비타민K1 (필로퀴논)

Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women.

1. J Bone Miner Res. 2007 Apr;22(4):509-19. doi: 10.1359/jbmr.070116. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. Bolton-Smith C(1), McMurdo ME, Paterson CR, Mole PA, Harvey JM, Fenton ST, Prynne CJ, Mishra GD,

The Differential Effects of Vitamin K Across Glycaemic Outcomes in Prediabetes and Type 2 Diabetes Mellitus.

1. Nutrients. 2026 Jan 14;18(2):269. doi: 10.3390/nu18020269. The Differential Effects of Vitamin K Across Glycaemic Outcomes in Prediabetes and Type 2 Diabetes Mellitus. Ahmed SR(1), Mokgalaboni K(1), Phoswa WN(1). Author information: (1)Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Florida Campus, Roodepoort 1710, South Africa. Background: Vitamin K has emerged as a promising regulator of glucose metabolism in preclinical studies. There is, however, scant evidence to support this promising potential in a clinical setting. Aim: The aim of this study was to confirm the effects of vitamin K supplementation on glycaemic parameters such as fasting blood glucose (FBG), fasting insulin (FI), glycated haemoglobin (HbA1c), insulin resistance (HOMA-IR), and homeostatic model of beta cell function (HOMA-β) across randomised controlled trials (RCTs). Materials and Methods: This meta-analysis used evidence from PubMed, Scopus, and manual screening. Only RCTs were considered for this meta-analysis of interventional studies. The Meta online tool was used to analyse data, with the results reported as either the mean or the standardised mean difference (SMD), alongside 95% confidence intervals (CI). Results: Only eight RCTs were found relevant and analysed; the age of those in the vitamin K group was 50.58 ± 6.91 years, and in the control group, it was 48.19 ± 5.41. The evidence showed a significant reduction in FBG, SMD = -0.22 (-0.39 to -0.05), HbA1c, MD = -1.00%, 95% CI (-1.92 to -0.07), and HOMA-IR, MD = -0.63, 95% CI (-1.20 to -0.06). However, no effect was observed on insulin (SMD = -0.39, 95% CI: -0.91 to 0.13, p = 0.15) and HOMA-β (MD = 6.56, 95% CI (-3.89 to 17.01), p = 0.2184. Low doses of vitamin K2 and vitamin K1 were associated with reduced HbA1c and HOMA-IR, respectively. An intervention of less than 12 weeks was associated with reduced HOMA-IR. Conclusions: This study showed a significant decrease in FBG, HbA1c, and HOMA-IR without affecting insulin or HOMA-β. Nevertheless, the limited number of trials with moderate quality warrants larger, longer-term RCTs with rigorous methodology and direct comparisons of vitamin K isoforms to better assess therapeutic potential. DOI: 10.3390/nu18020269 PMCID: PMC12845305 PMID: 41599883 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest.

Effect of vitamin K1 supplementation on coronary calcifications in hemodialysis patients: a randomized controlled trial.

2. J Nephrol. 2025 Mar;38(2):511-519. doi: 10.1007/s40620-024-02154-9. Epub 2024 Dec 16. Effect of vitamin K1 supplementation on coronary calcifications in hemodialysis patients: a randomized controlled trial. Macias-Cervantes HE(1), Ocampo-Apolonio MA(2), Guardado-Mendoza R(3), Baron-Manzo M(4), Pereyra-Nobara TA(5), Hinojosa-Gutiérrez LR(4), Escalante-Gutiérrez SE(6), Castillo-Velázquez MA(7), Aguilar-Guerrero R(6). Author information: (1)Internal Medicine Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México. hildamacer@gmail.com. (2)Nephrology Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México. (3)Metabolic Research Unit, Universidad de Guanajuato, León, Guanajuato, México. (4)Radiology Departament, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México. (5)Director of Health Education and Research, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México. (6)Internal Medicine Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México. (7)Cardiology Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México. BACKGROUND: Chronic kidney disease (CKD) is associated with several adverse cardiovascular outcomes, including coronary heart disease, heart failure, and arrhythmias. The severity of arterial calcifications predicts the risk of coronary heart disease and increases the risk of premature cardiovascular death. In experimental models, vitamin K1 supplementation appears to reduce coronary artery calcifications. METHODS: In this single-center clinical trial (NCT04247087 on 07/09/2019), we randomized 60 Mexican patients on chronic hemodialysis and a coronary calcification score > 10 Agatston units to receive 10 mg intravenous vitamin K1 or placebo at the end of the hemodialysis session thrice weekly for 12 months. The primary outcome was the progression of coronary artery calcifications as assessed by the absolute change in Agatston and coronary calcium volume scores. RESULTS: The baseline coronary calcium score was 112.50 (14-2027) Agatston units in the vitamin K1 group and  177 (10-2843); Agatston units in the placebo group (p = 0.71), and after 12 months, the coronary calcium score in the vitamin K1 group was 78.50 (10-1915)  Agatston units in the vitamin K1 group versus  344 (10-3323); Agatston units (p = 0.05) in the placebo group. Progression of coronary calcification was 20.8% in the vitamin K1 group versus 44% in the placebo group, with a relative risk (RR) of 0.45 (CI 95% 0.18-1.15). CONCLUSIONS: In the Mexican hemodialysis cohort enrolled in this study intravenous vitamin K1 supplementation reduced the progression of coronary artery calcifications by 55% compared with placebo over a 12-month follow-up period. © 2024. The Author(s) under exclusive licence to Italian Society of Nephrology. DOI: 10.1007/s40620-024-02154-9 PMID: 39680321 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest. Ethical approval: The study was approved by the Local Health Research Committee 501 of the Hospital de Especialidades No.1, Bajío, with institutional registration number R-2017–501-16. Informed consent to participate: It was conducted with the informed consent signed by the patients and under the General Health Law on Health Research (see Supplementary Information).

The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial.

3. Arch Osteoporos. 2023 Jun 20;18(1):83. doi: 10.1007/s11657-023-01288-w. The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial. Moore AE(1), Dulnoan D(1), Voong K(2), Ayis S(3), Mangelis A(3), Gorska R(2), Harrington DJ(2), Tang JCY(4)(5), Fraser WD(4)(5), Hampson G(6)(7)(8). Author information: (1)Osteoporosis Unit, Guy's Hospital, London, UK. (2)Nutristasis Unit, Synnovis Analytics, St Thomas' Hospital, London, UK. (3)School of Life Course and Population Sciences, Faculty of Life Sciences & Medicine, King's College London, Guy's Campus, London, UK. (4)Norwich Medical School, University of East Anglia, Norwich, UK. (5)Depts of Endocrinology and Clinical Biochemistry Norfolk and Norwich University Hospitals Trust, Norwich, UK. (6)Osteoporosis Unit, Guy's Hospital, London, UK. geeta.hampson@kcl.ac.uk. (7)Department of Chemical Pathology and Metabolic Medicine, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK. geeta.hampson@kcl.ac.uk. (8)Metabolic Bone Clinic, Department of Diabetes and Endocrinology, St Thomas' Hospital, London, UK. geeta.hampson@kcl.ac.uk. This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K1 supplementation led to a modest effect on parameters of hip geometry. PURPOSE: Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment. METHODS: We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K1 ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K1 (1 mg/day) arm, vitamin K2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed. RESULTS: Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K1 arm: -1.02[5.07], p = 0.03). CONCLUSION: The addition of vitamin K1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed. TRIAL REGISTRATION: The study was registered at Clinicaltrial.gov:NCT01232647. © 2023. The Author(s). DOI: 10.1007/s11657-023-01288-w PMCID: PMC10282078 PMID: 37338608 [Indexed for MEDLINE] Conflict of interest statement: "Amelia Moore, Dwight Dulnoan, Kieran Voong, Salma Ayis, Anastasios Mangelis, Renata Gorska, Dominic. J. Harrington and Jonathan CY Tang declare that they have no conflict of interests’. William D. Fraser has received past educational grants, speaker honoraria and been on advisory boards in relation to Vitamin D and all treatments for osteoporosis. Geeta Hampson has received speaker honoraria and been on advisory boards in relation to Vitamin D and all treatments for osteoporosis.

Vitamin K supplementation and bone mineral density in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial.

4. Nephrol Dial Transplant. 2023 Sep 29;38(10):2131-2142. doi: 10.1093/ndt/gfac315. Vitamin K supplementation and bone mineral density in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial. Levy-Schousboe K(1), Marckmann P(2), Frimodt-Møller M(3)(4), Peters CD(5), Kjærgaard KD(5), Jensen JD(5), Strandhave C(6), Sandstrøm H(7), Hitz MF(8)(9), Langdahl B(10)(11), Vestergaard P(12)(13)(14), Brasen CL(15)(16), Schmedes A(15), Madsen JS(15)(16), Jørgensen NR(9)(17), Frøkjær JB(14)(18), Frandsen NE(1), Petersen I(19), Hansen D(4)(9). Author information: (1)Department of Medicine, Zealand University Hospital, Roskilde, Denmark. (2)Department of Medicine Sønderborg-Tønder, Hospital Sønderjylland, Sønderborg, Denmark. (3)Steno Diabetes Center, Copenhagen, Denmark. (4)Department of Nephrology, Herlev University Hospital, Copenhagen, Denmark. (5)Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark. (6)Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark. (7)Department of Radiology, Zealand University Hospital, Roskilde, Denmark. (8)Department of Medicine, Zealand University Hospital, Køge, Denmark. (9)Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. (10)Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. (11)Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. (12)Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. (13)Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark. (14)Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. (15)Department of Biochemistry and Immunology, Lillebælt Hospital, University Hospital of Southern Denmark, Denmark. (16)Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. (17)Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark. (18)Department of Radiology, Aalborg University Hospital, Aalborg, Denmark. (19)Open Patient Data Explorative Network, Department of Clinical Research, University of Southern Denmark and Odense University Hospital, Odense, Denmark. Comment in Nephrol Dial Transplant. 2023 Sep 29;38(10):2105-2108. doi: 10.1093/ndt/gfad117. BACKGROUND: Vitamin K deficiency is highly prevalent in patients on dialysis and may contribute to their low bone mineral density (BMD) and increased risk of fracture. This study investigated the effect of menaquinone-7 (MK-7) supplementation on BMD in patients on chronic dialysis. METHODS: In a multicentre, double-blind, placebo-controlled intervention trial, 123 patients on chronic dialysis were randomised to a daily oral supplement of either MK-7 360 µg or placebo for 2 years. BMD of the distal radius (1/3, mid, ultradistal and total), femoral neck, lumbar spine (L1-L4) and whole body was assessed by dual-energy X-ray absorptiometry. Serum levels of vitamin K1 and MK-7 and plasma levels of total osteocalcin, dephosphorylated-uncarboxylated matrix Gla protein and protein induced by vitamin K absence II were measured to assess vitamin K status. RESULTS: After 2 years, an accelerated BMD loss of the 1/3 distal radius was found with MK-7 supplementation {mean difference of changes relative to placebo -0.023 g/cm2 [95% confidence interval (CI) -0.039 to -0.008]}, whereas the decrease in lumbar spine BMD seen in the placebo group was prevented [mean difference of changes between groups 0.050 g/cm2 (95% CI 0.015-0.085)]. No significant effects were observed at the remaining skeletal sites. Vitamin K status strongly improved in MK-7-supplemented participants. CONCLUSION: Compared with placebo, an accelerated BMD loss of the 1/3 distal radius was found after 2 years of MK-7 supplementation, whereas a decline in lumbar spine BMD was prevented. As such, MK-7 supplementation might modify BMD site-specifically in patients on dialysis. In aggregate, our findings do not support MK-7 supplementation to preserve bone in patients on dialysis. © The Author(s) 2022. Published by Oxford University Press on behalf of the ERA. DOI: 10.1093/ndt/gfac315 PMCID: PMC10539208 PMID: 36460034 [Indexed for MEDLINE] Conflict of interest statement: K.L.-S.’s salary was partially funded by Kappa Bioscience AS, the Danish Society of Nephrology and the Karen Elise Jensen Foundation during the RenaKvit trial. M.F.H. has received a research grant from Orkla Care AS. B.L. has received research grants from Amgen and honoraria for academic services from Amgen, UCB, Gilead, Astellas, AstraZeneca and Gedeon-Richter, unrelated to the RenaKvit trial. The remaining authors have nothing to declare.

Fat-Soluble Vitamin Supplementation Using Liposomes, Cyclodextrins, or Medium-Chain Triglycerides in Cystic Fibrosis: A Randomized Controlled Trial.

5. Nutrients. 2021 Dec 20;13(12):4554. doi: 10.3390/nu13124554. Fat-Soluble Vitamin Supplementation Using Liposomes, Cyclodextrins, or Medium-Chain Triglycerides in Cystic Fibrosis: A Randomized Controlled Trial. Nowak JK(1), Sobkowiak P(2), Drzymała-Czyż S(1)(3), Krzyżanowska-Jankowska P(1), Sapiejka E(4), Skorupa W(5), Pogorzelski A(6), Nowicka A(7), Wojsyk-Banaszak I(2), Kurek S(1), Zielińska-Psuja B(8), Lisowska A(1), Walkowiak J(1). Author information: (1)Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland. (2)Department of Pneumonology, Allergology and Clinical Immunology, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland. (3)Department of Bromatology, Poznan University of Medical Sciences, Marcelinska 42, 60-354 Poznan, Poland. (4)The Specialist Centre for Medical Care of Mother and Child, Polanki 119, 80-308 Gdańsk, Poland. (5)Department of Lung Diseases, Institute for Tuberculosis and Lung Diseases, Plocka 26, 01-138 Warsaw, Poland. (6)Department of Pneumology and Cystic Fibrosis, Institute of Tuberculosis and Lung Diseases, Rudnika 3, 34-700 Rabka-Zdroj, Poland. (7)Department of Pulmonology, Allergology and Respiratory Oncology, Poznan University of Medical Sciences, Szamarzewskiego 84, 60-569 Poznan, Poland. (8)Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30, 60-631 Poznan, Poland. Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of β-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients (n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19-28), body mass index of 20.6 kg/m2 [18.4-22.0], and forced expiratory volume in 1 s of 65% (44-84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR -44.3-86.1) vs. -38.8 ng/mL (-71.2-6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0-17.0) vs. +3.0 ng/mL (-4.0-7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33-6.52) vs. -0.34 µg/mL (-1.71-2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma). DOI: 10.3390/nu13124554 PMCID: PMC8706805 PMID: 34960106 [Indexed for MEDLINE] Conflict of interest statement: J.K.N. reports personal fees from Norsa Pharma within an EU-funded project and grant support from Biocodex. S.D.-C., P.K.-J. and A.L. report personal fees from Norsa Pharma within an EU-funded project. J.W. reports personal fees and grant support from Norsa Pharma within an EU-funded project, as well as personal fees and non-financial support from Biocodex, BGP Products, Chiesi, Hipp, Humana, Mead Johnson Nutrition, Merck Sharp & Dohme, Nestle, Nutricia, Roche, Sequoia Pharmaceuticals, and Vitis Pharma, alongside, outside the submitted work, grants, personal fees, and non-financial support from Nutricia Research Foundation Poland.

The effect of vitamin K1 on arterial calcification activity in subjects with diabetes mellitus: a post hoc analysis of a double-blind, randomized, placebo-controlled trial.

6. Am J Clin Nutr. 2022 Jan 11;115(1):45-52. doi: 10.1093/ajcn/nqab306. The effect of vitamin K1 on arterial calcification activity in subjects with diabetes mellitus: a post hoc analysis of a double-blind, randomized, placebo-controlled trial. Bellinge JW(1)(2), Francis RJ(1)(3), Lee SC(1)(2), Bondonno NP(4)(5), Sim M(1)(4), Lewis JR(1)(4)(6), Watts GF(1)(7), Schultz CJ(1)(2). Author information: (1)Division of Internal Medicine, Medical School, University of Western Australia, Perth, Western Australia, Australia. (2)Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia. (3)Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. (4)Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia. (5)School of Biomedical Sciences, University of Western Australia, Royal Perth Hospital, Perth, Western Australia, Australia. (6)Centre for Kidney Research, Children's Hospital Westmead, School of Public Health, University of Sydney, Westmead, New South Wales, Australia. (7)Cardiometabolic Service, Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia. BACKGROUND: Coronary and aortic artery calcifications are generally slow to develop, and their burden predicts cardiovascular disease events. In patients with diabetes mellitus, arterial calcification is accelerated and calcification activity can be detected using 18F-sodium fluoride positron emission tomography (18F-NaF PET). OBJECTIVES: We aimed to determine whether vitamin K1 supplementation inhibits arterial calcification activity in individuals with diabetes mellitus. METHODS: This was a post hoc analysis of the ViKCoVaC (effect of Vitamin-K1 and Colchicine on Vascular Calcification activity in subjects with Diabetes Mellitus) double-blind randomized controlled trial conducted in Perth, Western Australia. Individuals with diabetes mellitus and established coronary calcification (coronary calcium score > 10), but without clinical coronary artery disease, underwent baseline 18F-NaF PET imaging, followed by oral vitamin K1 supplementation (10 mg/d) or placebo for 3 mo, after which 18F-NaF PET imaging was repeated. We tested whether individuals randomly assigned to vitamin K1 supplementation had reduced development of new 18F-NaF PET positive lesions within the coronary arteries and aorta. RESULTS: In total, 149 individuals completed baseline and follow-up imaging studies. Vitamin K1 supplementation independently decreased the odds of developing new 18F-NaF PET positive lesions in the coronary arteries (OR: 0.35; 95% CI: 0.16, 0.78; P = 0.010), aorta (OR: 0.27; 95% CI: 0.08, 0.94; P = 0.040), and in both aortic and coronary arteries (OR: 0.28; 95% CI: 0.13, 0.63; P = 0.002). CONCLUSIONS: In individuals with diabetes mellitus, supplementation with 10 mg vitamin K1/d may prevent the development of newly calcifying lesions within the aorta and the coronary arteries as detected using 18F-NaF PET. Further long-term studies are needed to test this hypothesis.This trial was registered at anzctr.org.au as ACTRN12616000024448. © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition. DOI: 10.1093/ajcn/nqab306 PMID: 34637494 [Indexed for MEDLINE]

Vitamin K Supplementation for the Prevention of Cardiovascular Disease: Where Is the Evidence? A Systematic Review of Controlled Trials.

7. Nutrients. 2020 Sep 23;12(10):2909. doi: 10.3390/nu12102909. Vitamin K Supplementation for the Prevention of Cardiovascular Disease: Where Is the Evidence? A Systematic Review of Controlled Trials. Vlasschaert C(1), Goss CJ(1), Pilkey NG(1), McKeown S(2), Holden RM(1)(3). Author information: (1)Department of Medicine, Queen's University, Kingston, ON K7L 3V6, Canada. (2)Bracken Health Sciences Library, Queen's University, Kingston, ON K7L 2V5, Canada. (3)Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3V6, Canada. Matrix gla protein (MGP) is an important vitamin K-dependent inhibitor of vascular calcification. High levels of uncarboxylated, dephosphorylated MGP have been associated with vascular calcification and are responsive to vitamin K treatment. In this systematic review, we summarize the available evidence examining whether vitamin K supplementation improves surrogate measures of cardiovascular disease including artery and valve calcification, atherosclerosis and artery stiffening. Data from controlled trials of adults were obtained by searching Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Web of Science Core Collection. We identified nine randomized controlled trials for review, including trials of vitamin K1 or vitamin K2 supplementation, that assessed a surrogate measure of cardiovascular disease including arterial calcification, atherosclerosis or arterial stiffening. For each trial, the risk of bias was assessed applying Cochrane Collaboration methodology. The findings indicate that vitamin K does not consistently prevent progression of calcification, atherosclerosis or arterial stiffness. There may be some benefit in people with calcification at study entry. Studies were heterogenous, with relatively short follow-up and outcome measures were varied. While vitamin K supplementation clearly improves the carboxylation of dephosphoylated MGP, its role in mitigating vascular calcification is uncertain, based on current evidence. DOI: 10.3390/nu12102909 PMCID: PMC7598164 PMID: 32977548 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest.

Epigenome-wide association study reveals a molecular signature of response to phylloquinone (vitamin K1) supplementation.

8. Epigenetics. 2020 Aug;15(8):859-870. doi: 10.1080/15592294.2020.1734714. Epub 2020 Mar 5. Epigenome-wide association study reveals a molecular signature of response to phylloquinone (vitamin K1) supplementation. Westerman K(1)(2), Kelly JM(3), Ordovás JM(1)(4)(5), Booth SL(1)(3), DeMeo DL(6). Author information: (1)Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University , Boston, MA, USA. (2)Clinical and Translational Epidemiology Unit, Massachusetts General Hospital , Boston, MA. (3)Vitamin K Laboratory, JM-USDAHuman Nutrition Research Center on Aging at Tufts University , Boston, MA, USA. (4)IMDEA Alimentación, CEI, UAM , Madrid, Spain. (5)Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional De Investigaciones Cardiovasculares (CNIC) , Madrid, Spain. (6)Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital , Boston, MA, USA. Evidence suggests there are roles for vitamin K in various chronic disease outcomes, but population-level diet and supplement recommendations are difficult to determine due to high levels of variability in measures of status and response to intake compared to other nutrients. In this preliminary investigation, a blood-based epigenome-wide association study (EWAS) comparing responders and non-responders to phylloquinone (vitamin K1) supplementation (NCT00183001) was undertaken in order to better understand the molecular underpinnings of this observed variability. Responders (n = 24) and non-responders (n = 24) were identified in a prior 3-year phylloquinone supplementation trial based on their changes in plasma phylloquinone concentrations. Differential DNA methylation was identified in multiple regions with previously unknown relationships to phylloquinone absorption and metabolism, such as at the TMEM263 locus. A hypothesis-driven analysis of lipid-related genes highlighted a site in the NPC1L1 gene, supplementing existing evidence for its role in phylloquinone absorption. Furthermore, an EWAS for baseline plasma phylloquinone concentrations revealed a strong correlation between the epigenomic signatures of phylloquinone baseline status and response to supplementation. This work can guide future epigenomic research on vitamin K and contributes to the development of more personalized dietary recommendations for vitamin K. DOI: 10.1080/15592294.2020.1734714 PMCID: PMC7518702 PMID: 32090699 [Indexed for MEDLINE] Conflict of interest statement: The authors report no conflict of interest.

The Contribution of Lipids to the Interindividual Response of Vitamin K Biomarkers to Vitamin K Supplementation.

9. Mol Nutr Food Res. 2019 Dec;63(24):e1900399. doi: 10.1002/mnfr.201900399. Epub 2019 Oct 3. The Contribution of Lipids to the Interindividual Response of Vitamin K Biomarkers to Vitamin K Supplementation. Kelly JM(1), Ordovas JM(1), Matuszek G(1), Smith CE(1), Huggins GS(2), Dashti HS(3)(4), Ichikawa R(1), Booth SL(1). Author information: (1)Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, 02111, USA. (2)Molecular Cardiology Research Institute Center for Translational Genomics, Tufts Medical Center and Tufts University, Boston, MA, 02111, USA. (3)Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. (4)Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. SCOPE: A better understanding of factors contributing to interindividual variability in biomarkers of vitamin K can enhance the understanding of the equivocal role of vitamin K in cardiovascular disease. Based on the known biology of phylloquinone, the major form of vitamin K, it is hypothesized that plasma lipids contribute to the variable response of biomarkers of vitamin K metabolism to phylloquinone supplementation. METHODS AND RESULTS: The association of plasma lipids and 27 lipid-related genetic variants with the response of biomarkers of vitamin K metabolism is examined in a secondary analysis of data from a 3-year phylloquinone supplementation trial in men (n = 66) and women (n = 85). Year 3 plasma triglycerides (TG), but not total cholesterol, LDL-cholesterol, or HDL-cholesterol, are associated with the plasma phylloquinone response (men: β = 1.01, p < 0.001, R2  = 0.34; women: β = 0.61, p = 0.008, R2  = 0.11; sex interaction p = 0.077). Four variants and the TG-weighted genetic risk score are associated with the plasma phylloquinone response in men only. Plasma lipids are not associated with changes in biomarkers of vitamin K function (undercarboxylated osteocalcin and matrix gla protein) in either sex. CONCLUSION: Plasma TG are an important determinant of the interindividual response of plasma phylloquinone to phylloquinone supplementation, but changes in biomarkers of vitamin K carboxylation are not influenced by lipids. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. DOI: 10.1002/mnfr.201900399 PMCID: PMC8815429 PMID: 31533195 [Indexed for MEDLINE] Conflict of interest statement: CONFLICT OF INTEREST STATEMENT The authors have declared no conflict of interest.

Effects of nutritional intervention upon bone turnover in elderly hip fracture patients. Randomized controlled trial.

10. Clin Nutr ESPEN. 2019 Feb;29:52-58. doi: 10.1016/j.clnesp.2017.11.012. Epub 2018 Oct 30. Effects of nutritional intervention upon bone turnover in elderly hip fracture patients. Randomized controlled trial. Torbergsen AC(1), Watne LO(2), Frihagen F(3), Wyller TB(4), Mowè M(5). Author information: (1)Institute of Clinical Medicine, University of Oslo, Norway; Department of General Internal Medicine, Oslo University Hospital, Norway. Electronic address: a.c.torbergsen@medisin.uio.no. (2)Institute of Clinical Medicine, University of Oslo, Norway; Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Norway; Institute of Basic Medical Sciences, University of Oslo, Norway. (3)Orthopaedic Department, Oslo University Hospital, Norway. (4)Institute of Clinical Medicine, University of Oslo, Norway; Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Norway. (5)Institute of Clinical Medicine, University of Oslo, Norway; Department of General Internal Medicine, Oslo University Hospital, Norway. Comment in Clin Nutr ESPEN. 2019 Aug;32:166. doi: 10.1016/j.clnesp.2019.04.005. BACKGROUND AND AIM: Hip fracture patients are at great risk of malnutrition, but documentation of the effect of nutrition supplementation in this group is sparse and inconclusive. The aim of this study was to examine if personalized nutrition advice combined with vitamin K1, Ca and vitamin D could improve bone turnover 4 months after hip fracture. DESIGN: This is a preplanned sub study of a randomized controlled trial of orthogeriatric care. The intervention group received orthogeriatric care, including nutrition advice and supplementation. The control group received usual care at the orthopedic ward. Blood was drawn for measurements of a number of vitamins and of bone turnover markers upon admission and at four months follow up. RESULTS: 71 patients (31 in the intervention group and 40 controls) had available data at 4 months as well as at baseline. After four months, vitamin K1 and 25(OH)D were higher in the intervention group compared with controls; vitamin K1: 1.0 ± 1.2 vs 0.6 ± 0.6 ng/ml, p = 0.09, 25(OH)D: 60 ± 29 vs 43 ± 22 nmol/L, p = 0.01 when adjusted for baseline differences. In a secondary, unadjusted analysis, comprising all patients with available four months data (n = 136), the differences were statistically significant for vitamin K1 as well as 25(OH)D (p = 0.03 and p < 0.001, respectively). There was a non-significant increase in 25(OH)D in the intervention group from baseline to 4 months follow up, and a significant decrease in the control group. There was no difference in bone turnover markers between the two groups at 4 months follow up. A substantial loss of weight and physical function was found in both groups. CONCLUSIONS: The supplementation of 25(OH)D and vitamin K1 improved serum concentrations of these vitamins, but this did not translate into any improvement in the bone turnover markers. The RCT is registered in ClinicalTrials.govNCT01009268 and NCT01738776. Copyright © 2017. Published by Elsevier Ltd. DOI: 10.1016/j.clnesp.2017.11.012 PMID: 30661701 [Indexed for MEDLINE]

Prophylactic role of vitamin K supplementation on vascular inflammation in type 2 diabetes by regulating the NF-κB/Nrf2 pathway via activating Gla proteins.

11. Food Funct. 2018 Jan 24;9(1):450-462. doi: 10.1039/c7fo01491k. Prophylactic role of vitamin K supplementation on vascular inflammation in type 2 diabetes by regulating the NF-κB/Nrf2 pathway via activating Gla proteins. Dihingia A (1), Ozah D , Baruah PK , Kalita J , Manna P . Author information: (1)Biological Science and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India. pmanna2012@gmail.com. There is no previous study that has examined the relationship between circulating vitamin K1 (VK1) and vascular inflammation in type 2 diabetes (T2D). This study aims to examine the hypothesis that circulating VK1 deficiency may be associated with higher inflammation and insulin resistance in T2D patients and that VK1 supplementation regulates the NF-κB/Nrf2 pathway via activating VK-dependent Gla proteins and reduces vascular inflammation. The results showed that plasma VK1 levels were significantly lower and MCP-1, fasting glucose, HbA1c, and insulin resistance (HOMA-IR) were significantly higher in T2D patients compared to those in the controls. The lower levels of VK1 in T2D patients were significantly and inversely correlated with MCP-1 and HOMA-IR, which suggests that VK1 supplementation may reduce the vascular inflammation and insulin resistance in T2D. Using a high fat diet-fed T2D mice model this study further demonstrated that VK1 supplementation (1, 3, 5 μg per kg BW, 8 weeks) dose-dependently decreased the body weight gain, glucose intolerance, fasting glucose, glycated hemoglobin, HOMA-IR, and cytokine secretion (MCP-1 and IL-6) in T2D mice. Further cell culture studies showed that VK1 supplementation (1, 5, or 10 nM) decreased NF-κB phosphorylation and MCP-1 secretion and increased Nrf2 protein expression in high glucose (HG, 25 mM)-treated monocytes. Signal silencing studies with GGCX siRNA again depicted the role of VK-dependent Gla proteins in mediating the effect of VK1 on vascular inflammation in HG-treated cells. In conclusion, this study suggests that circulating VK1 has a positive effect in lowering vascular inflammation in T2D by regulating NF-κB/Nrf2 transcription factors via activating VK-dependent Gla proteins. DOI: 10.1039/c7fo01491k PMID: 29227493 [Indexed for MEDLINE]

Effect of 1-y oral supplementation with vitaminized olive oil on platelets from healthy postmenopausal women.

12. Nutrition. 2017 Oct;42:92-98. doi: 10.1016/j.nut.2017.06.013. Epub 2017 Jul 5. Effect of 1-y oral supplementation with vitaminized olive oil on platelets from healthy postmenopausal women. Vignini A(1), Nanetti L(1), Raffaelli F(1), Sabbatinelli J(2), Salvolini E(1), Quagliarini V(3), Cester N(3), Mazzanti L(1). Author information: (1)Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, School of Nutrition, Università Politecnica delle Marche, Ancona, Italy. (2)Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, School of Nutrition, Università Politecnica delle Marche, Ancona, Italy. Electronic address: J.sabbatinelli@pm.univpm.it. (3)Department of Obstetrics, Gynecology and Pediatrics, Senigallia Hospital, ASUR Marche, Ancona, Italy. OBJECTIVE: Olive oil is the main fat source in the Mediterranean diet and shows a protective role against aging and related diseases. Osteoporosis represents a serious health problem worldwide and is associated with an increased risk for fractures and mortality. Nutrition should be part of bone disease prevention strategies, especially in light of the aging population and the effect of diet on bone health. The aim of this study was to investigate whether oral supplementation with extra virgin olive oil (VOO) enriched with vitamins D3, K1, and B6 (VitVOO) is able to modify some physicochemical and functional plasma membrane properties and nitrosative stress markers status. METHODS: In this single-center, randomized placebo-controlled trial, 60 postmenopausal women were administered either VitVOO or placebo (PlaVOO). After 1 y of oral supplementation, platelet membrane fluidity changes, Na+/K+-ATPase activity, serum nitric oxide, and peroxynitrite levels were determined in participants. RESULTS: After 1 y (time 1), women taking VitVOO showed lower nitric oxide levels than those taking PlaVOO; the same trend was found for peroxynitrite levels. As far as membrane fluidity was concerned, a significant decrease in anisotropy of diphenylhexatriene and trimethylammonium-diphenylhexatriene at time 1 in VitVOO participants compared with PlaVOO was found. Finally, Na+/K+-ATPase activity showed a significant increase after VitVOO supplementation. CONCLUSION: The supplementation of VitVOO into the diet of postmenopausal women could represent a proper tool for platelet function and a useful strategy against nitrosative stress and related diseases, thus confirming the antioxidant role played by the added vitamins. Copyright © 2017 Elsevier Inc. All rights reserved. DOI: 10.1016/j.nut.2017.06.013 PMID: 28870486 [Indexed for MEDLINE]

US Pharmacopeial Convention safety evaluation of menaquinone-7, a form of vitamin K.

13. Nutr Rev. 2017 Jul 1;75(7):553-578. doi: 10.1093/nutrit/nux022. US Pharmacopeial Convention safety evaluation of menaquinone-7, a form of vitamin K. Marles RJ(1), Roe AL(1), Oketch-Rabah HA(1). Author information: (1)US Pharmacopeial Convention's Dietary Supplements Admission Evaluations Joint Standard Setting Subcommittee, US Pharmacopeial Convention, Rockville, Maryland, USA. US Pharmacopeial Convention, Rockville, Maryland, USA. Vitamin K plays important biological roles in maintaining normal blood coagulation, bone mineralization, soft tissue physiology, and neurological development. Menaquinone-7 is a form of vitamin K2 that occurs naturally in some animal-derived and fermented foods. It is also available as an ingredient of dietary supplements. Menaquinone-7 has greater bioavailability than other forms of vitamin K, which has led to increasing sales and use of menaquinone-7 supplements. This special article reviews the chemistry, nomenclature, dietary sources, intake levels, and pharmacokinetics of menaquinones, along with the nonclinical toxicity data available and the data on clinical outcomes related to safety (adverse events). In conclusion, the data reviewed indicate that menaquinone-7, when ingested as a dietary supplement, is not associated with any serious risk to health or with other public health concerns. On the basis of this conclusion, US Pharmacopeia monographs have been developed to establish quality standards for menaquinone-7 as a dietary ingredient and as a dietary supplement in various dosage forms. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. DOI: 10.1093/nutrit/nux022 PMID: 28838081 [Indexed for MEDLINE]

Oral Consumption of Vitamin K2 for 8 Weeks Associated With Increased Maximal Cardiac Output During Exercise.

14. Altern Ther Health Med. 2017 Jul;23(4):26-32. Oral Consumption of Vitamin K2 for 8 Weeks Associated With Increased Maximal Cardiac Output During Exercise. McFarlin BK, Henning AL, Venable AS. Background • Vitamin K1 and K2 are not typically common in a Western diet because they are found in a variety of fermented foods. Vitamin K2 in particular has been demonstrated to restore mitochondrial function and has a key role in production of mitochondrial adenosine triphosphate. Thus, it is reasonable to speculate that dietary supplementation with vitamin K2 could increase the function of muscle with high mitochondrial content (ie, skeletal and cardiac muscle). Objective • The purpose of this study was to determine if 8 wk of dietary supplementation with Vitamin K2 could alter cardiovascular responses to a graded cycle ergometer test. Design • The study was a randomized controlled trial. Setting • The study took place in the Applied Physiology Laboratory of the Department of Biological Sciences at the University of North Texas (Denton, TX, USA). Participants • Participants were aerobically trained males and female athletes (N = 26). Intervention • Participants were randomly assigned either to a control group that received a rice flour placebo or to an intervention group that received vitamin K2. For weeks 1 to 4, participants received 300 mg/d; for weeks 5 to 8, they received 150 mg/d. Subjects assigned to the control group received similar doses to mirror the intervention group. Subjects consumed the supplements during an 8-wk period while they maintained their typical exercise habits. Outcome Measures • At baseline and postintervention, participants completed a standard, graded exercise test on an electronically braked cycle ergometer. Before the test, participants were fitted with a mouth piece, and their oxygen consumption, carbon dioxide production, respiratory rate, and respiratory exchange ratio were measured. In addition, participants were fitted with skin-mounted electrodes that measured noninvasive cardiac output, stroke volume, and heart rate. To assess the cumulative exercise change, an area-under-the-curve (AUC) value was calculated separately for each outcome variable at each treatment time point. Results • Vitamin K2 supplementation was associated with a 12% increase in maximal cardiac output, with P = .031, with a trend toward an increase in heart-rate AUC, with P = .070. No significant changes occurred in stroke volume. Conclusions • Although vitamin K2 supplementation has previously been reported to improve cardiovascular function in diseased patients, to the research team's knowledge, the current study is the first to report its potential in active individuals. More research is needed to fully evaluate the potential effects of the observed effects. PMID: 28646812 [Indexed for MEDLINE]

Association of Dietary Vitamin K1 Intake With the Incidence of Cataract Surgery in an Adult Mediterranean Population: A Secondary Analysis of a Randomized Clinical Trial.

15. JAMA Ophthalmol. 2017 Jun 1;135(6):657-661. doi: 10.1001/jamaophthalmol.2017.1076. Association of Dietary Vitamin K1 Intake With the Incidence of Cataract Surgery in an Adult Mediterranean Population: A Secondary Analysis of a Randomized Clinical Trial. Camacho-Barcia ML(1), Bulló M(2), Garcia-Gavilán JF(1), Ruiz-Canela M(3), Corella D(4), Estruch R(5), Fitó M(6), García-Layana A(7), Arós F(8), Fiol M(9), Lapetra J(10), Serra-Majem L(11), Pintó X(12), García-Arellano A(13), Vinyoles E(6), Sorli JV(4), Salas-Salvadó J(2). Author information: (1)Human Nutrition Unit, Biochemistry and Biotechnology Department, University Hospital of Sant Joan de Reus, Reus, Spain. (2)Human Nutrition Unit, Biochemistry and Biotechnology Department, University Hospital of Sant Joan de Reus, Reus, Spain2Centro de Investigación Biomédica en Red Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain. (3)Centro de Investigación Biomédica en Red Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain3Department of Preventive Medicine and Public Health, Medical School, University of Navarra, Pamplona, Spain. (4)Centro de Investigación Biomédica en Red Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain4Department of Preventive Medicine, University of Valencia, Valencia, Spain. (5)Centro de Investigación Biomédica en Red Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain5Department of Internal Medicine, August Pi i Sunyer Institute of Biomedical Research, Hospital Clinic, University of Barcelona, Barcelona, Spain. (6)Centro de Investigación Biomédica en Red Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain6Cardiovascular Risk and Nutrition (Regicor Study Group), Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park, Barcelona, Spain. (7)Centro de Investigación Biomédica en Red Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain7Department of Ophthalmology, University of Navarra, Pamplona, Spain. (8)Centro de Investigación Biomédica en Red Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain8Department of Cardiology, Hospital Txangorritxu, Vitoria, Spain. (9)Centro de Investigación Biomédica en Red Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain9Department of Cardiology, Hospital Universitario Son Dureta, Palma de Mallorca, Spain. (10)Centro de Investigación Biomédica en Red Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain10San Pablo Health Center, Sevilla, Spain. (11)Centro de Investigación Biomédica en Red Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain11Research Institut of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas, Spain. (12)Centro de Investigación Biomédica en Red Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain12Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Barcelona, Spain. (13)Centro de Investigación Biomédica en Red Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain3Department of Preventive Medicine and Public Health, Medical School, University of Navarra, Pamplona, Spain13Emergency Department, Complejo Hospitalario de Navarra, Servicio Navarro de Salud-Osasunbidea, Pamplona, Spain. IMPORTANCE: Cataract, one of the most frequent causes of blindness in developed countries, is strongly associated with aging. The exact mechanisms underlying cataract formation are still unclear, but growing evidence suggests a potential role of inflammatory and oxidative processes. Therefore, antioxidant and anti-inflammatory factors of the diet, such as vitamin K1, could play a protective role. OBJECTIVE: To examine the association between dietary vitamin K1 intake and the risk of incident cataracts in an elderly Mediterranean population. DESIGN, SETTING, AND PARTICIPANTS: A prospective analysis was conducted in 5860 participants from the Prevención con Dieta Mediterránea Study, a randomized clinical trial executed between 2003 and 2011. Participants were community-dwelling men (44.2%) and women (55.8%), and the mean (SD) age was 66.3 (6.1) years. MAIN OUTCOMES AND MEASURES: Dietary vitamin K1 intake was evaluated using a validated food frequency questionnaire. The time to the cataract event was calculated as the time between recruitment and the date of the occurrence to cataract surgery, the time to the last visit of the follow-up, date of death, or the end of the study. Hazard ratios and 95% CIs for cataract incidence were estimated with a multivariable Cox proportional hazards model. RESULTS: Participants were community-dwelling men (44.2%; n = 868) and women (55.8%; n = 1086), and the mean (SD) age was 66.3 (6.1) years. After a median of 5.6 years follow-up, we documented a total of 768 new cataracts. Participants in the highest tertile of dietary vitamin K1 intake had a lower risk of cataracts than those in the lowest tertile (hazard ratio, 0.71; 95% CI, 0.58-0.88; P = .002), after adjusting for potential confounders. CONCLUSIONS AND RELEVANCE: High intake of dietary vitamin K1 was associated with a reduced risk of cataracts in an elderly Mediterranean population even after adjusting by other potential confounders. TRIAL REGISTRATION: isrctn.org: ISRCTN35739639. DOI: 10.1001/jamaophthalmol.2017.1076 PMCID: PMC5847084 PMID: 28494067 [Indexed for MEDLINE] Conflict of interest statement: Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Salas-Salvadó reports personal fees from Nuts for Life and from Nut and Dried Fruit Foundation, during the conduct of the study; personal fees from Danone SA, personal fees from Font Vella Lanjaron, personal fees from Eroski Distributors, and personal fees from Instituto Danone outside the submitted work. No other disclosures were reported.