct oral anticoagulants (DOACs) is superior to that of vitamin K antagonists (VKAs). In patients on hemodialysis, the comparative efficacy and safety of DOACs versus VKAs are unknown. METHODS: In the Valkyrie study, 132 patients on hemodialysis with atrial fibrillation were randomized to a VKA with a target INR of 2-3, 10 mg rivaroxaban daily, or rivaroxaban and vitamin K2 for 18 months. Patients continued the originally assigned treatment and follow-up was extended for at least an additional 18 months. The primary efficacy end point was a composite of fatal and nonfatal cardiovascular events. Secondary efficacy end points were individual components of the composite outcome and all-cause death. Safety end points were life-threatening, major, and minor bleeding. RESULTS: Median (IQR) follow-up was 1.88 (1.01-3.38) years. Premature, permanent discontinuation of anticoagulation occurred in 25% of patients. The primary end point occurred at a rate of 63.8 per 100 person-years in the VKA group, 26.2 per 100 person-years in the rivaroxaban group, and 21.4 per 100 person-years in the rivaroxaban and vitamin K2 group. The estimated competing risk-adjusted hazard ratio for the primary end point was 0.41 (95% CI, 0.25 to 0.68; P=0.0006) in the rivaroxaban group and 0.34 (95% CI, 0.19 to 0.61; P=0.0003) in the rivaroxaban and vitamin K2 group, compared with the VKA group. Death from any cause, cardiac death, and risk of stroke were not different between the treatment arms, but symptomatic limb ischemia occurred significantly less frequently with rivaroxaban than with VKA. After adjustment for competing risk of death, the hazard ratio for life-threatening and major bleeding compare"
    },
    {
      "pmid": "23525894",
      "title": "Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women.",
      "journal": "Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA",
      "year": "2013",
      "firstAuthor": "Knapen MH",
      "authorCount": 5,
      "publicationTypes": "Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",
      "doi": "10.1007/s00198-013-2325-6",
      "url": "https://pubmed.ncbi.nlm.nih.gov/23525894/",
      "abstract": "We have investigated whether low-dose vitamin K2 supplements (menaquinone-7, MK-7) could beneficially affect bone health. Next to an improved vitamin K status, MK-7 supplementation significantly decreased the age-related decline in bone mineral density and bone strength. Low-dose MK-7 supplements may therefore help postmenopausal women prevent bone loss. INTRODUCTION: Despite contradictory data on vitamin K supplementation and bone health, the European Food Safety Authorities (EFSA) accepted the health claim on vitamin K's role in maintenance of normal bone. In line with EFSA's opinion, we showed that 3-year high-dose vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation improved bone health after menopause. Because of the longer half-life and greater potency of the long-chain MK-7, we have extended these investigations by measuring the effect of low-dose MK-7 supplementation on bone health. METHODS: Healthy postmenopausal women (n = 244) received for 3 years placebo or MK-7 (180 mug MK-7/day) capsules. Bone mineral density of lumbar spine, total hip, and femoral neck was measured by DXA; bone strength indices of the femoral neck were calculated. Vertebral fracture assessment was performed by DXA and used as measure for vertebral fractures. Circulating uncarboxylated osteocalcin (ucOC) and carboxylated OC (cOC) were measured; the ucOC/cOC ratio served as marker of vitamin K status. Measurements occurred at baseline and after 1, 2, and 3 years of treatment. RESULTS: MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the l"
    },
    {
      "pmid": "35465686",
      "title": "Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.",
      "journal": "Circulation",
      "year": "2022",
      "firstAuthor": "Diederichsen ACP",
      "authorCount": 18,
      "publicationTypes": "Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",
      "doi": "10.1161/CIRCULATIONAHA.121.057008",
      "url": "https://pubmed.ncbi.nlm.nih.gov/35465686/",
      "abstract": "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 microg MK-7 plus 25 microg 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 cm(2) (95% CI, -0.09 to 0.12 cm(2); 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), "
    },
    {
      "pmid": "25694037",
      "title": "Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial.",
      "journal": "Thrombosis and haemostasis",
      "year": "2015",
      "firstAuthor": "Knapen MH",
      "authorCount": 6,
      "publicationTypes": "Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",
      "doi": "10.1160/TH14-08-0675",
      "url": "https://pubmed.ncbi.nlm.nih.gov/25694037/",
      "abstract": "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 microg 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-alpha (TNF-alpha) 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 betasignificantly 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 beta 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"
    },
    {
      "pmid": "31704740",
      "title": "Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study.",
      "journal": "Journal of the American Society of Nephrology : JASN",
      "year": "2020",
      "firstAuthor": "De Vriese AS",
      "authorCount": 10,
      "publicationTypes": "Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",
      "doi": "10.1681/ASN.2019060579",
      "url": "https://pubmed.ncbi.nlm.nih.gov/31704740/",
      "abstract": "BACKGROUND: Vitamin K antagonists (VKAs), although commonly used to reduce thromboembolic risk in atrial fibrillation, have been incriminated as probable cause of accelerated vascular calcification (VC) in patients on hemodialysis. Functional vitamin K deficiency may further contribute to their susceptibility for VC. We investigated the effect of vitamin K status on VC progression in 132 patients on hemodialysis with atrial fibrillation treated with VKAs or qualifying for anticoagulation. METHODS: Patients were randomized to VKAs with target INR 2-3, rivaroxaban 10 mg daily, or rivaroxaban 10 mg daily plus vitamin K2 2000 microg thrice weekly during 18 months. Systemic dp-ucMGP levels were quantified to assess vascular vitamin K status. Cardiac and thoracic aorta calcium scores and pulse wave velocity were measured to evaluate VC progression. RESULTS: Baseline dp-ucMGP was severely elevated in all groups. Initiation or continuation of VKAs further increased dp-ucMGP, whereas levels decreased in the rivaroxaban group and to a larger extent in the rivaroxaban+vitamin K2 group, but remained nevertheless elevated. Changes in coronary artery, thoracic aorta, and cardiac valve calcium scores and pulse wave velocity were not significantly different among the treatment arms. All cause death, stroke, and cardiovascular event rates were similar between the groups. Bleeding outcomes were not significantly different, except for a lower number of life-threatening and major bleeding episodes in the rivaroxaban arms versus the VKA arm. CONCLUSIONS: Withdrawal of VKAs and high-dose vitamin K2 improve vitamin K status in patients on hemodialysis, but have no significant favorable effect on VC progression. Severe bleeding complications may be lower with rivaroxaban than with VKAs."
    },
    {
      "pmid": "11180916",
      "title": "Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis.",
      "journal": "Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association",
      "year": "2000",
      "firstAuthor": "Iwamoto J",
      "authorCount": 3,
      "publicationTypes": "Clinical Trial, Journal Article, Randomized Controlled Trial",
      "doi": "",
      "url": "https://pubmed.ncbi.nlm.nih.gov/11180916/",
      "abstract": "The effect of the combined administration of vitamin D3 and vitamin K2 on bone mineral density (BMD) of the lumbar spine was examined in postmenopausal women with osteoporosis. Ninety-two osteoporotic women who were more than 5 years after menopause, aged 55-81 years, were randomly divided into four administration groups: vitamin D3 (1alpha hydroxyvitamin D3, 0.75 microg/day) (D group; n = 29), vitamin K2 (menatetrenone, 45 mg/day) (K group; n = 22), vitamin D3 plus vitamin K2 (DK group, n = 21), and calcium (calcium lactate, 2 g/day) (C group; n = 20). BMD of the lumbar spine (L2-L4) was measured by dual energy X-ray absorptiometry at 0, 1, and 2 years after the treatment started. There were no significant differences in age, body mass index, years since menopause, and initial BMD among the four groups. One-way analysis of variance (ANOVA) with repeated measurements showed a significant decrease in BMD in the C group (P < 0.001). Two-way ANOVA with repeated measurements showed a significant increase in BMD in the D and K groups compared with that in the C group (P < 0.05 and P < 0.001, respectively), and a significant increase in BMD in the DK group compared with that in the C, D, and K groups (P < 0.0001, P < 0.05 and P < 0.01, respectively). These findings indicate that combined administration of vitamin D3 and vitamin K2, compared with calcium administration, appears to be useful in increasing the BMD of the lumbar spine in postmenopausal women with osteoporosis."
    }
  ]
}