{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T01:34:58Z","timestamp":1770082498574,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Introduction: Vitamin D deficiency [25(OH)D &lt; 30 ng\/mL] is widely prevalent globally and the efforts to tackle it have been rather unsuccessful to date. Despite different cutoffs used to define it, many clinicians adhere to the 2011 Endocrine Society definition. We present a special treat-to-target protocol aiming to restore and maintain vitamin D sufficiency. Methods: We reviewed the efficacy and safety of our vitamin D supplementation protocol over 5 years, and compared it to a group of patients who self-reported never taking vitamin D supplements. We recorded the baseline, 2-month, and annual 25(OH)D (D) measurements, along with subjects\u2019 age, sex, BMI, history of osteoporosis, nephrolithiasis, nephrocalcinosis, and renal colics. According to our supplementation protocol, replenishment of vitamin D involves cholecalciferol dosing in two steps: a loading dose (LD) for 2 months and a maintenance dose (MD) thereafter. Please refer to the main text for loading and maintenance dose titration. Results: Of 8329 cases with vitamin D measurements, 2248 had adequate follow up data of 3524.5 patient-years and were included in the study: a total of 1575 intervention subjects and 673 controls, with an average follow-up of 18.8 months. Baseline vitamin D concentrations of 22.6 ng\/mL (controls) did not change significantly (2 months: 22.2; 1 year: 21.7; 2 years: 22.0; 3 years: 23.8; 4 years: 21.8; and 5 years: 22.1 ng\/mL), while concentrations of 21.9 ng\/mL (intervention group) reached and remained 40 ng\/mL (2 months: 41.0; 1 year: 39.4; 2 years: 39.0; 3 years: 39.3; 4 years: 40.4; and 5 years: 39.4 ng\/mL). Vitamin D adequacy was achieved in 91.6% of patients in the intervention arm compared to only 16.9% in controls (p &lt; 0.0001). Mean D and rates of adequacy were significantly higher over time in the intervention arm (p &lt; 0.0001). The incidence of renal adverse events or hypervitaminosis did not differ between groups (p &gt; 0.05). Conclusions: Our intervention protocol appears highly efficient in achieving and maintaining vitamin D adequacy over 5 years, with no increase in adverse events compared with controls, presenting it as an effective long-term strategy.<\/jats:p>","DOI":"10.3390\/nu18030477","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:12:46Z","timestamp":1770041566000},"page":"477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effects of Vitamin D Replacement with a High-Dose Treat-to-Goal Strategy"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2804-0859","authenticated-orcid":false,"given":"Rodis D.","family":"Paparodis","sequence":"first","affiliation":[{"name":"Hellenic Endocrine Network, 10563 Athens, Greece"},{"name":"Department of Medicine, Edward Hines Jr. VA Hospital, Hines, IL 60141, USA"},{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-7161","authenticated-orcid":false,"given":"Nikolaos","family":"Angelopoulos","sequence":"additional","affiliation":[{"name":"Hellenic Endocrine Network, 10563 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9594-1521","authenticated-orcid":false,"given":"Sarantis","family":"Livadas","sequence":"additional","affiliation":[{"name":"Hellenic Endocrine Network, 10563 Athens, Greece"},{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Athens Medical Center, 15125 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2308-0245","authenticated-orcid":false,"given":"Evangelos","family":"Karvounis","sequence":"additional","affiliation":[{"name":"Hellenic Endocrine Network, 10563 Athens, Greece"},{"name":"Center of Excellence in Endocrine Surgery, Euroclinic Hospital, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-8348","authenticated-orcid":false,"given":"Dimitrios","family":"Askitis","sequence":"additional","affiliation":[{"name":"Hellenic Endocrine Network, 10563 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2723-331X","authenticated-orcid":false,"given":"Juan C.","family":"Jaume","sequence":"additional","affiliation":[{"name":"Department of Medicine, Edward Hines Jr. VA Hospital, Hines, IL 60141, USA"},{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6083-3560","authenticated-orcid":false,"given":"Dimitrios T.","family":"Papadimitriou","sequence":"additional","affiliation":[{"name":"Hellenic Endocrine Network, 10563 Athens, Greece"},{"name":"Pediatric Endocrine Clinics, 15125 Athens, Greece"},{"name":"Faculty of Medicine, University of Thessaly, 41110 Larisa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.3945\/ajcn.115.120873","article-title":"Vitamin D deficiency in Europe: Pandemic?","volume":"103","author":"Cashman","year":"2016","journal-title":"Am. 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