{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:18:36Z","timestamp":1787192316624,"version":"build-2736575974"},"reference-count":98,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vitamin D, traditionally regarded as a nutrient, is increasingly recognized as a pharmacologically active secosteroid with pleiotropic effects extending beyond calcium homeostasis and bone integrity. Together with vitamin K2, it participates in the fine-tuning of mineral metabolism and vascular health, potentially modulating cardiometabolic risk through intertwined endocrine and paracrine pathways. Despite widespread fortification and supplementation, vitamin D deficiency remains a major global health concern, driven by limited sun exposure, obesity, and metabolic dysfunction. Observational and mechanistic studies consistently link low serum 25(OH)D concentrations with hypertension, insulin resistance, heart failure, and increased cardiovascular mortality. At the molecular level, vitamin D exerts pharmacological actions\u2014modulating the renin\u2013angiotensin\u2013aldosterone system, exerting anti-inflammatory and antifibrotic effects, and influencing endothelial and cardiomyocyte signaling. While experimental and epidemiological evidence suggests potential cardiovascular benefits, large randomized controlled trials (RCTs) provide conflicting results, particularly regarding hypertension and heart failure. However, these often-neutral results do not preclude a targeted action. On the contrary, clinical efficacy is strongly dependent on baseline deficiency status and the presence of metabolic cofactors. In this context, high-dose supplementation of Vitamin D, in combination with Vitamin K2 to prevent vascular calcification, elevates the supplement to a genuine pharmacological agent, with a distinct therapeutic potential for modulating cardiometabolic risk in selected patient subgroups. Emerging evidence supports the concept that vitamin D, when appropriately dosed and combined with K2, may act more as a low-potency pharmacological modulator than a simple nutritional supplement. This review synthesizes current mechanistic, observational, and interventional evidence, aiming to clarify whether vitamin D should be reclassified\u2014from a micronutrient to a pharmacologically relevant agent\u2014in cardiometabolic prevention and therapy, proposing a paradigm shift toward personalized and targeted dosing strategies, characteristic of precision pharmacology.<\/jats:p>","DOI":"10.3390\/ijms27010298","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T05:28:19Z","timestamp":1766986099000},"page":"298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Modulation of Cardiometabolic Risk by Vitamin D and K2: Simple Supplementation or Real Drug? Uncovering the Pharmacological Properties"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5415-1953","authenticated-orcid":false,"given":"Saverio","family":"D\u2019Elia","sequence":"first","affiliation":[{"name":"Cardiology Unit, University Hospital Luigi Vanvitelli, 80138 Naples, Italy"},{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia, 2, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2938-4728","authenticated-orcid":false,"given":"Roberta","family":"Bottino","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2190-7010","authenticated-orcid":false,"given":"Andreina","family":"Carbone","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital Luigi Vanvitelli, 80138 Naples, Italy"},{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Formisano","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Orlandi","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Sperlongano","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Castaldo","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Molinari","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Palladino","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7690-0347","authenticated-orcid":false,"given":"Mariarosaria","family":"Morello","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7146-7823","authenticated-orcid":false,"given":"Gisella","family":"Titolo","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia, 2, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco S.","family":"Loffredo","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"},{"name":"Vanvitelli Cardiology and Intensive Care Unit, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7824-6033","authenticated-orcid":false,"given":"Francesco","family":"Natale","sequence":"additional","affiliation":[{"name":"Vanvitelli Cardiology and Intensive Care Unit, Monaldi Hospital, 80131 Naples, Italy"},{"name":"Department of Life Science, Health, and Health Professions, Link Campus University, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7818-4952","authenticated-orcid":false,"given":"Plinio","family":"Cirillo","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples \u201cFederico II\u201d, Via Pansini, 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3802-7052","authenticated-orcid":false,"given":"Giovanni","family":"Cimmino","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital Luigi Vanvitelli, 80138 Naples, Italy"},{"name":"Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1600-0625.2010.01202.x","article-title":"Vitamin D: An ancient hormone","volume":"20","author":"Bikle","year":"2011","journal-title":"Exp. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Latic, N., and Erben, R.G. (2020). Vitamin D and Cardiovascular Disease, with Emphasis on Hypertension, Atherosclerosis, and Heart Failure. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186483"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rochel, N. (2022). Vitamin D and Its Receptor from a Structural Perspective. Nutrients, 14.","DOI":"10.3390\/nu14142847"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"R27","DOI":"10.1530\/EC-18-0432","article-title":"Vitamin D testing and treatment: A narrative review of current evidence","volume":"8","author":"Pilz","year":"2019","journal-title":"Endocr. Connect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5542","DOI":"10.1210\/en.2006-0946","article-title":"Minireview: Vitamin D receptor: New assignments for an already busy receptor","volume":"147","author":"Norman","year":"2006","journal-title":"Endocrinology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dankers, W., Colin, E.M., van Hamburg, J.P., and Lubberts, E. (2016). Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00697"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Grant, W.B., Boucher, B.J., Al Anouti, F., and Pilz, S. (2022). Comparing the Evidence from Observational Studies and Randomized Controlled Trials for Nonskeletal Health Effects of Vitamin D. Nutrients, 14.","DOI":"10.3390\/nu14183811"},{"key":"ref_8","unstructured":"Kaur, J., Khare, S., Sizar, O., and Givler, A. (2025). Vitamin D Deficiency. StatPearls, StatPearls Publishing."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1210\/clinem\/dgae290","article-title":"Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline","volume":"109","author":"Demay","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","unstructured":"Chauhan, K., Shahrokhi, M., and Huecker, M.R. (2025). Vitamin D. StatPearls, StatPearls Publishing."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1006\/pmed.1997.0175","article-title":"The role of nicotine in smoking-related cardiovascular disease","volume":"26","author":"Benowitz","year":"1997","journal-title":"Prev. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"346","DOI":"10.14336\/AD.2016.1021","article-title":"Vitamin D and Chronic Diseases","volume":"8","author":"Wang","year":"2017","journal-title":"Aging Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1016\/j.clnu.2020.12.025","article-title":"Vitamin D and cardiovascular health","volume":"40","author":"Vallecillo","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.annepidem.2008.12.014","article-title":"Ecological studies of ultraviolet B, vitamin D and cancer since 2000","volume":"19","author":"Grant","year":"2009","journal-title":"Ann. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jsbmb.2018.11.002","article-title":"Association of sun and UV exposure with blood pressure and cardiovascular disease: A systematic review","volume":"187","author":"Scragg","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.clnu.2025.04.017","article-title":"Real-world evidence for an association of vitamin D supplementation with atherosclerotic cardiovascular disease in the UK Biobank","volume":"49","author":"Sha","year":"2025","journal-title":"Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1210\/endrev\/bnae009","article-title":"Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows","volume":"45","author":"Giustina","year":"2024","journal-title":"Endocr. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"582S","DOI":"10.1093\/ajcn\/88.2.582S","article-title":"Pharmacokinetics of vitamin D toxicity","volume":"88","author":"Jones","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00223-012-9619-0","article-title":"Molecular mechanisms of vitamin D action","volume":"92","author":"Haussler","year":"2013","journal-title":"Calcif. Tissue Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1161\/CIRCRESAHA.113.301241","article-title":"Vitamin D and cardiovascular disease","volume":"114","author":"Norman","year":"2014","journal-title":"Circ. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1152\/physrev.00014.2015","article-title":"Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects","volume":"96","author":"Christakos","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"414","DOI":"10.2174\/157016109788340686","article-title":"Vitamin D and cardiovascular disease","volume":"7","author":"Krone","year":"2009","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1172\/JCI0215219","article-title":"1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system","volume":"110","author":"Li","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1080\/10408398.2020.1862753","article-title":"Functional effects of vitamin D: From nutrient to immunomodulator","volume":"62","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mandatori, D., Pelusi, L., Schiavone, V., Pipino, C., Di Pietro, N., and Pandolfi, A. (2021). The Dual Role of Vitamin K2 in \u201cBone-Vascular Crosstalk\u201d: Opposite Effects on Bone Loss and Vascular Calcification. Nutrients, 13.","DOI":"10.3390\/nu13041222"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/bs.afnr.2023.12.005","article-title":"Vitamin D and cardiovascular diseases","volume":"109","author":"Milazzo","year":"2024","journal-title":"Adv. Food Nutr. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.jcmg.2020.06.030","article-title":"Oral Calcium Supplements Associate With Serial Coronary Calcification: Insights From Intravascular Ultrasound","volume":"14","author":"Bazarbashi","year":"2021","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Aaseth, J.O., Finnes, T.E., Askim, M., and Alexander, J. (2024). The Importance of Vitamin K and the Combination of Vitamins K and D for Calcium Metabolism and Bone Health: A Review. Nutrients, 16.","DOI":"10.20944\/preprints202406.0766.v1"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"bvz038","DOI":"10.1210\/jendso\/bvz038","article-title":"Vitamin D: Newer Concepts of Its Metabolism and Function at the Basic and Clinical Level","volume":"4","author":"Bikle","year":"2020","journal-title":"J. Endocr. Soc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1007\/s00198-018-4520-y","article-title":"Is calcifediol better than cholecalciferol for vitamin D supplementation?","volume":"29","author":"Bouillon","year":"2018","journal-title":"Osteoporos. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/S0140-6736(10)61032-X","article-title":"Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): A randomised controlled trial","volume":"376","author":"Agarwal","year":"2010","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1161\/HYPERTENSIONAHA.108.113159","article-title":"Paricalcitol reduces albuminuria and inflammation in chronic kidney disease: A randomized double-blind pilot trial","volume":"52","author":"Alborzi","year":"2008","journal-title":"Hypertension"},{"key":"ref_34","first-page":"1","article-title":"Pharmacokinetics of Menaquinone-7 (Vitamin K2) in Healthy Volunteers","volume":"4","author":"Knapen","year":"2014","journal-title":"J. Clin. Trials"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.bone.2018.02.024","article-title":"Comparison of the effect of daily versus bolus dose maternal vitamin D(3) supplementation on the 24,25-dihydroxyvitamin D(3) to 25-hydroxyvitamin D(3) ratio","volume":"110","author":"Ketha","year":"2018","journal-title":"Bone"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/1475-2891-11-93","article-title":"Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women","volume":"11","author":"Sato","year":"2012","journal-title":"Nutr. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1182\/blood-2006-08-040709","article-title":"Vitamin K-containing dietary supplements: Comparison of synthetic vitamin K1 and natto-derived menaquinone-7","volume":"109","author":"Schurgers","year":"2007","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1160\/TH14-08-0675","article-title":"Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial","volume":"113","author":"Knapen","year":"2015","journal-title":"Thromb. Haemost."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s00198-013-2325-6","article-title":"Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women","volume":"24","author":"Knapen","year":"2013","journal-title":"Osteoporos. Int."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Fassio, A., Gatti, D., Rossini, M., Benini, C., Fracassi, E., Bertoldo, E., Viapiana, O., Milleri, S., Gatti, M., and Adami, G. (2021). Pharmacodynamics of Oral Cholecalciferol in Healthy Individuals with Vitamin D Deficiency: A Randomized Open-Label Study. Nutrients, 13.","DOI":"10.3390\/nu13072293"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1161\/01.HYP.30.2.150","article-title":"Ultraviolet light may contribute to geographic and racial blood pressure differences","volume":"30","author":"Rostand","year":"1997","journal-title":"Hypertension"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1097\/HJH.0000000000002231","article-title":"Vitamin D and blood pressure control among hypertensive adults: Results from NHANES 2001\u20132014","volume":"38","author":"Wright","year":"2020","journal-title":"J. Hypertens."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1161\/HYPERTENSIONAHA.114.03971","article-title":"Elimination of vitamin D receptor in vascular endothelial cells alters vascular function","volume":"64","author":"Ni","year":"2014","journal-title":"Hypertension"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1136\/bmj.285.6346.919","article-title":"Seasonal variation in arterial blood pressure","volume":"285","author":"Brennan","year":"1982","journal-title":"Br. Med. J. (Clin. Res. Ed.)"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.amjhyper.2007.01.017","article-title":"Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey","volume":"20","author":"Scragg","year":"2007","journal-title":"Am. J. Hypertens."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1093\/ajcn\/87.1.136","article-title":"Optimal vitamin D status attenuates the age-associated increase in systolic blood pressure in white Americans: Results from the third National Health and Nutrition Examination Survey","volume":"87","author":"Judd","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/j.amjcard.2008.06.067","article-title":"Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004)","volume":"102","author":"Kim","year":"2008","journal-title":"Am. J. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1161\/CIRCULATIONAHA.107.706127","article-title":"Vitamin D deficiency and risk of cardiovascular disease","volume":"117","author":"Wang","year":"2008","journal-title":"Circulation"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1161\/HYPERTENSIONAHA.107.087288","article-title":"Plasma 25-hydroxyvitamin D levels and risk of incident hypertension","volume":"49","author":"Forman","year":"2007","journal-title":"Hypertension"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1093\/ajh\/hpt051","article-title":"Hypertension, pulse, and other cardiovascular risk factors and vitamin D status in Finnish men","volume":"26","author":"Ke","year":"2013","journal-title":"Am. J. Hypertens."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Valer-Martinez, A., Bes-Rastrollo, M., Martinez, J.A., Martinez-Gonzalez, M.A., and Sayon-Orea, C. (2024). Vitamin D and the Risk of Developing Hypertension in the SUN Project: A Prospective Cohort Study. Nutrients, 16.","DOI":"10.3390\/nu16142351"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s10654-013-9790-2","article-title":"Vitamin D and risk of future hypertension: Meta-analysis of 283,537 participants","volume":"28","author":"Kunutsor","year":"2013","journal-title":"Eur. J. Epidemiol."},{"key":"ref_53","unstructured":"(1989). Nursing supply and demand. Am. Nurse, 21, 6\u20137."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1093\/ajh\/hpae103","article-title":"Associations of Vitamin D-Related Biomarkers With Hypertension and the Renin-Angiotensin System in Men and Women","volume":"37","author":"Wang","year":"2024","journal-title":"Am. J. Hypertens."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"14312","DOI":"10.1038\/s41598-024-64649-6","article-title":"Serum vitamin D, blood pressure and hypertension risk in the HUNT study using observational and Mendelian randomization approaches","volume":"14","author":"Jiang","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1161\/HYPERTENSIONAHA.111.00659","article-title":"Effect of vitamin D supplementation on blood pressure in blacks","volume":"61","author":"Forman","year":"2013","journal-title":"Hypertension"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1056\/NEJMoa1809944","article-title":"Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease","volume":"380","author":"Manson","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1001\/jama.2020.16909","article-title":"Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults: The DO-HEALTH Randomized Clinical Trial","volume":"324","author":"Vellas","year":"2020","journal-title":"JAMA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e075230","DOI":"10.1136\/bmj-2023-075230","article-title":"Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial","volume":"381","author":"Thompson","year":"2023","journal-title":"BMJ"},{"key":"ref_60","first-page":"1672","article-title":"Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: The VitDISH randomized controlled trial","volume":"173","author":"Witham","year":"2013","journal-title":"JAMA Intern. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1001\/jamainternmed.2015.0237","article-title":"Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data","volume":"175","author":"Beveridge","year":"2015","journal-title":"JAMA Intern. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"E03","DOI":"10.5888\/pcd17.190307","article-title":"Effect of Vitamin D on Blood Pressure and Hypertension in the General Population: An Update Meta-Analysis of Cohort Studies and Randomized Controlled Trials","volume":"17","author":"Zhang","year":"2020","journal-title":"Prev. Chronic Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.numecd.2016.04.011","article-title":"Effect of vitamin D3 supplementation on blood pressure in adults: An updated meta-analysis","volume":"26","author":"Golzarand","year":"2016","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1097\/HJH.0b013e32832f075b","article-title":"Effect of vitamin D on blood pressure: A systematic review and meta-analysis","volume":"27","author":"Witham","year":"2009","journal-title":"J. Hypertens."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJMoa1900906","article-title":"Vitamin D Supplementation and Prevention of Type 2 Diabetes","volume":"381","author":"Pittas","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"260","DOI":"10.2337\/dc12-1204","article-title":"High-dose vitamin D supplementation in people with prediabetes and hypovitaminosis D","volume":"36","author":"Davidson","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3721","DOI":"10.1210\/clinem\/dgaa594","article-title":"Vitamin D Supplementation for Prevention of Type 2 Diabetes Mellitus: To D or Not to D?","volume":"105","author":"Pittas","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.2337\/dc19-1708","article-title":"Effects of Vitamin D Supplementation on Prevention of Type 2 Diabetes in Patients With Prediabetes: A Systematic Review and Meta-analysis","volume":"43","author":"Zhang","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S2213-8587(20)30117-0","article-title":"Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): An open-label, parallel-group, randomised controlled trial","volume":"8","author":"Taheri","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1758-5996-5-8","article-title":"The effect of vitamin D on insulin resistance in patients with type 2 diabetes","volume":"5","author":"Talaei","year":"2013","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/S0140-6736(01)06580-1","article-title":"Intake of vitamin D and risk of type 1 diabetes: A birth-cohort study","volume":"358","author":"Hypponen","year":"2001","journal-title":"Lancet"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1136\/adc.2007.128579","article-title":"Vitamin D supplementation in early childhood and risk of type 1 diabetes: A systematic review and meta-analysis","volume":"93","author":"Zipitis","year":"2008","journal-title":"Arch. Dis. Child."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.3390\/nu5093551","article-title":"Vitamin D intake and risk of type 1 diabetes: A meta-analysis of observational studies","volume":"5","author":"Dong","year":"2013","journal-title":"Nutrients"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"bvab179","DOI":"10.1210\/jendso\/bvab179","article-title":"Ergocalciferol in New-onset Type 1 Diabetes: A Randomized Controlled Trial","volume":"6","author":"Nwosu","year":"2022","journal-title":"J. Endocr. Soc."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.2337\/dc10-0814","article-title":"No protective effect of calcitriol on beta-cell function in recent-onset type 1 diabetes: The IMDIAB XIII trial","volume":"33","author":"Bizzarri","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13098-022-00817-w","article-title":"Health-related quality of life in T1DM patients after high-dose cholecalciferol supplementation: Data from a pilot clinical trial","volume":"14","author":"Said","year":"2022","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1111\/1753-0407.12023","article-title":"Negativation of type 1 diabetes-associated autoantibodies to glutamic acid decarboxylase and insulin in children treated with oral calcitriol","volume":"5","author":"Papadimitriou","year":"2013","journal-title":"J. Diabetes"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5713","DOI":"10.1111\/dom.15941","article-title":"Efficacy of vitamin D supplementation on glycaemic control in type 2 diabetes: An updated systematic review and meta-analysis of randomized controlled trials","volume":"26","author":"Chen","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Farahmand, M.A., Daneshzad, E., Fung, T.T., Zahidi, F., Muhammadi, M., Bellissimo, N., and Azadbakht, L. (2023). What is the impact of vitamin D supplementation on glycemic control in people with type-2 diabetes: A systematic review and meta-analysis of randomized controlled trails. BMC Endocr. Disord., 23.","DOI":"10.1186\/s12902-022-01209-x"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13098-023-01010-3","article-title":"Effect of vitamin D supplementation on type 2 diabetes biomarkers: An umbrella of interventional meta-analyses","volume":"15","author":"Musazadeh","year":"2023","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3332","DOI":"10.1038\/s41467-025-58721-6","article-title":"Vitamin D supplementation vs. placebo and incident type 2 diabetes in an ancillary study of the randomized Vitamin D and Omega-3 Trial","volume":"16","author":"Tobias","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Nguyen, A.P., Kawi, J., Meraz, R., Wierenga, K.L., Angosta, A.D., Hamilton, M.A., Fonarow, G.C., and Evangelista, L.S. (2025). Hidden Malnutrition in Overweight and Obese Individuals with Chronic Heart Failure: Insights from the Pro-HEART Trial. Nutrients, 17.","DOI":"10.3390\/nu17162694"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jchf.2012.11.003","article-title":"A randomized controlled trial of high dose vitamin D3 in patients with heart failure","volume":"1","author":"Boxer","year":"2013","journal-title":"JACC Heart Fail."},{"key":"ref_84","first-page":"e202507","article-title":"Effect of vitamin D on renin concentration in chronic heart failure patients: A randomized placebo-controlled trial","volume":"2025","author":"Mghaieth","year":"2025","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1161\/HYPERTENSIONAHA.108.119602","article-title":"Expression of the vitamin d receptor is increased in the hypertrophic heart","volume":"52","author":"Chen","year":"2008","journal-title":"Hypertension"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1677\/JOE-08-0241","article-title":"Vitamin D reduces the expression of collagen and key profibrotic factors by inducing an antifibrotic phenotype in mesenchymal multipotent cells","volume":"200","author":"Artaza","year":"2009","journal-title":"J. Endocrinol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"177858","DOI":"10.1016\/j.ejphar.2025.177858","article-title":"Calcitriol deficiency reduces myocardial ATP production with disturbed mitochondrial dynamics and increased uncoupling protein 2 expression","volume":"1002","author":"Lee","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1093\/eurjhf\/hfr175","article-title":"Vitamin D deficiency is a predictor of reduced survival in patients with heart failure; vitamin D supplementation improves outcome","volume":"14","author":"Gotsman","year":"2012","journal-title":"Eur. J. Heart Fail."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s11897-017-0355-7","article-title":"Vitamin D and Heart Failure","volume":"14","author":"Brinkley","year":"2017","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1007\/s00394-018-1806-y","article-title":"Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure","volume":"58","author":"Cubbon","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"325","DOI":"10.31083\/j.rcm2411325","article-title":"Vitamin D on Cardiac Function in Heart Failure: A Systematic Review and Meta-Analysis of 10 RCTs","volume":"24","author":"Chen","year":"2023","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ijcard.2019.01.027","article-title":"Vitamin D supplementation of 4000 IU daily and cardiac function in patients with advanced heart failure: The EVITA trial","volume":"280","author":"Zittermann","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"dgaa432","DOI":"10.1210\/clinem\/dgaa432","article-title":"Vitamin D Status and Risk of All-Cause and Cause-Specific Mortality in a Large Cohort: Results From the UK Biobank","volume":"105","author":"Fan","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/nrcardio.2016.73","article-title":"Vitamin D and cardiovascular disease prevention","volume":"13","author":"Pilz","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1161\/CIRCULATIONAHA.121.057008","article-title":"Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial","volume":"145","author":"Diederichsen","year":"2022","journal-title":"Circulation"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1093\/ajcn\/nqz147","article-title":"The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: A randomized, double-blind, placebo-controlled trial","volume":"110","author":"Zwakenberg","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/ckj\/sfab017","article-title":"Vitamin K supplementation and arterial calcification in dialysis: Results of the double-blind, randomized, placebo-controlled RenaKvit trial","volume":"14","author":"Hansen","year":"2021","journal-title":"Clin. Kidney J."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Li, T., Wang, Y., and Tu, W.P. (2023). Vitamin K supplementation and vascular calcification: A systematic review and meta-analysis of randomized controlled trials. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1115069"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/298\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T05:31:36Z","timestamp":1766986296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,27]]},"references-count":98,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27010298"],"URL":"https:\/\/doi.org\/10.3390\/ijms27010298","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,27]]}}}